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Tsakonas, Georgios
Publications (3 of 3) Show all publications
Karamanis, G., Skalkidou, A., Tsakonas, G., Brandt, L., Ekbom, A., Ekselius, L. & Papadopoulos, F. C. (2014). Cancer incidence and mortality patterns in women with anorexia nervosa. International Journal of Cancer, 134(7), 1751-1757
Open this publication in new window or tab >>Cancer incidence and mortality patterns in women with anorexia nervosa
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2014 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 7, p. 1751-1757Article in journal (Refereed) Published
Abstract [en]

Caloric restriction in animals is an effective way to reduce carcinogenesis. Anorexia nervosa (AN) is considered a model of extreme caloric restriction in humans. The aim of our study was to assess cancer incidence and mortality in women with AN. A total of 6,009 women with at least one inpatient treatment for AN during the period 1973-2003 were included in the study. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were calculated. Overall, there was no statistically significant difference in cancer incidence compared to women in the general population. At a statistically significant or borderline significant level, a higher incidence for lung cancer and cancer of lymphoid, hematopoietic and related tissue was observed along with a reduced breast cancer incidence. Women with AN had twice as high mortality from cancer in general, and more specifically from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites. The increased lung cancer incidence may be due to smoking habits among women with AN. The worse prognosis with higher mortality from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites may be explained by AN-specific attitudes toward seeking medical care, adherence to treatment or worse biological precondition due to starvation and cachexia.

National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-209330 (URN)10.1002/ijc.28495 (DOI)000329579500023 ()24114497 (PubMedID)
Available from: 2013-10-16 Created: 2013-10-16 Last updated: 2017-12-06Bibliographically approved
Sooman, L., Ekman, S., Tsakonas, G., Jaiswal, A., Navani, S., Edqvist, P.-H., . . . Lennartsson, J. (2014). PTPN6 expression is epigenetically regulated and influences survival and response to chemotherapy in high-grade gliomas. Tumor Biology, 35(5), 4479-4488
Open this publication in new window or tab >>PTPN6 expression is epigenetically regulated and influences survival and response to chemotherapy in high-grade gliomas
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2014 (English)In: Tumor Biology, ISSN 1010-4283, E-ISSN 1423-0380, Vol. 35, no 5, p. 4479-4488Article in journal (Refereed) Published
Abstract [en]

Background: The prognosis of high-grade glioma patients is poor and the tumors are characterized by resistance to therapy. The aims of this study were to analyze the prognostic value of the expression of the protein tyrosine phosphatase, non-receptor type 6 (PTPN6, also referred to as SHP1) in high-grade glioma patients and the epigenetic regulation of the expression of PTPN6 and the role of its expression in chemotherapy resistance in glioma-derived cells.

Material and methods: PTPN6 expression was analyzed with immunohistochemistry in 89 high-grade glioma patients. Correlation between PTPN6 expression and overall survival was analyzed with Kaplan-Meier univariate analysis and Cox regression multivariate analysis. Differences in drug sensitivity to a panel of 16 chemotherapeutic drugs between PTPN6 overexpressing clones and control clones were analyzed in vitro with the fluorometric microculture cytotoxicity assay. Cell cycle analysis was done with Krishan staining and flow cytometry. Apoptosis was analyzed with a cell death detection ELISA kit as well as cleaved caspase-3 and caspase-9 Western blotting. Autophagy was analyzed with LC3B Western blotting. Methylation of the PTPN6 promoter was analyzed with bisulfite-Pyrosequencing and demethylation of PTPN6 was done with decitabine treatment.

Results: PTPN6 expression correlated in univariate analysis to poor survival for anaplastic glioma patients (p=0.026). In glioma-derived cell lines, overexpression of PTPN6 caused increased resistance (p<0.05) to the chemotherapeutic drugs bortezomib, cisplatin and melphalan. PTPN6 expression did not affect bortezomib-induced cell cycle arrest, apoptosis or autophagy. Low PTPN6 promoter methylation correlated to protein expression and the protein expression was increased upon demethylation in glioma-derived cells.

Conclusion: PTPN6 expression may be a factor contributing to poor survival for anaplastic glioma patients and in glioma-derived cells its expression is epigenetically regulated and influences the response to chemotherapy.

Keywords
high-grade glioma, PTPN6, SHP1, survival, chemotherapy, methylation
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-214761 (URN)10.1007/s13277-013-1590-5 (DOI)000335759800063 ()
Available from: 2014-01-09 Created: 2014-01-09 Last updated: 2018-01-11Bibliographically approved
Sooman, L., Lennartsson, J., Gullbo, J., Bergqvist, M., Tsakonas, G., Johansson, F., . . . Ekman, S. (2013). Vandetanib combined with a p38 MAPK inhibitor synergistically reduces glioblastoma cell survival. Medical Oncology, 30(3), 638
Open this publication in new window or tab >>Vandetanib combined with a p38 MAPK inhibitor synergistically reduces glioblastoma cell survival
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2013 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 30, no 3, p. 638-Article in journal (Refereed) Published
Abstract [en]

The survival for patients with high-grade glioma is poor, and only a limited number of patients respond to the therapy. The aim of this study was to analyze the significance of using p38 MAPK phosphorylation as a prognostic marker in high-grade glioma patients and as a therapeutic target in combination chemotherapy with vandetanib. p38 MAPK phosphorylation was analyzed with immunohistochemistry in 90 high-grade glioma patients. Correlation between p38 MAPK phosphorylation and overall survival was analyzed with Mann-Whitney U test analysis. The effects on survival of glioblastoma cells of combining vandetanib with the p38 MAPK inhibitor SB 203580 were analyzed in vitro with the median-effect method with the fluorometric microculture cytotoxicity assay. Two patients had phosphorylated p38 MAPK in both the cytoplasm and nucleus, and these two presented with worse survival than patients with no detectable p38 MAPK phosphorylation or phosphorylated p38 MAPK only in the nucleus. This was true for both high-grade glioma patients (WHO grade III and IV, n = 90, difference in median survival: 6.1 months, 95 % CI [0.20, 23], p = 0.039) and for the subgroup with glioblastoma patients (WHO grade IV, n = 70, difference in median survival: 6.1 months, 95 % CI [0.066, 23], p = 0.043). The combination of vandetanib and the p38 MAPK inhibitor SB 203580 had synergistic effects on cell survival for glioblastoma-derived cells in vitro. In conclusion, p38 MAPK phosphorylation may be a prognostic marker for high-grade glioma patients, and vandetanib combined with a p38 MAPK inhibitor may be useful combination chemotherapy for glioma patients.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-202678 (URN)10.1007/s12032-013-0638-0 (DOI)000323662900047 ()23783486 (PubMedID)
Available from: 2013-06-25 Created: 2013-06-25 Last updated: 2017-12-06Bibliographically approved
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