Association between NTCP hepatic expression and inflammation/fibrosis as well as gender-specific differences in chronic HBV-infected patients.

To investigate the relationship between the expression of hepatitis B virus (HBV) functional receptor sodium taurocholate cotransporting polypeptide (NTCP) with disease progression and gender-specific differences in chronic HBV-infected patients. Liver samples were collected from chronic HBV-infected patients who underwent percutaneous liver biopsy or liver surgery. HBV DNA levels and the mRNA and protein expression levels of NTCP in liver tissues were determined. The relationship between NTCP expression and HBV DNA levels, inflammatory activity, fibrosis, and gender-specific differences were analyzed. A total of 94 chronic HBV-infected patients were included. Compared with patients with a METAVIR score of A0-1 or F0-1, patients with score of A2 or F2/F3 had a relatively higher level of NTCP expression. NTCP levels were positively correlated with HBV DNA levels. The inflammatory activity scores and fibrosis scores of women <50 years were significantly lower than those of women ≥50 years and age-matched males. In patients with score A0-2 or F0-3, women <50 years have lower NTCP expression level compared to women ≥50 years and age-matched males. NTCP can promote the disease progression by affecting the viral load of HBV. The NTCP expression difference may be why male and postmenopausal women are more prone to disease progression than reproductive women.

Circulating microRNAs as diagnostic biomarkers for melanoma: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that circulating microRNAs (miRNAs) can be used as diagnostic biomarkers for melanoma. This study aimed to evaluate the diagnostic value of circulating miRNAs for melanoma. METHODS: A comprehensive literature search was conducted and the quality of the included literature was evaluated using QUADAS-2 (Quality Assessment for diagnostic accuracy studies), and the diagnostic accuracy was assessed by pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). We used Deeks' funnel plot to evaluate publication bias. RESULTS: The meta-analysis included 10 articles covering 16 studies, and the results showed that circulating miRNAs provide high diagnostic accuracy for melanoma. The overall pooled sensitivity was 0.87 (95% CI: 0.82-0.91), specificity was 0.81 (95% CI: 0.77-0.85), PLR was 4.6 (95% CI: 3.7-5.8), NLR was 0.16 (95% CI: 0.11-0.23), DOR was 29 (95% CI: 18-49), and AUC was 0.90 (95% CI: 0.87-0.92), respectively. Subgroup analysis showed better diagnostic value in miRNA clusters, European population, plasma miRNAs, and upregulated miRNAs compared to other subgroups. CONCLUSIONS: The results indicated that circulating microRNAs can be used as a non-invasive biomarker for the diagnosis of melanoma.

Role of Circular RNAs in the Pathogenesis of Malignant Melanoma.

Malignant melanoma is one of the most aggressive types of skin cancer. Thus, efficient diagnosis and treatment methods are crucial for advanced melanoma. Circular RNAs (circRNAs) have been regarded as a 'splicing noise' in the past decades. However, several circRNAs have been recently reported to be differentially expressed in melanoma, and the cell or tissue-specific expression makes these suitable candidate diagnostic or therapeutic biomarkers. In addition, emerging studies have confirmed that circular RNAs play pivotal roles in the proliferation, invasion, metastasis, and migration of malignant melanoma. However, specific pathogenic mechanisms between melanoma and circRNAs remain unclear. In the present study, it was summarized that circRNAs are associated with the pathogenesis of melanoma, including hsa_circ_0083444, hsa_circ_0005320, hsa_circ_0067531, hsa_circ_0084043, hsa_circ_0000082, hsa_circ_0016418, hsa_circ_0085533 and hsa_circ_0025039, hsa_circ_0001946, hsa_circ_0002770, hsa_circ_0079593, hsa_circ_0027247, hsa_circ_0017247, hsa_circ_0020710. These can provide potential diagnosis, treatment, and prognostication biomarkers for advanced melanoma in clinical applications.

Glutamine deficiency promotes recurrence and metastasis in colorectal cancer through enhancing epithelial-mesenchymal transition.

