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Bojmar, Linda
Publications (10 of 12) Show all publications
Kuninty, P. R., Bojmar, L., Tjomsland, V., Larsson, M., Storm, G., Östman, A., . . . Prakash, J. (2016). MicroRNA-199a and -214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor. OncoTarget, 7(13), 16396-16408
Open this publication in new window or tab >>MicroRNA-199a and -214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor
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2016 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 13, p. 16396-16408Article in journal (Refereed) Published
Abstract [en]

Pancreatic stellate cells (PSCs) are the key precursor cells for cancer-associated fibroblasts (CAFs) in pancreatic tumor stroma. Although depletion of tumor stroma is debatable, attenuation of PSC activity is still an interesting strategy to treat pancreatic cancer. In this study, we explored miRNA as therapeutic targets in tumor stroma and found miR-199a-3p and miR-214-3p induced in patient-derived pancreatic CAFs as well as in TGF-β-activated human PSCs (hPSCs). Inhibition of miR-199a or miR-214 using their hairpin inhibitors in hPSCs significantly inhibited their TGFβ-induced differentiation (gene and protein levels of α-SMA, Collagen, PDGFβR), migration and proliferation. Furthermore, heterospheroids of Panc-1 and hPSCs were prepared, which attained smaller size when hPSCs were transfected with anti-miR-199a or -214 than those transfected with control anti-miR. The conditioned medium obtained from TGFβ-activated hPSCs induced tumor cell proliferation and endothelial cell tube formation, but these effects were abrogated when hPSCs were transfected with anti-miR-199a or miR-214. Moreover, IPA analyses revealed signaling pathways related to miR-199a (TP53, mTOR, Smad1) and miR-214 (PTEN, Bax, ING4). Taken together, this study reveals miR-199a-3p and miR-214-3p as major regulators of PSC activation and PSC-induced pro-tumoral effects, representing them as key therapeutic targets in PSCs in pancreatic cancer.

Place, publisher, year, edition, pages
Impact press, 2016
National Category
Cancer and Oncology Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-122828 (URN)10.18632/oncotarget.7651 (DOI)000375692900085 ()
Note

Funding agencies: Swedish Research Council, Stockholm, Sweden [K7/60501283]

Vid tiden för disputationen förelåg publikationen endast som manuskript

Available from: 2015-11-26 Created: 2015-11-26 Last updated: 2018-01-10
Bojmar, L. (2015). Metastatic Mechanisms in Malignant Tumors. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Metastatic Mechanisms in Malignant Tumors
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The ultimate cause of cancer related deaths is metastasis. This thesis is about three of the main human cancers; breast, colorectal and pancreatic cancer, that together account for more than 25% of the cancer-related deaths worldwide. The focus of the thesis is the spread of cancer, metastasis, and the aim was to investigate mechanisms that can be of importance for this process. We analyzed patient samples to validate the role of epithelialto-mesenchymal transition in vivo and found regulations of many related factors. However, these changes tend to fluctuate along the metastatic process, something which makes targeting complicated. We, moreover, focused on the influence of the tumor microenvironment for metastatic spread. In pancreatic cancer, the stroma constitutes the main part of many tumors. We analyzed the crosstalk between tumor and stromal cell and focused on the mediating inflammatory factor interleukin-1 (IL-1) and regulation of microRNAs. The results showed that the most commonly mutated factor in pancreatic cancer, KRAS, associates with the expression of IL-1 and subsequent activation of stromal cells. Blocking KRAS signaling together with IL-1 blockage give a more pronounced effect on in vitro proliferation and migration of cancer cells and suggests the use of a combination therapy. The cancer-associated activation of the stroma was found to be related to changes in microRNA expression. microRNA was analyzed separately in epithelial cells and stromal cells after microdissection of matched samples of primary and secondary tumors of breast and colorectal cancers. miR-214 and miR-199a were upregulated in stroma associated with progressive tumors and in pancreatic cancer stroma we could show that their expression alters the activation of stromal cells and thereby the growth and migratory ability of associated pancreatic tumor cells. In  breast and colorectal cancers we found several common microRNAs to be up- or downregulated in line with progression. We could show that one of these candidates, miR-18a, had a prognostic value in metastatic breast cancer. To further develop these studies we analyzed this microRNA in circulating microvesicles, i.e. exosomes, and investigated their role in the preparation of a pre-metastatic niche. MicroRNAs are stable biomarkers in the circulation, especially protected in exosomes, which can moreover specifically deliver their message to recipient cells. These studies facilitate the understanding of metastatic behavior and suggest new targets to stop cancer metastasis.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. p. 91
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1487
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-122830 (URN)978-91-7685-934-6 (ISBN)
Public defence
2015-12-18, Hasselqvistsalen, Ingång 76, Hus 511, Campus US, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Note

The ISBN 987-91-7685-934-6 in the printed version is incorrect. The correct ISBN is  978-91-7685-934-6.

