Successful amphiphiles as the key to crystallization of membrane proteins: Bridging theory and practice

Background

Membrane proteins constitute a major group of proteins and are of great significance as pharmaceutical targets, but underrepresented in the Protein Data Bank. Particular reasons are their low expression yields and the constant need for cautious and diligent handling in a sufficiently stable hydrophobic environment substituting for the native membrane. When it comes to protein crystallization, such an environment is often established by detergents.

MicroRNA-195 and microRNA-378 mediate tumor growth suppression by epigenetical regulation in gastric cancer

The epigenetic regulation of microRNAs is one of several mechanisms underlying carcinogenesis. We found that microRNA-195 (miR-195) and microRNA-378 (miR-378) were significantly down-regulated in gastric cancer tissues and gastric cancer cell lines. The expression of miR-195 and miR-378 in gastric cancer cells was significantly restored by 5-aza-dC, a demethylation reagent. The low expression of miR-195 and miR-378 was closely related to the presence of promoter CpG island methylation. Treatment with miR-195/miR-378 mimics strikingly suppressed the growth of gastric cancer cells whereas promoted the growth of normal gastric epithelial cells. In contrast, administration of miR-195/miR-378 inhibitors significantly prevented the growth of normal gastric epithelial cells. Expression of cyclin-dependent kinase 6 and vascular endothelial growth factor was down-regulated by exogenous miR-195 and miR-378, respectively. In conclusion, miR-195 and miR-378 are abnormally expressed and epigenetically regulated in gastric cancer cell lines and tissues via the suppression of CDK6 and VEGF signaling, suggesting that miR-195 and miR-378 have tumor suppressor properties in gastric cancer.     

The impact of renin–angiotensin system,angiotensin І converting enzyme (insertion/deletion), and angiotensin ІІ type 1 receptor (A1166C) polymorphisms on breast cancer survival in Iran

Introduction

Several proteins of renin–angiotensin system (RAS) have been implicated in the process of growth promotion or inhibition of breast tissue and cancer cells. This study aimed to investigate the association between angiotensin I converting enzyme (ACE) insertion/deletion (I/D) and angiotensin receptor-1 (AGTR1) A1166C polymorphisms and survival of 110 women with breast cancer.

Materials and methods

The I/D and A1166C polymorphisms were evaluated by using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) in 110 breast cancer patients who had been treated between 2007 and 2009. Genomic DNA was extracted from a Formalin-Fixed Paraffin-Embedded (FFPE) tissue of breast cancer sample blocks. All the potential clinical and pathological prognostic variables were analyzed to establish the impact of I/D and A1166C polymorphisms on disease-free and overall survival rates. Disease-free and overall survival rates were the primary endpoints of the study.

Results

The ACE (I/D) polymorphism was associated with 3-year disease-free survival. Disease-free survival in DD carriers was significantly increased compared to ID plus II carriers (HR = 4.75; 95% CI, 1.39–16.24; p = 0.013). No significant association was found between AGTR1 (A1166C) and 3-year disease-free survival (p = 0.233). Also, the ACE (I/D) and AGTR1 (A1166C) polymorphisms were not associated with breast cancer overall survival.

Conclusion

The ACE (I/D) polymorphism was associated with 3-year disease-free survival of the women with breast cancer. Besides, disease-free survival in DD carriers was significantly increased compared to ID plus II carriers.     

C反应蛋白在结直肠癌患者中的表达及与预后的关系

摘要目的：4g讨C反应蛋白（CRr＇）在结直肠癌患者中的表达及与预后的关系。方法：采用免疫速率散射比浊法检测血清CRP,并与健康对照组进行比较,分析CRP与临床病理分期之间的关系,评价术前、术后CRP表达与预后的关系。结果：研究组术前CRP为（28．64±7．15）mg／L,术后降低为（7．83±1．03）mg／L,差异有统计学意义（P〈0．05）,都高于对照组的（1．13±0．28）mg／L,差异有统计学意义（P〈0．05）。CRP表达与年龄和性别中的表达差异无统计学意义（P〉0．05）,与T、N、M分期和分化程度有关（P〈0．05）。术前高、低CRP组的5年生存率分别为79．17％和95．24％,差异有统计学意义（P〈0．05）;术后高、低CRP组的5年生存率分别为85．00％和88．00％,差异无统计学意义（P〉0．05）。结论：结直肠癌与炎症反应密切相关,CRP在其发生、发展中发挥着重要作用,术前CRP水平对疾病的预后具有一定的预测价值。     

