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  • 101.
    Lindemann, Kristina
    et al.
    Oslo University Hospital, Norway; University of Sydney, Australia; Westmead Hospital, Australia.
    Gibbs, Emma
    University of Sydney, Australia.
    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. Karolinska Institute, Sweden.
    dePont Christensen, Rene
    University of Southern Denmark, Denmark.
    Woie, Kathrine
    Haukeland Hospital, Norway.
    Kalling, Marten
    Skåne University Hospital, Sweden.
    Auranen, Annika
    Tampere University Hospital, Finland.
    Grenman, Seija
    Turku University Hospital, Finland; University of Turku, Finland.
    Hoegberg, Thomas
    Skåne University Hospital Lund, Sweden.
    Rosenberg, Per
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Skeie-Jensen, Tone
    Oslo University Hospital, Norway.
    Hjerpe, Elisabet
    University of Southern Denmark, Denmark.
    Dorum, Anne
    Oslo University Hospital, Norway.
    Gebski, Val
    University of Sydney, Australia.
    Kristensen, Gunnar
    Oslo University Hospital, Norway; University of Oslo, Norway.
    Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist)2017Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 116, nr 4, s. 455-463Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. Methods: Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m(-2) or four weekly pegylated liposomal doxorubicin 40 mg m(-2)) or tamoxifen 40mg daily. The primary end point was HRQoL. Secondary end points were PFS by RECIST and overall survival (OS). Results: Between March 2002 and December 2007, 156 and 82 patients were randomised to chemotherapy and tamoxifen, respectively. In the chemotherapy arm, a significantly larger proportion of patients experienced a worsening in their social functioning. There was no difference in the proportion of patients experiencing improvement of gastrointestinal symptoms. Median PFS on tamoxifen was 8.3 weeks (95% CI, 8.0-10.4) compared with 12.7 weeks (95% CI, 9.0-16.3) on chemotherapy (HR, 1.54; 95% CI, 1.16-2.05; log-rank P = 0.003). There was no difference in OS between the treatment arms. Conclusions: Patients on chemotherapy had longer PFS but experienced more toxicity and poorer HRQoL compared with tamoxifen. Control over gastrointestinal symptoms was not better on chemotherapy. These data are important for patient counselling and highlight the need to incorporate HRQoL end points in studies of PROC.

  • 102.
    Lindstrom, Linda S.
    et al.
    Karolinska Inst, Sweden.
    Yau, Christina
    Univ Calif San Francisco, CA USA; Buck Inst Res Aging, CA USA.
    Czene, Kamila
    Karolinska Inst, Sweden.
    Thompson, Carlie K.
    Univ Calif San Francisco, CA USA.
    Hoadley, Katherine A.
    Univ North Carolina Chapel Hill, NC USA.
    vant Veer, Laura J.
    Univ Calif San Francisco, CA 94140 USA; Univ Calif San Francisco, CA 94143 USA.
    Balassanian, Ron
    Univ Calif San Francisco, CA 94140 USA.
    Bishop, John W.
    Univ Calif Davis, CA 95616 USA.
    Carpenter, Philip M.
    Univ Southern Calif, CA USA; Univ Calif Irvine, CA USA.
    Chen, Yunn-Yi
    Univ Calif San Francisco, CA 94140 USA.
    Datnow, Brian
    Univ Calif San Diego, CA 92093 USA.
    Hasteh, Farnaz
    Univ Calif San Diego, CA 92093 USA.
    Krings, Gregor
    Univ Calif San Francisco, CA 94140 USA.
    Lin, Fritz
    Univ Calif Irvine, CA USA.
    Zhang, Yanhong
    Univ Calif Davis, CA 95616 USA.
    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.
    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.
    Benz, Christopher C.
    Univ Calif San Francisco, CA USA; Buck Inst Res Aging, CA USA.
    Fornander, Tommy
    Karolinska Inst, Sweden.
    Borowsky, Alexander D.
    Univ Calif Davis, CA 95616 USA.
    Esserman, Laura J.
    Univ Calif San Francisco, CA USA.
    Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer2018Inngår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 110, nr 7, s. 726-733, artikkel-id djx270Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods: The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Raos quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results: A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P amp;lt; .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio (HR] = 1.98, 95% confidence interval (CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI -1.18 to 4.99). Conclusions: Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors.

  • 103.
    Lindström, L.
    et al.
    Karolinska universitetet, Södersjukhuset, 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.
    Fornander, T.
    Karolinska universitetet, Södersjukhuset, Sweden.
    Test identifierade patienter med mycket låg risk att dö i bröstcancer2017Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, nr 41Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    [No abstract available]

  • 104.
    Liu, Na
    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. State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an, China.
    Cox, Thomas R.
    Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
    Cui, Weiyingqi
    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.
    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.
    Holmlund, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Ping, Jie
    Shanghai Center for Bioinformation Technology, Shanghai, China.
    Jarlsfelt, Ingvar
    Department of Pathology, Ryhov Hospital, Jönköping, Sweden.
    Erler, Janine T.
    Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
    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.
    Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients.2017Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, nr 36, s. 60015-60024Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical significance of this expression. Nuclear LOX expression was significantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours was correlated with a high rate of distant metastasis and increased recurrence. Multivariable analysis showed that high nuclear LOX expression was also correlated with poor overall survival and disease free survival. Furthermore, we are the first to identify LOX enzyme isoforms (50 kDa and 32 kDa) within the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients.

    Fulltekst (pdf)
    fulltext
  • 105.
    Liu, Na
    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. Xi An Jiao Tong Univ, Peoples R China.
    Cui, Weiyingqi
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Jiang, Xia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Hebei Med Univ, Peoples R China.
    Zhang, Zhiyong
    Fourth Mil Med Univ, Peoples R China.
    Gnosa, Sebastian
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Ali, Zaheer
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Jensen, Lasse
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Jönsson, Jan-Ingvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för hematopoes och utvecklingsbiologi. Linköpings universitet, Medicinska fakulteten.
    Blockhuys, Stephanie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Lam, Eric W-F
    Imperial Coll London, England.
    Zhao, Zengren
    Hebei Med Univ, Peoples R China.
    Ping, Jie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Xie, Ning
    Xi An Jiao Tong Univ, Peoples R China.
    Kopsida, Maria
    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.
    Wang, Xin
    Fourth Mil Med Univ, Peoples R China.
    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.
    The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer2019Inngår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 104, nr 5, s. 1153-1164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose

    To explore whether the Rho protein is involved in the radioresistance of colorectal cancer and investigate the underlying mechanisms.

    Methods and Materials

    Rho GTPase expression was measured after radiation treatment in colon cancer cells. RhoB knockout cell lines were established using the CRISPR/Cas9 system. In vitro assays and zebrafish embryos were used for analyzing radiosensitivity and invasive ability. Mass cytometry was used to detect RhoB downstream signaling factors. RhoB and Forkhead box M1 (FOXM1) expression were detected by immunohistochemistry in rectal cancer patients who participated in a radiation therapy trial.

    Results

    RhoB expression was related to radiation resistance. Complete depletion of the RhoB protein increased radiosensitivity and impaired radiation-enhanced metastatic potential in vitro and in zebrafish models. Probing signaling using mass cytometry–based single-cell analysis showed that the Akt phosphorylation level was inhibited by RhoB depletion after radiation. FOXM1 was downregulated in RhoB knockout cells, and the inhibition of FOXM1 led to lower survival rates and attenuated migration and invasion abilities of the cells after radiation. In the patients who underwent radiation therapy, RhoB overexpression was related to high FOXM1, late Tumor, Node, Metastasis stage, high distant recurrence, and poor survival independent of other clinical factors.

    Conclusions

    RhoB plays a critical role in radioresistance of colorectal cancer through Akt and FOXM1 pathways.

  • 106.
    Liu, Yong
    et al.
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Chen, Xiao-Dong
    Sichuan University, Peoples R China.
    Yu, Jiang
    Sichuan University, Peoples R China.
    Chi, Jun-Lin
    Sichuan University, Peoples R China.
    Long, Fei-Wu
    Sichuan University, Peoples R China.
    Yang, Hong-Wei
    Sichuan University, Peoples R China.
    Chen, Ke-Ling
    Sichuan University, Peoples R China.
    Lv, Zhao-Ying
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Peng, Zhi-Hai
    Shanghai Jiao Tong University, Peoples R China.
    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. Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Deletion Of XIAP reduces the severity of acute pancreatitis via regulation of cell death and nuclear factor-kappa B activity2017Inngår i: Cell Death and Disease, ISSN 2041-4889, E-ISSN 2041-4889, Vol. 8, artikkel-id e2685Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Severe acute pancreatitis (SAP) still remains a clinical challenge, not only for its high mortality but the uncontrolled inflammatory progression from acute pancreatitis (AP) to SAP. Cell death, including apoptosis and necrosis are critical pathology of AP, since the severity of pancreatitis correlates directly with necrosis and inversely with apoptosis Therefore, regulation of cell death from necrosis to apoptosis may have practicably therapeutic value. X-linked inhibitor of apoptosis protein (XIAP) is the best characterized member of the inhibitor of apoptosis proteins (IAP) family, but its function in AP remains unclear. In the present study, we investigated the potential role of XIAP in regulation of cell death and inflammation during acute pancreatitis. The in vivo pancreatitis model was induced by the administration of cerulein with or without lipopolysaccharide (LPS) or by the administration of L-arginine in wild-type or XIAP-deficient mice, and ex vivo model was induced by the administration of cerulein+LPS in AR42J cell line following XIAP inhibition. The severity of acute pancreatitis was determined by serum amylase activity and histological grading. XIAP deletion on cell apoptosis, necrosis and inflammatory response were examined. Caspases activities, nuclear factor kappa B (NF-kappa B) activation and receptor-interacting protein kinase1 (RIP1) degradation were assessed by western blot. Deletion of XIAP resulted in the reduction of amylase activity, decrease of NF-kappa B activation and less release of TNF-alpha and IL-6, together with increased caspases activities and RIP1 degradation, leading to enhanced apoptosis and reduced necrosis in pancreatic acinar cells and ameliorated the severity of acute pancreatitis. Our results indicate that deletion of XIAP switches cell death away from necrosis to apoptosis and decreases the inflammatory response, effectively attenuating the severity of AP/SAP. The critical role of XIAP in cell death and inflammation suggests that inhibition of XIAP represents a potential therapeutic strategy for the treatment of acute pancreatitis.

    Fulltekst (pdf)
    fulltext
  • 107.
    Liu, Yong
    et al.
    Sichuan University, Peoples R China.
    Zhou, Dan
    Sichuan University, Peoples R China.
    Long, Fei-Wu
    Sichuan University, Peoples R China.
    Chen, Ke-Ling
    Sichuan University, Peoples R China.
    Yang, Hong-Wei
    Sichuan University, Peoples R China.
    Lv, Zhao-Yin
    Sichuan University, Peoples R China.
    Zhou, Bin
    Sichuan University, Peoples R China.
    Peng, Zhi-Hai
    Shanghai Jiao Tong University, Peoples R China.
    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. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China.
    Resolvin D1 protects against inflammation in experimental acute pancreatitis and associated lung injury2016Inngår i: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 310, nr 5, s. G303-G309Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure with considerable mortality. Recently, resolvin D1 (RvD1) as an endogenous anti-inflammatory lipid mediator has been confirmed to protect against many inflammatory diseases. This study was designed to investigate the effects of RvD1 in acute pancreatitis and associated lung injury. Acute pancreatitis varying from mild to severe was induced by cerulein or cerulein combined with LPS, respectively. Mice were pretreated with RvD1 at a dose of 300 ng/mouse 30 min before the first injection of cerulein. Severity of AP was assessed by biochemical markers and histology. Serum cytokines and myeloperoxidase (MPO) levels in pancreas and lung were determined for assessing the extent of inflammatory response. NF-kappa B activation was determined by Western blotting. The injection of cerulein or cerulein combined with LPS resulted in local injury in the pancreas and corresponding systemic inflammatory changes with pronounced severity in the cerulein and LPS group. Pretreated RvD1 significantly reduced the degree of amylase, lipase, TNF-alpha, and IL-6 serum levels; the MPO activities in the pancreas and the lungs; the pancreatic NF-kappa B activation; and the severity of pancreatic injury and associated lung injury, especially in the severe acute pancreatitis model. These results suggest that RvD1 is capable of improving injury of pancreas and lung and exerting anti-inflammatory effects through the inhibition of NF-kappa B activation in experimental acute pancreatitis, with more notable protective effect in severe acute pancreatitis. These findings indicate that RvD1 may constitute a novel therapeutic strategy in the management of severe acute pancreatitis.

    Fulltekst (pdf)
    fulltext
  • 108.
    Loftås, Per
    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, Kirurgiska kliniken ViN.
    Arbman, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    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.
    Edler, David
    Department of Surgery, Karolinska Institute, Stockholm, Sweden.
    Syk, Erik
    Department of Surgery, Ersta Hospital, Stockholm, Sweden.
    Hallböök, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    FXYD-3 expression in relation to local recurrence of rectal cancer2016Inngår i: Radiation Oncology Journal, ISSN 2234-1900, Vol. 34, nr 1, s. 52-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer.

