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Sphingosine-1-Phosphate Recruits Macrophages and Microglia and Induces a Pro-Tumorigenic Phenotype That Favors Glioma Progression.

Glioblastoma is the most aggressive brain tumor in adults. Treatment failure is predominantly caused by its high invasiveness and its ability to induce a supportive microenvironment. As part of this, a major role for tumor-associated macrophagesmicroglia (TAMs) in glioblastoma development was recognized. Phospholipids are important players in various fundamental biological processes, including tumor-stroma crosstalk, and the bioactive lipid sphingosine-1-phosphate (S1P) has been linked to glioblastoma cell proliferation, invasion, and survival. Despite the urgent need for better therapeutic approaches, novel strategies targeting sphingolipids in glioblastoma are still poorly explored. Here, we showed that higher amounts of S1P secreted by glioma cells are responsible for an active recruitment of TAMs, mediated by S1P receptor (S1PR) signaling through the modulation of Rac1RhoA. This resulted in increased infiltration of TAMs in the tumor, which, in turn, triggered their pro-tumorigenic phenotype through the inhibition of NFkB-mediated inflammation. Gene set enrichment analyses showed that such an anti-inflammatory microenvironment correlated with shorter survival of glioblastoma patients. Inhibition of S1P restored a pro-inflammatory phenotype in TAMs and resulted in increased survival of tumor-bearing mice. Taken together, our results establish a crucial role for S1P in fine-tuning the crosstalk between glioma and infiltrating TAMs, thus pointing to the S1P-S1PR axis as an attractive target for glioma treatment.

Thoracic Radiotherapy in Extensive Disease Small Cell Lung Cancer Multicenter Prospective Observational TRENDS Study.

(1) Introduction Small cell lung cancer (SCLC) is an aggressive tumor type, accounting for about 15% of all lung cancers. Radiotherapy (RT) plays a fundamental role in both early and advanced stages. Currently, in advanced disease, the use of consolidative chest RT should be recommended for patients with good response to platinum-based first-line chemotherapy, but its use has not yet been standardized. The present prospective study aims to evaluate the pattern of care of consolidative chest RT in patients with advanced stage SCLC, and its effectiveness in terms of disease control and tolerability. (2) Materials and methods This study was a multicenter prospective observational trial, proposed and conducted within the AIRO lung study group to evaluate the pattern of care of consolidative chest RT after first-line chemotherapy in patients with advanced SCLC. The patient and tumor characteristics, doses, fractionation and volumes of thoracic RT and prophylactic cranial irradiation (PCI), as well as the thoracic and extrathoracic response to the treatment, toxicity and clinical outcomes, were collected and analyzed. (3) Results From January 2017 to December 2019, sixty-four patients were enrolled. Median follow-up was 33 months. The median age was 68 years (range 42-81) 38 patients (59%) were male and 26 (41%) female. Carboplatin etoposide for 6 cycles was the most commonly used first-line therapeutic scheme (42%). With regard to consolidative chest RT, 56% of patients (35) received 30 Gy in 10 factions and 16 patients (26%) received 45 Gy in 15 sessions. The modulated intensity technique was used in 84.5% of cases, and post-chemotherapy macroscopic residual disease was the target volume in 87.5% of patients. Forty-four patients (69%) also underwent PCI. At the last follow-up, over 60% of patients did not experience chest disease progression, while 67% showed extrathoracic progression. At the first radiological evaluation after RT, complete response and stable disease were recorded in 6% and 46% of the cases, respectively. Two patients had a long-term complete response to the combined treatment. The brain was the first site of extrathoracic progression in 28%. 1y and 2y OS and PFS were 67%, 19%, 28% and 6%, respectively. Consolidative chest RT was well-tolerated in the majority of patients it was interrupted in three cases (due to G2 pulmonary toxicity, disease progression and clinical decay, respectively). Only 1 patient developed G3 asthenia. (4) Conclusions Consolidative chest RT has been shown to be useful in reducing the risk of thoracic disease progression and is absolutely well-tolerated in patients with advanced stage SCLC with good response after first-line chemotherapy. Among the Italian centers that participated in this study, there is still variability in the choice of fractionation and target volumes, although the guidelines contain clear recommendations. The aim of future research should be to clarify the role and modalities of chest RT in the era of immunotherapy in advanced-stage SCLC.

Progresses, Challenges, and Prospects of CRISPRCas9 Gene-Editing in Glioma Studies.

Glioma refers to a tumor that is derived from brain glial stem cells or progenitor cells and is the most common primary intracranial tumor. Due to its complex cellular components, as well as the aggressiveness and specificity of the pathogenic site of glioma, most patients with malignant glioma have poor prognoses following surgeries, radiotherapies, and chemotherapies. In recent years, an increasing amount of research has focused on the use of CRISPRCas9 gene-editing technology in the treatment of glioma. As an emerging gene-editing technology, CRISPRCas9 utilizes the expression of certain functional proteins to repair tissues or treat gene-deficient diseases and could be applied to immunotherapies through the expression of antigens, antibodies, or receptors. In addition, some research also utilized CRISPRCas9 to establish tumor models so as to study tumor pathogenesis and screen tumor prognostic targets. This paper mainly discusses the roles of CRISPRCas9 in the treatment of glioma patients, the exploration of the pathogenesis of neuroglioma, and the screening targets for clinical prognosis. This paper also raises the future research prospects of CRISPRCas9 in glioma, as well as the opportunities and challenges that it will face in clinical treatment in the future.

Are Thalamic Intrinsic Lesions Operable No-Mans Land Revisited by the Analysis of a Large Retrospective, Mono-Institutional, Cohort.

Thalamic gliomas represent a heterogeneous subset of deep-seated lesions for which surgical removal is advocated, although clear prognostic factors linked to advantages in performance status or overall survival are still lacking. We reviewed our Institutional Cancer Registry, identifying patients who underwent surgery for thalamic gliomas between 2006 and 2020. Associations between possible prognostic factors such as tumor volume, grade, the extent of resection and performance status (PS), and overall survival (OS) were evaluated using univariate and multivariate survival analyses. We found 56 patients 31 underwent surgery, and 25 underwent biopsy. Compared to biopsy, surgery resulted positively associated with an increase in the OS (hazard ratio, HR, at multivariate analysis 0.30, 95% confidence interval, CI, 0.12-0.75). Considering the extent of resection (EOR), obtaining GTRSTR appeared to offer an OS advantage in high-grade gliomas (HGG) patients submitted to surgical resection if compared to biopsy, although we did not find statistical significance at multivariate analysis (HR 0.53, 95% CI 0.17-1.59). Patients with a stable 3-month KPS after surgery demonstrated to have a better prognosis in terms of OS if compared to biopsy (multivariate HR 0.17, 95% CI, 0.05-0.59). Age and histological grades were found to be prognostic factors for this condition (

Sacrifice of Involved Nerve Root during Surgical Resection of Foraminal andor Dumbbell Spinal Neurinomas.

Even if usually needed to achieve the gross total resection (GTR) of spinal benign nerve sheath tumors (NSTs), nerve root sacrifice remains controversial regarding the risk of neurological deficit. For foraminal NSTs, we hypothesize that the involved root is poorly functional and thus can be safely sacrificed. All spinal benign NSTs with foraminal extension that underwent surgery from 2013 to 2021 were reviewed. The impacts of preoperative clinical status and patient and tumor characteristics on long-term outcomes were analyzed. Twenty-six patients were included, with a mean follow-up (FU) of 22.4 months. Functional motor roots (C5-T1, L3-S1) were involved in 14 cases. The involved nerve root was routinely sacrificed during surgery and GTR was obtained in 84.6% of cases. In the functional root subgroup, for patients with a pre-existing deficit (n 514), neurological aggravation persisted in one case at last FU (n 15), whereas for those with no preop deficit (n 914), a postoperative deficit persisted in one patient only (n 19). Preoperative radicular pain was the only characteristic significantly associated with an immediate postoperative motor deficit (

Pathogenesis Study of Glioma From Glioma Stem Cells, Genomic Tags, to Rodent Models.

Glioma remains the toughest brain tumor among all primary central nervous system (CNS) tumors ....

Long-Term Seizure Outcomes and Predictors in Patients with Dysembryoplastic Neuroepithelial Tumors Associated with Epilepsy.

To determine the predictors and the long-term outcomes of patients with seizures following surgery for dysembryoplastic neuroepithelial tumors (DNTs) Methods Clinical data were collected from medical records of consecutive patients of the Department of Neurosurgery of Sanbo Brain Hospital of Capital Medical University with a pathological diagnosis of DNT and who underwent surgery from January 2008 to July 2021. All patients were followed up after surgery for at least one year. We estimated the cumulative rate of seizure recurrence-free and generated survival curves. A log-rank (Mantel-Cox) test and a Cox proportional hazard model were performed for univariate and multivariate analysis to analyze influential predictors Results 63 patients (33 males and 30 females) were included in this study. At the final follow-up, 49 patients (77.8%) were seizure-free. The cumulative rate of seizure recurrence-free was 82.5% (95% confidence interval (CI) 71.8-91.3%), 79.0% (95% CI 67.8-88.6%) and 76.5% (95% CI 64.8-87.0%) at 2, 5, and 10 years, respectively. The mean time for seizure recurrence-free was 6.892 ± 0.501 years (95% CI 5.91-7.87). Gross total removal of the tumor and a short epilepsy duration were significant predictors of seizure freedom. Younger age of seizure onset, bilateral interictal epileptiform discharges, and MRI type 3 tumors were risk factors for poor prognosis Conclusions A favorable long-term seizure outcome was observed for patients with DNT after surgical resection. Predictor analysis could effectively guide the clinical work and evaluate the prognosis of patients with DNT associated with epilepsy.

Axial Attention Convolutional Neural Network for Brain Tumor Segmentation with Multi-Modality MRI Scans.

Accurately identifying tumors from MRI scans is of the utmost importance for clinical diagnostics and when making plans regarding brain tumor treatment. However, manual segmentation is a challenging and time-consuming process in practice and exhibits a high degree of variability between doctors. Therefore, an axial attention brain tumor segmentation network was established in this paper, automatically segmenting tumor subregions from multi-modality MRIs. The axial attention mechanism was employed to capture richer semantic information, which makes it easier for models to provide local-global contextual information by incorporating local and global feature representations while simplifying the computational complexity. The deep supervision mechanism is employed to avoid vanishing gradients and guide the AABTS-Net to generate better feature representations. The hybrid loss is employed in the model to handle the class imbalance of the dataset. Furthermore, we conduct comprehensive experiments on the BraTS 2019 and 2020 datasets. The proposed AABTS-Net shows greater robustness and accuracy, which signifies that the model can be employed in clinical practice and provides a new avenue for medical image segmentation systems.

Raman Spectroscopy on Brain Disorders Transition from Fundamental Research to Clinical Applications.

Brain disorders such as brain tumors and neurodegenerative diseases (NDs) are accompanied by chemical alterations in the tissues. Early diagnosis of these diseases will provide key benefits for patients and opportunities for preventive treatments. To detect these sophisticated diseases, various imaging modalities have been developed such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). However, they provide inadequate molecule-specific information. In comparison, Raman spectroscopy (RS) is an analytical tool that provides rich information about molecular fingerprints. It is also inexpensive and rapid compared to CT, MRI, and PET. While intrinsic RS suffers from low yield, in recent years, through the adoption of Raman enhancement technologies and advanced data analysis approaches, RS has undergone significant advancements in its ability to probe biological tissues, including the brain. This review discusses recent clinical and biomedical applications of RS and related techniques applicable to brain tumors and NDs.

Parkinsons Disease, It Takes Guts The Correlation between Intestinal Microbiome and Cytokine Network with Neurodegeneration.

Parkinsons disease is a progressive neurodegenerative disorder with motor, physical and behavioral symptoms that can have a profound impact on the patients quality of life. Most cases are idiopathic, and the exact mechanism of the diseases cause is unknown. The current hypothesis focuses on the gut-brain axis and states that gut microbiota dysbiosis can trigger inflammation and advances the development of Parkinsons disease. This systematic review presents the current knowledge of gut microbiota analysis and inflammation based on selected studies on Parkinsons patients and experimental animal models. Changes in gut microbiota correlate with Parkinsons disease, but only a few studies have considered inflammatory modulators as important triggers of the disease. Nevertheless, it is evident that proinflammatory cytokines and chemokines are induced in the gut, the circulation, and the brain before the development of the diseases neurological symptoms and exacerbate the disease. Increased levels of tumor necrosis factor, interleukin-1β, interleukin-6, interleukin-17A and interferon-γ can correlate with altered gut microbiota. Instead, treatment of gut dysbiosis is accompanied by reduced levels of inflammatory mediators in specific tissues, such as the colon, brain and serum andor cerebrospinal fluid. Deciphering the role of the immune responses and the mechanisms of the PD-associated gut microbiota will assist the interpretation of the pathogenesis of Parkinsons and will elucidate appropriate therapeutic strategies.

Brain Tumor Detection and Classification Using Deep Learning and Sine-Cosine Fitness Grey Wolf Optimization.

Diagnosing a brain tumor takes a long time and relies heavily on the radiologists abilities and experience. The amount of data that must be handled has increased dramatically as the number of patients has increased, making old procedures both costly and ineffective. Many researchers investigated a variety of algorithms for detecting and classifying brain tumors that were both accurate and fast. Deep Learning (DL) approaches have recently been popular in developing automated systems capable of accurately diagnosing or segmenting brain tumors in less time. DL enables a pre-trained Convolutional Neural Network (CNN) model for medical images, specifically for classifying brain cancers. The proposed Brain Tumor Classification Model based on CNN (BCM-CNN) is a CNN hyperparameters optimization using an adaptive dynamic sine-cosine fitness grey wolf optimizer (ADSCFGWO) algorithm. There is an optimization of hyperparameters followed by a training model built with Inception-ResnetV2. The model employs commonly used pre-trained models (Inception-ResnetV2) to improve brain tumor diagnosis, and its output is a binary 0 or 1 (0 Normal, 1 Tumor). There are primarily two types of hyperparameters (i) hyperparameters that determine the underlying network structure (ii) a hyperparameter that is responsible for training the network. The ADSCFGWO algorithm draws from both the sine cosine and grey wolf algorithms in an adaptable framework that uses both algorithms strengths. The experimental results show that the BCM-CNN as a classifier achieved the best results due to the enhancement of the CNNs performance by the CNN optimizations hyperparameters. The BCM-CNN has achieved 99.98% accuracy with the BRaTS 2021 Task 1 dataset.

Single-Cell Profiling Comparisons of Tumor Microenvironment between Primary Advanced Lung Adenocarcinomas and Brain Metastases and Machine Learning Algorithms in Predicting Immunotherapeutic Responses.

Brain metastasis (BM) occurs commonly in patients with lung adenocarcinomas. Limited evidence indicates safety and efficacy of immunotherapy for this metastatic tumor, though immune checkpoint blockade has become the front-line treatment for primary advanced non-small cell lung cancer. We aim to comprehensively compare tumor microenvironments (TME) between primary tumors (PT) and BM at single-cell resolution. Single-cell RNA transcriptomics from tumor samples of PT (N 23) and BM (N 16) and bulk sequencing data were analyzed to explore potential differences in immunotherapeutic efficacy between PT and BM of lung adenocarcinomas. Multiple machine learning algorithms were used to develop and validate models that predict responses to immunotherapy using the external cohorts. We found obviously less infiltration of immune cells in BM than PT, characterized specifically by deletion of anti-cancer CD8 Trm cells and more dysfunctional CD8 Tem cells in BM tumors. Meanwhile, macrophages and dendritic cells within BM demonstrated more pro-tumoral and anti-inflammatory effects, represented by distinct distribution and function of SPP1 and C1Qs tumor-associated microphages, and inhibited antigen presentation capacity and HLA-I gene expression, respectively. Besides, we also found the lack of inflammatory-like CAFs and enrichment of pericytes within BM tumors, which may be critical factors in shaping inhibitory TME. Cell communication analysis further revealed mechanisms of the immunosuppressive effects associated with the activation of some unfavorable pathways, such as TGFβ signaling, highlighting the important roles of stromal cells in the anti-inflammatory microenvironment, especially specific pericytes. Furthermore, pericyte-related genes were identified to optimally predict immunotherapeutic responses by machine learning models with great predictive performance. Overall, various factors contribute to the immunosuppressive TME within BM tumors, represented by the lack of critical anti-cancer immune cells. Meanwhile, pericytes may help shape the TME and targeting the associated mechanisms may enhance immunotherapy efficacy for BM tumors in patients with lung adenocarcinomas.

