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Journal of Molecular Histology Jun 2024Chemical carcinogen-induced oxidative stress has a key role in cell signaling linked to the development of cancer. Oxidative stress leads to oxidative damage to cellular...
Chemical carcinogen-induced oxidative stress has a key role in cell signaling linked to the development of cancer. Oxidative stress leads to oxidative damage to cellular membranes, proteins, chromosomes and genetic material. It is thought that compounds like hesperidin with high antioxidant and anticancer potential can reduce development of cancer induced by chemical carcinogens via neutralizing their oxidative damages. We investigated protective effect of hesperidin against N-Ethyl-N-Nitrosourea (ENU)-induced neurotoxicity, congenital abnormalities and possible brain cancer after exposure of mice during pregnancy as model of glioma. The mice were divided to four groups; control (normal saline), ENU (40 mg/kg daily for three consecutive days from the 17th to the 19th of pregnancy), hesperidin (pretreated with 25 mg/kg for 30 consecutive days, before mating) + ENU and hesperidin alone. Developmental toxicity parameters (the number of pregnant mice, stillbirths, abortion, live and dead offspring), behavioral tests (novel object recognition, open field and elevated plus maze) were performed. Moreover, the activity of butrylcholinesterase and acetylcholinesterase enzymes, oxidative markers and histopathological abnormalities were detected in brain tissue. Our data showed that conversely, the pretreatment of hesperidin reduces various degrees of developmental toxicity, neurobehavioral dysfunction, neurotoxicity, oxidative stress and histopathological abnormalities induced by ENU as a neurotoxic and carcinogenic agent in the next generation. In conclusion, pre-mating exposure with hesperidin may open new avenues for prevention of primary brain cancer in next generation and could be valuable for enhancing the antioxidant defense and minimizing the developmental and neurotoxicity of DNA alkylating agents.
PubMed: 38916842
DOI: 10.1007/s10735-024-10218-0 -
Palliative Medicine Jun 2024Family caregivers of people with high-grade glioma often report high rates of psychological distress, which has been attributed to the unique aspects of the disease and...
'It was never about me': A qualitative inquiry into the experiences of psychological support and perceived support needs of family caregivers of people with high-grade glioma.
BACKGROUND
Family caregivers of people with high-grade glioma often report high rates of psychological distress, which has been attributed to the unique aspects of the disease and onerous care demands. Clinical practice guidelines advocate for caregiver support from diagnosis through to end-of-life and bereavement. Yet, research has identified that caregivers' support needs are often overlooked.
AIM
To explore caregivers' experiences of psychological support and perceptions of what constitutes optimal psychological support for caregivers in the context of high-grade glioma.
DESIGN
Qualitative study involving semi-structured interviews with data analysed using reflexive thematic analysis.
SETTING/PARTICIPANTS
Eighteen current ( = 11) and bereaved ( = 7) family caregivers (73% female, aged 33-69 years) of adults with high-grade glioma participated. Interviews explored caregivers' perceptions of psychological support.
RESULTS
Two major themes were generated. The first theme, 'It was never about me', reflected caregivers prioritise for people with high-grade glioma to be well supported despite experiencing their own unmet psychological support needs. The second theme, 'Continuous, coordinated and personalised support', highlighted the importance of timely and tailored interventions addressing caregivers' practical, educational and emotional support needs throughout the illness journey.
CONCLUSIONS
Caregivers commonly prioritise the support needs of people with high-grade gliomas; yet, have their own distinct needs that vary throughout the illness. Primary care providers have a potential role in facilitating timely access to palliative care, practical support and brain tumour-specific psychological support to meet caregivers' diverse needs across the care continuum in the context of high-grade glioma.
PubMed: 38916277
DOI: 10.1177/02692163241261211 -
Ultrastructural Pathology Jun 2024Glioblastoma tumors are the most aggressive primary brain tumors that develop resistance to temozolomide (TMZ). Eribulin (ERB) exhibits a unique mechanism of action by...