BACKGROUND: Glutamine is the most abundant amino acid in the body and plays a vital role in colorectal cancer (CRC) cell metabolism. However, limited studies have investigated the clinical and prognostic significance of preoperative serum glutamine levels in patients with colorectal cancer, and the underlying mechanism has not been explored. METHODS: A total of 121 newly diagnosed CRC patients between 2012 and 2016 were enrolled in this study. Serum glutamine levels were detected, and their associations with clinicopathological characteristics, systemic inflammation markers, carcinoembryonic antigen (CEA) and prognosis were analysed. In addition, the effect of glutamine depletion on recurrence and metastasis was examined in SW480 and DLD1 human CRC cell lines, and epithelial-mesenchymal transition (EMT)-related markers were detected to reveal the possible mechanism. RESULTS: A decreased preoperative serum level of glutamine was associated with a higher T-class and lymph node metastasis (P < 0.05). A higher serum level of glutamine correlated with a lower CEA level (r = - 0.25, P = 0.02). Low glutamine levels were correlated with shorter overall survival (OS) and disease-free survival (DFS). Multivariate Cox regression analysis showed that serum glutamine was an independent prognostic factor for DFS (P = 0.018), and a nomogram predicting the probability of 1-, 3- and 5-year DFS after radical surgery was built. In addition, glutamine deficiency promoted the migration and invasion of CRC cells. E-cadherin, a vital marker of EMT, was decreased, and EMT transcription factors, including zeb1and zeb2, were upregulated in this process. CONCLUSIONS: This study elucidated that preoperative serum glutamine is an independent prognostic biomarker to predict CRC progression and suggested that glutamine deprivation might promote migration and invasion in CRC cells by inducing the EMT process.

Signal transducer and activator of transcription 3 cooperates with androgen receptor/cell cycle-related kinase signalling pathway in the progression of hepatitis B virus infection and gender differences.

The study aimed to investigate the role of androgen receptor (AR)/cell cycle-related kinase (CCRK) signalling pathway in chronic hepatitis B virus (HBV) infection and gender differences, and the contribution of AR regulatory factor signal transducer and activator of transcription 3 (STAT3) in it. AR, CCRK, and phosphorylated STAT3 expressions in liver tissues of chronic HBV-infected patients and non-HBV controls were determined by western blot and compared between genders. The relationships of expression levels with serum HBV DNA levels, liver inflammation activity, and fibrosis score were analysed in chronic HBV-infected patients. The relationships between expression levels of three proteins were also analysed. HBV-infected patients had significantly higher expression levels of AR, CCRK, and p-STAT3Tyr705 compared with controls (p < .01). The expression levels of AR, CCRK, and p-STAT3Tyr705 in chronic HBV-infected patients with severe inflammation were significantly higher than those with mild inflammation (p < .05). Expression levels in patients with heavier fibrosis (stage F4) were higher than in those with less fibrosis (stages F0-3) (p < .01). No gender differences were observed in AR, CCRK, and p-STAT3Tyr705 levels in non-HBV controls; higher levels were observed in HBV-infected males than in HBV-infected females (p < .05). AR, CCRK, and p-STAT3Tyr705 levels in liver tissues positively correlated with each other (p < .0001) and with serum HBV DNA levels (p < .0001). In conclusion, in this study, we first found concordant over-expression of AR, CCRK, and STAT3 in liver tissues of chronic HBV-infected patients who have not yet developed HCC, significantly correlated with the severity of the disease and showed gender differences. STAT3 may be a potential therapeutic co-target for chronic HBV infection.

A Meta-analysis of 37 Studies on the Effectiveness of Microsurgical Techniques for Lymphedema.

