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1.
Cancer Lett ; 469: 481-489, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31738958

RESUMO

Docetaxel-mediated chemotherapy is the first line therapy for metastatic castration-resistant prostate cancer (CRPC) patients, but its therapeutic benefit is limited by the development of resistance. Although Forkhead box protein M1 (FOXM1) has been implicated in prostate tumorigenesis and metastasis, its role in docetaxel resistance has not been studied. Here, we showed that FOXM1 expression was upregulated in the docetaxel resistant CRPC cell lines (PC3-DR and VCaP-DR) and knockdown of FOXM1 sensitized the cells to docetaxel both in vitro and in vivo. In addition, autophagy was found to be significantly enhanced in resistant cells. Moreover, FOXM1 overexpression cells showed increased autophagic flux and higher numbers of autophagosomes. Knockdown of ATG7, beclin-1 or cotreatment with chloroquine, partly restored sensitivity to docetaxel in the FOXM1-overexpressing cells. Mechanistically, FOXM1 targeted AMPK/mTOR to activate the autophagy pathway and altered docetaxel response in CRPC. These findings identify the role of FOXM1 as well as the mechanism underlying FOXM1 action in docetaxel sensitivity and may, therefore, aid in design of CRPC therapies.

2.
Asian J Androl ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31274477

RESUMO

Ectopic seminal tract opening is a rare congenital malformation. Until recently, there has been a lack of comprehensive reporting on the condition. The purpose of this retrospective study is to summarize the experience of diagnosis and treatment of this condition based on 28 clinical practice cases throughout the past 30 years. We conducted auxiliary examinations on such patients including routine tests, imaging examinations, and endoscopy. Among these 28 cases, there were ectopic opening of vas deferens into enlarged prostatic utricles (6 cases); ejaculatory ducts into enlarged prostatic utricles, Müllerian ducts cysts, and urethras (18 cases, 2 cases, and 1 case, respectively); and ectopic opening of the unilateral vas deferens and the contralateral ejaculatory duct into enlarged prostatic utricle (1 case). The size of the enlarged prostatic utricle, the type of ectopic seminal tract opening, and the opening's location effectively assisted in the selection of clinical treatment methods, including transurethral fenestration of the utricle, transurethral cold-knife incision, open operation, laparoscopic operation, and conservative treatment. Satisfactory effect was achieved during follow-up. In conclusion, a definite diagnosis and personalized treatment are especially important for patients with ectopic seminal tract opening.

4.
Oncol Rep ; 40(4): 2242-2250, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30066906

RESUMO

Resistance to docetaxel is a major clinical problem in castration­resistant prostate cancer (CRPC). We have previously reported that the combined inhibition of epidermal growth factor receptor (EGFR) and cyclooxygenase­2 (COX­2) led to an increased antitumor activity of docetaxel in CRPC. In the present study, we explored the efficacy of the combination of EGFR inhibition (by gefitinib) and COX­2 inhibition (by celecoxib) as a potential treatment for docetaxel­resistant CRPC. We established two docetaxel­resistant prostate cancer cell lines, PC3/DR and DU145/DR, by culturing PC3 and DU145 cells in docetaxel in a dose­escalating manner. The EGFR and COX­2 protein expression levels were determined. The effects of gefitinib and celecoxib on cell proliferation, apoptosis and invasion in vitro and in vivo were evaluated. In vitro changes in Bcl­2, FOXM1 and ABCB1 expression were analyzed. The expression of Ki­67 and cleaved­caspase­3 was also examined in DU145/DR tumor tissue. The enhanced expression of EGFR and COX­2 was observed in docetaxel­resistant CRPC relative to the parental cell lines. MTT, clone formation and fluorescence­activated cell sorting (FACS) analyses demonstrated that gefitinib and celecoxib in combination decreased cell viability and enhanced the rate of apoptosis when compared with either drug used alone. Additionally, the combination treatment was superior in inhibiting cell invasion and induced significant decreases in Bcl­2, FOXM1 and ABCB1 expression levels. Furthermore, the gefitinib­celecoxib combination inhibited DU145/DR tumor growth to a greater extent than either treatment used individually. The expression of Ki­67 was reduced, whereas cleaved­caspase­3 protein expression was increased in the tumors from the combination therapy group. In conclusion, the combined inhibition of EGFR and COX­2 by gefitinib and celecoxib may overcome docetaxel resistance in human CRPC. These findings provided a molecular basis for the clinical application of a novel combination therapy for docetaxel­resistant CRPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Celecoxib/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Próstata/patologia , Quinazolinas/farmacologia , Taxoides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/farmacologia , Docetaxel , Gefitinibe , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Cell Physiol Biochem ; 44(3): 1213-1223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29179219

RESUMO

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.


Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim , RNA Longo não Codificante/sangue , Doença Aguda , Área Sob a Curva , Biomarcadores/sangue , Estudos de Coortes , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Curva ROC , Transcriptoma , Transplante Homólogo
6.
Oncotarget ; 8(45): 79323-79336, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108311

RESUMO

Objective: We conducted this meta-analysis to examine the effect of remote ischemic conditioning (RIC) on contrast-induced acute kidney injury (CI-AKI) in patients undergoing intravascular contrast administrationon. Methods: Pubmed, Embase, and Cochrane Library were comprehensively searched to identify all eligible studies by 15th March, 2017. Risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI) were used to examine the treatment effect. The heterogeneity and statistical significance were assessed with Q-test and Z-test, respectively. Results: A total of 16 RCTs including 2175 patients were eventually analyzed. Compared with the control group, RIC could significantly decrease the incidence of CI-AKI (RR=0.58; 95% CI: 0.46, 0.74; P < 0.001), which was further confirmed by the trial sequential analysis. Subgroup analyses showed that remote ischemic preconditioning (RIPrC) and remote ischemic postconditioning (RIPoC) were both obviously effective, and perioperative hydration might enhance the efficiency of RIC. RIC also significantly reduced the major adverse cardiovascular events within six months. Conclusion: RIC, whether RIPrC or RIPoC, could effectively exert renoprotective role in intravascular contrast administration and reduce the incidence of relevant adverse events.

7.
J Cancer ; 8(13): 2643-2652, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28900502

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.

8.
Oncotarget ; 8(25): 41064-41077, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28455956

RESUMO

Resistance to docetaxel is a major clinical problem in advanced prostate cancer. The overexpression of AXL receptor tyrosine kinase (AXL) has been correlated with chemotherapeutic drug resistance. However, the role of AXL expression in docetaxel resistance in prostate cancer is yet unclear. In this study, we demonstrate that AXL is overexpressed and activated independent of Gas6 in docetaxel-resistant prostate cancer cells (PC3-DR and DU145-DR). Moreover, we show that forced overexpression of AXL in PC3 and DU145 cells is sufficient to induce resistance to docetaxel in these cell lines. Notably, genetic or pharmacologic inhibition of AXL in the resistant models suppressed cell proliferation, migration, invasion, and tumor growth, and these effects were significantly augmented when AXL inhibition was combined with docetaxel treatment. Mechanistically, we found that AXL inhibition led to reversion of the epithelial-mesenchymal transition (EMT) phenotype and decreased the expression of ATP-binding cassette B1 (ABCB1). Overall, our results identify AXL as an important mediator of docetaxel resistance in prostate cancer. We propose that AXL-targeted therapy, in combination with docetaxel, has the potential to improve the response to docetaxel therapy and reduce resistance induced by prolonged docetaxel therapy in prostate cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Benzocicloeptenos/administração & dosagem , Benzocicloeptenos/farmacologia , Linhagem Celular Tumoral , Docetaxel , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Interferência de RNA , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Taxoides/administração & dosagem , Taxoides/farmacologia , Triazóis/administração & dosagem , Triazóis/farmacologia
9.
PLoS One ; 12(1): e0170729, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28129389

