Human Glioma U251 Research Articles

Studying the Oncolytic Activity of Streptococcus pyogenes Strains Against Hepatoma, Glioma, and Pancreatic Cancer In Vitro and In Vivo.

Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A Streptococcus (GAS) strains for tumor treatment. This study aimed to investigate the oncolytic efficacy of S. pyogenes GUR and its M protein knockout mutant, S. pyogenes strain GURSA1, which was genetically constructed to minimize overall toxicity, against mouse hepatoma 22A, pancreatic cancer PANC02, and human glioma U251 cells, both in vitro and in vivo, using the C57BL/6 mouse model. The in vitro oncolytic cytotoxic activity of GAS strains was studied against human glioma U251, pancreatic cancer PANC02, murine hepatoma 22a, and normal skin fibroblast cells using the MTT assay and the real-time xCELLigence system. A syngeneic mouse model of hepatoma and pancreatic cancer was used to evaluate the in vivo oncolytic effect of GAS strains. Statistical analysis was conducted using Student's t-test and Mann-Whitney U-test with GraphPad Prism software. The in vitro model showed that the live S. pyogenes GUR strain had a strong cytotoxic effect (67.4 ± 1.9%) against pancreatic cancer PANC02 cells. This strain exhibited moderate (38.0 ± 1.8%) and weak (16.3 ± 5.4%) oncolytic activities against glioma and hepatoma cells, respectively. In contrast, the S. pyogenes GURSA1 strain demonstrated strong (86.5 ± 1.6%) and moderate (36.5 ± 1.8%) oncolytic activities against glioma and hepatoma cells. Additionally, the S. pyogenes GURSA1 strain did not exhibit cytotoxic activity against healthy skin fibroblast cells (cell viability 104.2 ± 1.3%, p = 0.2542). We demonstrated that tumor treatment with S. pyogenes GURSA1 significantly increased the lifespan of C57BL/6 mice with hepatoma (34 days, p = 0.040) and pancreatic cancer (32 days, p = 0.039) relative to the control groups (24 and 28 days, respectively). Increased lifespan was accompanied by a slowdown in tumor progression, as evidenced by a reduction in the growth of hepatoma and pancreatic cancer tumors under treatment with GAS strains in mice. Both S. pyogenes GUR and S. pyogenes GURSA1 strains demonstrated strong oncolytic activity against murine hepatoma 22a, pancreatic cancer PANC02, and human U251 glioma cells in vitro. In contrast, S. pyogenes GUR and GURSA1 did not show toxicity against human normal skin fibroblasts. The overall survival rate and lifespan of mice treated with S. pyogenes GURSA1, a strain lacking the M protein on its surface, were significantly higher compared to the control and S. pyogenes GUR strain groups.

Synthesis and anti-tumor activity of menthylamine derivatives: Focusing on the potent inhibitory effect of compound W8 on glioma growth

In this work, we successfully synthesized eight distinct compounds, comprising four chiral menthylamines and related derivatives. We evaluated their cytotoxic potential against a panel of human cancer cell lines, including human colon cancer HCT-116 cells, human esophageal squamous KYSE-150 cells, human breast cancer MCF-7 cells, and human glioma U87 cells. The U87 cells were chosen for a more in-depth investigation of their anti-tumor efficacy. Further exploration of the cytotoxicity mechanisms was conducted, complemented by in vivo studies using mice bearing tumors. These analyses unveiled the possible mechanisms by which menthylamide derivatives exert their anti-tumor effects. Notably, compound W8 demonstrated a potent inhibitory action against the proliferation of brain glioma cells. The findings from this research provide valuable insights that pave the way for the future application of menthylamides in cancer therapeutics.

Proteomic and cytokine profiling of a CTRP8-RXFP1 glioma mouse model.

