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Clinical And Laboratory Research On The Treatment Of Chronic Myelocytic Leukemia By Qudu Huayu Formula

Posted on:2006-04-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:H Y LiFull Text:PDF
GTID:1104360152497981Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Chronic myelocytic leukemia is one of obtaining and malignant cloning disease of hemopoietic stem cell. It involves in marrow mainly, lasting and processing increasement of leucocyte is its manifestation. Its classification includes different differentiation stages of granulocytic cell, main parts of them are below myelocytes and partial maturity. Its another character is most of patients have tumefactionl spleens. More than 90 percent patients' myelocytes have characteristic Ph chromosome or bcr/abl fusion gene. Most patients exist three or four years. Chronic myelocytic leukemia is one of malignant diseases which threaten to our health seriously. In recent years, how to treat chronic myelocytic leukemia, how to rise clinical effect and how to spread exist time and rise exist quality become focal point of investigation.The etiological factor of chronic myelocytic leukemia is extraordinarily complex. Radiation factor and chemical factor are very important. Smoking and drinking also can add more chances to have chronic myelocytic leukemia. Virus and genetic factor maybe are chronic myelocytic leukemia' s etiological factor, but somebody think of the possibility of multiagent. Basic mechanism which leads to chronic myelocytic leukemia is characteristic Ph chromosome in bone marrow. Ph chromosome is less than normal chromatosome of number 22. The reciprocal translocation of long arm distal end between number 9 and number 22 chromatosome become Philadelphia chromosome. Technical certification that reciprocal translocation between 3 area 4 cord of long arm of number 9 and 1 area lcord of number 22 constituents t(9; 22) (q34; q11) . Above 90 percent patients' myelocytes of metaphase dividing cell havethe abnormality of characteristic chromosome karyotype. About 5 percent patients' myelocytes have differentiated Philadelphia chromosome. The basic of molecular biology of Philadelphia chromosome is generearrangement of BCR/ABL. In lately years, more viewpoints make clear that BCR/ABL is one kind of anti-program death gene. It can conjugate or activate multi- signal correlation molecul in cells. This can not cause cells of CML death in time and every series of differentiated stage cells accumulate in hematopoietic tissue and blood. It can conjugate or activate many signal correlated molecul which cause the cells of CML could not die in time. Every Series and different differentiation stage cells accumulate in hematopoietic tissue and blood. Another people think stem cell of CML exist adhesive runctional defect which stem cells escape from interstitial portion of bone marrow and lead to incoordination between proliferation and differentiation and these unmature cells go straight through blood brain barrier of bone marrow easyily, then flow into blood circulation. Transcriptional mRNA of this fusion gene interprets protein molecular weight is 210Kda. This protein is called P210. Somebody think it is important to chronic period of chronic myelocytic leukemia. P210 posseses transparent reinforce PTK activity. This kind of enzyme is important to introduce signal convection among cells and interact normal build blood cell proliferation. Now that, it is clear that P210 can inhibit marrow cells apoptosis. Somebody support that the expression of cellular protein tyrosine level and binding ability of action obstructs normal signal conduction pathway. The cells are missing reactivity to circumference and influence the proliferation, adherence, differentiation and apoptosis. The cells develop canceration in the last. So it is important to find how to preclude or how to decrease gene expression of bcr/abl of CML, especially for rising the therapeutic efficacy and survival rate.The objective of treatment of CML is to ameliorate clinical symptom and abnormality of hematology for so many years. Now hydroxyurea is selected commonly in clinic. The second is INF. INF began to use from 1980. The effect of it is confirmed. But the bad thing is it is not advantageous to remission of cytogenetics and the period of existence when patients break medication and use little dosage. If patients use large dosage, one hand the cost is expensive, the other hand 20% patient can not tolerant ill effect. Following the investigation of pathogenesis of CML deeply, people have already knownthat patient have characteristic chromatosome of Ph, and then form fusion gene of BCR / ABL. The fusion gene of BCR / ABL develop fusion protein, the fusion protein has abnormily increasing activity of PTK, thus lead to occurrence and development of CML. Basis on this, people manufactured signal transduction inhibitor STI-571. STI-571 is derivative of 2-pyramine which can block binding site between ATP and Abl kinase selectively and inhibit phosphoric acidulation of tyrosine residue in kinase substrate of BCR / ABL. Enzyme loses its activation and prevention a series of signal transduction. But many people could not pay the cost. Somebody adopt chemistry therapy of association. Not only the ill effect is fairly serious but also the effect is nol good. Now mostly people think part of patient of CML can get fully recover from an illness by different gene stem cell remove. But incidence is high because of absence suitable donor and old recipient causing death GVHD. So , not everyone is benefited from different gene stem cell transplantation.It is a long time that the Traditional Chinese Medicine treated chronic myelocytic leukemia. The discussion of Traditional Chinese Medicine treating CML becomes focal point and hot spot. From early Liu shen wan to Da huang zhe chong wan, detoxication or the method of promoting blood circulation to remove stasis is basic treatment. Recently, arsenic trioxide or arsenious acid which is capital chemistry component of arsenic frost is detected and begin to use in clinic comprehensively. It is found that arsenic trioxide treat leukemia of M3 best by analysis of statistics. Besides that, it is detected from the investigation of response pattern of arsenic trioxide that arsenic trioxide can treat CML. Arsenic trioxide can decrease vital force and of level of TPK of protein tyrosine phosphoric acid of BCR/ABL and C—ABL of K562 and decrease confluence protein of BCR/ABL and STAT1 protein and control PTK activity of confluence protein of BCR/ABL. Arsenic trioxide treat leukemia makes it clear that traditional Chinese medicine has extraordinary wide prospect in treating CML.We use traditional theory of Traditional Chinese Medicine and bind main clinical situation of CML, think main pathogenesis of CML relating to stasis and toxin. Abundance of vicious qi of liu yin raids body or internal damage qiqing, not continence of diet, loss degree of work and rest lead to function derangement of viscera and organs. Thus qi and blood run abnormally. Qi andblood stay and become stasis if they can not run normally. Stasis accumulate in body, the chance of contact of toxin with body.In such suitable environment, toxin causes disease easily and lead to derangement of body function. Internal toxin develops. We call it from toxin to stasis and then to toxin. At the same time, Internal toxin can damage zhengqi of body, vicious invades our body easily, malignant circulation occurs in this way. Toxin and stasis have very close relationship, stasis can change into toxin, toxin can change into stasis also. Mechanism of toxin changing into stasis involves five parts. Firstly, toxin is tortured and smoked, the blood is fried and becomes stasis. Secondly, toxin burns meridian, blood flows out of vessel and changes into stasis. Thirdly, body fluid is wasted, blood stagnates and becomes stasis. Fourthly, stasis stagnates qi, blood stream is stopped. Fifthly, toxin of hot damages five viscera, blood stream miss its normal running. So we think that it is common change of stasis and toxin which is formed by interaction in process of CML. Toxin can not exist if without stasis, people can not get sick without stasis.We adopt toxin and stasis as themry, use the method of removing stasis and detoxication, like cures like and the method of promoting blood circulation to remove stasis are used to treat CML, precluding toxin and removing stasisat the same time. We conform basis preparation by chan shu, zhe chong, da huang, qi ye yi zhi hua. By in vitro experiment and clinical observation, we detect that the preparation of the method of removing stasis and detoxication can kill the cells of CML and decrease the expression of fusion gene of BCR/ABL. It also can increase the efficiency of treatment of CML and rise clinical effect.In the investigation of clinic, we observed patients of CML who have been final diagnosis in the affiliated hospital of Guangzhou University of TCM. Eighteen patients were divided into trial group of combination of TCM and western medicine and matched control group of simple using western medicine. Trial group use hydroxyurea according to routine project, at the same time add capsules of the preparation. Three times per day, two capsules every time. Matched control group only use hydroxyurea according to routine project. Two groups receptd the same support treatment of on the basis of symptom. One course is a month. Result: symptom of two groups both is improved obviously after treatment. Except dry mouth and throat, extremity hot, trial group isexcellent to matched control group ( p>0.05 ) . Physical sign of hepatosplenomegaly is improved also in two groups post-treatment comparing to pretreatment. Because of less cases, we did not statistics. The number of leucocyte, neutrophilic myelocyte and neutrophilic metamyelocyte of blood were improved in two groups in post-treatment. It is obviously different of leucocyte post-treatment between trial groups and matched control groups. Neutrophilic myelocyte and neutrophilic metamyelocyte of blood are not different in post-treatment(p>0. 05). In bone marrow, the degree of hyperplasia, the per cent of neutrophilic myelocyte, neutrophilic metamyelocyte and stab nutrophil are all improved. But the two groups are not different (p>0. 05) . Serum lactic dehydrogenase is improved in two groups after treatment, it is transparently different trial group than matched control group(p<0.01). The efficiency of treatment of trial group is 87. 5%, matched control group is 80%, trial group is not different from matched control group(p<0. 05).It is clear that prescription of detoxication and the method of removing stasis is effect in treating CML. It can rise remission rate of chronic phase of CML, change clinical symptom and life quality.In the investigation of experiment, we use the method of blood serum pharmacolog and do experiment in vitro. We add blood serum containing prescription of detoxication and the method of removing stasis, liu shen wan and hydroxyurea into K562 cells, cultivate together. Calculate inhibited rate in colorimetric method of MTT, detect apoptosis rate in flow cytometer through the method of TUNAL, detect the expression of mRNA of BCR/ABL in real-time Q-PCR. Result of MTT: blood serum containing detoxication and the method of removing stasis, liu shen wan and hydroxyurea all inhibit K562 cells, there is more different than blood serum of rabbit which don not contain drug(p<0.05). The tallest period of inhibit rate of prescription of detoxication and the method of removing stasis, liu shen wan occur at 24h, with time changing, inhibit rate began to descent, it became the lowest at 72h. But the hydroxyurea is at 72h, its inhibit rate is so low that prescription of detoxication and the method of removing stasis, liu shen wan are more excellent to it(p<0.05).At 24 hour, we detect apoptosis rate of K562 cells, three all can promote apoptosis of K562 cells , they are more obvious than blood serum of rabbit(p<0.05). Prescription of detoxication and the method of removing...
Keywords/Search Tags:leukemia, chronic, Qudu Huayu formula
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