Available from: 2015-11-26 Created: 2015-11-26 Last updated: 2018-01-10Bibliographically approved
Bojmar, L., Zhang, H., Costa da Silva, B., Karlsson, E., Olsson, H., Vincent, T., . . . Sandström, P. (2015). miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome.
Open this publication in new window or tab >>miR-18a is regulated between progressive compartments of cancers, and incorporated in exosomes with the potential of creating premetastatic niches and predict cancer outcome
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2015 (English)Manuscript (preprint) (Other academic)
Abstract [en]

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

National Category
Cancer and Oncology Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-122829 (URN)
Available from: 2015-11-26 Created: 2015-11-26 Last updated: 2018-01-10Bibliographically approved
Björnsson, B., Bojmar, L., Olsson, H., Sundqvist, T. & Sandström, P. (2015). Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver. World Journal of Gastroenterology, 21(6), 1775-1783
Open this publication in new window or tab >>Nitrite, a novel method to decrease ischemia/reperfusion injury in the rat liver
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2015 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 6, p. 1775-1783Article in journal (Refereed) Published
Abstract [en]

AIM: To investigate whether nitrite administered prior to ischemia/reperfusion (I/R) reduces liver injury.

METHODS: Thirty-six male Sprague-Dawley rats were randomized to 3 groups, including sham operated (n = 8), 45-min segmental ischemia of the left liver lobe (IR, n = 14) and ischemia/reperfusion (I/R) preceded by the administration of 480 nmol of nitrite (n = 14). Serum transaminases were measured after 4 h of reperfusion. Liver microdialysate (MD) was sampled in 30-min intervals and analyzed for glucose, lactate, pyruvate and glycerol as well as the total nitrite and nitrate (NOx). The NOx was measured in serum.

RESULTS: Aspartate aminotransferase (AST) at the end of reperfusion was higher in the IR group than in the nitrite group (40 ± 6.8 μkat/L vs 22 ± 2.6 μkat/L, P = 0.022). Similarly, alanine aminotransferase (ALT) was also higher in the I/R group than in the nitrite group (34 ± 6 μkat vs 14 ± 1.5 μkat, P = 0.0045). The NOx in MD was significantly higher in the nitrite group than in the I/R group (10.1 ± 2.9 μM vs 3.2 ± 0.9 μM, P = 0.031) after the administration of nitrite. During ischemia, the levels decreased in both groups and then increased again during reperfusion. At the end of reperfusion, there was a tendency towards a higher NOx in the I/R group than in the nitrite group (11.6 ± 0.7 μM vs 9.2 ± 1.1 μM, P = 0.067). Lactate in MD was significantly higher in the IR group than in the nitrite group (3.37 ± 0.18 mM vs 2.8 ± 0.12 mM, P = 0.01) during ischemia and the first 30 min of reperfusion. During the same period, glycerol was also higher in the IRI group than in the nitrite group (464 ± 38 μM vs 367 ± 31 μM, P = 0.049). With respect to histology, there were more signs of tissue damage in the I/R group than in the nitrite group, and 29% of the animals in the I/R group exhibited necrosis compared with none in the nitrite group. Inducible nitric oxide synthase (iNOS) transcription increased between early ischemia (t = 15) and the end of reperfusion in both groups.

CONCLUSION: Nitrite administered before liver ischemia in the rat liver reduces anaerobic metabolism and cell necrosis, which could be important in the clinical setting.

Place, publisher, year, edition, pages
Baishideng Publishing Group Co. Limited, 2015
Keywords
Ischemia-reperfusion injury; Nitrite; Liver ischemia; Liver surgery; Microdialysis; Nitric oxide; Inducible nitric oxide synthase
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-110262 (URN)10.3748/wjg.v21.i6.1775 (DOI)000349666300010 ()25684942 (PubMedID)
Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2017-12-05Bibliographically approved
Hoshino, A., Costa-Silva, B., Shen, T.-L., Rodrigues, G., Hashimoto, A., Tesic Mark, M., . . . Lyden, D. (2015). Tumour exosome integrins determine organotropic metastasis. Nature, 527(7578), 329-+
Open this publication in new window or tab >>Tumour exosome integrins determine organotropic metastasis
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2015 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 527, no 7578, p. 329-+Article in journal (Refereed) Published
Abstract [en]

