药物诱导细胞凋亡治疗肝癌

细胞凋亡(apoptosis)是细胞自然衰老、死亡的一种形式,是一切生物正常胚胎发生过程和人类发育过程细胞清除的正常途径。这一过程的紊乱,将导致人类发生多种疾病。许多研究资料表明,肿瘤的发生与细胞凋亡有密切关系,细胞凋亡异常在肿瘤发生和发展过程中具有非常重要的病理生理意义,细胞凋亡参与肿瘤的起始过程,并对癌症的发生起负相调控作用,Dive认为肿瘤的化疗、放疗的目的就是诱导肿瘤细胞凋亡。因此,在肝癌的治疗中不断地探讨新方法新途径,包括化疗药物、放射线、细胞因子、激素和基因编码等。近年来大量实验研究发现,肝癌细胞可以通过人为地触发细胞凋亡而被清除。其中药物诱导细胞凋亡对今后肝癌治疗研究提供了诱人的前景。不同种类的化学药物,生物药物和中药对不同种类肿瘤敏感细胞有促进凋亡作用。部分化疗药物、生物药在体外实验中能诱导肝癌细胞凋亡,如顺铂、环磷酰胺、阿霉素、细胞因子等。下面就药物诱导细胞凋亡治疗肝癌研究简要综述如下。     

完全切除的Ⅰ期，Ⅱ期和ⅢA期非小细胞肺癌术后放疗联合辅助化疗对生存率的影响：国际诺维本辅助治疗组织随机临床试验

研究背景:1998年术后放疗(post operative radiotherapy,PORT)的meta分析表明术后放疗相关死亡率风险增加21%,术后放疗的作用一直是探讨的热点.     

HPLC分离测定格列齐特片及其有关物质

目的：建立新的HPLC法分离测定格列齐特征及其有关物质。方法：色谱条件为：Shim-Pack VP-ODS(5um,150mm*4.6mm i.d.)色谱柱;甲醇－0．02mol/L磷酸（用三乙胺调节PH至3．5）,（70：30）为流动相;检测波长为229nm。结果：在50－300ug;/ml的浓度范围内线性关系良好。r=0.9999(n=6);平均回收率为100．5％,RSD为0．17％（n=6),重复进样RSD为0．12％（n=6),格列齐特及其有关物质得到基线分离。结论：本法简便,快速,准确,适用于格列齐特及其制剂的质量控制。     

Induction Of Endothelin-1 Expression By Glucose: An Effect Of Protein Kinase C Activation

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta 2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta 1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.     

Role of extracellular adenosine triphosphate in the cytotoxic T- lymphocyte-mediated lysis of antigen presenting cells

The lysis of antigen presenting cells (APCs) by cytotoxic T lymphocytes (CTLs) may be one mechanism whereby an immune response is downregulated by Staphylococcus superantigens. Disappearance of monocytes/macrophages from staphylococcal enterotoxin A (SEA)-activated peripheral blood mononuclear cell (PBMC) cultures, but not from control PBMC cultures was seen by flow cytometry. Recently, adenosine triphosphate (ATP) has been described as an effector molecule in CTL-mediated lysis of some murine tumor target cells. We have also shown that ATP caused the lysis of human macrophages, and that treatment of cells with interferon gamma (IFN gamma) rendered macrophages significantly more sensitive to ATP than untreated cells. To show that this purine nucleotide may play a role in modulating the immune system, we generated human CTLs that were stimulated with SEA, and used them as effector cells against SEA-pulsed autologous macrophages. CTLs were found to specifically lyse SEA-pulsed macrophages, while control, unpulsed, macrophages were unaffected. The addition of hexokinase, an enzyme that hydrolyzes ATP, significantly abrogated the killing of SEA-pulsed cells during the assay. In examining the mechanism of cytotoxicity, electron microscopy showed that macrophages incubated with both ATP and CTLs underwent necrosis, rather than apoptosis. From these results, it is suggested that ATP is released from CTLs during antigen presentation, and that IFN gamma- activated macrophages, which are inherently more sensitive to this mediator, are readily lysed and therefore removed from circulation, thus downregulating an immune response.     

