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Mutagenesis Associated with DNA-Damage-Stress Response 突变与dna损伤应激反应相关
Pub Date : 2016-04-05 DOI: 10.6000/1927-7229.2016.05.01.4
R. Skopec
In this manuscript we aim to take on the controversies in oncology, such as those related to costs and screening guidelines. Are we recently at new turning point with our existing methodology? During the past 30 years of evolution methods of awareness and screening have lead to an emphasis on early diagnoses of cancer and not only cancer. Recent trends and clinical trials show that these goals have not been met. International data demonstrate significant increase in early stage disease, without a proportional decrease in later-stage disease. We need to more differentiate in methodology because cancers are heterogenous with multiple paths, not all of which progress to metastases and death. This broader definition of disease named cancer must include also indolent disease that causes no harm during patients lifetime. Overdiagnosis and overtreatment result in billions of USD of wasted money. Our methodology must be completed with methods which take proper account of the real-life environment.
在这份手稿中,我们的目标是采取争议在肿瘤学,如那些有关的成本和筛选指南。我们最近是否处于现有方法的新转折点?在过去的30年里,意识和筛查方法的发展使人们重视癌症的早期诊断,而不仅仅是癌症。最近的趋势和临床试验表明,这些目标尚未实现。国际数据表明,早期疾病显著增加,而晚期疾病没有成比例减少。我们需要在方法上更加区分,因为癌症具有多种途径的异质性,并非所有的途径都进展为转移和死亡。这种更广泛的癌症定义还必须包括在患者一生中不会造成伤害的惰性疾病。过度诊断和过度治疗导致数十亿美元的金钱浪费。我们的方法论必须以适当考虑现实环境的方法来完成。
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引用次数: 2
Abiraterone Acetate in Patients with Advanced Castrate Resistant Prostate Cancer: Initial Real Life Experience in 2 Cancer Units 晚期去势抵抗性前列腺癌患者的醋酸阿比特龙:2个癌症单位的初始真实生活经验
Pub Date : 2016-04-05 DOI: 10.6000/1927-7229.2016.05.01.6
J. Zekri, A. Ramadan, Muthu Kumar, R. Haggag
Introduction : Abiraterone Acetate (AA) improves outcome of patients with castrate resistant prostate cancer (CRPC) and is currently recommended for chemo-naA¯ve patients and after progression on chemotherapy. We reviewed our initial experience with the use of AA in these patients. Patients and Methods : Forty six consecutive CRPC patients were treated with AA 1000 mg/day and prednisolone 5 mg twice daily in 2 cancer centres in England and Saudi Arabia. Treatment was continued until disease progression or unacceptable toxicity. Patients achieving prostate specific antigen decline (PSA) ≥ 50% were considered as marker responders. Results : Median age was 76 (52-91) years. 28 and 18 patients received AA in pre-chemotherapy and post-chemotherapy setting respectively. PSA marker response was achieved in 56.1% (23/41) assessable patients. Objective radiological response rate was seen in 31.6% (6/19) and stable disease in 15.8% (3/19) assessable patients. After a median follow up of 20 months, median time to PSA progression was 12 months (95% CI: 9.5-14.5) and median overall survival was not reached (mean = 21 months, 95% CI: 18-24.5). Toxicity was assessed in 18 patients. All grades adverse events of special interest were hypokalaemia (22%) and hypertension (11%). Conclusion : In daily clinical practice, AA is an effective treatment for patients with CRPC. It produces meaningful marker and objective responses, marker progression free survival and OS that are comparable to those reported in clinical trials. Monitoring of blood pressure and serum potassium is recommended.
