李岩防治肿瘤学术思想及岩龙胶囊对Lewis肺癌的作用
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摘要
目的：
1.探索中医肿瘤专家李岩教授的学术思想和临床经验,作为继承老中医经验,对中医肿瘤人才培养和学科建设有参考作用。
2.实验研究岩龙胶囊对Lewis(?)市癌瘤株转染的C57BL/6小鼠的作用,为该药临床治疗提供理论依据。
方法：
1.对中医肿瘤专家李岩教授防治恶性肿瘤的主要学术思想进行总结和探索。方法包括通读其著作,重点在《肿瘤临证备要》、《肝癌防治锦囊》、《肺癌防治锦囊》、《乳腺癌防治锦囊》、《鼻咽癌防治锦囊》、《肠道抗癌力》、《癌前病变》等,总结提炼学术思想成文；在临床肿瘤诊疗中随诊李教授,记录其经验的点滴,然后总结成文；列举病例说明李教授临床处方开药的经验。
2.通过实验研究李教授所研制的岩龙胶囊对小鼠Lewis(?)市癌的作用。方法：将50只成功接种Lewis(?)市癌瘤株的C57BL/6小鼠随机分为5组：岩龙胶囊高、中、低剂量组,阳性对照组,阴性对照组,每组10只。造模后第8天,前三组灌胃给中药,每天1次,药量分别是一岩龙胶囊高剂量组：4.4g/kg；岩龙胶囊中剂量：2.2g/kg；岩龙胶囊低剂量：1.1g/kg。阳性对照组腹腔注射顺铂注射液(DDP),每天1次,剂量是0.001g/kg；四组共给药7天。阴性对照组用等体积生理盐水灌胃,每天1次,共7天。停药后继续观察7天。记录小鼠一般情况,造模后第21天处死小鼠检测各项指标。
结果：
一、临床理论研究
(一)李岩教授防治恶性肿瘤学术思想主要体现在“五位一体”的中西医结合防治恶性肿瘤理念。
1.“医”方面指重视临床指导思想,通过诊治肿瘤病人总结抗癌临床经验和教训。早在20世纪70年代工作上提出恶性肿瘤防治研究的重点内容是：狠抓三早(早期发现、早期诊断、早期治疗)；中西医结合(包括少数民族医学)；猛攻三关(病因关、早诊关、治疗关),提高临床疗效。
2.“教”方面指注重培训具有中西医技术的“临床、理论、实验”三结合的肿瘤科专业人员。他通过建立肿瘤机构,因才施教,在两岸三地培养了数十名中西医结合肿瘤科医生。
3.“研”方面指科研工作时强调“三严”,重视方法,更重视设题。药物研究特点既要重视中医中药理论的辨证论治,又要尊重现代药理,还有重视实验对肿瘤和整体的作用。他曾以临床与实验对照筛选了上百种抗癌单味中药,曾进行单味药和复方中药的荷瘤动物和试管筛选实验,曾观察多种中药的急慢性药物毒性及抗癌作用和对抗机体免疫功能的作用机制。
4.“药”方面指研制临床有效中成药。他研制的岩龙胶囊可用治多种恶性肿瘤如肝癌、肺癌、白血病、乳腺癌等中医辨证属于毒热蕴结型。
5.“书”方面提倡总结撰写肿瘤防治研究工作以及临床的经验和教训,留后辈学习借鉴。他在肿瘤方面的著作共580多万言,具有很强的临床实用性。
(二)李岩防治恶性肿瘤的临床理论
1.恶性肿瘤的观点：第一,认为恶性肿瘤是一大类疾病,在防治研究中,既要重视其共同规律,也要重视其在不同部位、不同系统、不同机体的特殊规律,对临床上可以提前用药控制病情的发展尤为重要。第二,认为恶性肿瘤的另一个重要特点是复发和转移,在治疗各个阶段中,均应对这种可能性给于充分的重视、估计及措施。
2.恶性肿瘤的病因：要求掌握中西医对肿瘤的发病理论认识。他认为中医学病因内容与现代致癌因素有相近之处,也有特殊之类。两者既不能混为一谈,也不能“对号入座”。此外,特别提出要重视癌前病变的防治。
3.恶性肿瘤的诊断：他提倡中西医结合的诊断方法。既有中医的四诊八纲,也要结合西医的化验、影像、病理报告作为诊断依据。
4.恶性肿瘤的治疗：提倡中西医结合治疗。要求掌握西医常规治疗的理论,而中医治疗要掌握中药、针灸、气功、按摩、心理调摄、膳食六个疗法及护理方法。
5.恶性肿瘤的预后：必须严格按西医的要求按时复查肿瘤是否复发和转移,按需要调整治疗和预防方案,并认真和较长时间地采用中医药预防肿瘤的复发和转移。
(三)李岩防治恶性肿瘤的临床经验
1.李岩防治恶性肿瘤临床经验介绍
(1)鼻咽癌、乳腺癌、肺癌、肝癌、胰腺癌和大肠癌的中医诊治经验,包括辨证论治、手术和放化疗期间的饮食及禁忌、练功、危象、复查及癌前病变的治疗验方等。
鼻咽癌的论治包括：①肝郁犯肺,气血凝聚型,治宜丹栀逍遥散加减；②肺胃蕴热,灼液成痰型,治宜清气化痰丸加减；③风热毒邪,蕴结脏腑,堵塞肺络型,治宜羚角钩藤汤加减；④正气衰败,气血双亏型,治宜人参养荣汤加减。
乳腺癌的论治包括：①肝郁气滞型,治法宜逍遥散加减；②脾阳不振,痰湿不化型,治宜十六味流气饮加减；③火毒蕴结型,治宜连翘金贝煎；④气血两虚、肝脾不调型,治宜人参养荣汤加减。
肺癌的论治包括：①肺毒血热型,治宜小蓟饮子加减；②肺瘀痰结型,治宜平胃散加减；③肺热阴虚型,治宜清燥救肺汤加减。
肝癌的论治包括：①瘀毒不化型,治宜白蛇六味散加味；②热毒蕴结,肝著癖黄型,治宜龙胆泻肝汤加减；③邪实体虚,正不抗邪型,治宜香砂六君子汤和理中地黄丸加减：
胰腺癌的论治包括：①脾胃湿热型,治宜茵陈蒿汤合龙蛇羊泉汤加减；②肝脾瘀结型,治宜膈下逐瘀汤合黄连解毒汤加减；③心脾实热型,治宜清心莲子饮加减,。
大肠癌的论治包括：①湿热蕴结型,治宜槐花地榆汤合白头瓮汤加减；②瘀毒内蕴型,治宜膈下逐瘀汤加减；③脾胃虚弱型,治宜参苓白术散加减；④肾阳亏虚型,治宜附子理中汤加减；⑤气血亏虚型,治宜儿珍汤合归脾汤加减。
(2)中医配合西医治疗恶性肿瘤增效减毒的经验：①列举治疗经验说明手术与中医药配合。②列举治疗经验说明放疗与中医药配合。③列举治疗经验说明化疗与中医药配合。④总结活血化瘀法在肿瘤科的应用。
2.李教授肿瘤临床经验的应用
(1)中医肿瘤组方的技巧包括：①处方前明确三个时间：发病时间、确诊时间、治疗时间,有助于初步确定方中药物治疗的扶正力度和祛邪力度的比例。②处方时辨清三个因素——病因、病机和病位,以确定治疗方案中辨证+辨病的选方选药。③处方后三审处方：审病求因是否正确,审机理对否,审辨证是否无误,以患者药后能标本兼治为目的。
(2)列举胰腺癌和乳腺癌术后放疗后肺转移两个病例的治疗,分析李教授临床处方开药的经验。
(四)探索李岩肿瘤学术思想的体会与思考
1.倡议建设独立中医肿瘤学科。
2.总结学习李教授防治恶性肿瘤临床经验需重点掌握的五个要点。
3.“辨证+辨病”组方思维探索。
二、实验研究
岩龙胶囊对小鼠Lewis(?)市癌的作用及作用机制结果：
(一)岩龙胶囊高、中、低剂量组,阳性对照组的抑瘤率分别是11.48%、3.95%、3.71%、21.17%。瘤重指数统计中,岩龙胶囊组均能降低瘤重指数,与阴性对照组对比,岩龙胶囊高、低剂量组p值均<0.001,岩龙胶囊中剂量组p<0.01,均有显著统计学意义。
(二)岩龙胶囊高、中、低剂量组、阳性对照组的肺转移抑瘤率分别是55.77%、19.23%、61.54%、65.38%。岩龙胶囊高、低剂量组能减少肺癌小鼠的肺转移结节数,与阴性对照组对比,均p<0.05,都有统计学意义。
(三)岩龙胶囊高、中、低剂量组、阳性对照组小鼠体内CD4值分别是10.33±4.30、6.68±1.68、7.72±4.48、10.90±3.94,与阴性对照组(4.81±2.61)对比,岩龙胶囊高、低剂量组、阳性对照组P值分别是p<0.01、p<0.05、p<0.001,均有统计学意义。岩龙胶囊高、中、低剂量组、阳性对照组小鼠体内CD44V6值分别是4.69±1.38、4.78±2.01、7.42±2.12、4.48±1.92,与阴性对照组(9.37±2.37)对比,岩龙胶囊高、中、低剂量组和阳性对照组p值均<0.001,均有显著统计学意义。
结论：
1.李岩的学术思想体现在“医、教、研、药、书一五位一体”的中西医结合防治恶性肿瘤理念。
2.李岩防治恶性肿瘤理论和临床经验可供中医或中西医结合临床实践参考。
3.李岩研制的岩龙胶囊对小鼠Lewis肺癌及其肺转移有一定的抑制作用。
4、岩龙胶囊抑制小鼠Lewis(?)市癌的作用机制之一可能与升高CD4的表达有关；其抑制肿瘤转移的作用机制之一,可能与降低CD44V6的表达有关。
Objective
1Explore Traditional Chinese Medicine (TCM) oncologist Professor Li yan's academic thoughts and clinical experience for the successors to inheriting the old doctor of TCM on which leading to the building of a useful reference for the training of the doctors of TCM as well as the scientific medical contruction.
