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To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative T cell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial T cell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral T cell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies. [Display omitted] • PVVs are key structures for T cell recruitment to melanoma brain tumors • Anti-PD-1/CTLA-4 inhibitors boost T cell recruitment through PVVs • T cell recruitment and antitumor immunity is dependent on ICAM-1 expression on PVVs • ICAM-1 on PVVs correlates with T cell infiltration in human melanoma brain metastases How T cells are recruited to brain tumors from the blood remains unclear. Messmer et al. identify peritumoral venous vessels (PVVs) as key structures for T cell recruitment to melanoma brain tumors. PVVs are the sites of T cell extravasation and facilitated rapid T cell migration under immune checkpoint inhibition. T cell recruitment and antitumor immunity were dependent on ICAM-1. [ABSTRACT FROM AUTHOR]

Glioblastoma is a highly aggressive brain tumor for which there is no cure. The dire prognosis of this disease is largely attributable to a high level of heterogeneity, including the presence of a subpopulation of tumor‐initiating glioblastoma stem‐like cells (GSCs), which are refractory to chemo‐ and radiotherapy. Here, in an unbiased marine‐derived fungal extract screen, together with bioguided dereplication based on high‐resolution mass spectrometry, we identified malformin C to preferentially induce cell death in patient‐derived GSCs and explore the potential of this cyclic peptide as a therapeutic agent for glioblastoma. Malformin C significantly reduced tumor growth in an in vivo xenograft model of glioblastoma. Using transcriptomics and chemoproteomics, we found that malformin C binds to many proteins, leading to their aggregation, and rapidly induces the unfolded protein response, including autophagy, in GSCs. Crucially, chemical inhibition of translation using cycloheximide rescued malformin C‐induced cell death in GSCs, demonstrating that the proteotoxic effect of the compound is necessary for its cytotoxicity. At the same time, malformin C appears to accumulate in lysosomes, disrupting autophagic flux, and driving cells to death. Supporting this, malformin C synergizes with chloroquine, an inhibitor of autophagy. Strikingly, we observed that autophagic flux is differentially regulated in GSCs compared with normal astrocytes. The sensitivity of GSCs to malformin C highlights the relevance of proteostasis and autophagy as a therapeutic vulnerability in glioblastoma. [ABSTRACT FROM AUTHOR]

Introduction: The mutated in colorectal cancer (MCC) gene was initially identified as a candidate tumor suppressor gene in colorectal cancer, acting as a negative regulator of cell cycle progression. However, its functional roles in brain tumors, particularly glioblastoma, remain largely unexplored. This study reveals a significant association between MCC status and glioblastoma. Methods: We explored MCC expression in the glioblastoma database, patient samples, and cell lines. We investigated the proliferation and migration of the cell lines in MCC gene knockdown using small interfering RNA. Results: In vitro analyses revealed elevated protein and mRNA levels of MCC in several glioblastoma cell lines (U118MG and T98G). Silencing MCC expression via siRNA-mediated knockdown resulted in increased proliferation and migration of these cell lines. Supporting these findings, analyses of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx) databases confirmed higher MCC expression in glioblastoma tumors than in normal brain tissue. Importantly, we observed that high MCC expression was associated with poor prognosis in glioblastoma patients, highlighting its potential role in disease progression. Additionally, this study identifies a nuclear localization of MCC in the glioblastoma cell line. Discussion: These findings indicate that MCC expression is significantly upregulated in glioblastoma and may play a role in its pathophysiology, warranting further investigation. [ABSTRACT FROM AUTHOR]

Hyperlactatemia is common during tumor craniotomy, but the underlying pathophysiology is unclear. This study measured simultaneous arterial and jugular‐bulb lactate concentrations in patients undergoing brain tumor craniotomy to investigate the hypothesis that hyperlactatemia was associated with a net cerebrovascular lactate input. In 20 patients, arterial and jugular‐bulb blood was collected hourly from the start of surgery to 6 h postoperatively for measurement of lactate, glucose, and oxygen concentration. For each marker, data were analyzed using a linear mixed‐effects model with jugular‐bulb concentration as dependent variable, arterial concentration as fixed effect, and patient as random effect. Furthermore, we generated regression lines between arterial and jugular‐bulb concentrations. The slope of the regression line between arterial and jugular‐bulb lactate was 0.95 (95% CI 0.93–0.97, R2 = 0.98), indicating that increasing arterial lactate levels were associated with an increasingly positive net cerebrovascular balance (net input). The line crossed the identity line at 2.86 (95% CI 0.57–5.16) mmol/L, indicating that lower levels of lactate were associated with a negative net cerebrovascular balance (net output). This suggests a switch from net lactate output during normolactatemia towards net input during hyperlactatemia. Hyperlactatemia in tumor‐craniotomy patients probably does not originate from the brain. [ABSTRACT FROM AUTHOR]

Purpose: Studies have demonstrated that hormonal imbalance, such as elevated level of estrogen or reduced level of progesterone, was the main inducing factor of uterine leiomyoma (UL) development and some cancers. UL has been reported to be associated with several cancers in observational studies. However, the causal associations between UL and cancers remain unclear. Methods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal associations between UL and 16 site-specific cancers using the public databases. Four methods, namely, the inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode, were applied in our MR analysis. Sensitivity tests were also performed to evaluate the robustness of these causal associations. Results: The IVW analysis indicated that genetically predicted UL increased the risk of low malignant potential ovarian cancer [odds ratio (OR) = 1.22, 95% confidence interval (CI): 1.06-1.40, p = 0.004], serous ovarian cancer (OR = 1.29, 95% CI: 1.10-1.52, p = 0.002), invasive mucinous ovarian cancer (OR = 1.24, 95% CI: 1.08-1.44, p = 0.003), clear cell ovarian cancer (OR = 1.25, 95% CI: 1.03-1.51, p = 0.023), breast cancer (OR = 1.07, 95% CI: 1.02-1.11, p = 0.002), and brain tumor (OR = 1.23, 95% CI: 1.06-1.42, p = 0.007). Conversely, genetically predicted UL reduced the risk of gastric cancer (OR = 0.91, 95% CI: 0.85-0.98, p = 0.008). The causal effects were consistent in the sensitivity analysis. Conclusions: Our results demonstrated that UL exhibits a causal relationship with high risk of several cancers. We suggest reinforcing the cancer screening in UL patients to enable the early detection of cancers. [ABSTRACT FROM AUTHOR]

