不可逆电穿孔增强 CAR-T 细胞对实体瘤的浸润与选择性癌细胞裂解
Irreversible Electroporation Enhances Solid Tumor Infiltration and Selective Cancer Cell Lysis by CAR T Cells.
通过利用一种双用途转化策略——直接的癌细胞靶向细胞毒性和增强的CAR T细胞浸润——sIRE能够减轻肿瘤负荷,同时保持并增强CAR T细胞功能。
英文原题:Synchronous Jejunal Sarcomatoid Carcinoma and Incidentally Associated Localized Peritoneal Malignant Mesothelioma.
Synchronous Jejunal Sarcomatoid Carcinoma and Incidentally Associated Localized Peritoneal Malignant Mesothelioma.
他30年前有石棉接触史。
小肠肉瘤样癌(SCA)是一种罕见的小肠癌侵袭性变异型,预后较差。该肿瘤主要影响中老年患者。我们在此报告一例表现为贫血的67岁日本男性。他有30年前石棉暴露史。腹部计算机断层扫描(CT)显示小肠有一个6.5 cm的动脉瘤样扩张性肿块。胶囊内镜显示空肠内有一个大的环周出血性溃疡性病变。活检提示肉瘤样癌,随后进行了小肠部分切除以及邻近横结肠和网膜切除。除了T3N0M0空肠巨大肉瘤样癌(SCA)外,还偶然发现了一个3 mm的小局限性腹膜(网膜)恶性间皮瘤(LMM)。小肠和间皮恶性肿瘤同步出现极为罕见,避免错误的临床分期至关重要。由于对化疗和放疗反应较差,手术切除仍被认为是最好的一线治疗。针对p16/CDKN2A和9号染色体的双色荧光原位杂交(FISH)显示,SCA中p16/CDKN2A同源缺失,而LMM中为正常模式。甲硫腺苷磷酸化酶(MTAP)在SCA中为阴性,但在LMM中为阳性。两种肿瘤均持续表达BRCA1相关蛋白1(BAP1)。两种肿瘤中肿瘤坏死因子受体相关因子7(TRAF7)受到抑制,而神经细胞黏附分子L1前体(NCAML1/L1CAM)被激活。PD-L1在SCA中呈弥漫强表达,且与TIL(肿瘤浸润淋巴细胞)相关,这可能提示PD-L1靶向免疫治疗可用于治疗这种侵袭性癌症。PD-L1在LMM中呈局灶性表达。术后两年病程平稳。
Sarcomatoid carcinoma (SCA) of the small bowel is a rare aggressive variant of small intestinal cancer accompanying a poor prognosis. The tumor primarily affects middle-aged and elderly patients. We report herein a 67-year-old Japanese male who manifested anemia. He had a history of asbestos exposure 30 years earlier. An abdominal computed tomography (CT) scan showed a 6.5-cm aneurysmal, dilated mass of the small intestine. Capsule endoscopy revealed a large circumferential hemorrhagic ulcerative lesion in the jejunum. Biopsy indicated sarcomatoid carcinoma, and partial resection of the small bowel and adjacent transverse colon and omentum was performed. In addition to the T3N0M0 jejunal giant sarcomatoid carcinoma (SCA), a 3-mm small localized peritoneal (omental) malignant mesothelioma (LMM) was also incidentally included. Synchronous presentation of small intestinal and mesothelial malignancies is extremely rare, and the avoidance of incorrect clinical staging is critically important. Surgical resection is still considered the best first-line therapy, because of a poor response to chemotherapy and radiotherapy. Dual-color fluorescent in situ hybridization (FISH) for p16/CDKN2A and chromosome 9 indicated homologous deletion of p16/CDKN2A in SCA and a normal pattern in LMM. Methylthioadenosine phosphorylase (MTAP) was negative in SCA but positive in LMM. Both tumors consistently expressed BRCA1-associated protein 1 (BAP1). Tumor necrosis factor receptor-associated factor 7 (TRAF7) was suppressed, and neural cell adhesion molecule L1 precursor (NCAML1/L1CAM) was agitated in both tumors. Diffuse and strong expression of programmed death-ligand 1 (PD-L1) and the association of tumor-infiltrating lymphocytes in SCA may indicate a potential for PD-L1-targeted immunotherapy for treating this type of aggressive cancer. PD-L1 was focally expressed in LMM. The postoperative course was uneventful for two years.
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