    Materials and Methods: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81).

    Results: Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without.

    Conclusion: Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.

    Fulltekst (pdf)
    fulltext
  • 109.
    Loorents, Vera
    et al.
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rosell, Johan
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper.
    Salgado Willner, Helen
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    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.
    Health-related quality of life up to 1 year after radiotherapy in patients with head and neck cancer (HNC)2016Inngår i: SpringerPlus, E-ISSN 2193-1801, Vol. 5, nr 1, artikkel-id 669Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Detailed symptom specific descriptions of health-related quality of life (HRQOL), using validated questionnaires in patients with head and neck cancer (HNC) are sparse. The aim of the present study was to investigate HRQOL in patients with HNC up to 1 year after radiotherapy (RT), using two standardised questionnaires.

    Methods

    The data for the present study was originally collected in a randomised, prospective study. Forty-seven patients from two RT clinics in Sweden were included to investigate the secondary aim: HRQOL. Data was recorded at baseline, completion of RT, and 3, 6, 12 months after completed RT, using the questionnaire EORTC QLQ-C30-version 3 and the disease-specific module EORTC QLQ-H&N35.

    Results

    Most symptoms and functions deteriorated significantly by the end of RT, improved gradually by 3 and 6 months and reached baseline levels at 12 months after completed RT. However, 1 year after completed RT there were remaining significant problems in senses, dry mouth and sticky saliva.

    Conclusions

    Radiation therapy affects health-related quality of life in patients with head and neck cancer, both in the short and long term. Caregivers need management strategies for early detection and treatment of specific problems throughout the treatment period to help in the prevention of long-term symptoms.

    Fulltekst (pdf)
    fulltext
  • 110.
    Luo, B.
    et al.
    Sichuan Prov Peoples Hosp, Peoples R China; Sichuan Univ, Peoples R China.
    Yang, H. W.
    Sichuan Univ, Peoples R China.
    Long, F. W.
    Sichuan Univ, Peoples R China.
    Zhou, B.
    Sichuan Univ, Peoples R China.
    Lv, Z. Y.
    Sichuan Univ, Peoples R China.
    Cheng, K. L.
    Sichuan Univ, Peoples R China.
    Li, Y.
    Sichuan Univ, Peoples R China.
    Zhou, Z. G.
    Sichuan Univ, Peoples R China.
    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. Sichuan Univ, Peoples R China.
    Correction: Intratumoral polymorphism of peroxisome proliferator-activated receptor delta -87 T > C in colorectal cancer (vol 66, pg 609, 2019)2019Inngår i: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 66, nr 6, s. 1031-1031Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    n/a

  • 111.
    Luo, B.
    et al.
    Sichuan Prov Peoples Hosp, Peoples R China.
    Yang, H. W.
    Sichuan Univ, Peoples R China.
    Long, F. W.
    Sichuan Univ, Peoples R China.
    Zhou, B.
    Sichuan Univ, Peoples R China.
    Lv, Z. Y.
    Sichuan Univ, Peoples R China.
    Cheng, K. L.
    Sichuan Univ, Peoples R China.
    Li, Y.
    Sichuan Univ, Peoples R China.
    Zhou, Z. G.
    Sichuan Univ, Peoples R China.
    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. Sichuan Univ, Peoples R China; Sichuan Univ, Peoples R China.
    Intratumoral polymorphism of peroxisome proliferator-activated receptor delta-87 T > C in colorectal cancer2019Inngår i: Neoplasma (Bratislava), ISSN 0028-2685, E-ISSN 1338-4317, Vol. 66, nr 4, s. 609-618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Peroxisome proliferator-activated receptor delta (PPARD) is a nuclear receptor transcription factor whose single nucleotide polymorphism (SNP), especially PPARD -87 Tamp;gt;C (rs2016520), may play an important role in regulation of PPARD expression. However its expression patterns as well as contribution to colorectal cancer (CRC) are still controversial. In this study, the presence of the intratumoral heterogeneity of PPARD -87 Tamp;gt;C (rs2016520) polymorphism and its influence in CRC were investigated. Tumor masses from primary CRC patients were collected during the tumorectomy, specimens from different sites of the same tumor mass were sampled and stored individually. The SNP of PPARD -87 Tamp;gt;C was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and the expression of PPARD in vivo was observed by immunohistochemistry. The correlation of PPARD -87 Tamp;gt;C intra-tumoral polymorphism and the clinicopathological parameters of patients was analyzed statistically. Tumor samples were collected from 106 CRC patients (70 males and 36 females) with an average age of 61.04 +/- 13.67 years. A total number of 808 samples (7.60 +/- 1.60 per patient) were mainly harvested at peripheral superficial (n=376), central superficial (n=163), invasive front (n=112) and mesenteric cancer foci (n=42) of tumor tissues as well as cancerous adjacent mucosa (n=104). PCR-RFLP analysis showed that T/T (n=460, 56.9%) and T/C (n=334, 41.3%) were the main genotypes of -87 Tamp;gt;C among these samples. Furthermore, intratumoral genotype of -87 Tamp;gt;C was homogeneous in 90 patients and heterogeneous in other 16 patients. The intratumoral heterogeneity was related to patient age (p=0.016), tumor location (p=0.011) and the grade of differentiation (p=0.022). For patients with intratumoral heterogeneity, immunochemistry showed that the expressions of PPARD were not influenced by T/T or T/C genotypes. Intratumoral heterogeneity of PPARD -87 Tamp;gt;C widely existed in CRC, and associated with patient age, tumor location and differentiation. However, the immunochemistry assay revealed that there is no significant link between heterogeneity and expression of PPARD.

  • 112.
    Magic, Zeljana
    et al.
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Sandström, Josefine
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Perez Tenorio, Gizeh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Ephrin-B2 inhibits cell proliferation and motility in vitro and predicts longer metastasis-free survival in breast cancer2019Inngår i: International Journal of Oncology, ISSN 1019-6439, Vol. 55, nr 6, s. 1275-1286Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The tyrosine kinase receptor EphB4 and its ligand ephrin-B2 interact through cell-to-cell contacts. Upon interaction, EphB4 transmits bidirectional signals. A forward signal inside EphB4-expressing cells is believed to suppress tumor growth, while inside the ephrin-expressing cells, an oncogenic reverse signal arises. In breast cancer cells with a high EphB4 receptor expression the forward signal is low, in part due to the low expression of the ligand ephrin-B2. Therefore, we hypothesized that by re-introducing the ligand in EphB4-positive cells, tumor suppression could be induced by the stimulation of the forward signal. This question was addressed in vitro by the stable lentiviral infection of breast cancer cells with either wild-type EFNB2 or with a mutant EFNB2-5F, unable to transmit reverse signaling. Furthermore, we investigated ephrin-B and EphB4 protein expression in 216 paraffin-embedded tumors using immunohistochemistry. The in vitro results indicated that ephrin-B2 expression was associated with a lower cell proliferation, migration and motility compared with the control cells. These effects were more pronounced when the cells lacked the ability to transmit the reverse signal (B2-5F). In clinical material, ephrin-B protein expression was associated with a positive estrogen receptor (ER) status, a low HER-2 expression and was negatively associated with Nottingham histologic grade (NHG) III. Ephrin-B expression indicated a good prognosis, whereas EphB4 expression was associated with a shorter metastasis-free survival in univariate and multivariate analysis. Furthermore, the prognostic value of EFNB2 and EPHB4 was confirmed at the gene expression level in public datasets. Thus, on the whole, the findings of this study suggest that ephrin-B2 expression is associated with less proliferation and lower motility of breast cancer cells and with a longer patient survival in breast cancer.

    Fulltekst (pdf)
    fulltext
  • 113.
    Makitie, A.
    et al.
    Univ Helsinki, Finland; Helsinki Univ Hosp, Finland; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Ruuskanen, M.
    Turku Univ Hosp, Finland.
    Bentzen, J.
    Herlev Univ Hosp, Denmark.
    Brun, E.
    Lund Univ, Sweden.
    Gebre-Medhin, M.
    Lund Univ, Sweden.
    Friesland, S.
    Karolinska Univ Hosp, Sweden.
    Marsk, E.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Hammarstedt-Nordenvall, L.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Gille, E.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Reizenstein, J.
    Örebro Univ Hosp, Sweden.
    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.
    Farnebo, Lovisa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Logopedi, Audiologi och Otorhinolaryngologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken US.
    Rzepecki, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Haugen, H.
    Sahlgrens Univ Hosp, Sweden.
    Soderstrom, K.
    Umeå Univ, Sweden.
    Zackrisson, B.
    Umea Univ, Sweden.
    Bergstrom, S.
    Gävle Cent Hosp, Sweden.
    Loden, B.
    Karlstad Hosp, Sweden.
    Cederblad, L.
    Uppsala Univ Hosp, Sweden.
    Laurell, G.
    Uppsala Univ Hosp, Sweden.
    Smeland, E.
    Univ Hosp North Norway, Norway.
    Evensen, J. Folkvard
    Oslo Univ Hosp, Norway.
    Lund, J. A.
    Trondheim Reg and Univ Hosp, Norway.
    Tondel, H.
    Trondheim Reg and Univ Hosp, Norway.
    Karlsdottir, A.
    Haukeland Hosp, Norway.
    Johannsson, J.
    Landspitali Univ Hosp, Iceland.
    Johansen, J.
    Odense Univ Hosp, Denmark.
    Kristensen, C. A.
    Rigshosp, Denmark.
    Jensen, K.
    Aarhus Univ Hosp, Denmark.
    Andersen, L. J.
    Aalborg Hosp, Denmark.
    Koivunen, P.
    Oulu Univ Hosp, Finland.
    Korpela, M.
    Oulu Univ Hosp, Finland.
    Voutilainen, L.
    Kuopio Univ Hosp, Finland.
    Wigren, T.
    Tampere Univ Hosp, Finland.
    Minn, H.
    Turku Univ Hosp, Finland.
    Joensuu, H.
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    Overgaard, J.
    Aarhus Univ Hosp, Denmark.
    Saarilahti, K.
    Helsinki Univ Hosp, Finland; Univ Helsinki, Finland.
    The management and survival outcomes of nasopharyngeal cancer in the Nordic countries2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 4, s. 557-560Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    n/a

  • 114.
    Malmström, Annika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, LAH Linköping.
    Skovgaard Poulsen, Hans
    Rigshosp, Denmark.
    Henning Gronberg, Bjorn
    Norwegian University of Science and Technology, Norway; Trondheim Regional and University Hospital, Norway.
    Stragliotto, Giuseppe
    Karolinska University Hospital, Sweden.
    Hansen, Steinbjorn
    University of Southern Denmark, Denmark.
    Asklund, Thomas
    Karolinska University Hospital, Sweden; Umeå University, Sweden.
    Holmlund, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Dowsett, Joseph
    University of Southern Denmark, Denmark.
    Winther Kristensen, Bjarne
    University of Southern Denmark, Denmark.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    Henriksson, Roger
    Umeå University, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial2017Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 12, s. 1776-1785Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.

  • 115.
    Mattisson, Marie
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Johnson, Christina
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    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.
    Arestedt, Kristofer
    Linnaeus Univ, Sweden; Kalmar Cty Council, Sweden.
    Lindberg, Malou
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i västra Östergötland, 1177 Vårdguiden på telefon.
    Development and content validation of the Telenursing Interaction and Satisfaction Questionnaire (TISQ)2019Inngår i: Health Expectations, ISSN 1369-6513, E-ISSN 1369-7625, Vol. 22, nr 6, s. 1213-1222Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Caller satisfaction with telephone advice nursing (TAN) is generally high, and the interaction is essential. However, a valid questionnaire exploring caller satisfaction in TAN with focus on perceived interaction is lacking. Objective To develop and assess content validity and test-retest reliability of a theoretically anchored questionnaire, the Telenursing Interaction and Satisfaction Questionnaire (TISQ), that explores caller satisfaction in TAN by focusing on perceived interaction between the caller and the telenurse. Methods The study was performed in three stages. First, variables relevant for patient satisfaction in health care were identified through a literature search. Variables were then structured according to the Interaction Model of Client Health Behavior (IMCHB), which provided theoretical guidance. Items relevant for a TAN context were developed through consensus discussions. Then, evaluation and refinement were performed through cognitive interviews with callers and expert ratings of the Content Validity Index (CVI). Finally, test-retest reliability of items was evaluated in a sample of 109 individuals using intraclass correlation coefficients (ICC). Results The TISQ consists of 60 items. Twenty items cover perceived interaction in terms of health information, affective support, decisional control and professional/technical competence. Five items cover satisfaction with interaction and five items overall satisfaction. Remaining items reflect singularity of the caller and descriptive items of the call. The TISQ was found to exhibit good content validity, and test-retest reliability was moderate to good (ICC = 0.39-0.84). Conclusions The items in the TISQ form a comprehensive and theoretically anchored questionnaire with satisfactory content validity and test-retest reliability.

