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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 285: 121933, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36208578

RESUMO

Gliomas are the most common type of primary tumor originating in the central nervous system of adults. Tumor histological type, pathological grade, and molecular pathology are significant prognosis and predictive factors. In this study, we were aiming to predict histological type and molecular pathological features based on terahertz time-domain spectroscopy technology. Nine gliomas with different grades, one meningioma, and one lymphoma were enrolled. There were significant differences in terahertz absorption coefficient between normal brain tissue, tumoral-periphery, and tumoral-center tissue in specific frequency bands (0.2-1.4 THz). Histological type, pathological grade, and glioma-specific biomarkers were closely related to the terahertz absorption coefficient in both tumoral-periphery and tumoral-center tissues. Interestingly, tumoral-periphery showed more obvious differences than tumoral-center tissues in almost all aspects. All the results show that the terahertz technology has potential application value in the intraoperative real-time glioma recognition and diagnosis of glioma histological and molecular pathological features.


Assuntos
Neoplasias Encefálicas , Glioma , Espectroscopia Terahertz , Adulto , Humanos , Patologia Molecular , Glioma/diagnóstico , Espectroscopia Terahertz/métodos , Neoplasias Encefálicas/diagnóstico , Encéfalo
2.
Glia ; 71(1): 127-138, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35322459

RESUMO

High-grade gliomas constitute the most frequent and aggressive form of primary brain cancer in adults. These tumors express cannabinoid CB1 and CB2 receptors, as well as other elements of the endocannabinoid system. Accruing preclinical evidence supports that pharmacological activation of cannabinoid receptors located on glioma cells exerts overt anti-tumoral effects by modulating key intracellular signaling pathways. The mechanism of this cannabinoid receptor-evoked anti-tumoral activity in experimental models of glioma is intricate and may involve an inhibition not only of cancer cell survival/proliferation, but also of invasiveness, angiogenesis, and the stem cell-like properties of cancer cells, thereby affecting the complex tumor microenvironment. However, the precise biological role of the endocannabinoid system in the generation and progression of glioma seems very context-dependent and remains largely unknown. Increasing our basic knowledge on how (endo)cannabinoids act on glioma cells could help to optimize experimental cannabinoid-based anti-tumoral therapies, as well as the preliminary clinical testing that is currently underway.


Assuntos
Canabinoides , Glioma , Humanos , Adulto , Endocanabinoides/farmacologia , Glioma/patologia , Receptores de Canabinoides/metabolismo , Receptores de Canabinoides/uso terapêutico , Canabinoides/farmacologia , Transdução de Sinais , Microambiente Tumoral
3.
Neurosci Lett ; 792: 136937, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341927

RESUMO

GBM is the central nervous system's most aggressive and malignant tumor. TGF-ß expression is elevated in GBM, and it promotes invasion and EMT. TGF-ß regulates the expression of several lncRNAs, which promote glioma pathogenesis. Here we characterize the role of TGF-ß-induced lncRNA- LINC01711 in glioma pathogenesis. We show that LINC01711 expression is significantly upregulated in GBM tissues and is associated with poor overall survival of GBM patients. Loss-of-function studies illustrate that LINC01711 promotes proliferation, migration, and invasion in GBM. In addition, LINC01711 depletion sensitizes glioma cells to Temozolomide (TMZ) induced apoptosis by inhibiting ZEB1 expression. LINC01711 functions as a competing endogenous RNA for miR-34a and promotes ZEB1 expression to regulate invasion. Our findings suggest that LINC01711 is an attractive therapeutic target for GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , MicroRNAs , RNA Longo não Codificante , Humanos , Glioblastoma/metabolismo , Fator de Crescimento Transformador beta , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Crescimento Transformadores/uso terapêutico , Proliferação de Células , Neoplasias Encefálicas/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
4.
Bioorg Chem ; 130: 106237, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36402025

