MicroRNA-95-3p promoted the development of prostatic cancer via regulating DKK3 and activating Wnt/ß-catenin pathway.

OBJECTIVE: Previous studies have shown that microRNA-95-3p (miR-95-3p) plays a crucial role in multiple human cancers except for prostatic cancer (PCa). Therefore, the function of miR-95-3p was investigated in PCa in the present work. PATIENTS AND METHODS: The expression of miR-95-3p was measured by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) assay. Western blot assay was used to examine the protein expression of epithelial-mesenchymal transition (EMT) markers. In addition, the function of miR-95-3p was detected through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays. Dual Luciferase assay was applied to confirm the relationship between miR-95-3p and dickkopf-3 (DKK3). The tumor growth was observed through xenograft tumor formation assay. RESULTS: The upregulation of miR-95-3p was detected in PCa tissues and cell lines, which predicted poor prognosis of PCa patients. Moreover, miR-95-3p promoted cell proliferation, migration and invasion in PCa by targeting DKK3 and activating the Wnt/ß-catenin pathway. MiR-95-3p also promoted the tumor growth of PCa in vivo. Besides that, downregulation of DKK3 was identified in PCa and low DKK3 expression predicted poor prognosis of PCa patients. CONCLUSIONS: MiR-95-3p promoted the development of PCa via targeting DKK3 and activating the Wnt/ß-catenin pathway.

[Effect of single nucleotide polymorphisms of RS1826690 located in UGT2B4 gene on the pathological complete response to neoadjuvant chemotherapy in breast cancer patients].

Objective: To evaluate the association between single nucleotide polymorphisms (SNPs) of RS1826690 located in UGT2B4 gene and pathological complete response (pCR) to neoadjuvant chemotherapy in breast cancer patients. Methods: A total of 146 breast cancer patients were enrolled to detect the SNPs of RS1826690 by sequenom. The relationship between SNPs of RS1826690 and pCR, predictors of pCR were analyzed by univariate or multivariate analysis. Results: The frequency of CC, CT and TT genetype of RS1826690 was 20.6%, 39.7% and 39.7%, respectively. Of the 171 patients, pCR was achieved in 39 cases (26.7%), with CC allele in 14 cases, CT allele in 7 cases and TT allele in 18 cases, and statistically significant difference was observed (χ(2)=16.684, P=0.003). Multivariate logistic regression analysis showed that SNPs of RS1826690 was an independent predictor of pCR (95% CI: 2.311-28.810, P=0.001) . SNPs of RS1826690 was statistically associated with estrogen receptor (ER) status (χ(2)=7.872, P=0.020). Conclusion: SNPs of RS1826690 was associated with pCR, and breast cancer patients with CC allele were more likely to achieve pCR.

Quercetin induces protective autophagy and apoptosis through ER stress via the p-STAT3/Bcl-2 axis in ovarian cancer.

Quercetin (3,3',4',5,7-pentahydroxyflavone, Qu) is a promising cancer chemo-preventive agent for various cancers because it inhibits disease progression and promotes apoptotic cell death. In our previous study, we demonstrated that Qu could evoke ER stress to enhance drug cytotoxicity in ovarian cancer (OC). However, Qu-induced ER stress in OC is still poorly understood. Here, we demonstrated that Qu evoked ER stress to involve in mitochondria apoptosis pathway via the p-STAT3/Bcl-2 axis in OC cell lines and in primary OC cells. Unexpectedly, inhibition of ER stress did not reverse Qu-induced cell death. Further functional studies revealed that Qu-induced ER stress could activate protective autophagy concomitantly by activating the p-STAT3/Bcl-2 axis in this process. Moreover, the autophagy scavenger 3-MA was shown to enhance Qu's anticancer effects in an ovarian cancer mice xenograft model. These findings revealed a novel role of ER stress as a "double edge sword" participating in Qu-induced apoptosis of OC and might provide a new angle to consider in clinical studies of biological modifiers that may circumvent drug resistance in patients by targeting protective autophagy pathways.

Efficacy and influence factors of icotinib hydrochloride in treating advanced non-small cell lung cancer.

