Transferrin receptor in normal and neoplastic brain tissue: implications for brain-tumor immunotherapy

1990 ◽  
Vol 72 (6) ◽  
pp. 941-945 ◽  
Author(s):  
Lawrence Recht ◽  
Carmen O. Torres ◽  
Thomas W. Smith ◽  
Vic Raso ◽  
Thomas W. Griffin
Keyword(s):  
Brain Tumor ◽  
Brain Tissue ◽  
Transferrin Receptor ◽  
Malignant Tumors ◽  
Staining Pattern ◽  
Tumor Immunotherapy ◽  
Normal Brain ◽  
Human Brain Tissue ◽  
Neoplastic Tissue ◽  
Intense Staining

✓ The distribution of transferrin receptor (TfR) in normal human brain-tissue obtained at autopsy and in brain-tumor biopsy specimens from 27 patients was determined by immunohistochemistry using two specific murine monoclonal antibodies against human TfR. The tumors studied included 10 glioblastomas multiforme (GBM's), nine other glial tumors, and eight meningiomas. In normal brain, TfR was detected primarily in endothelial cells; rare glial cells also contained immunoreactive product. All tumors contained TfR-positive cells, although the intensity (number of cells stained) and pattern (focal vs. diffuse) of staining varied with the histopathological type of the tumor. Among gliomas, the most intense staining was seen in GBM's, especially in areas of pseudopalisading where virtually all cells were stained. A rough correlation between tumor grade, number of positively stained cells, and staining pattern was seen in the other astrocytic tumors. By contrast, all meningiomas demonstrated an identical and characteristic focal staining pattern. Considering the differential immunostaining for TfR between normal and neoplastic tissue, the authors conclude that TfR may be an appropriate target for monoclonal antibody-directed brain-tumor immunotherapy, especially in more malignant tumors such as GBM's.

Quantitative Measurements of Regional Glucose Utilization and Rate of Valine Incorporation into Proteins by Double-Tracer Autoradiography in the Rat Brain Tumor Model

1989 ◽  
Vol 9 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Michihiro Kirikae ◽  
Mirko Diksic ◽  
Y. Lucas Yamamoto
Keyword(s):  
Protein Synthesis ◽  
Brain Tumor ◽  
Rat Brain ◽  
Brain Tissue ◽  
Glucose Utilization ◽  
Tumor Model ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Rat Brain Tumor ◽  
Brain Tumor Model

We examined the rate of glucose utilization and the rate of valine incorporation into proteins using 2-[18F]fluoro-2-deoxyglucose and L-[1-14C]-valine in a rat brain tumor model by quantitative double-tracer autoradiography. We found that in the implanted tumor the rate of valine incorporation into proteins was about 22 times and the rate of glucose utilization was about 1.5 times that in the contralateral cortex. (In the ipsilateral cortex, the tumor had a profound effect on glucose utilization but no effect on the rate of valine incorporation into proteins.) Our findings suggest that it is more useful to measure protein synthesis than glucose utilization to assess the effectiveness of antitumor agents and their toxicity to normal brain tissue. We compared two methods to estimate the rate of valine incorporation: “kinetic” (quantitation done using an operational equation and the average brain rate coefficients) and “washed slices” (unbound labeled valine removed by washing brain slices in 10% thrichloroacetic acid). The results were the same using either method. It would seem that the kinetic method can thus be used for quantitative measurement of protein synthesis in brain tumors and normal brain tissue using [11C]-valine with positron emission tomography.

scholarly journals Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

2011 ◽  
Vol 115 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Pablo A. Valdés ◽  
Frederic Leblond ◽  
Anthony Kim ◽  
Brent T. Harris ◽  
Brian C. Wilson ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Fluorescence Imaging ◽  
Low Grade ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Neoplastic Tissue ◽  
Fluorescence Measurements ◽  
Significant Difference ◽  
Quantitative Fluorescence

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

scholarly journals Yes-associated protein (YAP) promotes progression of glioma and poor prognosis of human

2021 ◽  
Author(s):  
Fei Yan ◽  
Lele Du ◽  
Jiatao Lv ◽  
Haitao Zhang ◽  
Jianxin Zhu ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Brain Tissue ◽  
Malignant Tumors ◽  
Normal Brain ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Glioma Tissue ◽  
Normal Brain Tissue ◽  
Polymerase Chain ◽  
Relationship Of

