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1.
Clin Transplant ; 33(10): e13677, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31342552

RESUMO

BACKGROUND: This study aimed to explore the safety of donors with primary central nervous system tumors for kidney and liver transplantations. METHODOLOGY: Clinical data of 29 donors with primary CNS tumors in January 2007 to December 2017, as well as the follow-up data of 16 liver transplant recipients and 46 kidney transplant recipients, were analyzed. According to the risk factors, the high-risk group was classified as Group 1, the low-risk factors were classified as Group 2, and the unknown risk group was classified as Group 3. The incidence of donor-transmitted CNS tumors was calculated and compared. RESULTS: The duration from the diagnosis of 29 donors to donation was 5.67 ± 6.36 months. None of the liver and kidney transplant recipients who were followed up had tumor metastasis. Although the mean survival time of Group 1 was lower than that of Group 2 and Group 3, the Kaplan-Meier curve showed no significant difference in survival time. CONCLUSION: No obvious difference was observed between high-risk and low-risk and unknown risk CNS tumors in terms of the survival rate of transplants and tumor metastasis rate. High-risk CNS tumor donors can be used with the informed consent of recipients after a full evaluation.

2.
Oncotarget ; 7(34): 55529-55542, 2016 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-27487125

RESUMO

Since the tumor-oriented homing capacity of mesenchymal stem cells (MSCs) was discovered, MSCs have attracted great interest in the research field of cancer therapy mainly focused on their use as carries for anticancer agents. Differing from DNA-based vectors, the use of mRNA-based antituor gene delivery benefits from readily transfection and mutagenesis-free. However, it is essential to verify if mRNA transfection interferes with MSCs' tropism and their antitumor properties. TRAIL- and PTEN-mRNAs were synthesized and studied in an in vitro model of MSC-mediated indirect co-culture with DBTRG human glioma cells. The expression of TRAIL and PTEN in transfected MSCs was verified by immunoblotting analysis, and the migration ability of MSCs after anticancer gene transfection was demonstrated using transwell co-cultures. The viability of DBTRG cells was determined with bioluminescence, live/dead staining and real time cell analyzer. An in vivo model of DBTRG cell-derived xenografted tumors was used to verify the antitumor effects of TRAIL- and PTEN-engineered MSCs. With regard to the effect of mRNA transfection on MSCs' migration toward glioma cells, an enhanced migration rate was observed with MSCs transfected with all tested mRNAs compared to non-transfected MSCs (p<0.05). TRAIL- and PTEN-mRNA-induced cytotoxicity of DBTRG glioma cells was proportionally correlated with the ratio of conditioned medium from transfected MSCs. A synergistic action of TRAIL and PTEN was demonstrated in the current co-culture model. The immunoblotting analysis revealed the apoptotic nature of the cells death in the present study. The growth of the xenografted tumors was significantly inhibited by the application of MSCPTEN or MSCTRAIL/PTEN on day 14 and MSCTRAIL on day 28 (p<0.05). The results suggested that anticancer gene-bearing mRNAs synthesized in vitro are capable of being applied for MSC-mediated anticancer modality. This study provides an experimental base for further clinical anticancer studies using synthesized mRNAs.


Assuntos
Neoplasias Encefálicas/terapia , Terapia Genética/métodos , Glioma/terapia , Células-Tronco Mesenquimais/fisiologia , PTEN Fosfo-Hidrolase/genética , RNA Mensageiro/genética , Ligante Indutor de Apoptose Relacionado a TNF/genética , Animais , Neoplasias Encefálicas/patologia , Movimento Celular , Feminino , Glioma/patologia , Humanos , Camundongos , Transfecção , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Exp Ther Med ; 11(3): 988-992, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26998025

RESUMO

Effective use of all available donated organs is critical, in order to meet the increasing demand for transplants. The present study explored liver transplantation with livers that were donated following cardiac death (DCD). According to the guidelines established by The Red Cross Society of China, 42 DCD organs were procured. Selected donors were treated with extracorporeal membrane oxygenation (ECMO) prior to the organ retrieval. The present single-center study included 6 liver transplantations of DCD organs (5 liver transplants and 1 liver-kidney combined transplant). All 6 recipients had a successful recovery without significant complications. The serum alanine transaminase, total bilirubin and international normalized ratio returned to the normal levels within a short period of time following transplantation, and the liver function remained normal during the follow-up period, which lasted up to 24 months. The present report demonstrated the feasibility of orthotopic liver transplantation using DCD livers. The pre-conditioning DCD donors and optimization of the recipient's condition using ECMO, played a crucial role in ensuring the success of transplantation.

