Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

替加色罗大鼠体内药代动力学研究

目的　建立大鼠血浆中替加色罗的HPLC测定法 ,以测定大鼠ig替加色罗后的血药浓度 ,并对其药代动力学进行评价。方法　血浆样品加入内标后用乙酸乙酯提取 ,进行HPLC分析 ,流动相为甲醇 乙腈 水 (6 0∶8∶32 ,含 0 8%冰醋酸 ,0 4 %三乙胺 ,v/v) ,流速为 1 0ml/min ,检测波长为 310nm。大鼠ig 5 0、10 0、2 0 0mg·kg-1替加色罗后 ,测定其血浆中替加色罗的浓度 ,计算主要药动学参数。结果　血浆中替加色罗在 2 0 0ng/ml～ 80 0 0ng/ml浓度范围内线性关系良好 ,血浆中替加色罗的最低检测限为 1 0ng/ml。大鼠ig 5 0、10 0、2 0 0mg·kg 1替加色罗后 ,估算的末端相半衰期分别为 0 86、1 0 9、1 0 8h ,3种剂量的半衰期相近 ,AUC与剂量间呈良好的线性关系 (r =0 9996 )。结论　本实验建立的分析方法灵敏、准确、简便。在5 0～ 2 0 0mg·kg 1剂量范围内 ,替加色罗在大鼠体内符合线性药物动力学特征 ,平均半衰期为 1 0 1h。     

福建省469例健康咨询热线电话记录分析

目的了解福建省接受健康咨询热线的主要对象的特征以及求询的主要内容,为今后开展健康教育和行为干预提供依据。方法选取2004年1月至2005年2月接受电话咨询者469例资料进行分析,按咨询内容(性病艾滋病、寻医问药、生殖生育和心理卫生)进行分类整理,数据采用SPSS 11.5统计软件包进行统计分析。结果求询者中,男性占66.74%,女性占33.26%;年龄以29岁以下青年人居多,占49.89%;职业以工人(打工族)居首位,占48.83%;文化程度主要是初中以下人员,占60.77%;咨询内容涉及性病艾滋病问题最多,占45.42%。结论本热线求询者以男性中青年为主,大部分文化程度偏低,且多数有高危行为。利用咨询热线,对求询者进行心理、行为等健康教育具有积极意义。     

用正交法探讨过氧乙酸含量测定的影响因素

目的探讨过氧乙酸含量测定的影响因素.方法用正交法设计影响因素,碘量法测定其含量.结果高锰酸钾放置时间是影响过氧乙酸含量测定的主要因素.结论当滴加高锰酸钾液使供试液呈微红色时应迅速地完成实验操作.     

Analysis of parametric histogram from dynamic contrast‐enhanced MRI: application in evaluating brain tumor response to radiotherapy

Dynamic contrast‐enhanced MRI (DCE MRI) has been used to study tumor response to treatment for many years. In this study, the modified full width at half‐maximum (mFWHM), calculated from the wash‐in slope histogram, is proposed as a parameter for the evaluation of changes in tumor heterogeneity which respond to radiotherapy. Twenty‐five patients with brain tumors were evaluated and divided into the nonresponder group (n = 11) and the responder group (n = 14) according to the Response Evaluation Criteria in Solid Tumors (RECIST). All selected tumors were evaluated by mFWHM ratios of post‐ to pre‐therapy (the ratio was defined as the therapeutic mFWHM ratio, TMR). The changes in kurtosis of the histograms and the averaged K^trans within a tumor were also calculated for comparison. The receiver operating characteristic analysis and Kaplan–Meier curves were used to examine the diagnosis ability. The TMR values were significantly higher in nonresponders than in responders (p < 0.001). When compared with the other two parameters, the proposed method also demonstrated better sensitivity and specificity. When adopting the TMR for the estimation of prognosis after therapy, there was a significant difference between the population survival curves. In conclusion, the derived mFWHM reflects tumor heterogeneity, and the ability to depict patient survival probability from TMR corresponds well with that from RECIST. The results reveal that, in brain tumors, progression may be exhibited not only by tumor size, but also by tumor heterogeneity. Copyright © 2012 John Wiley & Sons, Ltd.     

Targeting cancer by binding iron: Dissecting cellular signaling pathways

Newer and more potent therapies are urgently needed to effectively treat advanced cancers that have developed resistance and metastasized. One such strategy is to target cancer cell iron metabolism, which is altered compared to normal cells and may facilitate their rapid proliferation. This is supported by studies reporting the anti-neoplastic activities of the clinically available iron chelators, desferrioxamine and deferasirox. More recently, ligands of the di-2-pyridylketone thiosemicarbazone (DpT) class have demonstrated potent and selective anti-proliferative activity across multiple cancer-types in vivo, fueling studies aimed at dissecting their molecular mechanisms of action. In the past five years alone, significant advances have been made in understanding how chelators not only modulate cellular iron metabolism, but also multiple signaling pathways implicated in tumor progression and metastasis. Herein, we discuss recent research on the targeting of iron in cancer cells, with a focus on the novel and potent DpT ligands. Several key studies have revealed that iron chelation can target the AKT, ERK, JNK, p38, STAT3, TGF-β, Wnt and autophagic pathways to subsequently inhibit cellular proliferation, the epithelial-mesenchymal transition (EMT) and metastasis. These developments emphasize that these novel therapies could be utilized clinically to effectively target cancer.