Pub Date : 2020-04-01DOI: 10.4103/glioma.glioma_8_20
E. Lyutfi, Reneta Georgieva, G. Stoyanov, D. Dzhenkov
Background and Aim: Glial tumors with astrocytic differentiation are the most common primary malignant brain tumors. Hans Joachim Scherer established histological criteria based on hematoxylin and eosin (H&E) staining, which form the basis of the World Health Organization (WHO) glial tumor grades. The aim of this study was to investigate the incidence of Scherer structures across different classes of WHO grade tumors with astrocytic differentiation and determine whether secondary structures can be used as a grade-defining tool. Materials and Methods: Tumor samples were obtained from 36 patients with central nervous system (CNS) tumors with astrocytic differentiation between February 2018 and March 2019. The study was approved by the Committee on Ethics for Scientific Research, Medical University—Varna “Prof. Dr. Paraskev Stoyanov,” Protocol no. 20 [1] on April 26, 2012. The presence or absence of primary Scherer structures (pseudopalisading necrosis, glomeruloid vascular proliferation) and secondary Scherer structures (subpial palisading, fascicular aggregation, satellitosis around neurons, and blood vessels) was analyzed in H&E stained samples. Results: The samples were divided into two groups: 28 glioblastoma multiforme (GBM) cases and 8 lower grade astrocytoma cases. All 28 GBM cases exhibited pseudopalisading necrosis. Glomeruloid vascular proliferation was present only in 89.3% of the GBM cases. The GBM group also showed 67.9% subpial palisading, 78.5% fascicular aggregation of tumor cells, 96.4% perineuronal, and 100% perivascular satellitosis. The lower grade astrocytoma group had 0% pseudopalisading necrosis and glomeruloid vascular proliferation. Among all cases of lower grade gliomas, 50.0% showed subpial palisading, 87.5% fascicular aggregation, 100% perineuronal, and 100% perivascular satellitosis. Conclusions: Secondary Scherer structures can be considered as natural phenomena in glial tumors but cannot be used as features for grading.
{"title":"Tumor growth patterns in central nervous system tumors with astrocytic differentiation","authors":"E. Lyutfi, Reneta Georgieva, G. Stoyanov, D. Dzhenkov","doi":"10.4103/glioma.glioma_8_20","DOIUrl":"https://doi.org/10.4103/glioma.glioma_8_20","url":null,"abstract":"Background and Aim: Glial tumors with astrocytic differentiation are the most common primary malignant brain tumors. Hans Joachim Scherer established histological criteria based on hematoxylin and eosin (H&E) staining, which form the basis of the World Health Organization (WHO) glial tumor grades. The aim of this study was to investigate the incidence of Scherer structures across different classes of WHO grade tumors with astrocytic differentiation and determine whether secondary structures can be used as a grade-defining tool. Materials and Methods: Tumor samples were obtained from 36 patients with central nervous system (CNS) tumors with astrocytic differentiation between February 2018 and March 2019. The study was approved by the Committee on Ethics for Scientific Research, Medical University—Varna “Prof. Dr. Paraskev Stoyanov,” Protocol no. 20 [1] on April 26, 2012. The presence or absence of primary Scherer structures (pseudopalisading necrosis, glomeruloid vascular proliferation) and secondary Scherer structures (subpial palisading, fascicular aggregation, satellitosis around neurons, and blood vessels) was analyzed in H&E stained samples. Results: The samples were divided into two groups: 28 glioblastoma multiforme (GBM) cases and 8 lower grade astrocytoma cases. All 28 GBM cases exhibited pseudopalisading necrosis. Glomeruloid vascular proliferation was present only in 89.3% of the GBM cases. The GBM group also showed 67.9% subpial palisading, 78.5% fascicular aggregation of tumor cells, 96.4% perineuronal, and 100% perivascular satellitosis. The lower grade astrocytoma group had 0% pseudopalisading necrosis and glomeruloid vascular proliferation. Among all cases of lower grade gliomas, 50.0% showed subpial palisading, 87.5% fascicular aggregation, 100% perineuronal, and 100% perivascular satellitosis. Conclusions: Secondary Scherer structures can be considered as natural phenomena in glial tumors but cannot be used as features for grading.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"67 - 70"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44973321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.4103/glioma.glioma_11_20
Jiabo Li, Xuya Wang, Luqing Tong, Xuejun Yang, D. Brat
Diffuse gliomas are a family of neoplastic diseases characterized by widespread infiltration of central nervous system structures by tumor cells displaying glial differentiation. Traditionally characterized by morphologic features of lineage and histologic differentiation, we now understand that diffuse gliomas contain multiple discrete molecular subsets, each with their own clinical and genetic characteristics. In the current molecular era, the World Health Organization 4th Edition update introduced classes of diffuse glioma according to the status of isocitrate dehydrogenase mutation, 1p/19q co-deletion, histone H3 mutation, and BRAF mutation. Additional studies have demonstrated the subset-specific prognostic significance and grading implications of epidermal growth factor receptor amplification, CDKN2A/B homozygous deletion, TERT promoter mutations, and whole chromosome 7 gain and whole chromosome 10 loss (+7/−10). These findings represent the beginning of the molecular era of diagnosis and grading. Additional studies will likely refine our current conceptions and further advance our ability to stratify risk and direct therapies. In this review, we discuss the current understanding of the molecular classification of diffuse gliomas.
{"title":"A contemporary molecular view of diffuse gliomas with implications for diagnosis","authors":"Jiabo Li, Xuya Wang, Luqing Tong, Xuejun Yang, D. Brat","doi":"10.4103/glioma.glioma_11_20","DOIUrl":"https://doi.org/10.4103/glioma.glioma_11_20","url":null,"abstract":"Diffuse gliomas are a family of neoplastic diseases characterized by widespread infiltration of central nervous system structures by tumor cells displaying glial differentiation. Traditionally characterized by morphologic features of lineage and histologic differentiation, we now understand that diffuse gliomas contain multiple discrete molecular subsets, each with their own clinical and genetic characteristics. In the current molecular era, the World Health Organization 4th Edition update introduced classes of diffuse glioma according to the status of isocitrate dehydrogenase mutation, 1p/19q co-deletion, histone H3 mutation, and BRAF mutation. Additional studies have demonstrated the subset-specific prognostic significance and grading implications of epidermal growth factor receptor amplification, CDKN2A/B homozygous deletion, TERT promoter mutations, and whole chromosome 7 gain and whole chromosome 10 loss (+7/−10). These findings represent the beginning of the molecular era of diagnosis and grading. Additional studies will likely refine our current conceptions and further advance our ability to stratify risk and direct therapies. In this review, we discuss the current understanding of the molecular classification of diffuse gliomas.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"38 - 44"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47615592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.4103/glioma.glioma_9_20
Lijuan Zhang
Brain imaging has been broadly applied in neuroscience for more than 40 years. A wide range of studies on glioma have been carried out based on structural and functional imaging to characterize tumor malignancy, search for biomarker, aid the therapeutic process, and predict the prognosis. As the mainstay of modern neuroimaging, magnetic resonance imaging provides superior resolution and multiple contrasts capturing the morphological, vascular, metabolic, and functional properties of glioma. Furthermore, the development of connectivity-based approach and network models innovates our understanding of glioma in terms of functional remodeling and plasticity at various levels. The focus of this presentation is to overview the challenges of glioma characterization based on conventional magnetic resonance imaging and the future perspective of incorporating connectivity-based approaches into the disease management of glioma.
{"title":"Glioma characterization based on magnetic resonance imaging: Challenge overview and future perspective","authors":"Lijuan Zhang","doi":"10.4103/glioma.glioma_9_20","DOIUrl":"https://doi.org/10.4103/glioma.glioma_9_20","url":null,"abstract":"Brain imaging has been broadly applied in neuroscience for more than 40 years. A wide range of studies on glioma have been carried out based on structural and functional imaging to characterize tumor malignancy, search for biomarker, aid the therapeutic process, and predict the prognosis. As the mainstay of modern neuroimaging, magnetic resonance imaging provides superior resolution and multiple contrasts capturing the morphological, vascular, metabolic, and functional properties of glioma. Furthermore, the development of connectivity-based approach and network models innovates our understanding of glioma in terms of functional remodeling and plasticity at various levels. The focus of this presentation is to overview the challenges of glioma characterization based on conventional magnetic resonance imaging and the future perspective of incorporating connectivity-based approaches into the disease management of glioma.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"61 - 66"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45726039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.4103/glioma.glioma_13_20
Kai Zhang, Xuejun Yang
Maximizing the extent of tumor removal and preserving maximal neurological function are always the fundamental objectives in brain tumor surgery. This has motivated neurosurgeons to try various ways to map brain functions before tumor resection. Navigated transcranial magnetic stimulation (nTMS) is a new noninvasive method for brain mapping, which has produced exceptional results in clinical practice in recent years. However, there are still many deficiencies which need to be addressed to make nTMS more suitable for clinical application and neuroscience research. In this review, we highlight the opportunities provided by nTMS mapping, analyze the shortcomings at a theoretical level, and then emphasize the possibilities and prospects of applying multimodal fusion nTMS.
{"title":"Navigated transcranial magnetic stimulation brain mapping: Achievements, opportunities, and prospects","authors":"Kai Zhang, Xuejun Yang","doi":"10.4103/glioma.glioma_13_20","DOIUrl":"https://doi.org/10.4103/glioma.glioma_13_20","url":null,"abstract":"Maximizing the extent of tumor removal and preserving maximal neurological function are always the fundamental objectives in brain tumor surgery. This has motivated neurosurgeons to try various ways to map brain functions before tumor resection. Navigated transcranial magnetic stimulation (nTMS) is a new noninvasive method for brain mapping, which has produced exceptional results in clinical practice in recent years. However, there are still many deficiencies which need to be addressed to make nTMS more suitable for clinical application and neuroscience research. In this review, we highlight the opportunities provided by nTMS mapping, analyze the shortcomings at a theoretical level, and then emphasize the possibilities and prospects of applying multimodal fusion nTMS.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"45 - 52"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47572304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.4103/glioma.glioma_7_20
Thara Tunthanathip, Niti Tawaranurak, Kanet Kanjanapradit
Extraneural metastasis of gliosarcoma (GS) is a rare event. In this report, we describe a 15-year-old girl with a frontal GS who underwent complete resection, but developed tumor recurrence requiring a second operation after 3 years. Eight months after the second operation, she presented with a left postauricular mass. The clinical, neuroimaging, and histopathological findings were described. We also conducted a literature review and identified 26 cases of GS with extraneural metastasis, including the current report. The prognosis of GS with extracranial metastasis was poor, with a median survival of approximately 8.0 months. The common metastatic organs were the lungs (65.4%), liver (34.6%), and skeleton (23.1%). We also discuss the pathogenesis of GS with extraneural metastasis. We report an unusual case of a pediatric patient with GS with extraneural metastasis, with a long survival. GS with extraneural metastasis should be considered as a differential diagnosis in patients with soft-tissue masses. This work was approved by the Ethics Committee of the Faculty of Medicine, Prince of Songkla University, Thailand (REC 62-259-10-1) on September 9, 2019.
{"title":"Extraneural metastatic gliosarcoma: A case report and review of the literature","authors":"Thara Tunthanathip, Niti Tawaranurak, Kanet Kanjanapradit","doi":"10.4103/glioma.glioma_7_20","DOIUrl":"https://doi.org/10.4103/glioma.glioma_7_20","url":null,"abstract":"Extraneural metastasis of gliosarcoma (GS) is a rare event. In this report, we describe a 15-year-old girl with a frontal GS who underwent complete resection, but developed tumor recurrence requiring a second operation after 3 years. Eight months after the second operation, she presented with a left postauricular mass. The clinical, neuroimaging, and histopathological findings were described. We also conducted a literature review and identified 26 cases of GS with extraneural metastasis, including the current report. The prognosis of GS with extracranial metastasis was poor, with a median survival of approximately 8.0 months. The common metastatic organs were the lungs (65.4%), liver (34.6%), and skeleton (23.1%). We also discuss the pathogenesis of GS with extraneural metastasis. We report an unusual case of a pediatric patient with GS with extraneural metastasis, with a long survival. GS with extraneural metastasis should be considered as a differential diagnosis in patients with soft-tissue masses. This work was approved by the Ethics Committee of the Faculty of Medicine, Prince of Songkla University, Thailand (REC 62-259-10-1) on September 9, 2019.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"76 - 81"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48566389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.4103/glioma.glioma_16_20
Yu Lin, Xuejun Yang
Glioma is the most refractory intracranial tumor, and its diffuse infiltrative growth characteristics make total resection impossible in a biological sense, especially when tumors invade eloquent brain areas. Thus, identifying the equilibrium between tumor resection and functional preservation remains a challenge in glioma surgery. The accurate identification of tumor boundaries, precise mapping of functional boundaries, and an in-depth understanding of functional plasticity are key factors for accomplishing this challenge. This article reviews these three key points and highlights potential perspectives for the development of glioma surgery.