2Experimental study of the function of Yanlong capsule dosing on C57BL/6mice with Lewis lung tumor lines transfected, in order to provide a theoretical basis for the clinical treatment of the above mentioned drug.
Methods
1Summarizing and exploring the academic thinking on the prevention and treatment of malignant tumors of TCM cancer expert Professor Li Yan. By thorough reading of his important books, such as "Tumor Clinical Preparatory Essential","Liver Cancer Prevention Tips","Nasopharyngeal Cancer Prevention Tips" etc, so as to record the experience learned and have them summed up in writing; cited cases which illustrate Professor Li's clinical drug prescription experience.
2Conduct experiment to study the function of action of the mice with Lewis lung carcinoma by the dosing of Yanlong capsule. Method:50successful inoculation of Lewis lung tumor strain C57BL/6mice were randomly divided into five groups, each group contain ten mice--they are low-dose, mid-dose and high-dose of Yanlong capsule groups, positive control group, and negative control group. After eight days, the first three groups were given to Yanlong capsule, once a day and the dosage are:Yanlong capsule high-dose roup-4.4g/kg, Yanlong capsule mid-dose group-2.2g/kg, Yanlong low-dose group-1.1g/kg; positive control group was injected intraperitoneally cisplatin (DDP) daily, these four groups were administered the medicine seven days. Observation was carried out for seven days after stopping the medicine. The general situation of the mice was recorded daily. After twenty-one days, the mice were to be killed after the detection of the indicators.
Results
1The Theoretical Study
1.1Professor Li Yan's prevention and treatment of malignant tumors academic thinking is mainly reflected in the "Five in one" of Chinese and Western medicine combined with the prevention and treatment of malignant tumors concept.
1.1.1In "Medical Care" aspect, he often emphasizes on the clinical guiding ideology, and through the diagnosis and treatment of patients with malignant tumors and to summarize the anti-cancer experience and lessons. Early in the1970s, he advocated the focus of the study of cancer prevention, which are: pay close attention early (early detection, early diagnosis and early treatment); integration of Chineses into Western medicine (including minority medicine); the completion of three processes (etiology, early diagnosis and related treatment). All the above improve clinical efficacy.
1.1.2In "Teaching" aspect, he placed the importance of training those oncology professionals with Chinese and Western medicine technology in the clinincal, theoretical and experimental field. By developing tumor institutions with his own teaching, he cultivated dozens of integrative medicine oncologist in PRC, Taiwan and Hongkong.
1.1.3In "Research" aspect, he required scientific research works to be carried out in an absolutely strict way, special attention should be placed to method and to the set questions. The drug research should not only attach importance to the diagnosis and treatment of TCM theory, in the meantime, respect should also be shown to modern pharmacology and the importance of the role of experiment of tumors and overall effect. He had once used the clinical and experimental contrast sifted through hundreds of anti-cancer single herbs. Single herbs and compound Chinese medicine were administered to tumor-bearing animals and in vitro screening experiments had been carried out by Professor Li. He made long term observation on a variety of Chinese medicine, acute and chronic toxicity, anti-cancer effects and the mechanism of confrontation of immune function.
