Role of obesity in colorectal carcinogenesis

The obesity is the second most frequent cause of death which can be prevented. It elevates the risk of cardiovascular diseases, diabetes mellitus type 2, cancers and premature mortality. Overweight and obesity responsible for 14% of cancer caused death in males, and 20% in females, respectively. Authors review the connection between obesity, metabolic syndrome and related metabolic alterations with colorectal cancers. They summarize the role of inflammation, hyperinsulinemia, insulin-like growth factor-I and adipokines in the colorectal carcinogenesis.     

A compartment model of carcinogenesis in lung cancer

A compartment model of carcinogenesis which describes separately the process of smoking-related lung cancer and that of smoking-unrelated lung cancer is presented. This model is well fitted to the equation representing the lung cancer incidence rate of the British physicians' cohort. The compartment model is shown to agree with the frozen type of incidence curve among ex-smokers. This model is biologically plausible in the context of the mechanism of carcinogenesis. For planning public health policies in a community and for health education based on smoking data, we calculated the change of risk after the cessation of smoking.     

The mechanism of lung carcinogenesis and smoking cessation

Mathematical modeling of risk of lung cancer upon smoking cessation suggests increasing risk, whereas the facts show decreasing mortality. This discordance is resolved by taking into account the mechanistically distinct steps in chemical carcinogenesis: (1) neoplastic conversion by genotoxic carcinogens and (2) neoplastic growth and development by agents with epigenetic and promoting effects. Tobacco smoke contains relatively small amounts of several types of genotoxic carcinogens, the effect of which is considerably and vitally enhanced by nongenotoxic promoting factors. Upon smoking cessation, the effect of the second type of agent is abruptly eliminated. Therefore, any preneoplastic lesions remain static or regress, whereas in the continuing smoker they progress. These sequences also apply, with different chemicals involved, in nutritional carcinogenesis.     

Problems and perspectives of occupational carcinogenesis]

Epidemiologic research has played an important role in identifying and confirming the carcinogenicity of chemicals. This was facilitated in the past by the high levels of exposure and by the simple correspondence between one exposure and one or few job titles. Today we are faced with a different picture: workers are exposed to complex mixtures, exposure levels have decreased while mobility of the work-force has increased. In this changing context, epidemiology needs new methodological tools to improve the validity of risk assessment. The most promising of these seem to be the new techniques of biochemical epidemiology and the development of job-exposure matrices. Among the more traditional tools, record-linkage studies may be relevant in identifying long-term occupational hazards. The methodological problems and the ethical and operative implications of these trends in research are discussed.     

Risk of prostate cancer in relation to polymorphisms of metabolic genes

The study of associations between genetic polymorphisms of metabolic enzymes and prostate cancer risk can provide insight into the potential etiologic role of xenobiotics in prostate cancer development. To date there is little evidence that the incidence of prostate cancer is influenced by any of the genetic polymorphisms described above. However, the number of subjects studied generally has been small, so it would be premature to conclude that the substances metabolized by enzymes encoded by these candidate genes are not of carcinogenic importance, or to conclude that the polymorphisms of these genes do not play a role in prostate cancer susceptibility. Larger-scale studies of these and other genes, such as genes that repair cellular damage and regulate cell growth, are needed. Since gene-gene and gene-environment interactions may contribute to cancer risk, it would be desirable to conduct studies in which both biomarkers (or other measures) of exposure and polymorphisms of multiple genes are examined.     

Role of macrophage tissue infiltration in metabolic diseases

PURPOSE OF REVIEW: White adipose tissue is necessary for optimal energy homeostasis and the excessive development of fat mass is clearly associated with the metabolic syndrome. The fact that adipocytes secrete a number of specific factors or 'adipokines' has forced a reassessment of the involvement of adipose tissue in a wide range of physiological and pathophysiological processes. Obesity has recently been described as a 'low-grade' inflammatory condition, a state proposed to represent a common determinator in the genesis of obesity-associated pathologies, i.e. diabetes and atherosclerosis. RECENT FINDINGS: Recent reports of an increase in the number of macrophages that infiltrate the fat mass in obese individuals led to the suggestion that adipose tissue itself is a source and site of inflammation. SUMMARY: This review summarizes recent data on the characterization of the macrophage population in fat tissue. Their origin, fate and activation will be considered. The potential involvement of adipose tissue macrophages in the development of insulin resistance and vascular pathologies, as well as in the control of adipose tissue growth and metabolism, will be examined.     

