Increased expression of aromatase cytochrome P450 enzyme is associated with prolactinoma invasiveness in post-menopausal women

Objectives To investigate the expression levels of aromatase cytochrome P450 enzyme (P450AROM) and related molecules—estrogen receptor-beta (ER-β), Ki-67, and p53—in prolactinoma tumor tissue from pre- and post-menopausal women, and to determine the associations of tumor invasiveness with expression levels of these genes. Methods This study recruited 90 patients with prolactinoma who underwent adenoidectomy between 2012 and 2017. Information was collected regarding clinical characteristics, hormones, laboratory tests, and magnetic resonance imaging-assessed tumor invasiveness. Expression levels of P450AROM, ER-β, Ki-67, and p53 were examined by immunohistochemistry in prolactinoma tissues. Results Increased P450AROM expression was found in invasive prolactinoma tissues in post-menopausal women, compared with its expression in non-invasive prolactinoma tissues. ER-β level was significantly higher in patients resistant to treatment with bromocriptine, a dopamine agonist. However, there were no differences in rate of resistance to treatment (8.2% vs. 3.4%) or expression levels of P450AROM, Ki-67, p53, and ER-β between pre- and post-menopausal patients. Conclusions Our results demonstrated that increased P450AROM expression in prolactinoma of post-menopausal women was positively associated with invasiveness. Moreover, ER-β level was higher in both pre- and post-menopausal patients who were resistant to dopamine agonist treatment.

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

Basic & Clinical Pharmacology & Toxicology ◽

10.1111/bcpt.13581 ◽

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

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

Archives of Toxicology ◽

10.1007/s00204-003-0477-4 ◽

2003 ◽

Vol 77 (10) ◽

pp. 555-560 ◽

Cited By ~ 22

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

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Prognostic Signicance of Cellular Iron Metabolism in Breast Cancer

Pakistan BioMedical Journal ◽

10.52229/pbmj.v1i1.35 ◽

2018 ◽

Vol 1 (1) ◽

Author(s):

Rizwan Ullah Khan ◽

Amber Hassan ◽

Imrana Tanvir ◽

Kashifa Ehsan

Keyword(s):

Breast Cancer ◽

Breast Carcinoma ◽

Ki 67 ◽

Luminal B ◽

Cellular Iron ◽

Menopausal Women ◽

New Strategy ◽

Poorly Differentiated ◽

Well Differentiated ◽

Post Menopausal

Breast carcinoma is among the most common malignancy in women. Abstract:Original ArticleAim of the present study was to evaluate the prognostic signicance of iron expression in the biopsies of patients with breast cancer Objective:24 breast biopsies were studied. 19 cases were poorly differentiated, 5 cases were moderately differentiated and there was no well differentiated case. Iron, Estrogen receptor (ER), Progesterone receptor (PR), HER2 and Ki-67 immunohistochemical staining was performed for all these cases. Methods: Among the 5 moderately differentiated cases, 3 (60%) were positive for iron staining and among 19 poorly differentiated cases, 11 cases (57.89%) were positive. More iron positive cases (7 out of 14) were triple positive belonging to Luminal B class. Out of 14 iron positive cases, 11 were positive for HER2, 10 for ER, 9 for PR and all positive for Ki-67. Results: Iron deciency in premenopausal and overload in post-menopausal women can contribute to the development of breast carcinoma. So, iron can be considered as a cheap and effective marker for the prognosis of breast cancer. Association between a rise in iron levels and HER2 expression may provide new strategy for breast cancer treatment.

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

Medical Principles and Practice ◽

10.1159/000494496 ◽

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.

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Drug Interactions of Macrolides: Emphasis on Dirithromycin

Annals of Pharmacotherapy ◽

10.1177/106002809703100314 ◽

1997 ◽

Vol 31 (3) ◽

pp. 349-356 ◽

Cited By ~ 28

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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