Effects of human plasma on lipid metabolism by 3T3-L1 cells

Differentiated 3T3-L1 cells were examined for the effect of human plasma on triacylglycerol synthesis and fatty acid release. Human plasma only increased lipogenesis 37% when obtained from subjects who had recently consumed a carbohydrate-rich meal compared to fasting, whereas fatty acid release was up to 2-fold higher with plasma from fasting subjects. The effects of plasma from different individuals varied cosiderably, but there was a positive correlation between the magnitude of the lipolytic and lipogenic stimulation. Since 3T3-L1 cells respond to plasma, they may be a useful system for investigations of the combined effects of lipogenic and lipolytic factors on adipose cell metabolism.     

The value of comparative effectiveness research: Projected return on investment of the RxPONDER trial (SWOG S1007)

ObjectiveThe objective of this study was to assess the value of research of the RxPONDER study, an ongoing comparative effectiveness RCT designed to evaluate a 21-gene profile in early stage, node-positive breast cancer.MethodsWe developed a disease-based decision-analytic model to compare use of the 21-gene profile versus standard care. Key clinical data were derived from SWOG-8814, an RCT of chemotherapy in lymph node-positive breast cancer. Other model parameters were obtained from published sources. Probabilistic simulations and value of information calculations were used to assess the expected value of sample information (EVSI) and the expected value of sample parameter information (EVSPI).ResultsThe cost of the RxPONDER trial is expected to be at least $27 million. The expected value of research of the RxPONDER trial ranged from $450 million to $1 billion, representing a return of 17 to 39 times the projected cost of the trial. The primary objective of RxPONDER, to assess survival, had the largest estimated value relative to other model inputs. The value of RxPONDER increased by $50 million to $100 million after stakeholder input on additional data collection.ConclusionThe RxPONDER study appears to represent a good investment of public research funds. Stakeholder engagement and assessment of the return on investment should be considered to optimize and quantify the value of comparative effectiveness studies.     

Metastatic Tumors of Unknown Origin: Ancillary Testing in Cytologic Specimens

The application of ancillary studies, such as immunostains, to cytopathology has improved the ability to make accurate diagnoses with precise subclassification. Even with these techniques, there are still aspiration and exfoliative cytology cases for which it remains difficult to definitively determine the source and/or subtype. This article focuses on the well-established and novel ancillary studies used in the modern era of cancer diagnoses in cytopathology, particularly in the diagnostic work-up of metastatic tumors without a known primary.     

Scalable learning method for feedforward neural networks using minimal-enclosing-ball approximation

Training feedforward neural networks (FNNs) is one of the most critical issues in FNNs studies. However, most FNNs training methods cannot be directly applied for very large datasets because they have high computational and space complexity. In order to tackle this problem, the CCMEB (Center-Constrained Minimum Enclosing Ball) problem in hidden feature space of FNN is discussed and a novel learning algorithm called HFSR-GCVM (hidden-feature-space regression using generalized core vector machine) is developed accordingly. In HFSR-GCVM, a novel learning criterion using L2-norm penalty-based $\epsilon$-insensitive function is formulated and the parameters in the hidden nodes are generated randomly independent of the training sets. Moreover, the learning of parameters in its output layer is proved equivalent to a special CCMEB problem in FNN hidden feature space. As most CCMEB approximation based machine learning algorithms, the proposed HFSR-GCVM training algorithm has the following merits: The maximal training time of the HFSR-GCVM training is linear with the size of training datasets and the maximal space consumption is independent of the size of training datasets. The experiments on regression tasks confirm the above conclusions.     

痘苗生长因子和胸苷激酶双基因缺失表达双荧光溶瘤痘病毒的构建及其对胰腺癌细胞的杀伤作用

［摘要］目的: 构建痘苗生长因子(vaccinia growth factor,VGF)和胸苷激酶(thymidine kinase,TK)双基因缺失同时表达绿色荧光蛋白（GFP）和DsRed双荧光的溶瘤痘病毒,并研究其对胰腺癌细胞的杀伤作用。方法: 在病毒TK基因处利用同源重组方法将病毒晚期启动子F17R调控的GFP基因和早晚期启动子SEL调控的DsRed基因克隆入缺失VGF基因的VSC20亲本病毒,构建同时缺失VGF和TK双基因的重组溶瘤痘病毒vvDD-GFP DsRed。同时利用CCK 8法和结晶紫染色法检测该病毒对胰腺癌细胞Patu8988和BxPC-3的杀伤作用。结果： 通过同源重组和软琼脂筛选获得vvDD-GFP-DsRed重组溶瘤痘病毒。CCK 8法结果显示,与MOI=0相比,MOI分别为1,10时,vvDD-GFP-DsRed对Patu8988细胞和BxPC-3细胞具有明显的杀伤作用,且在此范围内随MOI值增加杀伤效果逐渐增强(P均＜0.05)。与MOI=0相比,Patu8988细胞在MOI为0.01时存活率低(P＜0.05),且在结晶紫染色法测定中形成了明显的空斑。结论： 成功构建vvDD GFP DsRed重组溶瘤痘病毒,其对胰腺癌细胞具有明显的杀伤作用。     

