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家族性癌症:健康成员和患癌成员的自然杀伤细胞细胞毒性降低

Familial cancer: depressed NK-cell cytotoxicity in healthy and cancer affected members.

作者信息

Montelli T C, Peraçoli M T, Gabarra R C, Soares A M, Kurokawa C S

机构信息

Departamento de Neurologia e Psiquiatria, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, São Paulo, Brasil.

出版信息

Arq Neuropsiquiatr. 2001 Mar;59(1):6-10. doi: 10.1590/s0004-282x2001000100003.

DOI:10.1590/s0004-282x2001000100003
PMID:11299423
Abstract

Depressed natural killer (NK) cell activity has been showed in family members of patients with different types of cancer. The present work aimed to evaluate T cell subsets and NK cell cytotoxic activity in 15 members of a family with high incidence of tumors, such as glioblastoma, gastric, pancreas and colon rectal carcinoma, chronic myelocitic leukemia, melanoma and osteoblastoma. As controls, 19 healthy subjects with the age range equivalent were studied. The enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets were defined by monoclonal antibodies and NK cell cytotoxicity towards K562 target cells were evaluated by single cell-assay. The results showed in family members low percentage of total T cells (CD3+), and their CD4+ subset and impairment of CD4/CD8 ratio in relation to control group. All family members presented percentage of NK-target cell conjugate formation below the minimum value observed in control group. Thirteen people were examined and followed up during five years, in order to assure that there was no undiagnosed or unsuspected disease at the moment of evaluation. One of them developed osteoblastoma and other malignant melanoma. Two cancer patients, with glioblastoma and chronic myelocytic leukemia were studied during illness. All the corresponding values were comparable. The persistence of low percentage of conjugate formation may be related to a defect on adhesion molecules expression in the surface of NK cells that was probably responsible for the low activity of these cells presented by the family group. Thus, the inheritance mechanism of low adherence of NK cells should have a prognostic value in determining the risk of developing tumors.

摘要

不同类型癌症患者的家庭成员中已显示出自然杀伤(NK)细胞活性降低。本研究旨在评估一个肿瘤高发家族的15名成员的T细胞亚群和NK细胞的细胞毒性活性,该家族患有胶质母细胞瘤、胃癌、胰腺癌、结肠直肠癌、慢性粒细胞白血病、黑色素瘤和成骨细胞瘤等多种肿瘤。作为对照,研究了19名年龄范围相当的健康受试者。通过单克隆抗体确定CD3 +淋巴细胞及其CD4 +和CD8 +亚群的计数,并通过单细胞测定评估NK细胞对K562靶细胞的细胞毒性。结果显示,与对照组相比,家族成员中总T细胞(CD3 +)及其CD4 +亚群的百分比降低,且CD4/CD8比值受损。所有家族成员的NK靶细胞共轭形成百分比均低于对照组观察到的最小值。对13人进行了检查并随访了五年,以确保在评估时没有未诊断或未怀疑的疾病。其中一人患了成骨细胞瘤,另一人患了恶性黑色素瘤。对两名患有胶质母细胞瘤和慢性粒细胞白血病的癌症患者在患病期间进行了研究。所有相应值均具有可比性。共轭形成百分比持续较低可能与NK细胞表面粘附分子表达缺陷有关,这可能是导致该家族组中这些细胞活性较低的原因。因此,NK细胞低粘附性的遗传机制在确定患肿瘤风险方面应具有预后价值。

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