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Cytological Study Of Ultrasonically Activated HpD For Antitumor

Posted on:2004-11-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q H LiuFull Text:PDF
GTID:1104360092491562Subject:Zoology
Abstract/Summary:PDF Full Text Request
Through the studies of mouse SI80 ascitic tumor, SI 80 sarcoma in vivo, Ehrlich ascites cancer (EAC), cultured human colorectal carcinoma cells in-vitro (SW-480) and melanoma cells (LiBr), we picked out various sensitive threshold of different cells for killing effect of ultrasonically activated Hematoporphyrin derivatives (HpD), and preliminarily analysed the cytological molecular biology mechanism of ultrasound activating HpD for antitumor in aspect of changes of microstructure, ultramicrostructure, cytochemistry, molecular structure of different treated tumor cells. In this study, we found that under certain experimental condition, free radicals such as singlet oxygen ( O2) killing tumor cells really existed that foreign scholars have reported. But this was not the only way of Sonodynamic therapy (SDT) for antitumor. SDT had multiform models for antitumor and was influenced by different physical and chemical factors with complex biology elements. Especially, in this experiment, we found that low-intensity ultrasonically activated HpD could induce four kinds of tumor cells apoptosis for the first time. This demonstrated that in the mechanism of SDT, there are two ways for antitumor: hastened cells death and induced apoptosis. This conclusion had certain meaning to rich and develop SDT theory for advanced study of mechanism of SDT. This article mainly talked about some results as follow: 1. Study of SDT for anti S180 ascitic tumor and S180 sarcoma in vivo?Through the study of growth condition of SI 80 sarcoma by ultrasonically activated HpD, we picked out the effective lowest intensity of ultrasound (US) and treatment time for SI80 sarcoma. This experiment found that HpD had slight inhibition effect on tumor. Inhibition ratio of tumor volume was 3.19% and for weight, it was 0.39%. When intensity of ultrasound was 0.6 W/cm2, the growth inhibition ratio of US for tumor volume and weight were 57.07% and 39.9%, but at the same intensity, the growth inhibition ratio of US combined with HpD for tumor weight and volume in creased to 87.15% and 78.8%. Tumor-bearing mouse experiment showed that HpD had light effect on tumor growth. US alone had certain inhibition effect on tumor growth. And ultrasonically activated HpD could effectively inhibit tumor growth.?By observing the changes of structure and morpha of sarcoma cells which were treated with US under light microscope and transmission electron microscope, the outcomes illustrated that HpD had little influence on tumor cells. Both of single US and ultrasonically activated HpD had the effect to disrupt cells structure. The disruptive effect first displayed the damages of the membrane system and the inheritance information-expression system. And the mitochrondria was a sensitive cellular organ for SDT killing tumor cells.(3) This experiment used enzymic histochemistry to detect the influence of ultrasonically activated HpD on activity of cytochrome oxidase. We could get that HpD had slight effect on activity of tumor cytochrome oxidase and US had some effect. But HpD activated by US could let the activity ofcytochrome oxidase decrease obviously and this phenomenon appeared just Ih after we treated. After 3h and even 6h, the activity of cytochrome oxidase was lasting decrease. This change indicated that lasting decrease of cell eneger synthesizing function was a important factor for cell secondary damage.(4) Using scanning electron microscopy to observe the changes of surface structure of S180 ascitic tumor after we treated it with US at the same frequency but different intensity firstly, the conclusion explained that HpD had certain effect on cells. It mainly took on the reduction of microvilli. All of different intensity of US could injure the cell morpha and surface structure slight. But at the same intensity and treated time, HpD combined with US had the biggest effect of injury. Most of cells were disrupted to survivals or became cell remnants with bubble-like protusions. ?In the study of SDT for anti SI80 ascitis tumor and sarcoma in viv...
Keywords/Search Tags:ultrasound, Hematoporphyrin derivatives, tumor, cytology, apoptosis
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