RESUMO
BACKGROUND: Metastasis of prostate cancer (PCa) is largely affected by natural killer (NK) cells. This study aimed to clarify the mechanisms underlying tumor cells escaping from NK cells mediated by HIF-1α. METHODS: MiR-224 expression in lymphocytes and HIF-1α protein level in NK cells were determined by qRT-PCR and western blot, respectively. The amount of NKp46+ NK cells was detected with flow cytometry. The IFN-γ level was examined by enzyme linked immunosorbent assay (ELISA). NK cells were tested for cytolytic activity with a Non-Radioactive Cytotoxicity Assay, and treated with oxygenglucose deprivation (OGD) for hypoxia simulation. Interaction between miR-224 and NCR1 was evaluated with dual luciferase reporter assay. RESULTS: MiR-224 was down-regulated in lymphocytes isolated from prostate cancer tissues (nâ¯=â¯10). Overexpression of miR-224 protected prostate cancer from NK cells. HIF-1α increased miR-224 to inhibit the killing capability of NK cells on prostate cancer. MiR-224 controlled the expression of NCR1. Overexpression of miR-224 protected prostate cancer from NK cells through NCR1/NKp46 signaling. Suppression of HIF-1α enhanced the cytotoxicity of NK cells on prostate cancer via miR-224/NCR1 pathway. CONCLUSION: HIF-1α inhibits NCR1/NKp46 pathway through up-regulating miR-224, which affects the killing capability of NK cells on prostate cancer, thus inducing immune escape of tumor cells.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , MicroRNAs/metabolismo , Receptor 1 Desencadeador da Citotoxicidade Natural/metabolismo , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Evasão Tumoral/imunologia , Linhagem Celular , Citotoxicidade Imunológica , Regulação para Baixo , Humanos , Técnicas In Vitro , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Masculino , MicroRNAs/genética , Neoplasias da Próstata/genética , Transdução de Sinais , Evasão Tumoral/genética , Regulação para CimaRESUMO
Some physiological and ethical problems make it difficult to obtain semen samples from adolescents with varicocele (VC) and to directly evaluate their fertility. Therefore we can only rely on indirect methods to assess the influence of VC on the future fertility of the adolescent patients. Most of the VC adolescents may have normal semen parameters in the adulthood. Thus whether and when to intervene in adolescent VC remain a controversy in andrology. Physical examination is the most common method for screening adolescent VC and ultrasonography is very effective for its diagnosis and evaluation. Other important diagnostic indicators include the widely accepted testicular atrophy index, recently proposed peak retrograde venous flow, total testis volume, and scrotal temperature. Based on the latest literature, this review offers some proposals for the evaluation and intervention of adolescent VC.
Assuntos
Infertilidade Masculina/diagnóstico , Varicocele/diagnóstico , Adolescente , Humanos , Masculino , Sêmen , Análise do Sêmen , Testículo/patologiaRESUMO
OBJECTIVE: To investigate the safety and efficiency of the disposable circumcision suture device (DCSD) in the surgical treatment of phimosis and redundant prepuce. METHODS: We randomly assigned 249 outpatients with phimosis or redundant prepuce to be treated with DCSD (n = 129) and by conventional circumcision (CC, n = 120), respectively. Then we compared the safety and efficiency of the two strategies. RESULTS: Comparisons between DCSD and CC showed that the operation time was (4.02 +/- 0.69) vs (30.8 +/- 4.05) min, blood loss was (1.07 +/- 1.29) vs (8.72 +/- 2.15) ml, intraoperative pain score was 0.81 +/- 0.81 vs 2.42 +/- 1.15, 24-hour postoperative pain score was 1.84 +/- 1.02 vs 4.99 +/- 1.36, postoperative complication rate was 13. 95% (18/129) vs 9.17% (11/120), wound healing time was (13.99 +/- 9.06) vs (17.48 +/- 3.49) d, satisfaction with the penile appearance was 98.4% (127/129) vs 95% (109/120), and treatment cost was (2215.62 +/- 17.67) vs (576.47 + 15.58) Y RMB. DCSD exhibited obvious superiority over CC for shorter operation time, less blood loss, milder intraoperative pain, sooner wound healing, and better penile appearance, but it also had a higher rate of postoperative complications (P > 0.05) and involved more treatment cost than the latter (P < 0.05). CONCLUSION: The disposable circumcision suture device affords ideal clinical effects and therefore deserves clinical popularization.
