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(DE) -Ubiquitination in The TGF-β Pathway (DE) - TGF-β通路中的泛素化
Pub Date : 2013-08-16 DOI: 10.17303/JCRTO.2013.1.102
P. J. Eichhorn
Aberrations in the enzymes that modify ubiquitin moieties have been observed to cause a myriad of diseases, including cancer. Therefore a better understanding of these enzymes and their substrates will lead to the identification of prospective druggable targets. Here we discuss the role of ubiquitin modifying enzymes in the canonical TGF-β pathway highlighting the ubiquitin regulating enzymes, which may potentially be targeted by small molecule inhibitors.
已经观察到修饰泛素部分的酶的畸变会导致包括癌症在内的无数疾病。因此,更好地了解这些酶及其底物将有助于确定潜在的药物靶点。在这里,我们讨论了泛素修饰酶在典型TGF-β通路中的作用,突出了泛素调节酶,这些酶可能是小分子抑制剂的潜在靶点。
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引用次数: 2
A Putative Role of Organic Anion Transporting Polypeptides (Oatps) In Cell Survival of Hormone-Dependent Breast and Prostate Cancers 有机阴离子转运多肽(Oatps)在激素依赖性乳腺癌和前列腺癌细胞存活中的作用
Pub Date : 2013-08-08 DOI: 10.17303/JCRTO.2013.1.101
T. Nakanishi
Transporter proteins classified into the solute carrier (SLC) transporter superfamily are essential for import of nutrients for cell survival in organisms. In the last two decades, compelling evidence has accumulated that SLC transporters interact with clinically important anticancer agents and contribute to their pharmacokinetics, particularly the biopharmaceutical processes of absorption, elimination and distribution. Furthermore, many SLC transporters have been shown to be differentially upregulated in cancer cells, and this may represent an adaptive response to altered nutritional requirements. Thus, it is likely to utilize them as carrier for efficient drug delivery as well as pharmacological target to shut off the essential nutrients for cell growth of malignant tumors. This short review will introduce organic anion transporting polypeptides which recognize endo- and exogenous organic anionic compounds and recent findings about their upregulation in cancer cells. Besides, OATP-mediated sulfate conjugates of steroid hormone may contribute to cell survival and adapted growth under hormonedepleted conditions. Better understandings of pathophysiological role of OATPs likely provide key information to overcome hormone-refractory breast and prostate tumors.
被归类为溶质载体(SLC)转运蛋白超家族的转运蛋白在生物体中对细胞生存所需的营养物质的进口至关重要。在过去的二十年中,越来越多的令人信服的证据表明,SLC转运蛋白与临床重要的抗癌药物相互作用,并有助于其药代动力学,特别是吸收、消除和分布的生物制药过程。此外,许多SLC转运蛋白在癌细胞中表现出差异上调,这可能代表了对改变的营养需求的适应性反应。因此,有可能利用它们作为有效给药的载体,以及作为阻断恶性肿瘤细胞生长必需营养物质的药理靶点。本文将简要介绍识别内源性和外源性有机阴离子化合物的有机阴离子转运多肽及其在癌细胞中上调的最新发现。此外,ooatp介导的类固醇激素硫酸盐偶联物可能有助于激素缺乏条件下的细胞存活和适应性生长。更好地了解oops的病理生理作用可能为克服激素难治性乳腺和前列腺肿瘤提供关键信息。
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引用次数: 1
Safe Doses and Cancer Treatment Evaluation 安全剂量和癌症治疗评价
Pub Date : 2013-07-01 DOI: 10.13189/COR.2013.010102
Emad Y Moawad
The aim of this research is to check the efficacy of radiotherapy after execution that helps in preserving patients' rights against the randomized dose that settled statistically and assessed in standard models ignoring patient-specific factors. Based on studying a dose-response relationship, a mathematical model is presented describes the initial tumor energy (E0Tumor) prior therapy after treatment execution -even if it was not predetermined- by monitoring the tumor response along the treatment phases and compared to the applied dose energy (E0Dose). Our model allows mechanic risk predictions to be made at high radiotherapeutic doses as well as at low doses, besides to the second cancer risk prevention. Thus, the administered dose errors could be determined and consequently preserving patients' rights to evaluate the cancer treatment through the provided mathematical model. Reasons of tumor regrowth are either underestimation or overestimation of the administered dose; the safe dose of the successful treatment occurs only in the case of: E0Dose = E0Tumor, where tumor regrowth energy in such a case would be vanished. Dose assessment by ignoring patient-specific factors and using standard models is responsible for wide range of doses that lead to tumor regrowth and second cancer risks. Current approach suggests settling down a new protocol for the proper ranges of radionuclide doses based on a personalized staging system.
本研究的目的是检查放射治疗执行后的疗效,这有助于保护患者的权利,使其免受随机剂量的影响,这些随机剂量在标准模型中统计和评估,忽略了患者的具体因素。在研究剂量-反应关系的基础上,提出了一个数学模型,通过监测肿瘤在治疗阶段的反应并将其与应用剂量能(E0Dose)进行比较,来描述治疗前治疗后的初始肿瘤能量(E0Tumor),即使它不是预先确定的。我们的模型允许在高剂量和低剂量下进行机械风险预测,以及第二癌症风险预防。因此,可以确定给药剂量误差,从而通过所提供的数学模型保护患者评价癌症治疗的权利。肿瘤再生的原因是低估或高估了给药剂量;成功治疗的安全剂量只有在:E0Dose = E0Tumor的情况下才会出现,在这种情况下,肿瘤再生能量会消失。通过忽略患者特异性因素和使用标准模型进行剂量评估是导致肿瘤再生和二次癌症风险的大范围剂量的原因。目前的方法建议在个性化分期系统的基础上为放射性核素剂量的适当范围制定一个新的方案。
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引用次数: 15
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Journal of Cancer Research and Therapeutic Oncology
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