Glioblastoma tumors are the most aggressive primary brain tumors that develop resistance to temozolomide (TMZ). Eribulin (ERB) exhibits a unique mechanism of action by inhibiting microtubule dynamics during the G2/M cell cycle phase. We utilized the T98G human glioma cell line to investigate the effects of ERB and TMZ, both individually and in combination. The experimental groups were established as follows: control, E5 (5 nM ERB), T0.75 (0.75 mM TMZ), T1 (1.0 mM TMZ), and combination groups (E5+T0.75 and E5+T1). All groups showed a significant decrease in cell proliferation. Apoptotic markers revealed a time-dependent increase in annexin-V expression, across all treatment groups at the 48-hour time point. Caspase-3, exhibited an increase in the combination treatment groups at the 48-hour mark. Transmission electron microscopy (TEM) revealed normal ultrastructural features in the glioma cells of the control group. However, treatments induced ultrastructural changes within the spheroid glioblastoma model, particularly in the combination groups. These changes included a dose-dependent increase in autophagic vacuoles and apoptotic morphology of the cells. In conclusion, the similarity in the mechanism of action between ERB and TMZ suggests the potential for synergistic effects when combined. Our results highlight that this combination induced severe damage and autophagy in glioma spheroids after 48 hours.
PubMed: 38916264
DOI: 10.1080/01913123.2024.2371821 -
Neuro-oncology Jun 2024Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma...
BACKGROUND
Polygenic risk scores (PRS) aggregate the contribution of many risk variants to provide a personalized genetic susceptibility profile. Since sample sizes of glioma genome-wide association studies (GWAS) remain modest, there is a need to efficiently capture genetic risk using available data.
METHODS
We applied a method based on continuous shrinkage priors (PRS-CS) to model the joint effects of over 1 million common variants on disease risk and compared this to an approach (PRS-CT) that only selects a limited set of independent variants that reach genome-wide significance (P<5×10-8). PRS models were trained using GWAS stratified by histological (10,346 cases, 14,687 controls) and molecular subtype (2,632 cases, 2,445 controls), and validated in two independent cohorts.
RESULTS
PRS-CS was generally more predictive than PRS-CT with a median increase in explained variance (R2) of 24% (interquartile range=11-30%) across glioma subtypes. Improvements were pronounced for glioblastoma (GBM), with PRS-CS yielding larger odds ratios (OR) per standard deviation (OR=1.93, P=2.0×10-54 vs. OR=1.83, P=9.4×10-50) and higher explained variance (R2=2.82% vs. R2=2.56%). Individuals in the 80th percentile of the PRS-CS distribution had significantly higher risk of GBM (0.107%) at age 60 compared to those with average PRS (0.046%, P=2.4×10-12). Lifetime absolute risk reached 1.18% for glioma and 0.76% for IDH wildtype tumors for individuals in the 95th PRS percentile. PRS-CS augmented the classification of IDH mutation status in cases when added to demographic factors (AUC=0.839 vs. AUC=0.895, PΔAUC=6.8×10-9).
CONCLUSIONS
Genome-wide PRS has potential to enhance the detection of high-risk individuals and help distinguish between prognostic glioma subtypes.
PubMed: 38916140
DOI: 10.1093/neuonc/noae112 -
Histology and Histopathology Jun 2024SUMO Specific Peptidase 3 (SENP3) is involved in the occurrence and development of various cancers. However, its effects on gliomas have been barely reported. Herein,...
OBJECTIVE
SUMO Specific Peptidase 3 (SENP3) is involved in the occurrence and development of various cancers. However, its effects on gliomas have been barely reported. Herein, this research was designed to probe the potential mechanisms of SENP3 mediating beclin-1(BECN1) SUMO3 modification in autophagy in gliomas.
METHODS
SENP3 expression in gliomas was analyzed through bioinformatic information. Clinical samples of glioma tissues were collected and frozen. SENP3 expression was evaluated with western blot. In glioma cells, autophagy- and apoptosis-related proteins, viability, and apoptosis were assessed with western blot and immunofluorescence, the cell counting kit-8, and flow cytometry, respectively. The SUMO modification of BECN1 and interactions between BECN1 and PIK3C3 were identified with Ni-NTA pull-down and co-immunoprecipitation assays, respectively. The tumor formation assay was carried out in nude mice for in vivo validation.
RESULTS
Bioinformatics analysis predicted the overexpression of SENP3 in gliomas, which was confirmed in clinical samples and glioma cells. SENP3 silencing promoted autophagy and apoptosis and inhibited viability in glioma cells, which was counteracted by further autophagy inhibition. Mechanistically, SENP3 facilitated BECN1 deSUMOylation to mediate the SUMO3 modification of BECN1, thus impeding the formation of BECN1-PIK3C3 complexes. The loss of the SUMO part in BECN1 lowered the protein expression of LC3 and the value of LC3BII/LC3BI in glioma cells. Additionally, SENP3 silencing boosted autophagy and repressed tumor growth in mice, which was neutralized by further autophagy repression.