RESUMO

Amino acid metabolism is recognized as a target for medical imaging due to its increase in malignant cells. Several radiotracers with primary achievement and possible subsequent chances have been designed and tested to image amino acid metabolism. Here, we report a new amino acid conjugate, with the purpose of extending [99mTc][Tc-HYNIC/EDDA]-Met(O) for single photon emission tomography (SPECT) imaging. The S-oxo-l-methionine (Met(O)) amino acid hydrazinonicotinamide (HYNIC) chelator conjugate (HYNIC-Met(O)) was prepared, using Fmoc solid-phase synthesis, and was radiolabeled with [99mTc]technetium pertechnetate, using tricine and ethylenediamine-N,N-diacetic acid (EDDA) as co-ligands. In vitro cellular uptake profile and saturation binding of radiotracer were determined on C6 glioma cells. Biodistribution and imaging studies were carried out on rat bearing C6 tumor tissue grafts. [99mTc][Tc-HYNIC/EDDA]-Met(O) was prepared in high yield and radiochemical purity (>98 %). The partition coefficient result showed that radioconjugate was very hydrophilic. The radioconjugate indicated both high cell uptake and in vitro internalization. Low nanomolar dissociation constant (66.02 nM) in C6 glioma cells was obtained for it as well. [99mTc][Tc-HYNIC/EDDA]-Met(O) revealed magnificent tumor uptake at early time points, with 1.98 ± 0.33 % injected activity per gram tumor (% IA/g) at 30 min post injection. The tumor uptake continued for 1 and 2 h and was 0.45 ± 0.33 % IA/g at 4 h. The uptake in other organs decreased much more rapidly causing high tumor to normal organ ratios so that the highest ratio of 13.25 of tumor-to-muscle at 60 min after injection was obtained with high contrast in gamma imaging. These results point out a very favorable [99mTc]Tc-labeled amino acid for targeting amino acid metabolism through target system L amino acid transporter (LAT1) in malignant cells especially C6 glioma cells. [99mTc][Tc-HYNIC/EDDA]-Met(O) manifests extremely good distribution, excretion and imaging attributes. So it seems to be an appropriate nominate for clinical imaging.


Assuntos
Glioblastoma , Glioma , Animais , Ratos , Glioblastoma/diagnóstico por imagem , Aminoácidos , Distribuição Tecidual , Diagnóstico por Imagem , Etilenodiaminas , Compostos Radiofarmacêuticos/farmacologia
5.
Anticancer Res ; 42(5): 2665-2673, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35489774

RESUMO

BACKGROUND: The purpose of this study was to evaluate the association of specific threshold values for changes in metabolic metrics measured from 1H magnetic resonance spectroscopic imaging (MRSI) to survival of patients with high-grade glioma treated with multimodality therapy. PATIENTS AND METHODS: Forty-four patients with newly diagnosed high-grade glioma were prospectively enrolled. Serial MRI and MRSI scans provided measures of tumor choline, creatine, and N-acetylaspartate (NAA). Cox regression analyses adjusted for patient age, KPS, and delivery of concurrent chemotherapy were used to assess the association of changes in metabolic metrics with survival. RESULTS: Median follow-up time for patients at risk was 13.4 years. Overall survival (OS) was longer in patients with ≤20% increase (vs. >20%) in normalized choline (p=0.024) or choline/NAA (p=0.024) from baseline to week 4 of RT. During this period, progression-free survival (PFS) was longer in patients with ≤40% increase (vs. >40%) in normalized choline (p=0.013). Changes in normalized creatine, choline/creatine, and NAA/creatine from baseline to mid-RT were not associated with OS. From baseline to post-RT, changes in metabolic metrics were not associated with OS or PFS. CONCLUSION: Threshold values for serial changes in choline metrics on mid-RT MRSI associated with OS and PFS were identified. Metabolic metrics at post-RT did not predict for these survival endpoints. These findings suggest a potential clinical role for MRSI to provide an early assessment of treatment response and could enable risk-adapted therapy in clinical trial development and clinical practice.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Colina/metabolismo , Creatina/metabolismo , Glioma/diagnóstico por imagem , Glioma/metabolismo , Glioma/terapia , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos
6.
Medicine (Baltimore) ; 101(47): e32042, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451503

RESUMO

BACKGROUND: To fully understand the clinical features and prognosis of Glioblastoma (GBM), we extracted the data from the Surveillance, Epidemiology, and End Results (SEER) database and performed a series of analyses. METHODS: We retrospectively analyzed the data of 1674 patients with GBM obtained from the SEER database from 1983 to 2015. Kaplan-Meier analysis was performed to calculate the survival rate, and the log-rank test was used to analyze the survival outcomes. RESULTS: Older patients with GBM had a worse survival period (P < .05). Laterality had no effect on the prognosis (P > .05). Patients with high-grade gliomas may have a shorter lifespan (P < .05). In terms of overall survival (OS) and disease specificity, all 3 classical treatments failed to improve the life expectancy (P > .05). In adult patients with GBM, we found that age, tumor grade, surgery, radiotherapy, and chemotherapy were independent risk factors for all-cause mortality. In the univariate disease-specific analysis, age, tumor grade, surgery, radiotherapy, and chemotherapy were independent risk factors. However, in multivariate disease-specific analysis, the results showed that only tumor grade and surgery were independent risk factors for GBM. CONCLUSIONS: Older patients diagnosed with GBM have worse survival, and patients with glioma of higher grades have a shorter lifespan. Age, grade, surgery, radiation therapy, and chemotherapy were independent prognostic factors for patients with GBM.


Assuntos
Glioblastoma , Glioma , Adulto , Humanos , Glioblastoma/terapia , Estudos Retrospectivos , Prognóstico , Análise de Sobrevida
8.
Zhonghua Bing Li Xue Za Zhi ; 51(11): 1115-1122, 2022 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-36323540

RESUMO

Objective: To investigate the clinicopathological characteristics of H3K27-altered diffuse midline glioma (DMG), and to analyze DMG's prognostic factors, and subsequently, to study the possibility of using NTRK as a therapeutic target for DMG. Methods: A total of 232 DMG diagnosed at the Sanbo Brain Hospital, Capital Medical University, Beijing, China from July 2016 to March 2021 were collected. Their clinical, radiological and pathological features, the ratio of MGMT promoter methylation, expression of NTRK, and characteristics of NTRK gene fusion were analyzed. The prognostic values of different factors were also studied, including age, tumor location, histological grade, gene and protein expression of NTRK, and postoperative adjuvant therapy. Results: Among the 232 DMG cases, there were 8 patients with both primary and relapse tumors on the record. Thus, a total of 224 patients were analyzed, including 118 males and 106 females. There were 126 adults (>18 years of age) and 98 children (≤18 years of age). Notably, the most frequent location was thalamus (41/126, 32.5%) in adults, but brainstem (59/96, 60.2%) in children. The lesions showed T1 hypointensity or isointensity, and T2 hyperintensity. However, contrast enhancement patterns of the tumors varied, with many tumors lacking contrast-enhancing. The histological grades included grade 2 (9/224, 4.0%), grade 3 (41/224, 18.3%) and grade 4 (174/224, 77.7%). Two hundred and twenty-four DMGs were diffusely positive for H3K27M and negative for H3K27me3. The ratio of MGMT promoter methylation was low (1/45, 2.2%). One hundred and seventy-seven of the 224 cases (177/224, 79.0%) were positive for NTRK. Fifty cases were analyzed using fluorescence in situ hybridization. Among them, five DMGs (positive rate, 10.0%) were NTRK fusion positive. This study showed that there were no differences between adult and pediatric DMGs in histological grading, expression of NTRK, and NTRK gene fusion. One hundred and fifty-nine patients were included in the follow-up analysis (P>0.05). During the follow-up period, 109/159 patients (69.6%) died of the disease, with a median survival time of 12 months (range 1 to 55 months). Univariate log-rank analysis showed that age, location, surgical procedure and postoperative adjuvant therapy were associated with overall survivals of the DMG patients (P<0.05). Conclusions: The prognosis of DMG is poor overall. There are differences between adult and pediatric DMGs in anatomic location and prognosis, but not in other features. NTRK1 gene fusion is detected in 10.0% of the tumors. It suggests that TRK inhibitor might be a choice for treating DMG.


Assuntos
Glioma , Adulto , Masculino , Feminino , Humanos , Criança , Idoso de 80 Anos ou mais , Hibridização in Situ Fluorescente , Glioma/patologia , Prognóstico , Fusão Gênica , Regiões Promotoras Genéticas
9.
Int J Clin Pract ; 2022: 1629570, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36380750

RESUMO

To analyse the value of the apparent diffusion coefficient (ADC) in diffusion-weighted imaging (DWI) and the choline (Cho)/creatine (Cr) ratio and Cho/N-acetyl-aspartate (NAA) ratio in magnetic resonance spectroscopy (MRS) in the differential diagnosis between recurrent glioma and radiation injury. Chinese and English studies related to the diagnosis of recurrent glioma and radiation injury using DWI and MRS and published before 15 October 2022 were retrieved from PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, China Biomedical Literature Database, VIP Journal Database, and Wanfang Database for a meta-analysis. A total of 11 articles were included in this study. ADC was lower in the recurrent glioma group than in the radiation injury group (standardized mean difference = -1.29, 95% confidence interval (CI) (-1.87, -0.71), P < 0.001). The Cho/Cr ratio was higher in the recurrent glioma group than in the radiation injury group (weighted mean difference = 0.65, 95% CI (0.40, 0.90), and P < 0.001). The Cho/NAA ratio was higher in the recurrent glioma group than in the radiation injury group, as evidenced by the sensitivity analysis. The sensitivity and specificity of the Cho/Cr ratio were 0.85 (0.73-0.92) and 0.82 (0.67-0.91), respectively, and the area under the curve was 0.86. The sensitivity and specificity of the Cho/NAA ratio were 0.82 (0.66-0.91) and 0.94 (0.69-0.99), respectively, and the area under the curve was 0.93. This meta-analysis showed that ADC, Cho/Cr, and Cho/NAA ratios all had high sensitivity and specificity. Therefore, DWI combined with MRS can effectively improve the diagnosis of recurrent glioma and radiation injury.


Assuntos
Neoplasias Encefálicas , Glioma , Lesões por Radiação , Humanos , Diagnóstico Diferencial , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/diagnóstico , Glioma/diagnóstico por imagem , Glioma/patologia , Espectroscopia de Ressonância Magnética/métodos , Lesões por Radiação/diagnóstico , Ácido Aspártico , Creatina , Colina
10.
Folia Neuropathol ; 60(3): 346-354, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36382488

RESUMO

INTRODUCTION: The paper aimed to explore the mechanism of miR-137 in modulating glioma. MATERIAL AND METHODS: qRT-PCR detected miR-137 and E2F7 mRNA expression in cells. The protein expression of E2F7 was measured using Western blot assay. Cell proliferation, scratch healing, transwell and programmed cell death assays were conducted to examine the influences of the genes on the biological function of glioma cells. The dual-luciferase assay verified the interaction between miR-137 and E2F7. RESULTS: MiR-137 was lowly expressed in glioma cells, and E2F7 was highly expressed. MiR-137 suppressed progression and promoted programmed cell death of glioma cells. MiR-137 could target and negatively regulate E2F7 expression to further accelerate programmed cell death of glioma cells. CONCLUSIONS: It was found that miR-137 could target E2F7 to restrain cell progression and accelerate programmed cell death of glioma cells, which is helpful to search for new molecular therapeutic targets for glioma.


Assuntos
Glioma , MicroRNAs , Humanos , Regulação Neoplásica da Expressão Gênica/genética , Movimento Celular , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Glioma/genética , Proliferação de Células/genética , Fator de Transcrição E2F7/genética , Fator de Transcrição E2F7/metabolismo
11.
BMC Neurol ; 22(1): 420, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368999

RESUMO

BACKGROUND: Glioma is one of the most commonly occurring malignant brain cancers with high recurrence and mortality. Glioma stem cells (SCs) are a rare sub-group of glioma cells that play a critical role in tumor progression. Heat shock protein 90 (HSP90) is known to promote the stemness of glioma SCs. Here, we investigated the role of HSP90 in glioma SC metabolism, to reveal its potential as a novel therapeutic target. METHODS: Self-renewal assays were used to assess stemness. Cell migration, invasion and viability were measured using Transwell and CCK-8 assays, respectively. Tumor growth was evaluated in xenograft nude mouse models. The expression of known markers of stemness including CD44, A2B5, Oct4, Nestin, Lgr5, Sox2, CD24 were assessed by western blotting. HSP90 expression was assessed by western blotting and immunohistochemistry (IHC). Glucose consumption, lactic acid production and ATP levels were measured using commercially available kits. Extracellular acidification rates (ECAR) were measured using the Seahorse XFe/XF analyzer. RESULTS: HSP90 was upregulated in spheroid cells compared to parental cells. HSP90 facilitated the characteristics of SCs through enhancing self-renewal capacity, glucose consumption, lactic acid production, total ATP, ECAR and glycolysis. 2-DG, an inhibitor of glycolysis, reduced HSP90 expression and inhibited the stemness of glioma cells. CONCLUSIONS: We show that HSP90 accelerates stemness and enhances glycolysis in glioma cells. Inhibition of glycolysis with 2DG prevented stemness. This reveals new roles for HSP90 during glioma progression and highlights this protein as a potential target for much-needed anti-glioma therapeutics.