{"title":"Surgical resection of glioma involving eloquent brain areas: Tumor boundary, functional boundary, and plasticity consideration","authors":"Yu Lin, Xuejun Yang","doi":"10.4103/glioma.glioma_16_20","DOIUrl":"https://doi.org/10.4103/glioma.glioma_16_20","url":null,"abstract":"Glioma is the most refractory intracranial tumor, and its diffuse infiltrative growth characteristics make total resection impossible in a biological sense, especially when tumors invade eloquent brain areas. Thus, identifying the equilibrium between tumor resection and functional preservation remains a challenge in glioma surgery. The accurate identification of tumor boundaries, precise mapping of functional boundaries, and an in-depth understanding of functional plasticity are key factors for accomplishing this challenge. This article reviews these three key points and highlights potential perspectives for the development of glioma surgery.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"53 - 60"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49583715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.4103/glioma.glioma_10_20
G. Youssef, P. Wen
{"title":"Management of glioma patients during the coronavirus disease 2019 pandemic","authors":"G. Youssef, P. Wen","doi":"10.4103/glioma.glioma_10_20","DOIUrl":"https://doi.org/10.4103/glioma.glioma_10_20","url":null,"abstract":"","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"31 - 33"},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46026849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01DOI: 10.4103/glioma.glioma_29_19
H. Piao, Ye Zhang, Chengcheng Guo, Li Zhu, Lina Liu, U. Herrlinger, F. Sahm, Zhongping Chen
Background and Aim: The standard of care for patients with gliomas should follow established guidelines. In real-world management, however, the management sometimes deviates from these guidelines. We organized a discussion of real-world clinical cases and summarized different considerations from Chinese and European specialists.Case Presentation: A multidisciplinary team comprising experts from Europe and China discussed two patients with glioma treated at Sun Yat-sen University Cancer Center and Liaoning Cancer Hospital and Institute, China. Patient 1 was a 43-year-old man with a recurrent oligodendroglioma in the left frontal lobe diagnosed based on histology alone. He had undergone a biopsy and was diagnosed with an oligodendroglioma 3 years previously. He underwent chemoradiotherapy followed by 12 cycles of chemotherapy with temozolomide (TMZ), and complete remission was achieved. However, the tumor recurred within a short period of time and was resected by a second surgery. The pathologic diagnosis of the recurrent tumor was a glioblastoma because 1p/19q was intact when detected by sequencing. Pathologic consultation from another hospital still considered an anaplastic oligodendroglioma based on the positive result of 1p19q loss of heterozygosity (LOH) determined by fluorescence in situ hybridization. Patient 2 was a 50-year-old man with a left temporal glioblastoma. He underwent tumor resection but no radiotherapy. After seven cycles of TMZ (5/28-day regimen), his symptoms deteriorated, and his treatment was changed to a TMZ dose-dense regimen (7 days on/7 days off) and bevacizumab (7.5 mg/kg every 2 weeks), plus tumor-treating field therapy. Consultation Results: The pathological diagnosis based on biopsy for Patient 1 was an oligodendroglioma (World Health Organization Grade II), whereas the result of the second surgical sample was glioblastoma or anaplastic oligodendroglioma (questionable). Although the accuracy of fluorescence in situ hybridization for the detection of 1p/19q LOH requires improvement, 1p/19q LOH is typically not reconstituted in oligodendroglioma. More likely, it was due to sampling; a positive observation field may be missed with consequent negative results, and both oligodendroglioma (with 1p/19q co-deletion and isocitrate dehydrogenase mutation) and astrocytoma (without 1p/19q co-deletion) may exist. With respect to further treatment for cases such as Patient 1, both Chinese and European experts agree that procarbazine + lomustine chemotherapy is appropriate, while re-irradiation is suggested only if the tumor recurs outside the original radiotherapy field or within the radiotherapy field in the future. Considering the medical history, the rapid tumor regrowth without postoperative radiotherapy in Patient 2 was not surprising. After application of a rescue treatment regimen, the general condition of the patient improved, which may have resulted from the bevacizumab. A consensus was reached between the Chinese and Eur
