RESUMO
Renal angiomyolipoma (AML) is a benign tumor. However, rare cases of renal AML demonstrate aggressive behaviors such as tumor thrombus extension into the inferior vena cava (IVC). We successfully treated a case of epithelioid AML in the right kidney involving the IVC. We also reviewed and analyzed 45 case reports of the common type of AML. Radiologists and clinicians should know that epithelioid AML can be an aggressive tumor.
Assuntos
Angiomiolipoma/patologia , Neoplasias Renais/patologia , Células Neoplásicas Circulantes , Veia Cava Inferior , Adulto , Humanos , Masculino , Invasividade NeoplásicaRESUMO
OBJECTIVE: To retrospectively evaluate the safety and efficacy of flexible ureteroscopy (FURS) in combination with holmium laser lithotripsy for the treatment of bilateral upper urinary calculi. MATERIALS AND METHODS: The stone-free status was defined as the absence of any stones or asymptomatic status, or the presence of clinically insignificant residual fragments <4 mm, and was assessed by plain kidney, ureter, and bladder X-ray. The operative time, stone-free rates (SFRs), serum creatinine (SCr), and complications were recorded. RESULTS: During the operation, there was no bleeding, ureteral perforation, avulsion, and rupture. Postoperative hematuria was observed in 2 patients. SCr increased significantly on the first day after the procedure compared with the preoperative SCr, but after 4 weeks, the renal function significantly improved (p < 0.05). The SFR was 71.6% (63/88) on the first day after the first surgical procedure; it then increased to 86.4% (76/88) in the fourth week, and rose to 97.4% (76/78) after the second operation. CONCLUSION: The results demonstrated that FURS in combination with holmium laser lithotripsy represented a favorable less-invasive alternative with high SFR and acceptable complication rates in the treatment of bilateral upper urinary tract calculi.
Assuntos
Lasers de Estado Sólido , Litotripsia a Laser , Ureteroscópios , Cálculos Urinários/terapia , Adulto , Feminino , Hematúria/sangue , Hemorragia , Humanos , Litotripsia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Segurança do Paciente , Estudos Retrospectivos , Resultado do Tratamento , Ureteroscopia , Raios XRESUMO
Renal cell carcinoma (RCC) accounts for 3 % of all adult malignancies and is the most lethal urological cancer. Livin is a member of the inhibitor of apoptosis protein (IAP) family, which is associated with tumor resistance to radiotherapy and chemotherapy. Clinical data also showed that patients with high tumor grades and stages have higher expression levels of Livin in RCC cells. Autophagy is a survival mechanism activated in response to nutrient deprivation. A possible role of Livin in the autophagy of RCC cells has not been investigated; therefore, this pioneer study was carried out. Livin was silenced in RCC cells (slow virus infection [SVI]-shLivin cells) by lentiviral transfection. Then, mRNA and protein expression levels in the transfected cells were assessed by quantitative fluorescence PCR and Western blotting, respectively. In addition, acridine orange staining and electron microscopy were used to assess autophagy in SVI-shLivin cells. The cisplatin IC50 values for RCC cells were measured by the CCK8 assay. Potent antitumor activities were observed in xenograft mouse models generated with Livin-silenced RCC cells in terms of delayed tumor onset and suppressed tumor growth. These results suggested that Livin silencing could increase the chemotherapeutic sensitivity of RCC cells to cisplatin and induce autophagic cell death. A possible mechanism of Bcl-2 and Akt pathway involvement was discussed specifically in this study. Overall, Livin silencing induces apoptotic and autophagic cell death and increases chemotherapeutic sensitivity of RCC cells to cisplatin.