1.1.4In "Drug" aspect, he developed clinical effective Chinese patent medicine. His Yanlong capsule has been seen to a variety of malignant tumors which belong to toxic heat accumulate junction, such as liver cancer, lung cancer, leukemia, breast cancer etc.
1.1.5In "Book" aspect, he concluded cancer prevention and control research as well as clinical experience and lessons learned in writing for the younger generation to learn from. His writings in tumors have more than58millions words and have very strong practicability.
1.2Li Yan's clinical theory for the prevention and treatment of malignant tumors.
1.2.1View of malignant tumors:Firstly, cancer is a class of disease, in the prevention and treatment research, it is necessary to attach importance to the common pattern, but also has to attach importance to its in different position, and different systems and different body special pattern, that is particularly important in controlling illness development for those case of clinical drug use in the earlier stage. Secondly, another important feature of malignancy of tumors is recurrence and metastasis. In the various stages of treatment, full attention, estimation and measures should be given to deal with the possibility of the above said feature.
1.2.2Cause of malignant tumors:To master pathology understanding of Chinese and Western medicine on tumors incidence are required. He believed that TCM etiology and modern carcinogenic factors have similarities, but also different in many ways, so the two cannot be confused. In addition, he stated that particular attention should be paid to the prevention and treatment of precancerous lesions.
1.2.3Diagnosis of malignancy:He advocated the diagnostic methods of integrative medicine. There are the eight principles of the four diagnosis in TCM, but also combined with Western medicine's laboratory, radiograph and pathologic reports as a diagnostic tool.
1.2.4The treatment of malignant tumors:Promoting the integration of Chinese medicine treatment into Western medicine treatment. He required the grasping of the routine treatment theory of the conventional Western medicine, and on the other hand, the mastering of the treatment of traditional Chinese medicine, acupuncture, qigong, massage, psychological cultivation, dietary therapy and nursing methods.
1.2.5The prognosis of malignant tumors:It is necessary to strictly in accordance with the requirement of the Western timely review of tumor recurrence and metastasis, and adjust the treatment and prevention programs as needed. A serious and long term use of Chinese medicine is necessary in preventing tumor recurrence and metastasis.
1.3Li Yan's clinical experience in the prevention and treatment of malignant tumors.
1.3.1Introduction of Li Yan's clinical experience in prevention and treatment of cancer.
1.3.1.1The experience of Chinese medicine diagnosis and treatment on nasopharyngeal cancer, breast cancer, lung cancer, pancreatic cancer and colorectal cancer; are acquired by including the syndrome differentiation, diagnosis and treatment of TCM, diet and contraindications during surgery, radiotherapy and chemotherapy; exercising, emergency, regular review and precancerous lesions treatment prescription and so on.
1.3.1.2The experience of combined Chinese and Western medicine to improve efficiency and decrearetosicity in the treatment of malignant tumors.
1.3.1.2.1List the experience to illustrate the combination of surgery and TCM.
1.3.1.2.2List the experience to illustrate the combination of radiotherapy and TCM.
1.3.1.2.3List the experience to illustrate the combination of chemotherapy and TCM.
1.3.1.2.4Summarize the application of blood circulation by removing blood stasis in oncology.
1.3.2Application of Professor Li Yan's clinical experience.
1.3.2.1Tradition Chinese oncology prescription techniques include:
1.3.2.1.1Make clear three timing prescription:time of onset, time of diagnosis, time of treatment, this help initially identified the prescription medication righting efforts and eliminate pathogenic strength ratio.
1.3.2.1.2Figured out three factors when prescription--etiology, pathogenesis and disease location, in order to determine the treatment of dialectical plus identify disease for medicine selection.
1.3.2.1.3Three trial prescription after prescription:trial whether the cause of disease is correct, trial whether mechanism in true, trial syndrome differentiation is right; so that the patient's drug is treating the symptoms.
1.3.2.2List two cases of pancreatic cancer and lung metastasis in breast cancer after radiotherapy treatment to analysis Professor Li's experience of clinical prescriptions.
1.4Explore Professor Li Yan's tumor academic ideas and thinking.
1.4.1Initiate building an independent oncology of TCM.
1.4.2Mastered the key five points that if you want to learn Professor Li's clinical experience on prevention and treatment of malignant tumors.
1.4.3Explore the thinking formula of treatment based on syndrome differentiation and disease differentiation.
2The Experimental Study, Yanlong capsule effect on mice bearing Lewis lung carcinoma and the results of action of mechanism.
2.1The inhibition rates of Yanlong capsule high, medium and low dose groups, positive control group were11.48%,3.95%,3.71%and21.17%respectively. In tumor weight index statistics, Yanlong capsule can reduce tumor Weight index compared with the negative control group, the Yanlong capsule high and low dose group p-value<0.001, Yanlong capsule mid-dose group p<0.01, all have significant statistical significance.
2.2The inhibition rates of Yanlong capsule high, medium and low dose groups, positive control group of lung metastasis were55.77%,19.23%,61.54%and65.38%respectively, Yanlong capsule high and low dose groups could reduce the pulmonary metastasis nodule number of lung cancer in mice, compared with the negative control group, all p<0.05, was statistically significant.
2.3Yanlong capsule high and low dose groups, positive control group had increased the expression of CD4, compared with the negative control group, P values were p<0.01, p<0.05and p<0.001respectively, this was statistically significant. Yanlong capsule high, medium and low dose groups as well as positive control group can reduce the expression of CD44V6, compared with the negative control group, all p<0.001, was also statistically significant.
Conclusion
1Li Yan's academic thinking is reflected in the "medical, teaching, research, drug and book"-the integration of the five aspects, as well as the mode of combination of Chinese and Western medicine in the prevention and treatment of malignant tumors.
2Li Yan's theory on prevention and treatment of malignant tumors and his clinical experience can be the reference for the doctors of TCM and also for the clinical practice of the combination of traditional Chinese medicine and Western medicine.
3The Yanlong capsule developed by Professor Li Yan applied to mice bearing Lewis lung tumor has certain inhibitory effect on its lung cancer and pulmonary metastasis.
4Yan Long capsule dosed on mice bearing Lewis lung cancer, one mechanism of inhibition of Lewis'lung cancer may be associated with increased expression of CD4; one of mechanism that inhibit tumor metastasis may be associated with reduced expression of CD44V6.
