实验性衰老大鼠下颌下腺表皮生长因子及其mRNA的表达

目的 观察表皮生长因子(EGF)及EGFmRNA在实验性衰老大鼠下颌下腺中的表达变化.方法 选用Sprague-Dawley (SD)大鼠建立D-半乳糖亚急性衰老模型,通过观察大鼠外观特征及血清超氧化物歧化酶(SOD)、谷光甘肽过氧化物酶(GSH-PX)、总抗氧化能力(T-AOC)、以及丙二醛(MDA)以确定建模成功.取正常大鼠下颌下腺为对照组,用免疫组化及原位杂交法检测其下颌下腺EGF、EGFmRNA的阳性表达.结果 下颌下腺EGF阳性反应颗粒为浅棕色至深褐色,主要分布于颗粒曲管(GCT)细胞及纹状管细胞顶部胞质中,腺泡细胞为阴性.且同一导管内不同细胞的反应程度不同,有的细胞内颗粒清晰,着色深,有的着色浅.下颌下腺EGFmRNA杂交反应产物呈浅棕色或深褐色,主要分布于颗粒曲管和纹状管上皮细胞中,其上皮基底部胞质呈强阳性,细胞顶部呈弱阳性,腺泡未见阳性反应.正常组EGF、EGFmRNA表达明显高于模型组(P＜0.01).结论 EGF、EGFmRNA在实验性衰老大鼠下颌下腺表达较正常大鼠明显减少,结果证实衰老可明显影响大鼠下颌下腺分泌生物活性物质EGF的功能,其影响的环节在基因转录水平.     

Cancer chemoprevention by tea polyphenols through modulating signal transduction pathways

The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, PI3K, phosphatases, ras, raf, MAPK cascades, N x FB, I x B kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The I x B kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gallate (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of I x B x and I x B x in activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkappaB activation as well as c-myc, c-jun and c-fos expression.     

Neuregulin-1在心血管系统的研究进展

神经调节蛋白-1(neuregulin-1,NRG-1)是心血管系统中重要的信号蛋白,其在心脏发育及成熟心脏功能维持方面的作用已为人所知。目前研究表明其有可能成为心脏疾病新的治疗靶点。该文综述了关于NRG-1的一些最新的研究进展,旨在为NRG-1的临床应用提供理论依据。     

Pancreatic cancer: advances in medical therapy

Progress in the treatment of pancreatic cancer has been notably slow and modest in contrast to other cancers of the GI tract over the last 5 years. Pancreatic cancer still continues to be a devastating illness that is marked by the appearance of early metastatic disease, despite curative surgery and the relative chemoresistance of the disease. However, small incremental benefits have been seen, and point to areas of research and development over the subsequent years. Developments in adjuvant chemotherapy and the use of gemcitabine in combination with other cytotoxic agents or with biological agents have changed clinical practice. Given its poor outlook and the paucity of active therapies, even modest gains can lead to regulatory approval and, therefore, pancreatic cancer represents a common target for pharmaceutical companies. Newer agents are in development with the promise of further refinement in treatment selection based on molecular tumor characteristics.     

Treating systemic prostate cancer: emerging drug targets and therapies

Prostate cancer is the most common cancer among men and is the second most common cause of cancer death. Although more patients are now diagnosed with localised prostate cancer since the advent of prostate specific antigen (PSA) screening, 30 - 40% will develop recurrent disease even following definitive therapy with either surgery or radiation. Patients who develop recurrent disease may be treated with androgen deprivation strategies, however within 1 - 2 years, most patients will develop androgen independent prostate cancer (AIPC). While chemotherapy has been shown to have palliative benefit in this situation, there is no evidence of prolonged survival. Given the shear numbers of patients with this disease and its inexorable progression to AIPC for which no life prolonging therapy exists, there clearly is a need for improved treatment strategies for systemic prostate cancer. Research in this area includes testing combinations of previously studied chemotherapeutic agents as well as the identification and testing of novel agents. It is these drugs that are designed to target strategic pathways to improve survival and increase quality of life in these patients. In this paper, we will not review traditional chemotherapeutic agents but discuss several key potential areas of targeted therapy for prostate cancer.     

甘草锌对胃溃疡大鼠溃疡愈合及EGF EGFR的影响

目的:探讨甘草锌颗粒对胃溃疡大鼠模型溃疡愈合及胃组织EGF、EGFR蛋白表达的影响。方法:用醋酸烧灼法将Wistar大鼠制成胃溃疡模型,用HE染色、免疫组织化学法以及Western blot观察胃黏膜组织形态及EGF、EGFR蛋白表达的变化。结果:①HE染色显示甘草锌高剂量、中剂量组及雷尼替丁组较模型组黏膜厚度有所增加,溃疡周围炎性细胞侵润明显减少,纤维排列较整齐。②EGF、EGFR在正常胃组织表达呈弱阳性,甘草锌高剂量、中剂量组及雷尼替丁组表达明显增高,干草锌低剂量组、模型组及正常组EGF表达升高并不明显。③Western blot结果表明甘草锌高、中剂量组及雷尼替丁组的表达为阳性,其中高剂量组表达最强;正常对照组、模型组及甘草锌低剂量组表达较弱。结论:甘草锌能保护大鼠胃黏膜组织,降低胃溃疡大鼠模型的溃疡指数,改善溃疡的愈合质量,增加胃黏膜组织的EGFR的表达,促进溃疡愈合。     

不同治疗方案对病毒性角膜炎泪液EGF、Ig和补体C3的影响研究

[目的]探讨不同治疗方案对病毒性角膜炎泪液EGF、Ig和补体C3的影响。[方法]选取2008年5月～2010年2月于某院进行治疗的44例病毒性角膜炎患者为研究对象,将其随机分为对照组(阿昔洛韦组)22例和观察组(阿昔洛韦联合干扰素组)22例,后将两组患者的治疗效果、副作用发生率及治疗前后的泪液EGF、Ig和补体C3水平进行研究及比较。[结果]经研究比较发现,观察组的治疗总有效率高于对照组,副作用发生率低于对照组,观察组的IgA及IgG、补体C3水平高于对照组,而泪液EGF则低于对照组,P﹤0.05,差异均有统计学意义。[结论]在病毒性角膜炎的治疗中采用阿昔洛韦联合干扰素的治疗方案进行治疗效果佳,安全性高,对于降低泪液EGF、Ig和补体C3水平效果明显,值得推广应用。     

新生儿尿表皮生长因子的检测及临床意义

采用放射免疫法测定正常及窒息新生儿第1、3、7 d尿表皮生长因子(EGF)水平,并评价其与肾功能损害的关系。结果显示:正常足月儿尿EGF含量显著高于健康成人组,新生儿窒息后第1、3 d尿EGF/C_r值低于对照组,其降低的时间和程度与窒息的严重程度一致,第7 d升高并与对照组无显著差异;尿EGF/C_r值与血肌酐浓度呈负相关。以上结果表明,EGF参与了肾脏的成熟及窒息后肾损伤的修复过程,动态观察尿EGF水平的变化可作为判断窒息新生儿肾损伤的严重程度及肾小管损伤修复能力的指标。