4.
Oncotarget ; 6(42): 44179-90, 2015 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-26496034

RESUMO

Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events. As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable.


Assuntos
Exossomos/transplante , Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Proteínas Recombinantes de Fusão/imunologia , Linfócitos T/transplante , Animais , Sistema Livre de Células , Citocinas/imunologia , Citocinas/metabolismo , Exossomos/genética , Exossomos/imunologia , Exossomos/metabolismo , Engenharia Genética , Humanos , Ativação Linfocitária , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Receptores de Antígenos de Linfócitos T/biossíntese , Receptores de Antígenos de Linfócitos T/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismo
5.
Onco Targets Ther ; 7: 441-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24669193

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have been considered to hold great potential as ideal carriers for the delivery of anticancer agents since the discovery of their tumor tropism. This study was performed to demonstrate the effects of phosphatase and tensin homolog (PTEN) engineering on MSCs' capacity for cancer cell-oriented migration. METHODS: MSCs were engineered with a PTEN-bearing plasmid and the expression was confirmed with Western blotting. A human glioma cell line (DBTRG) was used as the target cell; DBTRG cell-oriented migration of MSCs was monitored with a micro speed photographic system. RESULTS: The expression of transfected PTEN in MSCs was identified by immunoblotting analysis and confirmed with cell viability assessment of target cells. The DBTRG cell-oriented migration of PTEN-engineered MSCs was demonstrated by a real-time dynamic monitoring system, and a phagocytosis-like action of MSCs was also observed. CONCLUSION: MSCs maintained their capacity for cancer cell-directed migration after they were engineered with anticancer genes. This study provides the first direct evidence of MSCs' tropism post-anticancer gene engineering.

6.
Int J Cancer ; 135(7): 1511-6, 2014 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24285244

RESUMO

Biobanks have played a decisive role in all aspects of the field of cancer, including pathogenesis, diagnosis, prognosis and treatment. The significance of cancer biobanks is epitomized through the appropriate application of various "-omic" techniques (omics). The mutually motivated relationship between biobanks and omics has intensified the development of cancer research. Human cancer tissues that are maintained in intravital biobanks (or living tissue banks) retain native tumor microenvironment, tissue architecture, hormone responsiveness and cell-to-cell signalling properties. Intravital biobanks replicate the structural complexity and heterogeneity of human cancers, making them an ideal platform for preclinical studies. The application of omics with intravital biobanks renders them more active, which makes it possible for the cancer-related evaluations to be dynamically monitored on a real-time basis. Integrating intravital biobank and modern omics will provide a useful tool for the discovery and development of new drugs or novel therapeutic strategies. More importantly, intravital biobanks may play an essential role in the creation of meaningful patient-tailored therapies as for personalized medicine.


Assuntos
Bancos de Espécimes Biológicos , Genômica/métodos , Metabolômica/métodos , Medicina de Precisão , Proteômica/métodos , Humanos
7.
Case Rep Transplant ; 2013: 532865, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24106636

RESUMO

It is critical to effectively use every available organ to meet the increasing demands for liver transplantation. Situs inversus is a rare congenital anomaly caused by obstruction of viscus rotation during embryonic development. Situs inversus was once regarded as a contraindication to liver transplantation because of the technical difficulties associated with the unique vascular anatomy and concern about achieving accurate graft positioning. Here, we present a successful case of liver transplantation using a graft from a donor with situs inversus totalis. The related experience will contribute to opening up new realms for the use of such rare organ resources.

8.
Pharmazie ; 67(9): 804-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23016456

RESUMO

The objective of the present study is to clearly evaluate the inhibitory effects of tacrolimus (tacro) on important UGT isoforms in human liver, including determination of inhibition kinetic type and calculation of inhibition kinetic parameters. An in vitro incubation system was used to investigate the inhibitory effect of tacro on UGT isoforms. The recombinant UGT isoforms were used as enzyme source, and a nonspecific substrate 4-methylumbelliferone (4-MU) was utilized as substrate. Among the tested UGT isoforms, UGT1A1, UGT1A3, UGT2B7 and UGT2B15 were strongly inhibited by tacro in a concentration-dependent manner. Dixon and Lineweaver-Burk plots showed that the inhibition of UGT1A1, UGT1A3, and UGT2B7 was all best fit to competitive inhibition type, and the inhibition of UGT2B15 was best fit to noncompetitive type. The inhibition kinetic parameters (Ki) were determined to be 4.7, 1.3, 1.9, and 4.3 microM for UGT1A1, UGT1A3, UGT2B7, and UGT2B15, respectively. Inhibition of these important UGT isoforms in human liver might be an important reason for clinically frequent drug-drug interaction between tacro and other drugs.


