Nervous System Cancer Research Articles

Serum CD133-Associated Proteins Identified by Machine Learning Are Connected to Neural Development, Cancer Pathways, and 12-Month Survival in Glioblastoma.

Glioma is the most prevalent type of primary central nervous system cancer, while glioblastoma (GBM) is its most aggressive variant, with a median survival of only 15 months when treated with maximal surgical resection followed by chemoradiation therapy (CRT). CD133 is a potentially significant GBM biomarker. However, current clinical biomarker studies rely on invasive tissue samples. These make prolonged data acquisition impossible, resulting in increased interest in the use of liquid biopsies. Our study, analyzed 7289 serum proteins from 109 patients with pathology-proven GBM obtained prior to CRT using the aptamer-based SOMAScan® proteomic assay technology. We developed a novel methodology that identified 24 proteins linked to both serum CD133 and 12-month overall survival (OS) through a multi-step machine learning (ML) analysis. These identified proteins were subsequently subjected to survival and clustering evaluations, categorizing patients into five risk groups that accurately predicted 12-month OS based on their protein profiles. Most of these proteins are involved in brain function, neural development, and/or cancer biology signaling, highlighting their significance and potential predictive value. Identifying these proteins provides a valuable foundation for future serum investigations as validation of clinically applicable GBM biomarkers can unlock immense potential for diagnostics and treatment monitoring.

Radiation-Induced Cognitive Decline: Challenges and Solutions.

Radiation therapy, a common treatment for central nervous system cancers, can negatively impact cognitive function, resulting in radiation-induced cognitive decline (RICD). RICD involves a decline in cognitive abilities such as memory and attention, likely due to damage to brain white matter, inflammation, and oxidative stress. The multifactorial nature of RICD poses challenges including different mechanisms of injury (neurogenesis, oxidative stress and neuroinflammation, dendritic structure alterations and vascular effects) and confounding factors like advanced age, and pre-existing conditions. Despite these challenges, several potential solutions exist. Neuroprotective agents like antioxidants can mitigate radiation damage, while cognitive rehabilitation techniques such as cognitive training and memory strategies improve cognitive function. Advanced imaging techniques like magnetic resonance imaging (MRI) help identify vulnerable brain areas, and proton therapy offers precise targeting of cancer cells, sparing healthy tissue. Multidisciplinary care teams are crucial for managing RICD's cognitive and psychological effects. Personalized medicine, using genetic and molecular data, can identify high-risk patients and tailor treatments accordingly. Emerging therapies, including stem cell therapy and regenerative medicine, offer hope for repairing or replacing damaged brain tissue. Addressing RICD is vital for cancer survivors, necessitating consideration of cognitive function and provision of appropriate support and resources for those experiencing cognitive decline.

Prevalence and concentration of aflatoxin M1 in breast milk in Africa: a meta-analysis and implication for the interface of agriculture and health

Breast milk is one of the many distinct forms of food that can be contaminated with aflatoxin M1 (AFM1). They may be consumed by eating contaminated foods, such as contaminated meat and crops, which would then be present in breast milk and cause health problems, including nervous system disorders and cancers of the lungs, liver, kidneys, and urinary tract. However, the prevalently inconsistent explanation of prevalence and concentration remains a big challenge. Thus, this meta-analysis was conducted to determine the prevalence and concentration of harmful chemicals in breast milk in an African context. The databases MEDLINE, PubMed, Embase, SCOPUS, Web of Science, and Google Scholar were searched for both published and unpublished research. To conduct the analysis, the collected data were exported to Stata version 18. The results were shown using a forest plot and a prevalence with a 95% confidence interval (CI) using the random-effects model. The Cochrane chi-square (I2) statistics were used to measure the studies' heterogeneity, and Egger's intercept was used to measure publication bias. This review included twenty-eight studies with 4016 breast milk samples and newborns. The analysis showed the overall prevalence and concentration of aflatoxin M1 in breast milk were 53% (95% CI 40, 65; i2 = 98.26%; P = 0.001). The pooled mean aflatoxin M1 concentration in breast milk was 93.02 ng/l. According to this study, the eastern region of Africa was 62% (95% CI 39–82) profoundly affected as compared to other regions of the continent. In subgroup analysis by publication year, the highest level of exposure to aflatoxins (68%; 95% CI 47–85) was observed among studies published from 2010 to 2019. This finding confirmed that more than half of lactating women’s breast milk was contaminated with aflatoxin M1 in Africa. The pooled mean aflatoxin M1 concentration in breast milk was 93.02 ng/l. According to this study, the eastern region of Africa was profoundly affected compared with other regions. Thus, the government and all stakeholders must instigate policies that mitigate the toxicity of aflatoxins in lactating women, fetuses, and newborns.

