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1.
Int J Surg ; 110(4): 2007-2024, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38349011

RESUMO

The success of solid organ transplantation (SOT) and the use of immunosuppressive agents offer hope to patients with end-stage diseases. However, the impact of post-transplant diabetes mellitus (PTDM) on SOT patients has become increasingly evident. In our study, we utilized the Scientific Registry of Transplant Recipients (SRTR) database to investigate the association between PTDM and patient survival in various types of organ transplantations, including liver, kidney, intestinal, heart, lung, and combined heart-lung transplantations (all P <0.001). Our findings revealed a negative effect of PTDM on the survival of these patients. Furthermore, we examined the effects of both generic and innovator immunosuppressive agents on the development of PTDM and the overall survival of different SOT populations. Interestingly, the results were inconsistent, indicating that the impact of these agents may vary depending on the specific type of transplantation and patient population. Overall, our study provides a comprehensive and systematic assessment of the effects of different immunosuppressive agents on prognosis, as well as the impact of PTDM on the survival of patients undergoing various types of SOT. These findings emphasize the need for further research and highlight the importance of optimizing immunosuppressive regimens and managing PTDM in SOT patients to improve their long-term outcomes.


Assuntos
Diabetes Mellitus , Imunossupressores , Transplante de Órgãos , Transplantados , Humanos , Imunossupressores/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Prognóstico , Transplantados/estatística & dados numéricos , Transplante de Órgãos/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Sistema de Registros , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/mortalidade
2.
Am J Transplant ; 23(9): 1319-1330, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37295719

RESUMO

Mouse kidney allografts are spontaneously accepted in select, fully mismatched donor-recipient strain combinations, like DBA/2J to C57BL/6 (B6), by natural tolerance. We previously showed accepted renal grafts form aggregates containing various immune cells within 2 weeks posttransplant, referred to as regulatory T cell-rich organized lymphoid structures, which are a novel regulatory tertiary lymphoid organ. To characterize the cells within T cell-rich organized lymphoid structures, we performed single-cell RNA sequencing on CD45+ sorted cells from accepted and rejected renal grafts from 1-week to 6-months posttransplant. Analysis of single-cell RNA sequencing data revealed a shifting from a T cell-dominant to a B cell-rich population by 6 months with an increased regulatory B cell signature. Furthermore, B cells were a greater proportion of the early infiltrating cells in accepted vs rejecting grafts. Flow cytometry of B cells at 20 weeks posttransplant revealed T cell, immunoglobulin domain and mucin domain-1+ B cells, potentially implicating a regulatory role in the maintenance of allograft tolerance. Lastly, B cell trajectory analysis revealed intragraft differentiation from precursor B cells to memory B cells in accepted allografts. In summary, we show a shifting T cell- to B cell-rich environment and a differential cellular pattern among accepted vs rejecting kidney allografts, possibly implicating B cells in the maintenance of kidney allograft acceptance.


Assuntos
Linfócitos B Reguladores , Camundongos , Animais , Transcriptoma , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Rim , Aloenxertos , Diferenciação Celular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto
3.
Am J Transplant ; 23(7): 935-945, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37080464

RESUMO

Advances in immunosuppression have been relatively stagnant over the past 2 decades, and transplant recipients continue to experience long-term morbidity associated with immunosuppression regimens. Strategies to reduce or eliminate the dosage of immunosuppression medications are needed. We discovered a novel administration strategy using the classic adjuvant alum to condition murine islet transplant recipients, known as adjuvant conditioning (AC), to expand both polymorphonuclear and monocytic myeloid-derived suppressive cells (MDSCs) in vivo. These AC MDSCs potently suppress T cell proliferation when cultured together in vitro. AC MDSCs also facilitate naïve CD4+ T cells to differentiate into regulatory T cells. In addition, we were able to demonstrate a significant delay in alloislet rejection compared with that by saline-treated control following adjuvant treatment in a MDSC-dependent manner. Furthermore, AC MDSCs produce significantly more interleukin (IL)-10 than saline-treated controls, which we demonstrated to be critical for the increased T cell suppressor function of AC MDSCs as well as the observed protective effect of AC against alloislet rejection. Our data suggest that adjuvant-related therapeutics designed to expand MDSCs could be a useful strategy to prevent transplant rejection and curb the use of toxic immunosuppressive regimens currently used in transplant patients.


