Catechol-O-methyltransferase Val158Met polymorphism and breast cancer risk in Asian population.

The association between the polymorphism of catechol-O-methyltransferase (COMT) Val158Met and breast cancer risk is still inconclusive. We performed a meta-analysis to derive a more precise estimation of the relationship. A total of 18 studies including 5,175 cases and 6,463 controls were involved in this meta-analysis. When all studies were pooled into the meta-analysis, no significantly elevated breast cancer risk was associated with all genetic models (for additive model: OR = 1.273, 95% CI = 0.947-1.711, P heterogeneity = 0.000; P = 0.110; for dominant model: OR = 1.080, 95% CI = 0.945-1.234, P heterogeneity = 0.001; P = 0.259; for recessive model: OR = 1.242, 95% CI = 0.941-1.641, P heterogeneity = 0.000; P = 0.126; for allele comparison model: OR = 1.096, 95% CI = 0.976-1.230, P heterogeneity = 0.000; P = 0.121). In the subgroup analysis by controls source, the same results were found in all genetic models. In summary, this meta-analysis suggests that the COMT Val158Met polymorphism is not a risk factor for breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Association between FAS 1377G>A polymorphism and breast cancer susceptibility: a meta-analysis.

Published studies on the association between FAS 1377G>A polymorphism and breast cancer susceptibility were inconclusive. To derive a more precise assessment of the association, a meta-analysis of published studies was performed. PubMed, Embase, and Web of Science were searched for eligible studies on the association between FAS 1377G>A polymorphism and breast cancer susceptibility. Five studies with a total of 2,905 cases and 3,090 controls were included into the meta-analysis. Overall, FAS 1377G>A polymorphism was significantly associated with increased susceptibility to breast cancer (for AA versus GG: odds ratio (OR) = 1.39, 95% confidence interval (95% CI) 1.12-1.72, P = 0.003; for AA/GA versus GG: OR = 1.18, 95% CI 1.06-1.32, P = 0.004; for AA versus GG/GA: OR = 1.28, 95% CI 1.05-1.56, P = 0.015). Subgroup analysis by ethnicity found that FAS 1377G>A polymorphism was significantly associated with increased susceptibility to breast cancer in Asians (for AA versus GG: OR = 1.48, 95% CI 1.16-1.89, P = 0.001; for AA/GA versus GG: OR = 1.24, 95% CI 1.06-1.46, P = 0.008; for AA versus GG/GA: OR = 1.35, 95% CI 1.08-1.69, P = 0.008), but the association was not found in Caucasians. Therefore, the findings of the meta-analysis suggest that FAS 1377G>A polymorphism is significantly associated with increased susceptibility to breast cancer in Asians.

The role of CD8+ T-cells in colorectal cancer immunotherapy.

Immunotherapy has been an advanced and effective approach to treating various types of solid tumors in recent years, and the most successful strategy is immune checkpoint inhibitors (ICIs), which have shown beneficial effects in patients with colorectal cancer (CRC). Drug resistance to ICIs is usually associated with CD8+ T-cells targeting tumor antigens; thus, CD8+ T-cells play an important role in immunotherapy. Unfortunately, Under continuous antigen stimulation, tumor microenvironment(TME), hypoxia and other problems it leads to insufficient infiltration of CD8+ T-cells, low efficacy and mechanism exhaustion, which have become obstacles to immunotherapy. Thus, this article describes the relationship between CRC and the immune system, focuses on the process of CD8+ T-cells production, activation, transport, killing, and exhaustion, and expounds on related mechanisms leading to CD8+ T-cells exhaustion. Finally, this article summarizes the latest strategies and methods in recent years, focusing on improving the infiltration, efficacy, and exhaustion of CD8+ T-cells, which may help to overcome the barriers to immunotherapy.

Association between the C3435T polymorphism of ABCB1/MDR1 gene (rs1045642) and colorectal cancer susceptibility : a meta-analysis based on 11,339 subjects.