    Fulltekst (pdf)
    fulltext
  • 116.
    Matulonis, Ursula A.
    et al.
    Dana-Farber Cancer Institute, Boston, USA.
    Walder, Lydia
    FIECON, Ltd, St Albans, United Kingdom.
    Nøttrup, Trine J
    Nordic Society of Gynaecological Oncology and Copenhagen University Hospital, Copenhagen, Denmark.
    Bessette, Paul
    PMHC and University of Sherbrooke, Canada.
    Mahner, Sven
    Arbeitsgemeinschaft Gynäkologische Onkologie and University of Munich, Munich, Germany.
    Gil-Martin, Marta
    Grupo Español de Investigación en Cáncer de Ovario and Institut Català dOncologia-IDIBELL, LHospitalet, Barcelona, Spain.
    Kalbacher, Elsa
    Groupe dInvestigateurs Nationaux pour lEtude des Cancers Ovariens and University Hospital Besançon, Besançon, France.
    Ledermann, Jonathan A
    National Cancer Research Institute and University College London Cancer Institute, London, United Kingdom.
    Wenham, Robert M
    H. Lee Moffitt Cancer Center, Tampa, USA.
    Woie, Kathrine
    Nordic Society of Gynaecological Oncology and Haukeland University Hospital, Bergen, Norway.
    Lau, Susie
    PMHC and Jewish General Hospital, Montreal, Québec, Canada.
    Marmé, Frederik
    Arbeitsgemeinschaft Gynäkologische Onkologie and Universitätsklinikum Heidelberg, Heidelberg, Germany.
    Casado Herraez, Antonio
    Grupo Español de Investigación en Cáncer de Ovario and Hospital Universitario San Carlos, Madrid, Spain.
    Hardy-Bessard, Anne-Claire
    Groupe dInvestigateurs Nationaux pour lEtude des Cancers Ovariens and Centre Amoricain DOncologie, Paris, France.
    Banerjee, Susana
    National Cancer Research Institute and The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom.
    Lindahl, Gabriel
    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. Nordic Society of Gynaecological Oncology, Sweden.
    Benigno, Benedict
    Northside Hospital, Atlanta, GA, USA.
    Buscema, Joseph
    Arizona Oncology, Tucson, AZ, USA.
    Travers, Karin
    TESARO A GSK Company, Waltham, MA, USA.
    Guy, Holly
    FIECON, Ltd, St Albans, United Kingdom.
    Mirza, Mansoor R.
    Nordic Society of Gynaecological Oncology and Copenhagen University Hospital, Copenhagen, Denmark.
    Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial2019Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 37, nr 34, s. 3183-3191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer.

    Fulltekst (pdf)
    fulltext
  • 117.
    Meng, Wen-Jian
    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. Sichuan University, Peoples R China.
    Pathak, Surajit
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Ding, Zhen-Yu
    Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Adell, Gunnar
    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.
    Holmlund, Birgitta
    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.
    Li, Yuan
    Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    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. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Special AT-rich sequence binding protein 1 expression correlates with response to preoperative radiotherapy and clinical outcome in rectal cancer2015Inngår i: Cancer Biology & Therapy, ISSN 1538-4047, E-ISSN 1555-8576, Vol. 16, nr 12, s. 1738-1745Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Our recent study showed the important role of special AT-rich sequence binding protein 1 (SATB1) in the progression of human rectal cancer. However, the value of SATB1 in response to radiotherapy (RT) for rectal cancer hasnt been reported so far. Here, SATB1 was determined using immunohistochemistry in normal mucosa, biopsy, primary cancer, and lymph node metastasis from 132 rectal cancer patients: 66 with and 66 without preoperative RT before surgery. The effect of SATB1 knockdown on radiosensitivity was assessed by proliferation-based assay and clonogenic assay. The results showed that SATB1 increased from normal mucosa to primary cancer, whereas it decreased from primary cancer to metastasis in non-RT patients. SATB1 decreased in primary cancers after RT. In RT patients, positive SATB1 was independently associated with decreased response to preoperative RT, early time to metastasis, and worse survival. SATB1 negatively correlated with ataxia telangiectasia mutated (ATM) and pRb2/p130, and positively with Ki-67 and Survivin in RT patients, and their potential interaction through different canonical pathways was identified in network ideogram. Taken together, our findings disclose for the first time that radiation decreases SATB1 expression and sensitizes cancer cells to confer clinical benefit of patients, suggesting that SATB1 is predictive of response to preoperative RT and clinical outcome in rectal cancer.

  • 118.
    Meng, Wen-Jian
    et al.
    Sichuan University, Peoples R China.
    Yang, Lie
    Sichuan University, Peoples R China.
    Ma, Qin
    Sichuan University, Peoples R China.
    Zhang, Hong
    University of Örebro, Sweden.
    Adell, Gunnar
    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.
    Arbman, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken ViN.
    Wang, Zi-Qiang
    Sichuan University, Peoples R China.
    Li, Yuan
    Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    Zhou, Zong-Guang
    Sichuan University, Peoples R China; Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    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. Sichuan University, Peoples R China; Sichuan University, Peoples R China.
    MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer2015Inngår i: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 94, nr 32Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The expression of abnormal microRNA (miRNA, miR) is a ubiquitous feature of colorectal cancer (CRC). The pathological features and clinical behaviors of synchronous CRC have been comprehensively described; however, the expression profile of miRNA and small nucleolar RNA (snoRNA) in synchronous CRC has not been elucidated. In the present study, the expression profile of miRNA and snoRNA in 5 synchronous CRCs, along with the matched normal colorectal tissue was evaluated by microarray. Function and pathway analyses of putative targets, predicted from miRNA-mRNA interaction, were performed. Moreover, we analyzed clinicopathological and molecular characteristics of 22 patients with synchronous CRC and 579 solitary CRCs in a retrospective cohort study. We found a global dysregulation of miRNAs, including an oncogenic miR-17-92 cluster and oncosuppressive miR-143-145 cluster, and snoRNAs in synchronous CRC. Differential miRNA rather than snoRNA expression was robust enough to distinguish synchronous cancer from normal mucosa. Function analysis of putative targets suggested that miRNA clusters may modulate multiple effectors of oncogenic pathways involved in the pathogenesis of synchronous CRC. A comparison of normal mucosa between synchronous and solitary CRC suggested a differential genetic background of synchronous CRC from solitary CRC during carcinogenesis. Compared with solitary cancer patients, synchronous cases exhibited multiple extra-colonic cancers (P=0.012), coexistence of adenoma (P=0.012), microsatellite instability (P=0.024), and less glucose transporter 1 (P=0.037). Aberrant miRNA expression profiles could potentially be used as a diagnostic tool for synchronous CRC. Our findings represent the first comprehensive miRNA and snoRNA expression signatures for synchronous CRC, implicating that the miRNAs and snoRNAs may present therapeutic targets for synchronous CRC.

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  • 119.
    Mi, Yushuai
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Dongyuan
    Shanghai Jiao Tong University, Peoples R China.
    Jiang, Weiliang
    Shanghai Jiao Tong University, Peoples R China.
    Weng, Junyong
    Shanghai Jiao Tong University, Peoples R China.
    Zhou, Chongzhi
    Shanghai Jiao Tong University, Peoples R China.
    Huang, Kejian
    Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Yu, Yang
    Shanghai Jiao Tong University, Peoples R China.
    Liu, Xisheng
    Shanghai Jiao Tong University, Peoples R China.
    Cui, Weiyingqi
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Zhang, Meng
    Fudan University, Peoples R China.
    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.
    Zhou, Zongguang
    Sichuan University, Peoples R China.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    Zhao, Senlin
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    Shanghai Jiao Tong University, Peoples R China.
    miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signalling activation2017Inngår i: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 389, s. 11-22Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

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  • 120.
    Mi, Yushuai
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Zhao, Senlin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Shanghai Jiao Tong University, Peoples R China.
    Zhang, Weihao
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Dongyuan
    Shanghai Jiao Tong University, Peoples R China.
    Weng, Junyong
    Shanghai Jiao Tong University, Peoples R China.
    Huang, Kejian
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Huimin
    Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Xin
    Zhejiang Prov Peoples Hospital, Peoples R China.
    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.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Shanghai Jiao Tong University, Peoples R China.
    Down-regulation of Barx2 predicts poor survival in colorectal cancer2016Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 478, nr 1, s. 67-73Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar family, has an important role in controlling the expression of cell adhesion molecules and has been reported in an increasing array of tumor types except colorectal cancer (CRC). The purpose of the current study was to characterize the expression of Barx2 and assess the clinical significance of Barx2 in CRC. First, we analyzed the expression of Barx2 in two independent public datasets from Oncomine. Subsequently, we evaluated Barx2 mRNA and protein expression by quantitative real-time PCR and western blotting, respectively. It was determined that Barx2 expression was lower in tumor tissues than in adjacent non-tumorous colorectal tissues of CRC patients, consistent with results from the public datasets. Subsequently, a tissue microarray containing 196 CRC specimens was evaluated for Barx2 expression by immunohistochemical staining. It was found that low expression of Barx2 significantly correlated with TNM stage, AJCC stage, differentiation, and relapse in patients with CRC. Patients with lower levels of Barx2 expression showed reduced disease-free survival and overall survival. Furthermore, a trend toward shorter overall survival in the patient group with Barx2-negative tumors independent of advanced AJCC stage and poor differentiation was determined by Kaplan-Meier survival analysis. Based on univariate and multivariate analyses, Barx2 expression was an independent prognostic factor for determining CRC prognosis. Taken together, low Barx2 expression was associated with the progression of CRC and could serve as a potential independent prognostic biomarker for patients with CRC. (C) 2016 The Authors. Published by Elsevier Inc.

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  • 121.
    Mi, Yushuai
    et al.
    Shanghai Jiao Tong University, Peoples R China.
    Zhao, Senlin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Shanghai Jiao Tong University, Peoples R China.
    Zhou, Chongzhi
    Shanghai Jiao Tong University, Peoples R China.
    Weng, Junyong
    Shanghai Jiao Tong University, Peoples R China.
    Li, Jikun
    Shanghai Jiao Tong University, Peoples R China.
    Wang, Zhanshan
    Shanghai Jiao Tong University, Peoples R China.
    Sun, Huimin
    Shanghai Jiao Tong University, Peoples R China.
    Tang, Huamei
    Shanghai Jiao Tong University, Peoples R China.
    Zhang, Xin
    Zhejiang Prov Peoples Hospital, Peoples R China.
    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.
    Peng, Zhihai
    Shanghai Jiao Tong University, Peoples R China.
    Wen, Yugang
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Shanghai Jiao Tong University, Peoples R China.
    Downregulation of homeobox gene Barx2 increases gastric cancer proliferation and metastasis and predicts poor patient outcomes2016Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 37, s. 60593-60608Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Barx2 is a Bar family homeodomain transcription factor shown to play a critical role in cell adhesion and cytoskeleton remodeling, key processes in carcinogenesis and metastasis. Using quantitative real-time PCR, Western blotting, and immunohistochemistry, we found that Barx2 is expressed at lower levels in human gastric cancer (GC) tissues than in adjacent normal mucosa. In a multivariate analysis, Barx2 expression emerged as an independent prognostic factor for disease-free and overall survival. Kaplan-Meier survival analysis showed a trend toward even shorter overall survival in the patient group with Barx2-negative tumors, independent of advanced UICC stage and tumor relapse. Using in vitro and in vivo assays, we demonstrated that under normal conditions Barx2 inhibited GC cell proliferation and invasiveness through inhibition of the Wnt/beta-catenin signaling pathway. These findings indicate that reduction or loss of Barx2 dis-inhibits GC cell proliferation and invasion, and that reduction in Barx2 could serve as an independent prognostic biomarker for poor outcome in GC patients.

