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https://www.readbyqxmd.com/read/28645468/aldhs-in-normal-and-malignant-hematopoietic-cells-potential-new-avenues-for-treatment-of-aml-and-other-blood-cancers
#1
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
#2
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
#3
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...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622146/relationship-between-various-maternal-conditions-and-lactic-acid-dehydrogenase-activity-in-umbilical-cord-blood-at-birth
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28583404/thermophilic-ethanol-fermentation-from-lignocellulose-hydrolysate-by-genetically-engineered-moorella-thermoacetica
#10
Farida Rahayu, Yuto Kawai, Yuki Iwasaki, Koichiro Yoshida, Akihisa Kita, Takahisa Tajima, Junichi Kato, Katsuji Murakami, Tamotsu Hoshino, Yutaka Nakashimada
A transformant of Moorella thermoacetica was constructed for thermophilic ethanol production from lignocellulosic biomass by deleting two phosphotransacetylase genes, pdul1 and pdul2, and introducing the native aldehyde dehydrogenase gene (aldh) controlled by the promoter from glyceraldehyde-3-phosphate dehydrogenase. The transformant showed tolerance to 540mM and fermented sugars including fructose, glucose, galactose and xylose to mainly ethanol. In a mixed-sugar medium of glucose and xylose, all of the sugars were consumed to produce ethanol at the yield of 1...
May 24, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28582728/mitochondrial-aldehyde-dehydrogenase-2-deficiency-compromises-therapeutic-effect-of-aldh-bright-cell-on-peripheral-ischemia
#11
Xiaolei Sun, Hong Zhu, Zhen Dong, Xiangwei Liu, Xin Ma, Shasha Han, Fei Lu, Peng Wang, Sanli Qian, Cong Wang, Cheng Shen, Xiaona Zhao, Yunzeng Zou, Junbo Ge, Aijun Sun
The autologous ALDH bright (ALDH(br)) cell therapy for ischemic injury is clinically safe and effective, while the underlying mechanism remains elusive. Here, we demonstrated that the glycolysis dominant metabolism of ALDH(br) cells is permissive to restore blood flow in an ischemic hind limb model compared with bone marrow mononuclear cells (BMNCs). PCR array analysis showed overtly elevated Aldh2 expression of ALDH(br) cells following hypoxic challenge. Notably, ALDH(br) cells therapy induced blood flow recovery in this model was reduced in case of ALDH2 deficiency...
May 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/28579829/natural-and-synthetic-progestins-enrich-cancer-stem-cell-like-cells-in-hormone-responsive-human-breast-cancer-cell-populations-in-vitro
#12
Sandy Goyette, Yayun Liang, Benford Mafuvadze, Matthew T Cook, Moiz Munir, Salman M Hyder
Clinical trials and studies have shown that combination estrogen/progestin hormone replacement therapy, but not estrogen therapy alone or placebo, increases breast cancer risk in postmenopausal women. Using animal models, we have previously shown that both natural and synthetic progestins (including medroxyprogesterone acetate [MPA], a synthetic progestin used widely in the clinical setting) accelerate the development of breast tumors in vivo and increase their metastasis to lymph nodes. Based on these observations, we have hypothesized that progestin-induced breast cancer tumor growth and metastasis may be mediated by an enrichment of the cancer stem cell (CSC) pool...
2017: Breast Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28579596/aldehyde-dehydrogenase-activity-identifies-a-subpopulation-of-canine-adipose-derived-stem-cells-with-higher-differentiation-potential
#13
Harumichi Itoh, Shimpei Nishikawa, Tomoya Haraguchi, Yu Arikawa, Shotaro Etoh, Toshie Iseri, Kenji Tani, Munekazu Nakaichi, Yasuho Taura, Kazuhito Itamoto
Adipose-derived stem cells (ADSCs) are abundant and readily obtained, and have been studied for their clinical applicability in regenerative medicine. Some surface antigens have been identified as markers of different ADSC subpopulations in mice and humans. However, it is unclear whether functionally distinct subpopulations exist in dogs. To address this issue, we evaluated aldehyde dehydrogenase (ALDH) activity-a widely used stem cell marker in mice and humans-by flow cytometry. Approximately 20% of bulk ADSCs showed high ALDH activity...
June 5, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28574664/ccl18-upregulates-slug-expression-to-promote-stem-cell-like-features-by-activating-mtor-pathway-in-oral-squamous-cell-carcinoma
#14
Hongfei Wang, Xueyi Liang, Mianxiang Li, Xiaoan Tao, Shanshan Tai, Zhaona Fan, Zhi Wang, Bin Cheng, Juan Xia
Chemokine (CC motif) ligand 18 (CCL18) is involved in the remodeling of tumor microenvironment and have critical roles in oncogenesis, invasiveness and metastasis. We previously investigated that CCL18 was overexpressed in primary oral squamous cell carcinoma (OSCC) tissues and associated with advanced clinical stage of OSCC patients. However, the underlying mechanisms of this CCL18-derived activity remains unidentified. This study showed exogenous CCL18 increased cell migration, invasion and induced cell epithelial-to-mesenchymal transition (EMT), displaying that E-cadherin, an epithelial marker, decreased and N-cadherin, a mesenchymal marker, increased, compared to negative control in OSCC cells...
June 2, 2017: Cancer Science
https://www.readbyqxmd.com/read/28566767/independent-effects-of-adh1b-and-aldh2-common-dysfunctional-variants-on-gout-risk
#15
Masayuki Sakiyama, Hirotaka Matsuo, Airi Akashi, Seiko Shimizu, Toshihide Higashino, Makoto Kawaguchi, Akiyoshi Nakayama, Mariko Naito, Sayo Kawai, Hiroshi Nakashima, Yutaka Sakurai, Kimiyoshi Ichida, Toru Shimizu, Hiroshi Ooyama, Nariyoshi Shinomiya
Gout is caused by hyperuricemia, with alcohol consumption being an established risk factor. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are crucial enzymes for alcohol metabolism. We recently performed a genome-wide association study of gout and a subsequent fine-mapping study which identified rs671 of ALDH2 as a gout locus. However, the association between gout and common variants of ADH1B has hitherto remained unreported, prompting us to investigate the association between gout and common dysfunctional variants of ADH1B (rs1229984) and ALDH2 (rs671)...
May 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28565875/smoothened-antagonist-gdc-0449-vismodegib-inhibits-proliferation-and-triggers-apoptosis-in-colon-cancer-cell-lines
#16
Chuanqing Wu, Shaobo Hu, Ji Cheng, Guobin Wang, Kaixiong Tao
The sonic hedgehog (Shh) pathway has been proven to be involved in embryonic development and cancer growth. GDC-0449, an antagonist of the hedgehog signaling receptor Smoothened (Smo), was recently approved by the US Food and Drug Administration as a prescription for skin basal cell carcinoma. However, the efficacy of GDC-0449 in the treatment of colon cancer and other malignancies, such as basal cell carcinoma and pancreatic cancer, has remained to be proven. The present study assessed the effect of GDC-0449 on the colon cancer cell lines Caco-2 and Ht-29...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28549374/metabolic-engineering-of-escherichia-coli-to-high-efficient-synthesis-phenylacetic-acid-from-phenylalanine
#17
Lihua Zhang, Qian Liu, Hong Pan, Xun Li, Daoyi Guo
Phenylacetic acid (PAA) is a fine chemical with a high industrial demand for its widespread uses. Whereas, microorganic synthesis of PAA is impeded by the formation of by-product phenethyl alcohol due to quick, endogenous, and superfluous conversion of aldehydes to their corresponding alcohols, which resulted in less conversation of PAA from aldehydes. In this study, an Escherichia coli K-12 MG1655 strain with reduced aromatic aldehyde reduction (RARE) that does duty for a platform for aromatic aldehyde biosynthesis was used to prompt more PAA biosynthesis...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28538665/molecular-basis-of-alcohol-related-gastric-and-colon-cancer
#18
REVIEW
Hye-Kyung Na, Ja Young Lee
Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28533269/pharmacological-enrollment-of-aldehyde-dehydrogenase-modulators-to-assist-treating-ischemia-reperfusion-induced-intestinal-injury-is-there-a-gap-to-be-bridged
#19
Laurent Dollé
This commentary highlights the research presented by Zhu et al. [1]. In this issue of the Clinical Science, the authors evaluated the protective effect of Alda-1 (a novel class of small molecule aldehyde dehydrogenase (ALDH2) activators) in the intestinal ischemia reperfusion (IR) injury. Remarkably, enhancing the ADLH2 activity by the use of Alda-1 can ameliorate several deleterious effects related to aldehydes, and may provide a better protection against an injury preestablished by IR. Together, an innovative metabolic strategy for treating patients with IR injury could be the use of ALDH modulators in a near future...
June 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28532411/aldehyde-dehydrogenase-2-2-knock-in-mice-show-increased-reactive-oxygen-species-production-in-response-to-cisplatin-treatment
#20
Jeewon Kim, Che-Hong Chen, Jieying Yang, Daria Mochly-Rosen
BACKGROUND: The aldehyde dehydrogenase (ALDH) enzyme family metabolizes and detoxifies both exogenous and endogenous aldehydes. Since chemotherapeutic agents, such as cisplatin, generate cytotoxic aldehydes and oxidative stress, and chemoresistant cancer cells express high levels of ALDH enzymes, we hypothesized that different ALDH expression within cells may show different chemosensitivity. ALDH2 has the lowest Km for acetaldehyde among ALDH isozymes and detoxifies acetaldehydes in addition to other reactive aldehydes, such as 4-hydroxy-nonenal, malondialdehyde and acrolein produced from lipid peroxidation by reactive oxygen species (ROS)...
May 22, 2017: Journal of Biomedical Science
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