Human Cytochrome P450 Cancer-Related Metabolic Activities and Gene Polymorphisms: A Review DOI Creative Commons
Innokenty M. Mokhosoev, Dmitry V. Astakhov, Alexander A. Terentiev

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1958 - 1958

Published: Nov. 26, 2024

Background: Cytochromes P450 (CYPs) are heme-containing oxidoreductase enzymes with mono-oxygenase activity. Human CYPs catalyze the oxidation of a great variety chemicals, including xenobiotics, steroid hormones, vitamins, bile acids, procarcinogens, and drugs. Findings: In our review article, we discuss recent data evidencing that same CYP isoform can be involved in both bioactivation detoxification reactions convert substrate to different products. Conversely, isoforms substrate, xenobiotic or procarcinogen, into either more less toxic product. These phenomena depend on type catalyzed reaction, tissue type, biological species. Since (CYP3A4, CYP1A1, CYP2D6, CYP2C8) primarily expressed liver, their metabolites induce hepatotoxicity hepatocarcinogenesis. Additionally, role drugs as substrates, inducers, inhibitors well implication nuclear receptors, efflux transporters, drug–drug interactions anticancer drug resistance. We highlight molecular mechanisms underlying development hormone-sensitive cancers, breast, ovarian, endometrial, prostate cancers. Key players these 2,3- 3,4-catechols estrogens, which formed by CYP1A2, CYP1B1. The catechols also produce quinones, leading formation protein DNA adducts contribute cancer progression. However, 2-hydroxy- 4-hydroxy-estrogens O-methylated derivatives along conjugated play cancer-protective roles. CYP17A1 CYP11A1, biosynthesis testosterone precursors, cancer, whereas conversion 5α-dihydrotestosterone sustained activation mutation androgen receptor implicated metastatic castration-resistant (CRPC). enzymatic activities influenced gene polymorphisms, although significant portion them have no effects. polymorphisms determine poor, intermediate, rapid, ultrarapid metabolizer genotypes, affect susceptibility. Despite limited statistically data, associations between risk, tumor size, status among various populations been demonstrated. Conclusions: metabolic diversity dual character effects underlie implications in, preliminarily, Variations interindividual variability provides options for personalized therapy.

Language: Английский

Microvascular Endothelium in Patients with Pancreatic Head Cancer and Relationship with Surgical Outcomes DOI Open Access
Sayakhat T. Olzhaev, Y. N. Shoykhet, К. С. Титов

et al.

Russian Journal of Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

BACKGROUND: The proportion of pancreatic cancer remains high in the overall incidence. Pancreatic ductal adenocarcinoma is a highly aggressive and lethal tumor. AIM: To evaluate microvascular endothelial function patients undergoing head surgery to establish correlation with surgical outcomes. MATERIALS AND METHODS: A prospective observational randomized study was conducted from 2009 2022. included two cohorts: healthy subjects (control group, n=40) diagnosed (patient n=95) who underwent Whipple procedure. assessment functional parameters endothelium measurements circulating cell count, von Willebrand factor (vWF), endothelium-dependent vasodilation. patient group divided into subgroups: main subgroup laparoscopic procedure (n=44) comparison consisted those laparotomy (n=51). In subgroup, were administered combination arginine glutamate (1.0 g daily) enalapril (2.5–5.0mg for treatment dysfunction. RESULTS: sums vWF significantly lower (7.0±1.4 93.6±23.3, respectively), whereas vasodilation higher (9.8±3.2) as compared control (p0.0001). population received dysfunction treatment, 4.2- 4.6-fold reduction levels, respectively, observed (p0.0001 both). Additionally, 4.0-fold increase documented count more than 7.0×104cells/L, 120%, less 10% during period risk early postoperative complications by 2.7, 1.9, 1.7times, respectively incidence non-surgical 28.4 24.2%, respectively. in-hospital mortality rate 5.3%. septic was2.5 3.1times lower, (p0.05). CONCLUSIONS: technique has been shown have protective effect on cancer, reducing complications. baseline vascular demonstrated correlate long-term adverse events, including relapses and/or metastases.

Language: Английский

Citations

0
Human Cytochrome P450 Cancer-Related Metabolic Activities and Gene Polymorphisms DOI Open Access
Innokenty M. Mokhosoev, Dmitry V. Astakhov, Alexander A. Terentiev

et al.

