• 【社论评论: SRD5A2中的低活性V89L变体与侵袭性前列腺癌风险相关: 在使用5-α-还原酶抑制剂的化学预防试验中观察到的不良反应的解释。】 复制标题 收藏 收藏
    DOI:10.1016/j.eururo.2007.04.010 复制DOI
    作者列表:Maier C
    BACKGROUND & AIMS: -2
    背景与目标: -2
  • 【姜黄素在癌症化学预防中的多个分子靶点。】 复制标题 收藏 收藏
    DOI:10.1208/aapsj080352 复制DOI
    作者列表:Thangapazham RL,Sharma A,Maheshwari RK
    BACKGROUND & AIMS: :Carcinogenesis encompasses 3 closely associated stages: initiation, progression, and promotion. Phytochemicals are nonnutritive components of plants that are currently being studied in chemoprevention of various diseases for their pleiotropic effects and nontoxicity. Cancer chemoprevention involves the use of either natural or synthetic chemicals to prevent the initiation, promotion, or progression of cancer. Curcumin is the active constituent of turmeric, which is widely used as a spice in Indian cooking. It has been shown to possess anti-inflammatory, antioxidant, and antitumor properties. Curcumin has also been shown to be beneficial in all 3 stages of carcinogenesis. Much of its beneficial effect is found to be due to its inhibition of the transcription factor nuclear factor kappa B (NF-kappaB) and subsequent inhibition of proinflammatory pathways. This review summarizes the inhibition of NF-kappaB by curcumin and describes the recently identified molecular targets of curcumin. It is hoped that continued research will lead to development of curcumin as an anticancer agent.
    背景与目标: : 癌变包括3个密切相关的阶段: 起始、进展和促进。植物化学物质是植物的非营养成分,目前正在研究各种疾病的化学预防,因为它们具有多效性和非毒性。癌症化学预防包括使用天然或合成化学物质来预防癌症的发生,促进或进展。姜黄素是姜黄的活性成分,姜黄在印度烹饪中被广泛用作香料。已证明具有抗炎,抗氧化和抗肿瘤特性。姜黄素也被证明在癌变的所有三个阶段都是有益的。发现其许多有益作用是由于其对转录因子核因子 κ B (NF-kappaB) 的抑制以及随后对促炎途径的抑制。这篇综述总结了姜黄素对NF-κ b的抑制作用,并描述了最近发现的姜黄素的分子靶标。希望继续研究将导致姜黄素作为抗癌剂的发展。
  • 【作者更正: 塞内加尔向10岁以下儿童大规模门到门提供季节性疟疾化学预防 (SMC) 的实施,覆盖范围和公平性。】 复制标题 收藏 收藏
    DOI:10.1038/s41598-018-25426-4 复制DOI
    作者列表:Bâ EH,Pitt C,Dial Y,Faye SL,Cairns M,Faye E,Ndiaye M,Gomis JF,Faye B,Ndiaye JL,Sokhna C,Gaye O,Cissé B,Milligan P
    BACKGROUND & AIMS: :A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
    背景与目标: : 更正这篇文章已经发表,是链接的HTML和PDF版本.该错误尚未在论文中修复。
  • 【乳腺癌化学预防: 抗雌激素他莫昔芬的风险效益效应。】 复制标题 收藏 收藏
    DOI:10.1517/14740338.1.3.253 复制DOI
    作者列表:Brown K
    BACKGROUND & AIMS: :The anti-oestrogen tamoxifen, which is widely used as adjuvant therapy for breast cancer, is undergoing evaluation as a chemopreventive agent in women at increased risk of developing this disease. Recent results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 prevention trial show a 49% reduction in breast cancer incidence in healthy, high-risk women. However, tamoxifen treatment has the serious side effect of increasing the incidence of endometrial cancer in women and long-term administration of tamoxifen causes hepatic tumours in rats. These liver tumours are induced via a genotoxic mechanism, but the mechanisms responsible for endometrial cancer in women are not yet known and are a focus of much debate. This review describes the findings from the chemoprevention trials and problems associated with the use of tamoxifen in this setting. The mechanism of carcinogenesis in rat liver is explained in detail and compared to the situation in humans, with a view to assessing the risks associated with tamoxifen therapy and predicting whether other anti-oestrogens might be safer alternatives.
