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Omics-based insights into therapy failure of pediatric B-lineage acute lymphoblastic leukemia 儿童b系急性淋巴细胞白血病治疗失败的组学分析
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.435
S. Alsagaby
B-lineage acute lymphoblastic leukemia (B-ALL) is the most common type of cancer seen in children and is characterized by a variable clinical course. Although there have been remarkable improvements in the therapy outcomes of pediatric B-ALL, treatment failure remains the leading-cause of death in 18% of the afflicted patients during the first 5 years after diagnosis. Molecular heterogeneities of pediatric B-ALL play important roles as determinants of the therapy response. Therefore, many of these molecular abnormalities have an established prognostic value in the disease. The present review discusses the omics-based revelations from epigenomics, genomics, transcriptomics and proteomics about treatment failure in pediatric B-ALL. Next it highlights the promise of the molecular aberration-targeted therapy to improve the treatment outcomes.
B系急性淋巴细胞白血病(B-ALL)是癌症中最常见的儿童类型,其特征是临床过程多变。尽管儿童B-ALL的治疗结果有了显著改善,但在诊断后的前5年,治疗失败仍然是18%的患者死亡的主要原因。儿童B-ALL的分子异质性作为治疗反应的决定因素起着重要作用。因此,这些分子异常中的许多在该疾病中具有既定的预后价值。本综述讨论了表观基因组学、基因组学、转录组学和蛋白质组学对儿童B-ALL治疗失败的基于组学的启示。接下来,它强调了分子畸变靶向治疗有望改善治疗效果。
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引用次数: 5
Epigenetic modification in the expression of p73 p73 - epigenetic target for anticancer therapy 表观遗传修饰p73 -抗肿瘤表观遗传靶点的表达
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.421
Faiza Naseer, M. Saleem
A p73 is a new member of p53 family of transcription factor, having two types. First is TAp73, transcriptionally active and expressed via upstream promoter as a tumor suppressor and vital apoptotic inductor, it also has a key role in cell cycle arrest/differentiation and Second is ΔNp73 that is transcriptionally inactive and expressed via downstream regulator as oncogenes. Both types are expressed in various isoforms, which originate from alternative splicing events at the C-terminus. Upon DNA damage, posttranslational modifications cause conformational changes in various amino acid residues via induction or inhibition of various proteins, which are present in the structural domains of p73. These modifications may cause up- or down-regulation of p73 expression levels, as well as alters the transcriptional activity and/or stability of the protein. In this review, we have made an effort to assemble all existing data regarding the role of p73, its modification and after effects in cancer.
p73是p53转录因子家族的新成员,有两种类型。首先是具有转录活性的TAp73,通过上游启动子作为肿瘤抑制因子和重要的凋亡诱导因子表达,它在细胞周期阻滞/分化中也起关键作用;其次是具有转录活性的ΔNp73,通过下游调节因子作为癌基因表达。这两种类型都以不同的异构体表达,这些异构体起源于c端不同的剪接事件。DNA损伤后,翻译后修饰通过诱导或抑制p73结构域中存在的各种蛋白质,引起各种氨基酸残基的构象变化。这些修饰可能导致p73表达水平的上调或下调,以及改变蛋白质的转录活性和/或稳定性。在这篇综述中,我们努力收集了所有关于p73在癌症中的作用、修饰及其后效的现有数据。
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引用次数: 0
Genomics meets immunity in pancreatic cancer: Current research and future directions for pancreatic adenocarcinoma immunotherapy 癌症基因组学与免疫的结合:胰腺癌免疫治疗的研究现状和未来方向
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.430
Jacob S. Bowers, Stefanie R. Bailey, M. Rubinstein, C. Paulos, E. Camp
Pancreatic adenocarcinoma (PDAC) remains a formidable disease that needs improved therapeutic strategies. Even though immunotherapy has revolutionized treatment for various solid tumor types, it remains largely ineffective in treating individuals with PDAC. This review describes how the application of genome-wide analysis is revitalizing the field of PDAC immunotherapy. Major themes include new insights into the body’s immune response to the cancer, and key immunosuppressive elements that blunt that antitumor immunity. In particular, new evidence indicates that T cell-based antitumor immunity against PDAC is more common, and more easily generated, than previously thought. However, equally common are an array of cellular and molecular defenses employed by the tumor against those T cells. These discoveries have changed how current immunotherapies are deployed and have directed development of novel strategies to better treat this disease. Thus, the impact of genomic analysis has been two-fold: both in demonstrating the heterogeneity of immune targets and defenses in this disease, as well as providing a powerful tool for designing and identifying personalized therapies that exploit each tumor’s unique phenotype. Such personalized treatment combinations may be the key to developing successful immunotherapies for pancreatic adenocarcinoma.
胰腺腺癌(PDAC)仍然是一种需要改进治疗策略的可怕疾病。尽管免疫疗法已经彻底改变了各种实体瘤类型的治疗方法,但它在治疗PDAC患者方面仍然基本上无效。本文综述了全基因组分析的应用如何振兴PDAC免疫治疗领域。主要主题包括对人体对癌症的免疫反应的新见解,以及削弱抗肿瘤免疫的关键免疫抑制因素。特别是,新的证据表明,基于T细胞的PDAC抗肿瘤免疫比以前认为的更常见,更容易产生。然而,同样常见的是肿瘤对这些T细胞的一系列细胞和分子防御。这些发现改变了当前免疫疗法的使用方式,并指导了新策略的发展,以更好地治疗这种疾病。因此,基因组分析的影响是双重的:既证明了这种疾病的免疫靶点和防御的异质性,也为设计和识别利用每种肿瘤独特表型的个性化治疗提供了强大的工具。这种个性化的治疗组合可能是开发成功的胰腺腺癌免疫疗法的关键。
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引用次数: 7
Prognostic significance of mutated genes in megakaryocytic disorders 突变基因在巨核细胞疾病中的预后意义
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.408
A. Asnafi, M. Mohammadi, Hadi Rezaeeyan, Nader Davari, N. Saki
Megakaryopoiesis is a process during which platelets that play a major role in hemostasis are produced due to differentiation and maturation of megakaryocytic precursors. Several genes, including oncogenes and tumor suppressor genes, play a role in the regulation of this process. This study was conducted to investigate the oncogenes and tumor suppressor genes as well as their mutations during the megakaryopoiesis process, which can lead to megakaryocytic disorders. Relevant literature was identified by a PubMed search (1998-2019) of English language papers using the terms ‘Megakaryopoiesis’, ‘Mutation’, ‘oncogenes’, and ‘Tumor Suppressor’. According to investigations, several mutations occur in the genes implicated in megakaryopoiesis, which abnormally induce or inhibit megakaryocyte production, differentiation, and maturation, leading to platelet disorders. GATA-1 is one of the important genes in megakaryopoiesis and its mutations can be considered among the factors involved in the incidence of these disorders. Considering the essential role of these genes (such as GATA- 1) in megakaryopoiesis and the involvement of their mutations in platelet disorders, study and examination of these changes can be a positive step in the diagnosis and prognosis of these diseases.
巨核生成是由巨核细胞前体分化和成熟而产生血小板的过程,血小板在止血中起主要作用。包括致癌基因和肿瘤抑制基因在内的几个基因在这一过程的调控中发挥作用。本研究旨在探讨巨核细胞形成过程中致癌基因和抑瘤基因及其突变对巨核细胞功能紊乱的影响。相关文献是通过PubMed检索(1998-2019)的英文论文,检索词为“巨核opoiesis”、“Mutation”、“oncogenes”和“Tumor Suppressor”。根据研究,与巨核生成有关的基因发生了一些突变,这些突变异常地诱导或抑制巨核细胞的产生、分化和成熟,导致血小板紊乱。GATA-1是巨核生成的重要基因之一,其突变可能是这些疾病发生的因素之一。考虑到这些基因(如GATA- 1)在巨核形成中的重要作用及其突变在血小板疾病中的参与,研究和检查这些变化可能是这些疾病的诊断和预后的积极步骤。
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引用次数: 1
CDK4/6 inhibitors in advanced breast cancer, what is beyond? CDK4/6抑制剂在晚期乳腺癌中的作用?
