Metabolic markers in blood can separate prostate cancer from benign prostatic hyperplasia

Background:

An individualised risk-stratified screening for prostate cancer (PCa) would select the patients who will benefit from further investigations as well as therapy. Current detection methods suffer from low sensitivity and specificity, especially for separating PCa from benign prostatic conditions. We have investigated the use of metabolomics analyses of blood samples for separating PCa patients and controls with benign prostatic hyperplasia (BPH).

Methods:

Blood plasma and serum samples from 29 PCa patient and 21 controls with BPH were analysed by metabolomics analysis using magnetic resonance spectroscopy, mass spectrometry and gas chromatography. Differences in blood metabolic patterns were examined by multivariate and univariate statistics.

Results:

By combining results from different methodological platforms, PCa patients and controls were separated with a sensitivity and specificity of 81.5% and 75.2%, respectively.

Conclusions:

The combined analysis of serum and plasma samples by different metabolomics measurement techniques gave successful discrimination of PCa and controls, and provided metabolic markers and insight into the processes characteristic of PCa. Our results suggest changes in fatty acid (acylcarnitines), choline (glycerophospholipids) and amino acid metabolism (arginine) as markers for PCa compared with BPH.     

内镜治疗消化道异物262例

目的总结消化道异物在内镜下的处理经验．方法１９８９年～１９９６年０３月消化道异物２６２例，男１７４例，女８８例；年龄１０月龄～７９岁；部位在食管内８４例，胃内１６７例，十二指肠６例，回肠２例，大肠３例．在内镜直视下按照异物的形态和大小，选择适合的异物钳，取出异物１８８例，设法让异物通过肠道排出体外６９例．结果２６２例患者中２５７例通过上述方法治疗后取得满意疗效，取出异物１８８例、排出异物６９例．仅５例治疗失败后（取出失败３例，排出失败２例）改为手术处理．内镜治疗消化道异物成功率为９８１％．结论经内镜治疗除空回肠以外的消化道异物是一种安全、有效的方法．     

Hematologic toxicity assessment in solid tumor patients treated with cetuximab: A pooled analysis of 18 randomized controlled trials

The role of cetuximab in treatment‐related hematologic toxicity is not clear. We performed a meta‐analysis of published randomized controlled trials (RCTs) to determine the overall risk of ≥grade 3 hematologic toxicity events (HTEs) associated with cetuximab. PubMed, EMBASE, and Web of Knowledge databases as well as abstracts presented at American Society of Clinical Oncology conferences and ClinicalTrials.gov were searched to identify relevant studies. Eligible studies included RCTs in which cetuximab in combination with chemotherapy or chemoradiotherapy was compared with chemotherapy or chemoradiotherapy alone. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed‐ or random‐effects models. A total of 11,234 patients with a variety of advanced solid tumors from 18 RCTs were included in the meta‐analysis. Compared with chemotherapy alone, the addition of cetuximab was associated with increased risks of ≥grade 3 leucopenia/neutropenia and anemia events in colorectal cancer, with RRs of 1.16 (95% CI 1.05–1.27, p = 0.002; incidence, 21.0 vs. 18.0%) and 2.67 (95% CI 1.53–4.65, p = 0.01; incidence, 4.0 vs. 2.0%), respectively. Cetuximab was also associated with an increased risk of leucopenia/neutropenia in nonsmall cell lung cancer (NSCLC) (RR: 1.15; 95% CI 1.08–1.22, p < 0.01). Additionally, K‐ras wild type in the case of colorectal cancer patients was more vulnerable to ≥grade 3 leucopenia or neutropenia events in cetuximab group (RR: 1.31; 95% CI 1.11–1.54, p = 0.001). With present evidence, cetuximab in conjunction with chemotherapy or chemoradiotherapy, compared with chemotherapy or chemoradiotherapy alone, was associated with increased slight risk of ≥grade 3 HTEs, especially in colorectal cancer and NSCLC.     

PTK7 regulates Id1 expression in CD44-high glioma cells

Background

CD44 is a molecular marker associated with molecular subtype and treatment resistance in glioma. More effective therapies will result from approaches aimed at targeting the CD44-high gliomas.

Methods

Protein tyrosine kinase 7 (PTK7) mRNA expression was analyzed based on The Cancer Genome Atlas glioblastoma dataset. PTK7 expression was depleted through lentivirus-mediated short hairpin RNA knockdown. Terminal deoxynucleotidyl transferase dUTP nick-end labeling was used to evaluate cell apoptosis following PTK7 knockdown. Gene expression analysis was performed on Affymetrix microarray. A nude mice orthotopic tumor model was used to evaluate the in vivo effect of PTK7 depletion.

Results

PTK7 is highly expressed in CD44-high glioblastoma and predicts unfavorable prognosis. PTK7 knockdown attenuated cell proliferation, impaired tumorigenic potential, and induced apoptosis in CD44-high glioma cell lines. Gene expression analysis identified inhibitor of DNA Binding 1 (Id1) gene as a potential downstream effector for PTK7. Overexpression of Id1 mostly restored the cell proliferation and colony formation attenuated by PTK7 depletion. PTK7 enhanced anchorage-independent growth in normal human astrocytes, which was attenuated by Id1 knockdown. Furthermore, PTK7 regulated Id1 expression through modulating TGF-β/Smad signaling, while pharmacological inhibition on TGF-β/Smad signaling or PTK7/Id1 depletion attenuated TGF-β–stimulated cell proliferation. PTK7 depletion consistently reduced Id1 expression, suppressed tumor growth, and induced apoptosis in a murine orthotopic tumor model, which could be translated into prolonged survival in tumor-bearing mice.

