scholarly journals Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients

2018 ◽  
Vol 28 (1) ◽  
pp. 56-62
Author(s):  
Cahit Kural ◽  
Arzu Kaya Kocdogan ◽  
Gulcin Güler Şimşek ◽  
Serpil Oğuztüzün ◽  
Pınar Kaygın ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Brain Tissue ◽  
Pituitary Adenomas ◽  
Normal Brain ◽  
Cytochrome P450 Enzyme ◽  
Intracranial Tumors ◽  
Glutathione S Transferase ◽  
Normal Brain Tissue ◽  
Tissue Samples ◽  
P450 Enzyme

Objective: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. Subjects and Methods: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016–2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. Results: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP­1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. Conclusion: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes.

scholarly journals Cerebral Blood Flow in Normal Brain Tissue of Patients with Intracranial Tumors

1996 ◽  
Vol 36 (10) ◽  
pp. 709-715 ◽  
Author(s):  
Yoshiya NAKAYAMA ◽  
Akira TANAKA ◽  
Shigehiko KUMATE ◽  
Shinya YOSHINAGA
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Tissue ◽  
Normal Brain ◽  
Intracranial Tumors ◽  
Normal Brain Tissue

scholarly journals GENE-53. IDENTIFICATION OF EPITHELIAL MEMBRANE PROTEIN 2 (EMP2) AS A MOLECULAR MARKER AND THERAPEUTIC TARGET IN MENINGIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi109-vi109
Author(s):  
Kunal Patel ◽  
Courtney Duong ◽  
Matthew Sun ◽  
Prasanth Romiyo ◽  
Sameer Kejriwal ◽  
...  
Keyword(s):  
Western Blot ◽  
Brain Tissue ◽  
Therapeutic Target ◽  
Normal Brain ◽  
Genetic Associations ◽  
Normal Brain Tissue ◽  
Tissue Samples ◽  
Molecular Alterations ◽  
Grade Ii ◽  
Epithelial Membrane Protein 2

Abstract BACKGROUND Intracranial meningiomas have been associated with a heterogenous set of genetic and molecular alterations. Despite these genetic associations, targeted therapies have been unable to increase survival in recurrent or residual meningiomas. There is a need for identification of therapeutic targets in meningioma. MATERIALS & METHODS Normal brain tissue from routine autopsy and tumor specimens from patients undergoing primary surgical resection of meningioma were analyzed. Pathologic diagnosis and grade were identified. Samples were stained with anti-EMP2 antisera and visualized with DAB (3,3’-Diaminobenzidine). Western blot analysis was carried out RESULTS In 17 patients with meningioma, there was statistically significant EMP2 staining in fresh brain tumor samples. EMP2 expression was confirmed and quantified with western blot which demonstrated significant positive expressivity. There were 12 grade I, 4 grade II, and 1 grade III meningiomas in our dataset and a significant trend towards increased EMP2 expression with higher grade. EMP2 expression was not identified in normal brain tissue samples from different locations including gray matter, white matter, and meninges in 3 control patients. CONCLUSIONS EMP2 is a protein associated with cell migration, invasion, and angiogenesis not identified in normal brain tissue but found in meningioma. EMP2 expression may be associated with increased tumor invasion and is a potential therapeutic target for residual or recurrent meningioma.

The role of cytochrome P450 enzyme genetic variants in cannabis hyperemesis syndrome—A case report

2021 ◽  
Author(s):  
Maxim Kuzin ◽  
Franziskos Xepapadakos ◽  
Isabel Scharrer ◽  
Marc Augsburger ◽  
Chin‐Bin Eap ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Case Report ◽  
Genetic Variants ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme ◽  
Cannabis Hyperemesis Syndrome

scholarly journals Neuroinflammatory changes of the normal brain tissue in cured mice following combined radiation and anti-PD-1 blockade therapy for glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariano Guardia Clausi ◽  
Alexander M. Stessin ◽  
Zirun Zhao ◽  
Stella E. Tsirka ◽  
Samuel Ryu
Keyword(s):  
Brain Tissue ◽  
Cranial Irradiation ◽  
Subcortical White Matter ◽  
Glioma Cell Line ◽  
Hippocampal Neurogenesis ◽  
Normal Brain ◽  
Long Term Effects ◽  
Normal Brain Tissue ◽  
Molecule Inhibitor

AbstractThe efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise. However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line and became long-term survivors after treatment with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed complete abolishment of hippocampal neurogenesis, but neural stem cells were well preserved in subventricular zone. In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.

Inter-species comparisons of hepatic cytochrome P450 enzyme levels in male ruminants

2003 ◽  
Vol 77 (10) ◽  
pp. 555-560 ◽  
Author(s):  
Miroslav Machala ◽  
Pavel Soucek ◽  
Jir� Neca ◽  
Robert Ulrich ◽  
Jir� Lamka ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme ◽  
Species Comparisons ◽  
Hepatic Cytochrome

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.

PET Study of Methionine Accumulation in Glioma and Normal Brain Tissue

1987 ◽  
Vol 11 (2) ◽  
pp. 208-213 ◽  
Author(s):  
Mats Bergström ◽  
Kaj Ericson ◽  
Lars Hagenfeldt ◽  
Mikael Mosskin ◽  
Hans von Holst ◽  
...  
Keyword(s):  
Brain Tissue ◽  
Normal Brain ◽  
Normal Brain Tissue

Quantitative Analysis of Mobile Proteins in Normal Brain Tissue by Amide Proton Transfer Imaging

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Kazuaki Sugawara ◽  
Tosiaki Miyati ◽  
Ryo Ueda ◽  
Daisuke Yoshimaru ◽  
Masanobu Nakamura ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Proton Transfer ◽  
Brain Tissue ◽  
Amide Proton ◽  
Normal Brain ◽  
Normal Brain Tissue ◽  
Amide Proton Transfer ◽  
Amide Proton Transfer Imaging

Drug Interactions of Macrolides: Emphasis on Dirithromycin

1997 ◽  
Vol 31 (3) ◽  
pp. 349-356 ◽  
Author(s):  
Vish S Watkins ◽  
Ron E Polk ◽  
Jennifer L Stotka
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Ethinyl Estradiol ◽  
Enzyme System ◽  
Cytochrome P450 Enzyme ◽  
Cytochrome P450 Enzymes ◽  
Kidney Transplant Recipients ◽  
P450 Enzyme ◽  
Cytochrome P450 Enzyme System ◽  
Clinically Significant

Objective To describe the drug interactions of dirithromycin, a new macrolide, and to compare them with those of other macrolides. Data Sources A literature search was performed using MEDLINE to identify articles published between January 1980 and July 1995 concerning the drug interactions of macrolides. Published abstracts were also examined. All studies using dirithromycin were performed under the sponsorship of Eli Lilly and Company. Data Synthesis Erythromycin, the first macrolide discovered, is metabolized by the cytochrome P450 enzyme system. By decreasing their metabolism, erythromycin can interact with other drugs metabolized by the cytochrome P450 enzymes. The lack of such interactions would be a desirable feature in a newer macrolide. We describe studies performed to detect any interactions of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, and ethinyl estradiol. The studies showed that dirithromycin, like azithromycin, is much less likely to cause the interactions detected with clarithromycin and erythromycin. A review of the literature showed differences among macrolides in their abilities to inhibit cytochrome P450 enzymes and, thus, to cause drug–drug interactions. Erythromycin and clarithromycin inhibit cytochrome P450 enzymes, and have been implicated in clinically significant interactions. Azithromycin and dirithromycin neither inhibit cytochrome P450 enzymes nor are implicated in clinically significant drug–drug interactions. Conclusions Dirithromycin, a new macrolide, does not inhibit the cytochrome P450 enzyme system. The concomitant use of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, or ethinyl estradiol was studied in pharmacokinetic and pharmacodynamic studies. In vitro, dirithromycin did not bind cytochrome P450. In healthy subjects, erythromycin increases the clearance of cyclosporine by 51%, whereas dirithromycin causes no significant changes in the pharmacokinetics of cyclosporine. In kidney transplant recipients, administration of dirithromycin was associated with a significant (p < 0.003) decrease of 17.4% in the clearance of cyclosporine. In patients taking low-dose estradiol, the administration of dirithromycin caused a significant (p < 0.03) increase of 9.9% in the clearance of ethinyl estradiol; escape ovulation did not occur. Unlike erythromycin and clarithromycin, dirithromycin had no significant effects on the pharmacokinetics of theophylline, terfenadine, or warfarin. The alterations typical of drug interactions that are based on inhibition of the cytochrome P450 system occurring with erythromycin and clarithromycin were not observed with dirithromycin.

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