| 1. |
- Kirilovas, Dmitrijus, et al.
(författare)
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Conversion of circulating estrone sulfate to 17β-estradiol by ovarian tumor tissue : A possible mechanism behind elevated circulating concentrations of 17β-estradiol in postmenopausal women with ovarian tumors
- 2007
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Ingår i: Gynecological Endocrinology. - : Informa UK Limited. - 0951-3590 .- 1473-0766. ; 23:1, s. 25-28
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Elevated serum levels of 17beta-estradiol (E2) are frequently found in postmenopausal women with ovarian tumors not classified as estrogen-producing. Conversion of circulating estrone sulfate (E1S) to E2 is one alternative way of E2 formation in target tissues in postmenopausal women. Our aim was to find out if conversion of circulating E1S to E2 by the tumor tissue could be a reason for elevated serum E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors. METHOD: Serum E2 was measured in 12 postmenopausal women with 'non-estrogen-producing' ovarian tumors (nine benign, three malignant). Total hydrolysis of and [3H]E2 formation from [3H]E1S by the tumor tissue homogenates was studied in vitro. RESULTS: Serum E2 showed significant positive correlations with total hydrolysis of and [3H]E2 formation from [3H]E1S in the total material as well as in the benign tumor subgroup. [3H]E2 formation was the most important independent variable. CONCLUSION: Conversion of circulating E1S to E2 by the tumor tissue could be one important reason for elevated S-E2 levels in postmenopausal women with 'non-estrogen-producing' ovarian tumors.
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| 2. |
- Bengtsson, Sofia, et al.
(författare)
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Large-scale proteomics analysis of human ovarian cancer for biomarkers
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:4, s. 1440-1450
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer is usually found at a late stage when the prognosis is often bad. Relative survival rates decrease with tumor stage or grade, and the 5-year survival rate for women with carcinoma is only 38%. Thus, there is a great need to find biomarkers that can be used to carry out routine screening, especially in high-risk patient groups. Here, we present a large-scale study of 64 tissue samples taken from patients at all stages and show that we can identify statistically valid markers using nonsupervised methods that distinguish between normal, benign, borderline, and malignant tissue. We have identified 217 of the significantly changing protein spots. We are expressing and raising antibodies to 35 of these. Currently, we have validated 5 of these antibodies for use in immunohistochemical analysis using tissue microarrays of healthy and diseased ovarian, as well as other, human tissues.
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| 3. |
- Hellman, Kristina, et al.
(författare)
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Differential tissue-specific protein markers of vaginal carcinoma
- 2009
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Ingår i: British Journal of Cancer. - : Cancer Research UK. - 0007-0920 .- 1532-1827. ; 100:8, s. 1303-1314
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Forskningsöversikt (refereegranskat)abstract
- The objective was to identify proteins differentially expressed in vaginal cancer to elucidate relevant cancer-related proteins. A total of 16 fresh-frozen tissue biopsies, consisting of 5 biopsies from normal vaginal epithelium, 6 from primary vaginal carcinomas and 5 from primary cervical carcinomas, were analysed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Of the 43 proteins identified with significant alterations in protein expression between non-tumourous and tumourous tissue, 26 were upregulated and 17 were downregulated. Some were similarly altered in vaginal and cervical carcinoma, including cytoskeletal proteins, tumour suppressor proteins, oncoproteins implicated in apoptosis and proteins in the ubiquitin-proteasome pathway. Three proteins were uniquely altered in vaginal carcinoma (DDX48, erbB3-binding protein and biliverdin reductase) and five in cervical carcinoma (peroxiredoxin 2, annexin A2, sarcomeric tropomyosin kappa, human ribonuclease inhibitor and prolyl-4-hydrolase beta). The identified proteins imply involvement of multiple different cellular pathways in the carcinogenesis of vaginal carcinoma. Similar protein alterations were found between vaginal and cervical carcinoma suggesting common tumourigenesis. However, the expression level of some of these proteins markedly differs among the three tissue specimens indicating that they might be useful molecular markers.
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| 4. |
- Hjerpe, Elisabet, et al.
(författare)
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HSP60 predicts survival in advanced serous ovarian cancer.
- 2013
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Ingår i: International Journal of Gynecological Cancer. - : Lippincott Williams & Wilkins. - 1048-891X .- 1525-1438. ; 23:3, s. 448-455
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Heat shock protein 60 (HSP60) plays an essential role in malignant cell survival. We evaluated the prognostic and treatment predictive value of HSP60 in advanced ovarian cancer.METHODS: Fresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 fulfilled the eligibility criteria, that is, International Federation of Gynecology and Obstetrics stage IIC-IV, serous/endometrioid tumors, platinum-based chemotherapy, and specimens with 50% tumor cells or greater. Heat shock protein 60 mRNA and protein expression was determined by real-time polymerase chain reaction and immunohistochemistry. We estimated the association between HSP60 and overall survival (OS) and platinum-free interval (PFI) by Cox proportional hazards models and its relationship with treatment response by Fisher's exact test. Median follow-up was 60 months.RESULTS: High HSP60 mRNA expression was associated with shorter OS (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.3-8.5) and PFI (HR, 3.3; 95% CI, 1.5-7.2). Likewise, high HSP60 protein expression was associated with shorter OS (HR, 3.2; 95% CI, 1.5-7.1) and PFI (HR, 2.6; 95% CI, 1.3-5.3). Median survival for patients with high HSP60 protein expression was 31 months compared with 55 months for low expression cases (P = 0.016). The impact on OS and PFI was even stronger in the subgroup of grade 3 serous tumors. All patients with low HSP60 levels responded to first-line chemotherapy.CONCLUSION: Heat shock protein 60 may identify groups of advanced serous ovarian cancer with different prognosis and treatment response.