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  • 122.
    Mirza, M. R.
    et al.
    Nordic Soc Gynecol Oncol, Denmark; Copenhagen University Hospital, Denmark.
    Monk, B. J.
    University of Arizona, AZ USA; Creighton University of Phoenix, AZ USA; Arizona Oncology Associates, AZ USA.
    Herrstedt, J.
    University of Southern Denmark, Denmark.
    Oza, A. M.
    University of Toronto, Canada.
    Mahner, S.
    Arbeitsgemeinschaft Gynakol Onkol, Germany; University of Munich, Germany.
    Redondo, A.
    GEICO, Spain; Hospital University of La Paz, Spain.
    Fabbro, M.
    French Investigator Grp Ovarian and Breast Cancer GIN, France; Institute Cancer Montpellier, France.
    Ledermann, J. A.
    UCL, England; UCL, England.
    Lorusso, D.
    Ist Nazl Tumori, Italy.
    Vergote, I.
    Luxembourg Gynecol Oncology Grp, Belgium; University of Leuven, Belgium.
    Ben-Baruch, N. E.
    Kaplan Medical Centre, Israel.
    Marth, C.
    AGO Austria, Austria; Medical University of Innsbruck, Austria.
    Madry, R.
    Central and Eastern European Gynecol Oncology Grp, Poland; Uniwersytet Medical Poznaniu, Poland.
    Christensen, R. D.
    University of Southern Denmark, Denmark.
    Berek, J. S.
    Stanford Comprehens Cancer Institute, CA USA.
    Dorum, A.
    Oslo University Hospital, Norway.
    Tinker, A. V.
    British Columbia Cancer Agency, Canada.
    du Bois, A.
    Kliniken Essen Mitte, Germany.
    Gonzalez-Martin, A.
    GEICO, Spain; MD Anderson Cancer Centre Madrid, Spain.
    Follana, P.
    GINECO, France; Centre Antoine Lacassagne, France.
    Benigno, B.
    Northside Hospital, GA USA.
    Rosenberg, Per
    Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Gilbert, L.
    McGill University, Canada.
    Rimel, B. J.
    Cedars Sinai Medical Centre, CA USA.
    Buscema, J.
    Arizona Oncology Associates, AZ USA.
    Balser, J. P.
    Veristat, MA USA.
    Agarwal, S.
    Tesaro, MA USA.
    Matulonis, U. A.
    Dana Farber Cancer Institute, MA 02115 USA.
    Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer2016Inngår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 375, nr 22, s. 2154-2164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. METHODS In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2: 1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. RESULTS Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P amp;lt; 0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. CONCLUSIONS Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274.)

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  • 123.
    Mirza, Mansoor Raza
    et al.
    NSGO, Denmark; Rigshosp, Denmark.
    Bergmann, Troels K.
    Odense Univ Hosp, Denmark.
    Mau-Sorensen, Morten
    Rigshosp, Denmark.
    Christensen, Rene dePont
    NSGO, Denmark; Univ Southern Denmark, Denmark.
    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. NSGO, Denmark.
    Birrer, Michael J.
    Univ Alabama Birmingham, AL USA.
    Jorgensen, Morten
    NSGO, Denmark; Rigshosp, Denmark.
    Roed, Henrik
    NSGO, Denmark; Rigshosp, Denmark.
    Malander, Susanne
    NSGO, Denmark; Lund Univ Hosp, Sweden.
    Nielsen, Flemming
    Univ Southern Denmark, Denmark.
    Lassen, Ulrik
    Rigshosp, Denmark.
    Brosen, Kim
    Univ Southern Denmark, Denmark.
    Bjorge, Line
    NSGO, Denmark; Univ Bergen, Norway; Haukeland Hosp, Norway.
    Maenpaa, Johanna
    NSGO, Denmark; Univ Tampere, Finland.
    A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV242019Inngår i: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 84, nr 4, s. 791-798Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial. Materials and methods In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D). Results Three of 12 enrolled patients had germline BRCA2 mutations. In cycle 1, nine patients experienced grade 3 toxicities: five with hypertension, three with anemia, and one with thrombocytopenia. There was one dose-limiting toxicity (grade 4 thrombocytopenia with niraparib 300 mg), thus the RP2D was bevacizumab 15 mg/kg with niraparib 300 mg. The response rate was 50%; disease was stabilized in a further 42%. Median progression-free survival was 11.6 (95% confidence interval 8.4-20.1) months. Niraparib pharmacokinetics were consistent with historical single-agent data. Overlapping exposure was observed across the dose ranges tested on days 1 and 21. Conclusions There was one dose-limiting toxicity; other adverse events were typical PARP inhibitor and antiangiogenic class effects. Niraparib-bevacizumab showed promising activity; Part 2 (vs bevacizumab) was recently reported and phase III comparison with standard-of-care therapy is planned.

  • 124.
    Mirza, Mansoor Raza
    et al.
    Nordic Soc Gynaecol Oncol, Denmark; Copenhagen Univ Hosp, Denmark.
    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. Nordic Soc Gynaecol Oncol, Denmark.
    Birrer, Michael
    Univ Alabama Birmingham, AL USA.
    Christensen, Rene DePont
    Nordic Soc Gynaecol Oncol, Denmark; Univ Southern Denmark, Denmark.
    Nyvang, Gitte-Bettina
    Nordic Soc Gynaecol Oncol, Denmark; Odense Univ Hosp, Denmark.
    Malander, Susanne
    Nordic Soc Gynaecol Oncol, Denmark; Lund Univ Hosp, Sweden.
    Anttila, Maarit
    Nordic Soc Gynaecol Oncol, Denmark; Kuopio Univ Hosp, Finland.
    Werner, Theresa L.
    Univ Utah, UT USA.
    Lund, Bente
    Nordic Soc Gynaecol Oncol, Denmark; Aalborg Univ Hosp, Denmark.
    Lindahl, Gabriel
    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. Nordic Soc Gynaecol Oncol, Denmark.
    Hietanen, Sakari
    Nordic Soc Gynaecol Oncol, Denmark; Turku Univ Hosp, Finland.
    Peen, Ulla
    Nordic Soc Gynaecol Oncol, Denmark; Hedev Univ Hosp, Denmark.
    Dimoula, Maria
    Nordic Soc Gynaecol Oncol, Denmark; Sahlgrens Univ Hosp, Sweden.
    Roed, Henrik
    Nordic Soc Gynaecol Oncol, Denmark; Copenhagen Univ Hosp, Denmark.
    Knudsen, Anja Or
    Nordic Soc Gynaecol Oncol, Denmark; Odense Univ Hosp, Denmark.
    Staff, Synnove
    Nordic Soc Gynaecol Oncol, Denmark; Tampere Univ, Finland; Tampere Univ, Finland; Univ Hosp, Finland.
    Vistisen, Anders Krog
    Aalborg Univ Hosp, Denmark.
    Bjorge, Line
    Nordic Soc Gynaecol Oncol, Denmark; Haukeland Hosp, Norway; Univ Bergen, Norway.
    Maenpaa, Johanna U.
    Nordic Soc Gynaecol Oncol, Denmark; Tampere Univ, Finland; Tampere Univ, Finland; Univ Hosp, Finland.
    Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial2019Inngår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 20, nr 10, s. 1409-1419Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Platinum-based chemotherapy is the foundation of treatment for platinum-sensitive recurrent ovarian cancer, but has substantial toxicity. Bevacizumab and maintenance poly(ADP-ribose) polymerase (PARP) inhibitors both significantly improve efficacy versus standard therapy, primarily in terms of progression-free survival, and offer the potential for chemotherapy-free treatment. AVANOVA2 compared niraparib and bevacizumab versus niraparib alone as definitive treatment for platinum-sensitive recurrent ovarian cancer. Methods This open-label, randomised, phase 2, superiority trial in 15 university hospitals in Denmark, Sweden, Finland, Norway, and the USA enrolled women aged 18 years or older with measurable or evaluable high-grade serous or endometrioid platinum-sensitive recurrent ovarian cancer. Patients had to have an Eastern Cooperative Oncology Group performance status of 0-2, and had to have previously received platinum-containing therapy for primary disease but amp;lt;= 1 prior non-platinum-containing regimen for recurrent disease. Previous treatment with bevacizumab or first-line maintenance PARP inhibitors was permitted. Eligible patients were randomly assigned 1:1 (by random permuted blocks with block sizes of two and four, no masking), stratified by homologous recombination deficiency status and chemotherapy-free interval, to receive once-daily oral niraparib 300 mg alone or with intravenous bevacizumab 15 mg/kg once every 3 weeks until disease progression. The primary endpoint was progression-free survival, assessed by the investigators in the intention-to-treat population after events in at least 62 patients. Safety was analysed in all patients who received at least one dose of study drug. This ongoing trial is registered with ClinicalTrials.gov , number NCT02354131. Findings Between May 23,2016, and March 6,2017,97 patients were enrolled and randomly assigned: 48 to niraparib plus bevacizumab and 49 to single-agent niraparib. Median follow-up was 16.9 months (IQR 15.4-20.9). Niraparib plus bevacizumab significantly improved progression-free survival compared with niraparib alone (median progression-free survival 11.9 months [95% CI 8.5-16.7] vs 5.5 months [3.8-6.3], respectively; adjusted hazard ratio [HR] 0.35 [95% CI 0.21-0.57], pamp;lt;0.0001). Grade 3 or worse adverse events occurred in 31 (65%) of 48 patients who received niraparib plus bevacizumab and 22 (45%) of 49 who received single-agent niraparib. The most common grade 3 or worse adverse events in both groups were anaemia (7 [15%] of 48 vs 9 [18%] of 49) and thrombocytopenia (5 [10%] vs 6 [12%]), and hypertension in the combination group (10 [21%] vs 0). Niraparib plus bevacizumab was associated with increased incidences of any-grade proteinuria (10 [21%] of 48 patients vs 0) and hypertension (27[56%] of 48 vs 11 [22%] of 49) compared with niraparib alone. No treatment-related deaths occurred. Interpretation The efficacy observed with this chemotherapy-free combination of approved agents in women with platinum-sensitive recurrent ovarian cancer warrants further evaluation. A randomised phase 3 trial investigating niraparib plus bevacizumab versus chemotherapy plus bevacizumab in platinum-sensitive recurrent ovarian cancer is planned. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

  • 125.
    Mishra, Ameet K.
    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.
    Abrahamsson, Annelie
    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.
    Fulvestrant inhibits growth of triple negative breast cancer and synergizes with tamoxifen in ER alpha positive breast cancer by up-regulation of ER beta2016Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, nr 35, s. 56876-56888Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The estrogen receptor-alpha (ER alpha) is used as a predictive marker for antiestrogen therapy in breast cancer patients. In addition to aromatase inhibitors, ER alpha can be targeted at the receptor level using the receptor modulator tamoxifen or by the pure anti-estrogen fulvestrant. The role of the second ER, ER-beta (ER beta), as a therapeutic target or prognostic marker in breast cancer is still elusive. Hitherto, it is not known if ER alpha+/ER beta+ breast cancers would benefit from a treatment strategy combining tamoxifen and fulvestrant or if fulvestrant exert any therapeutic effects in ER alpha-/ER beta+ breast cancer. Here, we report that fulvestrant up-regulated ER beta in ER alpha+/ER beta+ breast cancer and in triple negative ER beta+ breast cancers (ER alpha-/ER beta+). In ER alpha+/ER beta+ breast cancer, a combination therapy of tamoxifen and fulvestrant significantly reduced tumor growth compared to either treatment alone both in vivo and in vitro. In ER alpha-/ER beta+ breast cancer fulvestrant had potent effects on cancer growth, in vivo as well as in vitro, and this effect was dependent on intrinsically expressed levels of ER beta. The role of ER beta was further confirmed in cells where ER beta was knocked-in or knocked-down. Inhibition of DNA methyltransferase (DNMT) increased the levels of ER beta and fulvestrant exerted similar potency on DNMT activity as the DNMT inhibitor decitabine. We conclude that fulvestrant may have therapeutic potential in additional groups of breast cancer patients; i) in ER alpha+/ER beta+ breast cancer where fulvestrant synergizes with tamoxifen and ii) in triple negative/ER beta+ breast cancer patients, a subgroup of breast cancer patients with poor prognosis.

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  • 126.
    Morad, Vivian
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska fakulteten.
    Abrahamsson, Annelie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Kjölhede, Preben
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken 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.
    Adipokines and Vascular Endothelial Growth Factor in Normal Human Breast Tissue in Vivo - Correlations and Attenuation by Dietary Flaxseed2016Inngår i: Journal of mammary gland biology and neoplasia, ISSN 1083-3021, E-ISSN 1573-7039, Vol. 21, nr 1-2, s. 69-76Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Exposure to sex steroids increases the risk of breast cancer but the exact mechanisms are yet to be elucidated. Events in the microenvironment are important for carcinogenesis. Diet containing phytoestrogens can affect the breast microenvironment and alter the risk of breast cancer. It has previously been shown that estrogen regulates extracellular levels of leptin, adiponectin, and VEGF in normal breast tissue in vivo. Whether these proteins correlate in breast tissue in vivo or if diet addition of flaxseed, a major source of phytoestrogens in Western diets, alters adipokine levels in breast tissue are unknown. We used microdialysis to sample proteins of normal human breast tissue and abdominal subcutaneous fat in situ in 34 pre-and postmenopausal women. In vitro, co-culture of breast cancer cells and primary human adipocytes was used. In vivo, in normal breast tissue, a significant positive correlation between VEGF and leptin was detected. No correlations were found in fat tissue. Co-culture of adipocytes and breast cancer cells per se increased the secretion of VEGF and leptin and enhanced the effects of estradiol compared to culture of either cell type alone. In vitro, inhibition of VEGF diminished the release of leptin while inhibition of leptin had no influence on VEGF secretion. The levels of leptin decreased and adiponectin increased after a dietary addition of 25 g of flaxseed/day for one menstrual cycle. We conclude that VEGF and leptin correlate significantly in normal human breast tissue in vivo and that dietary addition of flaxseed affect adipokine levels in the breast.