Antitumor Activity of a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting LGR5 in Preclinical Models of Neuroblastoma.

Neuroblastoma (NB) is a cancer of the peripheral nervous system found in children under 15 years of age. It is the most frequently diagnosed cancer during infancy, accounting for ~12% of all cancer-related deaths in children. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a membrane receptor that is associated with the primary tumor formation and metastasis of cancers in the gastrointestinal system. Remarkably, high levels of LGR5 are found in NB tumor cells, and high LGR5 expression is strongly correlated with poor survival. Antibody-drug conjugates (ADCs) are monoclonal antibodies that are covalently linked to cell-killing cytotoxins to deliver the payloads into cancer cells. We generated an ADC with an anti-LGR5 antibody and pyrrolobenzodiazepine (PBD) dimer-based payload SG3199 using a chemoenzymatic conjugation method. The resulting anti-LGR5 ADC was able to inhibit the growth of NB cells expressing LGR5 with high potency and specificity. Importantly, the ADC was able to completely inhibit the growth of NB xenograft tumors in vivo at a clinically relevant dose for the PBD class of ADCs. The findings support the potential of targeting LGR5 using the PBD class of payload for the treatment of high-risk NBs.

Oligodendroglioma: a neurological perspective in Sub-saharan Africa.

Gliomas are a kind of brain cancer that develops from glial cells. Glial cells provide nourishment and energy to nerve cells, and they also preserve the blood-brain barrier. A primary cancer of the central nervous system (CNS) is oligodendroglioma. This suggests that it originates in the brain or spinal cord. While oligodendrogliomas can strike anyone at any age, the age range of 35 to 44 is when they most commonly occur. Oligodendrogliomas are rare in young people and more common in men than women. Based on anecdotal data, patients with oligodendroglioma may present management challenges in Africa. There are delays in diagnosis and referrals due to the scarcity of neuroimaging facilities. A wide range of strategies have been put forth to improve pathology services in low- and middle-income nations. Adequate mentorship, short-term visitor programs, overcoming supply chain constraints, establishing training standards, and establishing the role of pathologists in cancer screening and early diagnosis have all been proposed as solutions to this problem. To sum up, oligodendroglioma is one of the low-grade gliomas this study looked at. Brain cancer is a serious public health concern in Africa. Improved options for screening and therapy are required to better address this problem.

Current standards and the future role of hadrontherapy in the treatment of central nervous system tumors

IntroductionRadiation therapy is vital for treating central nervous system cancers (CNS), but traditional methods have limitations, especially in cases with high risks of side effects. Ion beam therapy, with its unique properties, offers a promising alternative for more precise and effective treatment, particularly in challenging scenarios.Materials and methodsThe presentation given at the symposium on hadrontherapy covered relevant literature for the utilization of ion beam therapy for pediatric CNS tumors, glioma, and meningeoma, as well as its role in re-irradiation. Emphasis was placed on new beam modalities, including carbon and helium ions, highlighting their potential benefits in improving treatment outcomes.ResultsThe results underscore the importance of preserving surrounding healthy tissue in pediatric malignancies’ radiation therapy. Proton irradiation achieves optimal target coverage while reducing radiation-induced side effects. Carbon ions show promise in glioma treatment, with ongoing trials validating their efficacy. Moreover, helium ion therapy demonstrates advantages in sparing normal tissue, making it a promising candidate for reintroduction into clinical routines. These findings highlight the potential of ion beam therapies in optimizing treatment outcomes while minimizing side effects, particularly in pediatric CNS tumors and gliomas.ConclusionResults support proton therapy for brain tumors, aiming to preserve cognitive function. Carbon ions could benefit select patients in primary treatment and for recurrent cases. Helium ion therapy combines advantages of protons and carbon ions, offering precise dose deposition and tissue sparing, making it suitable for clinical use.

