Nervous System Cancer Research Articles

Unlocking the promise of MANF in diseases: Mechanistic insights and therapeutic potentials.

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a ubiquitous neurotrophic factor that exhibits a variety of physiological functions and plays a critical role in the exploitation of therapeutic potential across a range of diseases, including cardiovascular disorders, nervous system diseases, metabolic imbalances, and cancers. In the context of cardiac diseases, MANF significantly promotes cardiomyocyte survival and improves cardiac functionality. Furthermore, MANF not only provides neuroprotection by shielding neurons from damage and promoting nerve regeneration in neurological disorders, but also involves in insulin resistance, lipid metabolism disturbances and fat-containing liver lesions. However, the oncogenic or tumor suppressive function of MANF in cancer remains unclear, requiring further investigation to elucidate its precise role in the process of cancer initiation and progression. This review aims to summarize the latest advancements in understanding the molecular pathways, intricate mechanisms, and therapeutic potential of MANF in the prevention and treatment of various diseases, emphasizing its multifaceted contributions to health and disease management.

Differential Replication and Oncolytic Effects of Zika Virus in Aggressive CNS Tumor Cells: Insights from Organoid and Tumoroid Models

Central nervous system (CNS) cancers are responsible for high rates of morbidity and mortality worldwide. Malignant CNS tumors such as adult Glioblastoma (GBM) and pediatric embryonal CNS tumors such as medulloblastoma (MED) and atypical teratoid rhabdoid tumors (ATRT) present relevant therapeutic challenges due to the lack of response to classic treatment regimens with radio and chemotherapy. Recent findings on the Zika virus’ (ZIKV) ability to infect and kill CNS neoplastic cells draw attention to the virus’ oncolytic potential. Studies demonstrating the safety of using ZIKV for treating malignant CNS tumors, enabling the translation of this approach to clinical trials, are scarce in the literature. Here we developed a co-culture model of mature human cerebral organoids assembled with GBM, MED or ATRT tumor cells and used these assembloids to test ZIKV oncolytic effect, replication potential and preferential targeting between normal and cancer cells. Our hybrid co-culture models allowed the tracking of tumor cell growth and invasion in cerebral organoids. ZIKV replication and ensuing accumulation in the culture medium was higher in organoids co-cultured with tumor cells than in isolated control organoids without tumor cells. ZIKV infection led to a significant reduction in tumor cell proportion in organoids with GBM and MED cells, but not with ATRT. Tumoroids (3D cultures of tumor cells alone) were efficiently infected by ZIKV. Interestingly, ZIKV rapidly replicated in GBM, MED, and ATRT tumoroids reaching significantly higher viral RNA accumulation levels than co-cultures. Moreover, ZIKV infection reduced viable cells number in MED and ATRT tumoroids but not in GBM tumoroids. Altogether, our findings indicate that ZIKV has greater replication rates in aggressive CNS tumor cells than in normal human cells comprising cerebral organoids. However, such higher ZIKV replication in tumor cells does not necessarily parallels oncolytic effects, suggesting cellular intrinsic and extrinsic factors mediating tumor cell death by ZIKV.

EPCO-23. LONGITUDINAL TRACKING AND LONG-READ CHROMATIN FIBER SEQUENCING OF HUMAN ASTROCYTES WITH TELOMERE DYSFUNCTION REVEALED ALTERED CHROMATIN ACCESSIBILITY AND INCREASED STRUCTURAL VARIATION

