Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Immunother Cancer ; 9(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34011536

RESUMO

BACKGROUND: Gamma-delta (γδ) T lymphocytes are primed to potently respond to pathogens and transformed cells by recognizing a broad range of antigens. However, adoptive immunotherapy with γδT cells has exhibited mixed treatment responses. Better understanding of γδT cell biology and stratifying healthy donors for allogeneic adoptive therapy is clinically needed to fully realize the therapeutic potential of γδT cells. METHODS: We examine 98 blood samples from healthy donors and measure their expansion capacity after zoledronate stimulation, and test the migration and cytotoxic effector function of expanded γδT cells in 2D culture, 3D tumor spheroid and patient-derived melanoma organoid assays. RESULTS: We find that γδT cell expansion capacity is independent of expansion methods, gender, age and HLA type. Basal γδT cell levels in Peripheral blood mononuclear cell (PBMC) correlate well with their expansion, migration and cytotoxic effector capacity in vitro. Circulating γδT cells with lower expression of PD-1, CTLA-4, Eomes, T-bet and CD69, or higher IFN-γ production expand better. γδT cells with central memory and effector memory phenotypes are significantly more abundant in good expanders. A cut-off level of 0.82% γδT cells in PBMC stratifies good versus poor γδT cell expansion with a sensitivity of 97.78%, specificity of 90.48% and area under the curve of 0.968 in a healthy individual. Donors with higher Vδ2 Index Score in PBMC have greater anti-tumor functions including migratory function and cytotoxicity. CONCLUSIONS: Our results demonstrate that the interindividual γδT cell functions correlate with their circulating levels in healthy donors. Examination of circulating γδT cell level may be used to select healthy donors to participate in γδT-based immunotherapies.

2.
Mol Ther ; 29(7): 2321-2334, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-33744468

RESUMO

Tumor cells increase glutamate release through the cystine/glutamate transporter cystine-glutamate exchange (xCT) to balance oxidative homeostasis in tumor cells and promote tumor progression. Although clinical studies have shown the potential of targeting programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling in melanoma, response rates are low. However, it remains unclear how glutamate metabolism affects anti-PD-1/PD-L1 treatment efficacy in melanoma. Here, we demonstrated that although inhibition of xCT either by pharmacological inhibitor (sulfasalazine [SAS]), approved by US Food and Drug Administration (FDA) for inflammatory diseases, or genetic knockdown induced reactive oxygen species (ROS)-related death in melanoma cells, inhibition of xCT significantly reduced the efficacy of anti-PD-1/PD-L1 immune checkpoint blockade through upregulating PD-L1 expression via the transcription factors IRF4/EGR1, as a consequence, exosomes carrying relatively large amounts of PD-L1 secreted from melanoma cells resulted in M2 macrophage polarization and reduced the efficacy of anti-PD-1/PD-L1 therapy in melanoma. Taken together, our results reveal that inhibition of xCT by SAS is a promising therapeutic strategy for melanoma; on the other hand, SAS treatment blunted the efficacy of anti-PD-1/PD-L1 via exosomal PD-L1-induced macrophage M2 polarization and eventually induced anti-PD-1/PD-L1 therapy resistance.

3.
Front Public Health ; 9: 630620, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692982

RESUMO

The outbreak of coronavirus disease-2019 (COVID-19) ineluctably caused social distancing and unemployment, which may bring additional health risks for patients with cancer. To investigate the association of the pandemic-related impacts with the health-related quality of life (HRQoL) among patients with melanoma during the COVID-19 pandemic, we conducted a cross-sectional study among Chinese patients with melanoma. A self-administered online questionnaire was distributed to melanoma patients through social media. Demographic and clinical data, and pandemic-related impacts (unemployment and income loss) were collected. HRQoL was determined by the Functional Assessment of Cancer Therapy-General (FACT-G) and its disease-specific module (the melanoma subscale, MS). A total of 135 patients with melanoma completed the study. The mean age of the patients was 55.8 ± 14.2 years, 48.1% (65/135) were male, and 17.04% (34/135) were unemployed since the epidemic. Unemployment of the patients and their family members and income loss were significantly associated with a lower FACT-G score, while the MS score was associated with the unemployment of the patients' family members. Our findings suggested that unemployment is associated with impaired HRQoL in melanoma patients during the COVID-19 epidemic.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , COVID-19/economia , COVID-19/psicologia , Melanoma/economia , Melanoma/psicologia , Qualidade de Vida/psicologia , Desemprego/psicologia , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Inquéritos e Questionários , Desemprego/estatística & dados numéricos
5.
Cancer Lett ; 503: 240-248, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33246091