Glioblastoma (GB) is the most prevalent and aggressive primary brain tumor with fatal outcome due to a lack of effective treatments. We previously identified C1q-tumor necrosis factor-related protein 8 (CTRP8), a new member of the adiponectin family, as a novel agonist of the relaxin family peptide receptor 1 (RXFP1) and showed that the CTRP8-RXFP1 ligand-receptor system facilitates increased invasiveness and chemoresistance in GB cells. In the present study, we have investigated the role of the CTRP8-RXFP1 signaling axis in glioma progression using an orthotopic mouse model xenografted with human U251 glioma cells stably expressing CTRP8 and RXFP1. Our results demonstrate that this in-vivo U251-CTRP8/RXFP1 glioma model promoted the formation of aggressive, highly proliferative glioma that resulted in significantly shorter survival times of xenografted mice. CTRP8/RXFP1 xenografts showed strongly elevated mitotic activity, increased expression of cathepsin B at the migrating front and promoted a pro-inflammatory tumor microenvironment characterized by a strong upregulation of cytokines, among them eotaxin-2 and-3, interleukin (IL)-6, IL-18 and others. Proteomic analysis of xenografted mouse brain identified both human and mouse proteome signatures unique to CTRP8/RXFP1 xenografts compared to U251 xenografts. In conclusion, our results suggest that co-expression of CTRP8 and RXFP1 promotes signaling pathways that generate unique tissue proteomic and inflammatory cytokine signatures which promote glioma aggressiveness. The CTRP-RXFP1 signaling pathway may represent an effective therapeutic target for the treatment of fast-progressing and currently untreatable GB.

Hypofractionated Radiation Therapy Suppresses Radioresistance in U87 Human Glioma Cells by Inhibiting Yap1 and Hsp90 Proteins.

Radiotherapy plays a vital role in the management of high-grade gliomas. However, the radio resistance of glioma cells limits the effect of radiation and drives recurrence inside the irradiated tumor volume leading to poor outcomes for patients. High-grade glioma cell radioresistance significantly contributes to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. An increasing body of evidence complies with the Yes Associated Protein 1 (Yap-1) and heat shock protein 90 (Hsp90) as biomarkers for radioresistance in glioma cells. A number of studies suggest the potential of radioresistance-associated factors as biomarkers and/ or novel therapeutic targets in glioma cells. Thus, it is essential for glioblastoma patients to identify robust druggable targets involved in radioresistance, optimizing irradiation protocol, and understanding their underlying molecular mechanisms. Therefore, in the present study, we hypothesized that hypofractionated Gamma Knife radiation therapy (HF-GKRT) could target Yap-1 and Hsp90 and downregulate the mechanism of radioresistance in high-grade glioma cells. For this purpose, expression levels of radioresistance markers Yap-1 and Hsp90 were evaluated after treatment with HF-GKRT, and this was compared with single fraction Gamma Knife radiation therapy (SF-GKRT) in U87MG primary human glioblastoma cell line model. This would help design a novel radiation therapy regimen for glioblastoma patients by reducing the risk of radioresistance.

Non-Immune-Mediated, p27-Associated, Growth Inhibition of Glioblastoma by Class-II-Transactivator (CIITA).

Previous works have shown that the expression of Class-II-Transactivator (CIITA) in tumor cells reduces the growth of glioblastoma (GB) in animal models, but immune effects cannot solely explain this. Here, we searched for immune-independent effects of CIITA on the proliferation of GB. Murine GL261 and human U87, GM2 and GM3 malignant glioma cells were transfected with CIITA. NSG (immunodeficient) and nude (athymic) mice were injected in the striatum with GL261-wildtype (-WT) and -CIITA, and tumor growth was assessed by immunohistology and luminescence reporter genes. Clonogenic, sphere-formation, and 3D Matrigel-based in vitro growth assays were performed to compare the growth of WT versus CIITA-expressing murine and human cells. Bulk RNA sequencing and RT2 qRT-PCR profiler arrays were performed on these four cell lines to assess RNA expression changes following CIITA transfection. Western blot analysis on several proliferation-associated proteins was performed. The intracerebral growth of murine GL261-CIITA cells was drastically reduced both in immunodeficient and athymic mice. Tumor growth was reduced in vitro in three of the four cell types. RNA sequencing and RT2 profiler array experiments revealed a modulation of gene expression in the PI3-Akt, MAPK- and cell-cycle regulation pathways following CIITA overexpression. Western blot analysis showed an upregulation of p27 in the growth-inhibited cells following this treatment. PDGFR-beta was downregulated in all cells. We did not find consistent regulation of other proteins involved in GB proliferation. Proliferation is drastically reduced by CIITA in GB, both in vivo and in vitro, notably in association with p27-mediated inhibition of cell-cycle pathways.