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| 5. |
- Hjerpe, Elisabet, et al.
(författare)
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Metabolic markers GAPDH, PKM2, ATP5B and BEC-index in advanced serous ovarian cancer.
- 2013
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Ingår i: BMC Clinical Pathology. - : BioMed Central (BMC). - 1472-6890. ; 113:30
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A deregulated energy metabolism is a hallmark of malignant disease that offers possible future targets for treatment. We investigated the prognostic value of the glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and pyruvate kinase type M2 (PKM2), mitochondrial β-F1-ATPase (ATP5B) and the bioenergetic cellular (BEC) index in advanced ovarian cancer.METHODS: Fresh tumor samples were prospectively collected from 123 patients undergoing primary surgery for suspected advanced ovarian cancer. Of these, 57 met the eligibility criteria; stage IIC-IV, serous or endometrioid subtype, specimens containing ≥ 50% tumor cells and patients receiving platinum-based chemotherapy. An adequate amount of mRNA could be extracted in all but one case, with a resultant study population of 56 patients. Eighty-six percent of cases had serous tumors, and 93% were grade 2-3. GAPDH, PKM2 and ATP5B mRNA- and protein expression was assessed by real-time PCR and immunohistochemistry. We estimated the association with platinum-free interval (PFI) and overall survival (OS) by Cox proportional hazards models. Median follow-up was 60 months.RESULTS: High GAPDH mRNA levels (HR 2.1, 95% CI 1.0-4.5) and low BEC-index (HR 0.47, 95% CI 0.23-0.95) were both independently associated with shorter PFI. Median PFI for patients with high GAPDH mRNA was 5.0 months compared to 10.1 months for low expression cases (p = 0.031). Similarly, median PFI for patients with low BEC-index based on mRNA was 5.3 months compared to 9.8 months for high BEC-index cases (p = 0.028).CONCLUSIONS: High GAPDH or low BEC-index mRNA expression indicate early disease progression in advanced serous ovarian cancer.
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| 6. |
- Lundgren, Caroline, et al.
(författare)
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2-DE protein expression in endometrial carcinoma
- 2006
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Ingår i: Acta Oncologica. - Oslo : Taylor & Francis. - 0284-186X .- 1651-226X. ; 45:6, s. 685-694
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to explore the protein expression pattern in normal endometrial mucosa (n = 5) and endometrial carcinoma ( n = 15) of low ( diploid) and high ( aneuploid) malignancy potential by two-dimensional gel electrophoresis (2-DE). The specimens were evaluated for histopathologic subtype, stage and grade in relation to DNA ploidy. A match-set consisting of five samples from normal endometrium, eight diploid and seven aneuploid tumours was created. All the diploid and three of the aneuploid tumours were of endometrioid subtype, while the remaining four were of uterine seropapillary type. There were 192 protein spots differentiating diploid tumours from normal endometrium and 238 protein spots were separating aneuploid tumours from normal endometrium (p < 0.01). A cluster analysis based on 52 significantly deviating protein spots within the groups showed clustering and separation of the normal endometrium, diploid and aneuploid tumours. In conclusion this study showed significant differences in protein expression between normal endometrium and endometrial carcinoma as well as between endometrial carcinoma of low and high malignancy potential. In future studies these results may provide useful in finding new sensitive prognostic markers for endometrial cancer.
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| 7. |
- Waldemarson, Sofia, et al.
(författare)
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Protein Expression Changes in Ovarian Cancer during the Transition from Benign to Malignant.
- 2012
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 11:5, s. 2876-2889
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial ovarian carcinoma has in general a poor prognosis since the vast majority of tumors are genomically unstable and clinically highly aggressive. This results in rapid progression of malignancy potential while still asymptomatic and thus in late diagnosis. It is therefore of critical importance to develop methods to diagnose epithelial ovarian carcinoma at its earliest developmental stage, that is, to differentiate between benign tissue and its early malignant transformed counterparts. Here we present a shotgun quantitative proteomic screen of benign and malignant epithelial ovarian tumors using iTRAQ technology with LC-MALDI-TOF/TOF and LC-ESI-QTOF MS/MS. Pathway analysis of the shotgun data pointed to the PI3K/Akt signaling pathway as a significant discriminatory pathway. Selected candidate proteins from the shotgun screen were further confirmed in 51 individual tissue samples of normal, benign, borderline or malignant origin using LC-MRM analysis. The MRM profile demonstrated significant differences between the four groups separating the normal tissue samples from all tumor groups as well as perfectly separating the benign and malignant tumors with a ROC-area of 1. This work demonstrates the utility of using a shotgun approach to filter out a signature of a few proteins only that discriminates between the different sample groups.
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