肿瘤多药耐药分子机制研究进展

化疗是治疗恶性肿瘤主要方法之一。然而不幸的是,先天或获得性耐药尤其是多药耐药的发生,最终导致化疗失败。因此,深入探讨多药耐药发生的分子机制,寻找可以有效预测肿瘤化疗敏感性的分子标志物以及逆转多药耐药的分子靶点,是提高化疗效果的有效途径。肿瘤多药耐药分子机制错综复杂,本文主要从DNA损伤修复、ABC转运蛋白家族表达和功能异常、肿瘤干细胞、拓扑异构酶活性改变、上皮间质转分化、谷胱甘肽-S-转移酶表达改变、表观遗传学修饰以及缺氧等方面对肿瘤多药耐药分子机制进行阐述。     

乳腺癌细胞中HuR调控PDFC的分子机制研究

目的:探讨乳腺癌细胞中HuR调控PDGFC的分子机制。方法:通过软件预测分析,乳腺癌细胞中PDGFC 3'UTR的HuR结合位点;在RNA免疫共沉淀实验中,加入PDGFC刺激后检测HuR与PDGFC mRNA的相互作用;通过构建PDGFC 3'UTR五个截短体,荧光素酶报告基因实验检测HuR调控PDGFC的结合位点。结果:软件预测分析发现,PDGFC 3'UTR可能存在五个HuR结合位点;RNA免疫共沉淀实验中,当加入PDGFC刺激后,HuR与PDGFC mRNA出现免疫共沉淀,证明HuR和PDGFC之间的直接相互作用;PDGFC mRNA3'UTR报告基因系统检测显示,第2个和第4个位点可与HuR结合调控PDGFC。结论:本研究揭示了乳腺癌细胞中HuR通过与PDGFC mRNA 3'UTR结合调控PDGFC的分子机制,为乳腺癌的临床诊断和治疗提供了新的思路。     

肥胖2型糖尿病患者神经肽Y水平与糖脂代谢的相关性分析

目的:探讨肥胖2型糖尿病患者神经肽Y(NPY)水平与糖脂代谢的相关性。方法:选择2017年7月至2019年7月我院接诊的134例肥胖2型糖尿病患者为本研究对象,设为观察组,并选择我院收治的2型糖尿病非肥胖患者100例作为对照组,分析腰围、腹围、臀围、BMI、腰臀比(WHR)、血清NPY、空腹血糖(FPG)、糖化血红蛋白(Hb Alc)、空腹胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平变化情况,及其之间的相关性分析。结果:观察组腹围、腰围、臀围、腰臀比及BMI水平均显著高于对照组,差异显著(P0.05);观察组患者血清NPY、FPG、Hb Alc水平显著高于对照组,FINS水平显著低于对照组,差异显著(P0.05);观察组患者血清TC、TG、LDL-C水平显著高于对照组,HDL-C水平显著低于对照组,差异显著(P0.05);将FPG、Hb Alc、FINS、TC、TG、LDL-C、HDL-C作为因变量,将血清NPY作为自变量,在相关性分析结果中显示,血清NPY和FPG、Hb Alc、TC、TG、LDL-C之间均呈正相关(r=0.399,0.173,0.435,0.451,0.376,P均0.05),血清NPY和FINS、HDL-C之间均呈负相关(r=-0.566,-0.223,P均0.05)。结论:在肥胖2型糖尿病患者中NPY水平显著升高,且与腹部脂肪增加、糖脂代谢显著相关。     

紫草素在消化系统肿瘤中的抗癌机制研究进展

消化系统肿瘤是威胁我国居民生命健康的重要杀手,其发病率和死亡率均占全部肿瘤的50%左右,研发高效安全的抗肿瘤药物是治疗消化系统肿瘤的基础。植物提取物是抗肿瘤药物的重要来源,紫草素(Shikonin)是一种存在于紫草科植物根茎中的药物成分,它对消化系统肿瘤细胞具有显著的杀伤效果。本文通过检索最近10年紫草素在消化系统肿瘤中发挥抗癌作用的相关文献,对紫草素及其衍生物在消化系统肿瘤中的抗癌机制进行系统归纳整理,并分析了今后紫草素应用于临床治疗消化系统肿瘤的研究方向,为进一步探索紫草素在消化系统肿瘤中的抗癌机制研究和新药研发提供理论依据。     

肿瘤浸润转移分子机制的研究进展

肿瘤浸润转移是多因素参与、多步骤完成的生物化学变化过程。人们已经逐渐认识到浸润转移不仅与肿瘤细胞有关,更是肿瘤细胞和肿瘤组织微环境复杂的相互作用的结果,其过程涉及多个分子作用机制和信号转导途径,包括细胞和细胞的黏附分子、细胞外基质降解、生长因子、趋化因子和淋巴血管生成因子等。本文综述了肿瘤浸润转移的分子机制。     

格列美脲联合艾塞那肽治疗肥胖2型糖尿病的疗效观察

目的:探讨格列美脲联合艾塞那肽治疗肥胖2型糖尿病患者的临床效果。方法:选择2016年1月到2019年1月我院收治的82例肥胖2型糖尿病患者作为本次研究的对象,并将其随机的分为研究组和对照组,每组41例。研究组患者给予格列美脲联合艾塞那肽进行治疗,对照组患者给予格列美脲治疗,观察和比较两组患者治疗前后空腹血糖、餐后2 h血糖、空腹和餐后2 h血清C肽、身体质量指数(body mass index, BMI)、总胆固醇(total cholesterol, TC)、甘油三酯(triglyceride, TG)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol, LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol, HDL-C)和糖化血红蛋白(glycosylated hemoglobin, HbAlC)水平的变化。结果:治疗后,两组患者空腹血糖、餐后2 h血糖水平均较治疗前明显降低,餐后2 h血清C肽水平均较治疗前明显升高,且研究组以上指标的改善程度较对照组更明显(P0.05)。两组患者治疗前后空腹血清C肽水平比较差异无统计学意义(P0.05);治疗后,两组患者BMI、TC、TG、LDL-C和HbAlC水平均较治疗前显著降低,HDL-C水平明显升高,而研究组BMI、TC、TG、LDL-C和HbAlC水平显著低于对照组(P0.05),HDL-C水平明显高于对照组(P0.05)。结论:格列美脲片联合艾塞那肽治疗肥胖2型糖尿病可有效的控制患者血糖,降低BMI,改善血脂水平。     

甲状腺癌诊断及预后相关分子标志物的研究进展

甲状腺结节是最常见的疾病之一,其精确诊断对于患者的有效临床管理十分重要。分子标志物是一项非常有效的诊断和预后评估工具,尤其在细胞学不确定的甲状腺癌结节。近年来,分子标志物的临床应用发展已经取得显著的进步。随着新一代基因检测技术的发展,能够同时检测多个基因,这不仅可为甲状腺癌的诊断提供依据,而且也可为预测甲状腺癌患者的预后提供参考,本文就甲状腺癌的诊断及预后相关的分子标志物进行综述。     

吸烟与癌症相关性的研究进展

研究肿瘤的易感性对理解认识肿瘤发生发展及诊断治疗都有重要意义,遗传危险因素与环境危险因素的相互作用决定了人体部分器官癌症的易感性。研究表明吸烟与肿瘤的发生发展密切相关。本文综述了基因多态性和吸烟协同促癌作用和机制,吸烟通过激活自噬等信号通路促进癌症发生、侵袭和转移及与癌症预后相关性的研究进展。     

活性氧诱导心律失常的分子生物学机制研究

心律失常特别是室性心律失常可能导致心源性猝死,已经成为临床上常见和重点问题。多种原因可能诱发心律失常如:冠状动脉粥样硬化性心脏病,瓣膜病,肥厚性心肌病等心脏源性病变,很多代谢性物质改变也可能增加心律失常的发生概率。近年发现活性氧可能是诱发各种心律失常的一个重要因素,活性氧不仅参与重要离子通道和转运受体的调控,同时本身也作为一个重要的第二信来调节一些关键酶的活性如:蛋白激酶A(PKA),蛋白激酶C(PKC),钙离子依赖性蛋白激酶II(CaMKII)。最近有研究发现长期的活性氧代谢紊乱可能引起细胞遗传物质如miRNA的改变,引起长期的心律失常如房颤。本文主要对活性氧导致心律失常的可能机制做一总结,为心律失常的防治提供一些可能潜在方向。     

二甲双胍抗肿瘤作用及其分子机制的研究进展

二甲双胍是全球范围内治疗2型糖尿病最常用的药物之一,具有使用方便、疗效好、价格低廉且毒副作用小等优点。近年来大量的流行病学研究及体内外实验研究发现二甲双胍能够用于多种肿瘤的治疗及预防,然而其分子机制尚不十分明确;主要包括调节体内胰岛素/IGF-1轴、激活AMPK信号通路、调控micro RNAs的表达、活化Caspase分子、阻断AGEs-RAGE系统等,这些机制为将来二甲双胍应用于肿瘤的预防及临床治疗提供了重要的理论依据。本文针对糖尿病治疗药物二甲双胍在抗肿瘤中的作用及其分子机制进行全面综述。     

葡萄糖和肿瘤坏死因子-α对内皮细胞中早期生长反应基因-1表达的影响

目的探讨葡萄糖和肿瘤坏死因子-α对内皮细胞中早期生长反应基因-1表达的影响。方法利用人脐静脉内皮细胞体外培养,予以25mmol/L葡萄糖和/或10ng/ml肿瘤坏死因子-α与内皮细胞共同孵育,运用蛋白免疫印迹方法检测细胞中早期生长反应基因-1蛋白的表达,运用酶联免疫吸附法检测纤溶酶原激活抑制物-1的表达。结果葡萄糖和肿瘤坏死因子-α均可增加早期生长反应基因-1的表达,两种因素共同作用产生协同作用。而且,葡萄糖和肿瘤坏死因子-α也可促进纤溶酶原激活抑制物-1的表达。细胞外调节蛋白激酶1/2的抑制剂(PD98059)可下调肿瘤坏死因子-α所诱导的早期生长反应基因-1、纤溶酶原激活抑制物-1的表达,而对葡萄糖所诱导的早期生长反应基因-1的表达无明显影响。结论肿瘤坏死因子-α可能通过细胞外调节蛋白激酶1/2路径促进早期生长反应基因-1和纤溶酶原激活抑制物-1表达。肿瘤坏死因子-α和葡萄糖可能通过不同的信号通路调节早期生长反应基因-1、纤溶酶原激活抑制物-1表达,在肥胖、糖尿病等代谢紊乱所致的血管并发症的发生中起到重要的作用。     

肿瘤的分子治疗新进展

肿瘤的发生、发展是一个多步骤、多基因参与的、复杂的系统性过程.分子治疗作为21世纪最有希望根治人类肿瘤的技术,其治疗技术的关键在于靶分子的选择,寻找合适的靶分子一直是分子治疗肿瘤的重要方向.针对近年来肿瘤治疗研究中发现的端粒酶靶标、抗血管生成基因靶标、apoptin、survivin、stathmin、autophagy、PUMA、转铁蛋白受体靶标和相应的治疗策略作一综述.     

Genetic variants of ghrelin in metabolic disorders

An increasing understanding of the role of genes in the development of obesity may reveal genetic variants that, in combination with conventional risk factors, may help to predict an individual's risk for developing metabolic disorders. Accumulating evidence indicates that ghrelin plays a role in regulating food intake and energy homeostasis and it is a reasonable candidate gene for obesity-related co-morbidities. In cross-sectional studies low total ghrelin concentrations and some genetic polymorphisms of ghrelin have been associated with obesity-associated diseases. The present review highlights many of the important problems in association studies of genetic variants and complex diseases. It is known that population-specific differences in reported associations exist. We therefore conclude that more studies on variants of ghrelin gene are needed to perform in different populations to get deeper understanding on the relationship of ghrelin gene and its variants to obesity.     

Relationship between plasma leptin and zinc levels and the effect of insulin and oxidative stress on leptin levels in obese diabetic patients

Leptin is thought to be a lipostatic signal that contributes to body weight regulation. Zinc plays an important role in appetite regulation also. Our aim is to evaluate the relationship between leptin and zinc in obese and nonobese type 2 diabetic patients and its relationship with oxidative stress and insulin. We studied 25 nonobese nondiabetic women (controls); 35 nonobese diabetic women; and 45 obese diabetic women. Plasma leptin concentration was determined by immunoradiometric assay. Thiobarbituric acid reactive substances (TBARS), markers of oxidative stress, were assayed by the spectrofotometric method. Plasma levels of zinc and insulin were measured by atomic absorption spectrophotometer and electrochemiluminescence methods, respectively. We found that nonobese diabetic patients had significantly lower zinc and higher TBARS levels than control subjects (P<0.01). There was no difference in plasma leptin levels between nonobese diabetic subjects and controls. Obese diabetic subjects had significantly higher plasma leptin, TBARS, and insulin levels and significantly lower plasma zinc levels than nonobese diabetic subjects (for each comparison; P<0.01). The univariate and multivariate analyses demonstrated a significant positive correlation between leptin and body mass index (P<0.01) and insulin (P<0.01), and a significant negative correlation between leptin and zinc in obese subjects. Additionally, TBARS levels was positive correlated with insulin and negative correlated with zinc in obese diabetic subjects. We conclude that zinc may be a mediator of the effects of leptin, although the detailed mechanism is still unknown and requires further investigation. Free radical induced mechanism(s) may be involved in this process.     

Ghrelin and glucose homeostasis

Ghrelin plays an important physiological role in modulating GH secretion, insulin secretion and glucose metabolism. Ghrelin has direct effects on pancreatic islet function. Also, ghrelin is part of a mechanism that integrates the physiological response to fasting. However, pharmacologic studies indicate the important obesogenic/diabetogenic properties of ghrelin. This is very likely of physiological relevance, deriving from a requirement to protect against seasonal periods of food scarcity by building energy reserves, predominantly in the form of fat. Available data indicate the potential of ghrelin blockade as a means to prevent its diabetogenic effects. Several studies indicate a negative correlation between ghrelin levels and the incidence of type 2 diabetes and insulin resistance. However, it is unclear if low ghrelin levels are a risk factor or a compensatory response. Direct antagonism of the receptor does not always have the desired effects, however, since it can cause increased body weight gain. Pharmacological suppression of the ghrelin/des-acyl ghrelin ratio by treatment with des-acyl ghrelin may also be a viable alternative approach which appears to improve insulin sensitivity. A promising recently developed approach appears to be through the blockade of GOAT activity, although the longer term effects of this treatment remain to be investigated.     

Lipotoxicity in the heart

Obesity and insulin resistance are associated with ectopic lipid deposition in multiple tissues, including the heart. Excess lipid may be stored as triglycerides, but are also shunted into non-oxidative pathways that disrupt normal cellular signaling leading to organ dysfunction and in some cases apoptosis, a process termed lipotoxicity. Various pathophysiological mechanisms have been proposed to lead to lipotoxic tissue injury, which might vary by cell type. Specific mechanisms by which lipotoxicity alter cardiac structure and function are incompletely understood, but are beginning to be elucidated. This review will focus on mechanisms that have been proposed to lead to lipotoxic injury in the heart and will review the state of knowledge regarding potential causes and correlates of increased myocardial lipid content in animal models and humans. We will seek to highlight those areas where additional research is warranted.     

肥胖者脂肪组织中TNF-α表达与脂肪细胞大小的相关性分析

目的探讨肥胖者网膜脂肪和皮下脂肪两处肿瘤坏死因子-α(TNF-α)蛋白的表达与脂肪细胞大小的相关性。方法选取正常体重者16名,中心型肥胖者32名拟行外科手术患者,术中取出网膜脂肪和皮下脂肪标本,测定脂肪细胞大小,采用western blot方法测定TNF-α蛋白表达。结果肥胖者网膜脂肪和皮下脂肪两处TNF-α蛋白的水平均比正常体重对照组表达高(P<0.01),肥胖者网膜脂肪组织TNF-α蛋白表达高于皮下脂肪(P<0.05),同时研究发现肥胖者皮下脂肪细胞和网膜脂肪细胞大小均明显大于正常体重组(P<0.05),且肥胖者网膜脂肪和皮下脂肪两处脂肪组织TNF-α蛋白表达与脂肪细胞大小呈正相关(网膜:r=0.808,P<0.01;皮下:r=0.452,P<0.05)。结论肥胖者网膜脂肪和皮下脂肪细胞增大,在肥胖相关胰岛素抵抗的发生中起到了重要的作用。