Assuntos
Glioma , Camundongos , Animais , Humanos , Linhagem Celular Tumoral , Glioma/patologia , Glicólise , Camundongos Nus , Glucose , Ácido Láctico/uso terapêutico , Trifosfato de Adenosina , Células-Tronco Neoplásicas/metabolismo
12.
Dis Markers ; 2022: 1292648, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36408463

RESUMO

Introduction: The global incidence of brain tumors, the most common of which is lower grade glioma (LGG), remains high. Pleckstrin homology domain-containing family A member 4 (PLEKHA4) has been reported to be related to tumor invasion and growth. However, its role and correlation with immunity in LGG remain elusive. Methods: We evaluated the expression pattern, prognostic value, biological functions, and immune effects of PLEKHA4 in LGG. We also analyzed the association between PLEKHA4 levels in different tumors, patient prognosis, and its role in tumor immunity. Depending on the type of research data, we used statistical methods such as Student's t-tests, Mann-Whitney U tests one-way ANOVA tests Kruskal-Wallis tests Pearson's or Spearman's correlation analysis Chi-square and Fisher's exact tests in this paper. Results and Conclusions. The results revealed that PLEKHA4 levels were markedly elevated in most tumors (such as LGG). High PLEKHA4 levels are associated with poor overall survival (OS), progression-free interval (PFI) rates, and disease-specific survival (DSS) in LGG patients. Cox regression analysis and nomograms showed that PLEKHA4 levels are independent prognostic factors for LGG patients. According to functional enrichment analysis, PLEKHA4 levels in LGG are associated with immune infiltration and immunotherapy. In conclusion, PLEKHA4 is a potential prognostic marker and immunotherapy target for LGG.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Prognóstico , Domínios de Homologia à Plecstrina , Glioma/patologia , Neoplasias Encefálicas/metabolismo , Análise de Regressão
13.
Curr Opin Neurol ; 35(6): 787-793, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36367045

RESUMO

PURPOSE OF REVIEW: Somatic point mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) are a defining feature of the majority of WHO grade 2-3 diffuse glioma and the most powerful positive prognostic factor for survival in gliomas. The purpose is to review experimental therapeutic approaches targeting IDH mutations in gliomas including small-molecule inhibitors, immunotherapies, and agents targeting mutant IDH-induced epigenetic and metabolic vulnerabilities. RECENT FINDINGS: Extensive preclinical work supports targeting mutant IDH (mIDH) in glioma. In heavily pretreated patients with mIDH glioma, enzyme inhibitors demonstrated to be well tolerated with preliminary evidence of clinical activity in nonenhancing tumors and enhancing tumors when used as single agents. In patients with newly diagnosed WHO grade 3 or 4 astrocytomas, a phase 1 study of a vaccine-targeting IDH1 R132H showed to be well tolerated and demonstrated immunogenicity with a 3-year progression-free and overall survival rates of 0.63 and 0.84, respectively. A variety of ongoing trials aim to target mIDH, including treatments with single agents or combinatory approaches in the upfront or recurrent setting. SUMMARY: mIDH are commonly found in gliomas and play a key role in gliomagenesis. This has led to studies using agents to directly inhibit them, immunotherapies, and epigenetic/metabolic drugs with varying and promising results. Ongoing studies may elucidate the precise role of these therapies and the best timing for treatment within the disease course.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/tratamento farmacológico , Glioma/genética , Isocitrato Desidrogenase/genética , Mutação , Inibidores Enzimáticos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética
14.
Curr Opin Neurol ; 35(6): 803-813, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36367046

RESUMO

PURPOSE OF REVIEW: Summarize principles behind various immunotherapy approaches for high and low-grade glioma in the context of recently completed clinical trials and the new insights they provide. RECENT FINDINGS: Despite the widespread success of therapies targeting the T-cell checkpoints programmed-death 1 and cytotoxic T lymphocyte antigen 4 in other malignancies, recent phase III trials in glioblastoma confirm the lack of efficacy of anti-programmed-death 1 monotherapy in more than 90% of patients. Vaccination approaches remain under investigation for high-grade glioma and have shown activity in some low-grade glioma patients. Chimeric antigen receptor T cells now feature a new generation of products engineered to potentially withstand glucocorticoid therapy. Oncolytic viral therapies have similarly advanced in sophistication, with drug-sensitive gene expression and tumor-selective modifications. Combinations of therapies hold promise for overcoming the numerous mechanisms of immune suppression in glioma. SUMMARY: Although immunotherapies have yet to show rates of efficacy compared with other malignancies, new knowledge of immunology and combination therapies brings hope for improved efficacy in the future.


Assuntos
Glioblastoma , Glioma , Humanos , Glioma/tratamento farmacológico , Imunoterapia , Glioblastoma/terapia , Terapia Combinada , Fatores Imunológicos/uso terapêutico
15.
Eur Rev Med Pharmacol Sci ; 26(21): 7813-7826, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36394729

RESUMO

OBJECTIVE: DEPDC1B, which encodes DEP domain-containing protein 1B, exerts pathogenic effects in diverse cancers, but no such effect has been reported in the case of lower-grade glioma (LGG). Therefore, we sought to investigate the relationship between DEPDC1B expression and the prognosis of patients with LGG and reveal the underlying molecular mechanism. MATERIALS AND METHODS: First, RT-qPCR and immunohistochemical staining were used to examine DEPDC1B mRNA and protein expression in LGG. Second, transcriptomic data were collected from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases to investigate the impact of DEPDC1B expression on LGG patients by using the Kaplan-Meier survival analysis, receiver operating characteristic analysis and Cox models. Third, the effects of DEPDC1B on LGG cell proliferation and migration were revealed using wound-healing and Cell Counting Kit-8 assays and Ki67 immunofluorescence staining. Fourth, the Tumor Immune Estimation Resource database was used to examine how DEPDC1B affects the LGG immune microenvironment, and gene set enrichment analysis was used to uncover the signaling pathways in which DEPDC1B is involved in LGG. RESULTS: DEPDC1B was significantly upregulated in both LGG cells and tissues, and high expression of DEPDC1B contributed to poor prognosis of LGG patients and represented an independent risk factor for LGG. Moreover, DEPDC1B knockdown reduced the proliferation and migration abilities of LGG cells. Lastly, DEPDC1B was found to be positively associated with multiple immune infiltrates and immune-checkpoint markers. CONCLUSIONS: Our findings indicate for the first time that DEPDC1B is a pathogenic gene in LGG. More importantly, we provide a new biomarker and immunotherapeutic target for improving the diagnosis and treatment of LGG patients.


Assuntos
Glioma , Humanos , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Prognóstico , Proliferação de Células , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Microambiente Tumoral , Proteínas Ativadoras de GTPase/genética
16.
Eur Rev Med Pharmacol Sci ; 26(21): 7938-7948, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36394742

RESUMO

OBJECTIVE: This study investigated the roles of dynamic susceptibility contrast (DSC) perfusion and multivoxel magnetic resonance spectroscopy (MRS) in grading brainstem glioma (BSG). PATIENTS AND METHODS: Our retrospective study comprised 12 patients, including 6 with pathology verified low-grade BSGs and 6 with high-grade BSGs. We examined differences in age, relative cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), and the metabolite ratios of choline (Cho)/N-acetyl aspartate (NAA) and Cho/creatine (Cr) between these two groups using the Mann-Whitney U test and Chi-square test. Receiver operating characteristic (ROC) curve analysis was used to establish cutoff values and assess their usefulness in grading BSG. RESULTS: The Cho/NAA metabolite ratio had the strongest preoperative predictive performance for identifying the correct histological grade among BSGs, with an area under the ROC curve (AUC) value of 0.944 (cutoff: 3.88, sensitivity [Se]: 83.3%; specificity [Sp]: 100%), followed by the Cho/Cr ratio (cutoff: 3.08; AUC: 0.917; Se: 83.3%; Sp: 100%), rCBF (cutoff: 3.56, AUC: 0.917; Se: 83.3%; Sp: 100%), rCBV (cutoff: 3.16, AUC: 0.889; Se: 100%; Sp: 66.7%), and age (cutoff: 9.5 years, AUC: 0.889; Se: 100%; Sp: 83.3%). CONCLUSIONS: rCBF and rCBV values comparing solid tumors with the normal brain parenchyma and the metabolite ratios for Cho/NAA and Cho/Cre may serve as useful indices for establishing BSG grading and provide important information when determining treatment planning and prognosis in patients with BSG.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Criança , Neoplasias Encefálicas/metabolismo , Estudos Retrospectivos , Glioma/diagnóstico por imagem , Glioma/metabolismo , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Creatina , Ácido Aspártico , Colina/metabolismo , Perfusão , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/metabolismo
17.
Acta Neuropathol Commun ; 10(1): 167, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397144

RESUMO

Since the introduction of integrated histological and molecular diagnoses by the 2016 World Health Organization (WHO) Classification of Tumors of the Nervous System, an increasing number of molecular markers have been found to have prognostic significance in infiltrating gliomas, many of which have now become incorporated as diagnostic criteria in the 2021 WHO Classification. This has increased the applicability of targeted-next generation sequencing in the diagnostic work-up of neuropathology specimens and in addition, raises the question of whether targeted sequencing can, in practice, reliably replace older, more traditional diagnostic methods such as immunohistochemistry and fluorescence in-situ hybridization. Here, we demonstrate that the Oncomine Cancer Gene Mutation Panel v2 assay targeted-next generation sequencing panel for solid tumors is not only superior to IHC in detecting mutation in IDH1/2 and TP53 but can also predict 1p/19q co-deletion with high sensitivity and specificity relative to fluorescence in-situ hybridization by looking at average copy number of genes sequenced on 1p, 1q, 19p, and 19q. Along with detecting the same molecular data obtained from older methods, targeted-next generation sequencing with an RNA sequencing component provides additional information regarding the presence of RNA based alterations that have diagnostic significance and possible therapeutic implications. From this work, we advocate for expanded use of targeted-next generation sequencing over more traditional methods for the detection of important molecular alterations as a part of the standard diagnostic work up for CNS neoplasms.


Assuntos
Glioma , Humanos , Glioma/diagnóstico , Glioma/genética , Glioma/patologia , Neuropatologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de RNA , DNA
18.
Neuro Oncol ; 24(Suppl 6): S25-S32, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322096

RESUMO

Maximal safe surgical resection plays a key role in the care of patients with gliomas. A range of technologies have been developed to aid surgeons in distinguishing tumor from normal tissue, with the goal of increasing tumor resection and limiting postoperative neurological deficits. Technologies that are currently being investigated to aid in improving tumor control include intraoperative imaging modalities, fluorescent tumor makers, intraoperative cell and molecular profiling of tumors, improved microscopic imaging, intraoperative mapping, augmented and virtual reality, intraoperative drug and radiation delivery, and ablative technologies. In this review, we summarize the aforementioned advancements in neurosurgical oncology and implications for improving patient outcomes.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/cirurgia , Imageamento por Ressonância Magnética/métodos , Glioma/cirurgia , Procedimentos Neurocirúrgicos/métodos
19.
Neuro Oncol ; 24(Suppl 6): S33-S41, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322098

RESUMO

To ensure excellent postoperative clinical outcomes while preserving critical neurologic function, neurosurgeons who manage patients with intra-axial brain tumors can use intraoperative technologies and tools to achieve maximal safe resection. Neurosurgical oncology revolves around safe and optimal extent of resection, which further dictates subsequent treatment regimens and patient outcomes. Various methods can be adapted for treating both primary and secondary intra-axial brain lesions. We present a review of recent advances and published research centered on different innovative tools and techniques, including fluorescence-guided surgery, new methods of drug delivery, and minimally invasive procedural options.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Glioma/patologia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Procedimentos Neurocirúrgicos/métodos
20.
Neuro Oncol ; 24(Suppl 6): S42-S51, 2022 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322099

RESUMO

Magnetic resonance imaging-guided laser interstitial thermal therapy (LITT) is an ablative procedure using heat from a laser to provide cytoreduction in tissue. It is a minimally invasive procedure that has been used in intracranial pathologies such as high-grade gliomas, metastatic lesions, epilepsy, and other lesions. While LITT may offer a more acceptable complication profile compared to open surgery, the role of laser therapy for intracranial lesions in current treatment paradigms continues to evolve. This review will focus on the background and application of LITT, the current evidence for its use, and future directions for the technology.


Assuntos
Neoplasias Encefálicas , Glioma , Hipertermia Induzida , Terapia a Laser , Humanos , Neoplasias Encefálicas/cirurgia , Glioma/cirurgia , Terapia a Laser/métodos , Hipertermia Induzida/métodos , Imageamento por Ressonância Magnética , Lasers
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