Antigen related to cell proliferation in malignant gliomas recognized by a human monoclonal antibody

1990 ◽  
Vol 73 (6) ◽  
pp. 901-908 ◽  
Author(s):  
Takashi Kokunai ◽  
Norihiko Tamaki ◽  
Satoshi Matsumoto
Keyword(s):  
Monoclonal Antibody ◽  
Cell Proliferation ◽  
Cultured Cells ◽  
Human Monoclonal Antibody ◽  
Malignant Gliomas ◽  
Fetal Brain ◽  
Glioma Cells ◽  
Normal Brain ◽  
Human Glioma ◽  
Brain Tissues

✓ A human monoclonal antibody (CLN-IgG) was produced from a human-human hybridoma derived from lymphocytes of a patient with cervical carcinoma. The reactivities of this antibody with various human glioma tissues and cultured glioma cells and the characterization of the antigen recognized by CLN-IgG on malignant glioma cells were analyzed and reported. CLN-IgG reacted with various human glioma cells and glioma tissues, especially glioblastoma, but did not react with normal brain tissues or fetal brain tissues. A large amount of antigen recognized by CLN-IgG was expressed on cell membranes of undifferentiated glioma cells and of glioma cells at the G2/M tumor growth phase in cycling cells. Antigen recognized by CLN-IgG was detected in only one of seven samples of cyst fluid, and was not detected in 27 serum samples or 18 samples of cerebrospinal fluid from glioma patients. CLN-IgG exhibited antibody-dependent cell cytotoxicity against U-251MG glioma cells and primary cultured cells of glioblastomas and anaplastic astrocytomas. These data suggest that the antigen recognized by CLN-IgG might be related to cell proliferation in malignant gliomas. Thus, CLN-IgG might be useful for immunotherapy or immunoimaging of malignant gliomas.

Detection of human glioma-associated antigen by rat monoclonal antibody raised against syngeneic rat glioma cells

1986 ◽  
Vol 65 (4) ◽  
pp. 495-502 ◽  
Author(s):  
Hideyuki Saya ◽  
Takashi Masuko ◽  
Takashi Kokunai ◽  
Hideo Yagita ◽  
Akihiro Ijichi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Cultured Cells ◽  
Periodic Acid ◽  
Glioma Cells ◽  
Immunoperoxidase Staining ◽  
Low Grade ◽  
Human Tissues ◽  
Human Glioma ◽  
Content Type ◽  
Rat Glioma

✓ A monoclonal antibody termed “FR77” was obtained from a hybridoma clone established by fusion between P3x63Ag8.653 mouse myeloma cells and spleen cells of a Fischer F344 rat hyperimmune to syngeneic 9L/R3 glioma cells. Immunoperoxidase staining of various cultured cells showed that FR77 was reactive to both rat and human glioma cells, but was not reactive with other nonglioma cells. Immunohistochemical examination of paraffin-embedded or cryostat-frozen sections of various human tissues revealed that FR77 was strongly reactive with glioblastoma, grade III astrocytoma, and craniopharyngioma; partially reactive with intracerebral primitive neuroectodermal tumor, pineoblastoma, and desmoplastic medulloblastoma; and weakly reactive with low-grade astrocytoma. It was not reactive with other types of brain tumors and normal human tissues tested. The FR77-defined antigen was observed to be predominantly localized in the cytoplasm of antigen-bearing cells as suggested by the immunostaining pattern, but part of it was also expressed on the cell surface of glioma cells as demonstrated by a complement-mediated cytotoxic test. Fractionation of the antigenic component and periodic acid treatment of tumor tissue bearing the FR77-defined antigen indicated that the antigen is of a neutral glycolipid nature and that the antigenic determinant to FR77 is present on its sugar portion.

scholarly journals EXTH-70. ENHANCEMENT OF ANTITUMOR ACTIVITY BY USING 5-ALA–MEDIATED SONODYNAMIC THERAPY TO INDUCE APOPTOSIS AND NECROSIS IN A MOUSE GLIOMA MODEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi97-vi97
Author(s):  
Satoshi Suehiro ◽  
Takanori Ohnishi ◽  
Akihiro Inoue ◽  
Daisuke Yamashita ◽  
Masahiro Nishikawa ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
High Intensity Focused Ultrasound ◽  
Control Group ◽  
Normal Brain ◽  
Sonodynamic Therapy ◽  
Cytotoxic Effects

Abstract OBJECTIVE High invasiveness of malignant gliomas frequently causes local tumor recurrence. To control such recurrence, novel therapies targeted toward infiltrating glioma cells are required. Here, we examined cytotoxic effects of sonodynamic therapy (SDT) combined with a sonosensitizer, 5-aminolevulinic acid (5-ALA), on malignant gliomas both in vitro and in vivo. METHODS In vitro cytotoxicity of 5-ALA-SDT was evaluated in U87 and U251 glioma cells and in U251Oct-3/4 glioma stemlike cells. Treatment-related apoptosis was analyzed using flow cytometry. Intracellular reactive oxygen species (ROS) were measured and the role of ROS in treatment-related cytotoxicity was examined. Effects of 5-ALA-SDT with high-intensity focused ultrasound (HIFU) on tumor growth, survival of glioma-transplanted mice, and histological features of the mouse brains were investigated. RESULTS The 5-ALA-SDT inhibited cell growth and changed cell morphology. Flow cytometric analysis indicated that 5-ALA-SDT induced apoptotic cell death. The 5-ALA-SDT generated higher ROS than in the control group, and inhibition of ROS generation completely eliminated the cytotoxic effects of 5-ALA-SDT. In the in vivo study, 5-ALA-SDT with HIFU greatly prolonged survival of the tumor-bearing mice compared with that of the control group (p < 0.05). Histologically, 5-ALA-SDT produced mainly necrosis of the tumor tissue in the focus area and induced apoptosis of the tumor cells in the perifocus area around the target of the HIFU-irradiated field. Normal brain tissues around the ultrasonic irradiation field of HIFU remained intact. CONCLUSIONS The 5-ALA-SDT was cytotoxic toward malignant gliomas. Generation of ROS by the SDT was thought to promote apoptosis of glioma cells. The 5-ALA-SDT with HIFU induced tumor necrosis in the focus area and apoptosis in the perifocus area of the HIFU-irradiated field. These results suggest that 5-ALA-SDT with HIFU may present a less invasive and tumor-specific therapy, not only for a tumor mass but also for infiltrating tumor cells in malignant gliomas.

scholarly journals A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody

2018 ◽  
Vol 93 (4) ◽  
Author(s):  
Aušra Domanska ◽  
Justin W. Flatt ◽  
Joonas J. J. Jukonen ◽  
James A. Geraets ◽  
Sarah J. Butcher
Keyword(s):  
Electron Microscopy ◽  
Monoclonal Antibody ◽  
High Resolution ◽  
Cultured Cells ◽  
Human Monoclonal Antibody ◽  
Neutralizing Antibody ◽  
Molecular Diagnostic ◽  
Diagnostic Tools ◽  
Human Parechovirus ◽  
Cryo Electron Microscopy

ABSTRACTHuman parechovirus 3 (HPeV3) infection is associated with sepsis characterized by significant immune activation and subsequent tissue damage in neonates. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and the lack of a vaccine or specific antiviral therapy. Toward the latter, we present a 2.8-Å-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody, AT12-015, using cryo-electron microscopy (cryo-EM) and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally, at high resolution, it was possible to model a stretch of RNA inside the virion and, from this, identify the key features that drive and stabilize protein-RNA association during assembly.IMPORTANCEHuman parechovirus 3 (HPeV3) is receiving increasing attention as a prevalent cause of sepsis-like symptoms in neonates, for which, despite the severity of disease, there are no effective treatments available. Structural and molecular insights into virus neutralization are urgently needed, especially as clinical cases are on the rise. Toward this goal, we present the first structure of HPeV3 in complex with fragments from a neutralizing monoclonal antibody. At high resolution, it was possible to precisely define the epitope that, when targeted, prevents virions from binding to cells. Such an atomic-level description is useful for understanding host-pathogen interactions and viral pathogenesis mechanisms and for finding potential cures for infection and disease.

scholarly journals Long non-coding RNA LBX2-AS1 enhances glioma proliferation through downregulating microRNA-491-5p

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Qunbang Chen ◽  
Jian Gao ◽  
Yingjia Zhao ◽  
Ruizhe Hou
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Glioma Cells ◽  
Annexin V ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter ◽  
Normal Brain ◽  
Lower Grade ◽  
Rt Pcr ◽  
Glioma Cell Proliferation

Abstract Background Dysregulation of lncRNAs is frequent in glioma and has emerged as an important mechanism involved in tumorigenesis. Previous analysis of Chinese Glioma Genome Atlas (CGGA) database indicated that LBX2-AS1 expression is one of differentially expression lncRNA between lower grade glioma (LGG) (grade II and III) and glioblastoma multiforme (GBM). However, the function and mechanism of LBX2-AS1 in glioma has not been evaluated yet. Methods Here, we analyzed the expression of LBX2-AS1 in GTEx data (normal brain), TCGA-LGG and TCGA-GBM. RT-PCR was performed to detect LBX2-AS1 in surgery obtained normal brain and glioma. CCK-8 kit and Annexin V-FITC-PI Apoptosis Detection Kit were used to study the function of LBX2-AS1 on glioma proliferation and apoptosis. Bioinformatic analysis, RNA immunoprecipitation, RT-PCR, western blotting and dual luciferase reporter assay were carried out to investigate the target miRNA of LBX2-AS1. The discovered mechanism was validated by the rescue assay. Results Following study of GTEx and TCGA data, LBX2-AS1 was significantly elevated in glioma compared with normal brain and in GBM compared with LGG. Higher expression of LBX2-AS1 was associated with poor prognosis of patients with glioma. Expression of LBX2-AS1 was positively correlated with pathology classification of glioma. Knockdown of LBX2-AS1 inhibited cell proliferation and induced cell apoptosis in glioma. LBX2-AS1 have complimentary binding site for tumor suppressor miR-491-5p and we showed that LBX2-AS1 sponged miR-491-5p to upregulate TRIM28 expression in glioma cells. TRIM28 overexpression attenuated the effect of LBX2-AS1 knockdown on glioma cells. Conclusions In conclusion, LBX2-AS1 was an increased lncRNA in glioma. Mechanistically, LBX2-AS1 promoted glioma cell proliferation and resistance to cell apoptosis via sponging miR-491-5p.

scholarly journals Pharmacological blockade of mGlu2/3 metabotropic glutamate receptors reduces cell proliferation in cultured human glioma cells

2003 ◽  
Vol 84 (6) ◽  
pp. 1288-1295 ◽  
Author(s):  
Mara D'Onofrio ◽  
Antonietta Arcella ◽  
Valeria Bruno ◽  
Richard T. Ngomba ◽  
Giuseppe Battaglia ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Glioma Cells ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Metabotropic Glutamate ◽  
Pharmacological Blockade

Synergistic cytotoxicity through the activation of multiple apoptosis pathways in human glioma cells induced by combined treatment with ionizing radiation and tumor necrosis factor–related apoptosis-inducing ligand

2007 ◽  
Vol 106 (3) ◽  
pp. 407-416 ◽  
Author(s):  
Motoo Nagane ◽  
Webster K. Cavenee ◽  
Yoshiaki Shiokawa
Keyword(s):  
Cell Death ◽  
Ionizing Radiation ◽  
Combination Treatment ◽  
Tumor Necrosis ◽  
Malignant Gliomas ◽  
Glioma Cells ◽  
Caspase 8 ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Necrosis Factor

Object Malignant gliomas remain incurable despite modern multimodality treatments. Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL), also known as Apo2L, a member of the TNF family, preferentially induces apoptosis in human tumor cells through its cognate death receptors DR4 or DR5, suggesting that it may serve as a potential therapeutic agent for intractable malignant gliomas. Here, the authors show that genotoxic ionizing radiation synergistically enhances TRAIL-induced cell death in human glioma cells expressing DR5. Methods Combination treatment with soluble human TRAIL plus radiation induced robust cell death, while each of them singly led to only limited cytotoxicity. The combination resulted in cleavage and activation of the apoptotic initiator caspase-8 and the effector caspase-3 as well as cleavage of Bid and another initiator caspase-9, a downstream component of the apoptosome. Accordingly, it augmented the release of cytochrome c from the mitochondria into the cytosol, as well as apoptosis-inducing factor. Synergistic cell death was suppressed by TRAIL-neutralizing DR5-Fc, caspase inhibitors, expression of dominant-negative Fasassociated protein with death domain and CrmA, which selectively blocks caspase-8, and overexpression of Bcl-XL. Finally, combination treatment had no influence on the viability of normal human astrocytes. Conclusions These results suggest that combination treatment with TRAIL and ionizing radiation kills human glioma cells through the activation of DR5-mediated death receptor pathways. This therapy involves direct activation of effector caspases as well as mitochondria-mediated pathways and provides a novel strategy in which TRAIL could be synergistically combined with DNA-damaging radiation.

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