Assuntos
Circuncisão Masculina/instrumentação , Fimose/cirurgia , Grampeadores Cirúrgicos , Equipamentos Descartáveis , Seguimentos , Humanos , Masculino , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the effects and mechanism of thymoquinone in the growth inhibition of bladder cancer both in vitro and in vivo. METHODS: After the treatment of thymoquinone, the cellular proliferation of human bladder cancer cell line BIU-87 was detected by the method of methyl thiazolyl tetrazolium (MTT). Flow cytometry (FCM) was used to determine the cellular apoptosis. And the location of nuclear factor (NF)-κB was identified by the method of immunofluorescent histochemistry. Western blotting was employed to detect the cellular expressions of NF-κB, survivin and XIAP. BIU-87 cells were injected subcutaneously into nude mice to establish a xenograft model. After 2 weeks of implantation, the mice were randomized into 2 groups (n = 8): (a) vehicle alone (control), (b) thymoquinone (5 mg/kg daily by intragastric intubation). All treatments lasted for 2 weeks. At Week 7 post-implantation, the mice were sacrificed and their tumor weights and inhibition rates evaluated. Immunohistochemistry was used to detect the positive expressions of Ki-67, NF-κB and XIAP in tumors. RESULTS: The proliferation of bladder cancer cells was inhibited significantly by thymoquinone at 20, 40, 80 µmol/L (81.2% ± 4.6%, 72.5% ± 6.5%, 58.4% ± 8.9% vs 100%, all P < 0.05). Apoptosis rate induced by thymoquinone was more significant than that of the control (7.6% ± 1.6%, 11.2% ± 2.1%, 14.3% ± 2.8%vs 1.6% ± 0.5%, all P < 0.05). Immunofluorescent histochemistry showed that thymoquinone could significantly lower the nuclear expression of NF-κB. The expressions of NF-κB and XIAP were down-regulated in BIU-87 cells after the treatment of thymoquinone. But thymoquinone had no effect on the expression of survivin. The final tumor weight showed significant decrease in the test group versus the control group ((0.41 ± 0.12) vs (0.89 ± 0.23) g, P < 0.05). Furthermore, the positive expressions of Ki-67, NF-κB and XIAP decreased in tumors after the administration of thymoquinone. CONCLUSION: Thymoquinone exerts anti-tumor effects on bladder cancer both in vitro and in vivo through the down-regulations of NF-κB and its regulated molecules such as XIAP.
Assuntos
Benzoquinonas/farmacologia , NF-kappa B/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Survivina , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismoRESUMO
Aim: Prostate cancer (PCa) is the sixth leading cause of cancer-related deaths in men throughout the world. This study aimed to investigate genes associated with the pathogenesis and prognosis of PCa. Materials & methods: Data of PCa cases were obtained from public datasets and were analyzed using an integrated bioinformatics strategy. Results: A total of 969 differential expression genes were identified. Moreover, GSE16560 and The Cancer Genome Atlas (TCGA) data showed a prognostic prompt function of the nine-gene signature, as well as in PCa with Gleason 7. Finally, majority of the nine hub genes were associated with drug sensitivity, mutational landscape, immune infiltrates and clinical characteristics of PCa. Conclusion: The nine-gene signature was correlated with drug sensitivity, mutational landscape, immune infiltrates, clinical characteristics and survival from PCa.
Assuntos
Perfilação da Expressão Gênica , Genômica , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/diagnósticoRESUMO
OBJECTIVE: To study the efficacy of interleukin-10 (IL-10) in the treatment of experimental autoimmune prostatitis (EAP) and its effect on the expressions of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1 ) in EAP rat models. METHODS: Thirty Wistar rats were equally and randomly divided into a control, an EAP and an IL-10 group. The controls were treated with normal saline, the EAP models were made by injection of purified prostate protein twice with immune adjuvant, and the IL-10 group included the EAP models subjected to IL-10 intervention. The infiltration of the inflammatory cells of the prostate tissue was detected by HE staining, the ultrastructure of the prostate cells and their surrounding cells observed by electron microscopy, and the levels of TNF-alpha and TGF-beta1 in the three groups determined by semi-quantitative RT-PCR assay. RESULTS: The EAP group showed significantly severer inflammation and higher levels of TNF-alpha and TGF-beta1 in the prostate tissue than the controls (P < 0.05). The IL-10 group exhibited significantly lessened inflammatory infiltration of the prostate tissue and decreased levels of TNF-alpha and TGF-beta as compared with the EAP group (P < 0.05). CONCLUSION: IL-10 could relieve inflammatory infiltration of the prostate tissue and inhibit the expressions of TNF-alpha and TGF-beta1 in EAP rats, which is suggestive of its therapeutic efficacy for autoimmune prostatitis.