CONCLUSION
SENP3 fosters the deSUMOylation of BECN1 to block the formation of BECN1-PIK3C3 complexes, thus restraining glioma cell autophagy.
PubMed: 38916106
DOI: 10.14670/HH-18-774 -
Frontiers in Immunology 2024Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong... (Review)
Review
Glioblastoma (GBM) is a highly malignant, invasive, and poorly prognosed brain tumor. Unfortunately, active comprehensive treatment does not significantly prolong patient survival. With the deepening of research, it has been found that gut microbiota plays a certain role in GBM, and can directly or indirectly affect the efficacy of immune checkpoint inhibitors (ICIs) in various ways. (1) The metabolites produced by gut microbiota directly affect the host's immune homeostasis, and these metabolites can affect the function and distribution of immune cells, promote or inhibit inflammatory responses, affect the phenotype, angiogenesis, inflammatory response, and immune cell infiltration of GBM cells, thereby affecting the effectiveness of ICIs. (2) Some members of the gut microbiota may reverse T cell function inhibition, increase T cell anti-tumor activity, and ultimately improve the efficacy of ICIs by targeting specific immunosuppressive metabolites and cytokines. (3) Some members of the gut microbiota directly participate in the metabolic process of drugs, which can degrade, transform, or produce metabolites, affecting the effective concentration and bioavailability of drugs. Optimizing the structure of the gut microbiota may help improve the efficacy of ICIs. (4) The gut microbiota can also regulate immune cell function and inflammatory status in the brain through gut brain axis communication, indirectly affecting the progression of GBM and the therapeutic response to ICIs. (5) Given the importance of gut microbiota for ICI therapy, researchers have begun exploring the use of fecal microbiota transplantation (FMT) to transplant healthy or optimized gut microbiota to GBM patients, in order to improve their immune status and enhance their response to ICI therapy. Preliminary studies suggest that FMT may enhance the efficacy of ICI therapy in some patients. In summary, gut microbiota plays a crucial role in regulating ICIs in GBM, and with a deeper understanding of the relationship between gut microbiota and tumor immunity, it is expected to develop more precise and effective personalized ICI therapy strategies for GBM, in order to improve patient prognosis.
Topics: Humans; Gastrointestinal Microbiome; Glioblastoma; Immune Checkpoint Inhibitors; Brain Neoplasms; Animals; Brain-Gut Axis; Fecal Microbiota Transplantation; Tumor Microenvironment
PubMed: 38915399
DOI: 10.3389/fimmu.2024.1401967 -
BMC Cancer Jun 2024Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Inhibitor of kappa B kinase interacting protein (IKBIP) has been reported to...
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide. Inhibitor of kappa B kinase interacting protein (IKBIP) has been reported to promote glioma progression, but its role in other cancers remains unclear. This study aimed to investigate the role of IKBIP and its underlying molecular mechanisms in ESCC.
METHODS
The mRNA expression of IKBIP was analyzed using multiple cancer databases. Immunohistochemistry was performed to detect IKBIP protein expression in ESCC tissues and adjacent normal tissues, and Kaplan‒Meier survival and Cox regression analyses were carried out. The effects of IKBIP knockdown (or overexpression) on ESCC cells were detected by cell viability, cell migration, flow cytometry and Western blot assays. LY-294002 was used to validate the activation of the AKT signaling pathway by IKBIP. Finally, the role of IKBIP in ESCC was verified in a xenograft model.
RESULTS
Both bioinformatics analysis and immunohistochemistry indicated that IKBIP expression in ESCC tissues was significantly increased and was associated with the prognosis of ESCC patients. In vitro experiments revealed that IKBIP knockdown significantly inhibited the proliferation and migration of ESCC cells, and induced cell apoptosis and G1/S phase arrest. Molecular mechanism results showed that the AKT signaling pathway was further activated after IKBIP overexpression, thereby increasing the proliferation and migration abilities of ESCC cells. In vivo study confirmed that IKBIP promoted the initiation and development of ESCC tumors in mice.
CONCLUSIONS
IKBIP plays a tumor-promoting role in ESCC and may serve as a predictive biomarker and a potential therapeutic target for ESCC.
Topics: Humans; Proto-Oncogene Proteins c-akt; Esophageal Squamous Cell Carcinoma; Animals; Esophageal Neoplasms; Signal Transduction; Mice; Cell Proliferation; Cell Line, Tumor; Cell Movement; Female; Male; Apoptosis; Prognosis; Gene Expression Regulation, Neoplastic; Mice, Nude; Adaptor Proteins, Signal Transducing; Middle Aged; Xenograft Model Antitumor Assays
PubMed: 38914958
DOI: 10.1186/s12885-024-12510-4 -
Scientific Reports Jun 2024Medulloblastoma is a malignant neuroepithelial tumor of the central nervous system. Accurate prediction of prognosis is essential for therapeutic decisions in...
Medulloblastoma is a malignant neuroepithelial tumor of the central nervous system. Accurate prediction of prognosis is essential for therapeutic decisions in medulloblastoma patients. We analyzed data from 2,322 medulloblastoma patients using the SEER database and randomly divided the dataset into training and testing datasets in a 7:3 ratio. We chose three models to build, one based on neural networks (DeepSurv), one based on ensemble learning that Random Survival Forest (RSF), and a typical Cox Proportional-hazards (CoxPH) model. The DeepSurv model outperformed the RSF and classic CoxPH models with C-indexes of 0.751 and 0.763 for the training and test datasets. Additionally, the DeepSurv model showed better accuracy in predicting 1-, 3-, and 5-year survival rates (AUC: 0.767-0.793). Therefore, our prediction model based on deep learning algorithms can more accurately predict the survival rate and survival period of medulloblastoma compared to other models.
Topics: Medulloblastoma; Humans; Deep Learning; Female; Male; SEER Program; Child; Prognosis; Cerebellar Neoplasms; Adolescent; Child, Preschool; Proportional Hazards Models; Survival Rate; Adult; Young Adult; Middle Aged; Neural Networks, Computer; Infant
PubMed: 38914641
DOI: 10.1038/s41598-024-65367-9 -
Scientific Data Jun 2024Hyperspectral (HS) imaging (HSI) technology combines the main features of two existing technologies: imaging and spectroscopy. This allows to analyse simultaneously the...
Hyperspectral (HS) imaging (HSI) technology combines the main features of two existing technologies: imaging and spectroscopy. This allows to analyse simultaneously the morphological and chemical attributes of the objects captured by a HS camera. In recent years, the use of HSI provides valuable insights into the interaction between light and biological tissues, and makes it possible to detect patterns, cells, or biomarkers, thus, being able to identify diseases. This work presents the HistologyHSI-GB dataset, which contains 469 HS images from 13 patients diagnosed with brain tumours, specifically glioblastoma. The slides were stained with haematoxylin and eosin (H&E) and captured using a microscope at 20× power magnification. Skilled histopathologists diagnosed the slides and provided image-level annotations. The dataset was acquired using custom HSI instrumentation, consisting of a microscope equipped with an HS camera covering the spectral range from 400 to 1000 nm.
Topics: Humans; Glioblastoma; Brain Neoplasms; Hyperspectral Imaging; Microscopy
PubMed: 38914542
DOI: 10.1038/s41597-024-03510-x -
Magnetic Resonance Imaging Jun 2024This review examines the advancements in magnetic resonance imaging (MRI) techniques and their pivotal role in diagnosing and managing gliomas, the most prevalent... (Review)
Review
This review examines the advancements in magnetic resonance imaging (MRI) techniques and their pivotal role in diagnosing and managing gliomas, the most prevalent primary brain tumors. The paper underscores the importance of integrating modern MRI modalities, such as diffusion-weighted imaging and perfusion MRI, which are essential for assessing glioma malignancy and predicting tumor behavior. Special attention is given to the 2021 WHO Classification of Tumors of the Central Nervous System, emphasizing the integration of molecular diagnostics in glioma classification, significantly impacting treatment decisions. The review also explores radiogenomics, which correlates imaging features with molecular markers to tailor personalized treatment strategies. Despite technological progress, MRI protocol standardization and result interpretation challenges persist, affecting diagnostic consistency across different settings. Furthermore, the review addresses MRI's capacity to distinguish between tumor recurrence and pseudoprogression, which is vital for patient management. The necessity for greater standardization and collaborative research to harness MRI's full potential in glioma diagnosis and personalized therapy is highlighted, advocating for an enhanced understanding of glioma biology and more effective treatment approaches.
PubMed: 38914147
DOI: 10.1016/j.mri.2024.06.004