RESUMO

OBJECTIVE: We conducted this meta-analysis of randomized controlled trials (RCTs) to investigate whether remote ischemic conditioning (RIC) could improve graft functions in kidney transplantation. METHODS: PubMed, Web of Science, and Cochrane Library were comprehensively searched to identify all eligible studies by October 5, 2016. The treatment effects were examined with risk ratio (RR) and weighted mean difference with the corresponding 95% confidence intervals (CI). The statistical significance and heterogeneity were assessed with both Z-test and Q-test. RESULTS: A total of six RCTs including 651 recipients, were eventually identified. Compared to the controls, RIC could reduce the incidence of delayed graft function (DGF) after kidney transplantation (random-effects model: RR = 0.89; fixed-effect model: RR = 0.84). However, the decrease did not reveal statistical significance. The subgroup analysis by RIC type demonstrated no significant difference among the three interventions in protecting renal allografts against DGF. Furthermore, no significant difference could be observed in the incidence of acute rejection, graft loss, 50% fall in serum creatinine, as well as the estimated glomerular filtration rate and hospital stay between the RIC and Control groups. CONCLUSIONS: This meta-analysis suggested that RIC might exert renoprotective functions in human kidney transplantation, and further well-designed RCTs with large sample size are warranted to assess its clinical efficacy.


Assuntos
Sobrevivência de Enxerto/fisiologia , Precondicionamento Isquêmico/métodos , Transplante de Rim , Rejeição de Enxerto/fisiopatologia , Humanos , Imunossupressão , Rim/lesões , Rim/fisiopatologia , Testes de Função Renal , Ensaios Clínicos Controlados Aleatórios como Assunto , Traumatismo por Reperfusão/fisiopatologia , Traumatismo por Reperfusão/terapia
10.
Zhonghua Nan Ke Xue ; 23(4): 302-308, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29714413

RESUMO

Objective: To explore the effect of the AXL expression on the chemosensitivity of prostate cancer PC-3 and DU145 cells to docetaxel and possible mechanisms. METHODS: Using Western blot, we examined the expressions of the AXL protein, p-AXL and Gas6 in the docetaxel-resistant PC-3 (PC-3-DR) and DU145 (DU145-DR) cells stimulated with gradually increased concentrations of docetaxel. We transfected the PC-3 and DU145 cells with negative NC ShRNA and AXL-ShRNA, respectively, which were confirmed to be effective, detected the proliferation, apoptosis and cycle distribution of the cells by CCK8, MTT and flow cytometry after treated with the AXL-inhibitor MP470 and/or docetaxel, and determined the expression of the ABCB1 protein in the PC-3-DR and DU145-DR cells after intervention with the AXL-inhibitor R428 and/or docetaxel. RESULTS: The expression of the AXL protein in the PC-3 and DU145 cells was significantly increased after docetaxel treatment (P <0.05). The expressions AXL and p-AXL were remarkably higher (P <0.05) while that of Gas6 markedly lower (P <0.05) in the PC-3 and DU145 than in the PC-3-DR and DU145-DR cells. The inhibitory effect of docetaxel on the proliferation and its enhancing effect on the apoptosis of the PC-3 and DU145 cells were significantly decreased at 48 hours after AXL transfection (P <0.05). MP470 obviously suppressed the growth and promoted the apoptosis of the PC-3-DR and DU145-DR cells, with a higher percentage of the cells in the G2/M phase when combined with docetaxel than used alone (P <0.05). R428 markedly reduced the expression of ABCB1 in the PC-3-DR and DU145-DR cells, even more significantly in combination with docetaxel than used alone (P <0.05). CONCLUSIONS: The elevated expression of AXL enhances the docetaxel-resistance of PC-3 and DU145 prostate cancer cells and AXL intervention improves their chemosensitivity to docetaxel, which may be associated with the increased cell apoptosis in the G2/M phase and decreased expression of ABCB1.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Taxoides/farmacologia , Apoptose/efeitos dos fármacos , Contagem de Células , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Docetaxel , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas/genética , Pirimidinas/farmacologia , RNA Interferente Pequeno , Receptores Proteína Tirosina Quinases/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/genética
11.
Tumour Biol ; 36(10): 8159-66, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25990459

