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Tumor angiogenesis is required for tumor growth and metastasis, and the Ang/Tie-2 axis plays a pivotal role in angiogenesis. B7-H3, a new member of the B7 family of costimulatory molecules, has a critical function in the T-cell-mediated antitumor immune response, and abnormal tumor B7-H3 expression is frequently associated with a poor prognosis. However, the relationship between B7-H3 and angiogenesis in clear cell renal carcinoma (ccRCC) remains unclear. In this study, we used immunohistochemical methods to detect tumor vascular expression of B7-H3 and Tie-2 in tissue microarrays of 82 ccRCC patient samples. According to the results, B7-H3 is highly expressed in the tumor vascular endothelium of ccRCC and is associated with the ccRCC grade and tumor-node-metastasis (TNM) stage. Although vascular Tie-2 expression was also correlated with T stage and lymph node metastasis, it was not related to ccRCC grade or distant metastasis. The microvessel density (MVD) labeled by CD34 was correlated with tumor grade and TNM stage. Expression of B7-H3 and Tie-2 was positively correlated, and the levels were positively associated with the MVD. Additionally, immunofluorescence staining revealed coexpression of B7-H3 and Tie-2 in the vascular endothelia of ccRCC. Collectively, our findings suggest that expression of B7-H3 and Tie-2 in ccRCC tumor vasculature is closely related to the progression and prognosis of the disease. Furthermore, B7-H3 possibly promotes ccRCC angiogenesis through the Tie-2 pathway. Thus, B7-H3 might serve as an effective endothelial marker for ccRCC prognosis and become a promising target for ccRCC anti-angiogenic-targeted therapy.

Increasing evidence suggests B7-H3 is aberrantly expressed in various cancers, though its prognostic significance in solid tumors remains controversial. We therefore performed a meta-analysis to clarify the prognostic value of B7-H3 expression in human solid tumors. The PubMed and Embase databases were searched, and 28 studies involving 4623 patients were ultimately included in the analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized as effect estimates to evaluate the association between B7-H3 expression and overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS). The pooled results showed B7-H3 was associated with poor OS (HR = 1.58; 95% CI: 1.32–1.90; P < 0.00001) and PFS (HR = 1.67; 95% CI: 1.05–2.65; P = 0.031), but not RFS (HR = 1.17; 95% CI: 0.89–1.53; P = 0.267). These results suggest B7-H3 is a negative predictor of OS and PFS in patients with solid tumors. B7-H3 may thus be a useful prognostic biomarker and therapeutic target for human solid tumors. However, further studies will be needed to more precisely determine the prognostic value of B7 H3 expression.

Prostate cancer is a heritable and clinically heterogeneous cancer. Both long non‐coding RNAs (lncRNAs) and microRNAs (miRs) have been implicated in the pathogenesis and development of prostate cancer. Analysis of microarray data indicated that the lncRNA LINC01207 was differentially expressed in prostate cancer. In silico analysis predicted the interaction between LINC01207 and miR‐1972 as well as the interaction between miR‐1972 and the mRNAs LIM and SH3 protein 1 (LASP1). Thus, we explored the role of LINC01207 and miR‐1972 in the growth and progression of prostate cancer. Quantitative real‐time polymerase chain reaction revealed that LINC01207 and LASP1 were highly expressed in prostate cancer, while miR‐1972 expression was lower. The interaction among LINC01207, miR‐1972, and LASP1 was confirmed by RNA‐fluorescence in situ hybridization, RNA immunoprecipitation, and dual luciferase reporter assay, which verified that LINC01207 could bind to miR‐1972 and downregulate miR‐1972, and miR‐1972 targeted LASP1 and negatively regulated its expression. Both in vitro and in vivo experiments found that silencing LINC01207 inhibited cell proliferation, migration, invasion and tumor formation and enhanced apoptosis in prostate cancer cells, suggesting that LINC01207 functioned as a tumor promoter in prostate cancer and that it may represent a novel therapeutic target.

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Castration-resistant prostate cancer (CRPC) is a heterogeneous disease with a high mortality rate. MicroRNA let-7b has been documented to act as a tumor suppressor in various cancers. The present study intends to explore how let-7b affects CRPC by influencing the Ras/Rho signaling pathway. The expression of neuroblastoma RAS viral oncogene homolog (NRAS) and let-7b in CRPC tissues and cells was determined. The binding relationship between let-7b and NRAS was predicted by the Targetscan website and verified by the dual luciferase reporter gene assay. Gain-of-function and loss-of-function approaches were used to investigate the relationship among let-7b, NRAS, and Ras/Rho signaling pathway as well as their effects on the proliferation, invasion, and apoptosis of CRPC cells. The tumor formation ability of nude mice was tested in vivo. Poorly expressed Let-7b and highly expressed NRAS were presented in CRPC tissues and androgen-independent cell line C4-2. NRAS was verified as a target gene of let-7b. Overexpression of let-7b or silencing of NRAS repressed C4-2 cell proliferation and invasion in vitro and tumor growth in vivo as well as induced C4-2 cell apoptosis in vitro through the blockage of the Ras/Rho signaling pathway. Let-7b overexpression or NRAS silencing reduced matrix metalloproteinase-2, matrix metalloproteinase-9, Bcl-2, cyclinD1, and CyclinB expression, but elevated Caspase3 expression in vivo and in vitro. Taken together, in CRPC, let-7b blocks the Ras/Rho signaling pathway by inhibiting NRAS expression, thereby inhibiting cell proliferation and invasion, and promoting cell apoptosis. Thus, let-7b targeting NRAS may be a potential therapeutic target for the repression of CRPC.Prostate cancer is a kind of noncutaneous cancer with the highest morbidity and the second highest mortality among men. 1 In recent years, advanced and metastatic prostate cancer have become a heavy burden that cannot be solved in short term in the healthcare system. 2 For metastatic prostate cancer, patients can only receive temporary disease control measures by blockading or castrating androgen. 3 Usually, prostate cancer may develop into a lethal form of castration-resistant prostate cancer (CRPC) within 2-3 years as the majority of patients resist to the treatment. 4 CRPC is historically considered as a kind of chemoresistant tumor with a palliative treatment only lasting 1-2 years. 5 It is a major challenge in the treatment of CRPC for lacking easily available and reliable biomarkers. 6 For the same, we conducted a series of experiments in the present study to explore new targets for CRPC treatment.Let-7b belongs to the microRNA let-7 family and usually acts as a tumor suppressor in different types of

Objective. To explore whether acupuncture and moxibustion can prevent disease progression of advanced gastric cancer patients completing second-line chemotherapy and, if so, the related mechanism. Method. Progression-free survival (PFS) and overall survival (OS) were main outcome measures. The real-time quantitative PCR was used to detect the expression of genes including T-bet, IFN-γ, GATA3, and IL-4 in peripheral blood mononuclear cells (PBMCs). IL-4, IL-6, Ca199, CRP, and IFN-γ in plasma levels were checked. Results. 170 patients were randomly assigned in a 3 : 2 ratio to receive either acupuncture and moxibustion or sham acupuncture until progression. 135 patients were included in the primary analysis. Both PFS and OS in treatment group were proven to be better than control group. Acupuncture and moxibustion promoted typical Th1 cells drifting, as confirmed by increased T-bet/IFN-γ and decreased GATA3/IL-4 in mRNA levels from PBMCs, as well as upregulating IFN-γ and downregulating IL-4 in plasma levels. IL-6, Ca199, and CRP in plasma levels were also reduced by acupuncture and moxibustion. Conclusions. Acupuncture and moxibustion can prolong PFS and OS of advanced gastric cancer patients completing second-line chemotherapy by reversing Th1/Th2 shift and attenuating inflammatory responses.

Objective: Despite radical treatment for aggressive muscle-invasive bladder cancer(MIBC), the prognosis remained poor. Programmed cell death ligand 1(PD-L1) plays an important role in suppressing immune responses.We investigate if PD-L1 and EMT synergistically contribute to MIBC progression. Methods: In vitro experiments, we evaluated the effects of PD-L1 on proliferation, invasion, migration of MIBC cells and studied the relationship between PD-L1 and CSC/EMT markers by overexpressing and knocking down PD-L. The association of PD-L1 with EMT was detected in MIBC human specimens and the synergistic effect of PD-L1and EMT was assessed by analysis of overall survival (OS). Results: Our data demonstrated that PD-L1 promotes proliferation, invasion and migration of MIBC cells. The positive correlation between PD-L1 and CSC/EMT markers was verified both in vitro experiments and in 130 MIBC specimens. Moreover, patients with positive PD-L1/positive EMT exhibited poorer overall survival than patients with other combinations. Conclusion: The close relationship between PD-L1 and EMT may offer potential therapeutic strategy that co-targeting PD-L1 and EMT may improve the prognosis of MIBC patients.