liu.seSearch for publications in DiVA
Endre søk
Begrens søket
1234567 1 - 50 of 339
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Capodanno, Alessandra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rzepecka, Anna
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Downregulation of tumor suppressive microRNAs in vivo in dense breast tissue of postmenopausal women2017Inngår i: Oncotarget, E-ISSN 1949-2553, Vol. 8, nr 54, s. 92134-92142Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Women with dense breast tissue on mammography are at higher risk of developing breast cancer but the underlying mechanisms are not well understood. De-regulation of microRNAs (miRNAs) has been associated with the onset of breast cancer. miRNAs in the extracellular space participate in the regulation of the local tissue microenvironment. Here, we recruited 39 healthy postmenopausal women attending their mammography-screen that were assessed having extreme dense or entirely fatty breasts (nondense). Microdialysis was performed in breast tissue and a reference catheter was inserted in abdominal subcutaneous fat for local sampling of extracellular compounds. Three miRNAs, associated with tumor suppression, miR-193b, miR-365a, and miR-452 were significantly down-regulated in dense breast tissue compared with nondense breast tissue. In addition, miR-452 exhibited significant negative correlations with several pro-inflammatory cytokines in vivo, which was confirmed in vitro by overexpression of miR-452 in breast cancer cells. No differences were found of miR-21, -29a, -30c, 146a, -148a, -203, or -451 in breast tissue and no miRs were different in plasma. Extracellular miRNAs may be among factors that should be included in studies of novel prevention strategies for breast cancer.

    Fulltekst (pdf)
    fulltext
  • 2.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Tissue specific expression of extracellular microRNA in human breast cancers and normal human breast tissue in vivo2015Inngår i: Oncotarget, E-ISSN 1949-2553, Vol. 6, nr 26, s. 22959-22969Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Extracellular circulating microRNAs (miRNAs) have been suggested to be biomarkers for disease monitoring but data are inconsistent, one reason being that blood miRNA is of heterogeneous origin. Here, we sampled extracellular microRNAs locally in situ using microdialysis. Three different cohorts of women were included; postmenopausal women with ongoing breast cancer investigated within the cancer and in normal adjacent breast tissue, postmenopausal women investigated in their normal healthy breast and subcutaneous fat before and after six weeks of tamoxifen therapy, premenopausal women during the menstrual cycle. Samples were initially screened using TaqMan array cards with subsequently absolute quantification. 124 miRNA were expressed in microdialysates. After absolute quantifications extracellular miRNA-21 was found to be significantly increased in breast cancer. In addition, the levels were significantly higher in pre-menopausal breast tissue compared with postmenopausal. In breast tissue of pre-menopausal women miRNA-21 exhibited a cyclic variation during the menstrual cycle and in postmenopausal women six weeks of tamoxifen treatment decreased miRNA-21 suggesting that this miRNA may be important for breast carcinogenesis. None of these changes were found in plasma or microdialysates from subcutaneous fat. Our data revealed tissue specific changes of extracellular circulating miRNAs that would be otherwise unraveled using blood samples.

    Fulltekst (pdf)
    fulltext
  • 3.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    Rasti Boroojeni, Fatemeh
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biofysik och bioteknik. Linköpings universitet, Tekniska fakulteten.
    Naeimipour, Sajjad
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biofysik och bioteknik. Linköpings universitet, Tekniska fakulteten.
    Reustle, Nina
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biofysik och bioteknik. Linköpings universitet, Tekniska fakulteten.
    Selegård, Robert
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biofysik och bioteknik. Linköpings universitet, Tekniska fakulteten.
    Aili, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biofysik och bioteknik. Linköpings universitet, Tekniska fakulteten.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Increased matrix stiffness enhances pro-tumorigenic traits in a physiologically relevant breast tissue- monocyte 3D model2024Inngår i: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 178, s. 160-169Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    High mammographic density, associated with increased tissue stiffness, is a strong risk factor for breast cancer per se . In postmenopausal women there is no differences in the occurrence of ductal carcinoma in situ (DCIS) depending on breast density. Preliminary data suggest that dense breast tissue is associated with a pro -inflammatory microenvironment including infiltrating monocytes. However, the underlying mechanism(s) remains largely unknown. A major roadblock to understanding this risk factor is the lack of relevant in vitro models. A biologically relevant 3D model with tunable stiffness was developed by cross -linking hyaluronic acid. Breast cancer cells were cultured with and without freshly isolated human monocytes. In a unique clinical setting, extracellular proteins were sampled using microdialysis in situ from women with various breast densities. We show that tissue stiffness resembling high mammographic density increases the attachment of monocytes to the cancer cells, increase the expression of adhesion molecules and epithelia-mesenchymal-transition proteins in estrogen receptor (ER) positive breast cancer. Increased tissue stiffness results in increased secretion of similar pro-tumorigenic proteins as those found in human dense breast tissue including inflammatory cytokines, proteases, and growth factors. ER negative breast cancer cells were mostly unaffected suggesting that diverse cancer cell phenotypes may respond differently to tissue stiffness. We introduce a biological relevant model with tunable stiffness that resembles the densities found in normal breast tissue in women. The model will be key for further mechanistic studies. Additionally, our data revealed several pro-tumorigenic pathways that may be exploited for prevention and therapy against breast cancer.

  • 4.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rzepecka, Anna
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Equal Pro-inflammatory Profiles of CCLs, CXCLs, and Matrix Metalloproteinases in the Extracellular Microenvironment In Vivo in Human Dense Breast Tissue and Breast Cancer2018Inngår i: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 8, artikkel-id 1994Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The inflammatory microenvironment affects breast cancer progression. Proteins that govern the inflammatory response are secreted into the extracellular space, but this compartment still needs to be characterized in human breast tissues in vivo. Dense breast tissue is a major risk factor for breast cancer by yet unknown mechanisms and no non-toxic prevention for these patients exists. Here, we used the minimal invasive technique of microdialysis for sampling of extracellular proteins in live tissues in situ in breast cancers of women before surgery and in healthy women having dense or non-dense breast tissue on mammography. Proteins were profiled using a proximity extension assay. Out of the 32 proteins assessed, 26 exhibited similar profiles in breast cancers and dense breast tissues; CCL-4, -7, -8, -11, -15, -16, -22, -23, and -25, CXCL-5, -8, -9, -16 as well as sIL-6R, IL-18, vascular endothelial growth factor, TGF-a, fibroblast growth factor 19, matrix metalloproteinase (MMP)-1, -2, -3, and urokinase-type plasminogen activator were all increased, whereas CCL-3, CX3CL1, hepatocyte growth factor, and MMP-9 were unaltered in the two tissues. CCL-19 and -24, CXCL-1 and -10, and IL-6 were increased in dense breast tissue only, whereas IL-18BP was increased in breast cancer only. Our results provide novel insights in the inflammatory microenvironment in human breast cancer in situ and define potential novel therapeutic targets. Additionally, we show previously unrecognized similarities of the pro-inflammatory microenvironment in dense breast tissue and breast cancer in vivo suggesting that anti-inflammatory breast cancer prevention trials for women with dense breast tissue may be feasible.

    Fulltekst (pdf)
    fulltext
  • 5.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rzepecka, Anna
    Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Increased nutrient availability in dense breast tissue of postmenopausal women in vivo2017Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikkel-id 42733Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Metabolic reprogramming is a hallmark of cancer. Nutrient availability in the tissue microenvironment determines cellular events and may play a role in breast carcinogenesis. High mammographic density is an independent risk factor for breast cancer. Whether nutrient availability differs in normal breast tissues with various densities is unknown. Therefore we investigated whether breast tissues with various densities exhibited differences in nutrient availability. Healthy postmenopausal women from the regular mammographic screening program who had either predominantly fatty breast tissue (nondense), n = 18, or extremely dense breast tissue (dense), n = 20, were included. Microdialysis was performed for the in vivo sampling of amino acids (AAs), analyzed by ultra-high performance liquid chromatography with tandem mass spectroscopy, glucose, lactate and vascular endothelial growth factor (VEGF) in breast tissues and, as a control, in abdominal subcutaneous (s.c.) fat. We found that dense breast tissue exhibited significantly increased levels of 20 proteinogenic AAs and that 18 of these AAs correlated significantly with VEGF. No differences were found in the s.c. fat, except for one AA, suggesting tissue-specific alterations in the breast. Glucose and lactate were unaltered. Our findings provide novel insights into the biology of dense breast tissue that may be explored for breast cancer prevention strategies.

    Fulltekst (pdf)
    fulltext
  • 6.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rzepecka, Anna
    Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Romu, Thobias
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Borga, Magnus
    Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Lundberg, Peter
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Kihlberg, Johan
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo2016Inngår i: Oncoimmunology, ISSN 2162-4011, E-ISSN 2162-402X, Vol. 5, nr 10, artikkel-id e1229723Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Inflammation is one of the hallmarks of carcinogenesis. High mammographic density has been associated with increased risk of breast cancer but the mechanisms behind are poorly understood. We evaluated whether breasts with different mammographic densities exhibited differences in the inflammatory microenvironment.Postmenopausal women attending the mammography-screening program were assessed having extreme dense, n = 20, or entirely fatty breasts (nondense), n = 19, on their regular mammograms. Thereafter, the women were invited for magnetic resonance imaging (MRI), microdialysis for the collection of extracellular molecules in situ and a core tissue biopsy for research purposes. On the MRI, lean tissue fraction (LTF) was calculated for a continuous measurement of breast density. LTF confirmed the selection from the mammograms and gave a continuous measurement of breast density. Microdialysis revealed significantly increased extracellular in vivo levels of IL-6, IL-8, vascular endothelial growth factor, and CCL5 in dense breast tissue as compared with nondense breasts. Moreover, the ratio IL-1Ra/IL-1 was decreased in dense breasts. No differences were found in levels of IL-1, IL-1Ra, CCL2, leptin, adiponectin, or leptin:adiponectin ratio between the two breast tissue types. Significant positive correlations between LTF and the pro-inflammatory cytokines as well as between the cytokines were detected. Stainings of the core biopsies exhibited increased levels of immune cells in dense breast tissue.Our data show that dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment and, if confirmed in a larger cohort, suggests novel targets for prevention therapies for women with dense breast tissue.

  • 7.
    Abrahamsson, Annelie
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Vazquez Rodriguez, Gabriela
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Fulvestrant-Mediated Attenuation of the Innate Immune Response Decreases ER+ Breast Cancer Growth In Vivo More Effectively than Tamoxifen2020Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 80, nr 20, s. 4487-4499Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Although blocking estrogen-dependent signaling is a cornerstone of adjuvant treatment for breast cancer, 25% of patients experience recurrent disease. Stroma events including innate immune responses are key in cancer progression. How different estrogen receptor (ER)-targeting therapies, including the partial agonist tamoxifen and the pure antagonist fulvestrant, affect the tumor stroma has not yet been elucidated. Fulvestrant is used in only postmenopausal patients, and its effects in the presence of estradiol remain undetermined. Here we observe that fulvestrant decreases ER+ breast cancer growth compared with tamoxifen in the presence of physiologic levels of estradiol in human breast cancer in nude mice and in murine breast cancer in immune-competent mice. Fulvestrant significantly inhibited macrophage and neutrophil infiltration in both models. These effects were corroborated in a zebrafish model where fulvestrant inhibited neutrophil- and macrophage-dependent cancer cell dissemination more effectively than tamoxifen. A comprehensive analysis of 234 human proteins released into the cancer microenvironment by the cancer cells sampled via microdialysis in vivo revealed that 38 proteins were altered following both treatments; 25 of these proteins were associated with immune response and were altered by fulvestrant only. Compared with tamoxifen, fulvestrant significantly affected inflammatory proteins released by murine stroma cells. Importantly, in vivo microdialysis of human ER+ breast cancer revealed that the majority of affected proteins in murine models were upregulated in patients. Together, these results suggest that fulvestrant targets ER+ breast cancer more effectively than tamoxifen even in the presence of estradiol, mainly by attenuation of the innate immune response. Significance: These findings demonstrate novel effects of the pure antiestrogen fulvestrant in ERthorn breast cancer and evaluate its effects under physiologic levels of estradiol, representative of premenopausal patients.

  • 8.
    Alevronta, Eleftheria
    et al.
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Karolinska Institute, Sweden.
    al-Abany, Massoud
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Nyberg, Tommy
    Karolinska Institute, Sweden.
    Lind, Helena
    Karolinska Institute, Sweden.
    Waldenstrom, Ann-Charlotte
    Sahlgrens Acad, Sweden; Sahlgrens University Hospital, Sweden.
    Olsson, Caroline
    Sahlgrens Acad, Sweden; Gothenburg University, Sweden.
    Dunberger, Gail
    Karolinska Institute, Sweden; Ersta Skondal University of Coll, Sweden.
    Bergmark, Karin
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden; Sahlgrens University Hospital, Sweden.
    Steineck, Gunnar
    Karolinska Institute, Sweden; Sahlgrens Acad, Sweden.
    Lind, Bengt K.
    Karolinska Institute, Sweden.
    Time-dependent dose-response relation for absence of vaginal elasticity after gynecological radiation therapy2016Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 120, nr 3, s. 537-541Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and purpose: To investigate the dose-response relation between the dose to the vagina and the patient-reported symptom absence of vaginal elasticity and how time to follow-up influences this relation. Material and methods: The study included 78 long-term gynecological cancer survivors treated between 1991 and 2003 with external beam radiation therapy. Of those, 24 experienced absence of vaginal elasticity. A normal tissue complication model is introduced that takes into account the influence of time to follow-up on the dose-response relation and the patients age. The best estimates of the dose-response parameters were calculated using Probit, Probit-Relative Seriality (RS) and Probit-time models. Log likelihood (LL) values and the Akaike Information Criterion (AIC) were used to evaluate the model fit. Results: The dose-response parameters for absence of vaginal elasticity according to the Probit and Probit-time models with the 68% Confidence Intervals (CI) were: LL = 39.8, D-50 = 49.7 (47.2-52.4) Gy, gamma(50) =1.40 (1.12-1.70) and LL = 37.4, D-50 = 46.9 (43.5-50.9) Gy, gamma(50) = 1.81 (1.17-2.51) respectively. Conclusions: The proposed model, which describes the influence of time to follow-up on the dose response relation, fits our data best. Our data indicate that the steepness of the dose-response curve of the dose to the vagina and the symptom absence of vaginal elasticity increases with time to follow-up, while D-50 decreases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 9.
    Ali, Zaheer
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Cui, Dongmei
    Sun Yat Sen Univ, Peoples R China.
    Yang, Yunlong
    Fudan Univ, Peoples R China.
    Tracey-White, Dhani
    UCL Inst Ophthalmol, England.
    Vazquez Rodriguez, Gabriela
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Moosajee, Mariya
    UCL Inst Ophthalmol, England.
    Ju, Rong
    Sun Yat Sen Univ, Peoples R China.
    Li, Xuri
    Sun Yat Sen Univ, Peoples R China.
    Cao, Yihai
    Karolinska Inst, Sweden.
    Jensen, Lasse
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Synchronized tissue-scale vasculogenesis and ubiquitous lateral sprouting underlie the unique architecture of the choriocapillaris2020Inngår i: Developmental Biology, ISSN 0012-1606, E-ISSN 1095-564X, Vol. 457, nr 2, s. 206-214Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The choriocapillaris is an exceptionally high density, two-dimensional, sheet-like capillary network, characterized by the highest exchange rate of nutrients for waste products per area in the organism. These unique morphological and physiological features are critical for supporting the extreme metabolic requirements of the outer retina needed for vision. The developmental mechanisms and processes responsible for generating this unique vascular network remain, however, poorly understood. Here we take advantage of the zebrafish as a model organism for gaining novel insights into the cellular dynamics and molecular signaling mechanisms involved in the development of the choriocapillaris. We show for the first time that zebrafish have a choriocapillaris highly similar to that in mammals, and that it is initially formed by a novel process of synchronized vasculogenesis occurring simultaneously across the entire outer retina. This initial vascular network expands by un-inhibited sprouting angiogenesis whereby all endothelial cells adopt tip-cell characteristics, a process which is sustained throughout embryonic and early post-natal development, even after the choriocapillaris becomes perfused. Ubiquitous sprouting was maintained by continuous VEGF-VEGFR2 signaling in endothelial cells delaying maturation until immediately before stages where vision becomes important for survival, leading to the unparalleled high density and lobular structure of this vasculature. Sprouting was throughout development limited to two dimensions by Bruchs membrane and the sclera at the anterior and posterior surfaces respectively. These novel cellular and molecular mechanisms underlying choriocapillaris development were recapitulated in mice. In conclusion, our findings reveal novel mechanisms underlying the development of the choriocapillaris during zebrafish and mouse development. These results may explain the uniquely high density and sheet-like organization of this vasculature.