An in-vivo treatment monitoring system for ion-beam radiotherapy based on 28 Timepix3 detectors

Ion-beam radiotherapy is an advanced cancer treatment modality offering steep dose gradients and a high biological effectiveness. These gradients make the therapy vulnerable to patient-setup and anatomical changes between treatment fractions, which may go unnoticed. Charged fragments from nuclear interactions of the ion beam with the patient tissue may carry information about the treatment quality. Currently, the fragments escape the patient undetected. Inter-fractional in-vivo treatment monitoring based on these charged nuclear fragments could make ion-beam therapy safer and more efficient. We developed an ion-beam monitoring system based on 28 hybrid silicon pixel detectors (Timepix3) to measure the distribution of fragment origins in three dimensions. The system design choices as well as the ion-beam monitoring performance measurements are presented in this manuscript. A spatial resolution of 4mm\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{4}\\,\\hbox {mm}}$$\\end{document} along the beam axis was achieved for the measurement of individual fragment origins. Beam-range shifts of 1.5mm\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${1.5}\\,\\hbox {mm}$$\\end{document} were identified in a clinically realistic treatment scenario with an anthropomorphic head phantom. The monitoring system is currently being used in a prospective clinical trial at the Heidelberg Ion Beam Therapy Centre for head-and-neck as well as central nervous system cancer patients.

Criteria for predicting the development of recurrent peripheral nerve sheas tumors

Peripheral nerve sheaths tumors (PNST) account for about 8 % of all nervous system cancers. The relapse rate ranges from 17.3 to 26.4 %, showing an upward trend. The causes and provoking factors for the development of relapses of PNST have not been fully studied. Purpose of the study: to establish criteria for predicting recurrence of PNST. Material and Methods. The study included 122 patients who were treated at the Department of Spine and Peripheral Nerve Surgery of A.I. Polenov Russian Research Neurosurgical Institute from 2009 to 2021. Among them, there were 87 (71.3 %) patients with primary PNST and 35 (28.7 %) patients with recurrent PNST. All patients underwent MRI and ENMG both before and after surgery. An immunohistochemical study of Ki67 and SO X10 markers was performed. Results. The majority of relapses occured within 1 year after surgery. In cases with radical removal of PNST, the risk of relapse was: 28.6 % for schwannomas 28.6 %, 37.1 % for neurofibromas and 34.3 % for MP NST 34.3 % (p≥0.05). The risk of developing relapse of PNST was 2.9 times higher in patients aged ≥49 years than in patients aged ≤48 years (p<0.004). The larger the initial size of the tumor, the higher the risk of relapse in the late postoperative period. The risk of developing relapse of MP NST was 8.79 times higher in patients with tumor size of greater than 11.5 cm than in patients with smaller tumor size (p<0.02). The of Ki67 level above 4.85 % in schwannomas and above 5.17 % in neurofibromas can predict relapse of PNST (p<0.05). Loss of SO X10 protein expression was associated with an increase in histological anaplasia of the tumor, which causes a high risk of relapse and an unfavorable clinical course of the disease. Conclusion. Despite radical (total) resection of PNST, the risk of relapse remains high. The pathological type of tumor, its size, levels of SO X10 and Ki67 markers, patient’s age, degree of preoperative neurological deficit and extent of surgery are significant criteria for predicting the development of relapse of PNST.

