Cross-border regulation of the STK39/MAPK14 pathway by Lycium barbarum miR166a to inhibit triple-negative breast cancer.

OBJECTIVE: To investigate the effects of Lycium barbarum miRNA166a (Lb-miR166a) on human gene expression regulation during the therapy for triple-negative breast cancer (TNBC). METHODS: Transcriptome sequencing was used to analyze the distribution and composition of miRNA in Lycium barbarum fruit. Lb-miR166a was introduced into TNBC MB-231 cells by lentiviral transfection to study its effects on cell proliferation, apoptosis, invasion, and metastasis both in vivo and in vitro. Bioinformatic and dual-luciferase assays identified the target gene of Lb-miR166a. The role of STK39 in TNBC progression was elucidated through clinical data analysis combined with cellular studies. The influence of Lb-miR166a on the STK39/MAPK14 pathway was confirmed using a target-specific knockout MB-231 cell line. RESULTS: Lb-miR166a was found to be highly expressed in Lycium barbarum. It inhibited MB-231 cell proliferation, invasion, and metastasis, and promoted apoptosis. STK39 was overexpressed in TNBC and was associated with increased invasiveness and poorer patient prognosis. Gene enrichment analysis and dual-luciferase assays demonstrated that Lb-miR166a regulates STK39 expression cross-border and inhibits MAPK14 phosphorylation, impacting the phosphorylation of downstream target genes. CONCLUSION: The downregulation of STK39 and subsequent inhibition of MAPK14 phosphorylation by Lb-miR166a leads to reduced proliferation, migration, and invasion of TNBC cells. These findings suggest a novel therapeutic strategy for TNBC treatment, highlighting possible clinical applications of Lb-miR166a in managing this aggressive cancer type.

TFAP2A downregulation mediates tumor-suppressive effect of miR-8072 in triple-negative breast cancer via inhibiting SNAI1 transcription.

BACKGROUND: Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined. METHODS: In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells. RESULTS: Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1, a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes. CONCLUSIONS: Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC.

A case report of low-dose apatinib in the treatment of advanced triple-negative breast cancer.

Background: The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific treatment target, the age of onset is relatively small, and the recurrence rate is relatively fast. The prognosis of breast cancer in different subtypes is the most unsatisfactory, with a 5-year survival rate of less than 15%. We report a typical case of metastatic advanced triple-negative breast cancer who responded well to apatinib mesylate after chemotherapy failure and achieved significant progression-free survival, which is relatively rare in triple-negative breast cancer with limited treatment means. Case Description: A 55-year-old female was surgically diagnosed as triple-negative breast cancer on April 17, 2015. After surgery, she had lung metastasis after standard adjuvant chemotherapy and radiotherapy. After receiving the NX regimen (vinorelbine, capecitabine) for 8 cycles, she progressed. Because the patient refused later, she was adjusted to apatinib mesylate, and serious adverse reactions occurred during the treatment process. By adjusting the drug dose, and low-dose apatinib treatment, the lung lesions were close to complete response (CR), reaching a progression-free survival period of 45 months. Conclusions: Low-dose apatinib may be a promising anti-tumor drug for triple-negative breast cancer patients, which needs more samples to verify. This case may provide a reference for the treatment selection of triple-negative metastatic breast cancer in the future.

Exploring the association between inflammatory biomarkers and gastric cancer development: A two-sample mendelian randomization analysis.