ImmunoPET Directed to the Brain A New Tool for Preclinical and Clinical Neuroscience.

Immuno-positron emission tomography (immunoPET) is a non-invasive in vivo imaging method based on tracking and quantifying radiolabeled monoclonal antibodies (mAbs) and other related molecules, such as antibody fragments, nanobodies, or affibodies. However, the success of immunoPET in neuroimaging is limited because intact antibodies cannot penetrate the blood-brain barrier (BBB). In neuro-oncology, immunoPET has been successfully applied to brain tumors because of the compromised BBB. Different strategies, such as changes in antibody properties, use of physiological mechanisms in the BBB, or induced changes to BBB permeability, have been developed to deliver antibodies to the brain. These approaches have recently started to be applied in preclinical central nervous system PET studies. Therefore, immunoPET could be a new approach for developing more specific PET probes directed to different brain targets.

Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.

Over the past two decades, novel hallmarks of cancer have been described, including the altered epigenetic landscape of malignant diseases. In addition to the methylation and hyd-roxymethylation of DNA, numerous novel forms of histone modifications and nucleosome remodeling have been discovered, giving rise to a wide variety of targeted therapeutic interventions. DNA hypomethylating drugs, histone deacetylase inhibitors and agents targeting histone methylation machinery are of distinguished clinical significance. The major focus of this review is placed on targeted epigenetic interventions in the most common pediatric malignancies, including acute leukemias, brain and kidney tumors, neuroblastoma and soft tissue sarcomas. Upcoming novel challenges include specificity and potential undesirable side effects. Different epigenetic patterns of pediatric and adult cancers should be noted. Biological significance of epigenetic alterations highly depends on the tissue microenvironment and widespread interactions. An individualized treatment approach requires detailed genetic, epigenetic and metabolomic evaluation of cancer. Advances in molecular technologies and clinical translation may contribute to the development of novel pediatric anticancer treatment strategies, aiming for improved survival and better patient quality of life.

Kinin B1 Receptor Mediates Bidirectional Interaction between Neuroinflammation and Oxidative Stress.

Hypertension is associated with increased expression of kinin B1 receptors (B1R) and increased levels of pro-inflammatory cytokines within the neurons. We previously reported that angiotensin II (Ang II) upregulates B1R expression and can induce neuroinflammation and oxidative stress in primary hypothalamic neurons. However, the order in which B1R activation, neuroinflammation, and oxidative stress occur has not yet been studied. Using primary hypothalamic neurons from neonatal mice, we show that tumor necrosis factor (TNF), lipopolysaccharides (LPS), and hydrogen peroxide (H

Effect of the Use of Gnrh Analogs in Low-Grade Cerebral Glioma.

Low-grade gliomas are the most common brain tumors in children. This tumor type presents a wide range of clinical, histological, and biological behaviors. In recent years, an association between estrogens and progesterone and the development of tumors has been suggested. A case of a 2-year-old girl is described with a low-grade brain tumor treated with chemotherapy and disease stabilization. The treatment with Decapeptyl® was initiated due to precocious puberty, and the tumor showed a decrease in its solid component-more than 50% of the initial size-three years after starting treatment. Several studies have described the influence of estrogen and progesterone on the development of gliomas, decreasing or increasing their expression in those tumors with greater aggressiveness, respectively. Despite the fact that the tumor-hormonal expression relationship in other tumor types has been evaluated, its role in the treatment of brain tumors remains unknown.

Risk factors of intraoperative blood loss and transfusion for pediatric patients undergoing brain tumor removal a retrospective cohort study.

Intraoperative blood loss is a major challenge in pediatric brain tumor removal. Several clinical and surgical factors may influence the occurrence of intraoperative blood loss and blood transfusion. This study aimed to identify the risk factors of intraoperative blood loss and intraoperative red blood cell (RBC) transfusion for pediatric patients undergoing brain tumor removal. A total of 297 pediatric patients undergoing brain tumor removal were selected in this retrospective, singlecenter study. Demographic data, laboratory data, imaging data, and surgical records were collected, and then independent risk factors for intraoperative blood loss and transfusion were identified using multivariate stepwise regression analysis. The median intraoperative blood loss in our cohort was 23.1 mlkg (IQR 10.0-60.0 mlkg). In total, 284 (95.6%) patients received intraoperative RBC transfusion, with a median amount of 0.2 Ukg (IQR 0.0-2.6 Ukg). Age (β -0.189 95% CI -1.359, -0.473 p < 0.001) preoperative hemoglobin level (β -0.141 95% CI -1.528, -0.332 p 0.003) anesthesia time (β 0.189 95% CI 0.098, 0.302 p < 0.001) unclear tumor boundary (β 0.100 95% CI 2.067, 41.053 p 0.031) tumor size (β 0.390 95% CI 14.706, 24.342 p < 0.001) and intraoperative continuous infusion of vasopressor (β 0.155 95% CI 13.364, 52.400 p 0.001) were independent predictors of intraoperative blood loss. Independent predictors of the need for RBC transfusion included age (β -0.268 95% CI -0.007, -0.004 p < 0.001) preoperative hemoglobin level (β -0.117 95% CI -0.005, -0.001 p 0.003) anesthesia time (β 0.221 95% CI 0.001, 0.001 p < 0.001) unclear tumor boundary (β 0.110 95% CI 0.024, 0.167 p 0.010) tumor size (β 0.370 95% CI 0.056, 0.092 p < 0.001) intraoperative continuous infusion of vasopressor (β 0.157 95% CI 0.062, 0.205 p < 0.001) and tumor grade (β 0.107 95% CI 0.007, 0.062 p 0.014). Overall, age, preoperative hemoglobin, tumor size, anesthesia time, continuous infusion of vasopressors, and unclear tumor boundary were the main determinants for intraoperative blood loss and RBC transfusion in pediatric patients undergoing brain tumor removal. Clinical trial registration no. ChiCTR1900024803 (ChiCTR.org).

Impact of peritumoral brain edema on pre- and postoperative clinical conditions and on long-term outcomes in patients with intracranial meningiomas.

Peritumoral brain edema (PTBE) is a common complication related to intracranial meningiomas. In several studies, researchers have investigated the pathogenesis of PTBE, and the factors involved in its development in patients with intracranial meningiomas have been reported. However, very little is known about the clinical effect of PTBE on patients with intracranial meningiomas therefore, a systematic examination of this matter is necessary. In this study, we performed a systematic examination of 696 patients with primary intracranial meningiomas to assess the effect of preoperative PTBE on preoperative symptoms, neurological deficits and postoperative complications, and long-term outcomes with a follow-up period of 16.8 years. We performed a univariate analysis and multiple regression for specific outcomes and adjusted for other relevant clinical factors. A total of 627 (90.1%) patients were symptomatic preoperatively. One hundred eighty-eight (90.8%) patients with small to moderate PTBE and 125 (98.4%) patients with severe PTBE presented with symptoms significantly more often than the 314 (86.7%) patients without PTBE (p < 0.001, univariate analysis). Cognitive deficits, palsy and seizure were significantly more present, preoperatively, in patients with PTBE than in patients without PTBE (p < 0.001, univariate analysis). Two hundred fifty-five (36.6%) patients experienced surgical and systemic complications postoperatively. The complication rate was significantly higher in patients with PTBE 41.5% for patients with small to moderate PTBE and 52.8% for patients with severe PTBE, compared to 28.2% of patients without PTBE (p < 0.001, univariate analysis). Furthermore, pre- and postoperative KPS scores were significantly lower in patients with PTBE (p < 0.001). Patients with PTBE required additional medical support significantly more often (p < 0.001) and had a significantly longer hospital stay (p < 0.001). The mortality rate was higher in patients with PTBE immediately after surgery and in the follow-up period however, the difference was not significant. The neurological condition of all patients improved in the follow-up and did not show significant differences between patients with and without preoperative PTBE (p 0.6361). Multiple logistic regression analyses revealed a significant association between PTBE and the presence of preoperative cognitive deficits, the incidences of seizure and postoperative complications, and low pre- and postoperative KPS scores. Preoperative PTBE significantly increased the incidences of specific preoperative symptoms, neurological deficits and postoperative complications in patients with intracranial meningiomas. After surgery, patients with preoperative PTBE required medical support significantly more often than patients without PTBE. However, all patients had favorable outcomes after surgery.

A radiomics-based deep learning approach to predict progression free-survival after tyrosine kinase inhibitor therapy in non-small cell lung cancer.

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a first-line therapy for non-small cell lung cancer (NSCLC) with EGFR mutations. Approximately half of the patients with EGFR-mutated NSCLC are treated with EGFR-TKIs and develop disease progression within 1 year. Therefore, the early prediction of tumor progression in patients who receive EGFR-TKIs can facilitate patient management and development of treatment strategies. We proposed a deep learning approach based on both quantitative computed tomography (CT) characteristics and clinical data to predict progression-free survival (PFS) in patients with advanced NSCLC after EGFR-TKI treatment. A total of 593 radiomic features were extracted from pretreatment chest CT images. The DeepSurv models for the progression risk stratification of EGFR-TKI treatment were proposed based on CT radiomic and clinical features from 270 stage IIIB-IV EGFR-mutant NSCLC patients. Time-dependent PFS predictions at 3, 12, 18, and 24 months and estimated personalized PFS curves were calculated using the DeepSurv models. The model combining clinical and radiomic features demonstrated better prediction performance than the clinical model. The model achieving areas under the curve of 0.76, 0.77, 0.76, and 0.86 can predict PFS at 3, 12, 18, and 24 months, respectively. The personalized PFS curves showed significant differences (p < 0.003) between groups with good (PFS > median) and poor (PFS < median) tumor control. The DeepSurv models provided reliable multi-time-point PFS predictions for EGFR-TKI treatment. The personalized PFS curves can help make accurate and individualized predictions of tumor progression. The proposed deep learning approach holds promise for improving the pre-TKI personalized management of patients with EGFR-mutated NSCLC.

The global prevalence of primary central nervous system tumors a systematic review and meta-analysis.

Primary central nervous system (CNS) tumors are a heterogeneous group of neoplasms, including benign and malignant tumors. Since there are many heterogeneities in the prevalence reported in previous studies on this type of tumor, this study was performed to determine the overall prevalence of different primary CNS tumors. The study was conducted as a systematic review and meta-analysis by searching international databases, including PubMed, Scopus, Science Direct, Web of science, and the Google Scholar search engine until August 2020. After transferring the studies to information management software (EndNote) and eliminating duplicate studies, the remaining studies were reviewed based on inclusion and exclusion criteria according to three stages of primary and secondary evaluation and qualitative evaluation. Comprehensive Meta-Analysis software, Begg, Mazumdar, and I After performing the systematic review steps, 80 studies were included for final analysis. Based on 8 studies, the prevalence of brain tumors was 70.9%. Also, studies on 7 other studies showed that the prevalence of spinal tumors was 12.2%. A review of 14 studies showed that the prevalence of neuroepithelial tumors was 34.7%. The analysis of 27 studies reported a prevalence of glioma tumors of 42.8%. Analyses performed on other studies showed that the prevalence of pituitary adenomas was 12.2%, embryonal tumors 3.1%, ependymal tumors 3.2%, meningiomas 24.1%, glial tumors 0.8%, astrocytic 20.3%, oligodendroglial 3.9%, glioblastoma 17.7%, schwannoma 6.7%, medulloblastoma 7.7% and Polycystic astrocytomas 3.8%. As a result, it can be stated that brain tumors are the most common type of primary CNS tumors. It was also observed that tumors involving neuroepithelial cells are more common in patients than other types of tumors.

Positron emission tomography (PET) with O-(2- Twenty-one children and young adults (13 males mean age, 8.6 ± 5.2 years range, 1-19 at initial diagnosis) with either newly diagnosed (n 5) or pretreated (n 16) CNS tumors were retrospectively analyzed. All patients had previously undergone neuro-oncological work-up including cranial magnetic resonance imaging. In all cases, The addition of

CNS penetration of methotrexate and its metabolite 7-hydroxymethotrexate in mice bearing orthotopic Group 3 medulloblastoma tumors and model-based simulations for children.

The brain penetration of methotrexate (MTX) and its metabolite 7-hydroxymethotrexate (7OHMTX) was characterized in non-tumor bearing mice and mice bearing orthotopic Group 3 medulloblastoma. Plasma pharmacokinetic studies and cerebral and ventricular microdialysis studies were performed in animals dosed with 200 or 1000 mgkg MTX by IV bolus. Plasma, braintumor extracellular fluid (ECF) and lateral ventricle cerebrospinal fluid (CSF) MTX and 7OHMTX concentration-time data were analyzed by validated LC-MSMS methods and modeled using a population-based pharmacokinetic approach and a hybrid physiologically-based model structure for the brain compartments. Brain penetration was similar for MTX and 7OHMTX and was not significantly different between non-tumor and tumor bearing mice. Overall, mean (±SD) model-derived unbound plasma to ECF partition coefficient K

Nanomedicine as potential cancer therapy via targeting dysregulated transcription factors.

Cancer as a disease possess quite complicated pathophysiological implications and is among the prominent causes of morbidity and mortality on global scales. Anti-cancer chemotherapy, surgery, and radiation therapy are some of the present-day conventional treatment options. However, these therapeutic paradigms own several retreats, including lack of specificity, non-targeted toxicological implications, inefficient drug delivery to targeted cells, and emergence of cancer resistance, ultimately causing ineffective cancer management. Owing to the advanced and better biophysical characteristic features and potentiality for the tailoring and customizations and in several fashions, nanotechnology can entirely transubstantiate the cancer identification and its managements. Additionally, nanotechnology also renders several answers to present-day mainstream limitations springing-up in anti-cancer therapeutics. Nanocarriers, owing to their outstanding physicochemical features including but not limited to their particle size, surface morphological features viz. shape etc., have been employed in nanomedicinal platforms for targeting various transcription factors leading to worthy pharmacological outcomes. This transcription targeting activates the wide array of cellular and molecular events like antioxidant enzyme-induction, apoptotic cell death, cell-cycle arrest etc. These outcomes are obtained after the activation or inactivation of several transcription factors and cellular pathways. Further, nanoformulations have been precisely calibrated and functionalized with peculiar targeting groups for improving their efficiency to deliver the drug-payload to specified and targeted cancerous cells and tissues. This review undertakes an extensive, across-the-board and all-inclusive approach consisting of various studies encompassing different types of tailored and customized nanoformulations and nanomaterials designed for targeting the transcription factors implicated in the process of carcinogenesis, tumor-maturation, growth and metastasis. Various transcription factors viz. nuclear factor kappa (NF-κB), signal transducer and activators of transcription (STAT), Cmyc and Twist-related protein 1 (TWIST1) along with several types of nanoparticles targeting these transcription factors have been summarized here. A section has also been dedicated to the different types of nanoparticles targeting the hypoxia inducing factors. Efforts have been made to summarize several other transcription factors implicated in various stages of cancer development, growth, progression and invasion, and their targeting with different kinds of nanomedicinal agents.

Molecular characterization, immune expression, and functional delineation of peroxiredoxin 1 in Epinephelus akaara.