    Fulltekst (pdf)
    fulltext
  • 10.
    Almlöv, Karin
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Woisetschläger, Mischa
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Medicinska fakulteten.
    Loftås, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Hallböök, Olof
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Elander, Nils
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Sandström, Per
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    MRI Lymph Node Evaluation for Prediction of Metastases in Rectal Cancer2020Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 40, nr 5, s. 2757-2763Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To explore whether the size and characteristics of the largest regional lymph node in patients with rectal cancer, based on magnetic resonance imaging (MRI), following neoadjuvant therapy and before surgery, is able to identify patients at high risk of developing metachronous metastases.

    Patients and Methods: A retrospective case–control study with data from the Swedish Colo-Rectal Cancer Registry. Forty patients were identified with metachronous metastases (M+), and 40 patients without metastases (M0) were matched as controls.

    Results: Patients with M+ disease were more likely to have a regional lymph node measuring ≥5 mm than patients with M0. (87% vs. 65%, p=0.02). There was also a significant difference between the groups regarding the presence of an irregular border of the largest lymph node (68% vs. 40%, p=0.01).

    Conclusion: Lymph nodes measuring ≥5 mm with/without displaying irregular borders at MRI performed after neoadjuvant therapy emerged as risk factors for metachronous metastases in patients with rectal cancer. Intensified follow-up programmes may be indicated in these patients.

    Fulltekst (pdf)
    fulltext
  • 11.
    Andersson, Ellen
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Albertsson, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Holmqvist, Annica
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    GRACE: Geriatric patients tReated with Avastin in CRC multiple linEs2017Inngår i: Clinical Practice, ISSN 2044-9038, E-ISSN 2044-9046, Vol. 14, nr 3, s. 175-182Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Continuous treatment with bevacizumab in elderly patients with mCRC: A phase IV prospective, open-label, single-arm trial to evaluate outcomes and safety with continuous bevacizumab treatment in combination with chemotherapy over disease progression.

  • 12.
    Apellániz-Ruiz, Maria
    et al.
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Tejero, Héctor
    Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain.
    Inglada-Pérez, Lucía
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
    Sánchez-Barroso, Lara
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Gutiérrez-Gutiérrez, Gerardo
    Neurology Section, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Calvo, Isabel
    Medical Oncology Department, Hospital Montepríncipe, Madrid, Spain. Medical Oncology Department, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Castelo, Beatriz
    Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
    Redondo, Andrés
    Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain.
    García-Donás, Jesus
    Gynecological and Genitourinary Tumors Programme, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Romero-Laorden, Nuria
    Gynecological and Genitourinary Tumors Programme, Centro Integral Oncológico Clara Campal, Madrid, Spain.
    Sereno, Maria
    Medical Oncology Department, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Merino, María
    Medical Oncology Department, Hospital Universitario Infanta Sofía, Madrid, Spain.
    Currás-Freixes, Maria
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Montero-Conde, Cristina
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Mancikova, Veronika
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden.
    Al-Shahrour, Fatima
    Translational Bioinformatics Unit, Spanish National Cancer Research Centre, Madrid, Spain.
    Cascon, Alberto
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain. ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain.
    Robledo, Mercedes
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain .
    Rodriguez-Antona, Cristina
    Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre, Madrid, Spain.ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain .
    Targeted sequencing reveals low-frequency variants in EPHA genes as markers of paclitaxel-induced peripheral neuropathy.2017Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, nr 5, s. 1227-1235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Neuropathy is the dose limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for inter-individual differences remain unexplained. In this study we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.

    EXPERIMENTAL DESIGN: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/ gene-based analyses were used to compare variant frequencies among neuropathy groups and Cox regression models were used to analyze neuropathy evolution along treatment.

    RESULTS: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low frequency non-synonymous variants in EPHA6 were present exclusively in patients with high neuropathy and all affected the ligand binding domain. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency non-synonymous variant carriers (HR=14.60, 95%CI=2.33-91.62, P=0.0042) and an independent cohort confirmed an increased neuropathy risk (HR=2.07, 95%CI=1.14-3.77, P=0.017). Combining the series gave an estimated 2.50-fold higher risk of neuropathy (95%CI=1.46-4.31; P=9.1x10(-4)).

    CONCLUSION: This first study sequencing EPHA genes revealed that low frequency variants in EPHA6, EPHA5 and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHAs neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs.

    Fulltekst (pdf)
    fulltext
  • 13.
    Ardenfors, Oscar
    et al.
    Stockholm University, Sweden.
    Gudowska, Irena
    Stockholm University, Sweden.
    Flejmer, Anna M.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Dasu, Alexandru
    The Skandion Clinic, Sweden.
    Impact of irradiation setup in proton spot scanning brain therapy on organ doses from secondary radiation2018Inngår i: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 180, nr 1-4, s. 261-266Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A Monte Carlo model of a proton spot scanning pencil beam was used to simulate organ doses from secondary radiation produced from brain tumour treatments delivered with either a lateral field or a vertex field to one adult and one paediatric patient. Absorbed doses from secondary neutrons, photons and protons and neutron equivalent doses were higher for the vertex field in both patients, but the differences were low in absolute terms. Absorbed doses ranged between 0.1 and 43 μGy.Gy−1 in both patients with the paediatric patient receiving higher doses. The neutron equivalent doses to the organs ranged between 0.5 and 141 μSv.Gy−1 for the paediatric patient and between 0.2 and 134 μSv.Gy−1 for the adult. The highest neutron equivalent dose from the entire treatment was 7 mSv regardless of field setup and patient size. The results indicate that different field setups do not introduce large absolute variations in out-of-field doses produced in patients undergoing proton pencil beam scanning of centrally located brain tumours.

  • 14.
    Ardern, Clare
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för fysioterapi. Linköpings universitet, Medicinska fakulteten. School of Allied Health, La Trobe University, Melbourne, Australia.
    Österberg, Annika
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för fysioterapi. Linköpings universitet, Medicinska fakulteten.
    Tagesson, Sofi
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för fysioterapi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Gauffin, Håkan
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Webster, Kate E.
    La Trobe University, Australia.
    Kvist, Joanna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för fysioterapi. Linköpings universitet, Hälsouniversitetet.
    Satisfaction With Knee Function After Primary Anterior Cruciate Ligament Reconstruction Is Associated With Self-Efficacy, Quality of Life, and Returning to the Preinjury Physical Activity2016Inngår i: Arthroscopy: The Journal of Arthroscopy And Related, ISSN 0749-8063, E-ISSN 1526-3231, Vol. 32, nr 8, s. 1631-1638Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To assess whether patient-reported outcomes (psychological factors, appraisals of knee function, and physical activity participation) were associated with satisfaction with knee function after anterior cruciate ligament (ACL) reconstruction. Methods: Participants who were aged 18 to 45 years and a minimum 12 months post primary ACL reconstruction completed a questionnaire battery evaluating knee self-efficacy, knee-related quality of life, self-reported function, and physical activity participation. Participants responses to the question "If you were to spend the rest of your life with your knee just the way it has been in the last week, would you feel.... (7-point ordinal scale; 1 = happy, 7 = unhappy)" were categorized as satisfied, mostly satisfied, or dissatisfied and used as the primary outcome. Ordinal regression was used to examine associations between independent variables and the primary outcome. Results: A total of 177 participants were included at an average of 3 years after primary ACL reconstruction. At follow-up, 44% reported they would be satisfied, 28% mostly satisfied, and 28% dissatisfied with the outcome of ACL reconstruction. There were significant differences in psychological responses and appraisal of knee function between the 3 groups (P = .001), and significantly more people in the satisfied group had returned to their preinjury activity (58%) than in the mostly satisfied (28%) and dissatisfied (26%) groups (P = .001). Multivariable analysis demonstrated that the odds of being satisfied increased by a factor of 3 with higher self-efficacy, greater knee-related quality of life, and returning to the preinjury activity. Conclusions: People who had returned to their preinjury physical activity and who reported higher knee-related self-efficacy and quality of life were more likely to be satisfied with the outcome of ACL reconstruction.

    Fulltekst (pdf)
    fulltext
  • 15.
    Asowed, Mustafa
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Elander, Nils
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Pettersson, Linn
    Ryhov Cty Hosp, Sweden.
    Ekholm, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Ryhov Cty Hosp, Sweden.
    Papantoniou, Dimitrios
    Ryhov Cty Hosp, Sweden; Uppsala Univ, Sweden.
    Activity and safety of KEES-an oral multi-drug chemo-hormonal metronomic combination regimen in metastatic castration-resistant prostate cancer2023Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 23, nr 1, artikkel-id 309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundMetastatic castration-resistant prostate cancer (mCRPC) remains a therapeutic challenge and evidence for late-line treatments in real-life is limited. The present study investigates the efficacy and safety of an oral metronomic chemo-hormonal regimen including cyclophosphamide, etoposide, estramustine, ketoconazole and prednisolone (KEES) administered in a consecutive biweekly schedule.MethodsA retrospective cohort study in two Swedish regions was conducted. Overall (OS) and progression-free survival (PFS), biochemical response rate (bRR) and toxicities were analyzed.ResultsOne hundred and twenty-three patients treated with KEES after initial treatment with at least a taxane or an androgen-receptor targeting agents (ARTA) were identified. Of those, 95 (77%) had received both agents and were the primary analysis population. Median (95% CI) OS and PFS in the pre-treated population were 12.3 (10.1-15.0) and 4.4 (3.8-5.5) months, respectively. Biochemical response, defined as >= 50% prostate-specific antigen (PSA) reduction, occurred in 26 patients (29%), and any PSA reduction in 59 (65%). PFS was independent of prior treatments used, and KEES seemed to be effective in late treatment lines. The bRR was higher compared to historical data of metronomic treatments in docetaxel and ARTA pre-treated populations. In multivariable analyses, performance status (PS) >= 2 and increasing alkaline phosphatase (ALP) predicted for worse OS. Nausea, fatigue, thromboembolic events and bone marrow suppression were the predominant toxicities.ConclusionsKEES demonstrated meaningful efficacy in heavily pre-treated CRPC patients, especially those with PS 0-1 and lower baseline ALP, and had an acceptable toxicity profile.

    Fulltekst (pdf)
    fulltext
  • 16.
    Aughton, Karen
    et al.
    Univ Liverpool, England.
    Elander, Nils
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Univ Liverpool, England.
    Evans, Anthony
    Univ Liverpool, England.
    Jackson, Richard
    Univ Liverpool, England.
    Campbell, Fiona
    Univ Liverpool, England.
    Costello, Eithne
    Univ Liverpool, England.
    Halloran, Christopher M.
    Univ Liverpool, England.
    Mackey, John R.
    Univ Alberta, Canada.
    Scarfe, Andrew G.
    Univ Alberta, Canada.
    Valle, Juan W.
    Univ Manchester, England.
    Carter, Ross
    Glasgow Royal Infirm, Scotland.
    Cunningham, David
    Royal Marsden Natl Hlth Serv NHS Fdn Trust, England.
    Tebbutt, Niall C.
    Austin Hlth, Australia.
    Goldstein, David
    Univ New South Wales, Australia.
    Shannon, Jennifer
    Univ Sydney, Australia.
    Glimelius, Bengt
    Uppsala Univ, Sweden.
    Hackert, Thilo
    Heidelberg Univ, Germany.
    Charnley, Richard M.
    Freeman Rd Hosp, England.
    Anthoney, Alan
    St James Univ Hosp, England.
    Lerch, Markus M.
    Univ Med Greifswald, Germany.
    Mayerle, Julia
    Univ Med Greifswald, Germany; Klinikum LMU Munchen Grosshadern, Germany.
    Palmer, Daniel H.
    Univ Liverpool, England.
    Buechler, Markus W.
    Heidelberg Univ, Germany.
    Ghaneh, Paula
    Univ Liverpool, England.
    Neoptolemos, John P.
    Heidelberg Univ, Germany.
    Greenhalf, William
    Univ Liverpool, England.
    hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA2021Inngår i: Cancers, ISSN 2072-6694, Vol. 13, nr 22, artikkel-id 5758Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Simple Summary: Recent clinical trials suggest that combination therapies that include either gemcitabine or 5-fluorouracil (5-FU) both give significant survival benefits for pancreatic cancer patients. The tumor level of the nucleoside transporter hENT1 is prognostic in patients treated with adjuvant gemcitabine but not adjuvant 5-FU. This work shows for the first time that hENT1 is only predictive of benefit from gemcitabine over 5-FU in patients with low levels of CDA transcript. A choice between adjuvant 5-FU based combination therapies (such as FOLFIRINOX) and gemcitabine-based therapy (e.g., GemCap) could be made based on a combination of hENT1 protein and CDA mRNA measured in a resected tumor.Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (p = 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (p = 0.02) and 26.4 v 14.6 months with 5-FU (p = 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient.

    Fulltekst (pdf)
    fulltext
  • 17. Bestill onlineKjøp publikasjonen >>
    Ax, Anna-Karin
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Exercise in patients with cancer: Effects on health-related quality of life, costs, and cost-effectiveness during oncological treatment2023Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background: Short and long-term side effects of oncological treatment negatively affect daily living and health-related quality of life (HRQoL) in patient with cancer. Exercise during treatment is beneficial for HRQoL, however evidence as to what exercise intensity is most optimal for improving HRQoL and cost-effectiveness is lacking. Cost-effectiveness is important information for decisionmakers when implementing healthcare interventions, such as exercise programmes. The overall aim of this thesis was to study functioning in daily life, HRQoL, costs, and cost-effectiveness of an exercise intervention of different exercise intensities in patients with cancer receiving oncological treatment. 

    Method: Study I was qualitative and explored how individuals with cancer receiving curative treatment and participating in an exercise intervention experienced their functioning in daily life. Semi-structured individual interviews (n =21) were performed and analysed with thematic analysis. Studies II–IV were quantitative and used data from a randomised controlled trial (RCT) of high-intensity (HI) and low-to-moderate-intensity (LMI) exercise of combined resistance and endurance training with or without self-regulatory behaviour change support. The RCT was preceded by a descriptive longitudinal study with usual care (UC). Participants were diagnosed with breast, prostate, or colon cancer and received (neo)adjuvant oncological treatment. Study II evaluated the effects on HRQoL of exercising at HI (n =288) and LMI (n =289) versus UC (n =89) up to 18 months after start of oncological treatment, using the EORTC QLQ-C30 questionnaire. Data were analysed using descriptive and multivariate statistics. Study III evaluated resource utilisation and societal costs of the exercise intervention in the RCT (n =534) versus UC (n =85), and of HI (n =269) versus LMI (n =265) exercise 18 months after start of oncological treatment. Societal costs included costs of healthcare resource utilisation (healthcare visits, hospitalisation, prescribed medication), productivity loss (disability pensions and sick leave), and the exercise intervention. Study IV evaluated the cost-effectiveness of the exercise intensities in the RCT (HI: n =99 and LMI: n =90) at 1-year follow-up post intervention. Cost data were retrieved from Study III and health outcome were collected using the EQ-5D-5L questionnaire and calculated for quality-adjusted life-years. Cost-effectiveness was evaluated as the incremental cost-effectiveness ratio (ICER). 