RESUMO

Pyruvate kinase M2 (PKM2), a key rate-limiting enzyme of glycolysis, is a critical regulator in tumor metabolism. PKM2 has been demonstrated to overexpressed in various cancers and promoted proliferation and metastasis of tumor cells. The errant expression of PKM2 has inspired people to investigate the function of PKM2 and the therapeutic potential in cancer. In addition, some studies have shown that the upregulation of PKM2 in tumor tissues is associated with the altered expression of lncRNAs and the poor survival. Therefore, researchers have begun to unravel the specific molecular mechanisms of lncRNA-mediated PKM2 expression in cancer metabolism. As the tumor microenvironment (TME) is essential in tumor development, it is necessary to identify the role of PKM2 in TME. In this review, we will introduce the role of PKM2 in different cancers as well as TME, and summarize the molecular mechanism of PKM2-related lncRNAs in cancer metabolism. We expect that this work will lead to a better understanding of the molecular mechanisms of PKM2 that may help in developing therapeutic strategies in clinic for researchers.

6.
J Med Internet Res ; 22(9): e22288, 2020 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-32845850

RESUMO

BACKGROUND: The outbreak of COVID-19 has profoundly influenced people's lifestyles; these impacts have varied across subgroups of people. The pandemic-related impacts on the health outcomes of people with dermatological conditions are unknown. OBJECTIVE: The aim of this paper was to study the association of COVID-19 pandemic-related impacts with health-related quality of life in patients with skin diseases. METHODS: This was a cross-sectional study among Chinese patients with skin diseases. A self-administered web-based questionnaire was distributed through social media. Demographic and clinical data and pandemic-related impacts (isolation status, income changes, and employment status) were collected. The main outcomes included perceived stress (Visual Analog Scale), symptoms of anxiety (Generalized Anxiety Disorder-7) and depression (9-Item Patient Health Questionnaire), quality of life (Dermatology Life Quality Index), and health utility mapping based on the EQ-5D-3L descriptive system. Multivariable logistic regression was used to investigate the associations. RESULTS: A total of 506 patients with skin diseases completed the survey. The mean age of the patients was 33.5 years (SD 14.0), and 217/506 patients (42.9%) were male. Among the 506 respondents, 128 (25.3%) were quarantined, 102 (20.2%) reported unemployment, and 317 (62.6%) reported decrease or loss of income since the pandemic. The pandemic-related impacts were significantly associated with impaired mental well-being and quality of life with different effects. Unemployment and complete loss of income were associated with the highest risks of adverse outcomes, with increases of 110% to 162% in the prevalence of anxiety, depression, and impaired quality of life. CONCLUSIONS: Isolation, income loss, and unemployment are associated with impaired health-related quality of life in patients with skin diseases during the COVID-19 pandemic.


Assuntos
Ansiedade/epidemiologia , Betacoronavirus , Infecções por Coronavirus/psicologia , Depressão/epidemiologia , Pneumonia Viral/psicologia , Qualidade de Vida , Dermatopatias/complicações , Desemprego/psicologia , Adulto , COVID-19 , China/epidemiologia , Infecções por Coronavirus/complicações , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Saúde Mental , Pandemias , Pneumonia Viral/complicações , Prevalência , SARS-CoV-2 , Fatores Socioeconômicos
7.
J Invest Dermatol ; 140(11): 2268-2279.e11, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32275977

RESUMO

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment and mediate tumor progression in various cancers. A previous study demonstrated that TRAF6 promotes the malignant phenotype of melanoma cells. However, the role of TRAF6 in melanoma CAFs remains unclear. In this study, we found that TRAF6 was significantly upregulated in CAFs adjacent to melanoma cells. Functional assays showed that TRAF6 promoted fibroblast proliferation and migration as well as MMP and α-SMA expression. Moreover, the expression of TRAF6 in fibroblasts promoted the malignant phenotype of melanoma cells in vitro and in vivo. Meanwhile, the intervention of TRAF6 expression in melanoma cells affected the activation of CAFs. We found that FGF19 was a key cytokine regulated by TRAF6 through NF-κB1 using luciferase assay and chromatin immunoprecipitation in melanoma cells. Because plasma FGF19 levels are elevated in patients with melanoma, it may significantly induce fibroblast activation in vitro and in vivo. Taken together, our results support that TRAF6 is a key molecule that mediates the interaction between melanoma cells and stromal fibroblasts, suggesting that TRAF6 is a potentially promising target in melanoma therapy.


