Pathogenesis of Ovarian Serous Carcinoma as the Basis for Immunologic Directed Diagnosis and Treatment. Project 3 - Development of Antigen-Specific Cancer Vaccines for the Control of Ovarian Cancer

2003 ◽  
Author(s):  
Robert J. Kurman ◽  
T. C. Wu
Keyword(s):  
Ovarian Cancer ◽  
Cancer Vaccines ◽  
Diagnosis And Treatment ◽  
Serous Carcinoma ◽  
Ovarian Serous Carcinoma ◽  
Specific Cancer

Serum biomarker discovery for ovarian serous carcinoma using novel proteomic methods

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16058-16058 ◽  
Author(s):  
J. A. Borgia ◽  
C. Frankenberger ◽  
K. Kaiser ◽  
S. E. McCormack ◽  
L. Usha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Biomarker Discovery ◽  
Tumor Resection ◽  
Stage I ◽  
Serum Biomarker ◽  
Serous Carcinoma ◽  
Major Surgery ◽  
Ovarian Serous Carcinoma ◽  
Baseline Subtraction ◽  
Operative Specimen

16058 Background: Ovarian serous carcinoma (OSC) is the most common ovarian cancer sub-type and fourth leading cause of cancer-related deaths for women in the US. Unfortunately, more than two-thirds of women with ovarian cancer present at an advanced stage, when prognosis is poor. Developing methods to detect ovarian cancer at stage I, when it is 90% curable by surgery, or at stage II where survival is 70%, offers the best prospect for changing the clinical course of this dread malignancy. Methods: Serum specimens were collected both before and 3–6 weeks after tumor resection for patients with Stage I/ II high-grade serous carcinoma. None suffered recurrence within 6 months. We collected 98 ‘paired’ (pre- and post operative) serum specimens; including 41 benign paired specimens for comparison. A SELDI-TOF mass spectrometer was used to generate the serum proteomic profiles, optimized for the 2,000–40,000 m/z range. All data analyses were performed in a blinded manner using Bioconductor, an extension of the R-project statistical platform (v2.2.0). Raw spectra were processed as follows: baseline subtraction, spectra normalization, and differential peak detection. Aligned peaks were sorted into groups, based on tumor pathology and pre- vs. post-operative specimen type, and compared using a two tailed homoscedastic t-test. Results: The proteomes of pre- and post-operative serum from 10 patients with OSC were evaluated for significant changes in composition and compared with a set of 8 ‘normal’ specimens (i.e. patients undergoing major surgery for benign disease). We identified 18 serum components common to all OSC pre-op specimens that were extensively reduced or absent (p < 0.05) after tumor resection and 26 components capable of discerning pre-op OSC from pre-op normal specimens (p < 0.05). Most notable of these are components with m/z ratios of 2029.1, 2203.6, 6442.3, and 6851.9, based on level of significance (p < 0.001). Conclusions: These results validate the power of our ‘pre- vs. post- operative’ analysis strategy for the identification of novel serum biomarker candidates. Efforts are currently focused on expanding the scope of our specimen bank and identifying the putative biomarker candidates via mass spectrometry. No significant financial relationships to disclose.

scholarly journals Epigenetic silencing of BLU through interfering apoptosis results in chemoresistance and poor prognosis of ovarian serous carcinoma patients

2013 ◽  
Vol 20 (2) ◽  
pp. 213-227 ◽  
Author(s):  
Ying-Cheng Chiang ◽  
Ming-Cheng Chang ◽  
Pao-Jen Chen ◽  
Meei-Maan Wu ◽  
Chang-Yao Hsieh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Multivariate Analysis ◽  
Poor Prognosis ◽  
Methylation Status ◽  
Progression Free Survival ◽  
Serous Carcinoma ◽  
Ovarian Cancer Cells ◽  
Advanced Stage ◽  
Ovarian Serous Carcinoma