    背景与目标: : 抗雌激素他莫昔芬被广泛用作乳腺癌的辅助治疗,目前正在接受评估,作为一种化学预防剂,在罹患这种疾病的风险增加的女性中。国家外科辅助乳房和肠项目 (NSABP) P-1预防试验的最新结果表明,健康,高危女性的乳腺癌发病率降低了49%。然而,他莫昔芬治疗具有增加女性子宫内膜癌发生率的严重副作用,并且长期服用他莫昔芬会导致大鼠肝肿瘤。这些肝脏肿瘤是通过遗传毒性机制诱导的,但是女性子宫内膜癌的机制尚不清楚,并且是许多争论的焦点。这篇综述描述了化学预防试验的发现以及在这种情况下使用他莫昔芬的相关问题。详细解释了大鼠肝脏的致癌机制,并将其与人类的情况进行了比较,以评估与他莫昔芬治疗相关的风险并预测其他抗雌激素药物是否可能是更安全的替代品。
  • 【女性结直肠癌: 激素替代疗法和化学预防。】 复制标题 收藏 收藏
    DOI:10.3109/13697137.2012.659450 复制DOI
    作者列表:Barnes EL,Long MD
    BACKGROUND & AIMS: :Colorectal cancer (CRC) accounts for 9.4% of new cancer diagnoses among women world-wide. CRC is the third leading cause of incident cancer among women in the United States and has immense impact on morbidity and mortality. We summarize data on CRC pathogenesis and risk in women. We also review the findings from the Women's Health Initiative (WHI) on CRC risk reduction associated with hormone replacement therapy (HRT) use. We then review observational studies since the WHI which evaluated HRT as a chemopreventive agent for CRC among women. The potential mechanisms behind the association between HRT use and CRC are also reviewed. We then discuss the requirements for implementation of chemopreventive agents, and why HRT should not be used for this indication given current knowledge. Further data on the risk-benefit profile of short-term HRT use are needed and will determine whether there is any future role for HRT use in the chemoprevention of CRC.
    背景与目标: : 结直肠癌 (CRC) 占全球女性新诊断癌症的9.4%。CRC是美国女性癌症发病率的第三大原因,对发病率和死亡率有巨大影响。我们总结了女性CRC发病机理和风险的数据。我们还回顾了妇女健康倡议 (WHI) 关于使用激素替代疗法 (HRT) 相关的CRC风险降低的发现。然后,我们回顾了自WHI以来的观察性研究,该研究评估了HRT作为女性CRC的化学预防剂。还回顾了HRT使用与CRC之间关联的潜在机制。然后,我们讨论了实施化学预防剂的要求,以及鉴于当前的知识,为什么不应将HRT用于此指示。需要有关短期HRT使用的风险效益的进一步数据,并将确定HRT使用在CRC化学预防中的未来作用。
  • 【抑制血管生成和内皮细胞功能是萝卜硫素介导的化学预防机制。】 复制标题 收藏 收藏
    DOI:10.1158/1535-7163.MCT-05-0324 复制DOI
    作者列表:Bertl E,Bartsch H,Gerhäuser C
    BACKGROUND & AIMS: :Sulforaphane, an aliphatic isothiocyanate, is a known cancer chemopreventive agent. Aiming to investigate antiangiogenic potential of sulforaphane, we here report a potent decrease of newly formed microcapillaries in a human in vitro antiangiogenesis model, with an IC50 of 0.08 micromol/L. The effects of sulforaphane on endothelial cell functions essential for angiogenesis were investigated in HMEC-1, an immortalized human microvascular endothelial cell line. Molecular signaling pathways leading to activation of endothelial cell proliferation and degradation of the basement membrane were analyzed by reverse transcription-PCR. Sulforaphane showed time- and concentration-dependent inhibitory effects on hypoxia-induced mRNA expression of vascular endothelial growth factor and two angiogenesis-associated transcription factors, hypoxia-inducible factor-1alpha and c-Myc, in a concentration range of 0.8 to 25 micromol/L. In addition, the expression of the vascular endothelial growth factor receptor KDR/flk-1 was inhibited by sulforaphane at the transcriptional level. Sulforaphane could also affect basement membrane integrity, as it suppressed transcription