scholarly journals Is an Immunosuppressive Microenvironment a Characteristic of Both Intra- and Extraparenchymal Central Nervous Tumors?

2021 ◽  
Vol 28 (1) ◽  
pp. 34-49
Author(s):  
Amina Soltani ◽  
Bela Kajtar ◽  
El Husseiny Mohamed Mahmud Abdelwahab ◽  
Anita Steib ◽  
Zsolt Horvath ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Alternative Therapy ◽  
Survival Rates ◽  
Background Information ◽  
Low Grade ◽  
Immune Microenvironment ◽  
Immunosuppressive Property ◽  
The Central Nervous System ◽  
Immunosuppressive Microenvironment ◽  
Tumor Types

In spite of intensive research, the survival rates of patients diagnosed with tumors of the central nervous system (CNS) have not improved significantly in the last decade. Immunotherapy as novel and efficacious treatment option in several other malignancies has failed in neuro-oncology likely due to the immunosuppressive property of the brain tissues. Glioblastoma (GBM) is the most aggressive malignant CNS neoplasm, while meningioma (MNG) is a mainly low grade or benign brain tumor originating from the non-glial tissues of the CNS. The aim of the current preliminary study is to compare the immune microenvironment of MNG and GBM as potential target in immunotherapy. Interestingly, the immune microenvironment of MNG and GBM have proved to be similar. In both tumors types the immune suppressive elements including regulatory T cells (Treg), tumor-associated macrophages (TAM) were highly elevated. The cytokine environment supporting Treg differentiation and the presence of indoleamine 2,3-dioxygenase 1 (IDO1) have also increased the immunosuppressive microenvironment. The results of the present study show an immune suppressive microenvironment in both brain tumor types. In a follow-up study with a larger patient cohort can provide detailed background information on the immune status of individual patients and aid selection of the best immune checkpoint inhibitor or other immune modulatory therapy. Immune modulatory treatments in combination with IDO1 inhibitors might even become alternative therapy for relapsed, multiple and/or malignant MNG or chemo-resistant GBM.

Prognostic histopathologic features of canine glial tumors

2021 ◽  
pp. 030098582110257
Author(s):  
Joshua L. Merickel ◽  
G. Elizabeth Pluhar ◽  
Aaron Rendahl ◽  
M. Gerard O’Sullivan
Keyword(s):  
Brain Tumor ◽  
Median Survival ◽  
Low Grade ◽  
Astrocytic Tumors ◽  
Translational Model ◽  
Poor Survival ◽  
Whole Brain ◽  
Tumor Types ◽  
Tumor Biopsies ◽  
Prognostic Data

Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed. Tumors were diagnosed as astrocytic, oligodendroglial, or undefined glioma using Comparative Brain Tumor Consortium criteria. Putative features of malignancy were evaluated, namely, mitotic counts, glomeruloid vascularization, and necrosis. For biopsies, dogs with astrocytic tumors lived longer than those with oligodendroglial or undefined tumor types (median survival 743, 205, and 144 days, respectively). Dogs with low-grade gliomas lived longer than those with high-grade gliomas (median survival 734 and 194 days, respectively). Based on analysis of tumor biopsies, low mitotic counts, absence of glomeruloid vascularization, and absence of necrosis correlated with increased survival (median 293, 223, and 220 days, respectively), whereas high mitotic counts, glomeruloid vascularization, and necrosis correlated with poor survival (median 190, 170, and 154 days, respectively). Mitotic count was the only histological feature in biopsy samples that significantly correlated with survival ( P < .05). Whole-brain analyses for those same histologic features had similar and more robust correlations, and were statistically significant for all features ( P < .05). The small size of biopsy samples may explain differences between biopsy and whole-brain tumor data. These findings will allow more accurate prognosis for gliomas.

scholarly journals Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1546 ◽  
Author(s):  
Alena Kopkova ◽  
Jiri Sana ◽  
Tana Machackova ◽  
Marek Vecera ◽  
Lenka Radova ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Low Grade ◽  
Tumor Type ◽  
Tumor Patients ◽  
Primary Tumors ◽  
Mirna Profiling ◽  
Tumor Types ◽  
Cns Malignancies