This study aimed to elucidate the potential causative links between inflammatory biomarkers and gastric cancer risk via a two-sample Mendelian randomization approach. Leveraging genome-wide association study (GWAS) data, we conducted a two-sample Mendelian randomization analysis. Instrumental variable selection for inflammatory markers - namely, tissue factor, monocyte chemotactic protein-1, E-selectin, interleukin 6 receptor, and fatty acid-binding protein 4 - was informed by SNP data from the IEU database. Strongly associated SNPs served as instrumental variables. We applied a suite of statistical methods, including Inverse Variance Weighted (IVW), Weighted Median Estimator (WME), MR-Egger, and mode-based estimates, to compute the odds ratios (ORs) that articulate the impact of these markers on gastric cancer susceptibility. The IVW method revealed that the interleukin 6 receptor was inversely correlated with gastric cancer progression (OR = 0.86, 95% CI = 0.74-0.99, P = .03), whereas fatty acid-binding protein 4 was found to elevate the risk (OR = 1.21, 95% CI = 1.05-1.39, P = .03). Instrumental variables comprised 5, 4, 7, 2, and 3 SNPs respectively. Convergent findings from WME, MR-Egger, and mode-based analyses corroborated these associations. Sensitivity checks, including heterogeneity, horizontal pleiotropy assessments, and leave-one-out diagnostics, affirmed the robustness and reliability of our instruments across diverse gastric malignancy tissues without substantial bias. Our research suggests that the interleukin 6 receptor potentially mitigates, while fatty acid-binding protein 4 may contribute to the pathogenesis of gastric cancer (GC). Unraveling the intricate biological interplay between inflammation and oncogenesis offers valuable insights for preemptive strategies and therapeutic interventions in gastric malignancy management.

Comprehensive Pan-Cancer Analysis of MTF2 Effects on Human Tumors.

Understanding oncogenic processes and underlying mechanisms to advance research into human tumors is critical for effective treatment. Studies have shown that Metal regulatory transcription factor 2（MTF2) drives malignant progression in liver cancer and glioma. However, no systematic pan-cancer analysis of MTF2 has been performed. Here, we use University of California Santa Cruz, Cancer Genome Atlas , Genotype-Tissue Expression data, Tumor Immune Estimation Resource, and Clinical Proteomic Tumor Analysis Consortium bioinformatics tools to explore differential expression of MTF2 across different tumor types. MTF2 was found to be highly expressed in the cancer lines that were available through the respective databases included in the study, and overexpression of MTF2 may lead to a poor prognosis in tumor patients such as glioblastoma multiforme, brain lower grade glioma, KIPAN, LIHC, adrenocortical carcinoma, etc. We also validated MTF2 mutations in cancer, compared MTF2 methylation levels in normal and primary tumor tissues, analyzed the association of MTF2 with the immune microenvironment, and validated the functional role of MTF2 in glioma U87 and U251 and breast cancer MDA-MB-231 cell lines by cytometry. This also indicates that MTF2 has a promising application prospect in cancer treatment.

Patients with inflammatory bowel disease and post-inflammatory polyps have an increased risk of colorectal neoplasia: A meta-analysis.