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  • 127.
    Mosrati, Mohamed Ali
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Malmström, Annika
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Region Östergötland, Närsjukvården i centrala Östergötland, LAH Linköping. Linköpings universitet, Medicinska fakulteten.
    Lysiak, Malgorzata
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Krysztofiak, Adam
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Hallbeck, Martin
    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.
    Milos, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Region Östergötland, Sinnescentrum, Neurokirurgiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Hallbeck, Anna-Lotta
    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.
    Bratthall, Charlotte
    Dist Hospital, Sweden.
    Strandeus, Michael
    Ryhov Hospital, Sweden.
    Stenmark Askmalm, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma2015Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, nr 18, s. 16663-16673Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Telomerase reverse transcriptase (TERT) activity is up-regulated in several types of tumors including glioblastoma (GBM). In the present study, 128 primary glioblastoma patients were examined for single nucleotide polymorphisms of TERT in blood and in 92 cases for TERT promoter mutations in tumors. TERT promoter mutations were observed in 86% of the tumors and of these, C228T (-124 bp upstream start codon) was detected in 75% and C250T (-146 bp) in 25% of cases. TERT promoter mutations were associated with shorter overall survival (11 vs. 20 months p = 0.002 and 12 vs. 20, p = 0.04 for C228T and C250T, respectively). The minor alleles of rs2736100 and rs10069690 SNPs, located in intron 2 and the promotor regions, respectively, were associated with an increased risk of developing GBM (p = 0.004 and 0.001). GBM patients having both TERT promoter mutations and being homozygous carriers of the rs2853669 C-allele displayed significantly shorter overall survival than those with the wild type allele. The rs2853669 SNP is located in a putative Ets2 binding site in the promoter (-246 bp upstream start codon) close to the C228T and C250T mutation hot spots. Interleukin-6 (IL-6) expression regulated by TERT promoter status and polymorphism, what leads us to think that TERT and IL-6 plays a significant role in GBM, where specific SNPs increase the risk of developing GBM while the rs2853669 SNP and specific mutations in the TERT promoter of the tumor lead to shorter survival.

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  • 128.
    Nordenskjold, A. E.
    et al.
    Southern Alvsborg Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Fohlin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum. Linköpings universitet, Medicinska fakulteten. Regional Cancer Centre South East Sweden, Linkoping, Sweden.
    Albertsson, P.
    Sahlgrens University Hospital, Sweden.
    Arnesson, Lars-Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Chamalidou, C.
    Southern Alvsborg Hospital, Sweden; Sahlgrens University Hospital, Sweden.
    Einbeigi, Z.
    Sahlgrens University Hospital, Sweden.
    Holmberg, E.
    Regional Cancer Centre, 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.
    Karlsson, P.
    Sahlgrens University Hospital, Sweden.
    No clear effect of postoperative radiotherapy on survival of breast cancer patients with one to three positive nodes: a population-based study2015Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 26, nr 6, s. 1149-1154Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In published radiotherapy trials, the failure rate in the control arm among patients with one to three positive nodes is high compared with that seen with modern adjuvant treatments. Therefore, the generalizability of the results has been questioned. The aim of the present study was to compare relative survival in breast cancer patients between two Swedish regions with screening mammography programs and adjuvant treatment guidelines similar with the exception of the indication of radiotherapy for patients with one to three positive nodes. Patients and methods: Between 1989 and 2006, breast cancer patients were managed very similarly in the west and southeast regions, except for indication for postoperative radiotherapy. In patients with one to three positive nodes, post-mastectomy radiotherapy was generally given in the southeast region (89% of all cases) and generally not given in the west region (15% of all cases). For patients with one to three positive nodes who underwent breast-conserving surgery, patients in the west region had breast radiotherapy only, while patients in the southeast region had both breast and lymph nodes irradiated. Results: The 10-year relative survival for patients with one to three positive lymph nodes was 78% in the west region and 77% in the southeast region (P = 0.12). Separate analyses depending on type of surgery, as well as number of examined nodes, also revealed similar relative survival. Conclusion: Locoregional postoperative radiotherapy has well-known side-effects, but in this population-based study, there was little or no influence of this type of radiotherapy on survival when one to three lymph nodes were involved.

  • 129.
    Nordenskjold, Anna
    et al.
    Sahlgrens Acad, Sweden; Southern Alvsborg Hospital, Sweden.
    Fohlin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Fornander, Tommy
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden; Regional Cancer Centre Stockholm Gotland, Sweden.
    Lofdahl, Britta
    St Göran Hospital, Sweden.
    Skoog, Lambert
    Karolinska University Hospital, Sweden.
    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.
    Progesterone receptor positivity is a predictor of long-term benefit from adjuvant tamoxifen treatment of estrogen receptor positive breast cancer2016Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 160, nr 2, s. 313-322Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The independent predictive information from progesterone receptor (PgR) positivity for breast cancer treated with tamoxifen has been questioned after an overview by the Early Breast Cancer Trialists Collaborative Group (EBCTCG). However, the studies in the overview were to a large content performed before modern PgR immunohistochemistry (IHC) was developed. We therefore investigated the predictive value of PgR determined with IHC in estrogen receptor (ER)-positive tumors from patients participating in the Stockholm trial of adjuvant tamoxifen therapy. The Stockholm Breast Cancer Study Group conducted a randomized trial during 1976 through 1990 comparing adjuvant tamoxifen versus control. The patients were stratified according to tumor size and lymph node status in high-risk and low-risk groups. In this study, we evaluated 618 patients with ER-positive "low-risk" breast cancer (size aecurrency sign 30 mm, lymph node-negative) for whom PgR was determined by IHC at one pathology laboratory. The median time of follow-up was 21 years. Patients with ER-positive tumors that were also PgR-positive by IHC did benefit from tamoxifen, while we could not show any long-term benefit for those with tumors positive for ER only (recurrence rate ratio 0.43, 95 % CI 0.29-0.62 and 0.87, 95 % CI 0.52-1.46, respectively). We further investigated the influence of different levels of PgR positivity on recurrence risk. The results show that at all receptor levels with aeyen10 % stained PgR-positive cells, the patients did benefit from tamoxifen. There was no clear linear trend in benefit with increasing proportion of stained cells. PgR positivity determined by IHC is a marker indicating long-term benefit from adjuvant tamoxifen in patients with ER-positive tumors.

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  • 130.
    Nyholm, Tufve
    et al.
    Umeå University, Sweden; Uppsala University, Sweden.
    Olsson, Caroline
    Gothenburg University, Sweden; Western Sweden Healthcare Reg, Sweden.
    Agrup, Måns
    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.
    Bjork, Peter
    Mälar Hospital, Sweden.
    Bjork-Eriksson, Thomas
    Sahlgrenska University Hospital, Sweden.
    Gagliardi, Giovanna
    Karolinska University Hospital, Sweden.
    Grinaker, Hanne
    Swedish Radiation Safety Authority, Sweden.
    Gunnlaugsson, Adalsteinn
    Lund University, Sweden.
    Gustafsson, Anders
    Cureos AB, Sweden.
    Gustafsson, Magnus
    Sahlgrenska University Hospital, Sweden.
    Johansson, Bengt
    Örebro University Hospital, Sweden; University of Örebro, Sweden.
    Johnsson, Stefan
    Kalmar County Hospital, Sweden.
    Karlsson, Magnus
    Umeå University, Sweden.
    Kristensen, Ingrid
    Lund University, Sweden.
    Nilsson, Per
    Lund University, Sweden.
    Nystrom, Leif
    Umeå University, Sweden.
    Onjukka, Eva
    Karolinska University Hospital, Sweden.
    Reizenstein, Johan
    University of Örebro, Sweden.
    Skonevik, Johan
    Umeå University, Sweden; Örebro University Hospital, Sweden.
    Soderstrom, Karin
    Umeå University, Sweden.
    Valdman, Alexander
    Karolinska University Hospital, Sweden.
    Zackrisson, Bjorn
    Umeå University, Sweden.
    Montelius, Anders
    Uppsala University, Sweden.
    A national approach for automated collection of standardized and population-based radiation therapy data in Sweden2016Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 119, nr 2, s. 344-350Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To develop an infrastructure for structured and automated collection of interoperable radiation therapy (RT) data into a national clinical quality registry. Materials and methods: The present study was initiated in 2012 with the participation of seven of the 15 hospital departments delivering RT in Sweden. A national RT nomenclature and a database for structured unified storage of RT data at each site (Medical Information Quality Archive, MIQA) have been developed. Aggregated data from the MIQA databases are sent to a national RT registry located on the same IT platform (INCA) as the national clinical cancer registries. Results: The suggested naming convention has to date been integrated into the clinical workflow at 12 of 15 sites, and MIQA is installed at six of these. Involvement of the remaining 3/15 RT departments is ongoing, and they are expected to be part of the infrastructure by 2016. RT data collection from ARIA (R), Mosaiq (R), Eclipse (TM), and Oncentra (R) is supported. Manual curation of RT-structure information is needed for approximately 10% of target volumes, but rarely for normal tissue structures, demonstrating a good compliance to the RT nomenclature. Aggregated dose/volume descriptors are calculated based on the information in MIQA and sent to INCA using a dedicated service (MIQA2INCA). Correct linkage of data for each patient to the clinical cancer registries on the INCA platform is assured by the unique Swedish personal identity number. Conclusions: An infrastructure for structured and automated prospective collection of syntactically inter operable RT data into a national clinical quality registry for RT data is under implementation. Future developments include adapting MIQA to other treatment modalities (e.g. proton therapy and brachytherapy) and finding strategies to harmonize structure delineations. How the RT registry should comply with domain-specific ontologies such as the Radiation Oncology Ontology (ROO) is under discussion. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 131.
    Paramita, Pragyan
    et al.
    Chettinad Acad Res and Educ, India.
    Subramaniam, Vimala Devi
    Chettinad Acad Res and Educ, India.
    Murugesan, Ramachandran
    Chettinad Acad Res and Educ, India.
    Gopinath, Madhumala
    Chettinad Acad Res and Educ, India.
    Ramachandran, Ilangovan
    Univ Madras, India.
    Ramalingam, Satish
    Chettinad Acad Res and Educ, India; SRM Inst Sci and Technol, India.
    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.
    Banerjee, Antara
    Chettinad Acad Res and Educ, India.
    Marotta, Francesco
    ReGenera RandD Int Aging Intervent, Italy; ReGenera RandD Int Aging Intervent, Peoples R China; VCC Prevent Med Promot Fdn, Peoples R China.
    Pathak, Surajit
    Chettinad Acad Res and Educ, India.
    Evaluation of potential anti-cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells2018Inngår i: IET Nanobiotechnology, ISSN 1751-8741, E-ISSN 1751-875X, Vol. 12, nr 6, s. 727-732Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Research dealing with early diagnosis and efficient treatment in colon cancer to improve patients survival is still under investigation. Chemotherapeutic agent result in high systemic toxicity due to their non-specific actions on DNA repair and/or cell replication. Traditional medicine such as Lycopodium clavatum (LC) has been claimed to have therapeutic potentials against cancer. The present study focuses on targeted drug delivery of cationic liposomal nanoformulated LC (CL-LC) in colon cancer cells (HCT15) and comparing the efficacy with an anti-colon cancer drug, 7-ethyl-10-hydroxy-camptothecin (SN38) along with its nanoformulated form (CL-SN38). The colloidal suspension of LC was made using thin film hydration method. The drugs were characterised using ultraviolet, dynamic light scattering, scanning electron microscopy, energy, dispersive X-ray spectroscopy. Invitro drug release showed kinetics of 49 and 89% of SN38 and LC, whereas CL-SN38 and CL-LC showed 73 and 74% of sustained drug release, respectively. Studies on morphological changes, cell viability, cytotoxicity, apoptosis, cancer-associated gene expression analysis of Bcl-2, Bax, p53 by real-time polymerase chain reaction and western blot analysis of Bad and p53 protein were performed. Nanoformulated LC significantly inhibited growth and increased the apoptosis of colon cancer cells indicating its potential anti-cancer activity against colon cancer cells.

