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Andrea Moretti, Jianfeng Li, Stefano Donini, Robert W Sobol, Menico Rizzi, Silvia Garavaglia
The aldehyde dehydrogenase family 1 member A3 (ALDH1A3) catalyzes the oxidation of retinal to the pleiotropic factor retinoic acid using NAD(+). The level of ALDHs enzymatic activity has been used as a cancer stem cell marker and seems to correlate with tumour aggressiveness. Elevated ALDH1A3 expression in mesenchymal glioma stem cells highlights the potential of this isozyme as a prognosis marker and drug target. Here we report the first crystal structure of human ALDH1A3 complexed with NAD(+) and the product all-trans retinoic acid (REA)...
October 19, 2016: Scientific Reports
Marjorie Flahaut, Nicolas Jauquier, Nadja Chevalier, Katya Nardou, Katia Balmas Bourloud, Jean-Marc Joseph, David Barras, Christian Widmann, Nicole Gross, Raffaele Renella, Annick Mühlethaler-Mottet
BACKGROUND: The successful targeting of neuroblastoma (NB) by associating tumor-initiating cells (TICs) is a major challenge in the development of new therapeutic strategies. The subfamily of aldehyde dehydrogenases 1 (ALDH1) isoenzymes, which comprises ALDH1A1, ALDH1A2, and ALDH1A3, is involved in the synthesis of retinoic acid, and has been identified as functional stem cell markers in diverse cancers. By combining serial neurosphere passages with gene expression profiling, we have previously identified ALDH1A2 and ALDH1A3 as potential NB TICs markers in patient-derived xenograft tumors...
October 10, 2016: BMC Cancer
M A Alabdullatif, M A Al Dhaibani, M Y Khassawneh, A W El-Hattab
Chromosomal microarray (CMA) has significantly improved diagnosing copy number variations (CNVs). Single nucleotide polymorphism (SNP) arrays confer additional utility in detecting regions of homozygosity (ROH). Investigating ROH for genes associated with recessive disorders for follow-up sequencing can aid in diagnosis. In this study, we performed a retrospective review of clinical and molecular data for 227 individuals from a highly consanguineous population who previously had a CMA. Pathogenic CNVs were identified in 32 (14%) cases; ROH suggesting uniparental disomy (UPD) in three (1%) cases, and an additional 25 (11%) individuals were diagnosed with recessive disorders caused by mutations in ROH candidate genes, thereby increasing the CMA diagnostic yield to 26%...
September 22, 2016: Clinical Genetics
Furkan U Ertem, Wenqian Zhang, Kyle Chang, Wan Mohaiza Dashwood, Praveen Rajendran, Deqiang Sun, Ala Abudayyeh, Eduardo Vilar, Maen Abdelrahim, Roderick H Dashwood
Intervention strategies in familial adenomatous polyposis (FAP) patients and other high-risk colorectal cancer (CRC) populations have highlighted a critical need for endoscopy combined with safe and effective preventive agents. We performed transcriptome profiling of colorectal adenomas from FAP patients and the polyposis in rat colon (Pirc) preclinical model, and prioritized molecular targets for prevention studies in vivo. At clinically relevant doses in the Pirc model, the drug Clotam (tolfenamic acid, TA) was highly effective at suppressing tumorigenesis both in the colon and in the small intestine, when administered alone or in combination with Sulindac...
October 5, 2016: International Journal of Cancer. Journal International du Cancer
Margaret Lois Thomas, Roberto de Antueno, Krysta Mila Coyle, Mohammad Sultan, Brianne Marie Cruickshank, Michael Anthony Giacomantonio, Carman Anthony Giacomantonio, Roy Duncan, Paola Marcato
Breast cancer stem cells (CSCs) can be identified by increased Aldefluor fluorescence caused by increased expression of aldehyde dehydrogenase 1A3 (ALDH1A3), as well as ALDH1A1 and ALDH2. In addition to being a CSC marker, ALDH1A3 regulates gene expression via retinoic acid (RA) signaling and plays a key role in the progression and chemotherapy resistance of cancer. Therefore, ALDH1A3 represents a druggable anti-cancer target of interest. Since to date, there are no characterized ALDH1A3 isoform inhibitors, drugs that were previously described as inhibiting the activity of other ALDH isoforms were tested for anti-ALDH1A3 activity...
November 2016: Molecular Oncology
Hoe Suk Kim, Minji Jung, Sul Ki Choi, Woo Kyung Moon, Seung Ja Kim
The mechanisms underlying breast cancer progression of ductal carcinoma in situ (DCIS) associated with fatty acids are largely unknown. In the present study, we compared the action of oleic acid (OA) on two human DCIS cell lines, MCF10DCIS.COM (ER/PR/HER2-negative) and SUM225 (HER2 overexpressed). OA led to a significant increase in proliferation, migration, lipid accumulation and the expression of lipogenic proteins, such as SREBP-1, FAS and ACC-1, in MCF10DCIS.COM cells but not SUM225 cells. The ALDHhigh subpopulation analyzed by the ALDEFLUOR assay was approximately 39...
2016: PloS One
V R Kasimanickam
Mammalian spermatogenesis involves highly regulated temporal and spatial dynamics, carefully controlled by several signalling processes. Retinoic acid (RA) signalling could have a critical role in spermatogenesis by promoting spermatogonia differentiation, adhesion of germ cells to Sertoli cells, and release of mature spermatids. An optimal testicular RA concentration is maintained by retinaldehyde dehydrogenases (ALDHs), which oxidize RA precursors to produce RA, whereas the CYP26 class of enzymes catabolizes (oxidize) RA into inactive metabolites...
August 28, 2016: Reproduction in Domestic Animals, Zuchthygiene
Peng Cheng, Jia Wang, Indrayani Waghmare, Stefania Sartini, Vito Coviello, Sunghak Kim, Ahmed Mohyeldin, Marat S Pavlyukov, Zhuo Zhang, Mutsuko Minata, Claudia L L Valentim, Rishi Raj Chhipa, Krishna P L Bhat, Biplab Dasgupta, Concettina La Motta, Madhuri Kango-Singh, Ichiro Nakano
Glioma stem-like cells (GSC) with tumor initiating activity orchestrate the cellular hierarchy in glioblastoma (GBM) and engender therapeutic resistance. Recent work has divided GSC into two subtypes with a mesenchymal (MES) GSC population as the more malignant subtype. In this study, we identify the FOXD1-ALDH1A3 signaling axis as a determinant of the MES GSC phenotype. The transcription factor FOXD1 is expressed predominantly in patient-derived cultures enriched with MES, but not with the proneural (PN) GSC subtype...
August 28, 2016: Cancer Research
I-Ying Kuo, Jayu Jen, Lien-Huei Hsu, Han-Shui Hsu, Wu-Wei Lai, Yi-Ching Wang
BACKGROUND: The incidence of lung adenocarcinoma (LUAD) is increasing worldwide with different prognosis even in early-stage patients. We aimed to identify a prognostic panel with multiple DNA methylation biomarkers to predict survival in early-stage LUAD patients of different racial groups. METHODS: The methylation array, pyrosequencing methylation assay, Cox regression and Kaplan-Meier analyses were conducted to build the risk score equations of selected probes in a training cohort of 69 Asian LUAD patients...
2016: Journal of Biomedical Science
Jennifer S Myers, Ariana K von Lersner, Qing-Xiang Amy Sang
Protein profiling studies of prostate cancer have been widely used to characterize molecular differences between diseased and non-diseased tissues. When combined with pathway analysis, profiling approaches are able to identify molecular mechanisms of prostate cancer, group patients by cancer subtype, and predict prognosis. This strategy can also be implemented to study prostate cancer in very specific populations, such as African Americans who have higher rates of prostate cancer incidence and mortality than other racial groups in the United States...
2016: Journal of Cancer
Kai Li, Xiaoguang Guo, Ziwei Wang, Xiaofeng Li, Youquan Bu, Xuefeng Bai, Liansheng Zheng, Ying Huang
Increased aldehyde dehydrogenase 1 (ALDH1) activity has been determined to be present in the stem cells of several kinds of cancers including gastric cancer (GC). Nevertheless, which ones of ALDH1's isoenzymes are leading to ALDH1 activity remains elusive. In this study, we examined the prognostic value and hazard ratio (HR) of individual ALDH1 isoenzymes in patients with GC using "The Kaplan-Meier plotter" database. mRNA high expression level of ALDH1A1 was not found to be significantly correlated with the overall survival (OS) of all patients with GC followed for 20 years, HR =0...
2016: OncoTargets and Therapy
Weier Bao, Matthew J Greenwold, Roger H Sawyer
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Previous studies have shown that miRNA regulation contributes to a diverse set of processes including cellular differentiation and morphogenesis which leads to the creation of different cell types in multicellular organisms and is thus key to animal development. Feathers are one of the most distinctive features of extant birds and are important for multiple functions including flight, thermal regulation, and sexual selection...
October 15, 2016: Gene
Justin A Colacino, Sean P McDermott, Maureen A Sartor, Max S Wicha, Laura S Rozek
Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH-/CD44+/CD24-) normal breast stem/progenitor cells following treatment with curcumin and piperine...
July 2016: Breast Cancer Research and Treatment
Krysta M Coyle, J Patrick Murphy, Dejan Vidovic, Ahmad Vaghar-Kashani, Cheryl A Dean, Mohammad Sultan, Derek Clements, Melissa Wallace, Margaret L Thomas, Amos Hundert, Carman A Giacomantonio, Lucy Helyer, Shashi A Gujar, Patrick W K Lee, Ian C G Weaver, Paola Marcato
Breast cancer subtyping, based on the expression of hormone receptors and other genes, can determine patient prognosis and potential options for targeted therapy. Among breast cancer subtypes, tumors of basal-like and claudin-low subtypes are typically associated with worse patient outcomes, are primarily classified as triple-negative breast cancers (TNBC), and cannot be treated with existing hormone-receptor-targeted therapies. Understanding the molecular basis of these subtypes will lead to the development of more effective treatment options for TNBC...
