槐耳清膏诱导肝癌小鼠移植瘤细胞凋亡的实验研究
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摘要
【背景】
原发性肝癌(PLC)已成为我国第二位恶性肿瘤病因,是最常见的恶性肿瘤之一。统计资料表明,全世界每年新发肝癌病例约45%在我国大陆。近20年来,我国肝癌死亡率增加了41.7%,可见我国肝癌高发的趋势已十分严峻[1]。研究发现,中医中药配合各种西医常规方法治疗中晚期原发性肝癌,具有明显改善临床症状及体征,提高生存质量,延长生存期等作用[2]。近年来,加大了对中药的开发力度,从中药中筛选提纯出有形成份,如中药多糖,进行抗肿瘤实验,取得了一定的进展,为中药抗癌提供了一条途径。
槐耳是生长在老龄中国槐树干上的一种药用真菌——槐栓菌(Trametes robiniophila Murr),其主要抗癌活性成分为蛋白多糖(PS-T)。现已有其成品——金克槐耳颗粒(国家一类新药)应用于临床。综合现代文献报道,槐耳颗粒在临床上已广泛应用于多种肿瘤的治疗,并取得了一定的疗效:1、消化系统肿瘤:槐耳配合常规化疗方案,能显著提高胃癌术后的5年生存率[3];槐耳配合化疗能提高大肠癌术后患者的免疫功能,减轻化疗毒性,改善造血功能[4];2、呼吸系统肿瘤:槐耳能显著改善非小细胞肺癌患者的免疫功能[5];3、血液肿瘤方面:单用槐耳治疗慢性粒细胞性白血病的总有效率可达80%[6];4、其它肿瘤:槐耳对乳腺癌肿瘤[7]也有良好的疗效。在阐述其抗肿瘤机制方面,也有进行了大量的实验研究。目前已有的槐耳作用于肝癌的基础实验表明,槐耳在体外可直接作用于肝癌细胞并诱导其凋亡[8],本实验将在此基础上,进一步研究槐耳诱导肝癌细胞凋亡的作用。
【目的】
1、体外观察槐耳清膏对人肝癌SMMC-7721细胞株的生长抑制作用;
2、观察槐耳清膏对肝癌小鼠移植瘤细胞的抑制作用,并初步探讨其作用机制。
【方法】
1、MTT法检测槐耳清膏在体外对肝癌细胞SMMC-7721细胞株的抑制率;
2、观察槐耳清膏对小鼠移植瘤的抑制作用及其诱导凋亡作用皮下注射H22小鼠肝癌细胞,造荷瘤小鼠的模型,分为A组(空白对照组)、B组(5-Fu组)、C组(槐耳清膏组)、D组(槐耳清膏+5-Fu组),用药结束后,称瘤重,计算抑瘤率;HE染色,观察瘤组织的病理学改变;TUNEL法检测各组肿瘤组织凋亡率;用免疫组织化学的方法检测移植瘤细胞组织相关凋亡蛋白Bcl-2、Bax的表达,初步探讨其诱导凋亡的可能机制。
【结果】
1、体外抑制细胞增殖实验:槐耳清膏对肝癌SMMC-7721细胞有明显的抑制作用,且随浓度增加而上升,呈剂量-效应关系,10 mg/ml槐耳清膏组与5 mg/ml槐耳清膏组的48 h抑制率分别达到65%和55%。
2、体内抑制肿瘤生长实验:A组(对照组)荷瘤小鼠移植瘤重量明显大于B组(5-Fu组)、C组(槐耳清膏组)和D组(槐耳清膏+5-Fu组)(P<0.05,P<0.05,P<0.05),B,C,D组抑瘤率分别为31.2%,27.1%,47.5%,提示槐耳清膏在体内具有抑制肿瘤生长的作用;且D组抑瘤率明显高于B,C组,差异有统计学意义(P<0.05),提示槐耳清膏联合5-Fu用药,可提高5-Fu抑制肿瘤的效果。
3、TUNEL法肿瘤组织细胞凋亡率的检测显示,凋亡率由高到低依次为:槐耳清膏联合5-Fu组、槐耳清膏组、5-Fu组、对照组,差异有统计学意义(P<0.05)。
4、相关凋亡蛋白Bcl-2的测定,免疫组化结果显示:对照组的Bcl-2阳性表达率为43.02±2.05%,明显高于5-Fu组、槐耳清膏组、槐耳清膏联合5-Fu组的阳性表达率,差异有统计学意义(P<0.05),表明槐耳清膏可下调荷瘤小鼠瘤组织细胞Bcl-2蛋白的表达。
5、相关凋亡蛋白Bax的测定,免疫组化结果显示:槐耳清膏联合5-Fu组的Bax阳性表达率87.88±9.72%,高于对照组、5-Fu组、槐耳清膏组,差异有统计学意义(P<0.05);对照组与槐耳清膏组的差异没有统计学意义(P>0.05),表明槐耳清膏联合5-Fu可增强Bax蛋白的表达。
【结论】
1、槐耳清膏在体外对肝癌SMMC-7721细胞有抑制其生长的作用;
2、槐耳清膏在体内可通过诱导凋亡抑制小鼠移植瘤生长;
3、槐耳清膏可下调Bcl-2基因蛋白表达,联合5-Fu上调Bax基因蛋白表达作用明显,认为槐耳清膏可能通过诱导荷瘤小鼠移植瘤组织细胞凋亡,抑制肿瘤生长。
BACKGROUND:
Primary liver cancer (PLC) has become the second cause of malignant tumors, which is one of the most common malignant tumor. Statistics showed that the new cases about 45 percent of liver cancer cases all over the world each year are in the mainland of our country, the incidence of liver cancer mortality was increased by 41.7% in the past 20 years. But in recent years, the study showed that treatment of traditional Chinese medicine with conventional Western medicine for advanced primary liver cancer has significant improvement in clinical symptoms and signs and improve quality of life, prolong survival time. In recent years, many Chinese herbal medicine have been developed. The components filtered and purified from Chinese herbal medicine, such as traditional Chinese medicine polysaccharide, have been used in anti-tumor experiments. Some progress has been made. It has provided a way for anticancer medicine.
