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Biomarkers for Bladder Cancer: Present Challenges and Recent Developments 膀胱癌的生物标志物:目前的挑战和最新进展
Pub Date : 2018-05-08 DOI: 10.12691/JCRT-6-2-2
Barnali Deb, Prashant Kumar
Bladder cancer is the most common carcinoma of the urinary system. Early detection and diagnosis of bladder cancer is a major challenge. Urine cytology has low sensitivity and specificity, especially for low-grade tumors. Cystoscopy is the gold standard for the detection and follow-up of bladder tumors. However, it is an expensive and invasive procedure and can fail to detect many bladder lesions such as carcinoma in situ (CIS). It is thus an unmet need to identify a robust set of biomarkers, which can improve the current diagnostic practice. During the last one decade, several bladder tumor markers have been identified for diagnosis, however, none of these diagnostic markers offer sufficient sensitivity and specificity to be routinely used in the clinics. Recent advancement in mass spectrometry (MS)-based quantitative proteomics has emerged as a powerful method to discover wide range of proteins in complex biological samples. In this review, we summarize the status of biomarkers currently identified and used for bladder cancer diagnosis.
膀胱癌是泌尿系统最常见的癌症。膀胱癌的早期发现和诊断是一项重大挑战。尿细胞学检查敏感性和特异性较低,特别是对低级别肿瘤。膀胱镜检查是膀胱肿瘤发现和随访的金标准。然而,它是一种昂贵的侵入性手术,并且不能检测到许多膀胱病变,如原位癌(CIS)。因此,识别一组强大的生物标志物是一个未被满足的需求,这可以改善当前的诊断实践。在过去的十年中,已经确定了几种膀胱肿瘤标志物用于诊断,然而,这些诊断标志物都没有提供足够的敏感性和特异性,无法在临床中常规使用。基于质谱(MS)的定量蛋白质组学的最新进展已经成为一种发现复杂生物样品中广泛蛋白质的有力方法。在这篇综述中,我们总结了目前识别和用于膀胱癌诊断的生物标志物的现状。
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引用次数: 0
In Silico Molecular Docking Studies of Rutin Compound against Apoptotic Proteins (Tumor Necrosis Factor, Caspase-3, NF-Kappa-B, P53, Collagenase, Nitric Oxide Synthase and Cytochrome C) 芦丁化合物抗凋亡蛋白(肿瘤坏死因子、Caspase-3、NF-Kappa-B、P53、胶原酶、一氧化氮合酶、细胞色素C)的硅基分子对接研究
Pub Date : 2018-04-27 DOI: 10.12691/jcrt-6-2-1
P. Jayameena, K. Sivakumari, K. Ashok, S. Rajesh
Rutin as a flavonoid compound contains many flavonoids having antitumor properties. Therefore, the present study was aimed to dock rutin compound with apoptotic proteins like TNF, Caspase-3, NF-Kappa-B, P53, Collagenase, Nitric Oxide Synthase and Cytohrome C by AutoDock software. The docking scores were highest in Nitric oxide synthase (-3.68 kcal/mol) followed by Tumor Necrosis Factor (-3.22 kcal/mol), Caspase-3 (-2.95 kcal/mol), Collagenase (-2.47 kcal/mol), Cytochrome C (-2.31 kcal/mol), NF-kappa-B (-1.8 kcal/mol) and P53 (-0.32 kcal/mol). The Log P value and lower hydrogen bond counts, confirming the ability of rutin compound for binding at the active sites of the receptor was determined by the in silico method. The potential drug candidate can further be validated by wet lab studies for its proper function.
芦丁作为一种类黄酮化合物,含有多种具有抗肿瘤特性的类黄酮。因此,本研究旨在通过AutoDock软件将芦丁化合物与TNF、Caspase-3、NF-Kappa-B、P53、胶原酶、一氧化氮合酶、细胞色素C等凋亡蛋白进行对接。对接得分最高的是一氧化氮合酶(-3.68 kcal/mol),其次是肿瘤坏死因子(-3.22 kcal/mol)、Caspase-3 (-2.95 kcal/mol)、胶原酶(-2.47 kcal/mol)、细胞色素C (-2.31 kcal/mol)、NF-kappa-B (-1.8 kcal/mol)和P53 (-0.32 kcal/mol)。Log P值和较低的氢键计数,证实了芦丁化合物在受体活性位点的结合能力。潜在的候选药物可以通过湿实验室研究进一步验证其适当的功能。
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引用次数: 5
Indole-3-carbinol: A Promising Hope for Cancer Therapy 吲哚-3-甲醇:癌症治疗的希望
Pub Date : 2018-04-17 DOI: 10.12691/JCRT-6-1-5
Ahmed M. Kabel, Eman A. Alharthi, Rana K. Alshehri, Afnan S. Alghamdi
Indole-3-carbinol (I3C) is a natural agent found in high amounts in cruciferous vegetables and is also available as dietary supplements. It is considered as a promising agent for the ongoing medical research due to its possible antioxidant, anti-inflammatory, anti-tumor, antiapoptotic and anti-atherogenic properties. Recent studies are directed towards assessment of the possible effects of I3C on various body organs including the heart, liver, kidney and the endocrine system. This mini-review sheds light on the different properties of I3C that make it a promising therapeutic agent for a wide variety of human diseases including cancer.
