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Circulating micrornas and long noncoding rnas: Liquid biomarkers in thoracic cancers 循环小rna和长链非编码rna:胸腔肿瘤的液体生物标志物
Pub Date : 2017-03-01 DOI: 10.4103/2395-3977.202226
Pablo Reclusa, A. Valentino, R. Sirera, M. Dietrich, L. Raez, C. Rolfo
Thoracic cancers are the leading causes of cancer-related deaths worldwide. Recent advances in genome and transcriptome analysis have allowed for the identification of numerous classes of noncoding RNAs (ncRNAs) that play important roles either in a biological process or human disease. microRNAs (miRNAs) are small, 19–22 nucleotides, ncRNAs that regulate posttranscriptional gene expression by binding to the 3' untranslated region (3'UTR) of their target mRNA. Conversely, long noncoding RNAs (lncRNAs) are a novel class of transcripts longer than 200 nucleotides that do not encode any proteins. Some lncRNAs can interact with miRNAs and act as repressors, impeding them to bind to their protein-coding targets. There is cumulative evidence that these ncRNAs contribute to the tumorigenic process regulating cell growth, apoptosis, and metastasis, and may serve as biomarkers in various types of tumors. In this review, we have summarized the important role of ncRNAs as promising biomarkers in liquid biopsy for the diagnosis and prognosis of thoracic malignancies such as lung cancer, mesothelioma, and thymoma.
胸癌是全球癌症相关死亡的主要原因。基因组和转录组分析的最新进展使鉴定出在生物过程或人类疾病中发挥重要作用的多种非编码rna (ncrna)成为可能。microRNAs (miRNAs)是一种小的,19-22个核苷酸的ncRNAs,通过结合其靶mRNA的3'非翻译区(3' utr)来调节转录后基因的表达。相反,长链非编码rna (lncRNAs)是一类新的转录物,长度超过200个核苷酸,不编码任何蛋白质。一些lncrna可以与mirna相互作用,并作为抑制物,阻止它们与蛋白质编码靶标结合。越来越多的证据表明,这些ncrna参与了调节细胞生长、凋亡和转移的致瘤过程,并可能在各种类型的肿瘤中作为生物标志物。在这篇综述中,我们总结了ncrna作为液体活检中有前景的生物标志物在胸部恶性肿瘤(如肺癌、间皮瘤和胸腺瘤)的诊断和预后中的重要作用。
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引用次数: 2
Stemness-Related Markers in Cancer. 癌症中的干细胞相关标志物。
Pub Date : 2017-01-01 Epub Date: 2017-06-08 DOI: 10.4103/ctm.ctm_69_16
Wenxiu Zhao, Yvonne Li, Xun Zhang

Cancer stem cells (CSCs), with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute towards a 'stemness' phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers and signaling pathways.

肿瘤干细胞(CSCs)具有自我更新能力和多谱系分化潜力,是肿瘤细胞的一个关键亚群,可以驱动肿瘤的发生、生长和对治疗的抵抗。像胚胎干细胞和成体干细胞一样,CSCs表达在正常体细胞中不表达的标记,因此被认为有助于“干性”表型。本文综述了目前对人类癌症中干细胞相关标志物的研究,重点关注了重要的转录因子、蛋白质表面标志物和信号通路。
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引用次数: 134
Stem cell-based approach in diabetes and pancreatic cancer management 基于干细胞的糖尿病和胰腺癌治疗方法
Pub Date : 2017-01-01 DOI: 10.4103/2395-3977.200857
Yizhou Jiang, Demeng Chen
Stem cell-mediated therapy is a promising strategy for treating pancreatic diseases such as Type-1 diabetes (T1D) and pancreatic cancers. Although islet transplantation has been reported to be an effective diabetes therapy, its worldwide application is extremely limited due to the shortage of donor islets and immune rejection problems. Stem cell-based approach for islet neogenesis in vivo could provide a promising alternative source of islets for treating diabetes. On the other hand, targeting the cancer stem cells could be very effective for the treatment of pancreatic cancers. In this review, we focused on the present progress in the field of adult pancreatic stem cells, stem cell-mediated strategies for treating T1D, and pancreatic cancer stem cells, while discussing of the possible challenges involved in them.
干细胞介导疗法是治疗胰腺疾病如1型糖尿病(T1D)和胰腺癌的一种有前途的策略。尽管胰岛移植已被报道为一种有效的糖尿病治疗方法,但由于供体胰岛的短缺和免疫排斥问题,其在全球范围内的应用受到极大限制。基于干细胞的胰岛体内新生方法可能为治疗糖尿病提供一个有希望的替代胰岛来源。另一方面,针对癌症干细胞的治疗可能对胰腺癌的治疗非常有效。在这篇综述中,我们重点介绍了成人胰腺干细胞、干细胞介导的T1D治疗策略和胰腺癌干细胞领域的最新进展,同时讨论了它们可能涉及的挑战。
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引用次数: 2
Markerless Four-Dimensional-Cone Beam Computed Tomography Projection-Phase Sorting Using Prior Knowledge and Patient Motion Modeling: A Feasibility Study. 基于先验知识和患者运动建模的无标记四维锥束计算机断层扫描投影相位排序的可行性研究。
Pub Date : 2017-01-01 Epub Date: 2017-12-29
Lei Zhang, Yawei Zhang, You Zhang, Wendy B Harris, Fang-Fang Yin, Jing Cai, Lei Ren

Aim: During cancer radiotherapy treatment, on-board four-dimensional-cone beam computed tomography (4D-CBCT) provides important patient 4D volumetric information for tumor target verification. Reconstruction of 4D-CBCT images requires sorting of acquired projections into different respiratory phases. Traditional phase sorting methods are either based on external surrogates, which might miscorrelate with internal structures; or on 2D internal structures, which require specific organ presence or slow gantry rotations. The aim of this study is to investigate the feasibility of a 3D motion modeling-based method for markerless 4D-CBCT projection-phase sorting.

Methods: Patient 4D-CT images acquired during simulation are used as prior images. Principal component analysis (PCA) is used to extract three major respiratory deformation patterns. On-board patient image volume is considered as a deformation of the prior CT at the end-expiration phase. Coefficients of the principal deformation patterns are solved for each on-board projection by matching it with the digitally reconstructed radiograph (DRR) of the deformed prior CT. The primary PCA coefficients are used for the projection-phase sorting.

Results: PCA coefficients solved in nine digital phantoms (XCATs) showed the same pattern as the breathing motions in both the anteroposterior and superoinferior directions. The mean phase sorting differences were below 2% and percentages of phase difference < 10% were 100% for all the nine XCAT phantoms. Five lung cancer patient results showed mean phase difference ranging from 1.62% to 2.23%. The percentage of projections within 10% phase difference ranged from 98.4% to 100% and those within 5% phase difference ranged from 88.9% to 99.8%.

Conclusion: The study demonstrated the feasibility of using PCA coefficients for 4D-CBCT projection-phase sorting. High sorting accuracy in both digital phantoms and patient cases was achieved. This method provides an accurate and robust tool for automatic 4D-CBCT projection sorting using 3D motion modeling without the need of external surrogate or internal markers.

目的:在肿瘤放疗过程中,车载四维锥束计算机断层扫描(4D- cbct)为肿瘤靶标验证提供了重要的患者四维体积信息。重建4D-CBCT图像需要将获得的投影分类到不同的呼吸期。传统的相位分选方法要么是基于可能与内部结构不相关的外部替代物;或二维内部结构,这需要特定的器官存在或缓慢的龙门旋转。本研究的目的是探讨一种基于三维运动建模的无标记4D-CBCT投影相位排序方法的可行性。方法:将模拟过程中获取的患者4D-CT图像作为先验图像。主成分分析(PCA)用于提取三种主要的呼吸变形模式。机载患者图像体积被认为是先前CT在终末阶段的变形。通过与变形前CT的数字重建x线照片(DRR)匹配,求解每个机载投影的主变形模式系数。主PCA系数用于投影阶段排序。结果:9个数字幻影(XCATs)的PCA系数解算结果与呼吸运动在正反方向和上下方向呈现相同的模式。9个XCAT幻影的平均相位分选差均小于2%,相位差< 10%的百分比为100%。5例肺癌患者的平均相位差为1.62% ~ 2.23%。相位差在10%以内的预测比例为98.4% ~ 100%,相位差在5%以内的预测比例为88.9% ~ 99.8%。结论:本研究验证了PCA系数用于4D-CBCT投影相位分选的可行性。在数字幻影和患者病例中都达到了很高的分类精度。该方法在不需要外部替代或内部标记的情况下,为3D运动建模的4D-CBCT投影自动分类提供了一种准确、稳健的工具。
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引用次数: 0
Autophagy regulated by miRNAs in colorectal cancer progression and resistance. mirna调控的自噬在结直肠癌进展和耐药中的作用。
Pub Date : 2017-01-01 Epub Date: 2017-06-08 DOI: 10.4103/ctm.ctm_64_16
Andrew Fesler, Hua Liu, Ning Wu, Fei Liu, Peixue Ling, Jingfang Ju

The catabolic process of autophagy is an essential cellular function that allows for the breakdown and recycling of cellular macromolecules. In recent years, the impact of epigenetic regulation of autophagy by non-coding microRNAs (miRNAs) has been recognized in human cancer. In colorectal cancer, Autophagy plays critical roles in cancer progression as well as resistance to chemotherapy, and recent evidence demonstrates that miRNAs are directly involved in mediating these functions. In this review, we will focus on the recent advancements in the field of miRNA regulation of autophagy in colorectal cancer.

自噬的分解代谢过程是一种基本的细胞功能,它允许细胞大分子的分解和再循环。近年来,非编码microRNAs (miRNAs)对自噬的表观遗传调控在人类癌症中的作用已被认识。在结直肠癌中,自噬在癌症进展和化疗耐药中起着至关重要的作用,最近的证据表明,mirna直接参与介导这些功能。在本文中,我们将重点介绍miRNA调控结直肠癌自噬的最新进展。
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引用次数: 13
Efficacy and safety of paclitaxel-based therapy and nonpaclitaxel-based therapy in advanced gastric cancer 紫杉醇为主和非紫杉醇为主治疗晚期胃癌的疗效和安全性
Pub Date : 2017-01-01 DOI: 10.4103/ctm.ctm_1_17
Tongwei Wu, X. Yang, M. An, W. Luo, Danxian Cai, Xiaolong Qi
Aim: To compare the efficacy and safety of paclitaxel-based therapy versus nonpaclitaxel-based therapy in patients with advanced gastric cancer (AGC). Methods: An adequate literature search in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology and European Society of Medical Oncology was conducted. Phase II/III randomized controlled trials that detected the efficacy and safety of paclitaxel-based therapy and nonpaclitaxel-based therapy in AGC patients were enrolled. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were included in the endpoints. Results: A total of 632 patients in seven studies of were reviewed. There was a significant difference in ORR between paclitaxel and placebo therapy (odd ratio [OR] =2.68, 95% confidence interval [CI] = 1.05–6.86, P = 0.04), but not between paclitaxel and irinotecan, cisplatin or docetaxel. As no first-line treatment, paclitaxel-based therapy significantly increased ORR (OR = 1.55, 95% CI = 1.02–2.34, P = 0.04, I2 = 0%). No significant differences were found in PFS and OS between paclitaxel- and nonpaclitaxel-based therapies. In addition, paclitaxel-based therapy generally decreased the risk of vomiting and stomatitis while increased the risks of leukopenia and sensory neuropathy. Conclusion: Paclitaxel-based therapy improved ORR in AGC patients as no first-line therapy, but no significant difference was observed for PFS and OS.
目的:比较紫杉醇为基础治疗与非紫杉醇为基础治疗晚期胃癌(AGC)的疗效和安全性。方法:在MEDLINE、EMBASE、Cochrane中央对照试验注册库、美国临床肿瘤学会和欧洲肿瘤医学学会进行充分的文献检索。纳入了以紫杉醇为基础治疗和非紫杉醇为基础治疗AGC患者的有效性和安全性的II/III期随机对照试验。终点包括总缓解率(ORR)、无进展生存期(PFS)、总生存期(OS)和不良事件。结果:回顾了7项研究共632例患者。紫杉醇与安慰剂治疗的ORR有显著差异(奇比[OR] =2.68, 95%可信区间[CI] = 1.05-6.86, P = 0.04),但紫杉醇与伊立替康、顺铂或多西他赛之间无显著差异。作为非一线治疗,紫杉醇为基础的治疗显著提高了ORR (OR = 1.55, 95% CI = 1.02-2.34, P = 0.04, I2 = 0%)。以紫杉醇和非紫杉醇为基础的治疗在PFS和OS方面没有显著差异。此外,紫杉醇为基础的治疗通常降低呕吐和口炎的风险,但增加白细胞减少和感觉神经病变的风险。结论:以紫杉醇为基础的治疗可改善AGC患者的ORR,而非一线治疗,但PFS和OS无显著差异。
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引用次数: 0
Clinical utility of interleukin-18 in breast cancer patients: A pilot study 白细胞介素-18在乳腺癌患者中的临床应用:一项初步研究
Pub Date : 2017-01-01 DOI: 10.4103/2395-3977.200855
Reecha A Parikh, T. Kobawala, T. Trivedi, M. Kazi, N. Ghosh
Aim: The aim of this study is to analyze the protein expression of interleukin 18 (IL-18) in patients with untreated breast cancer and further to evaluate its clinical efficacy in predicting treatment outcome. Methods: In the present study, a total of 50 untreated patients with invasive ductal carcinoma of breast were included in the study. Expression of IL-18 was studied by immunohistochemistry method. Statistical analysis was carried out using Statistical Package for Social Sciences statistical software and P ≤ 0.05 was considered statistically significant. Results: Seventy-two percent of the breast cancer patients showed the presence of cytoplasmic and/or nuclear IL-18 immunoreactivity. IL-18 expression was significantly and positively correlated with the stromal response (χ2 = 3.97, r = 0.282, P = 0.044). Further, the IL-18 immunoreactivity was significantly higher in patients with HER2 amplification as compared to luminal B (χ2 = 2.82, r = −0.523, P = 0.047) breast cancer patients. Moreover, a trend of increased IL-18 expression was observed in estrogen/progesterone receptor (ER/PR) negative patients as compared to ER/PR positive patients (χ2 = 3.41, r = −0.282, P = 0.066). Conclusion: IL-18 could be used as a potential predictive marker and guide clinicians for recommendations to newer treatment. It might serve as a potential therapeutic target to establish novel treatment approaches along with the current treatment protocol used.
目的:本研究的目的是分析白细胞介素18 (IL-18)在未经治疗的乳腺癌患者中的蛋白表达,并进一步评价其预测治疗结果的临床疗效。方法:本研究共纳入50例未经治疗的浸润性乳腺导管癌患者。免疫组织化学法检测IL-18的表达。采用Statistical Package for Social Sciences统计软件进行统计分析,P≤0.05为差异有统计学意义。结果:72%的乳腺癌患者表现出细胞质和/或核IL-18免疫反应性。IL-18表达与基质反应呈显著正相关(χ2 = 3.97, r = 0.282, P = 0.044)。此外,与luminal B乳腺癌患者相比,HER2扩增患者IL-18免疫反应性显著升高(χ2 = 2.82, r =−0.523,P = 0.047)。雌激素/孕激素受体(ER/PR)阴性患者IL-18表达明显高于ER/PR阳性患者(χ2 = 3.41, r = - 0.282, P = 0.066)。结论:IL-18可作为一种潜在的预测指标,指导临床医生推荐新的治疗方法。它可能作为一个潜在的治疗靶点,与目前使用的治疗方案一起建立新的治疗方法。
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引用次数: 5
Current and future systemic treatment options for advanced soft-tissue sarcoma beyond anthracyclines and ifosfamide 除蒽环类药物和异环磷酰胺外,目前和未来晚期软组织肉瘤的全身治疗选择
Pub Date : 2017-01-01 DOI: 10.4103/2395-3977.200858
N. Hindi, J. Martín-Broto
Sarcomas are rare, life-threatening, malignant tumors. Surgery is the cornerstone of therapy in the localized setting. About one-third of patients develop distant metastasis. In the metastatic setting, systemic therapy is the mainstay of treatment, and several second-line options are available, proving a modest survival increase for these patients. Trabectedin is an active drug with several described mechanisms of action. Although the objective response rate is low, about one-third of patients achieve disease stabilizations and a prolonged disease control. Interestingly, it has no accumulative toxicities. Pazopanib is the only targeted therapy approved for soft-tissue sarcoma (STS), with the exception of adipocytic sarcoma. Eribulin represents a recently approved therapeutic option for liposarcoma. Other drugs such as gemcitabine combinations, dacarbazine, and taxanes have also shown activity in second lines in advanced STS. The selection should be based on histologic subtype, patient characteristics, and toxicity profile among other factors. This review will summarize clinical development of the current and future therapeutic options for this heterogeneous group of diseases.
肉瘤是罕见的、危及生命的恶性肿瘤。手术是局部环境下治疗的基石。大约三分之一的患者会发生远处转移。在转移性肿瘤中,全身治疗是主要的治疗方法,还有一些二线治疗方案可供选择,证明这些患者的生存期有适度的增加。Trabectedin是一种具有多种作用机制的活性药物。虽然客观反应率较低,但约三分之一的患者实现了疾病稳定和较长时间的疾病控制。有趣的是,它没有累积毒性。Pazopanib是除脂肪细胞肉瘤外唯一被批准用于软组织肉瘤(STS)的靶向治疗。艾力布林是最近批准的脂肪肉瘤的治疗选择。其他药物如吉西他滨联合用药、达卡巴嗪和紫杉烷也在二线治疗晚期STS中显示出活性。选择应基于组织学亚型、患者特征和毒性特征等因素。这篇综述将总结目前和未来治疗这类异质疾病的临床发展。
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引用次数: 2
Genome-wide transcriptome analysis of prostate cancer tissue identified overexpression of specific members of the human endogenous retrovirus-K family 前列腺癌组织的全基因组转录组分析鉴定了人类内源性逆转录病毒k家族特定成员的过表达
Pub Date : 2017-01-01 DOI: 10.4103/2395-3977.200859
B. Sayanjali
Aim: Human endogenous retroviruses (HERVs) are integrated into the human genome and represent 8% of the total genome. A retrovirus is the most complete retroelement and is characterized by three defined sets of regions of genes: gag, pol, and env, flanking by long terminal repeats. Among different HERVs, the K family is one of those that have been most recently integrated into the human genome. Activation and expression of members of this family are shown to be connected with some human diseases including prostate cancer. Here, we showed the global expression pattern of HERV-K (HML-2) in prostate cancer tissue. Methods: Samples from 14 patients were subjected to whole transcriptome sequencing on rRNA-depleted samples. This analysis was performed through a distinct bioinformatics method and confirmed through a series of quantitative polymerase chain reaction and immunoblotting experiments. Results: For the first time, we showed the expression of gag protein in prostate cancer tissue both in sequencing results and also immunoblotting. This showed a higher expression of the gag protein in the tumor samples relative to benign samples. Conclusion: Overexpression of gag in the tumor can implicate a role within its overexpression in tumor tissue, either by acting on neighboring genes or through the activation of promoter transcription factors.
目的:人类内源性逆转录病毒(herv)被整合到人类基因组中,占总基因组的8%。逆转录病毒是最完整的逆转录元件,其特征是三组明确的基因区域:gag, pol和env,两侧是长末端重复序列。在不同的herv中,K家族是最近被整合到人类基因组中的家族之一。该家族成员的激活和表达被证明与包括前列腺癌在内的一些人类疾病有关。在这里,我们展示了HERV-K (HML-2)在前列腺癌组织中的全局表达模式。方法:对14例患者的rrna缺失样本进行全转录组测序。该分析通过一种独特的生物信息学方法进行,并通过一系列定量聚合酶链反应和免疫印迹实验得到证实。结果:我们首次在测序结果和免疫印迹中发现gag蛋白在前列腺癌组织中的表达。这表明肿瘤样本中gag蛋白的表达高于良性样本。结论:肿瘤中gag的过表达可能与肿瘤组织中gag的过表达有关,可能通过作用于邻近基因,也可能通过激活启动子转录因子。
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引用次数: 6
The genomic organization and function of IRX1 in tumorigenesis and development IRX1在肿瘤发生和发展中的基因组组织和功能
Pub Date : 2017-01-01 DOI: 10.4103/2395-3977.200856
Pengxing Zhang, Hongwei Yang, Xin Wang, Liang Wang, Yingduan Cheng, Yongsheng Zhang, Y. Tu
Iroquois homeobox (IRX), containing transcription factor family of homologous genes and proteins, is widely expressed in both vertebrates and invertebrates embryonic tissue expression profiles. They play a crucial role in the regionalization and patterning of tissues and organs during metazoan development. IRX1, belonging to the IRX gene family, codes for active proteins involved in the development of vertebrate nervous system and plays an important role in the development of various other organs during embryo development. It also plays a critical role in the tumor formation and is identified as both the oncogene or tumor suppressor gene in a variety of tumors. This review summarizes the recent discoveries on the genomic structure of IRX1 and the type classification in different species. More specifically, we focused on explaining the key role of IRX1 in tumorigenesis, and development of tumor and influence in biological processes of metazoans, which we hope will provide a better understanding of the mechanism of IRX1.
易洛魁同源盒(Iroquois homeobox, IRX)是一种包含同源基因和蛋白的转录因子家族,在脊椎动物和无脊椎动物胚胎组织表达谱中广泛表达。它们在后生动物发育过程中对组织和器官的区域化和模式化起着至关重要的作用。IRX1属于IRX基因家族,编码参与脊椎动物神经系统发育的活性蛋白,并在胚胎发育过程中对其他器官的发育起重要作用。它在肿瘤的形成中也起着至关重要的作用,在多种肿瘤中被确定为致癌基因或肿瘤抑制基因。本文综述了IRX1基因的基因组结构及其在不同物种中的分型研究进展。更具体地说,我们重点解释了IRX1在肿瘤发生中的关键作用,以及肿瘤的发展和对后生动物生物学过程的影响,希望能更好地理解IRX1的机制。
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引用次数: 3
期刊
Cancer Translational Medicine
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