Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, for which no specific targete d therapy is currently available. The present study aimed to examine the associations of ecotropic virus integration site 1 (EVI-1) and calreticulin (CRT) with other clinicopathological variables and the prognosis of patients with TNBC. The present retrospective cohort study reviewed the medical records of patients with TNBC treated in the Affiliated Hospitals of Jinzhou Medical University between January 2010 and June 2015. The protein expression levels of EVI-1 and CRT in tumor samples obtained from the patients were examined by immunohistochemical analysis. Univariate and multivariate regression analyses were used to identify associations between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Kaplan-Meier analysis was performed to observe the survival condition (DFS/OS) according to EVI-1 and CRT expression. A total of 88 TNBC patients were included in the present study. Tumor tissues in 52 (59.1%) patients were EVI-1 positive, and tumor tissues in 64 (72.7%) patients were CRT-positive, and these rates were significantly higher compared with those in the corresponding paracancerous tissues (P<0.05). Multivariate analysis revealed that EVI-1 and CRT expression levels were independent variables associated with OS and DFS, and high expression of both CRT and EVI-1 was significantly associated with decreased OS and DFS compared with the other subgroups (low EVI-1/low CRT expression, low EVI-1/high CRT expression and high EVI-1/low CRT expression) of patients with TNBC. EVI-1 and CRT expression in TNBC was significantly correlated with poor outcome. Evaluation of the EVI-1 and CRT status may provide insight into prognosis prediction for patients with TNBC.

Background: Docosahexaenoic acid(DHA) inhibits tumor growth and progression in various cancers, including lung cancer. However, the mechanisms involved remain unclear. The aim of this study was to identify the mechanism of DHA in inhibiting progression of non-small cell lung cancer (NSCLC) in vitro.Methods: The proliferation of A549 was tested by MTT, and cell apoptosis was analysed using flow cytometer. The migration and invasion were examined respectively by wound healing assay and Transwell invasion assay. The level of ROS (reactive oxygen species, ROS) was checked by DCF (dichlorodihydrofluorescein, DCF) production in cells. The apoptosis associated protein (caspase-3, PARP, Bax, Bcl-2 and survivin) and metastases associated proteins including HEF1, MMP9 and VEGF were detected by Western blot, and the same method was used in the expression of PI3K and Akt.Results: DHA inhibited proliferation and induced apoptosis of A549 cells. Moreover, it suppressed the invasion and metastasis of A549 cells, while downregulating the levels of metastasis-associated proteins, including HEF1, matrix metallopeptidase (MMP9), and vascular endothelial growth factor (VEGF), in a dose -dependent manner. In addition, DHA inactivated Akt phosphorylation. All of these responses were associated with the accumulation of intracellular ROS. DHA downregulated the level of antioxidant enzymes such as catalase, while the antioxidant Nacetyl-cysteine (NAC) reversed the effect of DHA, which further validated our findings.Conclusions: The present study demonstrates that DHA inhibits the development of non-small lung tumors through an ROS-mediated inactivation of the PI3K/Akt signaling pathway.

AIM:Apparent diffusion coefficient (ADC) value measurement of nodes in diffusion-weighted images (DWI) has been widely used for diagnosis and differential diagnosis of human tumors. We evaluated whether the ADC provided by DWI varies according to the state of estrogen receptors (ER) and progesterone receptors (PR) in breast cancer (BC). MATERIALS AND METHODS:English and Chinese electronic databases were searched for potentially relevant studies followed by a comprehensive literature search. Summary standardized mean difference (SMD) with 95% confidence interval (CI) was used for ER and PR category of ADC value with the use of the Z test. RESULTS:Final analysis from 6 eligible cohort studies between 2010 and 2012 were selected for inclusion. Overall estimates revealed that the mean ADC of ER-positive or PR-positive cancer was significantly lower than that of ER-negative or PR-negative breast cancer (ER- VS. ER+: SMD = 0.64, 95% CI: 0.02-1.27, P = 0.042; PR- VS. PR+: SMD = 0.45, 95% CI: 0.04-0.86, P = 0.032). Country-stratified analysis indicated the mean ADC of ER-positive cancer was significantly lower in China (SMD = 3.92, 95% CI: 2.22-5.62, P < 0.001). Further subgroup analysis by MRI machine type implied that ADC values may be a potential diagnostic indicator for PR levels in breast cancer only when using Non-Phillips 1.5T scanner (SMD = 0.88, 95% CI: 0.64-1.12, P < 0.001). CONCLUSION:ADC values vary significantly according to the ER and PR levels in BC patients, indicating that cancer heterogeneity affects imaging parameters. DWI could therefore be critical for clinical applications of ADC values.

