RESUMO
Lung cancer is the leading cause of cancer-related deaths， and standard treatments for lung cancer， including surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy， have shown significant clinical effects. However， current available treatment strategies are still unable to cure the disease. Since the majority of lung cancer patients are diagnosed at an advanced stage， surgical options are often lost， and the primary approach is typically a combination of radiotherapy and chemotherapy. However， the adverse reactions associated with these treatments limit their effectiveness and application， and the damage caused to normal tissues is often more severe than that inflicted on the tumor. Currently， traditional Chinese medicine （TCM） has been used as part of combination therapy for cancer treatment due to its unique system of syndrome differentiation， flexible compatibility， and safety and efficacy. TCM prescriptions and single drugs with multiple components and targets can simultaneously regulate multiple pathways. As reported， among numerous pathways involved in the regulation of lung cancer， the nuclear factor-κB （NF-κB） signaling pathway plays a key role in inducing cell transcription and is one of the main pathways involved in the occurrence and development of lung cancer. It can specifically regulate inflammatory responses， cell proliferation， apoptosis， invasion and metastasis， angiogenesis， and multidrug resistance in lung cancer. TCM prescriptions and single drugs can inhibit lung cancer cell proliferation， invasion， and metastasis， induce apoptosis and autophagy in lung cancer cells， suppress angiogenesis， regulate immune function， and treat multidrug resistance by regulating the NF-κB signaling pathway. Therefore， they play a role in intervening in lung cancer. However， there is currently a lack of systematic literature research that comprehensively summarizes and elucidates these aspects in China and abroad. Therefore， it is important to provide a systematic elucidation of the mechanism underlying the regulation of the NF-κB signaling pathway in lung cancer and review TCM interventions in lung cancer based on the NF-κB signaling pathway. This study is expected to provide references for the clinical application of lung cancer therapeutic drugs and the development of new drugs.
RESUMO
OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a consanguineous Chinese pedigree affected with Congenital coagulation factor XII (XII) deficiency.@*METHODS@#Members of the pedigree who had visited Ruian People's Hospital on July 12, 2021 were selected as the study subjects. Clinical data of the pedigree were reviewed. Peripheral venous blood samples were taken from the subjects. Blood coagulation index and genetic testing were carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#This pedigree has comprised 6 individuals from 3 generations, including the proband, his father, mother, wife, sister and son. The proband was a 51-year-old male with kidney stones. Blood coagulation test showed that his activated partial thromboplastin time (APTT) was significantly prolonged, whilst the FXII activity (FXII:C) and FXII antigen (FXII:Ag) were extremely reduced. The FXII:C and FXII:Ag of proband's father, mother, sister and son have all reduced to about half of the lower limit of reference range. Genetic testing revealed that the proband has harbored homozygous missense variant of c.1A>G (p.Arg2Tyr) of the start codon in exon 1 of the F12 gene. Sanger sequencing confirmed that his father, mother, sister and son were all heterozygous for the variant, whilst his wife was of the wild type. By bioinformatic analysis, the variant has not been included in the HGMD database. Prediction with SIFT online software suggested the variant is harmful. Simulation with Swiss-Pbd Viewer v4.0.1 software suggested that the variant has a great impact on the structure of FXII protein. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic.@*CONCLUSION@#The c.1A>G (p.Arg2Tyr) variant of the F12 gene probably underlay the Congenital FXII deficiency in this pedigree. Above finding has further expanded the spectrum of F12 gene variants and provided a reference for clinical diagnosis and genetic counseling for this pedigree.