Introduction: Childhood cancer survivors (CCS) are at risk of experiencing psychological distress years after completing cancer treatments. We aimed to assess the prevalence and associated risk factors affecting psychological distress and health-related quality of life (HRQOL) among CCS in Singapore, and compare with their siblings without a history of or existing cancer as control. Method: We recruited 143 young adult CCS aged ≥18 years attending survivorship clinics at KK Women's and Children's Hospital in Singapore who were in remission for ≥5 years and treatment-free for ≥2 years, and 57 siblings. CCS and siblings were matched at a 1:1 ratio based on sociodemographic factors yielding 46 pairs for comparison. Among CCS participants, 79 (55.2%) were male, 86 (60.1%) had leukaemia, 29 (20.3%) had solid tumours, 15 (10.5%) had lymphoma and 13 (9.1%) had brain tumours. All participants completed the Brief Symptom Inventory-18 (BSI-18) and Medical Outcomes Short Form-36 (MOS SF-36) questionnaires from August 2021 to July 2022. Results: There were 35 (24.5%) CCS who reported psychological distress in the BSI-18 Global Severity Index. Five (3.5%) and 31 (21.7%) CCS reported low HRQOL in the physical and mental composite scores, respectively. Mean scores between CCS and their siblings were not statistically significant across all domains of the BSI-18 and MOS SF-36. Associated risk factors for psychological distress and low HRQOL among CCS were history of psychiatric illness after cancer diagnosis and mood affected by the COVID-19 pandemic. Conclusion: CCS reported significant psychological distress and low HRQOL although they were not statistically different from their siblings. A holistic and risk factor-centric follow-up programme can aid early detection and mitigation of psychological late effects for CCS and their families. [ABSTRACT FROM AUTHOR]

Limited research has compared cognition of people with non-central nervous system metastatic cancer (NCM) vs. metastatic brain cancer (BM). This prospective cross-sectional study was comprised 37 healthy controls (HC), 40 NCM, and 61 BM completing 10 neuropsychological tests. The NCM performed below HCs on processing speed and executive functioning tasks, while the BM group demonstrated lower performance across tests. Tasks of processing speed, verbal fluency, and verbal memory differentiated the clinical groups (BM < NCM). Nearly 20% of the NCM group was impaired on at least three neuropsychological tests whereas approximately 40% of the BM group demonstrated the same level of impairment. [ABSTRACT FROM AUTHOR]

The present study conducted an extensive review of the literature that describes the molecular pathogenesis of cancer and glioblastoma multiforme (GBM), exploring physiological adaptation resulting from exercise training in the broader context of cancer and brain tumors, with a specific emphasis on GBM, aiming to discern the implications of exercise in improving the quality of life (QoL) of affecting patients. GBM is the predominant aggressive malignant primary brain tumor with a high mortality rate. GBM involves multiple pathways that can be targeted by exercise training. Exercise has shown its value in various other cancer types and offers a promising approach for GBM. Exercise training is regarded as a safe and feasible adjunctive treatment to improve the QoL of patients with brain tumors, including GBM. Nevertheless, further research is required in order to fully elucidate the mechanisms through which exercise affects cellular processes impacted by cancer and its treatments, with a specific focus on GBM. While exercise training guidelines have been established for cancer patients in general, there is currently a lack of specific guidelines tailored to patients with GBM. Clear guidelines are essential to assist clinicians in determining the most appropriate exercise type, intensity and frequency for patients to optimize their rehabilitation process. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme is a very aggressive type of cancer with high mortality and poor prognosis worldwide. Advanced treatment options with an understanding of the molecules and signalling mechanisms involved in this type of cancer have the potential to increase targeted therapy and decrease off-target effects, resistance, and recurrence. Glioblastoma multiforme (GBM) presents a complex tumour microenvironment with numerous cellular components and an extracellular matrix comprising multiple components. A deeper understanding of these components and corresponding signalling pathways can increase the success of immune checkpoint inhibitors in the treatment of GBM. The discovery of specific molecular changes and biomarkers has led to the investigation of tailored treatments for individual patients. Combination therapies targeting multiple pathways or utilizing different modalities are emerging as a promising strategy albeit with challenges in drug delivery to the brain. The review presents a comprehensive update of the various immunomodulatory signalling networks in GBM and highlights the corresponding therapeutic approaches by targeting them. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated, both in vitro and in animal models, the anti-tumor efficacy of high-dose ascorbate treatment against a variety of tumor entities, including glioblastoma, the most common and aggressive primary malignant brain tumor. The aim of this study was to investigate the effects of high-dose ascorbate as well as dehydroascorbic acid on human glioblastoma cell lines and to evaluate different treatment conditions for the combined administration of ascorbate with magnesium (Mg2+) and iron (Fe3+). Intracellular levels of reactive oxygen species and the induction of cell death following ascorbate treatment were also investigated. We demonstrated high cytotoxicity and antiproliferative efficacy of high-dose ascorbate in human glioblastoma cells, whereas much weaker effects were observed for dehydroascorbic acid. Ascorbate-induced cell death was independent of apoptosis. Both the reduction in cell viability and the ascorbate-induced generation of intracellular reactive oxygen species could be significantly increased by incubating the cells with Fe3+ before ascorbate treatment. This work demonstrates, for the first time, an increase in ascorbate-induced intracellular ROS formation and cytotoxicity in human glioblastoma cells by pre-treatment of the tumor cells with ferric iron, as well as caspase-3 independence of cell death induced by high-dose ascorbate. Instead, the cell death mechanism caused by high-dose ascorbate in glioblastoma cells shows evidence of ferroptosis. The results of the present work provide insights into the efficacy and mode of action of pharmacological ascorbate for the therapy of glioblastoma, as well as indications for possible approaches to increase the effectiveness of ascorbate treatment. [ABSTRACT FROM AUTHOR]

Chromosome Region Maintenance 1 (CRM1), also known as Exportin 1 (XPO1), is a protein that is critical for transport of proteins and RNA to the cytoplasm through the nuclear pore complex. CRM1 inhibition with small molecule inhibitors is currently being studied in many cancers, including leukemias, solid organ malignancies and brain tumors. We review the structure of CRM1, its role in nuclear export, the current availability of CRM1 inhibitors, and the role of CRM1 in a number of distinct cellular processes. A deeper understanding of how CRM1 functions in nuclear export as well as other cellular processes may allow for the development of additional novel CRM1 inhibitors. [ABSTRACT FROM AUTHOR]

