Vascular endothelial growth factor A,secreted in response to transforming growth factor-β1 under hypoxic conditions,induces autocrine effects on migration of prostate cancer cells

Hypoxia and transforming growth factor-β1 (TGF-β1) increase vascular endothelial growth factor A (VEGFA) expression in a number of malignancies. This effect of hypoxia and TGF-β1 might be responsible for tumor progression and metastasis of advanced prostate cancer. In the present study, TGF-β1 was shown to induce VEGFA₁₆₅ secretion from both normal cell lines (HPV7 and RWPE1) and prostate cancer cell lines (DU145 and PC3). Conversely, hypoxia-stimulated VEGFA₁₆₅ secretion was observed only in prostate cancer cell lines. Hypoxia induced TGF-β1 expression in PC3 prostate cancer cells, and the TGF-β type I receptor (ALK5) kinase inhibitor partially blocked hypoxia-mediated VEGFA₁₆₅ secretion. This effect of hypoxia provides a novel mechanism to increase VEGFA expression in prostate cancer cells. Although autocrine signaling of VEGFA has been implicated in prostate cancer progression and metastasis, the associated mechanism is poorly characterized. VEGFA activity is mediated via VEGF receptor (VEGFR) 1 (Flt-1) and 2 (Flk-1/KDR). Whereas VEGFR-1 mRNA was detected in normal prostate epithelial cells, VEGFR-2 mRNA and VEGFR protein were expressed only in PC3 cells. VEGFA₁₆₅ treatment induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in PC3 cells but not in HPV7 cells, suggesting that the autocrine function of VEGFA may be uniquely associated with prostate cancer. Activation of VEGFR-2 by VEGFA₁₆₅ was shown to enhance migration of PC3 cells. A similar effect was also observed with endogenous VEGFA induced by TGF-β1 and hypoxia. These findings illustrate that an autocrine loop of VEGFA via VEGFR-2 is critical for the tumorigenic effects of TGF-β1 and hypoxia on metastatic prostate cancers.     

双源CT低管电压降低冠状动脉CTA辐射剂量

目的 观察低管电压在体质指数(BMI)正常范围患者双源CT冠状动脉成像(CTA)中的应用,并评价其图像质量.方法 将65例BMI在正常范围并接受冠状动脉CTA检查的患者随机分为两组,A组管电压采用常规扫描120 kV,B组管电压采用100 kV,均采用回顾性心电门控螺旋扫描.对两组扫描的冠状动脉分别做图像处理,应用秩和检验比较两组患者冠状动脉段图像质量总体评分,两独立样本t检验比较两组患者的辐射剂量和对比剂用量. 结果 A组评价443段冠状动脉,B组评价451段冠状动脉.A组图像质量评价为优和良好的占97.74%,B组占97.56%.冠状动脉段图像质量评分两组之间比较差异无统计学意义(P=0.126).A组平均有效剂量为(15.04±2.42)mSv;B组平均有效剂量为(7.95±1.69)mSv,差异有统计学意义(P＜0.001).A组对比剂用量为(75.17±3.69)ml,B组对比剂用量为(62.27±3.42)ml,差异有统计学意义(P＜0.001). 结论 对于BMI在正常范围内的患者,冠状动脉CTA检查时管电压设为100 kV可在保证图像质量的同时显著降低辐射剂量和对比剂用量.     

支气管动脉内灌注化疗药物并发脊髓损伤的初步探讨

作者对３７例肺癌患者进行了１２５次支气管动脉造影和动脉内灌注化疗药物（顺铂、丝裂霉素、５－氟脲嘧啶），其中１例在灌注的同时加用５ｍｌ碘苯酯经乳化后进行支气管动脉栓塞。共发生３例脊髓损伤，１例在支气管动脉栓塞后即出现截瘫，另两例为术后第３～４ｄ出现右下肢麻木无力及小便困难，继而出现两下肢瘫痪及大小便失禁。症状出现后用激素、神经营养药及对症处理后均有好转。作者对并发脊髓损伤的原因、预防措施及治疗作了初步探讨。     