Assuntos
Células Supressoras Mieloides , Humanos , Animais , Camundongos , Imunossupressores/farmacologia , Monócitos , Linfócitos T CD8-Positivos , Terapia de Imunossupressão
4.
Am J Transplant ; 22(3): 705-716, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34726836

RESUMO

Intragraft events thought to be relevant to the development of tolerance are here subjected to a comprehensive mechanistic study during long-term spontaneous tolerance that occurs in C57BL/6 mice that receive life sustaining DBA/2 kidneys. These allografts rapidly develop periarterial Treg-rich organized lymphoid structures (TOLS) that form in response to class II but not to class I MHC disparity and form independently of lymphotoxin α and lymphotoxin ß receptor pathways. TOLS form in situ in the absence of lymph nodes, spleen, and thymus. Distinctive transcript patterns are maintained over time in TOLS including transcripts associated with Treg differentiation, T cell checkpoint signaling, and Th2 differentiation. Pathway transcripts related to inflammation are expressed in early stages of accepted grafts but diminish with time, while B cell transcripts increase. Intragraft transcript patterns at one week posttransplant distinguish those from kidneys destined to be rejected, that is, C57BL/6 allografts into DBA/2 recipients, from those that will be accepted. In contrast to inflammatory tertiary lymphoid organs (iTLOs) that form in response to chronic viral infection and transgenic Lta expression, TOLS lack high endothelial venules and germinal centers. TOLS represent a novel, pathogenetically important type of TLO that are in situ markers of regulatory tolerance.


Assuntos
Transplante de Rim , Tolerância ao Transplante , Animais , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Rim , Transplante de Rim/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA
5.
JCI Insight ; 5(18)2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32938831

RESUMO

In swine and nonhuman primates, kidney allografts can induce tolerance of heart allografts, leading to their long-term, immunosuppression-free survival. We refer to this phenomenon as kidney-induced cardiac allograft tolerance (KICAT). In this study, we have developed a murine model for KICAT to determine the underlining cellular/molecular mechanisms. Here, we show that spontaneously accepted DBA/2J kidneys in C57BL/6 recipients induce systemic tolerance that results in the long-term acceptance of DBA/2J heart allografts but not third-party cardiac allografts. The state of systemic tolerance of hearts was established 2 weeks after transplantation of the kidney, after which time, the kidney allograft is no longer required. Depletion of Foxp3+ T cells from these mice precipitated rejection of the heart allografts, indicating that KICAT is dependent on Treg function. Acceptance of kidney allografts and cotransplanted heart allografts did not require the thymus. In conclusion, these data show that kidney allografts induce systemic, donor-specific tolerance of cardiac allografts via Foxp3 cells, and that tolerance is independent of the thymus and continued presence of the kidney allograft. This experimental system should promote increased understanding of the tolerogenic mechanisms of the kidney.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/efeitos adversos , Tolerância Imunológica/imunologia , Rim/fisiologia , Linfócitos T Reguladores/imunologia , Tolerância ao Transplante , Animais , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Terapia de Imunossupressão , Transplante de Rim , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA
6.
Pathol Res Pract ; 216(8): 153021, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32703489

