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Beijing Da Xue Xue Bao. Yi Xue Ban =... Jun 2024To investigate the characteristics of the CD8 T cells infiltration from the 4 subtypes in medulloblastoma (MB), to analyze the relationship between CD8 T cells...
OBJECTIVE
To investigate the characteristics of the CD8 T cells infiltration from the 4 subtypes in medulloblastoma (MB), to analyze the relationship between CD8 T cells infiltration and prognosis, to study the function of C-X-C motif chemokine ligand 11 (CXCL11) and its receptor in CD8 T cells infiltration into tumors and to explore the potential mechanism, and to provide the necessary clinicopathological basis for exploring the immunotherapy of MB.
METHODS
In the study, 48 clinical MB samples (12 cases in each of 4 subtypes) were selected from the multiple medical center from 2012 to 2019. The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString PanCancer IO360 Panel (NanoString Technologies). Immunohistochemistry (IHC) staining of formalin-fixed, paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8 T cells in the MB four subtypes. Through bioinformatics analysis, the relationship between CD8T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated. The expression of CXCR3 receptor on the surface of CD8T cells in MB was verified by double immunofluorescence staining, and the underlying molecular mechanism of CD8T cells infiltration into the tumor was explored.
RESULTS
The characteristic index of CD8T cells in the WNT subtype of MB was relatively high, suggesting that the number of CD8T cells in the WNT subtype was significantly higher than that in the other three subtypes, which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus (GEO) database analysis by using R2 online data analysis platform. And the increase of CD8T cells infiltration was positively correlated with the patient survival. The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes. Immunofluorescence staining showed the presence of CXCL11 receptor, CXCR3, on the surface of CD8T cells, suggesting that the CD8T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3.
CONCLUSION
The CD8T cells infiltrate more in the WNT subtype MB than other subtypes. The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system, and the patients with more infiltration of CD8T cells in tumor have better prognosis. This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8T cells infiltration in MB, and give a new potential therapeutic target for the future immunotherapy of MB.
Topics: Humans; CD8-Positive T-Lymphocytes; Medulloblastoma; Receptors, CXCR3; Chemokine CXCL11; Prognosis; Lymphocytes, Tumor-Infiltrating; Cerebellar Neoplasms; Male; Female
PubMed: 38864138
DOI: 10.19723/j.issn.1671-167X.2024.03.019 -
Neuro-oncology Advances 2024There is no standard treatment for the recurrence of medulloblastoma, the most common malignant childhood brain tumor, and prognosis remains dismal. In this study, we...
BACKGROUND
There is no standard treatment for the recurrence of medulloblastoma, the most common malignant childhood brain tumor, and prognosis remains dismal. In this study, we introduce a regimen that is well-tolerated and effective at inducing remission.
METHODS
The primary objectives of this study were to assess tolerability of the regimen and overall response rate (ORR). A retrospective chart review of patients with recurrent medulloblastoma, treated at two institutions with a re-induction regimen of intravenous irinotecan and cyclophosphamide with oral temozolomide and etoposide, was performed. Demographic, clinicopathologic, toxicity, and response data were collected and analyzed.
RESULTS
Nine patients were identified. Median age was 5.75 years. Therapy was well-tolerated with no therapy-limiting toxicities and no toxic deaths. Successful stem cell collection was achieved in all 5 patients in whom it was attempted. ORR after 2 cycles was 78%. Three patients had a complete response, 4 patients had a partial response, 1 patient had stable disease, and 1 patient had progressive disease. Four patients are alive with no evidence of disease (NED), 2 patients are alive with disease, 2 patients have died of disease, and 1 patient died of toxicity related to additional therapy (NED at time of death).
CONCLUSIONS
This regimen is well-tolerated and effective. Tumor response was noted in the majority of cases, allowing patients to proceed to additional treatment with no or minimal disease. Further study of this regimen in a clinical trial setting is an important next step.
PubMed: 38863988
DOI: 10.1093/noajnl/vdae070 -
NMC Case Report Journal 2024Stroke-like migraine attacks after radiation therapy (SMART) syndrome, a delayed sequela of cranial radiotherapy encountered rarely, occurs due to transient neurological...