The association between ABCB1/MDR1 C3435T polymorphism and colorectal cancer has been evaluated. However, the results of these studies on the association remain inconsistent. To derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies of ABCB1/MDR1 C3435T polymorphism and colorectal cancer risk. Summary odds ratios (OR) and 95 % confidence interval (CI) for ABCB1/MDR1 C3435T polymorphism and colorectal cancer were calculated. Statistical analysis was performed with the Stata (Version 12.0). Thirteen case-control studies, a total of 11,339 persons including 5,485 cases and 5,854 controls, met the included criteria and thus were selected. Collectively, the results of the present study suggest that there were no significant associations of ABCB1/MDR1 C3435T polymorphism with colorectal cancer observed for all comparison models. In the subgroup analysis, the same results were detected for both Caucasian and Asian populations. The results of this meta-analysis suggest that ABCB1/MDR1 C3435T polymorphism might be not related to colorectal cancer susceptibility.

Association between polymorphisms of XRCC1 and ADPRT genes and ovarian cancer survival with platinum-based chemotherapy in Chinese population.

The role of DNA repair gene polymorphisms in cancer development, progression, and response to treatment has received increased attention. We conducted a prospective study to determine whether associations exist between two polymorphisms in XRCC1 and ADPRT and the outcomes of Chinese ovarian cancer patients treated with platinum-based chemotherapy. A total of 335 new cases of ovarian cancer were consecutively collected between May 2005 and May 2007. Follow-up lasted for 4 years, and the outcome measure was survival time. Individuals carrying XRCC1 194Trp/Trp had a longer survival time than did those with the Arg/Arg genotype. Similarly, those carrying XRCC1 399 Gln/Gln genotypes had 0.44-fold the risk of death than those with the Arg/Arg genotype. The combination of XRCC1 194 Trp allele and 399 Gln allele could decrease the death risk of ovarian cancer. In summary, this study is the first to evaluate the associations between polymorphisms in DNA repair gene polymorphism and the risk of ovarian cancer in Chinese population. Our study found a significant association between XRCC1 Arg399Gln and XRCC1 Arg194Trp polymorphism and the clinical outcome of ovarian cancer. Furthermore, studies with larger sample sizes are still needed to confirm these associations in Chinese population.

Efficacy and safety of Huachansu combined with adjuvant chemotherapy in resected colorectal cancer patients: a prospective, open-label, randomized phase II study.

Although some studies in China have suggested Huachansu (HCS) combined with chemotherapy is effective in the treatment of various cancers, there are few studies on colorectal cancer (CRC), especially in postoperative adjuvant chemotherapy. The aim of this study was to test the hypothesis that HCS combined with adjuvant chemotherapy would improve survival probability in resected CRC patients. This was a prospective, open-label, randomized phase II study. Patients with stage III or high-risk stage II resected CRC were randomly assigned to the chemotherapy and HCS + chemotherapy groups. The Chemotherapy group was treated with the FOLFOX regimen for ≥ 6 cycles or the CAPEOX regimen for ≥ 4 cycles. The HCS + chemotherapy group was treated with HCS on the basis of the chemotherapy group. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints were 3-year overall survival (OS) and toxicity. A total of 250 patients were included in this study (126 chemotherapy, 124 HCS + chemotherapy). There were significant differences in 3-year DFS between the two groups (median 28.7 vs. 31.6 months, respectively; P = 0.027), but no significant differences in 3-year OS between the two groups (median 32.7 vs. 34 months, respectively; P = 0.146). No patients experienced grade four adverse events, and the rates of leukopenia, neutropenia, and diarrhea in the HCS + chemotherapy group were lower than that those in the chemotherapy group. HCS combined with adjuvant chemotherapy after radical resection for patients with stage III or high-risk stage II CRC was demonstrated to be an effective and feasible treatment.

Efficacy and Safety of Bifidobacterium Quadruple Viable Bacteria Combined with Mesalamine against UC Management: A Systematic Review and Meta-Analysis.