1.探索中医肿瘤专家李岩教授的学术思想和临床经验,作为继承老中医经验,对中医肿瘤人才培养和学科建设有参考作用。
2.实验研究岩龙胶囊对Lewis(?)市癌瘤株转染的C57BL/6小鼠的作用,为该药临床治疗提供理论依据。
方法：
1.对中医肿瘤专家李岩教授防治恶性肿瘤的主要学术思想进行总结和探索。方法包括通读其著作,重点在《肿瘤临证备要》、《肝癌防治锦囊》、《肺癌防治锦囊》、《乳腺癌防治锦囊》、《鼻咽癌防治锦囊》、《肠道抗癌力》、《癌前病变》等,总结提炼学术思想成文；在临床肿瘤诊疗中随诊李教授,记录其经验的点滴,然后总结成文；列举病例说明李教授临床处方开药的经验。
2.通过实验研究李教授所研制的岩龙胶囊对小鼠Lewis(?)市癌的作用。方法：将50只成功接种Lewis(?)市癌瘤株的C57BL/6小鼠随机分为5组：岩龙胶囊高、中、低剂量组,阳性对照组,阴性对照组,每组10只。造模后第8天,前三组灌胃给中药,每天1次,药量分别是一岩龙胶囊高剂量组：4.4g/kg；岩龙胶囊中剂量：2.2g/kg；岩龙胶囊低剂量：1.1g/kg。阳性对照组腹腔注射顺铂注射液(DDP),每天1次,剂量是0.001g/kg；四组共给药7天。阴性对照组用等体积生理盐水灌胃,每天1次,共7天。停药后继续观察7天。记录小鼠一般情况,造模后第21天处死小鼠检测各项指标。
结果：
一、临床理论研究
(一)李岩教授防治恶性肿瘤学术思想主要体现在“五位一体”的中西医结合防治恶性肿瘤理念。
1.“医”方面指重视临床指导思想,通过诊治肿瘤病人总结抗癌临床经验和教训。早在20世纪70年代工作上提出恶性肿瘤防治研究的重点内容是：狠抓三早(早期发现、早期诊断、早期治疗)；中西医结合(包括少数民族医学)；猛攻三关(病因关、早诊关、治疗关),提高临床疗效。
2.“教”方面指注重培训具有中西医技术的“临床、理论、实验”三结合的肿瘤科专业人员。他通过建立肿瘤机构,因才施教,在两岸三地培养了数十名中西医结合肿瘤科医生。
3.“研”方面指科研工作时强调“三严”,重视方法,更重视设题。药物研究特点既要重视中医中药理论的辨证论治,又要尊重现代药理,还有重视实验对肿瘤和整体的作用。他曾以临床与实验对照筛选了上百种抗癌单味中药,曾进行单味药和复方中药的荷瘤动物和试管筛选实验,曾观察多种中药的急慢性药物毒性及抗癌作用和对抗机体免疫功能的作用机制。
4.“药”方面指研制临床有效中成药。他研制的岩龙胶囊可用治多种恶性肿瘤如肝癌、肺癌、白血病、乳腺癌等中医辨证属于毒热蕴结型。
5.“书”方面提倡总结撰写肿瘤防治研究工作以及临床的经验和教训,留后辈学习借鉴。他在肿瘤方面的著作共580多万言,具有很强的临床实用性。
(二)李岩防治恶性肿瘤的临床理论
1.恶性肿瘤的观点：第一,认为恶性肿瘤是一大类疾病,在防治研究中,既要重视其共同规律,也要重视其在不同部位、不同系统、不同机体的特殊规律,对临床上可以提前用药控制病情的发展尤为重要。第二,认为恶性肿瘤的另一个重要特点是复发和转移,在治疗各个阶段中,均应对这种可能性给于充分的重视、估计及措施。
2.恶性肿瘤的病因：要求掌握中西医对肿瘤的发病理论认识。他认为中医学病因内容与现代致癌因素有相近之处,也有特殊之类。两者既不能混为一谈,也不能“对号入座”。此外,特别提出要重视癌前病变的防治。
3.恶性肿瘤的诊断：他提倡中西医结合的诊断方法。既有中医的四诊八纲,也要结合西医的化验、影像、病理报告作为诊断依据。
4.恶性肿瘤的治疗：提倡中西医结合治疗。要求掌握西医常规治疗的理论,而中医治疗要掌握中药、针灸、气功、按摩、心理调摄、膳食六个疗法及护理方法。
5.恶性肿瘤的预后：必须严格按西医的要求按时复查肿瘤是否复发和转移,按需要调整治疗和预防方案,并认真和较长时间地采用中医药预防肿瘤的复发和转移。
(三)李岩防治恶性肿瘤的临床经验
1.李岩防治恶性肿瘤临床经验介绍
(1)鼻咽癌、乳腺癌、肺癌、肝癌、胰腺癌和大肠癌的中医诊治经验,包括辨证论治、手术和放化疗期间的饮食及禁忌、练功、危象、复查及癌前病变的治疗验方等。
鼻咽癌的论治包括：①肝郁犯肺,气血凝聚型,治宜丹栀逍遥散加减；②肺胃蕴热,灼液成痰型,治宜清气化痰丸加减；③风热毒邪,蕴结脏腑,堵塞肺络型,治宜羚角钩藤汤加减；④正气衰败,气血双亏型,治宜人参养荣汤加减。
乳腺癌的论治包括：①肝郁气滞型,治法宜逍遥散加减；②脾阳不振,痰湿不化型,治宜十六味流气饮加减；③火毒蕴结型,治宜连翘金贝煎；④气血两虚、肝脾不调型,治宜人参养荣汤加减。
肺癌的论治包括：①肺毒血热型,治宜小蓟饮子加减；②肺瘀痰结型,治宜平胃散加减；③肺热阴虚型,治宜清燥救肺汤加减。
肝癌的论治包括：①瘀毒不化型,治宜白蛇六味散加味；②热毒蕴结,肝著癖黄型,治宜龙胆泻肝汤加减；③邪实体虚,正不抗邪型,治宜香砂六君子汤和理中地黄丸加减：
胰腺癌的论治包括：①脾胃湿热型,治宜茵陈蒿汤合龙蛇羊泉汤加减；②肝脾瘀结型,治宜膈下逐瘀汤合黄连解毒汤加减；③心脾实热型,治宜清心莲子饮加减,。
大肠癌的论治包括：①湿热蕴结型,治宜槐花地榆汤合白头瓮汤加减；②瘀毒内蕴型,治宜膈下逐瘀汤加减；③脾胃虚弱型,治宜参苓白术散加减；④肾阳亏虚型,治宜附子理中汤加减；⑤气血亏虚型,治宜儿珍汤合归脾汤加减。
(2)中医配合西医治疗恶性肿瘤增效减毒的经验：①列举治疗经验说明手术与中医药配合。②列举治疗经验说明放疗与中医药配合。③列举治疗经验说明化疗与中医药配合。④总结活血化瘀法在肿瘤科的应用。
2.李教授肿瘤临床经验的应用
(1)中医肿瘤组方的技巧包括：①处方前明确三个时间：发病时间、确诊时间、治疗时间,有助于初步确定方中药物治疗的扶正力度和祛邪力度的比例。②处方时辨清三个因素——病因、病机和病位,以确定治疗方案中辨证+辨病的选方选药。③处方后三审处方：审病求因是否正确,审机理对否,审辨证是否无误,以患者药后能标本兼治为目的。
(2)列举胰腺癌和乳腺癌术后放疗后肺转移两个病例的治疗,分析李教授临床处方开药的经验。
(四)探索李岩肿瘤学术思想的体会与思考
1.倡议建设独立中医肿瘤学科。
2.总结学习李教授防治恶性肿瘤临床经验需重点掌握的五个要点。
3.“辨证+辨病”组方思维探索。
二、实验研究
岩龙胶囊对小鼠Lewis(?)市癌的作用及作用机制结果：
(一)岩龙胶囊高、中、低剂量组,阳性对照组的抑瘤率分别是11.48%、3.95%、3.71%、21.17%。瘤重指数统计中,岩龙胶囊组均能降低瘤重指数,与阴性对照组对比,岩龙胶囊高、低剂量组p值均<0.001,岩龙胶囊中剂量组p<0.01,均有显著统计学意义。
(二)岩龙胶囊高、中、低剂量组、阳性对照组的肺转移抑瘤率分别是55.77%、19.23%、61.54%、65.38%。岩龙胶囊高、低剂量组能减少肺癌小鼠的肺转移结节数,与阴性对照组对比,均p<0.05,都有统计学意义。
(三)岩龙胶囊高、中、低剂量组、阳性对照组小鼠体内CD4值分别是10.33±4.30、6.68±1.68、7.72±4.48、10.90±3.94,与阴性对照组(4.81±2.61)对比,岩龙胶囊高、低剂量组、阳性对照组P值分别是p<0.01、p<0.05、p<0.001,均有统计学意义。岩龙胶囊高、中、低剂量组、阳性对照组小鼠体内CD44V6值分别是4.69±1.38、4.78±2.01、7.42±2.12、4.48±1.92,与阴性对照组(9.37±2.37)对比,岩龙胶囊高、中、低剂量组和阳性对照组p值均<0.001,均有显著统计学意义。
结论：
1.李岩的学术思想体现在“医、教、研、药、书一五位一体”的中西医结合防治恶性肿瘤理念。
2.李岩防治恶性肿瘤理论和临床经验可供中医或中西医结合临床实践参考。
3.李岩研制的岩龙胶囊对小鼠Lewis肺癌及其肺转移有一定的抑制作用。
4、岩龙胶囊抑制小鼠Lewis(?)市癌的作用机制之一可能与升高CD4的表达有关；其抑制肿瘤转移的作用机制之一,可能与降低CD44V6的表达有关。
Objective
1Explore Traditional Chinese Medicine (TCM) oncologist Professor Li yan's academic thoughts and clinical experience for the successors to inheriting the old doctor of TCM on which leading to the building of a useful reference for the training of the doctors of TCM as well as the scientific medical contruction.
2Experimental study of the function of Yanlong capsule dosing on C57BL/6mice with Lewis lung tumor lines transfected, in order to provide a theoretical basis for the clinical treatment of the above mentioned drug.
Methods