  • 132.
    Pathak, Surajit
    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. CARE, India.
    Banerjee, Antara
    CARE, India.
    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. Department of Gastrointestinal Surgery , West China Hospital, Sichuan University , Chengdu , China.
    Nandy, Suman Kumar
    Univ Kalyani, India; North Eastern Hill Univ, India.
    Gopinath, Madhumala
    CARE, India.
    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.
    Significant expression of tafazzin (TAZ) protein in colon cancer cells and its downregulation by radiation2018Inngår i: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 94, nr 1, s. 79-87Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: To demonstrate the radiation responses of tafazzin (TAZ) protein in colon cancer. Methods: TAZ expression was examined in colon cancer cell lines SW480, KM12C, SW620 and KM12L4a. KM12C and KM12L4a cell lines were used for this experiment with exposure to X- and UV rays (mW/cm(2)). HCT15 cell line was used to test the expression of TAZ by using an anti-TAZ drug, namely 9-fluorenone, which is a Hippo-YAP/TAZ signaling inhibitor. The experimentation also involved exposing HCT15 cell line, to UV radiation. Cell proliferation and apoptosis studies were carried out. TAZ interactions with oncoproteins were screened and the oncoproteins Livin, MAC30 and FXYD-3 were considered for in silico protein-protein interaction studies. Results: TAZ protein was significantly downregulated after 2Gy radiations. 9-Fluorenone inhibited the expression of TAZ. Action of 9-fluorenone along with radiation, decreased the percentage of proliferation and increased apoptosis. Computational studies predicted that TAZ interacts with the oncoproteins Livin, MAC30 and FXYD-3. Conclusions: Our results suggest that TAZ plays a significant role in non-metastatic KM12C cells and is predominantly seen in the colon cancer cells isolated from primary stages of cancer. Thus, use of TAZ protein as a biomarker will be an efficient way to detect tumors in the early stages and treatment may be modulated with radiation before surgery/therapy.

  • 133.
    Pathak, Surajit
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Meng, Wen-Jian
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Sichuan University, Peoples R China.
    Kumar Nandy, Suman
    University of Kalyani, India.
    Ping, Jie
    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.
    Bisgin, Atil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Helmfors, Linda
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Waldmann, Patrik
    Linköpings universitet, Institutionen för datavetenskap, Statistik. Linköpings universitet, Filosofiska 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.
    Radiation and SN38 treatments modulate the expression of microRNAs, cytokines and chemokines in colon cancer cells in a p53-directed manner2015Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, nr 42, s. 44758-44780Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aberrant expression of miRNAs, cytokines and chemokines are involved in pathogenesis of colon cancer. However, the expression of p53 mediated miRNAs, cyto- and chemokines after radiation and SN38 treatment in colon cancer remains elusive. Here, human colon cancer cells, HCT116 with wild-type, heterozygous and a functionally null p53, were treated by radiation and SN38. The expression of 384 miRNAs was determined by using the TaqMan (R) miRNA array, and the expression of cyto- and chemokines was analyzed by Meso-Scale-Discovery instrument. Up- or down-regulations of miRNAs after radiation and SN38 treatments were largely dependent on p53 status of the cells. Cytokines, IL-6, TNF-alpha, IL-1 beta, Il-4, IL-10, VEGF, and chemokines, IL-8, MIP-1 alpha were increased, and IFN-gamma expression was decreased after radiation, whereas, IL-6, IFN-gamma, TNF-alpha, IL-1 beta, Il-4, IL-10, IL-8 were decreased, and VEGF and MIP-1 alpha were increased after SN38 treatment. Bioinformatic analysis pointed out that the highly up-regulated miRNAs, let-7f-5p, miR-455-3p, miR-98, miR-155-5p and the down-regulated miRNAs, miR-1, miR-127-5p, miR-142-5p, miR-202-5p were associated with colon cancer pathways and correlated with cyto- or chemokine expression. These miRNAs have the potential for use in colon cancer therapy as they are related to p53, pro- or anti-inflammatory cyto- or chemokines after the radiation and SN38 treatment.

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  • 134.
    Pathak, Surajit
    et al.
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    S, Sushmitha
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Banerjee, Antara
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Marotta, Francesco
    ReGenera Research Group for Aging-Intervention, Milano, Italy and San Babila Clinic, Healthy Aging Unit by Genomics and Biotechnology, Milano, Italy.
    Gopinath, Madhumala
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Murugesan, Ramachandran
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Zhang, Hong
    School of Medicine, Orebro University, Örebro, Sweden.
    B, Bhavani
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Girigoswami, Agnishwar
    Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India.
    Sollano, Jose
    Gastroenterology Department, University of Santo Tomas, Manila, The Philippines.
    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.
    Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients2018Inngår i: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, nr 7, s. 7739-7748Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS. Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS, validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.

    Fulltekst (pdf)
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  • 135.
    Paulsson, Janna
    et al.
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Rydén, Lisa
    Division of Surgery, Department of Clinical Sciences Lund UniversityLundSweden; Department of Surgery Skåne University Hospital Lund, Sweden.
    Strell, Carina
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Frings, Oliver
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Tobin, Nicholas P
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Fornander, Tommy
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    Bergh, Jonas
    Department of Oncology-PathologyCancer Center Karolinska, Karolinska InstitutetStockholmSweden; Radiumhemmet, Karolinska University Hospital Stockholm, Sweden.
    Landberg, Göran
    Department of Pathology Sahlgrenska Cancer Centre, University of Gothenburg 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.
    Östman, Arne
    Department of Oncology-Pathology Cancer Center Karolinska, Karolinska Institutet Stockholm, Sweden.
    High expression of stromal PDGFRß is associated with reduced benefit of tamoxifen in breast cancer2017Inngår i: The journal of pathology. Clinical research, ISSN 2056-4538, Vol. 3, nr 1, s. 38-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cancer-associated fibroblasts (CAFs) regulate tumour growth, metastasis and response to treatment. Recent studies indicate the existence of functionally distinct CAF subsets. Suggested mechanisms whereby CAFs can impact on treatment response include paracrine signalling affecting cancer cell drug sensitivity and effects on tumour drug uptake. PDGFRß is an important regulator of fibroblasts. Experimental studies have linked PDGFRß-positive fibroblasts to metastasis and also to reduced tumour drug uptake. This study has investigated the potential role of PDGFRß-positive fibroblasts in response to adjuvant tamoxifen treatment of breast cancer. Analyses of two breast cancer collections from randomised studies analysing adjuvant tamoxifen treatment in early breast cancer demonstrated significant benefit of tamoxifen in the group with low stromal PDGFRß, which was not observed in the group with high stromal PDGFRß. In general terms these findings provide novel evidence, derived from analyses of randomised clinical studies, of response-predictive capacity of a marker-defined subset of CAFs and, more specifically, identify stromal PDGFRß as a marker related to tamoxifen benefit in early breast cancer.

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    fulltext
  • 136.
    Pham, Tuan
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Prince Mohammad Bin Fahd Univ, Saudi Arabia.
    Fan, Chuanwen
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Sichuan Univ, Peoples R China.
    Pfeifer, Daniella
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten.
    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.
    Image-Based Network Analysis of DNp73 Expression by Immunohistochemistry in Rectal Cancer Patients2020Inngår i: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 10, artikkel-id 1551Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Rectal cancer is a disease characterized with tumor heterogeneity. The combination of surgery, radiotherapy, and chemotherapy can reduce the risk of local recurrence. However, there is a significant difference in the response to radiotherapy among rectal cancer patients even they have the same tumor stage. Despite rapid advances in knowledge of cellular functions affecting radiosensitivity, there is still a lack of predictive factors for local recurrence and normal tissue damage. The tumor protein DNp73 is thought as a biomarker in colorectal cancer, but its clinical significance is still not sufficiently investigated, mainly due to the limitation of human-based pathology analysis. In this study, we investigated the predictive value of DNp73 in patients with rectal adenocarcinoma using image-based network analysis.

    Methods: The fuzzy weighted recurrence network of time series was extended to handle multi-channel image data, and applied to the analysis of immunohistochemistry images of DNp73 expression obtained from a cohort of 25 rectal cancer patients who underwent radiotherapy before surgery. Two mathematical weighted network properties, which are the clustering coefficient and characteristic path length, were computed for the image-based networks of the primary tumor (obtained after operation) and biopsy (obtained before operation) of each cancer patient.

    Results: The ratios of two weighted recurrence network properties of the primary tumors to biopsies reveal the correlation of DNp73 expression and long survival time, and discover the non-effective radiotherapy to a cohort of rectal cancer patients who had short survival time.

    Conclusion: Our work contributes to the elucidation of the predictive value of DNp73 expression in rectal cancer patients who were given preoperative radiotherapy. Mathematical properties of fuzzy weighted recurrence networks of immunohistochemistry images are not only able to show the predictive factor of DNp73 expression in the patients, but also reveal the identification of non-effective application of radiotherapy to those who had poor overall survival outcome.

    Fulltekst (pdf)
    fulltext
  • 137.
    Pihl Lesnovska, Katarina
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    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.
    Hollman Frisman, Gunilla
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Hjortswang, Henrik
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap.
    Wenemark, Marika
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Verksamhetsutveckling vård och hälsa.
    The quality of care questionnaire: development of a valid measure for persons with inflammatory bowel disease2018Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, nr 9, s. 1043-1050Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and aims: Quality of care is important in lifelong illnesses such as inflammatory bowel disease (IBD). Valid, reliable and short questionnaires to measure quality of care among persons with IBD are needed. The aim of this study was to develop a patient-derived questionnaire measuring quality of care in persons with IBD.Methods and results: The development of the questionnaire The Quality of Care -Questionnaire (QoC-Q) was based on a literature review of studies measuring quality of care, and the results of two qualitative studies aiming to identify the knowledge need and perception of health care among persons with IBD. Further development and evaluation was done by focus groups, individual testing and cognitive interviews with persons with IBD, as well as evaluation by a group of professionals. After the development, the questionnaire was tested for validity and test-retest reliability in 294 persons with IBD.Conclusions: The QoC-Q is showing promising validity and reliability for measuring the subjective perception of quality of care. Further testing in clinical practice is suggested to assess if the QoC-Q can be used to evaluate care and areas of improvement in health care for persons living with IBD.

    Fulltekst (pdf)
    fulltext
  • 138.
    Pihl Lesnovska, Katarina
    et al.
    Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad.
    Hollman Frisman, Gunilla
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Anestesi- och intensivvårdskliniken VIN.
    Hjortswang, Henrik
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    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.
    Critical situations in daily life as experienced by patients with inflammatory bowel disease2016Inngår i: Gastroenterology Nursing, ISSN 1042-895X, Vol. 39, nr 3, s. 195-203Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Crohn disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), are chronic and have a fluctuating clinical course that impacts daily life. Daily life with a chronic disease involves thinking and worrying about the limitations that chronic disease causes. Knowledge about how patients who suffer from IBD manage critical incidents in daily life is lacking. The aim of the study was to describe how patients living with IBD experience critical incidents in daily life in relation to their disease and symptoms. Thirty adult patients were interviewed focusing on critical incidents in daily life. Data were analyzed using the critical incident technique. The study comprised 224 critical incidents and was grouped into 21 subcategories and 5 categories: losing bowel control, having a body that smells, being unable to meet own and others' expectations, not being believed or seen, and experiencing frustration due to side effects and ineffective treatment. These categories formed one main area describing the overall result "The bowels rule life." The uncertain nature of IBD created critical incidents in which the bowel ruled life, causing patients to avoid social interaction. It also placed considerable demands on the family and sometimes had a negative effect on the afflicted person's career.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

    Fulltekst (pdf)
    fulltext
  • 139.
    Pihl Lesnovska, Katarina
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Hollman Frisman, Gunilla
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken.
    Hjortswang, Henrik
    Region Östergötland, Hjärt- och Medicincentrum, Magtarmmedicinska kliniken. Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Hjelm, Katarina
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    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.
    Healthcare as perceived by persons with inflammatory bowel disease – a focus group study2017Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, Vol. 26, nr 21-22, s. 3677-3687Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The quality of care plays an important role in the life of persons with a chronic disease. In order to define what persons with inflammatory bowel disease perceive as high quality care, greater focus must be placed on the individual’s own perspective of living with the condition. Design: A qualitative exploratory study was conducted based on focus groups. Methods: Five focus groups were conducted with adult persons living with inflammatory bowel disease, fourteen men and twelve women aged 19-76 years. The interviews were performed between January and June 2014. Results: The perceptions of healthcare from the perspective of persons living with inflammatory bowel disease were summarized in two categories: “Professional attitudes of healthcare staff” and “Structure of the healthcare organization”. Persons with Inflammatory bowel disease want to be encountered with respect, experience trust and obtain information at the right time. They also expect shared decision-making, communication and to encounter competent healthcare professionals. Furthermore, the expectations on and perceptions of the structure of the healthcare organization comprises access to care, accommodation, continuity of care, as well as the pros and cons of specialized care. Conclusion: The findings show the importance of establishing a respectful and trusting relationship, facilitating healthcare staff and persons with inflammatory bowel disease to work as a team in fulfilling individual care needs – but there is room for improvement in terms of quality of care. Relevance to clinical practice: A person-centred approach, which place the individual and her/his family at the centre, considering them experts on their own health and enabling them to collaborate with healthcare staff, seems important to reach a high quality healthcare organization for patients with IBD.

