Disruption of p97/VCP induces autophagosome accumulation, cell cycle arrest and apoptosis in human choriocarcinoma cells.

Gestational choriocarcinoma is aggressive trophoblastic disease. The development, progression and the cure of this disease is not well-established. p97/Valosin containing protein has been shown to play critical roles in many cellular processes. In various cancers, higher expression of p97/VCP has been reported and targeting of p97/VCP with its spesific inhibitors or siRNA's (siVCP) in cancer therapy was suggested. However, no study is avaible about the expression and function of p97/VCP in gestational choriocarcinoma. Hence, the aim of the study was to evaluate effects of p97/VCP inhibitor, DBeQ and siVCP on choriocarcinoma cells. We use human placental choriocarcinoma cell line (Jeg3) as model to find out the effects of DBeQ and VCP siRNA's (siVCP) on apoptotic and autophagic pathway by immunflouroscence staining, Western blotting, qPCR and flow-cytometry. p97/VCP siRNA's and DBeQ induced accumulation of autophagic proteins, LC3II and p62 in the cytoplasm of Jeg3 cells detected. Concurrently, Jeg3 cells treated with DBeQ and siVCP demonstrated G0/G1 cell cycle arrest, accompanied by accumulation of poly-ubiquitinated proteins. Moreover, disruption of p97/VCP by siRNA and DBeQ inhibited cancer cell growth managing the caspases-3 and -7. Our results show that inhibition of p97/VCP activity with DBeQ and depletion of p97/VCP expression with siRNA in Jeg3 cells induce caspase activation, inhibits cell proliferation and leads to a defect in autophagosome maturation, thus providing potential target for the prevention and treatment of choriocarcinoma.

Is there any relationship between benign endometrial pathologies and metabolic status?

The aim of this study was to assess the relation between benign endometrial pathologies (polyp and/or hyperplasia without atypia) and the metabolic status (insulin resistance and metabolic syndrome) of the patients. A total of 168 cases were enrolled in the study. The patients were classified according to the presence of benign endometrial pathologies and their menopausal status. Then, the subjects were evaluated according to the metabolic syndrome criteria and the presence of an insulin resistance. The insulin resistance levels of the cases were analysed by four different methods. Obesity and a waist circumference of greater than 88 cm were observed significantly more in the study group with endometrial pathologies (p = .005 and p < .001, respectively). It was also observed that a fasting blood glucose level of higher than 110 mg/dL increased the risk of developing endometrial polyps and/or hyperplasia without atypia by almost five folds (OR: 5.26, 95% CI: 1.25-22.12). Furthermore, an insulin resistance was found to be significantly high in the study group (p = .002). Based on the observed significant relationship between an insulin resistance and benign endometrial pathologies, it can be concluded that insulin resistance plays an important role in the development of benign endometrial pathologies. Impact Statement What is already known on this subject? Metabolic anomalies such as obesity, type 2 diabetes, hypertension and dyslipidaemia play an important role in abnormal endometrial proliferation. Also, these metabolic anomalies have been known as risk factors for type I endometrial cancer. What the results of this study add? A significant relationship between an insulin resistance and benign endometrial pathologies was observed. What the implications are of these findings for clinical practice and/or further research? Based on this finding, we concluded that an insulin resistance may play an important role in the development of benign endometrial pathologies. The prevention and the treatment of obesity as a key factor of developing an insulin resistance, may reduce not only the incidence of malignant endometrial pathologies, but also the incidence of benign pathologies and of a malignant transformation.

Coexisting Primary Ovarian and Omental Hydatid Disease Mimicking an Ovarian Neoplasm: A Case Report.

Hydatid disease is a parasitic infection that most commonly affects the liver and lungs, although the disease can arise in any part of the body. Cysts may mimic many benign and malignant conditions. The diagnosis cannot be confirmed preoperatively in all cases. A 44-yr-old menopausal woman was admitted to the department of gynecology with complaints of abdominal distention. A fixed abdominopelvic mass was identified. Radiology revealed a 20-cm mass with branched septations and solid components. CA-125 level was 55 kU/L, and Risk of Malignancy Index-2 score was 880. These findings suggested the presence of an ovarian neoplasm, and laparotomy was performed. Cystic masses measuring 22 cm and 4 cm, originating from the omentum majus and left ovary, respectively, were found during surgery. Frozen-section analysis revealed hydatid disease. Infracolic omentectomy and total abdominal hysterectomy with bilateral salpingo-oopherectomy were performed. Results of a serum Echinococcus hemagglutination test performed immediately after surgery were negative. The patient was prescribed albendazole for 6 mo and discharged on the third postoperative day with no complaints. The incidence of hydatid disease in the female reproductive system is very rare; however, clinicians must be aware of this disease and take necessary precautions while operating because any spillage may lead to anaphylactic shock and increased risk of recurrence.