A Preliminary Study of Brain Gliomas with H17E2 Monoclonal Antibody: Immunoscintigraphy and Pharmacokinetics

1989 ◽  
Vol 4 (3) ◽  
pp. 135-141
Author(s):  
DV. Skarlos ◽  
J. Malamitsi ◽  
G B. Sivolapenko ◽  
N. Demakopoulos ◽  
G. Avgoustatos ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Urinary Excretion ◽  
Specific Antibody ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Placental Alkaline Phosphatase ◽  
High Grade ◽  
Iodine 131 ◽  
Brain Gliomas

Ten patients with relapsing high grade brain gliomas and one patient with low grade glioma were studied with a monoclonal antibody (H17E2) against placental alkaline phosphatase. In addition 2 patients with relapsing high grade glioma were studied with a non specific antibody (4D513/2118). 1 mCi of Iodine-131-labelled H17E2 was administered intracarotidly (i.c.) in two, and intravenously (i.v.) in 9 patients. Immunoscintigrams were taken at 0, 2, 24, 48 and 72 hours. Radioactivity was monitored in blood and urine. Tumour/non-tumour ratios were estimated (max. 2.45). All high grade gliomas receiving specific antibody irrespective of the route of administration, gave a positive immunoscintigraphic pattern, increasing in intensity with time. Disappearance of radioactivity in blood was biexpontential with a long component over 30 hours. Urinary excretion of radioactivity ranged from 3.7–21.7% of administered dose/day. The patient with low grade glioma and the patients receiving non specific monoclonal antibody showed a negative pattern, a fast blood clearance and a high urinary excretion. We conclude that a) Iodine-131 labelled H17E2 proved to be stable in vivo and produced satisfactory tumour localisation and b) i.v. route was as good as i.c.

TMOD-18. DIRECT IN VIVO CRISPR SCREEN IDENTIFIES COOPERATING TUMOR SUPPRESSORS THAT DRIVE PROGRESSION OF IDH1-MUTANT LOW-GRADE GLIOMA TO AGGRESSIVE GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi219-vi219
Author(s):  
Connor Yanchus ◽  
Kristen Drucker ◽  
Thomas Kollmeyer ◽  
Ricky Tsai ◽  
Lingyan Jiang ◽  
...  
Keyword(s):  
Low Grade Glioma ◽  
Malignant Progression ◽  
Mutant Mice ◽  
Low Grade ◽  
High Grade ◽  
Secondary Glioblastoma ◽  
Idh1 R132h ◽  
Idh Mutations ◽  
Crispr Screen

Abstract Low-grade glioma (LGG) are generally slowly growing brain cancers, that frequently undergo malignant progression to aggressive, secondary glioblastoma with a dismal prognosis. By combining genetically engineered Idh1-mutant mice with in vivo CRISPR gene editing we generated a mouse model faithfully recapitulating the founder mutations of LGG. Clonal activation of the neomorphic Idh1 R132H mutation cooperates with Trp53 and Atrx mutations to trigger development of brain tumors but only with ~30% penetrance and very long latency. To elucidate the molecular mechanisms underlying the malignant progression of IDH1-mutant LGG, we devised and deployed a direct in vivo CRISPR screen targeting genes commonly mutated in human IDH-mutant secondary glioblastoma. Stereotaxic delivery of a lentiviral sgRNA library targeting the mouse orthologs of these genes into the brain of Idh1 R132H ;Trp53;Atrx;Cas9 and control Idh1 wt ;Trp53;Atrx;Cas9 compound mutant mice resulted in rapid formation of tumors that recapitulate human Idh1-mutant glioblastoma. Deconvoluting the screen showed that PI3K pathway members Pten and Pik3ca as well as Notch1, Smarca4 and Fat1 are preferentially enriched in Idh1 R132H-tumors, while Rb1 and NF2 were enriched in Idh1 wt tumors. Co-mutation analysis further identified additional co-occurring driver combinations such as Bcor-Met, Olig2-Met, Olig2-Med12 or Bcor-Olig2. We validated the tumor suppressive function of Notch1 and Pten using conventional floxed knock-out alleles and found that Notch1 functions in a haploinsufficient manner. Interestingly, Idh1 R132H did not alter tumor latency or pathology in a high grade p53;Pten;Rb1 mutant background, indicating that the neomorphic IDH-mutations can drive low but not high grade glioma development. Our study provides a functional landscape of gliomagenesis suppressors in vivo.

scholarly journals TMOD-23. A NOVEL BRAF V600E LOW-GRADE GLIOMA MOUSE MODEL HIGHLIGHTS EXOMIC AND TUMOR IMMUNE ALTERATIONS AND DIFFERING THERAPEUTIC RESPONSES IN LOW- AND HIGH-GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii232-ii233
Author(s):  
Anne Marie Barrette ◽  
Lasse Meyer ◽  
Yoko Hirata ◽  
Stefan Grossauer ◽  
Edbert Lu ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Low Grade Glioma ◽  
Braf V600e ◽  
Common Mutation ◽  
Low Grade ◽  
High Grade ◽  
Checkpoint Inhibition ◽  
Immune Infiltrate ◽  
Low Grade Gliomas

Abstract Pediatric low-grade glioma (pLGG), the most common brain cancer in children, is difficult to treat especially at recurrence. The BRAF V600E mutation is the second most common mutation in pLGG, and in a high-risk group for progression is associated with deletion of the tumor suppressor CDKN2A. A better understanding of the factors contributing to progression, in particular the role of the immune infiltrate is needed, but studies have been hindered by the lack of low-grade glioma mouse models. We utilized transgenic mice with a cre-activatable (CA) allele of BRAF V600E to generate endogenous models for low-grade gliomas. We found that BRAF V600E expression cooperates with hemizygous CDKN2A deletion to induce low-grade gliomas, with tumors forming at a greater latency than by homozygous deletion. Cell line derivatives from low-grade lesions continue to grow slower upon orthotopic injection than those we previously derived from high-grade tumors. Murine LGG can progress to higher grade tumors within the mouse lifespan and we observe exomic changes and alterations in the tumor immune infiltrate associated with progression, the details of which will be discussed at the meeting. High-grade cells’ phenotypic changes within in vivo passage are accompanied by exomic changes. The high-grade glioma immune infiltrate is altered by dual MAPK pathway inhibition with dabrafenib and trametinib. Adding dual immune checkpoint inhibition by anti-PD-L1 and anti-CTLA-4 antibodies significantly extends survival of dabrafenib-trametinib dual treatment. Human BRAF V600E mutant tumors reportedly have a higher tumor immune infiltrate than that of BRAF wildtype gliomas, consistent with our murine RESULTS: Here we present a novel model for BRAF V600E mutant gliomas in mice that has a frequent rate of progression, similar to human BRAF V600E mutant gliomas, and an active immune infiltrate in high grade tumors which makes them susceptible to the immunostimulatory effects of dual checkpoint inhibition.

Abstract CT025: Dabrafenib plus trametinib in BRAF V600E-mutant high-grade (HGG) and low-grade glioma (LGG)

2021 ◽  
Author(s):  
Vivek Subbiah ◽  
Alexander Stein ◽  
Martin van den Bent ◽  
Antje Wick ◽  
Filip Y. de Vos ◽  
...  
Keyword(s):  
Low Grade Glioma ◽  
Braf V600e ◽  
Low Grade ◽  
High Grade

Low-Grade Glioma: High-Grade Tumor Recurrence

2019 ◽  
pp. 175-179
Author(s):  
Francesco Fabbiano ◽  
Jacopo Scaggiante ◽  
Andrea Wlderk ◽  
Gualtiero Innocenzi ◽  
Sergio Paolini ◽  
...  
Keyword(s):  
Tumor Recurrence ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade

scholarly journals SURG-32. THE USE OF 5-AMINOLEVULINIC ACID IN LOW-GRADE GLIOMA RESECTION: A SYSTEMATIC REVIEW

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi246-vi246
Author(s):  
Ahmad Almekkawi ◽  
Tarek El Ahmadieh ◽  
Karl Abi-Aad ◽  
Salah Aoun ◽  
Najib EL Tecle ◽  
...  
Keyword(s):  
Systematic Review ◽  
Quality Index ◽  
Aminolevulinic Acid ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Visualization Technology ◽  
Glioma Resection

Abstract BACKGROUND 5-aminolevulinic acid is a reliable tool for optimizing high-grade glioma resection. However, its efficacy in low-grade glioma resection remains unclear. OBJECTIVE To study the role of 5-aminolevulinic acid in low-grade glioma resection and assess positive fluorescence rates and effect on the extent of resection. METHODS A systematic review of PubMed, Google Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. Quality index of the selected papers using the Downs and Black criteria checklist was provided. RESULTS Twelve articles met the selection criteria with 244 histologically-confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n=60/244; 24.5%) demonstrated visual intra-operative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies, however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10–17) which correlated with an overall good quality. CONCLUSION There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection.

scholarly journals Cytotoxicity of Protein-Carbon Nanotubes on J774 Macrophages Is a Functionalization Grade-Dependent Effect

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Silvia Lorena Montes-Fonseca ◽  
Blanca Sánchez-Ramírez ◽  
Antonia Luna-Velasco ◽  
Carlos Arzate-Quintana ◽  
Macrina Beatriz Silva-Cazares ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Cytotoxic Effect ◽  
Surface Protein ◽  
Low Grade ◽  
High Grade ◽  
Dependent Effect ◽  
Chemical Substances ◽  
Raman And Infrared Spectroscopy

Carbon nanotubes (CNTs) are used as carriers in medicine due to their ability to be functionalized with chemical substances. However, cytotoxicity analysis is required prior to use forin vivomodels. The aim of this study was to evaluate the cytotoxic effect of CNTs functionalized with a 46 kDa surface protein fromEntamoeba histolytica(P46-CNTs) on J774A macrophages. With this purpose, CNTs were synthesized by spray pyrolysis and purified (P-CNTs) using sonication for 48 h. A 46 kDa protein, with a 4.6–5.4 pI range, was isolated fromE. histolyticaHM1:IMSS strain trophozoites using an OFFGEL system. The P-CNTs were functionalized with the purified 46 kDa protein, classified according to their degree of functionalization, and characterized by Raman and Infrared spectroscopy.In vitrocytotoxicity was evaluated by MTT, apoptosis, and morphological assays. The results demonstrated that P46-CNTs exhibited cytotoxicity dependent upon the functionalized grade. Contrary to what was expected, P46-CNTs with a high grade of functionalization were more toxic to J774 macrophages than P46-CNTs with a low grade of functionalization, than P-CNTs, and had a similar level of toxicity as UP-CNT. This suggests that the nature of the functionalized protein plays a key role in the cytotoxicity of these nanoparticles.

scholarly journals Combined cytotoxic effect of UV-irradiation and TiO2microbeads in normal urothelial cells, low-grade and high-grade urothelial cancer cells

2015 ◽  
Vol 14 (3) ◽  
pp. 583-590 ◽  
Author(s):  
Roghayeh Imani ◽  
Peter Veranič ◽  
Aleš Iglič ◽  
Mateja Erdani Kreft ◽  
Meysam Pazoki ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Cytotoxic Effect ◽  
Urothelial Cancer ◽  
Low Grade ◽  
High Grade ◽  
Urothelial Cells ◽  
Efficient Approach

Paper shows that internalization of the TiO2microbeads followed by the UV-irradiation is an efficient approach for killing cancer urothelial cells. Additionally, differentiation dependent differences in the sensitivity of the cells to the UV-irradiation are shown, and a model of photocatalytic treatment of thein vivobladder cancer is presented.

scholarly journals In vitro and In vivo Targeting Properties of Iodine-123- or Iodine-131–Labeled Monoclonal Antibody 14C5 in a Non–Small Cell Lung Cancer and Colon Carcinoma Model

2005 ◽  
Vol 11 (20) ◽  
pp. 7288-7296 ◽  
Author(s):  
Ingrid Burvenich ◽  
Steve Schoonooghe ◽  
Bart Cornelissen ◽  
Peter Blanckaert ◽  
Elisabeth Coene ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Monoclonal Antibody ◽  
Small Cell Lung Cancer ◽  
Colon Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Iodine 131 ◽  
Iodine 123

A Fibrin Specific Monoclonal Antibody which Interferes with the Fibrinolytic Effect of Tissue Plasminogen Activator

1988 ◽  
Vol 59 (03) ◽  
pp. 426-431 ◽  
Author(s):  
P E Gargan ◽  
V A Ploplis ◽  
J D Scheu
Keyword(s):  
Monoclonal Antibody ◽  
Cell Line ◽  
Specific Antibody ◽  
Myeloma Cell ◽  
Dependent Manner ◽  
Mouse Myeloma Cell Line ◽  
Release Assay ◽  
Dose Dependent ◽  
Mouse Myeloma

SummaryMonoclonal antibodies to human fibrin have been prepared from stable hybridomas, obtained by fusion of a mouse myeloma cell line (NS-1) and spleen cells of Balb/c mice immunized with a suspension of human fibrin. One cell line, DG1, producing a monoclonal antibody of the IgG1 κ subclass, reacted specifically with human fibrin (KD = 1.2 nM). Western blotting analysis indicates that DG1 crossreacts with the fibrin fragment D-dimer. Using both a chromogenic and an 125I-fibrin release assay it was illustrated that in the presence of the fibrin specific antibody the t-PA mediated generation of plasmin was significantly inhibited.An animal model system, developed to monitor thrombosis and induced reactive fibrinolysis, was used to investigate the interference of plasminogen activation, by the antibody, in vivo.This fibrin specific antibody prolonged the onset of reactive fibrinolysis in a dose dependent manner.

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