Operational Tolerance in Nonvascularized Transplant Models Induced by AR-C117977, a Monocarboxylate Transporter Inhibitor

Påhlman, Clara; Malm, Helene; Qi, Zhongquan; Veress, B; Ferguson, Douglas; Bundick, R. V.; Murray, Clare; Donald, David K.; Ekberg, Henrik

doi:10.1097/tp.0b013e318186b978

Cited by 7 publications

(7 citation statements)

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“…[295] Nevertheless, compound 86 , also known as AR-C117977, showed efficient immunosuppressive activities both in vitro and in vivo. [296] The structural optimization of these compounds led to the production of a less lipophilic and more water soluble derivative, AR-C155858 ( 89 ). This compound proved to efficiently bind to MCT1 with a K i value of 1.2 nM (human erythrocytes), and to potently inhibit both MCT1 and MCT2, by binding to an intracellular site of these transporters.…”

Section: Glycolytic Effectors As Potential Targets In Cancer Therapymentioning

confidence: 99%

Anticancer Agents That Counteract Tumor Glycolysis

2012

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Can we consider cancer as a “metabolic disease”? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have to deal with increased needs for both energy and biosynthetic intermediates, in order to support their growth and invasiveness. However, their high proliferation rate often generates regions that are not sufficiently oxygenated. Therefore, their carbohydrate metabolism has to rely mostly on a glycolytic process that is uncoupled from oxidative phosphorylation. This metabolic switch, also known as the “Warburg Effect”, constitutes a fundamental adaptation of the tumor cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumor glycolysis may constitute an attractive target for cancer therapy. This approach has often raised concerns that anti-glycolytic agents may cause serious side effects on normal cells. Actually, the key for a selective action against cancer cells can be found in their hyperbolic addiction to glycolysis, which may be exploited to generate new anti-cancer drugs showing minimal toxicity. In fact, there is growing evidence that supports many glycolytic enzymes and transporters as suitable candidate targets for cancer therapy. Herein we review some of the most relevant anti-glycolytic agents that have been investigated so far for the treatment of cancer.

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Section: Glycolytic Effectors As Potential Targets In Cancer Therapymentioning

confidence: 99%

Anticancer Agents That Counteract Tumor Glycolysis

2012

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“…Påhlman et al 21 evaluated the immunosuppressive limitations of AR-C117977, a immunosuppressant drug that maintains long-term graft survival and induces operational tolerance, and concluded that AR-C117977 combined with CsA resulted in significant prolongation of graft survival when compared with AR-C117977 or CsA monotherapy. Furthermore, CsA monotherapy did not avoid acute rejection.…”

Section: B Resultsmentioning

confidence: 99%

Parameters involved and viability of immunosuppression on islet allotransplantation procedure in rodents

Iuamoto¹,

Meyer²,

Chaib³

et al. 2014

Medical Express

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INTRODUCTION: Autoimmunity and rejection after transplantation must still be overcome in the technical development of islet transplantation for the treatment of type 1 diabetes. It is therefore necessary to inhibit rejection of islet grafts while maintaining the graft's ability to secrete insulin. Although the use of immunosuppressants reduces the acute rejection rate in transplant patients, long-term side effects must be prevented. OBJECTIVES: The aim of the present study is to organize and analyze the parameters of immunosuppression involved in experimental attempts of allotransplantation in rodents. METHODOLOGY: This review was performed using the Pubmed database to search for published articles containing the keywords "rodent islet transplantation". The inclusion criteria involved allotransplantation with rodents' islets and the reference lists of the publications retrieved that were eligible. The exclusion criteria involved isotransplantation, autotransplantation, and xenotransplantation such as transplantation in other species. RESULTS: Twenty studies related to allotransplantation were selected for this systematic review based on immunosuppression. CONCLUSION: New immunosuppressive drugs increased the survival rates of allotransplantation in rodents by reducing the side effects. The advances in immunosuppression raise the possibility of overcoming autoimmunity and rejection after allotransplantation.

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“…Jung et al 26 Balb/c → C57Bl/6 CD154 mAb (MR1) anti-ratos e ROS-A (Reactive Oxygen Specie-A) Cápsula renal ROS-A -53 dias, MR1 -82 dias, ROS-A+MR1 ->160 dias Påhlman et al 27 Balb/c → C57Bl/6J AR-C117977 (10 ou 30 mg/kg) ou CsA 20 mg/kg Cápsula renal CsA -16 dias AR-C117977, 10 mg/kg->100dias AR-C117977, 30 mg/kg -29,33 dias Wang et al 28 Balb/c → C57Bl/6 B7-H4 e Ad-LacZ Cápsula renal B7-H4 -aproximadamente 60 dias Ad-LacZaproximadamente > 20 dias …”

Section: Cápsula Renal 70%mentioning

confidence: 99%

Revisão sistemática sobre alotransplantes de ilhotas de Langerhans em roedores: análise de sítio de transplante e tempo de sobrevida

Iuamoto

Meyer

Chaib

et al. 2014

Rev. Med. (São Paulo)

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Iuamoto LR, Meyer A, Chaib E, D'Albuquerque LAC. Revisão sistemática sobre alotransplantes de ilhotas de Langerhans em roedores: análise de sítio de transplante e tempo de sobrevida / Systematic review of islet allotransplantation in rodents: analysis of transplantation site and survival time. Rev Med (São Paulo). 2014 out.-dez.;93(4):151-8. RESUMO:Introdução. A escassez de ilhotas é uma restrição importante ao uso de ilhotas pancreáticas para o desenvolvimento do alotransplante para o tratamento do diabetes tipo I. É necessário, portanto, desenvolver fonte ilimitada de células produtoras de insulina. Objetivos. Organizar e analisar dados sobre o sítio de transplante e o tempo de sobrevida relacionados a tentativas experimentais de alotransplante em roedores, a fim de permitir elaborar um modelo mais adequado para suprir a escassez de doadores de ilhotas. Metodologia. Realizamos uma revisão sistemática usando o banco de dados Pubmed para pesquisar artigos publicados que contenham as palavraschaves "rodent islet transplantation". Foram incluídos estudos envolvendo experimentos alotransplante de ilhotas de roedores e analisadas as listas de referências das publicações recuperadas. Artigos relacionados a isotransplantes, autotransplantes e xenotransplantes foram excluídos do estudo. Resultados. Um total de 30 estudos relacionados a alotransplantes em diferentes sítios de enxerto foram selecionados para a revisão sistemática baseados na relevância de seus dados e em sua atualização. O fígado e a cápsula renal são sítios que possibilitaram uma maior sobrevida das ilhotas transplantadas. Conclusão. O alotransplante em roedores é promissor e continua a se desenvolver em diversos centros. As taxas de sobrevivência de aloenxertos aumentaram com a utilização de diferentes medicamentos e locais de enxerto. DESCRITORES: Transplante de ilhotas pancreáticas;Hiperglicemia; Modelo animal; Aloenxertos; Imunossupressão; Literatura de revisão como assunto. ABSTRACT: Introduction. The scarcity of islets is an important use of pancreatic islets for the development of allograft for the treatment of diabetes type I. It is therefore necessary to develop unlimited source of insulin-producing cells restriction.Objectives. Organize and analyze parameters related to the site of transplantation and survival time related to experimental rodent allotransplantation attempts in order to allow the elaboration of the most suitable model to supply the scarcity of islet donors. Methodology. We performed a systematic review using the PubMed database to search published articles containing the keywords "rodent islet transplantation". We included studies involving allotransplantation experiments with rodents' islets and we reviewed the reference lists of the publications retrieved that were eligible. We excluded articles related to isotransplantation, autotransplantation and xenotransplantation such as transplantation in other species. Articles related to isotransplantations, transplantations and xenografts were excluded from the study. Results. A tot...

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Operational Tolerance in Nonvascularized Transplant Models Induced by AR-C117977, a Monocarboxylate Transporter Inhibitor

Cited by 7 publications

References 10 publications

Anticancer Agents That Counteract Tumor Glycolysis

Anticancer Agents That Counteract Tumor Glycolysis

Parameters involved and viability of immunosuppression on islet allotransplantation procedure in rodents

Revisão sistemática sobre alotransplantes de ilhotas de Langerhans em roedores: análise de sítio de transplante e tempo de sobrevida

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