ABSTRACT
Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.
ABSTRACT
Objective To detect the expression level of Taurine up?regulated gene 1( TUG1) in the re?nal cell carcinoma and paired paracancerous normal tissues,then explore the relationships between the expression level of TUG1 and clinical characteristics.Methods RNA was Extacted from the resected renal cell carcinoma tissues and paired paracancerous normal tissues of 46 patients respectively,by reverse transcription to get cDNA, the expression level of the TUG1 was detected by RT?qPCR, the relationship between the expression level of TUG1 and the clinicopathological characteristics was analyzed by statistically software. Results The expression of TUG1 in renal cell carcinoma was obviously lower than that in paired paracancerous normal tissues(0.533±0. 027 vs. 1.000±0.298,t=-3.350,P0.05).Conclusion The expression of TUG1 in renal cell carcinoma tissues are down?regulated,which also suggest that it may be re?lated to the tumorigenesis and development of renal cell carcinoma.
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Objective To investigate the function and regulatory mechanisms of VCAN gene and protein in metastatic prostate cancer.Methods The data of whole genomic expression profiles got from the prostate cancer metastasis were obtained from gene expression omnibus (GEO) database,a set of bioinformatics tools,such as BRB-Array Tools,protparam,SMART,SignalP 4.0,TMHMM,NetPhos2.0,PredictProtein,SWISS-MODEL,GO,KEGG and STRING softwares were used to accomplish data-mining and bioinformatics analysis.Results There were 73 co-expressed differentially genes in prostate cancer metastasis,21 up-regulated and 52 down-regulated.Bioinformatics analysis indicated that VCAN gene encoded 3396 amino acids,VCAN was also contained one Immunoglobulin domain,two hyaluronan-binding domain,one epidermal growth factor-like domain,one calcium-binding EGF-like domain,one C-type lectin domain and one domain abundant in complement control proteins,and a furthermore analysis suggested that VCAN played essential roles in such important biological function including cell adhesion,hyaluronic acid binding,calcium-binding,glycosaminoglycan binding,extracellular matrix and cell adhesion molecules.Conclusions Bioinformatics analysis had a high efficiency in analyzing microarray data and revealing internal biology information.VCAN may play an important role in the prostate cancer metastasis,Thus,VCAN might be a novel biomarker for the diagnosis of prostate cancer metastasis or a new target for its treatment.
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Objective To review the diagnosis and treatment of squamous cell carcinoma of renal pelvis. Methods The clinical data from October 1991 to May 2009 of eight cases of squamous cell carcinoma of renal pelvis were reviewed and analyzed retrospectively. The symptoms of the patients were hematuria (eight cases), pain (seven cases) and abdominal mass (one case). All patients underwent B-ultrasound and IVU examination and four cases underwent CT scan. Three cases were diagnosed as having a tumor before surgery. Five cases were diagnosed as renal calculus, two of the five cases were diagnosed by intraoperative frozen section. Radical nephroureterectomy were performed in four cases, nephrectomy in three cases and palliative resection in one case. Results Histological classification revealed that six cases were moderately differentiated, one case was well differentiated and one case was poorly differentiated. Two cases had stage pT1/pT2 and six cases had stage pT3/pT4. 2 cases had regional lymph nodes metastasis. Seven cases were followed-up. All patients died of tumor recurrence or metastasis. The median tumor specific survive time was six months (range from two months to 42 months). Conclusions Squamous cell carcinoma of renal pelvis is often occurs concurrently with urolithiasis which could lead to difficulty in diagnose before operation. As the most of the patients were diagnosed with advanced stage disease, squamous cell carcinoma of renal pelvis tended to early recurrence and metastasis and the prognosis was very poor.
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Objective Detecting of spermatozoal total RNAs by laboratory on chip gel electrophoresis so that it could provide better total RNAs for the sequent experiments, and spur the development of spermatozoal molecular biology. Methods Sperms of healthy adults were collected and then total RNAs were extracted by RNeasy mini kit(QIAGEN), detection and quality control were performed by loboratory on chip gel electrophoresis system. Meantime, the control RNAs were extracted from lymphocytes. Results It was found that there were a plenty of genes expressed in healthy sperms. Electrophoretic graphs showed that the total RNAs of spermatozoal had 2 bands which went ahead a little comparing to the normal somatic cells. The former peak appeared keenness, and the latter was broad and showed like a reversed U. The ratio of them was largely more than 2, no extra peaks were found in electrophoretic graph. Conclusion A simple,intuitionistic method to detect and control the quality of the healthy adults' spermatozoal total RNAs had been successfully constructed by using laboratory on chip gel electrophorosis.