A fundamental study about the new therapeutic stratedy with cell mediated immunity sysytem for uterine cervical cancer and CIN

细胞免疫系统治疗宫颈癌及CIN新策略的基础研究

• 批准号: 17591716
• 负责人: OKI Akinori
• 金额: $ 2.24万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591716/
• 关键词: HPV; HLA; cervical cancer; immunotherapy; 子宮頸癌; CIN

As a result of multi-institutions collaborative investigation intended to elucidate the natural history by observating CIN1/2, it developed that there were two steps by the process during carcinogenesis of CIN1/2. The study subjects consisted of 570 women aged 54 or younger with cytologically and histologically confirmed CIN 1/2. CIN cases included 479 CIN 1 and 91 CIN 2. The median follow-up time was 38.1 months. The 570 subjects were divided into 361 (63.3%) patients with regression, 172 (28.6%) patients with persistence and 46 (8.1%) patients with progression. The median regression time was 6.5 months and the median progression time was 17.9 months, suggesting that regression is an early event and progression is a late event in the national history of CIN 1/2. Thus, the first step is a step to persist without regression of the CIN1/2 within two years usually disappearing. The second step is the step that persisted CIN1/2 which continued progresses to CIN3. We used hazard ratio after … More adjustment of Age, CIN grade and HPV category to evaluate various prognostic factors, because the three factors were closely associated with both regression and progression in the univariate analysis. Age, CIN grade, HPV risk category, smoking, marital status, and number of sexual partners were significantly associated with CIN persistence, whereas CIN grade, HPV risk category and HLA class II allele (HLA DRB1*1302) had significant association with CIN progression.In such a background we paid attention to the type of HPV and the haplotype of the HLA Class I antigen in elements of the uterine cervix cancer.It is obvious that high-risk HPV infection is a direct trigger in the carcinogenesis of uterine cervix cancer, but evasion from virus immunity and tumor immunity by the host is indispensable in carcinogenesis process. These immune mechanism due to cell-mediated immunity through the T lymphocyte, and co-existence of HLA class I molecules and the HPV specific peptide is important for this system. The complex of HLA class I molecules with peptide consisting of around 9-10 amino acids, is recognized as an antigen by a T lymphocytes. The binding affinity of the peptide is HLA type specific, so that the immune response depends on the difference of the HLA haplotypes.13 kinds of cell lines, which were derived from cervical cancer, were analysed both HPV and HLA typings. HPV16 was detected by seven lines of those, and HPV18 was detected by three, and it was not detected from one. Three of seven HPV16 positive lines were positive for A*1101 and five of these positive for A*2401, but did not accumulate the HLA of seven HPV16 positive lines in a specific haplotype in B, C locus. The distribution in which locus did not have regional control and significant difference. About half in HLA A, B locus and about two-thirds in C locus were coverd by these seven HPV16 positive cell lines, A susceptibility of the cervical cancer by the difference of the HLA might be identified in future by comparing the HLA distribution of the uterine cervix cancer patient of the specific HPV (especially HPV16) positive with normal regional control. Less

由于旨在通过观察CIN1/2来阐明自然历史的多机构协作投资的结果，它发展出了CIN1/2癌发生期间的过程有两个步骤。该研究受试者由570名54岁以下的女性组成，具有细胞学和组织学确认的CIN 1/2。 CIN病例包括479 CIN 1和91 CIN 2。中位随访时间为38.1个月。将570名受试者分为361例（63.3％）的消退患者，172名（28.6％）持久性患者和46名（8.1％）患者的进展患者。中间回归时间为6.5个月，中位进展时间为17.9个月，这表明回归是早期的事件，而进展是CIN 1/2国家历史上的晚期事件。这是第一步是在两年内不消失CIN1/2的情况下持续存在的一步。第二步是持续cin1/2继续前进到CIN3的步骤。 ……在……对年龄，CIN等级和HPV类别进行更多调整之后，我们使用危险比来评估各种预后因素，因为三个因素与单变量分析中的回归和进展密切相关。年龄，年级，HPV风险类别，吸烟，婚姻状况和性伴侣的数量与CIN持久性显着相关，而CIN等级，HPV风险类别和HLA II类等位基因（HLA DRB1*1302）与CIN的进展有着显着关联。癌症。很明显，高风险的HPV感染是子宫颈癌的致癌作用的直接触发因素，但是宿主从病毒免疫学和肿瘤免疫学中进化是癌变过程中必不可少的。由于细胞介导的免疫学而引起的这些免疫学机制通过T淋巴细胞以及HLA I类分子的共存和HPV特异性肽的共存对于该系统很重要。 HLA I类分子与由大约9-10个氨基酸组成的肽的复合物被T淋巴细胞识别为抗原。肽的结合亲和力是HLA类型特异性的，因此免疫增强响应取决于HLA单倍型的差异。13种源自宫颈癌的细胞系均分析了HPV和HLA键入。 HPV16通过七个线检测到HPV16，并检测到HPV18，三个线未从一条中检测到。 a*1101的七个HPV16正线中有三个为阳性，其中五个为A*2401，但在B，C基因座的特定单倍型中并未积累七个HPV16正线的HLA。基因座没有区域控制和显着差异的分布。这七个HPV16阳性细胞系涵盖了HLA A，B基因座和C基因座中约三分之二的一半，通过将HLA的差异通过比较特定HPV16的特定HPV16阳性的子宫宫颈癌患者的HLA分布，可以通过比较HLA的差异来识别宫颈癌的敏感性。较少的

项目成果

Do we need a different strategy for HPV screening and vaccination in East Asia?

• DOI: 10.1002/ijc.22195
• 发表时间: 2006-12-01
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Miura, Shiho;Matsumoto, Koji;Yoshikawa, Hiroyuki
• 通讯作者: Yoshikawa, Hiroyuki

HPV感染と危険因子

HPV 感染和危险因素

• 发表时间: 2006
• 期刊: 産婦人科治療 93・6
• 作者: 沖明典;吉川裕之
• 通讯作者: 吉川裕之

コホート研究に基づくCIN1/2の管理方針と高危険部の抽出

基于队列研究的CIN1/2管理政策及高危区域提取

• 发表时间: 2006
• 期刊: 日本産婦人科学会誌 58巻・11号
• 作者: K.Matsumoto;T.Yasugi;A.Oki;T.Fujii;C.Negate;S.Sekiya;H.Hoshiai;Y.Taketani;T.Kanda;T.Kawana;H.Yoshikawa;沖 明典;沖 明典
• 通讯作者: 沖 明典

Identification of high-risk CIN 1/2 and its management based on a large scale cohort study of CIN 1/2 in Japan

基于日本CIN 1/2大规模队列研究的高危CIN 1/2识别及其管理

• 发表时间: 2006
• 期刊: Nippin Sanka-Hujinnka-gakkai zasshi Vol.58(11)
• 作者: Takeuchi T;Tsutsumi O;Ikezuki Y;Kamei Y;Osuga Y;Fujiwara T;Takai Y;Momoeda M;Yano T;Taketani Y.;A.Oki
• 通讯作者: A.Oki

IgG antibodies to HPV16, 52, 58 and 6 L1-capsids and spontaneous regression of cervical intraepithelial neoplasia

HPV16、52、58 和 6 L1 衣壳的 IgG 抗体与宫颈上皮内瘤变的自然消退

• 发表时间: 2006
• 期刊: Cancer Letters Vol.231(peer reviewed)
• 作者: K. Matsumoto;T. Yasugi;A. Oki;T. Fujii;C. Nagata;S. Sekiya;H. Hoshiai;Y. Taketani;T. Kanda;T. Kawana;H. Yoshikawa
• 通讯作者: H. Yoshikawa