    Results: Participants experienced impairments from oncological treatment but strove to maintain function in daily life. The exercise programme improved physical and psychological wellbeing during treatment (Study I). There were no significant differences in HRQoL between exercise intensities up to 1 year after the exercise intervention. The exercise groups scored significant better HRQoL compared to UC over time (Study II). There was no significant difference in mean societal costs between the exercise intervention and UC, nor between the exercise intensities (Study III). There was no significant difference in cost or in effect between the exercise intensities. Although the mean ICER indicated that HI was cost-effective compared to LMI, the uncertainty was large (Study IV). 

    Conclusion: Participating in an exercise programme during oncological treatment was a positive and supportive experience that contributed to increase physical and psychological wellbeing. Exercise of HI and LMI during oncological treatment had similar effect on HRQoL and societal costs. In addition, the exercise group had beneficial effects on HRQoL and no significant difference in societal costs compared to UC, meaning the exercise programme did not save or add societal cost. Thus, based on cost-effectiveness we suggest decisionmakers and clinicians implement exercise programmes including both HI and LMI in cancer care and recommend exercise regardless of intensity according to the patient’s preferences to improve or to maintain aspects of HRQoL during oncological treatment. 

    Delarbeid
    1. Exercise: A positive feature on functioning in daily life during cancer treatment – Experiences from the Phys-Can study
    Åpne denne publikasjonen i ny fane eller vindu >>Exercise: A positive feature on functioning in daily life during cancer treatment – Experiences from the Phys-Can study
    Vise andre…
    2020 (engelsk)Inngår i: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Nursing, Vol. 44, artikkel-id 101713Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Purpose

    Impaired functioning due to cancer treatment is a challenge for daily life. Exercise during treatment can improve functioning. However, research describing experiences of how exercise affects activities of daily life is limited. We aimed to explore how individuals with cancer receiving curative treatment and participating in an exercise intervention experienced their functioning in daily life.

    Methods

    Twenty-one participants were recruited from Phys-Can, an exercise intervention study. Semi-structured interviews were conducted after the intervention had finished, and data was analysed using thematic analysis.

    Results

    Two main themes evolved: “Striving to maintain a normal life in a new context” and “Struggling with impairments from side effects of cancer treatment”. The supervised group exercise proved popular, and participants reported positive effects on physical and psychological functioning, as well as social and informative support from other participants. Participants struggled with impaired cognitive and physical functioning and exhaustion. They strove to maintain a normal life by adjusting their activities.

    Conclusions

    Perceived physical and psychological benefits from exercise during cancer treatment suggest that exercise should be a part of cancer rehabilitation to facilitate activities and participation in daily life. Striving to maintain a normal life during cancer treatment is vital, and adjustments are needed to maintain activities and participation in daily life. Cancer nurses should motivate patients to engage in physical activity and encourage the introduction of exercise as part of their rehabilitation. They could also support patients in making adjustments to maintain functioning in daily life.

    sted, utgiver, år, opplag, sider
    Elsevier, 2020
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-162990 (URN)10.1016/j.ejon.2019.101713 (DOI)000523651500023 ()31877511 (PubMedID)
    Merknad

    Fulltext published under Creative Commons license CC BY-NC-ND 4.0

    https://creativecommons.org/licenses/by-nc-nd/4.0/

    Funding agencies: Department of Oncology, Linkoping University Hospital, Sweden; Region Ostergotland, Sweden; Swedish Cancer SocietySwedish Cancer Society; Swedish Research CouncilSwedish Research Council

    Tilgjengelig fra: 2020-01-09 Laget: 2020-01-09 Sist oppdatert: 2023-04-27bibliografisk kontrollert
    2. Short- and long-term effect of high versus low-to-moderate intensity exercise to optimise health-related quality of life after oncological treatment - results from the Phys-Can project
    Åpne denne publikasjonen i ny fane eller vindu >>Short- and long-term effect of high versus low-to-moderate intensity exercise to optimise health-related quality of life after oncological treatment - results from the Phys-Can project
    Vise andre…
    2022 (engelsk)Inngår i: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 30, s. 5949-5963Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Purpose This study aimed to evaluate the effect of high intensity (HI) vs low-to-moderate intensity (LMI) exercise on health-related quality of life (HRQoL) up to 18 months after commencement of oncological treatment in patients with breast, colorectal or prostate cancer. In addition, we conducted a comparison with usual care (UC). Methods Patients scheduled for (neo)adjuvant oncological treatment (n = 577) were randomly assigned to 6 months of combined resistance and endurance training of HI or LMI. A longitudinal descriptive study (UC) included participants (n = 89) immediately before the RCT started. HRQoL was assessed by EORTC QLQ-C30 at baseline, 3, 6 and 18 months (1 year after completed exercise intervention) follow-up. Linear mixed models were used to study the groups over time. Results Directly after the intervention, HI scored significant (P = 0.02), but not clinically relevant, higher pain compared with LMI. No other significant difference in HRQoL was found between the exercise intensities over time. Clinically meaningful improvements in HRQoL over time were detected within both exercise intensities. We found favourable significant differences in HRQoL in both exercise intensities compared with UC over time. Conclusion This study adds to the strong evidence of positive effect of exercise and shows that exercise, regardless of intensity, can have beneficial effects on HRQoL during oncological treatment and also for a substantial time after completion of an exercise intervention. In this study, for one year after. Implications for cancer survivors Patients can be advised to exercise at either intensity level according to their personal preferences, and still benefit from both short-term and long-term improvements in HRQoL.

    sted, utgiver, år, opplag, sider
    Heidelberg, Germany: Springer, 2022
    Emneord
    Cancer; Oncological treatment; Exercise; HRQoL
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-184562 (URN)10.1007/s00520-022-07016-3 (DOI)000779224400002 ()35391574 (PubMedID)2-s2.0-85127637021 (Scopus ID)
    Merknad

    Funding Agencies: Linköping University; Swedish Cancer Society; Swedish Research Council, European Commission; Region Östergötland, Sweden; Oncology Department Foundations Research Fund in Linköping, Sweden

    Tilgjengelig fra: 2022-05-03 Laget: 2022-05-03 Sist oppdatert: 2023-04-27bibliografisk kontrollert
    3. Long-term resource utilisation and associated costs of exercise during (neo)adjuvant oncological treatment: the Phys-Can project
    Åpne denne publikasjonen i ny fane eller vindu >>Long-term resource utilisation and associated costs of exercise during (neo)adjuvant oncological treatment: the Phys-Can project
    Vise andre…
    2022 (engelsk)Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 61, nr 7, s. 888-896Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background Exercise during oncological treatment is beneficial to patient health and can counteract the side effects of treatment. Knowledge of the societal costs associated with an exercise intervention, however, is limited. The aims of the present study were to evaluate the long-term resource utilisation and societal costs of an exercise intervention conducted during (neo)adjuvant oncological treatment in a randomised control trial (RCT) versus usual care (UC), and to compare high-intensity (HI) versus low-to-moderate intensity (LMI) exercise in the RCT. Methods We used data from the Physical Training and Cancer (Phys-Can) project. In the RCT, 577 participants were randomised to HI or to LMI of combined endurance and resistance training for 6 months, during oncological treatment. The project also included 89 participants with UC in a longitudinal observational study. We measured at baseline and after 18 months. Resource utilisation and costs of the exercise intervention, health care, and productivity loss were compared using analyses of covariance (RCT vs. UC) and t test (HI vs. LMI). Results Complete data were available for 619 participants (RCT HI: n = 269, LMI: n = 265, and UC: n = 85). We found no difference in total societal costs between the exercise intervention groups in the RCT and UC. However, participants in the RCT had lower rates of disability pension days (p < .001), corresponding costs (p = .001), and pharmacy costs (p = .018) than the UC group. Nor did we find differences in resource utilisation or costs between HI and LMI exercise int the RCT. Conclusion Our study showed no difference in total societal costs between the comprehensive exercise intervention and UC or between the exercise intensities. This suggests that exercise, with its well-documented health benefits during oncological treatment, produces neither additional costs nor savings.

    sted, utgiver, år, opplag, sider
    Taylor & Francis Ltd, 2022
    Emneord
    Cancer; exercise; health care costs; sick leave; costs; cost analysis
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-185605 (URN)10.1080/0284186X.2022.2075238 (DOI)000799825800001 ()35607981 (PubMedID)
    Merknad

    Funding Agencies|Swedish Cancer Society; Swedish Research Council; Region Ostergotland, Sweden

    Tilgjengelig fra: 2022-06-09 Laget: 2022-06-09 Sist oppdatert: 2023-05-04bibliografisk kontrollert
    4. Cost-effectiveness of different exercise intensities during oncological treatment in the Phys-Can RCT
    Åpne denne publikasjonen i ny fane eller vindu >>Cost-effectiveness of different exercise intensities during oncological treatment in the Phys-Can RCT
    Vise andre…
    2023 (engelsk)Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 62, nr 4, s. 414-421Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background

    Cost-effectiveness is important in the prioritisation between interventions in health care. Exercise is cost-effective compared to usual care during oncological treatment; however, the significance of exercise intensity to the cost-effectiveness is unclear. In the present study, we aimed to evaluate the long-term cost-effectiveness of the randomised controlled trial Phys-Can, a six-month exercise programme of high (HI) or low-to-moderate intensity (LMI) during (neo)adjuvant oncological treatment.

    Methods

    A cost-effectiveness analysis was performed, based on 189 participants with breast, colorectal, or prostate cancer (HI: n = 99 and LMI: n = 90) from the Phys-Can RCT in Sweden. Costs were estimated from a societal perspective, and included cost of the exercise intervention, health care utilisation and productivity loss. Health outcomes were assessed as quality-adjusted life-years (QALYs), using EQ-5D-5L at baseline, post intervention and 12 months after the completion of the intervention.

    Results

    At 12-month follow-up after the intervention, the total cost per participant did not differ significantly between HI (€27,314) and LMI exercise (€29,788). There was no significant difference in health outcome between the intensity groups. On average HI generated 1.190 QALYs and LMI 1.185 QALYs. The mean incremental cost-effectiveness ratio indicated that HI was cost effective compared with LMI, but the uncertainty was large.

    Conclusions

    We conclude that HI and LMI exercise have similar costs and effects during oncological treatment. Hence, based on cost-effectiveness, we suggest that decision makers and clinicians can consider implementing both HI and LMI exercise programmes and recommend either intensity to the patients with cancer during oncological treatment to facilitate improvement of health.

    sted, utgiver, år, opplag, sider
    Taylor & Francis, 2023
    Emneord
    Cancer, exercise, health, cost-effectiveness
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-193277 (URN)10.1080/0284186X.2023.2200149 (DOI)000971022300001 ()37074759 (PubMedID)
    Merknad

    Funding agencies: This work was supported by grants from the Swedish Cancer Society; the Swedish Research Council, and the Region Östergötland, Sweden.

    Tilgjengelig fra: 2023-04-27 Laget: 2023-04-27 Sist oppdatert: 2024-05-02bibliografisk kontrollert
    Fulltekst (pdf)
    fulltext
    Download (png)
    presentationsbild
  • 18.
    Ax, Anna-Karin
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Husberg, Magnus
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Johansson, Birgitta
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Demmelmaier, Ingrid
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Department of Sport Science and Physical Education, University of Agder, Kristiansand, Norway.
    Berntsen, Sveinung
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Department of Sport Science and Physical Education, University of Agder, Kristiansand, Norway.
    Sjövall, Katarina
    Faculty of Health Sciences, Kristianstad University, Kristianstad, Sweden.
    Börjeson, Sussanne
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten.
    Nordin, Karin
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Davidson, Thomas
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Cost-effectiveness of different exercise intensities during oncological treatment in the Phys-Can RCT2023Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 62, nr 4, s. 414-421Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Cost-effectiveness is important in the prioritisation between interventions in health care. Exercise is cost-effective compared to usual care during oncological treatment; however, the significance of exercise intensity to the cost-effectiveness is unclear. In the present study, we aimed to evaluate the long-term cost-effectiveness of the randomised controlled trial Phys-Can, a six-month exercise programme of high (HI) or low-to-moderate intensity (LMI) during (neo)adjuvant oncological treatment.

    Methods

    A cost-effectiveness analysis was performed, based on 189 participants with breast, colorectal, or prostate cancer (HI: n = 99 and LMI: n = 90) from the Phys-Can RCT in Sweden. Costs were estimated from a societal perspective, and included cost of the exercise intervention, health care utilisation and productivity loss. Health outcomes were assessed as quality-adjusted life-years (QALYs), using EQ-5D-5L at baseline, post intervention and 12 months after the completion of the intervention.

    Results

    At 12-month follow-up after the intervention, the total cost per participant did not differ significantly between HI (€27,314) and LMI exercise (€29,788). There was no significant difference in health outcome between the intensity groups. On average HI generated 1.190 QALYs and LMI 1.185 QALYs. The mean incremental cost-effectiveness ratio indicated that HI was cost effective compared with LMI, but the uncertainty was large.

    Conclusions

    We conclude that HI and LMI exercise have similar costs and effects during oncological treatment. Hence, based on cost-effectiveness, we suggest that decision makers and clinicians can consider implementing both HI and LMI exercise programmes and recommend either intensity to the patients with cancer during oncological treatment to facilitate improvement of health.

    Fulltekst (pdf)
    fulltext
  • 19.
    Ax, Anna-Karin
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Husberg, Magnus
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Johansson, Birgitta
    Uppsala Univ, Sweden; Uppsala Univ, Sweden.
    Demmelmaier, Ingrid
    Uppsala Univ, Sweden; Univ Agder, Norway.
    Berntsen, Sveinung
    Uppsala Univ, Sweden; Univ Agder, Norway.
    Sjövall, Katarina
    Kristianstad Univ, Sweden.
    Börjeson, Sussanne
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten.
    Nordin, Karin
    Uppsala Univ, Sweden.
    Davidson, Thomas
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Long-term resource utilisation and associated costs of exercise during (neo)adjuvant oncological treatment: the Phys-Can project2022Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 61, nr 7, s. 888-896Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Exercise during oncological treatment is beneficial to patient health and can counteract the side effects of treatment. Knowledge of the societal costs associated with an exercise intervention, however, is limited. The aims of the present study were to evaluate the long-term resource utilisation and societal costs of an exercise intervention conducted during (neo)adjuvant oncological treatment in a randomised control trial (RCT) versus usual care (UC), and to compare high-intensity (HI) versus low-to-moderate intensity (LMI) exercise in the RCT. Methods We used data from the Physical Training and Cancer (Phys-Can) project. In the RCT, 577 participants were randomised to HI or to LMI of combined endurance and resistance training for 6 months, during oncological treatment. The project also included 89 participants with UC in a longitudinal observational study. We measured at baseline and after 18 months. Resource utilisation and costs of the exercise intervention, health care, and productivity loss were compared using analyses of covariance (RCT vs. UC) and t test (HI vs. LMI). Results Complete data were available for 619 participants (RCT HI: n = 269, LMI: n = 265, and UC: n = 85). We found no difference in total societal costs between the exercise intervention groups in the RCT and UC. However, participants in the RCT had lower rates of disability pension days (p < .001), corresponding costs (p = .001), and pharmacy costs (p = .018) than the UC group. Nor did we find differences in resource utilisation or costs between HI and LMI exercise int the RCT. Conclusion Our study showed no difference in total societal costs between the comprehensive exercise intervention and UC or between the exercise intensities. This suggests that exercise, with its well-documented health benefits during oncological treatment, produces neither additional costs nor savings.