1Summarizing and exploring the academic thinking on the prevention and treatment of malignant tumors of TCM cancer expert Professor Li Yan. By thorough reading of his important books, such as "Tumor Clinical Preparatory Essential","Liver Cancer Prevention Tips","Nasopharyngeal Cancer Prevention Tips" etc, so as to record the experience learned and have them summed up in writing; cited cases which illustrate Professor Li's clinical drug prescription experience.
2Conduct experiment to study the function of action of the mice with Lewis lung carcinoma by the dosing of Yanlong capsule. Method:50successful inoculation of Lewis lung tumor strain C57BL/6mice were randomly divided into five groups, each group contain ten mice--they are low-dose, mid-dose and high-dose of Yanlong capsule groups, positive control group, and negative control group. After eight days, the first three groups were given to Yanlong capsule, once a day and the dosage are:Yanlong capsule high-dose roup-4.4g/kg, Yanlong capsule mid-dose group-2.2g/kg, Yanlong low-dose group-1.1g/kg; positive control group was injected intraperitoneally cisplatin (DDP) daily, these four groups were administered the medicine seven days. Observation was carried out for seven days after stopping the medicine. The general situation of the mice was recorded daily. After twenty-one days, the mice were to be killed after the detection of the indicators.
Results
1The Theoretical Study
1.1Professor Li Yan's prevention and treatment of malignant tumors academic thinking is mainly reflected in the "Five in one" of Chinese and Western medicine combined with the prevention and treatment of malignant tumors concept.
1.1.1In "Medical Care" aspect, he often emphasizes on the clinical guiding ideology, and through the diagnosis and treatment of patients with malignant tumors and to summarize the anti-cancer experience and lessons. Early in the1970s, he advocated the focus of the study of cancer prevention, which are: pay close attention early (early detection, early diagnosis and early treatment); integration of Chineses into Western medicine (including minority medicine); the completion of three processes (etiology, early diagnosis and related treatment). All the above improve clinical efficacy.
1.1.2In "Teaching" aspect, he placed the importance of training those oncology professionals with Chinese and Western medicine technology in the clinincal, theoretical and experimental field. By developing tumor institutions with his own teaching, he cultivated dozens of integrative medicine oncologist in PRC, Taiwan and Hongkong.
1.1.3In "Research" aspect, he required scientific research works to be carried out in an absolutely strict way, special attention should be placed to method and to the set questions. The drug research should not only attach importance to the diagnosis and treatment of TCM theory, in the meantime, respect should also be shown to modern pharmacology and the importance of the role of experiment of tumors and overall effect. He had once used the clinical and experimental contrast sifted through hundreds of anti-cancer single herbs. Single herbs and compound Chinese medicine were administered to tumor-bearing animals and in vitro screening experiments had been carried out by Professor Li. He made long term observation on a variety of Chinese medicine, acute and chronic toxicity, anti-cancer effects and the mechanism of confrontation of immune function.
1.1.4In "Drug" aspect, he developed clinical effective Chinese patent medicine. His Yanlong capsule has been seen to a variety of malignant tumors which belong to toxic heat accumulate junction, such as liver cancer, lung cancer, leukemia, breast cancer etc.
1.1.5In "Book" aspect, he concluded cancer prevention and control research as well as clinical experience and lessons learned in writing for the younger generation to learn from. His writings in tumors have more than58millions words and have very strong practicability.
1.2Li Yan's clinical theory for the prevention and treatment of malignant tumors.
1.2.1View of malignant tumors:Firstly, cancer is a class of disease, in the prevention and treatment research, it is necessary to attach importance to the common pattern, but also has to attach importance to its in different position, and different systems and different body special pattern, that is particularly important in controlling illness development for those case of clinical drug use in the earlier stage. Secondly, another important feature of malignancy of tumors is recurrence and metastasis. In the various stages of treatment, full attention, estimation and measures should be given to deal with the possibility of the above said feature.
1.2.2Cause of malignant tumors:To master pathology understanding of Chinese and Western medicine on tumors incidence are required. He believed that TCM etiology and modern carcinogenic factors have similarities, but also different in many ways, so the two cannot be confused. In addition, he stated that particular attention should be paid to the prevention and treatment of precancerous lesions.
1.2.3Diagnosis of malignancy:He advocated the diagnostic methods of integrative medicine. There are the eight principles of the four diagnosis in TCM, but also combined with Western medicine's laboratory, radiograph and pathologic reports as a diagnostic tool.
1.2.4The treatment of malignant tumors:Promoting the integration of Chinese medicine treatment into Western medicine treatment. He required the grasping of the routine treatment theory of the conventional Western medicine, and on the other hand, the mastering of the treatment of traditional Chinese medicine, acupuncture, qigong, massage, psychological cultivation, dietary therapy and nursing methods.
1.2.5The prognosis of malignant tumors:It is necessary to strictly in accordance with the requirement of the Western timely review of tumor recurrence and metastasis, and adjust the treatment and prevention programs as needed. A serious and long term use of Chinese medicine is necessary in preventing tumor recurrence and metastasis.
1.3Li Yan's clinical experience in the prevention and treatment of malignant tumors.
1.3.1Introduction of Li Yan's clinical experience in prevention and treatment of cancer.
1.3.1.1The experience of Chinese medicine diagnosis and treatment on nasopharyngeal cancer, breast cancer, lung cancer, pancreatic cancer and colorectal cancer; are acquired by including the syndrome differentiation, diagnosis and treatment of TCM, diet and contraindications during surgery, radiotherapy and chemotherapy; exercising, emergency, regular review and precancerous lesions treatment prescription and so on.
1.3.1.2The experience of combined Chinese and Western medicine to improve efficiency and decrearetosicity in the treatment of malignant tumors.
1.3.1.2.1List the experience to illustrate the combination of surgery and TCM.
1.3.1.2.2List the experience to illustrate the combination of radiotherapy and TCM.
1.3.1.2.3List the experience to illustrate the combination of chemotherapy and TCM.
1.3.1.2.4Summarize the application of blood circulation by removing blood stasis in oncology.
1.3.2Application of Professor Li Yan's clinical experience.
1.3.2.1Tradition Chinese oncology prescription techniques include:
1.3.2.1.1Make clear three timing prescription:time of onset, time of diagnosis, time of treatment, this help initially identified the prescription medication righting efforts and eliminate pathogenic strength ratio.
1.3.2.1.2Figured out three factors when prescription--etiology, pathogenesis and disease location, in order to determine the treatment of dialectical plus identify disease for medicine selection.
1.3.2.1.3Three trial prescription after prescription:trial whether the cause of disease is correct, trial whether mechanism in true, trial syndrome differentiation is right; so that the patient's drug is treating the symptoms.
1.3.2.2List two cases of pancreatic cancer and lung metastasis in breast cancer after radiotherapy treatment to analysis Professor Li's experience of clinical prescriptions.
1.4Explore Professor Li Yan's tumor academic ideas and thinking.
1.4.1Initiate building an independent oncology of TCM.
1.4.2Mastered the key five points that if you want to learn Professor Li's clinical experience on prevention and treatment of malignant tumors.
1.4.3Explore the thinking formula of treatment based on syndrome differentiation and disease differentiation.
2The Experimental Study, Yanlong capsule effect on mice bearing Lewis lung carcinoma and the results of action of mechanism.
2.1The inhibition rates of Yanlong capsule high, medium and low dose groups, positive control group were11.48%,3.95%,3.71%and21.17%respectively. In tumor weight index statistics, Yanlong capsule can reduce tumor Weight index compared with the negative control group, the Yanlong capsule high and low dose group p-value<0.001, Yanlong capsule mid-dose group p<0.01, all have significant statistical significance.
2.2The inhibition rates of Yanlong capsule high, medium and low dose groups, positive control group of lung metastasis were55.77%,19.23%,61.54%and65.38%respectively, Yanlong capsule high and low dose groups could reduce the pulmonary metastasis nodule number of lung cancer in mice, compared with the negative control group, all p<0.05, was statistically significant.
2.3Yanlong capsule high and low dose groups, positive control group had increased the expression of CD4, compared with the negative control group, P values were p<0.01, p<0.05and p<0.001respectively, this was statistically significant. Yanlong capsule high, medium and low dose groups as well as positive control group can reduce the expression of CD44V6, compared with the negative control group, all p<0.001, was also statistically significant.
Conclusion
1Li Yan's academic thinking is reflected in the "medical, teaching, research, drug and book"-the integration of the five aspects, as well as the mode of combination of Chinese and Western medicine in the prevention and treatment of malignant tumors.
2Li Yan's theory on prevention and treatment of malignant tumors and his clinical experience can be the reference for the doctors of TCM and also for the clinical practice of the combination of traditional Chinese medicine and Western medicine.
3The Yanlong capsule developed by Professor Li Yan applied to mice bearing Lewis lung tumor has certain inhibitory effect on its lung cancer and pulmonary metastasis.
4Yan Long capsule dosed on mice bearing Lewis lung cancer, one mechanism of inhibition of Lewis'lung cancer may be associated with increased expression of CD4; one of mechanism that inhibit tumor metastasis may be associated with reduced expression of CD44V6.
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[13]周岱翰.论中医肿瘤学在临床中的应用与前景[J].2009国际中医药肿瘤大会.
[14]史志萍.循证医学在中医肿瘤治疗研究中的存在问题和价值[J].2009年首届全国中西医肿瘤博士及中青医师论坛.
[15]潘伟光,刘宗潮,潘启超,等.中药复方龙葵合剂在动物体内外的抗癌药效[J].癌症,1996,16(6)：438.
[16]何其梅,陈积圣,刘晋华,等.岩龙抗癌液在中、晚期肝癌综合治疗中的应用[J].实用医学杂志,1998,14(6)：468.
[17]梁新文,林显敢,谢德荣,等.中晚期恶性肿瘤化疗辅以岩龙口服液的近期疗效[J].实用医学杂志,2000,16(4)：1320-1321.
[18]李春艳,王颖,刘浩,等C57BL/6近交系小鼠Lewis肺癌动物模型：建设性描述肺癌损害程度的指标[J].中国临床康复,2003,7(26)：3582-3583.
[19]潘玉真,殷东风,周立江,等.柴胡龙牡汤对Lewis肺癌小鼠细胞免疫功能的影响[J].临床中医学2011,16(3)：211-215.
[20]冯利,花宝金,朴炳奎,等.肺瘤平Ⅱ号对Lewis肺癌小鼠瘤细胞CD_(44)V6及CD_(49)表达的影响[J].中国新药杂志,2007,16(1)：33-35.
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[23]彭博,胡秦,王立为,等.蛇莓总酚的抗肿瘤作用及免疫学机制的初步探讨[J].中国药理学通报,2007,23(8)：1007-1009.
[24]吴培楠,段宏泉,姚智,等.蛇莓中具有抗癌活性的三萜类成分[J].中草药,2007,38(9)：1311-1313.
[25]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：630-631.
[26]Lee S J, Lim K T. Antioxidative effect ofglycoprotein isolatedfrom Solanum nigrum Linne on oxygen radicals and its cytoto-xic effect on the MCF-7 call [J].J Food Sci,2003,68(2):466.
[27]高思国,李冠业,丁霞.龙葵正丁醇提取物体外抗肿瘤活性的研究[J].江苏中医药,2010，42(11)：76-78.
[28]季宇彬,高世勇.龙葵碱诱导HepG2细胞的线粒体通路研究[J].中国药学杂志,2008,43(4)：272-275.
[29]梅全喜.广东地产药材研究[M].广东：上海科学技术出版社,2011：247-249.
[30]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：700-701.
[31]任靖,冯国楠,王敏伟,等.白英总苷抗肿瘤作用初步研究[J].肿瘤防治研究,2006,33(4)：262-264.
[32]刘淑华,魏仙凤,白美姣.白英畄体皂苷对肿瘤细胞的体外增殖抑制作用[J].江西中医药,2010,41(1)：71-73.
[33]Ren Y, Shen L, Zhang DW, DaiSJ Two new sesquitepenoids from Solanum lyratum with cytotoxic activities[J]. Chemical& pham aceutical bulletin,2009,57(4):408-410.
[34]万春霞.白英抗肿瘤研究进展[J].江西中医药,2010,41(12)：75-78.
[35]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：876-877.
[36]洪艳,刘煜敏,熊小红,等.当归多糖对放射损伤小鼠红细胞免疫功能和造血功能的保护作用[J].医药临床研究：2002,19(1)：31-32.
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[38]金海峰,吕宾,陈喆,等.温郁金二萜类化和物C对人结肠癌细胞SW620增殖的影响[J].医药导报：2011,30(2)：160-162.
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[40]袁淑兰,羊裔明,王修杰,等.丹参酮在治疗肿瘤药物中的应用[P].国家专利知识产权局发明专利公报.第16卷,第五期.申请号：99121460.9,公开号：CN1264580A
[41]贾志宇,陈彪,郭立华,等.丹参酮ⅡA对舌鳞状细胞癌细胞系TCA-83增殖和调亡的影响[J].实用口腔医学杂志：2012,28(1)：59-63.
[42]任牡丹,胡雅楠,和水详,等.丹参酮Ⅱ A对人肝癌细胞Ang-2及其受体Tie-2表达的影响[J].西安交通大学医学报：2012,33(2)：203-210.
[43]李健,武彪,李映良.丹参酮ⅡA对人乳腺癌细胞MDA-MB-231作用的实验研究[J].军医进修学院学报：2012,33(7)：754-756.
[44]吴庆庆.丹参酮Ⅱ A对肺腺癌NCI-H460细胞增殖和调亡的影响[J].实用医学杂志：2012,28(6)：877-879.
[45]刘宣,王炎,李丹光,等.丹参酮ⅡA对COX-2激活Wnt/β-catenin信号通路介导的人 肠癌细胞VEGF表达的调控作用[J].中华中医药杂志：2013,28(1)：108-112.
[46]王婷,何光源.隐丹参酮在人肝癌HepG2细胞中的抗肿瘤作用机制[D].中华中医药杂志华中科技大学硕士论文.2007.
[47]叶因涛,徐文清.隐丹参酮对宫颈癌细胞系Hela细胞放射增敏作用及其机制的研究[J].中国药理通讯.2009,26(002)：13-14.
[48]陈春雷,弓建华,缪辉来,等.隐丹参酮对人胆管癌HCCC-9810细胞中survivin基因表达的影响[J].广东医学.2011,32(23)：3028-3031.
[49]Park I J, Kim M J, Park 0 J, et al. Crytotanshinone sensitizes DU145 prostate cancer cells to Fas(APO1/Cd95)-mediated apoptosis though Bcl-2 and MAPK regulation [J]. Cancer Lett,2010,298(1):88-98.
[50]张玥,张英姿,徐天和,等.丹参素对子宫内膜癌KLE细胞体外抑制作用的实验研究[J].滨州医学院学报.2012,35(1)：5-9.
[51]罗军,靳风烁.肿瘤的免疫逃逸机制研究进展[J].肿瘤防治研究.2004,31(7)：454-456.
[52]陆金春,黄宇烽,张锡然等主编.英汉细胞与分子生物学词典[M].上海：第二军医大学出版社.2004：111-112.
[53]HaynesBF, liaoHX, pattonKL. Thetrans-memberanehyaluronatereceptor (cD44): mul-tiplefunctionsmultipleforms.CancerCells 1991; 3:347
[54]Arch r, wirthK, hofmannM, etal. Partici-pation innormal immune responses of ametas-tasis- inducing splice variant of CD44. Science 1992; 257:682
[55]UnderhillC. CD44:thehyaluronanreceptor. JCellSci1992; 103:293
[56]thomasL, etohT, stamenkovicI, etal. Mi-grotion of melanomacellsonhyaluronateisre-latedtoCD44expression. JInvestDermatol1993; 100:115
[57]廖军鲜,王凤计主编.脱落细胞诊断学及彩色图谱[M].天津：天津科学技术出版社.2003：15-16.
[2]李忠,白桦,张雅月,等.中医肿瘤学科现状分析与发展思路[J].2009国际中医药肿瘤大会.
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[12]朴炳奎.对中医肿瘤个体化治疗的思考[J].第三届国际中医、中西医结合肿瘤学术交流大会既第十二届全国中西医结合肿瘤学术大会.
[13]周岱翰.论中医肿瘤学在临床中的应用与前景[J].2009国际中医药肿瘤大会.
[14]史志萍.循证医学在中医肿瘤治疗研究中的存在问题和价值[J].2009年首届全国中西医肿瘤博士及中青医师论坛.
[15]潘伟光,刘宗潮,潘启超,等.中药复方龙葵合剂在动物体内外的抗癌药效[J].癌症,1996,16(6)：438.
[16]何其梅,陈积圣,刘晋华,等.岩龙抗癌液在中、晚期肝癌综合治疗中的应用[J].实用医学杂志,1998,14(6)：468.