不同移植方式建立兔VX2肝癌模型

目的利用不同方法建立兔VX2移植肝癌模型,选择最佳的建模方法。方法45只新西兰大白兔随机被分成3组,每组15只,分别采用开腹肝内VX2瘤块包埋法（A组）、CT定位下经皮穿刺肝脏后注射VX2瘤块悬液法（B组）、CT定位下经皮穿刺肝脏后推送VX2瘤块法（C组）制作肝癌模型,比较各组动物种植成功率及存活时间。结果A、B、C各组动物种植后3周的死亡率分别为26.7%、20.0%、0.0%,A、B两组与C组的差异有统计学意义（P〈0.05）。A、B、C各组动物种植后3周的成瘤率分别为53.3%、80.0%、93.3%,A组与B、C两组的差异有统计学意义（P〈0.05）。A、B、C组动物的平均生存期分别为（25.5±19.4）d（、37.5±15.7）d（、48.7±11.1）d,差异有统计学意义（P〈0.05）。所有种植成功的模型都得到病理学证实。结论成功建立了兔VX2肝癌模型;CT定位下经皮穿刺直接推送瘤块法的建模成功率明显高于其他两种方法。     

同种异体大鼠骨髓间充质干细胞共培养及多向分化潜能鉴定

目的 探讨同种异体大鼠骨髓间充质干细胞在体外的共培养,并行多向分化诱导鉴定。方法 分别通过全骨髓直接培养法及密度梯度法分离培养大鼠骨髓间充质干细胞,各传至第3代后,取等量细胞,混合后共培养,共培养之细胞再次传代后,分别进行成骨细胞、成脂肪细胞诱导,并分别行碱性磷酸酶、Von Cossa及油红染色鉴定。结果 全骨髓直接培养法原代细胞形态不均一,但是增殖能力好;密度梯度法分离得到的细胞较为均一,但增殖力不如全骨髓直接培养法。经过3代传代后,细胞均可获得相对纯化。共培养细胞增殖力较好,细胞形态较为均一,且未出现因免疫排斥导致的细胞死亡。共培养之大鼠骨髓间充质干细胞分别经诱导分化为成骨细胞和脂肪细胞形态（分别经碱性磷酸酶、Von Cossa染色和油红染色证实）。结论 采用全骨髓直接培养及密度梯度离心法,经3-5代培养后均可获得相对纯化之骨髓间充质干细胞。同种异体大鼠骨髓间充质干细胞共培养生长良好,不发生免疫排斥,证实该类细胞的免疫原性极低。在体外,大鼠骨髓间充质干细胞可诱导分化为成骨细胞、脂肪细胞,表明它具有多向分化潜能。     

乳腺癌耐药蛋白在急性髓性白血病中的表达和临床意义

目的探讨急性髓性白血病（AML）患者乳腺癌耐药蛋白（BCRP）的表达与临床耐药的关系。方法应用半定量反转录-聚合酶链反应（RT-PCR）,以MCF7乳腺癌细胞株、HL60白血病细胞株分别作为BCRP及MDR1 mRNA表达的参照标准,以β肌动蛋白（-βactin）为内对照,检测了54例AML患者BCRP mRNA的表达,其中8例患者测定MDR1 mRNA的表达,初步探讨BCRP表达在AML中的临床意义。结果AML中BCRP mRNA表达水平差异较大,BCRP表达由低到高依次为对照组、完全缓解组、初治敏感组和临床耐药组。其中临床耐药组BCRP阳性率显著高于对照组及完全缓解组,差异有统计学意义（P〈0.01及P〈0.05）,BCRP表达与MDR1表达无相关性（P〉0.05）。结论BCRP在AML中表达水平差异较大,与MDR1的表达无关,可能是AML患者临床耐药的一个独立的重要原因,是预后的不利因素。