Objective: To systematically assess effectiveness and safety of Bifidobacterium quadruple viable bacteria combined with mesalamine against ulcerative colitis (UC) in the Asian population. Methods: An electronic search was conducted in PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang databases for a random collection of controlled trials of Bifidobacterium quadruple viable bacteria combined with mesalamine against UC. Following data screening and extraction, a Cochrane risk assessment tool was adopted to evaluate the quality of the included studies, and RevMan 5.3 and Stata/SE 15.1 software were used for meta-analysis. Results: Nineteen articles which enrolled 1,707 subjects were included ultimately in this study. The experimental group performed better than the control group in improving the Mayo score (MD = -1.94, 95% CI = (-2.69, -1.19), P < 0.00001), increasing the total clinical efficiency (OR = 5.10, 95% CI (3.53, 7.38), P < 0.00001), reducing the levels of IL-8 (SMD = -1.79, 95% CI (-2.36, -1.12), P < 0.00001), increasing the levels of IL-4 (SMD = 1.00, 95% CI (0.60, 1.41), P < 0.00001), and reducing the levels of hsCRP (MD = -3.26, 95% CI (-4.28, -2.25), P < 0.00001), TNF-α (MD = -7.11, 95% CI (-9.23, -5.00), P < 0.00001), ox-LDL (MD = -14.46, 95% CI (-17.20, -11.72), P < 0.00001), and LPO (MD = -3.55, 95% CI (-4.70, -2.39), P < 0.0001) as well as increasing SOD level (SMD = 1.68, 95% CI (1.02, 2.35), P < 0.00001), and adverse reactions were substantially less than that of control (OR = 0.43, 95% CI = (0.28, 0.66), P = 0.0001). Conclusion: In conclusion, the current meta-analysis shows that Bifidobacterium quadruple viable bacterium combined with mesalamine has a satisfactory effect in the treatment of UC in China, and its safety is better than that of mesalamine or Bifidobacterium quadruple viable bacteria alone. However, randomized controlled trials with standardized designs and large sample sizes are still needed for further validation.

Influence of organoboron cross-linker and reservoir characteristics on filtration and reservoir residual of guar gum fracturing fluid in low-permeability shale gas reservoirs.

To effectively reduce the filtration rate of water-based fracturing fluid and promote the pressure holding effect of fracturing fluid in underground unconventional reservoirs, an efficient and clean organic-boron cross-linker was synthesized with boric acid and low alcohols. The results obtained that the synthesized organoboron cross-linker exhibits better fluid loss performance to water-based fracturing fluid than the commercially available cross-linker. This organoboron cross-linker allowed decreasing filtration coefficient more than 0.74 × 10-2 m3·min1/2 as a result of the network structure formed by the organoboron cross-linker and guar gum molecule. However, commercially available cross-linker exhibits a relatively large filtered mass of water more than 1.33 × 10-2 m3·min1/2 at the same condition. Meanwhile, the cross-linked guar gum fracturing fluid can significantly improve the fluid loss property with the increase of cross-linker content and pressure, and an increased fluid filtration gradually was revealed with increasing the reservoir temperature and current speed. Moreover, the damage of shale reservoir caused by the prepared boron cross-linker was only 11%, which was lower than 18% of the commercial boron cross-linker under the same conditions.

The impact of IGF-1R expression on the outcomes of patients with breast cancer: a meta-analysis.