RESUMO

Acute allograft rejection is the most common complication in organ transplantation leading to organ loss. Treg cells play an important role in preventing acute rejection, but they are unstable and easily lose function. Poly(ADP-ribose) polymerase 1(PARP-1) is involved in the differentiation stabilization of Treg cells, it has been suggested that PARP-1 inhibition could prevent acute rejection and prolong allograft survival. This study investigated AG14361 effects on acute allograft rejection. We used a fully MHC-mismatched murine heart transplantation model to compare the effect of PARP-1 inhibitor-AG14361 on alloimmunity to the control. Mice treated with PARP-1 inhibitors showed a longer median survival time of allografts (MS14 compared with the control group, MST was 8 days, and AG14361 was 6 days, P = 0.019). The combination of sirolimus and AG14361 significantly delayed allograft MST (AG14361 + sirolimus for 30 days, sirolimus for 16 days, P = 0.002). AG14361 markedly augmented the number of the CD25+FoxP3+ Treg cells in the graft and periphery. In addition, it could enhance the suppressive function of Treg cells by upregulating the level of CTLA-4, PD-1 and ICOS. In vivo, the Treg/Th17 ratio increased significantly in the AG14351 group compared to the control. In the combination with sirolimus treatment, AG14361 promoted the long-term allograft survival. Our results highlight novel effects of a PARP-1 inhibitor. PARP-1 inhibitor AG14361 may be a promising agent to attenuate acute allograft rejection as it can maintain the number and function of Treg cells in allografts.


Assuntos
Benzodiazepinas/farmacologia , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/métodos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Linfócitos T Reguladores/imunologia , Animais , Azulenos/farmacologia , Transplante de Coração/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores/efeitos dos fármacos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos
7.
Transplantation ; 104(1): 39-53, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31335760

RESUMO

BACKGROUND: DBA/2J kidney allografts, but not heart allografts, are spontaneously accepted indefinitely in C57BL/6 (B6) mice, through regulatory tolerance mechanism dependent on Foxp3 cells. In contrast, B6 kidneys are rejected within a week in DBA/2J recipients. We hypothesized that the tolerogenic difference of the kidneys might be due to differences in number or function of plasmacytoid dendritic cells (pDCs), because these cells are potent inducers of Foxp3 cells. METHODS: pDCs from murine bone marrow, native kidneys, and spontaneously accepted kidney allografts were analyzed using flow cytometry and immunohistochemical staining. Naive T cells were cocultured with pDCs in specific strain combinations and analyzed for FoxP3 induction and functionality. MEK/ERK and NFκB inhibitors were used to assess the regulatory T-cell induction pathways. pDCs and T-cell cultures were adoptively transferred before heterotopic heart transplantation to assess allograft survival. RESULTS: DBA/2J pDCs were more potent in inducing Foxp3 in B6 T cells than the reverse combination, correlating with survival of the kidney allografts. Foxp3 induction by pDCs in vitro was dependent on pDC viability, immaturity, and class II MHC mismatch and blocked by MEK/ERK and NFκB inhibition. pDC-induced Foxp3 T cells suppressed proliferation of B6 T cells in vitro, and adoptive transfer into B6 recipients 2 weeks before heterotopic DBA/2J heart transplantation resulted in prolonged allograft survival. CONCLUSIONS: These data suggest that pDC-induced regulatory T cells are dependent on downstream signaling effects and on strain-dependent, MHC class II disparity with naive T cells, which may explain organ- and strain-specific differences in spontaneous tolerance.


Assuntos
Células Dendríticas/imunologia , Sobrevivência de Enxerto/imunologia , Tolerância Imunológica , Transplante de Rim/efeitos adversos , Linfócitos T Reguladores/imunologia , Transferência Adotiva , Aloenxertos/imunologia , Animais , Comunicação Celular/imunologia , Separação Celular , Modelos Animais de Doenças , Citometria de Fluxo , Fatores de Transcrição Forkhead/imunologia , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/imunologia , Transplante de Coração , Humanos , Rim/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Linfócitos T Reguladores/metabolismo , Transplante Homólogo
8.
Cancer Lett ; 430: 215-223, 2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-29684419

