economical-efficient-protocol-for-isolating-culturing-bone-marrow

Economical and Efficient Protocol for Isolating and Culturing Bone Marrow-derived Dendritic Cells from Mice

The demand for dendritic cells (DCs) is gradually increasing as immunology research advances. However, DCs are rare in all tissues. The traditional method ...

The Second Hospital of Tianjin Medical University

The prognostic value of C-reactive protein (CRP) in metastatic renal cell carcinoma (RCC) patients receiving tyrosine kinase inhibitors (TKIs) has been investigated in previous studies; however, the results remain inconclusive. This study investigated the prognostic value of pretreatment CRP in patients with metastatic RCC treated with TKIs.

C-reactive protein is a predictor of prognosis in renal cell carcinoma patients receiving tyrosine kinase inhibitors: A meta-analysis.

The prognostic value of p53 expression in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain inconsistent. This study was performed to investigate the prognostic and clinicopathological significance of p53 protein expression in RCC.

Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis.

The prognostic significance of PD-L1 in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain controversial. The primary aim of this meta-analysis was to investigate the prognostic and clinicopathological significance of the PD-L1 expression in patients with RCC. Relevant literature was identified form PubMed, Embase, Web of Science and Cochrane library, which compared the prognostic significance between PD-L1 expression and RCC. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with PD-L1 were extracted from eligible studies. Heterogeneity was assessed using the I value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. A total of 1863 patients from ten eligible studies were analyzed. The results showed that PD-L1 expression is associated with poor overall survival in clear cell RCC (ccRCC) (HR = 2.76, 95%CI: 2.25-3.38, I = 14.4%, P < 0.001) and non-clear cell RCC (non-ccRCC) (HR = 2.77, 95%CI: 1.62-4.72, I = 28.8%, P < 0.001). In addition, PD-L1 expression was found to be significantly associated with primary tumor stage (OR = 1.76, 95%CI: 1.39-2.23; I = 56.3%), regional lymph node involvement (OR = 2.10, 95%CI: 1.48-2.98; I = 14.9%), distant metastases (OR = 2.69, 95%CI: 2.05-3.54; I = 0.0%), nuclear grade (OR = 1.72, 95%CI: 1.32-2.23; I = 79.4%) and histologic tumor necrosis (OR = 2.25, 95%CI: 1.59-3.18; I = 66.1%) in patients with RCC. The outcome stability was confirmed by sensitivity analysis. Both the Begg's funnel plot test (P = 0.276) and the Egger's (P = 0.388) verified that there was no publication bias within the included studies. This study suggests that PD-L1 expression is correlated with poor prognosis and advanced clinicopathological features in RCC patients.

Prognostic and clinicopathological significance of PD-L1 in patients with renal cell carcinoma: a meta-analysis based on 1863 individuals.

The prognostic value of plated-lymphocyte ratio (PLR) in multiple malignancies had been investigated in previous studies; however, its prognostic value in renal cell carcinoma (RCC) remains controversial. This study was performed to assess the prognostic value of preoperative PLR in RCC patients.

Platelet-lymphocyte ratio acts as an independent predictor of prognosis in patients with renal cell carcinoma.

The prognostic value of PBRM1 expression in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain inconclusive. We investigated the prognostic value and clinicopathological significance of PBRM1 protein expression in RCC.

Prognostic and clinicopathological value of PBRM1 expression in renal cell carcinoma.

The prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with castration-resistant prostate cancer (CRPC) had been investigated in previous studies; however, the results remain inconsistent. This study was aimed to investigate the prognostic value of NLR in CRPC patients.

Neutrophil-lymphocyte ratio is a predictor of prognosis in patients with castration-resistant prostate cancer: a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.21971.].

Correction: Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis.

von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome with poor survival. The current recommendations have proposed uniform surveillance strategies for all patients, neglecting the obvious phenotypic varieties. In this study, we aim to confirm the phenotypic heterogeneity in VHL disease and the underlying mechanism. A total of 151 parent-child pairs were enrolled for genetic anticipation analysis, and 77 sibling pairs for birth order effect analysis. Four statistical methods were used to compare the onset age of patients among different generations and different birth orders. The results showed that the average onset age was 18.9 years earlier in children than in their parents, which was statistically significant in all of the four statistical methods. Furthermore, the first-born siblings were affected 8.3 years later than the other ones among the maternal patients. Telomere shortening was confirmed to be associated with genetic anticipation in VHL families, while it failed to explain the birth order effect. Moreover, no significant difference was observed for overall survival between parents and children ( = 0.834) and between first-born patients and the other siblings ( = 0.390). This study provides definitive evidence and possible mechanisms of intra-familial phenotypic heterogeneity in VHL families, which is helpful to the update of surveillance guidelines.

Intra-Familial Phenotypic Heterogeneity and Telomere Abnormality in von Hippel- Lindau Disease: Implications for Personalized Surveillance Plan and Pathogenesis of VHL-Associated Tumors.

(1) Background: There are currently limited treatments for castration-resistant prostate cancer. Immunotherapy involving Sipuleucel-T has increasingly drawn attention for prostate cancer management. BCG plays a vital role in treating bladder cancer, mainly by inducing immune activation, but is rarely used for prostate cancer. (2) Methods: The TCGA database, PCR, and Western blotting were used to analyze the expression of STEAP1 in mouse and human tissues. Then, we constructed a fusion protein vaccine with  Ag85B and three repeated octapeptide epitopes of a six-transmembrane epithelial antigen of the prostate 1 (STEAP1), Ag85B-3×STEAP1. The uptake of the fusion protein vaccine by DCs was evaluated by confocal microscopy, and DC markers were detected using flow cytometry after incubation with the fusion protein. The immune response against prostate cancer was evaluated by the LDH assay and xenografts in vitro and in vivo. Then, the tumor microenvironment was determined using IHC and ELISA. In addition, the epitope was mutated using CRISPR-Cas9 to illustrate that the fusion protein elicited immunization against STEAP1. (3) Results: The TCGA database analysis, PCR, and Western blotting showed that STEAP1 was highly expressed in human and murine prostate cancer. After the uptake of the purified fusion protein vaccine by DCs, CD11c, CD80, CD86, and MHC II were upregulated and triggered a cytotoxic T lymphocyte (CTL) response against TRAMP-C1 and RM1 cells in vitro. Furthermore, the fusion protein vaccine inhibited tumor growth and improved the tumor microenvironment in vivo, with more CD3 cells and fewer FOXP3 cells in the tumor. Serum IFN-γ and IL-2 were significantly higher than in the control group, while IL-4 expression was lower, indicating that the fusion protein vaccine activated Th1 immunity. The immune response against prostate cancer was greatly suppressed when the antigen targets were knocked out using CRISPR-Cas9. (4) Conclusion: In summary, our results provide the first evidence that a vaccine based on a fusion protein consisting of Ag85B and a prostate cancer octapeptide epitope with complete Freund's adjuvant (CFA), triggers a robust immune response and inhibits tumor growth in murine prostate cancer.

Fusion Protein Vaccine Based on Ag85B and STEAP1 Induces a Protective Immune Response against Prostate Cancer.

 It has been reported that thymidine kinase 1 (TK1) was up-regulated in multiple malignancies and participated in the regulation of tumor malignant behavior. However, its specific role in prostate cancer (PCa) remains unclear.  TK1 expression in PCa patients and cell lines was identified via crossover analysis of the public datasets. A series of  experiments and  models was applied to investigate the function of TK1 in PCa. Functional enrichment analyses were further conducted to explore the underlying mechanism. Additionally, TISIDB was applied to explore the correlation between TK1 expression and tumor-infiltrating lymphocytes, immune subtypes, and immune regulatory factors.  TK1 expression was significantly up-regulated in PCa patients and cell lines. TK1 ablation inhibited tumor cell proliferation and migration potential, and  experiments showed that TK1 inactivation can significantly restrain tumor growth. Functional enrichment analysis revealed TK1-related hub genes (AURKB, CCNB2, CDC20, CDCA5, CDK1, CENPA, CENPM, KIF2C, NDC80, NUF2, PLK1, SKA1, SPC25, ZWINT), and found that TK1 was closely involved in the regulation of cell cycle. Moreover, elevated mRNA expression of TK1 was related with higher Gleason score, higher clinical stage, higher pathological stage, higher lymph node stage, shorter overall survival, and DFS in PCa patients. Particularly, TK1 represented attenuated expression in C3 PCa and was related with infiltration of CD4, CD8 T cells, and dendritic cells as well as immunomodulator expression.  Our study indicates that TK1 is a prognostic predictor correlated with poor outcomes of PCa patients, and for the first time represented that TK1 can promote the progression of PCa. Therefore, TK1 may be a potential diagnostic and prognostic biomarker, as well as a therapeutic target for PCa.

Shuanghe Peng

Department of Pathology

The Second Hospital of Tianjin Medical University

Economical and Efficient Protocol for Isolating and Culturing Bone Marrow-derived Dendritic Cells from Mice