Effect Of Antiangiogenic Drugs On Tumor Blood Vessels And The Development Of Zebrafish Blood Vessel And Its Clinical Efficacy In Combination With Radiotherapy

With the morbidity and mortality increasing year by year,cancer has become one of the serious threats to the public health in the world.The pathogenesis of cancer is complex,the physiological and biochemical processes are variable,and the treatment is difficult.Therefore,the effective prevention and control of cancer has attracted much attention.At present,the main treatment methods for malignant tumors are: surgery,radiation therapy,chemical drug therapy,hormone therapy,immunotherapy,targeted drug therapy,antiangiogenesis therapy,etc.To achieve the best therapeutic effect,different treatment methods or the combination of multiple therapies are chosen according to individual patient's condition.Among them,anti-angiogenesis therapy has become a new hot spot for clinical citation and research due to its advantages of high efficiency and low toxicity.Existing studies have shown that the process of angiogenesis is regulated by a variety of angiogenic factors.Vascular endothelial growth factor(VEGF)and its membrane receptors play an important role in regulating physiological and pathological angiogenesis,and have received extensive attention in clinical and basic scientific research.There are two main types of anti-vascular drugs used clinically: monoclonal antibodies such as bevacizumab and recombinant human endostatin,and small molecule tyrosine kinase inhibitors(TKIs)such as apatinib and Anlotinib.In recent years,the comprehensive treatment of tumors has developed rapidly,and the combined use of anti-vascular drugs and other treatment modes(radiotherapy,chemotherapy,etc.)has gradually become a research focus in clinic.This study aimed to investigate the effects of anti-angiogenic drugs on the normalization of tumor blood vessels,as well as the toxicity of anti-angiogenic drugs and their dynamic effects on normal angiogenesis.Our experimental results are as follows: 1.The results of 3D culture experimentof human brain microvascular endothelial cells show that: Apatinib and bevacizumab cannot effectively restore vascular endothelial cells to form blood vessels in the environment of 3D culture in vitro,that is,the effect on normalization of tumor blood vessels is weak,while endostar plays an active role in this process.2.The toxicity of Apatinib to zebrafish is concentration-dependent,with a lethal concentration of 0.295.mol / L andafter 3 days of treatment with Apatinib at a concentration of 0.05 mol / L,zebrafish embryos showed obvious pericardial edema and significant vascular developmentdefects.3.Through the in vivo imaging experiment of the transgenic zebrafish line,the effect of anti-angiogenic drugs on zebrafish angiogenesis was clearly observed.4.We cooperated with the Hubei Provincial Cancer Hospital and followed up 19 patients with tumor brain metastases who were treated with IMRT combined with anti-angiogenesisdrugs.The survival of patients was analyzed.The results showed that combined treatment can significantly extend the survival period.In summary,our research discloses the toxicity of anti-angiogenic drugs on living zebrafish embryos and the inhibition of angiogenesis,proves that Endo plays a positive role in the process of tumor blood vessel normalization,and confirmed that the combined therapy of IMRT and angiogenesis inhibitors can significantly improve patient survival.This study provides a theoretical basis for improving the safety of anti-angiogenic drugs in clinical application and developing new combined treatment strategy.