We have reported that SIAH1 is down-regulated and associated with apoptosis and invasion in human breast cancer. However, the molecular mechanisms leading to SIAH1 down-regulation remain to be elucidated. Here, we demonstrated that miR-107 directly down-regulates SIAH1 expression in human breast cancer cells. Over- expression of miR-107 reduced SIAH1 expression, promoted human breast cancer cell proliferation, colony formation, migration and invasion, and inhibited apoptosis. On the contrary, silencing of miR-107 increased SIAH1 expression and inhibited the tumor growth of MDA-MB-231 cells, a kind of triple-negative breast cancer (TNBC) cells, in vitro and in vivo. Our results reveal that miR-107 is an upstream regulator for SIAH1 down-regulation in human breast cancer cells and miR-107 provides a potential effective target for the treatment of TNBC. (c) 2015 Wiley Periodicals, Inc.

Cytochrome P450 1A1 (CYP1A1) usually metabolizes carcinogens to their inactive derivatives but occasionally converts the chemicals to more potent carcinogens. To date, many studies have evaluated the association between the CYP1A1 MspI and Ile462Val polymorphisms and renal cell carcinoma (RCC) risk, but the results have been conflicting. To more precisely evaluate the potential association, we carried out a meta-analysis of seven published case-control studies. The meta-analysis indicated that the MspI polymorphism was associated with an increased RCC risk (allele model: OR = 1.49, 95%CI 1.03–2.16; homozygous model: OR = 1.64, 95%CI 1.13–2.40; dominant model: OR = 1.72, 95%CI 1.07–2.76). No significant associations were found for the Ile462Val polymorphism for all genetic models. When stratified by smoking status, smokers carrying the variant Vt and Val allele were more susceptible to RCC (Vt allele: OR = 3.37, 95%CI = 2.24–5.06; Val allele: OR = 2.07, 95%CI = 1.34–3.19). These data indicate that the CYP1A1 MspI polymorphism significantly increased RCC risk, while the Ile462Val polymorphism was not associated with RCC. Among smokers, individuals with the CYP1A1 Vt allele and Val allele showed a significantly increased risk of RCC. More well-designed studies with larger samples are warranted to show the underlying mechanisms of CYP1A1 in the development of RCC.

Vitamin D receptor ( VDR ) gene polymorphisms have previously been associated with susceptibility to renal cell carcinoma, although the findings are inconsistent. This study therefore evaluated the association of three single nucleotide polymorphisms (SNPs) in VDR (FokI, BsmI, and TaqI) with the risk of renal cell carcinoma in five previous studies of a total of 1,510 cases and 2,101 controls identified from PubMed, Web of Science, Embase, and Wanfang databases. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were calculated, and stratified analysis by ethnicity was conducted for further estimation. All statistical analyses were conducted using STATA software. Obvious heterogeneity was noted among the five studies. The VDR BsmI polymorphism was not found to be associated with renal cell carcinoma risk, although subgroup analysis revealed a significant association with renal cell carcinoma risk in Asians (b vs B OR = 1.479, 95 % CI = 1.171–1.869, P OR = 0.001 and bb vs BB OR = 2.608, 95 % CI = 1.529–4.449, P OR = 0.001). No significant association was found between renal cell carcinoma risk and either FokI or TaqI polymorphisms in different models and populations. Further large-scale studies are required to confirm these conclusions.

