RESUMEN
BACKGROUNDS: The role of cytoreductive radical prostatectomy (cRP) for bone-metastatic prostate cancer (bmPCa) remains controversial. We aimed to figure out whether cRP and lymph node dissection (LND) can benefit bmPCa. METHODS: 11,271 PCa patients with bone metastatic burden from 2010 to 2019 were identified using SEER-Medicare. Overall survival (OS) and cancer-specific survival (CSS) rates were visualized using Kaplan-Meier plots. Multivariable Cox regression analyses were constructed to examine the effects of cRP and LND on survival, after stratifying to age, prostate specific antigen (PSA), clinical stages, Gleason score, metastatic burden, radiotherapy, and chemotherapy status. RESULTS: 317 PCa patients underwent cRP and cRP was increasingly performed for bmPCa from 2010 (2.2%) to 2019 (3.0%) (p < 0.05). In multi analyses, cRP was predisposed to a better OS or CSS in patients with age < 75, PSA < 98 ng/mL, bone-only metastatic sites or patients not receiving chemotherapy (all p < 0.05). For the patients undergoing cRP, LND especially extended LND was associated with a better OS or CSS (all p < 0.05). CONCLUSIONS: cRP might benefit OS or CSS in young patients with low PSA and bone-only metastatic sites not receiving chemotherapy. And a clear OS or CSS benefit of LND especially extended LND was observed in patients undergoing cRP.
Asunto(s)
Neoplasias Óseas , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Estados Unidos , Antígeno Prostático Específico , Ganglios Linfáticos/patología , Procedimientos Quirúrgicos de Citorreducción , Resultado del Tratamiento , Medicare , Escisión del Ganglio Linfático , Neoplasias de la Próstata/patología , Prostatectomía/efectos adversos , Neoplasias Óseas/secundarioRESUMEN
Prostate cancer is a heterogeneous disease and optimum gene targeting treatment is often impermissible. We aim to determine the intratumoral genomic heterogeneity of prostate cancer and explore candidate genes for targeted therapy. Exome sequencing was performed on 37 samples from 16 patients with prostate cancer. Somatic variant analysis, copy number variant (CNV) analysis, clonal evolution analysis and variant spectrum analysis were used to study the intratumoral genomic heterogeneity and genetic characteristics of metastatic prostate cancer. Our study confirmed the high intratumoral genetic heterogeneity of prostate cancer in many aspects, including number of shared variants, tumor mutation burden (TMB), variant genes, CNV burden, weighted genome instability index (wGII), CNV profiles, clonal evolutionary process, variant spectrum and mutational signatures. Moreover, we identified several common genetic characteristics of prostate cancer. Alterations of DNA damage repair genes, RTK/RAS pathway associated gene RASGRF1 and autophagy gene EPG5 may be involved in tumorigenesis in prostate cancer. CNV burden and DNA damage repair (DDR) genes may be associated with metastasis of prostate cancer.
Asunto(s)
Biomarcadores de Tumor/genética , Heterogeneidad Genética , Neoplasias de la Próstata/genética , Anciano , Anciano de 80 o más Años , Autofagia/genética , Proteínas Relacionadas con la Autofagia/genética , Evolución Clonal , Variaciones en el Número de Copia de ADN , Reparación del ADN/genética , Humanos , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo de Nucleótido Simple , Próstata/patología , Próstata/cirugía , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Proteínas de Transporte Vesicular/genética , Secuenciación del Exoma , ras-GRF1/genéticaRESUMEN
In order to study the in vitro culture and expansion of bone marrow mesenchymal stem cells in rats (rMSCs) and the possibility of rMSCs differentiation into retinal neural cells, the bone marrow-derived cells in SD rats were isolated and cultured in vitro. The retinal neural cells in SD rats were cultured and the supernatants were collected to prepare conditioned medium. The cultured rMSCs were induced to differentiate by two steps. Immunofluorescence method and anti-nestin, anti-NeuN, anti-GFAP and anti-Thy1.1 antibodies were used to identify the cells derived from the rMSCs. The results showed that the in vitro cultured rMSCs grew well and expanded quickly. After induction with two conditioned media, rMSCs was induced to differentiate into neural progenitor cells, then into retinal neural-like cells which were positive for nestin, NeuN, GFAP and Thy1.1 detected by fluorescence method. The findings suggested that rMSCs could be culture and expanded in vitro, and induced to differentiate into retinal neural-like cells.