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BACKGROUND: Prostate cancer (PCa) is poor response to the immunotherapy for its high heterogeneity of immune microenvironment. In this study, we aim to introduce a new immune subtype for PCa involving M2 tumour associated macrophages (M2-TAMs). METHODS: Three hundred and sixty-two PCa patients and matched normal prostate tissues were selected from the Cancer Genome Atlas and Gene Expression Omnibus databases. Patients' immune infiltration characters were then analyzed based on the gene expressions. The immune subtypes were identified by the method of unsupervised hierarchical clustering. Finally, the relationship between the M2-TAMs infiltration and anti-programmed death-ligand-1 (PD-L1) therapy was investigated in the IMvigor210 cohort. RESULTS: PCa expressed lower immune-related genes levels compared with the adjacent normal tissues. Based on the proved immunosuppressive mechanisms in PCa, tumour patients were classified into three independent subclasses with high infiltrated cytolytic activity (CYT), M2-TAMs and regulatory T cell (Tregs), respectively. Among these subtypes, M2-TAMs infiltration subtype showed the worst clinicopathological features and prognosis compared with the other two subtypes. The results of the IMvigor210 cohort demonstrated poor response of anti-PD-L1 therapy for patients with high M2-TAMs infiltration. CONCLUSION: Prostate tumours involved in significant immunosuppression, and high infiltration of M2-TAMs can be applied to predict the effect of anti-PD-L1 therapy.Key MessagesPCa patients can be classified into three immunotypes of high infiltrated CYT, M2-TAMS, and Tregs according to the immunosuppressive mechanisms.High M2-TAMs infiltration subtype reflected the worst clinical characters, immune infiltration, and lowest expression of immune checkpoint inhibitors among the three subclasses in PCa.High M2-TAMs infiltration predicts the low response rate of anti-PD-L1 therapy.
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Neoplasias da Próstata , Macrófagos Associados a Tumor , Humanos , Inibidores de Checkpoint Imunológico , Imunoterapia , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Microambiente TumoralRESUMO
OBJECTIVE@#To investigate the role of MTBP in regulating the migration and invasion of human prostate cancer cells.@*METHODS@#The baseline expressions of MTBP in 3 different human prostate cancer cells lines (22RV1, DU145 and Lncap) were detected using Western blotting. The cells were transfected with a small interfering RNA (siRNA) for MTBP knockdown or MTBP plasmid for MTBP overexpression, and 48 h later, the cells were examined for MTBP expression with Western blotting; the changes in the migration abilities of the cells were evaluated using wound healing assay and Transwell assay, and the cell invasiveness was assessed using Matrigel Transwell assay. The expression of E-cadherin protein, a marker of epithelial mesenchymal transition (EMT), was detected using Western blotting.@*RESULTS@#MTBP expression was the highest in DU145 cells followed by Lncap cells, and was the lowest in 22RV1 cells, indicating a positive correlation of MTBP expression with the level of malignancy of human prostate cancer cells. Transfection of the cells with siRNA or MTBP plasmids efficiently lowered or enhanced the expressions of MTBP in human prostate cancer cells. Wound healing assay showed that inhibition of MTBP expression decreased the migration ability of the prostate cancer cells, and MTBP overexpression significantly promoted the migration of the cells ( < 0.01). Transwell assay showed that MTBP knockdown significantly lowered the migration and invasion ability of the cells, while MTBP overexpression markedly increased the number of migrating and invading cells ( < 0.01); Western blotting results showed that MTBP knockdown increased the expression of E-cadherin protein, and MTBP overexpression decreased E-cadherin expression in the prostate cancer cells.@*CONCLUSIONS@#MTBP overexpression promotes the migration and invasion of human prostate cancer cells possibly relation to the induction of EMT.
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Humanos , Masculino , Antígenos CD , Metabolismo , Caderinas , Metabolismo , Proteínas de Transporte , Genética , Metabolismo , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Invasividade Neoplásica , Neoplasias da Próstata , Metabolismo , Patologia , RNA Interferente Pequeno , TransfecçãoRESUMO
<p><b>OBJECTIVE</b>To investigate the protective effect of bone marrow mesenchymal stem cells (BMSCs)-derived exosomesagainst testicular ischemia-reperfusion injury (IRI) in rats.</p><p><b>METHODS</b>Rat BMSCs were isolated, cultured and identified in theprimary culture. The exosomes were extracted from the BMSCs and characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. Twenty-four healthy male SD rats were randomly divided into shamoperation group, testicular IRI with saline treatment group and IRI with exosome treatment group. The contralateral testes ofthe rats were collected for pathological observation, aseessment of superoxide dismutase (SOD) and malondialdehyde (MDA), and detection of HMGB1, caspases-3 and cleaved caspase-3 expressions using Western blotting.</p><p><b>RESULTS</b>We successfullyobtained exosomes from rat BMSCs. Testicular IRI significantly impaired testicular spermatogenesis, which was markedlyimproved by treatment with the exosomes ( < 0.05). Testicular IRI also caused significant increase in the protein expression ofHMGB1, caspase-3 and cleaved caspase-3 in the testicular tissue, and treatment with the exosomes obviously amelioratedthese changes ( < 0.05).</p><p><b>CONCLUSIONS</b>BMSCs-derived exosomes protects against testicular IRI due to the anti-oxidant, antiinflammatory and anti-apoptosis activities of the exosomes.</p>