Bufalin is a traditional oriental medicine which is known to induce apoptosis in many tumor cells, and it is thus considered as a new anticancer therapeutic. By now, most of the studies of bufalin are in vitro, however in vivo evaluations of its therapeutic efficacy are less and are in great demand for its development toward anticancer drug. One of the problems probably hampering the development of bufalin is the lack of tumor selectivity, which may reduce the therapeutic effect as well as showing side effects. To overcome this drawback, in this study, we designed a tumor-targeted drug delivery system of bufalin based on enhanced permeability and retention (EPR) effect, by using biotinylated chitosan, resulting in bufalin encapsulating nanoparticles (Bu-BCS-NPs) with mean hydrodynamic size of 171.6 nm, as evidenced by dynamic light scattering and transmission electron microscope. Bu-BCS-NPs showed a relative slow and almost linear release of bufalin, and about 36.8% of bufalin was released in 24 h when dissolved in sodium phosphate buffer. Compared to native bufalin, Bu-BCS-NPs exhibited a stronger cytotoxicity against breast cancer MCF-7 cells (IC50 of 0.582 μg/ml vs 1.896 μg/ml of native bufalin). Similar results were also obtained in intracellular reactive oxygen species production, apoptosis induction, and decrease in mitochondria membrane potential. These results may contribute to the rapid intracellular uptake of nanoparticles, partly benefiting from the highly expressed biotin receptors in tumor cells. In vivo studies using MCF-7 tumor models in nude mice confirmed the remarkable therapeutic effect of Bu-BCS-NPs. These findings suggest the potential of Bu-BCS-NPs as an anticancer drug with tumor targeting property.

Renal cell carcinoma (RCC) is common renal malignancy within poor prognosis. TGF-β-activated kinase 1 (TAK1) plays vital roles in cell survival, apoptosis-resistance and carcinogenesis through regulating nuclear factor-κB (NF-κB) and other cancer-related pathways. Here we found that TAK1 inhibitors (LYTAK1, 5Z-7-oxozeanol (5Z) and NG-25) suppressed NF-κB activation and RCC cell (786-O and A489 lines) survival. TAK1 inhibitors induced apoptotic cytotoxicity against RCC cells, which was largely inhibited by the broad or specific caspase inhibitors. Further, shRNA-mediated partial depletion of TAK1 reduced 786-O cell viability whiling activating apoptosis. Significantly, TAK1 was over-expressed in human RCC tissues, and its level was correlated with phosphorylated NF-κB. Finally, kinase inhibition or genetic depletion of TAK1 enhanced the activity of vinblastine sulfate (VLB) in RCC cells. Together, these results suggest that TAK1 may be an important oncogene or an effective target for RCC intervention.

Tumor necrosis factor alpha (TNF-α) has been suggested to play an important role in the development and liver cancer. TNF-α 238 G/A polymorphism was hypothesized to increase the risk of liver cancer, but findings from previous studies were controversial. To explore a more precise estimation of the relationship between TNF-α 238 G/A polymorphism and liver cancer, we performed a meta-analysis. PubMed, Embase, and China Biology Medicine databases were searched for all publications on this association through March 12, 2013. Odds ratios (ORs) with its 95 % confidence intervals (CIs) were used to assess the strength of this association. Eleven studies with 1,406 liver cancer cases and 2,386 noncancer controls were included into this meta-analysis. Overall, there was a significant association between TNF-α 238 G/A polymorphism and increased risk of liver cancer under all three genetic models (A vs. G, OR 1.51, 95 % CI 1.20–1.89, P < 0.001, I 2 = 37.7 %; AG vs. GG, OR 1.49, 95 % CI 1.01–2.21, P = 0.045, I 2 = 53.2 %; AA/AG vs. GG, OR 1.76, 95 % CI 1.35–2.30, P < 0.001, I 2 = 36.5 %). The sensitivity analysis further strengthened the validity of the positive association. Subgroup analysis of nine studies from Asian countries showed that there was a significant association between TNF-α 238 G/A polymorphism and increased risk of liver cancer in Asians (A vs. G, OR 1.35, 95 % CI 1.03–1.76, P = 0.027, I 2 = 40.2 %; AA/AG vs. GG, OR 1.56, 95 % CI 1.14–2.15, P = 0.006, I 2 = 41.9 %). In conclusion, TNF-α 238 G/A polymorphism is significantly associated with increased risk of liver cancer, especially in Asians.

Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a molecular chaperone involved in multidrug resistance and antiapoptosis in some human tumors, but its regulatory mechanisms have not been revealed in esophageal squamous cell carcinoma (ESCC). In this study, 138 specimens of ESCC were analyzed. TRAP1 was overexpressed in ESCC, particularly in poorly differentiated tumors. To further explore the molecular regulatory mechanism, we constructed specific small interfering RNA-expressing vectors targeting Trap1, and knocked down Trap1 expression in the esophageal cancer cell lines ECA109 and EC9706. Knockdown of Trap1 induced increases in reactive oxygen species and mitochondrial depolarization, which have been proposed as critical regulators of apoptosis. The cell cycle was arrested in G2/M phase, and in vitro inhibition of cell proliferation was confirmed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and bromodeoxyuridine assays. Furthermore, re-expression of TRAP1 in Trap1 small interfering RNA-transfected ESCC cells restored cell proliferation and cell apoptosis. Bioluminescence of subcutaneously xenografted ESCC tumor cells demonstrated significant inhibition of in vivo tumor growth by Trap1 knockdown. This study shows that TRAP1 was overexpressed in most patients with ESCC, and caused an increase in antiapoptosis potency. TRAP1 may be regarded as a target in ESCC biotherapy.

The aim of this study was to identify the correlations of a common polymorphism (rs6774494 A > G) in the EVI-1 gene targeted by micro-RNA (miRNA)-206/133b with the pathogenesis of breast cancer (BC). A total of 196 unrelated ethnic Han Chinese women diagnosed with primary BC were consecutively recruited and 200 healthy controls were randomly selected from the same population-based cohort. Direct PCR sequencing assay was used to detection of rs6774494 A > G polymorphism in the EVI-1 gene. Real-time quantitative PCR (RT-PCR) analysis was performed to verify the alterations of the EVI1 messenger RNA (mRNA) levels. Kaplan–Meier analysis was used to investigate and to estimate the survival outcomes for each endpoint. All statistical analyses were performed with SPSS software (version 18.0, SPSS, Chicago, IL). Our results demonstrated that the carriers of EVI-1 AG genotype were more likely to develop BC when compared with the EVI-1 GG genotype (P = 0.034, OR = 1.26, 95% CI = 1.02 ∼ 1.57). In addition, it was found that patients with the G (AG + GG) allele of EVI-1 genetic variants were associated with higher risk of BC compared with the EVI-1 AA genotype (OR = 1.26, 95% CI = 1.02 ∼ 1.54, P = 0.028). The results of a subgroup analysis stratified by menopause revealed that in female post-menopause subgroup patients with the EVI-1 G allele were correlated with a higher risk of BC than those with the EVI-1 AA genotype (OR = 1.31, 95% CI = 1.00 ∼ 1.72, P = 0.054). Kaplan–Meier analyses suggested that carriers of the G allele (AG + GG) were associated with poorer overall survival (OS) and progression-free survival (PFS) compared with those with AA genotype (OS P = 0.042; PFS P = 0.036, respectively). The correlation analysis showed that EVI-1 mRNA levels were negatively associated with miRNA-206/133b levels in the carriers of the G allele (AG + GG) (r = −1.274, P < 0.05). Our findings provide evidence that the EVI-1 rs6774494 G > A polymorphism targeted by miRNA-206/133b may contribute to the pathogenesis of BC.

