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Protein Cell ; 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31814083


The author would like to add the below information in this correction. A similar study from Chao Lu group was published online on 5 September 2019 in Nature, entitled "The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape" (Weinberg et al., 2019). Although both the studies reported the preferential recognition of H3K36me2 by DNMT3A PWWP, ours in addition uncovered a stimulation function by such interaction on the activity of DNMT3A. On the disease connections, we used a NSD2 gain-of-function model which led to the discovery of potential therapeutic implication of DNA inhibitors in the related cancers, while the other study only used NSD1 and DNMT3A loss-of-function models.

Comput Struct Biotechnol J ; 17: 661-674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205619


The programmed cell death protein 1 (PD-1) pathway has received considerable attention due to its role in eliciting the immune checkpoint response of T cells, resulting in tumor cells capable of evading immune surveillance and being highly refractory to conventional chemotherapy. Application of anti-PD-1/PD-L1 antibodies as checkpoint inhibitors is rapidly becoming a promising therapeutic approach in treating tumors, and some of them have successfully been commercialized in the past few years. However, not all patients show complete responses and adverse events have been noted, suggesting a better understanding of PD-1 pathway mediated immunosuppression is needed to predict patient response and improve treatment efficacy. Here, we review the progresses on the studies of the mechanistic role of PD-1 pathway in the tumor immune evasion, recent clinical development and commercialization of PD-1 pathway inhibitors, the toxicities associated with PD-1 blockade observed in clinical trials as well as how to improve therapeutic efficacy and safety of cancer immunotherapy.

Sci Rep ; 7: 46278, 2017 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-28406238


Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB). 36S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method.

Cromatografia Líquida , Sulfeto de Hidrogênio/química , Espectrometria de Massas em Tandem , Animais , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Células Musculares/metabolismo , Ratos , Reprodutibilidade dos Testes , Saccharomycetales/enzimologia , Sensibilidade e Especificidade
PLoS One ; 11(3): e0150156, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26950930


An increasing number of studies have shown that the promising compound resveratrol treats multiple diseases, such as cancer and aging; however, the resveratrol mode-of-action (MoA) remains largely unknown. Here, by virtue of multiple omics approaches, we adopted fission yeast as a model system with the goal of dissecting the common MoA of the anti-proliferative activity of resveratrol. We found that the anti-proliferative activity of resveratrol is mainly due to its unique role of inhibiting the separation of sister cells, similar phenotype with the C2H2 zinc finger transcription factor Ace2 knock-out strain. Microarray analysis shown that resveratrol has extensive impact on the fission yeast transcription levels. Among the changed gene's list, 40% of up-regulated genes are Core Environmental Stress Responses genes, and 57% of the down-regulated genes are periodically expressed. Moreover, resveratrol leverages the metabolome, which unbalances the intracellular pool sizes of several classes of amino acids, nucleosides, sugars and lipids, thus reflecting the remodulated metabolic networks. The complexity of the resveratrol MoA displayed in previous reports and our work demonstrates that multiple omics approaches must be applied together to obtain a complete picture of resveratrol's anti-proliferative function.

Produtos Biológicos/farmacologia , Espaço Intracelular/metabolismo , Metaboloma/efeitos dos fármacos , Schizosaccharomyces/citologia , Schizosaccharomyces/genética , Estilbenos/farmacologia , Transcrição Genética/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Técnicas de Inativação de Genes , Espaço Intracelular/efeitos dos fármacos , Fenótipo , Resveratrol , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/metabolismo , Proteínas de Schizosaccharomyces pombe/genética , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética
Oncotarget ; 6(11): 8606-20, 2015 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-25825982


Cancer-associated isocitrate dehydrogenase (IDH) 1 and 2 mutations gain a new activity of reducing α-KG to produce D-2-hydroxyglutarate (D-2-HG), which is proposed to function as an oncometabolite by inhibiting α-KG dependent dioxygenases. We investigated the function of D-2-HG in tumorigenesis using IDH1 and IDH2 mutant cancer cell lines. Inhibition of D-2-HG production either by specific deletion of the mutant IDH1-R132C allele or overexpression of D-2-hydroxyglutarate dehydrogenase (D2HGDH) increases α-KG and related metabolites, restores the activity of some α-KG-dependent dioxygenases, and selectively alters gene expression. Ablation of D-2-HG production has no significant effect on cell proliferation and migration, but strongly inhibits anchorage independent growth in vitro and tumor growth in xenografted mouse models. Our study identifies a new activity of oncometabolite D-2-HG in promoting tumorigenesis.

Glutaratos/metabolismo , Isocitrato Desidrogenase/fisiologia , Proteínas de Neoplasias/fisiologia , Sarcoma/patologia , Animais , Adesão Celular , Divisão Celular , Linhagem Celular Tumoral , Movimento Celular , Deleção de Genes , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Isocitrato Desidrogenase/deficiência , Isocitrato Desidrogenase/genética , Ácidos Cetoglutáricos/antagonistas & inibidores , Masculino , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo , Oxigenases de Função Mista/metabolismo , Mutação de Sentido Incorreto , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/genética , Proteínas Recombinantes de Fusão/metabolismo , Sarcoma/genética , Sarcoma/metabolismo , Transfecção