BACKGROUND: Microsurgery is a new technique for lymphedema treatment. Its advantages and disadvantages remain controversial. This study is sought to collect clinical data from patients who underwent lymphovenous bypass and vascularized lymph node transplantation to explore whether surgical procedures can effectively treat lymphedema. METHODS: We performed a meta-analysis of the effectiveness of lymphatic microsurgery. We searched the databases of literature for articles in Chinese and English. These articles were graded for quality. Report details and outcomes were recorded. Data extraction, systematic review, and meta-analysis were performed. RESULTS: Thirty-seven studies were included. Patients who underwent microsurgery had a significantly better chance of achieving an excellent result than patients who received conservative treatment (odds ratio = 7.07). The affected limb circumference was reduced by approximately, 44.68% after the microsurgery. After the microsurgery, 63% of the patients did not need physiotherapy, and 96% were free from painful skin infections. Lymphography showed that lymphatic transport capacity was enhanced. Moreover, 12% of the patients reported that edema reappeared in the long-term, 26% required reoperation for unsatisfactory results, and 32% experienced lymphatic leakage. CONCLUSIONS: A vast majority of patients derive more benefit from lymphatic microsurgery than from conventional treatment. The advantages of lymphatic microsurgery outweigh the disadvantages for patients in the early and middle stages of chronic secondary lymphedema and patients in whom conventional treatment failed.

A meta-analysis of fractional CO2 laser combined with PRP in the treatment of acne scar.

This study aimed to analyze the effectiveness and safety of ablative fractional carbon dioxide laser systems (CO2 AFL) combined with autologous platelet-rich plasma (PRP) in the treatment of acne scars through the retrieval and collection of related literature to further guide the treatment of acne scars. We searched Web of Science, PubMed, Embase, Wanfang Data, Chinese National Knowledge Infrastructure, and VIP Database. All randomized and nonrandomized controlled trials on CO2 AFL combined with PRP in the treatment of acne scars were included, and Revman5.3 systematic review software was used in the meta-analysis. Nine studies were included in this meta-analysis. The data analysis results showed that the CO2 AFL combined with PRP treatment group showed significantly better results than the pure CO2 AFL control group in terms of clinical improvement score, clinical improvement rate, patient satisfaction, and crusting period. The results of this meta-analysis showed that CO2 AFL combined with PRP in the treatment of acne scars is more effective and safer than CO2 AFL alone.

Putative promoters within gene bodies control exon expression via TET1-mediated H3K36 methylation.

Hypermethylation of gene promoter has been indicated for the contribution of gene silencing, and DNA demethylating drugs, such as 5-aza-2'-deoxycytidine (DAC), has been used clinically for cancer treatment. However, the reason why a proportion of genes with hypermethylated promoter exhibit high expression levels remains unclear and this drug is not much successful as expected in use. Furthermore, CpG islands (CGIs) are found to be located in not only promotors, but also in gene bodies. By RNA-seq and reduced representation bisulfite sequencing, we found the mismatch between the level of promoter methylation and gene expression. By chromatin Immunoprecipitation-quantitative polymerase chain reaction and luciferase reporter assay, we identified putative promoters in gene body, and proved the activities of putative promoters were affected by the methylation level of the CGI nearby. DAC can reverse the DNA hypermethylation at promoter CGIs effectively but not the CGIs in gene body. We also found that TET1 could demethylate CGIs both in promoter and gene body. Furthermore, we revealed a novel mechanism that H3K36me3 could affect the activity of putative promoter, and 5hmC recruited MeCP2 and CREB1 as a coactivator to SETD2 promoter, to enhance its gene expression and result in increased H3K36me3 in gene body. Our results concluded that putative promoters existed in the gene bodies, and TET1 could influence the transcriptional activity of putative promoters by intragenic demethylation.

Prognostic Significance of Tumor-Infiltrating Lymphocyte Grade in Melanoma: A Meta-Analysis.