Brainmetastatic cancer poses a significant clinical challenge, with limited treatment options and poor prognosis for patients. In recent years, immunotherapy has emerged as a promising strategy for addressing brain metastases, offering distinct advantages over conventional treatments. This review explores the evolving landscape of tumor immunotherapy in the context of brain metastatic cancer, focusing on the intricate interplay between the tumor microenvironment (TME) and immunotherapeutic approaches. By elucidating the complex interactions within the TME, including the role of immune cells, cytokines, and extracellular matrix components, this review highlights the potential of immunotherapy to reshape the treatment paradigm for brain metastases. Leveraging immune checkpoint inhibitors, cellular immunotherapies, and personalized treatment strategies, immunotherapy holds promise in overcoming the challenges posed by the blood-brain barrier and immunosuppressive microenvironment of brain metastases. Through a comprehensive analysis of current research findings and future directions, this review underscores the transformative impact of immunotherapy on the management of brain metastatic cancer, offering new insights and opportunities for personalized and precise therapeutic interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain metastases (BMs), the most common type of cerebral tumor, are primarily associated with lung cancer, breast cancer, and melanoma. Patients typically present to the emergency department (ED) with insidious symptoms such as headaches, focal neurological deficits, seizures, and signs of increased intracranial pressure. Key symptomatic treatment in the ED includes corticosteroids to manage peritumoral edema, and carefully selected antiepileptic medications for tumor-related epileptic conditions. After stabilization, the treatment philosophy for BMs should prioritize effective yet minimally toxic options to maximize quality of life. Surgery is recommended for accessible BMs in patients with good performance status. Radiation therapy and systemic treatments, including chemotherapy, targeted therapy, and immunotherapy, are available options for managing disease progression. Given that over half of patients with BMs in the ED are admitted, a better understanding of avoidable hospitalizations is essential to differentiate those who can be safely discharged from those needing observation or hospitalization. Brain metastases (BMs) are the most prevalent type of cerebral tumor, significantly affecting survival. In adults, lung cancer, breast cancer, and melanoma are the primary cancers associated with BMs. Symptoms often result from brain compression, and patients may present to the emergency department (ED) with life-threatening conditions. The goal of treatment of BMs is to maximize survival and quality of life by choosing the least toxic therapy. Surgical resection followed by cavity radiation or definitive stereotactic radiosurgery remains the standard approach, depending on the patient's condition. Conversely, whole brain radiation therapy is becoming more limited to cases with multiple inoperable BMs and is less frequently used for postoperative control. BMs often signal advanced systemic disease, and patients usually present to the ED with poorly controlled symptoms, justifying hospitalization. Over half of patients with BMs in the ED are admitted, making effective ED-based management a challenge. This article reviews the epidemiology, clinical manifestations, and current treatment options of patients with BMs. Additionally, it provides an overview of ED management and highlights the challenges faced in this setting. An improved understanding of the reasons for potentially avoidable hospitalizations in cancer patients with BMs is needed and could help emergency physicians distinguish patients who can be safely discharged from those who require observation or hospitalization. [ABSTRACT FROM AUTHOR]

Simple Summary: The European Network for Rare Cancers (EURACAN) Task Force on Ultra-Rare Brain Tumors (domain 10, subdomain 10) has reviewed the literature extensively regarding primary meningeal melanocytic tumors, which are ultra-rare entities that affect primarily children and young adults and represent an unmet need in neuro-oncology. The review covers the main histological and molecular factors, radiological findings, clinical features, and therapeutic challenges. Further efforts are needed to collect more knowledge on these rare brain tumors to improve the diagnostic tools and provide novel treatment strategies. Background: Primary meningeal melanocytic tumors are ultra-rare entities with distinct histological and molecular features compared with other melanocytic or pigmented lesions, such as brain and leptomeningeal metastases from metastatic melanoma. Methods: The European Network for Rare Cancers (EURACAN) Task Force on Ultra-Rare Brain Tumors (domain 10, subdomain 10) performed a literature review from January 1985 to December 2023 regarding the epidemiologic and clinical characteristics, histological and molecular features, radiological findings, and efficacy of local treatments (surgery and radiotherapy) and systemic treatments for these entities. Results: Molecular analysis can detect specific mutations, including GNAQ, GNA11, SF3B1, EIF1AX, BAP1, that are typically found in circumscribed primary meningeal melanocytic tumors and not in other melanocytic lesions, whereas NRAS and BRAF mutations are typical for diffuse primary meningeal melanocytic tumors. The neuroimaging of the whole neuroaxis suggests a melanocytic nature of a lesion, depicts its circumscribed or diffuse nature, but cannot predict the tumor's aggressiveness. Gross-total resection is the first choice in the case of circumscribed meningeal melanocytoma and melanoma; conversely, meningeal biopsy may be reserved for patients with diffuse and multinodular leptomeningeal spread to achieve a definitive diagnosis. High-dose radiotherapy is rarely indicated in diffuse melanocytic tumors except as palliative treatment to alleviate symptoms. Last, a definitive advantage of a specific systemic treatment could not be concluded, as most of the data available derive from case reports or small cohorts. Conclusions: As primary meningeal melanocytic tumors are extremely rare, the correlations between the clinical characteristics, molecular profile, radiological findings at diagnosis and progression are weak, and poor evidence on the best therapeutic approach is available. There is a need to develop shared platforms and registries to capture more knowledge regarding these ultra-rare entities. [ABSTRACT FROM AUTHOR]

To determine the safety, feasibility, and potential effect of an 18-week exercise intervention for adults with primary brain cancer. Eligible patients were 12-26-weeks post-radiotherapy for brain cancer. The individually-prescribed weekly exercise was ≥150-minutes of moderate-intensity exercise, including two resistance-training sessions. The intervention was deemed "safe" if exercise-related, serious adverse events (SAE) were experienced by <10% of participants, and feasible if recruitment, retention, and adherence rates were ≥75%, and ≥75% compliance rates were achieved in ≥75% of weeks. Patient-reported and objectively-measured outcomes were assessed at baseline, mid-intervention, end-intervention, and 6-month follow-up, using generalized estimating equations. Twelve participants enrolled (51 ± 19.5 years, 5 females). There were no exercise-related SAEs. The intervention was feasible (recruitment:80%, retention:92%, adherence:83%). Participants completed a median of 172.8 (min:77.5, max:560.8) minutes of physical activity per week. 17% met the compliance outcome threshold for ≥75% of the intervention. Improvements in quality of life (mean change (95% CI): 7.9 units (1.9, 13.8)), functional well-being (4.3 units (1.4, 7.2)), depression (−2.0 units (−3.8, −0.2)), activity (112.8 min (42.1, 183.4)), fitness (56.4 meters (20.4, 92.5)), balance (4.9 s (0.9, 9.0)), and lower-body strength (15.2 kg (9.3, 21.1)) were observed end-intervention. Preliminary evidence support that exercise is safe and beneficial to the quality of life and functional outcomes for people with brain cancer.Registration: ACTRN12617001577303 The BRAin Cancer and Exercise (BRACE) study highlights the need for regular monitoring of disease- and treatment-related side effects which may present as barriers to exercise. Exercise prescription should be modified according to the presence and severity of disease- and treatment-related barriers. Adverse events observed, such as dizziness, highlight the importance of supervised exercise for people with brain cancer. If supervision is not possible, then exercise modes with low risk of harm from falls are recommended (e.g., walking, machine-based resistance training). [ABSTRACT FROM AUTHOR]