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma de Células Renais/patologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Antineoplásicos/farmacologia , Biomarcadores Tumorais , Western Blotting , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Técnicas Imunoenzimáticas , Proteínas Inibidoras de Apoptose/antagonistas & inibidores , Proteínas Inibidoras de Apoptose/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Renal cell carcinoma (RCC) is one of the most common malignancies in adults, and there is still no acknowledged biomarker for its diagnosis, prognosis, recurrence monitoring, and treatment stratification. Besides, little is known about the post-translational modification (PTM) of proteins in RCC. Here, we performed quantitative proteomic analysis on 12 matched pairs of clear cell RCC (ccRCC) and adjacent kidney tissues using liquid chromatography-tandem mass spectrometry (nanoLCMS/MS) and Progenesis LC-MS software (label-free) to identify and quantify the dysregulated proteins. A total of 1872 and 1927 proteins were identified in ccRCC and adjacent kidney tissues, respectively. Among these proteins, 1037 proteins were quantified by Progenesis LC-MS, and 213 proteins were identified as dysregulated proteins between ccRCC and adjacent tissues. Pathway analysis using IPA, STRING, and David tools was performed, which demonstrated the enrichment of cancer-related signaling pathways and biological processes such as mitochondrial dysfunction, metabolic pathway, cell death, and acetylation. Dysregulation of two mitochondrial proteins, acetyl-CoA acetyltransferase 1 (ACAT1) and manganese superoxide dismutase (MnSOD) were selected and confirmed by Western blotting and immunohistochemistry assays using another 6 pairs of ccRCC and adjacent tissues. Further mass spectrometry analysis indicated that both ACAT1 and MnSOD had characterized acetylation at lysine residues, which is the first time to identify acetylation of ACAT1 and MnSOD in ccRCC. Collectively, these data revealed a number of dysregulated proteins and signaling pathways by label-free quantitative proteomic approach in RCC, which shed light on potential diagnostic or prognostic biomarkers and therapeutic molecular targets for clinical intervention of RCC.
Assuntos
Carcinoma de Células Renais/genética , Proteínas de Neoplasias/biossíntese , Recidiva Local de Neoplasia/genética , Proteômica , Acetilação , Idoso , Biomarcadores Tumorais/biossíntese , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Cromatografia Líquida , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Prognóstico , Processamento de Proteína Pós-TraducionalRESUMO
The internal ribosome entry site (IRES) in the hepatitis C virus (HCV) RNA genome is essential for the initiation of viral protein synthesis. IRES domains adopt well-defined folds that are potential targets for antiviral translation inhibitors. We have determined the three-dimensional structure of the IRES subdomain IIa in complex with a benzimidazole translation inhibitor at 2.2 Å resolution. Comparison to the structure of the unbound RNA in conjunction with studies of inhibitor binding to the target in solution demonstrate that the RNA undergoes a dramatic ligand-induced conformational adaptation to form a deep pocket that resembles the substrate binding sites in riboswitches. The presence of a well-defined ligand-binding pocket within the highly conserved IRES subdomain IIa holds promise for the development of unique anti-HCV drugs with a high barrier to resistance.
Assuntos
Hepacivirus/genética , RNA Viral/química , Riboswitch , Benzimidazóis/farmacologia , Transferência Ressonante de Energia de Fluorescência , Ligantes , Modelos Moleculares , Conformação de Ácido Nucleico , Biossíntese de Proteínas/efeitos dos fármacosRESUMO
Tissue inhibitor of metalloproteinase-3 (TIMP-3) is one of a family of proteins inhibiting matrix metalloproteinases, which has also been identified as a mediator for checking inflammation. Meanwhile, it is well known that inflammation causes the activation of the immune response. However, it is not clear whether TIMP-3 plays a role in the immune system. In the present study, we demonstrated a novel function of TIMP-3 in Th1/Th2 polarization through its influence on the antigen-presenting cells. First, TIMP-3 was found strikingly up-regulated by IL-4 during the differentiation of human dendritic cells via the p38MAPK pathway. Second, the expression of costimulatory molecule-CD86 was repressed by TIMP-3. Besides, the induction of IL-12 in matured dendritic cells was significantly inhibited in a PI3K-dependent manner. Furthermore, dendritic cells matured in the presence of TIMP-3 could stimulate allogeneic naive T helper (Th) cells to display a prominent Th2 polarization. Importantly, in an autoimmune disorder-primary immune thrombocytopenia, TIMP-3 showed a statistically positive correlation with IL-4 and platelet count, but a negative correlation with IFN-γ in patient blood samples. Collectively, these in vitro and in vivo data clearly suggested a novel role of TIMP-3 in Th1/Th2 balance in humans.