of the predominant endothelial collagenase matrix metalloproteinase-2 and its tissue inhibitor of metalloproteinase-2. Migration of HMEC-1 cells in a wound healing assay was effectively prevented by sulforaphane at submicromolar concentrations, and we determined an IC50 of 0.69 micromol/L. In addition, within 6 hours of incubation, sulforaphane inhibited tube formation of HMEC-1 cells on basement membrane matrix at 0.1, 1, and 10 micromol/L concentrations. These effects were not due to inhibition of HMEC-1 cell proliferation; however, after 72 hours of incubation, sulforaphane nonselectively reduced HMEC-1 cell growth with an IC50 of 11.3 micromol/L. In conclusion, we have shown that sulforaphane interferes with all essential steps of neovascularization from proangiogenic signaling and basement membrane integrity to endothelial cell proliferation, migration, and tube formation. These novel antiangiogenic activities of sulforaphane are likely to contribute to its cancer chemopreventive and therapeutic potential.
    背景与目标: : 萝卜硫素,一种脂肪族异硫氰酸酯,是一种已知的癌症化学预防剂。为了研究萝卜硫素的抗血管生成潜力,我们在这里报告了在人体外抗血管生成模型中新形成的微毛细血管的有效减少,IC50为0.08 micromol/L。在永生化的人微血管内皮细胞系HMEC-1中研究了萝卜硫素对血管生成必不可少的内皮细胞功能的影响。通过逆转录PCR分析了导致内皮细胞增殖激活和基底膜降解的分子信号通路。萝卜硫素对缺氧诱导的血管内皮生长因子和两种血管生成相关转录因子 (低氧诱导factor-1alpha和c-Myc) 的mRNA表达具有时间和浓度依赖性的抑制作用,浓度范围为0.8至25微摩尔/升。此外,在转录水平上,萝卜硫素抑制了血管内皮生长因子受体KDR/flk-1的表达。萝卜硫素也可能影响基底膜的完整性,因为它抑制了主要的内皮胶原酶基质metalloproteinase-2及其组织metalloproteinase-2抑制剂的转录。亚微摩尔浓度的萝卜硫素有效地防止了伤口愈合试验中HMEC-1细胞的迁移,我们确定的IC50为0.69 micromol/L。此外,在孵育的6小时内,萝卜硫素以0.1、1和10 micromol/L的浓度抑制基底膜基质上HMEC-1细胞的管形成。这些作用不是由于抑制HMEC-1细胞增殖; 然而,在孵育72小时后,萝卜硫素非选择性地降低了HMEC-1细胞的生长,IC50为11.3微摩尔/升。总之,我们已经表明,萝卜硫烷干扰了从促血管生成信号和基底膜完整性到内皮细胞增殖,迁移和管形成的所有重要新生血管步骤。萝卜硫素的这些新的抗血管生成活性可能有助于其癌症的化学预防和治疗潜力。
  • 【肺癌化学预防: 中国林县的随机双盲试验。】 复制标题 收藏 收藏
    DOI:10.1158/1055-9965.EPI-06-0316 复制DOI
    作者列表:Kamangar F,Qiao YL,Yu B,Sun XD,Abnet CC,Fan JH,Mark SD,Zhao P,Dawsey SM,Taylor PR
    BACKGROUND & AIMS: :We examined the effect of supplementation with four different combinations of vitamins and minerals in the prevention of lung cancer mortality among 29,584 healthy adults from Linxian, China. In accord with a partial factorial design, the participants were randomly assigned to take either a vitamin/mineral combination or a placebo for 5.25 years. The combinations tested in this trial were as follows: factor A, retinol and zinc; factor B, riboflavin and niacin; factor C, ascorbic acid and molybdenum; factor D, beta-carotene, alpha-tocopherol, and selenium. Lung cancer deaths (n = 147) identified during the trial period (1986-1991) and 10 years after the trial ended (1991-2001) were the study outcome. No significant differences in lung cancer death rates were found for any of the four combinations of supplements tested in this study, using log-rank tests (all P values are >0.20) or Cox proportional hazards models adjusted for age, sex, commune, and other treatments. No significant interactions were seen for age, sex, or smoking status. Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian, China.