OBJECTIVE: To evaluate the efficacy and safety of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC) and discuss the influence factors on efficacy. PATIENTS AND METHODS: 120 treatment-experienced patients confirmed by pathology or cytology with stage III B-IV non-small cell lung cancer took icotinib hydrochloride and erlotinib orally until the occurrence of disease progression or serious adverse reactions. Then, the efficacy of icotinib hydrochloride and the related influence factors were analyzed. RESULTS: In icotinib hydrochloride group, the response rate and the disease control rate were 30.00% and 65.00%, and the median progression-free survival time was 179 days (95% CI: 103.21-254.78); in erlotinib group, the response rate and the disease control rate were 25.00% and 56.70%, and the median progression-free survival time was 121 days (95% CI: 95.05-146.94). Moreover, the objective response rate and the disease control rate of second-line therapy were both superior to the third-line and above therapy. The objective response rate of patients with complete response/partial response/stable disease after the first-line therapy was higher than that of patients without response after the first-line therapy (p<0.05), and the significant differences existed in the objective response rate and the disease control rate among mutant group, wild-type group, and unknown group (p<0.05). The response rate and the disease control rate of erythra group were higher than those of non-erythra group (p<0.05). It was showed in the univariate analysis that the progression-free survival was correlated with the smoking status and the epidermal growth factor receptor gene mutations. CONCLUSIONS: The icotinib hydrochloride is effective and safe in treating the treatment-experienced patients with advanced NSCLC, especially for patients with sensitive mutations.

[Platelet to lymphocyte ratio in peripheral blood and body mass index: novel independent prognostic factors in patients with melanoma].

Objective: To investigate whether platelet to lymphocyte ratio (PLR) in peripheral blood and body mass index (BMI) can be independent prognostic factors in patients with melanoma. Methods: Clinical date of 140 patients with melanoma in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital from January 1, 2010 to December 31, 2015 were analyzed retrospectively.Receiver operating characteristic (ROC) curve was performed the optimal cut-off value for PLR.The 140 patients were divided into high PLR group and low PLR group.According to "Guidelines for prevention and control of overweight and obesity in Chinese adults" , the patients were divided into high BMI group and low BMI group.The relationship between PLR, BMI with overall survival (OS), progression free survival (PFS) and disease free survival (DFS) were analyzed.The Kaplan-Meier method and Log rank test was used for univariate survival analysis and Cox proportional hazards regression model for multivariate analysis. Results: The optimal cut-off value of PLR determined by ROC curve was PLR=120.15, and BMI threshold was 24.Univariate survival analysis showed that PLR, BMI and clinical stage were the factors affecting the OS in patients (P<0.05). The median survival time (MST) was 21 months in the whole group and 17 months in the high PLR group, 34 months in the low PLR group, respectively; the MST in the high and low BMI group were 29 months and 13 months, respectively.The difference was statistically significant (P<0.05). The effects of PLR and BMI on PFS and DFS were not statistically significant.Cox multivariate analysis showed that PLR, BMI and clinical stage were independent prognostic factors of OS (P<0.05). And BMI was the only independent protective factor for OS, the risk of death decreased by 0.611 times, with each unit increased for BMI.Clinical subgroup analysis showed that PLR also was risk factor to the prognosis of patients with stage Ⅱ, Ⅲ, and Ⅳ (P<0.05). Conclusions: PLR is an independent prognostic risk factor for patients with melanoma, and BMI is an independent protective factor.PLR and BMI are important factors in prognostic evaluation of melanoma.

[Preliminary study for the roles and mechanisms of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles in the Lewis lung cancer mice].