Trametes robiniophila is medicinal fungi in aged Chinese Trametes tree (Trametes robiniophila Murr). Trametes robiniophila obtained by hot water contains a variety of organic ingredients and more than ten kinds of mineral material elements. The main active ingredient for anticancer protein is polysaccharide (PS-T). Now there are its products Jinke Huaier Granule (National Class One drug) for clinical application. Modern study reports show Huaier Granule clinically has been widely used in a variety of tumor treatment, and good effects have been achieved. 1. For digestive system tumors: 5years survival rate of gastric cancer has significantly increased;united chemotherapy drug can improve immune function in colorectal cancer patients, reduce the toxicity of chemotherapy and improve the hematopoietic function;2. For respiratory system cancer: Huaier can significantly improve the non-small cell lung cancer patient's immune function;3. For blood tumor: the treatment of chronic myelogenous leukemia have a total efficiency up to 80%;4. other cancer: Trametes robiniophila also has good effect for Breast Cancer. In explaining its anti-tumor mechanism, many experiments also have been carried out. Trametes robiniophila basic role in liver cancer experiments show that in vitro Trametes robiniophila has direct use on liver cancer cells and induces apoptosis. This experiment will be on this basis, further research Trametes robiniophilainduced apoptosis of hepatoma cells.
OBJECTIVE:
1.In vitro observing growth inhibition of human hepatocellular carcinoma SMMC-7721 cell lines on Trametes robiniophila;
2. To observe inhibition of hepatocell ular carcinoma cells in mice transplanted tumor and to explore its mechanism on Trametes robiniophila.
METHODS:
1. MTT assay the inhibitionrate of in hepatoma cells SMMC-7721 cell line by Trametes robiniophila in vitro.
2. To observe inhibition and induction of apoptosis of mouse transplanted tum or on Trametes robiniophila.
Subcutaneous injection of H22 hepatocarcinoma cells to mice, creating a model tumor-bearing mice , they were divided into A group (control group), B group (5-Fu group), C group (Group Trametes robiniophila) and D group (Trametes robiniop hila+5-Fu group), tumor weight was weighted at the end of treatment, calculating t he inhibition rate, HE staining is to observe pathological changes in tumor tissue; apoptosis in tumor tissue in each group rate by TUNEL assay;transplantation tum or related apoptosis protein Bcl-2, Bax expression, to explore its possible mechanis m of induction of apoptosis by immunohistochemical method.
RESULTS:
1.Inhibition of cell proliferation in vitro experiments: hepatocellular carcinoma SMMC-7721 cells were significantly inhibited by Trametes robiniophila and the concentration increases with the dose effect relationship, 10 mg/ml Trametes rob iniophila group and 5 mg/ml Trametes robiniophila group 48 h inhibition rate reached 65% and 55% respectively.
2. In vivo tumor growth inhibition experiment: the weight of tumor-bearing mice in A group was significantly is greater than B group (5-Fu group), C group (T rametes robiniophila) and D group (Trametes robiniophila +5-Fu group) (P<0.05, P<0.05, P <0.05), B, C, D Group inhibitory rates were 31.2% and 27.1%, 47.5% respectively, suggesting that Trametes robiniophila in the body can inhibit the growth of tumor;and the inhibition rate in D group was significantly higher than B, C group, (P<0.05), prompting Trametes robiniophila United 5-Fu drug, 5-Fu can enhance the effect of inhibiting tumor .
3.Tumor cell apoptosis rate by Tunel, detection showed that the apoptosis rate high to low as follows: Trametes robiniophila United 5-Fu group, Trametes robiniophila group, 5-Fu group and the control group, the difference has statistical significance (P<0.05).
4. Related apoptosis protein Bcl-2 determination, immuneohistochemical results showed that the control group of Bcl-2 positive expression rate is 43.02±2.05%, is significantly higher than 5-Fu group, Trametes robiniophila group, Trametes robiniophila United 5-Fu group.The positive expression rate, the difference has statisti cal significance (P<0.05), showed that clearance of Trametes robiniophila paste can be reduced tumor-bearing mice tumor cell Bcl-2 protein expression.
5.Related to the determination of apoptotic protein Bax, immunohistochemical results showed that: Trametes robiniophila united 5-Fu group Bax positive expression rate is 87.88±9.72%, which was higher than 5-Fu group, Trametes robiniophila group, (P <0.05);difference between the control group and Trametes robiniophila Group has no statistically significant (P>0.05). It showed that Trametes robiniophila united 5-Fu can enhance the expression of Bax protein.
CONCLUSIONS:
1.Trametes robiniophila in vitro have inhibited growth of hepatoma SMMC-7721 cells
2.Trametes robiniophila in vivo can inhibite tumor growth in mice by induction of apoptosis;
3.Trametes robiniophila can reduce Bcl-2 gene protein expression, united 5-Fu, Bax gene protein expression increase apparently, Trametes robiniophila may inhibit tumor growth in tumor-bearing mice by inducing apoptosis of transplanted tumor.
