Search Results (792)

Background: Cancer-related cognitive impairment (CRCI) is a significant concern for individuals with non-central nervous system (non-CNS) cancers, affecting memory, attention, executive functions, and processing speed. Non-pharmacological interventions, including digital cognitive rehabilitation, have shown promise in addressing CRCI. This systematic review investigates the efficacy of digital and computerized cognitive rehabilitation interventions in improving cognitive outcomes in non-CNS cancer patients. Method: A systematic search of the EMBASE, Scopus, and PubMed databases was conducted to identify studies on digital and computerized cognitive rehabilitation for non-CNS cancer patients. Studies were included if they involved computerized and digital cognitive rehabilitation for oncological patients and assessed the efficacy of the intervention. A total of 11 studies were selected, including randomized controlled trials and quasi-experimental designs. The quality of the studies was assessed using the Mixed Methods Appraisal Tool (MMAT). Data was synthesized using a narrative descriptive approach, and the results were summarized in a descriptive table. Results: The most frequently assessed cognitive domains included working memory, attention, executive functions, and processing speed. The majority of studies (n = 11) demonstrated significant immediate improvements in cognitive functions, particularly in working memory, executive functions, attention, and processing speed. Short-term follow-up (1–5 months) showed partial maintenance of these improvements, while long-term effects (6 months to 1 year) were more variable. Improvements in episodic memory were less consistent, particularly among breast cancer survivors. Discussion: Digital and computerized cognitive rehabilitation appears to be an effective intervention for CRCI, providing immediate cognitive benefits and some lasting improvements, especially in domains such as memory and attention. However, long-term effects remain variable, and further research is needed to explore the optimal duration of interventions and the potential advantages of personalized rehabilitation approaches. Full article

The blood–brain barrier (BBB) restricts therapeutic delivery to the central nervous system (CNS), hindering the treatment of neurological disorders, such as Alzheimer’s disease, Parkinson’s disease, brain cancers, and stroke. Aptamers, short single-stranded DNA or RNA oligonucleotides that can fold into unique 3D shapes and bind to specific target molecules, offer high affinity and specificity, low immunogenicity, and promising BBB penetration via receptor-mediated transcytosis targeting receptors such as the transferrin receptor (TfR) and low-density lipoprotein receptor-related protein 1 (LRP1). This review examines aptamer design through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) and its variants, mechanisms of BBB crossing, and applications in CNS disorders. Recent advances, including in silico optimization, in vivo SELEX, BBB chip-based MPS-SELEX, and nanoparticle–aptamer hybrids, have identified brain-penetrating aptamers and enhanced the brain delivery efficiency. This review highlights the potential of aptamers to transform CNS-targeted therapies. Full article

Background: Patients with primary central nervous system (CNS) tumors often experience fatigue and sleep disturbances, significantly impacting their quality of life. Exercise has been shown to improve these symptoms in various cancer populations. The aim of this study is to evaluate the effects of different types of exercise on fatigue and sleep in less-investigated CNS tumor patients. Methods: A literature search was conducted in PubMed, Scopus, Cochrane Library, and CINAHL. Eligible randomized and non-randomized studies evaluating exercise interventions in patients diagnosed with primary brain tumors were systematically reviewed, primarily using a narrative synthesis approach. Cancer-related fatigue and sleep-related outcomes were extracted as variables of interest. Where possible [≥2 Randomized Control Trials (RCTs) available for glioma patients], meta-analyses were conducted to assess the overall effects of physical therapy on the above-mentioned outcomes. Results: A total of 15 relevant intervention studies were identified, either RCTs or other types of studies, such as prospective feasibility cohort studies and case studies. A total of 448 participants were enrolled, with the majority diagnosed with glioma. There were single reports on pituitary adenoma after surgery and meningioma patients. In glioma patients, the overall effect of various modality exercise interventions on fatigue was non-significant, reflecting the heterogeneous characteristics of studies with diverse outcomes. However, meta-analysis focusing on combined exercise interventions (aerobic and resistance training) showed a positive effect on reducing fatigue in these patients [Standardized Mean Difference (SMD) = 0.866, p = 0.03]. Fatigue in glioma patients may also improve through yoga and Pilates. Aerobic but not strength exercise seems to improve sleep in glioma patients (SMD = 1.14, p = 0.02). Sleep quality may also improve through yoga and combined exercise. Conclusions: Certain types of exercise appear to effectively reduce fatigue and improve sleep in patients with CNS tumors. Future, well–controlled, multi-arm, larger-scale studies are necessary to resolve discrepancies, as well as to explore long-term outcomes and define factors influencing individualized exercise responses. Full article