Conclusions

PTK7 regulates Id1 expression in CD44-high glioma cell lines. Targeting PTK7 could be an effective strategy for treating glioma with high CD44 expression.     

重组人白介素-11(I)(百杰依)治疗恶性肿瘤化疗后血小板减少症13例临床观察

目的:观察重组人白介素-11(I)(百杰依)对恶性肿瘤患者因化疗所致血小板减少的疗效及不良反应。方法:化疗后发生Ⅲ级以上血小板减少(PLT≤50×109/L)即开始给予百杰依25μg/(kg·d)皮下注射,观察外周血小板变化,血小板升至100×109/L以上或绝对值升高50×109/L以及使用10支百杰依时停药。结果:患者采用百杰依治疗前后对比数据显示,化疗前血小板计数平均值为(136.0±36.84)×109/L,化疗后血小板最低值为(25.58±12.90)×109/L,血小板<50×109/L持续天数为(5.42±3.47)天,百杰依治疗结束时血小板计数平均值为(106.91±55.44)×109/L,平均用药天数(6.91±2.5)天。主要不良反应为头晕、注射部位疼痛、水肿。结论:重组人白介素-11(I)(百杰依)有升高化疗后血小板减少的作用,疗效显著,毒副反应可耐受。     

左右半大肠癌的差异

结直肠癌的发病率在发达国家呈下降趋势,与结肠镜筛查、人口老龄化、饮食结构调整、癌症和糖尿病发病率升高等有关,性别、种族、教育等因素也起一定作用。右半大肠癌中,低分化和晚期疾病比例高,腺癌中黏液成分多,易出现并发症和肠内第二原发肿瘤;而左半大肠癌多呈高分化,诊断时偏早期。分子机制上,右半大肠癌与错配修复基因密切相关,而左半大肠癌与 p53突变联系紧密。左、右半大肠癌存在众多表观和遗传学差异,可能属于两种不同的疾病,在临床工作和试验中应区别对待。     

SLC7A11基因表达沉默的肝癌细胞株的构建及筛选

目的:构建并筛选出SLC7A11基因表达沉默的肝癌LM3细胞株,为研究SLC7A11基因的表达沉默对肝癌发生发展的影响奠定基础。方法:针对SLC7A11基因的不同部位合成3个siRNA的寡核苷酸片段,分别将其克隆到真核表达载体p GPU6/GFP/Neo中。利用脂质体转染法分别将质粒导入肝癌LM3细胞,24小时后观察细胞内GFP表达情况,并通过real-time PCR及Western blot的方法比较各组细胞SLC7A11基因mRNA和蛋白的表达水平,然后用G418对转染细胞进行筛选培养。结果:经酶切分析及测序验证,成功构建了靶向沉默SLC7A11基因的真核表达质粒p GPU6-SLC7A11-siRNA;通过real-time PCR及Western blot的方法验证,成功筛选出SLC7A11基因表达沉默的肝癌LM3细胞株。结论:成功构建并筛选出SLC7A11基因表达沉默的肝癌细胞株,为进一步研究SLC7A11基因表达沉默对肝癌细胞发生发展的影响奠定了基础。     

RNAi沉默MCM7基因对人肝癌细胞SMMC-7721裸鼠移植瘤影响研究

目的探讨微小染色体维持蛋白7(miniehromosome maintenanceprotein7,MCM7)基因RNAi(RNA interference)的重组慢病毒载体,对人肝癌细胞SMMC-7721 MCM7基因表达和裸鼠移植瘤生长的影响。方法构建重组逆转录慢病毒载体MCM7-shRNA,以MCM7基因沉默重组慢病毒颗粒(LV-shRNA-MCM7)感染SMMC-7721细胞,作为实验组;以对照慢病毒颗粒(LV-shRNA-NC)感染SMMC-7721细胞,作为阴性对照组;空白对照组常规培养,不做任何处理。通过嘌呤霉素筛选出稳定转染细胞株。3组细胞分别接种至裸鼠皮下,建立人肝癌裸鼠移植瘤模型。观察裸鼠成瘤情况、移植瘤生长情况并绘制肿瘤生长曲线;4周后测定肿瘤体积和质量,并用RT-PCR、实时荧光定量PCR、蛋白质印迹法及免疫组织化学法检测移植瘤中MCM7的表达情况。结果 MCM7-shRNA慢病毒载体构建成功。裸鼠接种癌细胞后第6天均有肿瘤形成,与空白对照组和阴性对照组相比,实验组的肿瘤生长速度明显减慢,实验组、阴性对照组和空白对照组的瘤体平均体积分别为(27.72±7.80)、(81.86±10.91)和(79.75±16.61)mm3,差异有统计学意义,F=61.949,P<0.05;实验组、阴性对照组和空白对照组的瘤体平均质量分别为(0.19±0.06)、(0.501±0.14)和(0.509±0.18)g,差异有统计学意义,F=18.41,P<0.05。实验组MCM7mRNA的相对表达量为0.253±0.198,阴性对照组1.213±0.548,空白对照组1.201±0.744,实验组相比阴性对照组和空白对照组明显下降,差异有统计学意义,F=4.091,P<0.05;实验组MCM7蛋白相对表达量为0.207±0.015,阴性对照组1.116±0.062,空白对照组1.088±0.040,实验组相比阴性对照组和空白对照组明显下降,差异有统计学意义,F=292.778,P<0.05。MCM7蛋白在阴性对照组和空白对照组中阳性表达率均为100%(10/10),在实验组中为30%(3/10),实验组明显低于阴性对照组和空白对照组,差异有统计学意义,χ2=18.261,P<0.001。结论慢病毒沉默SMMC-7721细胞MCM7基因表达能有效抑制人肝癌裸鼠移植瘤的生长,MCM7基因可能成为肝癌基因治疗的有效靶点。