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Preliminary Study Of Effect Of Docetaxel-loaded Lipid Microbubbles Combined With Ultrasound Targeted Microbubbles Destruction On Rabbit VX2Cervical Lymph Node Metastatic Carcinoma

Posted on:2015-05-28Degree:MasterType:Thesis
Country:ChinaCandidate:T WangFull Text:PDF
GTID:2284330434456213Subject:Oral and clinical medicine
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It is asserted that the tongue cancer has the highest accidence inhuman’s oral and maxillofacial carcinomas, which is almost SCC. For thisreason that The flow of blood to the tongue is very rich, strong activity.Thepatients with tongue squamous carcinomas get the cervical lymph nodes inthe early days. Once the patients get cervical lymph node metastases, theclinical tumor stage, the plan of examination and treatment and theprognosis of the disease will be affected obviously. Thus it’s necessary forthe therapeutic schedule and the effect enhancement to diagnosis thecervical lymph nodes of the patients attacked by the tongue cancer as soonas possible. All this time The main treatment of tongue cancer is extendedresection and lymph nodes dissection operation combined withradiotherapy, chemotherapy and endocrine therapy. But there are still manynot equal to idea, for instance:Intraoperative resection rate is low, It isdifficult to remove Lymph node micrometastasis, evere deformities andevere deformities is high and so on. And in the process of radiation andchemotherapy because of the lack of targeted tumor cells and normal cells,at the same time of treatment can bring great toxicity and side effects to thebody. As a result, cervical lymph node metastases of effective treatment for tongue cancer research is especially important and urgent. In recent years,the lymph node targeted therapy (LTT) study for tongue cancer cervicallymph node metastases brings hope. LTT Research mainly is to look forgood targeting property, high curative effect, little side effects of the lymphnode targeted agents. At the same time, Drug-loading ultrasoundmicrobubble combined Ultrasound targeted microbubbles destruction(UTMD) technology, As a new tumor treatment, It has been on our radarattention gradually, more and more researchers both at home and abroadwill be applied to breast cancer, melanoma, and liver cancer in the study oftumor treatment.Docetaxel (Doc) is a kind of commonly used chemotherapy drugswith oral and maxillofacial good efficacy. Because of its own water solubleis poorer, prone to hemolysis, allergies and other adverse reactions, theinconvenience for clinical application. The study found that after loadingdocetaxel in lipid can significantly reduce the toxicity of drugs itself, at thesame time can keep the antitumor activity of the drug itself. Recent studiesof Kang Juan that docetaxel-loaded lipid microbubbles(DLLM) combinedwith UTMD for the treatment of primary tumors of liver cancer, theexperiment proved that the DLLM joint UTMD can obviously inhibit theexpression of related factor of angiogenesis and metastasis of liver cancer.In this paper after successfully established rabbits VX2cervical lymphnode metastatic carcinoma model[7]and the successful preparation ofDLLM[8], We have used UTMD to make the drug targeted release, Tostudy the treatment effect of DLLM combined with UTMD on rabbit VX2cervical lymph node metastatic carcinoma,;at the same time,the treatmentof malignant tumor lymphatic metastasis provides a new way of thinking.The content of this experiment includes the following two parts: PART1Study the effects of docetaxel-loaded lipid microbubbleswith ultrasound targeted microbubbles destruction on Proliferationand Apoptosis of rabbit VX2cervical lymph node metastaticcarcinomaObjective:To study the treatment effect of docetaxel-loaded lipidmicrobubbles contrast agent on rabbit VX2cervical lymph node metastaticcarcinoma.Methods:Thirty rabbits VX2cervical lymph node metastaticcarcinoma model were successfully established and were randomly dividedinto6groups. Volume and inhibition rate of cervical lymph nodemetastatic carcinoma in each group before and after the treatment weredetected and compared.TUNEL was used to observe apoptosis.Expressionof PCNA was detected by immunohistochemistry,then compared amongdifferent groups.Results: After the treatment,inhibition rate was higher in Egroup than in other groups(P<0.05), apoptotic index was higher in E groupthan in other groups(P<0.05) and proliferation index was lower in E groupthan in other groups (P<0.01).Conclusions: DLLM combined with UTMDcan inhibit the growth of the cervical lymph node metastatic carcinomafrom the macroscopic view.PART2Preliminary study of effect of docetaxel-loaded lipidmicrobubbles combined with ultrasound targeted microbubblesdestruction on rabbit VX2cervical Lymph node metastatic carcinomaObjective:To study the treatment effect of docetaxel-loaded lipidmicrobubbles(DLLM)combined with ultrasound targeted microbubblesdestruction(UTMD)on rabbit VX2cervical lymph node metastaticcarcinoma.Methods:Thirty rabbits VX2cervical lymph node metastaticcarcinoma model were successfully established and were randomly divided into6group(sA group, B group, C group, D group, E group, F group,n=5).A group used docetaxel, B group used DLLM,C group used docetaxel+UTMD,D group used lipid microbubbles+UTMD,E group used DLLM+UTMD and F group was control group. Expression of CD34andmicrovessel density (MVD) and vascular endothelial growth factor (VEGF)and matrix metalloproteinase-2(MMP2) were compared among differentgroups.Results:After the treatment, the expression of CD34and MVD andVEGF and MMP2was significantly lower in E group than in othergroups(P<0.01).Conclusions:DLLM combined with UTMD can inhibit thegrowth of the cervical lymph node metastatic carcinoma from themolecular level.
Keywords/Search Tags:Squamous cell carcinoma of tongue, Metastaticcarcinoma of cervical lymph node, Docetaxel, Ultrasound microbubbles, Ultrasound-targeted microbubble destruction(UTMD)
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