简介:醋酸阿比特龙(AA)改善去势抵抗性前列腺癌(CRPC)患者的预后,目前推荐用于未化疗的患者和化疗进展后的患者。我们回顾了我们在这些患者中使用AA的初步经验。患者和方法:在英国和沙特阿拉伯的2个癌症中心,连续46例CRPC患者接受AA 1000 mg/天和强的松龙5 mg/天两次的治疗。治疗持续到疾病进展或不可接受的毒性。前列腺特异性抗原下降(PSA)达到‰~ 50%的患者被认为是标志物应答者。结果:中位年龄为76(52-91)岁。化疗前和化疗后分别有28例和18例患者接受AA治疗。在56.1%(23/41)可评估的患者中,PSA标记物达到了应答。客观放射学应答率为31.6%(6/19),可评估患者的病情稳定率为15.8%(3/19)。中位随访20个月后,PSA进展的中位时间为12个月(95% CI: 9.5-14.5),中位总生存期未达到(平均21个月,95% CI: 18-24.5)。对18例患者进行了毒性评估。所有级别的特别关注的不良事件是低钾血症(22%)和高血压(11%)。结论:在日常临床实践中,AA是治疗CRPC患者的有效方法。它产生了有意义的标志物和客观反应,标志物无进展生存和OS,可与临床试验报告的结果相媲美。建议监测血压和血钾。
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引用次数: 2
Peritoneal Carcinomatosis and Multi-Organ Metastases are Prognostic Factors in Colorectal Cancer: A Retrospective Analysis 腹膜癌和多器官转移是结直肠癌的预后因素:回顾性分析
Pub Date : 2016-04-05 DOI: 10.6000/1927-7229.2016.05.01.1
J. Garde-Noguera, M. Gil-Raga, Asunción Juárez-Marroquí, S. Maciá-Escalante, Manuel Terradez-Gurrea, C. Camps-Herrero, A. Llombart-Cussac
Background : Peritoneal carcinomatosis and multi-organ metastases might be prognostic factors in patients with advanced colorectal cancer and inoperable metastases at diagnosis. Methods : A retrospective study was performed to examine the relationship between patient clinical characteristics and prognosis in patients with colorectal cancer and indication for first-line systemic chemotherapy. Results : One hundred and twelve patients were accrued. According to univariate analysis, peritoneal carcinomatosis, lack of primary tumour resection and multi-organ metastases were associated with poor overall survival. According to multivariate analysis, patients with peritoneal carcinomatosis and patients with multi-organ metastases had a shorter overall survival (12 vs 27.0 months, p<0.001 and 14,6 vs 27 months, p=0.007, respectively). Conclusions : Our results indicate that presence of peritoneal carcinomatosis and multi-organ metastases are independent predictors of poor outcome for patients with colorectal cancer undergoing first line treatment with standard chemotherapy.
背景:腹膜癌和多器官转移可能是晚期结直肠癌和不能手术转移患者的预后因素。方法:回顾性研究结直肠癌患者临床特征与预后与一线全身化疗指征的关系。结果:共收集患者112例。根据单因素分析,腹膜癌、缺乏原发肿瘤切除和多器官转移与总生存率低相关。多因素分析显示,腹膜癌患者和多器官转移患者的总生存期较短(分别为12 vs 27.0个月,p<0.001和14.6 vs 27个月,p=0.007)。结论:我们的研究结果表明,腹膜癌和多器官转移的存在是接受标准化疗一线治疗的结直肠癌患者预后不良的独立预测因素。
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引用次数: 0
Cancer Stem-Cell Related miRNAs: Novel Potential Targets for Metastatic Prostate Cancer 癌症干细胞相关mirna:转移性前列腺癌的新潜在靶点
Pub Date : 2015-12-11 DOI: 10.6000/1927-7229.2015.04.04.4
A. Singh, Anand P Khandwekar, Neeti Sharma
Globally Prostate Cancer is the second most commonly diagnosed and sixth leading cause of Cancer mortalities in men worldwide but currently there is no cure for metastatic castration-resistant prostate cancer (CRPC). Chemoresistance and metastasis are the main causes of treatment resistance and mortality in Prostate Cancer patients. Although several advances have been made to control yet there is an urgent need to investigate the mechanisms and pathways for chemoresistance and prostate cancer (PCa) metastasis. Cancer stem cells (CSCs), a sub-population of cancer cells characterised by self-renewal and tumor initiation, have gained intense attention as they not only play a crucial role in cancer relapse but also contribute substantially to chemoresistance. Contributing to the role of CSCs are the miRNAs which are known key regulators of the posttranscriptional regulation of genes involved in a wide array of biological processes including tumorigenesis. The altered expressions of miRNAs have been associated with not only with tumor development but also with invasion, angiogenesis, drug resistance, and metastasis. Thus identification of signature miRNA associated with EMT and CSCs would provide a novel therapeutic strategy for the improvement of current treatment thus leading to increase in patient’s survival.
