Thymoquinone affects hypoxia-inducible factor-1α expression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways.

BACKGROUND: Pancreatic cancer (PC) is associated with some of the worst prognoses of all major cancers. Thymoquinone (TQ) has a long history in traditional medical practice and is known for its anti-cancer, anti-inflammatory, anti-fibrosis and antioxidant pharmacological activities. Recent studies on hypoxia-inducible factor-1α (HIF-1α) and PC have shown that HIF-1α affects the occurrence and development of PC in many aspects. In addition, TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α. Therefore, we speculate whether TQ affects HIF-1α expression in PC cells and explore the mechanism. AIM: To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1α expression. METHODS: Cell counting kit-8 assay, Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity, migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial (hTERT-HPNE) cells. Quantitative real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1α mRNA and protein in PC cells. The effects of TQ on the HIF-1α protein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and co-immunoprecipitation. RESULTS: TQ significantly inhibited proliferative activity, migration, and invasion ability and promoted apoptosis of PANC-1 cells; however, no significant effects on hTERT-HPNE cells were observed. TQ significantly reduced the mRNA and protein expression levels of HIF-1α in PANC-1, AsPC-1, and BxPC-3 cells. TQ significantly inhibited the expression of the HIF-1α initial expression pathway (PI3K/AKT/mTOR) related proteins, and promoted the ubiquitination degradation of the HIF-1α protein in PANC-1 cells. TQ had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1α protein but affected the stability of the HIF-1α protein by inhibiting the interaction between HIF-1α and HSP90, thus promoting its ubiquitination degradation. CONCLUSION: The regulatory mechanism of TQ on HIF-1α protein expression in PC cells was mainly to promote the ubiquitination degradation of the HIF-1α protein by inhibiting the interaction between HIF-1α and HSP90; Secondly, TQ reduced the initial expression of HIF-1α protein by inhibiting the PI3K/AKT/mTOR pathway.

Retroperitoneal cavernous hemangioma misdiagnosed as lymphatic cyst: A case report and review of the literature.

BACKGROUND: Primary abdominal and retroperitoneal cavernous hemangioma is a vascular tumor and rarely seen in the clinic. Due to the lack of specific imaging features, retroperitoneal cavernous hemangioma cannot be diagnosed accurately. Some symptoms may develop with the enlargement of lesion volume or the occurrence of complications such as rupture or oppression. We report here a special case who was admitted with chronic abdominal pain. Admission examination suggested a retroperitoneal lymphatic duct cyst. Laparoscopic resection of the retroperitoneal mass was performed, and histological examination confirmed retroperitoneal cavernous hemangioma. CASE SUMMARY: The patient was a 43-year-old Tibetan woman with intermittent left lower abdominal pain and discomfort 3 years ago. Ultrasonography revealed a cystic mass in the retroperitoneum with clear boundaries, internal septa, and no blood flow signal. Computed tomography (CT) and magnetic resonance imaging (MRI) showed an irregular space-occupying mass in the retroperitoneum, and retroperitoneal lymphatic cyst was considered. Plain CT scanning showed multiple cyst-like hypo-intense shadows in the retroperitoneum, partially fused into a mass, and no obvious enhancement was found on enhanced scanning. MRI showed multiple irregular clump-like long T1 and long T2 signal shadows above the pancreas, within which linear short T2 signal shadows were seen. Diffusion-weighted imaging sequence showed hypo-signal shadows, without obvious enhancement on enhanced scanning. Ultrasound, CT, and MRI all suggested the possibility of retroperitoneal lymphatic cyst. However, the patient was finally diagnosed with retroperitoneal cavernous hemangioma by pathological examination. CONCLUSION: Retroperitoneal cavernous hemangioma is a benign lesion, and it is difficult to make a diagnosis preoperatively. Surgical resection may be the only treatment, which not only allows histopathological confirmation as a diagnostic purpose and excludes any risk of malignancy, but also avoids invasion of adjacent tissues, oppression, and other complications as a therapeutic goal.

The pretransplant neutrophil-lymphocyte ratio as a new prognostic predictor after liver transplantation for hepatocellular cancer: a systematic review and meta-analysis.