Abstract Background: Yes-associated protein(YAP) plays an important role in signal transduction and gene transcription regulation in 1 normal cells, with elevated and over-expressed YAP levels observed in various malignant tumors. The aim of this study was 2 to investigate the expression of YAP in malignant glioma, and to study the possible relationship of YAP expression with the 3 occurrence and development of malignant glioma. 4 Methods: Immunohistochemical staining was used to assess the expression of YAP and phosphor-YAP in malignant glioma 5 tissue and normal brain tissue, and their protein and mRNA levels were evaluated through Western blotting and reverse 6 transcription-polymerase chain reaction (RT-PCR), respectively. Normal brain tissue obtained from the functional lesion of 7 the epilepsy patients. After transfection of YAPsiRNA oligonucleotides or pcDNA3.1-hYAP plasmid, their effects on glioma 8 cells were investigated using western blot, cell proliferation, cycle, apoptosis and invasion, respectively. We conducted the 9 2 co-Immunoprecipitation to verify the combination of YAP and PPARγ, explore the mechanism of action. 10 Results: YAP-positive expression was found in 9 cases of normal brain and 60 cases of glioma. A significantly higher 11 expression of YAP in glioma tissue as compared with normal brain tissue at both protein and mRNA levels, and YAP proteins 12 mainly expressed and located in the nucleus and only a small percentage in the cytoplasm of glioma tissue. Phosphor-YAP 13 protein expression showed high staining of the cytoplasm, but no staining of the nuclear. While, with the enhancement of 14 the malignant degree, the cytoplasm YAP(p-YAP) expression is lower gradually than normal brain tissues. Further study in 15 glioma cell lines in which YAP was either overexpressed or depleted confirmed that YAP markedly promoted the cell 16 proliferation, cycle, invasion and inhibited the cell apoptosis. Moreover, YAP in company with PPARγ regulates the cell 17 proliferatin and effects the gliomagenesis. 18 Conclusion: These results indicate that YAP plays an important role in glioma and might be a useful therapeutic target of 19 glioma. 20

A Probability-Based Spectroscopic Diagnostic Algorithm for Simultaneous Discrimination of Brain Tumor and Tumor Margins from Normal Brain Tissue

2007 ◽  
Vol 61 (5) ◽  
pp. 548-557 ◽  
Author(s):  
Shovan K. Majumder ◽  
Steven Gebhart ◽  
Mahlon D. Johnson ◽  
Reid Thompson ◽  
Wei-Chiang Lin ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Brain Tissue ◽  
Diagnostic Algorithm ◽  
Simultaneous Discrimination ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Tumor Margins

Penetration of Nafcillin, Methicillin, and Cefazolin into Human Brain Tissue

Neurosurgery ◽  
1983 ◽  
Vol 12 (2) ◽  
pp. 142-147 ◽  
Author(s):  
Peter T. Frame ◽  
Chatrchai Watanakunakorn ◽  
Robert L. McLaurin ◽  
Ghahreman Khodadad
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tissue ◽  
Brain Biopsy ◽  
Normal Brain ◽  
Human Brain Tissue ◽  
Tissue Removal ◽  
Tissue Specimens ◽  
Abnormal Brain ◽  
Better Than

Abstract To determine the penetration of the antistaphylococcal antibiotics, nafcillin, methicillin, and cefazolin, into brain tissue, we gave to each of 27 patients undergoing craniotomy and brain biopsy one of the antibiotics in a 2-g intravenous infusion just before operation. At the time of brain tissue removal (30 to 225 minutes after the start of the infusion). a serum specimen was obtained, and tissue and serum were assayed for antibiotic concentration. Eleven of 13 brain specimens contained detectable nafcillin concentrations between 0.36 and 11 μg/g of tissue (mean. 2.7 μg/g for all 13 specimens). Fourteen of 18 brain tissue specimens contained detectable methicillin concentrations between 0.56 and 5.0 μg/g of tissue (mean, 2.0 μg/g for all 18 specimens). Ten of 11 brain tissue specimens contained detectable cefazolin concentrations between 2.0 and 40 μg/g of tissue (mean, 10.6 μg/g for all 11 specimens). Each antibiotic penetrated “abnormal” brain tissue better than “relatively normal” brain tissue. Because nafcillin is more active against Staphylococcus aureus, we conclude that nafcillin is preferable to methicillin for the therapy of central nervous system staphylococcal infections. Cefazolin achieves higher brain tissue concentrations than the penicillins, but has not been clinically evaluated for the therapy of central nervous system infections.

scholarly journals Accuracy of Raman spectroscopy in differentiating brain tumor from normal brain tissue

Oncotarget ◽  
2017 ◽  
Vol 8 (22) ◽  
pp. 36824-36831 ◽  
Author(s):  
Jing Zhang ◽  
Yimeng Fan ◽  
Min He ◽  
Xuelei Ma ◽  
Yanlin Song ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Brain Tumor ◽  
Brain Tissue ◽  
Normal Brain ◽  
Normal Brain Tissue

Plasminogen activator activity and molecular weight patterns in human brain tumors

1988 ◽  
Vol 68 (1) ◽  
pp. 73-79 ◽  
Author(s):  
Raymond Sawaya ◽  
Robert Highsmith
Keyword(s):  
Molecular Weight ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Human Brain ◽  
Plasminogen Activator ◽  
Malignant Tumors ◽  
Benign Tumors ◽  
Normal Brain ◽  
Human Brain Tumor ◽  
Content Type

✓ Fresh human brain-tumor samples were assayed for their plasminogen activator (PA) content. Specific molecular weight patterns were identified for each of five common brain tumors and for normal brain, suggesting a cell-specific origin of the various PA forms. Malignant tumors contained higher PA activity and a larger number of molecular weight patterns than benign tumors, with the exception of acoustic neurinomas. Irradiated tumors contained lower PA activity than nonirradiated tumors. Finally, a slight but definite correlation between brain edema and PA activity was detected. The future role of brain-tumor PA's for diagnostic and therapeutic purposes is discussed.

scholarly journals Preclinical evaluation of (S)-[18F]GE387, a novel 18-kDa translocator protein (TSPO) PET radioligand with low binding sensitivity to human polymorphism rs6971

2021 ◽  
Author(s):  
Nisha K. Ramakrishnan ◽  
Matthew Hird ◽  
Stephen Thompson ◽  
David J. Williamson ◽  
Luxi Qiao ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Rhesus Macaques ◽  
Biological Evaluation ◽  
Translocator Protein ◽  
Normal Brain ◽  
Human Brain Tissue ◽  
Peripheral Tissues ◽  
Low Sensitivity ◽  
The Brain

Abstract Purpose Positron emission tomography (PET) studies with radioligands for 18-kDa translocator protein (TSPO) have been instrumental in increasing our understanding of the complex role neuroinflammation plays in disorders affecting the brain. However, (R)-[11C]PK11195, the first and most widely used TSPO radioligand has limitations, while the next-generation TSPO radioligands have suffered from high interindividual variability in binding due to a genetic polymorphism in the TSPO gene (rs6971). Herein, we present the biological evaluation of the two enantiomers of [18F]GE387, which we have previously shown to have low sensitivity to this polymorphism. Methods Dynamic PET scans were conducted in male Wistar rats and female rhesus macaques to investigate the in vivo behaviour of (S)-[18F]GE387 and (R)-[18F]GE387. The specific binding of (S)-[18F]GE387 to TSPO was investigated by pre-treatment with (R)-PK11195. (S)-[18F]GE387 was further evaluated in a rat model of lipopolysaccharide (LPS)-induced neuroinflammation. Sensitivity to polymorphism of (S)-GE387 was evaluated in genotyped human brain tissue. Results (S)-[18F]GE387 and (R)-[18F]GE387 entered the brain in both rats and rhesus macaques. (R)-PK11195 blocked the uptake of (S)-[18F]GE387 in healthy olfactory bulb and peripheral tissues constitutively expressing TSPO. A 2.7-fold higher uptake of (S)-[18F]GE387 was found in the inflamed striatum of LPS-treated rodents. In genotyped human brain tissue, (S)-GE387 was shown to bind similarly in low affinity binders (LABs) and high affinity binders (HABs) with a LAB to HAB ratio of 1.8. Conclusion We established that (S)-[18F]GE387 has favourable kinetics in healthy rats and non-human primates and that it can distinguish inflamed from normal brain regions in the LPS model of neuroinflammation. Crucially, we have reconfirmed its low sensitivity to the TSPO polymorphism on genotyped human brain tissue. Based on these factors, we conclude that (S)-[18F]GE387 warrants further evaluation with studies on human subjects to assess its suitability as a TSPO PET radioligand for assessing neuroinflammation.

scholarly journals Segmenting and Classifiying the Brain Tumor from MRI Medical Images Based on Machine Learning Algorithms: A Review

2021 ◽  
pp. 50-61
Author(s):  
Omar Sedqi Kareem ◽  
Ahmed Khorsheed AL-Sulaifanie ◽  
Dathar Abas Hasan ◽  
Dindar Mikaeel Ahmed
Keyword(s):  
Brain Tumor ◽  
Brain Tissue ◽  
Machine Learning Algorithms ◽  
Medical Community ◽  
Tumor Segmentation ◽  
Normal Brain ◽  
Brain Tumor Segmentation ◽  
Non Invasive ◽  
Learning Techniques ◽  
The Brain

A brain tumor is a problem that threatens life and impedes the normal working of the human body. The brain tumor needs to be identified early for the proper diagnosis and effective treatment planning. Tumor segmentation from an MRI brain image is one of the most focused areas of the medical community, provided that MRI is non-invasive imaging. Brain tumor segmentation involves distinguishing abnormal brain tissue from normal brain tissue. This paper presents a systematic literature review of brain tumor segmentation strategies and the classification of abnormalities and normality in MRI images based on various deep learning techniques, interbreeding. It requires presentation and quantitative analysis, from standard segmentation and classification methods to the best class strategies.

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