Peroxiredoxin 1 is a member of the typical 2-Cys peroxiredoxin family, which serves diverse functions in gene expression, immune and inflammatory responses, and tumor progression. In this study, we aimed to analyze the structural, functional, and immunomodulatory properties of peroxiredoxin 1 from Epinephelus akaara (EaPrx1). The open reading frame of EaPrx1 is 597 base pairs in length, encoding 198 amino acids, with a molecular weight of approximately 22 kDa. The in silico analysis revealed that EaPrx1 shares a conserved thioredoxin fold and signature motifs that are critical for its catalytic activity and oligomerization. Further, EaPrx1 is closely related to Epinephelus lanceolatus Prx1 and clustered in the Fishes group of the vertebrate clade, revealing that EaPrx1 was conserved throughout evolution. In terms of tissue distribution, a high level of EaPrx1 expression was observed in the spleen, brain, and blood tissues. Likewise, in immune challenge experiments, significant transcriptional modulations of EaPrx1 upon lipopolysaccharide, polyinosinicpolycytidylic acid, and nervous necrosis virus injections were noted at different time points, indicating the immunological role of EaPrx1 against pathogenic infections. In the functional analysis, rEaPrx1 exhibited substantial DNA protection, insulin disulfide reduction, and tissue repair activities, which were concentration-dependent. EaPrx1pcDNA™ 3.1 ()-transfected fathead minnow cells revealed high cell viability upon arsenic toxicity, indicating the heavy metal detoxification activity of EaPrx1. Taken together, the transcriptional and functional studies imply critical roles of EaPrx1 in innate immunity, redox regulation, apoptosis, and tissue-repair processes in E. akaara.

Insufficient evidence to link human exposure to heavy metals with biomarkers of glioma.

Information on molecular mechanisms has implicated potential association between the concentrations of heavy metals and incidences of glioma, but experimental data on human brain tissue remain sparse. To address this data gap, 13 heavy metals were measured in 137 glioma and 35 non-glioma samples collected from 161 alive patients in Guangdong Province, China in 2019 - 2020. All target heavy metals were detected, suggesting they could cross the blood-brain barrier. Concentrations of Mn, Cu, and Zn were higher in glioma than in non-glioma samples, while those of Ni and Se were higher in non-glioma samples, probably suggesting that these five heavy metals are more prone to be altered by changing pathological conditions. In addition, CuZn, CrMn, CrSe, NiSe, PbMn, and PbSe were statistically different between glioma and non-glioma samples by a difference test and a multiple logistic regression model. These concentration ratios may serve as chemical markers to assist pathological analysis for differentiating between tumor and healthy tissues. However, no direct link between heavy metal concentrations or concentration ratios and biomarkers of glioma (i.e., tumor grade, P53, and Ki-67) was observed. No sufficient evidence was obtained to implicate the role of heavy metals in inducing glioma, largely caused by the limited number of samples. Different concentrations and concentration ratios of heavy metals may be the consequence rather than the cause of pathological changes in brain tumors.

Intracranial Subdural Fluid Accumulation Associated with a Choroid Plexus Carcinoma in a Dog.

Choroid plexus tumors are commonly described as intraventricular mass lesions and account for 7-10% of intracranial, primary tumors in dogs. A 3-year-old Shetland sheepdog was presented with a history of slowly progressive lethargy, vision impairment and cognitive deficits. On magnetic resonance imaging, a subdural fluid accumulation (SFA) overlying and compressing the left parietotemporal lobe as well as multifocal changes consisting of cyst-like lesions, supposed intra-axial brain lesions and mild, multifocal meningeal thickening and generalized contrast enhancement were identified. Cerebrospinal fluid (CSF) analysis showed a mononuclear pleocytosis with negative results for infectious agents. The dog was treated with prednisolone followed by burr hole craniotomy with puncture of the SFA, which macroscopically appeared to be CSF-like fluid. After initial improvement, the dog deteriorated despite continuation of prednisolone and cytarabine therapy and was euthanized four weeks after surgery. Histopathology was consistent with a disseminated, neuroinvasive choroid plexus carcinoma (CPC) that involved the entire neuroaxis including the meninges of the brain and spinal cord. Immunohistochemical examination showed a strong Kir7.1 and a heterogenous cytokeratin-immunoreactivity in neoplastic cells. In conclusion, a CPC should be considered as a possible cause of a SFA even in the absence of an intraventricular mass lesion.

The effect of damage to the white matter network and premorbid intellectual ability on postoperative verbal short-term memory and functional outcome in patients with brain lesions.

Cognitive reserve is the capacity to cope with cognitive decline due to brain damage caused by neurological diseases. Premorbid IQ has been investigated as a proxy for cognitive reserve. To date, no study has focused on the effects of premorbid IQ in patients with brain tumors, considering the damage to white matter tracts. We investigated whether a higher premorbid IQ has a beneficial impact on postoperative verbal short-term memory and functional outcomes in patients with brain tumors. A total of 65 patients with brain tumors (35 right and 30 left hemisphere lesions) and 65 healthy subjects participated in the study. We used multiple regression analysis to examine whether white matter tract damage and premorbid IQ affect postoperative verbal short-term memory, and the interaction effects of premorbid IQ with damage to white matter tract on postoperative verbal short-term memory. Path analysis was used to investigate the relationship between damage to the white matter tract and premorbid IQ on postoperative functional ability. Our results showed that damage to the left arcuate fasciculus affected postoperative functional ability through verbal short-term memory, working memory, and global cognition in patients with left hemisphere lesions. In the right hemisphere lesion group, high premorbid IQ had a positive effect on functional ability by mediating verbal short-term memory, verbal working memory, and global cognition. We found that damage to the eloquent pathway affected postoperative verbal short-term memory regardless of the premorbid IQ level. However, a higher premorbid IQ was associated with better postoperative verbal short-term memory and functional outcomes when the brain lesions were not located in a crucial pathway. Our findings suggest that premorbid IQ and damage to the white matter tracts should be considered predictors of postoperative functional outcomes.

Suicide Risk Among Individuals Diagnosed With Cancer in the US, 2000-2016.

Individuals diagnosed with cancer have elevated suicide risks compared with the general population. National estimates of suicide risks among individuals with cancer are lacking in the US, and knowledge about risk factors is limited. To provide contemporary estimates of suicide risks associated with cancer and to identify sociodemographic and clinical factors associated with suicide risks among individuals diagnosed with cancer. A population-based cohort of individuals diagnosed with cancer from January 1, 2000, to December 31, 2016, from 43 states in the US were followed up through December 31, 2016. Standardized mortality ratios (SMRs) were calculated adjusting for attained age at death, sex, and race and ethnicity groups to compare suicide risks in the cancer cohort vs the general US population. Cox proportional hazards regression models were fitted to identify cancer-specific risk factors of suicide among the cancer cohort. Analyses were conducted from October 27, 2020, to May 13, 2022. The main outcomes were risk of suicide death compared with the general population, measured by the standardized mortality ratio and risk of suicide death associated with sociodemographic and clinical factors among individuals with cancer. Diagnosis of cancer. Among a total of 16 771 397 individuals with cancer, 8 536 814 (50.9%) were 65 years or older at cancer diagnosis, 8 645 631 (51.5%) were male, 13 149 273 (78.4%) were non-Hispanic White, and 20 792 (0.1%) died from suicide. The overall SMR for suicide was 1.26 (95% CI, 1.24-1.28), with a decreasing trend (from an SMR of 1.67 95% CI, 1.47-1.88 in 2000 to 1.16 95% CI, 1.11-1.21 in 2016). Compared with the general population, elevated suicide risks were observed in the cancer cohort across all sociodemographic groups, with particularly high SMRs among Hispanic individuals (SMR, 1.48 95% CI, 1.38-1.58), Medicaid-insured individuals (SMR, 1.72 95% CI, 1.61-1.84), Medicare-insured individuals 64 years or younger (SMR, 1.94 95% CI, 1.80-2.07), or uninsured individuals (SMR, 1.66 95% CI, 1.53-1.80). Moreover, the highest SMR was observed in the first 6 months after the cancer diagnosis (SMR, 7.19 95% CI, 6.97-7.41). Among individuals diagnosed with cancer, relatively higher suicide risks (ie, hazard ratios) were observed for cancer types with a poor prognosis and high symptom burden in the first 2 years after diagnosis, including cancers of oral cavity and pharynx, esophagus, stomach, brain and other nervous system, pancreas, and lung. After 2 years, individuals with cancers subject to long-term quality-of-life impairments, such as oral cavity and pharynx, leukemia, female breast, uterine, and bladder, had higher suicide risks. In this cohort study of individuals with cancer, elevated suicide risks remained despite a decreasing trend during the past 2 decades. Suicide risks varied by sociodemographic and clinical factors. Timely symptom management and targeted psychosocial interventions are warranted for suicide prevention in individuals diagnosed with cancer.

α7 nicotinic acetylcholine receptor agonist improved brain injury and impaired glucose metabolism in a rat model of ischemic stroke.

Vagus nerve stimulation through the action of acetylcholine can modulate inflammatory responses and metabolism. α7 Nicotinic Acetylcholine Receptor (α7nAChR) is a key component in the biological functions of acetylcholine. To further explore the health benefits of vagus nerve stimulation, this study aimed to investigate whether α7nAChR agonists offer beneficial effects against poststroke inflammatory and metabolic changes and to identify the underlying mechanisms in a rat model of stroke established by permanent cerebral ischemia. We found evidence showing that pretreatment with α7nAChR agonist, GTS-21, improved poststroke brain infarction size, impaired motor coordination, brain apoptotic caspase 3 activation, dysregulated glucose metabolism, and glutathione reduction. In ischemic cortical tissues and gastrocnemius muscles with GTS-21 pretreatment, macrophagesmicroglia M1 polarization-associated Tumor Necrosis Factor-α (TNF-α) mRNA, Cluster of Differentiation 68 (CD68) protein, and Inducible Nitric Oxide Synthase (iNOS) protein expression were reduced, while expression of anti-inflammatory cytokine IL-4 mRNA, and levels of M2 polarization-associated CD163 mRNA and protein were increased. In the gastrocnemius muscles, stroke rats showed a reduction in both glutathione content and Akt Serine 473 phosphorylation, as well as an elevation in Insulin Receptor Substrate-1 Serine 307 phosphorylation and Dynamin-Related Protein 1 Serine 616 phosphorylation. GTS-21 reversed poststroke changes in the gastrocnemius muscles. Overall, our findings, provide further evidence supporting the neuroprotective benefits of α7nAChR agonists, and indicate that they may potentially exert anti-inflammatory and metabolic effects peripherally in the skeletal muscle in an acute ischemic stroke animal model.

Immunodetection of Pyruvate Carboxylase Expression in Human Astrocytomas, Glioblastomas, Oligodendrogliomas, and Meningiomas.

Pyruvate carboxylase (PC) is an enzyme catalyzing the carboxylation of pyruvate to oxaloacetate. The enzymatic generation of oxaloacetate, an intermediate of the Krebs cycle, could provide the cancer cells with the additional anaplerotic capacity and promote their anabolic metabolism. Recent studies revealed that several types of cancer cells express PC. The gained anaplerotic capability of cells mediated by PC correlates with their expedited growth, higher aggressiveness, and increased metastatic potential. By immunohistochemical staining and immunoblotting analysis, we investigated PC expression among samples of different types of human brain tumors. Our results show that PC is expressed by the cells in glioblastoma, astrocytoma, oligodendroglioma, and meningioma tumors. The presence of PC in these tumors suppose that PC could support the anabolic metabolism of their cellular constituents by its anaplerotic capability.

Localization patterns of speech and language errors during awake brain surgery a systematic review.

Awake craniotomy with direct electrical stimulation (DES) is the standard treatment for patients with eloquent area gliomas. DES detects speech and language errors, which indicate functional boundaries that must be maintained to preserve quality of life. During DES, traditional object naming or other linguistic tasks such as tasks from the Dutch Linguistic Intraoperative Protocol (DuLIP) can be used. It is not fully clear which speech and language errors occur in which brain locations. To provide an overview and to update DuLIP, a systematic review was conducted in which 102 studies were included, reporting on speech and language errors and the corresponding brain locations during awake craniotomy with DES in adult glioma patients up until 6 July 2020. The current findings provide a crude overview on language localization. Even though subcortical areas are in general less often investigated intraoperatively, still 40% out of all errors was reported at the subcortical level and almost 60% at the cortical level. Rudimentary localization patterns for different error types were observed and compared to the dual-stream model of language processing and the DuLIP model. While most patterns were similar compared to the models, additional locations were identified for articulationmotor speech, phonology, reading, and writing. Based on these patterns, we propose an updated DuLIP model. This model can be applied for a more adequate location-to-function language task selection to assess different linguistic functions during awake craniotomy, to possibly improve intraoperative language monitoring. This could result in a better postoperative language outcome in the future.

Clinical features and outcomes of pediatric intracranial gliomas results from single centers 226 cases and corroborated with SEER database.

Pediatric gliomas are the most common central nervous system (CNS) tumors in children and adolescents and show different clinical and histopathological characteristics from the adult. The prognostic factors were poorly defined in pediatric intracranial gliomas. We collected pediatric intracranial glioma cases in our institution between February 2011 and June 2022. The patient clinical data, tumor growth characteristics, treatments, and follow-up data were analyzed by Cox regression analysis to identify impact factors on the prognosis of pediatric intracranial glioma patients. To corroborate our data, an independent cohort of pediatric intracranial glioma from the Surveillance, Epidemiology, and End Results Program (SEER) database was analyzed. A total of 181 cases of pediatric low-grade glioma (PLGG) and 45 cases of pediatric high-grade glioma (PHGG) were included. In multivariate Cox regression analysis, tumor size > 59.5 mm (p 0.006) and non-gross total resection (non-GTR subtotal resection, STR, p 0.042 biopsy, p 0.012) were associated with decreased overall survival (OS) in PLGG patients. In PHGG patients, only chemotherapy (p 0.023) was associated with OS while tumor size was marginally prognostic for OS (p 0.051). Additional independent analysis of 2734 PLGG and 741 PHGG from the SEER database corroborated that larger tumor size was associated with decreased OS in LGG (p 0.001) and HGG (p < 0.001) patients, separately. In this study, we found that tumor size was a significant prognostic factor for the OS of PLGG patients in our series. Besides the tumor size, the extent of resection also independently impacted the prognosis of PLGG patients. While in PHGG patients, only chemotherapy was associated with improved OS and tumor size was marginally prognostic.

A Feature Extraction Using Probabilistic Neural Network and BTFSC-Net Model with Deep Learning for Brain Tumor Classification.

Brain Tumor Fusion-based Segments and Classification-Non-enhancing tumor (BTFSC-Net) is a hybrid system for classifying brain tumors that combine medical image fusion, segmentation, feature extraction, and classification procedures. to reduce noise from medical images, the hybrid probabilistic wiener filter (HPWF) is first applied as a preprocessing step. Then, to combine robust edge analysis (REA) properties in magnetic resonance imaging (MRI) and computed tomography (CT) medical images, a fusion network based on deep learning convolutional neural networks (DLCNN) is developed. Here, the brain images slopes and borders are detected using REA. To separate the sick region from the color image, adaptive fuzzy c-means integrated k-means (HFCMIK) clustering is then implemented. To extract hybrid features from the fused image, low-level features based on the redundant discrete wavelet transform (RDWT), empirical color features, and texture characteristics based on the gray-level cooccurrence matrix (GLCM) are also used. Finally, to distinguish between benign and malignant tumors, a deep learning probabilistic neural network (DLPNN) is deployed. according to the findings, the suggested BTFSC-Net model performed better than more traditional preprocessing, fusion, segmentation, and classification techniques. Additionally, 99.21% segmentation accuracy and 99.46% classification accuracy were reached using the proposed BTFSC-Net model. earlier approaches have not performed as well as our presented method for image fusion, segmentation, feature extraction, classification operations, and brain tumor classification. These results illustrate that the designed approach performed more effectively in terms of enhanced quantitative evaluation with better accuracy as well as visual performance.

Impact of COVID-19 Epidemic on Psycho-Oncological Distress in Neuro-Oncological Patients.

