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OBJECTIVE: The companion diagnosis for olaparib, a poly (ADP-ribose) polymerase inhibitor for prostate cancer, aims to detect BRCA1/2 gene variants. In clinical practice, the frequency of germline BRCA1/2 variants in patients receiving castration-resistant prostate cancer treatment is unknown. We aimed to evaluate the prevalence of germline BRCA1/2 variants and their relationship to prognosis and treatment efficacy in castration-resistant prostate cancer. METHODS: Between June 2021 and 2023, 92 patients receiving castration-resistant prostate cancer treatment were examined for germline BRCA1/2 variants using BRACAnalysis CDx®. Furthermore, the associations between BRCA1/2 pathogenic variants and clinical outcomes were assessed. RESULTS: Of the 92 patients referred for genetic testing, 6 (6.5%) carried germline pathogenic variants in BRCA1/2. The BRCA2 variant was the most frequent (n = 5), followed by BRCA1 variant (n = 1). Among the five variants in BRCA2, the p.Asp427Thrfs*3 variant was identified for the first time in prostate cancer. Overall survival from castration-resistant prostate cancer for patients with BRCA1/2 variants was significantly shorter than for patients without BRCA1/2 variants (P = 0.043). Progression-free survival of androgen receptor signaling inhibitors for patients with BRCA1/2 variants was significantly shorter than for those without (P = 0.003). Progression-free survival of taxane chemotherapy was significantly shorter in patients with BRCA1/2 variants than in those without (P = 0.0149). CONCLUSIONS: In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer.
Assuntos
Antineoplásicos , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Proteína BRCA1/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Proteína BRCA2/genética , Receptores Androgênicos/uso terapêutico , Prevalência , Japão/epidemiologia , Antineoplásicos/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Taxoides/uso terapêutico , Células GerminativasRESUMO
Weed is a major biological factor causing declines in crop yield. However, widespread herbicide application and indiscriminate weeding with soil disturbance are of great concern because of their environmental impacts. Site-specific weed management (SSWM) refers to a weed management strategy for digital agriculture that results in low energy loss. Deep learning is crucial for developing SSWM, as it distinguishes crops from weeds and identifies weed species. However, this technique requires substantial annotated data, which necessitates expertise in weed science and agronomy. In this study, we present a channel attention mechanism-driven generative adversarial network (CA-GAN) that can generate realistic synthetic weed data. The performance of the model was evaluated using two datasets: the public segmented Plant Seedling Dataset (sPSD), featuring nine common broadleaf weeds from arable land, and the Institute for Sustainable Agro-ecosystem Services (ISAS) dataset, which includes five common summer weeds in Japan. Consequently, the synthetic dataset generated by the proposed CA-GAN obtained an 82.63% recognition accuracy on the sPSD and 93.46% on the ISAS dataset. The Fréchet inception distance (FID) score test measures the similarity between a synthetic and real dataset, and it has been shown to correlate well with human judgments of the quality of synthetic samples. The synthetic dataset achieved a low FID score (20.95 on the sPSD and 24.31 on the ISAS dataset). Overall, the experimental results demonstrated that the proposed method outperformed previous state-of-the-art GAN models in terms of image quality, diversity, and discriminability, making it a promising approach for synthetic agricultural data generation.
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The prognosis for patients who achieve a pathologic complete response in bladder cancer is excellent, but the association between their prognosis and the tumor microenvironment is unclear. We investigated the tumor immune microenvironment of those with pathological complete response after platinum-based neoadjuvant chemotherapy for cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. Our retrospective study included 12 patients with pathological complete response who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. We assessed the density of several immune cell types in pretreatment and posttreatment tissues via multiplex fluorescence immunohistochemical analysis. The median age was 67 years; 10 patients were male. Nine (75%) and 3 (25%) patients were cT2 and cT3, respectively. The 5-year progression-free and overall survivals were 90% and 100%, respectively. The densities of regulatory T cells (Treg; CD3+CD4+FoxP3+ cell) were significantly decreased and almost disappeared in the tumor microenvironment of posttreatment tissue compared with pretreatment tissue. Other immune cells, such as effector T cells or M2 macrophages, were not significantly changed between posttreatment and pretreatment tissues. In pathological complete response, Tregs in the tumor immune microenvironment were significantly decreased after platinum-based chemotherapy for muscle-invasive bladder cancer. The temporary arresting of immune response in the tumor microenvironment may reflect a favorable prognosis due to the decrease of Tregs with tumor shrinkage and improve the host tumor immune response.
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Linfócitos T Reguladores , Neoplasias da Bexiga Urinária , Humanos , Masculino , Idoso , Feminino , Linfócitos T Reguladores/patologia , Estudos Retrospectivos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/patologia , Cistectomia , Resposta Patológica Completa , Imunidade , Músculos/patologia , Invasividade Neoplásica/patologia , Microambiente TumoralRESUMO
This is the first case report in which computed tomography (CT) images of a patient with emphysematous pyelonephritis (EPN) capture the time course of emphysema from onset to resolution through conservative treatment. To re-evaluate EPN, including refractory urinary tract infections, CT scans after 72 h might be helpful.