Glutamine is one of the main nutrients used by tumor cells for biosynthesis. Thus, targeted inhibition of glutamine metabolism may have anti-tumorigenic implications. In the present study, we aimed to evaluate the effects of glutamine on ovarian cancer cell growth. Three ovarian cancer cell lines, HEY, SKOV3, and IGROV-1, were assayed for glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis, cell stress, and glucose/glutamine metabolism. Our results revealed that administration of glutamine increased cell proliferation in all three ovarian cancer cell lines in a dose dependent manner. Depletion of glutamine induced reactive oxygen species (ROS) and expression of endoplasmic reticulum (ER) stress proteins. In addition, glutamine increased the activity of glutaminase (GLS) and glutamate dehydrogenase (GDH) by modulating the mTOR/S6 and MAPK pathways. Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. These studies suggest that targeting glutamine metabolism may be a promising therapeutic strategy in the treatment of ovarian cancer.
Vitamin D is a fat-soluble prohormone best known for its role in maintaining calcium homeostasis. Large numbers of epidemiological studies have shown that vitamin D plays an important role in cancer prevention by regulating cellular proliferation and metabolism. Studies of the cellular mechanism of vitamin D in ovarian cancer strongly suggest that it exhibits protective and antitumorigenic activities through genomic and nongenomic signal transduction pathways. These results indicate that vitamin D deficiency results in an increase in the risk of developing ovarian cancer and that vitamin supplements may potentially be an efficient way of preventing cancer. Consequently, this review describes the epidemiology, molecular mechanism and evidence linking vitamin D deficiency to ovarian cancer.Electronic supplementary materialThe online version of this article (10.1186/s13048-018-0443-7) contains supplementary material, which is available to authorized users.
Objectives The current study was aimed to evaluate the efficacy and toxicity of postoperative adjuvant chemotherapy (CT) combined with intracavitary brachytherapy (ICRT) in cervical cancer patients with intermediate-risk. Methods We analyzed the medical records of 558 patients who were submitted to radical surgery for Stage IB-IIA cervical cancer. A total of 172 of those 558 patients were considered intermediate-risk according to the GOG criteria. Among those 172 patients, 102 were subjected to CT combined with ICRT (CT+ICRT) and the remaining 70 patients were treated with concurrent chemoradiation (CCRT). The 3-year disease free survival (DFS), overall survival (OS), and complications of each group were evaluated and analyzed. Results No significant difference was observed in 3-year DFS or OS of the patients submitted to CT+ICRT and CCRT. Importantly, the frequencies of grade III to IV acute complications were significantly higher in patients submitted to CCRT than in those treated with CT+ICRT (Hematologic, P = 0.016; Gastrointestinal, P = 0.041; Genitourinary, P = 0.019). Moreover, the frequencies of grade III–IV late complications in patients treated with CCRT were significantly higher compared with CT+ICRT-treated patients (Gastrointestinal, P = 0.026; Genitourinary, P = 0.026; Lower extremity edema, P = 0.008). Conclusions Postoperative adjuvant CT+ICRT treatment achieved equivalent 3-year DFS and OS but low complication rate compared to CCRT treatment in early stage cervical cancer patients with intermediate-risk.
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