Pub Date : 2019-05-01DOI: 10.4103/glioma.glioma_15_19
Umm E. Hani Abdullah, A. Laghari, M. Khalid, Huzaifa Rashid, A. Jabbar, F. Mubarak, A. Hafiz, S. Shamim, S. Enam
To date, information on the management of specific neurosurgical tumors, such as glioma, in Pakistan remains scattered and scarce. Our review synthesizes the predicaments of glioma management routinely presented to the neurosurgery, medical oncology, radiation oncology, and radiology departments in Pakistan. Expert opinions were integrated from each of the relevant fields in the form of personal citations. The data presented in our review were collected from various PubMed and non-PubMed indexed articles, coupled with various health reports from the Government of Pakistan along with the World Health Organization. Through these data, it was postulated that the utilization of innovative and instrumental technologies is a constant struggle for neurosurgeons in Pakistan, considering the cost-effectiveness. Hence, this results in significant limitations for surgeons to provide the best outcome for their patients. As most Pakistanis (74%) pay out of pocket, measuring cost-effectiveness is extremely crucial. It was found that significant differences in intra-operative and postoperative care existed among various centers. Public sector institutions fared much worse. The role of diagnostics in glioma surgery is severely limited across centers in Pakistan and as such, research and training need to be addressed promptly. In order to achieve success in glioma management, the data in our article demonstrate various facets of health care that need to be addressed simultaneously and swiftly. Surgical access needs to be improved; only then, optimal management of glioma can be accomplished in Pakistan.
{"title":"Current management of glioma in Pakistan","authors":"Umm E. Hani Abdullah, A. Laghari, M. Khalid, Huzaifa Rashid, A. Jabbar, F. Mubarak, A. Hafiz, S. Shamim, S. Enam","doi":"10.4103/glioma.glioma_15_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_15_19","url":null,"abstract":"To date, information on the management of specific neurosurgical tumors, such as glioma, in Pakistan remains scattered and scarce. Our review synthesizes the predicaments of glioma management routinely presented to the neurosurgery, medical oncology, radiation oncology, and radiology departments in Pakistan. Expert opinions were integrated from each of the relevant fields in the form of personal citations. The data presented in our review were collected from various PubMed and non-PubMed indexed articles, coupled with various health reports from the Government of Pakistan along with the World Health Organization. Through these data, it was postulated that the utilization of innovative and instrumental technologies is a constant struggle for neurosurgeons in Pakistan, considering the cost-effectiveness. Hence, this results in significant limitations for surgeons to provide the best outcome for their patients. As most Pakistanis (74%) pay out of pocket, measuring cost-effectiveness is extremely crucial. It was found that significant differences in intra-operative and postoperative care existed among various centers. Public sector institutions fared much worse. The role of diagnostics in glioma surgery is severely limited across centers in Pakistan and as such, research and training need to be addressed promptly. In order to achieve success in glioma management, the data in our article demonstrate various facets of health care that need to be addressed simultaneously and swiftly. Surgical access needs to be improved; only then, optimal management of glioma can be accomplished in Pakistan.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"139 - 144"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45987112","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 : 2019-05-01DOI: 10.4103/glioma.glioma_10_19
Xiaoran Zhang, Aleksandra Safonova, A. Rao, N. Amankulor
Gliomas are the most common primary central nervous system malignancy and have an overall poor prognosis, despite aggressive treatment. Understanding the immune microenvironment of these fatal tumors will advance discovery of immune-related therapeutic targets. Natural killer (NK) cells are innate lymphoid cells that constitute the first line of host-tumor immune responses since these cells do not require prior sensitization or tumor antigen recognition to kill. NK cells kill tumor cells by recognizing stress-induced ligands expressed on tumor cells, thereby providing an efficient path to early tumor cytolysis. Dysregulation of NK-mediated immunity plays a prominent role in immune escape for glioblastoma (World Health Organization Grade IV gliomas) and for various low-grade diffuse gliomas. Thus, the biology of NK cells is fertile ground for identifying novel immunotherapeutic targets in glioma. This review discusses the biology of NK cells as well as the potential applications for immunotherapy in the treatment of gliomas.
{"title":"Role of natural killer cells in isocitrate dehydrogenase 1/2 mutant glioma pathogenesis and emerging therapies","authors":"Xiaoran Zhang, Aleksandra Safonova, A. Rao, N. Amankulor","doi":"10.4103/glioma.glioma_10_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_10_19","url":null,"abstract":"Gliomas are the most common primary central nervous system malignancy and have an overall poor prognosis, despite aggressive treatment. Understanding the immune microenvironment of these fatal tumors will advance discovery of immune-related therapeutic targets. Natural killer (NK) cells are innate lymphoid cells that constitute the first line of host-tumor immune responses since these cells do not require prior sensitization or tumor antigen recognition to kill. NK cells kill tumor cells by recognizing stress-induced ligands expressed on tumor cells, thereby providing an efficient path to early tumor cytolysis. Dysregulation of NK-mediated immunity plays a prominent role in immune escape for glioblastoma (World Health Organization Grade IV gliomas) and for various low-grade diffuse gliomas. Thus, the biology of NK cells is fertile ground for identifying novel immunotherapeutic targets in glioma. This review discusses the biology of NK cells as well as the potential applications for immunotherapy in the treatment of gliomas.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"133 - 138"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49661296","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 : 2019-05-01DOI: 10.4103/glioma.glioma_11_19
Alhaji Ali, Maryam Buji, A. Abubakar
Background and Aim: Brain tumors are a fairly common neurological problem in Nigeria and associated with a relatively low morbidity and mortality rate. Magnetic resonance imaging is the best imaging modality revealing precisely the tumor's location, patterns, and to some extent, the tumor characterization; however, only computed tomography (CT) is readily available in the study locality. In this study, we assessed the patterns of CT findings among patients diagnosed with a brain tumor using CT. Materials and Methods: This was a retrospective study, in which brain CT records of 40 cases of brain tumor diagnosed between January 2016 and August 2018 were reviewed, irrespective of patient age, sex, or clinical information. This study was approved by the Human Research Ethical Committee of the Federal Neuro-Psychiatric Hospital, Maiduguri (approval No. FNPH/GEN/092/VOLII) on December 22, 2015. Results: Of the 40 brain tumors diagnosed during the study, 17 (42%) cases were male and 23 (58%) were female. Their age range was 2–70 years (28.4 ± 20.2 years). About 22% of cases were extra-axial, whereas 31 (78%) were intra-axial. Twenty-seven (68%) patients had definitive diagnosis, with eight (20%) cases being meningioma, whereas 13 (32%) had nonspecific findings (a longer differential diagnosis). Conclusion: Meningioma was the most common type of brain tumor in this study despite the limitation of histopathology facility within the immediate locality. The low rate of glioma was probably due to few old adults included in the study.
{"title":"Patterns of computed tomographic findings in patients from Maiduguri, Nigeria, diagnosed with a brain tumor","authors":"Alhaji Ali, Maryam Buji, A. Abubakar","doi":"10.4103/glioma.glioma_11_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_11_19","url":null,"abstract":"Background and Aim: Brain tumors are a fairly common neurological problem in Nigeria and associated with a relatively low morbidity and mortality rate. Magnetic resonance imaging is the best imaging modality revealing precisely the tumor's location, patterns, and to some extent, the tumor characterization; however, only computed tomography (CT) is readily available in the study locality. In this study, we assessed the patterns of CT findings among patients diagnosed with a brain tumor using CT. Materials and Methods: This was a retrospective study, in which brain CT records of 40 cases of brain tumor diagnosed between January 2016 and August 2018 were reviewed, irrespective of patient age, sex, or clinical information. This study was approved by the Human Research Ethical Committee of the Federal Neuro-Psychiatric Hospital, Maiduguri (approval No. FNPH/GEN/092/VOLII) on December 22, 2015. Results: Of the 40 brain tumors diagnosed during the study, 17 (42%) cases were male and 23 (58%) were female. Their age range was 2–70 years (28.4 ± 20.2 years). About 22% of cases were extra-axial, whereas 31 (78%) were intra-axial. Twenty-seven (68%) patients had definitive diagnosis, with eight (20%) cases being meningioma, whereas 13 (32%) had nonspecific findings (a longer differential diagnosis). Conclusion: Meningioma was the most common type of brain tumor in this study despite the limitation of histopathology facility within the immediate locality. The low rate of glioma was probably due to few old adults included in the study.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"63 1","pages":"153 - 156"},"PeriodicalIF":0.0,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70735308","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}
Background and Aim: Guidelines recommend adjuvant treatment for patients with high-grade gliomas and low-grade gliomas with high risk of progression. In clinical practice, however, treatments may not conform to these suggested guidelines. In this study, we reviewed the treatments and outcomes in patients with gliomas at Sun Yat-Sen University Cancer Center (SYSUCC), China. Materials and Methods: Medical records and radiologic images of 1215 glioma patients who underwent surgery at the center from 2000 to 2017 were retrospectively reviewed, and their clinicopathological characteristics, treatment method, and overall survival (OS) were analyzed. The study was approved by the Ethics Committee of SYSUCC on February 20, 2019 (approval No. GZR2019-219). Results: A total of 1001 patients diagnosed with glioma (initially World Health Organization 2007 criteria, then 2016 criteria) were enrolled, including 90 patients with Grade I, 307 Grade II, 239 Grade III, and 365 Grade IV gliomas. A total of 331 of 604 patients with high-grade glioma (54.8%) and 159 of 397 with low-grade glioma (40.1%) received postsurgical radiotherapy, and 285 patients with high-grade tumors (47.1%) and 80 with low-grade tumors (20.2%) received adjuvant chemotherapy. The median OS was 17.5 months for Grade IV and 43.1 months for Grade III gliomas. The median OS of patients with low-grade glioma was not reached. The 5-year survival rates of patients with Grades I, II, III, and IV gliomas were 94.7%, 73.7%, 45.7%, and 18.6%, respectively. Multivariate analysis identified onset age, preoperative seizure, tumor location, pathological subtype, resection extent, and postsurgical treatment as independent predictors of OS in patients with high-grade gliomas. Patients with high-grade glioma who received postsurgical treatment had better survival than those without adjuvant therapy (Grade III: 52.6 vs. 20.3 months, P = 0.012; Grade IV: 22.6 vs. 12.1 months, P < 0.001). Among patients with diffuse low-grade gliomas, age, performance status, preoperative seizure, Ki-67 index, tumor subtype, and resection extent were associated with clinical outcomes. Conclusion: Glioma patients are not always treated according to guidelines. Although standard care may lead to favorable prognoses, individualized treatments may be more acceptable and result in better outcomes and should thus be considered in routine clinical practice.
{"title":"Real-world management and survival outcomes of patients with newly diagnosed gliomas from a single institution in China: A retrospective cohort study","authors":"Depei Li, Yinsheng Chen, Chengcheng Guo, Xiangheng Zhang, K. Sai, Chao Ke, Ji Zhang, Xiaobing Jiang, Zheng-he Chen, Fu-Hua Lin, Qunying Yang, Jian Wang, Yong-gao Mu, Zhongping Chen","doi":"10.4103/glioma.glioma_14_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_14_19","url":null,"abstract":"Background and Aim: Guidelines recommend adjuvant treatment for patients with high-grade gliomas and low-grade gliomas with high risk of progression. In clinical practice, however, treatments may not conform to these suggested guidelines. In this study, we reviewed the treatments and outcomes in patients with gliomas at Sun Yat-Sen University Cancer Center (SYSUCC), China. Materials and Methods: Medical records and radiologic images of 1215 glioma patients who underwent surgery at the center from 2000 to 2017 were retrospectively reviewed, and their clinicopathological characteristics, treatment method, and overall survival (OS) were analyzed. The study was approved by the Ethics Committee of SYSUCC on February 20, 2019 (approval No. GZR2019-219). Results: A total of 1001 patients diagnosed with glioma (initially World Health Organization 2007 criteria, then 2016 criteria) were enrolled, including 90 patients with Grade I, 307 Grade II, 239 Grade III, and 365 Grade IV gliomas. A total of 331 of 604 patients with high-grade glioma (54.8%) and 159 of 397 with low-grade glioma (40.1%) received postsurgical radiotherapy, and 285 patients with high-grade tumors (47.1%) and 80 with low-grade tumors (20.2%) received adjuvant chemotherapy. The median OS was 17.5 months for Grade IV and 43.1 months for Grade III gliomas. The median OS of patients with low-grade glioma was not reached. The 5-year survival rates of patients with Grades I, II, III, and IV gliomas were 94.7%, 73.7%, 45.7%, and 18.6%, respectively. Multivariate analysis identified onset age, preoperative seizure, tumor location, pathological subtype, resection extent, and postsurgical treatment as independent predictors of OS in patients with high-grade gliomas. Patients with high-grade glioma who received postsurgical treatment had better survival than those without adjuvant therapy (Grade III: 52.6 vs. 20.3 months, P = 0.012; Grade IV: 22.6 vs. 12.1 months, P < 0.001). Among patients with diffuse low-grade gliomas, age, performance status, preoperative seizure, Ki-67 index, tumor subtype, and resection extent were associated with clinical outcomes. Conclusion: Glioma patients are not always treated according to guidelines. Although standard care may lead to favorable prognoses, individualized treatments may be more acceptable and result in better outcomes and should thus be considered in routine clinical practice.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"96 - 104"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49057781","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 : 2019-03-01DOI: 10.4103/glioma.glioma_13_19
E. Wong
Tumor treating fields are alternating electric fields that have a therapeutic effect on newly diagnosed and recurrent glioblastomas. The fields act on cellular proteins with large dipole moment that are critical for tumor cells undergoing mitosis. This putative mechanism of mitotic disruption translates into a superior survival benefit for newly diagnosed glioblastoma patients when tested in a randomized clinical trial comparing tumor treating fields and temozolomide with temozolomide alone in the adjuvant setting. This review provides an updated summary of preclinical and clinical data, including the cell biology effects of tumor treating fields, computer simulation of the electric field distribution in patients, and the clinical efficacy data of this new therapeutic modality against glioblastoma.
{"title":"Tumor treating fields therapy for glioblastoma: An update","authors":"E. Wong","doi":"10.4103/glioma.glioma_13_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_13_19","url":null,"abstract":"Tumor treating fields are alternating electric fields that have a therapeutic effect on newly diagnosed and recurrent glioblastomas. The fields act on cellular proteins with large dipole moment that are critical for tumor cells undergoing mitosis. This putative mechanism of mitotic disruption translates into a superior survival benefit for newly diagnosed glioblastoma patients when tested in a randomized clinical trial comparing tumor treating fields and temozolomide with temozolomide alone in the adjuvant setting. This review provides an updated summary of preclinical and clinical data, including the cell biology effects of tumor treating fields, computer simulation of the electric field distribution in patients, and the clinical efficacy data of this new therapeutic modality against glioblastoma.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"61 - 67"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48617214","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 : 2019-03-01DOI: 10.4103/glioma.glioma_12_19
N. Ningaraj, D. Khaitan
Background and Aim: The overexpression and alternative splicing of calcium-activated potassium channel subunit alpha-1 (KCNMA1) that encodes large-conductance calcium-activated voltage-sensitive potassium (BKCa) channels are implicated in the development of human cancers. Dysfunctional angiogenesis in hypoxic tumors is a challenge to intravenous anticancer drug treatments. Hypoxic factors also lead to abnormal vascular functions posing hurdle for anticancer drug delivery to tumors. The aim of this study was to explore the role of BKCachannels in tumor angiogenesis, specifically with regard to release of vascular endothelial growth factor (VEGF). Materials and Methods: We subjected the glioma cells under hypoxia and normoxia and studied the expression and activity of BKCachannels in in vitro and in vivo tumor models. Then, we studied the proangiogenic factor, VEGF, in tumors and monitored the neoangiogenic process. The study protocol was approved by the Institutional Animal Care and Use Committee, Mercer University, Atlanta, GA, USA (approved No. A0706007_01) on July 20, 2007. Results: We presented in vivo and cell based in vitro experimental evidence on the direct and indirect interactions of BKCachannels with VEGF signaling. There was evidence that under hypoxia, glioma cells overexpressed KCNMA1 and increased VEGF secretion. By inhibiting KCNMA1, we showed that VEGF secretion was significantly reduced, thus potentially controlling angiogenesis, which has implications for vascular permeability and anticancer drug delivery. Moreover, there were differences in alternate splicing of KCNMA1 between normal and malignant cells under hypoxia and normoxia. Conclusion: We conclude that BKCachannels regulate hypoxia-induced angiogenesis. Therefore, serious effort is needed to better understand the molecular mechanisms of BKCachannelopathies triggering angiogenesis and progression of glioma. The modulators of BKCachannels could be viable in new anticancer therapeutics.
