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1.
Iran J Basic Med Sci ; 26(6): 701-707, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37275761

RESUMO

Objectives: To investigate the potential of Tropomyosin receptor kinase A (TrkA) for the treatment of interstitial cystitis/ bladder pain syndrome (IC/BPS). Materials and Methods: Sixty-four female rats were randomly assigned to the control and cyclophosphamide (CYP) groups. Quantitative reverse transcription polymerase chain reaction was utilized to detect the mRNA level of TrkA. Western blot analysis was used to measure the protein levels of TNF-α, IL-6, and TrkA. Immunostaining was used to detect the expression of TrkA in bladder sections. Contractility studies and urodynamic measurements were utilized to test the spontaneous contractions of detrusor muscle strips and the global bladder activity, respectively. Results: Rat models of chronic cystitis were successfully established. The mRNA and protein levels of TrkA were significantly increased in the bladders of CYP-treated rats. Also, results of immunohistochemical staining and immunofluorescence staining showed that increased TrkA expression in the CYP group was mainly observed in the urothelium layer and bladder interstitial Cajal-like cells (ICC-LCs) but not in the detrusor smooth muscle cells. The specific inhibitor of TrkA, GW441756 (10 µM), significantly suppressed the robust spontaneous contractions of detrusor muscle strips in the CYP group and alleviated the overall bladder overactivity of CYP-treated rats. However, the inhibitory effects of GW441756 (10 µM) on the spontaneous contractions of detrusor muscle strips and the overall bladder activity were eliminated after pretreatments with the specific blocker of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, ZD7288 (50 µM). Conclusion: Our results suggested that increased TrkA expression during chronic cystitis promotes the development of bladder overactivity by targeting the HCN channels.

2.
Heliyon ; 9(2): e13200, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36798767

RESUMO

Background and aims: Improved mortality prediction among intensive care unit (ICU) inpatients is a valuable and challenging task. Limited clinical data, especially with appropriate labels, are an important element restricting accurate predictions. Generative adversarial networks (GANs) are excellent generative models and have shown great potential for data simulation. However, there have been no relevant studies using GANs to predict mortality among ICU inpatients. In this study, we aim to evaluate the predictive performance of a variant of GAN called conditional medical GAN (c-med GAN) compared with some baseline models, including simplified acute physiology score II (SAPS II), support vector machine (SVM), and multilayer perceptron (MLP). Methods: Data from a publicly available intensive care database, the Medical Information Mart for Intensive Care III (MIMIC-III) database (v1.4), were included in this study. The area under the precision-recall curve (PR-AUC), area under the receiver operating characteristic curve (ROC-AUC), and F1 score were used to evaluate the predictive performance. In addition, the size of the dataset was artificially reduced, and the performance of the c-med GAN was compared in different size datasets. Results: The results showed that c-med GAN achieves the best PR-AUC, ROC-AUC, and F1 score compared with SAPS II, SVM, and MLP when training in the full MIMIC-III dataset. When the size of the dataset was reduced, the prediction performances of both MLP and c-med GAN were affected. However, the c-med GAN still outperformed MLP on smaller datasets and had less degradation. Conclusion: The prediction of in-hospital mortality based on the c-med GAN for ICU patients showed better performance than the baseline models. Despite some inadequacies, this model may have a promising future in clinical applications which will be explored by further research.

3.
Front Immunol ; 13: 1055304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505486

RESUMO

Background: Anoikis is a form of programmed cell death or programmed cell death(PCD) for short. Studies suggest that anoikis involves in the decisive steps of tumor progression and cancer cell metastasis and spread, but what part it plays in bladder cancer remains unclear. We sought to screen for anoikis-correlated long non-coding RNA (lncRNA) so that we can build a risk model to understand its ability to predict bladder cancer prognosis and the immune landscape. Methods: We screened seven anoikis-related lncRNAs (arlncRNAs) from The Cancer Genome Atlas (TCGA) and designed a risk model. It was validated through ROC curves and clinicopathological correlation analysis, and demonstrated to be an independent factor of prognosis prediction by uni- and multi-COX regression. In the meantime, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, immune infiltration, and half-maximal inhibitory concentration prediction (IC50) were implemented with the model. Moreover, we divided bladder cancer patients into three subtypes by consensus clustering analysis to further study the differences in prognosis, immune infiltration level, immune checkpoints, and drug susceptibility. Result: We designed a risk model of seven arlncRNAs, and proved its accuracy using ROC curves. COX regression indicated that the model might be an independent prediction factor of bladder cancer prognosis. KEGG enrichment analysis showed it was enriched in tumors and immune-related pathways among the people at high risk. Immune correlation analysis and drug susceptibility results indicated that it had higher immune infiltration and might have a better immunotherapy efficacy for high-risk groups. Of the three subtypes classified by consensus clustering analysis, cluster 3 revealed a positive prognosis, and cluster 2 showed the highest level of immune infiltration and was sensitive to most chemistries. This is helpful for us to discover more precise immunotherapy for bladder cancer patients. Conclusion: In a nutshell, we found seven arlncRNAs and built a risk model that can identify different bladder cancer subtypes and predict the prognosis of bladder cancer patients. Immune-related and drug sensitivity researches demonstrate it can provide individual therapeutic schedule with greater precision for bladder cancer patients.


Assuntos
RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Imunoterapia , Bexiga Urinária , Apoptose
4.
Front Genet ; 13: 990326, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36186475

RESUMO

Background: Bladder cancer (BCa), among the world's most common malignant tumors in the urinary system, has a high morbidity and mortality. Though cuproptosis is a new type of cell death mediated by lipoylated tricarboxylic acid (TCA) cycle proteins, the role of cuproptosis-related long noncoding RNAs (crlncRNAs) in bladder tumors awaits further elucidation. In this paper, we tried to explore how important crlncRNAs are for BCa. Methods: The crlncRNAs were first obtained through Pearson correlation analysis of the RNA-seq data and corresponding clinical data downloaded from The Cancer Genome Atlas (TCGA). Then, three lncRNAs were acquired by Cox regression and Lasso regression to build a prognostic model of crlncRNAs for verification. In the meantime, clinicopathological correlation analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, principal component analysis (PCA), immunoassay, and half-maximal inhibitory concentration prediction (IC50) were carried out. Then, an entire tumor was classified into two clusters by crlncRNA expression to further discuss the differences in prognosis, immune status and drug susceptibility among different subgroups. Results: We obtained a total of 152 crlncRNAs and built a risk model for screened crlncRNAs. We validated the model and found that calibration charts feature a high consistency in verifying nomogram prediction. Receiver operating characteristic (ROC) curve and univariate and multivariate Cox regression suggested that this model can be applied as an independent prognostic factor of bladder cancer due to its high accuracy. According to KEGG analysis, high-risk groups were enriched in cancer and immune-related pathways. During tumor immunoassay, noticeable differences were observed in both immune infiltration and checkpoints between high- and low-risk patients. Of the two subgroups divided among patients by consensus clustering, cluster 2 had a better prognosis, whereas cluster 1 had higher immunoreactivity scores, more immune cell infiltrations and immune checkpoint expressions, and different sensitivities to drugs. Conclusion: The research findings demonstrate that crlncRNAs can be used to predict the prognosis and immune microenvironment of patients suffering from BCa, and differentiate between BCa subgroups to improve the individual therapy of BCa.

5.
J Biomed Mater Res B Appl Biomater ; 109(6): 853-863, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33098184

RESUMO

Hyperbranched polyglycerol (HPG) is a biocompatible polyether polymer that is a potential colloid component in a preservation solution for suppressing interstitial edema during cold storage of a donor organ. This study evaluated the outcomes of kidney transplants after cold perfusion and storage with a HPG-based preservation solution (HPGS) in a pig model of kidney autotransplantation. The left kidneys of farm pigs (weighing 35-45 kg) were perfused with and stored in either cold HPGS or standard UW solution (UWS), followed by transplantation to the right side after right nephrectomy. The survival and function of transplants were determined by the urine output, and serum creatinine (SCr) and blood urea nitrogen (BUN) of recipients. Transplant injury was examined by histological analysis. Here, we showed that there was no significant difference between HPGS and UWS in the prevention of tissue edema, but HPGS was more effective than UWS for initial blood washout of kidney perfusion and for the prevention of cold ischemia injury during cold storage. After autotransplantation, the kidneys preserved with HPGS (HPG group) had better functional recovery than those with UWS (UW group), indicated by significantly more urine output and lower levels of SCr and BUN. The survived grafts in HPG group had less tissue damage than those in UW group. In conclusion, as compared to the UWS the HPGS has less negative impact on kidney cold ischemia during cold storage, resulting in improving immediate functional recovery after transplantation, suggesting that HPG is a promising colloid for donor kidney preservation.


Assuntos
Glicerol/farmacologia , Transplante de Rim , Rim , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos , Perfusão , Polímeros/farmacologia , Adenosina/farmacologia , Alopurinol/farmacologia , Animais , Glutationa/farmacologia , Insulina/farmacologia , Rim/metabolismo , Rim/fisiopatologia , Masculino , Rafinose/farmacologia , Suínos , Transplante Autólogo
6.
Zhonghua Nan Ke Xue ; 25(1): 29-34, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-32212502

RESUMO

OBJECTIVE: To investigate the long-term clinical value of prostate 125I brachytherapy (BT) combined with maximal androgen blockade (MAB) in the treatment of metastatic prostate cancer (mPCa). METHODS: We retrospectively analyzed the clinical data on 173 cases of mPCa treated by MAB (n = 126) or BT+MAB (n = 47) from December 2011 to December 2016 and followed up for 6-76 (44.17 ± 19.73) months. We compared the PSA level, prostate volume, IPSS, progression-free survival, and the rates of 3- and 5-year overall survival between the two groups. RESULTS: After treatment, the minimum PSA level was significantly lower in the BT+MAB than in the MAB group ï¼»3.77 ± 4.14ï¼½ vs ï¼»5.96 ± 7.01ï¼½ ng/ml, P = 0.046) and the time to reach the minimum level was shorter in the former than in the latter (ï¼»5.19 ± 2.83ï¼½ vs ï¼»6.52 ± 3.34ï¼½ mo, P = 0.016). The prostate volume was markedly reduced in both of the groups at 1, 3 and 5 years after treatment as compared with the baseline, even more significantly in the BT+MAB than in the MAB group (P < 0.01), though with no statistically significant difference between the two groups before treatment (P = 0.307). The IPSS was remarkably decreased in both of the groups at 1 and 3 years (P < 0.01) but showed no significant difference at 5 years after treatment as compared with the baseline (P > 0.05) or between the two groups before and after treatment (P > 0.05). The progression-free survival was obviously longer in the BT+MAB than in the MAB group (ï¼»37.29 ± 15.73ï¼½ vs ï¼»29.41 ± 14.37ï¼½ mo, P = 0.011), and the rates of 3- and 5-year overall survival were higher in the former than in the latter (74.60% and 60.70% vs 62.60% and 51.50%, P = 0.227 and P = 0.356). Kaplan-Meier survival curves showed no statistically significant difference in the overall survival between the two groups (P = 0.105). CONCLUSIONS: Both MAB and BT+MAB are effective therapies for mPCa, but the latter can achieve a longer progression-free survival.


Assuntos
Inibidores da Angiogênese , Braquiterapia , Radioisótopos do Iodo , Neoplasias da Próstata , Inibidores da Angiogênese/administração & dosagem , Terapia Combinada/normas , Humanos , Estimativa de Kaplan-Meier , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/radioterapia , Estudos Retrospectivos , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-29861778

RESUMO

Low-risk prostate cancer (PCa) does not require immediate treatment, but PCa progression after years of active surveillance will need the treatment. This study was to test the efficacy of immunostimulant Deep Immune (DI) in controlling PCa progression. DI is an extract of eight different medicinal herbs. In vitro activity of DI was determined by phagocytosis activation using flow cytometric analysis of fluorescence-labeled latex bead uptake, expression of immune-modulating 84 genes using PCRarray, and tumor killing using coculturing with immune cells. Anti-PCa activity of DI in vivo was examined in male TRAMP mice. In vitro DI stimulated phagocytosis and expression of a panel of inflammatory mediators (C4b, CXCL3, lymphotoxin, NOS2, TLR1, TNF, and TNFSF14) in cultured macrophages and increased tumor killing of both macrophages and TRAMP mouse splenocytes. Daily intake of this herbal product significantly suppressed the tumor size (P = 0.0368) with lower histopathologic scores (P = 0.0364) in TRAMP mice, which were associated with an increase in both splenocyte cytotoxicity against tumor cells and numbers of CD8 T cells, macrophages, and dendritic cells in the spleens in vivo. In conclusion, daily intake of DI prevents PCa progression in TRAMP mice, suggesting the possible effectiveness of the immunostimulant herbal products on prevention of PCa progression after diagnosis of low-risk PCa.

8.
Am J Transl Res ; 9(2): 429-441, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28337272

RESUMO

Minimizing donor organ injury during cold preservation (including cold perfusion and storage) is the first step to prevent transplant failure. We recently reported the advantages of hyperbranched polyglycerol (HPG) as a novel substitute for hydroxyethyl starch in UW solution for both cold heart preservation and cold kidney perfusion. This study evaluated the functional recovery of the kidney at reperfusion after cold preservation with HPG solution. The impact of HPG solution compared to conventional UW and HTK solutions on tissue weight and cell survival at 4°C was examined using rat kidney tissues and cultured human umbilical vein endothelial cells (HUVECs), respectively. The kidney protection by HPG solution was tested in a rat model of cold kidney ischemia-reperfusion injury, and was evaluated by histology and kidney function. Here, we showed that preservation with HPG solution prevented cell death in cultured HUVECs and edema formation in kidney tissues at 4°C similar to UW solution, whereas HTK solution was less effective. In rat model of cold ischemia-reperfusion injury, the kidneys perfused and subsequently stored 1-hour with cold HPG solution showed less leukocyte infiltration, less tubular damage and better kidney function (lower levels of serum creatinine and blood urea nitrogen) at 48 h of reperfusion than those treated with UW or HTK solution. In conclusion, our data show the superiority of HPG solution to UW or HTK solution in the cold perfusion and storage of rat kidneys, suggesting that the HPG solution may be a promising candidate for improved donor kidney preservation prior to transplantation.

9.
Biomed Pharmacother ; 90: 147-152, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28351777

RESUMO

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding with a greater affinity. Co-expression specific antigens and extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for its enhancement on G250/MN/CA IX (G250)-specific immune responses and its anti-tumor effects in renal carcinoma mice model. Consequently, we constructed a DNA vaccine containing the G250 and the CTLA-4 gene. Vaccination with the co-expression DNA not only induced much higher level of anti-CTLA4 and anti-G250 antibody, but also increased G250-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with G250-expressing tumors were generated. After injection into the tumor-bearing mouse model, the plasmid carrying the co-expression gene of CTLA4 and G250 showed stronger inhibition of tumor growth than the plasmid expressing CTLA4 or G250 alone. These observations emphasize the potential of the CTLA4 and G250 co-expression DNA vaccine, which could represent a promising approach for tumor immunotherapy.


Assuntos
Antígenos de Neoplasias/imunologia , Antígeno CTLA-4/imunologia , Linfócitos T Citotóxicos/imunologia , Vacinas de DNA/imunologia , Animais , Antígenos de Neoplasias/genética , Antígeno CTLA-4/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Marcação de Genes/métodos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos/genética , Plasmídeos/imunologia , Vacinação/métodos
10.
J Surg Res ; 205(1): 59-69, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27621000

RESUMO

BACKGROUND: Efficient and effective perfusion during organ procurement is required for the best prevention of donor organ injury preceding transplantation. However, current organ preservation solutions, including hydroxyethyl starch (HES)-based University of Wisconsin (UW) solution, do not always yield the best outcomes. Our previous study demonstrated that replacing HES with hyperbranched polyglycerol (HPG) reduced donor heart injury during cold storage. The current research was designed to examine the advantages of HPG-based solution for cold kidney perfusion. METHODS: Perfusion efficiency of HPG versus UW solution was tested using mouse kidneys at 4°C. The blood washout was evaluated by using a semiquantitative scoring system and tissue damage by histologic analysis. The interaction of HPG or UW solution with human red blood cells (RBCs) was examined by measuring RBC sedimentation and aggregation. RESULTS: The lower viscosity of HPG solution was correlated with faster and more efficient perfusion through donor kidneys as compared with UW. HPG solution was also more effective than UW in removing RBCs from the kidney and was associated with less tissue damage to donor kidneys. In vitro UW solution caused significant RBC sedimentation and hyperaggregation, whereas HPG showed minimal impact on RBC sedimentation and prevented RBC aggregation. CONCLUSIONS: This experimental study demonstrated that compared with UW, HPG solution was more efficient and effective in the removal of the blood from donor kidneys and offered better protection from donor tissue damage, suggesting that the HPG solution is a promising candidate to supplant standard UW solution for donor kidney perfusion in transplantation.


Assuntos
Glicerol , Rim/patologia , Soluções para Preservação de Órgãos , Perfusão/métodos , Polímeros , Animais , Sedimentação Sanguínea , Masculino , Camundongos Endogâmicos C57BL
11.
J Exp Clin Cancer Res ; 35: 60, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27037000

RESUMO

BACKGROUND: We conducted multiple microarray datasets analyses from clinical and xenograft tumor tissues to search for disease progression-driving oncogenes in prostate cancer (PCa). Sperm-associated antigen 5 (SPAG5) attracted our attention. SPAG5 was recently identified as an oncogene participating in lung cancer and cervical cancer progression. However, the roles of SPAG5 in PCa progression remain unknown. METHODS: SPAG5 expression level in clinical primary PCa, metastatic PCa, castration resistant PCa, neuroendocrine PCa, and normal prostate tissues was investigated. We established multiple in vivo xenografts models using patient-derived tissues and investigated SPAG5 expression trend in these models. We also investigated the functions of SPAG5 in vivo and in vitro studies. Luciferase reporter assays were performed to investigate potential miRNAs that can regulate SPAG5. RESULTS: We identified that SPAG5 expression was gradually increased in PCa progression and its level was significantly associated with lymph node metastasis, clinical stage, Gleason score, and biochemical recurrence. Our results indicated that SPAG5 knockdown can drastically inhibit PCa cell proliferation, migration, and invasion in vitro and supress tumor growth and metastasis in vivo. We identified that miR-539 can directly target SPAG5. Ectopic overexpression of miR-539 can drastically inhibit SPAG5 expression and the restoration of SPAG5 expression can reverse the inhibitory effects of miR-539 on PCa cell proliferation and metastasis. CONCLUSION: Our results collectively showed a progression-driving role of SPAG5 in PCa which can be regulated by miR-539, suggesting that miR-539/SPAG5 can serve as a potential therapeutic target for PCa.


Assuntos
Proteínas de Ciclo Celular/genética , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Gradação de Tumores , Análise de Sequência com Séries de Oligonucleotídeos
12.
Cell Immunol ; 283(1-2): 31-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23850961

RESUMO

OBJECTIVE: To investigate whether ESM-1 expression change reflects the impairment of endothelial cells and rejection after kidney transplantation, ESM-1 expression was detected under various immune states in this study. METHODS: Kidney transplantations were performed from BN to LEW rats. Syngenic LEW-LEW grafts were used as controls. The LEW recipient rats were divided into acute rejection (AR) group, ciclosporin A (CsA) group and control group. In each group, 10 rats were sacrificed at 1, 5, and 7d after operation, respectively, and blood and kidney samples were collected. In the rat model of kidney transplantation, ESM-1 mRNA and ESM-1 protein expression were detected in various immune states to verify if ESM-1 can reflect endothelial cell impairment sensitively. RESULTS: ESM-1 mRNA (1d vs. 3d, P<0.01;3d vs. 7d, P=0.018) and ESM-1 protein expression was upregulated significantly in the AR group (P<0.01, 5 and 7d), when compared to CsA group and control group. In CsA group, the cell apoptosis rate decreased when compared to AR group (P<0.01). Pathological impairment was more serious in AR group than in CsA group (P<0.01). CONCLUSIONS: Peripheral blood ESM-1 mRNA and ESM-1 protein expression in kidney grafts can reflect the severity of endothelial cell impairment. Thus, ESM-1 may be used as a new indicator for AR prediction and diagnosis. Nevertheless, further investigation is required to test if it meets the criteria for clinical utility.


Assuntos
Rejeição de Enxerto/metabolismo , Transplante de Rim/fisiologia , Proteoglicanas/metabolismo , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Rejeição de Enxerto/imunologia , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase em Tempo Real , Transplante Homólogo
13.
J Exp Clin Cancer Res ; 32: 10, 2013 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-23442927

RESUMO

BACKGROUND: Bladder transitional cell carcinoma greatly threatens human health all over the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) shows a strong apoptosis-inducing effect on a variety of cancer cells including bladder cancer. However, adenovirus-mediated TRAIL expression still showed cytotoxicity to normal cells mainly due to lack of tumor specificity. METHODS: To solve the problem, we applied miRNA response elements (MREs) of miR-1, miR-133 and miR-218 to confer TRAIL expression with specificity to bladder cancer cells. RESULTS: Expression of miR-1, miR-133 and miR-218 was greatly decreased in bladder cancer than normal bladder tissue. Luciferase assay showed that application of the 3 MREs was able to restrain exogenous gene expression to within bladder cancer cells. Subsequently, we constructed a recombinant adenovirus with TRAIL expression regulated by MREs of miR-1, miR-133 and miR-218, namely Ad-TRAIL-MRE-1-133-218. qPCR, immunoblotting and ELISA assays demonstrated that Ad-TRAIL-MRE-1-133-218 expressed in bladder cancer cells, rather than normal bladder cells. The differential TRAIL expression also led to selective apoptosis-inducing and growth-inhibiting effect of Ad-TRAIL-MRE-1-133-218 on bladder cancers. Finally, bladder cancer xenograft in mouse models further confirmed that Ad-TRAIL-MRE-1-133-218 effectively suppressed the growth of bladder cancers. CONCLUSIONS: Collectively, we demonstrated that MREs-based TRAIL delivery into bladder cancer cells was feasible and efficient for cancer gene therapy.


Assuntos
Carcinoma de Células de Transição/terapia , MicroRNAs/genética , Elementos de Resposta , Ligante Indutor de Apoptose Relacionado a TNF/genética , Neoplasias da Bexiga Urinária/terapia , Adenoviridae/genética , Animais , Apoptose/genética , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Sobrevivência Celular/genética , Feminino , Terapia Genética/métodos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/biossíntese , Ligante Indutor de Apoptose Relacionado a TNF/biossíntese , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Gene ; 513(1): 14-21, 2013 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23107766

RESUMO

BACKGROUND: Cytokines have been implicated in the acute rejection of solid organ transplantation. Many studies have investigated the association between recipient or donor IL-4 polymorphism and acute rejection, with different studies reporting inconclusive results. METHODS: We searched PUBMED and EMBASE until June 2012 to identify eligible studies investigating the association between IL-4 polymorphism with acute rejection after solid organ transplantation. Statistical analysis was performed using STATA10.0. RESULTS: A total of 12 studies were included. Pooled ORs suggested 1) no significant association was detected between recipient or donor IL-4 -590C/T polymorphism and acute rejection of solid allograft; 2) no significant association was detected between recipient IL-4 -33C/T polymorphism and acute rejection of solid allograft; 3) when stratified by transplantation type, IL-4 -590C/T polymorphism was associated with acute rejection of liver transplantation (T/T+C/T vs. C/C: OR=0.36, 95%CI=0.14-0.90); 4) significantly decreased risk of acute rejection was detected in recipient IL-4 -590*T-negative/donor T-positive genotype pairs than all other recipient-donor IL-4 -590T/C pairs (OR=0.14, 95%CI=0.03-0.66). CONCLUSIONS: Our meta-analysis suggested that recipient IL-4 -590C/T polymorphism was associated with acute rejection of liver transplantation, but nor renal or heart transplantation. It was also suggested that combined recipient IL-4 -590*T-negative/donor T-positive genotype may suffer decreased risk of acute rejection of solid allograft. Further well-designed studies with larger sample size were required to verify our findings, with focus on the association of IL-4 polymorphism with acute rejection in patients with liver transplantation and studies investigating combined recipient-donor genotype.