Assuntos
Polaridade Celular/genética , Células Dendríticas/fisiologia , Células Th1/fisiologia , Células Th2/fisiologia , Inibidor Tecidual de Metaloproteinase-3/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Polaridade Celular/efeitos dos fármacos , Polaridade Celular/imunologia , Células Cultivadas , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/fisiologia , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/metabolismo , RNA Interferente Pequeno/farmacologia , Células Th1/citologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/citologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Inibidor Tecidual de Metaloproteinase-3/antagonistas & inibidores , Inibidor Tecidual de Metaloproteinase-3/genética , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Adulto JovemRESUMO
Eg5 is critical for mitosis and overexpressed in various malignant tumors, which has now been identified as a promising target in cancer therapy. However, the anti-cancer activity of Eg5 inhibitor in renal cell carcinoma (RCC) remains an open issue. In this paper, we evaluated, for the first time, the therapeutic benefit of blocking Eg5 by S-(methoxytrityl)-L-cysteine (S(MeO)TLC) in RCC both in vitro and vivo. The expression of Eg5 was examined in clinical tissue samples and various kidney cell lines, including 293T, 786-0, and OS-RC-2. The anti-proliferative activity of Eg5 inhibitors, (S)-trityl-L-cysteine (STLC) and S(MeO)TLC, was evaluated by a cell viability assay. An apoptosis assay with Hoechst nuclear staining and flow cytometry was applied to investigate the efficacy of the S(MeO)TLC, which is more potent than STLC. Immunofluorescence was used to research the possible mechanism. Furthermore, in vivo studies were performed by using subcutaneous xenograft models, which were used to confirm its role as a potential anti-neoplastic drug. The Eg5 expression was detected in kidney cell lines and RCC tissues, which was low in normal kidney samples. STLC and S(MeO)TLC exhibited their optimal anti-proliferative activity in 72 h, and cells treated with S(MeO)TLC presented characteristic monoastral spindle phenotype in 24 h and apoptotic cells in 48 h. In vivo, S(MeO)TLC effectively suppressed tumor growth in subcutaneous xenograft models. Inhibition of Eg5 represses the proliferation of RCC in vitro and in vivo. All these findings collectively demonstrate that S(MeO)TLC, a potent Eg5 inhibitor, is a promising anti-cancer agent for the treatment of RCC.
Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Cisteína/análogos & derivados , Neoplasias Renais/tratamento farmacológico , Cinesinas/antagonistas & inibidores , Terapia de Alvo Molecular , Compostos de Tritil/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Renais/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cisteína/farmacologia , Feminino , Humanos , Neoplasias Renais/patologia , Cinesinas/análise , Camundongos , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We describe the exploration of N1-aryl-substituted benzimidazoles as ligands for the hepatitis C virus (HCV) internal ribosome entry site (IRES) RNA. The design of the compounds was guided by the co-crystal structure of a benzimidazole viral translation inhibitor in complex with the RNA target. Structure-binding activity relationships of aryl-substituted benzimidazole ligands were established that were consistent with the crystal structure of the translation inhibitor complex.