PURPOSE: The value of insulin-like growth factor 1 receptor (IGF-1R) for predicting survival of patients with breast cancer remains controversial. The purpose of this study was to perform a meta-analysis of the published data to attempt to clarify the impact of IGF-1R. METHODS: Studies published between January 1, 1990 and October 1, 2014 were identified using an electronic search to aggregate the available survival results. Studies were included if they reported detecting IGF-1R expression in the primary breast cancer and analyzed patient survival data according to IGF-1R status. The principal outcome measures were hazard ratios (HRs) for survival of IGF-1R-positive patients. Combined HRs and 95% confidence intervals (CIs) were estimated using fixed- or random-effects models according to between-study heterogeneity. RESULTS: Ten studies, involving 5,406 patients, satisfied our inclusion criteria. Data from five studies provided the impact of IGF-1R on overall survival (OS), three studies the impact on breast cancer-specific survival (BCSS), and seven studies the impact on disease-free survival (DFS). The results of meta-analysis showed that for DFS, membranous IGF-1R positivity was not a significant predictor. The combined HR for OS/BCSS was 0.63 (95% CI: 0.42-0.95, P=0.03), indicating that membranous IGF-1R positivity was a significant predictor of better survival. IGF-1R cytoplasmic positivity was significantly associated with longer DFS and OS/BCSS (combined HR: 0.56, 95% CI: 0.35-0.89, P=0.01; combined HR: 0.55, 95% CI: 0.35-0.85, P=0.008, respectively). The results of subgroup analysis suggested that membranous IGF-1R positivity in hormone-receptor-positive breast cancer was correlated with favorable DFS (combined HR: 0.61, 95% CI: 0.41-0.92, P=0.02) and OS/BCSS (combined HR: 0.73, 95% CI: 0.57-0.93, P=0.01). Membranous IGF-1R positivity in triple-negative breast cancer predicted worse DFS (combined HR: 1.86, 95% CI: 1.03-3.34, P=0.04). Membranous IGF-1R positivity in Her-2-positive or ER (estrogen receptor)-negative breast cancer was not found to be a significant prognostic indicator. CONCLUSION: The results of this meta-analysis suggest that IGF-1R expression has different prognostic values for patients with breast cancers of different molecular subtypes. It was a favorable prognostic indicator in unselected breast cancers and hormone-receptor-positive cancers, but indicated poor survival in triple-negative breast cancers.

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: a network meta-analysis.

The third-generation aromatase inhibitors (AIs: anastrozole, letrozole, and exemestane) have now become standard adjuvant endocrine treatment for postmenopausal estrogen receptor-positive breast cancer complementing chemotherapy and surgery. Because of the absence of direct head-to-head comparisons of these AIs, an indirect comparison is needed for individual treatment choice. In this network systemic assessment, the cardiovascular (CV) side effects in using anastrozole, letrozole, and exemestane based on original studies on AIs vs placebo or tamoxifen were compared. We integrated all available direct and indirect evidences. The odds ratio (OR) of severe CV events for indirect comparisons between exemestane and anastrozole was 1.41 (95% confidence interval [CI] =0.49-2.78), letrozole and anastrozole was 1.80 (95% CI =0.40-3.92), and letrozole and exemestane was 1.46 (95% CI =0.34-3.4). OR of subgroup risk for AIs and tamoxifen were all >1 except for thrombolism risk subgroup. The results showed that the total and severe CV risk ranking is letrozole, exemestane, and anastrozole in descending order. None of the AIs showed advantages in CV events than tamoxifen except for thromboembolism event incidence.

Numerical characterization of magnetically aligned multiwalled carbon nanotube-Fe3O4 nanoparticle complex.

Alignment states of one-dimensional multiwalled carbon nanotubes containing various contents of zero-dimensional ferriferrous oxide nanoparticles (MWCNT-Fe3O4) were numerically characterized. MWCNT-Fe3O4 complexes were successfully prepared via in situ surface-initiated atom transfer radical polymerization, followed by a coprecipitation process. The complexes showed strong magnetism, which endowed them with the ability to be aligned under the action of an external magnetic field. The intensity of the magnetic field, loading content of Fe3O4 nanoparticles, and viscosity of dispersing medium, however, all had substantial effects on the alignment degree. To evaluate the alignment effectively and quantitatively, an orientation tensor description based on marking the direction of a single MWCNT in a selected region of optical images was employed. The results showed that MWCNT-Fe3O4 complex containing 26 wt % of Fe3O4 nanoparticles achieved a desirable alignment in deionized water under a magnetic field intensity of 0.10 T. Accordingly, epoxy composites reinforced with such aligned MWCNT-Fe3O4 complexes displayed 12.3 and 10.9% enhancement in tensile strength and modulus, as well as 8.9 and 6.1% enhancement in flexural strength and modulus, respectively.

