RÉSUMÉ
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.
Sujet(s)
Phosphore , Polluants chimiques de l'eau , Charbon de bois , Fer/analyse , Eau , Polluants chimiques de l'eau/analyseRÉSUMÉ
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.
RÉSUMÉ
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.
Sujet(s)
Carcinogenèse/génétique , microARN/génétique , Protéines tumorales/génétique , Tumeurs de la prostate/génétique , Adulte , Sujet âgé , Animaux , Lignée cellulaire tumorale , Prolifération cellulaire/génétique , Régulation de l'expression des gènes tumoraux , Humains , Mâle , Souris , Adulte d'âge moyen , Métastase tumorale , Tumeurs de la prostate/anatomopathologie , Tumeurs de la prostate/radiothérapie , Radiotolérance/effets des médicaments et des substances chimiquesRÉSUMÉ
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.
Sujet(s)
Complexes de tri endosomique requis pour le transport/métabolisme , Récepteurs ErbB/métabolisme , Tumeurs de la prostate/métabolisme , Tumeurs de la prostate/anatomopathologie , Transduction du signal , Lignée cellulaire tumorale , Prolifération cellulaire , Multirésistance aux médicaments , Résistance aux médicaments antinéoplasiques , Humains , Mâle , Modèles biologiques , Invasion tumoraleRÉSUMÉ
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.
Sujet(s)
Antagonistes des récepteurs alpha-1 adrénergiques/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Symptômes de l'appareil urinaire inférieur/traitement médicamenteux , Tumeurs de la prostate/traitement médicamenteux , Sulfonamides/usage thérapeutique , Antagonistes des récepteurs alpha-1 adrénergiques/effets indésirables , Sujet âgé , Flutamide/administration et posologie , Goséréline/administration et posologie , Humains , Symptômes de l'appareil urinaire inférieur/étiologie , Mâle , Adulte d'âge moyen , Tumeurs de la prostate/complications , Qualité de vie , Indice de gravité de la maladie , Sulfonamides/effets indésirables , Tamsulosine , Facteurs temps , Urodynamique/effets des médicaments et des substances chimiquesRÉSUMÉ
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.
Sujet(s)
Lasers à solide , Lithotritie par laser , Urétéroscopes , Calculs urinaires/thérapie , Adulte , Femelle , Hématurie/sang , Hémorragie , Humains , Lithotritie , Mâle , Adulte d'âge moyen , Durée opératoire , Sécurité des patients , Études rétrospectives , Résultat thérapeutique , Urétéroscopie , Rayons XRÉSUMÉ
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.
Sujet(s)
Angiomyolipome/anatomopathologie , Tumeurs du rein/anatomopathologie , Cellules tumorales circulantes , Veine cave inférieure , Adulte , Humains , Mâle , Invasion tumoraleRÉSUMÉ
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.
Sujet(s)
Protéines adaptatrices de la transduction du signal/métabolisme , Apoptose/effets des médicaments et des substances chimiques , Autophagie/effets des médicaments et des substances chimiques , Néphrocarcinome/anatomopathologie , Cisplatine/pharmacologie , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Protéines IAP/métabolisme , Protéines tumorales/métabolisme , Protéines adaptatrices de la transduction du signal/antagonistes et inhibiteurs , Protéines adaptatrices de la transduction du signal/génétique , Animaux , Antinéoplasiques/pharmacologie , Marqueurs biologiques tumoraux , Technique de Western , Néphrocarcinome/traitement médicamenteux , Néphrocarcinome/métabolisme , Adhérence cellulaire/effets des médicaments et des substances chimiques , Mouvement cellulaire/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Femelle , Humains , Techniques immunoenzymatiques , Protéines IAP/antagonistes et inhibiteurs , Protéines IAP/génétique , Tumeurs du rein/traitement médicamenteux , Tumeurs du rein/métabolisme , Tumeurs du rein/anatomopathologie , Mâle , Souris , Souris de lignée BALB C , Souris nude , Adulte d'âge moyen , Grading des tumeurs , Protéines tumorales/antagonistes et inhibiteurs , Protéines tumorales/génétique , Stadification tumorale , Pronostic , ARN messager/génétique , Petit ARN interférent/génétique , Réaction de polymérisation en chaine en temps réel , RT-PCR , Taux de survie , Cellules cancéreuses en culture , Tests d'activité antitumorale sur modèle de xénogreffeRÉSUMÉ
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.