吲哚-3-甲醇(I3C)是一种在十字花科蔬菜中大量存在的天然物质,也可作为膳食补充剂使用。由于其可能具有抗氧化、抗炎、抗肿瘤、抗细胞凋亡和抗动脉粥样硬化的特性,被认为是一种有前景的医学研究药物。最近的研究旨在评估I3C对心脏、肝脏、肾脏和内分泌系统等各种身体器官可能产生的影响。这篇小型综述揭示了I3C的不同特性,使其成为包括癌症在内的多种人类疾病的有希望的治疗剂。
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引用次数: 1
LRRC超家族成员在肿瘤的研究进展The Progress of Research on LRRC Super Family Members in Cancer LRRC超家族成员在肿瘤的研究进展The Progress of Research on LRRC Super Family Members in Cancer
Pub Date : 2018-04-11 DOI: 10.12677/WJCR.2018.82013
史婧怡, 陈妍珂
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引用次数: 0
术中放射治疗应用于乳房保留手术——病例分析(2015~2018) 术中放射治疗应用于乳房保留手术——病例分析(2015~2018)
Pub Date : 2018-04-11 DOI: 10.12677/WJCR.2018.82011
容菁霞, 郑翠芬, 柯卉玲
Regular mammography screening project for Taiwanese women aged 45~69 years has been administered for about 15 years which has achieved a good result in detection of early breast cancer and reduction in breast cancer mortality. According to NCCN (National Comprehensive Cancer Network) guideline, breast conserving surgery (BCS) is recommended for low grade breast cancer, because it provides better cosmetic effect and life quality compared to radical mastectomy. BCS combined with post-operative whole breast irradiation is a standard therapy for low grade breast cancer in previous practice because it provided same overall survival as traditional mastectomy. Inevitably, whole breast irradiation may yield some skin complications such as skin fibrosis, sclerosis, telangiectasia and even cause hyperpigmentation of nipple-areolar complex with lack of elasticity. Moreover, it may result in deformity of ipsilateral breast and alter psychological effect. FDA has approved the administration of intraoperative radiation therapy (IORT) in patients with breast cancer undergoing breast conserving surgery since 2012. It provided same level of safety as traditional post-operative whole breast irradiation and avoided aforementioned side effects [1]. Our institute started to perform IORT in low grade breast cancer since 2015. 60 patients received IORT and there were no apparent immediate or delay complication since then. Besides, no local recurrence or distant metastasis was detected during cancer surveillance. IORT is considered as a safe and feasible option in treatment of low grade breast cancer.
