Glial Tumor Cells Research Articles

Toxicity of Large and Small Surface-Engineered Upconverting Nanoparticles for In Vitro and In Vivo Bioapplications.

In this study, spherical or hexagonal NaYF4:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells (rat glial tumor cell line) was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real-time proliferation assay. The comet assay was used to determine the oxidative damage of the UCNPs. An in vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. The proliferation assay revealed that the L-UCNPs were less toxic than S-UCNPs. The viability of rMSCs incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. The oxidative damage measured by the comet assay showed that neat L-UCNPs caused more oxidative damage to rMSCs than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.

Impact of Tailored Intensive Rehabilitation on Functional Independence and Quality of Life in Brain Tumor Patients: A Prospective Observational Study

Background: Brain tumors are a heterogeneous group causing disability. They significantly impact functional independence and quality of life. This study aims to investigate how tailored intensive rehabilitation affects brain tumor patients using the functional independency measure score.
 Materials and Methods: This is a prospective observational correctional study conducted in the department of Neurophysiotherapy and Neurosurgery at Nobel Medical College Teaching Hospital, Biratnagar over a period of 18 months. A total of 96 brain tumor patients who underwent surgery at a tertiary care centerduring the study period were included. Along with the demographic data, the diagnosis ofbrain tumor functional independency was assessed using the Functional Independence Measure Index.
 Results: A total of 96 brain tumor patients (44 males, 52 females, average age 55.6 years) were studied. The tumors' distribution showed variations, with glial tumors being the most frequent (36.4%). The Functional Independence Measure (FIM) Index was used to assess functional independence, yielding an average score of 82.5. Patients with meningioma had higher FIM scores (84.3) compared to glial cell tumor patients (80.1), although not statistically significant (p = 0.122).The study also explored correlations between FIM scores, hospital stay duration (average 9 days), and patient satisfaction. A weak positive correlation (r = 0.25) existed between FIM scores and hospital stay duration.A moderate positive correlation (r = 0.65) was found between FIM scores and patient satisfaction, suggesting higher satisfaction among patients with better functional independence.
 Conclusion: Intensive rehabilitation therapy shows promise in improving functional independence in brain tumor patients.

In vitro investigation of the effects of high-intensity therapeutic ultrasound (HITU) in glial tumor cell culture.

Amidst the evident challenges posed by brain tumors and the evident limitations of conventional treatment methodologies like surgery, radiotherapy, and chemotherapy, our primary objective was to probe the therapeutic potential of high-intensity therapeutic ultrasound (HITU). The aim was to introduce a safer, cost-effective, and efficient alternative to existing treatments, especially beneficial for inaccessible brain tumor sites and resource-constrained medical facilities. Leveraging post-1990s MR technology advancements, we employed the non-invasive HITU technique, akin to high-intensity focused ultrasound. This method directs acoustic energy to tissues, primarily inducing coagulation necrosis by absorbing energy and elevating tissue temperatures. Glial tumor cells were subjected to HITU to assess its effects. Upon applying HITU to glial tumor cells, significant alterations in cellular structural integrity were evident. The main action of HITU was the absorption of acoustic energy, leading to a notable temperature rise and coagulation necrosis. Flow cytometry indicated significant cellular changes post-HITU. ANOVA and t-test analyses showed a significant relationship between HITU application and time (p<0.05). The Shapiro-Wilk test revealed non-normal data distribution (p<0.05), leading to the use of nonparametric methods. The t-test results after HITU displayed significant differences (p<0.05) in cell counts and fluorescence intensity between control and treated groups. This result was consistent across multiple tests, indicating the reliability of the method in causing cellular damage to the tumor cells. Our laboratory analyses offer compelling evidence that HITU is not merely feasible but is also a promising non-invasive approach in the treatment paradigm of brain tumors. Standing distinctively apart from radiotherapy, HITU averts early, or late complications commonly associated with the former. While the path ahead mandates comprehensive research to ascertain its clinical utility, preliminary indications firmly posit HITU as a groundbreaking prospect in the management of brain tumors.

Evaluating interleukin-16 expression in patients with grade-3 and grade-4 glial cell tumors and healthy individuals.