Sujet(s)
Agranulocytes/métabolisme , microARN/génétique , Tumeurs de la prostate/diagnostic , Tumeurs de la prostate/génétique , Adulte , Sujet âgé , Marqueurs biologiques tumoraux , Régulation de l'expression des gènes tumoraux , Humains , Mâle , Adulte d'âge moyen , Grading des tumeurs , Stadification tumorale , Pronostic , Hyperplasie de la prostate/génétique , Tumeurs de la prostate/mortalité , Courbe ROC , RécidiveRÉSUMÉ
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.
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microARN/métabolisme , Tumeurs de la prostate/génétique , Tumeurs de la prostate/anatomopathologie , Protein Phosphatase 2/métabolisme , Séquence nucléotidique , Adhérence cellulaire , Prolifération cellulaire , Régulation de l'expression des gènes tumoraux , Techniques de knock-down de gènes , Humains , Mâle , microARN/génétique , Protein Phosphatase 2/génétique , Régulation positive/génétiqueRÉSUMÉ
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.
Sujet(s)
Sous-unité alpha du facteur-1 induit par l'hypoxie/biosynthèse , Prostate/croissance et développement , Prostate/métabolisme , Hyperplasie de la prostate/métabolisme , Adulte , Humains , Immunohistochimie , Mâle , Prostate/anatomopathologie , Hyperplasie de la prostate/anatomopathologie , Études rétrospectives , Jeune adulteRÉSUMÉ
PURPOSE: The aim of this study was to investigate the clinical significance of CD4(+) T cells in non-muscle-invasive bladder cancer (NMIBC) tissues in situ. METHODS: Immunohistochemistry was used to examine the distribution of CD4(+) T cells in 131 NMIBC tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival (OS) and recurrence-free survival (RFS). RESULTS: NMIBC patients were divided into two groups based on the median frequency of CD4(+) T cells (median, 1/×400 high resolution). On univariate analysis, CD4(+) T cell density was inversely associated with overall survival (P = 0.01). In those patients with high CD4(+) T density, 5-year OS rates was only 77%, compared with 86% in those with low density, respectively. Although CD4(+) T cell density showed no prognostic significance for RFS (P = 0.36), 5-year RFS rates of patients with high CD4(+) T density (58%) was lower than those of patients with low CD4(+) T density (65%, respectively). By multivariate analysis, tumor infiltrating CD4(+) T cell density emerged as an independent prognostic factor for OS (HR, 2.75; P = 0.004). In addition, no association was found between CD4(+) T cell density and any clinicopathological variables (P > 0.05). CONCLUSION: Our findings suggest that CD4(+) T cells could potentially serve as a poor prognostic marker for patients with NMIBC.