Central nervous system (CNS) malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic spread. Circulating microRNAs (miRNAs) were found in almost all human body fluids including cerebrospinal fluid (CSF), and they seem to be highly stable and resistant to even extreme conditions. The overall aim of our study was to identify specific CSF miRNA patterns that could differentiate among brain tumors. These new biomarkers could potentially aid borderline or uncertain imaging results onto diagnosis of CNS malignancies, avoiding most invasive procedures such as stereotactic biopsy or biopsy. In total, 175 brain tumor patients (glioblastomas, low-grade gliomas, meningiomas and brain metastases), and 40 non-tumor patients with hydrocephalus as controls were included in this prospective monocentric study. Firstly, we performed high-throughput miRNA profiling (Illumina small RNA sequencing) on a discovery cohort of 70 patients and 19 controls and identified specific miRNA signatures of all brain tumor types tested. Secondly, validation of 9 candidate miRNAs was carried out on an independent cohort of 105 brain tumor patients and 21 controls using qRT-PCR. Based on the successful results of validation and various combination patterns of only 5 miRNA levels (miR-30e, miR-140, let-7b, mR-10a and miR-21-3p) we proposed CSF-diagnostic scores for each tumor type which enabled to distinguish them from healthy donors and other tumor types tested. In addition to this primary diagnostic tool, we described the prognostic potential of the combination of miR-10b and miR-196b levels in CSF of glioblastoma patients. In conclusion, we performed the largest study so far focused on CSF miRNA profiling in patients with brain tumors, and we believe that this new class of biomarkers have a strong potential as a diagnostic and prognostic tool in these patients.

Nonenhancing tumors of the spinal cord

2007 ◽  
Vol 7 (4) ◽  
pp. 403-407 ◽  
Author(s):  
J. Bradley White ◽  
Gary M. Miller ◽  
Kennith F. Layton ◽  
William E. Krauss
Keyword(s):  
Spinal Cord ◽  
Common Finding ◽  
Subtotal Resection ◽  
Low Grade ◽  
Spinal Cord Tumors ◽  
Intramedullary Tumors ◽  
Intramedullary Spinal Cord ◽  
Tumor Invasiveness ◽  
The Central Nervous System ◽  
Tumor Types

Object Enhancement of pathological entities in the central nervous system is a common finding when the blood–brain barrier has been compromised. In the brain, the presence or absence of gadolinium enhancement is often an indicator of tumor invasiveness and/or grade. In the spinal cord, however, contrast enhancement has been shown in all tumor types, regardless of grade. In this study the authors explore the incidence of nonenhancing tumors of the spinal cord and the clinical course of patients with these lesions. Methods A retrospective analysis was conducted in which investigators examined the patterns of enhancement of histologically proven intramedullary spinal cord tumors that had been evaluated at the Mayo Clinic between 1998 and 2002. The tumors that did not enhance were the subject of this report. Results A total of 130 patients with intramedullary tumors were evaluated. Of those, 11 patients (9%) had tumors that did not enhance. Histologically, a majority of tumors were astrocytomas (eight low-grade and two high-grade lesions); one tumor was a subependymoma. Morphologically, most of the tumors were diffuse and none had associated cysts. Tumors spanned from two to seven levels and were located throughout the spinal cord (four cervical, three cervicothoracic, one thoracic, and three thoracolumbar). Biopsy procedures were performed in eight patients, subtotal resection was performed in two, and gross-total resection in one. After a mean follow-up period of 19 months, tumors remained stable in eight patients but progressed in three, two of whom died. Conclusions A number of intramedullary spinal cord tumors will not enhance after addition of contrast agents. The absence of enhancement does not imply the absence of tumor.

scholarly journals IMMU-03. CHARACTERIZING THE IMMUNE MICROENVIRONMENT OF PEDIATRIC BRAIN TUMORS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i27-i27
Author(s):  
Robert Galvin ◽  
Danielle Maeser ◽  
Robert Gruener ◽  
R Stephanie Huang
Keyword(s):  
Brain Tumor ◽  
Cns Tumors ◽  
Low Grade ◽  
High Grade ◽  
Immune Microenvironment ◽  
Data Set ◽  
Gene Signatures ◽  
Pediatric Brain ◽  
Cell Gene ◽  
Cns Malignancies

Abstract Therapy for pediatric central nervous system (CNS) malignancies can be toxic, and outcomes are suboptimal. Immunotherapy holds promise as a therapeutic avenue, but one of the challenges in its application is the poorly understood microenvironment of pediatric CNS tumors. The Children’s Brain Tumor Network released the Pediatric Brain Tumor Atlas, containing the expression profile of nearly 700 primary CNS tumors. To study the immune microenvironment, a classification from The Cancer Genome Atlas project is applied. High-grade lesions are predominantly lymphocyte deplete (C4, 80%) or immunologically quiet (C5, 7.6%). Low-grade lesions are more mixed with 43% C4, 26% C5, and a higher proportion of inflammatory subtype (C3, 28%). For survival parameters, immune subtype and tumor grade are associated. Using a multivariate cox regression model, the hazard ratio is 2.2 (0.86 – 5.4, p = 0.102) and 3.6 (1.2 – 10.9, p = 0.02) for C4 and C5, respectively. Deconvolution of immune cell gene signatures provides insight into the phenotype of lymphocyte infiltrate, which averages 8.6% (IQR 5.4% – 9.8%) across all samples. For high-grade samples, greater than median expression of T cell-, monocyte-, macrophage-, and B cell-gene signatures are each associated with decreased survival (p &lt; 0.05). Microglia gene signatures have decreased relative expression in high-grade samples compared to low-grade samples (p &lt; 0.001). It is hypothesized that the expression of inhibitory immunomodulators contributes to a pro-tumorigenic microenvironment and represent potential therapeutic targets. In the absence of normal samples in the data set, differential gene expression experiments between disease states can reveal upregulated immunomodulators. Focusing on diffuse midline glioma, immunologic pathways are downregulated. Furthermore, 9 inhibitory immunomodulators, including KDM1A, EZH2, CD276, and VTCN1, are significantly expressed relative to midline low-grade glioma with equivalent immune subtype. Overall, our analysis contributes to the understanding of the immune microenvironment and mechanisms of immune escape for pediatric CNS malignancies.

Comparison between neuroimaging classifications and histopathological diagnoses using an international multicenter brain tumor magnetic resonance imaging database

2006 ◽  
Vol 105 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Margarida Julià-Sapé ◽  
Dionisio Acosta ◽  
Carles Majós ◽  
Àngel Moreno-Torres ◽  
Pieter Wesseling ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Magnetic Resonance ◽  
Brain Tumors ◽  
Mr Imaging ◽  
High Specificity ◽  
Low Grade ◽  
Tumor Type ◽  
Glial Tumor ◽  
Predictive Values ◽  
Tumor Types

Object The aim of this study was to estimate the accuracy of routine magnetic resonance (MR) imaging studies in the classification of brain tumors in terms of both cell type and grade of malignancy. Methods The authors retrospectively assessed the correlation between neuroimaging classifications and histopathological diagnoses by using multicenter database records from 393 patients with brain tumors. An ontology was devised to establish diagnostic agreement. Each tumor category was compared with the corresponding histopathological diagnoses by dichotomization. Sensitivity, specificity, positive and negative predictive values (PPVs and NPVs, respectively), and the Wilson 95% confidence intervals (CI) for each were calculated. In routine reporting of MR imaging examinations, tumor types and grades were classified with a high specificity (85.2–100%); sensitivity varied, depending on the tumor type and grade, alone or in combination. The recognition of broad diagnostic categories (neuroepithelial or meningeal lesions) was highly sensitive, whereas when both detailed type and grade were considered, sensitivity diverged, being highest in low-grade meningioma (sensitivity 100%, 95% CI 96.2–100.0%) and lowest in high-grade meningioma (sensitivity 0.0%, 95% CI 0.0–65.8%) and low-grade oligodendroglioma (sensitivity 15%, 95% CI 5.2–36.0%). In neuroepithelial tumors, sensitivity was inversely related to the precision in reporting of grade and cellular origin; “glioma” was a frequent neuroimaging classification associated with higher sensitivity in the corresponding category. The PPVs varied among categories, in general being greater than their prevalence in this dataset. The NPV was high in all categories (69.8–100%). Conclusions The PPVs and NPVs provided in this study may be used as estimates of posttest probabilities of diagnostic accuracy using MR imaging. This study targets the need for noninvasively increasing sensitivity in categorizing most brain tumor types while retaining high specificity, especially in the differentiation of high- and low-grade glial tumor classes.

scholarly journals OTME-11. Characterizing the immunologic context of pediatric brain tumors

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii15-ii15
Author(s):  
Robert Galvin ◽  
Danielle Maeser ◽  
Robert Gruener ◽  
R Stephanie Huang
Keyword(s):  
Brain Tumor ◽  
Immune Cell ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Cns Tumors ◽  
Low Grade ◽  
High Grade ◽  
Immune Microenvironment ◽  
Data Set ◽  
Pediatric Brain

Abstract Therapy for pediatric central nervous system (CNS) malignancies can be toxic, and outcomes are suboptimal. Immunotherapy holds promise as a therapeutic avenue, but the poorly understood microenvironment limits its application. The Children’s Brain Tumor Network (CBTN) released the Pediatric Brain Tumor Atlas, containing expression profiles of nearly 700 primary CNS tumors. To study the immune microenvironment, a classification from The Cancer Genome Atlas project is applied. High-grade lesions are predominantly lymphocyte deplete (C4, 81%) or immunologically quiet (C5, 11%). Low-grade lesions are more mixed with 46% C4, 21% C5, and a higher proportion of inflammatory subtype (C3, 31%). For survival parameters, adjusting for tumor grade and extent of resection, the hazard ratio is 2.2 (0.78 – 6.3), p = 0.13) and 2.4 (0.6 – 10.0, p = 0.24) for C4 and C5, respectively. With no events among low-grade tumors, progression-free survival will be another useful metric and released by CBTN in April. Deconvolution of immune cell gene signatures among C4 samples reveals decreased abundance of T cells (OR 0.26, 0.1 – 0.5) yet increasing T-cell abundance is associated with decreased survival time in high-grade samples (HR 3.7, 1.4 – 10.1). Additionally, there are increased macrophage and decreased microglia signatures among high-grade samples and the C4 and C5 subtypes. It is hypothesized that expression of inhibitory immunomodulators contributes to a pro-tumorigenic microenvironment and represent potential therapeutic targets. In lieu of normal tissue in the data set, differential gene expression experiments between disease states reveals upregulated immunomodulators. Conventional immunomodulators, e.g. PDL1 and CTLA4, are expressed in low-grade samples with C3 subtype, which is abundant in craniopharyngioma. Alternative inhibitory immunomodulators, e.g. KDM1A, EZH2, CD276, are significantly expressed in high-grade samples including diffuse midline glioma. Overall, our analysis contributes to the understanding of the immune microenvironment and identifies potential mechanisms of immune escape among pediatric CNS tumors.

MOLECULAR AND GENETIC SUBTYPES OF OVARIAN CANCER: PROSPECTS FOR FURTHER STUDIES

2019 ◽  
Vol 65 (1) ◽  
pp. 56-62
Author(s):  
Alisa Villert ◽  
Larisa Kolomiets ◽  
Natalya Yunusova ◽  
Yevgeniya Fesik
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Molecular Subtypes ◽  
Survival Rates ◽  
Consensus Algorithm ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
High Grade ◽  
Ovarian Carcinomas ◽  
Genetic Subtypes

High-grade ovarian carcinoma is a histopathological diagnosis, however, at the molecular level, ovarian cancer represents a heterogeneous group of diseases. Studies aimed at identifying molecular genetic subtypes of ovarian cancer are conducted in order to find the answer to the question: can different molecular subgroups influence the choice of treatment? One of the achievements in this trend is the recognition of the dualistic model that categorizes various types of ovarian cancer into two groups designated high-grade (HG) and low-grade (LG) tumors. However, the tumor genome sequencing data suggest the existence of 6 ovarian carcinoma subtypes, including two LG and four HG subtypes. Subtype C1 exhibits a high stromal response and the lowest survival. Subtypes C2 and C4 demonstrate higher number of intratumoral CD3 + cells, lower stromal gene expression and better survival than sybtype C1. Subtype C5 (mesenchymal) is characterized by mesenchymal cells, over-expression of N-cadherin and P-cadherin, low expression of differentiation markers, and lower survival rates than C2 and C4. The use of a consensus algorithm to determine the subtype allows identification of only a minority of ovarian carcinomas (approximately 25%) therefore, the practical importance of this classification requires additional research. There is evidence that it makes sense to randomize tumors into groups with altered expression of angiogenic genes and groups with overexpression of the immune response genes, as in the angiogenic group there is a comparative superiority in terms of survival. The administration of bevacizumab in the angiogenic group improves survival, while the administration of bevacizumab in the immune group even worsens the outcome. Molecular subtypes with worse survival rates (proliferative and mesenchymal) also benefit most from bevacizumab treatment. This review focuses on some of the advances in understanding molecular, cellular, and genetic changes in ovarian carcinomas with the results achieved so far regarding the formulation of molecular subtypes of ovarian cancer, however further studies are needed.

Herbal Medicine for Glioblastoma: Current and Future Prospects

2020 ◽  
Vol 16 (8) ◽  
pp. 1022-1043
Author(s):  
Imran Khan ◽  
Sadaf Mahfooz ◽  
Mustafa A. Hatiboglu
Keyword(s):  
Cell Proliferation ◽  
Survival Rates ◽  
Standard Of Care ◽  
Natural Compounds ◽  
Treatment Modalities ◽  
Normal Brain ◽  
The Central Nervous System ◽  
Cycle Regulation ◽  
Immense Potential

Background: Glioblastoma is one of the most aggressive and devastating tumours of the central nervous system with short survival time. Glioblastoma usually shows fast cell proliferation and invasion of normal brain tissue causing poor prognosis. The present standard of care in patients with glioblastoma includes surgery followed by radiotherapy and temozolomide (TMZ) based chemotherapy. Unfortunately, these approaches are not sufficient to lead a favorable prognosis and survival rates. As the current approaches do not provide a long-term benefit in those patients, new alternative treatments including natural compounds, have drawn attention. Due to their natural origin, they are associated with minimum cellular toxicity towards normal cells and it has become one of the most attractive approaches to treat tumours by natural compounds or phytochemicals. Objective: In the present review, the role of natural compounds or phytochemicals in the treatment of glioblastoma describing their efficacy on various aspects of glioblastoma pathophysiology such as cell proliferation, apoptosis, cell cycle regulation, cellular signaling pathways, chemoresistance and their role in combinatorial therapeutic approaches was described. Methods: Peer-reviewed literature was extracted using Pubmed, EMBASE Ovid and Google Scholar to be reviewed in the present article. Conclusion: Preclinical data available in the literature suggest that phytochemicals hold immense potential to be translated into treatment modalities. However, further clinical studies with conclusive results are required to implement phytochemicals in treatment modalities.

scholarly journals Glioma with Leptomeningeal Spread Mimics Chronic Meningoencephalitis in a Young Adult

2021 ◽  
pp. 179-183
Author(s):  
Ann-Kristin Becker ◽  
Marta Leonora Frank ◽  
Michael Friese ◽  
Joachim Röther
Keyword(s):  
Brain Tumor ◽  
Back Pain ◽  
Young Adult ◽  
Lower Back Pain ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Who Grade ◽  
Leptomeningeal Spread ◽  
Lower Back ◽  
Uncommon Case

The most malignant type of intrinsic brain tumor is glioblastoma (WHO grade IV). Primary leptomeningeal spread is rare and leads to a variety of differential considerations, as there is no typical clinical or imaging pattern. Here we present a rare and uncommon case of a primary leptomeningeal glioblastoma in combination with a low-grade glioma in a 21-year-old male, initially presenting with only headache and lower back pain. The presented case illustrates the challenging differential considerations and the severe course of leptomeningeal glioblastomas.

Different effects of bronchoscopic interventions on children and adults with tracheobronchial mucoepidermoid carcinoma

2021 ◽  
pp. 030089162199589
Author(s):  
Zhang Jieli ◽  
Zhou Yunzhi ◽  
Zhang Nan ◽  
Zou Heng ◽  
Wang Hongwu ◽  
...  
Keyword(s):  
Mucoepidermoid Carcinoma ◽  
Argon Plasma Coagulation ◽  
Survival Rates ◽  
Argon Plasma ◽  
Rigid Bronchoscopy ◽  
Low Grade ◽  
High Grade ◽  
Adult Group ◽  
Histologic Grading ◽  
Comprehensive Therapy

Aims: To investigate the efficacy and safety of minimally invasive bronchoscopic interventions for patients with tracheobronchial mucoepidermoid carcinoma (MEC). Methods: Patients with tracheobronchial MEC were included in this retrospective study, and the clinical features, histologic grading, treatments, and cumulative survival rates were calculated. Patients were categorized into child (n = 16) and adult (n = 19) group according to their ages. Histologic grading, treatments, and survival status were compared between the two groups. Results: In pathology, high-grade MEC counts for 6.77% and 42.10% in the child and adult group, respectively. As tumor growth pattern was concerned, 93.33% and 21.05% tumors in the child and adult group present intratracheal type. Multiple bronchoscopic interventions were conducted, including rigid bronchoscopy, argon plasma coagulation (APC), dioxide carbon cryotherapy, and electric loop. Tumors could be removed by multiple bronchoscopic interventions. Bronchoscopy-associated complications were rare, including an oral mucosa injury and a glottis edema. In the child group, one patient underwent left upper lung lobectomy. In the adult group, lobectomy and/or chemotherapy and/or radiotherapy were conducted in seven patients. The 5-year survival rate was 100% and 68.90% in the child and the adult group, respectively. Conclusions: Almost all children have low-grade and intratracheal MEC; 2/5 adults have invasive high-grade MEC. Multiple bronchoscopic interventions are effective in erasing low-grade intratracheal MEC without severe complications. For high-grade invasive MEC, aggressive and comprehensive therapy should be considered.

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