Up to 40% of neuro-oncological patients already deal with high levels of distress under conventional circumstances. Due to COVID-19, pandemic hospital visitor rules have been restricted and patients did not receive the same level of supporting caregiver network as before COVID. The aim of the present study was to analyse the impact of the COVID pandemic on the prevalence of distress, anxiety and depression in neuro-oncological patients. Patients admitted for brain tumour surgery were screened regarding distress, anxiety and depression. Furthermore, aspects of patients quality of life and clinical data were covered. Retrospectively available data of patients treated pre-pandemic (group A) and throughout the COVID-19 pandemic (group B) were statistically analysed using Chi-square tests and independent-sample

Baicalin Reduces Immune Cell Infiltration by Inhibiting Inflammation and Protecting Tight Junctions in Ischemic Stroke Injury.

Ischemic stroke is a serious health hazard that lacks effective treatment strategies. This study aims to investigate baicalins effect on tight junctions and immune cell infiltration after ischemic stroke injury. Rat brain microvascular endothelial cells (BMECs) were treated with OGDR to establish an

Micro-ribonucleic acids (miRNAs) and a proteomic profile in lung adenocarcinoma cases with brain metastasis.

Brain metastasis (BM) is the main cause of death of individuals with lung adenocarcinoma (LAC). Biomarkers with high sensitivity and specificity for the early detection and treatment of BM of LAC urgently need to be identified. In this study, we analyzed the pathogenesis of LAC-induced BM by detecting micro-ribonucleic acid (miRNA) and proteome expression differences between primary LAC lesion and BM tissue specimens to identify biomarkers of LAC-associated BM and develop potential therapeutic targets. The miRNA and protein profiles of non-metastatic primary LAC and BM cases were examined to further explore the mechanism of BM. The roles and interactions of differential miRNAs and proteins were subject to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The interactions of differential miRNAs and proteins were analyzed by R software and depicted using Cytoscape. Compared to the LAC tissue specimens, 16 and 4 miRNAs showed increased and reduced levels, respectively, in the BM tissue specimens, and 53 proteins were upregulated, and 35 proteins were downregulated. The enrichment pathway analysis showed the nuclear factor kappa B (NF-κB) signaling and the primary immunodeficiency pathways played important roles in the pathogenetic mechanisms of BM in LAC. This study extended understandings of the regulatory network of miRNAs and proteins and provided novel insights into the pathogenic mechanisms of BM in LAC at the miRNA and protein levels.

Neuroprotective effects of nobiletin on cerebral ischemiareperfusion injury rats by inhibiting RhoROCK signaling pathway.

Nobiletin (NOB), an active natural flavonoid component of citrus, is used in Traditional Chinese Medicine for its anti-inflammatory activity, but its efficacy in cerebral ischemiareperfusion (IR) injury remains unclear. In a middle cerebral artery occlusion (MCAO) rat model, MCAO rats were administered (Sham group and MCAO model group treated with an equal volume of solvent, NOB group treated with 10 or 20 mgkg NOB) once a day for 7 days before cerebral ischemia and again after reperfusion, 2,3,5-triphenyltetrazolium chloride (TTC) staining was applied to assess the infarct area. Neurological function was evaluated by the modified neurological severity score and Morris water maze. The levels of inflammatory factors, interleukin 6 (IL-6), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α), were examined by enzyme-linked immunosorbent assay (ELISA). Histopathological staining evaluated neuron apoptosis in brain tissue. In an oxygen-glucose deprivation PC12 cell (OGD PC12) model, the proliferation, migration and apoptosis of OGD PC12 cells were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and cell migration assays and flow cytometry. The gene and protein expression levels of Ras homolog gene family, member A (Rho A), ras-related C3 botulinum toxin substrate 1 (Rac 1), Rho-associated kinase 1 (ROCK 1), ROCK 2 in the RhoROCK pathway were measured by Real-time PCR (RT-PCR), immunohistochemistry and western blot. In rats with cerebral IR injury, NOB significantly decreased the infarcted area, neuron apoptosis in brain tissue and expressions of IL-6, IL-1β, and TNF-α. It also improved neurological deficits in brain tissue and enhanced learning and memory ability. Further, NOB had a protective effect on OGD PC12 cells, increasing proliferation and migration and decreasing apoptosis. The expressions of Rho A, Rac 1, ROCK 1 and ROCK 2 were high in cerebral IR injury rats, but were downregulated by NOB in IR injury rats brain tissue and OGD PC12 cells. Nobiletin had a neuroprotective effect in rats with cerebral IR injury, and its potential mechanism is decreasing neuron apoptosis by inhibiting the RhoROCK signaling pathway. These results suggest NOB is a promising neuroprotective agent for patients with cerebral ischemia.

A pan-cancer and single-cell sequencing analysis of CD161, a promising onco-immunological biomarker in tumor microenvironment and immunotherapy.

CD161 has been linked to the appearance and development of various cancers. The mutation map and the variation of CNVs and SNVs of CD161 were displayed according to cBioportal and GSCALite. We also evaluated the pathway enrichment and drug sensitivity of CD161 according to GSCALite. We performed a single-cell sequencing analysis of cancer cells and T cells in melanoma. The cell communication patterns related to CD161 were further explored. Multiplex immunofluorescence staining of tissue microarrays was used to detect the association between CD161 expression and macrophages and T cells. A high CD161 level was related to neoantigens expression, pathway enrichment, and drug sensitivity. In addition, single-cell sequencing analysis showed that CD161 was mainly expressed in T cells, M1 and M2 Macrophages, neoplastic, microglial cells, neurons, and cancer cells in many tumor types. Further study on pseudotime trajectories and functional annotation of CD161 proved the critical role of CD161 in tumor progression and T cell immunity in melanoma. Multiplex immunofluorescence revealed that CD161 is closely correlated with the immune infiltration of T cells and macrophages in multiple cancers. In addition, high CD161 expression predicted a favorable immunotherapy response. CD161 is involved in the immune infiltration of T cells and macrophages and might be a promising target for tumor immunotherapy.

The role of cell membrane-coated nanoparticles as a novel treatment approach in glioblastoma.

Glioblastoma multiform (GBM) is the most prevalent and deadliest primary brain malignancy in adults, whose median survival rate does not exceed 15 months after diagnosis. The conventional treatment of GBM, including maximal safe surgery followed by chemotherapy and radiotherapy, usually cannot lead to notable improvements in the disease prognosis and the tumor always recurs. Many GBM characteristics make its treatment challenging. The most important ones are the impermeability of the blood-brain barrier (BBB), preventing chemotherapeutic drugs from reaching in adequate amounts to the tumor site, intratumoral heterogeneity, and roles of glioblastoma stem cells (GSCs). To overcome these barriers, the recently-developed drug-carrying approach using nanoparticles (NPs) may play a significant role. NPs are tiny particles, usually less than 100 nm showing various diagnostic and therapeutic medical applications. In this regard, cell membrane (CM)-coated NPs demonstrated several promising effects in GBM in pre-clinical studies. They benefit from fewer adverse effects due to their specific targeting of tumor cells, biocompatibility because of their CM surfaces, prolonged half-life, easy penetrating of the BBB, and escaping from the immune reaction, making them an attractive option for GBM treatment. To date, CM-coated NPs have been applied to enhance the effectiveness of major therapeutic approaches in GBM treatment, including chemotherapy, immunotherapy, gene therapy, and photo-based therapies. Despite the promising results in pre-clinical studies regarding the effectiveness of CM-coated NPs in GBM, significant barriers like high expenses, complex preparation processes, and unknown long-term effects still hinder its mass production for the clinic. In this regard, the current study aims to provide an overview of different characteristics of CM-coated NPs and comprehensively investigate their application as a novel treatment approach in GBM.

Paclitaxel Has a Reduced Toxicity Profile in Healthy Rats After Polymeric Micellar Nanoparticle Delivery.

Nanocarrier platforms have been indicated to have great potential in clinical practice to treat non-small cell lung cancer (NSCLC). Our previous Phase III clinical study revealed that polymeric micellar paclitaxel (Pm-Pac) is safe and efficacious in advanced NSCLC patients. However, the histopathological-toxicological profile of Pm-Pac in mammals remains unclear. We examined the Pm-Pac-induced antitumour effect in both A549H226 cells and A549H226-derived xenograft tumour models.. And then, we evaluated the short-term and long-term toxicity induced by Pm-Pac in healthy Sprague‒Dawley (SD) rats. The changes in body weight, survival, peripheral neuropathy, haematology, and histopathology were studied in SD rats administered Pm-Pac at different dosages. In the A549-derived xenograft tumour model, better therapeutic efficacy was observed in the Pm-Pac group than in the solvent-based paclitaxel (Sb-Pac) group when an equal dosage of paclitaxel was administered. Toxicity assessments in healthy SD rats indicated that Pm-Pac caused toxicity at an approximately 2- to 3-fold greater dose than Sb-Pac when examining animal body weight, survival, peripheral neuropathy, haematology, and histopathology. Interestingly, based on histopathological examinations, we found that Pm-Pac could significantly decrease the incidences of paclitaxel-induced brain and liver injury but could potentially increase the prevalence of paclitaxel-induced male genital system toxicity. This study introduces the toxicological profile of the engineered nanoparticle Pm-Pac and provides a novel perspective on the Pm-Pac-induced histopathological-toxicological profile in a rat model.

Radiosensitization with Gadolinium Chelate-Coated Gold Nanoparticles Prevents Aggressiveness and Invasiveness in Glioblastoma.

This study aimed to evaluate the radiosensitizing potential of AuDTDTPA(Gd) nanoparticles when combined with conventional external X-ray irradiation (RT) to treat GBM. Complementary biological models based on U87 spheroids including conventional 3D invasion assay, organotypic brain slice cultures, chronic cranial window model were implemented to investigate the impact of RT treatments (10 Gy single dose 5×2 Gy or 2×5 Gy) combined with AuDTDTPA(Gd) nanoparticles on tumor progression. The main tumor mass and its infiltrative area were analyzed. This work focused on the invading cancer cells after irradiation and their viability, aggressiveness, and recurrence potential were assessed using mitotic catastrophe quantification, MMP secretion analysis and neurosphere assays, respectively. In vitro clonogenic assays showed that AuDTDTPA(Gd) nanoparticles exerted a radiosensitizing effect on U87 cells, and in vivo experiments suggested a benefit of the combined treatment RT 2×5 Gy AuDTDTPA(Gd) compared to RT alone. Invasion assays revealed that invasion distance tended to increase after irradiation alone, while the combined treatments were able to significantly reduce tumor invasion. Monitoring of U87-GFP tumor progression using organotypic cultures or intracerebral grafts confirmed the anti-invasive effect of AuDTDTPA(Gd) on irradiated spheroids. Most importantly, the combination of AuDTDTPA(Gd) with irradiation drastically reduced the number, the viability and the aggressiveness of tumor cells able to escape from U87 spheroids. Notably, the combined treatments significantly reduced the proportion of escaped cells with stem-like features that could cause recurrence. Combining AuDTDTPA(Gd) nanoparticles and X-ray radiotherapy appears as an attractive therapeutic strategy to decrease number, viability and aggressiveness of tumor cells that escape and can invade the surrounding brain parenchyma. Hence, AuDTDTPA(Gd)-enhanced radiotherapy opens up interesting perspectives for glioblastoma treatment.

Intraluminal Small Bowel Metastasis From Primary Lung Cancer.

Lung cancer is the leading cause of cancer-related death worldwide, with frequent metastases to the brain, liver, adrenal glands, and bone. The incidence of intraluminal small bowel metastases of the lung is extremely rare and poorly documented within the literature. Few case studies have been published since the late 1980s and early 1990s. However, little is known about this rare form of metastasis. Small bowel metastatic disease has atypical symptoms that mimic a variety of other diseases as a result, signs and symptoms may be overlooked until the disease has progressed to a late stage. Signs of small bowel obstruction, symptomatic anemia, abdominal pain, and peritonitis are commonly reported signs and symptoms. Various modalities can be utilized for the workup of suspected small bowel metastasis, including positron emission tomography, computed tomography, and various forms of endoscopy. The prognosis for lung cancer patients with intestinal metastases is poor, with many only surviving months to a few years after diagnosis. Therefore, it is critical to consider small bowel masses as a differential diagnosis in a patient with primary lung cancer who demonstrates clinical signs consistent with symptomatic anemia secondary to gastrointestinal (GI) bleeding, peritonitis, or small bowel obstruction. We report an unusual case of intraluminal and fungating small bowel masses in a patient who had previously undergone lung resections and chemo-immunotherapy. She was diagnosed with non-small undifferentiated carcinoma with tumor necrosis over 12 years before disease recurrence in the bilateral lungs, right adrenal gland, bone, and small bowel. The discovery of the small bowel metastases occurred while undergoing treatment for advanced-stage disease. At this time, she completed chemo-immunotherapy and remained on maintenance immunotherapy. The patient also underwent a partial right adrenalectomy and radiotherapy to the right adrenal gland. Given that she was experiencing symptomatic anemia and further workup indicated that the GI masses were causing her anemia, she underwent palliative small bowel resection of the masses. The pathology results demonstrated that the masses originated from her primary lung cancer, confirming metastatic disease to the small bowel.

Incidence and survival of choroid plexus tumors in the United States.

There are limited data available on incidence and survival of patients with choroid plexus tumors (CPT). This study provides the most current epidemiological analysis of choroid plexus tumors from 2004 to 2017 in the United States. Data on 2013 patients with CPT were acquired from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute, from 2004 to 2017. CPT cases were classified by the following pathological subtypes choroid plexus papilloma (CPP), atypical choroid plexus papilloma (aCPP), and choroid plexus carcinoma (CPC). Frequencies and age-adjusted incidence rates (AAIR) per 100 000 and rate ratios per 100 000 (IRR) were reported for age, sex, race, and ethnicity for each pathological subtype with 95% confidence intervals (95% CI). Using CDCs National Program of Cancer Registries survival database, survival curves and hazard ratios (HRs) evaluated overall survival from 2001 to 2016. CPP had the highest overall incidence (AAIR 0.034, 95% CI 0.033-0.036), followed by CPC (AAIR 0.008, 95% CI 0.008-0.009) and aCPP (AAIR 0.005, 95% CI 0.005-0.006). Incidence was highest among children less than one year old among all subtypes (CPP AAIR 0.278 aCPP AAIR 0.140 CPC AAIR 0.195), reducing as patients aged. Overall survival was worse among patients with CPC, being five times more likely to die compared to patients with CPP (HR 5.23, 95% CI 4.05-7.54, This analysis is the most current and comprehensive study in the US on the incidence and survival for CPT. Population based statistics provide critical information in understanding disease characteristics, which impact patient care and prognosis.

The emotional journey of neuro-oncology Primary brain tumor patients share their experience during this life-threatening disease.

To achieve patient-centric quality care in neuro-oncology, all aspects of the disease and its impact on quality survival need to be considered. This includes the psychological consequences of a brain tumor diagnosis and subsequent life-altering experiences. Far too often the voice of our patients is unheard. Empowering patients to advocate for their own psychological needs is essential. Data were derived from four focus groups with adult patients with brain tumors ( Of the two themes presented, 14 codes emerged. Codes were classified into three broad categories Fear, Despair, and Resilience. The frequency of each category ranged from 31.4% to 34.7%. Example quotes and a discussion of each category follows. It is imperative that we include the patient perspective in the development of neuro-oncology programs, thereby considering the

Racial disparities in inpatient clinical presentation, treatment, and outcomes in brain metastasis.

Few studies have assessed the impact of race on short-term patient outcomes in the brain metastasis population. The goal of this study is to evaluate the association of race with inpatient clinical presentation, treatment, in-hospital complications, and in-hospital mortality rates for patients with brain metastases (BM). Using data collected from the National Inpatient Sample between 2004 and 2014, we retrospectively identified adult patients with a primary diagnosis of BM. Outcomes included nonroutine discharge, prolonged length of stay (pLOS), in-hospital complications, and mortality. Minority (Black, Hispanicother) patients were less likely to receive surgical intervention compared to White patients (odds ratio OR 0.70 95% confidence interval CI 0.66-0.74, Our analysis demonstrated that race is associated with disparate short-term outcomes in patients with BM. More efforts are needed to address these disparities, provide equitable care, and allow for similar outcomes regardless of care.

Neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in patients with newly diagnosed glioblastoma.

In addition to poor survival rates, individuals with glioblastoma (GBM) are at risk of neurocognitive impairment due to multiple factors. This study aimed to characterize neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms in newly diagnosed GBM patients and to examine whether neurobehavioral symptoms, fatigue, sleep, and depressive symptoms influence neurocognitive performance. This study was part of a prospective, inception cohort, single-arm exercise intervention in which GBM patients underwent a neuropsychological assessment shortly after diagnosis (median 4 weeks ie, baseline) and 3, 6, 12, and 18 months later, or until tumor progression. Here, we present baseline data. Forty-five GBM patients (mean age 55 years) completed objective neurocognitive tests, and self-report measures of neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms. Compared to normative samples, GBM patients scored significantly lower on all neurocognitive tests, with 34 (76%) patients exhibiting neurocognitive impairment. Specifically, 53% exhibited impairment in memory retention, 51% in executive function, 42% in immediate recall, 41% in verbal fluency, and 24% in attention. There were high rates of clinically elevated sleep disturbance (70%), fatigue (57%), depressive symptoms (16%), and neurobehavioral symptoms (27%). A multivariate regression analysis revealed that depressive symptoms are significantly associated with neurocognitive impairment. GBM patients are vulnerable to adverse outcomes including neurocognitive impairment, neurobehavioral symptoms, fatigue, sleep disturbance, and depressive symptoms shortly after diagnosis, prior to completing chemoradiation. Those with increased depressive symptoms are more likely to demonstrate neurocognitive impairment, highlighting the need for early identification and treatment of depression in this population.

Molecular marker testing and reporting completeness for adult-type diffuse gliomas in the United States.

A newly developed brain molecular marker (BMM) data item was implemented by US cancer registries for individuals diagnosed with brain tumors in 2018-including IDH and 1p19q-co-deletion statuses for adult-type diffuse gliomas. We thus investigated the testingreporting completeness of BMM in the United States. Cases of histopathologically confirmed glioblastoma, astrocytoma, and oligodendroglioma diagnosed in 2018 were identified in the National Cancer Database. Adjusted odds ratios (OR Among 8306 histopathologically diagnosed adult-type diffuse gliomas nationally, overall BMM testingreporting completeness was 81.1%. Compared to biopsy-only cases, odds of testingreporting increased for subtotal (OR Initial BMM testingreporting completeness for individuals with adult-type diffuse gliomas in the United States was promising, although patterns varied by hospital attributes and extent of resection.

Trends in the incidence of malignant central nervous system tumors in Brazil, 2000-2015.

In Brazil, 5870 new cases of malignant central nervous system tumors (MCNST) were estimated for men and 5220 for women for each year of the 2020-2022 triennium. The objective of this study was to analyze incidence rate trends and compare demographic characteristics of new MCNST cases according to tumor topographies in Brazil from 2000 to 2015. This study comprises an analytical cross-sectional assessment of secondary databases extracted from the Brazilian National Cancer Institute (INCA) website. Data comprised new neoplasm cases of meninges (C70), brain (C71), spinal cord, cranial nerves, and other central nervous system parts (C72) retrieved from 23 population-based cancer registries. A descriptive analysis was performed. Crude and age-adjusted incidence rates were calculated. Linear trends were calculated using a linear least squares regression for adjusted incidence rates versus time. A total of 24 986 new MCNST cases were recorded. The main topography was the brain (91.5%). Except for meninges tumors, where 62.4% of the cases were observed in women, MCNST cases were more frequent among men concerning the other evaluated topographies. All 3 topographies occurred predominantly in adult patients aged from 40- to 64-year-old. Between 2000 and 2015, incidence rates ranged from 5.12 to 4.95 (a 1.4% increase of per year 95% CI -4.0 to 6.8 The most frequent topography was the brain. Incidence rates of MCNST remained relatively stable over time in both sexes.

Impact of thyroid cancer on the cancer risk in patients with non-alcoholic fatty liver disease or dyslipidemia.

The raised prevalence of obesity has increased the incidence of obesity-related metabolic diseases such as dyslipidemia (DL) and non-alcoholic fatty liver disease (NAFLD), along with the development and progression of various types of cancer, including thyroid cancer. In this study, we investigated whether thyroid cancer in patients with DL and NAFLD could be a risk factor for other cancers. To achieve our goal, we generated two independent cohorts from our institution and from the National Health Insurance System in South Korea. Based on the ICD-10 code, we conducted exact matching (15 matching) and estimated the overall risk of thyroid cancer for other cancers in patients with DL or NAFLD. Univariate and multivariate analyses showed that the hazard ratio (HR) of thyroid cancer was 2.007 (95% Confidence Interval CI, 1.597-2.522) and 2.092 (95% CI, 1.546-2.829), respectively in the institutional cohort and 1.329 (95% CI, 1.153-1.533) and 1.301 (95% CI, 1.115-1.517), respectively in the nationwide cohort. Risk analysis revealed a significant increase in the HR in lip, tongue, mouth, lung, bone, joint, soft tissue, skin, brain, male cancers and lymphoma after thyroid cancer occurred. Thyroid cancer in patients with DL or NAFLD might be a valuable factor for predicting the development of other cancers.

Defining the role of mTOR pathway in the regulation of stem cells of glioblastoma.

The mechanistic target of rapamycin (mTOR), a serinethreonine kinase, functions by forming two multiprotein complexes termed mTORC1 and mTORC2. Glioblastoma (GBM) is a uniformly fatal brain tumor that remains incurable partly due to the existence of untreatable cancer stem cells (CSC). The pathogenesis of GBM is largely due to the loss of the tumor suppressor gene PTEN, which is implicated in the aberrant activation of the mTOR pathway. The major cause of tumor recurrence, growth, and invasion is the presence of the unique population of CSC. Resistance to conventional therapies appears to be caused by both extensive genetic abnormalities and dysregulation of the transcription landscape. Consequently, CSCs have emerged as targets of interest in new treatment paradigms. Evidence suggests that inhibition of the mTOR pathway can also be applied to target CSCs. Here we explored the role of the mTOR pathway in the regulation of stem cells of GBM by treating them with inhibitors of canonical PI3KAKTmTOR pathways such as rapamycin (mTORC1 inhibitor), PP242 (ATP binding mTORC12 inhibitor), LY294002 (PI3K inhibitor), and MAPK inhibitor, U0126. A significant number of GBM tumors expressed stem cell marker nestin and activated mTOR (pmTOR

Myrtenol Ameliorates Recognition Memories Impairment and Anxiety-Like Behaviors Induced by Asthma by Mitigating Hippocampal Inflammation and Oxidative Stress in Rats.

Asthma is related to neurochemical alterations which affect brain functions and lead to anxiety and cognitive dysfunctions. Myrtenol has sparked considerable interest due to its pharmacological effects, especially for the remediation of chronic disorders. Thus, the present research was designed to evaluate the impacts of myrtenol on anxiety-like behaviors, cognitive declines, inflammation, and oxidative stress in the hippocampus of asthmatic rats. Rats were allocated to five groups control, asthma, asthmavehicle, asthmamyrtenol, and asthmabudesonide. Asthma was elicited in the rats by ovalbumin, and the animals were then exposed to myrtenol inhalation. Anxiety-like behavior and memory were assessed by elevated plus maze (EPM) and novel object and location recognition tests. Interleukins (interleukin-6, -17, and -10), tumor necrosis factor α (TNF-α), and oxidative stress biomarkers such as malondialdehyde (MDA), superoxide dismutase (SOD), Glutathione peroxidase (GPX), and total antioxidant capacity (TAC) in the hippocampus were assessed by the ELISA method. The levels of IL-6, IL-17, TNF-α, and MDA decreased, but GPX, SOD, and TAC levels increased in the hippocampus of asthmatic animals due to myrtenol inhalation. Myrtenol diminished asthma-induced anxiety-like behaviors and cognitive deficits in asthmatic rats these effects might have been typically mediated by a reduction in inflammation and oxidative stress.

Procollagen type 1 N-terminal propeptide, neurofilament light chain, proinflammatory cytokines, and cognitive function in bipolar and major depressive disorders An exploratory study of brain- bone axis and systemic inflammation.

Higher levels of neurofilament light chain (NfL) and proinflammatory cytokines (i.e., tumor necrosis factor TNF-α) were observed in patients with bipolar disorder (BD) and major depressive disorder (MDD). Procollagen type 1 N-terminal propeptide (P1NP), a bone turnover biomarker, is related to MDD. The association among the brain-bone axis, systemic inflammation, and cognitive function remains unclear in severe affective disorders. Overall, 25 patients with BD, 24 with MDD, and 29 matched controls were enrolled in the current study and underwent the measurements of the NfL, P1NP, and proinflammatory cytokine levels and 1-back and 2-back working memory tasks. Generalized linear models (GLMs) were used to examine the aforementioned biomarkers between the groups and clarify the association with each other. GLMs showed increased levels of NfL (p 0.001, p 0.020) and P1NP (p 0.050, p 0.032) in the patients with BD and MDD than in the controls and suggested significant correlations between the NfL level and the mean time of the 2-back working memory task (p 0.038) and between P1NL and TNF-α levels (p < 0.001). Our study revealed the dysregulated brain-bone axis, indicated by elevated NfL and P1NP levels, and related cognitive impairment and systemic inflammation in the patients with BD and MDD. Additional studies are necessary to elucidate definite pathomechanisms underlying those conditions.

Fighting secondary triple-negative breast cancer in cerebellum A powerful aid from a medicinal mushrooms blend.

Breast cancer (BC) is the second most common cause of brain metastasis onset in patients, with the cerebellum accounting for the 33% of cases. In the current study, using a 4T1 triple-negative mouse BC model, we revealed that an orally administered medicinal mushrooms (MM) blend, rich in β-glucans, played a direct and specific anti-cancer action on cerebellar metastases, also bettering locomotor performances. The neuroprotective effect of the MM blend plays through (i) a direct and specific inhibition of cerebellar metastatization pattern typical of TNBC (with an induced reduction of about 50% of metastases density) and (ii) the regulation of apoptosis and proliferation-related genes, as suggested by expression changes of specific molecular markers, i.e. PCNA, p53, Bcl2, BAX, CASP9, CASP3, Hsp70 and AIF. Therefore, inhibiting the metastatization process, triggering a significant apoptosis increase, and lessening cell proliferation, this MM supplement, employed as adjuvant treatment in association with conventional therapy, could represent a promising approach, in the field of Integrative Oncology, for patients management in both prevention and treatment of brain metastases from BC.

Heritable defects in telomere and mitotic function selectively predispose to sarcomas.

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas.

Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma.

Brain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined. The cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data, indicating high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines. Differences in macrophages and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and its biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital (PUMCH). We further evaluated the clinical significance of BM-index and identified 7 drugs that potentially target BMAECs. This study clarified possible cellular origins and drivers of metastatic LUAD at single cell level, and laid a foundation for early detections of LUAD patients with a high risk of BM.

LP2, a stable lanthipeptide derived from cAng-(1-7), exerts myeloprotective action in mice.

Linear unstable angiotensins stimulate hematopoiesis. Here we address (1) Is cyclic angiotensin-(1-7) myeloprotective in mice (2) Is cyclic angiotensin-(1-7) stable in rat (3) Does LP2, a cyclic angiotensin-(1-7) with an N-terminal d-lysine, exert myeloprotective action in tumor-bearing mice Cyclic angiotensin-(1-7)s capacity to restore levels of blood platelets and white blood cells was studied in gemcitabine-treated mice. The stability of cyclic angiotensin-(1-7) in rat was measured in blood samples taken after injection or infusion. The capacity of LP2 to restore total bone marrow cell levels in mice after treatment with 5-fluoruracil was measured. In addition, the capacity of LP2 to counter anemia in tumor-bearing mice treated with erlotinib was measured. Cyclic angiotensin-(1-7) dose-dependently restored blood platelet levels in gemcitabine-treated mice, whereas its capacity to restore levels of white blood cells was less. In vivo aminoterminal breakdown of cyclic angiotensin-(1-7) yielded cyclic angiotensin-(2-7) and cyclic angiotensin-(3-7). LP2 significantly (p < .0001 at 100 μgkgday) restored bone marrow cell counts in mice after treatment with 5-fluoruracil. LP2 also significantly (p < .05) countered anemia in tumor-bearing mice treated with erlotinib. LP2 exerts myeloprotective action with perspectives for continuation of its clinical development.

Characterization of the Response of 9L and U-251N Orthotopic Brain Tumors to 3D Conformal Radiation Therapy.

In a study employing MRI-guided stereotactic radiotherapy (SRS) in two orthotopic rodent brain tumor models, the radiation dose yielding 50% survival (the TCD50) was sought. Syngeneic 9L cells, or human U-251N cells, were implanted stereotactically in 136 Fischer 344 rats or 98 RNU athymic rats, respectively. At approximately 7 days after implantation for 9L, and 18 days for U-251N, rats were imaged with contrast-enhanced MRI (CE-MRI) and then irradiated using a Small Animal Radiation Research Platform (SARRP) operating at 220 kV and 13 mA with an effective energy of ∼70 keV and dose rate of ∼2.5 Gy per min. Radiation doses were delivered as single fractions. Cone-beam CT images were acquired before irradiation, and tumor volumes were defined using co-registered CE-MRI images. Treatment planning using MuriPlan software defined four non-coplanar arcs with an identical isocenter, subsequently accomplished by the SARRP. Thus, the treatment workflow emulated that of current clinical practice. The study endpoint was animal survival to 200 days. The TCD50 inferred from Kaplan-Meier survival estimation was approximately 25 Gy for 9L tumors and below 20 Gy, but within the 95% confidence interval in U-251N tumors. Cox proportional-hazards modeling did not suggest an effect of sex, with the caveat of wide confidence intervals. Having identified the radiation dose at which approximately half of a group of animals was cured, the biological parameters that accompany radiation response can be examined.

Repressing effect of transformed ginsenoside Rg3-mix against LPS-induced inflammation in RAW264.7 macrophage cells.

Rg3-ginsenoside, a protopanaxadiol saponin, is a well-known adaptogen used for the prevention of cancer and inflammation. However, despite its distinct biological activity, the concentration of Rg3 in the total ginseng extract is insufficient for therapeutic applications. This study aims to convert PPD-class of major ginsenosides into a mixture of minor ginsenoside, to analyze its immune-regulatory role in macrophage cells. Using heat and organic acid treatment, three major ginsenosides, Rc, Rd, and Rb1, were converted into a mixture of minor ginsenosides, GRg3-mix Rg3(S), Rg3(R), Rg5, and Rk1. Purity and content analysis of the transformed compound were performed using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC), compared with their standards. Preceding with the anti-inflammatory activity of GRg3-mix, lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells were treated with various concentrations of GRg3-mix (6.25, 12.5, 25, and 50 μgmL). The cell viability assay revealed that the level of cell proliferation was increased, while the nitric oxide (NO) assay showed that NO production decreased dose-dependently in activated RAW264.7 cells. The obtained results were compared to those of pure Rg3(S) ≥ 98% (6.25, 12.5, and 25 μgmL). Preliminary analysis of the CCK-8 and NO assay demonstrated that GRg3-mix can be used as an anti-inflammatory mediator, but mRNA and protein expression levels were evaluated for further confirmation. The doses of GRg3-mix significantly suppressed the initially upregulated mRNA and protein expression of inflammation-related enzymes and cytokines, namely inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear transcription factor kappa B (NF-κB), tumor necrosis factor (TNF-α), and interleukins (IL-6 and IL1B), as measured by reverse transcription-polymerase chain reaction and western blotting. Our pilot data confirmed that the mixture of minor ginsenosides, namely GRg3-mix, has high anti-inflammatory activity and has an easy production procedure.

Histology of high-grade glioma samples resected using 5-ALA fluorescent headlight and loupe combination.