Background/Objectives: The latest National Comprehensive Cancer Network (NCCN) Central Nervous System (CNS) Guidelines recommend utilizing next-generation sequencing (NGS) to enable comprehensive genomic profiling (CGP) as the preferred approach for molecular characterization of central nervous system (CNS) malignancies. CNS malignancies present distinct challenges due to the infeasibility of tissue-based testing for many patients and the restrictive nature of the blood–brain barrier (BBB) making plasma-based liquid biopsy an ineffective alternative. Recent advances in liquid biopsy have extended molecular testing beyond plasma to include cerebrospinal fluid (CSF), which serves as a valuable source for tumor-derived nucleic acids. Methods: The Belay Summit™ 2.0 is a high-throughput CGP assay capable of detecting multiple variant types, including single nucleotide variants (SNVs) and small insertion and deletions (Indels), copy number variations (CNVs), gene fusions, splice variants, and immunotherapy biomarkers such as microsatellite instability (MSI) and tumor mutational burden (TMB). This study details the analytical and clinical validation of Summit™ 2.0 to assess its technical performance and clinical sensitivity. Analytical validation was conducted using 68 specimens, demonstrating robust and reproducible detection of all variant types with 15 ng of CSF-derived total nucleic acid (tNA). Results: The analytical sensitivity of the Belay Summit™ 2.0 assay for SNVs and Indels was determined to be 96.7% with a 100% limit of detection (LoD) at a variant allele frequency of 0.3%. Clinical validity was evaluated across a cohort of 118 CSF specimens, including both primary and metastatic CNS tumors, demonstrating 96% sensitivity and 98% specificity. Conclusions: These findings support the use of the Belay Summit™ 2.0 assay for accurate and reproducible genomic profiling of CNS tumors using tumor-derived nucleic acids from CSF in patients for whom tissue-based testing is considered infeasible, unsafe, or not deemed by the prescribing physician to be clinically appropriate. Full article

Distinct forms of non-apoptotic programmed cell death (PCD) play a central role in human and animal health and their signaling cascades provide pharmacological targets for therapeutic interventions. Non-apoptotic modalities of programmed cell death include well characterized forms, such as ferroptosis, necroptosis, pyroptosis, autophagy, paraptosis, as well as newly characterized varieties, such as cuproptosis, disulfidptosis, and erebosis. Each pathway exhibits unique molecular signaling signatures, ultrastructural characteristics, and functional outcomes that distinguish them from classical apoptosis. While pharmacological targets in the signaling cascade are promising objectives for overcoming apoptosis resistance in cancer therapy, inhibition of cell death in the myocardium or nervous system is critical for cytoprotection. This review provides detailed characterization and schematic visualization of cellular and subcellular hallmarks for each non-apoptotic PCD modality, facilitating their morphological identification. Understanding these diverse pathways is crucial for developing innovative therapeutic interventions in cancer, neurodegeneration, and inflammatory diseases. Full article