    Fulltekst (pdf)
    fulltext
  • 20.
    Ax, Anna-Karin
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Johansson, Birgitta
    Department of Immunology, Genetics and Pathology and Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Carlsson, Maria
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
    Nordin, Karin
    Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden; Department of Public Health, Sport and Nutrition, University of Agder, Kristiansand, Norway.
    Börjeson, Sussanne
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Exercise: A positive feature on functioning in daily life during cancer treatment – Experiences from the Phys-Can study2020Inngår i: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Nursing, Vol. 44, artikkel-id 101713Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose

    Impaired functioning due to cancer treatment is a challenge for daily life. Exercise during treatment can improve functioning. However, research describing experiences of how exercise affects activities of daily life is limited. We aimed to explore how individuals with cancer receiving curative treatment and participating in an exercise intervention experienced their functioning in daily life.

    Methods

    Twenty-one participants were recruited from Phys-Can, an exercise intervention study. Semi-structured interviews were conducted after the intervention had finished, and data was analysed using thematic analysis.

    Results

    Two main themes evolved: “Striving to maintain a normal life in a new context” and “Struggling with impairments from side effects of cancer treatment”. The supervised group exercise proved popular, and participants reported positive effects on physical and psychological functioning, as well as social and informative support from other participants. Participants struggled with impaired cognitive and physical functioning and exhaustion. They strove to maintain a normal life by adjusting their activities.

    Conclusions

    Perceived physical and psychological benefits from exercise during cancer treatment suggest that exercise should be a part of cancer rehabilitation to facilitate activities and participation in daily life. Striving to maintain a normal life during cancer treatment is vital, and adjustments are needed to maintain activities and participation in daily life. Cancer nurses should motivate patients to engage in physical activity and encourage the introduction of exercise as part of their rehabilitation. They could also support patients in making adjustments to maintain functioning in daily life.

    Fulltekst (pdf)
    fulltext
  • 21.
    Ax, Anna-Karin
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Johansson, Birgitta
    Uppsala Univ, Sweden.
    Lyth, Johan
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Nordin, Karin
    Uppsala Univ, Sweden.
    Börjeson, Sussanne
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Short- and long-term effect of high versus low-to-moderate intensity exercise to optimise health-related quality of life after oncological treatment - results from the Phys-Can project2022Inngår i: Supportive Care in Cancer, ISSN 0941-4355, E-ISSN 1433-7339, Vol. 30, s. 5949-5963Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose This study aimed to evaluate the effect of high intensity (HI) vs low-to-moderate intensity (LMI) exercise on health-related quality of life (HRQoL) up to 18 months after commencement of oncological treatment in patients with breast, colorectal or prostate cancer. In addition, we conducted a comparison with usual care (UC). Methods Patients scheduled for (neo)adjuvant oncological treatment (n = 577) were randomly assigned to 6 months of combined resistance and endurance training of HI or LMI. A longitudinal descriptive study (UC) included participants (n = 89) immediately before the RCT started. HRQoL was assessed by EORTC QLQ-C30 at baseline, 3, 6 and 18 months (1 year after completed exercise intervention) follow-up. Linear mixed models were used to study the groups over time. Results Directly after the intervention, HI scored significant (P = 0.02), but not clinically relevant, higher pain compared with LMI. No other significant difference in HRQoL was found between the exercise intensities over time. Clinically meaningful improvements in HRQoL over time were detected within both exercise intensities. We found favourable significant differences in HRQoL in both exercise intensities compared with UC over time. Conclusion This study adds to the strong evidence of positive effect of exercise and shows that exercise, regardless of intensity, can have beneficial effects on HRQoL during oncological treatment and also for a substantial time after completion of an exercise intervention. In this study, for one year after. Implications for cancer survivors Patients can be advised to exercise at either intensity level according to their personal preferences, and still benefit from both short-term and long-term improvements in HRQoL.

    Fulltekst (pdf)
    fulltext
  • 22.
    Axelsson, Lars
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Holmberg, Erik
    Reg Canc Ctr Western Sweden, Sweden; Univ Gothenburg, Sweden.
    Nyman, Jan
    Univ Gothenburg, Sweden.
    Hogmo, Anders
    Karolinska Univ Hosp, Sweden.
    Sjodin, Helena
    Karolinska Univ Hosp, Sweden.
    Gebre-Medhin, Maria
    Lund Univ Hosp, Sweden.
    von Beckerath, Mathias
    Orebro Univ Hosp, Sweden.
    Ekberg, Tomas
    Uppsala Univ Hosp, Sweden.
    Farnebo, Lovisa
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för sinnesorgan och kommunikation. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken.
    Talani, Charbél
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Spak, Lena Norberg
    Norrlands Univ Hosp, Sweden.
    Notstam, Isak
    Cty Hosp Sundsvall Harnosand, Sweden.
    Hammerlid, Eva
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Swedish National Multicenter Study on Head and Neck Cancer of Unknown Primary: Prognostic Factors and Impact of Treatment on Survival2021Inngår i: International Archives of Otorhinolaryngology, ISSN 1809-9777, E-ISSN 1809-4864, Vol. 25, nr 03, s. e433-e442Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients medical records from 2008 to 2012. Results Two-hundred and sixty HNCUP patients were included. The tumors were HPVpositive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age (p &lt; 0.001), performance status (p = 0.036), and N stage (p = 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and ( chemo) radiation and primary (chemo)

    Fulltekst (pdf)
    fulltext
  • 23.
    Bagge, Ebba
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Beiron, Ulrica
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Malander, Susanne
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Rosenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Pattern of endocrine treatment for epithelial ovarian cancer in the Southeast medical region of Sweden: a population-based study2019Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 58, nr 3, s. 320-325Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim of the study: Endocrine treatment (ET) is an alternative as salvage therapy in epithelial ovarian cancer (EOC) but the usage in routine care is unknown. We evaluated the treatment patterns and outcome of patients receiving ET for EOC in the Southeast medical region in Sweden.Method: Patients were identified through the population-based Southeast Quality Registry for gynaecological cancer. Inclusion criteria were: age 18 years, histologically verified EOC diagnosed 2000-2013, ET for 4 weeks. Coverage compared with the Swedish National Cancer Registry was 100%. Data extracted from medical records was collected by means of a study-specific Case Report Form. Last date of follow-up was February 1st, 2018. All statistics were descriptive.Results: Altogether 248 (18%) of 1414 patients were treated with ET. Most (49%) had received only one, and 34% two previous lines of chemotherapy. Time from last chemotherapy to ET was 4 months, range 0-55months. The reason for initiating ET was tumor progression (66%), chemotherapy related toxicity (29%) and maintenance (4%). Tamoxifen was prescribed in 94% of cases. Best response was partial (amp;lt; 5%) and stable disease (50%). No patient had a complete response. 194 (78%) patients received subsequent chemotherapy, of these 27% had 3-7 lines of chemotherapy. Duration of ET was a median 4 months (range 1-80 months). Median time from ET to subsequent chemotherapy was 5 months (range 0-79). The median overall survival was 45 months (range 9-173).Conclusion: In the Southeast region of Sweden, endocrine treatment for EOC was prescribed inconsistently and in various settings, usually initiated by a rising CA-125 level. Poorer documentation and irregular tumor response assessment were observed for endocrine treatment compared to chemotherapy.

  • 24.
    Banerjee, Antara
    et al.
    Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE) and Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Tamil Nadu, India.
    Chabria, Yashna
    Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE) and Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Tamil Nadu, India.
    Kanna N. R., Rajesh
    Department of Pathology, Faculty of Medicine, Chettinad Academy of Research & Education, Kelambakkam, Tamil Nadu, India.
    Gopi, Janani
    Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE) and Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Tamil Nadu, India.
    Rowlo, Praveen
    Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE) and Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Tamil Nadu, India.
    Sun, Xiao-Feng
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Pathak, Surajit
    Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE) and Chettinad Hospital and Research Institute (CHRI), Kelambakkam, Tamil Nadu, India.
    Role of Tumor Specific niche in Colon Cancer Progression and Emerging Therapies by Targeting Tumor Microenvironment2021Inngår i: Cell Biology and Translational Medicine, Volume 13: Stem Cells in Development and Disease / [ed] Kursad Turksen, Springer, 2021, 1, s. 177-192Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Colorectal cancer is the third most common form of cancer worldwide leading to escalating mortality rates and mainly includes hereditary, sporadic and colitis-associated cancer development. The escalated mortality rates is due to the limited treatment options as this form of cancer is usually not easy to diagnose in its early stages and are highly invasive leading to rapid metastasis of the malignant cells to the neighbouring tissue. In order to combat this limitation several chemotherapeutic regimens are now being combined with targeted therapies after the knowledge acquired on the inevitable effects of the tumor microenvironment on the colon cancer growth and progress. The colon tumor niche mainly consists of a large mass of tumor cells along with various immune cells, inflammatory cells, tumor macrophages and fibroblasts that infiltrate the tumor as it is a site of predominant inflammation. Among cells of the microenvironment, mesenchymal stem cells (MSCs) exhibiting ability to evolve into cancer associated fibroblasts (CAFs) have recently generated a major interest in the field. The physiological state of the tumor microenvironment is closely connected to discrete steps of tumorigenesis. The colon cancer cells elicit various factors with their direct interaction with MSCs or via paracrine fashion, which modulate these cells to promote cancer instead of performing their innate function of abating cancer progression. This review intends to highlight the necessity to exploit the cellular landscape of tumor microenvironment of colon cancer and a detailed understanding of the interactions between tumor epithelial cells and their stromal/inflammatory elements will aid in future perspectives for designing therapeutic regimens targeting tumor microenvironment to improve the clinical outcome of colon cancer.

  • 25.
    Banerjee, Antara
    et al.
    Chettinad Hosp & Res Inst CHRI, India.
    Deka, Dikshita
    Chettinad Hosp & Res Inst CHRI, India.
    Muralikumar, Makalakshmi
    Chettinad Hosp & Res Inst CHRI, India.
    Sun-Zhang, Alexander
    Karolinska Inst, Sweden.
    Bisgin, Atil
    Cukurova Technopolis, Turkey; Cukurova Univ, Turkey.
    Christopher, Cynthia
    Chettinad Hosp & Res Inst CHRI, India.
    Zhang, Hong
    Orebro Univ, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Pathak, Surajit
    Chettinad Hosp & Res Inst CHRI, India.
    A concise review on miRNAs as regulators of colon cancer stem cells and associated signalling pathways2023Inngår i: Clinical and Translational Oncology, ISSN 1699-048X, E-ISSN 1699-3055, Vol. 25, s. 3345-3356Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Despite recent therapy advances and a better understanding of colon cancer biology, it remains one of the major causes of death. The cancer stem cells, associated with the progression, metastasis, and recurrence of colon cancer, play a major role in promoting the development of tumour and are found to be chemo resistant. The stroma of the tumour, which makes up the bulk of the tumour mass, is composed of the tumour microenvironment. With the advent of theranostic and the development of personalised medicine, miRNAs are becoming increasingly important in the context of colon malignancies. A holistic understanding of the regulatory roles of miRNAs in cancer cells and cancer stem cells will allow us to design effective strategies to regulate miRNAs, which could lead to improved clinical translation and creating a potent colon cancer treatment strategy. In this review paper, we briefly discuss the history of miRNA as well as the mechanisms of miRNA and cancer stem cells that contribute to the tumour growth, apoptosis, and advancement of colon cancer. The usefulness of miRNA in colorectal cancer theranostic is further concisely reviewed. We conclude by holding a stance in addressing the prospects and possibilities for miRNA by the disclosure of recent theranostic approaches aimed at eradicating cancer stem cells and enhancing overall cancer treatment outcomes.

  • 26.
    Banerjee, Antara
    et al.
    Chettinad Acad Res & Educ CARE, India.
    Somasundaram, Indumathi
    Kolhapur Inst Technol, India.
    Das, Diptimayee
    Chettinad Acad Res & Educ CARE, India.
    Manoj, Samatha Jain
    Chettinad Acad Res & Educ CARE, India.
    Banu, Husaina
    Chettinad Acad Res & Educ CARE, India.
    Suresh, Pavane Mitta
    Chettinad Acad Res & Educ CARE, India.
    Paul, Sujay
    Tecnol Monterrey, Mexico.
    Bisgin, Atil
    Cukurova Univ, Turkiye.
    Zhang, Hong
    Orebro Univ, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Duttaroy, Asim K.
    Univ Oslo, Norway.
    Pathak, Surajit
    Chettinad Acad Res & Educ CARE, India.
    Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants2023Inngår i: Nutrients, E-ISSN 2072-6643, Vol. 15, nr 11, artikkel-id 2631Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.

    Fulltekst (pdf)
    fulltext
  • 27.
    Bashari, Mohanad
    et al.
    Asharqiah Univ, Oman.
    Ahmed, Hani
    Nanchang Univ, Peoples R China.
    Mustafa, Ayman Balla
    Misurata Univ, Libya.
    Riaz, Asad
    United Arab Emirates Univ, U Arab Emirates.
    Wang, Jinpeng
    Beijing Technol & Business Univ BTBU, Peoples R China.
    Saddick, Salina Yahya
    King Abdulaziz Univ, Saudi Arabia.
    Omar, Abdulkader Shaikh
    King Abdulaziz Univ, Saudi Arabia; Najla Bint Saud Al Saud Ctr Distinguished Res Biot, Saudi Arabia.
    Afifi, Mohamed
    Najla Bint Saud Al Saud Ctr Distinguished Res Biot, Saudi Arabia; Univ Jeddah, Saudi Arabia.
    Al-Farga, Ammar
    Univ Jeddah, Saudi Arabia.
    AlJumaiah, Lulwah Zeyad
    Univ Hail, Saudi Arabia.
    Abourehab, Mohammed A. S.
    Umm Al Qura Univ, Saudi Arabia.
    Belal, Amany
    Beni Suef Univ, Egypt; Taif Univ, Saudi Arabia.
    Khalifa, Mohamed Yassin Zaky
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Beni Suef Univ, Egypt.
    Fabrication and Characterization of Dextranase Nano-Entrapped Enzymes in Polymeric Particles Using a Novel Ultrasonication-Microwave Approach2023Inngår i: Catalysts, E-ISSN 2073-4344, Vol. 13, nr 1, artikkel-id 125Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the current study, a novel method to improve the nano-entrapment of enzymes into Ca-alginate gel was investigated to determine the synergistic effects of ultrasound combined with microwave shock (UMS). The effects of UMS treatment on dextranase enzymes loading effectiveness (LE) and immobilization yield (IY) were investigated. By using FT-IR spectra and SEM, the microstructure of the immobilized enzyme (IE) was characterized. Additionally, the free enzyme was used as a control to compare the reusability and enzyme-kinetics characteristics of IEs produced with and without UMS treatments. The results demonstrated that the highest LE and IY were obtained when the IE was produced with a US of 40 W at 25 kHz for 15 min combined with an MS of 60 W at a shock rate of 20 s/min for 20 min, increasing the LE and the IY by 97.32 and 78.25%, respectively, when compared with an immobilized enzyme prepared without UMS treatment. In comparison with the control, UMS treatment dramatically raised the Vmax, KM, catalytic, and specificity constant values for the IE. The outcomes suggested that a microwave shock and ultrasound combination would be an efficient way to improve the immobilization of enzymes in biopolymer gel.

    Fulltekst (pdf)
    fulltext
  • 28.
    Belal, Amany
    et al.
    Taif Univ, Saudi Arabia.
    Mahmoud, Rehab
    Beni Suef Univ, Egypt.
    Mohamed, Eman E.
    Beni Suef Univ, Egypt.
    Farghali, Ahmed
    Beni Suef Univ, Egypt.
    El-Ela, Fatma I. Abo
    Beni Suef Univ, Egypt.
    Gamal, Amr
    Beni Suef Univ, Egypt.
    Halfaya, Fatma Mohamed
    Beni Suef Univ, Egypt.
    Khaled, Esraa
    Beni Suef Univ, Egypt.
    Farahat, Abdelbasset A.
    Calif Northstate Univ, CA 95757 USA; Mansoura Univ, Egypt.
    Hassan, Ahmed H. E.
    Mansoura Univ, Egypt; Kyung Hee Univ, South Korea.
    Ghoneim, Mohammed M.
    AlMaarefa Univ, Saudi Arabia.
    Taha, Mohamed
    Beni Suef Univ, Egypt.
    Zaky Khalifa, Mohamed Yassin Zaky
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Beni Suef Univ, Egypt.
    A Novel Hydroxyapatite/Vitamin B-12 Nanoformula for Treatment of Bone Damage: Preparation, Characterization, and Anti-Arthritic, Anti-Inflammatory, and Antioxidant Activities in Chemically Induced Arthritic Rats2023Inngår i: Pharmaceuticals, E-ISSN 1424-8247, Vol. 16, nr 4, artikkel-id 551Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The usage of nanomaterials for rheumatoid arthritis (RA) treatment can improve bioavailability and enable selective targeting. The current study prepares and evaluates the in vivo biological effects of a novel hydroxyapatite/vitamin B-12 nanoformula in Complete Freunds adjuvant-induced arthritis in rats. The synthesized nanoformula was characterized using XRD, FTIR, BET analysis, HERTEM, SEM, particle size, and zeta potential. We synthesized pure HAP NPs with 71.01% loading weight percentages of Vit B12 and 49 mg/g loading capacity. Loading of vitamin B-12 on hydroxyapatite was modeled by Monte Carlo simulation. Anti-arthritic, anti-inflammatory, and antioxidant effects of the prepared nanoformula were assessed. Treated arthritic rats showed lower levels of RF and CRP, IL-1 beta, TNF-alpha, IL-17, and ADAMTS-5, but higher IL-4 and TIMP-3 levels. In addition, the prepared nanoformula increased GSH content and GST antioxidant activity while decreasing LPO levels. Furthermore, it reduced the expression of TGF-beta mRNA. Histopathological examinations revealed an improvement in joint injuries through the reduction of inflammatory cell infiltration, cartilage deterioration, and bone damage caused by Complete Freunds adjuvant. These findings indicate that the anti-arthritic, antioxidant, and anti-inflammatory properties of the prepared nanoformula could be useful for the development of new anti-arthritic treatments.

    Fulltekst (pdf)
    fulltext
  • 29.
    Belal, Amany
    et al.
    Taif Univ, Saudi Arabia.
    Mahmoud, Rehab
    Beni Suef Univ, Egypt.
    Taha, Mohamed
    Beni Suef Univ, Egypt.
    Halfaya, Fatma Mohamed
    Beni Suef Univ, Egypt.
    Hassaballa, Ahmed
    Wayne State Univ, MI 48202 USA; ZeroHarm LC, MI 48333 USA.
    Elbanna, Esraa Salah
    Beni Suef Univ, Egypt.
    Khaled, Esraa
    Beni Suef Univ, Egypt.
    Farghali, Ahmed
    Beni Suef Univ, Egypt.
    Abo El-Ela, Fatma I.
    Beni Suef Univ, Egypt.
    Mahgoub, Samar M.
    Beni Suef Univ, Egypt.
    Ghoneim, Mohammed M.
    AlMaarefa Univ, Saudi Arabia; Al Azhar Univ, Egypt.
    Zaky Khalifa, Mohamed Yassin Zaky
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Beni Suef Univ, Egypt.
    Therapeutic Potential of Zeolites/Vitamin B12 Nanocomposite on Complete Freunds Adjuvant-Induced Arthritis as a Bone Disorder: In Vivo Study and Bio-Molecular Investigations2023Inngår i: Pharmaceuticals, E-ISSN 1424-8247, Vol. 16, nr 2, artikkel-id 285Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rheumatoid arthritis (RA) is a long-term autoimmune disease. As nanotechnology has advanced, a growing number of nanodrugs have been used in the treatment of RA due to their unique physical and chemical properties. The purpose of this study was to assess the therapeutic potential of a novel zeolite/vitamin B12 nanocomposite (Nano ZT/Vit B12) formulation in complete Freunds adjuvant (CFA)-induced arthritis. The newly synthesized Nano ZT/Vit B12 was fully characterized using various techniques such as XRD, FT-IR, BET analysis, HERTEM, SEM, practical size, zeta potential, XRF, and EDX. The anti-arthritic, anti-inflammatory, and antioxidant activities as well as the immunomodulation effect of Nano ZT/Vit B12 on the CFA rat model of arthritis were examined. Histopathologic ankle joint injuries caused by CFA intrapedal injection included synovium hyperplasia, inflammatory cell infiltration, and extensive cartilage deterioration. The arthritic rats Nano ZT/Vit B12 supplementation significantly improved these effects. Furthermore, in arthritic rats, Nano ZT/Vit B12 significantly reduced serum levels of RF and CRP, as well as the levels of IL-1 beta, TNF-alpha, IL-17, and ADAMTS-5, while increasing IL-4 and TIMP-3 levels. Nano-ZT/Vit B12 significantly declined the LPO level and increased antioxidant activities, such as GSH content and GST activity, in the arthritic rats. In arthritic rats, Nano ZT/Vit B12 also reduced TGF-beta mRNA gene expression and MMP-13 protein levels. Collectively, Nano ZT/Vit B12 seems to have anti-arthritic, anti-inflammatory, and antioxidant properties, making it a promising option for RA in the future.

    Fulltekst (pdf)
    fulltext
  • 30.
    Berger, Karoline
    et al.
    Univ Gothenburg, Sweden.
    Rhost, Sara
    Univ Gothenburg, Sweden.
    Rafnsdottir, Svanheidur
    Univ Gothenburg, Sweden; Natl Univ Hosp Iceland, Iceland.
    Hughes, Eamon
    Univ Gothenburg, Sweden.
    Magnusson, Ylva
    Univ Gothenburg, Sweden.
    Ekholm, Maria
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Lund Univ, Sweden; Department of Oncology, Region Jönköping County, Jönköping, Sweden.
    Stål, Olle
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. 3 Department of Oncology, Region Jönköping County, Jönköping, Sweden.
    Ryden, Lisa
    Lund Univ, Sweden.
    Landberg, Goran
    Univ Gothenburg, Sweden.
    Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer2021Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 21, nr 1, artikkel-id 185Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. In this retrospective biomarker analysis, we aimed to determine whether tumor co-expression of progranulin and sortilin has prognostic and treatment predictive values for breast cancer patients. Methods We explored how co-expression of progranulin and sortilin was associated with established clinical markers by analyzing a tissue microarray including 560 randomized premenopausal breast cancer patients receiving either 2 years of tamoxifen treatment or no adjuvant treatment, with a median follow-up time of 28 years. Breast cancer-specific survival was analyzed using Kaplan-Meier and Cox Proportional Hazards regression models to assess the prognostic and predictive value of progranulin and sortilin in relation to known clinical markers. Results Co-expression of progranulin and sortilin was observed in 20% of the breast cancer samples. In untreated patients, prognostic considerations could be detailed separately from treatment prediction and the high progranulin and sortilin expressing subgroup was significantly associated with breast cancer-specific death in multivariable analyses (HR=2.188, CI: 1.317-3.637, p=0.003) along with tumor size, high tumor grade and lymph node positivity. When comparing the untreated patients with tamoxifen treated patients in the ER alpha positive subgroup, co-expression of progranulin and sortilin was not linked to tamoxifen resistance. Conclusion Data suggest that co-expression of progranulin and its receptor sortilin is a novel prognostic biomarker combination identifying a highly malignant subgroup of breast cancer. Importantly, this subpopulation could potentially be targeted with anti-sortilin based therapies.

    Fulltekst (pdf)
    fulltext
  • 31.
    Berntsen, Sveinung
    et al.
    Uppsala University, Sweden; University of Agder, Norway.
    Aaronson, Neil K.
    Netherlands Cancer Institute, Netherlands.
    Buffart, Laurien
    Vrije University of Amsterdam Medical Centre, Netherlands; Vrije University of Amsterdam Medical Centre, Netherlands.
    Börjeson, Sussanne
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Demmelmaier, Ingrid
    Uppsala University, Sweden.
    Hellbom, Maria
    Lund University, Sweden.
    Hojman, Pernille
    Copenhagen University Hospital, Denmark.
    Igelstrom, Helena
    Uppsala University, Sweden.
    Johansson, Birgitta
    Uppsala University, Sweden.
    Pingel, Ronnie
    Uppsala University, Sweden.
    Raastad, Truls
    Norwegian School Sport Science, Norway.
    Velikova, Galina
    University of Leeds, England.
    Asenlof, Pernilla
    Uppsala University, Sweden.
    Nordin, Karin
    Uppsala University, Sweden; University of Agder, Norway.
    Design of a randomized controlled trial of physical training and cancer ( Phys-Can) the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome2017Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, artikkel-id 218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cancer-related fatigue is a common problem in persons with cancer, influencing health-related quality of life and causing a considerable challenge to society. Current evidence supports the beneficial effects of physical exercise in reducing fatigue, but the results across studies are not consistent, especially in terms of exercise intensity. It is also unclear whether use of behaviour change techniques can further increase exercise adherence and maintain physical activity behaviour. This study will investigate whether exercise intensity affects fatigue and health related quality of life in persons undergoing adjuvant cancer treatment. In addition, to examine effects of exercise intensity on mood disturbance, adherence to oncological treatment, adverse effects from treatment, activities of daily living after treatment completion and return to work, and behaviour change techniques effect on exercise adherence. We will also investigate whether exercise intensity influences inflammatory markers and cytokines, and whether gene expressions following training serve as mediators for the effects of exercise on fatigue and health related quality of life. Methods/design: Six hundred newly diagnosed persons with breast, colorectal or prostate cancer undergoing adjuvant therapy will be randomized in a 2 x 2 factorial design to following conditions; A) individually tailored low-to-moderate intensity exercise with or without behaviour change techniques or B) individually tailored high intensity exercise with or without behaviour change techniques. The training consists of both resistance and endurance exercise sessions under the guidance of trained coaches. The primary outcomes, fatigue and health related quality of life, are measured by self-reports. Secondary outcomes include fitness, mood disturbance, adherence to the cancer treatment, adverse effects, return to activities of daily living after completed treatment, return to work as well as inflammatory markers, cytokines and gene expression. Discussion: The study will contribute to our understanding of the value of exercise and exercise intensity in reducing fatigue and improving health related quality of life and, potentially, clinical outcomes. The value of behaviour change techniques in terms of adherence to and maintenance of physical exercise behaviour in persons with cancer will be evaluated.

    Fulltekst (pdf)
    fulltext
  • 32.
    Bisgin, Atil
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Cukurova Univ, Turkey.
    Meng, Wen-Jian
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Adell, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Interaction of CD200 Overexpression on Tumor Cells with CD200R1 Overexpression on Stromal Cells: An Escape from the Host Immune Response in Rectal Cancer Patients2019Inngår i: Journal of Oncology, ISSN 1687-8450, E-ISSN 1687-8469, Vol. 2019, artikkel-id 5689464Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    CD200 imparts an immunoregulatory signal through its receptor, CD200R1, leading to the suppression of tumor specific immunity. The mechanism of CD200:CD200R1 signaling pathway is still uncertain. Our aim was to investigate the expression and localization of CD200 and its receptor CD200R1 and their clinical significance in rectal cancer patients. We examined the immunohistochemical expressions and localizations of CD200 and CD200R1 in 140 rectal cancer patients. Among the patients, 79 underwent the preoperative radiotherapy and the others were untreated prior to the surgery. In addition, 121 matched normal rectal mucosa samples were evaluated. The results of immunohistochemical analysis showed a strikingly high level of CD200 in tumor cells (p=0.001) and CD200R1 expression in normal mucosal epithelium and stromal cells. Importantly, CD200R1 was overexpressed in stromal cells of the metastatic cancer patients compared to patients without metastases (p=0.002). More than that, 87% of metastatic patients had a phenotype of upregulated CD200 in tumor cells accompanied by overexpressed CD200R1 in stromal cells. In addition, low levels of CD200 were correlated with improved overall survival in untreated patients. We showed that tumor-stroma communication through CD200 and its receptor interaction is selected in patients with high risk of relapse. High levels of these molecules support instigation of the far and local metastatic nest that provides solid ground for metastasis. Our current data also disclose a mechanism by which CD200:CD200R1 affects tumor progression and may strengthen the feasibility of targeting CD200 or CD200R1 as anticancer strategy.

    Fulltekst (pdf)
    fulltext
  • 33.
    Bjurberg, Maria
    et al.
    Lund Univ, Sweden.
    Holmberg, Erik
    Reg Canc Ctr West, Sweden; Sahlgrens Acad, Sweden.
    Borgfeldt, Christer
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Floter-Radestad, Angelique
    Karolinska Inst, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden.
    Hjerpe, Elisabet
    Visby Hosp, Sweden.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Marcickiewicz, Janusz
    Reg Canc Ctr West, Sweden; Halland Hosp, Sweden.
    Rosenberg, Per
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Primary treatment patterns and survival of cervical cancer in Sweden: A population-based Swedish Gynecologic Cancer Group Study2019Inngår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 155, nr 2, s. 229-236Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival. Methods: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma. Results: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p amp;lt; 0.001). In stage IIA1 74% had CTRL, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p amp;lt; 0.001). Stages III-IVA; amp;lt;40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p amp;lt; 0.001). RS stage IVB 7%. Conclusion: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy. (C) 2019 Elsevier Inc. All rights reserved.

  • 34.
    Björnsson, Bergthor
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Borrebaeck, Carl
    Lund Univ, Sweden.
    Elander, Nils
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Gasslander, Thomas
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Gawel, Danuta
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa.
    Gustafsson, Mika
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Jornsten, Rebecka
    Univ Gothenburg, Sweden; Chalmers Univ Technol, Sweden.
    Jung Lee, Eun Jung
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Yonsei Univ, South Korea.
    Li, Xinxiu
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa.
    Lilja, Sandra
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa.
    Martinez, David
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Bioinformatik. Linköpings universitet, Tekniska fakulteten.
    Matussek, Andreas
    Karolinska Univ Hosp, Sweden; Dept Lab Med, Sweden.
    Sandström, Per
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Schäfer, Samuel
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa.
    Stenmarker, Margaretha
    Futurum Acad Hlth and Care, Sweden; Inst Clin Sci, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Sysoev, Oleg
    Linköpings universitet, Institutionen för datavetenskap, Statistik och maskininlärning. Linköpings universitet, Filosofiska fakulteten.
    Zhang, Huan
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa.
    Benson, Mikael
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa.
    Digital twins to personalize medicine2020Inngår i: Genome Medicine, ISSN 1756-994X, E-ISSN 1756-994X, Vol. 12, nr 1, artikkel-id 4Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.