Assuntos
Antivirais/farmacologia , Benzimidazóis/farmacologia , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , RNA Viral/genética , RNA Viral/metabolismo , Ribossomos/metabolismo , Antivirais/síntese química , Antivirais/química , Benzimidazóis/síntese química , Benzimidazóis/química , Relação Dose-Resposta a Droga , Ligantes , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The highly conserved internal ribosome entry site (IRES) of hepatitis C virus (HCV) regulates translation of the viral RNA genome and is essential for the expression of HCV proteins in infected host cells. The structured subdomain IIa of the IRES element is the target site of recently discovered benzimidazole inhibitors that selectively block viral translation through capture of an extended conformation of an RNA internal loop. Here, we describe the development of a FRET-based screening assay for similarly acting HCV translation inhibitors. The assay relies on monitoring fluorescence changes that indicate rearrangement of the RNA target conformation upon ligand binding. Screening of a small pilot set of potential RNA binders identified a benzoxazole scaffold as a ligand that bound selectively to IIa IRES target and was confirmed as an inhibitor of in vitro viral translation. The screening approach outlined here provides an efficient method to discover HCV translation inhibitors that may provide leads for the development of novel antiviral therapies directed at the highly conserved IRES RNA.
Assuntos
Antivirais/farmacologia , Benzimidazóis/farmacologia , Benzoxazóis/farmacologia , Hepacivirus/genética , RNA Viral/antagonistas & inibidores , Ribossomos/efeitos dos fármacos , Ribossomos/genética , Sequência de Bases , Transferência Ressonante de Energia de Fluorescência , Genoma Viral , Hepacivirus/química , Programas de Rastreamento , Modelos Moleculares , Dados de Sequência Molecular , RNA Viral/química , RNA Viral/genética , RNA Viral/metabolismo , Ribossomos/metabolismo , Transdução de SinaisRESUMO
Effective removal and recovery of phosphorus (P) from the aquatic environment was of great significance for eutrophication control and P recovery. This study investigated the effects of different environmental conditions on P adsorption by biochar (BC) and the feasibility of applying the P-laden BC as a fertilizer for plant growth. The nano zero-valent iron (nZVI) modified reeds BC prepared at 700 °C (Fe-700-BC) had the maximum P adsorption capacity of 95.2 mg g-1, which was higher than those prepared at 300, 500, and 900 °C. The addition of Fe-700-BC reduced the concentration of total phosphorus (TP) in the overlying water, in which the soluble reactive phosphorus (SRP) almost completely removed, as well as had a certain inhibitory effect on the growth of algae. Simultaneously, Fe-700-BC reduced the contents of different fractions of P (weakly adsorbed inorganic phosphorus (WA-Pi), potential active inorganic phosphorus (PA-Pi), and Fe/Al-bound inorganic phosphorus (Fe/Al-Pi)) by adsorbing the soluble P released from the sediments, especially in the case of disturbance. Fe-700-BC had no significant effect on the diversity and richness of the microbial community in the sediment. Moreover, P-laden BC was safe and environmentally friendly for application in the soil and tended to increase stem and root length, fresh and dry weight at low doses (0.5 wt%) in wheat planting experiments. The present work could provide a reference for solving the problems related to eutrophication and P deficiency.
Assuntos
Fósforo , Poluentes Químicos da Água , Carvão Vegetal , Ferro/análise , Água , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: The goal of this study was to investigate the roles of PIM-1 in prostate cancer (CaP) cell proliferation and apoptosis, and to assess the potential of PIM-1 as a target for CaP therapy. METHODS: Using RNAi technology, we knocked down the expression of PIM-1 in PC-3 cell. After siRNA transfection, cell morphology, cell proliferation, cell cycle, and apoptosis rate were analyzed. PIM-1 siRNA with Lipofectamine were injected into xenograft models to evaluate its therapeutic effect. RESULTS: PIM-1 siRNA significantly inhibited PIM-1 expression. In vitro, silencing of the PIM-1 gene resulted in irregular cell morphology, decreased cell proliferation, inhibition of cell-cycle progression, and induction of apoptosis. Compared with control groups, intratumoral injection of PIM-1 siRNA with Lipofectamine in nude mice dramatically suppressed PC-3 tumor progression. CONCLUSIONS: PIM-1 could play important roles in the progression of CaP and may be an interesting target for CaP therapy.