Predictive Performance of Cardiovascular Risk Scores in Cancer Survivors From the UK Biobank

BackgroundCardiovascular preventive strategies are guided by risk scores with unknown validity in cancer cohorts. ObjectivesThis study aimed to evaluate the predictive performance of 7 established cardiovascular risk scores in cancer survivors from the UK Biobank. MethodsThe predictive performance of QRISK3, Systematic Coronary Risk Evaluation 2 (SCORE2)/Systematic Coronary Risk Evaluation for Older Persons (SCORE-OP), Framingham Risk Score, Pooled Cohort equations to Prevent Heart Failure (PCP-HF), CHARGE-AF, QStroke, and CHA2DS2-VASc was calculated in participants with and without a history of cancer. Participants were propensity matched on age, sex, deprivation, health behaviors, family history, and metabolic conditions. Analyses were stratified into any cancer, breast, lung, prostate, brain/central nervous system, hematologic malignancies, Hodgkin lymphoma, and non-Hodgkin lymphoma. Incident cardiovascular events were tracked through health record linkage over 10 years of follow-up. The area under the receiver operating curve, balanced accuracy, and sensitivity were reported. ResultsThe analysis included 31,534 cancer survivors and 126,136 covariate-matched controls. Risk score distributions were near identical in cases and controls. Participants with any cancer had a significantly higher incidence of all cardiovascular outcomes than matched controls. Performance metrics were significantly worse for all risk scores in cancer cases than in matched controls. The most notable differences were among participants with a history of hematologic malignancies who had significantly higher outcome rates and poorer risk score performance than their matched controls. The performance of risk scores for predicting stroke in participants with brain/central nervous system cancer was very poor, with predictive accuracy more than 30% lower than noncancer controls. ConclusionsExisting cardiovascular risk scores have significantly worse predictive accuracy in cancer survivors compared with noncancer comparators, leading to an underestimation of risk in this cohort.

OTHR-30. THE CLINICAL AND BIOLOGICAL LANDSCAPE OF CNS CANCERS IN CONSTITUTIONAL MISMATCH REPAIR DEFICIENCY: AN IRRDC COHORT STUDY

Abstract BACKGROUND Constitutional mismatch repair deficiency (CMMRD) is an aggressive cancer predisposition syndrome. As a lack of data contributes to management challenges and inferior outcomes, especially in central nervous system (CNS) cancers, we aimed to determine the clinical spectrum, cancer biology, and impact of genetics on patient survival. METHODS To determine the cancer spectrum, biology, estimated incidence, and impact of genotype on cancer onset and survival, including following surveillance and immunotherapy, we collected cross-sectional, longitudinal, and genomic data on CMMRD patients and their cancers registered to an international consortium. RESULTS We report 201 patients enrolled between 2007-2022 (median follow-up: 7.2 years). Overall, 194 (97%) patients developed 339 cancers. Cumulative cancer and CNS tumor incidence were 93% and 82% by age 20, respectively. Median time between cancers was 2 years. Although neoplasms developed in 15 organs and included early-onset adult cancers, CNS tumors had the earliest median age of diagnosis (9.7 years), were the most common cancer type (51%), and the main cause of death (p<0.0001). All cancers exhibited high mutation and microsatellite burden, and pathognomonic mutational signatures. CNS cancers were enriched for mutations in POLE/POLD1, TP53, IDH1, and RAS/MAPK compared to hematopoietic and other cancers. These mutations determined response to therapy. Germline MLH1/MSH2 variants caused earlier cancer and CNS tumor onset than PMS2/MSH6, and inferior survival (survival at 15 years: PMS2: 63%, MSH6: 49%, MLH1: 19%, MSH2: 0%, p<0.0001). Strikingly, frameshift/truncating variants within the same gene caused earlier cancers and inferior outcomes (p<0.0001). The deleterious impact of MLH1/MSH2 persisted despite overall improvement in survival following surveillance and immunotherapy. CONCLUSION The extreme cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis focusing on specific genotypes to perform precision approaches toward surveillance and immunotherapy. These data will guide the management of children and emerging adult survivors of CMMRD.