Stroke-like migraine attacks after radiation therapy (SMART) syndrome, a delayed sequela of cranial radiotherapy encountered rarely, occurs due to transient neurological deficits coupled with migraine episodes. This case report describes an occurrence of SMART syndrome in an individual 8 years after receiving medulloblastoma treatment. The subject, a 21-year-old male, experienced abrupt aphasia and right-sided hemiparesis. Arterial spin labeling (ASL) revealed initial cerebral hypoperfusion in the left temporal and parietal regions, with no tumor resurgence or notable ischemic alterations. Two days later, the symptoms disappeared completely; nevertheless, at that time, ASL presented cerebral hyperperfusion in the same lobule. The subject experienced a pulsating headache and nausea the next day. In the context of SMART syndrome, this fluctuation in cerebral blood flow indicated by ASL is a unique finding. The significance of this case lies in the documentation of the dynamic evolution of cerebral perfusion in SMART syndrome via ASL, thereby elucidating its underlying pathophysiology. As hemiplegic migraine shows a similar cerebral perfusion pattern to SMART syndrome, we inferred an unexplored but shared pathophysiology among hemiplegic migraine and SMART syndrome. Through this successful capture of these distinct cerebral blood flow alterations, from hypoperfusion to hyperperfusion, our understanding of the pathophysiological intricacies inherent to SMART syndrome will be enhanced.
PubMed: 38863579
DOI: 10.2176/jns-nmc.2024-0037 -
Aging Jun 2024SMARCD3 has recently been shown to be an important gene affecting cancer, playing an important role in medulloblastoma and pancreatic ductal adenocarcinoma. Therefore,...
BACKGROUND
SMARCD3 has recently been shown to be an important gene affecting cancer, playing an important role in medulloblastoma and pancreatic ductal adenocarcinoma. Therefore, we conducted this research to investigate the potential involvement of SMARCD3 across cancers and to offer recommendations for future studies.
METHODS
Utilizing information on 33 malignancies in the UCSC Xena database, SMARCD3 expression and its prognostic value were assessed. The tumor microenvironment was evaluated with the "CIBERSORT" and "ESTIMATE" algorithms. SMARCD3 and immune-related genes were analyzed using the TISIDB website. The pathways related to the target genes were examined using GSEA. MSI (microsatellite instability), TMB (tumor mutational burden), and immunotherapy analysis were used to evaluate the impact of target genes on the response to immunotherapy.
RESULTS
There is heterogeneity in terms of the expression and prognostic value of SMARCD3 among various cancers, but it is a risk factor for many cancers including uterine corpus endometrial cancer (UCEC), renal clear cell carcinoma (KIRC), and gastric adenocarcinoma (STAD). GSEA revealed that SMARCD3 is related to chromatin remodeling and transcriptional activation, lipid metabolism, and the activities of various immune cells. The TMB and MSI analyses suggested that SMARCD3 affects the immune response efficiency of KIRC, LUAD and STAD. Immunotherapy analysis suggested that SMARCD3 may be a potential immunotherapy target. RT-qPCR demonstrated the variation in SMARCD3 expression in KIRC, LUAD, and STAD.
CONCLUSION
Our study revealed that SMARCD3 affects the prognosis and immunotherapy response of some tumors, providing a direction for further research on this gene.
Topics: Humans; Biomarkers, Tumor; Prognosis; Tumor Microenvironment; Immunotherapy; Neoplasms; Microsatellite Instability; Gene Expression Regulation, Neoplastic; Chromosomal Proteins, Non-Histone
PubMed: 38862250
DOI: 10.18632/aging.205921 -
Pharmacology & Therapeutics Jun 2024Pediatric brain tumors are the leading cause of cancer-related deaths in children, with medulloblastoma (MB) being the most common type. A better understanding of these... (Review)
Review
Pediatric brain tumors are the leading cause of cancer-related deaths in children, with medulloblastoma (MB) being the most common type. A better understanding of these malignancies has led to their classification into four major molecular subgroups. This classification not only facilitates the stratification of clinical trials, but also the development of more effective therapies. Despite recent progress, approximately 30% of children diagnosed with MB experience tumor relapse. Recurrent disease in MB is often metastatic and responds poorly to current therapies. As a result, only a small subset of patients with recurrent MB survive beyond one year. Due to its dismal prognosis, novel therapeutic strategies aimed at preventing or managing recurrent disease are urgently needed. In this review, we summarize recent advances in our understanding of the molecular mechanisms behind treatment failure in MB, as well as those characterizing recurrent cases. We also propose avenues for how these findings can be used to better inform personalized medicine approaches for the treatment of newly diagnosed and recurrent MB. Lastly, we discuss the treatments currently being evaluated for MB patients, with special emphasis on those targeting MB by subgroup at diagnosis and relapse.
PubMed: 38857789
DOI: 10.1016/j.pharmthera.2024.108673 -
Cureus May 2024Background Sialic acid, a critical component for cell membrane integrity, undergoes complex biosynthesis involving enzymes like sialyltransferases (STs), impacting...
Background Sialic acid, a critical component for cell membrane integrity, undergoes complex biosynthesis involving enzymes like sialyltransferases (STs), impacting cancer progression. Aberrant sialylation by STs is implicated in cancer growth, invasion, and therapy resistance. Medulloblastoma (MB), a pediatric brain tumor with distinct subgroups and variable genetic alterations, poses uncertainty regarding the implications of sialylation. Methodology This study employs bioinformatic analyses on bulk and single-cell RNA-sequenced samples to explore atypical gene expressions linked to sialic acid metabolism in MB. A list of sialic biosynthesis-related genes was compiled using the STRING database. Data of MB samples from bulk and single-cell RNA sequencing were obtained from open-source repositories and were differentially analyzed, focusing on molecular subgroups (WNT, SHH, Group 3, and Group 4). The study employed survival analyses, specifically Cox regression, to analyze the overall survival (OS) data obtained through bulk RNA sequencing. Results Thirty-eight genes/proteins related to sialic acid metabolism were identified. Differential expression analysis between WNT and Group 3 and WNT and Group 4 revealed significant differences in seven and eleven genes, respectively, with consistent ST6GAL2 expression disparities (false discovery rate [FDR] -value < 0.01, log2FC > 0.58). Elevated ST6GAL2 expression correlated with improved OS, with mortality risk reductions ranging from 26% to 48% (-value < 0.006, Bonferroni-corrected threshold). Conclusions Elevated ST6GAL2 expression correlated with improved OS in diverse MB sample subsets, suggesting potential mechanisms in inhibiting tumor progression and enhancing immune response, requiring experimental validation.
PubMed: 38854216
DOI: 10.7759/cureus.59997 -
Translational Oncology Aug 2024Medulloblastoma is a type of brain cancer that primarily affects children. While chemotherapy has been shown to be effective in treating medulloblastoma, the development... (Review)
Review
Medulloblastoma is a type of brain cancer that primarily affects children. While chemotherapy has been shown to be effective in treating medulloblastoma, the development of chemotherapy resistance remains a challenge. One potential therapeutic approach is to selectively inhibit the inducible transcription factor called STAT3, which is known to play a crucial role in the survival and growth of tumor cells. The activation of STAT3 has been linked to the growth and progression of various cancers, including medulloblastoma. Inhibition of STAT3 has been shown to sensitize medulloblastoma cells to chemotherapy, leading to improved treatment outcomes. Different approaches to STAT3 inhibition have been developed, including small-molecule inhibitors and RNA interference. Preclinical studies have shown the efficacy of STAT3 inhibitors in medulloblastoma, and clinical trials are currently ongoing to evaluate their safety and effectiveness in patients with various solid tumors, including medulloblastoma. In addition, researchers are also exploring ways to optimize the use of STAT3 inhibitors in combination with chemotherapy and identify biomarkers that can predict treatment that will help to develop personalized treatment strategies. This review highlights the potential of selective inhibition of STAT3 as a novel approach for the treatment of medulloblastoma and suggests that further research into the development of STAT3 inhibitors could lead to improved outcomes for patients with aggressive cancer.
PubMed: 38852276
DOI: 10.1016/j.tranon.2024.102023 -
Health Science Reports Jun 2024Brain tumors are common, requiring physicians to have a precise understanding of them for accurate diagnosis and treatment. Considering that various histological tumor...
BACKGROUND AND AIM
Brain tumors are common, requiring physicians to have a precise understanding of them for accurate diagnosis and treatment. Considering that various histological tumor types present different cellularity, we conducted this research to examine the role of apparent diffusion coefficient (ADC) values in the differential diagnosis and pathologic grading of brain tumor types.
METHODS
In this cross-sectional study, we gathered pathology reports of histological samples of adult brain tumors. The tissue sample of brain tumors were examined histologically by a pathologist. The magnetic resonance imaging data of these patients were interpreted by a neuroradiologist. The measured ADC values and ADC ratios were calculated. Standard mean ADC values were expressed as 10 mm/s. The findings were compared according to the histological diagnosis of each tumor.
RESULTS
Sixty-eight patients were included in the study: 34 (50%) were male, and 34 (50%) were female. The average age of the patients was 51.69 + 16.40 years. In the examination of tumor type, 16 (23.5%) were astrocytoma, 9 (13.2%) were oligodendroglioma, 20 (29.4%) were glioblastoma, 4 (5.9%) were medulloblastoma, and 19 (27.9%) were metastatic tumors. the average value of ADC was statistically significantly different according to the pathological type of tumor ( < 0.001). The two-by-two comparison of average ADC among tumor types revealed significant differences, except for oligodendroglioma and glioblastoma (-value = 0.87) and glioblastoma and medulloblastoma (-value = 0.347). The average value of ADC and ADC ratio was statistically significantly different according to the pathological grade of the tumor ( < 0.001). In the two-by-two comparison of average ADC between all pathological grades of the tumor showed a significance difference except for Grade I and Grade II (-value = 0.355). The mean value of ADC and ADC ratio for glioblastoma and metastatic tumors showed no significant difference.
CONCLUSION
The assessment of brain tumor grade through ADC examination will help to estimate prognosis and devising suitable therapeutic strategies.
PubMed: 38841116
DOI: 10.1002/hsr2.2110 -
SA Journal of Radiology 2024Leptomeningeal dissemination is a rare manifestation of pilocytic astrocytoma. It may occur with higher-grade tumours like medulloblastoma, ependymoma and high-grade...
UNLABELLED
Leptomeningeal dissemination is a rare manifestation of pilocytic astrocytoma. It may occur with higher-grade tumours like medulloblastoma, ependymoma and high-grade glioma, but is extremely rare with low-grade glioma. There has been a growing number of reported cases documenting leptomeningeal dissemination of pilocytic astrocytoma in the medical literature.
CONTRIBUTION
Description of a World Health Organization (WHO) Grade I suprasellar pilocytic astrocytoma with leptomeningeal dissemination in the brain and spinal cord which showed progression of the leptomeningeal nodules without tumour upgrading on long-term follow-up.
PubMed: 38840827
DOI: 10.4102/sajr.v28i1.2876 -
Diagnostic and Interventional Radiology... Jun 2024This study aimed to detect supratentorial cortical and subcortical morphological changes in pediatric patients with infratentorial tumors.
PURPOSE
This study aimed to detect supratentorial cortical and subcortical morphological changes in pediatric patients with infratentorial tumors.
METHODS
The study included 24 patients aged 4-18 years who were diagnosed with primary infratentorial tumors and 41 age- and gender-matched healthy controls. Synthetic magnetization-prepared rapid gradient echo images of brain magnetic resonance imaging were generated using deep learning algorithms applied to T2-axial images. The cortical thickness, surface area, volume, and local gyrification index (LGI), as well as subcortical gray matter volumes, were automatically calculated. Surface-based morphometry parameters for the patient and control groups were compared using the general linear model, and volumes between subcortical structures were compared using the t-test and Mann-Whitney U test.
RESULTS
In the patient group, cortical thinning was observed in the left supramarginal, and cortical thickening was observed in the left caudal middle frontal (CMF), left fusiform, left lateral orbitofrontal, left lingual gyrus, right CMF, right posterior cingulate, and right superior frontal ( < 0.050). The patient group showed a volume reduction in the pars triangularis, paracentral, precentral, and supramarginal gyri of the left hemisphere ( < 0.05). A decreased surface area was observed in the bilateral superior frontal and cingulate gyri ( < 0.05). The patient group exhibited a decreased LGI in the right precentral and superior temporal gyri, left supramarginal, and posterior cingulate gyri and showed an increased volume in the bilateral caudate nucleus and hippocampus, while a volume reduction was observed in the bilateral putamen, pallidum, and amygdala ( < 0.05). The ventricular volume and tumor volume showed a positive correlation with the cortical thickness in the bilateral CMF while demonstrating a negative correlation with areas exhibiting a decreased LGI ( < 0.05).
CONCLUSION
Posterior fossa tumors lead to widespread morphological changes in cortical structures, with the most prominent pattern being hypogyria.
CLINICAL SIGNIFICANCE
This study illuminates the neurological impacts of infratentorial tumors in children, providing a foundation for future therapeutic strategies aimed at mitigating these adverse cortical and subcortical changes and improving patient outcomes.
PubMed: 38836466
DOI: 10.4274/dir.2024.242652