Sujet(s)
Lymphocytes T CD4+/immunologie , Carcinome transitionnel/immunologie , Lymphocytes TIL/immunologie , Tumeurs de la vessie urinaire/immunologie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Marqueurs biologiques tumoraux/immunologie , Carcinome transitionnel/mortalité , Carcinome transitionnel/anatomopathologie , Survie sans rechute , Femelle , Humains , Immunohistochimie , Estimation de Kaplan-Meier , Mâle , Adulte d'âge moyen , Pronostic , Modèles des risques proportionnels , Tumeurs de la vessie urinaire/mortalité , Tumeurs de la vessie urinaire/anatomopathologie , Jeune adulteRÉSUMÉ
Development of resistance to gemcitabine is a major concern in bladder cancer therapy, and the mechanism remains unclear. Eg5 has been recently identified as an attractive target in cancer chemotherapy, so novel targeted chemotherapy with Eg5 inhibitor is expected to improve the anticancer effect in gemcitabine-resistant bladder cancer. In this research, RT112-Gr cells were 350-fold less sensitive to gemcitabine than the parental cell lines, while KU7-Gr cells were 15-fold less sensitive to gemcitabine than the parental cell lines. Human OneArray Microarray analysis was performed to obtain broad spectrum information about the genes differentially expressed in RT112 and RT112-Gr cells. The anti-proliferative activity of S(MeO)TLC, an Eg5 inhibitor, was analyzed in RT112-Gr cell lines using a cell viability assay. Furthermore, the inhibitory effect was evaluated in vivo using subcutaneous xenograft tumor model. According to the result of Human OneArray GeneChip, RRM1 and RRM2 were up-regulated, while there was no significant change in Eg5. Trypan blue staining confirmed that in S(MeO)TLC and Gemcitabine combining S(MeO)TLC group cell viability were significantly decreased in RT112-Gr cells as compared with other groups. S(MeO)TLC and S(MeO)TLC+gemcitabine groups prominently suppressed tumor growth in comparison with other groups' in vivo. There were no significant differences in S(MeO)TLC and gemcitabine+S(MeO)TLC group in the effect of inhibition of bladder cancer in vivo and in vitro. Our data collectively demonstrated that S(MeO)TLC represents a novel strategy for the treatment of gemcitabine resistant bladder cancer.
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Cystéine/analogues et dérivés , Kinésine/antagonistes et inhibiteurs , Composés trityliques/pharmacologie , Tumeurs de la vessie urinaire/traitement médicamenteux , Animaux , Apoptose/effets des médicaments et des substances chimiques , Apoptose/génétique , Lignée cellulaire tumorale , Analyse de regroupements , Cystéine/pharmacologie , Désoxycytidine/analogues et dérivés , Désoxycytidine/pharmacologie , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Résistance aux médicaments antinéoplasiques/génétique , Femelle , Analyse de profil d'expression de gènes/méthodes , Régulation de l'expression des gènes tumoraux , Humains , Immunohistochimie , Kinésine/génétique , Kinésine/métabolisme , Souris de lignée BALB C , Séquençage par oligonucléotides en batterie , Interférence par ARN , RT-PCR , Ribonucleoside diphosphate reductase/effets indésirables , Ribonucleoside diphosphate reductase/génétique , Ribonucleoside diphosphate reductase/métabolisme , Charge tumorale/effets des médicaments et des substances chimiques , Charge tumorale/génétique , Protéines suppresseurs de tumeurs/génétique , Protéines suppresseurs de tumeurs/métabolisme , Tumeurs de la vessie urinaire/génétique , Tumeurs de la vessie urinaire/métabolisme , Tests d'activité antitumorale sur modèle de xénogreffe ,RÉSUMÉ
OBJECTIVES: To explore molecular mechanisms of bladder cancer (BC), network strategy was used to find biomarkers for early detection and diagnosis. METHODS: The differentially expressed genes (DEGs) between bladder carcinoma patients and normal subjects were screened using empirical Bayes method of the linear models for microarray data package. Co-expression networks were constructed by differentially co-expressed genes and links. Regulatory impact factors (RIF) metric was used to identify critical transcription factors (TFs). The protein-protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and clusters were obtained through molecular complex detection (MCODE) algorithm. Centralities analyses for complex networks were performed based on degree, stress and betweenness. Enrichment analyses were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. RESULTS: Co-expression networks and TFs (based on expression data of global DEGs and DEGs in different stages and grades) were identified. Hub genes of complex networks, such as UBE2C, ACTA2, FABP4, CKS2, FN1 and TOP2A, were also obtained according to analysis of degree. In gene enrichment analyses of global DEGs, cell adhesion, proteinaceous extracellular matrix and extracellular matrix structural constituent were top three GO terms. ECM-receptor interaction, focal adhesion, and cell cycle were significant pathways. CONCLUSIONS: Our results provide some potential underlying biomarkers of BC. However, further validation is required and deep studies are needed to elucidate the pathogenesis of BC.