Published: Oct. 29, 2024

Human CYP1-CYP4 families play crucial roles in the biosynthesis, bioactivation, and detoxification of a diverse range chemicals including xenobiotics, steroid hormones, vitamins, bile acids, procarcinogens, drugs. The same CYP isoform can be involved conversion different substrates via both bioactivation reactions depending on substrate type. Furthermore, convert to products tissue On contrary, isoforms variety products, either more toxic or less than their parent compound. metabolic diversity dual character biological effects dictate limited number cancer types, which CYPs are implicated. In our review, we highlight latest advancements current understanding molecular mechanisms development hormone-sensitive cancers tumors based dysregulated expression mutagenic adduct formation. We discuss variations activities gene polymorphisms, affect interindividual differences drug susceptibilities. show that there is only data indicating statistically significant association between polymorphisms among populations. involvement anticancer metabolism associated with drug-drug interactions resistance also discussed.

Language: Английский

Citations

3
Tumor microenvironment and cancer metastasis: molecular mechanisms and therapeutic implications DOI Creative Commons
Çıgır Biray Avci, Bakiye Göker Bağca, Masoud Nikanfar

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 12, 2024

The tumor microenvironment (TME) plays a crucial role in cancer development and metastasis. This review summarizes the current research on how TME promotes metastasis through molecular pathways, focusing key components, such as cancer-associated fibroblasts, immune cells, endothelial cytokines, extracellular matrix. Significant findings have highlighted that alterations cellular communication within enable cells to evade surveillance, survive, invade other tissues. highlights roles of TGF-β VEGF signaling promoting angiogenesis matrix remodeling, which facilitate Additionally, we explored metabolic reprogramming stromal influenced by nutrient availability TME, drives progression. study also evaluated therapeutic strategies targeting these interactions disrupt By providing multidisciplinary perspective, this suggests understanding basis can lead more effective therapies identify potential avenues for future research. Future should prioritize unraveling complex environment, could novel personalized treatments. Moreover, advancements technologies single-cell analysis, spatial transcriptomics, epigenetic profiling offer promising identifying new targets improving efficacy immunotherapies, particularly context

Language: Английский

Citations

3
Human Cytochrome P450 Cancer-Related Metabolic Activities and Gene Polymorphisms: A Review DOI Creative Commons
Innokenty M. Mokhosoev, Dmitry V. Astakhov, Alexander A. Terentiev

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(23), P. 1958 - 1958

Published: Nov. 26, 2024

Background: Cytochromes P450 (CYPs) are heme-containing oxidoreductase enzymes with mono-oxygenase activity. Human CYPs catalyze the oxidation of a great variety chemicals, including xenobiotics, steroid hormones, vitamins, bile acids, procarcinogens, and drugs. Findings: In our review article, we discuss recent data evidencing that same CYP isoform can be involved in both bioactivation detoxification reactions convert substrate to different products. Conversely, isoforms substrate, xenobiotic or procarcinogen, into either more less toxic product. These phenomena depend on type catalyzed reaction, tissue type, biological species. Since (CYP3A4, CYP1A1, CYP2D6, CYP2C8) primarily expressed liver, their metabolites induce hepatotoxicity hepatocarcinogenesis. Additionally, role drugs as substrates, inducers, inhibitors well implication nuclear receptors, efflux transporters, drug–drug interactions anticancer drug resistance. We highlight molecular mechanisms underlying development hormone-sensitive cancers, breast, ovarian, endometrial, prostate cancers. Key players these 2,3- 3,4-catechols estrogens, which formed by CYP1A2, CYP1B1. The catechols also produce quinones, leading formation protein DNA adducts contribute cancer progression. However, 2-hydroxy- 4-hydroxy-estrogens O-methylated derivatives along conjugated play cancer-protective roles. CYP17A1 CYP11A1, biosynthesis testosterone precursors, cancer, whereas conversion 5α-dihydrotestosterone sustained activation mutation androgen receptor implicated metastatic castration-resistant (CRPC). enzymatic activities influenced gene polymorphisms, although significant portion them have no effects. polymorphisms determine poor, intermediate, rapid, ultrarapid metabolizer genotypes, affect susceptibility. Despite limited statistically data, associations between risk, tumor size, status among various populations been demonstrated. Conclusions: metabolic diversity dual character effects underlie implications in, preliminarily, Variations interindividual variability provides options for personalized therapy.

Language: Английский

Citations

1