Assuntos
Fibroblastos Associados a Câncer/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Melanoma/patologia , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Melanoma/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/fisiologia , Fenótipo , Transcriptoma
8.
Oncogene ; 39(21): 4183-4197, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32291412

RESUMO

CD147, also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a transmembrane glycoprotein that is highly expressed in tumor cells, particularly melanoma cells, and plays critical roles in tumor cell metastasis through the regulation of matrix metalloprotease (MMP) expression. In this study, we identified Fyn as a novel interacting protein of CD147. Fyn is a member of the Src family of nonreceptor tyrosine kinases that regulates diverse physiological processes, such as T lymphocyte differentiation, through the TCR signaling pathway. Our findings demonstrated that Fyn directly phosphorylates CD147 at Y140 and Y183. Two phosphospecific antibodies against Y140 and Y183 were developed to validate the phosphorylation of CD147 by Fyn. Moreover, the CD147-FF (Y140F/Y183F) mutation impaired the interaction between CD147 and GnT-V, leading to decreased CD147 glycosylation and membrane recruitment. In addition, CD147-FF significantly blocked MMP-9 expression as well as cell migration. Moreover, we found that Fyn is overexpressed in clinical melanoma tissues as well as in melanoma cell lines. Knockdown of Fyn expression markedly attenuated the malignant phenotype of melanoma cells in vitro and in vivo through downregulation of CD147 phosphorylation, indicating that Fyn/CD147 is a potential target molecule in melanoma treatment. Finally, through virtual screening, we identified amodiaquine as a potential inhibitor targeting the Fyn/CD147 axis. Amodiaquine treatment dramatically inhibited the phosphorylation of CD147 by Fyn, thus attenuating melanoma cell growth and invasion in vitro and in vivo, suggesting that amodiaquine is a promising inhibitor for melanoma treatment.


Assuntos
Basigina/metabolismo , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Transdução de Sinais , Substituição de Aminoácidos , Basigina/genética , Linhagem Celular Tumoral , Glicosilação , Humanos , Metaloproteinase 9 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/genética , Melanoma/genética , Melanoma/patologia , Mutação de Sentido Incorreto , Metástase Neoplásica , Fosforilação/genética , Proteínas Proto-Oncogênicas c-fyn/genética
9.
Dermatology ; 235(5): 380-389, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269494

RESUMO

Autophagy, or self-eating, is an evolutionarily conserved process in which cytosol and organelles are sequestered within double-membrane vesicles that deliver the contents to the lysosome/vacuole for the degradation and recycling of cytoplasmic components in eukaryotes. It is well recognized that autophagy plays an important role in maintaining cellular homeostasis under physiological and pathophysiological con-ditions and the upregulation of autophagy may serve as an adaptive process to provide nutrients and energy when under stresses. Recently, studies have illustrated that autophagy is intricately related to skin diseases. This review provides a brief synopsis of the process of autophagy and aims to elucidate the roles of autophagy in different skin diseases and to highlight the need for increased research in the field.


Assuntos
Autofagia/fisiologia , Dermatopatias/fisiopatologia , Humanos
10.
Med Oncol ; 36(6): 50, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31037368

RESUMO

Skin cancer can be classified as cutaneous malignant melanoma, basal cell carcinoma, and squamous cell carcinoma. Due to the high level of morbidity and mortality, skin cancer has become a global public health issue worldwide while the pathogenesis of skin cancer is still unclear. It is necessary to further identify the pathogenesis of skin cancer and find candidate targets to diagnose and treat skin cancer. A variety of factors are known to be associated with skin cancer including N-glycosylation, which partly explained the malignant behaviors of skin cancer. In this review, we retrieved databases such as PubMed and Web of Science to elucidate its relationship between glycosylation and skin cancer. We summarized some key glycosyltransferases and proteins during the process of N-glycosylation related to skin cancer, which was helpful to unmask the additional mechanism of skin cancer and find some novel targets of skin cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Glicoproteínas/metabolismo , Neoplasias Cutâneas/metabolismo , Carcinoma Basocelular/enzimologia , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Glicosilação , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Humanos , Melanoma/enzimologia , Melanoma/metabolismo , Melanoma/patologia , Transdução de Sinais , Neoplasias Cutâneas/enzimologia , Neoplasias Cutâneas/patologia
11.
Oncogenesis ; 7(2): 17, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29463844