Introduction: The main mission of the Australian and New Zealand Children's Haematology and Oncology Group (ANZCHOG) is to develop and facilitate local access to the world's leading evidence‐based clinical trials for all paediatric cancers, including brain tumours, as soon as practically possible. Diffuse intrinsic pontine gliomas (DIPGs) — a subset of a larger group of tumours now termed diffuse midline glioma, H3K27‐altered (DMG) — are paediatric brain cancers with less than 10% survival at two years. In the absence of any proven curative therapies, significant recent advancements have been made in pre‐clinical and clinical research, leading many to seek integration of novel therapies early into standard practice. Despite these innovative therapeutic approaches, DIPG remains an incurable disease for which novel surgical, imaging, diagnostic, radiation and systemic therapy approaches are needed. Main recommendations: All patients with DIPG should be discussed in multidisciplinary neuro‐oncology meetings (including pathologists, neuroradiologists, radiation oncologists, neurosurgeons, medical oncologists) at diagnosis and at relapse or progression.Radiation therapy to the involved field remains the local and international standard of care treatment.Proton therapy does not yield a superior survival outcome compared with photon therapy and patients should undergo radiation therapy with the available modality (photon or proton) at their treatment centre.Patients may receive concurrent chemotherapy or radiation‐sensitising agents as part of a clinical trial.Biopsy should be offered to facilitate consideration of experimental therapies and eligibility for clinical trial participation.After radiation therapy, each patient should be managed individually with either observation or considered for enrolment on a clinical trial, if eligible, after full discussion with the family.Re‐irradiation can be considered for progressive disease. Changes in management as a result of the guideline: Every child diagnosed with DIPG should be offered enrolment on a clinical trial where available. Access to investigational drugs without biological rationale outside the clinical trial setting is not supported. In case of potentially actionable target identification with molecular profiling and absence of a suitable clinical trial, rational targeted therapies can be considered through compassionate access programs. [ABSTRACT FROM AUTHOR]

Harnessing the effector mechanisms of the immune system to combat brain tumors with antigen specificity and memory has been in research and clinical testing for many years. Government grant mechanisms and non-profit organizations have supported many innovative projects and trials while biotech companies have invested in the development of needed tools, assays and novel clinical approaches. The National Brain Tumor Society and the Parker Institute for Cancer Immunotherapy partnered to host a workshop to share recent data, ideas and identify both hurdles and new opportunities for harnessing immunotherapy against pediatric and adult brain tumors. Adoptively transferred cell therapies have recently shown promising early clinical results. Local cell delivery to the brain, new antigen targets and innovative engineering approaches are poised for testing in a new generation of clinical trials. Although several such advances have been made, several obstacles remain for the successful application of immunotherapies for brain tumors, including the need for more representative animal models that can better foreshadow human trial outcomes. Tumor and tumor microenvironment biopsies with multiomic analysis are critical to understand mechanisms of response and patient stratification, yet brain tumors are especially challenging for such biopsy collection. These workshop proceedings and commentary shed light on the status of immunotherapy in pediatric and adult brain tumor patients, including current research as well as opportunities for improving future efforts to bring immunotherapy to the forefront in the management of brain tumors.

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to a significant reduction in colony formation, lipid storage, acetyl-CoA levels and cell survival in vitro. In an ex vivo brain-tumor slice model, treatment with AD-8007 and AD-5584 reduced pre-formed tumors and synergized with irradiation in blocking BCBM tumor growth. Treatment with AD-8007 reduced tumor burden and extended survival in vivo. This study identifies selective brain-penetrant ACSS2 inhibitors with efficacy towards breast cancer brain metastasis. [ABSTRACT FROM AUTHOR]

Medulloblastomas (MBs) represent the most prevalent malignant solid tumors in kids. The conventional treatment regimen for MBs includes surgical removal of the tumor, followed by radiation and chemotherapy. However, this approach is associated with significant morbidity and detrimental side effects. Consequently, there is a critical demand for more precise and less harmful treatments to enhance the quality of life for survivors. CEP-18770, a novel proteasome inhibitor that targets the 20S subunit, has emerged as a promising candidate, due to its anticancer activity in metastatic solid tumors and multiple myeloma, coupled with an acceptable safety profile. In this study, we aimed to assess the anticancer efficacy of CEP-18770 by employing a variety of MB patient-derived cells and cell lines. Our preclinical investigations revealed that CEP-18770 effectively inhibits proteasome activity and induces apoptosis in MBs cells. Furthermore, we discovered that CEP-18770 and cisplatin, a current component of MB therapy, exhibit a synergistic apoptotic effect. This paper shows that CEP-18770 holds potential as an adjunctive treatment for MB tumors, thereby paving the way for more targeted and less toxic therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, researchers tackled the challenge of advancing therapies for malignant brain tumors, given the scarcity of clinically relevant and biologically accurate mouse models. They introduced a novel surgical technique for transplanting fresh human brain tumor samples into SCID mice, accurately mimicking the original tumor's location in the brain. Through this method, they successfully established 188 patient-derived orthotopic xenograft (PDOX) models from 408 brain tumor samples, preserving the histopathological and genetic traits of the original tumors. Success rates varied among tumor types, with high-grade glioma demonstrating the highest success rate. Overall, this technique presents a straightforward and effective approach for generating extensive cohorts of tumor-bearing mice for both biological investigations and preclinical drug evaluations, eliminating the necessity for a stereotactic frame. Background: Despite multimodality therapies, the prognosis of patients with malignant brain tumors remains extremely poor. One of the major obstacles that hinders development of effective therapies is the limited availability of clinically relevant and biologically accurate (CRBA) mouse models. Methods: We have developed a freehand surgical technique that allows for rapid and safe injection of fresh human brain tumor specimens directly into the matching locations (cerebrum, cerebellum, or brainstem) in the brains of SCID mice. Results: Using this technique, we successfully developed 188 PDOX models from 408 brain tumor patient samples (both high-and low-grade) with a success rate of 72.3% in high-grade glioma, 64.2% in medulloblastoma, 50% in ATRT, 33.8% in ependymoma, and 11.6% in low-grade gliomas. Detailed characterization confirmed their replication of the histopathological and genetic abnormalities of the original patient tumors. Conclusions: The protocol is easy to follow, without a sterotactic frame, in order to generate large cohorts of tumor-bearing mice to meet the needs of biological studies and preclinical drug testing. [ABSTRACT FROM AUTHOR]