Effect of interleukin-17A and interleukin-17F gene polymorphisms on the risk of gastric cancer in a Chinese population

We selected six tagged single-nucleotide polymorphisms (SNPs) in the IL-17A and IL-17F genes, and evaluated the relationship between the six common SNPs and H. pylori infection, tobacco smoking and subsites of gastric cancer in gastric cancer patients. Genotyping of IL-17A (rs2275913, rs3748067 and rs3819025) and IL-17A (rs763780, rs9382084, and rs12203582) was performed in a 384-well plate format on the MassARRAY® platform. An unconditional multiple logistical regression model was performed to determine the association between IL-17A and IL-17F genetic variations and gastric cancer risk. Unconditional logistic regression analysis showed that subjects carrying the rs2275913AA and rs3748067 TT genotypes were 1.70 and 3.45 times more likely to develop gastric cancer. Furthermore, rs2275913 and rs3748067 genetic variants significantly interacted with H. pylori infection on the risk of gastric cancer. The interaction between rs3748067 and rs9382084 genetic variants and tobacco smoking trend was significant. In addition, rs2275913, rs3748067 and rs9382084 genetic variants were only associated with non-cardia gastric cancer. The findings suggest that the rs2275913, rs3748067 and rs9382084 polymorphisms increase the risk of gastric cancer, and they interact with H. pylori infection, tobacco smoking and subsites of gastric cancer. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer.     

Clinicopathological characteristics of androgen receptor splicing variant 7 (AR-V7) expression in patients with castration resistant prostate cancer: A systematic review and meta‐analysis

Background Studies have shown that AR-V7 may be correlated with the poor prognosis of castration resistant prostate cancer (CRPC), however, clinicopathological characteristics of AR-V7 have not been fully elucidated.ObjectiveThis study aimed at evaluating the clinicopathological features of AR-V7 in CRPC patients.Materials and methodsTo evaluate the clinicopathological features of AR-V7 in CRPC patients. A search of PubMed, Embase, and Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma, AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Twenty-four trials published by February 2020 were included in this study.ResultsThe proportion of Gleason score ≥ 8 was found to be significantly higher in AR-V7-positive CRPC (69.5%) than negative (54.9%) (OR 1.68, 95% CI 1.25–2.25, p < 0.001), while the rates of T3/T4 stage (OR 1.16, 95% CI 0.60–2.24, p = 0.65) and N1 stage (OR 0.99, 95% CI 0.65–1.51, p = 0.96) were not statistically correlated with AR-V7 status. The AR-V7-positive patients exhibited a significantly higher proportion of any site metastasis (61.3% versus 35.0%; OR 2.19, 95% CI 1.57–3.05, p < 0.001) and bone metastasis (81.7% versus 69.0%; OR 1.97, 95% CI 1.44–2.69, p < 0.001), and a trend close to significance was expected in visceral metastasis (28.8% versus 22.1%; OR 1.29, 95% CI 0.96–1.74, p = 0.09). Incidences of pain in AR-V7-positive CRPC (54.6%) were significantly higher than in negative CRPC (28.1%; OR 4.23, 95% CI 2.52–7.10, p < 0.001), line with worse ECOG performance status (56.7% versus 35.0%, OR 2.18, 95% CI 1.51–3.16, P < 0.001). Limitations of the study include differences in sample sizes and designs, AR-V7 detection assays, as well as disease characteristics of the included studies.ConclusionsAR-V7 positivity is associated with a higher Gleason score, bone or any site metastasis, pain and worse ECOG performance scores in CRPC. However, it is not correlated with tumor stage or lymph node metastasis. More studies are needed to confirm these findings.     

