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https://www.readbyqxmd.com/read/28737489/nfatc2-enhances-tumor-initiating-phenotypes-through-the-nfatc2-sox2-aldh-axis-in-lung-adenocarcinoma
#1
Zhi-Jie Xiao, Jing Liu, Si-Qi Wang, Yun Zhu, Xu-Yuan Gao, Vicky Pui-Chi Tin, Jing Qin, Jun-Wen Wang, Maria Pik Wong
Tumor initiating cells (TIC) are dynamic cancer cell subsets that display enhanced tumor functions and resilience to treatment but the mechanism of TIC induction or maintenance in lung cancer is not fully understood. In this study, we show the calcium pathway transcription factor NFATc2 is a novel regulator of lung TIC phenotypes, including tumorspheres, cell motility, tumorigenesis, as well as in vitro and in vivo responses to chemotherapy and targeted therapy. In human lung cancers, high NFATc2 expression predicted poor tumor differentiation, adverse recurrence-free and cancer-specific overall survivals...
July 24, 2017: ELife
https://www.readbyqxmd.com/read/28732729/crystal-structures-of-an-atypical-aldehyde-dehydrogenase-having-bidirectional-oxidizing-and-reducing-activities
#2
Kyoungho Jung, Seung-Hye Hong, Ho-Phuong-Thuy Ngo, Thien-Hoang Ho, Yeh-Jin Ahn, Deok-Kun Oh, Lin-Woo Kang
Aldehyde dehydrogenases (ALDHs) are NAD(P)(+)-dependent oxidoreductases that catalyze the oxidation of a variety of aldehydes to their acid forms. In this study, we determined the crystal structures of ALDH from Bacillus cereus (BcALDH), alone, and in complex with NAD(+) and NADP(+). This enzyme can oxidize all-trans-retinal to all-trans-retinoic acid using either NAD(+) or NADP(+) with equal efficiency, and atypically, as a minor activity, can reduce all-trans-retinal to all-trans-retinol using NADPH. BcALDH accommodated the additional 2'-phosphate of NADP(+) by expanding the cofactor-binding pocket and upshifting the AMP moiety in NADP(+)...
July 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28731185/snail-maintains-metastatic-potential-cancer-stem-like-properties-and-chemoresistance-in-mesenchymal-mouse-breast-cancer-tubo%C3%A2-p2j-cells
#3
Sun Young Ma, Jin-Hee Park, Hana Jung, Sung-Min Ha, Yeonye Kim, Dong Hyen Park, Deuk Hee Lee, Sooyong Lee, In-Ho Chu, So Young Jung, Il-Hwan Kim, Il-Whan Choi, Chang Soo Choi, Saegwang Park
Snail, a zinc-finger transcriptional repressor of E-cadherin expression, is one of the key inducers of epithelial-mesenchymal transition (EMT) in epithelial cancer. In breast cancer, EMT has been associated with malignancies, including metastasis, cancer stem-like properties, and resistance to chemotherapy and radiotherapy. In this study, we analysed the role of Snail in the highly metastatic mesenchymal TUBO‑P2J mouse breast cancer cells, by loss of function using short hairpin RNA. Though silencing Snail did not restore the E-cadherin expression or induce morphological changes, Snail silencing significantly ablated in vitro and in vivo metastatic potentials...
July 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#4
Eliana Mc Tacconi, Xianning Lai, Cecilia Folio, Manuela Porru, Gijs Zonderland, Sophie Badie, Johanna Michl, Irene Sechi, Mélanie Rogier, Verónica Matía García, Ankita Sati Batra, Oscar M Rueda, Peter Bouwman, Jos Jonkers, Anderson Ryan, Bernardo Reina-San-Martin, Joannie Hui, Nelson Tang, Alejandra Bruna, Annamaria Biroccio, Madalena Tarsounas
Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. We demonstrate that inactivation of HR factors BRCA1, BRCA2, or RAD51 hypersensitizes cells to acetaldehyde treatment, in spite of the FA pathway being functional...
July 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28711668/genome-wide-characterization-and-expression-analysis-of-the-aldehyde-dehydrogenase-aldh-gene-superfamily-under-abiotic-stresses-in-cotton
#5
Xinlei Guo, Yuanyuan Wang, Hejun Lu, Xiaoyan Cai, Xingxing Wang, Zhongli Zhou, Chunying Wang, Yuhong Wang, Zhenmei Zhang, Kunbo Wang, Fang Liu
In plants, aldehyde dehydrogenases (ALDHs) function as 'aldehyde scavengers' by removing reactive aldehydes and thus play important roles in stress responses. To date, 30 ALDHs have been identified in Gossypium raimondii, whereas ALDHs have not been studied in Gossypium arboreum or in tetraploid cotton. In this study, we identified 30, 59 and 59 aldehyde dehydrogenase (ALDH) genes from G. arboreum, G. hirsutum and G. barbadense, respectively. Gene structure analysis revealed that members of the same family exhibit similar exon-intron structures and structural domains, and all members of the ALDH18 family possess a distinct AA-kinase domain...
July 12, 2017: Gene
https://www.readbyqxmd.com/read/28707729/sox11-promotes-invasive-growth-and-dcis-progression
#6
Erik Oliemuller, Naoko Kogata, Philip Bland, Divya Kriplani, Frances Daley, Syed Haider, Vandna Shah, Elinor J Sawyer, Beatrice A Howard
Here, we show that SOX11, an embryonic mammary marker, normally silent in postnatal breast cells, is expressed in many ER-negative (ER-) preinvasive DCIS lesions. Mature mammary epithelial cells engineered to express SOX11 displayed alterations in progenitor cell populations, including an expanded basal-like population with increased ALDH activity, and increased mammosphere-forming capacity. DCIS.com cells engineered to express SOX11 displayed increased ALDH activity, a feature of cancer stem cells. The CD44+/CD24-/ALDH+ cell population was increased in DCIS...
July 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28699108/the-role-of-epithelial-mesenchymal-transition-in-squamous-cell-carcinoma-of-the-oral-cavity
#7
Nina Zidar, Emanuela Boštjančič, Marija Malgaj, Nina Gale, Tadej Dovšak, Vojko Didanovič
Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism of cancer metastasizing, but strong evidence for EMT involvement in human cancer is lacking. Our aim was to compare oral spindle cell carcinoma (SpCC) as an example of EMT with oral conventional squamous cell carcinoma (SCC) with and without nodal metastases to test the hypothesis that EMT contributes to metastasizing in oral SCC. Thirty cases of oral SCC with and without nodal metastasis and 15 cases of SpCC were included. Epithelial (cytokeratin, E-cadherin), mesenchymal (vimentin, N-cadherin), and stem cell markers (ALDH-1, CD44, Nanog, Sox-2) and transcription repressors (Snail, Slug, Twist) were analyzed immunohistochemically...
July 12, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28690202/the-impact-of-methylphenidate-and-its-enantiomers-on-dopamine-synthesis-and-metabolism-in-vitro
#8
Jasmin Bartl, Ferruccio Palazzesi, Michele Parrinello, Leif Hommers, Peter Riederer, Susanne Walitza, Edna Grünblatt
Methylphenidate (MPH), a psychostimulant, is an effective first-line treatment for the symptoms associated with Attention-Deficit/Hyperactivity Disorder (ADHD). Although most MPH formulations are composed of the racemic 1:1 mixture of the two enantiomers (d- and l-threo), converging lines of evidence indicate that d-threo MPH seems to be superior to the l-isomer. We aimed to investigate whether MPH racemic mixture or pure enantiomers influence the enzyme activity of tyrosine hydroxylase (TH), monoamine oxidase B (MAO-B), catechol-O-methyltransferase (COMT), and aldehyde dehydrogenase (ALDH) in vitro in homogenates of rat PC12 cells incubated with racemic, d- and l-threo MPH (1nM up to 100μM), or a vehicle for control...
July 8, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28687067/genome-wide-characterization-of-the-aldehyde-dehydrogenase-gene-superfamily-in-soybean-and-its-potential-role-in-drought-stress-response
#9
Wei Wang, Wei Jiang, Juge Liu, Yang Li, Junyi Gai, Yan Li
BACKGROUND: Aldehyde dehydrogenases (ALDHs) represent a group of enzymes that detoxify aldehydes by facilitating their oxidation to carboxylic acids, and have been shown to play roles in plant response to abiotic stresses. However, the comprehensive analysis of ALDH superfamily in soybean (Glycine max) has been limited. RESULTS: In present study, a total of 53 GmALDHs were identified in soybean, and grouped into 10 ALDH families according to the ALDH Gene Nomenclature Committee and phylogenetic analysis...
July 7, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28676857/salinomycin-exerts-anticancer-effects-on-pc-3-cells-and-pc-3-derived-cancer-stem-cells-in-vitro-and-in-vivo
#10
Yunsheng Zhang, Luogen Liu, Fang Li, Tao Wu, Hongtao Jiang, Xianxun Jiang, Xiaobo Du, Yi Wang
Salinomycin is an antibiotic isolated from Streptomyces albus that selectively kills cancer stem cells (CSCs). However, the antitumor mechanism of salinomycin is unclear. This study investigated the chemotherapeutic efficacy of salinomycin in human prostate cancer PC-3 cells. We found that cytotoxicity of salinomycin to PC-3 cells was stronger than to nonmalignant prostate cell RWPE-1, and exposure to salinomycin induced G2/M phage arrest and apoptosis of PC-3 cells. A mechanistic study found salinomycin suppressed Wnt/β-catenin pathway to induce apoptosis of PC-3 cells...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28668843/the-diagnostic-significance-of-serum-alcohol-dehydrogenase-isoenzymes-and-aldehyde-dehydrogenase-activity-in-urinary-bladder-cancer-patients
#11
Karolina Orywal, Wojciech Jelski, Tadeusz Werel, Maciej Szmitkowski
BACKGROUND: The aim of this study was to investigate a potential role of alcohol dehydrogenase and aldehyde dehydrogenase as tumor markers for urinary bladder cancer. MATERIALS AND METHODS: Serum samples were obtained from 41 patients with bladder cancer and 52 healthy individuals. Class III and IV of ADH and total ADH activity were measured by the photometric method. For measurement of class I and II ADH and ALDH activity, the fluorometric method was employed. RESULTS: Significantly higher total activity of ADH was found in sera of both, low-grade and high-grade bladder cancer patients...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28645468/aldhs-in-normal-and-malignant-hematopoietic-cells-potential-new-avenues-for-treatment-of-aml-and-other-blood-cancers
#12
Maura Gasparetto, Clayton A Smith
Multiple studies have demonstrated that ALDH1A1 is elevated in hematopoietic stem cells (HSCs). As a means to better characterize such cells, we previously developed the fluorescent ALDH1A1 substrate Aldefluor to facilitate HSC identification and isolation. This has proven useful for counting and isolating HSCs from human bone marrow, peripheral blood and cord blood as well as stem cells in other tissues and organisms. Given the high level expression of ALDH1A1, we explored its biology and that of other ALDHs in HSCs and found that ALDH1A1 and ALDH3A1 were important in metabolizing reactive aldehydes (RAlds) and reactive oxygen species (ROS)...
June 20, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28645180/alcohol-metabolism-and-oesophageal-cancer-a-systematic-review-of-the-evidence
#13
Marco Matejcic, M J Gunter, Pietro Ferrari
Alcohol is a major risk factor for oesophageal squamous cell carcinoma (OSCC), the most prevalent histological subtype of oesophageal cancer (OC) worldwide. The metabolism of alcohol is regulated by specific enzymes whose activity and expression is influenced by genetic polymorphisms. We conducted a systematic review of current epidemiological evidence of the relationship between alcohol intake and OC risk, including the role of tobacco smoking and functional polymorphisms of dehydrogenases (ADHs) and aldehyde dehydrogenases (ALDHs)...
June 22, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28624784/mitochondrial-pyruvate-carrier-function-determines-cell-stemness-and-metabolic-reprogramming-in-cancer-cells
#14
Xiaoli Li, Gaoyang Han, Xiaoran Li, Quancheng Kan, Zhirui Fan, Yaqing Li, Yasai Ji, Jing Zhao, Mingzhi Zhang, Mantas Grigalavicius, Viktor Berge, Mariusz Adam Goscinski, Jahn M Nesland, Zhenhe Suo
One of the remarkable features of cancer cells is aerobic glycolysis, a phenomenon known as the "Warburg Effect", in which cells rely preferentially on glycolysis instead of oxidative phosphorylation (OXPHOS) as the main energy source even in the presence of high oxygen tension. Cells with dysfunctional mitochondria are unable to generate sufficient ATP from mitochondrial OXPHOS, and then are forced to rely on glycolysis for ATP generation. Here we report our results in a prostate cancer cell line in which the mitochondrial pyruvate carrier 1 (MPC1) gene was knockout...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622146/relationship-between-various-maternal-conditions-and-lactic-acid-dehydrogenase-activity-in-umbilical-cord-blood-at-birth
#15
Evangelos Patavoukas, Josefina Åberg-Liesaho, Cecilia Pegelow Halvorsen, Birger Winbladh, Eva Wiberg-Itzel
BACKGROUND: Lactic acid dehydrogenase (LDH) is a valuable marker for some of the most important diseases in newborns and the plasma LDH activity in newborns correlates well with conditions such as asphyxia. If LDH should be considered as a useful tool also in obstetric care, key factors associated with maternal health before and during pregnancy which could affect umbilical cord LDH activity need to be known. The aims of this study were to explore relationships between selected maternal conditions and arterial lactic acid dehydrogenase activity (aLDH) in umbilical cord blood at delivery...
June 15, 2017: Journal of Perinatal Medicine
https://www.readbyqxmd.com/read/28618138/expansion-of-umbilical-cord-blood-aldehyde-dehydrogenase-expressing-cells-generates-myeloid-progenitor-cells-that-stimulate-limb-revascularization
#16
David M Putman, Tyler T Cooper, Stephen E Sherman, Ayesh K Seneviratne, Mark Hewitt, Gillian I Bell, David A Hess
Uncompromised by chronic disease-related comorbidities, human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDH(hi) cells) stimulate blood vessel regeneration after intra-muscular transplantation. However, implementation of cellular therapies using UCB ALDH(hi) cells for critical limb ischemia, the most severe form of severe peripheral artery disease, is limited by the rarity (<0.5%) of these cells. Our goal was to generate a clinically-translatable, allogeneic cell population for vessel regenerative therapies, via ex vivo expansion of UCB ALDH(hi) cells without loss of pro-angiogenic potency...
June 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28607029/age-dependent-protein-abundance-of-cytosolic-alcohol-and-aldehyde-dehydrogenases-in-human-liver
#17
Deepak Kumar Bhatt, Andrea Gaedigk, Robin E Pearce, J Steven Leeder, Bhagwat Prasad
Hepatic cytosolic alcohol and aldehyde dehydrogenases (ADHs and ALDHs) catalyze the biotransformation of xenobiotics (e.g., cyclophosphamide and ethanol) and vitamin A. Because age-dependent hepatic abundance of these proteins is unknown, we quantified protein expression of ADHs and ALDH1A1 in a large cohort of pediatric and adult human livers by LC-MS/MS proteomics. Purified proteins were used as calibrators. Two to three surrogate peptides per protein were quantified in trypsin digests of liver cytosolic samples and calibrator proteins under optimal conditions of reproducibility...
June 12, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28604744/emp2-is-a-novel-therapeutic-target-for-endometrial-cancer-stem-cells
#18
M H Kiyohara, C Dillard, J Tsui, S R Kim, J Lu, D Sachdev, L Goodglick, M Tong, V F Torous, C Aryasomayajula, W Wang, P Najafzadeh, L K Gordon, J Braun, S McDermott, M S Wicha, M Wadehra
Previous studies have suggested that overexpression of the oncogenic protein epithelial membrane protein-2 (EMP2) correlates with endometrial carcinoma progression and ultimately poor survival from disease. To understand the role of EMP2 in the etiology of disease, gene analysis was performed to show transcripts that are reciprocally regulated by EMP2 levels. In particular, EMP2 expression correlates with and helps regulate the expression of several cancer stem cell associated markers including aldehyde dehydrogenase 1 (ALDH1)...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28603607/co-delivery-of-carboplatin-and-paclitaxel-via-cross-linked-multilamellar-liposomes-for-ovarian-cancer-treatment
#19
Xiaoyang Zhang, Yarong Liu, Yu Jeong Kim, John Mac, Rachel Zhuang, Pin Wang
Carboplatin (CPT) and paclitaxel (PTX) used in combination is one of the most effective treatments for ovarian cancer. However, the traditional combination methods used to co-administrate CPT and PTX showed limited clinical efficacy due to their distinct pharmacokinetics. Although much effort has been devoted to developing nanoparticles capable of encapsulating drugs with different lipophilicites, co-delivery of carboplatin with paclitaxel by a single nanoparticle has rarely been reported. Here, we encapsulated and delivered this drug combination to ovarian cancer cells at a controlled ratio by a previously reported crosslinked multilamellar liposome vesicle (cMLV)...
April 3, 2017: RSC Advances
https://www.readbyqxmd.com/read/28594837/genetic-variants-in-aldh1b1-and-alcohol-dependence-risk-in-a-british-and-irish-population-a-bioinformatic-and-genetic-study
#20
Michael J Way, M Adam Ali, Andrew McQuillin, Marsha Y Morgan
Alcohol is metabolized in the liver via the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Polymorphisms in the genes encoding these enzymes, which are common in East Asian populations, can alter enzyme kinetics and hence the risk of alcohol dependence and its sequelae. One of the most important genetic variants, in this regards, is the single nucleotide polymorphism (SNP) rs671 in ALDH2, the gene encoding the primary acetaldehyde metabolizing enzyme ALDH2. However, the protective allele of rs671 is absent in most Europeans although ALDH1B1, which shares significant sequence homology with ALDH2, contains several, potentially functional, missense SNPs that do occur in European populations...
2017: PloS One
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