Resveratrol (trans-3,4,5’ –trihydroxystilbene) is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3) was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS) generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.
The aim of this study was to investigate the expression of cyclooxygenase type-2 (COX-2) and its association with angiogenesis and clinicopathologic characteristics of colorectal carcinoma (CRC). COX-2 expression was detected by means of immunohistochemistry in a series of human tissue samples with CRC (n = 120), dysplasia tissue closely adjacent to carcinomas (n = 40) and normal colorectal mucosa (n = 40), and their expressions association with vascular endothelial growth factor (VEGF), CD31-labeled micorvessel density(MVD) in CRC and other clinicopathologic characteristics were investigated. The expression of COX-2 in CRC tissues (78.3%) was obviously higher than that in adjacent tissue and normal mucosal tissue (p<0.01). COX-2 expression was correlated significantly with the grading, advanced cancer, Dukes stage and lymph node metastasis, distant metastasis and VEGF (p<0.05). Our result demonstrates that COX-2 expression was significantly higher in earlier stages of CRC. It can be suggested that COX-2 expression may be important in the initial development of CRC. The findings of the present study suggest that COX-2 overexpression in CRC may be considered as a negative prognostic marker.
ObjectiveGastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a rare and heterogeneous group of tumors with varied biology and still constitute a diagnostic and therapeutic challenge for physicians of all specialties. In the present study, we aimed to review and study the clinicopathological characteristics of GEP-NENs applying the World Health Organization (WHO) 2010 grading criterion.MethodsA total of 48 patients were enrolled in the study. The study included patients diagnosed with GEP-NENs who were treated and followed up at our Hospital from January 2013 to December 2017. Data regarding clinicopathological features of the patients were retrospectively evaluated. The expression of neuroendocrine markers was measured using the immunohistochemical Ultra SensitiveTMS-P method of staining in 48 cases of primary GEP-NENs; and serum levels of neuron-specific enolase, carbohydrate an-tigen 19-9, and carcinoembryonic antigen in 36 GEP-NEN patients were measured using the electrochemiluminescence method.ResultsThe median age at presentation was 59.3 (range 48-82) years, and 39 cases (81.3%) were seen between the 5th and 6th decades. There was a male predilection (male: female=3:1). In 79.2% cases (38/48), tumors were hormonally nonfunctional. The most common presentation was abdominal pain, and the most frequent primary site of the tumor was the rectum, followed by the stomach (n = 15, 31.3%), colon (n = 5, 10.4%), and so on. Of the 48 tumors, 16 (33.3%) were G1, 6 (12.5%) cases were G2, 16 (33.3%) were neuroendocrine carcinoma (NEC), and 10 (20.8%) were mixed adenoneuroendocrine carcinoma (MANEC). According to the AJCC/UICC classification, 45.8% (n = 22) were diagnosed at low stage (stage I or II) while 54.2% (n = 26) were diagnosed at high stage (stage III or IV) (the majority of NEC, G3, and MANEC). A male preponderance was noted for all tumors except for G2 neoplasms, which showed no gender predilection. Thirty-nine patients underwent endoscopic biopsy. The lesions in 18.8% (n = 9) of the patients were indentified only radiologically. After the surgical procedures, 36 had at least one follow-up visit with a median follow-up duration of 5 months; the mean follow-up period was 28 ± 16 months. The one-year and three-year survival rates were 72.2% (26/36) and 61.1% (22/36), respectively. This study did not find an effect of grade 3 (G3) of tumor on the short-term clinical outcome of these patients. In the survival analysis, NEN G3, higher stage (stage III or IV) according to the AJCC/UICC classification (P < 0.05), and metastases at diagnosis (P < 0.05) were associated with poorer prognosis.ConclusionMost GEP-NENs are nonfunctional and nonspecific in presentation. The most frequent primary site of the tumor was the rectum and the commonest ages at diagnosis were the 5th and 6th decades. Endoscopic biopsy is the main diagnostic and histological grading method for GEP-NEN. In the survival analysis, NEN G3, a higher stage according to the AJCC/UICC classification, and metastases at diagnosis are associated with poorer prognosis.
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