BACKGROUND: Longstanding intestinal inflammation increases the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD). Accurately predicting the risk of colorectal neoplasia in the early stage is still challenging. Therefore, identifying visible warning markers of colorectal neoplasia in IBD patients is the focus of the current research. Post-inflammatory polyps (PIPs) are visible markers of severe inflammation under endoscopy. To date, there is controversy regarding the necessity of strengthened surveillance strategies for IBD patients with PIPs. AIM: To determine whether IBD patients with PIPs carryan increased risk of colorectal neoplasia. METHODS: Researchers searched the following databases up to July 31, 2021: MEDLINE (PubMed), MEDLINE (Ovid), EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wan-Fang Data, China Science and Technology Journal Database and Chinese BioMedical Literature Database. Cohort and case-control studies that compared the risk of colorectal neoplasia between IBD patients with or without PIPs and published in English or Chinese were included. Methodological quality was assessed using the Risk of Bias in Nonrandomized Studies-of Interventions assessment tool. The outcomes of interest were the rates of various grades of colorectal neoplasia. The pooled risk ratio (RR) and 95% confidence interval (95%CI) were calculated using the random-effects model. Begg's test and Egger's test were used to calculate the publication bias. Sensitivity and subgroup analyses were performed to verify the robustness of the results. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess the overall quality of evidence supporting the outcomes of interest. RESULTS: Nine studies involving 5424 IBD patients (1944 with PIPs vs 3480 without PIPs) were included. The overall bias in each included study ranged from moderate to serious. Compared with nonconcurrent PIPs, patients with PIPs had a higher risk of colorectal neoplasia (RR = 1.74, 95%CI: 1.35-2.24, P < 0.001, I2 = 81.4%; aHR = 1.31, 95%CI: 1.01-1.70, P = 0.04, I 2 = 26.2%; aOR = 2.62, 95%CI: 1.77-3.88, P < 0.001, I 2 = 0%), advanced colorectal neoplasia (RR = 2.07, 95%CI: 1.49-2.87, P < 0.001, I 2 = 77.4%; aHR = 1.63, 95%CI: 1.05-2.53, P = 0.03, I 2 = 10.1%) and colorectal cancer (RR = 1.93, 95%CI: 1.32-2.82, P = 0.001, I 2 = 83.0%). Publication bias was not observed in Begg's test or Egger's test. Sensitivity and subgroup analyses showed that the results are robust. The overall quality of evidence was assessed as moderate to low. CONCLUSION: IBD patients with PIPs may have an increased incidence of colorectal neoplasia.

ATF6α promotes prostate cancer progression by enhancing PLA2G4A-mediated arachidonic acid metabolism and protecting tumor cells against ferroptosis.

BACKGROUND: Despite the clinical success of androgen receptor (AR)-targeted therapies, prostate cancer (PCa) inevitably progresses to castration-resistant prostate cancer (CRPC). Transcription factor 6 α (ATF6α), an effector of the unfolded protein response (UPR) that modulates the cellular response to endoplasmic reticulum (ER) stress, has been linked to tumor development, metastasis, and relapse. However, the role of ATF6α in CRPC remains unclear. METHODS: The effect of ATF6α on the CRPC-like phenotype in PCa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carb-Oxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS), 5-Bromo-2-deoxyUridine (BrdU) incorporation analysis, and cell death assay. Mechanistically, bioinformatic analysis was utilized to evaluate the potential of PLA2G4A as the target of ATF6α. Moreover, Western blot analysis, real-time polymerase chain reaction, chromatin immunoprecipitation, arachidonic acid (AA), and prostaglandin E2 (PGE2) assays were performed to identify the regulatory effect of ATF6α on PLA2G4A. RESULTS: In this study, we found that the increase of ATF6α expression in response to androgen deprivation generates PCa cells with a CRPC-like phenotype. PCa cells with high levels of ATF6α expression are resistant to ferroptosis, and genetic and pharmacological inhibition of ATF6α could, therefore, promote the ferroptotic death of tumor cells and delay PCa progression. Molecular analyses linked ATF6α regulation of ferroptosis to the PLA2G4A-mediated release of AA and the resulting increase in PGE2 production, the latter of which acts as an antiferroptotic factor. CONCLUSIONS: This study defines ATF6α as a novel antiferroptotic regulator that exacerbates PCa progression. In addition, our data establish ATF6α-PLA2G4A signaling as an important pathological pathway in PCa, and targeting this pathway may be a novel treatment strategy.

Exposure to 50 Hz Extremely-Low-Frequency Magnetic Fields Induces No DNA Damage in Cells by Gamma H2AX Technology.

The current results for extremely-low-frequency magnetic fields (ELF-MF) on DNA damage are still debated. A sensitive indicator and systematic research are needed to assess the effects of ELF-MF. In this study, we used γH2AX as an early and sensitive molecular marker to evaluate the DNA damage effects of ELF-MF in vitro. Human amnion epithelial cells (FLs), human skin fibroblast cells (HSFs), and human umbilical vein endothelial cells (HUVECs) were exposed to 50 Hz ELF-MF at 0.4, 1, and 2 mT for 15 min, 1 h, and 24 h, respectively. After exposure, cells were subjected to γH2AX immunofluorescence and western blot. The results showed no significant difference in the average number of foci per cell, the percentage of γH2AX foci-positive cells, or the expression of γH2AX between the sham and 50 Hz ELF-MF exposure groups (P > 0.05). In conclusion, 50 Hz ELF-MF did not induce DNA damage in FLs, HSFs, or HUVECs, which was independent of the intensity or duration of the exposure.

Polycomb-like 2 regulates PRC2 components to affect proliferation in glioma cells.

INTRODUCTION: The Polycomb group (PcG) is an important family of transcriptional regulators that controls growth and tumorigenesis. The PcG mainly consists of two complexes, PRC1 and Polycomb Repressive Complex 2 (PRC2). Polycomb-like 2 (PCL2) is known to interact with the PRC2 protein. The role of PCL2 in the development and progression of glioma is unclear. METHODS: We use The Cancer Genome Atlas (TCGA) database to detect the expression of PCL2 in various tumors. 117 cases of clinical glioma (WHOI-IV) were collected, and PCL2 expression and localization were detected by immunohistochemical staining. Glioma cells U87/U251 were infected with overexpressed and interfered PCL2. CCK8 assay, colony formation assay, EdU method, cell cycle and apoptosis were used to detect cell proliferation and apoptosis. Western blot was used to detect the expression of PRC2-related core proteins. After DZNeP intervention, PRC2 protein expression was again measured to discuss the mechanism of PCL2 action. RESULTS: TCGA database results and immunohistochemical staining results suggest that PCL2 is highly expressed in gliomas. We found that the PCL2 gene promoted tumor cell proliferation, enhanced the colony formation ability, and increased S phase in the cell cycle. The overexpression of PCL2 upregulated the expression levels of EZH2 and EED (two core members of PRC2), decreased the expression of SUZ12, increased the level of H3K27 trimethylation (H3K27me3), H3K4 dimethylation (H3K4me2), and decreased H3K9 dimethylation (H3K9me2). The result after interfering with PCL2 was the opposite. CONCLUSIONS: As an important accessory protein of PRC2, PCL2 can not only change the expression of PRC2 components, but also affect the expression level of Histone methylation. Therefore, PCL2 may be an important hub for regulating the synergy among PRC2 members. This study revealed PCL2 as a new target for tumor research and open up a new avenue for future research in glioma.

Discovery of 1,3-Disubstituted 2,5-Diketopiperazine Derivatives as Potent Class I HDACs Inhibitors.

Histone deacetylases (HDACs) as attractive targets in many diseases therapies has been studied extensively, and its application in cancer research is the most important. Here, we developed a series of derivatives containing natural 2,5-diketopiperazine (DKP) skeleton. Several compounds exhibited distinct HDAC1 inhibitory activities, in particular 2a (IC50 = 405 nM). The selectivity profile for representative 2a indicated that this series of compounds had a preference for HDAC1-3. Additionally, 2a showed the best growth inhibitory activities against K562 and HL-60 tumor cell line with IC50 values of 4.23 and 4.16 µM, respectively. This work may lay the foundation for developing DKP-based HDAC inhibitors as a potential anticancer agent.

NLK interacts with 14­3­3ζ to restore the expression of E­cadherin.