表皮生长因子受体在乳腺癌中的研究进展

近几十年,在分子肿瘤的研究中发现一些能够促进肿瘤生长、存活的分子,为肿瘤的治疗带来了新的希望.表皮生长因子受体是最早发现的对抑制肿瘤具有重要意义的分子之一,大约50％的三阴性乳腺癌和炎性乳腺癌都过度表达表皮生长因子受体.表皮生长因子受体及其下游通路可以促进上皮问质转化、肿瘤细胞迁移以及肿瘤浸润.此外,由于凋亡信号转导的发生针对表皮生长因子受体治疗可以提高三阴性乳腺癌细胞化疗的敏感性.研究表明,表皮生长因子受体靶向治疗可能对三阴性乳腺癌和炎性乳腺癌的治疗具有重要作用.     

膦甲酸钠抗乙型肝炎病毒近期疗效观察

为观察磷甲酸钠抗乙型肝炎病毒（HBV）的近期疗效，将67例慢性乙型肝炎患者随机分为2组：治疗组47例，在常规保什治疗的基础上加用膦用甲酸钠；对照组20例，仅用常规保肝药物治疗。治疗前后观察患者功能、血清HBVDNA含量、乙肝病毒免疫学标志等的变化。结果显示，治疗2周后，治疗组肝功能均有恢复；47例患者中42例HBVDNA水平下降，以第1周明显，第2周时10例反跳；13例HBVDNA转阴，其中5例在用药1周后即转阴。30例HBeAg阳性患者中，2例出现血清转换，1例转为弱阳性。提示磷甲酸钠具有明显和快速的抑制乙肝病毒复制、降低病毒量的作用，可作为抗病毒序贯疗法的首程用药或联合用药的选择之一。     

人半月板纤维软骨细胞培养及生物学特性研究

为探索分离培养人半月板纤维软骨细胞的简便实用方法，采用胰蛋白酶和胶原酶联合消化的方法，简便快速地获得大量成活率高的人半月板纤维软骨细胞，在F－12培养液中进行原代和传代培养，并对传代培养纤维软骨细胞进行了免疫组化鉴定，光镜及超微结构的观察，结果显示，光镜下，原代培养细胞呈线形，单层排列，电镜可见细胞内有丰富的粗面内质网及线粒体，细胞呈多极性，表面有突起，纤维软骨细胞免疫组化Ⅱ型胶原染色阳性，提示本实验建立的人纤维软骨细胞分离培养方法是一种可行的方法。，     

利福平药动学对药物性肝损害的影响研究

目的：本文通过对利福平导致药物性肝损害机理的研究，寻找治疗结核病而不致造成药物性肝损-害的合理给药方案。方法：采用药动学和免疫学对利福平导致药物性肝损害机理进行研究。结果与结论：药物性肝损害可能是由于利福平代谢物引起，减少用量，提高血药浓度，减少代谢物形成是预防药物肝损害的有效途径。     

MK2 plays an important role for the increased vascular permeability that follows thermal injury

We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase > p38 > MK2 > HSP27.     

Targeting Nicotinamide Phosphoribosyltransferase as a Potential Therapeutic Strategy to Restore Adult Neurogenesis

Adult neurogenesis is the process of generating new neurons throughout life in the olfactory bulb and hippocampus of most mammalian species, which is closely related to aging and disease. Nicotinamide phosphoribosyltransferase (NAMPT), also an adipokine known as visfatin, is the rate‐limiting enzyme for mammalian nicotinamide adenine dinucleotide (NAD) salvage synthesis by generating nicotinamide mononucleotide (NMN) from nicotinamide. Recent findings from our laboratory and other laboratories have provided much evidence that NAMPT might serve as a therapeutic target to restore adult neurogenesis. NAMPT‐mediated NAD biosynthesis in neural stem/progenitor cells is important for their proliferation, self‐renewal, and formation of oligodendrocytes in vivo and in vitro. Therapeutic interventions by the administration of NMN, NAD, or recombinant NAMPT are effective for restoring adult neurogenesis in several neurological diseases. We summarize adult neurogenesis in aging, ischemic stroke, traumatic brain injury, and neurodegenerative disease and review the advances of targeting NAMPT in restoring neurogenesis. Specifically, we provide emphasis on the P7C3 family, a class of proneurogenic compounds that are potential NAMPT activators, which might shed light on future drug development in neurogenesis restoration.