Abstract Glioma is an aggressive cancer of the central nervous system that is genetically characterized by aneuploidy and frequent structural variation (SV). We sought to investigate the role of telomere dysfunction (TD) in shaping the SV landscape in glioma. Normal human astrocytes (NHA) were engineered to express viral E6E7 oncoproteins which are known to spontaneously trigger TD by suppressing p53/pRb. We hypothesized that NHA-E6E7 cells gradually accumulate SVs and aneuploidy over time because of progressive TD. We therefore longitudinally tracked bulk and single-cell clones of NHA-E6E7 cells for a period of over 6 months since viral infection. Overall, NHA-E6E7 cells demonstrate a growth benefit over primary NHA cells. We obtained Illumina short-read sequencing for NHA-E6E7 cells at multiple time points. Three time points were additionally selected for both Oxford Nanopore and PacBio HiFi long-read sequencing using the single-molecule chromatin fiber sequencing (fiber-seq) protocol. Copy number variation (CNV) analysis of short-read data showed deletion events in chromosome 13 as early as population doubling level (PDL) 48. K-mer based CNV analysis using the long-read data confirmed this finding and also detected deletion events in chromosome 7 at PDL 50. From the long-read data, we found an elevated number of SVs in NHA-E6E7 cells compared to the primary NHA cells. In particular, we detected telomere junctions and found that telomere-associated SVs were more prevalent in NHA-E6E7 cells compared to primary cells. Next, chromatin accessibility and regulatory elements were predicted from fiber-seq data with exogenous N6-methyladenosine (m6A) stencils. We observed large-scale chromatin actuation changes in various regulatory elements across the genome that intensified in later passages of NHA-E6E7 cells. For example, we found a decrease in the accessibility in FBXO7 which is a gene that maintains chromosome stability. Our preliminary results indicated that TD is an important mediator of structural variation in glioma.

BIOM-46. REAL-WORLD EXPERIENCE WITH CIRCULATING TUMOR DNA IN CEREBROSPINAL FLUID IN PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS

Abstract Next generation sequencing (NGS) of circulating tumor DNA (ctDNA) from cerebrospinal fluid (CSF) offers a minimally invasive approach to identify somatic alterations for individuals with central nervous system (CNS) cancers. Here, we review our ‘real world’ experience using a clinically validated, FDA-authorized platform, MSK-IMPACTTM, to comprehensively profile ctDNA from CSF samples with and without clinically documented CNS involvement by cancer (1007 samples, 711 patients). The patient cohort included patients with over 90 distinct tumor types of primary CNS and metastatic origin, with lung cancer (n = 188), breast cancer (n = 150), and glioma (n = 148) representing the most common broad categories. We identified genetic alterations (ctDNA-positive) in 489/922 (53.0%) CSF samples from patients with clinically documented CNS cancer. Over half of these ctDNA-positive samples (248, 50.7%) possessed a biomarker that was predictive of response to an FDA-approved drug (OncoKB level 1). Furthermore, the distribution of clinically actionable somatic alterations was consistent with tumor-type specific alterations across the AACR GENIE cohort. Of patients without clinical documentation of CNS cancer, none of these 85 CSF samples were ctDNA-positive (specificity = 100%). Successive CSF sequencing over time identified clonal evolution and the emergence of resistance mechanisms to therapies. ctDNA positivity corresponded with shortened overall survival after CSF collection (HR: 3.23, 95% CI: 2.58-4.05, P < 0.001). NGS of CSF cfDNA can detect clinically actionable somatic alterations in a large subset of CNS cancer patients and allows tracking of tumor evolution. Detection of somatic alterations in CSF may be a useful prognostic biomarker for survival in cancer patients.

EPID-38. GLOBAL DISPARITIES AND PROJECTIONS IN PEDIATRIC BRAIN AND CNS CANCERS: A COMPREHENSIVE ANALYSIS THROUGH 2050

Abstract BACKGROUND Brain and other central nervous system (CNS) cancers are the most prevalent solid tumors and the leading cause of death among children worldwide. This study investigates trends in the incidence, mortality, and global distribution of pediatric brain and other CNS cancers projected through 2050. METHODS Data on pediatric brain and other CNS cancer incidence and mortality were extracted from Globocan 2022 for children aged 0 to 14 years. Age-standardized incidence and mortality rates were calculated by continent, country, and Human Development Index (HDI) categories. RESULTS The Globocan dataset revealed 24,677 new cases and 12,249 deaths, corresponding to age-standardized incidence rates (ASIRs) of 1.3 and age-standardized mortality rates (ASMRs) of 0.62 per 100,000 population. Significant geographic disparities were observed: North America reported the highest incidence rate at 3.6, followed by Europe (2.2), Latin America (1.7), Oceania (1.4), Asia (1.3), and Africa (0.67). Europe recorded the highest mortality rate at 0.89, followed by Latin America (0.87), North America (0.70), Asia (0.66), and Africa (0.40). A country-specific analysis revealed that the highest incidence rates were in Montenegro (3.7), Estonia (3.4), and Austria (3.2), whereas the highest mortality rates were in Lithuania (2.1), Angola (2.0), and Honduras (1.7). Additionally, 37.82% of new cases and 40.71% of deaths occurred in high-HDI countries. Projections: The annual increase in incidence and mortality rates for brain and other CNS cancers is projected at 1.3% through 2050, with new cases expected to rise to 25,004 and deaths to 12,404. CONCLUSIONS The findings indicate a 23% decrease in brain and other CNS cancer cases in high-HDI countries by 2050, contrasted with a 45.3% increase in low-HDI countries. These disparities underscore the critical need for global health strategies that promote equitable healthcare access and advanced treatments to reduce the global burden of these cancers and address inequities in health outcomes.