    背景与目标: : 我们研究了在中国林县的29,584名健康成年人中补充四种不同的维生素和矿物质对预防肺癌死亡率的影响。根据部分因子设计,参与者被随机分配服用维生素/矿物质组合或安慰剂5.25年。在该试验中测试的组合如下: 因子A,视黄醇和锌; 因子B,核黄素和烟酸; 因子C,抗坏血酸和钼; 因子D,β-胡萝卜素,α-生育酚和硒。在试验期间 (1986-1991) 和试验结束后10年 (1991-2001) 确定的肺癌死亡 (n = 147) 是研究结果。使用log-rank检验 (所有p值均> 0.20) 或针对年龄,性别,公社和其他治疗方法进行校正的Cox比例风险模型,本研究中测试的四种补充剂组合中的任何一种在肺癌死亡率方面均无显着差异。在年龄,性别或吸烟状况方面未发现明显的相互作用。在中国林县,以营养补充水平补充维生素和矿物质的组合5.25年并没有降低这一营养不足人群的肺癌死亡率。
  • 【硝酸盐和NO-NSAIDs在癌症化学预防和治疗中的应用: 体外证据查询NO供体功能。】 复制标题 收藏 收藏
    DOI:10.1016/j.niox.2008.04.013 复制DOI
    作者列表:Dunlap T,Abdul-Hay SO,Chandrasena RE,Hagos GK,Sinha V,Wang Z,Wang H,Thatcher GR
    BACKGROUND & AIMS: :Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than one hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural "linker" as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery.
    背景与目标: : 在100多个出版物中报道的NO-ASA非捐赠非甾体抗炎药 (NO-NSAIDs) 家族的特性,特别是NCX 4016 (mno-asa) 和NCX 4040 (pno-asa),包括癌症化学预防和治疗中的阳性临床前数据。有证据表明,细胞培养物中NO-ASA的抗增殖,化学预防 (抗氧化剂/亲电反应元件 (is) 激活) 和抗炎活性被不能作为NO供体的x-asa衍生物复制。Pbr-asa和mbr-asa与NO-ASA同生异生,但不是没有供体。Pbr-asa复制了pNO-ASA的生物活性; pNO-ASA和pbr-asa均被生物激活为相同的醌甲基亲电试剂。Mno-asa的生物活性由mbr-asa复制; Mno-asa和mbr-asa被生物激活为不同的苄基亲电试剂。观察到的活性可能是通过醌和苄基亲电试剂捕获硫醇生物分子而引发的,从而导致GSH的消耗和含Cys的传感器蛋白的修饰。尽管所有含有与NCX 4040和NCX 4016相同的结构 “接头” 的NO-NSAIDs预期具有由对亲电代谢物的生物活化产生的活性,但该预期并不延伸到其他接头结构。硝酸盐需要代谢生物活化以释放NO生物活性,这通常在体外复制不佳,并且NO-NSAIDs在体内提供的NO生物活性在减轻NSAID胃毒性方面提供了已证明的治疗益处。X-asa药物的体内特性有待发现。
  • 【使用基因测试指导曾经进行过乳房活检的白人妇女的乳腺癌化学预防的经济评估。】 复制标题 收藏 收藏
    DOI:10.1007/s40258-014-0089-6 复制DOI
    作者列表:Green LE,Dinh TA,Hinds DA,Walser BL,Allman R
    BACKGROUND & AIMS: BACKGROUND:Tamoxifen therapy reduces the risk of breast cancer but increases the risk of serious adverse events including endometrial cancer and thromboembolic events. OBJECTIVES:The cost effectiveness of using a commercially available breast cancer risk assessment test (BREVAGen™) to inform the decision of which women should undergo chemoprevention by tamoxifen was modeled in a simulated population of women who had undergone biopsies but had no diagnosis of cancer. METHODS:A continuous time, discrete event, mathematical model was used to simulate a population of white women aged 40-69 years, who were at elevated risk for breast cancer because of a history of benign breast biopsy. Women were assessed for clinical risk of breast cancer using the Gail model and for genetic risk using a panel of seven common single nucleotide polymorphisms. We evaluated the cost effectiveness of using genetic risk together with clinical risk, instead of clinical risk alone, to determine eligibility for 5 years of tamoxifen therapy. In addition to breast cancer, the simulation included health states of endometrial cancer, pulmonary embolism, deep-vein thrombosis, stroke, and cataract. Estimates of costs in 