Ever since Stephen Pagets 1889 hypothesis, metastatic organotropism has remained one of cancers greatest mysteries. Here we demonstrate that exosomes from mouse and human lung-, liver-and brain-tropic tumour cells fuse preferentially with resident cells at their predicted destination, namely lung fibroblasts and epithelial cells, liver Kupffer cells and brain endothelial cells. We show that tumour-derived exosomes uptaken by organ-specific cells prepare the pre-metastatic niche. Treatment with exosomes from lung-tropic models redirected the metastasis of bone-tropic tumour cells. Exosome proteomics revealed distinct integrin expression patterns, in which the exosomal integrins alpha(6)beta(4) and alpha(6)beta(1) were associated with lung metastasis, while exosomal integrin alpha(v)beta(5) was linked to liver metastasis. Targeting the integrins alpha(6)beta(4) and alpha(v)beta(5) decreased exosome uptake, as well as lung and liver metastasis, respectively. We demonstrate that exosome integrin uptake by resident cells activates Src phosphorylation and pro-inflammatory S100 gene expression. Finally, our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-125329 (URN)10.1038/nature15756 (DOI)000365356800046 ()26524530 (PubMedID)
Note

Funding Agencies|MSK Cancer Center Support Grant/Core Grant [P30 CA008748]; National Cancer Institute [U01-CA169538]; National Institutes of Health [R01-CA169416]; United States Department of Defense [W81XWH-13-10249, W81XWH-13-1-0425]; Melanoma Research Alliance; Sohn Conference Foundation; Childrens Cancer and Blood Foundation; Manning Foundation; Hartwell Foundation; Fundacao para a Ciencia e a Tecnologia; Nancy C. and Daniel P. Paduano Foundation; Feldstein Foundation; Starr Cancer Consortium; Mary Kay Foundation; Pediatric Oncology Experimental Therapeutic Investigator Consortium (POETIC); James Paduano Foundation; Beth Tortolani Foundation; Malcolm Hewitt Weiner Foundation; Theodore A. Rapp Foundation; American Hellenic Educational Progressive Association 5th District Cancer Research Foundation; Charles and Marjorie Holloway Foundation; Sussman Family Fund; Lerner Foundation; Breast Cancer Alliance; Manhasset Womens Coalition Against Breast Cancer; Ministry of Science and Technology Taiwan [101-2918-I-002-016]; JSPS Postdoctoral Fellowships; Susan G. Komen Postdoctoral Fellowship

Available from: 2016-02-23 Created: 2016-02-19 Last updated: 2017-11-30
Björnsson, B., Winbladh, A., Bojmar, L., Sundqvist, T., Gullstrand, P. & Sandström, P. (2014). Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion. World Journal of Gastroenterology, 20(28), 9506-9512
Open this publication in new window or tab >>Conventional, but not remote ischemic preconditioning, reduces iNOS transcription in liver ischemia/reperfusion
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2014 (English)In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 28, p. 9506-9512Article in journal (Refereed) Published
Abstract [en]

AIM: To study the effects of preconditioning on inducible nitric oxide synthase (iNOS) and interleukin 1 (IL-1) receptor transcription in rat liver ischemia/reperfusion injury (IRI). METHODS: Seventy-two male rats were randomized into 3 groups: the one-hour segmental ischemia (IRI, n = 24) group, the ischemic preconditioning (IPC, n = 24) group or the remote ischemic preconditioning (R-IPC, n = 24) group. The IPC and R-IPC were performed as 10 min of ischemia and 10 min of reperfusion. The iNOS and the IL-1 receptor mRNA in the liver tissue was analyzed with real time PCR. The total Nitrite and Nitrate (NOx) in continuously sampled microdialysate (MD) from the liver was analyzed. In addition, the NOx levels in the serum were analyzed. RESULTS: After 4 h of reperfusion, the iNOS mRNA was significantly higher in the R-IPC (Delta Ct: 3.44 +/- 0.57) group than in the IPC (Delta Ct: 5.86 +/- 0.82) group (P = 0.025). The IL-1 receptor transcription activity was reduced in the IPC group (Delta Ct: 1.88 +/- 0.53 to 4.81 +/- 0.21), but not in the R-IPC group, during reperfusion (P = 0.027). In the MD, a significant drop in the NOx levels was noted in the R-IPC group (12.3 +/- 2.2 to 4.7 +/- 1.2 mu mol/L) at the end of ischemia compared with the levels in early ischemia (P = 0.008). A similar trend was observed in the IPC group (11.8 +/- 2.1 to 6.4 +/- 1.5 mu mol/L), although this difference was not statistically significant. The levels of NOx rose quickly during reperfusion in both groups. CONCLUSION: IPC, but not R-IPC, reduces iNOS and IL-1 receptor transcription during early reperfusion, indicating a lower inflammatory reaction. NOx is consumed in the ischemic liver lobe.