{"title":"East meets West for the treatment of glioma: A discussion of real-world cases","authors":"H. Piao, Ye Zhang, Chengcheng Guo, Li Zhu, Lina Liu, U. Herrlinger, F. Sahm, Zhongping Chen","doi":"10.4103/glioma.glioma_29_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_29_19","url":null,"abstract":"Background and Aim: The standard of care for patients with gliomas should follow established guidelines. In real-world management, however, the management sometimes deviates from these guidelines. We organized a discussion of real-world clinical cases and summarized different considerations from Chinese and European specialists.Case Presentation: A multidisciplinary team comprising experts from Europe and China discussed two patients with glioma treated at Sun Yat-sen University Cancer Center and Liaoning Cancer Hospital and Institute, China. Patient 1 was a 43-year-old man with a recurrent oligodendroglioma in the left frontal lobe diagnosed based on histology alone. He had undergone a biopsy and was diagnosed with an oligodendroglioma 3 years previously. He underwent chemoradiotherapy followed by 12 cycles of chemotherapy with temozolomide (TMZ), and complete remission was achieved. However, the tumor recurred within a short period of time and was resected by a second surgery. The pathologic diagnosis of the recurrent tumor was a glioblastoma because 1p/19q was intact when detected by sequencing. Pathologic consultation from another hospital still considered an anaplastic oligodendroglioma based on the positive result of 1p19q loss of heterozygosity (LOH) determined by fluorescence in situ hybridization. Patient 2 was a 50-year-old man with a left temporal glioblastoma. He underwent tumor resection but no radiotherapy. After seven cycles of TMZ (5/28-day regimen), his symptoms deteriorated, and his treatment was changed to a TMZ dose-dense regimen (7 days on/7 days off) and bevacizumab (7.5 mg/kg every 2 weeks), plus tumor-treating field therapy. Consultation Results: The pathological diagnosis based on biopsy for Patient 1 was an oligodendroglioma (World Health Organization Grade II), whereas the result of the second surgical sample was glioblastoma or anaplastic oligodendroglioma (questionable). Although the accuracy of fluorescence in situ hybridization for the detection of 1p/19q LOH requires improvement, 1p/19q LOH is typically not reconstituted in oligodendroglioma. More likely, it was due to sampling; a positive observation field may be missed with consequent negative results, and both oligodendroglioma (with 1p/19q co-deletion and isocitrate dehydrogenase mutation) and astrocytoma (without 1p/19q co-deletion) may exist. With respect to further treatment for cases such as Patient 1, both Chinese and European experts agree that procarbazine + lomustine chemotherapy is appropriate, while re-irradiation is suggested only if the tumor recurs outside the original radiotherapy field or within the radiotherapy field in the future. Considering the medical history, the rapid tumor regrowth without postoperative radiotherapy in Patient 2 was not surprising. After application of a rescue treatment regimen, the general condition of the patient improved, which may have resulted from the bevacizumab. A consensus was reached between the Chinese and Eur","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"24 - 29"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46080865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-01-01DOI: 10.4103/glioma.glioma_19_19
Sheng-Hua Chu, Yan-ling Ma