Background: Neuroblastoma is the most common extracranial solid malignancy in infants and children. High-risk neuroblastoma patients are commonly treated with temozolomide (TMZ), which typically exhibits a poor therapeutic response. Serotonin, also known as 5-hydroxytryptamine (5-HT), plays various essential functions in the human body. In the central nervous system, it serves as a neurotransmitter. Beyond its physiological roles, 5-HT has recently been identified as a potential growth factor for several human tumors, including gliomas and carcinoid tumors. Recent literature has demonstrated that 5-HT receptor antagonists can inhibit the growth of cancer cells. Furthermore, both 5-HT receptors and their antagonists have been identified as potential anticancer agents, suggesting their significance in the development of new treatment strategies. Objectives: The primary aim of this study was to examine the effects of 5-HT and 5-HT antagonists on tumor (neuroblastoma (SH-SY5Y)) and healthy cells (microglia (HMC3)) and determine the impact of their interaction with the anticancer agent TMZ on cell proliferation/viability and migration. Methods: The study explored the interaction between 5-HT, the 5-HT antagonist granisetron (GRN), the anticancer agent TMZ, and their combinations, specifically assessing their influence on cell proliferation, viability, and migration. Results: As a result, the single and combined applications of 5-HT, TMZ, and GRN, a 5-HT antagonist, inhibited cell growth and proliferation in SH-SY5Y, causing decreased cell viability. Additionally, the combination of 5-HT and GRN increased the efficacy of TMZ. Conclusions: The study findings revealed that 5-HT and 5-HT antagonists may have therapeutic effects by exhibiting antiproliferative effects in SH-SY5Y cells at high concentrations. Full article

Objectives: To determine the incidence of delayed methotrexate elimination (DME) and acute kidney injury (AKI) and their associations with clinical outcomes in patients receiving high-dose methotrexate (HDMTX) for cancer treatment. Methods: The HDMTX European Registry collected medical records data from 12 institutions in 5 European countries to investigate the clinical practice patterns of healthcare providers utilizing HDMTX for cancer treatment. Cancer types included were acute lymphoblastic leukemia (ALL), primary central nervous system lymphoma (PCNSL), non-Hodgkin lymphoma (NHL), osteosarcoma, and other CNS cancers. Primary endpoints were the incidence of DME and AKI; secondary endpoints were clinical outcomes, including hospital length of stay (LOS), delay in the subsequent course of treatment, methotrexate dose reduction, and omission of next course of treatment. Associations between the primary and secondary endpoints were analyzed with Chi-square and Wilcoxon rank-sum tests. Results: Among the 2501 total HDMTX courses analyzed, DME occurred in 302 courses (12.1%), and AKI in 384 courses (15.4%). DME incidence was highest in courses for PCNSL (18.2%) and NHL (17.2%); AKI incidence was highest in ALL courses (21.0%). Incidence of DME and AKI varied by age and methotrexate infusion duration among the different cancer types. Occurrence of DME was associated with longer delays prior to the next course of treatment, longer hospital LOS, and more frequent methotrexate dose reductions and dose omissions. Conclusions: While HDMTX is a very effective and safe treatment, administration of efficacious doses of methotrexate can lead to AKI and DME, and no single or combination of patient or treatment factors was found to reliably predict their occurrence. Thus, diligent monitoring of methotrexate levels is imperative for early detection and prompt management of nephrotoxicity in all settings where HDMTX treatment is administered. Full article

Cancer cachexia (CC) is a multifactorial, multi-organ syndrome characterized by systemic inflammation, metabolic dysregulation, anorexia, and progressive depletion of skeletal muscle and adipose tissue. Despite its high prevalence among patients with advanced malignancies, effective therapeutic options remain limited. Recent studies have elucidated the molecular underpinnings of CC and the therapeutic potential of natural herbs, highlighting the involvement of central nervous system regulation, adipose tissue, immune responses, gut microbiota, skeletal muscle, and disruptions in anabolic–catabolic signaling pathways such as mTOR, UPS, NF-κB, and STAT3. Persistent inflammation induces E3 ubiquitin ligases (Atrogin-1/MuRF-1) through cytokines including IL-6 and TNF-α, thereby impairing muscle homeostasis, while suppression of anabolic cascades such as IGF-1/mTOR further aggravates muscle atrophy. The limited efficacy and adverse effects of synthetic agents like megestrol acetate underscore the value of herbal therapies as safer adjunctive strategies. Botanicals such as Coicis Semen, Scutellaria baicalensis, and Astragalus demonstrate anti-inflammatory and muscle-preserving activities by modulating NF-κB, IL-6, and oxidative stress signaling. Numerous investigations indicate that these herbs downregulate MuRF-1 and Atrogin-1 expression, enhance appetite, and attenuate muscle loss, though they exhibit minimal influence on tumor suppression. While promising, current evidence remains largely preclinical and mechanistic validation is incomplete. This review consolidates contemporary insights into CC pathogenesis and the bioactivity of herbal interventions, highlighting the need for translational research to bridge preclinical findings with clinical applicability. Full article

