GSK-3β、Snail和E-cadherin在三阴乳腺癌组织中的表达及临床意义

目的 探讨GSK-3β、Snail和E-cadherin在三阴乳腺癌(TNBC)中表达及意义.方法 选择2006年9月至2013年9月收治的48例TNBC患者作为观察对象即TNBC组,并随机选出60例非TNBC患者作为对照即NTNBC组,应用免疫组织化学SP法检测GSK-3β、Snail和E-cadherin的表达情况,并进行统计分析.结果 TNBC组GSK-3β、Snail的阳性表达率显著高于NTNBC组(P＜0.05),E-cadherin的阳性表达率显著低于NTNBC组(P＜0.05).GSK-3β与Snail表达呈正相关(P＜0.05),与E-cadherin表达呈负相关(P＜0.05).结论Snail、GSK-3β、E-cadherin可能共同参与乳腺癌上皮间质转化过程,可成为综合评价TNBC的重要标志物.     

Synthesis and Biological Evaluations of Electrophilic Steroids Inspired by the Taccalonolides

Natural products have served as inspirational scaffolds for the design and synthesis of novel antineoplastic agents. Here we present our preliminary efforts on the synthesis and biological evaluation of a new class of electrophilic steroids inspired by the naturally occurring taccalonolides. We demonstrate that these simplified analogs exhibit highly persistent antiproliferative properties similar to the taccalonolides and retain activity against resistant cancer cell lines that warrants further preclinical development.     

Fine-needle Aspiration Cytology of the Breast

Fine-needle aspiration cytology (FNAC) is an established, highly accurate, and cost-effective method for diagnosing lesions in different organs, including the breast. The method is minimally invasive without unwanted side effects. FNAC forms part of the triple assessment of breast lesions. Despite some shortcomings of the reporting categories, FNAC as part of the triple assessment has proved its value in describing the findings most accurately. The diagnostic impact depends on experience of the operator, quality of preparation, and diagnostic skills of the cytopathologist. The highest accuracy is achieved at centers with a multidisciplinary approach. FNAC is often palpation guided from palpable breast masses, whereas ultrasonography guidance is more widely used on nonpalpable lesions. Inadequate sampling with FNAC is particularly seen in collagenous lesions and in submitted specimens sampled by physicians lacking experience with the FNAC procedure. A diagnostic biopsy is recommended when FNAC provides scant material. FNAC is considered to be a safe method for screening purposes, although moderately less sensitive than core needle biopsy. FNAC is most accurate when experienced cytopathologists are available to assess the adequacy of the aspirated material and advise on additional aspirations for ancillary tests when needed.     

Second-line Eribulin in Triple Negative Metastatic Breast Cancer patients. Multicentre Retrospective Study: The TETRIS Trial

Introduction: Large and consistent evidence supports the use of eribulin mesylate in clinical practice in third or later line treatment of metastatic triple negative breast cancer (mTNBC). Conversely, there is paucity of data on eribulin efficacy in second line treatment.Methods: We investigated outcomes of 44 mTNBC patients treated from 2013 through 2019 with second line eribulin mesylate in a multicentre retrospective study involving 14 Italian oncologic centres.Results: Median age was 51 years, with 11.4% of these patients being metastatic at diagnosis. Median overall survival (OS) and progression free survival (PFS) from eribulin starting were 11.9 (95%CI: 8.4-15.5) and 3.5 months (95%CI: 1.7-5.3), respectively. We observed 8 (18.2%) partial responses and 10 (22.7%) patients had stable disease as best response. A longer PFS on previous first line treatment predicted a better OS (HR=0.87, 95%CI: 0.77-0.99, p= 0.038) and a longer PFS on eribulin treatment (HR=0.92, 95%CI: 0.85-0.98, p=0.018). Progression free survival to eribulin was also favorably influenced by prior adjuvant chemotherapy (HR=0.44, 95%CI: 0.22-0.88, p=0.02). Eribulin was generally well tolerated, with grade 3-4 adverse events being recorded in 15.9% of patients.Conclusions: The outcomes described for our cohort are consistent with those reported in the pivotal Study301 and subsequent observational studies. Further data from adequately-sized, ad hoc trials on eribulin use in second line for mTNBC are warranted to confirm our findings.     

Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

Abnormal expression of long interspersed element-1 (LINE-1) has been implicated in drug resistance, while our previous study showed that chemotherapy drug paclitaxel (PTX) increased LINE-1 level with unknown mechanism. Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules (SGs). This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer (TNBC) cells. We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress, thereby adapting TNBC cells to chemotherapy drugs. Moreover, LINE-1 inhibitor efavirenz (EFV) could inhibit drug-induced SG to destabilize LINE-1. Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs. The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.     

Hepatitis C virus infection treatment: An era of game changer direct acting antivirals and novel treatment strategies

Abstract

Chronic hepatitis C virus infection and associated liver diseases represent a major health care burden all over the world. The current standard of care, i.e. peginterferon-alfa (PEG-IFNα) plus ribavirin (RBV) are associated with frequent and sometimes serious adverse effects and contraindications, which further limit their therapeutic efficacy. The approval of first and second generation HCV protease inhibitors represents a major breakthrough in the development of novel direct acting antivirals (DAAs) against different HCV genotypes and establishes a new standard of care for chronically infected HCV genotypes 1 patients. Similarly, next generation protease inhibitors and HCV RNA polymerase inhibitors have shown better pharmacokinetics and pharmacodynamics in terms of broader HCV genotypes coverage, better safety profile, fewer drug interactions and possible once daily administration than first generation direct acting antivirals. The testing of adenovirus-based vector vaccines, which escalates the innate and acquired immune responses against the most conserved regions of the HCV genome in chimpanzees and humans, may be a promising therapeutic approach against HCV infection in coming future. This review article presents up-to-date knowledge and recent developments in HCV therapeutics, insights the shortcomings of current HCV therapies and key lessons from the therapeutic potential of improved anti-HCV treatment strategies.     

Acute Effects of Dry Needling on Myofascial Trigger Points in the Triceps Surae of Ballet Dancers: A Pilot Randomized Controlled Trial

BackgroundThere is convincing evidence that dancers suffer injuries to the triceps surae musculature. Research on the immediate effects of dry needling (DN) is limited, and it is important to understand the acute effects of this treatment prior to performance.PurposeThe purpose of this pilot study was to assess the immediate effects of DN on myofascial trigger points in terms of skin surface temperature, pain, active and passive range of motion, and torque production in the triceps surae of ballet dancers.Study DesignRandomized, double-blinded pilot studyMethodsProfessional ballet dancers that fit inclusion and exclusion criteria (n=11) were randomly assigned to an experimental or control group. The dancers had three pre-determined standard point (SP) measurement spots that were used as a baseline for surface temperature comparisons. The dancers were also palpated for trigger point (TP) spots. Both SP and TP spots were marked for future measurements. The experimental group received DN, while the control group received sham DN (SHAM) to their bilateral calves at the TP spots. Immediately prior to and following treatment, both DN and SHAM groups were tested for skin surface temperature, pain, range of motion, and plantar flexion torque by blinded assessors. Paired t-tests and independent t-tests were performed to examine for differences between groups.ResultsThe surface temperature for the TP was higher than the SP measurements prior to intervention (Right calf p= .014; Left calf p= .031). There were no significant changes in VAS scale reported pain and ROM. The plantar flexion torque measurements showed an increase in the DN group of the left calf at the angular velocity of 60 degrees/sec.ConclusionThis was a unique pilot study examining the acute effects of DN on professional ballet dancers. The results were limited due to low sample size. However, the methodology for this study and surface temperature results invites future research.Level of evidenceLevel 1b     

中西医联合治疗Hp相关性胃溃疡的临床疗效及对相关炎性因子的影响

目的研究中西医联合治疗幽门螺杆菌(Hp)相关性胃溃疡患者的临床疗效及其对相关炎性因子的影响。方法选取2018年6月至2019年6月西安医学院第二附属医院收治的Hp相关性胃溃疡患者98例,按照交叉双盲法分为两组,对照组49例患者给予西医常规三联疗法治疗,观察组49例患者在此基础上联合理气护胃汤治疗。观察并比较两组治疗后Hp清除率及治疗总有效率。对比两组治疗前后反酸、烧心、疼痛等症状评分。对比两组治疗前后白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)等炎性因子水平。结果观察组治疗后Hp清除率及治疗总有效率均高于对照组,差异有统计学意义(P<0.05)。两组患者治疗前反酸、烧心、疼痛等症状评分差异均无统计学意义(P>0.05),治疗后各项症状评分指标数据显示观察组均低于对照组,差异有统计学意义(P<0.05)。治疗前两组患者IL-6、TNF-α、CRP水平差异均无统计学意义(P>0.05),治疗后IL-6、TNF-α、CRP水平观察组低于对照组,差异均有统计学意义(P<0.05)。结论采用常规三联疗法联合理气护胃汤治疗Hp相关性胃溃疡,可更好地清除Hp,且有效改善患者临床症状,同时降低机体炎性因子水平,达到更好疗效,值得推广。     

基于网络药理学和生物信息学方法的白藜芦醇治疗三阴性乳腺癌的机制研究

目的 探索白芦藜醇抗三阴性乳腺癌（Triple Negative Breast Cancer, TNBC）的潜在作用机制。方法 利用PharmMapper、SwissTargetPrediction、SuperPred、DrugBank数据库,筛选整合白芦藜醇的可能作用靶点。与CTD、DisGeNET、MalaCards数据库中筛选得到的TNBC靶点相映射后得到白芦藜醇抗TNBC的可能作用靶点。利用DAVID数据库对得到的靶点进行基因功能和通路注释分析,利用STRING数据库和Cytoscape软件构建靶点间的蛋白互作网络,筛选出核心靶点及核心模块。结果 共筛选得到422个白芦藜醇的可能作用靶点,1799个TNBC相关靶点,映射后共得到白芦藜醇治疗TNBC的潜在作用靶点130个,并从中进一步筛选出了10个核心基因（MAPK1,MAPK3,TP53,SRC,PIK3CA,AKT1,PIK3R1,MAPK8,PTPN11,JAK2）,KEGG通路富集提示核心基因主要涉及PI3K-Akt等信号通路。结论 白芦藜醇可能是通过靶向作用于多个靶点及通路,形成相互协调的作用网络从而发挥抗TNBC作用,其中PI3K/Akt通路可能发挥重要作用,为白芦藜醇在TNBC治疗方面的进一步研究提供参考。