Assuntos
Apoptose/fisiologia , Divisão Celular/fisiologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Interferente Pequeno/genética , Animais , Western Blotting , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Inativação Gênica , Humanos , Indicadores e Reagentes , Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Próstata/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
OBJECTIVES: To explore the applicability of the current prognostic models for nonmetastatic renal cell carcinoma in the Chinese population based on a single center experience. METHODS: Clinical and pathological variables of 653 nonmetastatic renal cell carcinoma patients were retrospectively reviewed. Seven models were used to predict the prognosis, including the Yaycioglu model, the Cindolo model, the University of California Los Angeles Integrated Staging System model, the stage, size, grade, and necrosis model, the Kattan nomogram, the Sorbellini nomogram and the Karakiewicz nomogram. Three different end-points were used for validation, including overall survival, cancer-specific survival, and recurrence-free survival. Survival was estimated using the Kaplan-Meier method. Discriminating ability was assessed using the Harrell's concordance-index. RESULTS: At the last follow up, 159 patients had died due to various causes, and disease recurrence occurred in 156 patients. The discriminating ability of all models was confirmed in the Chinese population. Nomograms discriminate better than algorithms, regardless of end-points. The Kattan nomogram was the most accurate, with the highest concordance-indexes of 0.752, 0.793 and 0.841 for overall survival, cancer-specific survival, and recurrence-free survival, respectively. CONCLUSIONS: The current prognostic models were developed and validated entirely based on Caucasian populations. This study defines the general applicability of the models for Chinese patients with nonmetastatic renal cell carcinoma treated with nephrectomy. The Kattan model was found to be the most accurate. The Cindolo model performed well in some situations, although only including clinical presentation and size of tumor. Therefore, models should be chosen according to different environments and purposes.
Assuntos
Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Causas de Morte , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Nefrectomia/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/cirurgia , Estudos de Coortes , Intervalos de Confiança , Feminino , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia/mortalidade , Complicações Pós-Operatórias/mortalidade , Probabilidade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Estatísticas não Paramétricas , Análise de Sobrevida , Adulto JovemRESUMO
Efficacy and safety of sorafenib in patients with advanced renal cancer were evaluated. Seventy-four patients with advanced renal cancer treated with sorafenib + interferon from January 2010 to August 2013 were included as the observation group. Another 53 renal cancer patients treated with interferon alone were included in the control group. Clinical data of those patients were retrospectively analyzed. Treatment plan: initial dose was 400 mg, twice a day. Additionally, patients in the interferon group were treated with another 300 MU every other day. Efficacy was evaluated according to RECIST criteria, and progression-free survival (PFS), overall survival (OS), and incidence of adverse reactions were recorded. In the observation group, a median OS was 15.3 months (range, 9-60 months), and a median PFS was 8.2 months (range, 2-36 months). There were 4 cases of complete remission (CR) (5.41%), 16 cases of partial remission (PR) (21.62%), 42 cases of stable disease (SD) (56.76%), 12 cases of disease progression (16.22%), and disease control rate (DCR) was 83.78% (62 cases). In the control group, median OS time was 12.5 months (range, 8-60 months), and the median PFS time was 9.3 months (range, 2-40 months). There were 2 cases of CR (3.77%), 11 cases of PR (20.75%), 20 cases of SD (37.74%), 20 cases of disease progression (37.74%), and DCR was 62.26% (33 cases). Disease control rate in the observation group was significantly higher than that in the control group (P<0.05). Main adverse events in the groups were skin reaction, fever, diarrhea, fatigue, rash, loss of appetite, hypertension, hair loss and liver function abnormality. Sorafenib-based targeted therapy for the treatment of advanced renal cancer has a higher rate of disease control, and the adverse reactions are controllable and tolerable.