Background: There is evidence that individuals of African ancestry, particularly those residing in Africa, suffer from an unfortunate amount of under-representation in cancer research worldwide. Aim: We aimed to analyze current research output and potentially predict future trends in neuro-oncological research in Africa. Investigating deficits in the field will assist in identifying top-performing countries, which ones face challenges, and how to solve them. Therefore, targeted interventions can be applied to overcome these challenges. Methods: We conducted a systematic computer-based search on the following databases (PubMed, Scopus, Web of Science, and Embase) for research articles related to the neuro-oncological field in Africa. We aimed to retrieve any article published in the period between 1 January 2000 and 10 January 2023. Results: We included 200 eligible articles in our study. The output of neuro-oncological research has been increasing over the past two decades, peaking in 2019. Among the included articles, clinical practice issues constituted the majority (80%), while public health-related topics accounted for 20% of the publications. Regarding the type of neurological tumor, neuroblastoma was the most common, with 26 articles (13%), meningioma with 21 (10.5%), and glioma with 16 articles (8%). Conclusion: The interest in African neuro-oncological research is increasing. Hence, there is a need for ongoing efforts to address issues with clinical practice and public health related to neurological tumors in the continent. Future studies should concentrate on filling in knowledge gaps and investigating novel methods for neuro-oncological conditions that affect African populations in terms of prevention, diagnosis, treatment, and management strategies. [ABSTRACT FROM AUTHOR]

Patients with pediatric brain tumor (PBT) can have memory deficits due to tumor location, medical complications, and treatment. The main objective of this study was to investigate whether the California Verbal Learning Test-Children's Version (CVLT-C; 1994) and briefer Child and Adolescent Memory Profile (ChAMP; 2015) similarly identify such deficits. Seventy-five patients with PBT ages 8--16 (x = 13.1 years, SD = 2.1) were administered the ChAMP or CVLT-C. Rote verbal learning, long-term retrieval, and recognition were analyzed using standardized z-scores. Analyses of differences between measures did not reach statistical significance. Both measures indicated significant downward shifts across free retrieval trials from normative means, with scores approximately 1/3 (ChAMP) to 1/2 (CVLT-C) SD below means across learning and long-term retrieval trials. Scores on recognition trials did not differ significantly from the normative mean. Post-hoc analyses using a subset of the sample who received cranial irradiation (n = 45) similarly found no significant differences between memory measures. Additional post-hoc examination of proportion of participants falling within or below the "below average" range (≤8th percentile) revealed comparable performance between the two measures, whereas the proportion of participants falling at or below 1.5 SDs below the mean on retrieval trials was lower using ChAMP Lists as compared to the CVLT-C. Given the ChAMP is less demanding in terms of time and effort and utilizes more updated and representative normative data, this study supports the ChAMP as a useful tool to evaluate learning and memory within this population. [ABSTRACT FROM AUTHOR]

Drug repurposing is promising because approving a drug for a new indication requires fewer resources than approving a new drug. Signature reversion detects drug perturbations most inversely related to the disease‐associated gene signature to identify drugs that may reverse that signature. We assessed the performance and biological relevance of three approaches for constructing disease‐associated gene signatures (i.e., limma, DESeq2, and MultiPLIER) and prioritized the resulting drug repurposing candidates for four low‐survival human cancers. Our results were enriched for candidates that had been used in clinical trials or performed well in the PRISM drug screen. Additionally, we found that pamidronate and nimodipine, drugs predicted to be efficacious against the brain tumor glioblastoma (GBM), inhibited the growth of a GBM cell line and cells isolated from a patient‐derived xenograft (PDX). Our results demonstrate that by applying multiple disease‐associated gene signature methods, we prioritized several drug repurposing candidates for low‐survival cancers. [ABSTRACT FROM AUTHOR]

Purpose: Glioblastoma (GBM) is an aggressive malignant brain tumor with 2 year survival rates of 6.7% (Stupp et al. in J Clin Oncol Off J Am Soc Clin Oncol 25:4127–4136, 2007; Mohammed et al. in Rep Pract Oncol Radiother 27:1026–1036, 2002). One key characteristic of the disease is the ability of glioblastoma cells to migrate rapidly and spread throughout healthy brain tissue (Lefranc et al. in J Clin Oncol Off J Am Soc Clin Oncol 23:2411–2422, 2005; Hoelzinger et al. in J Natl Cancer Inst 21:1583–1593, 2007). To develop treatments that effectively target cell migration, it is important to understand the fundamental mechanism driving cell migration in brain tissue. Several models of cell migration have been proposed, including the motor-clutch, bleb-based motility, and osmotic engine models. Methods: Here we utilized confocal imaging to measure traction dynamics and migration speeds of glioblastoma cells in mouse organotypic brain slices to identify the mode of cell migration. Results: We found that nearly all cell-vasculature interactions reflected pulling, rather than pushing, on vasculature at the cell leading edge, a finding consistent with a motor-clutch mode of migration, and inconsistent with an osmotic engine model or confined bleb-based migration. Reducing myosin motor activity, a key component in the motor-clutch model, was found to decrease migration speed at high doses for all cell types including U251 and 6 low-passage patient-derived xenograft lines (3 proneural and 3 mesenchymal subtypes). Variable responses were found at low doses, consistent with a motor-clutch mode of migration which predicts a biphasic relationship between migration speed and motor-to-clutch ratio. Targeting of molecular clutches including integrins and CD44 slowed migration of U251 cells. Conclusions: Overall we find that glioblastoma cell migration is most consistent with a motor-clutch mechanism to migrate through brain tissue ex vivo, and that both integrins and CD44, as well as myosin motors, play an important role in constituting the adhesive clutch. [ABSTRACT FROM AUTHOR]

The article focuses on recent developments and research in the field of oncology, particularly concerning Human immunodeficiency viruses and cancer, fatigue of T cells within tumors, and the promising potential of theranostics in neuro-oncology. It delves into the challenges faced by HIV-infected cancer patients, the metabolic mechanisms affecting T cell function in tumor microenvironments, and the emerging role of theranostics in diagnosing and treating brain tumors.

There is an urgent need for drug development in brain tumors. While current radiographic response assessment provides instructions for identifying large treatment effects in simple high- and low-grade gliomas, there remains a void of strategies to evaluate complex or difficult to measure tumors or tumors of mixed grade with enhancing and non-enhancing components. Furthermore, most patients exhibit some period of alteration in tumor growth after starting a new therapy, but simple response categorization (e.g., stable disease, progressive disease) fails to provide any meaningful insight into the depth or degree of potential "subclinical" therapeutic response. We propose a creative solution to these issues based on a tiered strategy meant to increase confidence in identifying therapeutic effects even in the most challenging tumor types, while also providing a framework for complex evaluation of combination and sequential treatment schemes. Specifically, we demonstrate the utility of digital "flipbooks" to quickly identify subtle changes in complex tumors. We show how a modified Levin criteria can be used to quantify the degree of visual changes, while establishing estimates of the association between tumor volume and visual inspection. Lastly, we introduce the concept of quantifying therapeutic response using control systems theory. We propose measuring changes in volume (proportional), the area under the volume vs. time curve (integral) and changes in growth rates (derivative) to utilize a "PID" controller model of single or combination therapeutic activity.

Imaging response assessment is a cornerstone of patient care and drug development in oncology. Clinicians/clinical researchers rely on tumor imaging to estimate the impact of new treatments and guide decision making for patients and candidate therapies. This is important in brain cancer, where associations between tumor size/growth and emerging neurological deficits are strong. Accurately measuring the impact of a new therapy on tumor growth early in clinical development, where patient numbers are small, would be valuable for decision making regarding late-stage development activation. Current attempts to measure the impact of a new therapy have limited influence on clinical development, as determination of progression, stability or response does not currently account for individual tumor growth kinetics prior to the initiation of experimental therapies. Therefore, we posit that imaging-based response assessment, often used as a tool for estimating clinical effect, is incomplete as it does not adequately account for growth trajectories or biological characteristics of tumors prior to the introduction of an investigational agent. Here, we propose modifications to the existing framework for evaluating imaging assessment in primary brain tumors that will provide a more reliable understanding of treatment effects. Measuring tumor growth trajectories prior to a given intervention may allow us to more confidently conclude whether there is an anti-tumor effect. This updated approach to imaging-based tumor response assessment is intended to improve our ability to select candidate therapies for later-stage development, including those that may not meet currently sought thresholds for "response" and ultimately lead to identification of effective treatments.

BackgroundThe Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) classifications to group records for clinically relevant statistical reporting. Newly identified genetic markers more accurately stratify patients than histology alone and were incorporated into the 2016 update to the WHO Classification.MethodsCBTRUS and consulting neuropathologists reviewed and aligned histology groupings with the 2016 WHO update. "Obsolete" (terms not currently in use) histology nomenclature along with their International Classification of Disease, Oncology 3rd edition (ICD-O-3) codes were identified, some histologies were reclassified to 2016 WHO, and new codes found in 2016 WHO were incorporated. An evaluation of the frequency of histology codes affected in the realignment process, and incidence and survival pre- and post-realignment was conducted.ResultsAfter review, 67 codes were noted as obsolete, 51 codes were reclassified, and 12 new codes were incorporated. Histology groups most affected were mesenchymal tumors and neuronal/mixed neuronal-glial tumors. Reorganization resulted in 2588 (0.65%) cases with grouping reassignment or reporting change, indicating that the 2016 WHO Classification revision has impacted the collection and reporting of primary brain and other CNS tumors.ConclusionThis work demonstrates the need to be responsive to changes in classification and coding in order to ensure the most up-to-date and accurate statistics for brain and CNS tumors. This will require collaboration from all stakeholders within the brain tumor community, so to have the ability to reconcile clinical practices and surveillance requirements.

Simple Summary: Anaplastic Lymphoma Kinase (ALK) is a protein linked to cancer growth. A review of scientific studies was conducted to understand ALK's role in certain brain tumors, particularly those not originating from glial cells (supportive cells in the brain) and located in the lower back part of the brain. From an initial pool of 992 studies, 16 were found to be relevant. These studies focused on 55 cases of tumors displaying ALK presence or ALK alterations, including medulloblastoma, lymphoma, histiocytosis, and other rare tumors. Studies mainly used tissue analysis and genetic testing to study ALK. Findings suggest that examining ALK can help in diagnosing and predicting the outcome of some of these brain tumors, especially medulloblastoma. Interestingly, many cases of brain histiocytosis (a rare condition) with ALK changes were found in this area. These findings point to the potential benefits of targeting ALK in treating certain brain tumors, a promising area for future research. Anaplastic Lymphoma Kinase (ALK) has been implicated in several human cancers. This review aims at mapping the available literature on the involvement of ALK in non-glial tumors localized in the posterior cranial fossa and at identifying diagnostic, prognostic, and therapeutic considerations. Following the PRISMA-ScR guidelines, studies were included if they investigated ALK's role in primary CNS, non-glial tumors located in the posterior cranial fossa. A total of 210 manuscripts were selected for full-text review and 16 finally met the inclusion criteria. The review included 55 cases of primary, intracranial neoplasms with ALK genetic alterations and/or protein expression, located in the posterior fossa, comprising of medulloblastoma, anaplastic large-cell lymphoma, histiocytosis, inflammatory myofibroblastic tumors, and intracranial myxoid mesenchymal tumors. ALK pathology was investigated via immunohistochemistry or genetic analysis. Several studies provided evidence for potential diagnostic and prognostic value for ALK assessment as well as therapeutic efficacy in its targeting. The available findings on ALK in posterior fossa tumors are limited. Nevertheless, previous findings suggest that ALK assessment is of diagnostic and prognostic value in medulloblastoma (WNT-activated). Interestingly, a substantial proportion of ALK-positive/altered CNS histiocytoses thus far identified have been localized in the posterior fossa. The therapeutic potential of ALK inhibition in histiocytosis warrants further investigation. [ABSTRACT FROM AUTHOR]

