RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A Case Report of Advanced Pulmonary Adenocarcinoma in a Dog Managed with Chemotherapy and Cytokine-Based Immunotherapy.
A Case Report of Advanced Pulmonary Adenocarcinoma in a Dog Managed with Chemotherapy and Cytokine-Based Immunotherapy.
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犬肺腺癌,尤其是晚期,预后较差且治疗选择有限。激活自然杀伤(NK)细胞的免疫治疗方法可能提供额外的临床获益。本报告描述了一只9岁已绝育雄性威尔士柯基犬患有晚期肺腺癌,接受化疗联合细胞因子为基础的NK细胞激活免疫治疗后的临床反应和生存结局。该犬表现为间歇性咳嗽、呼吸困难和发绀。影像学显示一个大的肺部肿块,疑似淋巴结转移(III期,T4N1M0)。细胞学检查确诊为肺腺癌。偶然发现一个与原发性肺肿瘤无关的脾脏髓脂肪瘤,并手术切除。治疗包括以长春瑞滨为基础的化疗和以细胞因子为基础的免疫治疗,使用白细胞介素(IL)-15、IL-12、IL-23和硒。因不良事件暂时停药后,给予细胞因子单药治疗,随后在进展为IV期并出现对侧肺转移时恢复联合治疗。影像学随访显示单药治疗期间疾病稳定,联合治疗期间生存期延长。该犬存活241天,包括IV期诊断后143天,超过了先前报道的结局。尽管未直接评估NK细胞功能,但这些发现提示,以细胞因子为基础的NK细胞免疫治疗与化疗联合时,可能有助于晚期犬肺腺癌的疾病控制和生存期延长。
Pulmonary adenocarcinoma in dogs, particularly in advanced stages, carries a poor prognosis with limited therapeutic options. Immunotherapeutic approaches that activate natural killer (NK) cells may provide additional clinical benefit. This report describes the clinical response and survival outcome of a 9-year-old neutered male Welsh Corgi with late-stage pulmonary adenocarcinoma treated with combined chemotherapy and cytokine-based NK cell-activating immunotherapy. The dog presented with intermittent coughing, dyspnea, and cyanosis. Imaging revealed a large pulmonary mass with suspected nodal metastasis (stage III, T4N1M0). Cytology confirmed pulmonary adenocarcinoma. A splenic myelolipoma, unrelated to the primary pulmonary tumor, was identified incidentally and surgically removed.
Treatment included vinorelbine-based chemotherapy and cytokine-based immunotherapy using interleukin (IL)-15, IL-12, IL-23, and selenium. After temporary discontinuation due to adverse events, cytokine monotherapy was administered, followed by resumed combination therapy upon stage IV progression with contralateral lung metastasis. Radiographic follow-up demonstrated disease stabilization during monotherapy and prolonged survival with combination therapy.
The dog survived for 241 days, including 143 days after stage IV diagnosis, exceeding previously reported outcomes. Although NK cell function was not directly evaluated, these findings raise the possibility that cytokine-based NK cell immunotherapy, when combined with chemotherapy, could have contributed to disease control and prolonged survival in advanced canine pulmonary adenocarcinoma.
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