    Fulltekst (pdf)
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  • 140.
    Ray-Coquard, I.
    et al.
    GINECO and Medical Oncology Department, Centre Léon Bérard, University Claude Bernard Lyon, Lyon, France.
    Cibula, D.
    AGO and Oncogynecologic Center, Department of Obstetrics and Gynecology, General Faculty Hospital, Charles University of Prague, Prague, Czech Republic.
    Mirza, M.R.
    NSGO and Department of Oncology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.
    Reuss, A.
    AGO and Coordinating Center for Clinical Trials, Philipps-University of Marburg, Marburg, Germany.
    Ricci, C.
    MITO and Division of Gynecologic Oncology, Department of Women and Childrens Health and Public Health, Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
    Colombo, N.
    MaNGO and European Institute of Oncology and University of Milan Bicocca, Milan, Italy.
    Koch, H.
    AGO Austria and Department of Obstetrics and Gynecology, Paracelsus Medical University, Salzburg, Austria.
    Goffin, F.
    BGOG and CHU de Liège, University of Liège, Liège, Belgium.
    González-Martin, A.
    GEICO and Medical Oncology Department, Clínica Universidad de Navarra, Madrid, Spain.
    Ottevanger, P.B.
    DGOG and Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, Netherlands.
    Baumann, K.
    AGO and Department of Gynecology, Klinikum der Stadt Ludwigshafen GmbH, Ludwigshafen, Germany.
    Bjørge, L.
    NSGO and Department of Gynecology, Haukeland Universitetssykehus, Bergen, Norway; Center for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
    Lesoin, A.
    GINECO and Department of Gynecologic Cancer and Medical Oncology, Centre Oscar Lambret, Lille, France.
    Burges, A.
    AGO and Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Germany.
    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.
    Gropp-Meier, M.
    AGO and Department of Gynecology and Obstetrics, Oberschwabenklinik, Krankenhaus St. Elisabeth, Ravensburg, Germany.
    Harrela, M.
    NSGO and Department of Gynoncology and Gynecology and Obstetrics, Kymenlaakso Central Hospital, Kotka, Finland.
    Harter, P.
    AGO and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
    Frenel, J.-S.
    GINECO and Centre René Gauducheau, Institut de Cancerologie de lOuest, Saint Herblain, France.
    Minarik, T.
    NSGO and National Institute of Oncology, Bratislava, Slovakia.
    Pisano, C.
    MITO and Department of Uro-Gynecologic Oncology, Istituto Nazionale per Io Studio e la Cura dei Tumori ‘Fondazione G. Pascale’ IRCCS, Naples, Italy.
    Hasenburg, A.
    AGO and Department of Obstetrics and Gynecology, University Medical Center, Mainz, Germany.
    Merger, M.
    Oncology Medicine, Boehringer Ingelheim International GmbH, Biberach, Germany.
    du, Bois A.
    AGO and Department of Gynecology and Gynecologic Oncology, Kliniken Essen Mitte, Essen, Germany.
    Final results from GCIG/ENGOT/AGO-OVAR 12, a randomised placebo-controlled phase III trial of nintedanib combined with chemotherapy for newly diagnosed advanced ovarian cancer2020Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 146, nr 2, s. 439-448Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AGO-OVAR 12 investigated the effect of adding the oral triple angiokinase inhibitor nintedanib to standard front-line chemotherapy for advanced ovarian cancer. At the primary analysis, nintedanib demonstrated significantly improved progression-free survival (PFS; primary endpoint) compared with placebo. We report final results, including overall survival (OS). Patients with primary debulked International Federation of Gynaecology and Obstetrics (FIGO) stage IIB–IV newly diagnosed ovarian cancer were randomised 2:1 to receive carboplatin (area under the curve 5 or 6) plus paclitaxel (175 mg/m2) on day 1 every 3 weeks for six cycles combined with either nintedanib 200 mg or placebo twice daily on days 2–21 every 3 weeks for up to 120 weeks. Between December 2009 and July 2011, 1,366 patients were randomised (911 to nintedanib, 455 to placebo). Disease was considered as high risk (FIGO stage III with amp;gt;1 cm residuum, or any stage IV) in 39%. At the final analysis, 605 patients (44%) had died. There was no difference in OS (hazard ratio 0.99, 95% confidence interval [CI] 0.83–1.17, p = 0.86; median 62.0 months with nintedanib vs. 62.8 months with placebo). Subgroup analyses according to stratification factors, clinical characteristics and risk status showed no OS difference between treatments. The previously reported PFS improvement seen with nintedanib did not translate into an OS benefit in the nonhigh-risk subgroup. Updated PFS results were consistent with the primary analysis (hazard ratio 0.86, 95% CI 0.75–0.98; p = 0.029) favouring nintedanib. The safety profile was consistent with previous reports. © 2019 UICC

  • 141.
    Roncolato, Felicia T
    et al.
    NHMRC Clinical Trials Centre, University of Sydney, Australia; Macarthur Cancer Therapy Centre, NSW, Australia; Australia New Zealand Gynaecological Oncology Group (ANZGOG), Australia.
    Berton-Rigaud, Dominique
    ICO Centre René Gauducheau, Saint Herblain, France.
    O'Connell, Rachel
    NHMRC Clinical Trials Centre, University of Sydney, Australia.
    Lanceley, Anne
    University College London, United Kingdom.
    Sehouli, Jalid
    Charite Berlin, Germany.
    Buizen, Luke
    NHMRC Clinical Trials Centre, University of Sydney, Australia.
    Okamoto, Aikou
    Jikei University School of Medicine, Japan.
    Aotani, Eriko
    Kitasato Academic Research Organization, Japan.
    Lorusso, Domenica
    MITO, Rome, Italy.
    Donnellan, Paul
    Galway University Hospital, Ireland; All-Ireland Oncology Research Group (ICORG), Ireland.
    Oza, Amit
    Princess Margaret Hospital, Canada.
    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. Karolinska Institutet, Stockholm, Sweden.
    Berek, Jonathan
    Stanford Women's Cancer Center, USA.
    Hilpert, Felix
    Klinik fur Gynakologie und Geburtshilfe, UKSH, Germany.
    Ledermann, Jonathan A
    CRUK and UCL Cancer Trials Centre, NCRI UK, United Kingdom.
    Kaminsky, Marie Christine
    ICL Institut de Cancérologie de Lorraine, Vandoeuvre-Les-Nancy, France.
    Stockler, Martin R
    NHMRC Clinical Trials Centre, University of Sydney, Australia.
    King, Madeleine T
    Psycho-oncology Research Group (PoCoG), School of Psychology, Central Clinical School, Sydney Medical School, University of Sydney, Australia.
    Friedlander, Michael
    Australia New Zealand Gynaecological Oncology Group (ANZGOG), Australia; Prince of Wales Hospital, Sydney, Australia.
    Validation of the modified Glasgow Prognostic Score (mGPS) in recurrent ovarian cancer (ROC): Analysis of patients enrolled in the GCIG Symptom Benefit Study (SBS)2018Inngår i: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 148, nr 1, s. 36-41, artikkel-id S0090-8258(17)31422-1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Modified Glasgow Prognostic Score (mGPS) is predictive of survival in many advanced cancers, but has not been evaluated in recurrent ovarian cancer (ROC). The aim was to determine validity of mGPS in ROC, investigate its associations with health related quality of life (HRQL) and ECOG performance status (PS).

    METHODS: mGPS is based on serum C reactive protein (CRP) and albumin, with scores ranging from 0 (least) to 2 (most). HRQL was measured with EORTC QLQ C-30 and OV-28. χ2 tests for trend were used to examine the relationship between HRQL, PS and mGPS. Cox proportional hazards regression was used to assess associations between mGPS, HRQL, clinicopathological factors, and overall survival (OS).

    RESULTS: Inflammatory markers were available in 516 of 948 patients in GCIG SBS. 200(39%) had potentially platinum sensitive ROC with ≥3 lines of chemotherapy, 316(61%) had platinum resistant ROC. 282(55%), 123(24%), 111(22%) had mGPS of 0, 1, 2, respectively. Median OS (months) was 18.1, 9.6, and 6.6 for mGPS 0, 1, and 2 respectively. mGPS was an independent predictor of OS after adjusting for PS and platinum sensitivity (p<0.001). mGPS remained a predictor of OS after adjusting for physical function, role function, global health status, abdominal/GI symptoms, and multiple clinicopathologic factors (p=0.02). Worse PS and higher mGPS were associated with poorer HRQL (p<0.001). Higher mGPS was associated with worse HRQL, independent of PS.

    CONCLUSION: The mGPS is an independent predictor of OS in ROC after adjusting for HRQL and clinicopathological factors. Higher mGPS is associated with worse HRQL independent of PS. mGPS is simple, inexpensive and may be suitable for clinical practice, clinical trial patient selection and stratification.

  • 142.
    Roncolato, Felicia T.
    et al.
    University of Sydney, Australia; ANZGOG, Australia; Macarthur Cancer Therapy Centre, Australia.
    Joly, Florence
    Centre Francois Baclesse, France.
    OConnell, Rachel
    University of Sydney, Australia.
    Lanceley, Anne
    UCL, England.
    Hilpert, Felix
    UKSH, Germany.
    Buizen, Luke
    University of Sydney, Australia.
    Okamoto, Aikou
    Jikei University, Japan.
    Aotani, Eriko
    Kitasato Academic Research Org, Japan.
    Pignata, Sandro
    IRCCS, Italy.
    Donnellan, Paul
    Galway University Hospital, Ireland.
    Oza, Amit
    University of Toronto, Canada.
    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. Karolinska Institute, Sweden.
    Berek, Jonathan S.
    Stanford Comprehens Cancer Institute, CA USA.
    Heitz, Florian
    KEM, Germany; KEM, Germany.
    Feeney, Amanda
    Cancer Research UK, England; UCL Cancer Trials Centre, England.
    Berton-Rigaud, Dominique
    ICO Centre Rene Gauducheau, France.
    Stockler, Martin R.
    University of Sydney, Australia; ANZGOG, Australia.
    King, Madeleine
    ANZGOG, Australia; University of Sydney, Australia.
    Friedlander, Michael
    ANZGOG, Australia; Prince Wales Hospital, Australia.
    Reducing Uncertainty: Predictors of Stopping Chemotherapy Early and Shortened Survival Time in Platinum Resistant/Refractory Ovarian Cancer-The GCIG Symptom Benefit Study2017Inngår i: The Oncologist, ISSN 1083-7159, E-ISSN 1549-490X, Vol. 22, nr 9, s. 1117-1124Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. Clinicians and patients often overestimate the benefits of chemotherapy, and overall survival (OS), in platinum resistant/refractory ovarian cancer (PRROC). This study sought to determine aspects of health-related quality of life and clinicopathological characteristics before starting chemotherapy that were associated with stopping chemotherapy early, shortened survival, and death within 30 days of chemotherapy. Materials and Methods. This study enrolled women with PRROC before starting palliative chemotherapy. Health-related quality of life was measured with EORTC QLQ-C30/QLQ-OV28. Chemotherapy stopped within 8 weeks of starting was defined as stopping early. Logistic regression was used to assess univariable and multivariable associations with stopping chemotherapy early and death within 30 days of chemotherapy; Cox proportional hazards regression was used to assess associations with progression-free and OS. Results. Low baseline global health status (GHS), role function (RF), physical function (PF), and high abdominal/gastrointestinal symptom (AGIS) were associated with stopping chemotherapy early (all pamp;lt;.007); low PF and RF remained significant after adjusting for clinicopathological factors (both pamp;lt;.0401). Most who stopped chemotherapy early had Eastern Cooperative Oncology Group Performance Score 0-1 at baseline (79%); PF, RF, and GHS remained independently significant predictors of stopping chemotherapy early in this subgroup. Death within 30 days of chemotherapy occurred in 14%. Low-GHS, RF, and PF remained significantly associated with death within 30 days of chemotherapy after adjusting for clinicopathological factors (all pamp;lt;.012). Conclusion. Women with low GHS, RF, or PF before starting chemotherapy were more likely to stop chemotherapy early, with short OS. Self-ratings of GHS, RF, and PF could improve patient-clinician communication regarding prognosis and help decision-making in women considering chemotherapy for PRROC.

  • 143.
    Rosell, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Regionalt Cancercentrum.
    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.
    Bengtsson, Nils-Olof
    Umeå University Hospital, Sweden.
    Fornander, Tommy
    Karolinska University Hospital, Sweden.
    Hatschek, Thomas
    Karolinska University Hospital, Sweden.
    Lindman, Henrik
    Uppsala University Hospital, Sweden.
    Malmstrom, Per-Olof
    Skåne University Hospital, Sweden.
    Wallgren, Arne
    Sahlgrens University Hospital, 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.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Long-term effects on the incidence of second primary cancers in a randomized trial of two and five years of adjuvant tamoxifen2017Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, nr 4, s. 614-617Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Tamoxifen is a well established treatment for breast cancer, but its long-term effects on the incidence of secondary cancers are not fully evaluated.Material and methods: We have studied 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after two years of tamoxifen, and who were randomized to receive totally two or five years of therapy.Results: Compared to patients randomized to two years of tamoxifen the incidence of contralateral breast cancer [hazard ratio (HR) 0.73; 95% CI 0.56-0.96] and of lung cancer (HR 0.45; 95% CI 0.27-0.77), especially squamous cell and small cell lung cancer, were reduced in the five-year group, and similar results were seen when restricting the analysis to the 10-year period after treatment stopped. An increased incidence of endometrial cancer was observed in the five-year group, but the excess risk decreased over time.Conclusion: Further studies of the effects of tamoxifen on the risk of different histological types of lung cancer are needed.