台湾45~69岁女性定期乳房x光检查项目已实施约15年,在早期乳腺癌的发现和降低乳腺癌死亡率方面取得了良好的效果。根据NCCN (National Comprehensive Cancer Network)指南,低级别乳腺癌推荐保乳手术(breast conservation surgery, BCS),因为与根治性乳房切除术相比,保乳手术能提供更好的美容效果和生活质量。在以前的实践中,BCS联合术后全乳照射是低级别乳腺癌的标准治疗方法,因为它提供了与传统乳房切除术相同的总生存率。全乳照射不可避免地会产生一些皮肤并发症,如皮肤纤维化、硬化、毛细血管扩张,甚至导致缺乏弹性的乳头-乳晕复合体色素沉着。此外,它可能导致同侧乳房畸形和改变心理效应。自2012年以来,FDA已批准对接受保乳手术的乳腺癌患者进行术中放疗(IORT)。其安全性与传统手术后全乳照射相同,且避免了上述副作用[1]。我院自2015年开始对低分级乳腺癌进行IORT治疗。60例患者接受IORT治疗,此后无明显的即时或延迟并发症。此外,在肿瘤监测期间未发现局部复发或远处转移。IORT被认为是治疗低级别乳腺癌的一种安全可行的选择。
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引用次数: 0
高危复发胃癌术后予香菇多糖维持治疗的临床观察Clinical Observation of Immunization Maintenance Treatment with Lentinan on Postoperative Gastric Cancer with High Risk Recurrence 高危复发胃癌术后予香菇多糖维持治疗的临床观察Clinical Observation of Immunization Maintenance Treatment with Lentinan on Postoperative Gastric Cancer with High Risk Recurrence
Pub Date : 2018-04-11 DOI: 10.12677/WJCR.2018.82010
陈苏娟, 李瑞中
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引用次数: 0
The Antioxidant Glycolysis Inhibitor (Citric Acid) Induces a Dose-dependent Caspase-mediated Apoptosis and Necrosis in Glioma Cells 抗氧化糖酵解抑制剂(柠檬酸)诱导剂量依赖性caspase介导的胶质瘤细胞凋亡和坏死
Pub Date : 2018-03-21 DOI: 10.12691/jcrt-6-1-4
S. Sayed, H. Baghdadi, Nassar Ayoub Abdellatif Omar, A. Allithy, N. Hablas, A. Fakhreldin, Reham A. Mariah, Momen El-shazley, M. Ayat, S. Mostafa, Mostafa Abu-el Naga, M. Abdel-Halim
Background: Glioma tumors are still a big challenge being incurable with current chemotherapy and radiotherapy treatments. Surgical treatment of glioma needs adjuvant effective targeting therapy for better glioma cell treatment. Citrate is a well-known antioxidant organic acid abundant in citrus fruits and is an inhibitor of glycolysis through targeting the glycolytic enzyme phosphofructokinase, one of the key enzymes of glycolysis. Citrate is a natural product that is formed inside mitochondria during Krebs cycle to the extent that Krebs cycle is often referred to as citric acid cycle. It was reported that glioma cells are driven by glycolysis where glioma cells upregulates the expression of glycolysis genes and enzymes. Objectives: This aim is to investigate effect of citrate on glioma cells viability, morphology and moge of glioma-induced cell death. Methodology: In this study, citrate-induced glioma cell death was investigated using MTT assay, western blot analysis and flowcytometric evaluation was done to C6 glioma cells. Results: Citrate induced a potent anti-glioma effect by significantly decreasing viability of C6 glioma cells in a dose-dependent manner. Flow cytometric analysis revealed that at 5 mM, citrate induced a caspase-dependent apoptotic glioma cell death. Higher doses of citrate (9 mM) induced necro-apoptotic glioma cell death. Conclusion: citrate may be a promising therapeutic treatment for glioma and glioblastoma. Citrate-rich fruits are strongly recommended as a nutritional treatment for glioma patients.
背景:神经胶质瘤仍然是一个巨大的挑战,目前的化疗和放疗治疗无法治愈。胶质瘤的手术治疗需要辅助有效的靶向治疗才能更好的治疗胶质瘤细胞。柠檬酸盐是一种众所周知的抗氧化有机酸,富含在柑橘类水果中,通过靶向糖酵解的关键酶之一磷酸果糖激酶而成为糖酵解的抑制剂。柠檬酸盐是在克雷布斯循环过程中在线粒体内形成的天然产物,克雷布斯循环通常被称为柠檬酸循环。据报道,胶质瘤细胞是由糖酵解驱动的,胶质瘤细胞上调糖酵解基因和酶的表达。目的:探讨枸橼酸盐对胶质瘤细胞活力、形态学及胶质瘤诱导细胞死亡的影响。方法:本研究采用MTT法、western blot法和流式细胞术对C6胶质瘤细胞进行评价,探讨柠檬酸盐诱导胶质瘤细胞死亡。结果:柠檬酸盐通过剂量依赖性地显著降低C6胶质瘤细胞的活力,诱导了有效的抗胶质瘤作用。流式细胞术分析显示,在5 mM时,柠檬酸盐诱导caspase依赖性凋亡胶质瘤细胞死亡。高剂量的柠檬酸盐(9 mM)诱导坏死-凋亡性胶质瘤细胞死亡。结论:枸橼酸盐可能是治疗胶质瘤和胶质母细胞瘤的有效药物。富含柠檬酸盐的水果被强烈推荐作为神经胶质瘤患者的营养治疗。
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引用次数: 1
3-bromopyruvate as a Promising Treatment for Hematological Cancer 3-溴丙酮酸作为一种有希望治疗血液病的药物
Pub Date : 2018-03-06 DOI: 10.12691/JCRT-6-1-3
M. Ayat
Many biological differences exist between cancer cells and normal cells that can act as potential targets in targeted cancer therapy. Hematological cancers e.g. lymphoma, leukemia and myeloma exhibit drug-resistance that ultimately results in deteriorated patients' conditions and high mortality rates. Resistance of hematological malignancy to conventional chemotherapy is attributed in part to upregulation of glucose oxidation (glycolysis) genes evidenced by gaining a promising chemosensitization effect upon adding a glycolysis inhibitor to chemotherapeutics. The promising anticancer agent 3-bromopyruvate (3BP) is a structural analog of both pyruvate and lactate. 3BP was reported to antagonize the Warburg effect (malignant phenotype where cancer cells utilize cytoplasmic glucose oxidation to produce ATP and lactate even in the presence of oxygen without making benefit of the generous ATP provision from glucose oxidation via mitochondrial pathways). Warburg effect deprives cancer cells from the high energetic yield achieved through utilizing mitochondrial pathways. 3BP is a promising antiglycolytic agent that targets major glycolysis enzymes (hexokinase II and glyceraldehyde-3-phosphate dehydrogenase. In this article, 3BP promising anticancer effects in treating lymphoma, leukemia and myeloma are discussed in addition to the mode of inhibition of Warburg effect using 3BP. In conclusion, 3BP is a promising anticancer drug (that will be more powerful upon proper pharmaceutical formulations) for treating hematological malignancies. 3BP is advisable to be included in treatment protocols in hematological cancers as a chemosensitizer or as a sole anticancer agent.
癌细胞和正常细胞之间存在许多生物学差异,这些差异可以作为靶向癌症治疗的潜在靶点。血液病癌症如淋巴瘤、白血病和骨髓瘤表现出耐药性,最终导致患者病情恶化和高死亡率。血液恶性肿瘤对常规化疗的耐药性部分归因于葡萄糖氧化(糖酵解)基因的上调,在化疗药物中添加糖酵解抑制剂获得了有希望的化学增敏效应。3-溴丙酮酸(3BP)是一种很有前景的抗癌药物,它是丙酮酸和乳酸的结构类似物。据报道,3BP可以拮抗Warburg效应(恶性表型,癌细胞利用细胞质葡萄糖氧化产生ATP和乳酸,即使在氧气存在的情况下,也没有通过线粒体途径利用葡萄糖氧化提供的大量ATP)。华宝效应剥夺了癌细胞通过利用线粒体途径获得的高能量产量。3BP是一种很有前途的抗糖酵解药物,主要作用于糖酵解酶(己糖激酶II和甘油醛-3-磷酸脱氢酶)。本文讨论了3BP在治疗淋巴瘤、白血病和骨髓瘤方面的抗癌作用,以及3BP抑制Warburg效应的方式。总之,3BP是一种很有前途的抗癌药物(在适当的药物配方下会更有效),用于治疗血液系统恶性肿瘤。建议将3BP作为化学增敏剂或单独的抗癌剂纳入血液病的治疗方案中。
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引用次数: 3
Comparison of Premenopousal and Postmenopausal Breast Cancer Cases in Terms of Demographic and Prognostic Factor 绝经前和绝经后乳腺癌病例的人口学和预后因素比较
Pub Date : 2018-02-27 DOI: 10.12691/JCRT-6-1-2
I. Kızıloglu, A. C. Acara, B. Bayar, S. Karaisli, E. Sari, E. Tarcan
Breast cancer is the second most common type of cancer in the world and it is the most frequently seen cancer type in women. In early stages involving small and monocenter tumors, surgical treatment with breast conserving surgery followed by radiotherapy is the most preferred treatment regimen. Similar to the size of the tumor, several prognostic factors determine survival in breast cancer patients. This study was conducted to evaluate prognostic factors and their relationship to the menopausal status of the patients. University Ataturk Training and Research Hospital, Izmir, Turkey with 573 patients diagnosed with breast cancer between January 2006 and December 2012. Patient age, menopausal status, tumor location surgical treatment information, treatment regimen was gathered using the registry system of the hospital. Male breast cancer patients and patients with insufficient data were excluded. The mean (±SD) age of the study population was determined as 55.9 (±12.9). Most of the patients (65.3%) included in the study were identified as post-menopausal (n=199). Post-menopausal women were detected with larger tumors (p=0.048), at a later stage (p=0.037), with higher KI-67 index (p=0.015) and received more adjuvant hormone therapy (p=0.036) when compared to the pre-menopausal women. Multi-centered studies are needed to evaluate prognostic factors and their relationship to the menopausal status of the patients in order to plan more precise personal treatment regimens.
