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Experimental Study On Photodynamic Therapy On The Inhibition And Side Effects Of Ascites In Mice

Posted on:2020-03-13Degree:MasterType:Thesis
Country:ChinaCandidate:Y H LangFull Text:PDF
GTID:2404330575485844Subject:Oncology
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Photodynamic Therapy(PDT),a locally targeted therapy that combines photosensitizer,light and oxygen,can selectively treat cancer by photodynamic response.Its main treatment process is as follows:after the photosensitizer is injected into the vein of the patient,it selectively accumulates in the tumor tissue,and then irradiates with specific wavelength of light;After the photosensitizer in tumor tissue is stimulated by the light energy,the energy of laser is transferred to oxygen molecules to produce reactive oxygen species(ROS),which reacts with intracellular substances to induce apoptosis and necrosis of tumor cells,thereby killing tumor cells.It has the advantages of good targeting,low toxicity,and protection of organ function.Hematoporphyrin derivative(HPD)is a complex preparation of porphyrin which is mainly composed of hematoporphyrin.It was officially approved for clinical PDT treatment in the late 1990s by the state.The trade name is HPD.It belongs to the first generation of photosensitizers and is the most widely used photosensitizer in PDT.It has definite efficacy and low toxicity,and is still used in clinical practice.For cancerous ascites,the commonly used treatments in the clinic are diuretic,repeated abdominal puncture or peritoneal catheterization,effusion,intraperitoneal injection of chemotherapy,anti-angiogenesis and the like.These treatment methods have their own shortcomings,such as some patients have greater response to intraperitoneal chemotherapy drugs,anti-angiogenic drugs are expensive,some patients can not tolerate their side effects,repeated abdominal puncture drainage,abdominal cavity catheters easily cause internal environmental disorders and affect patient activity.PDT has its unique advantages in the treatment of tumors,but there are few reports on the use of PDT in the treatment of cancerous ascites,and there is no more data to support the treatment.However,PDT as a minimally invasive treatment for tumors has a good therapeutic effect in most tumors.Whether the treatment of cancerous ascites can also exert its unique advantages.Therefore,we have developed a treatment plan for PDT for cancerous ascites,to explore the efficacy of PDT in ascites mice,and to evaluate whether PDT has obvious toxic effects on important organs in the body while being treated.ObjectiveTo evaluate the therapeutic effect of PDT on cancerous ascites and the effect of abdominal photodynamic therapy on important organs in the body.MethodsThe S180 Kunming mouse ascites model was established by intraperitoneal injection of S180 cells.Combined with clinical application,the experimental components were divided into 8 groups according to the administration mode,photosensitizer concentration and laser dose.The method of intraperitoneal administration was to treat mice with cancerous ascites with HPD 5 mg/Kg and 10 mg/Kg,laser doses of 1500 mW and 2000 mW,PDT treatment was performed on cancerous ascites mice 24 to 48 hours after administration.Record the weight and abdominal circumference of mice to determine the amount of ascites and the growth of abdominal tumors.Assessing the growth of ascites tumors using the ratio of weight gain in mice.The activity of ascites tumor cells was determined by trypan blue staining.HE staining was used to detect the heart,liver,kidney and partial colon function of each group of mice,and the effects of ascites and PDT on internal organs were determined.After the ascites was withdrawn,the mice in each group were visually observed for the presence or absence of intra-abdominal organ metastasis,intestinal adhesion,intestinal obstruction,and intestinal bleeding.ResultsAccording to the body weight and abdominal circumference results of each group,the weight and abdominal circumference of the cancerous ascites PDT group were decreased compared with the control group within 3 to 4 days after treatment,but after 7 days,the body weight and abdominal circumference of each experimental group were not statistically significant difference compared with the control group(P>0.05),mice with ascites grew faster than normal mice and abdominal circumference.The weight growth ratio showed that tumor gro.wth in ascites was inhibited within 3-4 days after PDT compared with the control group,and the difference between the peritoneal administration of 5mg/Kg light dose of 2000mW group and the intravenous administration of 5mg/Kg light dose of 1500mW group was statistically significant(P<0.05),However,on the 7th day,there was no significant difference between the groups(P>0.05).On the 7th day after PDT,trypan blue results showed that the activity of tumor cells in ascites of each experimental group was not significantly different from that of the control group.The results of HE staining showed that compared with the control group,in the photodynamic therapy experimental group,PDT had no obvious toxicity to the heart and kidney,and had necrosis effect on the directly irradiated part of the liver,hemorrhagic effect on the intestinal tract.Photodynamic therapy without ascites,equivalent to ascites.Macroscopic observation showed that the mice died within 3 days after PDT,with intestinal bleeding,hyperemia in the heart,liver and kidney,no obvious intestinal obstruction,and some mice in the experimental group had slight intestinal adhesion.ConclusionPhotodynamic therapy can reduce ascites production in mice with S180 ascites tumor on the 3rd to 4th day of treatment,but no longer inhibits ascites in more than 1 week.Photodynamic therapy has inflammation and necrosis effects on the tissues directly irradiated by laser light in mice,and has no obvious side effects on unirradiated parts of tissues.There was no significant difference between the inhibition of ascites and the effects of toxic and side effects by intravenous injection and intraperitoneal injection.
Keywords/Search Tags:Photodynamic therapy, cancerous ascites, intraperitoneal, HPD
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