PurposeThe aim of this study was to determine whether CD8+ T lymphocyte and its checkpoint-associated module programmed cell death protein 1 (PD-1)/main ligand of PD-1 (PD-L1) pathway impact overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs).Materials and methodsA total of 231 mRCC patients, from 2007 to 2017, treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were included in the study analyses. CD8, PD-1, and PD-L1 was assessed by immunohistochemistry on continuous paraffin-embedded slides. Kaplan–Meier method and COX regression model were applied in the survival analyses.ResultsBaseline characteristics were comparable between the training (n=118) and validation (n=113) sets. Patients with high CD8+ T lymphocytes infiltration and low PD-1 expression had longer survival in both sets (P=0.0106 and P=0.0047 in training set, P=0.0291 and P=0.0011 in validation set, respectively). However, survival stratified by PD-L1 was only insignificant or marginally significant. Multivariable analyses verified that CD8+ T lymphocytes, together with PD-1, but not tumor infiltrating mononuclear cells or tumor cells PD-L1, were independent prognostic factors (training set [HR 3.202, 95% CI 1.433–7.153, P=0.011] and validation set [HR 4.012, 95% CI 2.354–6.838, P<0.001]). Subsequent analysis revealed that the PD-1 high/CD8 low group had shorter survival (16 months) than PD-1 low/CD8 high group (51 months, P<0.0001). Combining the International Metastatic Renal Cancer Database Consortium system with the PD-1/CD8 model exhibited much better accuracy for the prediction of OS.ConclusionOur findings suggest that abundant CD8+ T cells are significantly associated with longer OS in mRCC patients treated with TKIs. The most influential checkpoint-associated molecule, PD-1, assisted CD8+ T cell-stratified patients and could be used as a better predictive and prognostic factor for the mRCC patients.
Our findings suggest that pseudocapsule status has good prognostic implications in renal cell carcinoma. Lack of a pseudocapsule certainly had a remarkably adverse impact on the patient outcome. Accessibility in use and cost makes pseudocapsule status a potential cost-effective parameter in clinical practice.
In this work, a novel synthetic path for preparing semi-armotic components modified polyamide 6 was developed by caprolactam as solvent of purified terephthalic acid and 1,6-hexanediamine. First, the ring opening reaction and poly-addition of caprolactam were initiated by 1,6-hexanediamine to generate a prepolymer containing amino groups in both ends, then followed by the poly-condensation reaction with purified terephthalic acid, a long chain copolymer was produced, which the reaction time was reduced by 4 h compared with conventional hydrolytic ring-opening polymerization of pure caprolactam. By varying the ratio of terephthalic acid and 1,6-hexanediamine, a series of copolymers with different number average molecular weight and physical properties were prepared. Analytical results showed that the conversion percentage of caprolactam is significantly increased by the proposed method. Furthermore, this new copolymers exhibited excellent transparence and high decomposition temperature. Besides, the copolymers with average molecular weight !15,000 present good mechanical properties, making it a potentially useful application in plastics, textile yarn, and membranes. V C 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 959-967
SETD2 is a potential prognostic biomarker for overall survival and progression-free survival prediction in patients with metastatic renal cell carcinoma receiving targeted therapy. However, it remains to be seen whether this is generalizable to other ethnicities and prospective external validation is required.
Galangin, a flavonoid extracted from the root of the Alpinia officinarum Hence, has been shown to have anticancer properties against several types of cancer cells. However, the influence of galangin on human renal cancer cells remains to be elucidated. In the present study, proliferation of 786-0 and Caki-1 cells was suppressed following exposure to various doses of galangin. Cell invasion and wound healing assays were used to observe the effect of galangin on invasion and migration. The results demonstrated that Galangin inhibited cell invasion by suppressing the epithelial mesenchymal transition (EMT), with an increase in the expression of E-cadherin and decreased expression levels of N-cadherin and vimentin. The apoptosis induced by galangin was analyzed by flow cytometry. The results revealed that galangin induced apoptosis in a dose-dependent manner. The accumulation of reactive oxygen species (ROS) is an important contributing factor for the apoptosis of various types of cancer cell. The dichlorofluorescein-diacetate method was used to determine the level of ROS. Galangin induced the accumulation of intracellular ROS and malondialdehyde, and decreased the activities of total antioxidant and superoxide dismutase in renal cell carcinoma cells. Galangin exerted an antiproliferative effect and inhibited renal cell carcinoma invasion by suppressing the EMT. This treatment also induced apoptosis, accompanied by the production of ROS. Therefore, the present data suggested that galangin may have beneficial effects by preventing renal cell carcinoma growth, inhibiting cell invasion via the EMT and inducing cell apoptosis.
Anaphylatoxin C5a and its receptor C5aR on cancer cells constitute a vital axis to cancer progression. In this study, we measured C5aR level by immunohistochemistry in the same cohort of our previous C5a research, and C5a-C5aR axis status was determined by synthesizing C5a and C5aR data. C5aR was an adverse independent prognostic factor for ccRCC patients. Kaplan-Meier analyses revealed the unique position of both C5a and C5aR high population in postoperative survival, based on which patients were then shunted into C5a-C5aR enriched and non-enriched groups. Obviously, C5a-C5aR enriched patients significantly had a poorer overall survival (OS) and recurrence free survival (RFS) compared with non-enriched ones, and the independence of C5a-C5aR axis was verified by multivariable analyses (HR 2.118, P = 0.001 for OS, HR 1.715, P = 0.035 for RFS). Established nomograms based on our findings reflected much better predicting accuracy in contrast with most common used TNM and Fuhrman systems. Meanwhile, consistent with HR, C5a-C5aR axis in this study held its advantages over C5a and C5aR for OS prediction by c-index analyses, rather than RFS prediction.
Non-small cell lung carcinoma (NScLc) accounts for 85% of all lung cancers and the five-year survival rate is ~1% in the late stage. circular RNAs (circRNAs) were reported to be involved in the progression of diverse human cancers. However, the role of circ-ACACA in NSCLC progression remains elusive. Quantitative polymerase chain reaction was conducted to detect the expression levels of circ-ACACA and microRNA (miR)-1183 in NScLc tissues and cells. A Cell Counting Kit-8 assay and transwell assay were employed to check proliferation and migration, respectively. Metabolic alternations in NSCLC cells were monitored by the Seahorse XFe96 analyzer. The protein levels of cellular myelocytomatosis, matrix metallopeptidase 9, glucose transporter 1, phosphatase and tensin homolog, phosphoinositide 3-kinases (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (PKB) and p-PKB in samples were measured by western blotting. The interaction between circ-AcAcA and miR-1183 was predicted by circular RNA Interactome, which was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft tumor model was established to investigate the biological roles of circ-ACACA in vivo. The level of circ-ACACA was markedly upregulated in NSCLC tissues and cells, which was contrary to the expression of miR-1183. Knockdown of circ-AcAcA inhibited proliferation and migration of NScLc cells and also reduced the glycolysis rate. In addition, miR-1183 was a target of circ-ACACA and its downregulation reversed circ-ACACA silencing-mediated inhibitory impact on NSCLC progression. Further studies indicated that circ-AcAcA regulated the PI3K/PKB pathway through interacting with miR-1183 and downregulation of circ-AcAcA suppressed tumor growth. Knockdown of circ-ACACA impeded NSCLC progression by sponging miR-1183 and inactivating the PI3K/PKB signaling pathway.
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