Connexin 43 hemichannels and related diseases

Abstract Connexin 43 (Cx43) protein forms hemichannels (connexons) and gap junctions, with hemichannels consisting of six Cx43 molecules and gap junctions formed by two hemichannels. While gap junctions are prevalent in organs like the heart and liver, hemichannels are found in specific cell types, such as astrocytes and osteocytes. They allow the passage of small molecules (<1.5 kDa) between the cytoplasm and extracellular matrix. Cx43 hemichannels have emerged as potential therapeutic targets in various diseases, including central nervous system disorders, bone-related diseases, diabetic complications, wound healing, and cancers. Aberrant hemichannel opening can worsen conditions by releasing inflammatory elements, such as causing gliosis in neuronal cells. Conversely, functional hemichannels may inhibit cancer cell growth and metastasis. Recent studies are revealing new mechanisms of Cx43 hemichannels, broadening their therapeutic applications and highlighting the importance of regulating their activity for improved disease outcomes.

CTNI-23. DIFFERENT GUT MICROBIOTA COMPOSITION IS ASSOCIATED WITH CHEMOTHERAPY EFFICACY IN PATIENTS WITH DIFFERENT TYPES OF CENTRAL NERVOUS SYSTEM CANCER

Abstract BACKGROUND The relationship between central nervous system cancers and the gut microbiota (GM) is not well understood. The purpose of this study is to retrospective analyze the differences between the composition of the gut microbiota in patients with different neurologic tumors and their correlation with chemotherapy efficacy. METHODS A total of 44 patients participated in the study and were divided into four groups: gliocytoma (GA), medulloblastoma (MB), germ cell tumors (GT), and diffuse large B-cell lymphoma (DB) based on their pathological diagnosis. Fecal samples were collected from patients for 16S amplicon sequencing to analyze GM composition. Moreover, all the patients were classified into completed response (CR), stable disease (SD), and progressive disease (PD) groups based on the clinical outcomes of chemotherapy. PLS-DA analysis and heatmap analysis were used to reveal the correlation between GM composition and outcomes of chemotherapy. RESULTS Phyla taxa comparison showed the detailed GM composition among these four groups. The phylum of Bacteroidetes was higher in GA group when compared to the other groups. And the phylum of Fusobacteria could only be found in GA and MB groups while the phylum of Verrucomicrobia showed a significant accumulation in DB group. the genera of Ruminococcus, Gemmiger, and Parasutterella were accumulated in the patients with the completed response of chemotherapy. Besides, patients in SD group had higher abundance of the genera of Prevotella, Tyzzerella, and Odoribacter. While patients in PD group showed the higher abundance of Streptcoccus, Fusobacterium, Lachnospira, and Holemanella. CONCLUSION We firstly drew the GM composition profile of the patients with GA, MB, GT, and DB to show the different GM composition of the diseases. Moreover, the gut microbiota composition correlates with chemotherapy outcomes in central nervous system cancer patients so may serve as a potential biomarker for predicting chemotherapy efficacy.