The 2025 Canadian Breast Cancer Symposium (CBCS) brought together patients, clinicians and researchers from across Canada to discuss advances shaping personalized breast cancer care. Key updates in systemic therapy highlighted expanding treatment options, including CDK4/6 inhibitors, oral SERDs, PI3K/AKT-targeted therapies, and antibody–drug conjugates across early and metastatic settings. Radiation oncology sessions emphasized treatment de-escalation, featuring evidence for ultra-hypofractionation, selective omission of nodal irradiation, and stereotactic strategies to manage oligoprogression. Surgical presentations focused on reducing morbidity through tailored axillary management and emerging techniques to prevent lymphedema. Advances in the management of central nervous system metastases underscored the growing synergy between stereotactic radiotherapy and CNS-active systemic therapies. Informed by patient testimony and advocacy perspectives, experts reflected on persistent gaps in diagnosis, access, and survivorship that shape priorities for future improvements. Together, these insights outline key directions that help to refine clinical practice and guide future research. Full article

Glioblastoma (GBM) is one of the most common and aggressive primary malignant tumors of the central nervous system, accounting for about half of all gliomas in adults. Despite intensive research and advances in molecular biology, genomics, and modern neuroimaging techniques, the prognosis for patients with GBM remains extremely poor. Despite the implementation of multimodal treatment involving surgery, radiotherapy, and chemotherapy with temozolomide, the average survival time of patients is only about 15 months. This is primarily due to the complex biology of this cancer, which involves numerous genetic and epigenetic abnormalities, as well as a highly heterogeneous tumor structure and the presence of glioblastoma stem cells with self renewal capacity. Mutations and abnormalities in genes such as IDH-wt, EGFR, PTEN, TP53, TERT, and CDKN2A/B are crucial in the pathogenesis of GBM. In particular, IDH-wt status (wild-type isocitrate dehydrogenase) is one of the most important identification markers distinguishing GBM from other, more favorable gliomas with IDH mutations. Frequent EGFR amplifications and TERT gene promoter mutations lead to the deregulation of tumor cell proliferation and increased aggressiveness. In turn, the loss of function of suppressor genes such as PTEN or CDKN2A/B promotes uncontrolled cell growth and tumor progression. The immunosuppressive tumor microenvironment also plays an important role, promoting immune escape and weakening the effectiveness of systemic therapies, including immunotherapy. The aim of this review is to summarize the current state of knowledge on the epidemiology, classification, pathogenesis, diagnosis, and treatment of glioblastoma multiforme, as well as to discuss the impact of recent advances in molecular and imaging diagnostics on clinical decision-making. A comprehensive review of recent literature (2018–2025) was conducted, focusing on WHO CNS5 classification updates, novel biomarkers (IDH, TERT, MGMT, EGFR), and modern diagnostic techniques such as liquid biopsy, radiogenomics, and next-generation sequencing (NGS). The results of the review indicate that the introduction of integrated histo-molecular diagnostics in the WHO 2021 classification has significantly increased diagnostic precision, enabling better prognostic and therapeutic stratification of patients. Modern imaging techniques, such as advanced magnetic resonance imaging (MRI), positron emission tomography (PET), and radiomics and radiogenomics tools, allow for more precise assessment of tumor characteristics, prediction of response to therapy, and monitoring of disease progression. Contemporary molecular techniques, including DNA methylation profiling and NGS, enable in-depth genomic and epigenetic analysis, which translates into a more personalized approach to treatment. Despite the use of multimodal therapy, which is based on maximum safe tumor resection followed by radiotherapy and temozolomide chemotherapy, recurrence is almost inevitable. GBM shows a high degree of resistance to treatment, which results from the presence of stem cell subpopulations, dynamic clonal evolution, and the ability to adapt to unfavorable microenvironmental conditions. Promising preclinical and early clinical results show new therapeutic strategies, including immunotherapy (cancer vaccines, checkpoint inhibitors, CAR-T therapies), oncolytic virotherapy, and Tumor Treating Fields (TTF) technology. Although these methods show potential for prolonging survival, their clinical efficacy still needs to be confirmed in large studies. The role of artificial intelligence in the analysis of imaging and molecular data is also increasingly being emphasized, which may contribute to the development of more accurate predictive models and therapeutic decisions. Despite these advancements, GBM remains a major therapeutic challenge due to its high heterogeneity and treatment resistance. The integration of molecular diagnostics, artificial intelligence, and personalized therapeutic strategies that may enhance survival and quality of life for GBM patients. Full article