June 6, 2016: Oncotarget
Ronald Schilderink, Caroline Verseijden, Jurgen Seppen, Vanesa Muncan, Gijs R van den Brink, Tim T Lambers, Eric A van Tol, Wouter J de Jonge
In the intestinal mucosa, retinoic acid (RA) is a critical signaling molecule. RA is derived from dietary vitamin A (retinol) through conversion by aldehyde dehydrogenases (aldh). Reduced levels of short-chain fatty acids (SCFAs) are associated with pathological microbial dysbiosis, inflammatory disease, and allergy. We hypothesized that SCFAs contribute to mucosal homeostasis by enhancing RA production in intestinal epithelia. With the use of human and mouse epithelial cell lines and primary enteroids, we studied the effect of SCFAs on the production of RA...
June 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Yu-Mei Ma, Shan Zhao
Aldehyde dehydrogenase 1 (ALDH1) activity has been used as a functional stem cell marker to isolate cancer stem cells in different cancer types, including ovarian cancer. However, which ALDH1's isoenzymes are contributing to ALDH1 activity in ovarian cancer remains elusive. In addition, the prognostic value of an individual ALDH1 isoenzyme in ovarian cancer is not clear. Thus, we accessed the prognostic value of ALDH1 isoenzymes in ovarian cancer patients through the "Kaplan-Meier plotter" online database, which can be used to determine the effect of the genes on ovarian cancer prognosis...
2016: OncoTargets and Therapy
Zamira Gibb, Sarah R Lambourne, Benjamin J Curry, Sally E Hall, Robert J Aitken
Although stallion spermatozoa produce significant quantities of reactive oxygen species, a lag between 4-hydroxynonenal (4HNE) adduction and the loss of motility in stallion spermatozoa suggests the presence of a robust aldehyde detoxification mechanism. Because there is a paucity of studies characterizing the role of aldehyde dehydrogenase (ALDH) in sperm functionality, the aim of this study was to ascertain the relationship between 4HNE production and motility and ALDH expression by stallion spermatozoa. PCR analysis revealed the presence of the ALDH1A3, ALDH1B1, and ALDH2 isoforms in these cells...
June 2016: Biology of Reproduction
Ming-Huang Chen, Jing-Jie Weng, Chi-Tung Cheng, Ren-Chin Wu, Shih-Chiang Huang, Chiao-En Wu, Yi-Hsiu Chung, Chun-Yu Liu, Mu-Hsin Chang, Ming-Han Chen, Kun-Chun Chiang, Ta-Sen Yeh, Yeu Su, Chun-Nan Yeh
PURPOSE: Intrahepatic cholangiocarcinoma is a fatal primary liver cancer resulting from diagnosis at an advanced stage. Understanding the mechanisms of drug resistance and metastasis of cholangiocarcinoma may improve the disease prognosis. Enhanced aldehyde dehydrogenase (ALDH) activity is suggested to be associated with increased drug resistance and the metastasis. This study aims to investigate the roles of the ALDH isoforms in cholangiocarcinoma. EXPERIMENTAL DESIGN: Aldefluor assays, RT-PCR, and Western blot analysis were used to identify the major ALDH isoforms contributing to Aldefluor activity in human cholangiocarcinoma cell lines...
August 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ruthala Kalyani, Ji-Yeon Lee, Hyehyun Min, Heejei Yoon, Myoung Hee Kim
Identifying Hoxc8 target genes is at the crux of understanding the Hoxc8-mediated regulatory networks underlying its roles during development. However, identification of these genes remains difficult due to intrinsic factors of Hoxc8, such as low DNA binding specificity, context-dependent regulation, and unknown cofactors. Therefore, as an alternative, the present study attempted to test whether the roles of Hoxc8 could be inferred by simply analyzing genes frequently coexpressed with Hoxc8, and whether these genes include putative target genes...
May 31, 2016: Molecules and Cells
Jia-Xin Shen, Jing Liu, Guan-Wu Li, Yi-Teng Huang, Hua-Tao Wu
Aldehyde dehydrogenase 1 (ALDH1) consists of a family of intracellular enzymes, highly expressed in stem cells populations of leukemia and some solid tumors. Up to now, 6 isoforms of ALDH1 have been reported. However, the expression patterns and the identity of ALDH1 isoenzymes contributing to ALDH1 activity, as well as the prognostic values of ALDH1 isoenzymes in cancers all remain to be elucidated. Here, we studied the expressions of ALDH1 transcripts in gastric cancer (GC) compared with the normal controls using the ONCOMINE database...
May 3, 2016: Oncotarget
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