scholarly journals In vitro labeling of glioma cells with gadofluorine M enhancesT1 visibility without affecting glioma cell growth or motility

2008 ◽  
Vol 59 (5) ◽  
pp. 1014-1020 ◽  
Author(s):  
Ingo S. Nolte ◽  
Sevil Gungor ◽  
Ralf Erber ◽  
Elena Plaxina ◽  
Johann Scharf ◽  
...  
Keyword(s):  
Cell Growth ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Gadofluorine M

scholarly journals IL-10 Promotes Glioma Cell Growth and Invasion via Upregulation of KPNA2 In vitro

2019 ◽  
Author(s):  
Zihao Zhang ◽  
Xiaoming Huang ◽  
Jie Li ◽  
Haitao Fan ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cell Growth ◽  
Glioma Cell ◽  
Causes Of Death ◽  
Glioma Cells ◽  
Primary Brain Tumor ◽  
Dual Function ◽  
Quantitative Real Time Pcr ◽  
High Incidence ◽  
Important Significance

Abstract Background: Glioma is one of the leading causes of death worldwide with high incidence, recurrence and mortality. IL-10 is a cytokine with dual function in many types of tumors. Although IL-10 is overexpressed and promotes tumor progression in human primary brain tumor, the mechanisms are largely unknown. Methods: Glioma cells were treated with different dosages of IL-10. The cell growth was detected by CCK8, and the invasion was measured by Transwell. The relative expression of mRNAs was detected by Quantitative real-time PCR (q-PCR). Results: We found that IL-10 treatment significantly enhanced glioma cell growth and invasion. And KPNA2 was significantly upregulated after treatment with IL-10. By performing knockdown experiments, we found that the glioma cell growth and invasion were significantly declined. Conclusions: The results indicated that knockdown of KPNA2 significantly inhibited the growth and invasion of glioma cells. And IL-10 promotes glioma progression via upregulation of KPNA2. This study will be of important significance and provides a potential target for treatment of patients with glioma. Keywords: Cell growth, cell invasion, glioma, IL-10, KPNA2.

scholarly journals IL-10 Promotes Glioma Cell Growth and Invasion via Upregulation of KPNA2 In vitro

2019 ◽  
Author(s):  
Zihao Zhang ◽  
Xiaoming Huang ◽  
Jie Li ◽  
Haitao Fan ◽  
Fan Yang ◽  
...  
Keyword(s):  
Cell Growth ◽  
Glioma Cell ◽  
Causes Of Death ◽  
Glioma Cells ◽  
Primary Brain Tumor ◽  
Dual Function ◽  
Quantitative Real Time Pcr ◽  
High Incidence ◽  
Important Significance

Abstract Background Glioma is one of the leading causes of death worldwide with high incidence, recurrence and mortality. IL-10 is a cytokine with dual function in many types of tumors. Although IL-10 is overexpressed and promotes tumor progression in human primary brain tumor, the mechanisms are largely unknown. Methods Glioma cells were treated with different dosages of IL-10. The cell growth was detected by CCK8, and the invasion was measured by Transwell. The relative expression of mRNAs was detected by Quantitative real-time PCR (q-PCR). Results We found that IL-10 treatment significantly enhanced glioma cell growth and invasion. And KPNA2 was significantly upregulated after treatment with IL-10. By performing knockdown experiments, we found that the glioma cell growth and invasion were significantly declined. Conclusions The results indicated that knockdown of KPNA2 significantly inhibited the growth and invasion of glioma cells. And IL-10 promotes glioma progression via upregulation of KPNA2. This study will be of important significance and provides a potential target for treatment of patients with glioma.

