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The oncogenicity of Epstein-Barr virus: Being “more or less” is to be concerned 爱泼斯坦-巴尔病毒的致癌性:“多多少少”值得关注
Pub Date : 2016-05-16 DOI: 10.14800/CCM.1300
Jianhong Lu, L. Zuo, Shujuan Du, Lingzhi Liu
Epstein-Barr virus (EBV) ubiquitously infects human beings and is associated with several malignancies. However, the mechanism of the viral oncogenicity remains largely to be understood. In our investigations, we have reported a tumor model in which that EBV facilitated the tumorigenesis in epithelial cells latently infected by EBV genome. Using this model, we have found several clues and further confirmed them for the viral pathogenesis. We have recently reported that the EBV copy number is related with the potential malignancy of the infected cells, corresponding to the activation level of LMP1 and NF-κB signaling. Though the DNA load in patient blood has been well-documented as an potential indicator of EBV-related diseases, this was the first experimental model to verify that the EBV copy number in cancer cells directly correlates with the tumorigenesis. We emphasize that not only “with or without” but also “more or less” should be concerned in EBV-related approaches at gene expression level or in genome context.
爱泼斯坦-巴尔病毒(EBV)普遍感染人类,并与几种恶性肿瘤有关。然而,病毒致癌性的机制在很大程度上仍有待了解。在我们的研究中,我们报道了一个肿瘤模型,其中EBV促进了EBV基因组潜伏感染的上皮细胞的肿瘤发生。利用该模型,我们发现了一些线索,并进一步证实了病毒的发病机制。我们最近报道EBV拷贝数与感染细胞的潜在恶性程度有关,与LMP1和NF-κB信号的激活水平相对应。虽然患者血液中的DNA负荷已被充分证明是EBV相关疾病的潜在指标,但这是第一个验证癌细胞中EBV拷贝数与肿瘤发生直接相关的实验模型。我们强调,在基因表达水平或基因组背景下,ebv相关方法不仅应该关注“有或没有”,而且应该关注“多或少”。
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引用次数: 2
How close are we to real time optical margin control in head and neck oncologic surgery 在头颈部肿瘤手术中,我们离实时光学边缘控制还有多远
Pub Date : 2016-05-16 DOI: 10.14800/CCM.1305
B. Miles
The quest for negative margins during head and neck oncologic surgery continues to challenge surgeons worldwide. Current technological advances offer significant promise to advance the field and improve operative margin detection. This review focuses on current optical technology, which has been evaluated for intraoperative margin control in head and neck oncologic surgery for possible application in optical margin control. Many of the current systems have technical limitations and there is no current standard technology being applied in the field of head and neck oncology to enhance intraoperative margin control. Surgeons continue to rely on intraoperative frozen section analysis, however many optical systems have shown high rates of sensitivity and specificity when discriminating benign from malignant tissue. These technologies shows significant promise for intraoperative margin control and may be enhanced by targeted molecular imaging, or spectral analysis, in the future. Translational trials are rare and are the key to the path of independence from frozen section analysis.
在头颈部肿瘤手术中寻找负切缘继续挑战着全世界的外科医生。目前的技术进步为推进该领域和改善手术边缘检测提供了巨大的希望。本文综述了目前光学技术在头颈部肿瘤手术术中边缘控制中的应用,并对其应用前景进行了评价。目前许多系统存在技术上的局限性,在头颈部肿瘤领域目前还没有标准的技术来加强术中切缘控制。外科医生继续依赖术中冷冻切片分析,然而许多光学系统在区分良性和恶性组织时显示出很高的灵敏度和特异性。这些技术显示了术中边缘控制的重大前景,未来可能会通过靶向分子成像或光谱分析来增强。翻译试验是罕见的,是独立于冰冻切片分析的关键。
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引用次数: 3
Adverse effects of 5-fluorouracil: Focus on rare side effects 5-氟尿嘧啶的不良反应:关注罕见的副作用
Pub Date : 2016-04-26 DOI: 10.14800/CCM.1266
S. Thomas, Zhuliet Grami, Sharvil Mehta, Kushal Patel
5-fluorouracial (5-FU) is an antimetabolite chemotherapy drug.  5-FU has many adverse effects like any other chemotherapy agent as it has effects not only on cancer cells, but healthy cell as well. Serious side effects which are uncommon (occurring in about 1% of patients) and will be the focus of this paper are cardiac effects, hyperammonemia or encephalopathy and neurologic effects. There are many other side effects associated with 5-FU.  In this paper we will discuss the rare side effects and alternatives on what to do if they occur during treatment based on case reports.
5-氟尿嘧啶(5-FU)是一种抗代谢化疗药物。和其他化疗药物一样,5-FU有很多副作用,因为它不仅对癌细胞有影响,对健康细胞也有影响。不常见的严重副作用(约1%的患者发生)是本文的重点,包括心脏效应、高氨血症或脑病和神经系统效应。5-FU还有很多其他的副作用。在本文中,我们将根据病例报告讨论罕见的副作用和治疗过程中发生的替代方法。
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引用次数: 21
Dihydroartemisinin is a newly defined STAT3 inhibitor that may be of multiple potential uses in cancer treatment 双氢青蒿素是一种新定义的STAT3抑制剂,可能在癌症治疗中具有多种潜在用途
Pub Date : 2016-04-22 DOI: 10.14800/CCM.1254
Xiaomin Li, L. Jia, Xiu-ying Lu, Yupeng Shen, Zhen Li, Q. Song
Accumulating evidence from epidemiological, pharmacological and case control studies has shown that dihydroartemisinin (DHA), one of first-line antimalarial drugs recommended by World Health Organization (WHO), possesses antineoplastic activity and selective cytotoxicity to a variety of human cancer cell model systems. Although some antitumor mechanisms of DHA have been confirmed, the findings from the previous studies are insufficient to fully reveal the whole picture of tumor suppression by DHA. In a recent investigation, we demonstrated that DHA exhibits antitumor properties against a variety of human HNSCC cells both in vitro and in vivo. The underlying mechanism involves selective inhibition of Jak2/STAT3 signaling. By specific inhibition of STAT3 activation, DHA exerted the chemotherapeutic efficacy, including reduction in cell viability and migratory capability, along with induction of G1 phase cell cycle arrest and apoptosis in HNSCC cells. All of data suggested that DHA may be a potent inhibitor of STAT3 that can be potentially used to treat patients with HNSCC, as well as other human cancers harboring STAT3 activation.
流行病学、药理学和病例对照研究积累的证据表明,双氢青蒿素(DHA)是世界卫生组织(世卫组织)推荐的一线抗疟药物之一,具有抗肿瘤活性和对多种人类癌细胞模型系统的选择性细胞毒性。虽然DHA的一些抗肿瘤机制已被证实,但以往的研究结果不足以充分揭示DHA抑制肿瘤的全貌。在最近的一项研究中,我们证明了DHA在体外和体内对多种人类HNSCC细胞具有抗肿瘤特性。潜在的机制涉及Jak2/STAT3信号的选择性抑制。DHA通过特异性抑制STAT3的激活,在HNSCC细胞中发挥化疗效果,包括降低细胞活力和迁移能力,以及诱导G1期细胞周期阻滞和凋亡。所有数据表明,DHA可能是STAT3的有效抑制剂,可以潜在地用于治疗HNSCC患者,以及其他携带STAT3激活的人类癌症。
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引用次数: 3
Second-hand smoke (SHS), a cocktail of toxic chemicals, cannot be ignored 二手烟(SHS)是一种有毒化学物质的混合物,不容忽视
Pub Date : 2016-04-12 DOI: 10.14800/CCM.1253
R. Rafiq, N. Dar
Tobacco use is the leading cause of preventable diseases and premature deaths worldwide . Its use killed 100 million people in the 20th century and if current trends continue, tobacco will kill one billion people in 21st century, with 80 percent of these deaths from low and middle income countries . Despite, the massive death toll, almost a billion men and 250 million women smoke in the world. Half of the male smokers live in low and middle income countries . However, smokers don’t pay alone; the unfortunate victims who unnecessarily suffer are the secondhand smokers.
烟草使用是全世界可预防疾病和过早死亡的主要原因。它的使用在20世纪导致1亿人死亡,如果目前的趋势继续下去,烟草将在21世纪导致10亿人死亡,其中80%的死亡来自低收入和中等收入国家。尽管死亡人数巨大,但世界上仍有近10亿男性和2.5亿女性吸烟。半数男性吸烟者生活在低收入和中等收入国家。然而,吸烟者并不会独自付出代价;那些不必要地遭受痛苦的不幸受害者是二手吸烟者。
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引用次数: 0
Immune-checkpoint blockade aptamers as a feasible clinical alternative to monoclonal antibodies 免疫检查点阻断适体作为单克隆抗体的可行临床替代品
Pub Date : 2016-04-12 DOI: 10.14800/CCM.1247
F. Pastor
The recent U.S. FDA approval of monoclonal antibodies against CTLA4 (ipilimumab) and PD1 (nivolumab and pembrolizumab), together with the increasing number of clinical trials for new immune-checkpoint blockade antibodies in monotherapy and in combinations, have emphasized the therapeutic potential of using immunomodulatory antibodies to elicit an effective protective immunity for cancer immunotherapy. However, the treatment of cancer patients with immune-checkpoint blockade antibodies, not devoid of toxicity, is associated with severe auto-inflammatory immune responses. It is urgent to identify new therapeutic immune-checkpoint blockade reagents with more manageable side effects. The chemically synthesized single-strand oligonucleotide aptamers have substantial advantages versus antibodies in terms of cost production and handling side effects.
最近美国FDA批准了针对CTLA4 (ipilimumab)和PD1 (nivolumab和pembrolizumab)的单克隆抗体,以及越来越多的新的免疫检查点阻断抗体在单一治疗和联合治疗中的临床试验,都强调了使用免疫调节抗体在癌症免疫治疗中引发有效保护性免疫的治疗潜力。然而,用免疫检查点阻断抗体治疗癌症患者,并非没有毒性,与严重的自身炎症免疫反应相关。迫切需要发现新的治疗性免疫检查点阻断试剂,其副作用更易于控制。化学合成的单链寡核苷酸适配体在生产成本和处理副作用方面与抗体相比具有实质性的优势。
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引用次数: 1
The advancement of tumor microenvironment in pancreatic carcinoma 胰腺癌肿瘤微环境的研究进展
Pub Date : 2016-04-12 DOI: 10.14800/CCM.1248
N. Pu, Guo-chao Zhao, Y. Lv, Wenchuan Wu
Pancreatic cancer is the known kind of tumor biologically featured as high malignancy, lack of effective methods for diagnosis and treatment. Tumor microenvironment is generally considered as an important promotor in tumor invasion and metastasis. This review aims to deeply understand the mechanism of the tumor progression and validly provide the evidence for diagnosis and treatment by means focusing on the advances in the research of pancreatic cancer in the fields of stromal cells, inflammation and hypoxia in the tumor microenvironment of pancreatic carcinoma.
胰腺癌是生物学上已知的高恶性肿瘤,缺乏有效的诊断和治疗方法。肿瘤微环境被普遍认为是肿瘤侵袭转移的重要促进因子。本文通过对胰腺癌肿瘤微环境中基质细胞、炎症和缺氧等方面的研究进展进行综述,旨在深入了解肿瘤进展机制,为胰腺癌的诊断和治疗提供有效依据。
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引用次数: 2
Gallbladder's clear cell renal cell carcinoma metastasis: A systematic review of the literature 胆囊透明细胞肾细胞癌转移:文献系统回顾
Pub Date : 2016-04-04 DOI: 10.14800/CCM.1240
C. Ruiz, M. Zizzo, L. Ugoletti, A. Giunta, C. Pedrazzoli
Renal cell carcinoma (RCC) represents 2% of all cancers, being the clear cell subtype the most common among renal tumors (70-80%). RCC is well know for its capacity to metastasize in an early stage of the disease, gallbladder metastases are consider extremly rare. The symptomatology goes from asymptomatic to cholecystitis like-symptoms. Ultrasonography, may be often, the first diagnostic tool, tumors can appear under different hyperechoic masses without acoustic shadowing. Metastasectomy has gained a wide consensus because of the possibility of extending survival, keeping in mind the importance of selection of the ideal candidate for it. The surgical procedure will be chosen upon the extent of the disease, it may go from a simple cholecystectomy to a cholecystectomy associated with a wedge/right hepatic lobectomy for curative purposes.
肾细胞癌(RCC)占所有癌症的2%,是肾肿瘤中最常见的透明细胞亚型(70-80%)。众所周知,肾细胞癌在疾病的早期阶段具有转移的能力,胆囊转移被认为是极其罕见的。症状从无症状到胆囊炎样症状。超声检查通常是第一诊断工具,肿瘤可出现在不同的高回声肿块下,无声影。转移瘤切除术已经获得了广泛的共识,因为有可能延长生存期,记住选择理想的候选者的重要性。手术方式将根据疾病的严重程度来选择,可以是简单的胆囊切除术,也可以是胆囊切除术合并楔形/右肝叶切除术以达到治疗目的。
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引用次数: 1
Single nucleotide polymorphisms and risk factors predictive of pancreatic adenocarcinoma 单核苷酸多态性和预测胰腺腺癌的危险因素
Pub Date : 2016-03-28 DOI: 10.14800/CCM.1231
E. Martinez, F. Silvy, D. Lombardo, E. Mas
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote an early diagnosis and efficient follow-up, therefore avoiding its development. Single nucleotide polymorphisms, or SNPs, constitute the most abundant form of genetic variation in the human genome. SNPs are markers of diverse populations or individuals, yet also can be associated with differences in susceptibility or severity of certain diseases and/or individual responses to drugs. Many SNPs have previously been identified in studies of healthy subjects and patients with different alleles of a given gene. To date, around forty SNPs from the human genome have been correlated with predisposition to PDAC by pan-genomic studies or genome wide association studies (GWAS). However, parts of the human genome located within the GC-rich repeated domain of chromosomes are unsuitable for GWAS. Unfortunately, of those forty SNPs none are currently used in routine clinical protocols as potential biomarkers for PDAC. Exon 11 of the bile salt-dependent lipase gene ( BSDL ) plays a key role in pancreatic disease and encodes variable number of tandem repeat (VNTR) sequences, therefore Martinez et al . [Oncotarget. 2015; 6: 39855-39864.] hypothesized that a genetic link exists between mutations in VNTR loci and predisposition to pancreatic cancer (PC). Authors reported that the c.1719C>T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC group versus 27.30% in the control group). Notably, the odds ratio (OR) of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that the T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. Furthermore, a robust method using probes for droplet digital (dd)-PCR was designed to specifically discriminate the C/C major from C/T or T/T minor genotypes. Altogether, Martinez et al . propose that detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of these patients, particularly if associated with other potential risk factors of PC.
胰腺导管腺癌(PDAC)是一种破坏性疾病,在诊断后几个月内无症状进展直至死亡。确定高危人群应促进早期诊断和有效随访,从而避免其发展。单核苷酸多态性(snp)构成了人类基因组中最丰富的遗传变异形式。snp是不同人群或个体的标志,但也可能与某些疾病的易感性或严重程度的差异和/或个体对药物的反应有关。许多snp先前已经在健康受试者和具有不同等位基因的患者的研究中被确定。迄今为止,通过泛基因组研究或基因组全关联研究(GWAS),大约有40个来自人类基因组的snp与PDAC易感性相关。然而,人类基因组中位于染色体富含gc重复结构域的部分不适合GWAS。不幸的是,在这40个snp中,目前没有一个被用于常规临床方案中作为PDAC的潜在生物标志物。胆汁盐依赖性脂肪酶基因(BSDL)的外显子11在胰腺疾病中起关键作用,并编码可变数量的串联重复序列(VNTR)序列,因此Martinez等人。[Oncotarget。2015;6: 39855 - 39864。假设VNTR位点突变与胰腺癌易感性之间存在遗传联系。作者报道,BSDL VNTR中存在的c.1719C>T转位(SNP rs488087)可能是确定患PC风险人群的有用标记(发生率:PC组为63.90%,对照组为27.30%)。值得注意的是,T等位基因的比值比(OR)为4.7,高于已经确定的其他疑似预测PC的snp的比值比。对肿瘤胰腺组织的进一步研究表明,T等位基因可能有利于Kras G12R/G12D体细胞突变,这是与生存率降低相关的负面预后因素。此外,还设计了一种使用液滴数字(dd)-PCR探针的稳健方法,以特异性区分C/C主要基因型与C/T或T/T次要基因型。总之,马丁内斯等人。建议在rs488087 SNP中检测到T等位基因,应对这些患者进行深入随访,特别是与PC的其他潜在危险因素相关的患者。
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引用次数: 2
Imaging the role of the tumor microenvironment in tumor progression and metastasis 成像肿瘤微环境在肿瘤进展和转移中的作用
Pub Date : 2016-03-28 DOI: 10.14800/CCM.1206
R. Hoffman
The use of fluorescent proteins for imaging in vivo, pioneered by our laboratory, revolutionalized the in vivo study of cancer in mouse models to visualize tumor growth and progression.  With the use of multiple colored fluorescent proteins, we developed imaging of the tumor microenvironment (TME) by color-coding cancer and stromal cells, and demonstrated the essential role of tumor-associated host cells in tumor progression and metastasis. Color-coded imaging of the TME has also enabled important discoveries of its cellular components.
我们的实验室率先使用荧光蛋白进行体内成像,彻底改变了小鼠模型中癌症的体内研究,以观察肿瘤的生长和进展。我们利用多种彩色荧光蛋白,通过对肿瘤和基质细胞进行彩色编码,建立了肿瘤微环境(TME)成像,并证明了肿瘤相关宿主细胞在肿瘤进展和转移中的重要作用。TME的彩色编码成像也使其细胞成分的重要发现成为可能。
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引用次数: 1
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Cancer cell & microenvironment
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