Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized t...Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized therapeutic options. However, due to the intrinsic invasion and metastasis features and the resistance to chemotherapy, the survival rate of glioblastoma patients remains unsatisfactory. To improve the current situation, much more research is needed to provide comprehensive knowledge of GBM. In this review, we summarize the latest updates on GBM treatment and invasion. Firstly, we review the traditional and emerging therapies that have been used for GBM treatment. Given the limited efficiency of these therapies, we further discuss the role of invasion in GBM recurrence and progression, and present current research progress on the mode and mechanisms of GBM invasion.展开更多
Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on...Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.展开更多
Glioblastoma multiforme(GBM), the literal apogee on the hierarchy of malignant brain tumors, remains one of the greatest therapeutic challenges in oncology andmedicine. Historically this may be contextualized in the f...Glioblastoma multiforme(GBM), the literal apogee on the hierarchy of malignant brain tumors, remains one of the greatest therapeutic challenges in oncology andmedicine. Historically this may be contextualized in the fact that the medical and scientific communities have had a very elementary understanding of its intricate and complex pathophysiology. The last 10-15 years have yielded a number of studies that have elucidated much of the molecular and genetic complexities of GBM that underlie its pathogenesis. Excitingly, some of these discovered genetic mutations and molecular profiles in GBM have demonstrated value in prognostication and utility in predicting response to treatment. Despite this, however, treatment options for patients have remained somewhat limited. These treatment options are expected to expand with the availability of new data and with the transition of novel treatment modalities from animal to human studies. This paper will have a threefold objective: provide an overview of the traditional paradigm in understanding and treating GBM, describe recent discoveries in the molecular pathogenesis of GBM against this historical backdrop, and acquaint the reader with new treatment modalities that hold significant therapeutic potential for patients.展开更多
基金supported by National Natural Science Foundation of China (Grant No. 82003764 to L.F.)Universities Natural Science Research Project of Jiangsu Province (Grant No. 19KJB350001to L.F.)。
文摘Glioblastoma multiforme(GBM) is an essentially incurable brain tumor, which has been explored for approximately a century. Nowadays, surgical resection, chemotherapy, and radiation therapy are still the standardized therapeutic options. However, due to the intrinsic invasion and metastasis features and the resistance to chemotherapy, the survival rate of glioblastoma patients remains unsatisfactory. To improve the current situation, much more research is needed to provide comprehensive knowledge of GBM. In this review, we summarize the latest updates on GBM treatment and invasion. Firstly, we review the traditional and emerging therapies that have been used for GBM treatment. Given the limited efficiency of these therapies, we further discuss the role of invasion in GBM recurrence and progression, and present current research progress on the mode and mechanisms of GBM invasion.
基金supported by grants from the National Institutes of Health (NIH) [No. K25CA129173 (MMA), R01CA122031 (ASA), and 1R01CA160216 (ASA)]
文摘Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM.
文摘Glioblastoma multiforme(GBM), the literal apogee on the hierarchy of malignant brain tumors, remains one of the greatest therapeutic challenges in oncology andmedicine. Historically this may be contextualized in the fact that the medical and scientific communities have had a very elementary understanding of its intricate and complex pathophysiology. The last 10-15 years have yielded a number of studies that have elucidated much of the molecular and genetic complexities of GBM that underlie its pathogenesis. Excitingly, some of these discovered genetic mutations and molecular profiles in GBM have demonstrated value in prognostication and utility in predicting response to treatment. Despite this, however, treatment options for patients have remained somewhat limited. These treatment options are expected to expand with the availability of new data and with the transition of novel treatment modalities from animal to human studies. This paper will have a threefold objective: provide an overview of the traditional paradigm in understanding and treating GBM, describe recent discoveries in the molecular pathogenesis of GBM against this historical backdrop, and acquaint the reader with new treatment modalities that hold significant therapeutic potential for patients.