DDDR-13. OPTIMIZING BRAIN CANCER THERAPY: BALANCING TUMOR ERADICATION AND NORMAL TISSUE PRESERVATION WITH BPM31510

Abstract The challenges translating glioblastoma therapies lie in safeguarding normal neuronal and glial tissue. Considering that the central nervous system has the lowest regenerative capacity, the exclusive focus on tumor eradication while neglecting normal tissue response, impedes proper healing. This oversight leads to toxicities ultimately culminating in patient demise with marginal gain in survival. BPM31510 is a nanodispersion encapsulating highly hydrophobic oxidized Coenzyme Q10 (CoQ10), allowing for delivery of supraphysiological CoQ10 concentrations into cancer cells. Initial investigations demonstrated differential responsiveness between cancer and non-cancer cells in vitro, an effect associated with high superoxide levels exclusively in cancer cells. To evaluate this divergence between cancer and non-cancer cells, a competitive co-culture cell-based assay was developed with labeled pairs of glioblastoma and non-cancer cells incubated up to three weeks with various concentrations of BPM31510 to ascertain optimal concentration leading to preferential growth of non-cancer cells. Human astrocyte (HA), mouse fibroblast (NIH 3T3), and rat astrocyte (TNC1) cells were paired with U251 human glioma, mouse GL261 and rat C6 glioma, respectively. Cell growth and spatial extent of the plate containing non-cancer or tumor cells were monitored every other day. Using doxorubicin as control, no dosage was discerned in which non-cancer cells exhibited advantage over tumor cells (i.e., either cultures became all tumor cells or both cell lines were eradicated). Using various concentrations of BPM31510, we identified an optimal dose in which cancer cells diminished while non-cancer cells predominated, reflected by markedly elevated mitochondrial superoxide levels in cancer cells prior to cell death. A co-culture cell-based assay was developed to identify an optimal dose of BPM31510 with selective preservation of non-cancer cells alongside tumor cell death. This approach elucidates developing a “fine tuning” strategy, wherein BPM31510 is titrated over time, thereby promoting normal tissue and healing, and ultimately leading to superior and prolonged functional outcomes.

Monocarboxylate transporter dependent mechanism is involved in proliferation, migration, and invasion of human glioblastoma cell lines via activation of PI3K/Akt signaling pathway.

Glioblastoma multiforme is one of the most common primary tumors of the central nervous system, with a very poor prognosis. Cancer cells have been observed to upregulate pH regulators, such as monocarboxylate transporters (MCTs), with an increase in MCT4 expression being observed in several malignancies. MCT4/ recombinant cluster of differentiation 147 (CD147) transporter complex was reported to stimulate vascular endothelial growth factor (VEGF) via the phosphatidylinositol 3 kinase (PI3K) /protein kinase B (Akt) pathway, which has been proven to mediate glioblastoma invasion and migration. The present study aimed to clarify the role of the MCT4/CD147 transporter complex in glioblastoma cell proliferation, migration, and invasion. In this work, lentiviral vectors were used to overexpress MCT4/CD147 and small interfering RNA (siRNA) was used to silence MCT4/CD147 in the human glioma cell lines U87 and U251, respectively. The effects on cell proliferation, migration and invasiveness, as well as the protein expression levels of MCT4 and CD147, extracellular lactate content and Akt activation were assessed by MTT, wound-healing and invasion assays, western blotting and colorimetric method, respectively. The analysis results suggested that cell proliferation, migration, invasion, and Akt activation were decreased by siRNA in all cell lines, but were increased by lentivirus-mediated MCT4 overexpression. These findings suggest that inhibiting the activity and expression of the MCT4/CD147 transporter complex via metabolic-targeting drugs, particularly in cells with a high rate of glycolysis, should be explored as a novel strategy for glioblastoma treatment.

Crucial roles of exosomes secreted from ganglioside GD3/GD2-positive glioma cells in enhancement of the malignant phenotypes and signals of GD3/GD2-negative glioma cells.

Neuroectoderm-derived tumors characteristically express gangliosides such as GD3 and GD2. Many studies have reported that gangliosides GD3/GD2 enhance malignant phenotypes of cancers. Recently, we reported that human gliomas expressing GD3/GD2 exhibited enhanced malignant phenotypes. Here, we investigated the function of GD3/GD2 in glioma cells and GD3/GD2-expressing glioma-derived exosomes. As reported previously, transfectant cells of human glioma U251 MG expressing GD3/GD2 showed enhanced cancer phenotypes compared with GD3/GD2-negative controls. When GD3/GD2-negative cells were treated with exosomes secreted from GD3/GD2-positive cells, clearly increased malignant properties were observed. Furthermore, increased phosphorylation of signaling molecules was detected after 5-15 min of exosome treatment, ie, higher tyrosine phosphorylation of platelet-derived growth factor receptor, focal adhesion kinase, and paxillin was found in treated cells than in controls. Phosphorylation of extracellular signal-regulated kinase-1/2 was also enhanced. Consequently, it is suggested that exosomes secreted from GD3/GD2-positive gliomas play important roles in enhancement of the malignant properties of glioma cells, leading to total aggravation of heterogenous cancer tissues, and also in the regulation of tumor microenvironments.

Effect of circFOXM1/miR-218-5p on the proliferation, apoptosis and migration of glioma cells.

This study aimed to explore the influence of circFOXM1/miR-218-5p molecular axis in the proliferation, apoptosis and migration of glioma cells. The levels of circFOXM1 and miR-218-5p in glioma and adjacent tissues were tested by qRT-PCR. Cultured human glioma U251 cells were randomly split into groups: si-NC, si-circFOXM1, miR-NC, miR-218-5p, si-circFOXM1+anti-miR-NC, si-circFOXM1+anti-miR-218-5p. MTT method, plate clone formation, flow cytometry and Transwell experiments were utilized for detecting the proliferation, clone formation, apoptosis and migration of glioma cells. Dual-luciferase reporter experiment authenticated the targeted relation of circFOXM1 and miR-218-5p. Western blot tested the levels of E-cadherin and N-cadherin. CircFOXM1 was upregulated while miR-218-5p was low expressed in glioma tissues versus normal tissues. After circFOXM1 silence or miR-218-5p overexpression, miR-218-5p level was increased, and cell apoptosis rate and E-cadherin expression were enhancive, whereas cell proliferation, cell clone formation and migration abilities, and N-cadherin level were reduced. CircFOXM1 could affect miR-218-5 level by negative regulation. Furthermore, miR-218-5p silence could reverse the stimulative influence of si-circFOXM1 on apoptosis rate, and E-cadherin level, and the repressive effect on cell viability, cell number of colony formation and migration, and N-cadherin expression. Inhibition of circFOXM1 expression could block the proliferation, clone formation, and migration and induce apoptosis of glioma cells by upregulating miR-218-5p.

Methylseleninic acid inhibits human glioma growth in vitro and in vivo by triggering ROS-dependent oxidative damage and apoptosis.

Selenium-containing agents showed novel anticancer activity by triggering pro-oxidative mechanism. Studies confirmed that methylseleninic acid (MeSe) displayed broad-spectrum anti-tumor activity against kinds of human cancers. However, the anticancer effects and mechanism of MeSe against human glioma growth have not been explored yet. Herein, the present study showed that MeSeA dose-dependently inhibited U251 and U87 human glioma cells growth in vitro. Flow cytometry analysis indicated that MeSe induced significant U251 cells apoptosis with a dose-dependent manner, followed by the activation of caspase-7, caspase-9 and caspase-3. Immunofluorescence staining revealed that MeSe time-dependently caused reactive oxide species (ROS) accumulation and subsequently resulted in oxidative damage, as convinced by the increased phosphorylation level of Ser428-ATR, Ser1981-ATM, Ser15-p53 and Ser139-histone. ROS inhibition by glutathione (GSH) effectively attenuated MeSe-induced ROS generation, oxidative damage, caspase-3 activation and cytotoxicity, indicating that ROS was an upstream factor involved in MeSe-mediated anticancer mechanism in glioma. Importantly, MeSe administration in nude mice significantly inhibited glioma growth in vivo by inducing apoptosis through triggering oxidative damage. Taken together, our findings validated the possibility that MeSe as a selenium-containing can act as potential tumor chemotherapy agent for therapy of human glioma.

Borneol promotes autophagic degradation of HIF-1α and enhances chemotherapy sensitivity in malignant glioma.

Gliomas are characterized by high mortality rates and resistance. Even with conventional chemotherapy the prognosis of glioblastoma remains poor. Many medications are not optimally effective due to limited bioavailability. The bioavailability of medicine can be enhanced by borneol, a monoterpenoid substance. In this study, we investigated the effect of borneol, a commonly used Chinese medicine, on chemosensitivity in C6 glioma and U251 human glioma cell lines and elucidated its therapeutic molecular targets. The chemosensitivity-inducing effects of borneol in C6 and U251 cells were examined using CCK8 and clonal formation assays. The mechanism underlying the effect of borneol was evaluated through immunohistochemistry and western blotting assays. Further, the number of autophagosomes was determined via transmission electron microscopy. Finally, the chemical sensitization effect of borneol was evaluated in SD rats after C6 orthotopic tumor transplantation. Borneol increased cytotoxicity in C6 and U251 cells in response to temozolomide (TMZ). In addition, through transmission electron microscopy, western blotting, and immunohistochemical tests, we found that borneol combined with TMZ significantly increased the level of autophagy and that hypoxia inducible factor-1(HIF-1α) is a candidate target through which borneol enhances the cytotoxic effect of TMZ. Borneol's ability to enhance HIF-1α degradation was counteracted following the administration of autophagy inhibitors. In vivo, borneol treatment was found to enhance the anticancer effect of TMZ and delay tumor progression, and this effect was closely related to its ability to promote the autophagic degradation of HIF-1α. HIF-1α might be a valid therapeutic target of borneol, which can be potentially applied as a chemosensitizing drug used for glioma treatment.

Preparation of transferrin-targeted temozolomide nano-micelles and their anti-glioma effect.

This study aims to develop brain-targeted temozolomide (TMZ) nanograins using the biodegradable polymer material PEG-PLA as a carrier. The model drug TMZ was encapsulated within the polymer using targeted nanotechnology. Key characteristics such as appearance, particle size, size distribution, drug loading capacity, in vitro release rate, stability, and anti-tumor effects were systematically evaluated through in vitro experiments. Transmission electron microscopy (TEM) and Malvern size analyzer were employed to observe the morphological and particle size features of the TMZ nanospheres at various time points to assess stability. The effects of TMZ nanograins on glioma cell viability and apoptosis were evaluated using MTT assays and flow cytometry. The targeted TMZ nano-micelles were successfully synthesized. After loading and targeted modifications, the particle size increased from 50.7 to 190 nm, indicating successful encapsulation of TMZ. The average particle size of the nano-micelles remained stable around 145 ± 10 nm at 1 day, 15 days, and 30 days post-preparation. The release rate of the nano-micelles was monitored at 2 h, 12 h, 24 h, and 48 h post-dialysis, ultimately reaching 95.8%. Compared to TMZ alone, the TMZ-loaded PEG-PLA nano-micelles exhibited enhanced cytotoxicity and apoptosis in glioma cells. This was accompanied by increased mitochondrial membrane potential and reactive oxygen species (ROS) levels following treatment with the TMZ nano-micelles. TMZ-loaded nano-micelles demonstrated a gradual release profile and significantly enhanced inhibitory effects on human glioma U251 cells compared to TMZ alone. The findings suggest that TMZ-loaded PEG-PLA nano-micelles may offer a more effective therapeutic approach for glioma treatment.

Methionine restriction of glioma does not induce MGMT and greatly improves temozolomide efficacy in an orthotopic nude-mouse model: A potential curable approach to a clinically-incurable disease

