RESUMO
Chimeric antigen receptor T (CAR-T) cell therapy has exhibited a substantial clinical response in hematological malignancies, including B-cell leukemia, lymphoma, and multiple myeloma. Therefore, the feasibility of using CAR-T cells to treat solid tumors is actively evaluated. Currently, multiple basic research projects and clinical trials are being conducted to treat lung cancer with CAR-T cell therapy. Although numerous advances in CAR-T cell therapy have been made in hematological tumors, the technology still entails considerable challenges in treating lung cancer, such as on-target, of-tumor toxicity, paucity of tumor-specific antigen targets, T cell exhaustion in the tumor microenvironment, and low infiltration level of immune cells into solid tumor niches, which are even more complicated than their application in hematological tumors. Thus, progress in the scientific understanding of tumor immunology and improvements in the manufacture of cell products are advancing the clinical translation of these important cellular immunotherapies. This review focused on the latest research progress of CAR-T cell therapy in lung cancer treatment and for the first time, demonstrated the underlying challenges and future engineering strategies for the clinical application of CAR-T cell therapy against lung cancer.
Assuntos
Imunoterapia Adotiva/métodos , Neoplasias Pulmonares/terapia , Animais , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais , Técnicas de Cultura de Células , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Gerenciamento Clínico , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Engenharia Genética , Humanos , Imunomodulação , Imunoterapia Adotiva/efeitos adversos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo , Resultado do TratamentoRESUMO
Parkinson's disease (PD) is a disease that involves brain damage and is associated with neuroinflammation, mitochondrial damage, and cell aging. However, the pathogenic mechanism of PD is still unknown. Sequencing data and proteomic data can describe the fluctuation of molecular abundance in diseases at the mRNA level and protein level, respectively. In order to explore new targets in the pathogenesis of PD, the study analyzed molecular changes from the database by combining transcriptomic and proteomic analysis. Differentially expressed genes and differentially abundant proteins were summarized and analyzed. Enrichment and cluster analysis emphasized the importance of neurotransmitter release, mitochondrial damage, and vesicle transport. The molecular network revealed a subnetwork of 9 molecules related to SCNA and TH and revealed hub gene with differential expression at both mRNA and protein levels. It found that ACHE and CADPS could be used as new targets in PD, emphasizing that impaired nerve signal transmission and vesicle transport affect the pathogenesis of PD. Our research emphasized that the joint analysis and verification of transcriptomics and proteomics were devoted to understanding the comprehensive views and mechanism of pathogenesis in PD.
Assuntos
Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Proteínas/genética , Proteínas/metabolismo , Substância Negra/metabolismo , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Análise por Conglomerados , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Doença de Parkinson/patologia , RNA Mensageiro/genética , Substância Negra/patologia , Transcriptoma , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismoRESUMO
OBJECTIVE: To summarize the clinical characteristics and outcome of patients with long-QT syndrome (LQTs) accompanied with torsade de pointes. METHODS: Thirty-two eligible patients were included in this study. Clinical and electrocardiographic data were analyzed and telephone or out-patient follow-up were made in all patients. RESULTS: There were 15 patients with inherited LQTs (h-LQTs) and 17 patients with acquired LQTs (a-LQTs). There are more women (n = 24) than men (n = 8). ß blockers, potassium and magnesium supplement were the basic therapy for h-LQTs patients, bivent pacemaker was implanted in 2 patients and implantable cardioverter defibrillator was implanted in 5 patients. Ventricular tachyarrhythmias and syncope occurred in 4 patients during (39.4 ± 25.1) months follow-up. In 17 a-LQTs patients, one patient with dilated cardiomyopathy died suddenly and another patient with implanted cardioverter defibrillator experienced one ventricular tachycardia during (30.9 ± 13.3) months follow-up. CONCLUSIONS: The prognosis in h-LQTs and a-LQTs patients with structure heart disease is poor. ICD or CRT-D therapy is suggestive for a-LQTs patients with structure heart disease.