2012 US dollars were based on Medicare reimbursement rates reported in the literature and utilities for modeled health states were calculated as an average of utilities reported in the literature. A 50-year time horizon was used to observe lifetime effects including survival benefits. RESULTS:For those women at intermediate risk of developing breast cancer (1.2-1.66 % 5-year risk), the incremental cost-effectiveness ratio for the combined genetic and clinical risk assessment strategy over the clinical risk assessment-only strategy was US$47,000, US$44,000, and US$65,000 per quality-adjusted life-year gained, for women aged 40-49, 50-59, and 60-69 years, respectively (assuming a price of US$945 for genetic testing). Results were sensitive to assumptions about patient adherence, utility of life while taking tamoxifen, and cost of genetic testing. CONCLUSIONS:From the US payer's perspective, the combined genetic and clinical risk assessment strategy may be a moderately cost-effective alternative to using clinical risk alone to guide chemoprevention recommendations for women at intermediate risk of developing breast cancer.
    背景与目标:
  • 【转移相关蛋白1介导的膳食芪对前列腺癌化学预防和治疗的抗肿瘤和抗癌活性。】 复制标题 收藏 收藏
    DOI:10.1016/j.semcancer.2020.02.012 复制DOI
    作者列表:Levenson AS
    BACKGROUND & AIMS: :Dietary bioactive polyphenols that demonstrate beneficial biological functions including antioxidant, anti-inflammatory, and anticancer activity hold immense promise as effective and safe chemopreventive and chemosensitizing natural anticancer agents. The underlying molecular mechanisms of polyphenols' multiple effects are complex and these molecules are considered promising targets for chemoprevention and therapy. However, the development of novel personalized targeted chemopreventive and therapeutic strategies is essential for successful therapeutic outcomes. In this review, we highlight the potential of metastasis-associated protein 1 (MTA1)-targeted anticancer and antitumor effects of three dietary stilbenes, namely resveratrol, pterostilbene, and gnetin C, for prostate cancer management. MTA1, an epigenetic reader and master transcriptional regulator, plays a key role in all stages of prostate cancer progression and metastasis. Stilbenes inhibit MTA1 expression, disrupt the MTA1/histone deacetylase complex, modulate MTA1-associated Epi-miRNAs and reduce MTA1-dependent inflammation, cell survival, and metastasis in prostate cancer in vitro and in vivo. Overall, the MTA1-targeted strategies involving dietary stilbenes may be valuable for effective chemoprevention in selected subpopulations of early stage prostate cancer patients and for combinatorial strategies with conventional chemotherapeutic drugs against advanced metastatic prostate cancer.