Aims: To explore how long‐term and late effects of paediatric brain tumours influence the everyday lives of survivors at various ages and their parents. Design: A qualitative interview study using reflexive thematic analysis. Methods: We conducted individual interviews and focus groups with 14 paediatric brain tumour survivors aged 9–52 years and 16 parents, which were audiorecorded and transcribed. We inductively analyzed the data using Braun and Clarke's reflexive thematic analysis. Inductively derived themes were then mapped onto the components of the International Classification of Functioning, Disability and Health framework to examine the survivors' everyday functioning. Results: All survivors experienced ongoing long‐term and late effects but with considerable variations in how these restricted the survivors' functioning and thus their ability to participate in everyday life activities (e.g. social, educational and work activities). All survivors expressed an explicit focus on and use of different strategies to manage their perceived functional limitations and participation restrictions. Many survivors expressed discrepancies between their own goals, expectations and actual abilities post‐cancer; making them very aware of their limitations. In addition, many survivors and parents experienced ongoing concerns about the survivors' future, including the risk of late effects, relapse or other complications. Conclusion: A wide range of long‐term and late effects continue to affect the survivors and their parents' functioning and everyday lives. Their ongoing needs emphasize the importance of comprehensive, life‐long follow‐up care, as recommended. Implications for the Profession and/or Patient Care: The complex challenges across the biopsychosocial realms faced by the survivors supports the call for multidisciplinary survivorship care. Nurses are well positioned to lead such care, as they are trained to provide holistic care and thereby support survivors' functioning and activity participation in everyday life. Reporting Method: We used the COREQ guidelines when reporting the study. Patient or Public Contribution: Two user representatives (one young adult PBT survivor and one mother of a PBT survivor) ensured the relevance and quality of the semi‐structured interview guides prior to the interviews with the survivors and parents. The guides were sent to the user representatives by mail, and they provided their written feedback by mail to the first author. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) plays a key role in brain tumours but can negatively impact functional outcomes and quality of life. The aim of this study was to analyse anti-neural and onconeural autoantibodies and markers of blood–brain barrier (BBB) disruption in patients with primary brain cancer undergoing RT. Materials and methods. A prospective study was conducted on 45 patients with a brain tumour scheduled for intensity-modulated radiotherapy. Assessments were performed at baseline, post-RT, and at three months. We measured serum levels of BBB disruption biomarkers and anti-neural, onconeural, and organ-specific antibodies. Results. Antibodies against nucleosome antigens and neuronal surface antigens were detected in 85% and 3% of cases, respectively; anti-neural and onconeural antibodies were observed in 47% and 5.8%. In 44% patients, ≥2 antibody types were detected. No significant changes in BBB biomarkers were observed. Conclusion. The findings of this study show that a humoral immune response is common in patients undergoing RT for brain cancer. This response appears to be non-organ specific but rather directed against nucleosome antigens, but onconeural antibodies were uncommon, suggesting a low risk of a neurological paraneoplastic syndrome. Our data suggested that radiotherapy may not affect BBB integrity, but larger studies are needed to better characterise the pathophysiological effects of RT. [ABSTRACT FROM AUTHOR]

Research on the development of photodynamic therapy for the treatment of brain tumors has shown promise in the treatment of this highly aggressive form of brain cancer. Analysis of both in vivo studies and clinical studies shows that photodynamic therapy can provide significant benefits, such as an improved median rate of survival. The use of photodynamic therapy is characterized by relatively few side effects, which is a significant advantage compared to conventional treatment methods such as often-used brain tumor surgery, advanced radiotherapy, and classic chemotherapy. Continued research in this area could bring significant advances, influencing future standards of treatment for this difficult and deadly disease. [ABSTRACT FROM AUTHOR]

Methylphenidate has an established role in the management of attention-deficit hyperactivity disorder and attentional deficit secondary to brain injury. Increasingly, methylphenidate is considered for the attentional deficit in paediatric brain tumour survivors. A small number of studies have explored the benefit of methylphenidate in this population; however, studies are of short duration and do not address the impact of medium to long-term use of methylphenidate on intellectual function. We identified six patients who are survivors of a paediatric brain tumour aged 12–18 years with greater than three years of use of methylphenidate for inclusion in a clinical case series. We used this patient cohort to identify key questions to inform a future long-term cohort study. Linear mixed model and reliable change index analyses were performed on the data. Reliable change index analyses showed benefits to working memory (n = 3), processing speed (n = 2), and full-scale IQ (n = 4) performance for some patients. This exploratory case series suggests the potential medium to long-term benefit of methylphenidate in brain tumour survivorship, indicating the need for larger, appropriately powered studies. These patient data, alongside a discussion of learning points from our previously published studies, are used as a conduit for the identification of questions relating to the use of methylphenidate in a paediatric brain tumour. [ABSTRACT FROM AUTHOR]

Objectives: The growing population of survivors of childhood brain tumors present the challenge of long-term quality of survival. The domains most affected by tumor and treatment are those implicated in development of typical intellectual functions: attention, working memory, and processing speed, with consequent effects upon function and quality of life. In this paper we present service evaluation data on the 12-month effect upon processing speed, visual and auditory attentional domains in 29 patients receiving methylphenidate aged 5-16 years (Mean=10.6). Methods: Patients received immediate-release methylphenidate and were converted to modified-release as appropriate. Mean optimal dose of immediate-release methylphenidate was 0.34 mg/kg per dose (range 0.2-0.67). Results: Patients showed a significant positive impact of methylphenidate on attention in all tests of selective visual attention from the Test of Everyday Attention for Children 2. A significant improvement was also shown on response time. Significant change was not found on psychometric measures of sustained auditory or visual attention, or selective auditory attention. Ratings of Health-Related Quality of Life showed a positive benefit of methylphenidate at 12 months. Side effects were minimal and not statistically significant. Conclusions: Survivors of childhood brain tumor with attentional and processing speed deficit show clinical benefit from methylphenidate. [ABSTRACT FROM AUTHOR]