Background/Objectives: This study explored the epidemiology of Status Epilepticus (SE) in Kazakhstan. Methods: Utilizing data from the National Health System from 2014 to 2023, we investigated the age-standardized incidence rate (ASIR) of SE. The authors employed restricted mean survival time (RMST) models to evaluate how sex, older age, epilepsy, history of cerebrovascular diseases (CVD), central nervous system (CNS) infections, brain tumors, and cancer affected survival during 30 days through the fifth year following hospital admission for SE. Results: This study included 14,010 patients. The ASIR per 100,000 increased threefold, from 4.15 (95% CI: 3.85; 4.46) in 2014 to 12.12 (95% CI: 11.64; 17.59) in 2023, with a sharp increase during the COVID-19 pandemic. The 30-day and 5-year mortality were 2.10% and 8.85%, respectively. The RMST identified that all-cause mortality was driven by elderly age, brain tumors, and cancer, where the difference in survival increased from one day at baseline to over a year by the fifth year. The effects of CVD, CNS infections, and sex on survival were substantially lower. However, epilepsy was associated with a better prognosis. Conclusions: We observed an incremental increase in the SE incidence over a decade. Our findings warrant actions to resolve issues related to rescue medicines to improve SE outcomes in both country and region. It may be a priority for elderly patients and those with systemic tumors. Further research is needed to understand the role of epilepsy in SE epidemiology, with emphasis on design-related biases. Full article

Background and Clinical Significance: DNA methylation profiling has revolutionized the classification of central nervous system (CNS) tumors, providing insights into tumor prognosis, recurrence, and personalized treatments. However, a significant challenge remains in classifying rare or molecularly undefined high-grade gliomas (HGGs) that fail to match existing methylation reference classes. This study evaluates the clinical, histopathological, and molecular characteristics of three unclassifiable cases through a retrospective analysis. Methylation profiling was performed by the National Institute of Health based on the 11b6 and 12b6 of the Heidelberg classifier, as well as the National Cancer Institute/Bethesda classifier. The cases were evaluated for histopathological features, molecular markers, and clinical outcomes. Case Presentation: We present three adult patients with histologically confirmed HGGs that were unclassifiable by standard DNA methylation profiling. All patients presented with diverse clinical and radiographic findings. Histopathological examination confirmed high-grade glial neoplasms in each case. However, methylation profiling failed to yield clear matches for any known class. Instead, profiling suggested indeterminate IDH-wildtype neoplasms with aggressive clinical courses. Following treatment, one patient experienced disease progression and died, while the other two remained without evidence of recurrence at follow-up. Conclusions: These cases underscore the persistent diagnostic challenges posed by CNS tumors that are unclassifiable by current DNA methylation, highlighting the urgent need for expanded reference datasets. While methylation profiling has transformed the field of tumor diagnostics, its limitations still exist. Enhanced collaboration to broaden diagnostic categories is essential to broaden diagnostic classifiers. Until these tools are refined, integration of clinical, histological, and molecular findings is imperative to optimize patient management, improve classification accuracy, and optimize therapeutic outcomes. Unclassifiable HGGs represent a critical gap in CNS tumor diagnostics. Addressing this requires global collaboration to enrich methylation databases. In the interim, a multimodal diagnostic strategy remains essential for the management of these challenging tumors. Full article

Brain tumors, both malignant and non-malignant, represent a persistent global health challenge. Differences in diagnosis, treatment, and outcomes are influenced by race, ethnicity, socioeconomic status (SES), and geographical location. Brain and central nervous system (CNS) tumors rank 19th in global cancer incidence and 12th in cancer-related mortality. U.S. Incidence is higher in females and individuals with greater socioeconomic means, contrasting with global patterns where males are more affected. Glioblastoma has a wide variation in incidence and survival by state, with rural regions showing higher mortality despite lower incidence, often due to reduced access to specialized care. Non-Hispanic Black children with CNS tumors experience higher mortality than their White peers, even after adjusting for SES. Outcomes are generally poorer in low- and middle-income countries, where healthcare infrastructure remains limited. Biological and genetic differences may also influence treatment response and tumor behavior across population groups. This review outlines key variations in brain tumor care, with a key focus on the United States, and emphasizes the need for patient-centered strategies to ensure timely diagnosis, consistent treatment, and improved outcomes. Full article

Mesoporous silica nanoparticles (MSNs) are among the most adaptable nanocarriers in modern pharmaceutics, characterized by a high surface area, tunable pore size, controllable morphology, and excellent biocompatibility. These qualities enable effective encapsulation, protection, and the delivery of drugs in a specific area and, therefore, MSNs are powerful platforms for the targeted and controlled delivery of drugs and theragnostic agents. Over the past ten years and within the 2021–2025 period, the advancement of MSN design has led to the creation of hybrid nanostructures into polymers, lipids, metals, and biomolecules that have yielded multifunctional carriers with enhanced stability, responsiveness, and biological activities. The current review provides a review of the synthesis methods, surface functionalization techniques, and physicochemical characterization techniques that define the next-generation MSN-based delivery systems. The particular focus is put on stimuli-responsive systems, such as redox, pH, enzyme-activated, and light-activated systems, that enable delivering drugs in a controlled and localized manner. We further provide a summary of the biomedical use of MSNs and their hybrids such as in cancer chemotherapy, gene and nucleic acid delivery, antimicrobial and vaccine delivery, and central nervous system targeting, supported by recent in vivo and in vitro studies. Important evaluations of biocompatibility, immunogenicity, degradation, and biodistribution in vivo are also provided with a focus on safety in addition to the regulatory impediments to clinical translation. The review concludes by saying that there are still limitations such as large-scale reproducibility, long-term toxicity, and standardization by the regulators, and that directions are being taken in the future in the fields of smart programmable nanocarriers, green synthesis, and sustainable manufacture. Overall, mesoporous silica and hybrid nanoparticles represent a breakthrough technology in the nanomedicine sector with potentials that are unrivaled in relation to targeted, controlled, and personalized therapeutic interventions. Full article

Endothelial-to-mesenchymal transition (EndMT) is a cellular program implicated in fibrosis, vascular remodeling, and the tumor microenvironment across multiple organs. We synthesize mechanistic pathways including TGF-β/SMAD, non-canonical (MAPK, PI3K/AKT, Rho/ROCK), Notch, and Wnt/β-catenin cascades. Their crosstalk with hypoxia, inflammatory cues, and epigenetic mechanisms can drive loss of endothelial identity and acquisition of mesenchymal characteristics. We outline disease contexts in the heart, lungs, kidneys, liver, central nervous system, and cancer, highlighting context-dependent contributory roles of EndMT. Therapeutically, we review pathway-targeted agents, epigenetic inhibitors, microRNA-based strategies, antibodies/biologics, small molecules and natural compounds, and cell- and gene-based interventions. Finally, we outline a translational roadmap that pairs patient-derived iPSC/organoid and organ-on-a-chip platforms to stratify EndMT states and prioritize targets. We also explore combination regimens that integrate multi-pathway modulation with epigenetic and immune approaches, aiming to deliver clinically meaningful anti-fibrotic benefits while better preserving physiological signaling. Full article