The Nemo­like kinase (NLK), a conserved serine/threonine kinase, plays a critical role in the regulation of a variety of transcription factors, with important roles in determining cell fate. Although recent studies have demonstrated decreased expression patterns of NLK in various types of human cancer, the functional mechanism of NLK in cancer development has not been elucidated. Here, in the present study overexpression of NLK was found to inhibit the growth and migration of the non­small cell lung cancer A549 cell line. NLK was subsequently found to interact with 14­3­3ζ (also known as YWHAZ), which is responsible for E­cadherin silencing during epithelial­mesenchymal transition (EMT). Furthermore, NLK overexpression was able to restore the expression of E­cadherin inhibited by 14­3­3ζ. Notably, NLK interacts with 14­3­3ζ and prevents its dimerization, which is essential for 14­3­3ζ stability and function. By fusing two copies of the 14­3­3ζ gene, via a Gly­rich linker, a non­dissociable dimer of 14­3­3ζ was formed. It was found that NLK was unable to restore the expression of E­cadherin inhibited by the overexpression of the fused dimer of 14­3­3ζ. In addition, the increased ability of migration induced by the overexpression of fused 14­3­3ζ dimer could not be altered by NLK overexpression. The results from the present study indicate that NLK is a negative regulator of 14­3­3ζ and plays a tumor suppressive role in the inhibition of cancer cell migration.

Tumor-promoting properties of miR-8084 in breast cancer through enhancing proliferation, suppressing apoptosis and inducing epithelial-mesenchymal transition.

BACKGROUND: Breast cancer is one of the most frequent malignancies and the second leading cause of cancer-related mortality in women. MicroRNAs play a key role in breast cancer development and progression. microRNA(miR)-8084 has been observed an aberrant expression in breast cancer. However, the functions and regulatory axes of miR-8084, particularly in breast cancer, were not entirely clear. METHODS: miR-8084 expression in breast cancer were investigated in a GEO dataset by in silico analysis and in 42 paired tumor tissues by qPCR. The effects of deregulation of miR-8084 on breast cancer cell proliferation, migration and invasion in vitro and tumorigenicity in vivo were examined by colony-formation assay, wound healing assay, transwell assay and nude mouse subcutaneous tumor formation model. The target gene of miR-8084 were predicted by TargetScan and miRDB, and confirmed by luciferase reporter system. The roles of miR-8084 in the breast cancer cell proliferation, apoptosis and epithelial-mesenchymal transition (EMT) were investigated by MTS, FACS and associated-marker detection by western blot. RESULTS: miR-8084 is significantly up-regulated in both serum and malignant tissues from the source of breast cancer patients. miR-8084 promotes the proliferation of breast cancer cells by activating ERK1/2 and AKT. Meanwhile miR-8084 inhibits apoptosis by decreasing p53-BAX related pathway. miR-8084 also enhances migration and invasion by inducing EMT. Moreover, the tumor suppressor ING2 is a potential target of miR-8084, and miR-8084 regulatory axes contribute to pro-tumor effect, at least partially through regulating ING2. CONCLUSION: Our results strongly suggest that miR-8084 functions as an oncogene that promotes the development and progression of breast cancer, and miR-8084 is a potential new diagnostic marker and therapeutic target of breast cancer.

Analysis of Treatment of 3 Patients with Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is an acute liver decompensation that occurs within 4 weeks on the basis of chronic liver disease. At present, the treatments of ACLF include general supportive treatment, etiological treatment, prevention and treatment of complications, artificial liver treatment, and liver transplantation. Many studies suggest that stem cell therapy may become a new treatment for patients with ACLF. Our department has also tried the application of this treatment. Now, there are three cases of stem cell therapy for patients with ACLF by our department which will be briefly reported.

Effect of vitamin D on the learning and memory ability of FGR rat and NMDA receptor expression in hippocampus.

The aim of this study is to investigate the effect of vitamin D (VD) on the learning and memory ability of fetal growth restriction (FGR) rat and the expression of NMDA receptor in hippocampus. The FGR models of rat were established through passive smoking, and divided into two groups randomly, i.e. the control group and the observation group. Rats were fed regular diet with the addition of VD in the observation group. The serum level of 25(OH)-D3 was assayed in both groups of the rats at different time points using ELISA, and the learning and memory ability of rat aged 30 days were evaluated using Morris water maze and passive avoidance test. In addition, we also compared the brain weight of rats at different age and detected the mRNA expression of NRI subunit of NMDA receptor of hippocampus of rats aged 30 days using quantitative RT-PCR. After 7 days, the serum level of 25(OH)D3 in rats of the observation group was significantly higher than that of the control group (P<0.05); during the Morris water maze, we found no significant difference in comparison of the latency between the two groups in the first 2 days (P>0.05), but from the 3rd day, the latency of the observation group was shorter than that in the control group (P<0.05); in the passive avoidance test, no significant difference was identified when comparing the electric shock times between the two groups in the first 2 days, but from the 3rd day, the electric shock times in the observation group were significantly lower than those in the control group (P<0.05); the brain weight of rats in the observation group on the 1st, 7th and 14th day were all lower than those in the control group (P<0.05), but the comparison of brain weight at 21st and 30th day showed no significant difference (P>0.05) between the two groups. We also found that the mRNA and protein expression of NRI subunit of NMDA receptor in hippocampus was significantly higher in the observation group than in the control group (P<0.05). VD can increase the learning and memory ability of FGR rats, significantly ameliorating the cognitive dysfunction of FGR rat and improving the learning and memory ability of rats, which may be related to the upregulation of NRI subunit of NMDA receptor.

Zinc improves learning and memory abilities of fetal growth restriction rats and promotes trophoblast cell invasion and migration via enhancing STAT3-MMP-2/9 axis activity.

Fetal growth restriction (FGR) is a well-known risk factor for cognitive dysfunction, especially for learning and memory abilities. However, knowledge about prevention and treatment methods of learning and memory abilities of fetal are limit. Here, Morris water maze and passive avoidance tests showed zinc supplementation could protect the impairment of the learning and memory abilities caused by FGR. As accumulating evidence suggested that insufficiency of placental trophoblast cell invasion was closely related to FGR fetal neurodevelopmental dysplasia, we further explored the relationship between zinc supplementation during pregnancy and placental trophoblast. Microarray identified 346 differently expressed genes in placental tissues with and without zinc supplementation, and GO and KEGG analyses showed these differently expressed genes were highly enriched in cell invasion and migration and STAT3 pathway. Protein-protein interaction(PPI) analysis found that STAT3 interacted with matrix metalloproteinase-2/9 (MMP-2/9). In vivo, western blot results authenticated that the expression levels of phospho-STAT3, STAT3, MMP-2 and MMP-9 were up-regulated in placental tissues after zinc treatment. To validate whether zinc could promotes trophoblast cell invasion and migration via enhancing STAT3-MMP-2/9 activity. In vitro, Transwell assay was performed, and we observed that abilities of invasion and migration were obviously increased in zinc treated trophoblast cells. And phospho-STAT3, STAT3, MMP-2 and MMP-9 expression levels were correspondingly increased in zinc treated trophoblast cells, which were dose-dependent. Moreover, gain-of-function and loss-of-function of STAT3 confirmed that zinc promotes cell invasion and migration via regulating STAT3 mediated up-regulation of MMP-2/9 activity. We propose that activation of MMP-2/9 mediated by STAT3 may contribute to invasion and migration of trophoblast cells, which improved neurodevelopmental impairment of FGR rats probably via contributing to placental development. Our findings are the first to show a possible mechanism of reversing neurodevelopmental impairment of FGR rats by zinc supplementation, holding promise for the development of novel therapeutic modalities for learning and memory abilities impairment caused by FGR.

Extremely Low Frequency Magnetic Fields Do Not Induce DNA Damage in Human Lens Epithelial Cells In Vitro.

Non-ionizing radiations, e.g., radiofrequency electromagnetic fields, could induce DNA damage and oxidative stress in human lens epithelial cells (LECs) which can be early events in cataractogenesis. Extremely low frequency magnetic fields (ELF MF) as another common form of man-made electromagnetic fields has been considered as suspected human carcinogen by International Agency for Research on Cancer (IARC) and become a focus that people play more and more attentions to. This study aimed to determine whether ELF MF can induce DNA damage in cultured human LECs at a relatively low intensity. Human LECs were exposed or sham-exposed to a 50 Hz ELF MF which produced by a well-designed exposure system at the intensity of 0.4 mT. DNA damage in human LECs was examined by the phosphorylated form of histone variant H2AX (γH2AX) foci formation assay and further explored with western blot, flow cytometry, and alkaline comet assay. Immunofluorescence analysis showed that 0.4 mT ELF MF did not significantly increase γH2AX foci formation in human LECs after 2, 6, 12, 24, or 48 hr exposure. No significant differences had been detected in γH2AX expression level between the ELF MF- and sham-exposure groups, while no obvious chromosomal DNA fragmentation was detected by alkaline comet assay after ELF MF exposure. The results indicate an absence of genotoxicity in ELF MF-exposed human epithelial cells and do not support the hypothesis that environmental ELF MF might be causally led to genomic instability via chromosomal damage response processes. Neither short nor long term continuous exposure to 50 Hz ELF MF at 0.4 mT could induce DNA damage in human lens epithelial cells in vitro.

Expression of CXCR2 and its clinical significance in human colorectal cancer.

In the present study, we detected CXC chemokine receptor-2 (CXCR2) CXCR2 expression in patients with colorectal cancer (CRC) and investigated the correlation of CXCR2 expression with clinicopathological variables. CXCR2 expression levels in 46 cancerous tissues, 20 colonic benign tumour tissues, and 30 normal colonic mucosa tissues were examined at both the mRNA level and protein level by using reverse transcription polymerase chain reaction (RT-PCR) and two-step immunohistochemical staining, respectively. We found that the positive rate of CXCR2 protein expression in cancer tissue samples was 69.6%. RT-PCR results confirmed that CXCR2 expression was significantly higher in tumour tissues compared with benign tumour and normal mucosa tissues (P < 0.05). When 46 colorectal cancer patients were divided into groups according to the clinical stage, lymph node metastasis and liver metastasis, we found that CXCR2 expression increased in patients with lymph node metastasis (P < 0.05), and its expression was much higher in stage III and IV cancers than stage I and II cancers. These findings suggest that CXCR2 expression in CRC patients may be a potential molecular biomarker for evaluation of tumour growth and invasion.

PSCA rs2294008 C > T polymorphism contributes to gastric and bladder cancer risk.

BACKGROUND: Previous studies suggested genetic variations in PSCA (prostate stem cell antigen) may confer the susceptibility of cancer. Many case-control studies have reported the relationship between PSCA rs2294008 C > T polymorphism and cancer, especially gastric cancer and bladder cancer. However, the results are inconsistent. This meta-analysis is aimed at evaluating the association of rs2294008 polymorphism with cancer risk. METHODS: The databases of PubMed, ISI Web of Knowledge, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for related publications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Fixed models were used when heterogeneity among studies was not detected, otherwise the random model was used. RESULTS: Twenty-six studies from 24 articles with 30,050 multiple cancer cases and 51,670 controls were pooled into this meta-analysis. The results showed that the rs2294008 polymorphism was associated with increased cancer risk in any genetic model (T vs C, OR: 1.18, 95% CI: 1.08-1.28; TT vs CC, OR: 1.36, 95% CI: 1.14-1.62; TC vs CC, OR: 1.29, 95% CI: 1.17-1.44; TT + TC vs CC, OR: 1.32, 95% CI: 1.18-1.49; TT vs TC + CC, OR: 1.15, 95% CI: 1.02-1.30). In stratified analysis by cancer type, we found that the T allele had a significant high risk of gastric and bladder cancer, but not in other cancers. In subgroup analysis by ethnicity, increased cancer risk was found in both Asians and Caucasians. CONCLUSION: Our study suggested that the PSCA rs2294008 C > T polymorphism is a risk factor for cancer, especially in gastric and bladder cancer.