Objective: To undertake an economic evaluation of a telehealth psychological support intervention for patients with primary brain tumor (PBT). Methods: A within‐trial cost‐utility analysis over 6 months was performed comparing a tailored telehealth‐psychological support intervention with standard care (SC) in a randomized control trial. Data were sourced from the Telehealth Making Sense of Brain Tumor (Tele‐MAST) trial survey data, project records, and administrative healthcare claims. Quality‐adjusted life years (QALYs) were calculated based on the EuroQol‐5D‐5L. Non‐parametric bootstrapping with 2000 iterations was used to determine sampling uncertainty. Multiple imputation was used for handling missing data. Results: The Tele‐MAST trial included 82 participants and was conducted in Queensland, Australia during 2018–2021. When all healthcare claims were included, the incremental cost savings from Tele‐MAST were ‐AU$4,327 (95% CI: −$8637, −$18) while incremental QALY gains were small at 0.03 (95% CI: −0.02, 0.08). The likelihood of Tele‐MAST being cost‐effective versus SC was 87% at a willingness‐to‐pay threshold of AU$50,000 per QALY gain. When psychological‐related healthcare costs were included only, the incremental cost per QALY gain was AU$10,685 (95% CI: dominant, $24,566) and net monetary benefits were AU$534 (95% CI: $466, $602) with a 65% likelihood of the intervention being cost‐effective. Conclusions: Based on this small randomized controlled trial, the Tele‐MAST intervention is a cost‐effective intervention for improving the quality of life of people with PBT in Australia. Patients receiving the intervention incurred significantly lower overall healthcare costs than patients in SC. There was no significant difference in costs incurred for psychological health services. [ABSTRACT FROM AUTHOR]

Background: Thalamic pain syndrome (TPS) is an enigmatic and rare condition. Thalamic pain syndrome is under the umbrella of central pain syndrome, which is classically associated with multiple sclerosis, spinal cord injury, postamputation, epilepsy, stroke, tumor, and Parkinson's disease. The mainstay treatment of TPS is polypharmacy. There is uncertainty about the intermediate options to manage medication‐resistant TPS before resorting to invasive, and often expensive, intracranial therapies. Stellate ganglion block (SGB) has shown promise in reducing TPS symptoms of the upper extremity and face following a thalamic ischemic event. Aims: Discuss the effect and potential utility of SGB on ipsilateral headache, facial, and upper extremity neuropathic pain due to thalamic malignancies. Materials and Methods: A review of two patient records that underwent SGB for treatment of TPS of oncologic origin. Results: We present two cases of the successful use of SGB for the treatment of oncologic‐related TPS for patients who had failed other conservative pharmacologic measures. Discussion: Chronic pain is a complex experience that often simultaneously involves psychosocial, neuropathic, and nociceptive constituents. Among advanced cancer patients, factors such as an individual's spirituality, psychological stressors, and views on their mortality add layers of intricacy in addressing their pain. While TPS has been characterized in both stroke populations and oncologic populations, the treatment of SGB for pain relief in TPS has been limited to the stroke population. Repeated SGB worked to alleviate the ipsilateral headache, facial, and upper extremity pain in these two patients. The benefits of utilization of SGB, with the possibility of pain relief, within the thalamic malignancy population cannot be understated. Conclusion: In summary, ultrasound‐guided SGB may be considered in patients with TPS due to thalamic cancer, before pursuing more invasive intracranial surgeries to treat pain. [ABSTRACT FROM AUTHOR]

Cancer of the central nervous system (CNS) can crosstalk systemically and locally in the tumor microenvironment and has become a topic of attention for tumor initiation and advancement. Recently studied neuronal and cancer interaction fundamentally altered the knowledge about glioma and metastases, indicating how cancers invade complex neuronal networks. This review systematically discussed the interactions between neurons and cancers and elucidates new therapeutic avenues. We have overviewed the current understanding of direct or indirect communications of neuronal cells with cancer and the mechanisms associated with cancer invasion. Besides, tumor‐associated neuronal dysfunction and the influence of cancer therapies on the CNS are highlighted. Furthermore, interactions between peripheral nervous system and various cancers have also been discussed separately. Intriguingly and importantly, it cannot be ignored that exosomes could mediate the "wireless communications" between nervous system and cancer. Finally, promising future strategies targeting neuronal–brain tumor interactions were reviewed. A great deal of work remains to be done to elucidate the neuroscience of cancer, and future more research should be directed toward clarifying the precise mechanisms of cancer neuroscience, which hold enormous promise to improve outcomes for a wide range of malignancies. [ABSTRACT FROM AUTHOR]

Context: Primary brain tumor (PBT) causes poor prognosis and significant complications, which include movement problems such as balance disorders, failed return to work, and daily life activities. Objectives: The aim of the present study is to estimate the prevalence of PBT in Iran, using a meta-analysis method. Methods: This meta-analysis study was conducted in Iran in 2023 and articles published until the beginning of 2023 were included in the study, using the English keywords of brain cancer, brain tumor, tumor prevalence, prevalence, cancer, nervous system cancer, and their Persian equivalents. Data analysis was carried out, using CMA software. Results: After the initial search, 890 articles on BT were found, and 21 eligible articles were included in the meta-analysis. Also, the prevalence of brain cancer is 4% (95%CI:3.3-4.8) in men and 2.9% (95%CI: 2.3-3.6) in women. Conclusions: According to the result, the BT incidence rate is 4% for males and 2.9% for females. Therefore, it is necessary to take necessary preventive measures in this regard. [ABSTRACT FROM AUTHOR]

BackgroundCognitive impairment and cerebral microbleeds (CMBs) are long-term side-effects of cranial radiation therapy (RT). Previously we showed that memory function is disrupted in young patients and that the rate of cognitive decline correlates with CMB development. However, vascular injury alone cannot explain RT-induced cognitive decline. Here we use resting-state functional MRI (rsfMRI) to further investigate the complex mechanisms underlying memory impairment after RT.MethodsNineteen young patients previously treated with or without focal or whole-brain RT for a brain tumor underwent cognitive testing followed by 7T rsfMRI and susceptibility-weighted imaging for CMB detection. Global brain modularity and efficiency, and rsfMRI signal variability within the dorsal attention, salience, and frontoparietal networks were computed. We evaluated whether MR metrics could distinguish age- and sex-matched controls (N = 19) from patients and differentiate patients based on RT exposure and aggressiveness. We also related MR metrics with memory performance, CMB burden, and risk factors for cognitive decline after RT.ResultsCompared to controls, patients exhibited widespread hyperconnectivity, similar modularity, and significantly increased efficiency (p < 0.001) and network variability (p < 0.001). The most abnormal values were detected in patients treated with high dose whole-brain RT, having supratentorial tumors, and who did not undergo RT but had hydrocephalus. MR metrics and memory performance were correlated (R = 0.34-0.53), though MR metrics were more strongly related to risk factors for cognitive worsening and CMB burden with evidence of functional recovery.ConclusionsMR metrics describing brain connectivity and variability represent promising candidate imaging biomarkers for monitoring of long-term cognitive side-effects after RT.