{"title":"Inflection point in glioma growth and angiogenesis driven by potassium channels","authors":"N. Ningaraj, D. Khaitan","doi":"10.4103/glioma.glioma_12_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_12_19","url":null,"abstract":"Background and Aim: The overexpression and alternative splicing of calcium-activated potassium channel subunit alpha-1 (KCNMA1) that encodes large-conductance calcium-activated voltage-sensitive potassium (BKCa) channels are implicated in the development of human cancers. Dysfunctional angiogenesis in hypoxic tumors is a challenge to intravenous anticancer drug treatments. Hypoxic factors also lead to abnormal vascular functions posing hurdle for anticancer drug delivery to tumors. The aim of this study was to explore the role of BKCachannels in tumor angiogenesis, specifically with regard to release of vascular endothelial growth factor (VEGF). Materials and Methods: We subjected the glioma cells under hypoxia and normoxia and studied the expression and activity of BKCachannels in in vitro and in vivo tumor models. Then, we studied the proangiogenic factor, VEGF, in tumors and monitored the neoangiogenic process. The study protocol was approved by the Institutional Animal Care and Use Committee, Mercer University, Atlanta, GA, USA (approved No. A0706007_01) on July 20, 2007. Results: We presented in vivo and cell based in vitro experimental evidence on the direct and indirect interactions of BKCachannels with VEGF signaling. There was evidence that under hypoxia, glioma cells overexpressed KCNMA1 and increased VEGF secretion. By inhibiting KCNMA1, we showed that VEGF secretion was significantly reduced, thus potentially controlling angiogenesis, which has implications for vascular permeability and anticancer drug delivery. Moreover, there were differences in alternate splicing of KCNMA1 between normal and malignant cells under hypoxia and normoxia. Conclusion: We conclude that BKCachannels regulate hypoxia-induced angiogenesis. Therefore, serious effort is needed to better understand the molecular mechanisms of BKCachannelopathies triggering angiogenesis and progression of glioma. The modulators of BKCachannels could be viable in new anticancer therapeutics.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"105 - 115"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48818222","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 : 2019-03-01DOI: 10.4103/glioma.glioma_9_19
S. Lehrer, P. Rheinstein
Background and Aim: Cognitive deficits in low-grade glioma are well documented. Patients with glioma who are carriers of the apolipoprotein E (APOE) e4 allele may have increased memory problems and executive dysfunction. While APOE is ranked the number one Alzheimer's disease (AD) susceptibility gene, many other susceptibility genes have been identified in genome-wide association studies. This study aimed to analyze the expression of APOE and the next 23 ranked AD susceptibility genes in malignant gliomas to identify significantly co-occurrent genes. Materials and Methods: To identify the most important AD susceptibility genes, the AlzGene database (http://www.alzgene.org/) was consulted, which displays this information and regularly updates it. To analyze AD susceptibility genes in glioma, The Cancer Genome Atlas, a project begun in 2005, was used to catalog genetic mutations responsible for cancer, employing genome sequencing and bioinformatics. The cBioPortal for cancer genomics and the UCSC Xena browser were used to analyze the data in The Cancer Genome Atlas. Results: APOE and CD33 were the only significantly co-occurrent genes in 514 low-grade glioma tumor samples. APOE was altered in 1.8% of cases and CD33 in 3%. Heatmap indicates that the two genes tend to coexpress. The most common alteration was deep deletion. The cBioPortal and the Xena browser cannot distinguish or identify the alleles of APOE or CD33. Conclusions: AD patients with one or more APOE e4 alleles, having one or more copies of the CD33 risk allele (rs3865444 C), are at increased risk of cognitive decline compared to APOE E4 carriers, no doubt reflected by the co-occurrence of APOE and CD33 alterations in the gliomas. Better understanding of the interaction of genes and cognition in glioma patients may lead to new opportunities to personalize cancer therapy.
背景和目的：低级别脑胶质瘤的认知缺陷有很好的记录。携带载脂蛋白E（APOE）e4等位基因的神经胶质瘤患者可能会出现记忆力问题和执行功能障碍。虽然APOE被列为阿尔茨海默病（AD）的头号易感基因，但在全基因组关联研究中已经发现了许多其他易感基因。本研究旨在分析恶性胶质瘤中APOE和接下来的23个AD易感基因的表达，以确定显著共存的基因。材料和方法：为了鉴定最重要的AD易感基因，AlzGene数据库(http://www.alzgene.org/)为了分析神经胶质瘤中的AD易感性基因，癌症基因组图谱（The Cancer Genome Atlas），一个始于2005年的项目，被用来利用基因组测序和生物信息学对导致癌症的基因突变进行编目。癌症基因组学cBioPortal和UCSC Xena浏览器用于分析癌症基因组图谱中的数据。结果：在514例低级别胶质瘤中，APOE和CD33是唯一显著共存的基因。在1.8%的病例中APOE发生改变，在3%的病例中CD33发生改变。热图显示这两个基因倾向于共表达。最常见的改变是深度缺失。cBioPortal和Xena浏览器无法区分或识别APOE或CD33的等位基因。结论：与APOE e4携带者相比，具有一个或多个APOE e4等位基因（rs3865444c）的AD患者认知能力下降的风险增加，这无疑反映在胶质瘤中同时存在APOE和CD33改变。更好地了解神经胶质瘤患者基因和认知的相互作用可能会为个性化癌症治疗带来新的机会。
{"title":"Alzheimer's disease susceptibility genes in low-grade glioma","authors":"S. Lehrer, P. Rheinstein","doi":"10.4103/glioma.glioma_9_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_9_19","url":null,"abstract":"Background and Aim: Cognitive deficits in low-grade glioma are well documented. Patients with glioma who are carriers of the apolipoprotein E (APOE) e4 allele may have increased memory problems and executive dysfunction. While APOE is ranked the number one Alzheimer's disease (AD) susceptibility gene, many other susceptibility genes have been identified in genome-wide association studies. This study aimed to analyze the expression of APOE and the next 23 ranked AD susceptibility genes in malignant gliomas to identify significantly co-occurrent genes. Materials and Methods: To identify the most important AD susceptibility genes, the AlzGene database (http://www.alzgene.org/) was consulted, which displays this information and regularly updates it. To analyze AD susceptibility genes in glioma, The Cancer Genome Atlas, a project begun in 2005, was used to catalog genetic mutations responsible for cancer, employing genome sequencing and bioinformatics. The cBioPortal for cancer genomics and the UCSC Xena browser were used to analyze the data in The Cancer Genome Atlas. Results: APOE and CD33 were the only significantly co-occurrent genes in 514 low-grade glioma tumor samples. APOE was altered in 1.8% of cases and CD33 in 3%. Heatmap indicates that the two genes tend to coexpress. The most common alteration was deep deletion. The cBioPortal and the Xena browser cannot distinguish or identify the alleles of APOE or CD33. Conclusions: AD patients with one or more APOE e4 alleles, having one or more copies of the CD33 risk allele (rs3865444 C), are at increased risk of cognitive decline compared to APOE E4 carriers, no doubt reflected by the co-occurrence of APOE and CD33 alterations in the gliomas. Better understanding of the interaction of genes and cognition in glioma patients may lead to new opportunities to personalize cancer therapy.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"116 - 121"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46850090","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 : 2019-03-01DOI: 10.4103/glioma.glioma_6_19
S. Joseph, N. Ahmed, M. Hegde
Chimeric antigen receptors (CARs) are genetically engineered transmembrane cell receptors consisting of an antigen-binding ectodomain fused to an activating intracellular T-cell signaling chain. Grafting CAR molecules on T-cells enables targeted killing of tumors. The gene therapy approach of modifying autologous patient immune cells with CARs has now moved from the research bench to early-phase clinical trials in patients with refractory, recurrent, and nonresectable glioblastoma. This is a review of the state of the science in the field of CAR T-cells for glioblastoma and an update on the completed and ongoing clinical trials available at the Clinical Trials Registry (www.clinicaltrials.gov). Here, we also discuss insights gained from the clinical trials of CAR T-cells against glioblastoma and innovative approaches to improve their efficacy.
{"title":"Chimeric antigen receptor T-cells for glioblastoma: The journey ahead","authors":"S. Joseph, N. Ahmed, M. Hegde","doi":"10.4103/glioma.glioma_6_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_6_19","url":null,"abstract":"Chimeric antigen receptors (CARs) are genetically engineered transmembrane cell receptors consisting of an antigen-binding ectodomain fused to an activating intracellular T-cell signaling chain. Grafting CAR molecules on T-cells enables targeted killing of tumors. The gene therapy approach of modifying autologous patient immune cells with CARs has now moved from the research bench to early-phase clinical trials in patients with refractory, recurrent, and nonresectable glioblastoma. This is a review of the state of the science in the field of CAR T-cells for glioblastoma and an update on the completed and ongoing clinical trials available at the Clinical Trials Registry (www.clinicaltrials.gov). Here, we also discuss insights gained from the clinical trials of CAR T-cells against glioblastoma and innovative approaches to improve their efficacy.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"88 - 95"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41881815","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 : 2019-03-01DOI: 10.4103/glioma.glioma_4_19
Zhenghui Ma, Huandi Zhou, Qing Chang, X. Xue
Glioblastoma (GBM) is the most common malignant tumor of the central nervous system in adults. GBM is characterized by violent invasion and poor prognosis. Commonly, there are three main conventional methods to treat GBM, surgery, radiotherapy, and chemotherapy. GBM patients have a median survival ranging from 12 to 15 months, with all tumors developing, at some point, resistance to chemotherapy. There is recently growing interest in the relationship between microRNAs (miRNAs) and chemotherapy resistance in GBM. This paper aims to explore the molecular mechanism, by which miRNAs participate in the formation of chemotherapy resistance in GBM. Here, we summarize the published data relating miRNA to chemotherapy resistance in GBM. We discuss the relationship between mechanisms that miRNA impact upon and provide insight into potential future studies and clinical therapeutics.
{"title":"MicroRNA-based chemoresistance in glioblastoma","authors":"Zhenghui Ma, Huandi Zhou, Qing Chang, X. Xue","doi":"10.4103/glioma.glioma_4_19","DOIUrl":"https://doi.org/10.4103/glioma.glioma_4_19","url":null,"abstract":"Glioblastoma (GBM) is the most common malignant tumor of the central nervous system in adults. GBM is characterized by violent invasion and poor prognosis. Commonly, there are three main conventional methods to treat GBM, surgery, radiotherapy, and chemotherapy. GBM patients have a median survival ranging from 12 to 15 months, with all tumors developing, at some point, resistance to chemotherapy. There is recently growing interest in the relationship between microRNAs (miRNAs) and chemotherapy resistance in GBM. This paper aims to explore the molecular mechanism, by which miRNAs participate in the formation of chemotherapy resistance in GBM. Here, we summarize the published data relating miRNA to chemotherapy resistance in GBM. We discuss the relationship between mechanisms that miRNA impact upon and provide insight into potential future studies and clinical therapeutics.","PeriodicalId":12731,"journal":{"name":"Glioma","volume":"2 1","pages":"83 - 87"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45715367","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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