RESUMO

Bladder cancer ranks the second most common genitourinary tract cancer, and muscle-invasive bladder cancer (MIBC) accounts for approximately 25 % of all bladder cancer cases with high mortality. In the current study, with a total of 202 treatment-naïve primary MIBC patients identified from The Cancer Genome Atlas dataset, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in MIBC, with the aim to investigate the relationship of miRNA expression with the progression and prognosis of MIBC, and generate a miRNA signature of prognostic capabilities. In the progression-related miRNA profiles, a total of 47, 16, 3, and 84 miRNAs were selected for pathologic T, N, M, and histologic grade, respectively. Of the eight most important progression-related miRNAs, four (let-7c, mir-125b-1, mir-193a, and mir-99a) were significantly associated with survival of patients with MIBC. Finally, a four-miRNA signature was generated and proven as a promising prognostic parameter. In summary, this study identified the specific miRNAs associated with the progression and aggressiveness of MIBC and a four-miRNA signature as a promising prognostic parameter of MIBC.


Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Musculares/genética , Neoplasias Musculares/mortalidade , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Idoso , Carcinoma Papilar/genética , Carcinoma Papilar/mortalidade , Carcinoma Papilar/patologia , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/patologia
12.
Int J Clin Exp Pathol ; 8(2): 1128-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25972999

RESUMO

BACKGROUND: Ischemic preconditioning (IPC) could protect against subsequent renal ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain far from complete. Hence, we explored the effects of IPC on the renal and systemic hemodynamic changes, renal function and morphology, as well the involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and nitric oxide (NO). METHODS: Male Sprague-Dawley rats were randomly divided into five groups after right-side nephrectomy: Sham group (surgery without vascular clamping); IRI group (the left renal artery was clamped for 45 min); IPC group (pretreated with 15 min of ischemia and 10 min of reperfusion); IPC + vehicle group (administrated with 0.9% saline 5 min before IPC); and IPC + N(G)-nitro-L-arginine methylester (L-NAME) group (pretreated with L-NAME 5 min prior to IPC). The renal and systemic hemodynamic parameters, renal function and morphology, as well as eNOS, iNOS, and NO expression levels in the kidneys were measured at the indicated time points after reperfusion. RESULTS: IPC rats exhibited significant improvements in renal function, morphology, and renal artery blood flow (RABF), without obvious influence on the systemic hemodynamics and renal vein blood flow. Increased eNOS, iNOS, and NO expression levels were detected in the kidneys of IPC rats 24 h after reperfusion. Furthermore, the beneficial effects were fully abolished by the administration of L-NAME. CONCLUSIONS: The results suggest that IPC contributes to early restoration of RABF, probably through eNOS/iNOS-mediated NO production, thereby alleviating the renal dysfunction and histological damage caused by IRI.


Assuntos
Precondicionamento Isquêmico/métodos , Rim/irrigação sanguínea , Traumatismo por Reperfusão/fisiopatologia , Animais , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
13.
Sci Rep ; 5: 10328, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-25981392

RESUMO

Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of kidney cancers. In the present study, we identified 58 treatment-naïve primary chRCC patients from The Cancer Genome Atlas dataset and analyzed the genome-wide microRNA (miRNA) expression profiles, with the aim to assess the relationship of miRNA expression with the progression and prognosis of chRCC. Overall, a total of 105 miRNAs were found to be differentially expressed between tumor and the adjacent normal tissues from 22 chRCC patients. In the unpaired condition (58 chRCC vs. 22 normal tissues), 77 (96.3%) samples were distinguished correctly by the signatures. In the progression-related profiles, 27 miRNAs were selected for pathologic T and 9 for lymph node involvement. In the survival analyses, the expression levels of mir-191, mir-19a, mir-210, and mir-425 were significantly associated with both recurrence-free survival (RFS) and overall survival, while mir-210 was proven as an independent prognostic factor in terms of RFS. In summary, miRNAs are expressed differentially in chRCC, and unique expression of miRNAs is associated with the progression and prognosis of chRCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , MicroRNAs/genética , Transcriptoma , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma de Células Renais/mortalidade , Análise por Conglomerados , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Carga Tumoral
14.
Medicine (Baltimore) ; 94(16): e767, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25906110