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.416
Amrallah A. Mohammed, Hanaa Rashied, F. M. Elsayed
Resistant to hormonal treatment considered the main clinical challenge in the management of advanced breast cancer (ABC). The use of CDK4/6 inhibitors (CDK4/6I) may change the treatment landscape. In this mandated review, we will focus on the applicable role of CDK4/6I in the management of HR+/HER2- ABC, mechanisms of resistance, and promising future implementation.
对激素治疗的抵抗被认为是晚期乳腺癌(ABC)治疗的主要临床挑战。使用CDK4/6抑制剂(CDK4/6I)可能会改变治疗前景。在这篇强制性的综述中,我们将重点关注CDK4/6I在HR+/HER2- ABC治疗中的适用作用、耐药机制以及未来的实施前景。
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引用次数: 8
Thrombocytopenia in solid tumors: Prognostic significance. 实体瘤中的血小板减少症:预后意义。
IF 3.1 Q2 ONCOLOGY Pub Date : 2019-05-14 eCollection Date: 2019-01-14 DOI: 10.4081/oncol.2019.413
Majid Ghanavat, Mina Ebrahimi, Hassan Rafieemehr, Mahmood Maniati, Masumeh Maleki Behzad, Saeid Shahrabi

Solid tumors are a heterogeneous group of malignancies that result from out-of-control proliferation of cells. Thrombocytopenia is a common complication among patients with solid tumors that predispose them to bleeding disorders. The aim of this review article is to investigate the underlying mechanisms of the risk and incidence of thrombocytopenia in solid tumors. It can be argued that thrombocytopenia is a poor prognostic factor in solid tumors that can result from several factors such as polymorphism and mutation in some transcription factors and cytokines involved in megakaryocytic maturation or from the adverse effects of treatment. Therefore, an understanding of the exact mechanism of thrombocytopenia pathogenesis in each stage of solid tumors can help in developing therapeutic strategies to decrease bleeding complications in these malignancies.

实体瘤是一类异质性恶性肿瘤,是细胞增殖失控的结果。血小板减少症是实体瘤患者常见的并发症,容易导致出血性疾病。这篇综述文章旨在研究实体瘤患者血小板减少风险和发病率的内在机制。可以说,血小板减少是实体瘤预后不良的一个因素,可能由多种因素导致,如参与巨核细胞成熟的一些转录因子和细胞因子的多态性和突变,或治疗的不良反应。因此,了解实体瘤各期血小板减少的确切发病机制有助于制定治疗策略,减少这些恶性肿瘤的出血并发症。
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引用次数: 0
Prognostic significance of aberrant CD5 expression in B-cell leukemia. CD5异常表达在b细胞白血病中的预后意义。
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-04-18 eCollection Date: 2019-01-14 DOI: 10.4081/oncol.2019.400
Kaveh Jaseb, Daryush Purrahman, Saeid Shahrabi, Majid Ghanavat, Hadi Rezaeean, Najmaldin Saki

Aberrant expression of CD5 (as a T-cell marker) is seen in some leukemia and lymphoma of B lineage origin. Given that the signaling resulting from the expression of this marker plays an essential role in the development of leukemia and lymphoma, evaluating the expression of this marker is of paramount importance. Therefore, our goal in this study was to investigate the prognostic importance of CD5 expression in B-cell leukemia and lymphoma. We evaluate CD5 expression in normal and leukemic B-cells by identifying relevant literature through a PubMed search (1998-2018) of English language papers using the terms: 'CD5,' 'B-cell,' 'Leukemia,' and 'Lymphoma.' We are doing this thorough comparison of results from CD5 positive and negative cases to make a correct decision about prognostic importance of CD5 expression in these malignancies. In a number of B-cell malignancies, CD5 is expressed in varying degrees. Due to the different origins and characteristics of these malignancies, the results of CD5 expression evaluations are heterogeneous and impossible to generalize. However, CD5 expression is sometimes associated with clinicopathologic findings, more invasive clinical course, and even resistance to treatment (specifically in DLBCL) among CD5- positive patients, which appears to be a function of CD5 signaling and its downstream factors such as STAT3. Depending on the type of malignancy, CD5 expression is associated with good or bad prognosis, which can be used as an auxiliary prognostic factor to assess the clinical course of B-cell malignancies. Moreover, the difference in expression levels of CD5 in a variety of B-cell malignancies allows for differential diagnosis of these malignancies, which can be helpful when diagnosis is difficult.

CD5(作为一种t细胞标志物)的异常表达见于某些B系起源的白血病和淋巴瘤。鉴于该标志物的表达所产生的信号在白血病和淋巴瘤的发展中起着至关重要的作用,因此评估该标志物的表达至关重要。因此,我们本研究的目的是探讨CD5表达在b细胞白血病和淋巴瘤中的预后重要性。我们通过PubMed检索(1998-2018)的英文论文,通过使用术语“CD5”、“b细胞”、“白血病”和“淋巴瘤”来识别相关文献,评估正常和白血病b细胞中的CD5表达。我们正在对CD5阳性和阴性病例的结果进行彻底的比较,以对CD5表达在这些恶性肿瘤中的预后重要性做出正确的决定。在许多b细胞恶性肿瘤中,CD5在不同程度上表达。由于这些恶性肿瘤的起源和特征不同,CD5表达评估的结果是异质的,不可能概括。然而,CD5表达有时与CD5阳性患者的临床病理表现、更具侵袭性的临床病程,甚至对治疗的耐药性(特别是DLBCL)有关,这似乎是CD5信号传导及其下游因子(如STAT3)的功能。根据不同的恶性肿瘤类型,CD5表达与预后好坏相关,可作为评估b细胞恶性肿瘤临床病程的辅助预后因素。此外,CD5在各种b细胞恶性肿瘤中表达水平的差异使得这些恶性肿瘤的鉴别诊断成为可能,这在诊断困难时是有帮助的。
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引用次数: 9
Prospects for repurposing CNS drugs for cancer treatment. 中枢神经系统药物用于癌症治疗的前景。
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-04-17 eCollection Date: 2019-01-14 DOI: 10.4081/oncol.2019.411
Mohamed Abdelaleem, Hossam Ezzat, Muhammed Osama, Adel Megahed, Waleed Alaa, Ahmed Gaber, Ayman Shafei, Alaa Refaat
Drug repurposing is the idea of using an already approved drug for another disease or disorder away from its initial use. This new approach ensures the reduction in high cost required for developing a new drug in addition to the time consumed, especially in the tumor disorders that show an unceasing rising rate with an unmet success rate of new anticancer drugs. In our review, we will review the anti-cancer effect of some CNS drugs, including both therapeutic and preventive, by searching the literature for preclinical or clinical evidence for anticancer potential of central nervous system drugs over the last 8 years period (2010-2018) and including only evidence from Q1 journals as indicated by Scimago website (www.scimagojr.com). We concluded that Some Central Nervous system drugs show a great potential as anti-cancer in vitro, in vivo and clinical trials through different mechanisms and pathways in different types of cancer that reveal a promising evidence for the repurposing of CNS drugs for new indications.
药物再利用是指将一种已经获得批准的药物用于治疗另一种疾病或紊乱,而不是最初的用途。这种新方法不仅节省了开发新药所需的高成本,而且节省了时间,特别是在抗癌新药成功率不断上升的肿瘤疾病中。在我们的综述中,我们将通过检索过去8年(2010-2018年)关于中枢神经系统药物抗癌潜力的临床前或临床证据的文献,回顾一些中枢神经系统药物的抗癌作用,包括治疗和预防两方面,并且仅包括Scimago网站(www.scimagojr.com)显示的Q1期刊的证据。我们得出结论,一些中枢神经系统药物在体外、体内和临床试验中,通过不同的机制和途径,在不同类型的癌症中显示出巨大的抗癌潜力,这为中枢神经系统药物的新适应症的重新利用提供了有希望的证据。
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引用次数: 22
Adherence to oral pharmacological treatment in cancer patients: Systematic review. 癌症患者口服药物治疗的依从性:系统评价。
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-04-16 eCollection Date: 2019-01-14 DOI: 10.4081/oncol.2019.402
Melissa Perdomo Claros, Claudia Viviana Marín Messa, Herney Andrés García-Perdomo

The objective was to identify the best-validated scale for assessing oral pharmacological adherence in oncology patients. A bibliographic search was performed in MEDLINE via Ovid, EMBASE, CENTRAL and LILACS. We included all studies in which a validation of adherence scales to oral pharmacological treatment was performed in oncology patients older than 18 years without gender distinction. We excluded studies that included newly diagnosed patients. No statistical analysis was performed due to the nature of the study. A total of 4609 studies were found. After screening, six studies were selected for qualitative analysis. In the analysis of the six included studies, a total of 855 patients older than 18 years with oncological diagnoses were found. Two of the studies, Bagcivan et al. and Amorim et al., used scales that show acceptable validity and reliability to adequately measure adherence to pharmacological treatment in each of the patients. In this way, the quality of patient care and success in pharmacological treatments can be guaranteed. According to the results obtained in the evaluation of biases and analysis of psychometric properties, the best-validated scales are as follows: Adherence Determinants Questionnaire (ADQ) (Brazilian version) and the Oral Chemotherapy Adherence Scale (OCAS). These are valid, reliable and useful scales that can be adapted to any cultural context.

目的是确定评估肿瘤患者口服药物依从性的最佳有效量表。在MEDLINE中通过Ovid、EMBASE、CENTRAL和LILACS进行文献检索。我们纳入了所有对年龄大于18岁的肿瘤患者进行口服药物治疗依从性量表验证的研究,没有性别区分。我们排除了包括新诊断患者的研究。由于研究的性质,未进行统计分析。总共发现了4609项研究。经筛选,选取6项研究进行定性分析。在对六项纳入的研究的分析中,共发现了855名年龄大于18岁的肿瘤诊断患者。Bagcivan et al.和Amorim et al.两项研究使用了具有可接受效度和可靠性的量表来充分衡量每位患者对药物治疗的依从性。这样,就可以保证病人护理的质量和药物治疗的成功。根据偏倚评估和心理测量特性分析的结果,最有效的量表为依从性决定因素问卷(ADQ)(巴西版)和口服化疗依从性量表(OCAS)。这些都是有效、可靠和有用的量表,可以适应任何文化背景。
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引用次数: 11
A comprehensive overview of mitochondrial DNA 4977-bp deletion in cancer studies. 线粒体DNA 4977-bp缺失在癌症研究中的全面概述。
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-04-16 eCollection Date: 2019-01-14 DOI: 10.4081/oncol.2019.409
Abdul Aziz Mohamed Yusoff, Wan Salihah Wan Abdullah, Siti Zulaikha Nashwa Mohd Khair, Siti Muslihah Abd Radzak

Mitochondria are cellular machines essential for energy production. The biogenesis of mitochondria is a highly complex and it depends on the coordination of the nuclear and mitochondrial genome. Mitochondrial DNA (mtDNA) mutations and deletions are suspected to be associated with carcinogenesis. The most described mtDNA deletion in various human cancers is called the 4977-bp common deletion (mDNA4977) and it has been explored since two decades. In spite of that, its implication in carcinogenesis still unknown and its predictive and prognostic impact remains controversial. This review article provides an overview of some of the cellular and molecular mechanisms underlying mDNA4977 formation and a detailed summary about mDNA4977 reported in various types of cancers. The current knowledges of mDNA4977 as a prognostic and predictive marker are also discussed.

线粒体是产生能量必不可少的细胞机器。线粒体的生物发生是一个高度复杂的过程,它依赖于细胞核和线粒体基因组的协调。线粒体DNA (mtDNA)突变和缺失被怀疑与致癌有关。在各种人类癌症中被描述最多的mtDNA缺失被称为4977-bp共同缺失(mDNA4977),它已经被探索了20年。尽管如此,其在癌变中的意义仍然未知,其预测和预后影响仍然存在争议。本文综述了mDNA4977形成的一些细胞和分子机制,并详细总结了mDNA4977在各种类型癌症中的报道。本文还讨论了目前关于mDNA4977作为预后和预测标志物的知识。
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引用次数: 32
期刊
Oncology Reviews
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