Emodin inhibits LOVO colorectal cancer cell proliferation via the regulation of the Bcl-2/Bax ratio and cytochrome c.

In this study, the effect of emodin and its mechanism of action were investigated in LOVO colorectal cancer cells. Cell growth was determined using a Cell Counting kit-8 assay, and the results demonstrated that emodin significantly inhibited the growth of LOVO cells in a concentration-dependent manner. In order to investigate the anticancer mechanism of emodin, reverse transcription polymerase chain reaction assays were performed to determine the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) expression ratio in LOVO colorectal cancer cells following treatment with emodin. The results showed that emodin induced a significant increase in the Bax expression level and a marked reduction of the Bcl-2 expression level in LOVO cells. In addition, emodin was found to have an inhibitory effect on the mitochondrial membrane potential and the results from the western blot analysis revealed that cytochrome c was released from the mitochondria to the cytoplasm. In combination, these results suggest that emodin inhibits cancer cell growth via the regulation of the Bcl-2/Bax ratio and by its effect on the mitochondrial apoptosis pathway.

Association of 677 C>T (rs1801133) and 1298 A>C (rs1801131) polymorphisms in the MTHFR gene and breast cancer susceptibility: a meta-analysis based on 57 individual studies.

OBJECTIVE: The 677 C>T and 1298 A>C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene have been widely reported and considered to have a significant effect on breast cancer risk, but the results are inconsistent. A meta-analysis based on 57 eligible studies was carried out to clarify the role of MTHFR gene polymorphisms in breast cancer. METHODS AND RESULTS: Eligible articles were identified by searching databases including PubMed, Web of Science, EMBASE, CNKI and CBM for the period up to August 2012. Finally, a total of 57 studies were included in this meta-analysis. Crude ORs with 95% CIs were used to assess the association between the MTHFR polymorphisms and breast cancer risk. The pooled ORs were performed with additive model, dominant model and recessive model, respectively. Subgroup analysis was also performed by ethnicity. The statistical heterogeneity across studies was examined with χ2-based Q-test. A meta-analysis was performed using the Stata 12.0 software. Overall, the 677 C allele was significantly associated with breast cancer risk (OR = 0.942, 95%CI = 0.898 to 0.988) when compared with the 677 T allele in the additive model, and the same results were also revealed under other genetic models. Simultaneously, the 1298 A allele was not associated with the breast cancer susceptibility when compared with the 1298 C allele (OR = 0.993, 95%CI = 0.978 to 1.009). Furthermore, analyses under the dominant, recessive and the allele contrast model yielded similar results. CONCLUSIONS: The results of this meta-analysis suggest that 677 C>T polymorphism in the MTHFR gene may contribute to breast cancer development. However, the 1298 A>C polymorphism is not significantly associated with increased risks of breast cancer.

DNA repair pathway genes and lung cancer susceptibility: a meta-analysis.

OBJECTIVE: DNA repair pathway genes have been implicated to play an important role in the development of lung cancer. However, contradictory results are often reported by various studies, making it difficult to interpret them. So in this meta-analysis, we have assessed the association between lung cancer risk and two DNA repair pathway genes. XRCC1 and ERCC2, by analyzing 67 published case-control studies. RESEARCH DESIGN AND METHODS: We searched PubMed, Embase and Web of Science using terms "XRCC1" or "XPD" or "ERCC2" and "lung cancer" on August 1, 2012. Three criteria were applied to select included studies for resulting studies. Information was carefully extracted by two investigators independently. We used pooled odds ratio (OR) to assess the effect of a polymorphism, and a dominant model was applied where genotypes that contain the non-reference allele were combined together. All the calculations were performed using STATA version 11.0. MAIN OUTCOME MEASURES AND RESULTS: Three common nonsynonymous polymorphisms in XRCC1, codon 194, codon 280 and codon 399, and two common nonsynonymous polymorphisms in ERCC2, codon 312 and codon 751, were analyzed. The result showed in total population, Lys751Gln in ERCC2 is associated with an increase of lung cancer risk, with a summary OR as 1.15. No association was found for any other polymorphisms. When studies were stratified by ethnicity, the risk effect of Lys751Gln in ERCC2 was found only in Caucasians, not in Asians. CONCLUSIONS: In conclusion, Lys751Gln in ERCC2 is associated with lung cancer, and the risk effect probably exists in Caucasians. By contrast, polymorphisms in XRCC1 are less likely to be susceptible to lung cancer risks.

Bioinformatics analysis reveals disturbance mechanism of MAPK signaling pathway and cell cycle in Glioblastoma multiforme.

BACKGROUND & OBJECTIVES: To analyze the reversal gene pairs and identify featured reversal genes related to mitogen-activated protein kinases (MAPK) signaling pathway and cell cycle in Glioblastoma multiforme (GBM) to reveal its pathogenetic mechanism. METHODS: We downloaded the gene expression profile GSE4290 from the Gene Expression Omnibus database, including 81 gene chips of GBM and 23 gene chips of controls. The t test was used to analyze the DEGs (differentially expressed genes) between 23 normal and 81 GBM samples. Then some perturbing metabolic pathways, including MAPK (mitogen-activated protein kinases) and cell cycle signaling pathway, were extracted from KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway database. Cancer genes were obtained from the database of Cancer Gene Census. The reversal gene pairs between DEGs and cancer genes were further analyzed in MAPK and cell cycle signaling pathway. RESULTS: A total 8523 DEGs were obtained including 4090 up-regulated and 4433 down-regulated genes. Among them, ras-related protein rab-13(RAB13), neuroblastoma breakpoint family member 10 (NBPF10) and disks large homologue 4 (DLG4) were found to be involved in GBM for the first time. We obtained MAPK and cell cycle signaling pathways from KEGG database. By analyzing perturbing mechanism in these two pathways, we identified several reversal gene pairs, including NRAS (neuroblastoma RAS) and CDK2 (cyclin-dependent kinase 2), CCND1 (cyclin D1) and FGFR (fibroblast growth factor receptor). Further analysis showed that NRAS and CDK2 were positively related with GBM. However, FGFR2 and CCND1 were negatively related with GBM. INTERPRETATION & CONCLUSIONS: These findings suggest that newly identified DEGs and featured reversal gene pairs participated in MAPK and cell cycle signaling pathway may provide a new therapeutic line of approach to GBM.

Predictive value of XRCC1 and XRCC3 gene polymorphisms for risk of ovarian cancer death after chemotherapy.

OBJECTIVE: To investigate any association between XRCC1 and XRCC3 polymorphisms and outcome of platinum-based chemotherapy in ovarian cancer patients. METHODS: With a prospective study design was cases were consecutively collected from January 2005 to January 2007. All 310 included patients were followed-up until the end of January 2010. Genotyping of XRCC1 and XRCC3 polymorphisms was conducted by TaqMan Gene Expression assays. RESULTS: A total of 191 patients died during follow-up. Our study showed a lower survival rate in XRCC1 399 Arg/Arg genotype than Gln/ Gln, with a significant increased risk of death (HR=1.69, 95%CI=1.07-2.78). Similarly, those carrying XRCC3 Thr/ Thr genotype had a increased risk as compare to the Met/Met genotype, with a HR (95% CI) of 1.90 (1.12-3.41). There was no significant association between XRCC1 Arg194Trp and XRCC1Arg280His gene polymorphisms and ovarian cancer death. CONCLUSION: Our study demonstrates that polymorphisms in DNA repair genes have roles in the susceptibility and survival of ovarian cancer patients.