Epithelial ovarian carcinoma is usually present at the advanced stage, during which the patients generally have poor prognosis. Our study aimed to evaluate the correlation of gene methylation and the clinical outcome of patients with advanced-stage, high-grade ovarian serous carcinoma. The methylation status of eight candidate genes was first evaluated by methylation-specific PCR and capillary electrophoresis to select three potential genes including DAPK, CDH1, and BLU (ZMYND10) from the exercise group of 40 patients. The methylation status of these three genes was further investigated in the validation group consisting of 136 patients. Patients with methylated BLU had significantly shorter progression-free survival (PFS; hazard ratio (HR) 1.48, 95% CI 1.01–2.56, P=0.013) and overall survival (OS; HR 1.83, 95% CI 1.07–3.11, P=0.027) in the multivariate analysis. Methylation of BLU was also an independent risk factor for 58 patients undergoing optimal debulking surgery for PFS (HR 2.37, 95% CI 1.03–5.42, P=0.043) and OS (HR 3.96, 95% CI 1.45–10.81, P=0.007) in the multivariate analysis. A possible mechanism of BLU in chemoresistance was investigated in ovarian cancer cell lines by in vitro apoptotic assays. In vitro studies have shown that BLU could upregulate the expression of BAX and enhance the effect of paclitaxel-induced apoptosis in ovarian cancer cells. Our study suggested that methylation of BLU could be a potential prognostic biomarker for advanced ovarian serous carcinoma.

scholarly journals Breast Carcinomatous Lymphangitis as an Unusual Presentation of Ovarian Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2106
Author(s):  
Barbara Muoio ◽  
Giorgio Treglia ◽  
Paola Migliora ◽  
Maria Del Grande
Keyword(s):  
Ovarian Cancer ◽  
Diagnostic Laparoscopy ◽  
Unusual Presentation ◽  
Serous Carcinoma ◽  
Ovarian Serous Carcinoma ◽  
Abdomen Ct ◽  
History Of ◽  
Ovarian Lesion ◽  
The Right ◽  
Ovarian Masses

We describe the case of a 45-year-old woman with an unusual presentation of metastatic ovarian cancer. The patient presented to the oncological clinic with a three-week history of skin rash on the right breast. She underwent a chest and abdomen CT scan, which showed skin thickening of the right breast, right pleural effusion and bilateral cystic ovarian masses. Biopsy of a left ovarian lesion by diagnostic laparoscopy revealed the presence of ovarian serous carcinoma. Biopsy of the breast skin lesion revealed the presence of carcinomatous lymphangitis and immunohistochemistry documented the ovarian origin.

scholarly journals Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Stefanie M. Ueda ◽  
Kai Lee Yap ◽  
Ben Davidson ◽  
Yuan Tian ◽  
Vivek Murthy ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Fatty Acid Synthase ◽  
Dominant Negative ◽  
Serous Carcinoma ◽  
Ovarian Cancer Cells ◽  
Primary Tumors ◽  
Ovarian Serous Carcinoma ◽  
Skov3 Cells

Our previous reports demonstrated that NAC1, a BTB/POZ domain-containing nuclear protein, upregulates in recurrent ovarian serous carcinoma and participates in developing drug resistance in cancer cells. The current study applies quantitative proteomics to identify the proteins controlled by NAC1 by comparing the proteomes of SKOV3 cells with and without expression of a dominant negative NAC1 construct, N130. From the proteins that are downregulated by N130 (upregulated by NAC1), we chose to further characterize fatty acid synthase (FASN). Similar to change in protein level, the FASN transcript level in SKOV3 cells was significantly reduced by N130 induction or by NAC1 knockdown. Immunohistochemistry showed that NAC1 and FASN immunointensities in ovarian serous carcinoma tissues had a highly significant correlation (P<.0001). Moreover, we found that recurrent serous carcinomas exhibited higher FASN immunointensities than their matched primary tumors (P<.001). Multivariate analysis showed that an FASN staining score of >1 in serous carcinomas was associated with a worse overall survival time (P<.01). Finally, C93, a new FASN inhibitor, induced massive apoptosis in carboplatin/paclitaxel resistant ovarian cancer cells. In conclusion, we show that NAC1 is essential for FASN expression in ovarian serous carcinomas and the expression of FASN significantly correlates with tumor recurrence and disease aggressiveness. The dependence of drug resistant tumor cells on FASN suggests a potential application of FASN-based therapeutics for recurrent ovarian cancer patients.

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