Overexpression of sigma1 receptor and its positive associations with pathologic TNM classification in esophageal squamous cell carcinoma

Sigma1 receptor (sigma1R), a significant protein, has been found to be frequently upregulated in human tumor cells and tissues. It has been demonstrated that sigma1R is involved in proliferation and adhesion of cancer cells. However, the significance of sigma1R expression in esophageal squamous cell carcinoma (ESCC) remains unclear. In this article, by a series of methods, the authors examined the expression of sigma1R protein in ESCC cell lines and tissues. Flow cytometry indicated intense staining of sigma1R in ESCC cells. Immunocytochemistry staining demonstrated that sigma1R was mainly distributed in cytoplasm and nucleus in ESCC cell lines. Western blotting was performed to characterize the relative expression of sigma1R in different ESCC cell lines. Moreover, different levels of sigma1R were presented from normal epithelium to carcinoma by immunohistochemistry analysis, which demonstrated that sigma1R was highly expressed in tumors. Association analysis showed significant correlations between total sigma1R protein levels and pathologic TNM (pTNM) classification of tumors (r=0.216, p=0.011). Furthermore, the sigma1R in the nucleus was significantly correlated with pTNM classification and lymph node metastasis (r=0.263, p=0.002, and r=0.269, p=0.002, respectively). These data indicated that sigma1R may serve as a potential predictive factor for pTNM classification and tumor development in ESCC.     

The role of chemokine and chemokine receptor gene variants on the susceptibility and clinicopathological characteristics of bladder cancer

The gene variants of the chemokine and chemokine receptor genes associated with inflammation may be involved in cancer initiation and progression. The aim of this study was to explore the possible association of monocyte chemoattractant protein-1 (MCP-1) A2518G, stromal cell derived factor 1 (SDF-1) 3′A and chemokine receptors CCR2A V64I, CCR5 Δ32, CCR5 59029 and CXCR4 gene polymorphisms with the risk and clinicopathological characteristics of bladder cancer (BC) in a Turkish population.     

Functionality of nitrated acetylcholine receptor: the two-step formation of nitrotyrosines reveals their differential role in effectors binding

The presence of nitrotyrosines is associated with several neurodegenerative pathologies. We evaluated the functionality of the nicotinic acetylcholine receptor possessing nitrotyrosines. The spectrum of the nitrated receptor displays an absorption band characteristic of ortho-nitrophenol. The presence of carbamylcholine in the agonist site prevented the effect of nitration by tetranitromethane in some conditions. The nitration occurred with two discrete steps and pointed out the differential involvement of tyrosines in the binding of acetylcholine and neurotoxin. We concluded that at least two residues involved in agonist binding can be nitrated, which bring similar contributions to the binding energy of the neurotransmitter.     

miR-34a is associated with clinical outcome of colorectal cancer patients

Aberrant expression of microRNA-34a (miR-34a) has been reported to be involved in the tumorigenesis and progression of various classes of malignancies. However, its role in colorectal cancer (CRC) has not been completely clarified. In the current study, we have investigated the clinical significance of miR-34a. MiR-34a expression in forty-three cases of colorectal cancer tissues decreased significantly compared to that in the adjacent non-tumorous colorectal tissues (P＜0.05), as detected by real-time quantitative RT-PCR (qRT-PCR). Significantly, the expression of miR-34a was correlated with infiltration depth and clinical TNM stage (P <0.05). The miR-34a however had no correlation with other features, such as age, gender, site, tumor sizes, lymph node metastasis, serous membrane infiltration ( all P> 0.05). MiR-34a is a tumor suppressor miRNA that plays a vital role in the oncogenesis and progression of colorectal cancer. This study suggests that miR-34a may be a new tumor marker or prognostic factor in colorectal cancer. The strategies to increase miR-34a level might be a critical targeted therapy for CRC in the future.