| Glioma is the most common primary malignant tumor in intracranial,accounting for about 40%-60%of intracranial tumors.It originates from ependymal and glial cells.According to the 2016 WHO Central Nervous System Tumor Classification,gliomas are classified into grade Ⅰ-Ⅳ,among which WHO Ⅰ and WHO Ⅱ are low-grade gliomas(LGG),and WHO Ⅲ and WHO Ⅳ are high-grade gliomas(HGG).Among them,the grade Ⅳ is glioblastoma(GBM),the most malignancy tumor.The incidence of glioma is increasing year by year,especially among the elderly over 65 years old.The annual incidence of glioma in China is 3-6 per 100,000 people,and the annual death toll is 30,000 Worldwide,the incidence is approximately 7 per 100,000 people per year.Epidemiological statistics showed that the incidence of glioma in male patients was significantly higher than that in female patients,which was about male:female=1.5～2:1,and the trend was more obvious in young and middle-aged patients.Glioblastoma representing a highly heterogeneous group of neoplasms that are among the most aggressive,drug-resistant and challenging cancers to treat,the current treatment method is a comprehensive treatment based on the operation,including:radiation therapy,chemotherapy,tumor treating fields(TTFields),anti-angiogenesis therapy and immune therapy,etc..Patients with GBM currently receive a dire prognosis,with a median overall survival(OS)between 1-1.5 year based on the comprehensive treatment.Glioma is extremely difficult to treat and brings great harm and burden to the society and the family.With the rapid development of science and technology and continual progress of scientific research,the diagnosis and treatment of glioma have been significantly improved at histological,molecular,or single cell level,but the outcome of glioma is still not significantly improved.The types of chemotherapy drugs for glioma are limited,because of the blood-brain barrier(BBB).Currently,the primary first-line chemotherapy drug is temozolomide(TMZ),but almost with ineffective and drug resistance,and the purpose of individualized precise treatment cannot be achieved.Glioma is difficult to treat and has a poor prognosis.There is a great need to develop new therapies,to improve overall survival time and quality of life for these patients.Recent efforts in drug development for slowing glioma progression has focused on targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting glioma.Glioma cell metabolism provides ample scope for the identification of new therapeutic targets.Based on our previous research,this study intends to further explore the mechanism of glucose and lipid metabolism in glioma cell and molecular imaging of glioma.1.The clinical significance of serum testosterone level monitoring in patient with glioma.The preoperative and postoperative serum testosterone levels of glioma patients and the control group were detected,and the clinical significance of serum testosterone in the diagnosis and treatment of glioma patients was analyzed and compared.Compared with the control group,the serum testosterone levels of glioma patients in both the low-grade glioma group and the high-grade glioma group were significantly higher than those in the control group,and the difference was statistically significant(p<0.001).According to the comparison of detection results of serum testosterone levels in glioma of all levels,there was no correlation between serum testosterone level and glioma level,and the difference was not statistically significant.In the glioma group,the serum testosterone level decreased with tumor resection,and reached relative homeostasis 6 days after the operation.In the control group,the changes of serum testosterone were not obvious after the operation.Moreover,the change of serum testosterone was more obvious in the glioma group,and the difference between the two groups was statistically significant as the serum testosterone level reached a lower level after tumor resection.Therefore,the decrease of serum testosterone edema glioma tissue after excision may be the synthesis and secretion of glioma cells.2.The feasibility study of testosterone as a non-invasive diagnosis of glioma was further explored by means of in vitro fresh brain glioma tissue 9.4T MRI spectrum imaging and dynamic monitoring MRI and spectrum analysis of in rat orthotopic GBM models.It is the first time to report the peak of testosterone wave could be identified in MRS.The MRS result of glioma tissue in vitro under 9.4T is consistent with in vivo under 3.0T.The expression of testosterone in glioma was significantly increased compared with the control group(P<0.01).The expression of testosterone is related to the formation and progression of glioma in nude mice,MRS can be used as an important technique to assess the diagnosis and treatment response of gliomas.3.The serum testosterone level of glioma patients was significantly higher than that of non-glioma patients,but the specific mechanism was unknown.The testosterone level in serum of glioma patients was higher than that of the control group,and the testosterone in cerebrospinal fluid was significantly higher than serum without increase of serum PSA level.Therefore,testosterone maybe synthesized and secreted from glioma cells,can be a biomarker candidate for noninvasive diagnosis of glioma.4.Abnormal glucose and lipid metabolism in glioma is associated with its malignant progression.Glucose could regulate the biological activity of glioma cells through SCAP-SREBP2-Gluts-testosterone/AR pathway.SREBP2,on the one hand,increases glucose absorption through glucose transporters(GLUTs),and on the other hand increases the synthesis cholesterol,testosterone,promotes glioma cell proliferation and differentiation.Based on theory of glioma cell synthesis and secretion testosterone,the glioma cells were treated with abiraterone acetate,the activity of glioma cells decreased accompanied by the decrease of AR,SREBP2,CYP17 and SCAP. |
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