This study evaluated the change in IL-16 levels in patients with high-grade glial tumors undergoing radiotherapy (RT) and healthy individuals (control group). Serum IL-16 levels of 35 high-grade glioma patients receiving radiotherapy (RT) and 30 healthy individuals were compared. We compared the IL-16 levels before (RT0) and after the (RT1) and IL-16 levels were measured and the relationship of this change with other characteristics such as age, gender, weight, height, and blood test results. The RT0-IL-16 level was approximately 15 pg/ml higher than the RT1 measurement in the patient group. The mean RT0-IL-16 levels in the patient group were approximately 10 pg/ml higher than the mean IL-16 levels in the control group. Likewise, at the RT1 time-point, the mean IL-16 levels for the patient group were approximately 5 pg/ml lower than the mean IL-16 for the control group. The mean RT0-RT1-IL-16 value tended to be higher in female patients than in male patients. The application of RT reduces the overall IL-16 levels, suggesting the efficacy of RT, as well as the role of IL-16 in tumorigenesis.

HGG-18. SINGLE CELL RNA-SEQ ANALYSIS OF PEDIATRIC HIGH-GRADE GLIOMA PATIENT SAMPLES IDENTIFIES COMMON GLIAL AND IMMUNE CELL TYPES THAT HELP TO EXPLAIN HETEROGENEITY AND TUMORIGENESIS

Abstract BACKGROUND Pediatric high-grade gliomas (PHGG) are aggressive, undifferentiated central nervous system (CNS) tumors. PHGG comprises subtypes that differ phenotypically, histologically and by cellular composition. Despite intensive research, overall survival rates have remained for decades around 2% for diffuse midline glioma (DMG) and 20% for non-DMG PHGG. We hypothesized that PHGG’s heterogeneity, a key difficulty in devising therapies, results from functional and lineage differences in tumor cell types. METHODS Using 19 PHGG samples from our institution’s pediatric brain tumor bank, we constructed a single-cell RNA-Seq (scRNA-Seq) dataset that included tumor and immune cells, generated predicted cell types by mapping the scRNA-Seq data onto known cell types, and performed differential gene expression and geneset enrichment analyses. We acquired bulk RNA-Seq and DNA methylation data to characterize overall tumor properties. RESULTS Samples consisted of several principal tumor cell types, including cells with astrocyte characteristics, oligodendrocyte progenitor cell (OPC) characteristics, and cells that expressed OPC markers but had slight enrichment in mesenchymal and inflammatory gene expression (OPC-like/Mes cells). We also found a potential stemlike population that expressed neural stem cell markers. The predicted astrocytes, OPCs and OPC-like/Mes cells differed in their gene expression profiles, pathway enrichment, and tendency to proliferate as assessed from expression of cell cycle genes. A combined microglia/macrophage population, strongly enriched in mesenchymal and inflammatory gene expression, may serve to induce inflammatory gene expression in tumor cells. Key conclusions from the scRNA-Seq analysis were validated using multi-channel immunofluorescence staining. CONCLUSIONS PHGG comprises a small stemlike population and varying proportions of proliferating glial lineage tumor cells. CNS-resident microglia/macrophages may trigger mesenchymal gene expression in PHGG. We will use our results to investigate the roles of PHGG’s diverse tumor cell populations in resistance to radiotherapy and to develop treatments to target individual cell types comprising PHGG.

Development of DNA aptamers for visualization of glial brain tumors and detection of circulating tumor cells

Here, we present DNA aptamers capable of specific binding to glial tumor cells invitro, exvivo, and invivo for visualization diagnostics of central nervous system tumors. We selected the aptamers binding specifically to the postoperative human glial primary tumors and not to the healthy brain cells and meningioma, using a modified process of systematic evolution of ligands by exponential enrichment to cells; sequenced and analyzed ssDNA pools using bioinformatic tools and identified the best aptamers by their binding abilities; determined three-dimensional structures of lead aptamers (Gli-55 and Gli-233) with small-angle X-ray scattering and molecular modeling; isolated and identified molecular target proteins of the aptamers by mass spectrometry; the potential binding sites of Gli-233 to the target protein and the role of post-translational modifications were verified by molecular dynamics simulations. The anti-glioma aptamers Gli-233 and Gli-55 were used to detect circulating tumor cells in liquid biopsies. These aptamers were used for in situ, exvivo tissue staining, histopathological analyses, and fluorescence-guided tumor and PET/CT tumor visualization in mice with xenotransplanted human astrocytoma. The aptamers did not show invivo toxicity in the preclinical animal study. This study demonstrates the potential applications of aptamers for precise diagnostics and fluorescence-guided surgery of brain tumors.

NIMG-106. WHAT’S BEHIND TSPO PET LABELLING: DIGGING FOR THE HISTOLOGICAL, CELLULAR AND MOLECULAR CORRELATES

Abstract TSPO is frequently upregulated in glioblastoma. Despite its use as an imaging biomarker for PET in glioma, the interpretation is challenging due to the heterogeneity of cell populations that could contribute to the TSPO-PET signal. We therefore dissected TSPO labelling in connection with the underlying histopathological and molecular features in biopsy samples from glioma patients. Comparing regions of high and low TSPO-PET signal in 58 patients, we assessed TSPO protein expression and expression of cell differentiation markers by use of immunohistochemistry on consecutive sections and by multiplex stains. Our results suggest that apart from microglia and macrophages the glial tumor cells relevantly contribute to the overall TSPO signal in glioma patients. To identify hallmarks and GO terms associated with TSPO labelling/expression we next performed RNAseq in 33 patients. Using DESeq2 followed by FUMA and Reactome as well as GSEA with normalized counts, we identified three TSPO-dependent functional clusters, i.e. apoptosis/DNA repair, extracellular matrix organization and immune system. On the DNA level, we analyzed the TSPO promoter by direct bisulfite sequencing suggesting that a loss of TSPO methylation may mechanistically contribute to the TSPO overexpression observed in high-grade gliomas. Exceeding our investigations on glioma biopsies we stained tissue microarrays (130 individuals) for TSPO that cover a broader spectrum of both human brain pathologies (13 different entities) and non-neoplastic tissues (14 different brain regions). We here found a high degree of heterogeneity of TSPO expression between entities and regions. Merging this information with TSPO-PETs from respective patients/brain regions allows to generate a map of TSPO expression in healthy and diseased brain for clinical use. Altogether, our approach of integrating histological, molecular and imaging data will provide unique insights into TSPO-PET enrichment patterns which may help to better understand and to comprehensively describe the clinical relevance of this novel imaging biomarker.

DIPG-54. p53 pathway reactivation as a therapeutic strategy in diffuse intrinsic pontine glioma

TP53 is the most frequently mutated tumor suppressor with somatic alterations found in approximately 50% of all human cancers. In the remaining TP53 wild-type (WT) tumors, functional inactivation of the p53 pathway may be achieved through a variety of other mechanisms, including gene deletion, epigenetic silencing, and/or alterations in prominent negative regulators, including MDM2/MDM4 and PPM1D. These alterations block p53 activity and lead to uncontrolled cell proliferation and oncogenesis in a majority of cancers, including the highly aggressive, universally fatal glial cell tumors of childhood, known as Diffuse Intrinsic Pontine Gliomas (DIPGs). DIPGs are inoperable due to their location within the brainstem. Available treatment options, including radiotherapy, have had a palliative effect at best, with almost all children succumbing to the disease within 18 months of diagnosis. Recent advances have led to an improved understanding of the biological underpinnings of this disease and identification of recurrent genetic alterations that represent potential therapeutic targets for these patients. Prominent among these targets in DIPGs with WT p53 status (50%) are MDM2/4 and PPM1D, whose suppression lead to p53 reactivation specifically in the WT p53 context. We have undertaken a combination of approaches to better understand the therapeutic potential of MDM2 and PPM1D inhibition in DIPG, characterizing the genomic, transcriptomic, and cell-state changes that drive resistance, and identifying novel vulnerabilities that can be exploited with combination therapies towards a cure.

β-Catenin marks proliferating endothelial cells in glioblastoma

BackgroundAngiogenesis is a key process in the growth and maintenance of tumors. The Wnt signaling pathway is required for angiogenesis of the central nervous system though development of the blood–brain barrier and subsequent proliferation of endothelial cells during tumor growth. However, the specificity of the Wnt pathway in regulating endothelial cells of different central nervous systems remains to be investigated. Materials & methodsPatient-derived tissue samples from 35 paraffin-embedded tumors were used to assess β-catenin immunoexpression. Tumor samples consisted of the following pathologies: grade II diffuse astrocytoma, glioblastoma, hemangioblastoma, and metastatic adenocarcinoma (lung or breast primary). Average percent reactivity was recorded as a mean observed in ten high-power fields. The following scale was used to grade immunoreactivity: 0 = immunonegative, 1 = 1–25% reactive, 2 = 26–50% reactive, 3 = 51–75% reactive, 4 = 76–100% reactive. ResultsWhile we did not observe nuclear expression of β-catenin in any samples, there was uniform cytoplasmic expression of β-catenin within glial tumor cells. There was a clear distinction in tumor endothelial cells whereby diffuse staining was noted in areas of microvascular hyperplasia in GBM and a less immunoreactive profile in low-grade astrocytomas. By contrast, non-glial tumors, contained very minimal cytoplasmic β-catenin expression in tumor and stromal cells and were devoid of immunoreactivity in endothelial cells. Conclusionβ-catenin is unique marker of proliferating endothelial cells in GBM. Therapies targeting the spatial and structural heterogeneity inherent to GBM may prove to be efficacious and result in an improved survivorship.

Analysis of Factors Affecting 5-ALA Fluorescence Intensity in Visualizing Glial Tumor Cells-Literature Review.

Glial tumors are one of the most common lesions of the central nervous system. Despite the implementation of appropriate treatment, the prognosis is not successful. As shown in the literature, maximal tumor resection is a key element in improving therapeutic outcome. One of the methods to achieve it is the use of fluorescent intraoperative navigation with 5-aminolevulinic acid. Unfortunately, often the level of fluorescence emitted is not satisfactory, resulting in difficulties in the course of surgery. This article summarizes currently available knowledge regarding differences in the level of emitted fluorescence. It may depend on both the histological type and the genetic profile of the tumor, which is reflected in the activity and expression of enzymes involved in the intracellular metabolism of fluorescent dyes, such as PBGD, FECH, UROS, and ALAS. The transport of 5-aminolevulinic acid and its metabolites across the blood–brain barrier and cell membranes mediated by transporters, such as ABCB6 and ABCG2, is also important. Accompanying therapies, such as antiepileptic drugs or steroids, also have an impact on light emission by tumor cells. Accurate determination of the factors influencing the fluorescence of 5-aminolevulinic acid-treated cells may contribute to the improvement of fluorescence navigation in patients with highly malignant gliomas.

Interaction of Glia Cells with Glioblastoma and Melanoma Cells under the Influence of Phytocannabinoids.

Brain tumor heterogeneity and progression are subject to complex interactions between tumor cells and their microenvironment. Glioblastoma and brain metastasis can contain 30–40% of tumor-associated macrophages, microglia, and astrocytes, affecting migration, proliferation, and apoptosis. Here, we analyzed interactions between glial cells and LN229 glioblastoma or A375 melanoma cells in the context of motility and cell–cell interactions in a 3D model. Furthermore, the effects of phytocannabinoids, cannabidiol (CBD), tetrahydrocannabidiol (THC), or their co-application were analyzed. Co-culture of tumor cells with glial cells had little effect on 3D spheroid formation, while treatment with cannabinoids led to significantly larger spheroids. The addition of astrocytes blocked cannabinoid-induced effects. None of the interventions affected cell death. Furthermore, glial cell-conditioned media led to a significant slowdown in collective, but not single-cell migration speed. Taken together, glial cells in glioblastoma and brain metastasis micromilieu impact the tumor spheroid formation, cell spreading, and motility. Since the size of spheroid remained unaffected in glial cell tumor co-cultures, phytocannabinoids increased the size of spheroids without any effects on migration. This aspect might be of relevance since phytocannabinoids are frequently used in tumor therapy for side effects.

Pigmented ependymoma, a tumor with predilection for the middle-aged adult: case report with methylation classification and review of 16 literature cases.

Ependymomas have rarely been described to contain pigment other than melanin, neuromelanin, lipofuscin or a combination. In this case report, we present a pigmented ependymoma in the fourth ventricle of an adult patient and review 16 additional cases of pigmented ependymoma from the literature. A 46-year-old female showed up with hearing loss, headaches, and nausea. Magnetic resonance imaging revealed a 2.5 cm contrast-enhancing cystic mass in the fourth ventricle, which was resected. Intraoperatively, the tumor appeared grey-brown, cystic, and was adherent to the brainstem. Routine histology revealed a tumor with true rosettes, perivascular pseudorosettes and ependymal canals consistent with ependymoma, but also showed chronic inflammation and abundant distended pigmented tumor cells that mimicked macrophages in frozen and permanent sections. The pigmented cells were positive for GFAP and negative for CD163 consonant with glial tumor cells. The pigment was negative for Fontana-Masson, positive for Periodic-acid Schiff and autofluorescent, which coincide with characteristics of lipofuscin. Proliferation indices were low and H3K27me3 showed partial loss. H3K27me 3 is an epigenetic modification to the DNA packaging protein Histone H3 that indicates the tri-methylation of lysine 27 on histone H3 protein. This methylation classification was compatible with a posterior fossa group B ependymoma (EPN_PFB). The patient was clinically well without recurrence at three-month post-operative follow-up appointment. Our analysis of all 17 cases, including the one presented, shows that pigmented ependymomas are most common in the middle-aged with a median age of 42 years and most have a favorable outcome. However, one patient that also developed secondary leptomeningeal melanin accumulations died. Most (58.8%) arise in the 4th ventricle, while spinal cord (17.6%) and supratentorial locations (17.6%) were less common. The age of presentation and generally good prognosis raise the question of whether most other posterior fossa pigmented ependymomas may also fall into the EPN_PFB group, but additional study is required to address that question.

Clinicopathological study of pineal gland lesions

Background: Pineal parenchymal tumors are the second most common form of pineal tumor.Aims: To study the incidence, age distribution, gender distribution of pineal region tumors and post-operative outcome.Materials and Methods: The present study is a prospective study comprising 20 cases of Pineal Region tumors, studied over a two and half year period. Data related to all cases were retrieved from archives. Available clinical data including, patient age, sex, clinical features, Imaging and surgical findings, tumor histology, outcome were also received from the Department of Neurosurgery Medical record Department. All pineal region tumors received at Neurosurgery department with adequate pre-operative; intra-operative and postoperative information were included in the study. Pineal region tumors comprising the Pineal parenchymal cell tumors, Germ cell tumors, Glial cell tumors, and other miscellaneous tumors and cysts.Results: Most common age group for the pineal region tumors is second and third decade and the Male to Female ratio is 1:1. Malignant nature of pineal region tumors is 17 cases incidence being 85%. Predominant grade of the pineal region tumors are grade I tumors commonest presenting symptoms being headache and vomiting. Commonest clinical sign is papilledema of features suggestive raised intracranial pressure. Most of patients presented at delayed stage with large tumor and morbid state with hydrocephalus, majority of the patients underwent shunt surgery before definitive surgery, some patients underwent external ventricular drainage simultaneously after surgery. No surgical mortality, one patient detoriated after third post operative day did not recovered and died. Inpatient had developed meningitis, sepsis didn't recover and died. Mortality 2 cases. Medium follow up period is one year. Three cases followed recurrent symptoms advised radiotherapy. Two cases came with shunt malfunction. Conclusion: Many of the approaches are interchangeable and they are depending on anatomical location and surgeon s choice and experience.

"Smart" nanoscalpel for microsurgery of glial tumors of the human brain

We studied the effectiveness of magnetomechanical therapy in the treatment of brain glial tumors using magnetic nanodiscs functionalized with DNA aptamers to human brain tumor glial cells. • Materials and methods. The formation of a model of human glioblastoma was carried out by intracranial injection of tumor cells of glioblastoma obtained from a patient with glioblastoma. Antitumor therapy was carried out using nanodiscs modified with the Gli233 aptamer. The growth of the glial tumor was monitored using NMR tomography. • Results and discussion. Therapy of a glial tumor during 4 sessions of magnetomechanical therapy using a "smart" nanoscalpel in MF (10Hz, 100Oe) led to a significant reduction in its size, while glial tumors in mice that were treated with nanodiscs modified with nonspecific aptamers continued to increase in size. • Conclusion. Microsurgery using three-layer magnetic nanodisks with a quasi-dipole structure (Au/Ni/Au) modified with the specific for glial cells Gli233 aptamer (“smart” nanoscalpel) is effective for the treatment of human glial tumors in the brain.

Transmembrane Protein TMEM230, a Target of Glioblastoma Therapy.

Glioblastomas (GBM) are the most aggressive tumors originating in the brain. Histopathologic features include circuitous, disorganized, and highly permeable blood vessels with intermittent blood flow. These features contribute to the inability to direct therapeutic agents to tumor cells. Known targets for anti-angiogenic therapies provide minimal or no effect in overall survival of 12–15 months following diagnosis. Identification of novel targets therefore remains an important goal for effective treatment of highly vascularized tumors such as GBM. We previously demonstrated in zebrafish that a balanced level of expression of the transmembrane protein TMEM230/C20ORF30 was required to maintain normal blood vessel structural integrity and promote proper vessel network formation. To investigate whether TMEM230 has a role in the pathogenesis of GBM, we analyzed its prognostic value in patient tumor gene expression datasets and performed cell functional analysis. TMEM230 was found necessary for growth of U87-MG cells, a model of human GBM. Downregulation of TMEM230 resulted in loss of U87 migration, substratum adhesion, and re-passaging capacity. Conditioned media from U87 expressing endogenous TMEM230 induced sprouting and tubule-like structure formation of HUVECs. Moreover, TMEM230 promoted vascular mimicry-like behavior of U87 cells. Gene expression analysis of 702 patients identified that TMEM230 expression levels distinguished high from low grade gliomas. Transcriptomic analysis of patients with gliomas revealed molecular pathways consistent with properties observed in U87 cell assays. Within low grade gliomas, elevated TMEM230 expression levels correlated with reduced overall survival independent from tumor subtype. Highest level of TMEM230 correlated with glioblastoma and ATP-dependent microtubule kinesin motor activity, providing a direction for future therapeutic intervention. Our studies support that TMEM230 has both glial tumor and endothelial cell intracellular and extracellular functions. Elevated levels of TMEM230 promote glial tumor cell migration, extracellular scaffold remodeling, and hypervascularization and abnormal formation of blood vessels. Downregulation of TMEM230 expression may inhibit both low grade glioma and glioblastoma tumor progression and promote normalization of abnormally formed blood vessels. TMEM230 therefore is both a promising anticancer and antiangiogenic therapeutic target for inhibiting GBM tumor cells and tumor-driven angiogenesis.

Pathology of Gliomas and the Role Immunotherapy Plays in Combatting Glioma Proliferation

Glioma, a type of tumor arising from the brain and/or spinal cord, is a relatively broad term, encompassing three main types of glial cell tumors: astrocytoma, ependymoma, and oligodendroglioma. A prognosis for a glioma can often be extremely poor, with an overall survival rate of 54.84%. With around 20,000 gliomas being diagnosed each year, it is imperative that effective treatments are developed for management of these tumors. A popular treatment pathway for the treatment of gliomas is surgery along with chemo-radiation therapy such as Temozolomide. This current treatment plan, though, has a moderate effect on lengthening glioma patients’ prognoses. The average survival of this plan is 3 to 6 months. New treatments in the field of immunotherapies may have promising effects for glioma patients’ prognoses. Arising developments in immunotherapy glioma treatment and management is an important field to investigate to further improve the effectivity of cancer treatment for glioma patients. Certain immunotherapies in trials have proven to make impactful improvements to glioma prognoses, one trial showing an increase of 2 months in median survival. This literature review will focus on the pathology and characteristics of the proliferation of malignant glioma cells and the role immunotherapy plays in combatting glioma proliferation

Retinal tumors in adults: Part2 nonvascular tumors of retina and retinal pigment epithelium

Retinal tumors are aheterogeneous group of congenital and acquired lesions. In the second part of the article retinocytic and glial cell tumors of the retina, tumors of the retinal pigment epithelium, malignant tumors, such as lymphomas and metastases are presented. In benign and malignant tumors visual symptoms, such as exudative retinal detachment occur, which often lead to irreversible visual impairments. Because visual symptoms are often amanifestation of systemic diseases, the ophthalmologist plays an important role in the accurate and early diagnosis of retinal tumors. This article reviews the most important clinical and diagnostic features of retinal tumors in adults, the systemic associations and the literature on currently available treatment strategies.

Antitumor efficiency of combination of bortezomib and themosolomide on subcutaneous PDX-model of human glioblastoma.

e15011 Background: Poor clinical effects of standard treatment for glioblastoma determine the need for the development of new therapeutic strategies. Aberrant functioning of the proteasome system, as well as activation of the HIF-1α signaling pathway, are characteristic of glial tumor cells; they can be considered as potential therapeutic targets in the treatment of malignant brain tumors. One of the possible options for improving the results of glioblastoma treatment may involve strategies for inhibiting the HIF-1α pathway. Bortezomib, a proteasome inhibitor, can block the biological effects of HIF-1α. Bortezomib showed a pronounced antitumor effect in in vitro testing on various models of solid malignant tumors, giving grounds for further studies of its effectiveness in vivo. Patient-derived xenograft (PDX) models are characterized by a variety of cell subclones and are therefore considered the most reliable tool for predicting therapeutic responses. Methods: A PDX model of glioblastoma was created in 20 Balb/c Nude mice implanted with a subcutaneously inoculated human glioblastoma. Temozolomide (0.5 mg/kg), bortezomib (0.25 mg/kg), or a combination of temozolomide and bortezomib were administered intraperitoneally daily for 21 days. The tumor histotype was confirmed by histological analysis (staining with hematoxylin and eosin). The antitumor effect was determined by the inhibition of tumor growth (ITG%), the volume of tumor nodes, and the index of tumor growth. Results: The highest value of the inhibition of tumor growth (ITG%) was registered in the group of animals receiving a combination of temozolomide and bortezomib – 85.38%. The values in the groups receiving temozolomide or bortezomib monotherapy were 57.32% and 63.11%, respectively. Conclusions: An analysis of the antitumor efficacy of bortezomib combined with temozolomide in human subcutaneous PDX-glioblastomas demonstrated their synergistic effect.

Preparation of primary glial tumor cell lines

Objective. The aim of this work was to obtain the primary cell lines of brain malignant tumors using the explant method.&#x0D; Materials and methods. Thirteen patients of both sexes, aged 22 to 66, were recruited. The tumor material of the patients was fragmented and placed in flasks with complete nutrient medium for glial tumor cells. Subsequently, the material was photographed at various stages of cultivation, the cell morphology was determined, and the rate of monolayer formation at the zero and first passages was assessed.&#x0D; Results. As a result, thirteen primary human cell lines of glial tumors were obtained: six glioblastoma lines, two glioblastoma lines with anaplastic astrocytoma, one anaplastic oligodendroglioma line, one diffuse astrocytoma line, one oligoastrocytoma line and one diffuse protoplasmic astrocytoma line, one anaplastic astrocytoma line. In the culture of diffuse astrocytoma, there were observed the cells forming a network at the bottom of the flask. In the culture of anaplastic astrocytoma at a confluence of 3050 %, fibroblast-like cells were presented, and at a confluence of 100 %, a monolayer was formed with cells intimately adjacent to each other. In the culture of oligoastrocytoma, both fibroblast-like cells and islets of closely intertwined fusiform cells were observed. The same was typical for the cells of diffuse protoplasmic astrocytoma. Anaplastic oligodendroglioma during the first week of cultivation was represented mainly by round cells with a contrast agent, which subsequently attached and actively proliferated. At a confluence of 3080 %, fibroblast-like cells were observed, and at 100 %, spindle-shaped cells closely adjacent to each other. In cultures of glioblastomas, no specific character of cell growth was revealed: spindle-shaped, fibroblast-like cells and cells with long processes forming a network were encountered. Glioblastoma cultures against the background of anaplastic astrocytoma were represented by a network of cells with long processes.&#x0D; At the zero passage, the rate of formation of a 100 % confluence monolayer ranged from 22 to 85 days. At the first passage, the cells reached a full monolayer within 4 to 25 days. At the zero passage, the longest time among all the samples to form the monolayer with a 100 % confluence needed glioblastoma lines on average 59 days. The shortest time to reach a 100 % confluence was required for cells of diffuse astrocytoma, anaplastic oligodendroglioma and glioblastoma against the background of anaplastic astrocytoma 2224 days.&#x0D; Conclusions. In our work, it was shown that the explant method ensures the production of viable cells of glial tumors and the possibility of their further cultivation.

Therapeutic pathomorphosis in malignant glioma tissues after photodynamic therapy with сhlorin e6 (reports of two clinical cases)

In recent years, photodynamic therapy (PDT) has been increasingly introduced into the surgical practice of treating malignant neoplasms. In this publication, the authors show the appearance of therapeutic pathomorphosis in vivo in human malignant glioma cells after intraoperative photodynamic therapy. Tissue samples obtained 10–14 days after PDT revealed nuclear and cytoplasmic signs indicating apoptosis, necrosis, and autophagy. A decrease in the proliferative activity of glial tumor cells and their higher death count were detected.. Immunohistochemical analysis shows decreases expression of Ki-67 cell proliferation marker and decreased amount of transcription factor protein p53.