Place, publisher, year, edition, pages
Baishideng Publishing Group Co. Limited, 2014
Keywords
Ischemia-reperfusion injury; Preconditioning; Remote preconditioning; Liver ischemia; Liver surgery; Microdialysis; Nitric oxide; inducible nitric oxide synthase; interleukin-1 receptor
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-109589 (URN)10.3748/wjg.v20.i28.9506 (DOI)000339389800032 ()25071345 (PubMedID)
Available from: 2014-08-21 Created: 2014-08-21 Last updated: 2017-12-05
Tjomsland, V., Bojmar, L., Sandström, P., Bratthall, C., Messmer, D., Spångeus, A. & Larsson, M. (2013). IL-1α Expression in Pancreatic Ductal Adenocarcinoma Affects the Tumor Cell Migration and Is Regulated by the p38MAPK Signaling Pathway. PLoS ONE, 8(8)
Open this publication in new window or tab >>IL-1α Expression in Pancreatic Ductal Adenocarcinoma Affects the Tumor Cell Migration and Is Regulated by the p38MAPK Signaling Pathway
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8Article in journal (Refereed) Published
Abstract [en]

The interplay between the tumor cells and the surrounding stroma creates inflammation, which promotes tumor growth and spread. The inflammation is a hallmark for pancreatic adenocarcinoma (PDAC) and is to high extent driven by IL-1α. IL-1α is expressed and secreted by the tumor cells and exerting its effect on the stroma, i.e. cancer associated fibroblasts (CAF), which in turn produce massive amount of inflammatory and immune regulatory factors. IL-1 induces activation of transcription factors such as nuclear factor-κβ (NF-κβ), but also activator protein 1 (AP-1) via the small G-protein Ras. Dysregulation of Ras pathways are common in cancer as this oncogene is the most frequently mutated in many cancers. In contrast, the signaling events leading up to the expression of IL-1α by tumor cells are not well elucidated. Our aim was to examine the signaling cascade involved in the induction of IL-1α expression in PDAC. We found p38MAPK, activated by the K-Ras signaling pathway, to be involved in the expression of IL-1α by PDAC as blocking this pathway decreased both the gene and protein expression of IL-1α. Blockage of the P38MAPK signaling in PDAC also dampened the ability of the tumor cell to induce inflammation in CAFs. In addition, the IL-1α autocrine signaling regulated the migratory capacity of PDAC cells. Taken together, the blockage of signaling pathways leading to IL-1α expression and/or neutralization of IL-1α in the PDAC microenvironment should be taken into consideration as possible treatment or complement to existing treatment of this cancer.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-97445 (URN)10.1371/journal.pone.0070874 (DOI)000323097300061 ()
Note

Funding Agencies|Swedish Research Council|AI52731|VINNMER (Vinnova)||Medical Research Council of Southeast Sweden||Swedish Society of Medicine||

Available from: 2013-09-12 Created: 2013-09-12 Last updated: 2017-12-06
Pena, C., Virtudes Cespedes, M., Bradic Lindh, M., Kiflemariam, S., Mezheyeuski, A., Edqvist, P.-H., . . . Ostman, A. (2013). STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer. Cancer Research, 74(4), 1287-1297
Open this publication in new window or tab >>STC1 Expression By Cancer-Associated Fibroblasts Drives Metastasis of Colorectal Cancer
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2013 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 4, p. 1287-1297Article in journal (Refereed) Published
Abstract [en]

Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression of PDGF receptors on stromal CAFs is associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification of the secreted glycoprotein stanniocalcin-1 (STC1) as a mediator of metastasis by PDGF receptor function in the setting of colorectal cancer. PDGF-stimulated fibroblasts increased migration and invasion of cocultured colorectal cancer cells in an STC1-dependent manner. Analyses of human colorectal cancers revealed significant associations between stromal PDGF receptor and STC1 expression. In an orthotopic mouse model of colorectal cancer, tumors formed in the presence of STC1-deficient fibroblasts displayed reduced intravasation of tumor cells along with fewer and smaller distant metastases formed. Our results reveal a mechanistic basis for understanding the contribution of PDGF-activated CAFs to cancer metastasis. Cancer Res; 73(4); 1287-97.

Place, publisher, year, edition, pages
American Association for Cancer Research, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90068 (URN)10.1158/0008-5472.CAN-12-1875 (DOI)000315029800004 ()
Note

Funding Agencies|Swedish Research Council|60016002|VINNOVA||Swedish Cancer Society|11 0371|National Health and Medical Research Council of Australia project grant||

Available from: 2013-03-21 Created: 2013-03-19 Last updated: 2017-12-06
Bojmar, L., Karlsson, E., Ellegård, S., Olsson, H., Björnsson, B., Hallböök, O., . . . Sandström, P. (2013). The Role of MicroRNA-200 in Progression of Human Colorectal and Breast Cancer. PLoS ONE, 8(12), 84815
Open this publication in new window or tab >>The Role of MicroRNA-200 in Progression of Human Colorectal and Breast Cancer
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. 84815-Article in journal (Refereed) Published
Abstract [en]

The role of the epithelial-mesenchymal transition (EMT) in cancer has been studied extensively in vitro, but involvement of the EMT in tumorigenesis in vivo is largely unknown. We investigated the potential of microRNAs as clinical markers and analyzed participation of the EMT-associated microRNA-200 ZEB E-cadherin pathway in cancer progression. Expression of the microRNA-200 family was quantified by real-time RT-PCR analysis of fresh-frozen and microdissected formalin-fixed paraffin-embedded primary colorectal tumors, normal colon mucosa, and matched liver metastases. MicroRNA expression was validated by in situ hybridization and after in vitro culture of the malignant cells. To assess EMT as a predictive marker, factors considered relevant in colorectal cancer were investigated in 98 primary breast tumors from a treatment-randomized study. Associations between the studied EMTmarkers were found in primary breast tumors and in colorectal liver metastases. MicroRNA-200 expression in epithelial cells was lower in malignant mucosa than in normal mucosa, and was also decreased in metastatic compared to non-metastatic colorectal cancer. Low microRNA-200 expression in colorectal liver metastases was associated with bad prognosis. In breast cancer, low levels of microRNA-200 were related to reduced survival and high expression of microRNA-200 was predictive of benefit from radiotheraphy. MicroRNA-200 was associated with ER positive status, and inversely correlated to HER2 and overactivation of the PI3K/AKT pathway, that was associated with high ZEB1 mRNA expression. Our findings suggest that the stability of microRNAs makes them suitable as clinical markers and that the EMT-related microRNA-200 - ZEB - E-cadherin signaling pathway is connected to established clinical characteristics and can give useful prognostic and treatment-predictive information in progressive breast and colorectal cancers.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-103717 (URN)10.1371/journal.pone.0084815 (DOI)000328745100188 ()
Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2019-02-11
Winbladh, A., Björnsson, B., Trulsson, L., Bojmar, L., Sundqvist, T., Gullstrand, P. & Sandström, P. (2012). N-acetyl cysteine improves glycogenesis after segmental liver ischemia and reperfusion injury in pigs. Scandinavian Journal of Gastroenterology, 47(2), 225-236
Open this publication in new window or tab >>N-acetyl cysteine improves glycogenesis after segmental liver ischemia and reperfusion injury in pigs
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2012 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 47, no 2, p. 225-236Article in journal (Refereed) Published
Abstract [en]

Abstract Objective. N-acetylcysteine (NAC) is an antioxidative molecule known to protect liver tissue from oxygen radical species generated during ischemia and reperfusion (IR). Nutritional and toxicology studies have shown that NAC also improves glucose metabolism and glycogen stores. We hypothesized that NAC improves glycogenesis and that impaired glycogenesis is a key element in IR injury. Material and Methods. In an experimental model, 80 min of segmental liver ischemia was induced in 16 pigs and the reperfusion was followed for 360 min. Eight animals received NAC 150 mg/kg as a bolus injection followed by an infusion of NAC 50 mg/kg/h intravenously. Results. AST and leukocyte density were lower in the NAC-treated animals, unrelated to the glutathione levels or apoptosis. Glycogen stores returned to a higher degree in the NAC-treated animals and microdialysis revealed lower levels of lactate during the reperfusion phase. Nitrite/Nitrate levels in the NAC group were lower in both serum and microdialysates, indicating that NAC scavenges radical nitrosative species. Conclusions. NAC treatment improves glycogenesis after liver IR injury and reduces the level of intraparenchymal lactate during reperfusion, possibly due to the scavenging of radical nitrosative species.

Place, publisher, year, edition, pages
Informa Healthcare, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-74184 (URN)10.3109/00365521.2011.643480 (DOI)
Available from: 2012-01-20 Created: 2012-01-20 Last updated: 2017-12-08
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