Angiogenesis-related gene expression profile with independent prognostic value in advanced ovarian carcinoma.

BACKGROUND Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients. METHODOLOGY/PRINCIPAL FINDINGS RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001). CONCLUSIONS/SIGNIFICANCE It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma.

Loss of ovarian hormones increases salt-sensitivity in normotensive women

Salt sensitivity (SS) is associated with an elevated risk of developing hypertension(HTN) and is an independent risk factor for cardiovascular (CV) morbidity and mortality. Cross-sectional studies have suggested that postmenopausal women are more salt sensitive than premenopausal women. The purpose of the present study was to investigate prospectively the prevalence of SS among healthy premenopausal women and determine whether the loss of ovarian hormones increases SS.

Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition.

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

Surgical menopause increases salt sensitivity of blood pressure

Salt sensitivity of blood pressure is associated with an elevated risk of developing hypertension (HTN) and is an independent risk factor for cardiovascular disease. The prevalence of HTN increases after menopause. The aim of this study was to investigate prospectively whether the loss of ovarian hormones increases the occurrence of salt sensitivity among healthy premenopausal women. We enrolled 40 normotensive, nondiabetic women (age 47.2+/-3.5), undergoing hysterectomy-oophorectomy for nonneoplastic processes and not on hormone replacement, to determine the effect of changes in sodium intake on blood pressure the day before and subsequently 4 months after surgical menopause. Salt loading was achieved using a 2-L normal saline infusion and salt depletion produced by 40 mg of intravenous furosemide. A decrease >10 mm Hg in systolic blood pressure between salt loading and salt depletion was used to define salt sensitivity. Before and after menopause, salt-sensitive women exhibited higher waist/hip and waist/thigh ratios (P<0.01). Although all of the women remained normotensive, the prevalence of salt sensitivity was significantly higher after surgical menopause (21 women; 52.5%) than before (9 women; 22.5%; P=0.01), because 12 (38.7%) salt-resistant women developed salt sensitivity after menopause. In summary, we demonstrated that the prevalence of salt sensitivity doubled as early as 4 months after surgical menopause, without an associated increase in blood pressure. Epidemiological studies indicate that development of HTN may not occur until 5 to 10 years after menopause. The loss of ovarian hormones may unmask a population of women prone to salt sensitivity who, with aging, would be at higher risk for the subsequent development of HTN and cardiovascular disease.

Vertebral artery occlusion after chemotherapy

We present a patient who experienced a stroke due to vertebral artery occlusion after chemotherapy

Endometriosis: alternative methods of medical treatment.

Endometriosis is an inflammatory estrogen-dependent disease defined by the presence of endometrial glands and stroma at extrauterine sites. The main purpose of endometriosis management is alleviating pain associated to the disease. This can be achieved surgically or medically, although in most women a combination of both treatments is required. Long-term medical treatment is usually needed in most women. Unfortunately, in most cases, pain symptoms recur between 6 months and 12 months once treatment is stopped. The authors conducted a literature search for English original articles, related to new medical treatments of endometriosis in humans, including articles published in PubMed, Medline, and the Cochrane Library. Keywords included "endometriosis" matched with "medical treatment", "new treatment", "GnRH antagonists", "Aromatase inhibitors", "selective progesterone receptor modulators", "anti-TNF α", and "anti-angiogenic factors". Hormonal treatments currently available are effective in the relief of pain associated to endometriosis. Among new hormonal drugs, association to aromatase inhibitors could be effective in the treatment of women who do not respond to conventional therapies. GnRH antagonists are expected to be as effective as GnRH agonists, but with easier administration (oral). There is a need to find effective treatments that do not block the ovarian function. For this purpose, antiangiogenic factors could be important components of endometriosis therapy in the future. Upcoming researches and controlled clinical trials should focus on these drugs.