5-Aminolevulinic acid (5-ALA) fluorescence-guided resection of high-grade gliomas (HGG) increases the extent of resection (EOR) and progression-free survival. The headlamploupe combination has been introduced as a method of performing fluorescent-guided surgery. This study aims to understand the correlation between fluorescent intensity and histology and between residual fluorescence and radiographic EOR utilizing the headlamploupe device. Intraoperative samples resected using the headlamploupe device from 14 patients were labeled as PINK, VAGUE, or NEGATIVE depending on the degree of fluorescence. Histological assessment of microvascular proliferation, necrosis, and cell density was performed, and samples were classified as histologically consistent with glioblastoma (GBM), high-grade infiltrating glioma (HGIG), IG, or non-diagnostic (NDX). The presence of intraoperative residual fluorescence was compared to EOR on post-operative MRI. There was a significant difference in cell density comparing PINK, VAGUE, and NEGATIVE specimens (ANOVA, p < 0.00001). The PPV of PINK for GBM or HGIG was 88.4% (3843). The NPV of NEGATIVE for IG or NDX was 74.4% (2939). The relationship between the degree of fluorescence determination and histological results was significant (X The headlamploupe device provides information about histology, cell density, and necrosis with similar PPV for tumor to the operative microscope. Safe complete resection of florescence has a PPV of 100% for radiographic GTR and should be the goal of surgery.

A real-world study of second or later-line osimertinib in patients with EGFR T790M-positive NSCLC the final ASTRIS data.

Osimertinib is a drug that blocks the activity of a protein called EGFR on cancer cells, reducing their growth and spread. ASTRIS is the largest real-world study that evaluated the outcomes with osimertinib treatment for patients with advanced non-small-cell lung cancer (NSCLC), and the EGFR T790M mutation, who had received previous treatment for their cancer. There were 3014 patients included in this study. The main aim of this study was to measure the time at which half of the patients were still alive after starting osimertinib treatment, this was 22.8 months. The study also measured the time at which half of the patients had experienced worsening (progression) of their cancer (11.1 months) and the time when half of the patients had stopped receiving osimertinib treatment (13.5 months). None of the patients experienced any unexpected side effects of the treatment. These data are consistent with those observed in comparable clinical trials with osimertinib, supporting the use of osimertinib treatment for patients with advanced NSCLC and the EGFR T790M mutation after their initial cancer treatment has stopped working.

Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy.

Pineocytoma is a rare tumor. It is rare for pineocytoma to present as leptomeningeal metastasis. We present a rare case of pineocytoma with malignant transformation and leptomeningeal metastasis after subtotal tumor resection and adjuvant radiotherapy. This case was a 58-year-old male with an unsteady gait for 2 months. Enhanced brain magnetic resonance imaging revealed a heterogeneous mass involving the pineal region. The initial pathological diagnosis of pineocytoma was confirmed after subtotal tumor resection. Two years after adjuvant radiotherapy to the primary site, the magnetic resonance imaging showed C2 and T2 metastatic lesions, with the final pathological diagnosis being pineal parenchymal tumor (PPT) with intermediate differentiation after the removal of T2 intramedullary tumor. After that adjuvant radiotherapy at the cervical and thoracic spinal cord was completed. There was no recurrence of the tumor 1 year after the radiotherapy. We report a rare case of pineocytoma with malignant transformation to PPT with intermediate differentiation and leptomeningeal dissemination.

All-in-One Nanowire Assay System for Capture and Analysis of Extracellular Vesicles from an

Extracellular vesicles (EVs) have promising potential as biomarkers for early cancer diagnosis. The EVs have been widely studied as biological cargo containing essential biological information not only from inside vesicles such as nucleic acids and proteins but also from outside vesicles such as membrane proteins and glycolipids. Although various methods have been developed to isolate EVs with high yields such as captures based on density, size, and immunoaffinity, different measurement systems are needed to analyze EVs after isolation, and a platform that enables all-in-one analysis of EVs from capture to detection in multiple samples is desired. Since a nanowire-based approach has shown an effective capability for capturing EVs

Improving crossing of multiple bio-delivery barriers by a novel bio-interface design based on hydrophobic nanoparticle surfaces.

Biological delivery remains a major challenge in biotechnology, partly because it is often not enough to overcome a single delivery barrier. It is highly desirable, yet rarely available, to design delivery carriers with both simple structures and the ability to cross multiple delivery barriers with high efficiency. Herein, we describe a distinct design (dubbed SDot) of delivery carriers with a single structural feature that can enhance the crossing of multiple delivery barriers. The bio-interface (the interface with a biological environment) of an SDot nanoparticle is highly hydrophobic, thus enhancing its interactions with lipid membranes, which are the primary components of many bio-delivery barriers. We used quantum dots (QDs) as the model core material of SDots and conjugated them with a RGD peptide. Thus-formed SDots-RGD demonstrated greatly improved abilities of cellular uptake and transcytosis in a brain tumor cell line, U87MG, compared with the conventional nanoparticle counterpart with a hydrophilic bio-interface (wQDs-RGD). Further, after loading a microtubule-binding anticancer drug, paclitaxel (PTX), onto the nanoparticle surface of SDots-RGD, the resulting drug formulation PTXSDots-RGD displayed excellent ability of intracellular targeting to microtubules in U87MG cells. In a small animal cancer model, PTXSDots-RGD exhibited significantly higher ability to slow down brain tumor growth than that of PTXwQDs-RGD and free PTX. Taken together, these experimental results indicated the significant potential of SDots-RGD for bio-delivery, although the possible long-term toxicity of QDs used as the core material needs to be addressed in future work by replacing QDs with clinically approved materials.

The Short-Term Outcome of Seizure and Anti-epileptic Use After Cranial Surgery A Retrospective Record Review.

Objectives The study aims to correlate craniotomies and their effect on epileptic activity and to assess the impact of prophylaxis anti-epileptic drugs (AEDs) used to prevent seizure activity after craniotomy. Method This was a mono-center retrospective review of patients undergoing craniotomy from 2010-2021 at King Abdulaziz University Hospital (KAUH), a tertiary center in Jeddah, Saudi Arabia. The patients were divided into two groups depending on preoperative anti-epileptic drug usage and the occurrence of seizures after the surgery. Out of 192, 24.6% had a seizure before the surgery, while the rest reported no seizure activity. We used descriptive statistics to categorize the study population and applied t-test and chi-square to compare different groups and outcomes. Results One-hundred-ninety-two patients were studied 24.6% had preoperative seizure history and 82.1% were on prophylactic AEDs. The incidence of post-craniotomy seizures was 7.6% in patients with anti-epileptic prophylaxis and 2.7% in those without prophylaxis before the surgery. Almost three-quarters of the patients (72.4%) had surgery for brain tumor resection and redo-craniotomy while the rest (25.5%) were for intracranial hemorrhages (p0.052). On multivariate analysis, the primary predictor of post-craniotomy seizures was the preoperative history of seizures. Finally, the administration of AEDs does not prevent seizure occurrence after craniotomy (p0.153). Moreover, the type of prophylaxis and reason for the surgery played no significant role in seizure occurrence. Conclusion Post-craniotomy seizures were common, and preoperative AEDs for primary seizure prevention were not associated with a lower incidence of seizures after craniotomy.

Adrenal Liposarcoma A Novel Presentation of Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) syndrome results from genetic sequence variations of the tumor suppressor MEN1 gene, which codes for the protein menin. Individuals with MEN1 are prone to developing multiple tumors involving the endocrine and nonendocrine organs. MEN1 associated with liposarcomas has not been documented previously. We highlight a case of MEN1 presenting with a metastatic adrenal liposarcoma. A 41-year-old Hispanic man with a history of nephrolithiasis and skin lesions presented to the emergency department with abdominal pain. He was found to have a right adrenal mass measuring 7.9 cm with extension into the liver and primary hyperparathyroidism. He had multiple paternal first-degree relatives with similar skin lesions, hypercalcemia, and tumors of the brain, thoracic cavity, abdomen, and thyroid. The mass was identified as a metastatic pleiomorphic adrenal liposarcoma on surgical pathology. Genetic testing revealed a germline pathogenic sequence variation of the MEN1 gene. Liposarcomas are rare malignant tumors with an annual incidence of 2.5 cases per 1 million. Although lipoma formation is a commonly described manifestation of MEN1, liposarcomas have not been associated with MEN1 previously. A potential mechanism of this association is through the role of menin in inducing adipocyte differentiation via peroxisome proliferator-activated receptor-γ activation, a highly expressed protein in liposarcomas. Liposarcomas should be included in the differential of MEN1-related tumors.

Establishment and verification of a nomogram to predict tumor-specific mortality risk in triple-negative breast cancer a competing risk model based on the SEER cohort study.

Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis, and traditional survival analysis methods are biased when predicting mortality. To predict the risk of death in patients with triple-negative breast cancer more precisely, a competing risk model was developed. The clinicopathological data of the TNBC patients from 2010 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. The data were assigned into a training set and testing set at a ratio of 73 in a randomized pattern. Univariate and multivariate competing risk models were applied to find the independent prognostic factors. A prediction nomogram for cancer-specific mortality (CSM) risk was constructed. The accuracy and discrimination of the nomogram were assessed using receiver operating characteristic (ROC) area under the curve (AUC), concordance index (C-index), and a calibration curve using the training and testing sets, respectively. A total of 28,430 TNBC patients were randomly grouped into the training set (n19,900) and the testing set (n8,530). The median time for follow-up was 59 1-107 months. A total of 7,014 (24.67%) patients died, among whom 4,801 (68.45%) died from breast cancer and 2,213 (31.55%) due to non-breast cancer events. The independent risk factors were primary site of tumor, grade, tumor-node-metastasis (TNM) stage, T stage, approach of surgery, chemotherapy, axillary lymph node metastases, brain metastases, and liver metastases. The prediction nomogram was constructed by using the aforementioned variables. The 1-, 3-, and 5-year AUC of CSM were predicted to be 0.856, 0.81, and 0.782, respectively, in the training set, and 0.856, 0.81, and 0.782 in the testing set, respectively. The C-index of the nomogram was 0.801 and 0.799 in the training and testing sets, respectively. As confirmed by the validation and training calibration curves, the nomogram was consistent with the results. We used competing risk models to identify risk factors for CSM and constructed a CSM risk prediction nomogram for TNBC patients, that may be utilized to predict CSM risk in TNBC patients clinically and assist in the creation of individualised clinical treatment options.

Encouraging probiotics for the prevention and treatment of immune-related adverse events in novel immunotherapies against malignant glioma.

Among the malignant tumors in the central nervous system (CNS), glioma is the most challenging tumor to the public society, which accounts for the majority of intracranial malignant tumors with impaired brain function. In general, conventional therapies are still unable to provide an effective cure. However, novel immunotherapies have changed the treatment scene giving patients a greater potential to attain long term survival, improved quality of life. Having shown favorable results in solid tumors, those therapies are now at a cancer research hotspot, which could even shrink the growth of glioma cells without causing severe complications. However, it is important to recognize that the therapy may be occasionally associated with noteworthy adverse action called immune-related adverse events (IRAEs) which have emerged as a potential limitation of the therapy. Multiple classes of mediators have been developed to enhance the ability of immune system to target malignant tumors including glioma but may also be associated with the IRAEs. In addition, it is probable that it would take long time after the therapy to exhibit severe immune-related disorders. Gut microbiota could play an integral role in optimal immune development andor appropriate function for the cancer therapy, which is a vital component of the multidirectional communication between immune system, brain, and gut, also known as gut-brain-immune axis. Here, we show the potential effects of the gut-brain-immune axis based on an engram theory for the innovative treatment of IRAEs.

New phase therapeutic pursuits for targeted drug delivery in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is known as the most aggressive and prevalent brain tumor with a high mortality rate. It is reported in people who are as young as 10 years old to as old as over 70 years old, exhibiting inter and intra tumor heterogeneity. There are several genomic and proteomic investigations that have been performed to find the unexplored potential targets of the drug against GBM. Therefore, certain effective targets have been taken to further validate the studies embarking on the robustness in the field of medicinal chemistry followed by testing in clinical trials. Also, The Cancer Genome Atlas (TCGA) project has identified certain overexpressed targets involved in the pathogenesis of GBM in three major pathways, i.e., tumor protein 53 (p53), retinoblastoma (RB), and receptor tyrosine kinase (RTK)rat sarcoma virus (Ras)phosphoinositide 3-kinase (PI3K) pathways. This review focuses on the compilation of recent developments in the fight against GBM thus, directing future research into the elucidation of pathogenesis and potential cure for GBM. Also, it highlights the potential biomarkers that have undergone extensive research and have promising prognostic and predictive values. Additionally, this manuscript analyses the advent of gene therapy and immunotherapy, unlocking the way to consider treatment approaches other than, or in addition to, conventional chemo-radiation therapies. This review study encompasses all the relevant research studies associated with the pathophysiology, occurrence, diagnostic tools, and therapeutic intervention for GBM. It highlights the evolution of various therapeutic perspectives against GBM from the most conventional form of radiotherapy to the recent advancement of genecellimmune therapy. Further, the review focuses on various targeted therapies for GBM including chemotherapy sensitization, radiotherapy, nanoparticles based, immunotherapy, cell therapy, and gene therapy which would offer a comprehensive account for exploring several facets related to GBM prognostics.

Corrigendum Prescription preferences of antiepileptic drugs in brain tumor patients an international survey among EANO members.

This corrects the article DOI 10.1093nopnpab059..

Perceptions and experiences of the subjective well-being of people with glioblastoma a longitudinal phenomenological study.

Glioblastoma (GBM) is a devastating form of brain cancer, with a short life expectancy. In addition to this poor prognosis, people with GBM often experience symptoms that may have a profound impact on their subjective well-being (SWB). The aim of this study was to investigate the lived experiences and perceptions of people with GBM regarding their SWB. The study adopted a longitudinal, hermeneutical phenomenological approach. Twenty-seven interviews were conducted with 15 patients over a period of two years. Most participants were interviewed twice on a face-to-face basis (during combined chemotherapy and radiotherapy, and again during adjuvant chemotherapy). The hermeneutic circle was used to guide data analysis. Data analysis identified four key themes that depicted the lived experiences and perceptions of SWB of people with GBM. Experience of the disease focuses on the impact of diagnosis, symptoms and side effects. Daily life relates to daily activities, family roles, work and social lives. Coping includes the importance of normality and goal-setting. Experiences of care focuses on the impact of the treatment schedule, experiences of care and impressions of the monitoring of QoL. SWB is affected by a variety of factors throughout the GBM disease and treatment journey. The findings of this study suggest that healthcare professionals can enhance the SWB of people with GBM by providing personalized care that supports people to set themselves goals for the future and retain a degree of normality wherever possible.

Inhibition of Protein Disulfide Isomerase (PDIA1) Leads to Proteasome-Mediated Degradation of Ubiquitin-like PHD and RING Finger Domain-Containing Protein 1 (UHRF1) and Increased Sensitivity of Glioblastoma Cells to Topoisomerase II Inhibitors.

Glioblastoma (GBM) is the most aggressive brain tumor, and the prognosis remains poor with current available treatments. PDIA1 is considered a promising therapeutic target in GBM. In this study, we demonstrate that targeting PDIA1 results in increased GBM cell death by topoisomerase II (Top-II) inhibitors resulting in proteasome-mediated degradation of the oncogenic protein UHRF1. Combination of the PDIA1 inhibitor, bepristat-2a, produces strong synergy with doxorubicin, etoposide, and mitoxantrone in GBM and other cancer cell lines. Our bioinformatics analysis of multiple datasets revealed downregulation of

Awake craniotomy for operative treatment of brain gliomas - experience from University Medical Centre Ljubljana.

Awake craniotomy is a neurosurgical technique that allows neurophysiological testing with patient cooperation during the resection of brain tumour in regional anaesthesia. This allows identification of vital functional (i.e. eloquent) brain areas during surgery and avoidance of their injury. The aim of the study was to present clinical experience with awake craniotomy for the treatment of gliomas at the University Medical Centre Ljubljana from 2015 to 2019. Awake craniotomy was considered in patients with a gliomas near or within the language brain areas, in all cases of insular lesions and selected patients with lesions near or within primary motor brain cortex. Each patient was assessed before and after surgery. During the 5-year period, 24 awake craniotomies were performed (18 male and 6 female patients average age 41). The patients cooperation, discomfort and perceived pain assessed during the awake craniotomy were in majority of the cases excellent, slight, and moderate, respectively. After surgery, mild neurological worsening was observed in 13% (324) of patients. Gross total resection, in cases of malignant gliomas, was feasible in 60% (610) and in cases of low-grade gliomas in 29% (414). The surgery did not have important negative impact on functional status or quality of life as assessed by Karnofsky score and Short-Form 36 health survey, respectively (p > 0.05). The results suggest that awake craniotomy for treatment of gliomas is feasible and safe neurosurgical technique. The proper selection of patients, preoperative preparation with planning, and cooperation of medical team members are necessary for best treatment outcome.

Anti-Vascular Endothelial Growth Factor Therapy Abolishes Glioma-Associated Endothelial Cell-Induced Tumor Invasion.

Tumor-remodeled endothelial cells not only facilitate the formation of tumor angiogenesis but also promote tumorigenesis. In this study, we aimed to explore the interaction between glioma-associated endothelial cells (GAEs) and glioma cells. We found that different subtypes of glioma owned distinct GAE abundance. Glioma patients with high GAE abundance exhibited poor prognosis. Both the results of the bioinformatics analysis and the in vitro co-culture system assay revealed that GAE promoted glioma cell invasion. Besides, anti-vascular endothelial growth factor (VEGF) therapy partially abolished the effects of GAE on gliomas. Moreover, anti-VEGF therapy upregulated IL-2 expression in GAE, and exogenous IL-2 administration inhibits GAE-induced glioma cell invasion. Collectively, our present study provides a novel outstanding of the interaction between GAE and glioma cells.

Influence of the Cultivation Conditions of the Glioblastoma Neurosphere on the Expression of MALAT1 and LINCROR Long Non-coding RNA Genes.

Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor. One of the reasons for the resistance of GBM to treatment is the extreme heterogeneity of the tumor and, in particular, the presence of cancer stem cells (CSCs) in the population of glioblastoma cells. In this work, we investigated the effect of conditions that reduce the proportion of CSCs in the GBM cell population on the levels of long noncoding RNAs (lincROR and MALAT1) involved in the formation of the phenotype of glioblastoma cancer stem cells. We have shown that culturing under conditions that cause a decrease in cell stemness (when fetal bovine serum is added to the culture medium) affected the content of these transcripts in the cells of most of the analyzed lines, a decrease in the level of the positive stemness regulator lincROR and an increase in the content of MALAT1 were noted.

Artificial intelligence-based locoregional markers of brain peritumoral microenvironment.

In malignant primary brain tumors, cancer cells infiltrate into the peritumoral brain structures which results in inevitable recurrence. Quantitative assessment of infiltrative heterogeneity in the peritumoral region, the area where biopsy or resection can be hazardous, is important for clinical decision making. Here, we derive a novel set of Artificial intelligence (AI)-based markers capturing the heterogeneity of tumor infiltration, by characterizing free water movement restriction in the peritumoral region using Diffusion Tensor Imaging (DTI)-based free water volume fraction maps. We leverage the differences in the peritumoral region of metastasis and glioblastomas, the former consisting of vasogenic versus the latter containing infiltrative edema, to extract a voxel-wise deep learning-based peritumoral microenvironment index (PMI). Descriptive characteristics of locoregional hubs of uniformly high PMI values are then extracted as AI-based markers to capture distinct aspects of infiltrative heterogeneity. The proposed markers are utilized to stratify patients survival and IDH1 mutation status on a population of 275 adult-type diffuse gliomas (CNS WHO grade 4). Our results show significant differences in the proposed markers between patients with different overall survival and IDH1 mutation status (t test, Wilcoxon rank sum test, linear regression p < 0.01). Clustering of patients using the proposed markers reveals distinct survival groups (logrank p < 10

Dose reduction of hippocampus using HyperArc planning in postoperative radiotherapy for primary brain tumors.

To compare dosimetric parameters for the hippocampus, organs at risk (OARs), and targets of volumetric modulated arc therapy (VMAT), noncoplanar VMAT (NC-VMAT), and HyperArc (HA) plans in patients undergoing postoperative radiotherapy for primary brain tumors. For 20 patients, HA plans were generated to deliver 40.05 to 60 Gy for the planning target volume (PTV). In addition, doses for the hippocampus and OARs were minimized. The VMAT and NC-VMAT plans were retrospectively generated using the same optimization parameters as those in the HA plans. For the hippocampus, the equivalent dose to be administered in 2 Gy fractions (EQD

Proteome-based insights for IDH-mutant glioma classification.

In this issue, Bader et al.

Immunogenomic analysis of human brain metastases reveals diverse immune landscapes across genetically distinct tumors.

Brain metastases (BrMs) are the most common form of brain tumors in adults and frequently originate from lung and breast primary cancers. BrMs are associated with high mortality, emphasizing the need for more effective therapies. Genetic profiling of primary tumors is increasingly used as part of the effort to guide targeted therapies against BrMs, and immune-based strategies for the treatment of metastatic cancer are gaining momentum. However, the tumor immune microenvironment (TIME) of BrM is extremely heterogeneous, and whether specific genetic profiles are associated with distinct immune states remains unknown. Here, we perform an extensive characterization of the immunogenomic landscape of human BrMs by combining whole-exomewhole-genome sequencing, RNA sequencing of immune cell populations, flow cytometry, immunofluorescence staining, and tissue imaging analyses. This revealed unique TIME phenotypes in genetically distinct lung- and breast-BrMs, thereby enabling the development of personalized immunotherapies tailored by the genetic makeup of the tumors.

Endoplasmic Reticulum Stress in the Brain Tumor Immune Microenvironment.

Immunotherapy has emerged as a powerful strategy for halting cancer progression. However, primary malignancies affecting the brain have been exempt to this success. Indeed, brain tumors continue to portend severe morbidity and remain a globally lethal disease. Extensive efforts have been directed at understanding how tumor cells survive and propagate within the unique microenvironment of the central nervous system (CNS). Cancer genetic aberrations and metabolic abnormalities provoke a state of persistent endoplasmic reticulum (ER) stress that in turn promotes tumor growth, invasion, therapeutic resistance, and the dynamic reprogramming of the infiltrating immune cells. Consequently, targeting ER stress is a potential therapeutic approach. In this work, we provide an overview of how ER stress response is advantageous to brain tumor development, discuss the significance of ER stress in governing anti-tumor immunity, and put forth therapeutic strategies of regulating ER stress in order to augment the effect of immunotherapy for primary CNS tumors.

Active remodeling of capillary endothelium via cancer cell-derived MMP9 promotes metastatic brain colonization.

Crossing the blood-brain barrier is a crucial, rate-limiting step of brain metastasis. Understanding of the mechanisms of cancer cell extravasation from brain microcapillaries is limited as the underlying cellular and molecular processes cannot be adequately investigated using in vitro models and end-point in vivo experiments. Using ultrastructural and functional imaging, we demonstrate that dynamic changes of activated brain microcapillaries promote the mandatory first steps of brain colonization. Successful extravasation of arrested cancer cells occurred when adjacent capillary endothelial cells (ECs) entered into a distinct remodeling process. After extravasation, capillary loops were formed, which was characteristic of aggressive metastatic growth. Upon cancer cell arrest in brain microcapillaries, matrix-metalloprotease 9 (MMP9) was expressed. Inhibition of MMP29 and genetic perturbation of MMP9 in cancer cells, but not the host, reduced EC projections, extravasation, and brain metastasis outgrowth. These findings establish an active role of ECs in the process of cancer cell extravasation, facilitated by crosstalk between the two cell types. This extends our understanding of how host cells can contribute to brain metastasis formation and how to prevent it.

Targeting de novo lipid synthesis induces lipotoxicity and impairs DNA damage repair in glioblastoma mouse models.

Deregulated de novo lipid synthesis (DNLS) is a potential druggable vulnerability in glioblastoma (GBM), a highly lethal and incurable cancer. Yet the molecular mechanisms that determine susceptibility to DNLS-targeted therapies remain unknown, and the lack of brain-penetrant inhibitors of DNLS has prevented their clinical evaluation as GBM therapeutics. Here, we report that YTX-7739, a clinical-stage inhibitor of stearoyl CoA desaturase (SCD), triggers lipotoxicity in patient-derived GBM stem-like cells (GSCs) and inhibits fatty acid desaturation in GSCs orthotopically implanted in mice. When administered as a single agent, or in combination with temozolomide (TMZ), YTX-7739 showed therapeutic efficacy in orthotopic GSC mouse models owing to its lipotoxicity and ability to impair DNA damage repair. Leveraging genetic, pharmacological, and physiological manipulation of key signaling nodes in gliomagenesis complemented with shotgun lipidomics, we show that aberrant MEKERK signaling and its repression of the energy sensor AMP-activated protein kinase (AMPK) primarily drive therapeutic vulnerability to SCD and other DNLS inhibitors. Conversely, AMPK activation mitigates lipotoxicity and renders GSCs resistant to the loss of DNLS, both in culture and in vivo, by decreasing the saturation state of phospholipids and diverting toxic lipids into lipid droplets. Together, our findings reveal mechanisms of metabolic plasticity in GSCs and provide a framework for the rational integration of DNLS-targeted GBM therapies.

Inhibition of autophagy in microglia and macrophages exacerbates innate immune responses and worsens brain injury outcomes.

Excessive and prolonged neuroinflammation following traumatic brain injury (TBI) contributes to long-term tissue damage and poor functional outcomes. However, the mechanisms contributing to exacerbated inflammatory responses after brain injury remain poorly understood. Our previous work showed that macroautophagyautophagy flux is inhibited in neurons following TBI in mice and contributes to neuronal cell death. In the present study, we demonstrate that autophagy is also inhibited in activated microglia and infiltrating macrophages, and that this potentiates injury-induced neuroinflammatory responses. Macrophagemicroglia-specific knockout of the essential autophagy gene

Lysine-specific histone demethylase 1A (KDM1ALSD1) inhibition attenuates DNA double strand break repair and augments efficacy of temozolomide in glioblastoma.

Efficient DNA repair in response to standard chemo and radiation therapies often contribute to GBM therapy resistance. Understanding the mechanisms of therapy resistance and identifying the drugs that enhance the therapeutic efficacy of standard therapies may extend the survival of GBM patients. In this study, we investigated the role of KDM1ALSD1 in DNA double strand break (DSB) repair and combination of KDM1A inhibitor and TMZ in vitro and in vivo using patient derived GSCs. Brain-bioavailability of the KDM1A inhibitor (NCD38) was established using LS-MSMS. Effect of combination of KDM1A knockdown or inhibition with TMZ was studied using cell viability and self-renewal assays. Mechanistic studies were conducted using CUTTag-seq, RNA-seq, RT-qPCR, Western blot, HR and NHEJ reporter, immunofluorescence, and comet assays. Orthotopic murine models were used to study efficacy in vivo. TCGA analysis showed KDM1A is highly expressed in TMZ treated GBM patients. Knockdown or knockout or inhibition of KDM1A enhanced TMZ efficacy in reducing the viability and selfrenewal of GSCs. Pharmacokinetic studies established that NCD38 readily crosses the BBB. CUTTag-seq studies showed that KDM1A is enriched at the promoters of DNA repair genes and RNA-seq studies confirmed that KDM1A inhibition reduced their expression. Knockdown or inhibition of KDM1A attenuated HR and NHEJ-mediated DNA repair capacity and enhanced TMZ mediated DNA damage. Combination of KDM1A knockdown or inhibition and TMZ treatment significantly enhanced survival of tumor bearing mice. Our results provide evidence that KDM1A inhibition sensitizes GBM to TMZ via attenuation of DNA DSB repair pathways.

Osimertinib for EGFR-Mutant Non-Small-Cell Lung Cancer Central Nervous System Metastases Current Evidence and Future Perspectives on Therapeutic Strategies.

Central nervous system (CNS) metastases are common in non-small-cell lung cancer (NSCLC) and associated with poor prognosis and high disease burden. Effective options are needed to treat CNS metastases, and delay or prevent their formation. For epidermal growth factor receptor mutation-positive (EGFRm) advanced NSCLC and brain metastases, upfront EGFR-tyrosine kinase inhibitors (TKIs) are recommended by the joint European Association of Neuro-Oncology-European Society for Medical Oncology and experts. While early-generation EGFR-TKIs have limited CNS efficacy, the third-generation, irreversible, EGFR-TKI osimertinib has potent efficacy in NSCLC CNS metastases. This review discusses the CNS data of osimertinib in the context of therapeutic strategies and future prospects based on expert review of published literature and relevant clinical, real-world, and ongoing studies in this setting. Osimertinib penetrates the blood-brain barrier and achieves greater exposure in the brain compared with other EGFR-TKIs. Osimertinib has demonstrated CNS efficacy, including in leptomeningeal metastases, in EGFRm advanced disease. In EGFRm stage IB-IIIA NSCLC, adjuvant osimertinib reduced CNS disease recurrence versus placebo. The burden and poor prognosis of CNS metastases necessitate more therapeutic options for their management and reduced risk of recurrence in patients with EGFRm NSCLC. Clinical studies are ongoing in advanced disease to investigate osimertinib combinations with chemotherapyradiation therapy and optimal treatment post-CNS progression with osimertinib. Further prospective research evaluating treatments using CNS-specific endpoints and evaluating CNS resistance is needed to improve outcomes for patients with CNS metastases.

Pituitary enlargement in patients with cerebrospinal fluid drainage due to ventricular shunt insertion know the condition and do not mistake for adenoma.

Childhood hydrocephalus patients treated by ventriculo-peritoneal (v.-p.) shunting are sometimes referred years after this therapy for evaluation of suspicious pituitary enlargement. Since pituitary size has been shown to depend on cerebrospinal fluid (CSF) pressure, we assume this phenomenon to be caused by shunt overdrainage. Therefore, we studied pituitary size and morphology in shunted hydrocephalus patients with radiological signs of high CSF drainage. Retrospective study of pituitary size and morphology in 15 shunted patients with non-tumoral hydrocephalus and 7 shunted hydrocephalus patients due to childhood brain tumor compared to a population mean. In five brain tumor patients also pre- and postsurgical comparisons were performed. Pituitary mid-sagittal size and pituitary volume were significantly higher in both hydrocephalus groups, compared to the population mean (midsagittal size t 5.91 p < 0.001 pituitary volume, t 3.03 p 0.006). In patients available for pre- and postoperative comparison, there was also a significant increase in pituitary size and volume postoperatively (mean preoperative midsagittal height 2.54 ± 1.0 mm vs. 6.6 ± 0.7 mm post-surgery mean pre-operative pituitary volume 120.5 ± 69.2 mm Our results confirmed a significant increase in pituitary size and volume, mimicking pituitary pathology, after v.-p. shunt insertion. This phenomenon can be explained by the Monro-Kellie doctrine, stating that intracranial depletion of CSF-as caused by v.p. shunting-leads to compensatory intracranial hyperemia, especially in the venous system, with the consequence of engorged venous sinuses, most likely responsible for enlargement of the pituitary gland.

VEGF gene polymorphisms in Iranian patients with intracranial glioblastoma.

Glioblastoma is one of the most common malignant brain tumors in adults with poor prognosis. Neovascularization is one of the characteristics of these tumors, which is associated with overexpression of vascular endothelial growth factor (VEGF). Accordingly, single nucleotide polymorphisms of this gene could play an important role in structural and functional alterations leading to overexpression of this gene in GBM. A total number of 49 patients with GBM and 50 healthy controls were included in the current study. The Genomic DNA was extracted from brain tumortissue samples, and after purification assessment, the alleles, and genotypes of rs3025039 and rs2010963 polymorphisms of the VEGF gene were investigated using T-ARMS-PCR. The T allele of rs3025039 was 2.79 times more frequent in GBM patients compared to controls (P0.01). Moreover, the CT genotype was 2.83 times more common among patients (P0.015), while the CC was more frequent in controls (P0.009). The mean overall survival was significantly different between three genotypes of rs3025039, with the longest survival time in CT genotype (15.10±5.21, P0.041). Besides, rs2010963, was significantly associated with GBM occurrence, with the G allele being 1.96 times more frequent in patients (P0.01), as well as the GG genotype, which was 7.87 times more common in patients (P<0.001). Polymorphisms of VEGF could potentially play a role in pathogenesis of GBM, as the allele and genotype distributions of rs3025039 and rs2010963 SNPs were significantly associated with GBM occurrence.

Rotary Structural Color Spindles from Droplet Confined Magnetic Self-Assembly.

Structural colors materials are profoundly explored owing to their fantastic optical properties and widespread applications. Development of structural color materials bearing flexible morphologies and versatile functionalities is highly anticipated. Here, a droplet-confined, magnetic-induced self-assembly strategy for generating rotary structural color spindles (SCSPs) by fast solvent extraction is proposed. The as-prepared SCSPs exhibit an orderly close-packed lattice structure, thus appearing brilliant structural colors that serve as encoding tags for multiplexed bioassays. Besides, benefitting from the abundant specific surface area, biomarkers can be labeled on the SCSPs with high efficiency for specific detection of analytes in clinical samples. Moreover, the directional magnetic moment arrangement enables contactless magnetic manipulation of the SCSPs, and the resultant rotary motions of the SCSPs generates turbulence in the detection solution, thus significantly improving the detection efficiency and shortening the detection time. Based on these merits, a portable point-of-care-testing strip integrating the rotary SCSPs is further constructed and the capability and advantages of this platform for multiplexed detection of tumor-related exosomes in clinical samples are demonstrated. This study offers a new way for the control of bottom-up self-assembly and extends the configuration and application values of colloidal crystal structural colors materials.

A Highly Translatable Dual-arm Local Delivery Strategy To Achieve Widespread Therapeutic Coverage in Healthy and Tumor-bearing Brain Tissues.

Drug delivery nanoparticles (NPs) based entirely on materials generally recognized as safe that provide widespread parenchymal distribution following intracranial administration via convection-enhanced delivery (CED) are introduced. Poly(lactic-co-glycolic acid) (PLGA) NPs are coated with various poloxamers, including F68, F98, or F127, via physical adsorption to render particle surfaces non-adhesive, thereby resisting interactions with brain extracellular matrix. F127-coated PLGA (F127PLGA) NPs provide markedly greater distribution in healthy rat brains compared to uncoated NPs and widespread coverage in orthotopically-established brain tumors. Distribution analysis of variously-sized F127PLGA NPs determines the average rat brain tissue porosity to be between 135 and 170 nm while revealing unprecedented brain coverage of larger F127PLGA NPs with an aid of hydraulic pressure provided by CED. Importantly, F127PLGA NPs can be lyophilized for long-term storage without compromising their ability to penetrate the brain tissue. Further, 65- and 200-nm F127PLGA NPs lyophilized-reconstituted and administered in a moderately hyperosmolar infusate solution show further enhance particle dissemination in the brain via osmotically-driven enlargement of the brain tissue porosity. Combination of F127PLGA NPs and osmotic tissue modulation provides a means with a clear regulatory path to maximize the brain distribution of large NPs that enable greater drug loading and prolong drug release.

Safety of the utilization of telemedicine for brain tumor neurosurgery follow-up.

There is a need to evaluate the outcomes of patients who underwent brain tumor surgery with subsequent telemedicine or in-person follow-up during the COVID-19 pandemic. We retrospectively included all patients who underwent surgery for brain tumor resection by a single neurosurgeon at our Institution from the beginning of the COVID-19 pandemic restrictions (March 2020) to August 2021. Outcomes were assessed by stratifying the patients using their preference for follow-up method (telemedicine or in-person). Three-hundred and eighteen (318) brain tumor patients who were included. The follow-up method of choice was telemedicine (TM) in 185 patients (58.17%), and in-person (IP) consults in 133 patients. We found that patients followed by TM lived significantly farther, with a median of 36.34 miles, compared to a median of 22.23 miles in the IP cohort ( Telehealth follow-up alternatives may be safely offered to patients after brain tumor surgery, thereby reducing patient burden in those with longer distances to the hospital or special situations as the COVID-19 pandemic.

Evaluation of setup errors of immobilization device for radiation therapy in companion animals.

Intensity-modulated radiotherapy (IMRT), which allows generating steep dose gradients, is a beneficial treatment for companion animals with adjacent target and risk organs. IMRT is essential for high setup accuracy for avoiding overdose to risk organs, and optimal radiotherapy is important for evaluating the setup accuracy of companion animals. To use an immobilization device to evaluate setup errors in radiotherapy for companion animals. We calculated setup errors in radiotherapy for 386 animals (dogs and cats 3,261 registration images) that underwent radiotherapy between 2016 and 2022. The companion animals were immobilized with a customized bite block and vacuum lock device. A quantile-quantile plot with 95% confidence interval (CI) was used to evaluate the histogram of the setup errors, and the systematic and random setup errors were calculated for each region (brain, head and neck, chest and abdomen, pelvis, and spine). The setup error in each direction presented an extremely narrow-interval histogram, with the following lower and upper 95% CIs cranial-caudal (-0.08, -0.06 cm) left-right (-0.04, -0.02 cm) and dorsal-ventral (-0.13, -0.11 cm). The mean systematic setup error was 0.16 cm (range 0.12-0.36 cm), and the random error was 0.15 cm (range 0.08-0.34 cm). The pelvis showed the highest systematic and random setup errors (mean 0.36 and 0.23 cm, respectively). The use of an immobilization device enables highly accurate radiotherapy for companion animals (95% CI < 0.15 cm).

A data assimilation framework to predict the response of glioma cells to radiation.

We incorporate a practical data assimilation methodology into our previously established experimental-computational framework to predict the heterogeneous response of glioma cells receiving fractionated radiation treatment. Replicates of 9L and C6 glioma cells grown in 96-well plates were irradiated with six different fractionation schemes and imaged via time-resolved microscopy to yield 360- and 286-time courses for the 9L and C6 lines, respectively. These data were used to calibrate a biology-based mathematical model and then make predictions within two different scenarios. For Scenario 1, 70% of the time courses are fit to the model and the resulting parameter values are averaged. These average values, along with the initial cell number, initialize the model to predict the temporal evolution for each test time course (10% of the data). In Scenario 2, the predictions for the test cases are made with model parameters initially assigned from the training data, but then updated with new measurements every 24 hours via four versions of a data assimilation framework. We then compare the predictions made from Scenario 1 and the best version of Scenario 2 to the experimentally measured microscopy measurements using the concordance correlation coefficient (CCC). Across all fractionation schemes, Scenario 1 achieved a CCC value (mean ± standard deviation) of 0.845 ± 0.185 and 0.726 ± 0.195 for the 9L and C6 cell lines, respectively. For the best data assimilation version from Scenario 2 (validated with the last 20% of the data), the CCC values significantly increased to 0.954 ± 0.056 (p 0.002) and 0.901 ± 0.061 (p 8.9e-5) for the 9L and C6 cell lines, respectively. Thus, we have developed a data assimilation approach that incorporates an experimental-computational system to accurately predict the in vitro response of glioma cells to fractionated radiation therapy.

Improved U-Net based on cross-layer connection for pituitary adenoma MRI image segmentation.

Pituitary adenoma is a common neuroendocrine neoplasm, and most of its MR images are characterized by blurred edges, high noise and similar to surrounding normal tissues. Therefore, it is extremely difficult to accurately locate and outline the lesion of pituitary adenoma. To sovle these limitations, we design a novel deep learning framework for pituitary adenoma MRI image segmentation. Under the framework of U-Net, a newly cross-layer connection is introduced to capture richer multi-scale features and contextual information. At the same time, full-scale skip structure can reasonably utilize the above information obtained by different layers. In addition, an improved inception-dense block is designed to replace the classical convolution layer, which can enlarge the effectiveness of the receiving field and increase the depth of our network. Finally, a novel loss function based on binary cross-entropy and Jaccard losses is utilized to eliminate the problem of small samples and unbalanced data. The sample data were collected from 30 patients in Quzhou Peoples Hospital, with a total of 500 lesion images. Experimental results show that although the amount of patient sample is small, the proposed method has better performance in pituitary adenoma image compared with existing algorithms, and its Dice, Intersection over Union (IoU), Matthews correlation coefficient (Mcc) and precision reach 88.87, 80.67, 88.91 and 97.63%, respectively.

Food Color Additives in Hazardous Consequences of Human Health An Overview.

Food color additives are used to make food more appetizing. The United States Food and Drug Administration (FDA) permitted nine artificial colorings in foods, drugs, and cosmetics, whereas the European Union (EU) approved five artificial colors (E-104, 122, 124, 131, and 142) for food. However, these synthetic coloring materials raise various health hazards. The present review aimed to summarize the toxic effects of these coloring food additives on the brain, liver, kidney, lungs, urinary bladder, and thyroid gland. In this respect, we aimed to highlight the scientific evidence and the crucial need to assess potential health hazards of all colors used in food on human and nonhuman biota for better scrutiny. Blue 1 causes kidney tumor in mice, and there is evidence of death due to ingestion through a feeding tube. Blue 2 and Citrus Red 2 cause brain and urinary bladder tumors, respectively, whereas other coloring additives may cause different types of cancers and numerous adverse health effects. In light of this, this review focuses on the different possible adverse health effects caused by these food coloring additives, and possible ways to mitigate or avoid the damage they may cause. We hope that the data collected from in vitro or in vivo studies and from clinical investigations related to the possible health hazards of food color additives will be helpful to both researchers and the food industry in the future.

Circular RNA hsacirc0075323 promotes glioblastoma cells proliferation and invasion via regulation of autophagy.

Protein p62 (sequestosome 1) encoded by gene SQSTM1 plays a vital role in mediating protectively selective autophagy in tumor cells under stressed conditions. CircSQSTM1 (hsacirc0075323) is a circular transcript generated from gene SQSTM1 (chr5179260586-179260782) by back-splicing. However, the potential role of hsahsacirc0075323 in glioblastoma (GBM) remains unclear. Here, we aimed to explore the biological function of hsacirc0075323 in GBM and its relationship with autophagy regulation. Hsacirc0075323 is highly expressed in GBM cells and mainly locates in the cytoplasm. Inhibition of hsacirc0075323 in U87-MG and T98G cells attenuated proliferation and invasion ability significantly, while upregulation of has circ0075323 enhanced proliferation and migration of U251-MG and A172 cells. Mechanistically, depletion of hsacirc0075323 in GBM cells resulted in impaired autophagy, as indicated by increased expression of p62 and decreased expression of LC3B. Hsacirc0075323 regulates p62-mediated autophagy pathway to promote GBM progression and may serve as a prognostic biomarker potentially.

Stem cell-nanomedicine system as a theranostic bio-gadolinium agent for targeted neutron capture cancer therapy.

The potential clinical application of gadolinium-neutron capture therapy (Gd-NCT) for glioblastoma multiforme (GBM) treatment has been compromised by the fast clearance and nonspecific biodistribution of gadolinium-based agents. We have developed a stem cell-nanoparticle system (SNS) to actively target GBM for advanced Gd-NCT by magnetizing umbilical cord mesenchymal stem cells (UMSCs) using gadodiamide-concealed magnetic nanoparticles (Gd-FPFNP). Nanoformulated gadodiamide shielded by a dense surface composed of fucoidan and polyvinyl alcohol demonstrates enhanced cellular association and biocompatibility in UMSCs. The SNS preserves the ability of UMSCs to actively penetrate the blood brain barrier and home to GBM and, when magnetically navigates by an external magnetic field, an 8-fold increase in tumor-to-blood ratio is achieved compared with clinical data. In an orthotopic GBM-bearing rat model, using a single dose of irradiation and an ultra-low gadolinium dose (200 μg kg

Imaging findings of supratentorial embryonal tumor with multilayered rosettes in children.

We analyzed and summarized the imaging characteristics and clinical data of seven pediatric supratentorial embryonal tumors with multilayered rosettes (ETMR). There were four boys and three girls aged from two to six years old. Pediatric supratentorial ETMR often presented large cystic and solid mass, calcification, significant mass effect and mild peritumoral edema. The solid part often showed heterogeneous mild enhancement. In combination with the location of tumor and age of onset, the typical imaging manifestations of supratentorial ETMR in children are valuable for accurate diagnosis. 本文回顾性分析7例幕上多层菊形团样胚胎性肿瘤患儿的临床及影像学资料，男4例，女3例，年龄26岁。结果发现儿童幕上多层菊形团样胚胎性肿瘤常表现为较大囊实性肿瘤，有钙化，占位效应显著，轻度的瘤周水肿，常表现为轻度不均匀强化。影像学表现结合患者发病年龄及部位，可提高其诊断准确率。.

Construction and analysis of functional network of hemi-brain in patients with brain tumors before and after anesthesia based on resting-state functional magnetic resonance imaging.

Nanoparticles in the diagnosis and treatment of cancer metastases Current and future perspectives.

Metastasis accounts for greater than 90% of cancer-related deaths. Despite recent advancements in conventional chemotherapy, immunotherapy, targeted therapy, and their rational combinations, metastatic cancers remain essentially untreatable. The distinct obstacles to treat metastases include their small size, high multiplicity, redundancy, therapeutic resistance, and dissemination to multiple organs. Recent advancements in nanotechnology provide the numerous applications in the diagnosis and prophylaxis of metastatic diseases, including the small particle size to penetrate cell membrane and blood vessels and their capacity to transport complex molecular cargo particles to various metastatic regions such as bones, brain, liver, lungs, and lymph nodes. Indeed, nanoparticles (NPs) have demonstrated a significant ability to target specific cells within these organs. In this regard, the purpose of this review is to summarize the present state of nanotechnology in terms of its application in the diagnosis and treatment of metastatic cancer. We intensively reviewed applications of NPs in fluorescent imaging, PET scanning, MRI, and photoacoustic imaging to detect metastasis in various cancer models. The use of targeted NPs for cancer ablation in conjunction with chemotherapy, photothermal treatment, immuno therapy, and combination therapy is thoroughly discussed. The current review also highlights the research opportunities and challenges of leveraging engineering technologies with cancer cell biology and pharmacology to fabricate nanoscience-based tools for treating metastases.

Retrospective dataset and survey analyses identify gaps in data collection for craniopharyngioma and priorities of patients and families affected by the disease.

Craniopharyngioma is a rare, low-grade tumor located in the suprasellar region of the brain, near critical structures like the pituitary gland. Here, we concurrently investigate the status of clinical and genomic data in a retrospective craniopharyngioma cohort and survey-based data to better understand patient-relevant outcomes associated with existing therapies and provide a foundation to inform new treatment strategies. Clinical, genomic, and outcome data for a retrospective cohort of patients with craniopharyngioma were collected and reviewed through the Childrens Brain Tumor Network (CBTN) database. An anonymous survey was distributed to patients and families with a diagnosis of craniopharyngioma to understand their experiences throughout diagnosis and treatment. The CBTN repository revealed a large proportion of patients (40 - 70%) with specimens that are available for sequencing but lacked relevant quality of life (QoL) and functional outcomes. Frequencies of reported patient comorbidities ranged from 20 to 25%, which is significantly lower than historically reported. Survey results from 159 patientsfamilies identified differences in treatment considerations at time of diagnosis versus time of recurrence. In retrospective review, patients and families identified preference for therapy that would improve QoL, rather than decrease risk of recurrence (mean 3.9 vs. 4.4 of 5) and identified endocrine issues as having the greatest impact on patients lives. This work highlights the importance of prospective collection of QoL and functional metrics alongside robust clinical and molecular correlates in individuals with craniopharyngioma. Such comprehensive measures will facilitate biologically relevant therapeutic strategies that also prioritize patient needs.

Targeting Microglial Metabolic Rewiring Synergizes with Immune Checkpoint Blockade Therapy for Glioblastoma.

Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)-dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2-) or microglia-specific Nr4a2 (Nr4a2flflCx3cr1cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8 T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacological NR4A2 inhibition attenuated the pro-tumorigenic TIME, and targeting the NR4A2 or SQLE enhanced therapeutic efficacy of immune checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2-SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer.