Hypoxia as a Modulator of Inflammation and Immune Response in Cancer.

A clear association between hypoxia and cancer has heretofore been established; however, it has not been completely developed. In this sense, the understanding of the tumoral microenvironment is critical to dissect the complexity of cancer, including the reduction in oxygen distribution inside the tumoral mass, defined as tumoral hypoxia. Moreover, hypoxia not only influences the tumoral cells but also the surrounding cells, including those related to the inflammatory processes.

Transcriptional Regulation of Yin-Yang 1 Expression through the Hypoxia Inducible Factor-1 in Pediatric Acute Lymphoblastic Leukemia.

Yin-Yang transcription factor 1 (YY1) is involved in tumor progression, metastasis and has been shown to be elevated in different cancers, including leukemia. The regulatory mechanism underlying YY1 expression in leukemia is still not understood. Bioinformatics analysis reveal three Hypoxia-inducible factor 1-alpha (HIF-1α) putative binding sites in the YY1 promoter region.

The rs776746 variant of CYP3A5 is associated with intravenous midazolam plasma levels and higher clearance in critically ill Mexican paediatric patients.

What Is Known And Objective: Midazolam is a drug that is metabolized by cytochrome P450 (CYP450) enzymes, particularly CYP3A4 and CYP3A5. The presence of single-nucleotide polymorphisms (SNPs) in the genes encoding these enzymes, such as CYP3A4*1B which is associated with low enzyme expression and activity and CYP3A5*3, has been associated with decrease in enzymatic activity and reduced drug clearance, with potential effects on drug levels and/or toxicity. The present study was conducted to determine the frequencies of the allelic variants of the CYP3A4 (rs2740574) and CYP3A5 (rs776746) genes and their effects on the plasma levels and clearance of intravenous midazolam in critically ill Mexican paediatric patients.

Hypoxia as a modulator of cytochromes P450: Overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia.

Low levels of oxygen (hypoxia) have been reported in solid tumours. This hypoxic microenvironment modulates the expression of genes linked to a more aggressive disease. However, it is unclear if the expression of drug-metabolizing enzymes as cytochromes P450 (CYPs) is affected by hypoxia in cancer.

Microenvironment-regulated lncRNA-HAL is able to promote stemness in breast cancer cells.

Multicellular Tumor Spheroids culture (MCTS) is an in vitro model mimicking the characteristics of the tumor microenvironment, such as hypoxia and acidosis, resulting in the presence of both proliferating and quiescent cell populations. lncRNA's is a novel group of regulatory molecules that participates in the acquisition of tumorigenic phenotypes. In the present work we evaluated the oncogenic association of an uncharacterized lncRNA (lncRNA-HAL) in the tumorigenic phenotype induced by the MCTS microenvironment.

Hypoxia increases chemoresistance in human medulloblastoma DAOY cells via hypoxia‑inducible factor 1α‑mediated downregulation of the CYP2B6, CYP3A4 and CYP3A5 enzymes and inhibition of cell proliferation.

Medulloblastomas are among the most frequently diagnosed pediatric solid tumors, and drug resistance remains as the principal cause of treatment failure. Hypoxia and the subsequent activation of hypoxia‑inducible factor 1α (HIF‑1α) are considered key factors in modulating drug antitumor effectiveness, but the underlying mechanisms in medulloblastomas have not yet been clearly understood. The aim of the present study was to determine whether hypoxia induces resistance to cyclophosphamide (CPA) and ifosfamide (IFA) in DAOY medulloblastoma cells, whether the mechanism is dependent on HIF‑1α, and whether involves the modulation of the expression of cytochromes P450 (CYP)2B6, 3A4 and 3A5 and the control of cell proliferation.

Data mining of pediatric medulloblastoma microarray expression reveals a novel potential subdivision of the Group 4 molecular subgroup.

Medulloblastoma is the most common type of solid brain tumor in children. This type of embryonic tumor is highly heterogeneous and has been classified into 4 molecular subgroups based on their gene expression profiles: WNT, SHH, Group 3 (G3) and Group 4 (G4). WNT and SHH tumors exhibit the specific dysregulation of genes and pathways, whereas G3 and G4 tumors, two of the more frequent subtypes, are the least characterized.

A case of cervical cancer expressed three mRNA variant of Hyaluronan-mediated motility receptor.

Cervical cancer is the second malignancy in Mexico, little is known about the prognostic factors associated with this disease. Several cellular components are important in their transformation and progression. Alternative mRNA splice is an important mechanism for generating protein diversity, nevertheless, in cancer unknown mRNA diversity is expressed.

The relationship among IL-13, GSTP1, and CYP1A1 polymorphisms and environmental tobacco smoke in a population of children with asthma in Northern Mexico.

Exposure to environmental tobacco smoke (ETS) during early childhood increases the risk of developing asthma. The intention of this study was to genotype a population of children from Coahuila state in Northern Mexico and to determine whether polymorphisms of the CYP1A1, GSTP1, and IL13 genes are associated with exposure to ETS and subsequently a higher risk for asthma. IL13 plays an important role in the development of allergic response, particularly those related with airway inflammation.

Induction of CYP1A1 and CYP2E1 in rat liver by histamine: binding and kinetic studies.

Histamine (HA) may bind to cytochrome P450 (CYP450) in rat liver microsomes. The CYP450-HA complex seems to regulate some cellular processes such as proliferation. In the present work, it is shown that HA increases the activity and protein level of CYP1A1 and CYP2E1, in vivo.