Immunological functions of heat shock proteins (HSPs) have long been recognized. In this study we aimed to efficiently purify HSP70 from renal cell carcinoma and test it as a tumor antigen for pulsing dendritic cells in vitro. HSP70 was purified from renal cell carcinoma specimens by serial column chromatography on Con A-sepharose, PD-10, ADP-agarose and DEAE-cellulose, and finally subjected to fast protein liquid chromatography (FPLC). Dendritic cells derived from the adherent fraction of peripheral blood mononuclear cells were cultured in the presence of IL-4 and GM-CSF and exposed to tumor HSP70. After 24 hours, dendritic cells were phenotypically characterized by flow cytometry. T cells obtained from the non-adherent fraction of peripheral blood mononuclear cells were then co-cultured with HSP70-pulsed dendritic cells and after 3 days T cell cytotoxicity towards primary cultured renal cell carcinoma cells was examined by Cell Counting Kit-8 assay. Dendritic cells pulsed in vitro with tumor-derived HSP70 expressed higher levels of CD83, CD80, CD86 and HLA-DR maturation markers than those pulsed with tumor cell lysate and comparable to that of dendritic cells pulsed with tumor cell lysate plus TNF-α. Concomitantly, cytotoxic T-lymphocytes induced by HSP70-pulsed dendritic cells presented the highest cytotoxic activity. There were no significant differences when using homologous or autologous HSP70 as the tumor antigen. HSP70 can be efficiently purified by chromatography and induces in vitro dendritic cell maturation in the absence of TNF-α. Conspecific HSP70 may effectively be used as a tumor antigen to pulse dendritic cells in vitro.

Aims: Many existing studies have demonstrated that pituitary tumor transforming gene (PTTG) expression may contribute to the development of pituitary adenomas (PAs), but individually published studies showed inconclusive results. This meta-analysis aimed to derive a more precise estimation of the relationships of PTTG expression with tumor invasiveness and microvessel density of pituitary adenomas. Methods: We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through September 1st, 2013. Meta-analysis was performed using the STATA 12.0 software. The crude odds ratio (OR) with 95% confidence interval (CI) was calculated. Results: Fifteen clinical cohort studies were included with a total of 752 pituitary adenoma patients. The meta-analysis results revealed that patients with invasive pituitary adenomas had higher positive expression of PTTG than those of noninvasive patients (OR=6.68, 95% CI=3.72-11.99, p<0.001). We also found a significant difference in the microvessel density between invasive and noninvasive patients (OR=1.81, 95% CI=0.39-3.23, p<0.001). No publication bias was detected in this meta-analysis (all p>0.05). Conclusion: The present meta-analysis suggests that PTTG expression may be associated with tumor invasiveness and microvessel density of pituitary adenomas. Thus, detection of PTTG expression may be useful for the prediction of malignancy degree in pituitary adenomas.

X-ray repair cross-complementing group 3 (XRCC3) plays a vital role in maintaining the stability of genome by homologous recombination repair for DNA double-strand breaks. The genetic polymorphism of XRCC3 C241T has been implicated in lung cancer risk, but the findings across published studies in Asians are inconsistent and inconclusive. To estimate the precise association of XRCC3 C241T polymorphism with lung cancer risk, a meta-analysis of all currently available studies in Asians was performed. A comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases was conducted for eligible studies based on the inclusion criteria. The pooled odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to assess the association. Besides, subgroup analysis and sensitivity analysis were also performed for further estimation. Seven available studies with a total of 7,398 subjects were finally included into this meta-analysis. The overall ORs indicated that the XRCC3 C241T polymorphism was not associated with a lung cancer risk among Asians in all genetic contrast modes (ORT allele vs. C allele = 1.08, 95 % CI 0.95-1.24, P OR = 0.252; ORTT vs. CC = 1.30, 95 % CI 0.69-2.45, P OR = 0.426; ORCT vs. CC = 1.07, 95 % CI 0.93-1.24, P OR = 0.363; ORTT + CT vs. CC = 1.08, 95 % CI 0.94-1.24, P OR = 0.300; ORTT vs. CC + CT = 1.29, 95 % CI 0.68-2.43, P OR = 0.439). We failed to identify significant association between the XRCC3 C241T polymorphism and risk of lung cancer in Chinese and population-based studies. Interestingly, the pooled ORs in hospital-based studies indicated that the XRCC3 C241T variant carriers were more susceptible to lung cancer (ORT allele vs. C allele = 1.27, 95 % CI 1.04-1.56, P OR = 0.019; ORCT vs. CC = 1.26, 95 % CI 1.01-1.57, P OR = 0.045; ORTT + CT vs. CC = 1.28, 95 % CI 1.03-1.59, P OR = 0.027). Sensitivity analysis confirmed the stability and liability of all results. This meta-analysis suggests that the XRCC3 C241T polymorphism may not exert a risk effect on the lung cancer risk in Asians, although a statistically significant association was observed among the hospital-based studies. Thus, the precise relationship between the XRCC3 C241T variant and lung cancer risk needs further confirmation in future studies with large available data.