乳腺癌是世界上第二常见的癌症,也是女性中最常见的癌症。在早期涉及小和单中心肿瘤时,手术治疗保乳手术加放疗是最优选的治疗方案。与肿瘤的大小类似,一些预后因素决定了乳腺癌患者的生存。本研究旨在评估预后因素及其与患者绝经状态的关系。土耳其伊兹密尔的阿塔图尔克大学培训和研究医院在2006年1月至2012年12月期间诊断出573名乳腺癌患者。使用医院注册系统收集患者年龄、绝经状况、肿瘤位置、手术治疗信息、治疗方案。排除男性乳腺癌患者和资料不充分的患者。研究人群的平均(±SD)年龄为55.9岁(±12.9岁)。纳入研究的大多数患者(65.3%)被确定为绝经后(n=199)。与绝经前妇女相比,绝经后妇女肿瘤较大(p=0.048),晚期(p=0.037), KI-67指数较高(p=0.015),接受的辅助激素治疗较多(p=0.036)。需要多中心研究来评估预后因素及其与患者绝经状态的关系,以便制定更精确的个人治疗方案。
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引用次数: 0
Oleuropein is a Powerful Sensitizer of Doxorubicin-mediated Killing of Prostate Cancer Cells and Exerts Its Action via Induction of Autophagy 橄榄苦苷是阿霉素介导的前列腺癌细胞杀伤的强致敏剂,并通过诱导自噬发挥其作用
Pub Date : 2018-02-26 DOI: 10.12691/JCRT-4-4-2
A. Papachristodoulou, M. Tsoukala, D. Benaki, S. Kostidis, K. Gioti, N. Aligiannis, H. Pratsinis, D. Kletsas, A. Skaltsounis, E. Mikros, R. Tenta
The phenolic component Oleuropein (OLEU), a bioactive natural product, has recently shown antiproliferative properties. Doxorubicin (DXR) is an anthracycline present in many chemotherapeutic schemes, although limited due to its cardio-toxic effects. Important research effort has been devoted therefore, to reducing DXR toxicity without compromising its antitumor efficacy. The anticancer actions of DXR and OLEU were assessed, on PC-3 prostate cancer cells, while cell cycle distribution and rate of apoptosis were assessed by flow cytometry. The autophagic process was determined via immunoblotting and immunofluorescent staining. Finally, cell extracts were analyzed by NMR spectroscopy. The present study showed that both DXR and OLEU inhibited PC-3 cells proliferation, while the co-treatment with DXR and OLEU resulted in an additive inhibition. Although the addition of OLEU to DXR did not alter significantly the cell cycle distribution, exhibited by each treatment alone, and produced a marginal increase on the rate of apoptosis, both compounds produced a remarkable induction of autophagy. In addition, treated cells exhibited significant metabolite alterations. This study demonstrates that OLEU, a basic component of the everyday diet, is capable of lowering significantly the cytotoxic dose of DXR, while obtaining an important anti-proliferative effect in prostate cancer cells.
橄榄苦苷(OLEU)是一种具有生物活性的天然产物,最近显示出抗增殖特性。阿霉素(DXR)是一种蒽环类药物,存在于许多化疗方案中,尽管由于其心脏毒性作用而受到限制。因此,在不影响其抗肿瘤功效的情况下降低DXR毒性的重要研究工作已经投入。采用流式细胞术观察DXR和OLEU对PC-3前列腺癌细胞的抑癌作用,并观察细胞周期分布和凋亡率。通过免疫印迹和免疫荧光染色测定自噬过程。最后,利用核磁共振光谱对细胞提取物进行分析。本研究表明,DXR和OLEU均能抑制PC-3细胞的增殖,而DXR和OLEU共处理则具有加性抑制作用。虽然将OLEU添加到DXR中并没有显著改变细胞周期分布,并且对细胞凋亡率产生了轻微的增加,但两种化合物都产生了显著的自噬诱导作用。此外,处理过的细胞表现出显著的代谢物改变。本研究表明,OLEU作为日常饮食的基本成分,能够显著降低DXR的细胞毒剂量,同时对前列腺癌细胞具有重要的抗增殖作用。
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引用次数: 8
期刊
The Journal of Cancer Research
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