Hydroxyl safflower yellow B combined with doxorubicin inhibits the proliferation of human breast cancer MCF-7 cells

Doxorubicin (DOX) is currently the preferred chemotherapeutic agent for breast cancer, and hydroxyl safflower yellow B (HSYB) has a tumor growth-inhibiting activity. The present study aimed to investigate the effects of HSYB combined with DOX on the proliferation of human breast cancer MCF-7 cells and explore the underlying mechanism. MTT and cell colony formation assays revealed that the proliferation rate of MCF-7 cells was signifiscantly decreased after HSYB and DOX treatment. Combined HSYB and DOX treatment significantly decreased the expression levels of BCL-2 in MCF-7 cells, while the expression levels of apoptosis-associated proteins, including cleaved caspase-9, BAX and cleaved caspase-3, were markedly increased. Furthermore, flow cytometry and western blot analysis demonstrated that combined HSYB and DOX treatment stimulated an increase in intracellular reactive oxygen species and promoted the release of cytochrome c, leading to apoptosis. The current data suggested that the combination of HSYB and DOX may have marked antitumor activity.     

唑来膦酸联合化疗治疗实体瘤骨转移临床观察

目的:探讨唑来膦酸联合化疗治疗实体瘤骨转移的临床疗效。方法:102例实体瘤患者随机分为治疗组和对照组各51例,对照组予常规化疗,治疗组加用唑来膦酸静滴,评价止痛、骨转移灶修复及生活质量改善疗效,测定TNF-α、IL-6、MMP-2、MMP-9和血钙含量,记录治疗过程中的不良反应。结果:治疗组止痛有效率为86.3%,骨转移灶修复有效率为54.9%,生活质量改善有效率为72.5%,均明显优于对照组(P<0.05或P<0.01);治疗组治疗后TNF-α、IL-6、MMP-2、MMP-9和血钙含量均明显下降(P<0.01),且均明显优于对照组(P<0.01);与对照组相比,主要不良反应是一过性发热(P<0.01)。结论:唑来膦酸联合化疗治疗实体瘤骨转移疗效肯定,不良反应可耐受。     

Simple and accurate determination of CYP2D6 gene copy number by a loop-mediated isothermal amplification method and an electrochemical DNA chip

BackgroundA combination technology of a loop-mediated isothermal amplification (LAMP) method and an electrochemical DNA chip has been developed. In this study, the CYP2D6 gene copies were detected by this technology for determination of the functional CYP2D6*5 and CYP2D6*2 × 2 alleles.MethodsA set of LAMP primers was designed to coamplify the CYP2D6 gene, but not the CYP2D6*36, and the CYP2D8P gene, which would enable determination of the CYP2D6 gene copies by relatively comparing with the amount of the amplified products of CYP2D6 and CYP2D8P. The LAMP products were reacted with the electrochemical DNA chip using the DNA detection system Genelyzer? that automatically controls hybridization reaction, washing, and electrochemical detection. To test the feasibility of the system, 16 samples that have various combinations of copy numbers were selected from pooled samples previously genotyped according to empirically well-authorized Southern blotting-based RFLP methods.ResultsThe CYP2D6 gene copies were consistent with the previous genotypes except a rare CYP2D6*18 allele probably due to mutation near the primer region. The results were completely reproducible in a blind test and were given within 1.5 h.ConclusionsThis method offers a simple and accurate determination of the CYP2D6 gene copies and is expected to contribute to personalized medicine.     

Prodrug-based nano-drug delivery system for co-encapsulate paclitaxel and carboplatin for lung cancer treatment

Context: Paclitaxel (PTX) and carboplatin (CBP) are widely used for the combined chemotherapy of non-small cell lung cancer (NSCLC). However, the development of multidrug resistance of cancer cells, as well as systemic toxic side effects resulting from nonspecific localization of anticancer drugs to non-tumor areas are major obstacles to the success of chemotherapy in treating cancers.

Objective: This study aimed to engineer a prodrug-based nano-drug delivery system for co-encapsulate hydrophilic (CBP) and hydrophobic anti-tumor drugs (PTX). This system was expected to resolve the multidrug resistance cause by single drug, and the dual-drug-loaded liposome was also planned to specifically target the cancer cells without obvious influence on normal cells and tissues.

Methods: In this paper, PLGA-PEG-CBP was synthesized by the conjugation between the carboxylic group of PLGA-PEG-COOH and the amino group of CBP. Then, self-assembled nanoparticles for combination delivery of PTX and PLGA-PEG-CBP (PTX/CBP NPs) were prepared by solvent displacement technique. The in vitro and in vivo anti-tumor efficacy was assessed in NCL-H460 human non-small cell lung carcinoma cell line.

Results: PTX/CBP NPs achieved the highest cytotoxic effect among all formulations in vitro, as compared with single drug delivery NPs. In vivo investigation on NSCLC animal models showed that co-delivery of PTX and CBP possessed high tumor-targeting capacity and strong anti-tumor activity.

Conclusions: The PTX/CBP NPs constructed in this research offers an effective strategy for targeted combinational lung cancer therapy.     

内皮抑素-血管内皮细胞抑制因子重组腺病毒对同型半胱氨酸致人血管内皮细胞损伤的拮抗作用

目的探讨内皮抑素(ENDO)-血管内皮细胞抑制因子(VEGI)重组腺病毒对同型半胱氨酸(Hcy)致人血管内皮细胞损伤的拮抗作用。方法应用内皮抑素-血管内皮细胞抑制因子融合蛋白重组腺病毒(Ad-hENDOVEGI151)转染Hcy损伤的人血管内皮细胞ECV304,用免疫印迹法检测受染细胞融合蛋白的表达,用自动生化分析仪检测乳酸脱氢酶(LDH)漏出量,用台盼蓝染色法计算细胞存活率,用ELISA检测肿瘤坏死因子α(TNF-α)、单核细胞趋化蛋白1(MCP-1)的表达。结果制备的重组腺病毒具有较高的转基因效率,Ad-hENDO-VEGI151重组腺病毒能够在ECV304细胞中表达41 kDa大小的融合蛋白,Hcy(0.1~1.0 mmol/L)呈浓度依赖性地增加细胞LDH漏出量和降低细胞存活率,重组腺病毒能够有效地拮抗Hcy对人血管内皮细胞的损伤作用(P0.05)。结论内皮抑素-血管内皮细胞抑制因子重组腺病毒对Hcy致人血管内皮细胞损伤有拮抗作用,为治疗高同型半胱氨酸血症等疾病提供新的思路。     

Hormone replacement therapy and the risk of colorectal cancer: a meta-analysis

Objective: To review systematically the association between hormone replacement therapy (HRT) and the risk of developing or dying from colorectal cancer.Data Sources: We searched the English-language literature using MEDLINE, Current Contents, CancerLit, and bibliographies of selected studies.Methods of Study Selection: We included studies that specifically addressed the association of HRT with colorectal cancer, had adequate controls, and had retrievable risk estimates. We excluded letters, reviews, and multiple publications of the same data.Tabulation, Integration, and Results: Studies were evaluated independently by two of the authors. The exposures of interest were ever, recent, or former use of HRT, and the main outcome measures were colon and rectal cancer incidence and mortality. To reduce the risk of a “healthy estrogen user” bias, we defined recent HRT use as either at time of assessment or within the previous year. The most adjusted risk estimates were extracted. We used a random-effects model to calculate summary relative risks (RRs) and confidence intervals (CIs). Recent use of HRT was associated with a 33% reduction in the risk of colon cancer (RR = 0.67; 95% CI 0.59, 0.77). Protection was limited to recent users; the risk of colon cancer with ever use of HRT was 0.92 (95% CI 0.79, 1.08). Duration of use was not significant. Three studies addressed the risk of fatal colon cancer; the summary RR for death from colon cancer in HRT users was 0.72 (95% CI 0.64, 0.81) compared with nonusers. Rectal cancer incidence was not associated with HRT.Conclusion: The risk of colon cancer may be decreased among recent postmenopausal HRT users. Although data are limited, the risk of fatal colon cancer also may be lower in HRT users.     

A molecular electrostatic potential study of phenothiazine dopaminergic antagonists

The recognition of the dopaminergic receptor by antagonists has been studied for a set of phenothiazine compounds. This study was based on molecular electrostatic potential (MEP) calculations. The first step of the recognition involves the interaction of the nitrogen atom of the chain fragment of the series of phenothiazines: promazines, perazines and phenazines. The second step involves the adaptation of the aromatic fragment deduced from the examination of the molecular orientation vector. The simultaneous influences of the orientation vector and of a binding step parameter, the energy of the lower unoccupied molecular orbital (LUMO), on the variation of activity of a series of promazines were studied.The variations of the structural parameters which induce a counterclockwise rotation of the orientation vector, in a range of about 70 degrees, are related to activity increases.     

A Retrospective Study on the Clinicopathologic Characteristics and Outcomes of 179 Cases of Synchronous and Metachronous Bilateral Breast Cancer in China

ObjectiveTo investigate the clinicopathologic characteristics and outcome of bilateral breast cancer (BBC) in the Chinese population.MethodsA retrospective study was conducted on 7797 cases with primary breast cancer, including 7618 cases of unilateral breast cancer (UBC) and 179 cases of BBC. Among the latter, there were 108 cases of synchronous BBC (SBBC) and 71 cases of metachronous BBC (MBBC).ResultsIn the present study, the incidence of SBBC and MBBC are 1.39% and 0.91% among the general population, respectively. In comparison of UBC and BBC, SBBC and MBBC, there are significant differences in the common clinicopathological characteristics, such as pathologic stage, hormone receptor (HR) status and molecular type. In respect of the surgical treatment of BBC, 49.72% of the patients chose mastectomy. The 3-year disease free survival (DFS) for SBBC and MBBC are 94.4% and 96.9%, respectively. There is no difference in the overall survival (OS) and DFS between SBBC and MBBC. The histological grade and type of surgery on tumors of both sides are important influencing factors of DFS in the BBC patients.ConclusionThere are statistical differences in the clinicopathological characteristics and outcomes between SBBC and MBBC among the Chinese population. Therefore, the treatment of BBC patients should be individualized.