British Journal of Biomedical Science最新文献

Background: Vitamin D derivatives and their receptor (VDR) are immune-response modulators in many diseases including malignancies, metabolic conditions, and infections. We hypothesized that one or more variants of VDR single nucleotide polymorphisms (SNPs) are associated with hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients. Materials and Methods: A total of 861 subjects were recruited and classified as spontaneous viral clearance (SVC, n = 127), chronic hepatic cirrhosis (CHC, n = 392), and HCC (n = 342). Standard routine laboratory tests were performed and clinical features noted. All individuals were genotyped for seven SNPs spanning the VDR using real-time PCR. Results: Genotype frequencies of SNPs rs7970376, rs11568820, rs4516035, rs2228570 (Fok1), rs1544410 (Bsm-1), and rs731236 (Taq1), but not rs739837, were variously altered in CHC and HCC compared with SVC, and in HCC compared to CHC (all p < 0.001). The most powerful was rs7970376, which brought an OR (95% CI) of 7.14 (4.64-10.98) for HCC compared to SVC (p = 0.001). The carriage of the AGTAC haplotype of five SNPs were linked to CHC compared to SVC at OR 2.88 [95% CI 1.2-6.9] (p = 0.017) and with HCC compared to CHC at OR 1.54 [95% CI = 1.04-2.27 (p = 0.031). Conclusion: SNPs in VDR may have a potential role in the outcomes of patients with HCV infection. VDR SNPs; rs7970376, rs11568820, rs4516035, rs2228570 (Fok1), rs1544410 (Bsm-1), and rs731236 (Taq1) could be used as molecular markers to predict the risk of HCC.

Introduction: Diabetes is a leading risk factor for cardiovascular disease (CVD), the pathophysiology of both being linked to metabolic, endothelial, renal, angiogenic and platelet abnormalities. We hypothesised that abnormalities in these systems are more adverse in those whose CVD is compounded by diabetes, compared to those with diabetes or CVD alone. Materials and methods: Serum or plasma from 66 patients with diabetes alone, 76 with CVD alone, and 70 with both diabetes and CVD i.e. diabetic cardiovascular disease, was probed for markers of angiogenesis [angiopoietin 1 and 2, vascular endothelial growth factor (VEGF) and endoglin], metabolic [soluble receptor for advanced glycation products (sRAGE), leptin, lipocalin-2, interleukin-8, and cystatin-C], the endothelium (von Willebrand factor, endothelial microparticles and soluble E selectin)], and the platelet (platelet microparticles and soluble P selectin) by ELISA, Luminex or flow cytometry. Results: VEGF (p = 0.04), von Willebrand factor (p = 0.001) and endothelial microparticles (p = 0.042) were all higher in diabetic cardiovascular disease than in diabetes alone and cardiovascular disease alone. Soluble E selectin was higher in diabetic cardiovascular disease than in diabetes alone (p = 0.045), whilst cystatin-C (p = 0.004) and soluble P selectin (p < 0.001) were higher in diabetes and diabetic cardiovascular disease than in cardiovascular disease alone. There were no differences in angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, or interleukin-8. Conclusion: Angiopoietin 1 or 2, endoglin, sRAGE, leptin, lipocalin-2, interleukin-8, and cystatin-c cannot differentiate diabetes from cardiovascular disease, or both conditions combined. Our data point to a more adverse endothelial (von Willebrand factor, endothelial microparticles), and angiogenic profile (VEGF) in those with diabetic cardiovascular disease, supporting the view that this group should be targeted more aggressively.

Background: Evidences suggest that single nucleotide polymorphisms (SNPs) can be considered as potential biomarkers for disease progression and therapeutic response in cervical cancer. The present study investigated the association of CYP1A1 T>C (rs4646903), CYP1A1 A>G (rs1048943), CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), XRCC1 G>A (rs25487), XRCC2 G>A (rs3218536) and XRCC3 C>T (rs861539) polymorphisms with treatment outcome of cisplatin based chemoradiation (CRT). Methods: Total 227 cervical cancer cases, treated with the same chemoradiotherapy regimen were selected for the study. Genotyping analysis was performed by PCR-restriction fragment length polymorphisms (PCR-RFLP). Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST). Association of all clinical data (responses, recurrence and survival of patients) and single nucleotide polymorphisms (SNPs) was analysed by using SPSS (version 21.0). Results: Patients with TA/AA genotype of CYP2E1 T>A polymorphism showed significantly poor response while those with GC/CC genotype of RAD51 G>C showed better response (p = 0.008, p = 0.014 respectively). Death was significantly higher in patients with GG genotypes of RAD51 G>C and XRCC1 G>A (p = 0.006, p = 0.002 respectively). Women with GC+CC genotype of RAD51 G>C and AG+GG of XRCC1 showed better survival and also reduced risk of death (HR = 0.489, p = 0.008; HR = 0.484, p = 0.003 respectively). Conclusion: Results suggested that CYP2E1 T>A (rs6413432), RAD51 G>C (rs1801320), and XRCC1 G>A (rs25487) polymorphisms may be used as predictive markers for clinical outcomes in cervical cancer patients undergoing cisplatin based concomitant chemoradiotherapy.

