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1.
Biochemistry ; 58(18): 2293-2296, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31021072

RESUMO

Blocking the PD-L1/PD-1 interaction with an antibody produces a durable response in patients with diverse advanced cancers. However, it remains elusive on whether the engagement of PD-L1 to PD-1 leads to tumor-intrinsic signaling. In this study, we aim to explore novel protein substrates participating in transducing this tumor-intrinsic PD-L1 signaling. To this end, we performed a BioID (proximity-dependent biotin identification) assay, in which we fused PD-L1 to BirA* (a promiscuous mutant of bacterial biotin ligase BirA) and overexpressed it in the lung adenocarcinoma A549 cell line. Through streptavidin affinity capture and mass spectrometry analysis, we identified 57 candidate proteins including 18 PD-L1/PD-1-interaction-dependent neighbors. In addition to this, 9 out of 57 candidates were involved in the EGFR signaling pathway, which is known to play a critical role in tumorigenesis and multiple therapeutic resistances of lung cancer. This study will provide a new insight in understanding tumor-intrinsic PD-L1-signaling effectors of lung cancer.


Assuntos
Adenocarcinoma/metabolismo , Antígeno B7-H1/metabolismo , Biotina/metabolismo , Neoplasias Pulmonares/metabolismo , Transdução de Sinais , Células A549 , Adenocarcinoma/patologia , Carbono-Nitrogênio Ligases/genética , Carbono-Nitrogênio Ligases/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Espectrometria de Massas , Mutação , Receptor de Morte Celular Programada 1/metabolismo , Ligação Proteica , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo
2.
Int Immunopharmacol ; 56: 143-147, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29414644

RESUMO

OBJECTIVES: This retrospective study aimed to investigate the prognostic value of pre-treatment platelet-to-lymphocyte ratio (PLR), which is an inflammatory indicator, in patients with melanoma. METHODS: Patients in this retrospective analysis were admitted between January 1, 2010 and December 31, 2015 in Henan Cancer Hospital. Receiver operating characteristic (ROC) curve was performed the optimal cut-off value for PLR. The 140 patients were divided into two groups: high PLR group and low PLR group. The relationship between PLR and overall survival (OS) was analyzed. The Kaplan-Meier and Log rank tests were used for univariate survival analysis and Cox proportional hazards regression model for multivariate analysis. RESULTS: The optimal cut-off value of PLR determined by ROC curve was 120.15. Univariate and Cox multivariate survival analysis all showed that PLR and clinical stage were factors affecting OS in melanoma patients (P < 0.05). The overall median OS was 21.0 months (95% confidence interval (CI): 18.1-23.9), for 17.0 months in the high PLR group, and 34.0 months in the low PLR group (hazard ratio: 0.436, 95% CI: 0.291-0.652, P < 0.001), respectively. Clinical subgroup analysis showed that PLR was a risk factor in patients with stage II, III, and IV disease (P < 0.05). CONCLUSION: The elevated PLR was an independent prognostic predictor for OS in patients with melanoma.


Assuntos
Células Sanguíneas/imunologia , Plaquetas/imunologia , Linfócitos/imunologia , Melanoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Contagem de Células , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Padrões de Referência , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
3.
Onco Targets Ther ; 10: 4687-4690, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29026316

RESUMO

Endometrial cancer is the most prevalent gynecological malignancy in the USA, and its treatment involves surgery, chemotherapy, and radiotherapy. Cytokine-induced killer (CIK) cell-based treatments have shown antitumor activity against several solid tumors. However, to the best of our knowledge, there are no reports yet of CIK immunotherapy in the treatment of endometrial cancer, and consequently, little is known about its efficacy and safety. Here, we report a case of an endometrial cancer patient receiving a combination treatment with CIK cells immunotherapy and chemotherapy. Assessment for clinical features was carried out after every two cycles of CIK immunotherapy and chemotherapy. No severe toxicity was observed after infusion of CIK cells. After 4 cycles of treatment, the patient achieved complete response and showed elevated Karnofsky Performance Status scores with an overall survival time of 13.6 months. The combination therapy improved the quality of life and prolonged patient survival time, which suggested that CIK cell therapy might be a potentially beneficial option for endometrial cancer.

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