PURPOSE: Tumor-infiltrating lymphocytes (TILs) in primary melanoma are considered to represent the host's antitumor immune response; however, whether TILs can independently predict survival remains controversial. This meta-analysis evaluated the prognostic value of TIL grade for survival in patients with melanoma. METHODS: We identified studies from the PubMed, Web of Science, and China National Knowledge Infrastructure databases to assess the prognostic impact of TIL grade in patients with melanoma. We estimated the combined hazard ratios (HRs) for overall survival (OS), disease-free survival, and disease-specific survival (DSS) at 5 years and end point using either fixed-effect or random-effect models depending on heterogeneity. RESULTS: A total of 13 observational studies including 7,633 patients were enrolled. In the univariate analysis, brisk TIL grade was significantly more strongly correlated with better 5-year OS, 5-year DSS, and end point DSS compared with those of nonbrisk or absent TILs (HR 0.62, 95% CI 0.44-0.88, I2 = 0; HR 0.53, 95% CI 0.30-0.96, I2 = 11%; and HR 0.51, 95% CI 0.30-0.87, I2 = 0, respectively). Compared with absent TIL grade, brisk TIL grade was associated with better 5-year OS and end point OS (HR 0.68, 95% CI 0.50-0.93, I2 = 40% and HR 0.65, 95% CI 0.52-0.83, I2 = 0, respectively). Nonbrisk TIL grade was associated with better end point DSS (HR 0.60, 95% CI 0.44-0.83, I2 = 7%). The multifactor analysis showed that brisk TIL grade was related to better DSS (HR 0.50, 95% CI 0.30-0.90), and nonbrisk or absent TIL grade was correlated with poor DSS (HR 8.7, 95% CI 2.7-40.3). CONCLUSION: Patients with brisk TIL grade had a better prognosis. TIL level deserves further investigation to support the conclusion that it should be routinely included in the pathological report of primary melanoma and in future American Joint Committee on Cancer staging revisions.

Tet methylcytosine dioxygenase 1 promotes hypoxic gene induction and cell migration in colon cancer.

Ten-eleven translocation 1 (TET1), a widely reported DNA demethylation protein, has been associated with tumorigenesis and metastasis. However, whether TET1 is an oncogene or tumor suppressor gene has been controversial; the mechanism of how TET1 affects cancer progression remains unclear. The current study aims to investigate how TET1 is changed in the tumor microenvironment and to explore the mechanisms of how TET1 affects colon cancer progression. Because hypoxia prevails on solid tumors, we established an important connection between hypoxia and DNA demethylation in tumorigenesis. By qPCR and RNA interference (RNAi) technology, we found that hypoxia increased TET1 expression with a hypoxia-inducible factor-1-alpha (HIF-1α)-dependent manner. By CHIP-qPCR and pyrosequencing technology, we demonstrated that TET1 regulated the target gene expression of HIF-1α through HIF-1α binding to hypoxia-responsive elements (HREs), and HIF-1α binding to HREs depended on CpG methylation levels. By Cell Counting Kit-8 (CCK-8) and transwell assay, we showed that loss of TET1 did not affect cell proliferation but inhibited migration. We also identified two novel gene mutants of TET1 in 120 paired tumor/normal tissue specimens by DNA sequencing and found that TET1 E2082K mutant blocked the TET1-enhanced cell migration. Our results showed that the downregulation of TET1 rescued the abnormally high levels of gene expression resulting from hypoxia in tumors and reduced the migration activity of tumor cells, suggesting a therapeutic role by interference with TET1 in colon cancer treatment. By demonstrating that hypoxia upregulated TET1 and that TET1 drove HIF-1α-responsive genes, we showed that an epigenetic mechanism and tumor microenvironment-driven models coexisted and mutually affected colon cancer.

Fusion with mesenchymal stem cells differentially affects tumorigenic and metastatic abilities of lung cancer cells.