RESUMO

Papillary renal cell carcinoma (pRCC) is the second most prevalent subtype of kidney cancers. In the current study, we analyzed the global microRNA (miRNA) expression profiles in pRCC, with the aim to evaluate the relationship of miRNA expression with the progression and prognosis of pRCC.A total of 163 treatment-naïve primary pRCC patients were identified from the Cancer Genome Atlas dataset and included in this retrospective observational study. The miRNA expression profiles were graded by tumor-node-metastasis information, and compared between histologic subtypes. Furthermore, the training-validation approach was applied to identify miRNAs of prognostic values, with the aid of Kaplan-Meier survival, and univariate and multivariate Cox regression analyses. Finally, the online DAVID (Database for Annotation, Visualization, and Integrated Discover) program was applied for the pathway enrichment analysis with the target genes of prognosis-associated miRNAs, which were predicted by 3 computational algorithms (PicTar, TargetScan, and Miranda).In the progression-related miRNA profiles, 26 miRNAs were selected for pathologic stage, 28 for pathologic T, 16 for lymph node status, 3 for metastasis status, and 32 for histologic types, respectively. In the training stage, the expression levels of 12 miRNAs (mir-134, mir-379, mir-127, mir-452, mir-199a, mir-200c, mir-141, mir-3074, mir-1468, mir-181c, mir-1180, and mir-34a) were significantly associated with patient survival, whereas mir-200c, mir-127, mir-34a, and mir-181c were identified by multivariate Cox regression analyses as potential independent prognostic factors in pRCC. Subsequently, mir-200c, mir-127, and mir-34a were confirmed to be significantly correlated with patient survival in the validation stage. Finally, target gene prediction analysis identified a total of 113 target genes for mir-200c, 37 for mir-127, and 180 for mir-34a, which further generated 15 molecular pathways.Our results identified the specific miRNAs associated with the progression and aggressiveness of pRCC, and 3 miRNAs (mir-200c, mir-127, and mir-34a) as promising prognostic factors of pRCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , MicroRNAs/biossíntese , Fatores Etários , Idoso , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores Sexuais
15.
Biomed Pharmacother ; 69: 29-33, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25661334

RESUMO

PURPOSE: Current evidence suggests that preconditioning with erythropoietin (EPO) can protect against ischemia reperfusion injury in rodents. However, randomized controlled trials (RCTs) assessing the efficacy and safety of high-dose EPO in kidney transplantation have yielded inconclusive results. Herein, we performed a meta-analysis of RCTs to assess whether the administration of high-dose EPO can improve graft function and the potential adverse events. METHODS: Relevant RCT studies that investigated high-dose EPO on graft function after kidney transplantation were comprehensively searched in Pubmed, Embase, and Cochrane Library until July 10, 2014. All statistical analyses were performed using Review Manager 5.0 and STATA 12.0. RESULTS: A total of 4 RCTs involving 356 patients were identified. Comprehensively, a trend of reduction in the incidence of delayed graft function could be observed in the EPO group (EPO vs. placebo groups: RR=0.88); however, the result did not reach the significance level (95% CI, 0.72-1.08; P=0.21). Furthermore, no significant difference in the incidences of adverse events was observed between the two groups. CONCLUSIONS: The current meta-analysis indicates that the administration of high-dose EPO is, to some extent, prone to protect kidney function without increasing the susceptibility to adverse events.


Assuntos
Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Transplante de Rim , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervalos de Confiança , Relação Dose-Resposta a Droga , Eritropoetina/efeitos adversos , Humanos , Transplante de Rim/efeitos adversos , Viés de Publicação
16.
J Cancer Res Clin Oncol ; 141(7): 1291-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25633718