Sujet(s)
Régulation de l'expression des gènes tumoraux , Réseaux de régulation génique , Tumeurs de la vessie urinaire/génétique , Théorème de Bayes , Analyse de profil d'expression de gènes , Gene Ontology , Humains , Cartes d'interactions protéiques , Facteurs de transcription/génétique , Facteurs de transcription/métabolisme , Vessie urinaire/métabolisme , Vessie urinaire/anatomopathologie , Tumeurs de la vessie urinaire/diagnostic , Tumeurs de la vessie urinaire/métabolismeRÉSUMÉ
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.
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Néphrocarcinome/génétique , Protéines tumorales/biosynthèse , Récidive tumorale locale/génétique , Protéomique , Acétylation , Sujet âgé , Marqueurs biologiques tumoraux/biosynthèse , Néphrocarcinome/diagnostic , Néphrocarcinome/anatomopathologie , Chromatographie en phase liquide , Femelle , Régulation de l'expression des gènes tumoraux , Humains , Mâle , Spectrométrie de masse , Adulte d'âge moyen , Protéines tumorales/génétique , Récidive tumorale locale/diagnostic , Récidive tumorale locale/anatomopathologie , Pronostic , Maturation post-traductionnelle des protéinesRÉSUMÉ
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.
Sujet(s)
Antinéoplasiques/pharmacologie , Néphrocarcinome/traitement médicamenteux , Cystéine/analogues et dérivés , Tumeurs du rein/traitement médicamenteux , Kinésine/antagonistes et inhibiteurs , Thérapie moléculaire ciblée , Composés trityliques/pharmacologie , Animaux , Apoptose/effets des médicaments et des substances chimiques , Néphrocarcinome/anatomopathologie , Points de contrôle du cycle cellulaire/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale , Cystéine/pharmacologie , Femelle , Humains , Tumeurs du rein/anatomopathologie , Kinésine/analyse , Souris , Souris de lignée BALB C , Tests d'activité antitumorale sur modèle de xénogreffeRÉSUMÉ
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.
Sujet(s)
Antiviraux/pharmacologie , Benzimidazoles/pharmacologie , Hepacivirus/effets des médicaments et des substances chimiques , Hepacivirus/génétique , ARN viral/génétique , ARN viral/métabolisme , Ribosomes/métabolisme , Antiviraux/synthèse chimique , Antiviraux/composition chimique , Benzimidazoles/synthèse chimique , Benzimidazoles/composition chimique , Relation dose-effet des médicaments , Ligands , Modèles moléculaires , Structure moléculaire , Relation structure-activitéRÉSUMÉ
The internal ribosome entry site (IRES) in the 5' untranslated region (UTR) of the hepatitis C virus (HCV) genome initiates translation of the viral polyprotein precursor. The unique structure and high sequence conservation of the 5' UTR render the IRES RNA a potential target for the development of selective viral translation inhibitors. Here, we provide an overview of approaches to block HCV IRES function by nucleic acid, peptide, and small molecule ligands. Emphasis will be given to the IRES subdomain IIa, which currently is the most advanced target for small molecule inhibitors of HCV translation. The subdomain IIa behaves as an RNA conformational switch. Selective ligands act as translation inhibitors by locking the conformation of the RNA switch. We review synthetic procedures for inhibitors as well as structural and functional studies of the subdomain IIa target and its ligand complexes.
Sujet(s)
Hepacivirus/effets des médicaments et des substances chimiques , Biosynthèse des protéines/effets des médicaments et des substances chimiques , Ribosomes/effets des médicaments et des substances chimiques , Régions 5' non traduites , Hepacivirus/génétique , Modèles moléculairesRÉSUMÉ
The preparation and crystal structure of 8-chloro-1H-pyrrolo[2,3-b]phenazine 5-oxide (1) are described. Compound 1 formed dark purple crystals from deeply colored solution in methanol. Crystal plates were in the triclinic system, P-1 space group with unit cell parameters a = 6.9514(8), b = 9.1568(10), c = 10.2067(11), α = 84.509(2), ß = 82.936(2), γ = 72.357(2) and a cell volume of 613.25(12) A-3. The title compound which contains the first example of the extensively conjugated pyrrolo-phenazine N-oxide system exhibits strong light absorption in the green to cyan wavelength range which disappears upon protonation.
RÉSUMÉ
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.