The purpose of the article: The MIR137 gene acts as a tumor-suppressor gene in colon and gastric cancers. The aim of this study was to investigate the association of functional variable number tandem repeat (VNTR) polymorphism rs58335419 locating in the upstream of the MIR137 gene with the risk of colon and gastric cancers. Materials and methods: Totally, 429 individuals were contributed in the study, including 154 colon and 120 gastric cancer patients and 155 healthy controls. The target VNTR was genotyped using PCR and electrophoresis for all samples. Statistical analysis was performed using SPSS 21.0 software and by T, χ2 and logistic regression tests. Results: Excluding the rare genotypes, our results showed that genotype 3/5 (95% CI = 1.08-3.73, OR = 2.01, p = 0.026) significantly increased the risk of colon cancer but not gastric cancer (95% CI = 0.88-3.30, OR = 1.70, p = 0.114). Also, in the stratification analysis for VNTRs and sex, genotypes 3/4 (95% CI = 1.00-6.07, OR = 2.46, p = 0.049) and 3/5 (95% CI = 1.25-7.18, OR = 2.99, p = 0.014) significantly increased the risk of colon cancer in men but not in women. In addition, all genotypes including the rare genotypes as a group, significantly increase the risk of gastric (95% CI = 1.14-3.00, OR = 1.85, p = 0.012) and colon (95% CI = 1.38-3.43, OR = 2.17, p = 0.001) cancers compared to the genotype 3/3 as a reference. Conclusion: The results show that increasing the copy of VNTR in the MIR137 gene, increases the risk of colon and gastric cancers and can serve as a marker for susceptibility to colon and gastric cancers.

Round cells in seminal fluid are defined as either leucocytes or immature germ cells. Laboratories undertaking semen analysis often report these combined as a concentration, with no further review, comment or direction for clinician action or review. Although numerous publications discuss the possible clinical relevance of these cells (particularly leucocytes) in infertility, the methods employed to differentiate them are often beyond the scope of most diagnostic laboratories. This paper aims to support healthcare scientists in understanding the clinical significance of round cells and aid their identification, differentiation and interpretation. This will support the quality of care the patient receives and direct clinicians to further considerations that may be appropriate for their patient and should consequently reduce indiscriminate and unnecessary use of antibiotics.

Background: There are isolated reports of mutations in genes for isocitrate dehydrogenases (IDH1 and IDH2), but few have been examined in a large number of different malignancies. We aimed to analyze mutational prevalence of these genes in a large series of cancers and determine their significance in most mutated phenotype. Methods: We analyzed the frequencies of IDH1 and IDH2 mutations in 14,726 malignancies of 37 cancers. Furthermore, we examined these mutations in the most frequent cancer (gliomas, 923 cases) from a single cohort, and determined their clinical significance. Results: IDH1 mutations were present in 3% (473/14,726) of cancers. The highest frequencies were in oligodendrogliomas (91/102, 89%), anaplastic oligodendrogliomas (40/46, 87%), and diffuse astrocytomas (89/116, 77%). IDH2 mutation was detected in <1% (83/14,726) of cancers, but were present in 13% (6/46) of anaplastic oligodendrogliomas, 9% (9/102) of oligodendrogliomas, and in 5% (2/39) of cutaneous squamous cell carcinomas. Further analyses of 923 gliomas revealed 34 and 1% of IDH1 and IDH2 mutations, respectively. In up to 342 months of follow-up, IDH1 and IDH2 mutations were significantly linked with better overall (OS) (both p = 0.01) and progression-free survival (PFS) (p = 0.01; p = 0.004), respectively. Conclusion: IDH1 and IDH2 are often mutated in a tissue-specific manner, most commonly in gliomas. Mutation in both genes is linked to OS and PFS. Our findings suggest that these genes are promising therapeutic targets and strong prognostic biomarkers in gliomas.