茶对二甲基苯并蒽诱发金黄色地鼠口腔癌预防作用的研究

选用二甲基苯并蒽（ Ｄ Ｍ Ｂ Ａ）诱发的金黄色地鼠口腔癌模型,研究绿茶、茶色素和混合茶对口腔癌的预防作用,并探讨其防癌机制。试验设阳性对照组（局部涂０５％ Ｄ Ｍ Ｂ Ａ,每周３次,共１５周）、３个饮茶试验组（在涂 Ｄ Ｍ Ｂ Ａ２周前开始分别饮１５％ 绿茶、０１％ 茶色素和０５％ 混合茶至１５周实验结束）和阴性对照组（仅涂丙酮）。结果表明,与阳性对照组相比,绿茶、茶色素和混合茶组对平均瘤数目的抑制率分别为４２６％ 、５０８％ 和６７２％ ,平均瘤负荷抑制率分别为７９４％ 、８８５％ 和９５５％ ;在３组中以混合茶对口腔癌的抑制效果最强。在涂 Ｄ Ｍ Ｂ Ａ 后的第６、１０和１５周,３个茶试验组中均见到口腔上皮细胞微核形成,每核银染核仁组织区（ Ａｇ Ｎ Ｏ Ｒ）颗粒数目和表皮生长因子受体（ Ｅ Ｇ Ｆ Ｒ）的表达低于阳性对照组。表明饮茶对 Ｄ Ｍ Ｂ Ａ 诱发的动物口腔癌有明显的预防作用,而茶预防 Ｄ Ｍ Ｂ Ａ 引起的粘膜细胞 Ｄ Ｎ Ａ 损伤和抑制粘膜细胞增殖可能是其预防口腔癌的重要作用机制。     

Role of cytokines in the metabolic response to stress

Clinical trials with cytokine inhibitors have failed to show efficacy and confirm preclinical findings in sepsis and systemic inflammatory response syndromes. However, a better understanding of the pathogenesis of sepsis syndrome, and of proinflammatory cytokine signal transduction pathways, including the role of nuclear factor kappa B and inflammation-induced apoptosis, have provided new therapeutic opportunities for cytokine and anticytokine therapies.     

补体在放射性肺损伤中的作用与机制

目的 探明补体在⁶⁰Coγ射线单次20 Gy胸部照射所致小鼠放射性肺损伤中的作用。方法 ⁶⁰Coγ射线单次20 Gy胸部照射C57BL/6小鼠,观察早期(15 d内)肺组织炎性反应和后期(30 d、180 d)肺纤维化,ELISA测定照射后1 d、3 d、7 d、15 d、30 d、180 d肺组织C2、C3a、C4、C5b-9含量,RT-PCR检测Beas-2B细胞照射后补体mRNA的表达。结果 照射后小鼠放射性肺损伤表现为早期炎性反应和晚期纤维化。补体C2、C4和C5b-9复合物在照射后早期(3 d或7 d)增高(P <0.05),可能与照射引起的炎性反应有关。补体C3a在照射后3～180 d均明显高于对照组水平,提示其与放射性肺损伤关系密切。照射细胞中,补体C2、C3的mRNA表达增高,而C4、C5的m RNA水平无变化。结论 不同补体在放射性肺损伤中的反应存在差异,其中补体C3a与放射性肺损伤关系极为密切,提示通过调控补体C3a及其受体可能是防治放射性肺损伤的新途径。     

细胞周期蛋白D1在石英致人细胞恶性转化中的作用

目的探讨细胞周期蛋白D1在石英致人胚肺成纤维细胞(HELF)恶性转化过程中所起的作用。方法采用基因重组与基因导入的方法将表达正义和反义细胞周期蛋白D1 RNA的pXJ41-细胞周期蛋白D1导入石英恶性转化HELF细胞中。采用原位杂交和免疫组化的方法检测细胞中细胞周期蛋白D1基因表达情况,分析细胞周期蛋白D1导入前后细胞生长速度、倍增时间、细胞周期分布、软琼脂克隆形成能力的改变。结果石英诱导HELF细胞恶性转化过程中细胞周期蛋白D1基因过表达,反义细胞周期蛋白D1 RNA可抑制石英恶性转化细胞的生长增殖。与石英恶性转化细胞相比,反义pXJ41-细胞周期蛋白D1转染细胞培养至第8天时,生长速率下降58．69％,倍增时间从21．0h延长到31．4h,G1期细胞比例从45．1％增加到52．7％,S期细胞比例由40．3％下降到33．1％,克隆形成率显著下降,克隆明显变小。结论细胞周期蛋白D1的异常表达与石英恶性转化细胞有密切的关系,高水平表达的细胞周期蛋白D1对维持恶性转化细胞的恶性性状起重要的作用。     

Role of ghrelin polymorphisms in obesity based on three different studies

OBJECTIVE: Associations between preproghrelin DNA variants and obesity-related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study. RESEARCH METHODS AND PROCEDURES: Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction. RESULTS: Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p = 0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the lowest FM (p < 0.001). Met72 carrier status (Met72+) was associated with lower FM (p = 0.026) and higher insulin-like growth factor-1 levels (p = 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p < 0.05) in SOS subjects whose BMI was < or =25 kg/m(2) than in those with BMI >25 kg/m(2) (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence of hypertension than noncarriers (23.9%). DISCUSSION: Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.     