AIM: Recently, many reports showed that the pretransplant neutrophil-lymphocyte ratio (NLR) may be correlated with the prognosis of patients undergoing liver transplantation (LT) for hepatocellular cancer (HCC). However, their results still remained controversial. Thus we performed a meta-analysis of 13 studies to estimate the prognostic value of pretransplant NLR. METHODS: Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to September 2017. Hazard ratio (HR) or odds ratio (OR) with its 95% CI was used to evaluate the association between elevated NLR and the prognosis or clinical features of liver cancer patients. RESULTS: A total of 13 studies including 1936 patients were included in this meta-analysis. Elevated pretransplant NLR had a close association with the overall survival (HR: 2.22; 95% CI: 1.34-3.68), recurrence-free survival (HR: 3.77; 95% CI: 2.01-7.06) and disease-free survival (HR: 2.51; 95% CI: 1.22-5.15) of patients undergoing LT for HCC, respectively. In addition, elevated NLR was associated with the presence of vascular invasion (OR: 2.39; 95% CI: 1.20-4.77) and Milan criteria (OR: 0.26; 95% CI: 0.17-0.40). CONCLUSION: The results of this meta-analysis showed that elevated pretransplant NLR may be used as a new prognostic predictor after LT for HCC.

Association between fibroblast growth factor receptor-2 gene polymorphism and risk of breast cancer in Chinese populations: A HuGE review and meta-analysis.

AIM OF STUDY: To evaluate the effect of fibroblast growth factor receptor.2. (FGFR2) on genetic susceptibility for breast cancer. (BC) in Chinese populations. MATERIALS AND METHODS: A computerized literature search was carried out in PubMed, Chinese Biomedical Database. (CBM), and Chinese National Knowledge Infrastructure. (CNKI) to collect relevant articles. Pooled odds ratio. (OR) and 95% confidence interval. (CI) were used to assess the strength of the associations. RESULTS: A total of 21 articles involving a total of 15 polymorphisms of the FGFR2 gene were included in the meta-analysis. Due to the limited studies for rs17102287, rs2981578, rs3135718, rs3803662, rs3750817, rsl0510097, rsl7542768, rs13387042, and rs1982073; we only pooled the six polymorphisms. (rs11200014, rs1219648, rs2420946, rs2912778, rs2981579, and rs2981582) into this meta. ANALYSIS: Overall, significantly increased BC risk was associated with five polymorphisms. (rs2981579, rs2981582, rs1219648, rs2420946, and rs2912778) when all studies were pooled into the meta. ANALYSIS: When stratified by ethnicity and source of controls, similar results were also detected. However, for rs2981579 no significant association was found among Chinese Han in all genetic models. CONCLUSION: Our meta-analysis suggests that FGFR2 is likely an important genetic marker contributing to susceptibility of BC. We recommend that these single nucleotide polymorphisms to be included in future association studies and functional assays.

Methylenetetrahydrofolate reductase polymorphisms and susceptibility to esophageal cancer in Chinese populations: a meta-analysis.

Although many epidemiologic studies investigated the methylenetetrahydrofolate reductase (MTHFR) polymorphisms and their associations with esophageal cancer, definite conclusions could not be drawn. To clarify the effects of MTHFR polymorphisms on the risk of esophageal cancer, a meta-analysis was here performed in Chinese populations. A total of 16 studies including 3,040 cases and 4,127 controls were involved in this meta- analysis. Overall, significant associations were found between the MTHFR C677T polymorphism and esophageal cancer risk when all studies in Chinese populations were pooled into the meta-analysis (T vs. C, OR = 1.19, 95% CI = 1.06-1.34; TT vs. CC, OR = 1.35, 95% CI = 1.07-1.70; TT+ CT vs. CC, OR = 1.29, 95% CI = 1.08-1.54; TT vs. CC + CT, OR = 1.19, 95% CI = 1.03-1.37). In subgroup analyses stratified by ethnicity and source of controls, the same results were found in Kazakh (TT vs. CC, OR = 1.38, 95% CI = 1.02-1.87; TT + CT vs. CC, OR = 1.50, 95% CI = 1.03-2.18), in not stated populations (T vs. C, OR = 1.24, 95% CI = 1.08-1.42; TT vs. CC, OR = 1.47, 95% CI = 1.10-1.96; TT + CT vs. CC, OR = 1.30, 95% CI = 1.05-1.60; TT vs. CC + CT, OR = 1.32, 95% CI = 1.12-1.56), and in hospital-based studies (T vs. C, OR = 1.34, 95% CI = 1.19-1.51; TT vs. CC, OR = 1.81, 95% CI = 1.37-2.39; TT + CT vs. CC, OR = 1.51, 95% CI = 1.26-1.83; and TT vs. CC + CT, OR = 1.39, 95% CI = 1.13-1.70). In conclusion, this meta-analysis provides evidence that the MTHFR C677T polymorphism contributes to esophageal cancer development in Chinese populations.