RESUMO

Clinical data indicates that T cells can be recruited to bladder cancer (BCa), yet the impact of T cells on BCa progression remains unclear. In the present study, we found that T cells were recruited more to BCa tissues than to the surrounding normal bladder tissues. Results from an in vitro co-culture system also found that BCa recruited more CD4+ T cells than did normal bladder cells. The recruiting of T cells to BCa tissues may increase the proliferation and invasion of BCa cells. Mechanistic studies revealed that infiltrating T cells stimulate BCa estrogen receptor beta (ERß) signaling and consequently increase the expression of MET proto-oncogene, receptor tyrosine kinase (c-MET), through either direct binding to its promoter or via modulation of IL-1 expression. Interruption of ERß/c-MET or ERß/IL-1/c-MET signaling via ERß-shRNA, IL-1 antagonist, or the c-MET inhibitor, SU11274, could partially reverse the T cell-enhanced BCa cell invasion and proliferation. Finally, the mouse BCa model with xenografted BCa 5637 cells with T (HH) cells confirmed the results of in vitro co-culture studies showing that infiltrating T cells could promote BCa metastasis via modulation of the ERß/c-MET or ERß/IL-1/c-MET signaling pathways. These findings may provide a new therapeutic approach to better combat BCa progression via targeting these newly identified signaling pathways.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Receptor beta de Estrogênio/metabolismo , Interleucina-1/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Neoplasias da Bexiga Urinária/patologia , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cistectomia , Progressão da Doença , Receptor beta de Estrogênio/antagonistas & inibidores , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Indóis/farmacologia , Interleucina-1/antagonistas & inibidores , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Piperazinas/farmacologia , Regiões Promotoras Genéticas/genética , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/metabolismo , Pirazóis/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sulfonamidas/farmacologia , Regulação para Cima/efeitos dos fármacos , Bexiga Urinária/citologia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/cirurgia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Cell Prolif ; 51(4): e12452, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29569766

RESUMO

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is characterized histologically by accumulation of cholesterol esters, cholesterol and other neutral lipids. Lysosomal acid lipase (LAL) is a critical enzyme involved in the cholesterol ester metabolism. Here, we sought to determine whether LAL could orchestrate metabolism of cholesterol esters in order to promote ccRCC progression. MATERIALS AND METHODS: Quantitative reverse-transcription PCR and western blots were conducted to assess the expression of LAL in human ccRCC tissues. We analysed the relationship between LAL levels and patient survival using tissue microarrays. We used cell proliferation assays, colony formation assays, cell death assays, metabolic assays and xenograft tumour models to evaluate the biological function and underlying mechanisms. RESULTS: LAL was up-regulated in ccRCC tissue. Tissue microarray analysis revealed higher levels of LAL in advanced grades of ccRCC, and high LAL expression indicated lower patient survival. Suppressing LAL expression not only blocked the utilization of cholesterol esters but also impaired proliferation and cellular survival. Furthermore, immunohistochemistry staining showed that LAL expression was correlated with Akt phosphorylation. Suppressing LAL expression decreased the phosphorylation level of Akt and Src and reduced the level of 14,15-epoxyeicosatrienoic acids in ccRCC cells. Supplement of 14,15-epoxyeicosatrienoic acids rescued proliferation in vitro and in vivo. CONCLUSIONS: LAL promoted cell proliferation and survival via metabolism of epoxyeicosatrienoic acids and activation of the Src/Akt pathway.


Assuntos
Carcinoma de Células Renais/patologia , Ésteres do Colesterol/metabolismo , Esterol Esterase/metabolismo , Animais , Ácido Araquidônico/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Esterol Esterase/análise , Esterol Esterase/antagonistas & inibidores , Esterol Esterase/genética , Regulação para Cima , Quinases da Família src/metabolismo
10.
Biochem Biophys Res Commun ; 483(2): 867-873, 2017 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-28069380