RESUMO

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers in adults, and microRNAs (miRNAs) differentially expressed in ccRCC tumors have been identified and proposed to predict prognosis. In the present study, we comprehensively analyzed the genome-wide miRNA expression profiles in ccRCC, with the aim to generate a tumor-specific miRNA signature of prognostic values. METHODS: The miRNA profiles in tumor and the adjacent normal tissue were analyzed, and the association of the differentially expressed miRNAs with patient survival was examined with univariate Cox regression analysis. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate, and multivariate Cox regression analyses. RESULTS: A total of 147 miRNAs were found differentially expressed between tumor and matched non-tumor tissues from 58 ccRCC patients. The prognostic values of these differentially expressed miRNAs were subsequently analyzed in the 411 ccRCC patients, and 22 miRNAs were found significantly correlated with patient survival. Finally, a tumor-specific miRNA signature of 22 miRNAs was generated and validated as an independent prognostic parameter. CONCLUSIONS: A tumor-specific miRNA signature consisting of 22 miRNAs was identified and validated as an independent prognostic factor, which could serve as a novel biomarker for ccRCC prognostication and help in predicting treatment outcome.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , MicroRNAs/genética , Transcriptoma , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/diagnóstico , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Especificidade de Órgãos/genética , Prognóstico , Análise de Sobrevida
17.
Med Oncol ; 32(1): 332, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25428376

RESUMO

Human cancers are endowed with sustained vascularization capability, and their growth, invasion, and metastasis are vascularization dependent. Recently, accumulated body of evidence suggests that endothelial progenitor cells (EPCs) can support vasculogenesis and induce angiogenesis through paracrine mechanisms. In addition, numerous clinical studies have revealed the increase in the number of EPCs in the peripheral blood of cancer patients and demonstrated the correlation of circulating EPCs (CEPCs) with the clinical outcomes. This review highlights current enrichment procedures and methods for the detection of CEPCs and different biomarkers to identify CEPCs as well as the functions of EPCs in tumor vascularization. Furthermore, we systematically review available studies on the clinical relevance of CEPCs in cancer patients to explore the potential diagnostic and prognostic values of CEPCs. Although several contrasting results exist, CEPCs can conceivably serve as a promising biomarker for the early diagnosis, prognosis prediction, and treatment response indication in the future. Additionally, further well-designed clinical studies with larger sample size and unique, specific enumeration procedures are warranted to achieve further insight into the clinical implications of CEPCs.


Assuntos
Biomarcadores Tumorais/sangue , Células Progenitoras Endoteliais , Neoplasias/sangue , Neovascularização Patológica/sangue , Humanos , Oncologia/métodos , Oncologia/tendências
18.
Gene ; 551(1): 86-91, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25168891

RESUMO

The wide application of prostate-specific antigen (PSA) has contributed to the early diagnosis and improved management of prostate cancer (PCa). Accumulating evidence has suggested the involvement of genetic components in regulating serum PSA levels, and several single nucleotide polymorphisms (SNPs) have been identified by genome-wide association studies (GWASs). However, the GWASs' results have the limited power to identify the causal variants and pathways. After the quality control filters, a total of 330,540 genotyped SNPs from one GWAS with 657 PCa-free Caucasian males were included for the identify candidate causal SNPs and pathways (ICSNPathway) analysis. In addition, the genotype-phenotype association analysis has been conducted with the data from HapMap database. Overall, a total of four SNPs in three genes and six pathways were identified by ICSNPathway analysis, which in total provided three hypothetical mechanisms. First, CYP26B1 rs2241057 polymorphism (nonsynonymous coding) which leads to a Leu-to-Ser amino acid shift at position 264, was implicated in the pathways including meiosis, proximal/distal pattern formation, and M phase of meiotic cell cycle. Second, CLIC5 rs3734207 and rs11752816 polymorphisms (regulatory region) to the 2 iron, 2 sulfur cluster binding pathway through regulating expression levels of CLIC5 mRNA. Third, rs4819522 polymorphism (nonsynonymous coding) leads to a Thr-to-Met transition at position 350 of TBX1 and involves in the pathways about gland and endocrine system development. In summary, our results demonstrated four candidate SNPs in three genes (CYP26B1 rs2241057, CISD1 rs2251039, rs2590370, and TBX1 rs4819522 polymorphisms), which were involved in six potential pathways to influence serum PSA levels.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Proteínas Mitocondriais/genética , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/genética , Proteínas com Domínio T/genética , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Grupo com Ancestrais do Continente Europeu , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Projeto HapMap , Humanos , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Proteínas Mitocondriais/metabolismo , Polimorfismo de Nucleotídeo Único , Ácido Retinoico 4 Hidroxilase , Proteínas com Domínio T/metabolismo
19.
Hum Immunol ; 75(8): 827-32, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24952208

