ABSTRACT
OBJECTIVE: Endometrial cancer, in developed countries, is the most common malignancy of the female genital tract. Surgery and radiotherapy are successful in many patients but systemic and recurrent diseases have no consistently effective treatments, and for high grade advanced disease the prognosis is poor. The study investigated characteristics of adrenomedullin in endometrial cancer to assist in identifying targets for developing treatments. METHODS: Endometrial samples of women with and without cancer, and the Ishikawa cell line were used to investigate adrenomedullin mRNA regulation, peptide expression, adrenomedullin secretion and effects of adrenomedullin on VEGF secretion. RESULTS: Expression of adrenomedullin mRNA was upregulated compared to that in healthy post-menopausal endometria. Adrenomedullin secretion was increased by cobalt chloride in this study. Secretion was reduced by the naturally-occurring compounds, (-)-epigallocatechin gallate (EGCG) and 3,4',5-trihydroxystilbene (resveratrol), which we have previously demonstrated to also suppress VEGF secretion in endometrial tumour tissue. We noted, for the first time, that adrenomedullin enhanced VEGF secretion from tumour cells. CONCLUSIONS: Increased adrenomedullin expression may result in amplifying both tumorigenic and angiogenic activities. A substantial impact on growth of tumours may result in vivo as a consequence of the synergism between adrenomedullin and VEGF. Adrenomedullin, which has altered cellular characteristics in tumour compared to healthy tissue, offers an understudied target with potential to modify endometrial cancer behaviour, complementing other treatments.
Subject(s)
Adenocarcinoma/metabolism , Adrenomedullin/metabolism , Biomarkers, Tumor/metabolism , Endometrial Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Vascular Endothelial Growth Factor A/metabolism , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adrenomedullin/antagonists & inhibitors , Adrenomedullin/genetics , Biomarkers, Tumor/genetics , Case-Control Studies , Catechin/analogs & derivatives , Catechin/metabolism , Cell Line, Tumor , Cobalt/metabolism , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Humans , Neoplasm Grading , RNA, Messenger/metabolism , Resveratrol , Stilbenes/metabolism , Up-RegulationABSTRACT
OBJECTIVE: The objective of this study was to compare the sensitivity of cervical cytology using conventional smears and SurePath liquid-based cytology (LBC). DESIGN: Prospective randomised evaluation of diagnostic test. SETTING: A single institution colposcopy clinic. POPULATION: Women attending first visit colposcopy appointments were offered entry into the study. METHODS: Cervical cytology samples from 913 women of age 16-75 years were randomly processed as SurePath LBC or conventional smears. Conventional smears were taken for 453 women and a SurePath LBC taken for 451 women. Cytology results were correlated with colposcopic findings and histology from colposcopic biopsies, treatment and follow up. MAIN OUTCOME MEASURES: To compare the sensitivity of SurePath LBC and conventional smears for histologically proven abnormality. Other outcome measures include a comparison of their sensitivity for high-grade abnormalities and their satisfactory rate. RESULTS: Accounting for all randomised samples, there was a trend towards improved sensitivity for SurePath LBC (79.1 versus 73.7%, P = 0.1). However, excluding unsatisfactory cytology (and samples not taken) eliminated this trend; the sensitivity for both LBC and conventional smears for any epithelial abnormality was 81%. With a threshold of atypical squamous cells of uncertain significance (ASC-US), both SurePath LBC and conventional smears had a sensitivity of 92% for high-grade lesions. SurePath LBC was less likely to be reported as unsatisfactory (2.7 versus 9.1%, P < 0.0001). CONCLUSIONS: In this context, with a threshold of ASC-US, both SurePath LBC and conventional smears offer high sensitivity for the detection of CIN2/3, but SurePath LBC is less likely to be reported as unsatisfactory.
Subject(s)
Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Adolescent , Adult , Aged , Ambulatory Care , Colposcopy/methods , Female , Humans , Middle Aged , Prospective Studies , Sensitivity and Specificity , Vaginal Smears/methods , Young AdultABSTRACT
⺠Ovarian small cell carcinoma usually occurs in adolescents or young adults. ⺠Long term survival of advanced stage disease is extremely rare. ⺠Fertility may be conserved and should be considered as part of management.
ABSTRACT
Thirty-two patients with epithelial ovarian cancer received paclitaxel 175 mg/m2, by 3-hour infusion, in this prospective phase 2 study. All patients had relapsed or progressed after initial cisplatin/cyclophosphamide therapy. Thirteen patients received paclitaxel as second line therapy, 14 as third line therapy and 5 as fourth line therapy. One patient was excluded from efficacy analysis, due to a severe anaphylactic reaction to the first cycle of paclitaxel therapy. Of the 31 evaluable patients, complete remission was observed in 3 patients (9.7%) and partial remission in 11 patients (35.5%), with a total response rate of 45.2%. The median survival from diagnosis for the 31 evaluable patients was 32.5 months and the median survival following therapy with paclitaxel was 12.2 months (range 4-27 months). The 3 patients who achieved a complete response remain alive, at greater than 20 months, since commencing paclitaxel. Twelve patients (38.7%) who achieved a partial response, or had stable disease, had a median survival, after paclitaxel treatment, of greater than 18 months. This study confirms the activity of paclitaxel in relapsed ovarian cancer and demonstrates a prolonged survival benefit in greater than one third of this group of patients.