    背景与目标: : 具有有益生物功能 (包括抗氧化,抗炎和抗癌活性) 的膳食生物活性多酚具有作为有效和安全的化学预防和化学敏感性天然抗癌剂的巨大前景。多酚多重作用的潜在分子机制很复杂,这些分子被认为是化学预防和治疗的有希望的靶标。然而,开发新的个性化靶向化学预防和治疗策略对于成功的治疗效果至关重要。在这篇综述中,我们强调了三种饮食中的stilbenes (白藜芦醇,紫檀草和gnetin C) 靶向转移相关蛋白1 (MTA1) 的抗癌和抗肿瘤作用在前列腺癌管理中的潜力。MTA1是一种表观遗传学读者和主要的转录调节因子,在前列腺癌进展和转移的所有阶段都起着关键作用。Stilbenes在体外和体内抑制前列腺癌中的MTA1表达,破坏MTA1/组蛋白脱乙酰基酶复合物,调节MTA1-associated Epi-mirna并降低MTA1-dependent炎症,细胞存活和转移。总体而言,涉及膳食stilbenes的MTA1-targeted策略对于早期前列腺癌患者的选定亚群中的有效化学预防以及与常规化学治疗药物联合治疗晚期转移性前列腺癌的策略可能是有价值的。
  • 【cyclooxygenase-2抑制剂对结直肠癌的化学预防: 前进两步,后退一步。】 复制标题 收藏 收藏
    DOI:10.1016/S1470-2045(07)70139-0 复制DOI
    作者列表:Bertagnolli MM
    BACKGROUND & AIMS: :Chronic inflammation is a tissue-specific process implicated in several diseases of an aging population, including cancer, cardiovascular disease, and arthritis. Cyclooxygenase-2 (COX-2) is a mediator of acute and chronic inflammation, and drugs designed to specifically target this enzyme have achieved widespread clinical use. Unfortunately, randomised trials of selective COX-2 inhibitors for cancer prevention have shown that beneficial effects in one type of tissue can be accompanied by toxic effects in another. These trials documented a significant reduction in adenoma formation in patients at high risk for colorectal cancer, with reductions in advanced disease occurrence from 28-66% over 3 years. As a result, these studies provided important evidence for the involvement of COX-2 in early colorectal tumorigenesis. In the same patients, however, these placebo-controlled clinical trials revealed a little-understood relation between COX-2 and maintenance of cardiovascular integrity. During the 3 years of treatment, patients who received selective COX-2 inhibitors were 1.3-3.4-times more likely to have serious cardiovascular events than those treated with placebo. This article will discuss the biological rationale for using selective COX-2 inhibitors in cancer chemoprevention, and outline new avenues of research into toxic effects and tissue specificity that are necessary to allow their successful use in patients at risk for colorectal cancer.
    背景与目标: : 慢性炎症是一种组织特异性过程,涉及人口老龄化的几种疾病,包括癌症,心血管疾病和关节炎。Cyclooxygenase-2 (COX-2) 是急性和慢性炎症的介质,设计专门针对该酶的药物已获得广泛的临床应用。不幸的是,选择性COX-2抑制剂用于预防癌症的随机试验表明,在一种类型的组织中的有益作用可能伴随着另一种类型的毒性作用。这些试验记录了大肠癌高危患者腺瘤形成的显着减少,并在3年内将晚期疾病发生率从28-66% 降低。结果,这些研究为COX-2参与早期结直肠肿瘤发生提供了重要证据。然而,在同一患者中,这些安慰剂对照的临床试验揭示了COX-2与维持心血管完整性之间的关系。在3年的治疗期间,接受选择性COX-2抑制剂的患者发生严重心血管事件的可能性比接受安慰剂治疗的患者高1.3-3.4倍。本文将讨论在癌症化学预防中使用选择性COX-2抑制剂的生物学原理,并概述对毒性作用和组织特异性的研究的新途径,以使其成功用于具有结直肠癌风险的患者。
  • 【硒对动物肝癌的化学预防和可能的人类应用。】 复制标题 收藏 收藏
    DOI:10.1007/BF02990140 复制DOI
    作者列表:Yu SY,Chu YJ,Li WG
    BACKGROUND & AIMS: :An inverse correlation between geographic distribution of liver cancer incidence and the selenium (Se) contents of whole blood and grains was observed in Qidong county, Jiangsu province, a high liver cancer area of the People's Republic of China. Animal experiments demonstrated that supplementation of Se reduced the incidence of liver cancer in rats exposed to aflatoxin B1. Se was also shown to inhibit the growth of transplanted tumors. A lower incidence of liver preneoplastic alterations and reduction of hepatitis B virus infection in ducks by Se-supplementation was observed, and three pilot studies for a Se-intervention trial on human liver cancer were carried out on the residents of Qidong county. A protective effect on the cellular DNA damage induced by aflatoxin B1 was observed in lympocytes from human with Se-supplements.