    Fulltekst (pdf)
    fulltext
  • 35.
    Block, Keith I.
    et al.
    Block Centre Integrat Cancer Treatment, IL 60077 USA.
    Gyllenhaal, Charlotte
    Block Centre Integrat Cancer Treatment, IL 60077 USA; National Cancer Centre, South Korea.
    Lowe, Leroy
    Getting Know Canc, Canada; University of Lancaster, England.
    Amedei, Amedeo
    University of Florence, Italy.
    Ruhul Amin, A. R. M.
    University of Florence, Italy.
    Amin, Amr
    University of Florence, Italy.
    Aquilano, Katia
    United Arab Emirates University, U Arab Emirates.
    Arbiser, Jack
    Atlanta Vet Adm Medical Centre, GA USA; Emory University, GA USA.
    Arreola, Alexandra
    University of Roma Tor Vergata, Italy.
    Arzumanyan, Alla
    University of N Carolina, NC 27599 USA.
    Salman Ashraf, S.
    Temple University, PA 19122 USA.
    Azmi, Asfar S.
    United Arab Emirates University, U Arab Emirates.
    Benencia, Fabian
    Wayne State University, MI USA.
    Bhakta, Dipita
    Ohio University, OH 45701 USA.
    Bilsland, Alan
    SASTRA University, India.
    Bishayeen, Anupam
    University of Glasgow, Scotland.
    Blain, Stacy W.
    Larkin Health Science Institute, FL USA.
    Block, Penny B.
    Block Centre Integrat Cancer Treatment, IL 60077 USA.
    Boosani, Chandra S.
    Suny Downstate Medical Centre, NY USA.
    Carey, Thomas E.
    Creighton University, NE 68178 USA.
    Carnero, Amancio
    University of Michigan, MI USA.
    Carotenuto, Marianeve
    CSIC, Spain; Centre Ingn Genet and Biotecnol Avanzate, Italy.
    Casey, Stephanie C.
    University of Naples Federico II, Italy.
    Chakrabarti, Mrinmay
    Stanford University, CA 94305 USA.
    Chaturvedi, Rupesh
    University of S Carolina, SC USA.
    Zhuo Chen, Georgia
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Chenx, Helen
    Jawaharlal Nehru University, India.
    Chen, Sophie
    University of British Columbia, Canada.
    Charlie Chen, Yi
    Ovarian and Prostate Cancer Research Lab, England; Alderson Broaddus University, PA USA.
    Choi, Beom K.
    National Cancer Centre, South Korea.
    Rosa Ciriolo, Maria
    United Arab Emirates University, U Arab Emirates.
    Coley, Helen M.
    University of Surrey, England.
    Collins, Andrew R.
    University of Oslo, Norway.
    Connell, Marisa
    Jawaharlal Nehru University, India.
    Crawford, Sarah
    So Connecticut State University, CT 06515 USA.
    Curran, Colleen S.
    University of Wisconsin, WI USA.
    Dabrosin, Charlotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Damia, Giovanna
    Ist Ric Farmacol Mario Negri, Italy.
    Dasgupta, Santanu
    University of Texas Health Science Centre Tyler, TX USA.
    DeBerardinis, Ralph J.
    University of Texas SW Medical Centre Dallas, TX 75390 USA.
    Decker, William K.
    Baylor Coll Med, TX 77030 USA.
    Dhawan, Punita
    Vanderbilt University, TN 37212 USA.
    Diehl, Anna Mae E.
    Duke University, NC 27710 USA.
    Dong, Jin-Tang
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Ping Dou, Q.
    United Arab Emirates University, U Arab Emirates.
    Drew, Janice E.
    University of Aberdeen, Scotland.
    Elkord, Eyad
    United Arab Emirates University, U Arab Emirates.
    El-Rayes, Bassel
    Emory University, GA 30322 USA.
    Feitelson, Mark A.
    University of N Carolina, NC 27599 USA.
    Felsher, Dean W.
    University of Naples Federico II, Italy.
    Ferguson, Lynnette R.
    University of Auckland, New Zealand.
    Fimognari, Carmela
    University of Auckland, New Zealand.
    Firestone, Gary L.
    University of Bologna, Italy.
    Frezza, Christian
    University of Calif Berkeley, CA 94720 USA.
    Fujii, Hiromasa
    University of Cambridge, England.
    Fuster, Mark M.
    Nara Medical University, Japan.
    Generali, Daniele
    University of Calif San Diego, CA 92103 USA; University of Calif San Diego, CA 92103 USA.
    Georgakilas, Alexandros G.
    University of Trieste, Italy.
    Gieseler, Frank
    Azienda Osped Ist Ospitalieri Cremona, Italy.
    Gilbertson, Michael
    National Technical University of Athens, Greece.
    Green, Michelle F.
    University Hospital Schleswig Holstein, Germany.
    Grue, Brendan
    Getting Know Canc, Canada.
    Guha, Gunjan
    Ohio University, OH 45701 USA.
    Halicka, Dorota
    Duke University, NC USA.
    Helferich, William G.
    Dalhousie University, Canada.
    Heneberg, Petr
    New York Medical Coll, NY 10595 USA.
    Hentosh, Patricia
    University of Illinois, IL 61820 USA.
    Hirschey, Matthew D.
    University Hospital Schleswig Holstein, Germany.
    Hofseth, Lorne J.
    Charles University of Prague, Czech Republic.
    Holcombe, Randall F.
    Old Domin University, VA USA.
    Honoki, Kanya
    Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan.
    Hsu, Hsue-Yin
    University of S Carolina, SC 29208 USA.
    Huang, Gloria S.
    Mt Sinai School Med, NY USA.
    Jensen, Lasse D.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Jiang, Wen G.
    Cardiff University, Wales.
    Jones, Lee W.
    Mem Sloan Kettering Cancer Centre, NY 10021 USA.
    Karpowicz, Phillip A.
    University of Windsor, Canada.
    Nicol Keith, W.
    SASTRA University, India.
    Kerkar, Sid P.
    Mayo Clin, MN USA.
    Khan, Gazala N.
    Henry Ford Hospital, MI 48202 USA.
    Khatami, Mahin
    National Institute Heatlh, MD USA.
    Ko, Young H.
    University of Maryland BioPark, MD USA.
    Kucuk, Omer
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Kulathinal, Rob J.
    University of N Carolina, NC 27599 USA.
    Kumar, Nagi B.
    University of S Florida, FL USA.
    Kwon, Byoung S.
    National Cancer Centre, South Korea; Tulane University, LA 70118 USA.
    Le, Anne
    Johns Hopkins University, MD USA.
    Lea, Michael A.
    Rutgers State University, NJ USA.
    Lee, Ho-Young
    Seoul National University, South Korea.
    Lichtor, Terry
    Rush University, IL 60612 USA.
    Lin, Liang-Tzung
    Taipei Medical University, Taiwan.
    Locasale, Jason W.
    Cornell University, NY 14853 USA.
    Lokeshwar, Bal L.
    Georgia Regents University, GA USA.
    Longo, Valter D.
    University of So Calif, CA USA.
    Lyssiotis, Costas A.
    University of Michigan, MI USA; University of Michigan, MI USA.
    MacKenzie, Karen L.
    Childrens Cancer Institute Australia, Australia.
    Malhotra, Meenakshi
    McGill University, Canada.
    Marino, Maria
    University of Rome Tre, Italy.
    Martinez-Chantar, Maria L.
    Technology Pk Bizkaia, Spain.
    Matheu, Ander
    Biodonostia Institute, Spain.
    Maxwell, Christopher
    Jawaharlal Nehru University, India.
    McDonnell, Eoin
    University Hospital Schleswig Holstein, Germany.
    Meeker, Alan K.
    Johns Hopkins University, MD 21205 USA.
    Mehrmohamadi, Mahya
    Cornell University, NY USA.
    Mehta, Kapil
    University of Texas MD Anderson Cancer Centre, TX 77030 USA.
    Michelotti, Gregory A.
    Duke University, NC 27710 USA.
    Mohammad, Ramzi M.
    United Arab Emirates University, U Arab Emirates.
    Mohammed, Sulma I.
    Purdue University, IN 47907 USA.
    James Morre, D.
    Mor NuCo Inc, IN USA.
    Muqbil, Irfana
    United Arab Emirates University, U Arab Emirates.
    Muralidhar, Vinayak
    Harvard University, MA USA; MIT, MA 02139 USA.
    Murphy, Michael P.
    MRC Mitochondrial Biol Unit, England.
    Purnachandra Nagaraju, Ganji
    Emory University, GA 30322 USA.
    Nahta, Rita
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Niccolai, Elena
    University of Florence, Italy.
    Nowsheen, Somaira
    Mayo Clin, MN USA.
    Panis, Carolina
    State University of West Parana, Brazil.
    Pantano, Francesco
    University of Campus Bio Med, Italy.
    Parslow, Virginia R.
    University of Auckland, New Zealand.
    Pawelec, Graham
    University of Tubingen, Germany.
    Pedersen, Peter L.
    Johns Hopkins University, MD USA.
    Poore, Brad
    Johns Hopkins University, MD USA.
    Poudyal, Deepak
    Charles University of Prague, Czech Republic.
    Prakash, Satya
    McGill University, Canada.
    Prince, Mark
    University of Michigan, MI USA.
    Raffaghello, Lizzia
    Ist Giannina Gaslini, Italy.
    Rathmell, Jeffrey C.
    University Hospital Schleswig Holstein, Germany.
    Kimryn Rathmell, W.
    University of Roma Tor Vergata, Italy.
    Ray, Swapan K.
    Stanford University, CA 94305 USA.
    Reichrath, Joerg
    Saarland University Hospital, Germany.
    Rezazadeh, Sarallah
    University of Rochester, NY 14627 USA.
    Ribatti, Domenico
    University of Bari, Italy.
    Ricciardiello, Luigi
    National Cancer Institute Giovanni Paolo II, Italy.
    Brooks Robey, R.
    University of Bologna, Italy; White River Junct Vet Affairs Medical Centre, VT USA.
    Rodier, Francis
    Geisel School Medical Dartmouth, NH USA; University of Montreal, Canada.
    Vasantha Rupasinghe, H. P.
    Institute Cancer Montreal, Canada.
    Luigi Russo, Gian
    University of Montreal, Canada.
    Ryan, Elizabeth P.
    Dalhousie University, Canada.
    Samadi, Abbas K.
    Sanus Biosciences, San Diego, CA, United States.
    Sanchez-Garcia, Isidro
    CNR, Italy.
    Sanders, Andrew J.
    Cardiff University, Wales.
    Santini, Daniele
    University of Campus Bio Med, Italy.
    Sarkar, Malancha
    Colorado State University, CO 80523 USA.
    Sasada, Tetsuro
    Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
    Saxena, Neeraj K.
    University of Salamanca, Spain.
    Shackelford, Rodney E.
    University of Miami, FL USA.
    Shantha Kumara, H. M. C.
    St Lukes Roosevelt Hospital, NY 10025 USA.
    Sharma, Dipali
    Kurume University, Japan.
    Shin, Dong M.
    Winship Cancer Institute of Emory University, Atlanta, GA, United States.
    Sidransky, David
    University of Maryland, MD 21201 USA.
    David Siegelin, Markus
    Louisiana State University, LA 71105 USA.
    Signori, Emanuela
    Johns Hopkins University, MD 21205 USA; Johns Hopkins University, MD USA.
    Singh, Neetu
    Johns Hopkins University, MD USA; King Georges Medical University, India.
    Sivanand, Sharanya
    Columbia University, NY USA; University of Penn, PA 19104 USA.
    Sliva, Daniel
    Institute Translat Pharmacol, Italy; Purdue Research Pk, IN USA.
    Smythe, Carl
    University of Sheffield, England.
    Spagnuolo, Carmela
    University of Montreal, Canada.
    Stafforini, Diana M.
    University of Utah, UT USA.
    Stagg, John
    University of Utah, UT USA.
    Subbarayan, Pochi R.
    University of Montreal, Canada.
    Sundin, Tabetha
    University of Miami, FL USA.
    Talib, Wamidh H.
    Sentara Healthcare, VA USA.
    Thompson, Sarah K.
    Appl Science University, Jordan.
    Tran, Phuoc T.
    Royal Adelaide Hospital, Australia.
    Ungefroren, Hendrik
    Azienda Osped Ist Ospitalieri Cremona, Italy.
    Vander Heiden, Matthew G.
    MIT, MA 02139 USA.
    Venkateswaran, Vasundara
    Johns Hopkins University, MD USA; University of Toronto, Canada.
    Vinay, Dass S.
    Tulane University, LA USA.
    Vlachostergios, Panagiotis J.
    Johns Hopkins University, MD USA; New York University, NY USA.
    Wang, Zongwei
    Johns Hopkins University, MD USA; Harvard University, MA USA.
    Wellendx, Kathryn E.
    Columbia University, NY USA; University of Penn, PA 19104 USA.
    Whelan, Richard L.
    St Lukes Roosevelt Hospital, NY 10025 USA.
    Yang, Eddy S.
    University of Alabama Birmingham, AL USA.
    Yang, Huanjie
    Harbin Institute Technology, Peoples R China.
    Yang, Xujuan
    Dalhousie University, Canada.
    Yaswen, Paul
    Lawrence Berkeley National Lab, CA USA.
    Yedjou, Clement
    Jackson State University, MS USA.
    Yin, Xin
    Nara Medical University, Japan.
    Zhu, Jiyue
    Washington State University, WA USA.
    Zollo, Massimo
    CSIC, Spain; Centre Ingn Genet and Biotecnol Avanzate, Italy.
    Designing a broad-spectrum integrative approach for cancer prevention and treatment2015Inngår i: Seminars in Cancer Biology, ISSN 1044-579X, E-ISSN 1096-3650, Vol. 35, s. S276-S304Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.

    Fulltekst (pdf)
    fulltext
  • 36.
    Blockhuys, S.
    et al.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Celauro, E.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Hildesjö, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Feizi, A.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Fierro-González, J.C.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Wittung-Stafshede, P.
    Department Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden .
    Defining the human copper proteome and analysis of its expression variation in cancers.2017Inngår i: Metallomics : integrated biometal science, ISSN 1756-591X, Vol. 9, nr 2, s. 112-123Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Copper (Cu) is essential for living organisms, and acts as a cofactor in many metabolic enzymes. To avoid the toxicity of free Cu, organisms have specific transport systems that 'chaperone' the metal to targets. Cancer progression is associated with increased cellular Cu concentrations, whereby proliferative immortality, angiogenesis and metastasis are cancer hallmarks with defined requirements for Cu. The aim of this study is to gather all known Cu-binding proteins and reveal their putative involvement in cancers using the available database resources of RNA transcript levels. Using the database along with manual curation, we identified a total of 54 Cu-binding proteins (named the human Cu proteome). Next, we retrieved RNA expression levels in cancer versus normal tissues from the TCGA database for the human Cu proteome in 18 cancer types, and noted an intricate pattern of up- and downregulation of the genes in different cancers. Hierarchical clustering in combination with bioinformatics and functional genomics analyses allowed for the prediction of cancer-related Cu-binding proteins; these were specifically inspected for the breast cancer data. Finally, for the Cu chaperone ATOX1, which is the only Cu-binding protein proposed to have transcription factor activities, we validated its predicted over-expression in patient breast cancer tissue at the protein level. This collection of Cu-binding proteins, with RNA expression patterns in different cancers, will serve as an excellent resource for mechanistic-molecular studies of Cu-dependent processes in cancer.

    Fulltekst (pdf)
    fulltext
  • 37.
    Blockhuys, Stephanie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Chalmers, Sweden.
    Liu, Na
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rani Agarwal, Nisha
    Chalmers, Sweden.
    Enejder, Annika
    Chalmers, Sweden.
    Loitto, Vesa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    X-radiation enhances the collagen type I strap formation and migration potentials of colon cancer cells2016Inngår i: Oncotarget, E-ISSN 1949-2553, Vol. 7, nr 44, s. 71390-71399Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rectal cancer treatment still fails with local and distant relapses of the disease. It is hypothesized that radiotherapy could stimulate cancer cell dissemination and metastasis. In this study, we evaluated the effect of X-radiation on collagen type I strap formation potential, i.e. matrix remodeling associated with mesenchymal cell migration, and behaviors of SW480, SW620, HCT116 p53(+/+) and HCT116 p53(-/-) colon cancer cells. We determined a radiation-induced increase in collagen type I strap formation and migration potentials of SW480 and HCT116 p53(+/+). Further studies with HCT116 p53(+/+), indicated that after X-radiation strap forming cells have an increased motility. More, we detected a decrease in adhesion potential and mature integrin beta 1 expression, but no change in non-muscle myosin II expression for HCT116 p53(+/+) after X-radiation. Integrin beta 1 neutralization resulted in a decreased cell adhesion and collagen type I strap formation in both sham and X-radiated conditions. Our study indicates collagen type I strap formation as a potential mechanism of colon cancer cells with increased migration potential after X-radiation, and suggests that other molecules than integrin beta 1 and non-muscle myosin II are responsible for the radiation-induced collagen type I strap formation potential of colon cancer cells. This work encourages further molecular investigation of radiation-induced migration to improve rectal cancer treatment outcome.

    Fulltekst (pdf)
    fulltext
  • 38.
    Blockhuys, Stephanie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Chalmers University of Technology, Sweden.
    Rani Agarwal, Nisha
    Chalmers University of Technology, Sweden; McMaster University, Canada; McMaster University, Canada.
    Hildesjö, Camilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Jarlsfelt, Ingvar
    Ryhov Hospital, Sweden.
    Wittung-Stafshede, Pernilla
    Chalmers University of Technology, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Second harmonic generation for collagen I characterization in rectal cancer patients with and without preoperative radiotherapy2017Inngår i: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, nr 10, artikkel-id 106006Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the tumor, reduce local recurrence, and improve patient survival. Still, the treatment outcome varies significantly and new biomarkers are desired. Collagen I (Col-I) is a potential biomarker, which can be visualized label-free by second harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by RT in surgical tissue, with the aim to evaluate the clinical significance of RT-induced Col-I changes. First, we established a procedure for quantitative evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We discovered that the Col-I intensity and anisotropy were higher in the tumor invasive margin than in the inner tumor and normal mucosa, and RT increased and decreased the intensity in inner tumor and normal mucosa, respectively. Furthermore, higher Col-I intensity in the inner tumor was related to increased distant recurrence in the non-RT group but to longer survival in the RT group. In conclusion, we present a new application of SHG for quantitative analysis of Col-I in surgical material, and the first data suggest Col-I intensity as a putative prognostic biomarker in rectal cancer. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 39.
    Blomstrand, Hakon
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Batra, Atul
    All India Inst Med Sci, India.
    Cheung, Winson Y.
    Univ Calgary, Canada.
    Elander, Nils
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Real-world evidence on first- and second-line palliative chemotherapy in advanced pancreatic cancer2021Inngår i: World Journal of Clinical Oncology, ISSN 2218-4333, Vol. 12, nr 9, s. 787-799Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    In spite of recent diagnostic and therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. As most patients are not amenable to curative intent treatments, optimized palliative management is highly needed. One key question is to what extent promising results produced by randomized controlled trials (RCTs) correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial. To answer such questions, real-world evidence is necessary. The present paper reviews and discusses the current literature on first- and second-line palliative chemotherapy in PDAC. Notably, a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens, i.e. gemcitabine plus nab-paclitaxel (GnP) and folfirinox (FFX), is similar in RCTs and real-life populations. Outcomes of second-line therapy following failure of first-line regimens are still dismal, and considerable uncertainty of the optimal management remains. Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence, such as FFX followed by GnP or vice versa, are urgently needed. Finally, the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC.

    Fulltekst (pdf)
    fulltext
  • 40.
    Blomstrand, Hakon
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Green, Henrik
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, S-58758 Linkoping, Sweden.
    Fredrikson, Mats
    Linköpings universitet, Medicinska fakulteten, Forum Östergötland.
    Gransmark, Emma
    Kalmar Cty Hosp, Sweden.
    Björnsson, Bergthor
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Elander, Nils
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Clinical characteristics and blood/serum bound prognostic biomarkers in advanced pancreatic cancer treated with gemcitabine and nab-paclitaxel2020Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 20, nr 1, artikkel-id 950Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    In recent years treatment options for advanced pancreatic cancer have markedly improved, and a combination regimen of gemcitabine and nab-paclitaxel is now considered standard of care in Sweden and elsewhere. Nevertheless, a majority of patients do not respond to treatment. In order to guide the individual patient to the most beneficial therapeutic strategy, simple and easily available prognostic and predictive markers are needed.

    Methods

    The potential prognostic value of a range of blood/serum parameters, patient-, and tumour characteristics was explored in a retrospective cohort of 75 patients treated with gemcitabine/nab-paclitaxel (Gem/NabP) for advanced pancreatic ductal adenocarcinoma (PDAC) in the South Eastern Region of Sweden. Primary outcome was overall survival (OS) while progression free survival (PFS) was the key secondary outcome.

    Result

    Univariable Cox regression analysis revealed that high baseline serum albumin (> 37 g/L) and older age (> 65) were positive prognostic markers for OS, and in multivariable regression analysis both parameters were confirmed to be independent prognostic variables (HR 0.48, p = 0.023 and HR = 0.47, p = 0.039,). Thrombocytopenia at any time during the treatment was an independent predictor for improved progression free survival (PFS) but not for OS (HR 0.49, p = 0.029, 0.54, p = 0.073), whereas thrombocytopenia developed under cycle 1 was neither related with OS nor PFS (HR 0.87, p = 0.384, HR 1.04, p = 0.771). Other parameters assessed (gender, tumour stage, ECOG performance status, myelosuppression, baseline serum CA19–9, and baseline serum bilirubin levels) were not significantly associated with survival.

    Conclusion

    Serum albumin at baseline is a prognostic factor with palliative Gem/NabP in advanced PDAC, and should be further assessed as a tool for risk stratification. Older age was associated with improved survival, which encourages further studies on the use of Gem/NabP in the elderly.

    Fulltekst (pdf)
    fulltext
  • 41.
    Blomstrand, Hakon
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Olsson, Hans
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för neurobiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi.
    Green, Henrik
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Dept Forens Genet & Forens Toxicol, Natl Board Forens Med, Linkoping, Sweden.
    Björnsson, Bergthor
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Elander, Nils
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Clatterbridge Canc Ctr NHS FT, England.
    Impact of resection margins and para-aortic lymph node metastases on recurrence patterns and prognosis in resectable pancreatic cancer - a long-term population-based cohort study2023Inngår i: HPB, ISSN 1365-182X, E-ISSN 1477-2574, Vol. 25, nr 12, s. 1531-1544Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Pancreatic cancer remains a leading cause of cancer-related death. To individualise management and improve survival, more accurate prognostic models are needed.Methods: All patients resected for pancreatic ductal adenocarcinoma in a tertiary Swedish centre during 2009-2019 were thoroughly analysed with regards to pathological and clinical parameters including tumour grade, resection margin status, para-aortic lymph node engagement (node station 16), and systemic treatment.Results: The study cohort included 275 patients. Overall median survival was 21.2 months (95% CI 17.5-24.8). Year of resection, margin status (R1 subdivided into R1(1mm)/R1(ink)), perineural invasion, differentiation grade, TNM stage, and adjuvant therapy were independent factors with significant impact on survival. Margin status also significantly affected recurrence-free survival and relapse patterns, with local and peritoneal relapses being associated with R1-status (p &lt; 0.001 and p = 0.007). Presence of paraaortic lymph node metastases was associated with shorter recurrence-free survival as compared to N1 status only.Conclusion: Survival in resected pancreatic cancer is improving over time. Resection margin status is a key factor affecting recurrence patterns and prognosis. Given the poor recurrence-free survival in node station 16 metastasised patients, the rational for resection remains in doubt, and improved treatment strategies for this patient group is necessary.

  • 42.
    Blomstrand, Hakon
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi. Ryhov Cty Hosp, Sweden.
    Scheibling, Ursula
    Ryhov Cty Hosp, Sweden.
    Bratthall, Charlotte
    Kalmar Cty Hosp, Sweden.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, S-58758 Linkoping, Sweden.
    Elander, Nils
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Real world evidence on gemcitabine and nab-paclitaxel combination chemotherapy in advanced pancreatic cancer2019Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, artikkel-id 40Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundIn the recent phase III trial MPACT the combination of gemcitabine and nab-paclitaxel (Gem/NabP) showed increased overall survival compared to gemcitabine alone in the treatment of advanced pancreatic ductal adenocarcinoma (aPDA). Until now there has been limited information on the clinical benefit and toxicity of the combination regimen in a real world setting. In addition the value for patients with locally advanced rather than metastatic aPDA has been unclear, since the former category of patients was not included in the MPACT trial.MethodsA multicentre retrospective observational study in the South Eastern Region of Sweden was performed, with the first 75 consecutive patients diagnosed with aPDA (both locally advanced and metastatic disease) who received first-line treatment with Gem/NabP.ResultsIn the overall population median progression free survival (PFS) and overall survival (OS) were 5.2 (3.4-7.0 95% CI) and 10.9 (7.8-14.0 95% CI) months, respectively. Patients with metastatic disease displayed a median OS of 9.4 (4.9-13.9) and a median PFS of 4.5 (3.3-5.7) months whereas the same parameters in the locally advanced subgroup were 17.1 (7.6-26.6) and 6.8 (5.2-8.4) months, respectively. Grade 3-4 hematologic toxicity was recorded: Neutropenia, leukopenia, thrombocytopenia, and anaemia were observed in 23, 20, 5, and 4% of patients, respectively. Dose reductions were performed in 80% of the patients.ConclusionThis study confirms the effectiveness and safety of first-line Gem/NabP in both locally advanced and metastatic PDA in a real world setting.

    Fulltekst (pdf)
    fulltext
  • 43.
    Bojmar, Linda
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Zhang, Haiying
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Costa da Silva, Bruno
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Karlsson, Elin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Olsson, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Vincent, Theresa
    Departments of Physiology and Biophysics and Cell and Developmental Biology, Weill Cornell Medical College, New York, USA / Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Lyden, David
    Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health, Meyer Cancer Center, Weill Cornell Medical College, New York, USA.
    Sandström, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome2015Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The ultimate cause of death for many cancer patients is the spread of the cancer via metastasis. Even so, there are still a lack of knowledge regarding the metastasis process. This study was performed to investigate the role of metastamirs in exosomes and their metastatic patterns. We used the well-established isogeneic murine cancer model of low metastatic 67NR cells, mimicking luminal/basal breast tumors, and highly metastatic 4T1 cells with characteristics of basal breast  tumors. We studied the exosomal properties and pre-metastatic effects in this metastasis model and compared human materials and exosomes of several other tumor types. Our data clearly demonstrated that exosomes from the highly metastatic cells home to the metastatic organs of their parental cells whereas exosomes from cells with low metastatic potential mostly located to lymph nodes. The exosome protein cargos also resembled their parental cells and potentially affects their target organs, and cells, differently. Furthermore, the exosomes from the highly metastatic cells had a more pronounced effect on tumor growth and pre-metastatic changes than the low metastatic exosomes. The microRNA-18a, a predictor of metastasis, was present to a higher extent in metastatic exosomes as compared to low metastatic exosomes, and altered the tumor progressive properties. Our findings support the role of exomirs as important players in the metastatic process, the value as biomarkers and potential therapeutic targets.

  • 44.
    Borgfeldt, Christer
    et al.
    Lund Univ, Sweden.
    Holmberg, Erik
    Reg Canc Ctr West, Sweden.
    Marcickiewicz, Janusz
    Halland Hosp, Sweden.
    Stålberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ Hosp, Sweden.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Flöter-Rådestad, Angelique
    Karolinska Univ Hosp, Sweden.
    Bjurberg, Maria
    Lund Univ, Sweden; Lund Univ, Sweden.
    Dahm-Kähler, Pernilla
    Sahlgrens Acad, Sweden.
    Hellman, Kristina
    Karolinska Univ Hosp, Sweden.
    Hjerpe, Elisabet
    Visby Hosp, Sweden.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken US.
    Rosenberg, Per
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi.
    Högberg, Thomas
    Lund Univ, Sweden.
    Survival in endometrial cancer in relation to minimally invasive surgery or open surgery: a Swedish Gynecologic Cancer Group (SweGCG) study2021Inngår i: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 21, nr 1, artikkel-id 658Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BackgroundThe aim of this study was to analyze overall survival in endometrial cancer patients FIGO stages I-III in relation to surgical approach; minimally invasive (MIS) or open surgery (laparotomy).MethodsA population-based retrospective study of 7275 endometrial cancer patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed from 2010 to 2018. Cox proportional hazard models were used in univariable and multivariable survival analyses.ResultsIn univariable analysis open surgery was associated with worse overall survival compared with MIS hazard ratio, HR, 1.39 (95% CI 1.18-1.63) while in the multivariable analysis, surgical approach (MIS vs open surgery) was not associated with overall survival after adjustment for known risk factors (HR 1.12, 95% CI 0.95-1.32). Higher FIGO stage, non-endometrioid histology, non-diploid tumors, lymphovascular space invasion and increasing age were independent risk factors for overall survival.ConclusionThe minimal invasive or open surgical approach did not show any impact on survival for patients with endometrial cancer stages I-III when known prognostic risk factors were included in the multivariable analyses.

    Fulltekst (pdf)
    fulltext
  • 45.
    Bostner, Josefine
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Alayev, Anya
    Yeshiva Univ, NY 10033 USA.
    Berman, Adi Y.
    Yeshiva Univ, NY 10033 USA.
    Fornander, Tommy
    Karolinska Inst, Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Holz, Marina K.
    Yeshiva Univ, NY 10033 USA; Albert Einstein Coll Med, NY 10467 USA; Albert Einstein Coll Med, NY 10467 USA.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Raptor localization predicts prognosis and tamoxifen response in estrogen receptor-positive breast cancer2018Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 168, nr 1, s. 17-27Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Deregulated PI3K/mTOR signals can promote the growth of breast cancer and contribute to endocrine treatment resistance. This report aims to investigate raptor and its intracellular localization to further understand its role in ER-positive breast cancer. Raptor protein expression was evaluated by immunohistochemistry in 756 primary breast tumors from postmenopausal patients randomized to tamoxifen or no tamoxifen. In vitro, the MCF7 breast cancer cell line and tamoxifen-resistant MCF7 cells were studied to track the raptor signaling changes upon resistance, and raptor localization in ER alpha-positive cell lines was compared with that in ER alpha-negative cell lines. Raptor protein expression in the nucleus was high in ER/PgR-positive and HER2-negative tumors with low grade, features associated with the luminal A subtype. Presence of raptor in the nucleus was connected with ER alpha signaling, here shown by a coupled increase of ER alpha phosphorylation at S167 and S305 with accumulation of nuclear raptor. In addition, the expression of ER alpha-activated gene products correlated with nuclear raptor. Similarly, in vitro we observed raptor in the nucleus of ER alpha-positive, but not of ER-negative cells. Interestingly, raptor localized to the nucleus could still be seen in tamoxifen-resistant MCF7 cells. The clinical benefit from tamoxifen was inversely associated with an increase of nuclear raptor. High cytoplasmic raptor expression indicated worse prognosis on long-term follow-up. We present a connection between raptor localization to the nucleus and ER alpha-positive breast cancer, suggesting raptor as a player in stimulating the growth of the luminal A subtype and a possible target along with endocrine treatment.

    Fulltekst (pdf)
    fulltext
  • 46.
    Bostner, Josefine
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Karlsson, Elin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Bivik Eding, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Perez-Tenorio, Gizeh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Franzén, Hanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Konstantinell, Aelita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Fornander, Tommy
    Karolinska University Hospital, Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    S6 kinase signaling: tamoxifen response and prognostic indication in two breast cancer cohorts2015Inngår i: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 22, nr 3, s. 331-343Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Detection of signals in the mammalian target of rapamycin (mTOR) and the estrogen receptor (ER) pathways may be a future clinical tool for the prediction of adjuvant treatment response in primary breast cancer. Using immunohistological staining, we investigated the value of the mTOR targets p70-S6 kinase (S6K) 1 and 2 as biomarkers for tamoxifen benefit in two independent clinical trials comparing adjuvant tamoxifen with no tamoxifen or 5 years versus 2 years of tamoxifen treatment. In addition, the prognostic value of the S6Ks was evaluated. We found that S6K1 correlated with proliferation, HER2 status, and cytoplasmic AKT activity, whereas high protein expression levels of S6K2 and phosphorylated (p) S6K were more common in ER-positive, and low-proliferative tumors with pAKT-s473 localized to the nucelus. Nuclear accumulation of S6K1 was indicative of a reduced tamoxifen effect (hazard ratio (HR): 1.07, 95% CI: 0.53-2.81, P=0.84), compared with a significant benefit from tamoxifen treatment in patients without tumor S6K1 nuclear accumulation (HR: 0.42, 95% CI: 0.29-0.62, Pless than0.00001). Also S6K1 and S6K2 activation, indicated by pS6K-t389 expression, was associated with low benefit from tamoxifen (HR: 0.97, 95% CI: 0.50-1.87, P=0.92). In addition, high protein expression of S6K1, independent of localization, predicted worse prognosis in a multivariate analysis, P=0.00041 (cytoplasm), P=0.016 (nucleus). In conclusion, the mTOR-activated kinases S6K1 and S6K2 interfere with proliferation and response to tamoxifen. Monitoring their activity and intracellular localization may provide biomarkers for breast cancer treatment, allowing the identification of a group of patients less likely to benefit from tamoxifen and thus in need of an alternative or additional targeted treatment.

    Fulltekst (pdf)
    fulltext
  • 47.
    Bruun, Jarle
    et al.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Kolberg, Matthias
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Ahlquist, Terje C.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway.
    Royrvik, Ellen C.
    Oslo University Hospital, Norway; University of Oslo, Norway; University of Oxford, England.
    Nome, Torfinn
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Leithe, Edward
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Lind, Guro E.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Merok, Marianne A.
    Oslo University Hospital, Norway; University of Oslo, Norway; Oslo University Hospital, Norway.
    Rognum, Torleiv O.
    University of Oslo, Norway; Norwegian Institute Public Heatlh, Norway.
    Bjorkoy, Geir
    University of Coll Sor Trondelag, Norway.
    Johansen, Terje
    University of Tromso, Norway.
    Lindblom, Annika
    Karolinska Institute, Sweden.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Svindland, Aud
    University of Oslo, Norway; Oslo University Hospital, Norway.
    Liestol, Knut
    University of Oslo, Norway; Fac Math and Nat Science, Norway.
    Nesbakken, Arild
    Oslo University Hospital, Norway; University of Oslo, Norway; Oslo University Hospital, Norway; University of Oslo, Norway.
    Skotheim, Rolf I.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway; Fac Math and Nat Science, Norway.
    Lothe, Ragnhild A.
    Oslo University Hospital, Norway; Oslo University Hospital, Norway; University of Oslo, Norway; University of Oslo, Norway.
    Regulator of Chromosome Condensation 2 Identifies High-Risk Patients within Both Major Phenotypes of Colorectal Cancer2015Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 21, nr 16, s. 3759-3770Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: Colorectal cancer has high incidence and mortality worldwide. Patients with microsatellite instable (MSI) tumors have significantly better prognosis than patients with microsatellite stable (MSS) tumors. Considerable variation in disease outcome remains a challenge within each subgroup, and our purpose was to identify biomarkers that improve prediction of colorectal cancer prognosis. Experimental Design: Mutation analyses of 42 MSI target genes were performed in two independent MSI tumor series (n = 209). Markers that were significantly associated with prognosis in the test series were assessed in the validation series, followed by functional and genetic explorations. The clinical potential was further investigated by immunohistochemistry in a population-based colorectal cancer series (n = 903). Results: We identified the cell-cycle gene regulator of chromosome condensation 2 (RCC2) as a cancer biomarker. We found a mutation in the 50 UTR region of RCC2 that in univariate and multivariate analyses was significantly associated with improved outcome in the MSI group. This mutation caused reduction of protein expression in dual luciferase gene reporter assays. siRNA knockdown in MSI colon cancer cells (HCT15) caused reduced cell proliferation, cell-cycle arrest, and increased apoptosis. Massive parallel sequencing revealed few RCC2 mutations in MSS tumors. However, weak RCC2 protein expression was significantly associated with poor prognosis, independent of clinical highrisk parameters, and stratifies clinically important patient subgroups with MSS tumors, including elderly patients (greater than 75 years), stage II patients, and those with rectal cancer. Conclusions: Impaired RCC2 affects functional and clinical endpoints of colorectal cancer. High-risk patients with either MSI or MSS tumors can be identified with cost-effective routine RCC2 assays. (C) 2015 AACR.

    Fulltekst (pdf)
    fulltext
  • 48.
    Burocziova, Monika
    et al.
    Czech Acad Sci, Czech Republic.
    Burdova, Kamila
    Czech Acad Sci, Czech Republic.
    Martinikova, Andra S.
    Czech Acad Sci, Czech Republic.
    Kasparek, Petr
    Czech Acad Sci, Czech Republic.
    Kleiblova, Petra
    Charles Univ Prague, Czech Republic.
    Danielsen, Stine A.
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Borecka, Marianna
    Charles Univ Prague, Czech Republic.
    Jenikova, Gabriela
    Czech Acad Sci, Czech Republic.
    Janeckova, Lucie
    Czech Acad Sci, Czech Republic.
    Pavel, Jozef
    Czech Acad Sci, Czech Republic.
    Zemankova, Petra
    Charles Univ Prague, Czech Republic.
    Schneiderova, Michaela
    Charles Univ Prague, Czech Republic; Gen Fac Hosp Prague, Czech Republic.
    Schwarzova, Lucie
    Gen Fac Hosp Prague, Czech Republic; Charles Univ Prague, Czech Republic.
    Ticha, Ivana
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken. Gen Fac Hosp Prague, Czech Republic; Charles Univ Prague, Czech Republic.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Jiraskova, Katerina
    ASCR, Czech Republic.
    Liska, Vaclav
    Charles Univ Prague, Czech Republic.
    Vodickova, Ludmila
    ASCR, Czech Republic; Charles Univ Prague, Czech Republic; Charles Univ Prague, Czech Republic.
    Vodicka, Pavel
    ASCR, Czech Republic; Charles Univ Prague, Czech Republic; Charles Univ Prague, Czech Republic.
    Sedlacek, Radislav
    Czech Acad Sci, Czech Republic.
    Kleibl, Zdenek
    Charles Univ Prague, Czech Republic.
    Lothe, Ragnhild A.
    Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway.
    Korinek, Vladimir
    Czech Acad Sci, Czech Republic.
    Macurek, Libor
    Czech Acad Sci, Czech Republic.
    Truncated PPM1D impairs stem cell response to genotoxic stress and promotes growth of APC-deficient tumors in the mouse colon2019Inngår i: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 10, artikkel-id 818Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein phosphatase magnesium-dependent 1 delta (PPM1D) terminates cell response to genotoxic stress by negatively regulating the tumor suppressor p53 and other targets at chromatin. Mutations in the exon 6 of the PPM1D result in production of a highly stable, C-terminally truncated PPM1D. These gain-of-function PPM1D mutations are present in various human cancers but their role in tumorigenesis remains unresolved. Here we show that truncated PPM1D impairs activation of the cell cycle checkpoints in human non-transformed RPE cells and allows proliferation in the presence of DNA damage. Next, we developed a mouse model by introducing a truncating mutation in the PPM1D locus and tested contribution of the oncogenic PPM1D(T) allele to colon tumorigenesis. We found that p53 pathway was suppressed in colon stem cells harboring PPM1D(T) resulting in proliferation advantage under genotoxic stress condition. In addition, truncated PPM1D promoted tumor growth in the colon in Apc(min) mice and diminished survival. Moreover, tumor organoids derived from colon of the Apc(min)Ppm1d(T/+) mice were less sensitive to 5-fluorouracil when compared to Apc(min)Ppm1d(+/+)and the sensitivity to 5-fluorouracil was restored by inhibition of PPM1D. Finally, we screened colorectal cancer patients and identified recurrent somatic PPM1D mutations in a fraction of colon adenocarcinomas that are p53 proficient and show defects in mismatch DNA repair. In summary, we provide the first in vivo evidence that truncated PPM1D can promote tumor growth and modulate sensitivity to chemotherapy.

    Fulltekst (pdf)
    fulltext
  • 49.
    Busch, Susann
    et al.
    Gothenburg University, Sweden.
    Sims, Andrew H.
    University of Edinburgh, Scotland.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Ferno, Marten
    Lund University, Sweden.
    Landberg, Goran
    Gothenburg University, Sweden; University of Manchester, England.
    Loss of TGF beta Receptor Type 2 Expression Impairs Estrogen Response and Confers Tamoxifen Resistance2015Inngår i: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, nr 7, s. 1457-1469Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    One third of the patients with estrogen receptor alpha (ER alpha)-positive breast cancer who are treated with the antiestrogen tamoxifen will either not respond to initial therapy or will develop drug resistance. Endocrine response involves crosstalk between ER alpha and TGF beta signaling, such that tamoxifen non-responsiveness or resistance in breast cancer might involve aberrant TGF beta signaling. In this study, we analyzed TGF beta receptor type 2 (TGFBR2) expression and correlated it with ER alpha status and phosphorylation in a cohort of 564 patients who had been randomized to tamoxifen or no-adjuvant treatment for invasive breast carcinoma. We also evaluated an additional four independent genetic datasets in invasive breast cancer. In all the cohorts we analyzed, we documented an association of low TGFBR2 protein and mRNA expression with tamoxifen resistance. Functional investigations confirmed that cell cycle or apoptosis responses to estrogen or tamoxifen in ER alpha-positive breast cancer cells were impaired by TGFBR2 silencing, as was ER alpha phosphorylation, tamoxifen-induced transcriptional activation of TGF beta, and upregulation of the multidrug resistance protein ABCG2. Acquisition of low TGFBR2 expression as a contributing factor to endocrine resistance was validated prospectively in a tamoxifen-resistant cell line generated by long-term drug treatment. Collectively, our results established a central contribution of TGF beta signaling in endocrine resistance in breast cancer and offered evidence that TGFBR2 can serve as an independent biomarker to predict treatment outcomes in ER alpha-positive forms of this disease.

  • 50.
    Campbell, Rachel
    et al.
    Univ Sydney, Australia.
    Costa, Daniel S. J.
    Univ Sydney, Australia.
    Stockler, Martin R.
    Univ Sydney, Australia.
    Lee, Yeh Chen
    Univ Sydney, Australia; Australia New Zealand Gynaecol Oncol Grp ANZGOG, Australia; Prince Wales Hosp, Australia.
    Ledermann, Jonathan A.
    NCRI UK, England.
    Berton, Dominique
    GINECO Grp Invest Nationaux Etud Canc Ovariens, France; Ctr Rene Gauducheau, France.
    Sehouli, Jalid
    Arbeitsgesmeinschaft Gynakol Onkol Studiengrp AGO, Germany; North Eastern German Soc Gynecol Oncol NOGGO, Germany; Charite, Germany.
    Roncolato, Felicia T.
    Univ Sydney, Australia; Australia New Zealand Gynaecol Oncol Grp ANZGOG, Australia; Prince Wales Hosp, Australia; Campbelltown Hosp, Australia.
    Connell, Rachel O.
    Univ Sydney, Australia.
    Okamoto, Aikou
    Japanese Gynecol Oncol Grp JGOG, Japan; Jikei Univ, Japan.
    Bryce, Jane
    Ist Nazl Tumori IRCCS, Italy; Ascens St John Clin Res Inst, OK USA.
    Oza, Amit M.
    Princess Margaret Consortium PMHC, Canada; Univ Toronto, Canada.
    Åvall Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Nordic Soc Gynaecol Oncol NSGO, Denmark; Karolinska Inst, Sweden.
    Berek, Jonathan S.
    Cooperat Gynecol Oncol Investigators COGI, CA USA; Stanford Univ, CA USA.
    Lanceley, Anne
    UCL, England.
    Joly, Florence
    GINECO Grp Invest Nationaux Etud Canc Ovariens, France; Ctr Francois Baclesse, France.
    Hilpert, Felix
    Arbeitsgesmeinschaft Gynakol Onkol Studiengrp AGO, Germany; North Eastern German Soc Gynecol Oncol NOGGO, Germany; Krankenhaus Jerusalem, Germany.
    Feeney, Amanda
    NCRI UK, England.
    Kaminsky, Marie C.
    GINECO Grp Invest Nationaux Etud Canc Ovariens, France; Alexis Vautrin, France.
    Diamante, Katrina
    Univ Sydney, Australia.
    Friedlander, Michael L.
    Australia New Zealand Gynaecol Oncol Grp ANZGOG, Australia; Prince Wales Hosp, Australia.
    King, Madeleine T.
    Univ Sydney, Australia.
    Measure of Ovarian Symptoms and Treatment concerns (MOST) indexes and their associations with health-related quality of life in recurrent ovarian cancer2022Inngår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 166, nr 2, s. 254-262Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose. The Measure of Ovarian Symptoms and Treatment (MOST) concerns is a validated patient-reported symptom assessment tool for assessing symptom benefit and adverse effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC). We aimed to examine (i) how symptoms within MOST symptom indexes track together (i.e. co-occur) and (ii) the association between MOST symptom indexes and key aspects of health-related quality of life (HRQL). Method. A prospective cohort of women with ROC completed the MOST-T35, EORTC QLQ-C30 and EORTC QLQ-OV28 at baseline and before each cycle of chemotherapy. Analyses were conducted on baseline and end -of-treatment data. Exploratory factor analysis and hierarchical cluster analysis identified groups of co-occurring symptoms. Path models examined associations between MOST symptom indexes and HRQL. Results. Data from 762 women at baseline and 681 at treatment-end who completed all 22 symptom-specific MOST items and at least one HRQL measure were analysed. Four symptom clusters emerged at baseline and treatment-end: abdominal symptoms, symptoms associated with peripheral neuropathy, nausea and vomiting, and psychological symptoms. Psychological symptoms (MOST-Psych) and symptoms due to disease (ovarian cancer) or treatment (MOST-DorT) were associated with poorer scores on QLQ-C30 and OV28 functioning do-mains and worse overall health at both time points. Conclusion. Four MOST symptom clusters were consistent across statistical methods and time points. These findings suggest that routine standardized assessment of psychological and physical symptoms in clinical prac-tice with MOST plus appropriate symptom management referral pathways is an intervention for improving HRQL that warrants further research. (c) 2022 Elsevier Inc. All rights reserved.

1234567 1 - 50 of 339
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf