Necrotizing fasciitis secondary to bevacizumab treatment for metastatic rectal adenocarcinoma

Bevacizumab is a recombinant humanized monoclonal antibody that selectively blocks the activity of vascular endothelial growth factor (VEGF) receptor and it is used in metastatic colorectal patients. We present here a case of fatal necrotizing fasciitis in a patient during bevacizumab treatment for colorectal cancer. In our review of the literature, necrotizing fasciitis was not reported before or during bevacizumab treatment.KEY WORDS: Adverse drug reactions, bevacizumab, colorectal cancer, necrotizing fasciitis     

The cost-effectiveness of biomarkers for predicting the development of oesophageal adenocarcinoma

BACKGROUND: The recommended surveillance strategy for oesophageal adenocarcinoma may prevent as few as 50% of cancer deaths. Tissue biomarkers have been proposed to identify high-risk patients. AIM: To determine performance characteristics of an ideal biomarker, or panel of biomarkers, that would make its use more cost-effective than the current surveillance strategy. METHODS: We created a Markov model using data from published literature, and performed a cost-utility analysis. The population consisted of 50-year-old Caucasian men with gastro-oesophageal reflux, who were monitored until age 80. We examined strategies of observation only, current practice (dysplasia-guided surveillance), surveillance every 3 months for patients with a positive biomarker (biomarker-guided surveillance), and oesophagectomy immediately for a positive biomarker (biomarker-guided oesophagectomy). The primary outcome was the threshold cost and performance characteristics needed for a biomarker to be more cost-effective than current practice. RESULTS: Regardless of the cost, the biomarker needs to be at least 95% specific for biomarker-guided oesophagectomy to be cost-effective. For biomarker-guided surveillance to be cost-effective, a $100 biomarker could be 80% sensitive and specific. CONCLUSIONS: Biomarkers predicting the development of oesophageal adenocarcinoma would need to be fairly accurate and inexpensive to be cost-effective. These results should guide the development of biomarkers for oesophageal adenocarcinoma.     

Prognostic and predictive biomarkers of abdominal aortic aneurysm growth rate

Objectives:

To test the utility of clinical and circulating biomarkers to predict abdominal aortic aneurysm (AAA) growth rate and response to doxycycline therapy.

Methods:

Plasma samples were obtained in the Pharmaceutical Aneurysm Stabilization Trial that tested the effect of doxycycline (n?=?44) vs. placebo (n?=?49) in patients with a 35–50?mm AAA. Approximately 200 biomarkers were evaluated in a candidate approach that included markers of matrix turnover and cathepsin S activity and a broad-based approach of predominantly inflammation-related and clinical biomarkers.

Results:

In a recursive partitioning based analysis, total cholesterol, baseline AAA size, and apolipoprotein B were prognostic of AAA growth in the placebo group whereas elastin and biglycan degradation products were predictive of AAA growth with doxycycline treatment. Univariate analysis of these biomarkers showed that baseline total cholesterol (r?=?0.38, unadjusted P?=?0.011), apolipoprotein B (r?=?0.41, unadjusted P?=?0.005), and baseline AAA size (r?=?0.35, unadjusted P?=?0.013) correlated with AAA growth in the placebo but not the doxycycline group. Elastin fragments were associated with 18 month AAA growth (r?=?0.33, unadjusted P?=?0.031) in the doxycycline group.

Limitations:

Limitations of this study include small sample size, a retrospective growth analysis, and translatability of the method used to measure the analytes.

Conclusions:

This study implies that total cholesterol, baseline AAA size, and apolipoprotein B are predictors of AAA growth. Levels of elastin and biglycan fragments are predictive of doxycycline effects on AAA growth and provide a clue towards this unexpected negative effect.     

Molecular and clinical analysis of predictive biomarkers in non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-specific death in the USA and Europe. Over the last two decades, the pathogenetic mechanisms and the molecular alterations of NSCLC have been investigated more intensively, a number of potential therapeutic targets have been identified and new agents against specific molecular targets have been introduced in the treatment of NSCLC. Acquired abnormalities in the genes encoding RAS, p53, KRAS, EGFR and ALK, are particularly important in this field. Whenever targetable mutations are not found, the research of other genetic abnormalities can be useful to personalize chemotherapy. The attention has been focused, in particular, on the endonuclease excision repair cross-complementing1 and BRCA1 status. The use of antimetabolite drugs and the level of expression of their cellular targets seem to be correlated and influence the clinical efficacy of those agents. This review will focus on the role of predictive biomarkers for the treatment of non-small cell lung cancer.     

An overview of children as a special population--relevance to predictive biomarkers

There has been an increasing focus on children as a special population in the fields of toxicology and epidemiology. At the same time, there has been considerable improvement in the technology for defining normal development and pathways of pathogenesis. Increased support of these areas has culminated in stronger research programs and greater professional involvement in addressing the specific challenges of applying new techniques and data to the improvement of children's health. Part of these challenges relates to the ever changing environment of the child. Not only does a child's anatomy, physiology, and metabolism change with time, but their lifestyle and awareness change as well. All of these can have a significant impact on a child's exposure and the potential of that exposure to have an effect on health and development. This paper will provide a brief overview of the susceptibility of the child relative to sensitive developmental life stages, the changing nature of exposure parameters during development, and how these factors can impact the relevance of predictive biomarkers of chemical toxicity in children.     

人直肠癌中血管内皮生长因子受体3的表达及其意义

目的 探讨血管内皮生长因子受体3(VEGFR-3)在人直肠癌发生、发展和淋巴结转移中的作用.方法 选用31例手术切除并经病理切片确诊为直肠腺痛的癌组织及其中的14例淋巴结(9例腺癌转移阳性,4例腺癌转移阴性)石蜡标本,采用免疫组织化学方法 检测VEGFR-3在癌组织和淋巴结内的表达.结果 31例直肠腺癌组织的癌细胞质中,VEGFR-3显色阳性者20例(64.5%).14例淋巴结中,VEGFR-3显色阳性者9例(64.3%,4例显色于无腺癌转移淋巴细胞内).结论 VEGFR-3在直肠癌组织和淋巴结中均有较高表达,可促进癌细胞转移.     

磁共振对于直肠部分黏液腺癌的诊断价值

目的分析直肠部分黏液腺癌的磁共振表现,探讨直肠部分黏液腺癌的磁共振特征。方法比较19例直肠部分黏液腺癌患者正常直肠,直肠腺癌部分及黏液部分的信号差异。结果 T1WI序列,正常直肠信号强度与直肠腺癌部分信号强度相近,差异无统计学意义(P>0.05),直肠腺癌部分信号强度低于黏液部分信号强度,差异无统计学意义(P>0.05),正常直肠信号高于直肠腺癌黏液成分,差异有统计学意义(P<0.05);T2WI序列,正常直肠信号强度低于直肠腺癌部分信号强度,差异有统计学意义(P<0.05),直肠腺癌部分信号强度低于黏液部分信号强度差异有统计学意义(P<0.05),正常直肠信号强度低于直肠腺癌黏液成分差异有统计学意义(P<0.05);表观扩散系数(ADC)值,正常直肠低于直肠腺癌部分,差异有统计学意义(P<0.05),直肠腺癌部分低于黏液部分,差异有统计学意义(P<0.05),正常直肠低于直肠黏液部分,差异有统计学意义(P<0.05)。结论直肠部分黏液腺癌患者的正常直肠、腺癌部分及黏液部分信号不同,磁共振对于病变病理类型的区分具有一定的鉴别诊断价值,DWI联合磁共振常规扫描可提高诊断效能。     

直肠胃肠道间质瘤的外科治疗

目的：探讨直肠胃肠道间质瘤（gastrointestinal stromal tumor,GIST）外科治疗的疗效及安全性。方法回顾性分析本院2006年1月~2011年1月收治的44例直肠GIST患者的临床资料,观察治疗效果及预后。结果根治手术组的手术时间、住院时间长于姑息手术组,术中出血量多于姑息手术组,住院费用、并发症发生率率高于姑息手术组（P＜0.05）;两组的复发转移率、生存率差异无统计学意义（P＞0.05）。结论根治性、姑息性手术的转归相似,而姑息性手术具有更好的安全性,是保证患者预后及生存质量的较佳选择。     

直肠腺癌组织TNFRSF7、TNFSF7基因mRNA表达

目的 检测直肠腺癌组织及癌旁10 cm正常组织TNFRSF7、TNFSF7基因表达.方法 采集9例直肠腺癌及癌旁10 cm正常组织样本,采用原位杂交法检测直肠腺癌组织TNFRSF7、TNFSF7基因表达.将"信号评分"(染色强度评分×染色面积)作为每个样本的原位杂交染色评分,结果 TNFRSF7、TNFSF7生物素标记探针在直肠腺癌细胞中的杂交信号可见于所有直肠腺癌及相应癌旁10 cm直肠黏膜上皮.细胞质区域杂交信号的强度较胞核区为弱,TNFRSF7杂交信号的强度较TNFSF7为弱.直肠腺癌组织中TNFRSF7、TNFSF7基因mRNA信号评分均高于癌旁10 cm正常黏膜组织.结论 TNFRSF7、TNFSF7 mRNA在直肠癌组织中高表达,可作为判断肿瘤分期、指导治疗和预后判断的参考指标.     

Neoadjuvant therapy for triple-negative breast cancer: potential predictive biomarkers of activity and efficacy of platinum chemotherapy,PARP- and immune-checkpoint-inhibitors

ABSTRACT

Introduction

Despite recent advances in the molecular characterization of triple-negative breast cancer (TNBC), the standard treatment for early-stage TNBC is represented by the historically used anthracycline and taxane-based chemotherapy. In this modern era of precision medicine, several new therapeutic strategies and novel agents have been investigated in the neoadjuvant setting of TNBC, in order to individualize treatment.     

Recent advances in biomarkers for cancer diagnosis and treatment

With the availability of new technologies and the increased interest of medical practitioners to use molecular biomarkers in early detection and diagnosis, and in the prediction of therapeutic treatment efficacy and clinical outcomes, the academic and research institutions, as well as the pharmaceutical industry, have increased their efforts to develop novel molecular biomarkers for several human diseases, including cancer. The identification of molecular biomarkers also enables the development of a new generation of diagnostic products and to integrate diagnostics and therapeutics. This integrated approach will aid in 'individualizing' the medical practice. Here, we address issues related to the development of biomarkers, novel technological platforms used for drug development, future technologies and strategies for validating biomarkers for their clinical utility.     

Identification of immune-related biomarkers in adrenocortical carcinoma: Immune-related biomarkers for ACC

Emerging evidence has suggested that the tumor microenvironment, including immune infiltration, plays a crucially important role in tumor progression. Nevertheless, limited studies have been conducted on this topic in adrenocortical carcinoma. The present study aimed to explore the immune-related biomarkers in adrenocortical carcinoma. CIBERSORT was used to estimate the abundances of 22 kinds of immune cells, and univariable Cox analysis was performed to find survival-related immune cells with both Overall Survival (OS) and Progression-Free Interval (PFI). DESeq2 was applied to find differentially expressed genes between adrenocortical carcinoma and normal control samples; subsequently, weighted correlation network analysis and protein-protein interaction (PPI) network analysis were conducted to identify immune-related hub genes. xCell, TISIDB, and MsigDB were searched to validate the immune associations of hub genes. Eventually, univariable Cox and Kaplan–Meier analysis were used to assess the prognostic implications of the hub gene with the GEO database. Consequently, we identified two hub immune-related genes (ERN1, CEP55), GSEA revealed that both were mainly involved in tumor progression and immune response. ROC analysis indicated that ERN1 can accurately predict the 1-, 3-, and 5-year PFI, and CEP55 had the best performance for the prediction of both OS and PFI compared with other traits. Univariable Cox and Kaplan–Meier analysis showed that both genes have a significant effect on prognosis. Furthermore, both hub genes were validated in GEO datasets. The hub genes can provide better insights into tumor microenvironment and serve as potential biomarkers for immunotherapy in adrenocortical carcinoma.     

与肺动脉高压诊断和精准治疗相关的新型生物标志物

肺动脉高压是一类以肺血管阻力进行性升高为主要特征的疾病,致残率和病死率都很高。由于多种疾病均可导致肺动脉高压的发生,因此其机制研究发展迅速,也出现了针对肺高压多种发病机制及其不同环节而研发的新型靶向药。综述目前与肺动脉高压发病机制相关的新型生物标志物,并将其按照功能进行分类,包括内皮细胞功能失调、炎症、表观遗传学、心脏功能、氧化应激、细胞外基质等内容,为该病的临床早期诊断、疾病分型、严重程度判断等提供有效依据,进而为精准治疗以及新药研发提供依据。     

贝伐珠单抗联合化疗治疗晚期肺腺癌

目的观察贝伐珠单抗联合化疗在晚期肺腺癌一线治疗方面的疗效和安全性。方法 94例初治晚期肺腺癌患者随机分为贝伐珠单抗联合化疗组(联合化疗组,n=44)和单纯化疗组(n=50)。联合化疗组给予贝伐珠单抗(7.5 mg·kg-1)+培美曲塞(500 mg·m-2)+卡铂(300 mg·m-2)治疗,单纯化疗组给予培美曲塞(500 mg·m-2)+卡铂(300 mg·m-2)治疗,两组患者均以21 d为一个周期,用药6个周期,均为化疗第1日静脉给药。比较两组的疗效、不良反应及肿瘤标志物肿瘤特异性生长因子(TSGF)、癌胚抗原(CEA)和细胞角蛋白19片段(CK-19)的变化。结果联合化疗组与单纯化疗组的缓解率分别为57%和34%,疾病控制率分别为86%和64%(P<0.05);中位无进展生存期分别为8.4个月和6.1个月,中位总生存期分别为15.1个月和11.9个月(P<0.01),一年生存率分别为55%和34%(P<0.05)。联合化疗组治疗后的TSGF、CEA和CK-19水平均显著低于单纯化疗组(P<0.01)。联合化疗组较单纯化疗组增加的不良反应主要是高血压,但均为Ⅰ~Ⅱ度,经治疗后均可控制。结论贝伐珠单抗联合化疗在晚期肺腺癌一线治疗中疗效明显,且未增加严重不良反应,具有很好的临床应用前景。