RESUMEN
PURPOSE: Intraductal carcinoma of the prostate (IDC-P) is a histological subtype that differs from conventional acinar adenocarcinoma in terms of its origin, appearance, and pathological features. For IDC-P, there is currently no recognized best course of action, and its prognosis is unclear. The goal of this study is to analyze independent prognostic factors in IDC-P patients and to develop and validate a nomogram to predict overall survival (OS) and cancer-specific survival (CSS). METHODS: Clinical data for IDC-P patients were collected from the Surveillance, Epidemiology, and End Results database. To identify the independent variables influencing prognosis, multivariate Cox regression analysis was performed. A nomogram model was created utilizing these variables after comparing the variations in OS and CSS among various subgroups using KaplanâMeier curves. Internal validation of the nomograms was verified using the bootstrap resampling method. RESULTS: The study included 280 IDC-P patients in total. Marital status, summary stage, grade, and the presence of lung metastases were significant factors impacting OS, and CSS was significantly influenced by marital status, summary stage, AJCC stage, the presence of lung metastases, the presence of bone metastases, and PSA according to univariate and multivariate Cox regression models (P < 0.05). Nomogram models were created to estimate OS and CSS using these parameters. The OS prediction model's C-index was 0.744, whereas the CSS prediction model's C-index was 0.831. CONCLUSION: We developed and verified nomogram models for the prediction of 1-, 3-, and 5-year OS and CSS in patients with IDC-P. These nomograms serve as a resource for evaluating patient prognosis, therapy, and diagnosis, ultimately improving clinical decision-making accuracy.
Asunto(s)
Carcinoma Intraductal no Infiltrante , Neoplasias Pulmonares , Neoplasias de la Próstata , Masculino , Humanos , Próstata , Nomogramas , Pronóstico , Programa de VERFRESUMEN
Herpes zoster (HZ) is caused by the reactivation of latent varicella-zoster virus (VZV) from the sensory ganglia due to aging or immunosuppression. Glycoprotein E (gE) is a widely used vaccine antigen for specific humoral and cellular immune responses. Immediate early protein 63 (IE63) is expressed during latency, suggesting that it is a potential antigen against HZ reactivation. In this study, HZ DNA vaccines encoding gE, IE63, IE63-2A-gE (where 2A is a self-cleaving sequence), or IE63-linker-gE were developed and investigated for immunogenicity in mice. The results showed that each HZ DNA vaccine induced VZV-specific antibody production. The neutralizing antibody titer elicited by IE63-2A-gE was comparable to that elicited by gE or live attenuated HZ vaccine (LAV). IE63-2A-gE-induced gE or IE63-specific INF-γ+ T cell frequencies in splenocytes were comparable to those of LAV. Furthermore, IE63-2A-gE, gE, or IE63 led to a significant increase in IFN-γ (IE63 stimulation) and IL-2 (gE stimulation) secretion compared to LAV, showing a Th1-biased immune response. Moreover, IE63-2A-gE and gE induced cytotoxic activity of CD8+ T cells compared to that of LAV. This study elucidates that the IE63-2A-gE DNA vaccine can induce both humoral and cell-mediated immune responses, which provides a candidate for the development of an HZ vaccine.
Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster , Proteínas Inmediatas-Precoces , Vacunas de ADN , Animales , Anticuerpos Antivirales , Linfocitos T CD8-positivos , Glicoproteínas , Herpesvirus Humano 3/genética , Proteínas Inmediatas-Precoces/genética , Ratones , Proteínas del Envoltorio Viral/genéticaRESUMEN
Avian-origin influenza A (H7N9) viruses emerged as human pathogens in China in early 2013 and have killed >100 persons. Influenza vaccines are mainly manufactured using egg-based technology which could not meet the surging demand during influenza pandemics. In this study, we evaluated cell-based influenza H7N9 vaccines in ferrets. An egg-derived influenza H7N9 reassortant vaccine virus was adapted in MDCK cells. Influenza H7N9 whole virus vaccine antigen was manufactured using a microcarrier-based culture system. Immunogenicity and protection of the vaccine candidates with three different formulations (300 µg aluminum hydroxide, 1.5 µg HA, and 1.5 µg HA plus 300 µg aluminum hydroxide) were evaluated in ferrets. In ferrets receiving two doses of vaccination, geometric mean titers of hemagglutination (HA) inhibition and neutralizing antibodies were <10 and <40 for the control group (adjuvant only), 17 and 80 for the unadjuvanted (HA only) group, and 190 and 640 for the adjuvanted group (HA plus adjuvant), respectively. After challenge with wild-type influenza H7N9 viruses, virus titers in respiratory tracts of the adjuvanted group were significantly lower than that in the control, and unadjuvanted groups. MDCK cell-derived influenza H7N9 whole virus vaccine candidate is immunogenic and protective in ferrets and clinical development is highly warranted.