RESUMO

BACKGROUND: Human leukocyte antigen-G (HLA-G) is involved in the development and progression of human cancers, and numerous molecular epidemiological studies have been conducted to explore the potential relationship of HLA-G 14-bp insertion/deletion (ins/del) polymorphism with cancer risk. However, results from published studies were inconclusive. METHODS: Both PUBMED and EMBASE databases were searched comprehensively to identify eligible studies investigating the association of HLA-G 14-bp ins/del polymorphism with cancer risk. Statistical analysis was performed by using STATA 12.0 and Review Manager 5.0. RESULTS: Fourteen eligible studies with 2340 cancer patients and 3967 controls were included and analyzed with odds ratio (OR) and its corresponding 95% confidence interval (CI). Overall, no significant association between HLA-G 14-bp ins/del polymorphism and overall cancer risk was detected in all comparison models. Further subgroup analyses based on ethnicity and cancer types demonstrated the significant association among Asians (ins/del vs. del/del: OR = 0.80, 95% CI, 0.66-0.95; ins/ins+ins/del vs. del/del: OR = 0.80, 95% CI, 0.65-0.97) and for breast cancer (ins allele vs. del allele: OR = 0.76, 95% CI, 0.61-0.96; ins/ins vs. del/del: OR = 0.57, 95% CI, 0.37-0.87; and ins/ins vs. ins/del+del/del: OR = 0.60, 95% CI, 0.42-0.87). CONCLUSION: This study suggested that HLA-G 14-bp ins/del polymorphism might contribute to breast cancer susceptibility and overall cancer risk among Asians. Further well-designed studies with larger sample size are warranted to validate our conclusion.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Antígenos HLA-G/genética , Mutação INDEL , Neoplasias/genética , Polimorfismo Genético , Alelos , Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/etnologia , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Antígenos HLA-G/imunologia , Humanos , Masculino , Neoplasias/etnologia , Neoplasias/imunologia , Neoplasias/patologia , Razão de Chances , Risco
20.
PLoS One ; 9(4): e93938, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24705444

RESUMO

BACKGROUND: Transforming growth factor-beta 1(TGF-ß1) is involved in the development of acute rejection (AR) episodes in solid organ transplant recipients; and a number of studies have been conducted to investigate the combined effects of human TGF-ß1 gene (TGFB1) +869 T/C and +915 G/C polymorphisms on AR risk. However, the results obtained are inconclusive. METHODS: Eligible studies that investigated the haplotypic association between TGFB1 +869 T/C and +915 G/C polymorphisms and AR risk were comprehensively searched in the PUBMED, EMBASE, China National Knowledge Infrastructure, and Wanfang Database. Statistical analyses were performed by using STATA 12.0 and Review Manager 5.0. RESULTS: Fourteen eligible studies with 565 AR cases and 1219 non-AR cases were included. Overall, a significantly decreased risk was detected in patients carried with intermediate producer (IP) haplotypes (T/C G/C, T/T G/C, and C/C G/G) and/or low producer (LP) haplotypes (C/C G/C, C/C C/C, T/T C/C, and T/C C/C) compared with high producer (HP) haplotypes (T/T G/G and T/C G/G; IP vs. HP: OR = 0.75, 95% CI, 0.58-0.96, P heterogeneity  = 0.238; IP/LP vs. HP: OR  = 0.77, 95% CI, 0.61-0.98, P heterogeneity  = 0.144). In addition, subgroup analysis by transplant types demonstrated a similar association in patients receiving heart transplant (IP vs. HP: OR  = 0.32, 95% CI, 0.14-0.73, P heterogeneity  = 0.790; IP/LP vs. HP: OR  = 0.41, 95% CI, 0.20-0.85, P heterogeneity  = 0.320). CONCLUSIONS: The current meta-analysis and systematic review indicated that recipient TGFB1 HP haplotypes were significantly associated with an increased risk for AR in solid organ transplant recipients, particularly patients receiving cardiac allograft.


Assuntos
Rejeição de Enxerto/genética , Transplante de Órgãos/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Fator de Crescimento Transformador beta1/genética , Haplótipos/genética , Humanos , Razão de Chances
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