Crosstalk Between the Nervous System and Colorectal Cancer.

The nervous system is the dominant regulatory system in the human body. The traditional theory is that tumors lack innervation. However, an increasing number of studies have shown complex bidirectional interactions between tumors and the nervous system. Globally, colorectal cancer (CRC) is the third most common cancer. With the rise of tumor neuroscience, the role of nervous system imbalances in the occurrence and development of CRC has attracted increasing amounts of attention. However, there are still many gaps in the research on the interactions and mechanisms involved in the nervous system in CRC. This article systematically reviews emerging research on the bidirectional relationships between the nervous system and CRC, focusing on the following areas: (1) Effects of the nervous system on colon cancer. (2) Effects of CRC on the nervous system. (3) Treatment of CRC associated with the nervous system.

An osteolytic lesion of the proximal ulna in a patient with Maffucci syndrome: a case report

Maffucci syndrome is a rare, congenital, and nonhereditary syndrome characterized by the occurrence of multiple enchondromas and hemangiomas. According to previous studies, patients diagnosed with Maffucci syndrome have a higher risk of developing malignant tumors, such as ovarian cancer, pancreatic cancer, breast cancer, and central nervous system cancer, in addition to malignant transformations of enchondromas. The authors report a case of a 37-year-old male patient with Maffucci syndrome who presented with multiple enchondromas and hemangiomas. This patient’s presentation and management are discussed, along with a review of the literature. Maffucci syndrome should be expected when encountering a patient with multiple enchondromas and suspected hemangiomas in the limbs. Even if benign lesions such as enchondromas or hemangiomas are diagnosed, regular follow-up is required to monitor for malignant transformations and the development of malignant tumors in other organs.

Perspective and Therapeutic Potential of the Noncoding RNA-Connexin Axis.

Noncoding RNAs (ncRNAs) are a class of nucleotide sequences that cannot be translated into peptides. ncRNAs can function post-transcriptionally by splicing complementary sequences of mRNAs or other ncRNAs or by directly engaging in protein interactions. Over the past few decades, the pervasiveness of ncRNAs in cell physiology and their pivotal roles in various diseases have been identified. One target regulated by ncRNAs is connexin (Cx), a protein that forms gap junctions and hemichannels and facilitates intercellular molecule exchange. The aberrant expression and misdistribution of connexins have been implicated in central nervous system diseases, cardiovascular diseases, bone diseases, and cancer. Current databases and technologies have enabled researchers to identify the direct or indirect relationships between ncRNAs and connexins, thereby elucidating their correlation with diseases. In this review, we selected the literature published in the past five years concerning disorders regulated by ncRNAs via corresponding connexins. Among it, microRNAs that regulate the expression of Cx43 play a crucial role in disease development and are predominantly reviewed. The distinctive perspective of the ncRNA-Cx axis interprets pathology in an epigenetic manner and is expected to motivate research for the development of biomarkers and therapeutics.

Global, national, and regional burden of brain and central nervous system cancer in youth under 20 from 1990-2019: A benchmarking analysis.