Background: Breast cancer is a multifactorial disease whose genetic susceptibility is related to polymorphic variants of cell proliferation and migration pathways. Variants in AXIN2 and TCF7L2 in the Wnt-β catenin pathway have been associated with different types of cancer; however, little is known about its role in breast cancer. This study tests the hypothesis of links between AXIN2 rs1133683 and rs2240308, and TCF7L2 rs7903146 and rs12255372 variants in breast cancer. Methods: Peripheral blood samples were obtained from 404 women (202 patients and 202 control females). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology was used to identify the gene variants. Results: The AXIN2 rs2240308 (C > T), and TCF7L2 rs7903146 (C > T) and rs12255372 (G > T) variants were associated with breast cancer and with age, TNM stage, and histologic-molecular subtype (p = 0.001). Likewise, the haplotype T-T in the TCF7L2 gene (rs7903146-rs12253372) was significantly related with breast cancer (OR = 2.66, 95%, CI = 1.64-4.30, p = 0.001). Conclusion: Our data show a link between AXIN2 rs2240308 and TCF7L2 rs7903146 and rs12255372 variants in breast cancer, and speculate this may be important in pathogenesis.

Background and Aim: Diabetes mellitus (DM) is a chronic disorder with diabetic retinopathy (DR) as one of its main microvascular outcomes, being a prime cause of vision loss. Dysregulation of microRNAs (miRNAs) has been associated with some diabetic microvascular complications such as diabetic retinopathy. This hypothesised changes in the serum of miR-93 and miR-152 in diabetes and diabetic retinopathy. Methods: The study cohort consisted of 80 healthy volunteers, 80 type 2 diabetic patients, and 80 diabetic retinopathy patients, of whom 40 had proliferative (PDR) and 40 non-proliferative retinopathy (NPDR). Serum fasting and 2-hour postprandial glucose (2hPP), glycated haemoglobin (HbA1c), fasting insulin, and HOMA-IR were evaluated by routine methods, miR-93 and miR-152 expression by quantitative real-time PCR. Results: FBG, 2hPP, fasting insulin, HOMA-IR, and miR-152 showed an increasing trend across groups while miR-93 showed a decreasing trend (all p < 0.001). Binary logistic regression analysis for prediction of DR found that the most significant were miR-152 (OR 1.37, 95% CI: 1.18-1.58, <0.001), BMI (1.13, [1.07-1.31], p = 0.004), duration of disease (1.29 [1.04-1.6] p = 0.018), and miR-152 (0.01, [0.0-0.47] p = 0.019). The most significant predictors of PDR were miR-152 (OR = 1.47, 95% CI: 1.12-1.92, p = 0.005), HOMA-IR (2.66 [1.30-5.45] p = 0.007), and miR-93 (0.25 [0.07-0.86] p = 0.028). Conclusion: MiR-93 and miR-152 can differentiate patients with diabetes and those with DR. Both miRNAs might be potential biomarkers for diabetes and diabetic retinopathy, and specifically for proliferative diabetic retinopathy.

Objective: To study the optimal cut-off value of thyroglobulin measurement in a fine-needle aspiration (FNA-Tg) in diagnosing malignant lymph nodes and benign lymph nodes (LNs) according to the thyroid tissue status. Methods: A total of 517 LNs were aspirated: 401 preoperative LNs, 42 LNs after subtotal thyroidectomy and 74 suspected LNs after total thyroidectomy. The cut-off value of FNA-Tg was obtained from receiver operating characteristic (ROC) analysis. The cut-off value with the best diagnostic performance was then obtained by comparing different cut-off values from other studies. Results: LN FNA-Tg levels differed between preoperative and total thyroid disease (p < 0.001) and subtotal thyroidectomy and total thyroidectomy (p = 0.03), but not between preoperative and subtotal thyroidectomy (p = 1.00). Accordingly, those 443 LNs with preoperative and subtotal thyroidectomy were compared to those 74 without thyroid tissue. The optimal cut-off value in thyroid tissue group was 19.4 ng/ml and the area under the ROC curve (AUC) was 0.95 (95% CI 0.92-0.97). The optimal cut-off value in thyroid tissue absence group was 1.2 ng/ml and the AUC was 0.93 (0.85-0.98). After the analysis and comparison of multiple cut-off values, the optimal diagnostic performance was still found to be 19.4 ng/ml and 1.2 ng/ml. Conclusion: The influential factors of FNA-Tg are still controversial, and the optimal cut-off value of FNA-Tg can be determined based on the presence or absence of thyroid tissue. FNA-Tg can be used as an important auxiliary method for diagnosing cervical metastatic LNs of thyroid cancer.