OBJECTIVE: To comparatively observe the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the Lewis lung cancer mice and to explore the mechanisms of Rg3 and PEG-PLGA-Rg3 nanoparticle anti-cancer in vivo. METHODS: Lewis lung cancer mouse model was established and 60 mice were randomly divided into 5 groups with twelve in each group: PEG-PLGA-Rg3 nanoparticles group(Rg3-N), PEG-PLGA group (PEG), Rg3 group (Rg3), normal control group(C), saline control group(NS), and received intragastric administration for 14 days. The weights of the mice were measured every 2 days and the weight curves were obtained. At the same time, the color pattern, activity and mental status were observed. The mice were sacrificed when the administration was over, and the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on tumor weight, and the tumor:weight ratios were analysed. In addition, the tumor microvessel density (MVD) was measured by immunohistochemical staining with anti-CD31 antibody to compare the effects of Rg3 and PEG-PLGA-Rg3 nanoparticles on the tumor angiogenesis in vivo. Furthermore, the levels of such angiogenesis and proliferation factors as MMP-9, HIF-1α, VEGF, Ki-67 were examined by RT-PCR, Western blot and immunohistochemistry to explore the internal molecular mechanisms of anti-tumor effects in vivo. RESULTS: The trends of variation of the mice weights in NS group and PEG group were rising early but declining later. In contrast, the trends of the other three groups were rising early and became stable later. In comparison with NS group, the mice of Rg3 group and Rg3-N group had better general status: brighter color, more active and better spirit. Compared with NS group,the tumor weight in PEG group, Rg3 group and Rg3-N group showed no significant difference but the tumor:weight ratio and MVD in Rg3 group and Rg3-N group declined significantly (P<0.01). Besides, there was no significant difference between Rg3 group and Rg3-N group. At the same time, the level of VEGF mRNA, the protein expression of MMP-9, HIF-1α, VEGF in Rg3 group and Rg3-N group decreased compared with NS group. Furthermore, the level of each index above-mentioned in Rg3-N group was lower than that in Rg3 group. The expression of Ki-67 in PEG group, Rg3 group and Rg3-N group showed no significant difference compared with NS group. CONCLUSION: Rg3 and PEG-PLGA-Rg3 nanoparticle may suppress the expression of VEGF, MMP-9 and HIF-1α in Lewis lung cancer mice, thereby indirectly contributing to their antitumor effects and alleviating the mice's general status. In addition, PEG-PLGA nanoparticles embedding can promote Rg3 antitumor effect in vivo.

Bio-informatics analysis of renal carcinoma gene matrix metalloproteinase-7.

BACKGROUND: Renal cancer is one of the common malignant tumors of the urinary system, seriously threatening human being's health. The current discoveries, however, are far enough for efficient and secure treatment of renal cancer. AIMS: The aim was to explore the mechanism of matrix metalloproteinase-7 (MMP-7) protein in renal carcinoma cell metastasis by bioinformatics analysis. MATERIALS AND METHODS: Bioinformatics methods were used to analyze the composition of amino acids, as well as transmembrane structure, coiled coils, subcellular localization, signal peptide, functions and structures at all levels. RESULTS AND CONCLUSIONS: It showed that the gene MMP-7 totally had 1131 bp. A peptide chain containing 267 amino acids was encoded in the coding region. Based on random coil, α helix, and further super-helix, it had formed a stable neutral hydrophilic protein. The subcellular location analysis indicated that the protein was located outside the cell. The mature peptide started from the 18th amino acid, and its front-end was the sequence of the signal peptide, belonging to the secreted protein. Analysis of the functional domain showed that this protein had two functional domains, the PG binding domain, and the zinc finger binding domain. Moreover, the protein, which was cross-linked with it, was also one related to cancer cell proliferation and metastasis. To sum up, MMP-7 is a stable neutral hydrophilic secreted protein, and it may play a vital role in the invasion and metastasis of cancer cells.

Growth factor activity of IL-6 in the synovial fluid of patients with rheumatoid arthritis.

OBJECTIVE: We set out to determine whether the ability of synovial fluids (SF) in patients with rheumatoid arthritis (RA) to facilitate the proliferation of synovial tissue-derived fibroblastic cell lines was related to the presence of growth factors and/or cytokines. METHODS: The growth factor activity of 20 RA SF was measured by their ability to induce anchorage-independent growth of the rat NRK-49F (49F) fibroblastic strain. The presence of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) was also assessed using neutralising anti-TGF-beta or anti-PDGF-AB mAbs. Cytokines were measured by functional assays or ELISA: RESULTS: We observed a correlation between growth factor activity and the IL-6 levels in SF. Both were correlated to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in SF and serum. IL-6 (at concentrations above 10(4) U/ml), synergized with growth factors in the induction of the anchorage independent (AI) growth of 49F cells. Pretreatment of SF with a neutralising anti-IL-6 mAb substantially reduced the capacity of these SF to induce AI growth of 49F cells, confirming the growth factor activity of IL-6 in this test. In contrast, IL-6 alone or in association with PDGF, epidermal growth factor (EGF) or TGF-beta had no effect on the anchored growth of synovial tissue-derived fibroblasts, and treatment of SF with a neutralising anti-IL-6 mAb did not affect their ability to increase the growth rate of synovial tissue-derived fibroblasts. CONCLUSIONS: These results strongly suggest that IL-6 is responsible for the observed correlation between the growth factor activity of SF and inflammatory indexes such as ESR and CRP. However, neither IL-6 nor PDGF were responsible for the observed positive effect of SF on synovial fibroblastic cell lines.