Reconstructing the regulatory programs underlying the phenotypic plasticity of neural cancers

Nervous system cancers exhibit diverse transcriptional cell states influenced by normal development, injury response, and growth. However, the understanding of these states’ regulation and pharmacological relevance remains limited. Here we present “single-cell regulatory-driven clustering” (scregclust), a method that reconstructs cellular regulatory programs from extensive collections of single-cell RNA sequencing (scRNA-seq) data from both tumors and developing tissues. The algorithm efficiently divides target genes into modules, predicting key transcription factors and kinases with minimal computational time. Applying this method to adult and childhood brain cancers, we identify critical regulators and suggest interventions that could improve temozolomide treatment in glioblastoma. Additionally, our integrative analysis reveals a meta-module regulated by SPI1 and IRF8 linked to an immune-mediated mesenchymal-like state. Finally, scregclust’s flexibility is demonstrated across 15 tumor types, uncovering both pan-cancer and specific regulators. The algorithm is provided as an easy-to-use R package that facilitates the exploration of regulatory programs underlying cell plasticity.

US Cancer Mortality Trends Among Asian and Pacific Islander Populations

Cancer is the leading cause of death among Asian American individuals and the second leading cause of death among Native Hawaiian and Pacific Islander people. To evaluate longitudinal cancer mortality trends from 1999 to 2020 among Asian American and Pacific Islander populations in the US by demographic characteristics. This cross-sectional study used the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database to obtain age-adjusted cancer death rates among Asian American and Pacific Islander individuals of all ages between January 1, 1999, and December 31, 2020. Data were analyzed from January 12 to March 19, 2024. Age, sex, cancer type, and US census regions. Trends and average annual percent changes (AAPCs) in age-adjusted cancer-specific mortality (CSM) rates for non-Hispanic Asian American and Pacific Islander populations were estimated by cancer type, age, sex, and region using Joinpoint regression. Between 1999 and 2020, 305 386 Asian American and Pacific Islander individuals (median [IQR] age, 69.5 [58.5-79.2] years; 51.1% male) died of cancer in the US. Overall, the CSM rate decreased by 1.5% annually. Men experienced a greater CSM rate decrease (AAPC, -1.8%; 95% CI, -2.2% to -1.3%) compared with women (AAPC, -1.1%; 95% CI: -1.2% to -1.0%). For women, death rates decreased for most cancer types but increased for uterine (AAPC, 2.5%; 95% CI, 2.0%-3.0%) and brain and central nervous system (AAPC, 1.4%; 95% CI: 0.7%-2.1%) cancers. Colorectal cancer mortality rates increased among men aged 45 to 54 years (AAPC, 1.3%; 95% CI, 0.5%-2.1%). Liver and intrahepatic bile duct cancer mortality increased for both men and women in all US census regions, uterine cancer mortality increased in all regions for women, and pancreatic cancer mortality increased in the Midwest for both men and women. Although these findings show an overall decrease in CSM among Asian American and Pacific Islander populations, specific cancer types exhibited increased mortality rates, with further disparities by sex and age. Targeted, culturally adapted clinical and public health interventions are needed to narrow disparities in cancer mortality.

Global, regional, and national burden of brain and central nervous system cancers for males from 1990 to 2021 and its predicted level in the next 25 years.

A study of the global burden of cerebral and central nervous system (CNS) cancers from the Global Burden of Diseases (GBD) indicates that these cancers significantly contribute to morbidity and mortality internationally. To fully understand the global impact of CNS cancer, expanded research efforts are essential. We analyzed the temporal trend of the disease burden from 1990 to 2021 and made projections for the expected burden from 2020 through 2044. We tapped into GBD 2021 Study data to evaluate CNS cancer incidence and trends among males. Prevalence was assessed with DisMod-MR, trends via cluster analysis, and Estimated Annual Percentage Change (EAPC) calculated via linear regression. Forecasts for 2022-2044 used APC and BAPC models, with a P-value < 0.05 considered significant. Analyses relied on R software 4.0.2. In 2021, males experienced between 148,118 and 232,469 new brain and CNS cancer cases, indicating increased global burden from 1990 to 2021. An observed link between the prevalence's EAPCs and Human Development Indices (HDIs) suggests higher incidence in more developed regions. Projections using the APC model suggest rising numbers of cases and losses in Disability-Adjusted Life Years (DALYs) from 2020 to 2044, while Age-Standardized Rates (ASRs) are expected to decrease overall. In summary, a higher Socio-Demographic Index (SDI) correlates with better outcomes for CNS cancer due to early medical interventions in regions with strong healthcare systems. This demonstrates the need for equitable healthcare policies that focus on improving diagnostic capabilities and professional training to enhance survival rates universally.