MRI evaluation of the levator ani muscle: anatomic correlations and practical applications

Summary A comparative study of serial anatomic sections in the transverse, frontal and sagittal planes with corresponding MRI sections of the pelvis allowed the authors to define the most suitable sectional planes and MRI modes for a morphologic study of the levator ani muscle. This study shows the value of MRI examination in the assessment of anorectal malformations.

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Les muscles elevateurs de l'anus en IRM. Corrélations anatomiques et applications pratiques

Résumé A partir de l'étude comparative de coupes anatomiques dans les plans transversal, frontal, sagittal et des coupes IRM correspondantes du petit bassin, les auteurs déterminent quels sont les plans de coupe et les modes IRM les plus performants pour l'étude morphologique des muscles élévateurs de l'anus. Cette étude montre l'intérêt de l'examen IRM dans le bilan des malformations ano-rectales opérées.

     

银耳多糖对小鼠脾细胞内游离钙离子浓度的影响

为进一步探讨银耳多糖(TP)免疫调节作用的机制,建立了特异性荧光探针Fura-2测定脾细胞内游离钙离子浓度的方法,观察TP对脾细胞内游离钙离子浓度的影响。结果表明,TP在一定剂量范围内可以剂量依赖方式增加脾细胞内游离钙离子的浓度,并与ConA有协同作用。在外钙为零时,TP对内钙释放无影响,钙通道阻断剂维拉帕米(verapamil 10μg·mL^-1)可阻断TP升高脾细胞内游离钙离子浓度的作用。     

Alcohol Consumption and Risk of Gastric Cancer: The Japan Collaborative Cohort Study

BackgroundAlcohol consumption is a potential risk factor for gastric cancer. However, findings from cohort studies that examined the relationship between alcohol consumption and gastric cancer risk among Japanese population are not conclusive.MethodsA total of 54,682 Japanese men and women participating in the Japan Collaborative Cohort study completed a questionnaire, including alcohol consumption information. The Cox proportional hazard model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsAfter a median 13.4-year follow-up, we documented 801 men and 466 women incident cases of gastric cancer. Alcohol consumption was associated with increased risk of gastric cancer among men (HRs in ex-drinkers and current alcohol consumption of <23 g, 23–<46 g, 46–<69 g, and ≥69 g/d categories versus never drinkers were 1.82; 95% CI, 1.38–2.42, 1.41; 95% CI, 1.10–1.80, 1.47; 95% CI, 1.17–1.85, 1.88; 95% CI, 1.48–2.38, and 1.85; 95% CI, 1.35–2.53, respectively, and that for 10 g increment of alcohol consumption after excluding ex-drinkers was 1.07; 95% CI, 1.04–1.10). The association in men was observed for cardia and non-cardia gastric cancer (HRs in the highest alcohol consumption category versus never drinkers were 9.96; 95% CI, 2.22–44.67 for cardia cancer and 2.40; 95% CI, 1.64–3.52 for non-cardia cancer). However, no such trend was observed in women.ConclusionsAlcohol consumption is associated with increased risk of gastric cancer among Japanese men, regardless of anatomical subsite of the cancer.Key words: gastric cancer, alcohol, JACC study     

The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming (alpha) subunits of voltage-gated Na+ (Na(v)) channels. The neurological phenotypes seen in Fgf14-/- mice and the identification of an FGF14 missense mutation (FGF14(F145S)) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14(F145S) reduces Na(v) alpha subunit expression at the axon initial segment, attenuates Na(v) channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14(F145S) does not interact directly with Na(v) channel alpha subunits. Rather, FGF14(F145S) associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Na(v) alpha subunits, suggesting that the mutant FGF14(F145S) protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Na(v) channel alpha subunits and altering neuronal excitability.