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Aldh1a1

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https://www.readbyqxmd.com/read/29773902/nedd9-promotes-oncogenic-signaling-a-stem-mesenchymal-gene-signature-and-aggressive-ovarian-cancer-growth-in-mice
#1
Rashid Gabbasov, Fang Xiao, Caitlin G Howe, Laura E Bickel, Shane W O'Brien, Daniel Benrubi, Thuy-Vy Do, Yan Zhou, Emmanuelle Nicolas, Kathy Q Cai, Samuel Litwin, Sachiko Seo, Erica A Golemis, Denise C Connolly
Neural precursor cell expressed, developmentally downregulated 9 (NEDD9) supports oncogenic signaling in a number of solid and hematologic tumors. Little is known about the role of NEDD9 in ovarian carcinoma (OC), but available data suggest elevated mRNA and protein expression in advanced stage high-grade cancers. We used a transgenic MISIIR-TAg mouse OC model combined with genetic ablation of Nedd9 to investigate its action in the development and progression of OC. A Nedd9-/- genotype delayed tumor growth rate, reduced incidence of ascites, and reduced expression and activation of signaling proteins including SRC, STAT3, E-cadherin, and AURKA...
May 18, 2018: Oncogene
https://www.readbyqxmd.com/read/29767973/discovery-of-orally-bioavailable-quinoline-based-aldehyde-dehydrogenase-1a1-aldh1a1-inhibitors-with-potent-cellular-activity
#2
Shyh-Ming Yang, Natalia J Martinez, Adam Yasgar, Carina Danchik, Catrine Johansson, Yuhong Wang, Bolormaa Baljinnyam, Amy Q Wang, Xin Xu, Pranav Shah, Dorian Cheff, Xinran S Wang, Jacob Roth, Madhu Lal-Nag, James Edward Dunford, Udo C T Oppermann, Vasilis Vasiliou, Anton Simeonov, Ajit Jadhav, David J Maloney
Aldehyde dehydrogenases (ALDHs) are responsible for the metabolism of aldehydes (exogenous and endogenous) and possess vital physiological and toxicological functions in areas such as CNS, inflammation, metabolic disorders, and cancers. Overexpression of certain ALDHs (e.g. ALDH1A1) are important biomarkers in cancers and cancer stem cells (CSCs) indicating the potential need for the identification and development of small molecule ALDH inhibitors. Herein, a newly designed series of quinoline-based analogs of ALDH1A1 inhibitors is described...
May 16, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29763427/correction-a-high-content-assay-enables-the-automated-screening-and-identification-of-small-molecules-with-specific-aldh1a1-inhibitory-activity
#3
Adam Yasgar, Steven A Titus, Yuhong Wang, Carina Danchik, Shyh-Ming Yang, Vasilis Vasiliou, Ajit Jadhav, David J Maloney, Anton Simeonov, Natalia J Martinez
[This corrects the article DOI: 10.1371/journal.pone.0170937.].
2018: PloS One
https://www.readbyqxmd.com/read/29752431/ddb2-represses-ovarian-cancer-cell-dedifferentiation-by-suppressing-aldh1a1
#4
Tiantian Cui, Amit Kumar Srivastava, Chunhua Han, Dayong Wu, Nissar Wani, Lu Liu, Zhiqin Gao, Meihua Qu, Ning Zou, Xiaoli Zhang, Ping Yi, Jianhua Yu, Erica H Bell, Shyh-Ming Yang, David J Maloney, Yanfang Zheng, Altaf A Wani, Qi-En Wang
Cancer stem cells (CSCs), representing the root of many solid tumors including ovarian cancer, have been implicated in disease recurrence, metastasis, and therapeutic resistance. Our previous study has demonstrated that the CSC subpopulation in ovarian cancer can be limited by DNA damage-binding protein 2 (DDB2). Here, we demonstrated that the ovarian CSC subpopulation can be maintained via cancer cell dedifferentiation, and DDB2 is able to suppress this non-CSC-to-CSC conversion by repression of ALDH1A1 transcription...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748529/expression-of-aldehyde-dehydrogenase-1a1-aldh1a1-as-a-prognostic-biomarker-in-colorectal-cancer-using-immunohistochemistry
#5
Wangshuo Yang, Yang Wang, Wei Wang, Zhuming Chen, Guang Bai
BACKGROUND The expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is increased in several human tumors, including colorectal carcinoma (CRC). The aim of this study was to compare the expression ALDH1A1 in CRC tumor tissue compared with non-tumor adjacent tissue (NAT), using immunohistochemistry (IHC), and to determine whether the expression of the ALDH1A1 protein was associated with prognostic factors in CRC. MATERIAL AND METHODS Formalin-fixed paraffin-embedded (FFPE) tissue from 424 patients diagnosed with CRC, and 196 matched NATs were used to prepare tissue microarrays (TMAs)...
May 7, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29748374/the-microrna-371-373-cluster-represses-colon-cancer-initiation-and-metastatic-colonization-by-inhibiting-the-tgfbr2-id1-signaling-axis
#6
Pit Ullmann, Fabien Rodriguez, Martine Schmitz, Steffen K Meurer, Komal Qureshi-Baig, Paul Felten, Aurélien Ginolhac, Laurent Antunes, Sonia Frasquilho, Nikolaus Zügel, Ralf Weiskirchen, Serge Haan, Elisabeth Letellier
The vast majority of colorectal cancer (CRC)-related deaths can be attributed to metastatic spreading of the disease. Therefore, deciphering molecular mechanisms of metastatic dissemination is a key prerequisite to improve future treatment options. With this aim, we took advantage of different CRC cell lines and recently established primary cultures enriched in colon cancer stem cells (CSCs) - also known as tumor-initiating cells (TICs) - to identify genes and microRNAs (miRNAs) with regulatory functions in CRC progression...
May 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29727961/pyrethroid-insecticide-lambda-cyhalothrin-induces-hepatic-cytochrome-p450-enzymes-oxidative-stress-and-apoptosis-in-rats
#7
María-Aránzazu Martínez, Irma Ares, José-Luis Rodríguez, Marta Martínez, David Roura-Martínez, Victor Castellano, Bernardo Lopez-Torres, María-Rosa Martínez-Larrañaga, Arturo Anadón
This study aimed to examine in rats the effects of the Type II pyrethroid lambda-cyhalothrin on hepatic microsomal cytochrome P450 (CYP) isoform activities, oxidative stress markers, gene expression of proinflammatory, oxidative stress and apoptosis mediators, and CYP isoform gene expression and metabolism phase I enzyme PCR array analysis. Lambda-cyhalothrin, at oral doses of 1, 2, 4 and 8mg/kg bw for 6days, increased, in a dose-dependent manner, hepatic activities of ethoxyresorufin O-deethylase (CYP1A1), methoxyresorufin O-demethylase (CYP1A2), pentoxyresorufin O-depentylase (CYP2B1/2), testosterone 7α- (CYP2A1), 16β- (CYP2B1), and 6β-hydroxylase (CYP3A1/2), and lauric acid 11- and 12-hydroxylase (CYP4A1/2)...
August 1, 2018: Science of the Total Environment
https://www.readbyqxmd.com/read/29718361/alcohol-metabolism-in-the-progression-of-human-nonalcoholic-steatohepatitis
#8
Hui Li, Erica Toth, Nathan J Cherrington
Alcohol metabolism is a well-characterized biological process that is dominated by the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) families. Nonalcoholic steatohepatitis (NASH) is the advanced inflammatory stage of nonalcoholic fatty liver disease (NAFLD) and is known to alter the metabolism and disposition of numerous drugs. The purpose of this study was to investigate the alterations in alcohol metabolism processes in response to human NASH progression. Expression and function of ADHs, ALDHs and catalase were examined in normal, steatosis, NASH (fatty) and NASH (not fatty) human liver samples...
April 27, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29682513/lung-cancer-stem-cells-origin-characteristics-and-therapy
#9
REVIEW
D Prabavathy, Y Swarnalatha, Niveditha Ramadoss
Cancer stem cells (CSCs) have gained an increasing attention recently in cancer research. CSCs have ability to generate new tumor through their stem cell properties, essentially self-renewal potential and differentiation into multiple cell lineages. Extensive evidences report that CSCs are resistant to many conventional therapies and mediate tumor recurrence. CSCs of lung cancer are well recognized by their specific markers such as CD133, CD44, ABCG2 and ALDH1A1 together with the CSC characteristics including spheroid and colony formation...
2018: Stem Cell Investigation
https://www.readbyqxmd.com/read/29665144/disulfiram-copper-targets-stem-cell-like-aldh-population-of-multiple-myeloma-by-inhibition-of-aldh1a1-and-hedgehog-pathway
#10
Na Jin, Xiaojian Zhu, Fanjun Cheng, Liling Zhang
Multiple myeloma stem cells (MMSCs) have been considered as the major cause resulting in relapse. Eradicating MMSCs may be an effective strategy to improve the outcome of multiple myeloma (MM). Increased activity of aldehyde dehydrogenase (ALDH) has been found in MMSCs, but whether inhibiting ALDH activity can eliminate MMSCs remains unknown. Disulfiram (DS) has been reported as an inhibitor of ALDH, and increasing studies showed it has anti-cancer effects in a copper (Cu)-dependent manner. In this study, we isolated ALDH+ cells of MM by Aldefluor assay and demonstrated they possessed tumorigenesis capacities in vitro and in vivo...
April 17, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29649113/new-and-old-genes-associated-with-primary-and-established-responses-to-paclitaxel-treatment-in-ovarian-cancer-cell-lines
#11
Monika Świerczewska, Andrzej Klejewski, Maciej Brązert, Dominika Kaźmierczak, Dariusz Iżycki, Michał Nowicki, Maciej Zabel, Radosław Januchowski
Development of drug resistance is the main reason for low chemotherapy effectiveness in treating ovarian cancer. Paclitaxel (PAC) is a chemotherapeutic drug used in the treatment of this cancer. We analysed the development of PAC resistance in two ovarian cancer cell lines. Exposure of drug-sensitive cell lines (A2780 and W1) to PAC was used to determine the primary response. An established response was determined in PAC-resistant sublines of the A2780 and W1 cell lines. qRT-PCR was performed to measure the expression levels of specific genes...
April 12, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29622580/disruption-of-ifn-i-signaling-promotes-her2-neu-tumor-progression-and-breast-cancer-stem-cells
#12
Luciano Castiello, Paola Sestili, Giovanna Schiavoni, Rosanna Dattilo, Domenica M Monque, Fiorella Ciaffoni, Manuela Iezzi, Alessia Lamolinara, Antonella Sistigu, Federica Moschella, Anna Maria Pacca, Daniele Macchia, Maria Ferrantini, Ann Zeuner, Mauro Biffoni, Enrico Proietti, Filippo Belardelli, Eleonora Arico
Type I interferon (IFN-I) is a class of antiviral immunomodulatory cytokines involved in many stages of tumor initiation and progression. IFN-I acts directly on tumor cells to inhibit cell growth, and indirectly by activating immune cells to mount antitumor responses. To understand the role of endogenous IFN-I in spontaneous, oncogene-driven carcinogenesis, we characterized tumors arising in Her2/neu transgenic (neuT) mice carrying a nonfunctional mutation in the IFN-I receptor (IFNAR1). Such mice are unresponsive to this family of cytokines...
April 5, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29609731/neural-retina-specific-aldh1a1-controls-dorsal-choroidal-vascular-development-via-sox9-expression-in-retinal-pigment-epithelial-cells
#13
So Goto, Akishi Onishi, Kazuyo Misaki, Shigenobu Yonemura, Sunao Sugita, Hiromi Ito, Yoko Ohigashi, Masatsugu Ema, Hirokazu Sakaguchi, Kohji Nishida, Masayo Takahashi
VEGF secreted from retinal pigment epithelial (RPE) cells is responsible for the choroidal vascular development; however, the molecular regulatory mechanism is unclear. We found that Aldh1a1 -/- mice showed choroidal hypoplasia with insufficient vascularization in the dorsal region, although Aldh1a1, an enzyme that synthesizes retinoic acids (RAs), is expressed in the dorsal neural retina, not in the RPE/choroid complex. The level of VEGF in the RPE/choroid was significantly decreased in Aldh1a1 -/- mice, and RA-dependent enhancement of VEGF was observed in primary RPE cells...
April 3, 2018: ELife
https://www.readbyqxmd.com/read/29604293/immune-cell-production-of-interleukin-17-induces-stem-cell-features-of-pancreatic-intraepithelial-neoplasia-cells
#14
Yu Zhang, Michelle Zoltan, Erick Riquelme, Hanwen Xu, Ismet Sahin, Susana Castro-Pando, Maria Fernanda Montiel, Kyle Chang, Zhengyu Jiang, Jianhua Ling, Sonal Gupta, William Horne, Melissa Pruski, Huamin Wang, Shao-Cong Sun, Guillermina Lozano, Paul Chiao, Anirban Maitra, Steven D Leach, Jay K Kolls, Eduardo Vilar Sanchez, Timothy C Wang, Jennifer M Bailey, Florencia McAllister
BACKGROUND & AIMS: Little is known about how the immune system affects stem cell features of pancreatic cancer cells. Immune cells that produce interleukin 17 A (IL17A) in the chronically inflamed pancreas (chronic pancreatitis) contribute to PanIN initiation and progression. We investigated the effects of IL17A signaling exerts on pancreatic cancer progenitor cells and the clinical relevance of this phenomena. METHODS: We performed studies with Mist1Cre;LSLKras;Rosa26mTmG (KCiMist ;G) and Kras(G12D); Trp53(R172H); Pdx1-Cre (KPC) mice (which upon tamoxifen induction spontaneously develop pancreatic intraepithelial neoplasias, PanINs) and control littermates...
March 28, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29574154/pdlim5-identified-by-label-free-quantitative-proteomics-as-a-potential-novel-biomarker-of-papillary-thyroid-carcinoma
#15
Xiaodan Wei, Yuan Zhang, Shoujun Yu, Shasha Li, Wenguo Jiang, Yanping Zhu, Yuxue Xu, Chunhua Yang, Geng Tian, Jia Mi, Jonas Bergquist, Miaoqing Zhao, Fangzhou Song
In order to better understand the mechanisms underlying the development of papillary thyroid carcinoma (PTC), and to identify new potential biomarkers, high-resolution label-free mass spectrometry was performed on PTC tissues and adjacent normal thyroid tissues from six patients. In this process, 2788 proteins were identified, out of which 49 proteins presented significant differences between PTC tissues and adjacent normal thyroid tissues. Gene ontology revealed that the majority of these proteins are involved in the catalytic activity and binding...
March 23, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29568968/screening-of-potential-biomarkers-in-uterine-leiomyomas-disease-via-gene-expression-profiling-analysis
#16
Xuhui Liu, Yanfei Liu, Jingrong Zhao, Yan Liu
The present study aimed to screen potential biomarkers for uterine leiomyomas disease, particularly target genes associated with the mediator of RNA polymerase II transcription subunit 12 (MED12) mutation. The microarray data of GSE30673, including 10 MED12 wild-type myometrium, 8 MED12 mutation leiomyoma and 2 MED12 wild-type leiomyoma samples, were downloaded from the Gene Expression Omnibus database. Compared with myometrium samples, differently-expressed genes (DEGs) in the MED12 mutation and wild-type leiomyoma samples were identified using the Limma package...
March 15, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29568377/molecular-profiling-of-aldh1-colorectal-cancer-stem-cells-reveals-preferential-activation-of-mapk-fak-and-oxidative-stress-pro-survival-signalling-pathways
#17
Radhakrishnan Vishnubalaji, Muthurangan Manikandan, Mohamed Fahad, Rimi Hamam, Musaad Alfayez, Moustapha Kassem, Abdullah Aldahmash, Nehad M Alajez
Tumour heterogeneity leads to variable clinical response and inaccurate diagnostic and prognostic assessment. Cancer stem cells (CSCs) represent a subpopulation responsible for invasion, metastasis, therapeutic resistance, and recurrence in many human cancer types. However, the true identity of colorectal cancer (CRC) SCs remains elusive. Here, we aimed to characterize and define the gene expression portrait of CSCs in CRC-model SW403 cells. We found that ALDH+ positive cells are clonogenic and highly proliferative; their global gene expression profiling-based molecular signature revealed gene enrichment related to DNA damage, MAPK, FAK, oxidative stress response, and Wnt signalling...
March 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29555661/salivary-gland-cancer-patient-derived-xenografts-enable-characterization-of-cancer-stem-cells-and-new-gene-fusions-associated-with-tumor-progression
#18
Stephen Keysar, Justin Eagles, Bettina Miller, Brian C Jackson, Farshad N Chowdhury, Julie Reisinger, Tugs-Saikhan Chimed, Phuong N Le, J Jason Morton, Hilary Somerset, Marileila Varella-Garcia, Aik-Choon Tan, John I Song, Daniel W Bowles, Mary E Reyland, Antonio Jimeno
PURPOSE: Salivary gland cancers (SGC) frequently present with distant metastases many years after diagnosis, suggesting a cancer stem cell (CSC) subpopulation that initiates late recurrences; however current models are limited both in their availability and suitability to characterize these rare cells. EXPERIMENTAL DESIGN: Patient-derived xenografts (PDX) were generated by engrafting patient tissue onto nude mice from one acinic cell carcinoma (AciCC), four adenoid cystic carcinoma (ACC), and three mucoepidermoid carcinoma (MEC) cases, which were derived from successive relapses from the same MEC patient...
March 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29545617/evaluation-of-the-selective-toxic-effect-of-the-charge-switchable-diethyldithiocarbamate-loaded-nanoparticles-between-hepatic-normal-and-cancerous-cells
#19
Marwa M Abu-Serie
Liver cancer is mainly originated by cancer stem cells (CSCs). Due to difference in pH between normal and tumor cell microenvironments, targeting hepatic CSCs exploiting pH-dependent charge switchable nanoparticles (NPs) is extremely required to limit nonselective toxicity to normal hepatocytes (NHCs) and to completely eliminate the root of cancer origin. In this study, NPs were prepared from cationic chitosan and then coated with anionic albumin namely uncoated and coated NPs, respectively. Both NPs were loaded with diethyldithiocarbamate (DDC) which is an inhibitor of the critical enzyme, aldehyde dehydrogenase (ALDH) 1A1, for CSCs survival...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29458040/pharmacological-inhibition-of-jak3-enhances-the-antitumor-activity-of-imatinib-in-human-chronic-myeloid-leukemia
#20
Kenta Yagi, Akira Shimada, Toshiaki Sendo
Imatinib (IMA) is the standard treatment for CML; however, stopping IMA sometimes results in disease relapse, which suggests that leukemic stem cells (LSCs) remain in such patients, even after complete molecular remission has been achieved. Therefore, new strategies will be required to eradicate LSCs. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is part of the BCR-ABL signaling network, and it is activated in CML, especially in LSCs. JAK2 is known to be associated with CML survival, but the role of JAK3 in CML remains unknown...
April 15, 2018: European Journal of Pharmacology
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