Growth suppression and astrocytic differentiation of glioma cells by interleukin-1

1994 ◽  
Vol 81 (3) ◽  
pp. 402-410 ◽  
Author(s):  
Satoshi Tanaka ◽  
Tadashi Nagashima ◽  
Shinya Manaka ◽  
Tomokatsu Hori ◽  
Shigeru Yasumoto
Keyword(s):  
Cell Growth ◽  
Cell Lines ◽  
Glioma Cell ◽  
Interleukin 1 ◽  
Glioma Cells ◽  
Growth Suppression ◽  
Transient Growth ◽  
Glioma Cell Lines ◽  
Astrocytic Differentiation

✓ The effect of recombinant human interleukin-1 (rHuIL-1) derivatives on human glioma cell lines was examined in vitro. Five glioma cell lines, U-251 MG, U-373 MG, U-87 MG, A-172, and T98G, were incubated in medium containing 1% fetal calf serum and various concentrations of different types of rHuIL-1: OCT-43 (rHuIL-1β), OCT-7000 (rHuIL-1α), and OCT-8000 (rHuIL-1α). The high-affinity IL-1 receptors were expressed in the U-251 MG and U-373 MG cell lines, and rHuIL-1 was found to suppress cell growth and to induce morphological differentiation of these cell lines. Growth inhibition occurred in a dose-dependent manner in concentrations or rHuIL-1 ranging between 1 and 100 ng/ml. Interestingly, rHuIL-1 induced a transient growth of glioma cells shortly after administration, then suppressed cell growth with accompanying elongation of cytoplasmic processes. This unique process of transient growth stimulation followed by growth suppression was parallel to the efficacy of bromodeoxyuridine uptake in the rHuIL-1-treated cells. Concomitantly, accumulation of glial fibrillary acidic protein and cyclic adenosine monophosphate contents was observed in four glioma cell lines. Continuous rHuIL-1 treatment for longer than 30 days elicited irreversible astrocytic terminal differentiation. These results indicate that IL-1 is an effector on the growth regulation of glioma cells, resulting in astrocytic differentiation in vitro.

scholarly journals The glutamine antagonist prodrug JHU-083 slows malignant glioma growth and disrupts mTOR signaling

2020 ◽  
Author(s):  
Alex Shimura Yamashita ◽  
Marina da Costa Rosa ◽  
Vittorio Stumpo ◽  
Rana Rais ◽  
Barbara S Slusher ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Protein Expression ◽  
Glioma Cell ◽  
D1 Protein ◽  
Glioma Cells ◽  
Mtor Signaling ◽  
Glutamine Metabolism ◽  
Cyclin D1 Protein

Abstract Background Metabolism reprogramming is a common feature in cancer, and it is critical to facilitate cancer cell growth. Isocitrate Dehydrogenase 1/2 (IDH1 & IDH2) mutations (IDHmut) are the most common genetic alteration in glioma grade II and III and secondary glioblastoma and these mutations increase reliance on glutamine metabolism, suggesting a potential vulnerability. In this study, we tested the hypothesis that the brain penetrant glutamine antagonist prodrug JHU-083 reduces glioma cell growth. Material and Methods We performed cell growth, cell cycle, and protein expression in glutamine deprived or Glutaminase (GLS) gene silenced glioma cells. We tested the effect of JHU-083 on cell proliferation, metabolism, and mTOR signaling in cancer cell lines. An orthotopic IDH1R132H glioma model was used to test the efficacy of JHU-083 in vivo. Results Glutamine deprivation and GLS gene silencing reduced glioma cell proliferation in vitro in glioma cells. JHU-083 reduced glioma cell growth in vitro, modulated cell metabolism, and disrupted mTOR signaling and downregulated Cyclin D1 protein expression, through a mechanism independent of TSC2 modulation and glutaminolysis. IDH1R132H isogenic cells preferentially reduced cell growth and mTOR signaling downregulation. In addition, guanine supplementation partially rescued IDHmut glioma cell growth, mTOR signaling, and Cyclin D1 protein expression in vitro. Finally, JHU-083 extended survival in an intracranial IDH1mut glioma model and reduced intracranial pS6 protein expression. Conclusion Targeting glutamine metabolism with JHU-083 showed efficacy in preclinical models of IDHmut glioma and measurably decreased mTOR signaling.

scholarly journals Histone methyltransferase SUV39H2 regulates cell growth and chemosensitivity in glioma via regulation of hedgehog signaling

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ran Wang ◽  
Lilin Cheng ◽  
Xi Yang ◽  
Xin Chen ◽  
Yifeng Miao ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Hedgehog Signaling ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Normal Tissues

Abstract Background Malignant glioma is one of the essentially incurable tumors with chemoresistance and tumor recurrence. As a histone methyltransferase, SUV39H2 can trimethylate H3K9. SUV39H2 is highly expressed in many types of human tumors, while the function of SUV39H2 in the development and progression of glioma has never been elucidated. Methods RT-qPCR and IHC were used to test SUV39H2 levels in glioma tissues and paired normal tissues. The clinical relevance of SUV39H2 in glioma was analyzed in a public database. Colony formation assays, CCK-8 assays, and flow cytometry were conducted to explore the role of SUV39H2 in the growth of glioma cells in vitro. A cell line-derived xenograft model was applied to explore SUV39H2’s role in U251 cell proliferation in vivo. Sphere formation assays, RT-qPCR, flow cytometry, and IF were conducted to illustrate the role of SUV39H2 in the stemness and chemosensitivity of glioma. Luciferase reporter assays and WB were applied to determine the function of SUV39H2 in Hh signaling. Results SUV39H2 was highly expressed in glioma tissues relative to normal tissues. SUV39H2 knockdown inhibited cell proliferation and stemness and promoted the chemosensitivity of glioma cells in vitro. In addition, SUV39H2 knockdown also significantly inhibited glioma cell growth in vivo. Moreover, we further uncovered that SUV39H2 regulated hedgehog signaling by repressing HHIP expression. Conclusions Our findings delineate the role of SUV39H2 in glioma cell growth and chemosensitivity as a pivotal regulator of the hedgehog signaling pathway and may support SUV39H2 as a potential target for diagnosis and therapy in glioma management.

scholarly journals Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

2021 ◽  
Author(s):  
Xuyang Lv ◽  
Jiangchuan Sun ◽  
Linfeng Hu ◽  
Ying Qian ◽  
Chunlei Fan ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

Interfering With Hyaluronic Acid Metabolism Suppresses Glioma Cell Proliferation by Regulating Autophagy

2020 ◽  
Author(s):  
Tao Yan ◽  
Xin Chen ◽  
Hua Zhan ◽  
Penglei Yao ◽  
Ning Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Hyaluronic Acid ◽  
Tumor Microenvironment ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Glioma Cell ◽  
Glioma Cells

Abstract BackgroundThe tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. Whereas the role of abnormal HA metabolism in glioma remains unclear. MethodsThe expression level of hyaluronic acid (HA) was analyzed by ELISA assay and proteins such as HAS3, CD44, P62, LC3, CCND1 and CCNB1 were measured with Western blot analysis. The cell viability and proliferation were measured by MTT and KI67 immunofluorescence staining respectively. Autophagic vesicles and autophagosomes were quantified by transmission electron microscopy (TEM) and GFP-RFP-LC3 fluorescence analysis respectively. Cell cycle was analyzed by flowcytometry and Western blot analysis. Immunohistochemical (IHC) staining was used to detect expression levels of HA, Ki67, HAS3 and CD44 in human and mouse tumor tissues. Lentivirus constructed HAS3 and CD44 knockout stable glioma cells were transplanted to BALB/C nude mice for in vivo experiments. 4-Methylumbelliferone (4MU) was also used to treat glioma bearing mice for verifing its anti-tumor ability. The expression curve of HAS3, CD44 and the disease-free survival (DFS) curves for HAS3, CD44 in patients with LGG and GBM was performed based on TCGA database. ResultsAs shown in the present study, HA, hyaluronic acid synthase 3 (HAS3) and a receptor of HA named CD44 are expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 or blocking CD44 inhibited the proliferation of glioma cells in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and further maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-Methylumbelliferone (4-MU), a small competitive inhibitor of UDP with the ability to penetrate the blood-brain barrier (BBB), also inhibited the proliferation of glioma cells in vitro and in vivo. ConclusionApproaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.

scholarly journals 2036 Extracellular matrix as a novel approach to glioma therapy

2018 ◽  
Vol 2 (S1) ◽  
pp. 11-12
Author(s):  
Mark H. Murdock ◽  
Jordan T. Chang ◽  
George S. Hussey ◽  
Nduka M. Amankulor ◽  
Johnathan A. Engh ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Urinary Bladder ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Time Lapse ◽  
Cell Types ◽  
Neoplastic Cells ◽  
Novel Approach ◽  
Primary Glioma

OBJECTIVES/SPECIFIC AIMS: Gliomas are the most lethal and common primary tumor type in the central nervous system across all age groups; affected adults have a life expectancy of just 14 months. As glioma cells invade the surrounding normal parenchyma they remodel the composition and ultrastructure of the surrounding extracellular matrix (ECM), suggesting that the native (i.e., “normal”) microenvironment is not ideal for their survival and proliferation. Recent reports describe suppressive and/or lethal effects of mammalian ECM hydrogels derived from normal (nonneoplastic) sources upon various cancer types. ECM-based bioscaffolds placed at sites of neoplastic tissue resection in humans have never been reported to facilitate cancer recurrence. The objective of the present research is to evaluate mammalian ECM as a novel approach to glioma therapy. METHODS/STUDY POPULATION: ECM hydrogels from porcine dermis, small intestine, and urinary bladder were produced as described previously. Primary glioma cells were graciously supplied by Drs. Nduka Amankulor and Johnathan Engh, and U-87 MG were ordered through ATCC. Cells were plated onto tissue culture plastic at ~60% confluence and allowed to attach for 24 hours before treatment. The saline-soluble fraction (SSF) of ECM was obtained by mixing lyophilized, comminuted ECM with 0.9% saline for 24 hours then filtering the resulting mixture through a 10 kDa molecular weight cutoff column. All assays and kits were followed according to the manufacturer’s instructions. Cell viability was measured via MTT assay (Vybrant® MTT Cell Proliferation Assay, Invitrogen) and by live/dead staining (LIVE/DEAD® Cell Imaging Kit, Invitrogen). Time lapse videos were created by taking images every 20 minutes for 18 hours (phase-contrast) or every 10 minutes for 12 hours (darkfield). NucView reagent was ordered from Biotium. Temozolomide was ordered through Abmole. All in vivo work was conducted according to protocols approved by the University of Pittsburgh’s IACUC office. RESULTS/ANTICIPATED RESULTS: ECM hydrogels derived from porcine dermis, small intestine, or urinary bladder all decreased the viability of primary glioma cells in vitro, with urinary bladder extracellular matrix (UBM) having the most dramatic effects. The SSF of UBM (UBM-SSF), devoid of the fibrillar, macromolecular components of ECM, was sufficient to recapitulate this detrimental effect upon neoplastic cells in vitro and was used for the remainder of the experiments described herein. In a cell viability assay normalized to the media treatment, non-neoplastic CHME5 and N1E-115 cells scored 103% and 114% after 48 hours when treated with UBM-SSF and 2 primary high-grade glioma cell types scored 17% and 30.5% with UBM-SSF (n=2). Phase-contrast time-lapse video showed CHME5 and HFF thriving in the presence of UBM-SSF for 18 hours while most primary glioma cells shriveled and died within this time. Darkfield time-lapse video of wells containing Nucview dye, fluorescent upon cleavage by active caspase-3, confirmed that within 12 hours most primary glioma cells underwent apoptosis while CHME5 and HFF did not. In culture with primary astrocytes, high grade primary glioma cells, and U-87 MG glioma cells for 24 hours, UBM-SSF was found to significantly increase the population of primary astrocytes compared with media (p<0.05) while decreasing the 2 glioma cell types to approximately one-third as many cells as the media control (p<0.0001). A dose-response of temozolomide from 0 to 10,000 μM showed that when treating 2 non-neoplastic cell types (CHME5 and HFF) and 2 types of primary glioma cell there was no difference in survivability at any concentration. Contrasted to this, a dose-response of UBM-SSF from 350 to 7000 μg/mL showed that the non-neoplastic cells survived significantly better than the glioma cells at concentrations of 875 μg/mL and upward (p<0.05). In preliminary animal experiments, large primary glioma tumors in the flanks of athymic nude mice were resected and replaced with either UBM SSF or Matrigel (an ECM product of neoplastic cell origin). After 7 days the resection sites with UBM-SSF had little tumor regrowth if any compared with the dramatic recurrence seen in the Matrigel injection sites (n=2). In a separate survival study comparing PBS to UBM-SSF injections in the flank-resection model, all animals given PBS had to be sacrificed at 9, 11, and 11 days (n=3) whereas animals given UBM-SSF were sacrificed at 15, 24, and 39 days (n=3), indicating a moderate increase in survival due to the UBM-SSF. DISCUSSION/SIGNIFICANCE OF IMPACT: Since the introduction of the pan-cytotoxic chemotherapeutic agent TMZ in 2005, the standard of care for patients with glioblastoma multiforme has not improved. These findings indicate that non-neoplastic ECM contains potent bioactive regulators capable of abrogating malignancy. Our in vitro data suggest these molecules appear to have no deleterious effect on non-neoplastic cells while specifically inducing apoptosis in glioma cells. Our in vivo data suggest that these molecules may be useful in delaying glioma recurrence, thus resulting in extended lifespan. Delivering soluble fractions of ECM to a tumor site may represent a novel approach to glioma therapy, sidestepping traditional cytotoxic therapies in favor of utilizing putative endogenous anti-tumor pathways.

Effect and mechanism of YB-1 knockdown on glioma cell growth, migration, and apoptosis

2020 ◽  
Vol 52 (2) ◽  
pp. 168-179 ◽  
Author(s):  
Huilin Gong ◽  
Shan Gao ◽  
Chenghuan Yu ◽  
Meihe Li ◽  
Ping Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Glioma Cell ◽  
Cell Transformation ◽  
Malignant Cell ◽  
Protein Levels ◽  
Glioma Progression

Abstract Y-box binding protein 1 (YB-1) is manifested as its involvement in cell proliferation and differentiation and malignant cell transformation. Overexpression of YB-1 is associated with glioma progression and patient survival. The aim of this study is to investigate the influence of YB-1 knockdown on glioma cell progression and reveal the mechanisms of YB-1 knockdown on glioma cell growth, migration, and apoptosis. It was found that the knockdown of YB-1 decreased the mRNA and protein levels of YB-1 in U251 glioma cells. The knockdown of YB-1 significantly inhibited cell proliferation, colony formation, and migration in vitro and tumor growth in vivo. Proteome and phosphoproteome data revealed that YB-1 is involved in glioma progression through regulating the expression and phosphorylation of major proteins involved in cell cycle, adhesion, and apoptosis. The main regulated proteins included CCNB1, CCNDBP1, CDK2, CDK3, ADGRG1, CDH-2, MMP14, AIFM1, HO-1, and BAX. Furthermore, it was also found that YB-1 knockdown is associated with the hypo-phosphorylation of ErbB, mTOR, HIF-1, cGMP-PKG, and insulin signaling pathways, and proteoglycans in cancer. Our findings indicated that YB-1 plays a key role in glioma progression in multiple ways, including regulating the expression and phosphorylation of major proteins associated with cell cycle, adhesion, and apoptosis.

scholarly journals Growth suppression of glioma cells using HDAC6 inhibitor, tubacin

Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 221-226 ◽  
Author(s):  
Changjiang Yin ◽  
Pibao Li
Keyword(s):  
Cancer Research ◽  
Glioma Cell ◽  
Alkylating Agent ◽  
Radiation Treatment ◽  
Combined Treatment ◽  
Specific Inhibitor ◽  
Glioma Cells ◽  
Histone Deacetylase 6 ◽  
Hdac6 Inhibitor

AbstractIn cancer research, autophagy has been revealed as one of the major ways to maintain the metabolism of cancer cells, including glioma cells, through protein degradation. Meanwhile, autophagy is also regarded as a kind of mechanism to protect glioma cells from a harmful stimulus, such as chemical and radiation treatment. So, the inhibition of autophagy may be very helpful in curing glioma. This study aimed to determine the effect of autophagic inhibition on glioma cells using tubacin, a specific inhibitor of histone deacetylase 6(HDAC6). According to the results, tubacin inhibited the growth of both U251 and LN229 cells, which was accompanied by lower HDAC6 activity and accumulated autophagosome. The inhibition of HDCA6 also led to accumulation of autophagosome and death of glioma cells. Moreover, the combined treatment of tubacin and temozolomide, an alkylating agent used to treat glioblastoma, induced more severe glioma cell death. Thus, it can be concluded that inhibition of HDAC6 suppressed growth and drug resistance of glioma cells in-vitro through autophagic suppression and blocking of fusion of autophagosome and lysosome.

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