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Evolving management of positive regional lymph nodes in melanoma: Past, present and future directions. 黑色素瘤中阳性区域淋巴结的演变管理:过去,现在和未来的方向。
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-11-28 eCollection Date: 2019-07-22 DOI: 10.4081/oncol.2019.433
Rachel A Fayne, Francisco I Macedo, Steven E Rodgers, Mecker G Möller

Sentinel lymph node (SLN) biopsy has become the standard of care for lymph node staging in melanoma and the most important predictor of survival in clinically node-negative disease. Previous guidelines recommend completion lymph node dissection (CLND) in cases of positive SLN; however, the lymph nodes recovered during CLND are only positive in a minority of these cases. Recent evidence suggests that conservative management (i.e. observation) has similar outcomes compared to CLND. We sought to review the most current literature regarding the management of SLN in metastatic melanoma and to discuss potential future directions.

前哨淋巴结(SLN)活检已成为黑素瘤淋巴结分期的标准护理,也是临床上淋巴结阴性疾病中最重要的生存预测指标。以前的指南建议在SLN阳性的病例中进行完全淋巴结清扫(CLND);然而,在CLND期间恢复的淋巴结仅在少数病例中呈阳性。最近的证据表明,与CLND相比,保守治疗(即观察)具有相似的结果。我们试图回顾关于SLN在转移性黑色素瘤中的治疗的最新文献,并讨论潜在的未来方向。
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引用次数: 10
Renal toxicity with mammalian target of rapamycin inhibitors: A meta-analysis of randomized clinical trials. 雷帕霉素抑制剂对哺乳动物的肾毒性:随机临床试验的荟萃分析。
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-11-25 eCollection Date: 2019-07-22 DOI: 10.4081/oncol.2019.455
Ravi K Paluri, Guru Sonpavde, Charity Morgan, Jacob Rojymon, Anastasia Hartzes Mar, Radhika Gangaraju

A meta-analysis of randomized clinical trials (RCT) was done to determine the relative risk (RR) of acute kidney injury (AKI) with the use of mammalian target of rapamycin (mTOR) inhibitors. Citations from PubMed/Medline, clinical trials.gov, package inserts and abstracts from major conferences were reviewed to include RCTs comparing arms with or without mTOR inhibitors. The RR of all grade AKI in patients taking mTOR inhibitors compared to patients not on mTOR inhibitors was 1.55 (95% CI: 1.11 to 2.16, P=0.010). There was no significant difference in the risk of high-grade AKI for the two groups (RR=1.29, P=0.118, 95% CI: 0.94 to 1.77). There was no significant difference in the incidence rates for either all grade or high-grade AKI between the two groups. There was no publication bias and the trials were of high quality per Jadad scoring.

一项随机临床试验(RCT)的荟萃分析,以确定使用哺乳动物雷帕霉素靶点(mTOR)抑制剂的急性肾损伤(AKI)的相对风险(RR)。我们对PubMed/Medline、临床试验网站、说明书和主要会议摘要的引用进行了回顾,包括比较有或没有mTOR抑制剂组的随机对照试验。服用mTOR抑制剂的患者与未服用mTOR抑制剂的患者相比,所有级别AKI的RR为1.55 (95% CI: 1.11至2.16,P=0.010)。两组发生高级别AKI的风险无显著差异(RR=1.29, P=0.118, 95% CI: 0.94 ~ 1.77)。两组间所有级别或高度AKI的发生率均无显著差异。没有发表偏倚,按照Jadad评分,试验质量高。
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引用次数: 8
Efficacy and safety profiles of programmed cell death-1/programmed cell death ligand-1 inhibitors in the treatment of triple-negative breast cancer: A comprehensive systematic review. 程序性细胞死亡-1/程序性细胞凋亡配体-1抑制剂治疗癌症三阴性乳腺癌的疗效和安全性:一项全面的系统综述。
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-10-10 eCollection Date: 2019-07-22 DOI: 10.4081/oncol.2019.425
Gilbert Lazarus, Jessica Audrey, Anthony William Brian Iskandar

Triple-negative breast cancer (TNBC) is associated with worse prognosis, with limited treatment regiments available and higher mortality rate. Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) showed great potentials in treating malignancies and may serve as potential therapies for TNBC. This systematic review aims to evaluate the efficacy and safety profiles of PD-1/PD-L1 inhibitors in the treatment of TNBC. Literature search was performed via PubMed, EBSCOhost, Scopus, and CENTRAL databases, selecting studies which evaluated the use of anti-PD-1/PDL1 for TNBC from inception until February 2019. Risk of bias was assessed by the Newcastle-Ottawa Scale (NOS). Overall, 7 studies evaluating outcomes of 1395 patients with TNBC were included in this systematic review. Anti-PD-1/PD-L1 showed significant antitumor effect, proven by their promising response (objective response rate (ORR), 18.5-39.4%) and survival rates (median overall survival (OS), 9.2-21.3 months). Moreover, anti- PD-1/PD-L1 yielded better outcomes when given as first-line therapy, and overexpression of PD-L1 in tumors showed better therapeutic effects. On the other hands, safety profiles were similar across agents and generally acceptable, with grade ≥3 treatment- related adverse effects (AEs) ranging from 9.5% to 15.6% and no new AEs were experienced by TNBC patients. Most grade ≥3 AEs are immune-mediated, which are manifested as neutropenia, fatigue, peripheral neuropathy, and anemia. PD-1/PD-L1 inhibitors showed promising efficacy and tolerable AEs, and thus may benefit TNBC patients. Further studies of randomized controlled trials with larger populations are needed to better confirm the potential of these agents.

癌症三阴性(TNBC)与更差的预后相关,可用的治疗方案有限,死亡率较高。靶向程序性细胞死亡-1(PD-1)或程序性细胞坏死配体1(PD-L1)的免疫检查点抑制剂在治疗恶性肿瘤方面显示出巨大潜力,并可能成为TNBC的潜在疗法。本系统综述旨在评估PD-1/PD-L1抑制剂治疗TNBC的疗效和安全性。通过PubMed、EBSCOhost、Scopus和CENTRAL数据库进行文献检索,选择从开始到2019年2月评估抗PD-1/PDL1用于TNBC的研究。采用纽卡斯尔-渥太华量表(NOS)评估偏倚风险。总体而言,本系统综述包括7项评估1395名TNBC患者结果的研究。抗PD-1/PD-L1显示出显著的抗肿瘤作用,其有希望的应答(客观应答率(ORR),18.5-9.4%)和生存率(中位总生存期(OS),9.2-21.3个月)证明了这一点。此外,当作为一线治疗时,抗PD-1/PD-L1产生了更好的结果,并且PD-L1在肿瘤中的过表达显示出更好的治疗效果。另一方面,不同药物的安全性相似,一般可接受,≥3级的治疗相关不良反应(AE)范围为9.5%至15.6%,TNBC患者没有出现新的AE。大多数≥3级AE是免疫介导的,表现为中性粒细胞减少、疲劳、周围神经病变和贫血。PD-1/PD-L1抑制剂显示出良好的疗效和可耐受的不良事件,因此可能使TNBC患者受益。需要对更大人群的随机对照试验进行进一步研究,以更好地确认这些药物的潜力。
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引用次数: 18
Current promising treatment strategy for glioblastoma multiform: A review. 多形性胶质母细胞瘤目前有前景的治疗策略:综述。
IF 3.1 Q2 ONCOLOGY Pub Date : 2019-07-25 eCollection Date: 2019-07-22 DOI: 10.4081/oncol.2019.417
Sanjib Bahadur, Arvind Kumar Sahu, Pragya Baghel, Suman Saha

Glioblastoma multiform (GBM) is a heterogeneous group of primary neoplasm resistant to conventional therapies. Due to their infiltrative nature it not fully isolated by aggressive surgery, radiation and chemotherapy showing poor prognosis in glioma patients. Unfortunately, diagnosed patients die within 1.5-2 year treatment schedule. Currently temozolomide (TMZ) is the first choice for the prognosis of GBM patients. TMZ metabolites methyl triazen imidazol carboxamide form complex with alkyl guanine alkyl transferase (O6 MGMT- DNA repair protein) induced DNA damage following resistance properties of TMZ and inhibit the overall survival of the patients. Last few decades different TMZ conjugated strategy is developed to overcome the resistance and enhance the chemotherapy efficacy. The main aim of this review is to introduce the new promising pharmaceutical candidates that significantly influence the therapeutic response of the TMZ in context of targeted therapy of glioblastoma patients. It is hoped that this proposed strategy are highly effective to overcome the current resistance limitations of TMZ in GBM patients and enhance the survival rate of the patients.

多形性胶质母细胞瘤(GBM)是一组对传统治疗具有耐药性的异质性原发性肿瘤。由于其浸润性,在神经胶质瘤患者中,未通过积极的手术、放疗和化疗完全分离,显示预后不良。不幸的是,确诊患者在1.5-2年的治疗计划内死亡。目前替莫唑胺(TMZ)是GBM患者预后的首选药物。TMZ代谢产物甲基三氮杂咪唑甲酰胺与烷基鸟嘌呤烷基转移酶(O6-MGMT-DNA修复蛋白)形成复合物,诱导TMZ抗性后的DNA损伤,并抑制患者的总体生存。在过去的几十年里,人们开发了不同的TMZ结合策略来克服耐药性并提高化疗疗效。这篇综述的主要目的是介绍在胶质母细胞瘤患者的靶向治疗中显著影响TMZ治疗反应的新的有前景的候选药物。希望这一策略能非常有效地克服目前TMZ在GBM患者中的耐药性限制,提高患者的生存率。
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引用次数: 0
MCT4 has a potential to be used as a prognostic biomarker - a systematic review and meta-analysis MCT4具有作为预后生物标志物的潜力——一项系统综述和荟萃分析
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.403
Arslaan Javaeed, S. Ghauri
The role of several metabolic changes, such as hypoxia and acidosis, in the tumour environment has caught the attention of researchers in cancer progression and invasion. Lactate transport is one of the acidosis-enhancing processes that are mediated via monocarboxylate transporters (MCTs). We conducted a systematic review and meta-analysis to investigate the expression of two cancer-relevant MCTs (MCT1 and MCT4) and their potential prognostic significance in patients with metastasis of different types of cancer. Studies were included if they reported the number of metastatic tissue samples expressing either low or high levels of MCT1 and/or MCT4 or those revealing the hazard ratios (HRs) of the overall survival (OS) or disease-free survival (DFS) as prognostic indicators. During the period between 2010 and 2018, a total of 20 articles including 3831 patients (56.3% males) were identified. There was a significant association between MCT4 expression (high versus low) and lymph node metastasis [odds ratio (OR)=1.87, 95% confidence interval (CI)=1.10-3.17, P=0.02] and distant metastasis (OR=2.18, 95%CI=1.65-2.86, P<0.001) and the correlation remained significant for colorectal and hepatic cancer in subgroup analysis. For survival analysis, patients with shorter OS periods exhibited a higher MCT4 expression [hazard ratio (HR)=1.78, 95%CI=1.49-2.13, P<0.001], while DFS was shorter in patients with high MCT1 (HR=1.48, 95%CI=1.04-2.10, P=0.03) and MCT4 expression (HR=1.70, 95%CI=1.19-2.42, P=0.003) when compared to their counterparts with low expression levels. Future research studies should consider the pharmacologic inhibition of MCT4 to effectively inhibit cancer progression to metastasis.
一些代谢变化,如缺氧和酸中毒,在肿瘤环境中的作用已经引起了研究人员对癌症进展和侵袭的关注。乳酸转运是通过单羧酸转运体(mct)介导的酸中毒增强过程之一。我们通过系统回顾和荟萃分析,探讨两种与癌症相关的mct (MCT1和MCT4)在不同类型癌症转移患者中的表达及其潜在的预后意义。如果研究报告了表达低或高水平MCT1和/或MCT4的转移组织样本的数量,或那些显示总生存期(OS)或无病生存期(DFS)的风险比(hr)作为预后指标的研究被纳入。2010 - 2018年共纳入文献20篇,患者3831例(男性56.3%)。在亚组分析中,MCT4表达与淋巴结转移[比值比(OR)=1.87, 95%可信区间(CI)=1.10 ~ 3.17, P=0.02]和远处转移(OR=2.18, 95%CI=1.65 ~ 2.86, P<0.001)有显著相关性,在结直肠癌和肝癌中仍有显著相关性。对于生存分析,OS期较短的患者MCT4表达较高[风险比(HR)=1.78, 95%CI=1.49-2.13, P<0.001],而高MCT1 (HR=1.48, 95%CI=1.04-2.10, P=0.03)和MCT4表达的患者(HR=1.70, 95%CI=1.19-2.42, P=0.003)的DFS较低表达水平的患者短。未来的研究应考虑MCT4的药理抑制,以有效地抑制癌症的进展到转移。
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引用次数: 21
Recent trends in predictive biomarkers for determining malignant potential of oral potentially malignant disorders 预测口腔潜在恶性疾病的恶性潜能的生物标志物的最新趋势
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.424
G. Sarode, S. Sarode, Nikunj Maniyar, N. Sharma, Sujata Yerwadekar, S. Patil
Despite of the tremendous advancements in the field of cancer prevention, detection and treatment, the overall prognosis of oral squamous cell carcinoma (OSCC) still remains poor. This can be partly imparted to the lack of early detection of oral potentially malignant disorders (OPMDs), especially those at a higher risk of progression into OSCC. Over years, various specific and non-specific markers have been introduced that could predict the malignant transformation of OPMDs; however detail information on these OPMD markers in a concise manner is lacking. Moreover, their use on daily clinical basis still remains questionable. With continuous research in the field of cytology and genomics, several contemporary biomarkers have been discovered that are not yet foregrounded and proved to be more promising than those used conventionally. Here, in the present paper, we overview several recently concluded predictive biomarkers with special emphasis on their role in molecular pathogenesis of OSCC transformation. These markers can be used for risk assessment of malignant transformation in patients with OPMDs as well as for prophylactic conciliation and fair management of the high-risk OPMD patient group.
尽管在癌症的预防、检测和治疗领域取得了巨大的进步,但口腔鳞状细胞癌(OSCC)的整体预后仍然很差。这可能部分归因于缺乏对口腔潜在恶性疾病(OPMDs)的早期检测,特别是那些有较高进展为OSCC风险的疾病。多年来,各种特异性和非特异性标记物被引入,可以预测OPMDs的恶性转化;然而,缺乏这些OPMD标记物的简明详细信息。此外,它们在日常临床基础上的使用仍然存在疑问。随着细胞学和基因组学领域的不断研究,人们发现了一些当代生物标志物,这些标志物尚未被发现,并被证明比传统的生物标志物更有前景。在本文中,我们概述了最近得出的几种预测性生物标志物,特别强调了它们在OSCC转化的分子发病机制中的作用。这些标志物可用于OPMD患者恶性转化的风险评估,也可用于OPMD高危患者群体的预防性调解和公平管理。
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引用次数: 13
Potential effect of probiotics in the treatment of breast cancer 益生菌治疗癌症的潜在疗效
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.422
L. Mendoza
Breast cancer is one of the most important causes of cancerrelated morbidity and mortality in the world. Probiotics, as functional food, have the potential to act against breast cancer, as evidenced by cell-based and animal model experiments. Probiotic may be useful in prevention or treatment of breast cancer by modulating the gastrointestinal bacteria and the systemic immune system. However, large-scale clinical trials and intensive research are mandatory to confirm the in vitro and in vivo results and exploring the probiotics-related metabolic, immune, and molecular mechanisms in breast cancer. This current review summarizes the available data related to probiotics and their potential role in the treatment of breast cancer.
癌症是世界上与癌症相关的发病率和死亡率的最重要原因之一。益生菌作为功能性食物,具有对抗癌症的潜力,基于细胞和动物模型的实验证明了这一点。益生菌可以通过调节胃肠道细菌和全身免疫系统来预防或治疗癌症。然而,大规模的临床试验和深入的研究是必须的,以确认体外和体内结果,并探索益生菌相关的代谢、免疫和分子机制在乳腺癌症。本综述总结了与益生菌相关的现有数据及其在癌症治疗中的潜在作用。
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引用次数: 50
Therapeutic options for ampullary carcinomas. A review 壶腹癌的治疗选择。回顾
IF 3.6 Q2 ONCOLOGY Pub Date : 2019-07-22 DOI: 10.4081/oncol.2019.440
Dileep Kumar Reddy Regalla, R. Jacob, A. Manne, R. Paluri
Ampullary Carcinoma arises from a histologically heterogeneous region where three different epithelia converge. Even though Ampullary Carcinoma has a superior prognosis compared to pancreatic and biliary ductal neoplasms, at least half of the patients turn up at an advanced stage that limits the treatment prospects. In addition to surgery for early-stage disease, several studies have shown that chemoradiotherapy confers additional benefits in the management of Ampullary Carcinoma. Analogously, chemotherapy plays a crucial role in treating advanced Ampullary Carcinoma with distant metastasis/recurrences. Although, stage of the disease, lymph node status, and histo-morphology are three critical prognostic variables, recently much attention is being placed on the genetic landscape of Ampullary Carcinoma. In this review, we have discussed various studies describing the role of chemoradiation and chemotherapy in the treatment of early and advanced stage Ampullary Carcinoma. Also, we have summarized the molecular landscape of Ampullary Carcinoma and the novel therapeutic strategies which could possibly target the genetic alterations involving the tumor cells.
壶腹癌起源于三个不同上皮细胞汇聚的组织学异质区域。尽管与胰腺和胆管肿瘤相比,壶腹癌的预后更好,但至少有一半的患者处于晚期,这限制了治疗前景。除了早期疾病的手术外,几项研究表明,放化疗在壶腹癌的治疗中还具有额外的益处。类似地,化疗在治疗有远处转移/复发的晚期壶腹癌中起着至关重要的作用。尽管疾病的分期、淋巴结状况和组织形态学是三个关键的预后变量,但最近人们对壶腹癌的遗传景观给予了极大的关注。在这篇综述中,我们讨论了各种描述放化疗和化疗在早期和晚期壶腹癌治疗中的作用的研究。此外,我们还总结了壶腹癌的分子结构和新的治疗策略,这些策略可能针对涉及肿瘤细胞的基因改变。
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引用次数: 13
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
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Oncology Reviews
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