刘嘉湘教授辨治肝癌经验

辨治肝癌，依据肝脏的生理特点及肝癌的病理变化遣方用药。肝喜疏泄条达而恶抑郁，疏通气血是刘师治疗肝癌的基本法则。由于肝癌发生的实质在于肝脏的阴阳失去平衡，治疗的目的在于调和阴阳。临床上需根据疾病的症状及发展的不同阶段，采取补肝益气法、健脾理气法或养阴柔肝法，兼以解毒利湿、化瘀散结，达到补泻结合，取效良好     

Characterization of cell death events induced by anti-neoplastic drugs cisplatin, paclitaxel and 5-fluorouracil on human hepatoma cell lines: Possible mechanisms of cell resistance.

Two different hepatoma cell lines were incubated for 48h with chemotherapeutic drugs cisplatin, paclitaxel and 5-FU to determine their ability to induce cytotoxicity and DNA fragmentation as well as to modify the expression of some cell death-related genes that could be involved in the resistance to therapy. We observed that cisplatin and paclitaxel induced cytotoxicity, but significant differences between both cell lines, were found only in the case of paclitaxel. At 48h, apoptosis was clearly present in Hep3B cells treated with cisplatin and HepG2 cells treated with paclitaxel. 5-FU induced cytotoxicity in both cell lines but only at higher concentrations than the other two drugs, triggering apoptosis and necrosis in HepG2 cells and only necrosis in Hep3B. When a time course was performed for the first 8h of treatment to elucidate the initial mechanism of cell death responsible for DNA fragmentation, we observed that 5-FU in Hep3B, and cisplatin in both cell lines, induces primary necrosis, whereas at the concentration tested here, paclitaxel clearly triggers apoptosis in both cell lines. HepG2 cells were weakly sensitive to 5-FU in the first 8h of treatment, so the primary mechanism of cell death was not clear, but results seem to indicate that it could be apoptosis. At 48h, Bax was not up-regulated with any of the treatments, whereas cisplatin was able to induce Bcl-xL down-regulation in both cell lines. Treatment with 5-FU also down-regulated Bcl-xL in HepG2 cells. We also measured variations in the expression of survivin, an inhibitor of apoptosis that has also been involved in mitototic catastrophe. Hep3B cells seem to show an increase in protein levels with all treatments. Exposure to paclitaxel resulted in the highest effect. In the case of HepG2 cells, there was a decrease in survivin expression when cells were treated with 5FU and paclitaxel, both treatments showing complete loss of the protein. Using an antibody that recognizes unprocessed caspase-3, we observed that the enzyme was assumingly activated in HepG2 cells treated with 5FU and paclitaxel, but only weakly after treatment with cisplatin. Hep3B cells did not show activation since the levels of the pro-enzyme remained the same as that in the control. In conclusion, the three drugs tested in this study could induce cell death, with paclitaxel being more effective inducing apoptosis. 5FU was only effective at high doses and its mechanism seems to be primarily related to necrosis in Hep3B and probably apoptosis in HepG2. Cisplatin mechanism of cell death is probably mediated by the decrease in anti-apoptotic protein Bcl-xL whereas paclitaxel and 5FU are decreasing the apoptosis inhibitor survivin. According to pro-enzyme levels, caspase-3 was only activated in HepG2 cells, whereas in the case of Hep3B cells the mechanisms of toxicity appear to be caspase-3-independent at the time and concentrations tested in this study. The resistance of Hep3B cells to death induced by chemotherapy could be related to an increase in the expression of IAP survivin, which can decrease cell response to the treatment or even switch the type of death from apoptosis to another kind, making therapy less efficient.     

鼻咽癌在不同高发区人群中的发病差异

目的：探索在广东省不同鼻咽癌高发区人群中发病差异，探讨相关病因发病因素。方法：１９８６～１９９５年对广东省四会市、广州市近６万人前瞻性研究，通过对两地人群鼻咽癌检出率，ＥＢＶＶＣＡ／ＩｇＡ阳性率，阳性人群癌前病变，癌变检出率，并以Ｌｏｇｉｓｔｉｃ多元回归分析其差异。结果：发现四会地区人群与广州地区人群相比：①高鼻咽癌检出率；②ＥＢＶＶＣＡ／ＩｇＡ阳性人群高合并鼻咽粘膜癌前病变；③ＥＢＶＶＣＡ／ＩｇＡ阳性人群高鼻咽癌检出率；④鼻咽粘膜癌前病变高癌变率。结论：ＥＢＶ感染与肿瘤遗传易感性在鼻咽癌发病上是否起着协同或加强作用值得进一步研究。     