RESUMO

TRAF6, a well-known adapter molecule, plays pivotal role in TLR/IL-1R associated signaling pathway. Although TRAF6 has been shown to have oncogenic activity in various malignant tumors, the details remain unclear. In this study, we demonstrated that TRAF6 facilitates Ras (G12V) and EGF-induced cellular transformation through EGFR. Silencing of TRAF6 expression significantly downregulated AP-1 activity, as well as MMP-2,9 expression after EGF stimulation. Furthermore, we found that TRAF6 plays an essential role in cutaneous squamous cell carcinoma (cSCC) malignant phenotypes, affecting cell growth and migration. CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is over-expressed in tumors and induces tumorigenesis. Our results showed that CD147 formed complex with EGFR and TRAF6. Knockdown of TRAF6 disrupted the CD147-EGFR complex, thereby inducing EGFR endocytosis. Therefore, TRAF6 might be a novel molecular target for cSCC prevention or therapy.

12.
Curr Pharm Des ; 23(29): 4410-4421, 2017 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-28699528

RESUMO

CD147 is a membrane protein belonging to immunoglobulin superfamily and expressed in the cell membrane, which is also named with an extracellular matrix metalloproteinase inducer (EMMPRIN) because this molecule induces adjacent fibroblasts or tumor cells to produce MMPs, facilitating tumor cells migration and invasion. Accumulating evidences have shown that CD147 is over-expressed in various tumors, including melanoma, liver cancer, and lung cancer, and orchestrates tumor cell proliferation, apoptosis, invasion and metastasis, multidrug resistance and glycolysis through critical molecules such as MMPs, MCTs, Caveolin-1, and VEGF. In this review, we focus on understanding the characteristics of CD147 in various biological functions, including physiological and pathological processes. Recent novel studies have shown that CD147 is not only a potential diagnostic marker but also a therapeutic target for chemotherapy or the diagnosis of cancer.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Membrana/metabolismo , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Humanos , Terapia de Alvo Molecular
13.
Bioresour Technol ; 143: 461-6, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23831745

RESUMO

The performance response of eight vertical flow constructed wetlands (VFCWs) to different influent COD/N ratios and intermittent aeration in domestic wastewater treatment was investigated. Almost complete nitrification was obtained by intermittent aeration, which well developed alternate anaerobic and aerobic conditions for nitrification and denitrification. Sufficient carbon source supply resulted from influent COD/N ratio of 10 simultaneously obtained high removals of COD (96%), ammonia nitrogen (99%) and total nitrogen (90%) in intermittently aerated VFCWs. In all non-aerated VFCWs, poor nitrification was observed due to oxygen deficiency whilst high COD/N ratios further led to lower COD and nitrogen removal efficiency. The results suggest that intermittent aeration combined with high influent COD/N ratios could achieve high nitrogen removal in VFCWs.


Assuntos
Ar , Análise da Demanda Biológica de Oxigênio , Nitrogênio/química , Nitrogênio/isolamento & purificação , Áreas Alagadas , Aerobiose , Anaerobiose
14.
Bioresour Technol ; 141: 117-22, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23561957

RESUMO

In this study, an intermittent-aerated subsurface flow constructed wetland (SFCW) A was set up to assess its performance in decentralized rural sewage treatment. A conventional SFCW B and a subsurface wastewater infiltration system (SWIS C) were also constructed for comparison. Alternate anaerobic and aerobic conditions were well developed by intermittent aeration. High removal of organic pollutants (29.3 gm(-2) d(-1)), ammonium nitrogen (3.5 gm(-2) d(-1)) and total nitrogen (3.3 gm(-2) d(-1)) were obtained simultaneously in SFCW A compared with SFCW B and SWIS C. Fluorescence in situ hybridization analysis proved that the intermittent aeration obviously enhanced the growth of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) in SFCW A. These results suggest that intermittent aeration strategy is reliable to enhance the performance of SFCWs in decentralized rural sewage treatment.


Assuntos
Nitrogênio/química , Purificação da Água/métodos , Áreas Alagadas , Amônia/metabolismo , Análise da Demanda Biológica de Oxigênio , Hibridização in Situ Fluorescente , Nitrogênio/análise , Oxirredução , Oxigênio/química , Projetos Piloto , Esgotos/química , Movimentos da Água
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...