在全球范围内,前列腺癌是男性癌症死亡的第二大常见诊断和第六大原因,但目前尚无治愈转移性去势抵抗性前列腺癌(CRPC)的方法。化疗耐药和转移是前列腺癌患者耐药和死亡的主要原因。尽管在控制前列腺癌(PCa)方面取得了一些进展,但迫切需要研究化疗耐药和前列腺癌转移的机制和途径。癌症干细胞(Cancer stem cells, CSCs)是一种以自我更新和肿瘤启动为特征的癌细胞亚群,由于它们不仅在癌症复发中起着至关重要的作用,而且在化疗耐药中起着重要作用,因此受到了广泛的关注。在CSCs中起作用的是mirna,这些mirna是参与包括肿瘤发生在内的一系列生物过程的基因转录后调节的关键调节因子。mirna表达的改变不仅与肿瘤的发展有关,还与侵袭、血管生成、耐药和转移有关。因此,识别与EMT和CSCs相关的特征miRNA将为改善当前治疗提供一种新的治疗策略,从而提高患者的存活率。
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引用次数: 1
pH Monitoring of Tumor Microenvironment and Low Volume of Urine in Experimental Rats 实验大鼠肿瘤微环境与低尿量pH监测
Pub Date : 2015-12-11 DOI: 10.6000/1927-7229.2015.04.04.3
T. Kisková, Steffekova Zuzana, Karasova Martina, Kokosova Natalia
The pH monitoring of the tumor microenvironment in vivo seems to be in fact complicated and technically quite challenging nowadays. Also the strategy of measuring urine pH of a little amount is not fully solved. Thus, the aim of our study was to monitor pH of urine samples (< 0.1 ml) and of tumor microenvironment of anesthetized rats in a minimal invasive way. The small urine volumes of rats or mice make pH measurements difficult, as standard pH electrodes usually need a minimal volume of several milliliters to function. The manual micromanipulator together with a needle-type housed pH microsensor offers a simple and effective way to do so. Our results show that pH of urine and tumor microenvironment was lower in tumor bearing rats compared to healthy subjects. The unique technology of pH microsensors could be a promising way to monitor the pH in many experimental designs and clinical praxis
目前,肿瘤微环境的pH监测似乎是一个复杂的技术难题。少量测定尿液pH值的策略也没有完全解决。因此,我们的研究目的是通过微创方法监测麻醉大鼠尿液样本(< 0.1 ml)的pH值和肿瘤微环境。大鼠或小鼠的尿液量小,使得pH值测量变得困难,因为标准的pH电极通常需要几毫升的最小体积才能发挥作用。手动微操作器与针式封装pH微传感器一起提供了一种简单有效的方法来做到这一点。结果表明,荷瘤大鼠尿液pH值和肿瘤微环境pH值均低于健康大鼠。pH微传感器的独特技术在许多实验设计和临床应用中具有广阔的应用前景
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引用次数: 0
The Role of the IGF Axis in Epithelial-to-Mesenchymal Transition during the Progression of Prostate Cancer 前列腺癌进展过程中IGF轴在上皮向间质转化中的作用
Pub Date : 2015-12-11 DOI: 10.6000/1927-7229.2015.04.04.5
R. Mansor, A. Bahl, J. Holly, C. Perks
Prostate cancer is the second most common lethal cancer in men worldwide. Despite the fact that the prognosis for patients with localized disease is good, many patients succumb to metastatic disease with the development of resistance to hormone treatments. This is normally termed castration-resistant prostate cancer (CRPC). The development of metastatic, castration-resistant prostate cancer has been associated with epithelial-to-mesenchymal transition (EMT), a process where cancer cells acquire a more mesenchymal phenotype with enhanced migratory potential, invasiveness and elevated resistance to apoptosis. The main event in EMT is the repression of epithelial markers such as E-cadherin and upregulation of mesenchymal markers such as N-cadherin, vimentin and fibronectin. The insulin-like growth factor (IGF) signalling axis is essential for normal development and maintenance of tissues, including that of the prostate, and dysregulation of this pathway contributes to prostate cancer progression and malignant transformation. It is becoming increasingly clear that one of the ways in which the IGF axis impacts upon cancer progression is through promoting EMT. This review will explore the role of EMT in prostate cancer progression with a specific focus on the involvement of the IGF axis and its downstream signalling pathways in regulating EMT in prostate cancer.