Cell fusion plays a crucial role in cancer progression and leads to massive aberrant changes in chromosome and gene expression involved in tumor metastasis. Cancer cells can fuse with many cell types, including stromal cells, epithelial cells, macrophages, and endothelial cells. Mesenchymal stem cells (MSCs) have been reported to migrate and incorporate into tumor sites during cancer progression. However, the underlying mechanism of stem cell fusion in tumor metastasis has not been fully deciphered. In this research, we established a cell fusion model between lung cancer cells and MSCs in vitro. We found that the hybrid cells showed enhanced metastatic capacity with increased expression of MMP-2 and MMP-9, whereas the proliferation ability was inhibited and cell cycle was blocked in the G0 /G1 phase with elevated expression of p21, p27, and p53. Moreover, the hybrid cells lost epithelial morphology and exhibited an epithelial-mesenchymal transition (EMT) change with downregulation of E-cadherin and upregulation of N-cadherin, Vimentin, α-SMA and Fibronectin1. Meanwhile, the expressions of EMT transcription factors, including Snail1, Slug, Twist1, Zeb1, and Zeb2, were also increased in hybrid cells. More important, the fusion hybrids acquired stem cell-like properties, which exhibited increased expression stem cell transcription factors Oct4, Sox2, Nanog, Kif4 as well as Bmi1. Taken together, our results suggested that cell fusion between lung cancer cells and MSCs offered enhanced metastatic capacity and characteristics of cancer stem cell by undergoing EMT. This study will contribute to explaning the origin of lung cancer stem cells and to elucidate the role of cell fusion in cancer metastasis.

Correction to: Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis.

Following publication of the original article [1], the authors reported an error in affiliation 5.

miR-30 Family Reduction Maintains Self-Renewal and Promotes Tumorigenesis in NSCLC-Initiating Cells by Targeting Oncogene TM4SF1.

Increasing evidence indicates that tumor-initiating cells (TICs) are responsible for the occurrence, development, recurrence, and development of the drug resistance of cancer. MicroRNA (miRNA) plays a significant functional role by directly regulating targets of TIC-triggered non-small-cell lung cancer (NSCLC), but little is known about the function of the miR-30 family in TICs. In this study, we found the miR-30 family to be downregulated during the spheroid formation of NSCLC cells, and patients with lower miR-30a/c expression had shorter overall survival (OS) and progression-free survival (PFS). Moreover, transmembrane 4 super family member 1 (TM4SF1) was confirmed to be a direct target of miR-30a/c. Concomitant low expression of miR-30a/c and high expression of TM4SF1 correlated with a shorter median OS and PFS in NSCLC patients. miR-30a/c significantly inhibited stem-like characteristics in vitro and in vivo via suppression of its target gene TM4SF1, and then it inhibited the activity of the mTOR/AKT-signaling pathway. Thus, our data provide the first evidence that TM4SF1 is a direct target of miR-30a/c and miR-30a/c inhibits the stemness and proliferation of NSCLC cells by targeting TM4SF1, suggesting that miR-30a/c and TM4SF1 may be useful as tumor biomarkers for the diagnosis and treatment of NSCLC patients.

Proteogenomic characterization and comprehensive integrative genomic analysis of human colorectal cancer liver metastasis.

BACKGROUND: Proteogenomic characterization and integrative and comparative genomic analysis provide a functional context to annotate genomic abnormalities with prognostic value. METHODS: Here, we analyzed the proteomes and performed whole exome and transcriptome sequencing and single nucleotide polymorphism array profiling for 2 sets of triplet samples comprised of normal colorectal tissue, primary CRC tissue, and synchronous matched liver metastatic tissue. RESULTS: We identified 112 CNV-mRNA-protein correlated molecules, including up-regulated COL1A2 and BGN associated with prognosis, and four strongest hot spots (chromosomes X, 7, 16 and 1) driving global mRNA abundance variation in CRC liver metastasis. Two sites (DMRTB1R202H and PARP4V458I) were revealed to frequent mutate only in the liver metastatic cohort and displayed dysregulated protein abundance. Moreover, we confirmed that the mutated peptide number has potential prognosis value and somatic variants displayed increased protein abundance, including high MYH9 and CCT6A expression, with clinical significance. CONCLUSIONS: Our proteogenomic characterization and integrative and comparative genomic analysis provides a new paradigm for understanding human colon and rectal cancer liver metastasis. TRIAL REGISTRATION: ClinicalTrials, NCT02917707. Registered 28 September 2016, https://clinicaltrials.gov/ct2/show/NCT02917707 .

