RESUMEN
Tyrosine kinase inhibitors (TKI) significantly reduce the risk of recurrence and metastasis and prolong survival in patients with gastrointestinal stromal tumors (GIST), but drug resistance is often inevitable. Immunotherapy has been proven effective in multiple solid tumors, but the efficacy in GIST is unclear. The efficacy of immunotherapy depends on the tumor microenvironment (TME). Tumor-infiltrating immune cells and immune checkpoints are important components of TME, which not only participate in the regulation of tumor immune response but are also the key target of immunotherapy. A comprehensive analysis of them can clarify the mechanism of tumor immune escape. This review found that there are abundant tumor-infiltrating immune cells in GIST, which play an important role in tumor immune surveillance and escape. Although early clinical studies have shown that patients with GIST have a good tolerance to immunotherapy, the curative effect is not satisfactory. Therefore, how to select the responders of immunotherapy and coordinate the relationship between immunotherapy and TKIs is the key issue to be explored. At the same time, the gradual deepening of basic research and large sample prospective clinical trials will certainly provide more strategies for the application of immunotherapy in GIST.
Asunto(s)
Humanos , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Estudios Prospectivos , Inmunoterapia/métodos , Microambiente Tumoral , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
To understand the mutational characteristics of ATP7B gene of hepatolenticular degeneration in Xinjiang region. 24 cases were diagnosed as hepatolenticular degeneration and the exon of ATP7B gene was detected in some of their siblings and parents. A total of 45 ATP7B gene mutations (93.75%) were detected in 24 cases, of which 14 cases were homozygous mutations or compound heterozygous mutations, six cases were heterozygous mutations and four cases were no mutations. A total of 24 gene mutations and 14 SNPS were detected, including 8 new mutations: c.251C > A, c.121A > c, c.2945C > A, c.2194C > T, c.2947T > c, c.3626T > A, c.3662_3664del, c.3557G > T. The most common mutations were c.2621C > T (p.A874V) [16.7% (4/24)] and c.2333G > T (p.R778L) [12.5% (3/24)]. A total of 4 cases were diagnosed as pre-symptomatic. In this study, the most common mutation in the ATP7B gene is A874V. The most common genetic mutations in Han and Uyghur patients were different. The most common mutation in Han and Uyghur patients is R778L and A874V. Exon 11 is the gene mutations hot spot for patients with hepatolenticular degeneration in Xinjiang region, and is one of the priority exons to be detected when screening patients with suspected hepatolenticular degeneration.
RESUMEN
Avian Pasteurella multocida is an agent of fowl cholera. The protective effect achieved through orthodox vaccines is not ideal. The research on novel vaccines against avian Pasteurella multocida is imperative. In this study, the genes encoding outer membrane protein H and A [OmpH and OmpA] were cloned into the eukaryotic expression vector pcDNA3.1[+] and the recombinant plasmids, namely DNA vaccines [pOMPH and pOMPA] were obtained. Five groups of chickens [n=20 per group] were intramuscularly injected with the two recombinant plasmids, attenuated live vaccine, control vector pcDNA[3.1[+]] and PBS, respectively. The immune responses and protective efficacy were evaluated after immunization by serological and challenging. A significant increase in serum antibody levels was observed in chickens vaccinated with the attenuated live vaccine and the two DNA vaccines. Additionally, the lymphocyte proliferation [SI values] were higher in chickens immunized with the attenuated live vaccine and the two DNA vaccines than in those vaccinated with pcDNA[3.1[+]] and PBS [P<0.05]. Furthermore, the two DNA vaccines provided partial protection to the vaccinated chickens; however, the protective efficacy was inferior to that provided by the attenuated live vaccine