前列腺癌是世界范围内男性中第二常见的致命癌症。尽管局部疾病患者的预后良好,但许多患者因对激素治疗产生耐药性而死于转移性疾病。这通常称为去势抵抗性前列腺癌(CRPC)。转移性、去势抵抗性前列腺癌的发展与上皮-间质转化(EMT)有关,这是一种癌细胞获得更多间质表型的过程,具有增强的迁移潜力、侵袭性和对细胞凋亡的抗性。EMT的主要事件是上皮标记物如E-cadherin的抑制和间质标记物如N-cadherin、vimentin和纤维连接蛋白的上调。胰岛素样生长因子(IGF)信号轴对包括前列腺在内的组织的正常发育和维持至关重要,该通路的失调有助于前列腺癌的进展和恶性转化。越来越清楚的是,IGF轴影响癌症进展的方式之一是通过促进EMT。本文将探讨EMT在前列腺癌进展中的作用,特别关注IGF轴及其下游信号通路在前列腺癌中调节EMT的作用。
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引用次数: 1
TCTP silencing in ovarian cancer cells results in actin cytoskeleton remodeling and motility increase 卵巢癌细胞中TCTP沉默导致肌动蛋白细胞骨架重塑和运动性增加
Pub Date : 2015-12-11 DOI: 10.6000/1927-7229.2015.04.04.1
Yianzhu Liu, Li Zhang, N. Tejpal, J. Kubiak, R. Ghobrial, X. Li, M. Kloc
Translationally Controlled Tumor-associated Protein (TCTP) plays a role in a plethora of normal and cancer cell functions including cell cycle progression, cell growth and metastasis. Our previous studies showed that TCTP interacts with cellular cytoskeleton and is localized, in cell-type specific manner, on actin filaments in various types of ovarian cancer cells. Here we used small interfering RNA (siRNA) for silencing TCTP expression in human ovarian surface epithelial noncancerous cell line HIO180, ovarian carcinoma cell lines SKOV3 and OVCAR3 and analyzed effect of TCTP silencing on actin cytoskeleton and cell motility. We show that a down regulation of TCTP caused dramatic restructuring and redistribution of actin filaments in HIO180, SKOV3 and OVCAR3 cells and resulted in cell motility increase. This previously unidentified dependence of actin cytoskeleton remodeling and cell motility on TCTP level might be responsible for high metastatic potential and aggressiveness of ovarian cancer cells and will help to pinpoint novel targets for anticancer therapies .
翻译控制肿瘤相关蛋白(TCTP)在细胞周期进程、细胞生长和转移等多种正常细胞和癌细胞功能中发挥重要作用。我们之前的研究表明,TCTP与细胞骨架相互作用,并以细胞类型特异性的方式定位于各种类型卵巢癌细胞的肌动蛋白丝上。本实验采用小干扰RNA (siRNA)沉默人卵巢表面上皮非癌细胞系HIO180、卵巢癌细胞系SKOV3和OVCAR3中TCTP的表达,分析TCTP沉默对肌动蛋白细胞骨架和细胞运动的影响。我们发现,TCTP的下调导致HIO180、SKOV3和OVCAR3细胞中肌动蛋白丝的重组和重新分配,并导致细胞运动增加。这种先前未被发现的肌动蛋白细胞骨架重塑和细胞运动对TCTP水平的依赖性可能是卵巢癌细胞高转移性和侵袭性的原因,并将有助于确定抗癌治疗的新靶点。
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引用次数: 1
Extracellular HSP90 in Cancer Invasion and Metastasis: From Translational Research to Clinical Prospects 细胞外热休克蛋白90在肿瘤侵袭和转移中的作用:从转化研究到临床前景
Pub Date : 2015-12-11 DOI: 10.6000/1927-7229.2015.04.04.7
D. Thomaidou, E. Patsavoudi
During the last decade, the extracellular molecular chaperone HSP90 (eHSP90) has been identified as a critical effector in cancer cell invasion and metastasis by virtue of its interaction with a diverse cohort of molecules that serve as key nodal points in oncogenic pathways. Thus eHSP90 has most recently emerged as a novel target in cancer therapeutics, subsequently becoming the focus of several drug development efforts. This review highlights recent studies on the mechanisms through which eHSP90 exhibits its tumor cell invasion action. It also presents latest efforts to translate this cumulative knowledge into clinical practice to disable eHSP90-driven metastasis.