    背景与目标: : 在中华人民共和国肝癌高发地区江苏省祁东县,观察到肝癌发病率的地理分布与全血和谷物中的硒 (Se) 含量呈负相关。动物实验表明,补充硒可降低暴露于黄曲霉毒素b1的大鼠的肝癌发生率。还显示Se抑制移植肿瘤的生长。观察到通过补充硒在鸭中肝脏肿瘤前改变的发生率较低,减少了乙型肝炎病毒,并对祁东县居民进行了三项针对人类肝癌的硒干预试验的试点研究。在添加硒补充剂的人淋巴细胞中观察到对黄曲霉毒素B1诱导的细胞DNA损伤的保护作用。
  • 【间隙连接细胞间通讯作为生物学的 “罗塞塔石”,以系统生物学的方式理解干细胞行为,表观遗传毒理学机制,化学预防和化学疗法。】 复制标题 收藏 收藏
    DOI:10.1007/s00232-007-9072-6 复制DOI
    作者列表:Trosko JE
    BACKGROUND & AIMS: :In spite of the early speculation by Loewenstein that one of the critical distinguishing phenotypes of cancers from normal cells was the dysfunction of gap junctional intercellular communication (GJIC), this hypothesis has not captured the attention of most birth defects and cancer researchers. Moreover, even with later demonstrations that factors that influence normal development and carcinogenesis by modulating GJIC, such as chemical teratogens and tumor-promoting chemicals, inflammatory factors, hormones and growth factors, antisense connexin genes, knockout mouse models, human inherited mutated connexin genes, si-connexin RNA, chemopreventive and chemotherapeutic chemicals, it is rare that one sees any reference to these studies by the mainstream investigators in these fields. Based on the assumption that the evolutionarily conserved connexin genes found in metazoans are needed for normal development and the maintenance of health and T. Dobzhansky's statement "Nothing in biology makes sense except in the light of evolution," a short review of the roles of endogenous and exogenous modulators of GJIC will be made in the context of the multistage, multimechanism process of carcinogenesis, the stem cell theory of carcinogenesis, the discovery and characterization of normal adult stem "cancer stem" cells and the observation that two distinct classes of GJIC-deficient cancer cells are known. The implications of these observations to a "systems biological" view of the role of gap junctions and the nutritional prevention and treatment of several chronic diseases and cancer will be discussed.