BACKGROUND As a negative regulator of P53, MDM2 plays an important role in carcinogenesis; a polymorphism in its promoter region. SNP309 T>G, is known to increase the expression of MDM2, thus being considered related to higher susceptibility to neoplasia. However, no agreement has been achieved regarding its effects on gastric cancer. METHODS The present systematic meta-analysis was performed based on comprehensive literature search from Pubmed, Web of science and CBM databases. RESULTS It was suggested from 6 independent studies that the GG genotype is associated with a significantly increased risk of gastric cancer (Recessive: OR = 1.43, 95% CI = 1.08-1.91, P = 0.013), and subgroup analysis also confirmed the relationship (English publications-recessive model: OR = 1.45, 95% CI = 1.10-1.91, P = 0.009; Studies in China-recessive model: OR = 1.58, 95% CI = 1.08-2.30, P = 0.017). No publication bias was detected. CONCLUSION The meta-analysis indicated a significant inverse association between GG genotype carriage and elevated risk of gastric cancer. However, more studies and detailed information are needed to fully address the topic.

OBJECTIVE:To explore the effect of TRAIL combined resveratrol on proliferation and apoptosis in MDA-MB-231 breast cancer cell line.METHODS: The proliferation were detected by MTT assay and colony formation in soft agar.DAPI staining and flow cytometry were used to analyze cell apoptosis.The expression of DR4 and DR5 on the surface of MDA-MB-231 cell were examined by flow cytometry.RESULTS: After treatement with 50 ng/mL TRAIL combined with 50 and 100 μmol/L resveratrol for 14 d,the colony forming rates in sofe agar were(2.49±0.08)% and(1.38±0.07)%,and difference was significant compered with that of group treated with TRAIL or resveratrol alone(P0.01).After cells were exposed to 50 ng/mL TRAIL combined with 50 and 100μmol/L resveratrol for 12 h,the inhibitory rate were(62.43±2.07)% and(87.32±1.44)%,and the apoptotic percentage were(53.59±1.44)% and(73.72±1.96)%(P0.01).After treatment with 50,100 and 200 μmol/L resveratrol for 12 h,the fluorescence index of DR4 and DR5 on the surface of cells were 1.80±0.07,2.11±0.14,2.59±0.16 and 2.16±0.08,2.92±0.25,3.90±0.06,respectively,and there was significant difference compared with control group,whose FI values were 1.52±0.04 and 1.61±0.13(P0.05).CONCLUSIONS: TRAIL combined with resveratrol can inhibite proliferation and induce apoptosis.One of the mechanism of synergetic effect may be related to the up-regulation of protein level of DR4 and DR5.

Objective To investigate the effects of resveratrol on cell growth,migration,and invasion of human breast cancer cell line MDAMB-231. Methods MTT assay and soft agar colony formation assay were used to detect the effects of resveratrol on cell growth. The effects of resveratrol on cell migration and invasion were determined by Transwell migration assay and Transwell invasion assay,respectively. Results Resveratrol (25 to 200 μmol/L)inhibited the growth of MDA-MB-231 cells in a timeand concentration-dependent manner (P 0.01). The colony formation rate of MDA-MB-231 cells decreased with the increase in the concentrations of resveratrol. After being treated with resveratrol of 25,50,100 and 200 μmol/L for 24 hours,the invasive and migratory ability of MDA-MB-231 cells was significantly inhibited (P 0.01). Conclusion Resveratrol could inhibit the growth of MDA-MB-231 cells,and the invasive and migratory ability of MDA-MB231 cells is also inhibited by resveratrol through degrading extracellular matrix.

To investigate the apoptosis of human pancreatic carcinoma PC3 cells induced by the combination of all-trans retinoic acid (ATRA) with interferon alpha (IFN-α).