Association between Fat-Soluble Vitamin Metabolic Process and Glioma Progression.

Although multimodality therapy has recently advanced, patients with glioblastoma, one of the most aggressive and deadly types of central nervous system cancer, have a very poor prognosis and rare long-term survival. Vitamins are essential organic nutrients that play a pivotal role in maintaining homeostasis, and various studies have demonstrated the implication of vitamins in the pathophysiology of gliomas. Herein, we aimed to investigate the association of the vitamin metabolic pathway and the corresponding candidate genes for the malignancy, aggressiveness, and poor prognosis of gliomas using The Cancer Genome Atlas database of patients with gliomas. We demonstrated that fat-soluble vitamin metabolic processes are prominently associated with glioma grade, molecular biomarkers, molecular subtypes, and clinical outcomes. Moreover, we identified the key genes related to the fat-soluble metabolic pathway in gliomas using differentially expressed gene analysis. Among them, the expression of the vitamin K epoxide reductase complex subunit 1 (VKORC1), encoding VKOR essential for the vitamin K-dependent γ-carboxylation of target proteins, was prominently associated with not only malignancy, aggressiveness, and poor prognosis of gliomas but also the representative signal pathways related to glioma pathogenesis. Moreover, the inactivation of Vkorc1 by RNA interference decreased the proliferation and migration potential of glioma cells in vitro. Collectively, these findings reveal the pivotal role of fat-soluble vitamin and vitamin K metabolic processes in the pathophysiology of gliomas, thereby identifying a potential target for drug development for the treatment of malignant gliomas.

The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study.

The aim of this study was to determine the association between insulin glargine usage and the potential increase in cancer risk among the Lithuanian population diagnosed with type 2 diabetes mellitus (T2DM). A retrospective cohort study was conducted. The cohort of insulin users was established by identifying all male and female patients diagnosed with T2DM, as recorded in the National Health Insurance Fund database between 1 January 2000 and 31 December 2012. The risk of cancer among insulin glargine users was compared with the risk in non-glargine insulin users. Cox proportional hazard models were used to estimate hazard ratios (HR) and their 95% confidence intervals (CI). The overall cancer risk for all sites combined showed no significant difference (HR 0.84, 95% CI 0.67-1.05). Although a general decrease in the risk of cancers was observed at most sites for glargine users, the use of insulin glargine was associated with a non-significant increase in the risk of mouth and pharynx, stomach, non-melanoma skin, breast, cervical, ovarian, and central nervous system cancers. There was a tendency for a lower risk of colon, rectum, rectosigmoid, and anus cancer among glargine users (HR 0.45, 95% CI 0.18-1.12, p = 0.09). Our research contributes to the growing body of evidence showing that insulin glargine is not associated with an increased risk of all cancers or specific types of cancer.

Synthesis of chlorotoxin functionalized metallic nanoparticles and their in vitro evaluation of cytotoxic effects in nervous system cancer cell lines

The treatment of glioblastoma (GB) and neuroblastoma (NB) remains a challenge, as current chemotherapies are plagued with systemic toxicity, drug resistance, and inadequate blood–brain barrier (BBB) penetration. Therefore, novel therapeutic strategies with high specificity and the capacity to bypass the BBB are required. Chlorotoxin (CTX) selectively targets gliomas and neuroectodermal tumors, hence the use of CTX-targeted nanoparticles (NPs) represents a promising therapeutic approach for nervous system (NS) cancers. Bimetallic NPs composed of two metals such as gold-platinum NPs (AuPtNPs) exhibit enhanced anticancer properties compared to single-metal NPs, however their application in studying NS tumors has been relatively limited. CTX-functionalized monometallic gold NPs (CTX-AuNPs) and bimetallic gold-platinum NPs (CTX-AuPtNPs) were synthesized in this study. The NPs were characterized by Ultraviolet-Visible Spectroscopy (UV–vis), Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) and Fourier Transform Infra-Red Spectroscopy (FTIR). Cytotoxicity of NPs was investigated in cancer (U87 and SH-SY5Y) and non-cancer (KMST-6) cells using the water-soluble tetrazolium (WST)-1 assay. The CTX-AuNPs and CTX-AuPtNPs had a core size of ∼5 nm. The CTX-AuPtNPs showed significant anticancer activity in U87 cells possibly due to the synergistic effects of combined metals. Findings obtained from this study demonstrated that CTX can be used to target NS cancers and that bimetallic NPs could be effective in their treatment. More studies are required to investigate the mechanisms of NPs toxicity, and further explore the hyperthermia treatment of NS cancer using the CTX-AuPtNPs.

Optimizing cancer classification: a hybrid RDO-XGBoost approach for feature selection and predictive insights

The identification of relevant biomarkers from high-dimensional cancer data remains a significant challenge due to the complexity and heterogeneity inherent in various cancer types. Conventional feature selection methods often struggle to effectively navigate the vast solution space while maintaining high predictive accuracy. In response to these challenges, we introduce a novel feature selection approach that integrates Random Drift Optimization (RDO) with XGBoost, specifically designed to enhance the performance of cancer classification tasks. Our proposed framework not only improves classification accuracy but also offers valuable insights into the underlying biological mechanisms driving cancer progression. Through comprehensive experiments conducted on real-world cancer datasets, including Central Nervous System (CNS), Leukemia, Breast, and Ovarian cancers, we demonstrate the efficacy of our method in identifying a smaller subset of unique and relevant genes. This selection results in significantly improved classification efficiency and accuracy. When compared with popular classifiers such as Support Vector Machine, K-Nearest Neighbor, and Naive Bayes, our approach consistently outperforms these models in terms of both accuracy and F-measure metrics. For instance, our framework achieved an accuracy of 97.24% in the CNS dataset, 99.14% in Leukemia, 95.21% in Ovarian, and 87.62% in Breast cancer, showcasing its robustness and effectiveness across different types of cancer data. These results underline the potential of our RDO-XGBoost framework as a promising solution for feature selection in cancer data analysis, offering enhanced predictive performance and valuable biological insights.

Chemical Composition of Clay Soil Analysis and Potential Health Risks: Experimental Study in Tshwane District, Gauteng Province

The practise of geophagy is common amongst women of childbearing age from different geographic locations, including South Africa, regardless of their social and economic status such as their level of education, race, marital status, income or occupation. This study aimed to examine the women of childbearing age in Tshwane District, Gauteng Province, South Africa. An experimental study was conducted at the laboratory to examine the chemical composition of clay soil ingested by geophagic women of childbearing age. Thirty-nine clay soil samples were collected from study participants attending antenatal care services and family planning at public healthcare facilities of Tshwane District, Gauteng Province, and subjected to geochemical analysis. The concentrations of vanadium, manganese, chromium, and barium were detected in quantities exceeding 100 mg/kg in almost all samples. Cadmium, mercury and silver were detected in low concentrations below 1 mg/kg in all samples. The practice of geophagy amongst women of childbearing age has been reported to be associated with detrimental health outcomes and risks such as iron deficiency anaemia, constipation, shortness of breath, maternal and childhood mortalities and morbidities, neurological and central nervous system disorder, death, appendicitis, cancers, teratogenic risks, and ulcers. The chemical composition of clay soil eaten by geophagic women of childbearing age contains potentially harmful substances, thus the practise of geophagy is toxic and should be discouraged to protect public health.

Deep Proteome Analysis of Cerebrospinal Fluid from Pediatric Patients with Central Nervous System Cancer.