[17]梁新文,林显敢,谢德荣,等.中晚期恶性肿瘤化疗辅以岩龙口服液的近期疗效[J].实用医学杂志,2000,16(4)：1320-1321.
[18]李春艳,王颖,刘浩,等C57BL/6近交系小鼠Lewis肺癌动物模型：建设性描述肺癌损害程度的指标[J].中国临床康复,2003,7(26)：3582-3583.
[19]潘玉真,殷东风,周立江,等.柴胡龙牡汤对Lewis肺癌小鼠细胞免疫功能的影响[J].临床中医学2011,16(3)：211-215.
[20]冯利,花宝金,朴炳奎,等.肺瘤平Ⅱ号对Lewis肺癌小鼠瘤细胞CD_(44)V6及CD_(49)表达的影响[J].中国新药杂志,2007,16(1)：33-35.
[21]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：2116.
[22]段泾云,刘小平,李秦.蛇莓抗肿瘤作用研究[J].中草药,1998,14(3)：28.
[23]彭博,胡秦,王立为,等.蛇莓总酚的抗肿瘤作用及免疫学机制的初步探讨[J].中国药理学通报,2007,23(8)：1007-1009.
[24]吴培楠,段宏泉,姚智,等.蛇莓中具有抗癌活性的三萜类成分[J].中草药,2007,38(9)：1311-1313.
[25]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：630-631.
[26]Lee S J, Lim K T. Antioxidative effect ofglycoprotein isolatedfrom Solanum nigrum Linne on oxygen radicals and its cytoto-xic effect on the MCF-7 call [J].J Food Sci,2003,68(2):466.
[27]高思国,李冠业,丁霞.龙葵正丁醇提取物体外抗肿瘤活性的研究[J].江苏中医药,2010，42(11)：76-78.
[28]季宇彬,高世勇.龙葵碱诱导HepG2细胞的线粒体通路研究[J].中国药学杂志,2008,43(4)：272-275.
[29]梅全喜.广东地产药材研究[M].广东：上海科学技术出版社,2011：247-249.
[30]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：700-701.
[31]任靖,冯国楠,王敏伟,等.白英总苷抗肿瘤作用初步研究[J].肿瘤防治研究,2006,33(4)：262-264.
[32]刘淑华,魏仙凤,白美姣.白英畄体皂苷对肿瘤细胞的体外增殖抑制作用[J].江西中医药,2010,41(1)：71-73.
[33]Ren Y, Shen L, Zhang DW, DaiSJ Two new sesquitepenoids from Solanum lyratum with cytotoxic activities[J]. Chemical& pham aceutical bulletin,2009,57(4):408-410.
[34]万春霞.白英抗肿瘤研究进展[J].江西中医药,2010,41(12)：75-78.
[35]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：876-877.
[36]洪艳,刘煜敏,熊小红,等.当归多糖对放射损伤小鼠红细胞免疫功能和造血功能的保护作用[J].医药临床研究：2002,19(1)：31-32.
[37]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：1316-1317.
[38]金海峰,吕宾,陈喆,等.温郁金二萜类化和物C对人结肠癌细胞SW620增殖的影响[J].医药导报：2011,30(2)：160-162.
[39]江苏新医学院主编,中药大辞典[M].上海：上海科学技术出版社,2002：478-480.
[40]袁淑兰,羊裔明,王修杰,等.丹参酮在治疗肿瘤药物中的应用[P].国家专利知识产权局发明专利公报.第16卷,第五期.申请号：99121460.9,公开号：CN1264580A
[41]贾志宇,陈彪,郭立华,等.丹参酮ⅡA对舌鳞状细胞癌细胞系TCA-83增殖和调亡的影响[J].实用口腔医学杂志：2012,28(1)：59-63.
[42]任牡丹,胡雅楠,和水详,等.丹参酮Ⅱ A对人肝癌细胞Ang-2及其受体Tie-2表达的影响[J].西安交通大学医学报：2012,33(2)：203-210.
[43]李健,武彪,李映良.丹参酮ⅡA对人乳腺癌细胞MDA-MB-231作用的实验研究[J].军医进修学院学报：2012,33(7)：754-756.
[44]吴庆庆.丹参酮Ⅱ A对肺腺癌NCI-H460细胞增殖和调亡的影响[J].实用医学杂志：2012,28(6)：877-879.
[45]刘宣,王炎,李丹光,等.丹参酮ⅡA对COX-2激活Wnt/β-catenin信号通路介导的人 肠癌细胞VEGF表达的调控作用[J].中华中医药杂志：2013,28(1)：108-112.
[46]王婷,何光源.隐丹参酮在人肝癌HepG2细胞中的抗肿瘤作用机制[D].中华中医药杂志华中科技大学硕士论文.2007.
[47]叶因涛,徐文清.隐丹参酮对宫颈癌细胞系Hela细胞放射增敏作用及其机制的研究[J].中国药理通讯.2009,26(002)：13-14.
[48]陈春雷,弓建华,缪辉来,等.隐丹参酮对人胆管癌HCCC-9810细胞中survivin基因表达的影响[J].广东医学.2011,32(23)：3028-3031.
[49]Park I J, Kim M J, Park 0 J, et al. Crytotanshinone sensitizes DU145 prostate cancer cells to Fas(APO1/Cd95)-mediated apoptosis though Bcl-2 and MAPK regulation [J]. Cancer Lett,2010,298(1):88-98.
[50]张玥,张英姿,徐天和,等.丹参素对子宫内膜癌KLE细胞体外抑制作用的实验研究[J].滨州医学院学报.2012,35(1)：5-9.
[51]罗军,靳风烁.肿瘤的免疫逃逸机制研究进展[J].肿瘤防治研究.2004,31(7)：454-456.
[52]陆金春,黄宇烽,张锡然等主编.英汉细胞与分子生物学词典[M].上海：第二军医大学出版社.2004：111-112.
[53]HaynesBF, liaoHX, pattonKL. Thetrans-memberanehyaluronatereceptor (cD44): mul-tiplefunctionsmultipleforms.CancerCells 1991; 3:347
[54]Arch r, wirthK, hofmannM, etal. Partici-pation innormal immune responses of ametas-tasis- inducing splice variant of CD44. Science 1992; 257:682
[55]UnderhillC. CD44:thehyaluronanreceptor. JCellSci1992; 103:293
[56]thomasL, etohT, stamenkovicI, etal. Mi-grotion of melanomacellsonhyaluronateisre-latedtoCD44expression. JInvestDermatol1993; 100:115
[57]廖军鲜,王凤计主编.脱落细胞诊断学及彩色图谱[M].天津：天津科学技术出版社.2003：15-16.