原发性肝癌HBV感染模式与AFP水平相关性研究

目的:探讨原发性肝癌(PHC)患者乙肝病毒(HBV)感染模式与血清甲胎蛋白(AFP)水平的关系。方法:应用酶免疫检测法(ELISA)、聚合酶链反应(PCR)及放射免疫技术分别测定100例原发性肝癌患者血清乙型肝炎病毒指标(HBV-M)及AFP。结果:100例PHC患者中,HBV-M阳性88例(88％),阴性12例(12％),HBV-M阳性者AFP水平高于阴性者147 ng/mL,二者有非常显著性意义(P<0.01),且HBV-M阳性者AFP升高(68.4％)的比例明显高于HBV-DNA阴性者(31.6％)(P<0.01)。PHC患者HBV感染模式分析中,HBsAg、HBeAb、HBcAb阳性和HBV-DNA阳性最多,为56例(63.6％),其次为HBsAg、HBeAg、HBcAb和HBV-DNA阳性,为9例(10.2％)。结论:HBV是原发性肝癌发生的重要原因,在PHC患者中,AFP升高与HBV感染、复制相关。     

14年间住院病人主要病因和死因变化趋势

目的　探讨 1990～ 2 0 0 3年住院病人的主要病因和死因及变化趋势的方向、强度。方法　分析我院 1990～ 2 0 0 3年录入广东省卫生厅“广东省医院统计病案管理系统”的统计资料 ,计算住院病人主要疾病、死亡病因 1990～ 1999年、2 0 0 0～ 2 0 0 3年两个阶段的年均构成比 ,观察顺位变化 ,用回归分析的方法计算变化趋势。结果　 1) 1990～ 1999年主要住院病因顺位是消化系统疾病 (15 .6 2 % )、损伤和中毒 (13.16 % )、循环系统疾病 (11.2 4 % )、呼吸系统疾病 (10 .4 7% )、恶性肿瘤 (10 .4 3% ) ;2 0 0 0～ 2 0 0 3年顺位是循环系统疾病 (16 .4 1% ) (其中缺血性心脏病占 2 2 .98% ,脑血管病占 39.6 8% ) ,损伤和中毒(12 .80 % )、消化系统疾病 (11.76 % )、呼吸系统疾病 (9.5 3% )、恶性肿瘤 (8.73% ) ,循环系统疾病呈显著上升趋势 (B =4 .2 6 ,P <0 .0 5 ) ,消化系统疾病呈显著下降趋势 (B =- 3.17,P <0 .0 5 ) ;2 ) 1990～ 2 0 0 3年住院死因顺位为恶性肿瘤 (2 9.2 9% )、循环系统疾病 (2 5 .91% )、损伤和中毒 (12 .6 3% )、呼吸系统疾病(6 .18% ) ,消化系统疾病 (5 .77% ) ;2 0 0 0～ 2 0 0 3年恶性肿瘤呈显著下降趋势 (B =- 3.88,P <0 .0 5 ) ,循环系统疾病呈上升趋势但无显著性 (B =0 .84 ,P >0     

针对表皮生长因子受体的靶向治疗研究进展

部分上皮性肿瘤中存在着表皮生长因子受体(EGFR)的过度表达,EGFR的高表达与细胞恶变、肿瘤的增殖、转移和肿瘤血管形成等相关.以EGFR为靶点的抗肿瘤治疗具有特异、广谱、高效的特点.现综述目前已进入临床研究程序的针对EGFR的分子靶向药物研究进展.     

膀胱全切非管状乙状结肠膀胱成形术（附六例报告）

对６例多发性浸润性膀胱癌而膀胱颈部及尿道无侵犯的患者在膀胱前列腺全切后以非管状乙状结肠原位代膀胱。经３～２５个月的随访，除１例仍有轻度尿失禁伴轻度排尿困难外，余５例手术后６个月以上者非管状乙状结肠膀胱容量大、压力低，经尿道排尿、排空完全、自控性好，无全身营养障碍及水电酸碱紊乱，节省肠管，手术简便。     

肿瘤蛋白质组学在信号传导通路、肿瘤标志物等方面的研究

肿瘤是一个多因素的疾病 ,在其的发生、发展过程中 ,分子生物学事件的复杂性日益受到人们的重视。随着基因组全序列测定的完成 ,蛋白质组学的研究得到了广泛的关注。应用蛋白质组学的方法 ,可以对细胞生长、分化过程中的蛋白质与细胞信号传导通路上的蛋白质之间的相互作用进行更为深入的研究 ,因而有希望发现控制肿瘤生物学行为的诸多蛋白质和信号分子。