Search results for "Aldehyde dehydrogenase"
showing 10 items of 46 documents
Aldehyde Dehydrogenase 1-Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer
2009
Abstract Purpose: To examine the role of cancer stem cells (CSC) in mediating metastasis in inflammatory breast cancer (IBC) and the association of these cells with patient outcome in this aggressive type of breast cancer. Experimental Design: CSCs were isolated from SUM149 and MARY-X, an IBC cell line and primary xenograft, by virtue of increased aldehyde dehydrogenase (ALDH) activity as assessed by the ALDEFLUOR assay. Invasion and metastasis of CSC populations were assessed by in vitro and mouse xenograft assays. Expression of ALDH1 was determined on a retrospective series of 109 IBC patients and this was correlated with histoclinical data. All statistical tests were two sided. Log-rank …
HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion.
2008
The cancer stem cell hypothesis proposes that cancers arise in stem/progenitor cells through disregulation of self-renewal pathways generating tumors, which are driven by a component of 'tumor-initiating cells' retaining stem cell properties. The HER2 gene is amplified in 20-30% of human breast cancers and has been implicated in mammary tumorigenesis as well as in mediating aggressive tumor growth and metastasis. We demonstrate that HER2 overexpression drives mammary carcinogenesis, tumor growth and invasion through its effects on normal and malignant mammary stem cells. HER2 overexpression in normal mammary epithelial cells (NMEC) increases the proportion of stem/progenitor cells as demons…
Resistance factors in colon cancer tissue and the adjacent normal colon tissue: glutathione S-transferases alpha and pi, glutathione and aldehyde deh…
1998
Abstract Glutathione S -transferases (GST) α and π , glutathione (GSH) and aldehyde dehydrogenase (ADH) were determined in colorectal cancer tissue specimens and in the adjacent normal colon tissue. The median contents in normal and cancer tissue were 8.1 (2.3–30.3) (5–95% quantiles) and 15.1 (5.3–50.3) μ g/mg protein for GST π ( P =0.035), 0.0 (0.0–1.4) and 0.4 (0.0–3.5) μ g/mg protein for GST α ( P =0.019), 7.3 (1.3–22.7) and 5.6 (2.3–26.0) μ g/mg protein for GSH ( P =0.171) and 30.8 (13.0–42.0) and 23.2 (9.0–32.9) μ g/mg protein for ADH ( P =0.0017), respectively. Thus, the mean GST α and π both significantly increased in colon cancer compared to the adjacent normal tissue, which underli…
Draft genome of a novel methanotrophic Methylobacter sp. from the volcanic soils of Pantelleria Island
2021
AbstractThe genus Methylobacter is considered an important and often dominant group of aerobic methane-oxidizing bacteria in many oxic ecosystems, where members of this genus contribute to the reduction of CH4 emissions. Metagenomic studies of the upper oxic layers of geothermal soils of the Favara Grande, Pantelleria, Italy, revealed the presence of various methane-oxidizing bacteria, and resulted in a near complete metagenome assembled genome (MAG) of an aerobic methanotroph, which was classified as a Methylobacter species. In this study, the Methylobacter sp. B2 MAG was used to investigate its metabolic potential and phylogenetic affiliation. The MAG has a size of 4,086,539 bp, consists …
Drug-metabolizing enzymes in the skin of man, rat, and pig.
2007
The mammalian skin has long been considered to be poor in drug metabolism. However, many reports clearly show that most drug metabolizing enzymes also occur in the mammalian skin albeit at relatively low specific activities. This review summarizes the current state of knowledge on drug metabolizing enzymes in the skin of human, rat, and pig, the latter, because it is often taken as a model for human skin on grounds of anatomical similarities. However only little is known about drug metabolizing enzymes in pig skin. Interestingly, some cytochromes P450 (CYP) have been observed in the rat skin which are not expressed in the rat liver, such as CYP 2B12 and CYP2D4. As far as investigated most d…
Nitrate tolerance as a model of vascular dysfunction: Roles for mitochondrial aldehyde dehydrogenase and mitochondrial oxidative stress
2008
Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents. The mechanisms underlying nitrate tolerance remain incompletely defined and are likely multifactorial. One mechanism seems to be a diminished bioconversion of nitroglycerin, another seems to be the induction of vascular oxidative stress, and a third may include neurohumoral adaptations. Recent studies have revealed that mitochondrial reactive oxygen…
Dual disruption of aldehyde dehydrogenases 1 and 3 promotes functional changes in the glutathione redox system and enhances chemosensitivity in nonsm…
2020
AbstractAldehyde dehydrogenases (ALDHs) are multifunctional enzymes that oxidize diverse endogenous and exogenous aldehydes. We conducted a meta-analysis based on The Cancer Genome Atlas and Gene Expression Omnibus data and detected genetic alterations in ALDH1A1, ALDH1A3, or ALDH3A1, 86% of which were gene amplification or mRNA upregulation, in 31% of nonsmall cell lung cancers (NSCLCs). The expression of these isoenzymes impacted chemoresistance and shortened survival times in patients. We hypothesized that these enzymes provide an oxidative advantage for the persistence of NSCLC. To test this hypothesis, we used genetic and pharmacological approaches with DIMATE, an irreversible inhibito…
The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats
2017
Hyperglycemia associated with inflammation and oxidative stress is a major cause of vascular dysfunction and cardiovascular disease in diabetes. Recent data reports that a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), empagliflozin (Jardiance®), ameliorates glucotoxicity via excretion of excess glucose in urine (glucosuria) and significantly improves cardiovascular mortality in type 2 diabetes mellitus (T2DM). The overarching hypothesis is that hyperglycemia and glucotoxicity are upstream of all other complications seen in diabetes. The aim of this study was to investigate effects of empagliflozin on glucotoxicity, β-cell function, inflammation, oxidative stress and endothel…
Heme oxygenase-1: a novel key player in the development of tolerance in response to organic nitrates.
2007
Objective— Nitrate tolerance is likely attributable to an increased production of reactive oxygen species (ROS) leading to an inhibition of the mitochondrial aldehyde dehydrogenase (ALDH-2), representing the nitroglycerin (GTN) and pentaerythrityl tetranitrate (PETN) bioactivating enzyme, and to impaired nitric oxide bioactivity and signaling. We tested whether differences in their capacity to induce heme oxygenase-1 (HO-1) might explain why PETN and not GTN therapy is devoid of nitrate and cross-tolerance. Methods and Results— Wistar rats were treated with PETN or GTN (10.5 or 6.6 μg/kg/min for 4 days). In contrast to GTN, PETN did not induce nitrate tolerance or cross-tolerance as assess…
ALDH1A3 Mutations Cause Recessive Anophthalmia and Microphthalmia
2013
Anophthalmia and microphthalmia (A/M) are early-eye-development anomalies resulting in absent or small ocular globes, respectively. A/M anomalies occur in syndromic or nonsyndromic forms. They are genetically heterogeneous, some mutations in some genes being responsible for both anophthalmia and microphthalmia. Using a combination of homozygosity mapping, exome sequencing, and Sanger sequencing, we identified homozygosity for one splice-site and two missense mutations in the gene encoding the A3 isoform of the aldehyde dehydrogenase 1 (ALDH1A3) in three consanguineous families segregating A/M with occasional orbital cystic, neurological, and cardiac anomalies. ALDH1A3 is a key enzyme in the…