2084 Background: Brain and central nervous system (CNS) cancer ranks as the second leading cause of death among all cancer-related fatalities globally in individuals under 20 years old. Despite its significance, there is a notable dearth of data on brain and CNS cancer in this age group, necessitating a comprehensive cross-country comparison. Methods: Utilizing the Global Burden of Disease study framework, we estimated the prevalence, incidence, deaths, and disability-adjusted life years (DALYs) attributable to brain and CNS cancer by age, sex, year, and location across 204 countries and territories from 1990-2019. Results: The total prevalence increased from 153,334 (95%UI: 111,452-233,819) in 1990 to 212,459 (164,908-245,556) in 2019, with incidence rising from 47,373 (32,635-74,710) in 1990 to 47,600 (36,572-55,194) in 2019. Notably, the annual percentage change (APC) in deaths decreased by 21% (56-15), and DALYs by 22% (57-15) from 1990-2019. Sub-Saharan Africa and the African Union exhibited the highest APC increase in deaths, while Southeast Asia, East Asia, and Oceania experienced the most significant decrease. The highest APC in incidence occurred in the 10-14 years age group at 27%, with a slight increase of 1% in deaths observed in the 10-19 years age group. Females bore a higher burden compared to males, with APC in prevalence at 29% versus 51%, and incidence at -4% versus 7%. Conclusions: Brain and CNS cancer accounted for 9.55% of deaths among individuals under 20 globally in 2019. While the overall global trend has shown an increase over the last three decades, females exhibit a higher burden. Despite a decrease in deaths over the same period, strategies must be implemented to combat this burden, emphasizing the importance of early investigation and management, particularly in resource-limited settings worldwide. [Table: see text]

The role of the ubiquitin ligase UBE4B in neural tumors in adults and children.

e14034 Background: In cancers of the nervous system such as neuroblastoma (NB), the ubiquitin ligase UBE4B directly ubiquitinates growth factor receptors (GFRs), influencing their trafficking and lysosomal degradation. While the diverse functions of UBE4B are acknowledged, we hypothesize that UBE4B expression has distinct associations with outcomes in pediatric versus adult nervous system cancers. We examined the impact of UBE4B expression on glioblastoma (GBM) development, growth, and metastasis by correlating its expression with patient outcomes across age groups. Methods: Glioblastoma samples that were IDH1/2 wild type (n = 2072) underwent DNA (592-gene/whole-exome) and RNA (whole transcriptome) sequencing at Caris Life Sciences. Samples were stratified by UBE4B expression (transcripts per million – TPM) quartiles for all GBM tumors (Q4: H and Q1: L) and by patient age at the time of tissue collection (younger: < 30 years; older: > 60 years). Cell infiltration in the tumor microenvironment was inferred by quanTIseq. Gene expression profiles were analyzed for transcriptomic signature predictive of response to immunotherapy. Overall survival (OS) was derived from insurance claims data, and Kaplan-Meier estimates were calculated. Mann-Whitney U and Chi-square/Fisher-Exact tests were applied were appropriate, with p-values adjusted for multiple comparison. Results: UBE4B expression was similar between younger (n = 57) and older (n = 1115) glioblastoma patients (median: 24.7 vs. 21.6 TPM, p = 0.17). In younger patients, those with high UBE4B expression showed improved OS compared to low expressors (24.9 vs 19.2 months [mos]; HR = 0.41, 95% CI 0.15 – 1.11, p = 0.07). However, UBE4B expression was not associated with OS among older GBM patients (13.5 vs 12.9 mos; HR 1.10 95% CI 0.9 – 1.3, p = 0.33). Within the younger cohorts, higher expression of growth factor receptor genes was observed in high compared to low UBE4B expression ( EGFR: 96.57 vs. 7.07 TPM, p = 0.0092; RET: 0.99 vs. 0.30 TPM, p = 0.018; NTRK2: 236.9 vs. 29.5 TPM, p = 0.084). Concurrent mutation of PDGFRA was also exclusively observed in UBE4B-high tumors (42.9% vs. 0% in UBE4B-L, p = 0.024). Transcriptomic analysis, however, showed that UBE4B-high tumors had lower IFN-g signature scores compared to UBE4B-L (-0.62 vs. -0.41 arbitrary units, p = 0.02). M1 macrophage cell fractions were lower in UBE4B-high compared to UBE4B-low (median: 0.33% vs. 3.38%, p = 0.005), while the fraction of B cells was significantly higher (median: 9.57% vs. 8.14%, p = 0.009). Conclusions: Higher UBE4B expression in younger GBM cases correlated with improved OS suggesting it may have utility as a prognostic biomarker. Increased expression of GFRs in younger patients with high UBE4B expression may provide rationale for new treatment strategies in these patients. Future work may prioritize designing drug targets for UBE4B, offering therapeutic opportunities, especially for younger GBM patients.

Biological Insights and Radiation-Immuno-Oncology Developments in Primary and Secondary Brain Tumors.

Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts, they often cause significant mortality and morbidity across all ages. Radiotherapy (RT) remains the main treatment for brain cancers, improving associated symptoms, improving tumor control, and inducing a cure in some. However, the ultimate goal of cancer treatment, to improve a patient's survival, remains elusive for many CNS cancers, especially primary tumors. Over the years, there have thus been many preclinical studies and clinical trials designed to identify and overcome mechanisms of resistance to improve outcomes after RT and other therapies. For example, immunotherapy delivered concurrent with RT, especially hypo-fractionated stereotactic RT, is synergistic and has revolutionized the clinical management and outcome of some brain tumors, in particular brain metastases (secondary brain tumors). However, its impact on gliomas, the most common primary malignant CNS tumors, remains limited. In this review, we provide an overview of radioresistance mechanisms, the emerging strategies to overcome radioresistance, the role of the tumor microenviroment (TME), and the selection of the most significant results of radiation-immuno-oncological investigations. We also identify novel therapeutic opportunities in primary and secondary brain tumors with the purpose of elucidating current knowledge and stimulating further research to improve tumor control and patients' survival.

Distinct roles of TREM2 in central nervous system cancers and peripheral cancers

Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM. Genetic or pharmacological TREM2 deficiency promotes GBM progression invivo. Single-cell and spatial sequencing reveals downregulated TREM2 in GBM-infiltrated myeloid cells. TREM2 negatively correlates with immunosuppressive myeloid and Tcell exhaustion signatures in GBM. We further demonstrate that during GBM progression, CNS-enriched sphingolipids bind TREM2 on myeloid cells and elicit antitumor responses. Clinically, high TREM2 expression in myeloid cells correlates with better survival in GBM. Adeno-associated virus-mediated TREM2 overexpression impedes GBM progression and synergizes with anti-PD-1 therapy. Our results reveal distinct functions of TREM2 in CNS cancers and support organ-specific myeloid cell remodeling in cancer immunotherapy.

Isocucurbitacin B inhibits glioma growth through PI3K/AKT pathways and increases glioma sensitivity to TMZ by inhibiting hsa-mir-1286a.

Aim: Glioma accounts for 81% of all cancers of the nervous system cancers and presents one of the most drug-resistant malignancies, resulting in a relatively high mortality rate. Despite extensive efforts, the complete treatment options for glioma remain elusive. The effect of isocucurbitacin B (isocuB), a natural compound extracted from melon pedicels, on glioma has not been investigated. This study aims to investigate the inhibitory effect of isocuB on glioma and elucidate its underlying mechanisms, with the objective of developing it as a potential therapeutic agent for glioma. Methods: We used network pharmacology and bioinformatics analysis to predict potential targets and associated pathways of isocuB in glioma. Subsequently, the inhibitory effect of isocuB on glioma and its related mechanisms were assessed through Counting Kit-8 (CCK-8), wound healing, transwell, Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and other in vitro experiments, alongside tumor formation experiments in nude mice. Results: Based on this investigation, it suggested that isocuB might inhibit the growth of gliomas through the PI3K-AKT and MAPK pathways. Additionally, we proposed that isocuB may enhance glioma drug sensitivity to temozolomide (TMZ) via modulation of hsa-mir-1286a. The CCK-8 assay revealed that isocuB exhibited inhibitory effects on U251 and U87 proliferation and outperformed TMZ. Wound healing and transwell experiments showed that isocuB inhibited the invasion and migration of U251 cells by suppressing the activity of MMP-2/9, N-cadherin, and Vimentin. The TdT-mediated dUTP-biotin nick end labeling (TUNEL) and flow cytometry (FCM) assays revealed that isocuB induced cell apoptosis through inhibition of BCL-2. Subsequently, we conducted RT-qPCR and WB experiments, which revealed that PI3K/AKT and MAPK pathways might be involved in the mechanism of the inhibition isocuB on glioma. Additionally, isocuB promoted the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a. Furthermore, we constructed TMZ-resistant U251 strains and demonstrated effective inhibition by isocuB against these resistant strains. Finally, we confirmed that isocuB can inhibit tumor growth in vivo through experiments on tumors in nude mice. Conclusion: IsocuB may protect against glioma by acting on the PI3K/AKT and MAPK pathways and promote the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a.

Echinacea: Bioactive Compounds and Agronomy.

For centuries, medicinal plants have been used as sources of remedies and treatments for various disorders and diseases. Recently, there has been renewed interest in these plants due to their potential pharmaceutical properties, offering natural alternatives to synthetic drugs. Echinacea, among the world's most important medicinal plants, possesses immunological, antibacterial, antifungal, and antiviral properties. Nevertheless, there is a notable lack of thorough information regarding the echinacea species, underscoring the vital need for a comprehensive review paper to consolidate existing knowledge. The current review provides a thorough analysis of the existing knowledge on recent advances in understanding the physiology, secondary metabolites, agronomy, and ecology of echinacea plants, focusing on E. purpurea, E. angustifolia, and E. pallida. Pharmacologically advantageous effects of echinacea species on human health, particularly distinguished for its ability to safeguard the nervous system and combat cancer, are discussed. We also highlight challenges in echinacea research and provide insights into diverse approaches to boost the biosynthesis of secondary metabolites of interest in echinacea plants and optimize their large-scale farming. Various academic databases were employed to carry out an extensive literature review of publications from 2001 to 2024. The medicinal properties of echinacea plants are attributed to diverse classes of compounds, including caffeic acid derivatives (CADs), chicoric acid, echinacoside, chlorogenic acid, cynarine, phenolic and flavonoid compounds, polysaccharides, and alkylamides. Numerous critical issues have emerged, including the identification of active metabolites with limited bioavailability, the elucidation of specific molecular signaling pathways or targets linked to echinacoside effects, and the scarcity of robust clinical trials. This raises the overarching question of whether scientific inquiry can effectively contribute to harnessing the potential of natural compounds. A systematic review and analysis are essential to furnish insights and lay the groundwork for future research endeavors focused on the echinacea natural products.

Healthcare spending versus mortality in central nervous system cancer: Has anything changed?

The financial implications of central nervous system (CNS) cancers are substantial, not only for the healthcare service and payers, but also for the patients who bear the brunt of direct, indirect, and intangible costs. This study sought to investigate the impact of healthcare spending on CNS cancer survival using recent US data. This study used public data from the Disease Expenditure Project 2016 and the Global Burden of Disease Study 2019. The primary outcome was the annual healthcare spending trend from 1996 and 2016 on CNS tumors adjusted for disease prevalence, alongside morbidity and mortality. Secondary outcomes included drivers of change in healthcare expenditures for CNS cancers. Subgroup analysis was performed stratified by age group, expenditure type, and care type provided. There was a significant increase in total healthcare spending on CNS cancers from $2.72 billion (95% CI: $2.47B to $2.97B) in 1996 to $6.85 billion (95% CI: $5.98B to $7.57B) in 2016. Despite the spending increase, the mortality rate per 100 000 people increased, with 5.30 ± 0.47 in 1996 and 7.02 ± 0.47 in 2016, with an average of 5.78 ± 0.47 deaths per 100 000 over the period. The subgroups with the highest expenditure included patients aged 45 to 64, those with private insurance, and those receiving inpatient care. This study highlights a significant rise in healthcare costs for CNS cancers without corresponding improvements in mortality rate, indicating a mismatch of healthcare spending, contemporary advances, and patient outcomes as it relates to mortality.