RESUMO
Distant metastasis is the worst prognostic factor for PCa patients. It has been reported that miR-449a enhances radiosensitivity of prostate cancer cells, but the function of miR449a in metastasis of prostate cancer is mainly unknown. In the present study, we strove to investigate the function and diagnostic value of miR-449a in metastasis of prostate cancer. qRT-PCR was used to quantify the expression of miR449a and PrLZ in PCa cell lines and tissues. we found that miR449a expression was decreased in PCa cell lines. Moreover, miR449a was downregulated in PCa tissues, especially in primary lesion tissues of metastatic PCa patients. CCK8, FACS, transwell and tube formation assay were performed to assess growth and metastasis of PCa cells in vitro. Lentivirus mediated miR-449a overexpression suppressed proliferation of LNcap and PC-3, and miR-449a also significantly inhibited invasion and angiogenesis ability of LNcap and PC-3. IHC showed that PrLZ was upregulated in PCa tissues. Luciferase assay and western blotting verified that miR-449a targeted PrLZ expression. Moreover, PrLZ shRNA also significantly suppressed proliferation and metastasis of LNcap and PC-3. In addition, western blotting revealed that miR-449a overexpression and PrLZ shRNA all remarkably inhibited the stemness features in LNcap and PC-3. Furthermore, BALB/c nude mouse subcutaneous xenograft model was uesd to verify the function of miR-449a and PrLZ. Our results showed that miR-449a and PrLZ shRNA significantly suppressed PC-3 tumorigenesis and metastasis in vivo. Our studies suggested that miR-449a decreased in malignant process of PCa and was accompanied by excess expression of PrLZ. The loss of miR-449a caused PrLZ overexpression regulated prostate cancer progression and metastasis via regulating the stemness features of prostate cancer cells. The diagnostic value of miR-449a as a distant metastasis predictor of PCa needs further investigation.
Assuntos
Carcinogênese/genética , MicroRNAs/genética , Proteínas de Neoplasias/genética , Neoplasias da Próstata/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Tolerância a Radiação/efeitos dos fármacosRESUMO
PURPOSE: To assess the effectiveness and safety of tamsulosin combined with androgen deprivation therapy (ADT) for lower urinary tract symptoms (LUTS) in advanced prostate cancer (PC) patients. METHODS: Ninety PC patients with moderate-to-severe LUTS randomized into two groups of 45 each. One group received ADT (group 1), and the other received ADT plus tamsulosin (group 2) for 24 weeks. The outcome measures were changes in the International Prostate Symptom Score (IPSS), IPSS obstructive and irritative subscores, quality of life (QoL), maximum urinary flow rate (Q max), post-voiding residual (PVR) and prostate-specific antigen (PSA) from baseline. The treatment response was monitored at 8, 16 and 24 weeks. RESULTS: Both ADT monotherapy and ADT plus tamsulosin significantly improved IPSS,QoL score, Q max and PVR at the end of the treatment period. ADT plus tamsulosin had a greater impact on total IPSS, IPSS obstructive subscore, QoL and PVR at week 8 and week 16 than ADT monotherapy. Tamsulosin group showed greater improvement in Q max than ADT group. Significant improvements of IPSS, IPSS obstructive subscore and QoL were achieved at early treatment stage (week 8) in group 2, whereas similar improvements were achieved at week 16 in group 1. There were no significant differences in IPSS, IPSS subscores, QoL and PVR between the two groups at week 24. CONCLUSIONS: Additional administration of tamsulosin showed significantly greater and sooner relief in LUTS than ADT monotherapy, with good acceptability. It is feasible that ADT is used alone after 16-24 weeks of combination therapy.
Assuntos
Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Sulfonamidas/uso terapêutico , Antagonistas de Receptores Adrenérgicos alfa 1/efeitos adversos , Idoso , Flutamida/administração & dosagem , Gosserrelina/administração & dosagem , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/complicações , Qualidade de Vida , Índice de Gravidade de Doença , Sulfonamidas/efeitos adversos , Tansulosina , Fatores de Tempo , Urodinâmica/efeitos dos fármacosRESUMO
Previous studies showed that HCRP1 is decreased in tumor cells compared with normal tissue, and functions as a tumor suppressor. However, its expression pattern and function in human prostate cancer remain unclear. In this study we examined HCRP1 expression in prostate cancer cell lines via western blotting. Thereafter, we performed CCK-8 assay and matrigel invasion assay after cells were transfected with HCRP1 overexpression plasmid or siRNA. We further investigated the possible mechanism involved in HCRP1's regulation to prostate cancer cell proliferation and invasion. We found that HCRP1 negatively regulates EGFR activity and expression of its downstream proteins. Moreover, we found that HCRP1 is negatively correlated with multi-drug resistant related proteins after cells were treated with paclitaxel, cisplatin or gefitinib, indicating its inhibiting effect of chemotherapy resistance. In summary, our results provided evidence that HCRP1 is a negative regulator in prostate cancer progression, metastasis and multi-drug resistance.
Assuntos
Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Receptores ErbB/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais , Linhagem Celular Tumoral , Proliferação de Células , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Masculino , Modelos Biológicos , Invasividade NeoplásicaRESUMO
OBJECTIVE: To scan for mutations of polycystic kidney disease 1 gene (PKD1) in Chinese population in order to find some features about Chinese patients and a better approach to detect mutations. METHODS: Twenty-five PKD-affected individuals from twenty-one unrelated genealogies and sixteen controls participated in the study. Thirty-five blood samples and six tissues were obtained after receiving informed consent and were in accordance with institutional ethical guidelines. Genomic DNA was isolated from peripheral blood using standard procedures. PCR amplification of genomic DNA was performed to generate the aimed fragments. Amplified fragments were analyzed by denaturing gradient gel electrophoresis (DGGE). A GC clamp was attached to the 5' primer. After that, the abnormal fragments were sequenced on freshly amplified specific PCR products with the dideoxynucleotide chain termination method. Sequencing was performed for all samples to evaluate DGGE. RESULTS: Aimed fragments of exons 44 and 45 were amplified. DGGE detected eleven abnormal PCR fragments. Two novel mutations were identified by sequencing, included one nonsense mutation (C12217T) and one frameshift (12431delCT). In addition, one polymorphism (A50747C) was identified. The mutation detection rate is 8% in our study. CONCLUSION: Two novel pathogenic mutations were detected, including one nonsense mutation (C12217T) and one frameshift (12431delCT).
Assuntos
Mutação , Rim Policístico Autossômico Dominante/genética , Proteínas/genética , Povo Asiático/genética , Códon sem Sentido , Análise Mutacional de DNA , Éxons/genética , Saúde da Família , Feminino , Mutação da Fase de Leitura , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Canais de Cátion TRPPRESUMO
Prostate cancer is the leading cause of cancer deaths among men in the worldwide, it's important to find new prognostic factors and therapeutic targets. microRNAs play critical roles in the development and progression of prostate cancer. Here we revealed miR-1301 promoted prostate cancer progression. miR-1301 was upregulated in prostate cancer tissues and cells, overexpression of miR-1301 promoted anchorage-dependent and -independent growth using MTT analysis, colony formation analysis and soft agar growth analysis, whereas knockdown of miR-1301 suppressed anchorage-dependent and -independent growth. We also found overexpression of miR-1301 inhibited p27 expression and promoted Cyclin D1 expression, whereas knockdown of miR-1301 reduced this effect, suggesting miR-1301 promoted the G1/S transition. These results suggested miR-1301 promoted cell proliferation of prostate cancer. microRNAs can inhibit target mRNA translation or/and induce mRNA degradation, we found tumor suppresser PPP2R2C was the target of miR-1301, simultaneous downregualtion of PPP2R2C and miR-1301 promoted anchorage-dependent and -independent growth. These findings suggested miR-1301 promoted prostate cancer proliferation by inhibiting PPP2R2C, and might a therapeutic target for prostate cancer.
Assuntos
MicroRNAs/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteína Fosfatase 2/metabolismo , Sequência de Bases , Adesão Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , MicroRNAs/genética , Proteína Fosfatase 2/genética , Regulação para Cima/genéticaRESUMO
BACKGROUND: Benign prostatic hyperplasia (BPH) is one of the most common diseases in middle-age or older men. Increasing evidence has shown that BPH is associated with hypoxia microenvironment. METHODS: We retrospectively collected patient data and tissue samples from fetal prostates(FP), normal prostates(NP), intra-acinar of BPH, peri-acinar of BPH, prostate cancers and sarcomas of prostate. The expression of HIF-1α, as well as VEGF was visualized by immunohistochemistry and statistically analyzed with clinical parameters. RESULTS: Expression of HIF-lα was observed in intra-acinar of BPH (69.5%), prostate cancer (85.7%) and all FPs, while NP and peri-acinar of BPH tissues were all stained negative. HIF-lα levels in FPs and the malignant tumors were higher than BPH tissues(p < 0.05), and the expression of HIF-lα in intra-acinar of BPH was higher than NP and peri-acinar of BPH (p < 0.05). The expression of HIF-lα was correlated with the weight of intra-acinar of prostate (p < 0.05). And patients with prostate weight larger that 72.45g were prone to have HIF-lα moderate-positive expression, according to the ROC curve (AUC = 0.734, 95%CI = 0.630-0.838). Moreover, the risk of acute urine retention (AUR) for HIF-lα moderate-positive patients increased significantly (OR=5.517, 95%CI = 2.434-12.504). CONCLUSIONS: HIF-lα expression is increased in highly proliferative prostate tissues and correlated with the weight of intra-acinar prostate. Moreover, HIF-lα is also an independent risk factor for AUR occurrence in BPH patients.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/biossíntese , Próstata/crescimento & desenvolvimento , Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Adulto , Humanos , Imuno-Histoquímica , Masculino , Próstata/patologia , Hiperplasia Prostática/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To evaluate the effects of microRNA-21 (miR-21) in peripheral blood mononuclear cells (PBMC) in the diagnosis and prognosis of prostate cancer (PCa). METHODS: Proved by pathologic biopsy, 92 patients diagnosed with PCa and also underwent resection operation and 85 patients with benign prostatic hyperplasia (BPH) were selected in this study, as well as 97 healthy volunteers were chosen as the control group. PBMC were extracted to examine the relative expression of miR-21 by real time reverse transcriptase-polymerase chain reaction (RT-PCR). The relative operating characteristic (ROC) curves were drew to analyze the diagnosis value of PCa. The survival function curves were made by Kaplan-Meier method to show the miR-21 expression levels of PCa patients. The Log-rank test was adopted to compare the differences among the different groups. The Cox proportional hazard risk regression analysis was used to screen the independent factors affected the PCa patients. RESULTS: The expression levels of miR-21 in PCa group were increased compared to BPH and control group (P < 0.05). The expression of miR-21 was significantly correlated with the Gleason score, clinical stages, bone metastasis and tumor recurrence (all P < 0.05). ROC curves demonstrated that the area under the curve of PCa and BPH distinguished by the miR-21 were 0.974 and 95% confidence intervals (95% CI) were 0.956â¼ 0.993. The sensitivity and specificity were 93.5% and 92.9%. ROC curves demonstrated that the area under the curve of PCa and control group distinguished by the miR-21 were 0.984 and 95% CI were 0.972â¼ 0.997. The sensitivity and specificity were 94.6% and 92.8%. The results of Kaplan-Meier Method demonstrated that the miR-21 expression levels were related to the prognosis of PCa (all P < 0.05). The results of the COX analysis suggested that the miR-21 expression level, tumor recurrence and bone metastasis could be the independent factors affected the prognosis of PCa patients (all P < 0.05). CONCLUSION: miR-21 is highly expressed in the PCa patients, which could be the molecule biomarker of diagnosis and prognosis of PCa.