RESUMO

Accumulating evidence has linked deregulation of microRNA-495 (miR-495) to tumorigenesis; however, its function in tumor progression is controversial. This work was undertaken to explore the expression and biological roles of miR-495 in bladder cancer. The expression of miR-495 was examined in 67 pairs of bladder cancer and adjacent normal bladder tissues. The roles of miR-495 in bladder cancer cell proliferation and invasion in vitro and tumorigenesis in vivo were determined. Direct target gene(s) mediating the activity of miR-495 in bladder cancer cells was identified. It was found that miR-495 was expressed at greater levels in bladder tissues and cell lines. High expression of miR-495 was significantly associated with larger tumor size, advanced TNM stage, and lymph node metastasis. Overexpression of miR-495 significantly promoted bladder cancer cell proliferation and invasion, whereas inhibition of miR-495 suppressed cell proliferation and invasion. PTEN, a well-defined tumor suppressor was identified to be a target gene of miR-495. A significant inverse correlation between miR-495 and PTEN expression was noted in bladder cancer tissues (r = -0.3094, P = 0.0125). Overexpression of miR-495 led to reduction of PTEN expression in bladder cancer cells. Rescue experiments showed that enforced expression of PTEN impaired miR-495-mediated bladder cancer proliferation and invasion. In vivo mouse studies demonstrated that overexpression of miR-495 accelerated the growth of subcutaneous bladder cancer xenografts, which was associated with downregulation of PTEN. Overall, these findings indicate that miR-495 upregulation contributes to bladder cancer cell growth, invasion, and tumorigenesis by targeting PTEN and offer a potential therapeutic target for bladder cancer.


Assuntos
MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias da Bexiga Urinária/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , PTEN Fosfo-Hidrolase/antagonistas & inibidores , Regulação para Cima , Neoplasias da Bexiga Urinária/enzimologia , Neoplasias da Bexiga Urinária/patologia
11.
Oncotarget ; 7(19): 27142-57, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27049827

RESUMO

Metabolic alterations underlying clear cell renal cell carcinoma (ccRCC) progression include aerobic glycolysis, increased pentose phosphate pathway activity and reduced oxidative phosphorylation. Phosphofructokinase (PFK), a key enzyme of the glycolytic pathway, has L, M, and P isoforms with different tissue distributions. The mRNA level of the platelet isoform of phosphofructokinase (PFKP) is reported to be up-regulated in ccRCC patients. However, it remains unclear whether PFKP plays an important role in promoting aerobic glycolysis and macromolecular biosynthesis to support cell proliferation in ccRCC. Here we found that the up-regulated PFKP became the predominant isoform of PFK in human ccRCC. Suppression of PFKP not only impaired cell proliferation by inducing cell cycle arrest and apoptosis, but also led to decreased glycolysis, pentose phosphate pathway and nucleotide biosynthesis, accompanied by activated tricarboxylic acid cycle in ccRCC cells. Moreover, we found that p53 activation contributed to cell proliferation and metabolic defects induced by PFKP knockdown in ccRCC cells. Furthermore, suppression of PFKP led to reduced ccRCC tumor growth in vivo. Our data indicate that PFKP not only is required for metabolic reprogramming and maintaining cell proliferation, but also may provide us with a valid target for anti-renal cancer pharmaceutical agents.


Assuntos
Carcinoma de Células Renais/genética , Proliferação de Células/genética , Neoplasias Renais/genética , Fosfofrutoquinases/genética , Idoso , Animais , Apoptose/genética , Plaquetas/enzimologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Glicólise/genética , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Via de Pentose Fosfato/genética , Fosfofrutoquinases/metabolismo , Interferência de RNA , Transplante Heterólogo , Adulto Jovem
12.
Mol Med Rep ; 12(5): 6533-46, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26397152