Assuntos
Rejeição de Enxerto/genética , Interleucina-4/genética , Transplante de Órgãos , Polimorfismo Genético , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Transplante Homólogo/imunologia
15.
Urology ; 80(3): 738.e1-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22608803

RESUMO

OBJECTIVE: To investigate the value of dynamic monitoring of endothelial cell specific molecule-1 (ESM-1) in diagnosing acute rejection after renal transplantation. METHODS: ESM-1 expression was observed in peripheral blood circulating endothelial cells and renal allografts after renal transplantation, and was compared to the flow cytometry (FCM) results of urine HLA-DR(+) lymphocytes. RESULTS: In patients with acute rejection, ESM-1 mRNA and protein expression increased significantly (P < .01). Real-time polymerase chain reaction detection of ESM-1 mRNA in peripheral blood cells was more sensitive and specific than FCM detection of urine HLA-DR(+) lymphocytes. Moreover, real-time PCR detection is characterized by convenient sampling and good reproducibility. CONCLUSION: ESM-1 is a new marker for endothelial cell activation. However, its significance during acute rejection in renal transplantation is still unclear. Our study demonstrates that ESM-1 may reflect the degree of endothelial cell injury in renal allografts, and that it may serve as a highly sensitive and specific marker for acute rejection after renal transplantation.


Assuntos
Rejeição de Enxerto/imunologia , Transplante de Rim , Proteínas de Neoplasias/fisiologia , Proteoglicanas/fisiologia , Doença Aguda , Adulto , Feminino , Humanos , Masculino
16.
Chin Med J (Engl) ; 124(9): 1431-4, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21740759

RESUMO

BACKGROUND: The incidence of urinary lithiasis following kidney transplantation is very low, and decision-supporting data are not available. The aim of this study was to review the diagnosis and treatment of urinary lithiasis following kidney transplantation, which is of realistic significance to reduce urinary lithiasis following kidney transplantation, prolong the survival of renal allografts. METHODS: The incidence, diagnosis and treatment of urinary lithiasis in ten patients following kidney transplantation were analyzed retrospectively. Seven out of these patients had stones sized approximately 0.4 - 1.1 cm, and they were treated with low-voltage, low-frequency extracorporeal shock-wave lithotripsy (ESWL). Two patients had stones sized < 0.3 cm and they underwent cystoscopy and ureteroscopy. The ureteral catheter endoscopes were inserted in a retrograde manner to mobilize stones repeatedly. After elimination of obstruction, a ureteral double J stent was indwelt. One patient had a pelvic stone (1.2 cm), which was removed surgically. RESULTS: The major clinical manifestations were hematuria, oliguria or anuria. Some patients were asymptomatic and they were diagnosed through laboratory tests and imaging examinations, e.g., ultrasonography. After elimination of obstruction, subjective symptoms disappeared in all patients, and the function of renal allografts recovered. A six-month follow-up indicated no remnant stones or lithiasis relapse. CONCLUSIONS: The diagnosis and treatment of renal allograft lithiasis are challenging. After prompt and appropriate treatment, the prognosis was satisfactory, and permanent renal functional impairment did not occur in most patients.


Assuntos
Transplante de Rim/efeitos adversos , Litotripsia , Urolitíase/etiologia , Urolitíase/terapia , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
17.
Zhonghua Nan Ke Xue ; 16(11): 1016-8, 2010 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-21218646

RESUMO

OBJECTIVE: To investigate the method and clinical efficacy of laparoscopic excision of seminal vesicle cyst. METHODS: Laparoscopic excision of seminal vesicle cyst was performed under general anaesthesia in two patients with symptomatic seminal vesicle cyst confirmed by ultrasonography and CT scanning preoperatively. The sizes of the seminal vesicle cysts were 3.3 cm x 3.7 cm x 2.5 cm and 4.1 cm x 4.3 cm x 5.3 cm, respectively. RESULTS: The operations were performed successfully in both the patients, with the operation time of 140 min and 100 min, blood loss of 50 ml and 20 ml, and postoperative stay of 6 days. The patients were followed up for 6 and 7 months, respectively. All the preoperative symptoms disappeared, and no complications and recurrence were found. CONCLUSION: Laparoscopic excision of seminal vesicle cyst, with a good visual field, refined procedure, minimal invasiveness and rapid recovery, is a safe and effective surgical option for patients with seminal vesicle cyst.


Assuntos
Cistos/cirurgia , Doenças dos Genitais Masculinos/cirurgia , Glândulas Seminais/cirurgia , Adulto , Humanos , Laparoscopia , Masculino
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