  • 144.
    Rosenberg, Per
    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.
    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.
    Staf, Christian
    Reg Canc Ctr, Sweden; Sahlgrens Univ Hosp, Sweden.
    Bjurberg, Maria
    Skane Univ Hosp, Sweden.
    Borgfeldt, Christer
    Lund Univ, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Hellman, Kristina
    Karolinska Inst, Sweden.
    Hjerpe, Elisabet
    Karolinska Inst, Sweden.
    Holmberg, Erik
    Reg Canc Ctr, Sweden; Sahlgrens Univ Hosp, Sweden; Univ Gothenburg, Sweden.
    Stalberg, Karin
    Uppsala Univ, Sweden.
    Tholander, Bengt
    Uppsala Univ, 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.
    Hogberg, Thomas
    Lund Univ, Sweden.
    Data quality in the Swedish Quality Register of Gynecologic Cancer - a Swedish Gynecologic Cancer Group (SweGCG) study2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 3, s. 346-353Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: The aim of this study is to evaluate the quality of data on endometrial (EC) and ovarian, fallopian tube, peritoneal, abdominal or pelvic cancers (OC) registered in the Swedish Quality Register of Gynecologic Cancer (SQRGC).Method: A random sample of 500 patients was identified in the SQRGC and their medical charts were reviewed for re-abstraction of 31 selected core variables by an independent validator. The data in the SQRGC and the re-abstracted data were compared. The data were collected from 25 hospitals evenly distributed throughout Sweden. The main outcomes were comparability, timeliness, completeness and validity. Coverage was compared with the National Cancer Register (NCR). Timeliness was defined as the speed of registration i.e. when patients were registered in the SQRGC relative to date of diagnosis. Internationally accepted coding systems for stage, grading and histologic type were used ensuring a high degree of comparability. Correlations were estimated using Pearsons correlation coefficient and Cohens kappa coefficient.Results: The completeness was 95%. The timeliness was 88-91% within 12 months of diagnosis. The median degree of agreement between re-abstracted data and data in the SQRGC was 82.1%, with a median kappa value of 0.73 for ordinate variables and a median Pearsons correlation coefficient of 0.96. The agreements for the type of surgery were 76% (95% CI 70-81%; kappa 0.49) and type of primary treatment 90% (95% CI 87-94%; kappa 0.85) in OC and in EC 88% (95% CI 84-93%; kappa 0.84). The agreements for the FIGO stage were in OC and EC 74% (95% CI 68-80%; kappa 0.69) and 87% (95% CI 82-91%; kappa 0.79), respectively.Conclusions: The data in the Swedish Quality Register for Gynecologic Cancer are of adequate quality in order to be used as a basis for research and to evaluate possible differences in treatment, lead times and treatment results.

  • 145.
    Salehi, Sahar
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Brandberg, Yvonne
    Karolinska Inst, 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.
    Suzuki, Chikako
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Johansson, Hemming
    Karolinska Inst, Sweden.
    Legerstam, Berit
    Karolinska Inst, Sweden.
    Falconer, Henrik
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Long-term quality of life after comprehensive surgical staging of high-risk endometrial cancer - results from the RASHEC trial2018Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, nr 12, s. 1671-1676Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: The health-related quality of life (HRQoL) outcomes after comprehensive surgical staging including infrarenal paraaortic lymphadenectomy in women with high-risk endometrial cancer (EC) are unknown. Our aim was to investigate the long-term HRQoL between robot-assisted laparoscopic surgery (RALS) and laparotomy (LT). Patients and Methods: A total of 120 women with high-risk stage I-II EC were randomised to RALS or LT for hysterectomy, bilateral salpingoophorectomy, pelvic and infrarenal paraaortic lymphadenectomy in the previously reported Robot-Assisted Surgery for High-Risk Endometrial Cancer trial. The HRQoL was measured with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-30) and its supplementary questionnaire module for endometrial cancer (QLQ-EN24) questionnaire. Women were assessed before and 12 months after surgery. In addition, the EuroQol Eq5D non-disease specific questionnaire was used for descriptive analysis. Results: There was no difference in the functional scales (including global health status) in the intention to treat analysis, though LT conferred a small clinically important difference (CID) over RALS in cognitive functioning albeit not statistically significant -6 (95% CI-14 to 0, p = .06). LT conferred a significantly better outcome for the nausea and vomiting item though it did not reach a CID, 4 (95% CI 1 to 7, p = .01). In the EORTC-QLQ/QLQ-EN24, no significant differences were observed. Eq5D-3L questionnaire demonstrated a higher proportion of women reporting any extent of mobility impairment 12 months after surgery in the LT arm (p = .03). Conclusion: Overall, laparotomy and robot-assisted surgery conferred similar HRQoL 12 months after comprehensive staging for high-risk EC.

  • 146.
    Salehi, Sahar
    et al.
    Karolinska Inst, Sweden; 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.
    Brandberg, Yvonne
    Karolinska Inst, Sweden.
    Johansson, Hemming
    Karolinska Inst, Sweden.
    Suzuki, Chikako
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Falconer, Henrik
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Lymphedema, serious adverse events, and imaging 1 year after comprehensive staging for endometrial cancer: results from the RASHEC trial2019Inngår i: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, nr 1, s. 86-93Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Objectives In the Robot Assisted Surgery for High Risk Endometrial Cancer (RASHEC) trial, patients with high-risk endometrial cancer were randomly assigned to robot-assisted laparoscopic surgery (RALS) or laparotomy for pelvic and infrarenal para-aortic lymph node dissection. We here report on self-reported lower limb lymphedema (LLL), lymphocyst formation, ascites, and long-term serious adverse events 12 months after surgery. Patients and methods Patients were enrolled between 2013 and 2016, and 96 patients were included in the per protocol analysis, evenly distributed between RALS and laparotomy. Self-reported LLL was recorded using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for endometrial cancerEN24, assessed before and 12 months after surgery. Computed tomography was assessed at baseline, 3, and 12 months. Medical charts were reviewed for serious adverse events and hospital admissions 31 to 365 days after surgery. Results At 12 months after laparotomy and RALS, 61% and 50% patients, respectively, reported LLL (p = 0.31). In univariate analysis, the mean score of LLL at 12 months was significantly higher for laparotomy than for RALS (p amp;lt; 0.05) and for those without abdominal drainage (p = 0.02), but was not independently associated with LLL in the multivariate analysis. Imaging showed no significant difference in lymphocyst formation or ascites between surgical modalities. No difference was found in serious adverse events and admissions to hospital for any reason. There was no agreement between lymphocyst formation or ascites and self-reported LLL. Conclusion Follow-up 1 year after comprehensive surgical staging for high-risk endometrial cancer showed no differences in self-reported LLL, findings on imaging, or SAE between laparotomy and robot-assisted surgery.

  • 147.
    Salehi, Sahar
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, 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. Karolinska Institute, Sweden.
    Legerstam, Berit
    Karolinska University Hospital, Sweden.
    Carlson, Joseph W.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Falconer, Henrik
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Robot-assisted laparoscopy versus laparotomy for infrarenal paraaortic lymphadenectomy in women with high-risk endometrial cancer: A randomised controlled trial2017Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 79, s. 81-89Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To investigate if robot-assisted laparoscopic surgery (RALS) was non-inferior to laparotomy (LT) in harvesting infrarenal paraaortic lymph nodes in patients with presumed stage IeII high-risk endometrial cancer. Patients and methods: Patients with histologically proven endometrial cancer, presumed stage IeII with high-risk tumour features, were randomised to hysterectomy, bilateral salpingo-oophorectomy, pelvic and paraaortic lymphadenectomy by either RALS or LT. Primary outcome was paraaortic lymph node count. Secondary outcomes were perioperative events, postoperative complications and total health care cost. Results: Overall 120 patients were randomised and 96 patients were included in the per protocol analysis. Demographic, clinical and tumour characteristics were evenly distributed between groups. Mean (+/- SD) paraaortic lymph node count was 20.9 (+/- 9.6) for RALS and 22 (+/- 11, p = 0.45) for LT. The difference of means was within the non-inferiority margin (-1.6, 95% CI -5.78, 2.57). Mean pelvic node count was lower after RALS (28 +/- 10 versus 22 +/- 8, p amp;lt; 0.001). There was no difference in perioperative complications or readmissions between the groups. Operation time was longer (p amp;lt; 0.001) but total blood loss less (amp;lt;0.001) and hospital stay shorter (amp;lt;0.001) in RALS group than LT group. Health care costs for RALS was significantly lower (mean difference $1568 USD/(sic)1225 Euro, p amp;lt; 0.05). Conclusion: Our results demonstrate non-inferiority in paraaortic lymph node count, comparable complication rates, shorter hospital length and lower total cost for RALS over laparotomy. Generalisability of the latter finding requires a high-volume setting and high surgical proficiency. In women with high-risk endometrial cancer confined to the uterus, RALS is a valid treatment modality. Clinical trials registrations: ClinicalTrials.gov NCT01847703. (C) 2017 Elsevier Ltd. All rights reserved.

  • 148.
    Schroeder, Brock
    et al.
    Biotheranostics, Inc., San Diego, CA USA.
    Zhang, Yi
    Biotheranostics, Inc., San Diego, CA 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.
    Fornander, Tommy
    Karolinska Institute, Stockholm, Sweden.
    Brufsky, Adam
    University of Pittsburgh School of Medicine, Pittsburgh, PA USA.
    Sgroi, Dennis C
    Massachusetts General Hospital, Boston, MA USA.
    Schnabel, Catherine A.
    Biotheranostics, Inc., San Diego, CA USA.
    Risk stratification with Breast Cancer Index for late distant recurrence in patients with clinically low-risk (T1N0) estrogen receptor-positive breast cancer2017Inngår i: NPJ breast cancer, ISSN 2374-4677, Vol. 3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Patients with early-stage, hormone receptor-positive breast cancer with favorable clinicopathologic features are often not recommended for extended endocrine therapy. However, even patients with T1N0 disease remain at significant risk of distant recurrence up to 15 years following 5 years of endocrine therapy, highlighting the need for further stratification based on individualized risk to select patients for extended endocrine therapy. In this study, the incremental utility of genomic classification to stratify clinically low-risk patients for late distant recurrence was evaluated using the Breast Cancer Index. In 547 T1N0 patients from two cohorts that were disease-free at 5 years post-diagnosis, Breast Cancer Index categorized 32 and 36% from each cohort, respectively, with high risk of late distant recurrence that was associated with significantly reduced distant recurrence-free survival (86.7 and 89.6%) between years 5-15 and 5-10 compared to Breast Cancer Index low risk (95.4%; P?=?0.0263 and 98.4%; P?=?0.008). Findings support consideration of genomic classification in clinically low-risk hormone receptor-positive patients to identify candidates for extended endocrine therapy.

    Fulltekst (pdf)
    fulltext
  • 149.
    Seoud, Muhieddine
    et al.
    Amer University of Beirut, Lebanon.
    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.
    Fujiwara, Keiichi
    Saitama Medical University, Japan.
    Targeted therapy in gynecologic cancers: Ready for prime time?2015Inngår i: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 131, s. S150-S152Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    n/a

  • 150.
    Skoglund, Karin
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Richter, Johan
    Skåne University Hospital, Sweden.
    Olsson-Stromberg, Ulla
    Uppsala University, Sweden.
    Bergquist, Jonas
    Uppsala University, Sweden.
    Aluthgedara, Warunika
    Uppsala University, Sweden.
    Ubhayasekera, S. J. Kumari A.
    Uppsala University, Sweden.
    Vikingsson, Svante
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Svedberg, Anna
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Söderlund, Stina
    Uppsala University, Sweden.
    Sandstedt, Anna
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Johnsson, Anders
    Region Östergötland, Närsjukvården i västra Östergötland, Medicinska specialistkliniken.
    Aagesen, Jesper
    Ryhov County Hospital, Sweden.
    Alsenhed, Jonas
    Vastervik Hosp, Dept Internal Med, Västervik, Sweden.
    Hägg, Staffan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Lotfi, Kourosh
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Hematologiska kliniken US.
    Green, Henrik
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden.
    In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia2016Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 38, nr 2, s. 230-238Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Cytochrome P450 3A (CYP3A) isoenzyme metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML). The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in patients with CML. Methods: Forty-three patients with CML were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. Results: Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to nonoptimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P = 0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. Conclusions: The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.

    Fulltekst (pdf)
    fulltext
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