    背景与目标: : 尽管Loewenstein早期推测癌症与正常细胞的关键区别表型之一是间隙连接细胞间通讯 (GJIC) 功能障碍,但该假设并未引起大多数出生缺陷和癌症研究人员的注意。此外,即使后来证明通过调节GJIC影响正常发育和致癌的因素,例如化学致畸物和促进肿瘤的化学物质,炎症因子,激素和生长因子,反义连接蛋白基因,敲除小鼠模型,人类遗传的突变连接蛋白基因,si-连接蛋白RNA,化学预防和化学治疗化学物质,很少有人看到这些领域的主流研究人员对这些研究的任何参考。基于这样的假设,即在后生动物中发现的进化上保守的连接蛋白基因对于正常发育以及维持健康和T是必需的。Dobzhansky的声明 “除了从进化的角度来看,生物学上没有任何意义”,将在致癌的多阶段,多机制过程,干细胞理论的背景下,对GJIC的内源性和外源性调节剂的作用进行简短回顾。致癌,正常成人干细胞 “癌症干细胞” 的发现和表征,以及已知两类不同的GJIC缺陷癌细胞的观察。将讨论这些观察结果对间隙连接的作用以及几种慢性疾病和癌症的营养预防和治疗的 “系统生物学” 观点的影响。
  • 【氟他胺治疗前列腺上皮内瘤变的男性: 一项随机,安慰剂对照的化学预防试验。】 复制标题 收藏 收藏
    DOI:10.1097/00045391-200607000-00002 复制DOI
    作者列表:Alberts SR,Novotny PJ,Sloan JA,Danella J,Bostwick DG,Sebo TJ,Blute ML,Fitch TR,Levitt R,Lieberman R,Loprinzi CL
    BACKGROUND & AIMS: :High-grade prostatic intraepithelial neoplasia (HGPIN) has been identified as a premalignant change in the prostate that indicates increased risk of the subsequent development of prostate adenocarcinoma. Prior studies have suggested that androgen deprivation therapy causes a regression of HGPIN. We therefore conducted a chemoprevention trial assessing the efficacy of flutamide in reducing the rate of prostate adenocarcinoma development in men with HGPIN. Men with biopsyproven HGPIN but no evidence of prostate adenocarcinoma were randomized in a double-blind manner to either flutamide 250 mg/d or a placebo. Treatment was continued for 1 year. Repeat biopsies were obtained at 12 and 24 months. Quality of life and toxicities related to treatment were also measured. Sixty patients were randomized and began therapy with either flutamide or placebo. At 1 year, 14% of men receiving flutamide and 10% of men receiving placebo had developed prostate adenocarcinoma. Flutamide-associated toxicities were mild to moderate in severity. Quality-of-life measures did not show any differences between the 2 groups. This study showed no evidence of benefit from flutamide as a chemoprevention agent in men with HGPIN.
    背景与目标: : 高度前列腺上皮内瘤变 (HGPIN) 已被确定为前列腺的恶变,表明随后发生前列腺腺癌的风险增加。先前的研究表明,雄激素剥夺疗法会导致HGPIN的消退。因此,我们进行了一项化学预防试验,评估了氟他胺在降低HGPIN男性前列腺腺癌发生率中的功效。具有经活检证实的HGPIN但没有前列腺腺癌证据的男性以双盲方式随机分配给氟他胺250 mg/d或安慰剂。治疗持续1年。在12个月和24个月获得重复活检。还测量了与治疗相关的生活质量和毒性。60例患者被随机分组,开始使用氟他胺或安慰剂治疗。在1年时,14% 接受氟他胺的男性和10% 接受安慰剂的男性发展为前列腺腺癌。氟他胺相关毒性的严重程度为轻度至中度。生活质量指标在两组之间没有显示任何差异。这项研究没有证据表明氟他胺作为HGPIN男性的化学预防剂会受益。
  • 【非裔美国男性前列腺癌的化学预防。】 复制标题 收藏 收藏
    DOI:10.1177/107327481602300413 复制DOI
    作者列表:Kumar NB,Pow-Sang JM,Spiess PE,Park JY,Chornokur G,Leone AR,Phelan CM
    BACKGROUND & AIMS: BACKGROUND:Recommendations for cancer screening are uncertain for the early detection or prevention of prostate cancer in African American men. Thus, chemoprevention strategies are needed to specifically target African American men. METHODS:The evidence was examined on the biological etiology of disparities in African Americans related to prostate cancer. Possible chemopreventive agents and biomarkers critical to prostate cancer in African American men were also studied. RESULTS:High-grade prostatic intraepithelial neoplasia may be more prevalent in African American men, even after controlling for age, prostate-specific antigen (PSA) level, abnormal results on digital rectal examination, and prostate volume. Prostate cancer in African American men can lead to the overexpression of signaling receptors that may mediate increased proliferation, angiogenesis, and decreased apoptosis. Use of chemopreventive agents may be useful for select populations of men. CONCLUSIONS:Green tea catechins are able to target multiple pathways to address the underlying biology of prostate carcinogenesis in African American men, so they may be ideal as a chemoprevention agent in these men diagnosed with high-grade prostatic intraepithelial neoplasia.
    背景与目标:

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