Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins

Background: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear. Materials and Methods: A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting. Ingenuity pathway analysis revealed metabolomic pathway changes. Results: A total of 189 proteins were identified with restricted criteria. Combined treatment targeting the proteasome-ubiquitin pathway resulted in re-sensitisation of drug-resistant cells. In addition, examination of five surgical biopsies of ovarian tissues revealed α-enolase (ENOA), elongation factor Tu, mitochondrial (EFTU), glyceraldehyde-3-phosphate dehydrogenase (G3P), stress-70 protein, mitochondrial (GRP75), apolipoprotein A-1 (APOA1), peroxiredoxin (PRDX2) and annexin A (ANXA) as candidate biomarkers of drug-resistant disease. Conclusion: Proteomics combined with pathway analysis provided information for an effective combined treatment approach overcoming drug resistance. Analysis of cell lines and tissues revealed potential prognostic biomarkers for ovarian cancer

Primary vaginal adenocarcinoma of intestinal type or occult metastatic colon cancer: a diagnostic dilemma from a vaginal skin tag

Anna Louise Russell,1 Ben Haagsma,2 Thumuluru Kavitha Madhuri3,4 1Department of Gynae-Oncology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK; 2Department of Histopathology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK; 3Department of Gynaecological Oncology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, UK; 4Department of Experimental Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford, UK Abstract: The presentation of a new vaginal lesion could represent a variety of diagnoses from benign warts to more sinister primary malignancies. Rarely, a new lesion could represent a metastatic deposit from a malignancy elsewhere in the body. Colonic carcinomas are the third most common malignancy, frequently metastasising to the liver and lung. There have been a small number of cases in the literature reporting vaginal metastases from colonic carcinoma and this is usually indicative of advanced disseminated disease. We present an interesting case of a 65-year-old female with a strong family history of bowel cancer who originally presented with a vaginal skin tag that was biopsied and found to be a moderately differentiated adenocarcinoma. The immunohistochemistry profile was cytokeratin (CK) 20 positive/CK 7 negative, highly suggestive of a bowel cancer primary. However, subsequent extensive radiological and endoscopic investigations failed to identify a colonic primary tumor. The vaginal lesion was successfully excised, and no systemic treatments were warranted. To date, no primary cancer has been identified; the patient remains asymptomatic with no clinical signs of disease recurrence 5 years following her initial diagnosis. This case represents a diagnostic dilemma between two very rare diagnoses of either a vaginal metastasis from an occult colonic primary tumor or a primary vaginal adenocarcinoma of endometrioid morphology demonstrating intestinal immunophenotype. Organizing colonic screening is recommended in view of the high risk of colonic adenocarcinoma. Keywords: skin tag, vaginal cancer, metastases, occult malignancy, colon cancer, villiform, intestinal villiform, endometrioi

Use of neutral plasma coagulation in groin node dissection for vulvar malignancy: a novel technique

Thumuluru Kavitha Madhuri, Anil Tailor, Simon Butler-ManuelDepartment of Gynaecological Oncology, The Royal Surrey County Hospital, Guildford, Surrey, UKAbstract: Vulvar cancer is an uncommon disease with approximately 1000 cases reported annually in the UK. Lymph node involvement is an important prognostic indicator. Vulvectomy and bilateral groin node dissection are the preferred surgical treatments for early disease and increase survival. However, significant morbidity with lymphocyst formation and wound breakdown has been reported in more than 50% of cases. We report the first case following use of the PlasmaJet® neutral argon coagulation system to reduce postoperative lymphocyst formation.Keywords: lymphocyst formation, wound, lymphodem

The impact of age on first-line chemotherapy treatment of epithelial ovarian cancer and primary peritoneal carcinoma

Background: Standard treatment for epithelial ovarian (EOC) and primary peritoneal (PP) cancer is combination of surgery and chemotherapy. Most commonly used first-line drugs are carboplatin and paclitaxel (C/P). Treatment decisions involving elderly patients are complex and single agent carboplatin (C) is often preferred. To help the decision process we analysed the toxicity profile and outcome for elderly patients treated first line with both: C/P and C alone. Methods: A retrospective analysis of 82 elderly patients (> 75 years) treated for EOC and PP cancer between April 1996 and October 2009 was performed. Age, comorbidities, CA-125 at diagnosis, histology, stage, outcome of cytoreductive surgery (CRS), chemotherapy regimen, toxicity and clinical response were recorded. Results: The majority, 76% (63/82) of patients had serous ovarian cancer with 58.5% presenting as FIGO stage 3c, median CA-125 of 340.2 U/mL (range: 5-5702). 67.1% (55/82) had CRS with 61.9% (34) optimally debulked. 84.2% of patients (69/82) received chemotherapy and were therefore evaluable for the purpose of this analysis. 94.2% (65/69) completed treatment (mean number of cycles = 5.1). 35.4% (23/65) received C/P and 63.1% (41/65) received single agent C. The commonest complication was peripheral neuropathy- 56.5% (13/23) in combination arm. Treatment was deferred mainly due to haematological toxicity: neutropaenia - 13.9% (6/43) in the C arm and 11.1% (3/27) in C/P; grade 3/4 thrombocytopaenia-4 (3-C, 1-P/C); grade 3-anaemia-1 (C). Dose reduction was required for 46.1% (12/26) in the combination arm and 25.5% (11/43) in the C arm. There were 35 dose delays-34.6% (9/26) C/P and 60.4% (26/43) C. Median survival for this group of patients was 21.3months. Median PFS was 8.8 months in C/P arm and 7 months in the C arm (95% CI-0.71 to1.8-not statistically significant). Conclusions: The toxicity of combination treatment with C/P is comparable to single agent C in elderly population with frequent dose delays and dose reductions. Initial assessment of comorbidities and performance status is essential however effort should be made to offer patients optimal treatment with the combination regimen

Escobar syndrome in three male patients of same family

We describe three male individuals from a consanguineous south Indian family affected with the multiple pterygium syndrome (Escobar syndrome). Common clinical features included short stature, multiple pterygium, skeletal anomalies, and normal intelligence. The first report of this condition was made in 1902 from this same place (Pondicherry) and the disease received its present popular name Escobar syndrome in 1982. The genetic defect for this condition was identified in 2006 as mutation in the fetal acetylcholine receptor