Assuntos
Inibidores Enzimáticos , Glucuronosiltransferase/antagonistas & inibidores , Imunossupressores/farmacologia , Tacrolimo/farmacologia , Biotransformação , Glucuronídeos/metabolismo , Humanos , Himecromona/análogos & derivados , Himecromona/metabolismo , Indicadores e Reagentes , Isoenzimas/antagonistas & inibidores , Cinética , Fígado/enzimologia , Fígado/metabolismo , Proteínas Recombinantes/química
9.
World J Stem Cells ; 3(11): 96-103, 2011 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-22180830

RESUMO

Cancer remains one of the leading causes of mortality and morbidity throughout the world. To a significant extent, current conventional cancer therapies are symptomatic and passive in nature. The major obstacle to the development of effective cancer therapy is believed to be the absence of sufficient specificity. Since the discovery of the tumor-oriented homing capacity of mesenchymal stem cells (MSCs), the application of specific anticancer gene-engineered MSCs has held great potential for cancer therapies. The dual-targeted strategy is based on MSCs' capacity of tumor-directed migration and incorporation and in situ expression of tumor-specific anticancer genes. With the aim of translating bench work into meaningful clinical applications, we describe the tumor tropism of MSCs and their use as therapeutic vehicles, the dual-targeted anticancer potential of engineered MSCs and a putative personalized strategy with anticancer gene-engineered MSCs.

10.
Nan Fang Yi Ke Da Xue Xue Bao ; 31(12): 2085-6, 2011 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-22200719

RESUMO

OBJECTIVE: To explore the effect of CD40 blockade in suppressing acute rejection of renal graft in rats. METHODS: With Wistar rats as the donor and male SD rats as the recipients, rat models of acute renal graft rejection was established. The rat models were divided into therapy group and control group, and in the former group, CD40 ligand (CD40L) monoclonal antibody was injected daily for 4 consecutive days starting on the next day following kidney transplantation. On day 5 after the transplantation, the renal graft was harvested for histological examination, and graft rejection was evaluated semiquantitatively. RESULTS: The mean semiquantitative score of the renal graft was 0.63∓0.52 in the therapy group, significantly lower than that of the control group (3.72∓1.48, P<0.05). CONCLUSION: CD40L monoclonal antibody can inhibit acute renal graft in rats.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD40/antagonistas & inibidores , Ligante de CD40/imunologia , Rejeição de Enxerto/tratamento farmacológico , Transplante de Rim , Animais , Anticorpos Monoclonais/farmacologia , Antígenos CD40/imunologia , Feminino , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Rim/efeitos adversos , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Wistar
11.
Anticancer Res ; 31(11): 3705-12, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22110190

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have attracted great interest in cancer therapy since the discovery of their tumor tropism. This study was performed to investigate the effects of TNF-related apoptosis-inducing ligand (TRAIL)-engineered MSCs on hepatocellular carcinoma (HCC) cells (HepG2) under different culture conditions. MATERIALS AND METHODS: MSCs engineered with non-secreting TRAIL (MSC(TRAIL-GFP)) (GFP, green fluorescence protein) and secreting TRAIL (MSC(stTRAIL)) were used for the direct co-cultures, and conditioned media (CM) from corresponding cultures were applied to HepG2 as indirect co-cultures. Immunoblotting, ELISA and FACS analysis were used to detect the expression of TRAIL and TRAIL receptors. Cell death was assessed using live/dead assay. RESULTS: Death receptor (DR) 5 was identified on the HepG2 cells. The expression of TRAIL was confirmed in the cell lysates (MSC(TRAIL-GFP) >MSC(stTRAIL)) and the conditioned media (MSC(stTRAIL) >MSC(TRAIL-GFP)). Higher cell death was observed in high MSC/HepG2 ratio co-cultures. HepG2 cell death was proportionally related to CM from MSC(TRAIL-GFP) and MSC(stTRAIL). CONCLUSION: MSCs exhibit intrinsic inhibition of HepG2 which is potentiated by TRAIL-transfection.


Assuntos
Apoptose , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Células-Tronco Mesenquimais/patologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Adulto , Western Blotting , Cadáver , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/terapia , Células Cultivadas , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Células-Tronco Mesenquimais/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia
12.
Di Yi Jun Yi Da Xue Xue Bao ; 23(6): 614-5, 618, 2003 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-12810392

RESUMO

OBJECTIVE: To establish a simple and reliable rat model of simultaneous liver and kidney transplantation. METHODS: The simultaneous transplantation was performed in healthy male SD rats as the recipients and other SD rats of either gender as the donors. The donor liver and kidney were resected simultaneously and grafted into the recipients whose corresponding organs were previously removed. Anastomosis of the portal vein and the inferior vein cava (IVC) inferior to the kidney between the graft and the recipient was performed by a double cuff method, followed by end-to-side anastomosis of the IVC superior to the liver between the donor and the recipient. The urethra and bile duct were anastomised using a simple inside bracket. RESULTS: The time for blood vessel anastomosis and for recipient operation were reduced, with a success rate of 73.3% in the operations. The function of the grafted liver and kidney remained normal. CONCLUSION: This rat model of simultaneous liver-kidney transplantation is simple and reliable.


Assuntos
Transplante de Rim/métodos , Transplante de Fígado/métodos , Anastomose Cirúrgica , Animais , Feminino , Masculino , Modelos Animais , Veia Porta/cirurgia , Ratos , Ratos Sprague-Dawley , Veia Cava Inferior/cirurgia
13.
Di Yi Jun Yi Da Xue Xue Bao ; 23(5): 439-41, 2003 May.
Artigo em Chinês | MEDLINE | ID: mdl-12754123

RESUMO

OBJECTIVE: To assess the value of intermittent contrast second harmonic imaging (SHI) incorporating acoustic densitometry in the diagnosis of acute renal allograft rejection in comparison with color Doppler flow imaging (CDFI) for determining the resistance index (RI). METHODS: Eight canine models of acute renal allograft rejection were established, subjected subsequently to examinations with SHI and acoustic densitometry to determine the acoustic density. Color flow Doppler was also performed to determine RI, and serum creatinine (Cr) levels were measured. RESULTS: The time-intensity curve (TIC) showed that the area under the curve, the peak intensity (PI) and RI all had linear correlation with serum Cr levels, with the correlation coefficient gamma of 0.978, 0.972 and 0.708 respectively (by SPSS10.0). CONCLUSION: Intermittent contrast SHI is effective to evaluate the perfusion of renal allograft, and when combined with acoustic densitometry, the resultant TIC parameters are in closer correlation with acute renal allograft rejection than RI.


Assuntos
Rejeição de Enxerto/diagnóstico por imagem , Transplante de Rim/imunologia , Ultrassonografia Doppler em Cores , Doença Aguda , Animais , Creatinina/sangue , Densitometria , Cães , Feminino , Masculino , Circulação Renal , Transplante Homólogo
14.
Di Yi Jun Yi Da Xue Xue Bao ; 23(4): 332-4, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12697466

RESUMO

OBJECTIVE: To investigate the effect of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNF-alpha mAb) in alleviating renal ischemia-reperfusion injury. METHODS: Fifty normal male Sprague-Dawley rats were randomly divided into 3 groups, namely group A that was subjected to ischemia-reperfusion injury with intravenous administration of anti-TNF-alpha mAb (0.1mg/kg.b.w.) 5 min before reperfusion (treatment group), group B with the same injury followed by saline administration in the same manner (control group), and group C with only anesthetization and leparotomy but not ischemia (sham operation group). Routine assays were performed for testing the levels of blood creatine (Cr), blood urea nitrogen (BUN), plasma TNF-alpha and the cell apoptosis. Ultrastructure of the kidney was also observed. RESULTS: Renal ischemia-reperfusion resulted in significant increase of the levels of Cr, BUN and TNF-alpha in the plasma (P<0.01), but these effects were offset by administration of anti-TNF-alpha mAb (P<0.01). In group B, widespread pathological changes and cell apoptosis were observed in the renal tissue following renal ischemia-reperfusion injury, while similar changes were scarcely visible in group A due to the protective effect of intravenous administration of anti-TNF-alpha mAb 5 min before reperfusion. CONCLUSION: Renal ischemia-reperfusion injury can be alleviated by anti-TNF-alpha mAb treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Fator de Necrose Tumoral alfa/imunologia , Animais , Modelos Animais de Doenças , Isquemia/complicações , Nefropatias/complicações , Masculino , Ratos , Ratos Sprague-Dawley
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