Methylenetetrahydrofolate reductase polymorphisms, folate, and cancer risk: a paradigm of gene-nutrient interactions in carcinogenesis

Recent epidemiologic studies suggest that common polymorphisms of methylenetetrahydrofolate reductase (MTHFR) with allele frequencies up to 35% in the general North American population may modulate cancer risk. In some cancers, folate and other nutrients involved in the MTHFR metabolic pathway appear to interact with MTHFR polymorphisms to further modify cancer risk. In carcinogenesis, MTHFR polymorphisms thus provide a paradigm of gene-nutrient interactions, an emerging and important topic in the field of nutrition and cancer. Furthermore, MTHFR polymorphisms and MTHFR-nutrient interactions provide an opportunity to identify an ideal target group of individuals, at high risk of developing cancer, for rational, effective, and safe chemoprevention using these nutrients.     

代谢酶基因多态性与结直肠癌的易感性

目的研究代谢酶细胞色素P450（cytochrome P450s,CYP）1A1、谷胱甘肽转移酶（glutathione—S-transferase,GST）M1和T1、尿苷二磷酸葡萄糖醛酸转移酶（UDPglucumnosyltransferase,UGT）1A7基因多态性与结直肠癌的易感性及其交互作用。方法2002年5月在浙江省嘉善县开展的现场病例对照研究及单纯病例研究,获得140例结直肠癌患者和343名健康对照,用PCR-限制性片段长度多态性等方法检测CYP1A1、GSTM1、GSTT1和UGT1A7的基因多态,并应用非条件logistic回归方法进行数据分析。结果CYPIA1 MspI多态（非编码区T6235C）C／C基因型、T／C和C／C基因型者相对于T／T基因型者的OR值分别为0．493（95％CI：0．254—0．956）和0．638（95％CI：0．427—0．952）,具有统计学意义;GSTM1、GSTT1非缺陷型与缺陷型的分布频率对照组和病例组比较差异无统计学意义;对照组和病例组UGT1A7变异／变异型基因与野生纯合型基因比较差异有统计学意义（OR=2．501,95％CI：1．456—4．296）。单纯病例研究分析,CYP1A1与GSTT1、GSTM1与GSTT1对结直肠癌的发生存在交互作用,COR值分别为2．617（95％CI：1．015—6．752）和3．935（95％CI：1．323—11．706）;而CYPlAl与GSTM1、CYP1A1与UGT1A7之间无交互作用。结论CYP1A1 MspI变异型可降低机体对结直肠癌的易感性,而UGT1A7的变异／变异基因型可增加结直肠癌的罹患风险,CYP1A1与GSTT1、GSTM1与GSTT1对结直肠癌的发生存在交互作用。     

Association of cytokine gene polymorphisms with rate of decline in lung function

OBJECTIVE:: To investigate whether genetic variants involved in cytokine expression are associated with the age-related rate of decline in forced expiratory volume in 1 second (FEV1). METHODS:: Functional polymorphisms in the TNFalpha, TGFbeta1, IL-1beta, IL-1RN, IL-13, and IL-8 genes were investigated in 374 active firefighters with at least five pulmonary function tests. RESULTS:: A protective effect was found between the presence of the TGFbeta1 -509 TT genotype and rate of decline in FEV1 (P = 0.043). Carrying an A allele at TNFalpha -308 (P = 0.010) and GG genotype at TNFalpha -238 (P = 0.028) was associated with a more rapid rate of FEV1 decline. The TNFalpha -308A/-238G haplotype was also associated with an increased rate of decline as compared with the other haplotypes. CONCLUSIONS:: Interindividual variability in progressive decline in FEV1 may be explained in part by genetic variations within genes involved in inflammatory responses.     

中国成年女性一碳单位代谢通路关联基因多态性位点地域分布特征

目的对中国16个省和2个直辖市的成年女性MTHFR和MTRR基因多态性分布特征进行分析,描绘一碳单位代谢通路关联的MTHFR C677T、 MTHFR A1298C和MTRR A66G基因多态性位点在中国的整体分布形态。方法在中国知网、万方数据库、维普中文科技期刊数据库、百度学术上,搜索关键词为"MTHFR"、"MTRR"、"女性"、"基因单核苷酸多态性"的中文文献。纳入的文献可以提供各种基因型对应成年女性的人数,或通过所提供的基因型频率可以计算出对应成年女性的人数。两人分工协作完成数据提取工作,并将提取到的数据以省或直辖市为单位进行合并,计算出各个省及直辖市各种基因型及等位基因分布频率。结果中国成年女性MTHFR 677TT基因型和677T等位基因频率自南向北逐渐稳固升高。MTHFR 1298CC在中国成年女性中占比极小。A1298C和C677T基因两者呈现连锁不平衡,TT/AA基因频率分布特征呈现出自北向南逐渐降低的趋势,在全国范围内TT/AC、 TT/CC和CT/CC的基因型频率均为0。MTRR 66AA在中国成年女性群体中占34%~58%,北部略高于南部;MTRR 66GG占5%~17%。结论基因多态性的风险评估可纳入针对神经管缺陷的一级预防措施。