原发性肝癌(PLC)已成为我国第二位恶性肿瘤病因,是最常见的恶性肿瘤之一。统计资料表明,全世界每年新发肝癌病例约45%在我国大陆。近20年来,我国肝癌死亡率增加了41.7%,可见我国肝癌高发的趋势已十分严峻[1]。研究发现,中医中药配合各种西医常规方法治疗中晚期原发性肝癌,具有明显改善临床症状及体征,提高生存质量,延长生存期等作用[2]。近年来,加大了对中药的开发力度,从中药中筛选提纯出有形成份,如中药多糖,进行抗肿瘤实验,取得了一定的进展,为中药抗癌提供了一条途径。
槐耳是生长在老龄中国槐树干上的一种药用真菌——槐栓菌(Trametes robiniophila Murr),其主要抗癌活性成分为蛋白多糖(PS-T)。现已有其成品——金克槐耳颗粒(国家一类新药)应用于临床。综合现代文献报道,槐耳颗粒在临床上已广泛应用于多种肿瘤的治疗,并取得了一定的疗效:1、消化系统肿瘤:槐耳配合常规化疗方案,能显著提高胃癌术后的5年生存率[3];槐耳配合化疗能提高大肠癌术后患者的免疫功能,减轻化疗毒性,改善造血功能[4];2、呼吸系统肿瘤:槐耳能显著改善非小细胞肺癌患者的免疫功能[5];3、血液肿瘤方面:单用槐耳治疗慢性粒细胞性白血病的总有效率可达80%[6];4、其它肿瘤:槐耳对乳腺癌肿瘤[7]也有良好的疗效。在阐述其抗肿瘤机制方面,也有进行了大量的实验研究。目前已有的槐耳作用于肝癌的基础实验表明,槐耳在体外可直接作用于肝癌细胞并诱导其凋亡[8],本实验将在此基础上,进一步研究槐耳诱导肝癌细胞凋亡的作用。
【目的】
1、体外观察槐耳清膏对人肝癌SMMC-7721细胞株的生长抑制作用;
2、观察槐耳清膏对肝癌小鼠移植瘤细胞的抑制作用,并初步探讨其作用机制。
【方法】
1、MTT法检测槐耳清膏在体外对肝癌细胞SMMC-7721细胞株的抑制率;
2、观察槐耳清膏对小鼠移植瘤的抑制作用及其诱导凋亡作用皮下注射H22小鼠肝癌细胞,造荷瘤小鼠的模型,分为A组(空白对照组)、B组(5-Fu组)、C组(槐耳清膏组)、D组(槐耳清膏+5-Fu组),用药结束后,称瘤重,计算抑瘤率;HE染色,观察瘤组织的病理学改变;TUNEL法检测各组肿瘤组织凋亡率;用免疫组织化学的方法检测移植瘤细胞组织相关凋亡蛋白Bcl-2、Bax的表达,初步探讨其诱导凋亡的可能机制。
【结果】
1、体外抑制细胞增殖实验:槐耳清膏对肝癌SMMC-7721细胞有明显的抑制作用,且随浓度增加而上升,呈剂量-效应关系,10 mg/ml槐耳清膏组与5 mg/ml槐耳清膏组的48 h抑制率分别达到65%和55%。
2、体内抑制肿瘤生长实验:A组(对照组)荷瘤小鼠移植瘤重量明显大于B组(5-Fu组)、C组(槐耳清膏组)和D组(槐耳清膏+5-Fu组)(P<0.05,P<0.05,P<0.05),B,C,D组抑瘤率分别为31.2%,27.1%,47.5%,提示槐耳清膏在体内具有抑制肿瘤生长的作用;且D组抑瘤率明显高于B,C组,差异有统计学意义(P<0.05),提示槐耳清膏联合5-Fu用药,可提高5-Fu抑制肿瘤的效果。
3、TUNEL法肿瘤组织细胞凋亡率的检测显示,凋亡率由高到低依次为:槐耳清膏联合5-Fu组、槐耳清膏组、5-Fu组、对照组,差异有统计学意义(P<0.05)。
4、相关凋亡蛋白Bcl-2的测定,免疫组化结果显示:对照组的Bcl-2阳性表达率为43.02±2.05%,明显高于5-Fu组、槐耳清膏组、槐耳清膏联合5-Fu组的阳性表达率,差异有统计学意义(P<0.05),表明槐耳清膏可下调荷瘤小鼠瘤组织细胞Bcl-2蛋白的表达。
5、相关凋亡蛋白Bax的测定,免疫组化结果显示:槐耳清膏联合5-Fu组的Bax阳性表达率87.88±9.72%,高于对照组、5-Fu组、槐耳清膏组,差异有统计学意义(P<0.05);对照组与槐耳清膏组的差异没有统计学意义(P>0.05),表明槐耳清膏联合5-Fu可增强Bax蛋白的表达。
【结论】
1、槐耳清膏在体外对肝癌SMMC-7721细胞有抑制其生长的作用;
2、槐耳清膏在体内可通过诱导凋亡抑制小鼠移植瘤生长;
3、槐耳清膏可下调Bcl-2基因蛋白表达,联合5-Fu上调Bax基因蛋白表达作用明显,认为槐耳清膏可能通过诱导荷瘤小鼠移植瘤组织细胞凋亡,抑制肿瘤生长。
BACKGROUND:
Primary liver cancer (PLC) has become the second cause of malignant tumors, which is one of the most common malignant tumor. Statistics showed that the new cases about 45 percent of liver cancer cases all over the world each year are in the mainland of our country, the incidence of liver cancer mortality was increased by 41.7% in the past 20 years. But in recent years, the study showed that treatment of traditional Chinese medicine with conventional Western medicine for advanced primary liver cancer has significant improvement in clinical symptoms and signs and improve quality of life, prolong survival time. In recent years, many Chinese herbal medicine have been developed. The components filtered and purified from Chinese herbal medicine, such as traditional Chinese medicine polysaccharide, have been used in anti-tumor experiments. Some progress has been made. It has provided a way for anticancer medicine.
Trametes robiniophila is medicinal fungi in aged Chinese Trametes tree (Trametes robiniophila Murr). Trametes robiniophila obtained by hot water contains a variety of organic ingredients and more than ten kinds of mineral material elements. The main active ingredient for anticancer protein is polysaccharide (PS-T). Now there are its products Jinke Huaier Granule (National Class One drug) for clinical application. Modern study reports show Huaier Granule clinically has been widely used in a variety of tumor treatment, and good effects have been achieved. 1. For digestive system tumors: 5years survival rate of gastric cancer has significantly increased;united chemotherapy drug can improve immune function in colorectal cancer patients, reduce the toxicity of chemotherapy and improve the hematopoietic function;2. For respiratory system cancer: Huaier can significantly improve the non-small cell lung cancer patient's immune function;3. For blood tumor: the treatment of chronic myelogenous leukemia have a total efficiency up to 80%;4. other cancer: Trametes robiniophila also has good effect for Breast Cancer. In explaining its anti-tumor mechanism, many experiments also have been carried out. Trametes robiniophila basic role in liver cancer experiments show that in vitro Trametes robiniophila has direct use on liver cancer cells and induces apoptosis. This experiment will be on this basis, further research Trametes robiniophilainduced apoptosis of hepatoma cells.
OBJECTIVE:
1.In vitro observing growth inhibition of human hepatocellular carcinoma SMMC-7721 cell lines on Trametes robiniophila;
2. To observe inhibition of hepatocell ular carcinoma cells in mice transplanted tumor and to explore its mechanism on Trametes robiniophila.
METHODS:
1. MTT assay the inhibitionrate of in hepatoma cells SMMC-7721 cell line by Trametes robiniophila in vitro.
2. To observe inhibition and induction of apoptosis of mouse transplanted tum or on Trametes robiniophila.
Subcutaneous injection of H22 hepatocarcinoma cells to mice, creating a model tumor-bearing mice , they were divided into A group (control group), B group (5-Fu group), C group (Group Trametes robiniophila) and D group (Trametes robiniop hila+5-Fu group), tumor weight was weighted at the end of treatment, calculating t he inhibition rate, HE staining is to observe pathological changes in tumor tissue; apoptosis in tumor tissue in each group rate by TUNEL assay;transplantation tum or related apoptosis protein Bcl-2, Bax expression, to explore its possible mechanis m of induction of apoptosis by immunohistochemical method.
RESULTS:
1.Inhibition of cell proliferation in vitro experiments: hepatocellular carcinoma SMMC-7721 cells were significantly inhibited by Trametes robiniophila and the concentration increases with the dose effect relationship, 10 mg/ml Trametes rob iniophila group and 5 mg/ml Trametes robiniophila group 48 h inhibition rate reached 65% and 55% respectively.
2. In vivo tumor growth inhibition experiment: the weight of tumor-bearing mice in A group was significantly is greater than B group (5-Fu group), C group (T rametes robiniophila) and D group (Trametes robiniophila +5-Fu group) (P<0.05, P<0.05, P <0.05), B, C, D Group inhibitory rates were 31.2% and 27.1%, 47.5% respectively, suggesting that Trametes robiniophila in the body can inhibit the growth of tumor;and the inhibition rate in D group was significantly higher than B, C group, (P<0.05), prompting Trametes robiniophila United 5-Fu drug, 5-Fu can enhance the effect of inhibiting tumor .
3.Tumor cell apoptosis rate by Tunel, detection showed that the apoptosis rate high to low as follows: Trametes robiniophila United 5-Fu group, Trametes robiniophila group, 5-Fu group and the control group, the difference has statistical significance (P<0.05).
4. Related apoptosis protein Bcl-2 determination, immuneohistochemical results showed that the control group of Bcl-2 positive expression rate is 43.02±2.05%, is significantly higher than 5-Fu group, Trametes robiniophila group, Trametes robiniophila United 5-Fu group.The positive expression rate, the difference has statisti cal significance (P<0.05), showed that clearance of Trametes robiniophila paste can be reduced tumor-bearing mice tumor cell Bcl-2 protein expression.
5.Related to the determination of apoptotic protein Bax, immunohistochemical results showed that: Trametes robiniophila united 5-Fu group Bax positive expression rate is 87.88±9.72%, which was higher than 5-Fu group, Trametes robiniophila group, (P <0.05);difference between the control group and Trametes robiniophila Group has no statistically significant (P>0.05). It showed that Trametes robiniophila united 5-Fu can enhance the expression of Bax protein.
CONCLUSIONS:
1.Trametes robiniophila in vitro have inhibited growth of hepatoma SMMC-7721 cells
2.Trametes robiniophila in vivo can inhibite tumor growth in mice by induction of apoptosis;
3.Trametes robiniophila can reduce Bcl-2 gene protein expression, united 5-Fu, Bax gene protein expression increase apparently, Trametes robiniophila may inhibit tumor growth in tumor-bearing mice by inducing apoptosis of transplanted tumor.
引文
[1]吴孟超.原发性肝癌治疗的进展.中华医学信息导报,2002,(1):10-11
[2]凌昌全,陈喆,朱德增,等.中西医结合治疗中晚期原发性肝癌313例.世界华人消化杂志,2001,9(1):114-115
[3]姚建高,韩少良,朱冠宝,等.Ⅲ期胃癌术后联合化疗与金克的疗效.中国肿瘤,2003;12(10):606-608
[4]袁明,黄桂林,李志刚,等.槐耳颗粒配合化疗对大肠癌患者术后免疫功能的影响.中国肿瘤,2005,14(7):487-488
[5]姚亚民,马智勇,赵艳秋.金克冲剂合并化疗治疗非小细胞肺癌4l例.中国肿瘤,2001,10(3):184-185
[6]邱仲川,陈佩,胡琦.金克对慢性粒细胞性白血病细胞因子的影响.中国瘤,2000,9(12):W001-W002
[7]钟少文,江慧玲,刘鑫,等.金克槐耳颗粒治疗IV期乳腺癌.中国肿瘤,2003,12(12):754-755
[8]任建庄,郑传胜,冯敢生,等.槐耳清膏体外抑制肝癌细胞生长的实验研究.临床放射学杂志,2008,27(12):1778-1781
[9]Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics.CA-Cancer J Clin,2005,55:74-108
[10]吴孟超.原发性肝癌的诊断及治疗进展.中国医学科学院学报,2008,30(4):363-365
[11]钦伦秀,孙惠川,汤钊猷.原发性肝癌研究进展—2006沪港国际肝病大会纪要.中华外科杂志,2006,44(15):1070-1074
[12]Ahn,Fla SL.Hepatocellular carcinoma.Dison,2004,50(10):556-573
[13]Valle W,Dangoor A,Beech,et a1.Treatent of inoperable hepatocellular carcinoa with pegylatedliposoal doxorubicin(PLD):results of a phase II study. Cancer,2005,92(4):628-630
[14]刘学军.浅谈中西医结合治疗肿瘤的系统观.中国中医药信息杂志,2008,15(11):4-5
[15]侯凤刚,凌昌全.原发性肝癌病因病机及其演化规律.安徽中医学院学报,2003,22(1):54-56
[16]庄毅.真菌抗癌药物槐耳颗粒的研制.中国肿瘤,1999,8(12):540-543
[17]程若川,王建忠.槐耳的研制及临床应用.昆明医学院学报,2003, (1):101-103
[18]郑有合,刘英杰,景琴,等.槐耳颗粒对晚期原发性肝癌疗效分析.医学信息,2006,19(10):245-147
[19]唐云,李荣,吴欣.槐耳颗粒对乳腺癌患者术后免疫功能调节作用的观察.军医进修学院学报,2006,27(3):170-171
[20]李立新,叶胜龙,王艳红,等.槐耳浸膏诱导肝癌细胞凋亡的实验研究.中国临床医学,2005,12(6):1152-1153
[21]金小顺,耿小平,朱立新,等.槐耳清膏体外诱导人肝癌细胞凋亡的实验研究.肝胆外科杂志,2007,15(2):148-151 [ 22 ]Cheng EH,Wei C,Weiler S,et al.BCL-2,BCL-X(L) sequester BH3 domain only moleculespreventing BAX and BAK-mediated mitochondrial apoptosis.Cell,2001,8(3):705
[23]阙劲松,高世洪.槐耳颗粒联合介入疗法治疗原发性肝癌的疗效观察.临床和实验医学杂志,2007,6(5):151
[24]庄毅.真菌抗癌药物槐耳颗粒的研制.中国肿瘤,1999,8(12):540-543
[25]黄涛,孔庆志,卢宏达,等.槐耳清膏诱导人肺腺癌细胞A549凋亡的实验研究.中华结核和呼吸杂志,2001,24:487
[26]李玉林.病理学.北京:人民卫生出版社,2005,9
[27]张芷旋,范羽,周清华,等.槐耳清膏对人高转移大细胞肺癌细胞L9981血管生成相关基表达的影响.中国肺癌杂志,2006,9(2):137-142
[28]李立新,叶胜龙,王艳红,等.槐耳浸膏干预荷瘤裸鼠肝癌转移的实验研究.肝脏,2006,11(6):404-406
[29]庄毅.真菌抗癌药物槐耳颗粒的研制.中国肿瘤,1999,8(12):540-543
[30]陈大兴,陈孝平,张万广.槐耳清膏治疗肝癌的实验研究.中国普通外科杂志,2004,13(8):578-582
[31]周进,李德春,匡玉庭.金克(槐耳清膏)抑制胰腺癌细胞Panc-1生长转移的实验研究.苏州大学学报(医学版),2005,25(2):226-228
[32]程若川,汤礼贵,兰丽琴,等.槐耳清膏诱导人直肠癌HR8348细胞凋亡的实验研究.中国普外基础与临床杂志,2003,10(6):568-571
[33]李保庆,李勇,王其彰,等.槐耳颗粒对食管癌细胞凋亡及免疫功能的影响.中国肿瘤,2003,12(12):752-753.
[34]王家顿,谢大兴,陈金明,等.抗癌药物诱导Molt-4细胞凋亡的周期时相性分析.中国肿瘤,2002,11(9):533-534
[35]Eastman A,Rigas JR. Modulation of apoptosis signaling pathways and cell cycle regulation. Semin Oncol,1999,26:7-16
[36]Lawry J.Detection of apoptosis by the TUNEL assay.Methods Mol Med,2004,88:183-190 [ 37 ]Ross T,OlivierR,MonneyL,et al.Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c.Nature,1998,391(6666):441-442
[38]Guo B,Zhai D,Cabezas E,et al.Huanin peptide suppresses apoptosis by interfering with Bax activation.Nature,2003,423(6938):456-461
[39]Olie RA,Hafner C,Kutel R,et al.Bcl-2 and bcl-xL antisense oligonucleotides induce Apoptosis in melanoma cell of different clinical stages.J Invest Dermatol,2002,118(3):505-512
[40]Soernson CM,Rogers SA,Korsmeyer SJ,et a1.Fylminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice.Am J Physiol,1995,268(1 Pt 2):F73-F81
[41]Oltvai ZN,Milliman CL,Korsmeyer S J.Bcl-2 heteordimerizes in vivo With Conserved homolog, Bax, that accelerates programmed cell death.Cell,1993,74(4):609-619.
[42]Knudson CM,Tung KS,Tourtellote WG,et a1.Bax-deficient mice with lymphoid hyperplasia and male germ cell death.Science,1995,270(5233):96-99
[43]Sawa H ,Kobayashi T,Mukai K, et al.Bax overexpression enhances cytochrome c release from mitochondria and sensitizes KATOI11 gastric cancer cells to chemotherapeutic agentinduced apoptosis.Int J Oncol,2000,16(4):745-749
[44]Green DR,Reed JC.Mitochondria and apoptosis.Science,1998,281(5381):1309-1312
[45]Stur I,Papadopoulos S,Hille brand T,et al.Ipaired Bax protein expression in Breast cancer:utational and lysis of the Bax and the P53 gene.Int J Cancer,2000,87:517-521
[46]Kulig E,in L,Qian X ,et al.Apoptosis in nontuorous and neoplastic huan Pituitaires:expression of the Bcl-2 faily of proteins.Apathol,1999,154(3):767-774
[47]Nicholson DW,Thornberry NA.Apoptosis. Life and death decisions.Science,2003,299(6504):223-226 [ 48 ]Konopleva M,Tari AM,Estrov Z,et al.Liposomal Bcl-2 antisense oligonucleotides enhance proliferation,sensitize acute myeloid leukemia to cytosine-arabinoside,and induce apoptosis independent of other antiapoptotic proteins.Blood,2000,95(12):3929-3938
[49]豆长明,李继承.中药抗肿瘤作用机制研究态势评析.中医药学刊,2003,21(3):361-363
[50]徐中文.中医药治疗肝癌应注意的几个问题.辽宁中医学院学报,2005,7(1):41-42
[1]邓叔群.中国的真菌.北京:科技出版社,1963,515
[2]李时珍.槐耳.本草纲目下册(菜部)二十八卷.北京:人民卫生出版社,1982,1712
[3]庄毅.抗癌新药槐耳冲剂的研究.中国药学杂志,1998,33(5):273-275
[4]陈慎宝,丁如宁.槐耳菌质成分对小鼠免疫功能的影响.食用菌学报,1995,2(1):21-25
[5]陆鹏,陈莉,陆正鑫.实验性肝癌中比较槐耳与IL22对PTEN和IL2R阳性细胞的影响.现代中西医结合杂志,2004,13(15):1982-1985
[6]庄毅.真菌抗癌药物槐耳颗粒的研制.中国肿瘤,1999,8(12):540-543
[7]周进,李德春,匡玉庭.金克(槐耳清膏)抑制胰腺癌细胞Panc-1生长转移的实验研究.苏州大学学报(医学版),2005,25(2):226-228
[8]金小顺,耿小平,朱立新,等.槐耳清膏体外诱导人肝癌细胞凋亡的实验研究.肝胆外科杂志,2007,15(2):148-151
[9]黄涛,孔庆志,卢宏达.槐耳清膏对耐顺铂人肺腺癌细胞系A549DDP逆转的实验研究.中国药师,2002,5(9):517-519
[10]程若川,汤礼贵,兰丽琴.槐耳清膏诱导人直肠癌HR8348细胞凋亡的实验研究.中国肿瘤,2003,12(2):122-124
[11]王家顿,谢大兴,陈金明,等.抗癌药物诱导Molt24细胞凋亡的周期时相性分析.中国肿瘤,2002,11(9):533-534
[12]陈信义,刘江涛.肿瘤多药耐药性与中药逆转研究.中西医结合学报,2007,1(3):221-225
[13]张玉宝,张国强,王劲松,等.槐耳颗粒在乳腺癌综合治疗中的作用及其机制.中国肿瘤临床与康复,2004,11(6):512-515
[14]陈孝平,何松青,赵旭,等.槐耳清膏联合肿瘤坏死因子相关凋亡诱导配体对肝癌细胞生长的影响.中华外科杂志,2005,43(23):1524-1527
[15]李焕荣,李秀荣.中医药抑制肿瘤血管生成抗肿瘤转移的可行性探讨.中西医结合学报,2007,5(4):378-382
[16]陈大兴,陈孝平,张万广.槐耳清膏治疗肝癌的实验研究.中国普通外科杂志,2004,13(8):578-582
[17]许戈良,荚卫东,马金良,等.槐耳浸膏体外抑制血管生成的实验研究.中国药理学通报,2003,19(12):1410-1412
[18]张芷旋,范羽,周清华,等.槐耳清膏对人高转移大细胞肺癌细胞L9981血管生成相关基因表达的影响.中国肺癌杂志,2006,9(2):137-142
[19]蒋梅,周岱翰.槐耳冲剂治疗中晚期原发性肝癌98例.上海中医药杂志,2004,38(6):21-22
[20]李凯,陶京,李弢,等.吉西他滨联和槐耳治疗无法切除胰腺癌的临床疗效.临床外科杂志,2007,15(4):240-242
[21]邓艾平,毛德莉.槐耳颗粒治疗消化系统恶性肿瘤74例临床观察.中国医院药学杂志,2005,25(5):453-454
[22]袁明,黄桂林,李志刚,等.槐耳颗粒配合化疗对大肠癌患者术后免疫功能的影响.中国肿瘤,2005,14(7):487-488
[23]姚建高,韩少良,朱冠宝,等.Ⅲ期胃癌术后联合化疗与金克的疗效.中国肿瘤,2003,12(10):606-608
[24]姚亚民,马智勇,赵艳秋.金克冲剂合并化疗治疗非小细胞肺癌4l例.中国肿瘤,2001,10(3):184-185
[25]李学兵.金克槐耳颗粒对Ⅲ期非小细胞肺癌患者免疫细胞活性的影响.临床肺科杂志,2006,11(4):472-473
[26]钟少文,江慧玲,刘鑫,等.金克槐耳颗粒治疗Ⅳ期乳腺癌.中国肿瘤,2003,12(12):754-755
[27]付美兰,郭丽英,玛依怒尔,等.槐耳颗粒对43例晚期乳腺癌化疗患者造血及免疫功能的影响.肿瘤学杂志,2005,11(4):318
[28]陈前军,赖熙雯,司徒红林,等.乳腺癌术前行槐耳颗粒联合化疗临床疗效.中国肿瘤,2004,13(5):330-331.
[29]邱仲川,陈佩,胡琦.金克对慢性粒细胞性白血病细胞因子的影响.中国肿瘤,2000,9(12):W001-W002
[30]赵文生.金克联合化疗对复发性非何杰金淋巴瘤的疗效.中国肿瘤,1999,8(5):237-238
[31]修忠标,朱夏.金克对骨肉瘤的化疗增效及减毒作用的临床观察.福建中医学院学报,2004,14(1):30-31
[1]何裕民.正确认识中医治疗肿瘤.家庭医生,2005,(9):21
[2]凌昌全.肿瘤治疗存在的问题及中西医结合的研究重点.中西医结合学报,2003,1(3):168-170
[3]沈晔华,宋明志,黄雯霞.中西医结合治疗71例乳腺癌术后患者的疗效分析.中西医结合学报,2003,1(1):30
[4]李佩文,毕国文,刘宝宽,等.参芪扶正注射液配合化疗治疗恶性肿瘤的临床观察.中国中药杂志,2000,25:115-117
[5]阙华发,陈红风,徐杰男,等.生命质量与中医药治疗恶性肿瘤临床疗效评价标准探讨,中西医结合学报,2005,7(4):254
[6]郑展,徐振晔.表皮生长因子受体及其信号转导通路与中西药肿瘤靶向治疗.中西医结合学报,2005,7(4):320
[7]黄承良,刘厚东.全反式维甲酸诱导分化治疗对胃癌患者免疫功能的影响.中国普外基础与临床杂志,2001,8(3):166-168
[8]Wang ZY,Chen Z.Differentiation and apoptosis induction therapy in acute promyelocytic leukaemia.Lancet Oncology,2000,l:101-106
[9]王振义.诱导分化治疗中的问题.中国肿瘤,2002,11(1):3-4
[10]张蓓,胡丕丽.中西医结合治疗对肿瘤患者生存质量的影响.中华肿瘤杂志,2003,5(3):304
[11]马晓燕.系统观认知方式与中医学认知方式之比较.医学与哲学,2000,21(9):41-42
[2]凌昌全,陈喆,朱德增,等.中西医结合治疗中晚期原发性肝癌313例.世界华人消化杂志,2001,9(1):114-115
[3]姚建高,韩少良,朱冠宝,等.Ⅲ期胃癌术后联合化疗与金克的疗效.中国肿瘤,2003;12(10):606-608
[4]袁明,黄桂林,李志刚,等.槐耳颗粒配合化疗对大肠癌患者术后免疫功能的影响.中国肿瘤,2005,14(7):487-488
[5]姚亚民,马智勇,赵艳秋.金克冲剂合并化疗治疗非小细胞肺癌4l例.中国肿瘤,2001,10(3):184-185
[6]邱仲川,陈佩,胡琦.金克对慢性粒细胞性白血病细胞因子的影响.中国瘤,2000,9(12):W001-W002
[7]钟少文,江慧玲,刘鑫,等.金克槐耳颗粒治疗IV期乳腺癌.中国肿瘤,2003,12(12):754-755
[8]任建庄,郑传胜,冯敢生,等.槐耳清膏体外抑制肝癌细胞生长的实验研究.临床放射学杂志,2008,27(12):1778-1781
[9]Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics.CA-Cancer J Clin,2005,55:74-108
[10]吴孟超.原发性肝癌的诊断及治疗进展.中国医学科学院学报,2008,30(4):363-365
[11]钦伦秀,孙惠川,汤钊猷.原发性肝癌研究进展—2006沪港国际肝病大会纪要.中华外科杂志,2006,44(15):1070-1074
[12]Ahn,Fla SL.Hepatocellular carcinoma.Dison,2004,50(10):556-573
[13]Valle W,Dangoor A,Beech,et a1.Treatent of inoperable hepatocellular carcinoa with pegylatedliposoal doxorubicin(PLD):results of a phase II study. Cancer,2005,92(4):628-630
[14]刘学军.浅谈中西医结合治疗肿瘤的系统观.中国中医药信息杂志,2008,15(11):4-5
[15]侯凤刚,凌昌全.原发性肝癌病因病机及其演化规律.安徽中医学院学报,2003,22(1):54-56
[16]庄毅.真菌抗癌药物槐耳颗粒的研制.中国肿瘤,1999,8(12):540-543
[17]程若川,王建忠.槐耳的研制及临床应用.昆明医学院学报,2003, (1):101-103
[18]郑有合,刘英杰,景琴,等.槐耳颗粒对晚期原发性肝癌疗效分析.医学信息,2006,19(10):245-147
[19]唐云,李荣,吴欣.槐耳颗粒对乳腺癌患者术后免疫功能调节作用的观察.军医进修学院学报,2006,27(3):170-171
[20]李立新,叶胜龙,王艳红,等.槐耳浸膏诱导肝癌细胞凋亡的实验研究.中国临床医学,2005,12(6):1152-1153
[21]金小顺,耿小平,朱立新,等.槐耳清膏体外诱导人肝癌细胞凋亡的实验研究.肝胆外科杂志,2007,15(2):148-151 [ 22 ]Cheng EH,Wei C,Weiler S,et al.BCL-2,BCL-X(L) sequester BH3 domain only moleculespreventing BAX and BAK-mediated mitochondrial apoptosis.Cell,2001,8(3):705
[23]阙劲松,高世洪.槐耳颗粒联合介入疗法治疗原发性肝癌的疗效观察.临床和实验医学杂志,2007,6(5):151
[24]庄毅.真菌抗癌药物槐耳颗粒的研制.中国肿瘤,1999,8(12):540-543
[25]黄涛,孔庆志,卢宏达,等.槐耳清膏诱导人肺腺癌细胞A549凋亡的实验研究.中华结核和呼吸杂志,2001,24:487
[26]李玉林.病理学.北京:人民卫生出版社,2005,9
[27]张芷旋,范羽,周清华,等.槐耳清膏对人高转移大细胞肺癌细胞L9981血管生成相关基表达的影响.中国肺癌杂志,2006,9(2):137-142
[28]李立新,叶胜龙,王艳红,等.槐耳浸膏干预荷瘤裸鼠肝癌转移的实验研究.肝脏,2006,11(6):404-406
[29]庄毅.真菌抗癌药物槐耳颗粒的研制.中国肿瘤,1999,8(12):540-543
[30]陈大兴,陈孝平,张万广.槐耳清膏治疗肝癌的实验研究.中国普通外科杂志,2004,13(8):578-582
[31]周进,李德春,匡玉庭.金克(槐耳清膏)抑制胰腺癌细胞Panc-1生长转移的实验研究.苏州大学学报(医学版),2005,25(2):226-228
[32]程若川,汤礼贵,兰丽琴,等.槐耳清膏诱导人直肠癌HR8348细胞凋亡的实验研究.中国普外基础与临床杂志,2003,10(6):568-571
[33]李保庆,李勇,王其彰,等.槐耳颗粒对食管癌细胞凋亡及免疫功能的影响.中国肿瘤,2003,12(12):752-753.
[34]王家顿,谢大兴,陈金明,等.抗癌药物诱导Molt-4细胞凋亡的周期时相性分析.中国肿瘤,2002,11(9):533-534
[35]Eastman A,Rigas JR. Modulation of apoptosis signaling pathways and cell cycle regulation. Semin Oncol,1999,26:7-16
[36]Lawry J.Detection of apoptosis by the TUNEL assay.Methods Mol Med,2004,88:183-190 [ 37 ]Ross T,OlivierR,MonneyL,et al.Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c.Nature,1998,391(6666):441-442
[38]Guo B,Zhai D,Cabezas E,et al.Huanin peptide suppresses apoptosis by interfering with Bax activation.Nature,2003,423(6938):456-461
[39]Olie RA,Hafner C,Kutel R,et al.Bcl-2 and bcl-xL antisense oligonucleotides induce Apoptosis in melanoma cell of different clinical stages.J Invest Dermatol,2002,118(3):505-512
[40]Soernson CM,Rogers SA,Korsmeyer SJ,et a1.Fylminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice.Am J Physiol,1995,268(1 Pt 2):F73-F81
[41]Oltvai ZN,Milliman CL,Korsmeyer S J.Bcl-2 heteordimerizes in vivo With Conserved homolog, Bax, that accelerates programmed cell death.Cell,1993,74(4):609-619.
[42]Knudson CM,Tung KS,Tourtellote WG,et a1.Bax-deficient mice with lymphoid hyperplasia and male germ cell death.Science,1995,270(5233):96-99
[43]Sawa H ,Kobayashi T,Mukai K, et al.Bax overexpression enhances cytochrome c release from mitochondria and sensitizes KATOI11 gastric cancer cells to chemotherapeutic agentinduced apoptosis.Int J Oncol,2000,16(4):745-749
[44]Green DR,Reed JC.Mitochondria and apoptosis.Science,1998,281(5381):1309-1312
[45]Stur I,Papadopoulos S,Hille brand T,et al.Ipaired Bax protein expression in Breast cancer:utational and lysis of the Bax and the P53 gene.Int J Cancer,2000,87:517-521
[46]Kulig E,in L,Qian X ,et al.Apoptosis in nontuorous and neoplastic huan Pituitaires:expression of the Bcl-2 faily of proteins.Apathol,1999,154(3):767-774
[47]Nicholson DW,Thornberry NA.Apoptosis. Life and death decisions.Science,2003,299(6504):223-226 [ 48 ]Konopleva M,Tari AM,Estrov Z,et al.Liposomal Bcl-2 antisense oligonucleotides enhance proliferation,sensitize acute myeloid leukemia to cytosine-arabinoside,and induce apoptosis independent of other antiapoptotic proteins.Blood,2000,95(12):3929-3938
[49]豆长明,李继承.中药抗肿瘤作用机制研究态势评析.中医药学刊,2003,21(3):361-363
[50]徐中文.中医药治疗肝癌应注意的几个问题.辽宁中医学院学报,2005,7(1):41-42
[1]邓叔群.中国的真菌.北京:科技出版社,1963,515
[2]李时珍.槐耳.本草纲目下册(菜部)二十八卷.北京:人民卫生出版社,1982,1712
[3]庄毅.抗癌新药槐耳冲剂的研究.中国药学杂志,1998,33(5):273-275
[4]陈慎宝,丁如宁.槐耳菌质成分对小鼠免疫功能的影响.食用菌学报,1995,2(1):21-25
[5]陆鹏,陈莉,陆正鑫.实验性肝癌中比较槐耳与IL22对PTEN和IL2R阳性细胞的影响.现代中西医结合杂志,2004,13(15):1982-1985
[6]庄毅.真菌抗癌药物槐耳颗粒的研制.中国肿瘤,1999,8(12):540-543
[7]周进,李德春,匡玉庭.金克(槐耳清膏)抑制胰腺癌细胞Panc-1生长转移的实验研究.苏州大学学报(医学版),2005,25(2):226-228
[8]金小顺,耿小平,朱立新,等.槐耳清膏体外诱导人肝癌细胞凋亡的实验研究.肝胆外科杂志,2007,15(2):148-151
[9]黄涛,孔庆志,卢宏达.槐耳清膏对耐顺铂人肺腺癌细胞系A549DDP逆转的实验研究.中国药师,2002,5(9):517-519
[10]程若川,汤礼贵,兰丽琴.槐耳清膏诱导人直肠癌HR8348细胞凋亡的实验研究.中国肿瘤,2003,12(2):122-124
[11]王家顿,谢大兴,陈金明,等.抗癌药物诱导Molt24细胞凋亡的周期时相性分析.中国肿瘤,2002,11(9):533-534
[12]陈信义,刘江涛.肿瘤多药耐药性与中药逆转研究.中西医结合学报,2007,1(3):221-225
[13]张玉宝,张国强,王劲松,等.槐耳颗粒在乳腺癌综合治疗中的作用及其机制.中国肿瘤临床与康复,2004,11(6):512-515
[14]陈孝平,何松青,赵旭,等.槐耳清膏联合肿瘤坏死因子相关凋亡诱导配体对肝癌细胞生长的影响.中华外科杂志,2005,43(23):1524-1527
[15]李焕荣,李秀荣.中医药抑制肿瘤血管生成抗肿瘤转移的可行性探讨.中西医结合学报,2007,5(4):378-382
[16]陈大兴,陈孝平,张万广.槐耳清膏治疗肝癌的实验研究.中国普通外科杂志,2004,13(8):578-582
[17]许戈良,荚卫东,马金良,等.槐耳浸膏体外抑制血管生成的实验研究.中国药理学通报,2003,19(12):1410-1412
[18]张芷旋,范羽,周清华,等.槐耳清膏对人高转移大细胞肺癌细胞L9981血管生成相关基因表达的影响.中国肺癌杂志,2006,9(2):137-142
[19]蒋梅,周岱翰.槐耳冲剂治疗中晚期原发性肝癌98例.上海中医药杂志,2004,38(6):21-22
[20]李凯,陶京,李弢,等.吉西他滨联和槐耳治疗无法切除胰腺癌的临床疗效.临床外科杂志,2007,15(4):240-242
[21]邓艾平,毛德莉.槐耳颗粒治疗消化系统恶性肿瘤74例临床观察.中国医院药学杂志,2005,25(5):453-454
[22]袁明,黄桂林,李志刚,等.槐耳颗粒配合化疗对大肠癌患者术后免疫功能的影响.中国肿瘤,2005,14(7):487-488
[23]姚建高,韩少良,朱冠宝,等.Ⅲ期胃癌术后联合化疗与金克的疗效.中国肿瘤,2003,12(10):606-608
[24]姚亚民,马智勇,赵艳秋.金克冲剂合并化疗治疗非小细胞肺癌4l例.中国肿瘤,2001,10(3):184-185
[25]李学兵.金克槐耳颗粒对Ⅲ期非小细胞肺癌患者免疫细胞活性的影响.临床肺科杂志,2006,11(4):472-473
[26]钟少文,江慧玲,刘鑫,等.金克槐耳颗粒治疗Ⅳ期乳腺癌.中国肿瘤,2003,12(12):754-755
[27]付美兰,郭丽英,玛依怒尔,等.槐耳颗粒对43例晚期乳腺癌化疗患者造血及免疫功能的影响.肿瘤学杂志,2005,11(4):318
[28]陈前军,赖熙雯,司徒红林,等.乳腺癌术前行槐耳颗粒联合化疗临床疗效.中国肿瘤,2004,13(5):330-331.
[29]邱仲川,陈佩,胡琦.金克对慢性粒细胞性白血病细胞因子的影响.中国肿瘤,2000,9(12):W001-W002
[30]赵文生.金克联合化疗对复发性非何杰金淋巴瘤的疗效.中国肿瘤,1999,8(5):237-238
[31]修忠标,朱夏.金克对骨肉瘤的化疗增效及减毒作用的临床观察.福建中医学院学报,2004,14(1):30-31
[1]何裕民.正确认识中医治疗肿瘤.家庭医生,2005,(9):21
[2]凌昌全.肿瘤治疗存在的问题及中西医结合的研究重点.中西医结合学报,2003,1(3):168-170
[3]沈晔华,宋明志,黄雯霞.中西医结合治疗71例乳腺癌术后患者的疗效分析.中西医结合学报,2003,1(1):30
[4]李佩文,毕国文,刘宝宽,等.参芪扶正注射液配合化疗治疗恶性肿瘤的临床观察.中国中药杂志,2000,25:115-117
[5]阙华发,陈红风,徐杰男,等.生命质量与中医药治疗恶性肿瘤临床疗效评价标准探讨,中西医结合学报,2005,7(4):254
[6]郑展,徐振晔.表皮生长因子受体及其信号转导通路与中西药肿瘤靶向治疗.中西医结合学报,2005,7(4):320
[7]黄承良,刘厚东.全反式维甲酸诱导分化治疗对胃癌患者免疫功能的影响.中国普外基础与临床杂志,2001,8(3):166-168
[8]Wang ZY,Chen Z.Differentiation and apoptosis induction therapy in acute promyelocytic leukaemia.Lancet Oncology,2000,l:101-106
[9]王振义.诱导分化治疗中的问题.中国肿瘤,2002,11(1):3-4
[10]张蓓,胡丕丽.中西医结合治疗对肿瘤患者生存质量的影响.中华肿瘤杂志,2003,5(3):304
[11]马晓燕.系统观认知方式与中医学认知方式之比较.医学与哲学,2000,21(9):41-42