RESUMO

Aristolochic acid (AA) is a carcinogenic, mutagenic and nephrotoxic compound commonly isolated from members of the plant family of Aristolochiaceae (such as Aristolochia and Asarum) and used in Chinese herbal medicine. Use of AA and AA­containing plants causes chronic kidney disease (CKD) and upper urinary tract carcinoma (UUC); however, the underlying mechanism remains to be defined. miRNAs regulate a number of biological processes, including cell proliferation, differentiation and metabolism. This study explored differentially expressed miRNAs between AA­induced upper urothelial tract cancer (AAN­UUC) and non­AAN­UUC tissues. Patients with AAN­UUC and non­AAN­UUC (n=20/group) were recruited in the present study. Five tissue samples from each group were used for miRNA microarray profiling and the rest of the tissue samples were subjected to reverse transcription-quantitative polymerase chain reaction analysis including seven selected miRNAs for confirmation. A total of 29 miRNAs were differentially expressed between AAN­UUC and non­AAN­UUC tissues (P<0.05). TargenScan and Gene ontology analyses predicted the functions and targeted genes of these differentially expressed miRNAs, i.e. Akt3, FGFR3, PSEN1, VEGFa and AR. Subsequently, expression of the selected differentially expressed miRNAs (Hsa­miR­4795­5p, Hsa­miR­488, Hsa­miR­4784, Hsa­miR­330, Hsa­miR­3916, Hsa­miR­4274 and Hsa­miR­181c) was validated in another set of tissue samples. A total of 29 miRNAs were identified to be differentially expressed between AAN­UUC and non­AAN­UUC tissues and these miRNA target genes in FGFR3 and Akt pathways, which regulate cell growth and tumor progression, respectively.


Assuntos
Ácidos Aristolóquicos/toxicidade , Carcinógenos/toxicidade , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Neoplásico/genética , Neoplasias Urológicas/genética , Idoso , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Presenilina-1/genética , Presenilina-1/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Neoplásico/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Neoplasias Urológicas/induzido quimicamente , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/patologia , Urotélio/efeitos dos fármacos , Urotélio/metabolismo , Urotélio/patologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
13.
Asian J Androl ; 17(1): 74-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25248652

RESUMO

Conventional meta-analyses have shown inconsistent results for the efficacy of various treatments of varicoceles. Therefore, we performed a multiple-treatment meta-analysis to assess the effectiveness and safety of 10 methods of varicocelectomy and embolization/sclerotherapy. We systematically reviewed 35 randomized controlled trials and observational studies, from 1966 to August 5, 2013, which compared any of the following treatments for varococeles: laparoscopic, retroperitoneal, open inguinal and subinguinal varicocelectomy, microsurgical subinguinal and inguinal varicocelectomy, percutaneous venous embolization, Tauber antegrade sclerotherapy, retrograde sclerotherapy and expectant therapy (no treatment). Inguinal and subinguinal microsurgery, open inguinal, laparoscopic varicocelectomy showed a significant advantage over expectant therapy in terms of pregnancy rates (odds ratio (OR): 3.48, 2.68, 2.92 and 2.90, respectively). Compared with retroperitoneal open surgery, inguinal microsurgery showed an improvement of sperm density (mean difference (MD): 10.60, 95% confidence interval (CI): 1.92-19.60) and sperm motility (MD: 9.09, 95% CI: 4.88-13.30). Subinguinal and inguinal microsurgery outperformed retroperitoneal open surgery in terms of recurrence (OR: 0.05, 0.06 respectively). Tauber antegrade sclerotherapy and subinguinal microsurgery were associated with the lowest risk of hydrocele formation. The odds of overall complication, compared with retroperitoneal open varicocelectomy, were lowest for inguinal microsurgery (OR = 0.07, 95% CI: 0.02-0.19), followed by subinguinal microsurgery (OR = 0.09, 95% CI: 0.02-0.19). Inguinal and subinguinal micro-varicocelectomy had the highest pregnancy rates, significant increases in sperm parameters, with low odds of complication. These results warrant additional properly conducted randomized controlled clinical studies with larger sample sizes.


Assuntos
Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Varicocele/cirurgia , Feminino , Humanos , Laparoscopia/métodos , Masculino , Gravidez , Taxa de Gravidez , Resultado do Tratamento
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