The cerebrospinal fluid (CSF) is a key matrix for discovery of biomarkers relevant for prognosis and the development of therapeutic targets in pediatric central nervous system malignancies. However, the wide range of protein concentrations and age-related differences in children makes such discoveries challenging. In addition, pediatric CSF samples are often sparse and first prioritized for clinical purposes. The present work focused on optimizing each step of the proteome analysis workflow to extract the most detailed proteome information possible from the limited CSF resources available for research purposes. The strategy included applying sequential ultracentrifugation to enrich for extracellular vesicles (EV) in addition to analysis of a small volume of raw CSF, which allowed quantification of 1351 proteins (+55% relative to raw CSF) from 400 μL CSF. When including a spectral library, a total of 2103 proteins (+240%) could be quantified. The workflow was optimized for CSF input volume, tryptic digestion method, gradient length, mass spectrometry data acquisition method and database search strategy to quantify as many proteins a possible. The fully optimized workflow included protein aggregation capture (PAC) digestion, paired with data-independent acquisition (DIA, 21 min gradient) and allowed 2989 unique proteins to be quantified from only 400 μL CSF, which is a 340% increase in proteins compared to analysis of a tryptic digest of raw CSF.

An Optimized Liquid Chromatography-Mass Spectrometry Method for Ganglioside Analysis in Cell Lines.

Gangliosides are glycosphingolipids composed of a sialylated glycan head group and a ceramide backbone. These anionic lipids form lipid rafts and play crucial roles in regulating various proteins involved in signal transduction, adhesion, and cell-cell recognition. Neuroblastoma, a pediatric cancer of the sympathetic nervous system, is treated with intensive chemotherapy, radiation, and an antibody targeting the GD2 ganglioside. Gangliosides are critical in neuroblastoma development and serve as therapeutic targets, making it essential to establish a reliable, rapid, and cost-effective method for profiling gangliosides, particularly one capable of isomeric separation of intact species. In this study, liquid chromatography-mass spectrometry (LC-MS) was optimized using standard gangliosides, followed by the optimization of sphingolipid extraction methods from cell lines by comparing Folch and absolute methanol extraction techniques. Percent recovery and the number of identified sphingolipids were used to evaluate the analytical merits of these methods. A standard gangliosides calibration curve demonstrated excellent linearity (R2 = 0.9961-0.9975). The ZIC-HILIC column provided the best separation of ganglioside GD1 isomers with a 25 min runtime. GD1a elutes before GD1b on the ZIC-HILIC column. Absolute methanol yielded better percent recovery (96 ± 7) and identified 121 different sphingolipids, the highest number between the two extraction methods. The optimized method was applied to profile gangliosides in neuroblastoma (COG-N-683), pancreatic cancer (PSN1), breast cancer (MDA-MB-231BR), and brain tumor (CRL-1620) cell lines. The ganglioside profile of the neuroblastoma cell line COG-N-683 showed an inverse relationship between GD1 and GD2. Ceramide, Hex1Cer, GM1, and GM3 were highly abundant in CRL-1620, PSN1, and MDA-MB-231BR, respectively. These results suggest that our method provides a sensitive, reliable, and high-throughput workflow for ganglioside profiling across different cell types.

Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling

ABSTRACTProteoglycans and their proteolytic fragments diffuse into biological fluids such as plasma, serum, urine, or synovial fluid, where they can be detected by antibodies or mass‐spectrometry. Neopeptides generated by the proteolysis of proteoglycans are recognized by specific neoepitope antibodies and can act as a proxy for the activity of certain proteases. Proteoglycan and proteoglycan fragments can be potentially used as prognostic, diagnostic, or theragnostic biomarkers for several diseases characterized by dysregulated extracellular matrix remodeling such as osteoarthritis, rheumatoid arthritis, atherosclerosis, thoracic aortic aneurysms, central nervous system disorders, viral infections, and cancer. Here, we review the main mechanisms accounting for the presence of soluble proteoglycans and their fragments in biological fluids, their potential application as diagnostic, prognostic, or theragnostic biomarkers, and highlight challenges and opportunities ahead of their clinical translation.

Genetic and clinical characteristics of genetic tumor syndromes in the central nervous system cancers: Implications for clinical practice

Genetic and clinical characteristics of genetic tumor syndromes in the central nervous system cancers: Implications for clinical practice

Research on the comprehensive child life intervention program (CCLIP) for adjusting medical fear in children with central nervous system (CNS) cancers: a randomized controlled trial study protocol

BackgroundMedical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children’s quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life.MethodsThis study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction.DiscussionThis study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families.Trial registrationThis study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.