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<p><b>OBJEVTIVE</b>To investigate the expression of cysteine-rich secretory protein 2 (CRISP2) in spermatozoa of patients with asthenozoospermia and explore its clinical significance.</p><p><b>METHOS</b>Semen samples were collected from 24 normal volunteers and 24 patients with asthenozoospermia for detecting CRISP2 mRNA and protein expressions using qRT-PCR and Western blotting, respectively. The correlation of CRISP2 expressions with sperm morphology, progressive motility and fertility prognosis were analyzed in patients with asthenozoospermia.</p><p><b>RESULTS</b>CRISP2 protein expression was obviously lowered in the ejaculated spermatozoa of patients with asthenozoospermia as compared to the normal volunteers, but no significant difference in CRISP2 mRNA expression was found between the two groups. Correlation analysis showed that CRISP2 protein expression was positively correlated with normal sperm morphology (r=0.6182, P=0.0037) and progressive motility (r=0.6309, P=0.0029). Follow-up study of the patients revealed a higher fertility rate in patients with a relatively high CRISP2 protein expression than in those with low CRISP2 protein expression (80.0% vs 20.0%, P=0.0230).</p><p><b>CONCLUSION</b>The expression level of CRISP2 protein is positively correlated with normal sperm morphology and progressive motility. A reduced CRISP2 protein expression indicates poor fertility prognosis of patients with asthenozoospermia, suggesting the potential value of CRISP2 as a novel therapeutic target for treating asthenozoospermia.</p>
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Humanos , Masculino , Astenozoospermia , Metabolismo , Estudos de Casos e Controles , Fertilidade , Seguimentos , Glicoproteínas , Metabolismo , RNA Mensageiro , Motilidade dos Espermatozoides , Espermatozoides , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To define the clinicopathological risk factors of intravesical recurrence of primary transitional cell carcinoma of the ureter after surgical intervention.</p><p><b>METHODS</b>Patients with primary carcinoma of the ureter treated between January 2000 and December 2010 were retrospectively analyzed. The intravesical recurrence-free survival rate was calculated using Kaplan-Meier method. Multivariate analysis was conducted with Cox's regression.</p><p><b>RESULTS</b>A total of 104 patients were enrolled, who were followed up for a median of 46 months (13-89 months). Thirty-nine of the patients showed postoperative intravesical recurrence. Urine exfoliative cytology (P=0.000), number of tumors (P=0.006), tumor grade (P=0.039) and co-existence of bladder tumor (P=0.014) were found to independently influence the postoperative intravesical recurrence. Patients with more risk factors had poorer intravesical recurrence-free survival.</p><p><b>CONCLUSION</b>Urine exfoliative cytology, number of tumors, tumor grade and co-existence of bladder tumor are independent risk factors for postoperative intravesical recurrence of primary transitional cell carcinoma of the ureter. Close follow-up and rigorous treatment are essential for patients with high risk factors.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células de Transição , Patologia , Cirurgia Geral , Causalidade , Recidiva Local de Neoplasia , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Neoplasias Ureterais , Patologia , Cirurgia Geral , Neoplasias da Bexiga Urinária , PatologiaRESUMO
Objective To explore the risk factors of inguinal metastasis in squamous cell carcinoma of the penis, screening lymph node metastasis high-risk patients. Methods The clinical and pathological data of 81 consecutive patients with squamous cell carcinoma of the penis were analyzed retrospectively. Age at presentation ranged from 27 to 81 years with a median of 49 years. Course of disease within one year of patients with 46 cases (56.8%), 1 year above 35 eases (43.2 %). Seventyfive patients underwent bilateral inguinal lymph node dissection, and 6 patients had unilateral inguinal lymph node dissection. Clinical stage of the primary tumor was assigned according to the 2002 TNM staging system. Variables included patients' age, redundant prepuce and/or phimosis, tumor site,size, number, macroscopic growth pattern, histological grade, inguinal physical examination and the size of inguinal lymph nodes. Results Of the 81 patients, 42 (51.9%) were staged as pN+ and 39 (48. 1%) as pN0. Metastases occurred in 32.0% (16/50) of G1, 78.3% (18/23) of G2 and 100. 0%(8/8) of G3 cases, with significant differences among them (P= 0. 015). According to the inguinal lymph node physical examination results, 63 were staged as clinically node-positive (cN+) and 18 as clinically node-negative (cN0). Metastases occurred in 63. 5% (40/63) of cases of cN+, as compared with 11.1% (2/18) of cases of cN0(P=0. 012). At a median follow up of 40 months (ranged 2-127 months), the 5-year disease free survival rates for positive and negative inguinal lymph nodes metastasis were 71.4% and 92.3%, respectively (P=0. 005) , and the 5-year cancer specific survival rates were 79.0% and 91.4%, respectively (P=0.001). Conclusions Inguinal physical examination and histological grade were the strongest predictors of inguinal metastasis. The patients with inguinal lymph nodes metastasis have lower 5-year disease free survival rates and cancer specific survival rates,and should receive positive treatment measures.
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Objective To explore the etiology,mechanism and treatment of diarrhea after(pancreatoduodenectomy).Methods Based on the clinical data of 159 cases of pancreatoduodenectomy(performed) in the recent one and half years,the pathogenesis of post-pancreatoduodenectomy diarrhea was(analyzed) and the effect of different treatments was observed.Results Seventy-one cases had diarrhea,with an incidence of 44.7%.Tweenty-two cases had bacterial infection of the intestinal tract and 4 cases had fungus infection.The incidence of infection was 36.6%.In 64 cases diarrhea was relieved with effective treatment,accounting for 90.1% of all cases.Seven cases with chronic diarrhea had additional treatment with oral pancreatic enzyme and symptoms were relieved 2 weeks after treatment.Conclusions Diarrhea is frequently observed in patients after pancreatoduodenectomy,and the majority of them can be cured with(treatment) selected according to the pathogenesis.