Glioma is a highly recalcitrant disease with a 5-year survival of 6.8 %. Temozolomide (TMZ), first-line therapy for glioma, is more effective in O6-methylguanine-DNA methyltransferase (MGMT)-negative gliomas than in MGMT-positive gliomas as MGMT confers resistance to TMZ. Methionine restriction is effective for many cancers in mouse models including glioma. The concern is that methionine restriction could induce MGMT by decreasing DNA methylation and confer resistance to TMZ. In the present study, we investigated the efficacy of combining methionine restriction with TMZ for the treatment of MGMT-negative glioma, and whether methionine restriction induced MGMT. Human MGMT-negative U87 glioma cells were used to determine the efficacy of TMZ combined with methionine restriction. Recombinant methioninase (rMETase) inhibited U87 glioma growth without induction of MGMT in vitro. The combination of rMETase and TMZ inhibited U87 cell proliferation more than either agent alone in vitro. In the orthotopic nude-mouse model, the combination of TMZ and a methionine-deficient diet was much more effective than TMZ alone: two mice out of five were cured of glioma by the combination. No mice died during the treatment period. Methionine restriction enhanced the efficacy of TMZ in MGMT-negative glioma without inducing MGMT, demonstrating potential clinical promise for improved outcome of a currently incurable disease.

Cytotoxic effects of nerve growth factor and its combinations with chemotherapeutic drugs on anaplastoc astrocytoma, glioblastoma and medubloblastoma cells <i>in vitro</i>

BACKGROUND: Currently, the effectiveness of the treatment of malignant tumors using surgical resection, radiotherapy and chemotherapy is insufficient. Therefore, new research is needed to find alternative molecules with antitumor effects. It is known that nerve growth factor (NGF) inhibits invasion, migration, and angiogenesis of tumor cells. Studying the effects of NGF on brain tumors, as well as its combinations with chemotherapy drugs used in medicine, may contribute to the development of new treatment regimens for malignant neoplasms in the central nervous system. AIM: The purpose of this study is an exploration the molecular and cellular mechanisms of anticancer effects of individual and combined preparations of NGF and chemotherapeutic drugs on brain tumor cells (gliomas C6, U251, anaplastic astrocytoma, glioblastoma and medulloblastoma). MATERIALS AND METHODS: The study was performed on rat glioma C6, human U251 glioma cell lines, as well as on primary cells of anaplastic astrocytoma (n = 9), glioblastoma (n = 9) and medulloblastoma (n = 38) patients. The cytotoxicity of chemotherapeutic drugs, NGF and their combinations against tumor cells was assessed using the MTT assay. The expression of TrkA and p75 receptors on anaplastic astrocytoma, glioblastoma and medulloblastoma cells was assessed by immunofluorescence analysis using anti-TrkA and anti-p75 monoclonal antibodies. RESULTS: Nerve growth factor exhibits in vitro cytotoxic activity that exceeds the activity of chemotherapy drugs towards rat glioma C6, human U251, anaplastic astrocytoma (AA), glioblastoma (GBM) and medulloblastoma cells. The cytotoxic activity of NGF in combination with chemotherapy drugs is significantly higher than the activity of the individual NGF drug against medulloblastoma cells, while against anaplastic astrocytoma cells it is comparable to the indicators of the isolated action of NGF, and lower for glioblastoma cells. The effectiveness of the cytotoxic effect of the combinations NGF + cisplatin and NGF + temozolomide (TMZ) on AA and GBM cells correlates with both the expression of TrkA, p75 receptors, and their coexpression, indicating that expression indicators can be considered as markers of tumor cell sensitivity to NGF. CONCLUSIONS: The data obtained allow us to consider NGF as a potential anticancer drug for the treatment of brain tumors. Thus, NGF can act as a potential anticancer drug for the development of new therapeutic regimens for brain tumors.

Transmembrane and Ubiquitin-Like Domain-Containing 1 Promotes Glioma Growth and Indicates Unfavorable Prognosis.

Ubiquitin-related proteins have garnered increasing attention for their roles in tumorigenesis. Transmembrane and ubiquitin-like domain-containing 1 (TMUB1) is a recently discovered protein in the ubiquitin-like domain family, yet its involvement in glioma remains poorly understood. This study is aimed at investigating the functional significance and clinical relevance of TMUB1 in glioma. We conducted a comprehensive analysis using two cohorts: a retrospective glioma cohort from our hospital and The Cancer Genome Atlas (TCGA) cohort. The mRNA levels of TMUB1 were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Clinical associations of TMUB1 in these cohorts were evaluated using correlation tests, chi-square tests, and survival analyses. Additionally, we performed TMUB1 knockdown in U87 and LN-229 human glioma cell lines, and cellular growth was assessed through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Our results revealed that TMUB1 expression was elevated in glioma tissues compared to normal brain tissues. Notably, lower TMUB1 expression correlated with favorable characteristics such as lower World Health Organization (WHO) grade and 1p/19q codeletion. Moreover, patients with higher TMUB1 levels in glioma tissues exhibited worse prognosis in both TCGA cohort and our retrospective cohort, underscoring its prognostic significance in gliomas. Cellular experiments demonstrated that TMUB1 silencing suppressed the growth of glioma cells. TMUB1 emerges as a novel and clinically relevant prognostic biomarker for gliomas. Targeting TMUB1 holds promise as a potential strategy for glioma treatment. This study contributes valuable insights into the multifaceted role of TMUB1 in glioma pathogenesis and its potential as a diagnostic and therapeutic target.

Exploring biological activity and In-vitro anticancer effects of a new biomaterial derived from Schiff base isolated from Homarus americanus (Lobster) shell waste

In this study, chitin, a valuable biopolymer material, was extracted from lobster (Homarus americanus) shell waste using a chemical method. Afterward, the biopolymer was added to a mixture of the precursor (β-diketone and acidhydrazide) and monochloroacetic acid to prepare the biomaterial/hydrazone-based O-carboxymethyl chitosan Schiff base compounds. The prepared biomaterials were studied for potential biological applications, such as antimicrobial, antioxidant, wound healing, cytotoxicity, phosphate inhibition, and anticancer studies. The inhibition of alkaline phosphatase (ALP) enzyme was recorded using UV–Vis spectrophotometry. Wound healing studies of biopolymer materials and their derivatives were studied to RAW 264.7 (murine monocyte / macrophage) cells by scratch wound healing analysis. Additionally, using MTT analysis the in-vitro, anticancer efficacies (cell viability/cell proliferation/cytotoxicity) were conducted for SK-MEL-28 (human melanoma cells), MDA-MB-231 (human breast cancer cells), and the U87 (human glioma brain cells). The half maximal inhibitory concentration (IC50) values for SK-MEL-28 cells had 0.71 μg/mL at 24 h, and was a potent activity as compared to U-87 (35.98 μg/mL) and MDA-MB-231 (18.31 μg/mL) cells. The water-soluble / swelling nature of prepared biomaterials is utilized in the bio-ink formulation by the incorporation of the biopolymers such as cellulose, sodium alginate, gelatin, hyaluronic acid, and laponite RDS for potential biomedical applications.

Radiosynthesis and biological evaluation of [18F]AG-120 for PET imaging of the mutant isocitrate dehydrogenase 1 in glioma

Glioma are clinically challenging tumors due to their location and invasiveness nature, which often hinder complete surgical resection. The evaluation of the isocitrate dehydrogenase mutation status has become crucial for effective patient stratification. Through a transdisciplinary approach, we have developed an 18F-labeled ligand for non-invasive assessment of the IDH1R132H variant by using positron emission tomography (PET) imaging. In this study, we have successfully prepared diastereomerically pure [18F]AG-120 by copper-mediated radiofluorination of the stannyl precursor 6 on a TRACERlab FX2 N radiosynthesis module. In vitro internalization studies demonstrated significantly higher uptake of [18F]AG-120 in U251 human high-grade glioma cells with stable overexpression of mutant IDH1 (IDH1R132H) compared to their wild-type IDH1 counterpart (0.4 vs. 0.013% applied dose/µg protein at 120 min). In vivo studies conducted in mice, exhibited the excellent metabolic stability of [18F]AG-120, with parent fractions of 85% and 91% in plasma and brain at 30 min p.i., respectively. Dynamic PET studies with [18F]AG-120 in naïve mice and orthotopic glioma rat model reveal limited blood-brain barrier permeation along with a low uptake in the brain tumor. Interestingly, there was no significant difference in uptake between mutant IDH1R132H and wild-type IDH1 tumors (tumor-to-blood ratio[40−60 min]: ~1.7 vs. ~1.3). In conclusion, our preclinical evaluation demonstrated a target-specific internalization of [18F]AG-120 in vitro, a high metabolic stability in vivo in mice, and a slightly higher accumulation of activity in IDH1R132H-glioma compared to IDH1-glioma. Overall, our findings contribute to advancing the field of molecular imaging and encourage the evaluation of [18F]AG-120 to improve diagnosis and management of glioma and other IDH1R132H-related tumors.

NIMG-19. TUMOR PARAMETERS AFFECTED BY NANOCOMBRESTATIN THERAPY IN AN EXPERIMENTAL RAT MODEL OF GLIOMA

Abstract INTRODUCTION: of polymeric nanoparticles in cancer therapeutics is widely investigated since nanomedicine often enables the intratumoral delivery of drugs with increased efficacy with minimal side effects. In this study magnetic resonance imaging (MRI) monitoring was employed to study the therapeutic effect of nanocombretastatin (G3-CA4) in an orthotopic glioma model. Water insoluble combretastatin (CA4) was conjugated to a small-sized water soluble G3-succinimic acid PAMAM dendrimer. Tumor growth and vascular parameters were assessed non-invasively using MRI. In the brain, intravenously (iv) administered magnetic resonance (MR) contrast agents (CAs) can be used to measure the biomarkers of tumor perfusion - the blood-to-brain transvascular transfer constant (K-trans), tumor plasma volume (Vp), the extravascular extracellular space (Ve) and the blood volume (VD) in cerebral tumors. K-trans, Vp, Ve and VD showed the discrimination of tumorous vasculature responding to CA4 and G3-CA4 therapies from tumorous tissues. The average K-trans, Vp, Ve and VD decreased significantly 24 hours after G3-CA4 treatment. The results showed that G3-CA4 caused a change in tumor vasculature as measured with DCE-MRI. These effects were homogenous throughout the U-251 tumor. However, CA4 did not show any change in tumor vasculature. Imaging, histological and molecular signatures of the primary glioblastoma were compared. Large necrotic area was found together with destroyed blood vessels at the core of the tumor leaving viable tissue at the rim of the tumor. In vivo studies proved that the cytotoxicity of G3-CA4 conjugate was more effective against human U-251 tumor while CA4 alone was ineffective. Therefore, we have accomplished the effective transvascular delivery of G3-CA4 into human U251 glioma tumor with a compromised blood brain tumor barrier. In vivo studies proved that the cytotoxicity of G3-CA4 conjugate is more effective against human U-251 tumor than that of free CA4.

Retracted] Effect of CCL2 siRNA on proliferation and apoptosis in the U251 human glioma cell line.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the VEGF western blotting data shown in Fig.4A on p.3392 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office never received a reply.The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 3387‑3394, 2017; DOI: 10.3892/mmr.2017.6995].

Precise Construction of Dual-Promising Anticancer Drugs Associated with Gold Nanomaterials on Glioma Cancer Cells.

Multiple chemodrugs with nanotechnology have proven to be an effective cancer treatment technique. When taken combined, cabazitaxel (CTX) and cisplatin (PT) have more excellent cytotoxic effects than drugs used alone in the chemotherapy of several different cancers. However, several severe side effects are associated with using these chemotherapy drugs in cancer patients. Gold nanomaterials (AuNMs) are promising as drug carriers because of their small diameter, easy surface modifications, good biocompatibility, and strong cell penetration. This work aimed to determine the CTX and PT encapsulated with AuNMs against human glioma U87 cancer cells. The fabrication of the AuNMs achieved a negative surface charge, polydispersity index, and the mean sizes. The combined cytotoxic effect of CTX and PT bound to AuNMs was greater than that of either drug alone when tested on U87 cells. The half inhibitory concentration (IC50) values for free PT were 54.7 μg/mL (at 24 h) and 4.8 g μg/mL (at 72 h). Results acquired from the MTT assay show cell growth decreases time- and concentration-dependent AuNMs, free CTX, free PT, and AuNMs@CTX/PT-induced cytotoxicity and, ultimately, the cell death of U87 cells via apoptosis. The biochemical apoptosis staining techniques investigated the cells' morphological changes of the cells (acridine orange and ethidium bromide (AO-EB) and nuclear staining (DAPI) techniques). The AO-EB and nuclear staining results reveal that the NPs effectively killed cancer cells. Furthermore, the flow cytometry analysis examined the mode of cell death. Therefore, AuNMs@CTX/PT has excellent potential in the cancer therapy of different cancer cells.