Clinical analysis of ascitic fluid in patients with liver cirrhosis and hepatocellular carcinoma

To investigate the clinical significance of ascitic fluid in patients with a malignancy, an abdominal paracentesis to evaluate the ascitic fluid was performed in 10 patients with a hepatocellular carcinoma (HCC) and in 7 patients with liver cirrhosis (LC). The AFP levels in the ascitic fluid and in the serum of the HCC patients was found be significantly higher than that of the LC patients. In addition, the ratio of albumin/total protein in ascitic fluid was also higher in the HCC patients. However, no significant findings were uncovered with regard to the concentration of lipid in ascitic fluid, in either type of patient although 2 HCC patients were found to have a very high concentration of total cholesterol. The cytological findings provided no reliable marker because of significant number of false negatives in the HCC patients. Also, there was no significant difference between the fibronectin levels in the ascitic fluid of either type of patients. This finding differs from previous studies, and suggests that the fibronectin levels in the ascitic fluid may not be a useful marker in determining a malignancy.     

A Large-scale, Hospital-based Case-Control Study of Risk Factors of Breast Cancer According to Menopausal Status

We conducted a large-scale, hospital-based case-control study to evaluate differences and similarities in the risk factors of female breast cancer according to menopausal status. This study is based on a questionnaire survey on life style routinely obtained from outpatients who first visited the Aichi Cancer Center Hospital between January 1, 1988 and December 31, 1992. Among 36,944 outpatients, 1,186 women with breast cancer detected by histological examination were taken as the case group (607 premenopausal women and 445 postmenopausal women) and 23,163 women confirmed to be free of cancer were selected as the control group. New findings and reconfirmed factors of breast cancer were as follows. 1) The risk of at least one breast cancer history among subjects' first-degree relatives was relatively high among pre- as well as post-menopausal women. 2) A protective effect of physical activity against breast cancer was observed among both pre- and post-menopausal women. 3) Dietary control decreased the risk of premenopausal breast cancer. 4) Current smoking and drinking elevated the risk of breast cancer in premenopausal women. 5) Decreasing trends of breast cancer risk were associated with intake of bean curd, green-yellow vegetables, potato or sweet potato, chicken and ham or sausage in premenopausal women, while in postmenopausal women a risk reduction was associated with a more frequent intake of boiled, broiled and/or raw fish (sashimi). Further study will be needed to clarify the age group- and/or birth cohort-specific risk factors for breast cancer among the young generation in Japan.     

Alcohol, smoking, and dietary status and susceptibility to malignant lymphoma in Japan: results of a hospital-based case-control study at Aichi Cancer Center.

Recent increase in the incidence of malignant lymphoma (ML) suggests possible involvement of lifestyle or environmental factors in its genesis. However, evidence for an effect of lifestyle factors, especially diet, on ML risk among Japanese is lacking. To explore the possibility that lifestyle factors exert an influence, we have conducted a hospital-based case-control study with 333 histologically confirmed ML cases and 55904 non-cancer controls who first visited Aichi Cancer Center Hospital between 1988 and 1997. Multiple logistic regression analysis showed regular alcohol consumption to be associated with reduced risk of ML, whereas no risk change was observed for smoking. Some other factors including intake of vegetables (carrots and pumpkin), pork and fish showed partial associations, but their significance needs further clarification. From the previous study on genetic background for ML [Matsuo et al., Blood, 97, 3205 - 3209 (2001)], genetic variation combined with limited environmental factors should be targeted in future studies.     

谷胱甘肽转硫酶T1、M1基因型和烟酒茶嗜好与食管癌、胃癌

目的 :研究谷胱甘肽转硫酶T1、M1(GSTT1、GSTM 1)基因多态性和烟酒茶嗜好及其相互作用与食管癌、胃癌易感性的关系。方法 :在上消化道癌高发区淮安市进行了病例 -对照研究 (食管癌 141例 ,胃癌 15 3例 ;人群对照 2 2 3例 ) ,调查研究对象的烟酒茶嗜好习惯 ,以多重PCR方法分析GSTT1、GSTM1基因型。结果 :食管癌组GSTM1-基因型频度 (75 .18% )显著高于对照组 (5 9.6 4 % ,P =0 .0 0 2 4 ;多因素调整OR =2 .33,95 %CI =1.39～ 3.92 )。吸烟或不饮茶与GSTM 1 基因型在增加食管癌发生的风险中有明显的协同作用。在GSTT1 基因型者中 ,吸烟习惯显著增加食管癌、胃癌的危险性 ;在GSTM1 基因型者中 ,经常饮酒显著增加食管癌、胃癌的危险性。结论 :食管癌、胃癌的发生与生活习惯、GSTM1和GSTT1基因型以及它们的相互作用有关。     

亚甲基四氢叶酸还原酶基因C677T多态性与食管癌易感性的关系

目的　研究亚甲基四氢叶酸还原酶 (MTHFR)基因C6 77T多态性及其和烟酒茶嗜好相互作用与食管癌易感性的关系。方法　在上消化道癌高发区淮安市进行了一个病例 对照研究 (食管癌 93例 ,人群对照 2 0 0例 ) ,调查研究对象的生活习惯 ,采用PCR RFLP技术检测研究对象的MTHFR基因型。结果　 1.食管癌组和对照组中MTHFR变异型等位基因携带者分别占 6 6 .7%和 6 8.5 % ,其差异无统计学显著性。 2 .在MTHFR野生型基因携带者中 ,吸烟习惯显著增加食管癌发生的危险性 (OR =3.2 2 ,95 %CI:1.0 9～ 9.5 3)。在MTHFR变异型基因携带者中 ,经常饮酒者发生食管癌的危险性显著升高 (OR =2 .30 ,95 %CI :1.0 2～ 2 .5 7)。在野生型和变异型基因携带者中 ,有饮茶习惯者发生食管癌的危险性均显著降低。结论　MTHFR基因的多态性影响吸烟、饮酒与食管癌之间的关系。调查生活习惯、同时检测MTHFR基因型有助于食管癌的预防。     

广东省潮汕地区半定量食物频率调查表的制定

目的制定潮汕地区的半定量食物频率调查表,为饮食与疾病之间的医学研究提供工具。方法以潮州、汕头(包括南澳县)城乡地区为中心随机抽取若干家庭,并以家庭为单位,以3 d食物称重记录法进行膳食调查,建立潮汕地区城乡家庭膳食资料数据库;在以各种食物提供的营养素量为基础进行食物种类筛选的基础上,再以逐步进入法进行多元回归分析对初选食物项目进行再次筛选,并确定食物的频度、食用量。结果共有417个家庭完成调查(城市200个,农村217个),其3 d消耗的食物种类512种,其中城市443种,农村417种。初次筛选出的食物种类数城市194种,农村183种,城乡合计233种;再次筛选结果为城市157种,农村160种,城乡合计196种;最后125种食物被包括在半定量食物频率调查表中,每种食物对应有7个层次的摄入频率和6个层次的食用量。半定量食物频率调查表中的食物项目提供的营养素覆盖率平均超过90%。结论以417个城乡家庭膳食资料为基础建立潮汕地区食物“金标准”数据库并以该数据库资料为依据,按照系统方法和步骤制定潮汕地区食物半定量食物频率调查表是切实可行的。     

Gene-environment interaction between an aldehyde dehydrogenase-2 (ALDH2) polymorphism and alcohol consumption for the risk of esophageal cancer

Aldehyde dehydrogenase-2 (ALDH2) degrades acetaldehyde metabolized from ethanol. Its encoding gene ALDH2 has a functional polymorphism: ALDH2 Glu487LYS: An association between this polymorphism and esophageal cancer among alcoholics has been reported. To further evaluate the gene-environment interaction, a hospital-based case-control study was conducted. Cases were 102 patients with histologically confirmed esophageal cancer and controls were 241 non-cancer outpatients of Aichi Cancer Center. ALDH2 genotypes were examined by a PCR-CTPP method developed in our laboratory, which does not require a digestion stage. Logistic regression analysis was employed for estimation of relative risk and gene-environment interaction. The allele frequency for ALDH2 Lys487 was 0.28, consistent with previous reports. The age, sex, smoking and drinking status adjusted odds ratio for the ALDH2 Glu/Lys and Lys/Lys genotypes as compared with the Glu/Glu genotype was 3.43 (95% CI 1.74-6.75). The odds ratio for heavy drinking was 49.6 (14.5-169.4) among Lys487 carriers and 7.84 (2.77-22.2) for the Glu/Glu genotype. The gene-environment interaction between alcohol drinking and the ALDH2 Lys487 allele was 6.84 (2.39-19.6), whereas no significant interaction was obtained with smoking status. Although limited because of its prevalent case-control design, our study revealed a strong gene-environment interaction between ALDH2 polymorphism and heavy alcohol consumption. Taking the observed high risk of esophageal cancer in association with the ALDH2 Lys487 allele into consideration, reducing alcohol intake may be most protective among Lys487 allele carriers of this polymorphism.     

饮食营养素摄取与结直肠癌的发病风险

[目的]探讨饮食总能量、蛋白质、脂肪和碳水化合物摄取与结直肠癌发病风险的关系.[方法]在江苏省进行的一项病例对照研究,用包括83种食物摄取频度和摄取量的问卷表,凋查了342例结直肠癌患者和393例健康对照的饮食状况,计算各类饮食营养素的平均每日摄取量,采用三分位法分析营养素摄取与结直肠癌发病风险的关系,OR值计算采用非条件Logistic回归方法.[结果]结肠癌组脂肪摄取量显著高于对照组;直肠癌组总能量和蛋白质摄取量显著低于对照组:结、直肠癌组的碳水化合物摄取量均显著低于对照组.在调整可疑混杂因素的影响后,总能量和碳水化合物摄取量高显著降低结直肠癌的发病风险,脂肪摄取量高显著增加结直肠癌的发病风险.但在营养素互相调整后,总能量、蛋白质和脂肪摄取对结、直肠癌的发病风险的影响无统计学意义,而增加碳水化合物的摄取可显著降低结、直肠癌的发病风险(结肠癌OR=0.44,95%CI:0.28～0.71;直肠癌OR=0.51,95%CI:0.36～0.74).[结论]饮食营养素摄取影响结直肠癌的发病风险,增加碳水化合物摄取可预防结直肠癌的发生.     

Antitumor effect of fibrin glue containing temozolomide against malignant glioma

Temozolomide (TMZ), used to treat glioblastoma and malignant glioma, induces autophagy, apoptosis and senescence in cancer cells. We investigated fibrin glue (FG) as a drug delivery system for the local administration of high‐concentration TMZ aimed at preventing glioma recurrence. Our high‐power liquid chromatography studies indicated that FG containing TMZ (TMZ‐FG) manifested a sustained drug release potential. We prepared a subcutaneous tumor model by injecting groups of mice with three malignant glioma cell lines and examined the antitumor effect of TMZ‐FG. We estimated the tumor volume and performed immunostaining and immunoblotting using antibodies to Ki‐67, cleaved caspase 3, LC3 and p16. When FG sheets containing TMZ (TMZ‐FGS) were inserted beneath the tumors, their growth was significantly suppressed. In mice treated with peroral TMZ plus TMZ‐FGS the tumors tended to be smaller than in mice whose tumors were treated with TMZ‐FGS or peroral TMZ alone. The TMZ‐FGS induced autophagy, apoptosis and senescence in subcutaneous glioma tumor cells. To assess the safety of TMZ‐FG for normal brain, we placed it directly on the brain of living mice and stained tissue sections obtained in the acute and chronic phase immunohistochemically. In both phases, TMZ‐FG failed to severely damage normal brain tissue. TMZ‐FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma.