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Aldh1a1

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https://www.readbyqxmd.com/read/28326165/neurochemical-and-motor-changes-in-mice-with-combined-mutations-linked-to-parkinson-s-disease
#1
Xiang Bai, Margaret Chia-Ying Wey, Paul Anthony Martinez, Chao Shi, Elizabeth Fernandez, Randy Strong
Considerable evidence suggests that oxidative stress plays a role in the pathogenesis of Parkinson's disease (PD), the most prevalent neurodegenerative movement disorder. Reduced expression of aldehyde dehydrogenase-1 (ALDH1) and glutathione peroxidase-1 (GPX1), enzymes that function to detoxify aldehydes and hydroxyl radicals, respectively, has been reported in the substantia nigra of patients who died with PD. To determine whether deficiency in these two genes contributes to the pathogenesis of PD, mice were generated with homozygous null mutations of both Aldh1a1 (the murine homolog of ALDH1) and Gpx1 genes [knockout (KO) mice]...
2017: Pathobiology of Aging & Age related Diseases
https://www.readbyqxmd.com/read/28280079/targeted-therapy-for-a-subset-of-acute-myeloid-leukemias-that-lack-expression-of-aldehyde-dehydrogenase-1a1
#2
Maura Gasparetto, Shanshan Pei, Mohammad Minhajuddin, Nabilah Khan, Daniel A Pollyea, Jason R Myers, John M Ashton, Michael W Becker, Vasilis Vasiliou, Keith R Humphries, Craig T Jordan, Clayton A Smith
Aldehyde dehydrogenase 1A1 (ALDH1A1) activity is high in hematopoietic stem cells and functions in part to protect stem cells from reactive aldehydes and other toxic compounds. In contrast, we found that ~25% of all acute myeloid leukemias expressed low or undetectable levels of ALDH1A1 and that this ALDH1A1- subset of leukemias correlates with good prognosis cytogenetics. ALDH1A1- cell lines as well as primary leukemia cells were found to be sensitive to treatment with compounds that directly and indirectly generate toxic ALDH substrates including 4-hydroxynonenal and the clinically relevant compounds arsenic trioxide and 4-hydroperoxycyclophosphamide...
March 9, 2017: Haematologica
https://www.readbyqxmd.com/read/28259926/suppression-of-cancer-stem-like-phenotypes-in-nci-h460-lung-cancer-cells-by-vanillin-through-an-akt-dependent-pathway
#3
Songpol Srinual, Pithi Chanvorachote, Varisa Pongrakhananon
Cancer stem cells (CSCs) have been reported as a major cause of cancer metastasis and the failure of cancer treatment. Cumulative studies have indicated that protein kinase B (Akt) and its downstream signaling pathway, including CSC markers, play a critical role in the aggressive behavior of this cancer. In this study, we investigated whether vanillin, a major component in Vanilla planifolia seed, could suppress cancer stemness phenotypes and related proteins in the human non-small cell lung cancer NCI‑H460 cell line...
February 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28219011/inhibition-of-the-aldehyde-dehydrogenase-1-2-family-by-psoralen-and-coumarin-derivatives
#4
Cameron D Buchman, Thomas D Hurley
Aldehyde dehydrogenase 2 (ALDH2), one of 19 ALDH superfamily members, catalyzes the NAD(+)-dependent oxidation of aldehydes to their respective carboxylic acids. In this study, we further characterized the inhibition of four psoralen and coumarin derivatives toward ALDH2 and compared them to the ALDH2 inhibitor daidzin for selectivity against five ALDH1/2 isoenzymes. Compound 2 (Ki = 19 nM) binds within the aldehyde-binding site of the free enzyme species of ALDH2. Thirty-three structural analogs were examined to develop a stronger SAR profile...
March 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#5
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193222/phosphorylation-dependent-regulation-of-aldh1a1-by-aurora-kinase-a-insights-on-their-synergistic-relationship-in-pancreatic-cancer
#6
Jing Wang, Kumar Nikhil, Keith Viccaro, Lei Chang, Jacoba White, Kavita Shah
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are key underlying causes that promote extensive metastasis, drug resistance, and tumor recurrence in highly lethal pancreatic cancer. The mechanisms leading to EMT and CSC phenotypes are not fully understood, which has hindered the development of effective targeted therapies capable of improving treatment outcomes in patients with pancreatic cancer. RESULTS: We show a central role of Aurora kinase A (AURKA) in promoting EMT and CSC phenotypes via ALDH1A1, which was discovered as its direct substrate using an innovative chemical genetic screen...
February 13, 2017: BMC Biology
https://www.readbyqxmd.com/read/28184944/exploration-of-bladder-cancer-molecular-mechanisms-based-on-mirna-mrna-regulatory-network
#7
Wenfeng Li, Jia Liu, Di Zou, Xiaye Cai, Jingying Wang, Jinmeng Wang, Li Zhu, Liang Zhao, Rongying Ou, Yunsheng Xu
To explore the complex molecular mechanisms of bladder cancer, mRNA and miRNA expression profiles were combined for systematic analyses. A total of 18 common differentially expressed genes (DEGs) were identified from two mRNA expression datasets which consisted of 206 tumor and 74 normal tissues. Then, survival analysis based on the SurvExpress database showed that the common DEGs were able to significantly differentiate low- and high-risk groups in 4 public bladder cancer datasets (p<0.01). Notably, the tumor and normal samples were able to be almost clearly classified into 4 groups based on these identified common DEGs...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28179308/renieramycin-m-attenuates-cancer-stem-cell-like-phenotypes-in-h460-lung-cancer-cells
#8
Natchanun Sirimangkalakitti, Supakarn Chamni, Khanit Suwanborirux, Pithi Chanvorachote
BACKGROUND/AIM: Cancer stem cells (CSCs) are a subpopulation of cancer cells that possess self-renewal and differentiation capacities. CSCs contribute to drug-resistance, cancer recurrence and metastasis, thus development of CSC-targeted therapeutic strategies has recently received significant attention in cancer research. In this study, the potential efficacy of renieramycin M (RM) isolated from the sponge Xestospongia species, was examined against lung CSCs. MATERIALS AND METHODS: Colony and spheroid formation assays, as well as western blotting analysis of lung CSC protein markers were employed to determine the CSC-like phenotypes of H460 lung cancer cells after treatment with RM at non-toxic concentrations...
2017: Anticancer Research
https://www.readbyqxmd.com/read/28148901/c-ebp%C3%AE-1-promotes-transformation-and-chemoresistance-in-ewing-sarcoma-cells
#9
Jamie D Gardiner, Lisa M Abegglen, Xiaomeng Huang, Bryce E Carter, Elizabeth A Schackmann, Marcus Stucki, Christian N Paxton, R Lor Randall, James F Amatruda, Angelica R Putnam, Heinrich Kovar, Stephen L Lessnick, Joshua D Schiffman
CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28129349/a-high-content-assay-enables-the-automated-screening-and-identification-of-small-molecules-with-specific-aldh1a1-inhibitory-activity
#10
Adam Yasgar, Steven A Titus, Yuhong Wang, Carina Danchik, Shyh-Ming Yang, Vasilis Vasiliou, Ajit Jadhav, David J Maloney, Anton Simeonov, Natalia J Martinez
Aldehyde dehydrogenase enzymes (ALDHs) have a broad spectrum of biological activities through the oxidation of both endogenous and exogenous aldehydes. Increased expression of ALDH1A1 has been identified in a wide-range of human cancer stem cells and is associated with cancer relapse and poor prognosis, raising the potential of ALDH1A1 as a therapeutic target. To facilitate quantitative high-throughput screening (qHTS) campaigns for the discovery, characterization and structure-activity-relationship (SAR) studies of small molecule ALDH1A1 inhibitors with cellular activity, we show herein the miniaturization to 1536-well format and automation of a high-content cell-based ALDEFLUOR assay...
2017: PloS One
https://www.readbyqxmd.com/read/28122729/zinc-suppresses-stem-cell-properties-of-lung-cancer-cells-through-protein-kinase-c-mediated-beta-catenin-degradation
#11
Chuanpit Ninsontia, Preeyaporn Plaimee Phiboonchaiyanan, Chayanin Kiratipaiboon, Pithi Chanvorachote
Highly tumorigenic cancer stem cells (CSCs) residing in most cancers are responsible for cancer progression and treatment failure. Zinc is an element regulator of several cell functions; however, its role in regulation of stem cell program in lung cancer has not been demonstrated. The present study reveals for the first time that zinc can suppress stem cell properties of lung cancer cells. Such findings were proved in different lung cancer cell lines (H460, H23, and H292) and it was found that CSC markers (CD133 and ALDH1A1), stem cell-associated transcription factors (Oct4, Nanog, and Sox-2), and the ability to form tumor spheroid were dramatically suppressed by zinc treatments...
January 25, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28046028/predictive-value-of-stemness-factor-sox2-in-gastric-cancer-is-associated-with-tumor-location-and-stage
#12
Lang Yang, Jun-Feng Xu, Qian Kang, Ai-Qin Li, Peng Jin, Xin Wang, Yu-Qi He, Na Li, Tao Cheng, Jian-Qiu Sheng
Cancer stem cells (CSCs) are thought to be the "root" of cancer. Although stemness-related factors ALDH1A1 and Sox2 have been used as markers to identify gastric CSCs, the expression pattern and significance of these factors in gastric cancer have not been sufficiently demonstrated. In this study, the expressions of ALDH1A1 and Sox2 were detected by immunohistochemistry in 122 gastric cancer specimens. And the correlation between Sox2 or ALDH1A1 expression and clinicopathological parameters and overall survival data were analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/27994520/evaluation-of-breast-cancer-stem-cells-and-intratumor-stemness-heterogeneity-in-triple-negative-breast-cancer-as-prognostic-factors
#13
Fang Yang, Lulu Cao, Zijia Sun, Juan Jin, Hehui Fang, Wenwen Zhang, Xiaoxiang Guan
Triple-negative breast cancer (TNBC) is a tumor subtype with aggressive behavior and poor clinical outcome for lacking effective therapies. Breast cancer stem cells (BCSCs) have been suggested to have tumor-initiating properties, but it remains unclear whether their presence contributes to the increased aggressiveness and poor prognosis of TNBC. Also, the breast cancers display frequent inter- and intra-tumor heterogeneity, which adds the complexity in diagnosis and predicting prognosis. Here we investigated the clinical relevance and prognostic value of the BCSC markers, CD44(+)/CD24(-), aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and CD133 in 88 TNBC cases...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27987372/six1-maintains-tumor-basal-cells-via-transforming-growth-factor-%C3%AE-pathway-and-associates-with-poor-prognosis-in-esophageal-cancer
#14
Takao Nishimura, Masashi Tamaoki, Rie Komatsuzaki, Naohide Oue, Hirokazu Taniguchi, Masayuki Komatsu, Kazuhiko Aoyagi, Keiko Minashi, Fumiko Chiwaki, Hisashi Shinohara, Yuji Tachimori, Wataru Yasui, Manabu Muto, Teruhiko Yoshida, Yoshiharu Sakai, Hiroki Sasaki
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors. Although improvement in both surgical techniques and neoadjuvant chemotherapy has been achieved, the 5-year survival rate of locally advanced tumors was, at best, still 55%. Therefore, elucidation of mechanisms of the malignancy is eagerly awaited. Epithelial-mesenchymal transition (EMT) by transforming growth factor-β (TGF-β) has been reported to have critical biological roles for cancer cell stemness, whereas little is known about it in ESCC...
February 2017: Cancer Science
https://www.readbyqxmd.com/read/27987347/integrated-analysis-reveals-candidate-mrna-and-their-potential-roles-in-uterine-leiomyomas
#15
Liping Xia, Yan Liu, Yan Fu, Shengyi Dongye, Dewei Wang
AIM: Uterine leiomyomas (UL) are the most common pelvic tumors, and the etiology and pathophysiology are not well understood. We aimed to elucidate the genes responsible for UL development. METHODS: Integrated analyses of four datasets of mRNA profiling for UL were performed. Functional annotation of differentially expressed genes (DEG) was used to systematically characterize the global expression profiles. The UL-specific protein-protein interaction network was constructed...
January 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/27919680/aldh1a1-induces-resistance-to-chop-in-diffuse-large-b-cell-lymphoma-through-activation-of-the-jak2-stat3-pathway
#16
Jinqiong Jiang, Yiping Liu, Youhong Tang, Li Li, Ruolan Zeng, Shan Zeng, Meizuo Zhong
Although the majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), chemoresistance is a common cause of treatment failure. This study aims to investigate the significance of aldehyde dehydrogenase (ALDH) 1A1 expression and the mechanism by which ALDH1A1 is involved in chemoresistance of DLBCL cells. ALDH1A1 expression levels were upregulated in patients with stable or progressive disease after CHOP treatment and positively correlated with expression of STAT3 and p-STAT3...
December 2, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27917503/responses-of-a549-human-lung-epithelial-cells-to-cristobalite-and-%C3%AE-quartz-exposures-assessed-by-toxicoproteomics-and-gene-expression-analysis
#17
Ngoc Q Vuong, Patrick Goegan, Francesco De Rose, Dalibor Breznan, Errol M Thomson, Julie S O'Brien, Subramanian Karthikeyan, Andrew Williams, Renaud Vincent, Premkumari Kumarathasan
In this study, we used cytotoxicity assays, proteomic and gene expression analyses to examine the difference in response of A549 cells to two silica particles that differ in physical properties, namely cristobalite (CR) and α-quartz (Min-U-Sil 5, MI). Cytotoxicity assays such as lactate dehydrogenase release, 5-bromo-2'-deoxyuridine incorporation and cellular ATP showed that both silica particles could cause cell death, decreased cell proliferation and metabolism in the A549 human lung epithelial cells. While cytotoxicity assays revealed little difference between CR and MI exposures, proteomic and gene expression analyses unveiled both similar and unique molecular changes in A549 cells...
December 5, 2016: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/27915972/resistance-to-cell-death-and-its-modulation-in-cancer-stem-cells
#18
Ahmad R Safa
Accumulating evidence has demonstrated that human cancers arise from various tissues of origin that initiate from cancer stem cells (CSCs) or cancer-initiating cells. The extrinsic and intrinsic apoptotic pathways are dysregulated in CSCs, and these cells play crucial roles in tumor initiation, progression, cell death resistance, chemo- and radiotherapy resistance, and tumor recurrence. Understanding CSC-specific signaling proteins and pathways is necessary to identify specific therapeutic targets that may lead to the development of more efficient therapies selectively targeting CSCs...
2016: Critical Reviews in Oncogenesis
https://www.readbyqxmd.com/read/27900016/expression-of-aldehyde-dehydrogenase-family-1-member-a1-and-high-mobility-group-box-1-in-oropharyngeal-squamous-cell-carcinoma-in-association-with-survival-time
#19
Xu Qian, Annekatrin Coordes, Andreas M Kaufmann, Andreas E Albers
Despite the development of novel multimodal treatment combinations in advanced oropharyngeal squamous cell carcinoma (OSCC), outcomes remain poor. The identification of specifically validated biomarkers is required to understand the underlying molecular mechanisms, to evaluate treatment efficiency and to develop novel therapeutic targets. The present study, therefore, examined the presence of aldehyde dehydrogenase family 1 member A1 (ALDH1A1) and high mobility group box 1 (HMGB1) expression in primary OSCC and analyzed the impact on survival time...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27899990/microarray-analysis-of-differentially-expressed-genes-and-linker-genes-associated-with-the-molecular-mechanism-of-colorectal-cancer
#20
Xingjie Shen, Meng Yue, Fansheng Meng, Jingyu Zhu, Xiaoyan Zhu, Yakun Jiang
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and remains the third leading cause of cancer-associated mortality. The present study aimed to fully elucidate the pathogenesis of CRC and identify associated genes in tumor development. Microarray GSE44076, GSE41328 and GSE44861 datasets were downloaded from the Gene Expression Omnibus database and integrated with meta-analysis. Differentially-expressed genes (DEGs) were identified from CRC samples compared with adjacent non-cancerous controls using the Limma package in R, followed by functional analysis using the Database for Annotation, Visualization, and Integrated Discovery online tool...
November 2016: Oncology Letters
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