在过去的十年中,细胞外分子伴侣HSP90 (eHSP90)已被确定为癌细胞侵袭和转移的关键效应物,因为它与多种分子相互作用,这些分子在致癌途径中充当关键节点。因此,eHSP90最近成为癌症治疗的新靶点,随后成为几种药物开发工作的焦点。本文综述了近年来有关eHSP90侵袭肿瘤的研究进展。它还介绍了将这些累积知识转化为临床实践以禁用ehsp90驱动的转移的最新努力。
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引用次数: 1
Standardized Extract of the Persian Gulf Sponge, Axinella Sinoxea Selectively Induces Apoptosis through Mitochondria in Human Chronic Lymphocytic Leukemia Cells 波斯湾海绵标准提取物Axinella Sinoxea通过线粒体选择性诱导人慢性淋巴细胞白血病细胞凋亡
Pub Date : 2015-12-11 DOI: 10.6000/1927-7229.2015.04.04.2
A. Salimi, Mehrnoush Pir Saharkhiz, A. Motallebi, Enayatollah Seydi, A. Mohseni, M. Nazemi, J. Pourahmad
Sponges are important components of the Persian Gulf animal communities. The marine sponges of the genus Axinella sinoxea is are a genus of sponges in the family Axinellidae . Species of Axinella sinoxea occur in the India, Pacific Oceans and also Persian Gulf. Chronic lymphocytic leukemia (CLL) is a disease characterized by the relentless accumulation of CD5 + B lymphocytes. CLL is the most common leukemia in adults, about 25–30% of all leukemias. In this study B lymphocytes mitochondria (both cancerous and non-cancerous) were isolated using differential centrifugation from peripheral blood samples and succinate dehydrogenase activity, mitochondrial reactive oxygen species (ROS) production, collapse of mitochondrial membrane potential (MMP), mitochondrial swelling and finally release of cytochrome C were examined following the addition of methanolic extract of Axinella sinoxea . Our results showed that only in mitochondria isolated from cancerous BUT NOT normal lymphocytes a significant (P < 0.05) increase in mitochondrial ROS formation, MMP collapse, mitochondrial swelling and cytochrome c release. These results showed that Axinella sinoxea extract has a selective toxicity on chronic lymphocytic leukemia lymphocytes and their mitochondria and hence may be considered as a promising anti CLL candidate for further studies needed as a supplement for cancer patients in the future
海绵是波斯湾动物群落的重要组成部分。青霉属海绵是青霉科海绵的一个属。Axinella sinoxea的种类出现在印度,太平洋和波斯湾。慢性淋巴细胞白血病(CLL)是一种以CD5 + B淋巴细胞持续积累为特征的疾病。CLL是成人中最常见的白血病,约占所有白血病的25% - 30%。本研究采用差速离心法分离外周血B淋巴细胞线粒体(癌性和非癌性),并检测添加青霉甲醇提取物后琥珀酸脱氢酶活性、线粒体活性氧(ROS)生成、线粒体膜电位(MMP)衰竭、线粒体肿胀和细胞色素C最终释放。我们的研究结果表明,只有从癌性淋巴细胞中分离的线粒体,而不是正常淋巴细胞,线粒体ROS形成、MMP塌陷、线粒体肿胀和细胞色素c释放显著(P < 0.05)增加。这些结果表明,青霉提取物对慢性淋巴细胞白血病淋巴细胞及其线粒体具有选择性毒性,因此可能被认为是一种有前景的抗CLL候选物,需要在未来的进一步研究中作为癌症患者的补充
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引用次数: 9
Neuroendocrine Differentiation and Epithelial to Mesenchymal Transition in Prostate Cancer: cAMP-Dependent Signaling as a Therapeutic Target 前列腺癌的神经内分泌分化和上皮向间质转化:camp依赖信号作为治疗靶点
Pub Date : 2015-12-11 DOI: 10.6000/1927-7229.2015.04.04.6
C. Myers
Prostate cancer exhibits both epithelial to mesenchymal transition and neuroendocrine differentiation. The major barrier to targeting epithelial to mesenchymal transition is that it is heavily involved with normal biology, such as wound repair. In prostate cancer, cAMP can trigger both neuroendocrine differentiation and epithelial to mesenchymal transition in a Snail-dependent manner We will review inhibition of cAMP-signaling as a target for drug development with the goal of simultaneously blocking both neuroendocrine differentiation and epithelial to mesenchymal transition in a tissue and tumor selective manner.
前列腺癌表现为上皮向间质转化和神经内分泌分化。靶向上皮细胞向间充质细胞转化的主要障碍是它与正常生物学密切相关,例如伤口修复。在前列腺癌中,cAMP可以以蜗牛依赖的方式触发神经内分泌分化和上皮向间质转化。我们将回顾cAMP信号的抑制作为药物开发的靶点,目的是同时以组织和肿瘤选择性的方式阻断神经内分泌分化和上皮向间质转化。
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引用次数: 0
期刊
Journal of Analytical Oncology
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