Background and Aim: Our previous study demonstrated that SLC22A18 downregulation through promoter methylation and Sequence binding protein 1 (SATB1) upregulation are associated with the development and progression of glioma. This study aimed to examine the effect of combined SLC22A18 and short hairpin RNA (shRNA) targeting SATB1 gene therapy on glioma growth and invasion. Materials and Methods: Here, a combined gene therapy to upregulate SLC22A18 and downregulate SATB1 in malignant glioma was evaluated both in vitro and in vivo. Glioma U251 cells overexpressing SLC22A18 and underexpressing SATB1 were generated to investigate the effects of these changes on cell survival, as measured by the methyl thiazol tetrazolium assay, and on cell invasion, as measured by cell invasion and migration assays. In addition, analysis of the cell cycle was performed using flow cytometry in vitro. The animal experiments were approved by the Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Zhongnan Hospital of Wuhan University Ethics Committees (approval No. ZNHWHU0389, NTPHSHJTUSM046). Results: The upregulation of SLC22A18 and downregulation of SATB1 significantly inhibited growth and invasion in vitro and reduced in vivo tumor growth of human glioma U251 cells. Furthermore, we revealed that U251 cells were arrested at the G0/G1 phase. Similar data for apoptotic glioma cell death were obtained in tumor cells from an in vivo glioma xenograft model after transfection. At the same total dose, the therapeutic effect was markedly better in the glioma xenografts transfected with both SLC22A18 gene and SATB1 short hairpin RNA (shRNA) expression vectors compared with tumors transfected with either agent alone. The levels of SLC22A18 and SATB1 protein expression were respectively increased and decreased in the glioma cells.Conclusion: These results demonstrate that combination treatment with SLC22A18 gene and SATB1 shRNA expression vectors effectively inhibits the growth of human malignant glioma cells both in vitro and in glioma xenografts in vivo, suggesting a promising novel strategy for glioma therapy that warrants further study.
{"title":"Evaluation of combination gene therapy with SLC22A18 upregulation and sequence binding protein 1 downregulation for glioma U251 cells in vitro and in vivo","authors":"Sheng-Hua Chu, Yan-ling Ma","doi":"10.4103/glioma.glioma_19_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_19_19","url":null,"abstract":"Background and Aim: Our previous study demonstrated that SLC22A18 downregulation through promoter methylation and Sequence binding protein 1 (SATB1) upregulation are associated with the development and progression of glioma. This study aimed to examine the effect of combined SLC22A18 and short hairpin RNA (shRNA) targeting SATB1 gene therapy on glioma growth and invasion. Materials and Methods: Here, a combined gene therapy to upregulate SLC22A18 and downregulate SATB1 in malignant glioma was evaluated both in vitro and in vivo. Glioma U251 cells overexpressing SLC22A18 and underexpressing SATB1 were generated to investigate the effects of these changes on cell survival, as measured by the methyl thiazol tetrazolium assay, and on cell invasion, as measured by cell invasion and migration assays. In addition, analysis of the cell cycle was performed using flow cytometry in vitro. The animal experiments were approved by the Ethics Committee of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Zhongnan Hospital of Wuhan University Ethics Committees (approval No. ZNHWHU0389, NTPHSHJTUSM046). Results: The upregulation of SLC22A18 and downregulation of SATB1 significantly inhibited growth and invasion in vitro and reduced in vivo tumor growth of human glioma U251 cells. Furthermore, we revealed that U251 cells were arrested at the G0/G1 phase. Similar data for apoptotic glioma cell death were obtained in tumor cells from an in vivo glioma xenograft model after transfection. At the same total dose, the therapeutic effect was markedly better in the glioma xenografts transfected with both SLC22A18 gene and SATB1 short hairpin RNA (shRNA) expression vectors compared with tumors transfected with either agent alone. The levels of SLC22A18 and SATB1 protein expression were respectively increased and decreased in the glioma cells.Conclusion: These results demonstrate that combination treatment with SLC22A18 gene and SATB1 shRNA expression vectors effectively inhibits the growth of human malignant glioma cells both in vitro and in glioma xenografts in vivo, suggesting a promising novel strategy for glioma therapy that warrants further study.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"3 1","pages":"16 - 23"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48144453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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