Ginkgolic acid induces interplay between apoptosis and autophagy regulated by ROS generation in colon cancer.

Presently, developing effective anti-colon cancer drugs still remains to be important. Ginkgolic acids (GA), as a botanical drug extracted from the seed coat of Ginkgo biloba L., possess various bioactive properties. Our findings, for the first time, indicated that GA suppressed colon cancer cell proliferation, migration and invasion. GA led to cell death through G0/G1 phase arrest. In addition, apoptosis was significantly induced by GA treatment. The intrinsic apoptosis pathway was included, proved by the release of cytochrome c (Cyto-c) from the mitochondria into the cytosol. GA-induced autophagy was supported by the dose-dependent increase of LC3BII, autophagy-related gene-5 (ATG-5) and Beclin-1. Notably, silencing ATG-5 further reduced the cell viability and enhanced apoptosis in GA-treated colon cancer cells, indicating that GA-induced apoptosis rather than autophagy contributes to colon cancer cell death. And mammalian target of rapamycin complex 1 (mTORC1) was dose-dependently reduced by GA, evidenced by the reduction of p-mTOR, p-p70 ribosomal S6 kinase (p70s6k) and p-pras40. Moreover, GA markedly resulted in reactive oxygen species (ROS) generation, along with increased H2O2 and O2-. However, blocking ROS generation using its scavenger, NAC, significantly recovered GA-induced cells death, supported by the increase of cell viability, and the decrease of apoptosis. The expressions of autophagy- and cell cycle arrest-related molecules, as well as mTORC1 were also reversed by N-acetyl-l-cysteine (NAC) in GA-treated cells. In vivo, GA reduced tumor growth without toxicity to animals. In conclusion, our study illustrated that GA caused G0/G1 phase arrest and triggered intrinsic apoptosis and autophagy modulated by ROS generation in human colon cancer, elucidating that GA might be considered as a potential agent for colon cancer therapy.

Effect of Duration of Ex Vivo Ischemia Time and Storage Period on RNA Quality in Biobanked Human Renal Cell Carcinoma Tissue.

BACKGROUND: RNA degradation is a major problem in tissue banking, and the effects of the ex vivo ischemia time, storage time, and transport conditions on RNA integrity and gene expression have not been well understood. METHODS: A total of 100 fresh-frozen clear cell carcinoma tissues and matched normal tissues during five storage periods (≤6, 7-12, 13-18, 19-24, and 25-30 months) were chosen to detect RNA quality. At surgery, fresh kidney cancer tissues from five patients were cut into pieces and snap frozen. Additional fresh tissue pieces were (1) left at room temperature, (2) kept on ice, or (3) placed in normal saline before being snap frozen after 0.5, 1, 2, or 4 h. RNA integrity was determined by microchip electrophoresis, and gene expression was analyzed by real-time polymerase chain reaction. RESULTS: Altogether, 82 % of kidney cancer specimens banked using a standardized protocol yielded RNA with an RNA integrity number of ≥7 (7.77 ± 0.95, 7.87 ± 0.37, 7.15 ± 1.46, 8.10 ± 0.64, and 7.11 ± 1.08 during the five storage periods, respectively). RNA remained intact after 4 h on ice, whereas degradation was found in tissues left at room temperature or in saline. Expression of genes in certain functional pathways changed during storage under three conditions. CONCLUSIONS: More than 80 % of the banked kidney cancer biospecimens collected following a standardized protocol yielded high-quality RNA. Fresh human cancer tissue samples should be transported on ice before biobanking to avoid a major reduction in RNA quality. The presented data should be considered in attempts to further standardize tissue biospecimen collection and banking.

Eyelid sporotrichosis: Unique clinical findings in 72 patients.

Sporotrichosis on the eyelids is uncommon and has been rarely reported. As the largest series of 72 adults and children with eyelid sporotrichosis from Jilin ̀P̀̀rovince in China, this study provides useful information for the improved diagnosis and treatment of sporotrichosis.

Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function.

Diabetes-induced testicular cell death is due predominantly to oxidative stress. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an important transcription factor in controlling the antioxidative system and is inducible by sulforaphane (SFN). To test whether SFN prevents diabetes-induced testicular cell death, an insulin-defective stage of type 2 diabetes (IDS-T2DM) was induced in mice. This was accomplished by feeding them a high-fat diet (HFD) for 3 mo to induce insulin resistance and then giving one intraperitoneal injection of streptozotocin to induce hyperglycemia while age-matched control mice were fed a normal diet (ND). IDS-T2DM and ND-fed control mice were then further subdivided into those with or without 4-mo SFN treatment. IDS-T2DM induced significant increases in testicular cell death presumably through receptor and mitochondrial pathways, shown by increased ratio of Bax/Bcl2 expression and cleavage of caspase-3 and caspase-8 without significant change of endoplasmic reticulum stress. Diabetes also significantly increased testicular oxidative damage and inflammation. All of these diabetic effects were significantly prevented by SFN treatment with upregulated Nrf2 expression. These results suggest that IDS-T2DM induces testicular cell death presumably through caspase-8 activation and mitochondria-mediated cell death pathways and also by significantly downregulating testicular Nrf2 expression and function. SFN upregulates testicular Nrf2 expression and its target antioxidant expression, which was associated with significant protection of the testis from IDS-T2DM-induced germ cell death.

Association of glutathione S-transferase M1, T1, and P1 polymorphisms with renal cell carcinoma: evidence from 11 studies.

The glutathione S-transferases (GSTs) are a gene superfamily of phase II metabolic enzymes that has attracted a considerable attention as a candidate gene for renal cell carcinoma (RCC) based on its enzyme function as a key factor in biotransformation pathways. In the past decade, a number of case-control studies were conducted to investigate the association of GST genetic polymorphisms and RCC risk. However, studies on the association between GST (GSTM1, GSTT1, and GSTP1) polymorphisms and RCC remain to be conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 2,189 cases and 3,817 controls from 11 case-control studies was performed. Overall, the summarized odds ratio for RCC of the GSTM1 null and GSTT1 null polymorphisms was 1.02 (95% confidence interval (CI) 0.91-1.15, P = 0.70) and 1.28 (95% CI 0.96-1.72, P = 0.09), respectively. No significant results were observed in heterozygous and homozygous genotypes when compared with wild-type genotype for GSTP1 I105V polymorphism. However, the GSTM1-GSTT1 interaction analysis showed that the dual null genotype of GSTM1/GSTT1 was significantly associated with an increased RCC risk (odds ratio (OR) = 1.42, 95% CI 1.14-1.76, P = 0.001). In the stratified analyses by ethnicity, significant gene-disease association was obtained among Asians for GSTT1 and GSTP1 polymorphisms. In our meta-analysis, the associations between variations of GSTs and RCC may vary in different ethnic populations, and the interaction between unfavorable GST genotypes may exist.

Differential gene expression of the key signalling pathway in para-carcinoma, carcinoma and relapse human pancreatic cancer.

Pancreatic cancer (PC) has a high rate of mortality and a poorly understood mechanism of progression. Investigation of the molecular mechanism of PC and exploration of the specific markers for early diagnosis and specific targets of therapy are key points to prevent and treat PC effectively and to improve their prognosis. In our study, expression profiles experiment of para-carcinoma, carcinoma and relapse human PC was performed using Agilent human whole genomic oligonucleotide microarrays with 45 000 probes. Differentially expressed genes related with PC were screened and analysed further by Gene Ontology term analysis and Kyoto encyclopaedia of genes and genomes pathway analysis. Our results showed that there were 3853 differentially expressed genes associated with pancreatic carcinogenesis and relapse. In addition, our study found that PC was related to the Jak-STAT signalling pathway, PPAR signalling pathway and Calcium signalling pathway, indicating their potential roles in pancreatic carcinogenesis and progress.