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Aldh cancer

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
Yoshihiro Kokubo
Hypertension is one of the strongest risk factor for cardiovascular disease. Recently, accumulating evidence also indicates that hypertension has been linked with non-cardiovascular diseases including dementia, cancer, oral health diseases and so on. In general, elderly individuals tend to have multiple diseases as getting older. Preventing of hypertension is also benefit for other diseases.In the Hisayama Study, hypertension increased the risk of vascular dementia, but were not associated with an increased risk of Alzheimer disease, and that subjects with hypertension in midlife and normotension and hypertension in late-life increased risks of incident vascular dementia...
September 2016: Journal of Hypertension
Deeksha Pal, Venkatesh Kolluru, Balaji Chanderashekar, Becca V Baby, Mazzy Aman, Suman Suman, Suman Sirimulla, Mary Ann Sanders, Praveen Seshabhatter, Houda Alatassi, Murali K Ankem, Chendil Damodaran
We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues...
October 18, 2016: Molecular Carcinogenesis
Li Lin, David Jou, Yina Wang, Haiyan Ma, Tianshu Liu, James Fuchs, Pui-Kai Li, Jiagao Lü, Chenglong Li, Jiayuh Lin
Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer including pancreatic cancer. Whether STAT3 is activated in stem cell-like pancreatic cancer cells and the effect of STAT3 inhibition, is still unknown. Flow cytometry was used to isolate pancreatic cancer stem-like cells which are identified by both aldehyde dehydrogenase (ALDH)-positive (ALDH+) as well as cluster of differentiation (CD) 44-positive/CD24-positive subpopulations (CD44+/CD24+)...
October 12, 2016: International Journal of Oncology
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
Karolina Orywal, Wojciech Jelski, Tadeusz Werel, Maciej Szmitkowski
OBJECTIVES: Studies on alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the sera of patients with malignant neoplasms show that cancer cells in many organs may release ADH isoenzymes into the blood. The aim of this study was to investigate the differences in the activity of ADH isoenzymes and ALDH in the sera of patients with bladder cancer (BCa), and with different grades of the disease. MATERIAL AND METHODS: Blood samples were taken from 39 patients with BCa (15 patients with low-grade and 24 with high-grade BCa) and from 60 healthy subjects...
October 8, 2016: Acta Biochimica Polonica
Y J Yang, Z B Li, G R Zhang, L J Wu, J Y Yu, L J Hu, Y L Zhou, H D Wang, D Liang
Biological changes in Snail-overexpressed SGC7901 cells were studied by establishing a pEGFP-C1-Snail carrier. The significance of Snail in epithelial-mesenchymal transition (EMT) as well as the invasion and metastatic capacity of gastric cancer cells was also discussed; moreover, we attempted to verify the probable cancer stem cell characteristics of Snail-overexpressed cells. A pEGFP-C1-Snail eukaryotic expression plasmid was constructed and pEGFP-C1(-) and pEGFP-C1-Snail plasmids were extracted and transfected into SGC7901 cells using Lipofectamine 2000...
August 29, 2016: Genetics and Molecular Research: GMR
Yang Yu, Yu-Yi Wang, Yi-Qin Wang, Xia Wang, Yan-Yang Liu, Jian-Tao Wang, Chi Du, Li Wang, Mei Li, Feng Luo, Ming Jiang
Antiangiogenic therapy is becoming a promising option for cancer treatment. However, many investigations have recently indicated that these therapies may have limited efficacy, and the cancers in most patients eventually develop resistance to these therapies. There is considerable recently acquired evidence for an association of such resistance with cancer stem-like cells (CSLCs). Here, we used xenograft tumor murine models to further suggest that antiangiogenic agents actually increase the invasive and metastatic properties of lung cancer cells...
October 5, 2016: Scientific Reports
Ching-Wen Chang, Yu-Syuan Chen, Chien-Chih Chen, Ik-On Chan, Chin-Chu Chen, Sen-Je Sheu, Ting-Wei Lin, Shiu-Huey Chou, Chung-Ji Liu, Te-Chang Lee, Jeng-Fan Lo
Cancer initiating cells (CICs) represent a subpopulation of cancer cells, which are responsible for tumor growth and resistance to chemotherapy. Herein, we first used a cell-based aldehyde dehydrogenase (ALDH) activity assay to identify that YMGKI-2 (also named as Ergone), an active component purified from Antrodia cinnamomea Mycelia extract (ACME), effectively abrogated the ALDH activity and abolished the CICs in head and neck squamous cell carcinoma cells (HNSCCs). Consequently, YMGKI-2 treatment suppressed self-renewal ability and expression of stemness signature genes (Oct-4 and Nanog) of sphere cells with enriched CICs...
September 22, 2016: Oncotarget
Jiangang Yu, Xiaohong Liao, Luying Li, Lei Lv, Xiuling Zhi, Jerry Yu, Ping Zhou
Tumor stem cell theory may well explain a variety of malignant behaviors of tumors. Cells undergoing epithelial-mesenchymal transition (EMT) share many characteristics with tumor stem cells. Our previous studies showed that extracellular -5'- nucleotidase (CD73), one of the important surface markers of mesenchymal stem cells, may promote growth and metastasis of breast cancer cells both in vivo and in vitro. In this study, we assessed breast cancer stem cell (BCSC) markers [acetaldehyde dehydrogenase (ALDH)(+) and CD44(+)CD24(-)] in various breast cancer cell lines with flow cytometry after overexpression (by lentivirus infection) or suppression (by siRNA interference) of CD73...
September 26, 2016: In Vitro Cellular & Developmental Biology. Animal
Yoshihiro Kokubo
Hypertension is one of the strongest risk factor for cardiovascular disease. Recently, accumulating evidence also indicates that hypertension has been linked with non-cardiovascular diseases including dementia, cancer, oral health diseases and so on. In general, elderly individuals tend to have multiple diseases as getting older. Preventing of hypertension is also benefit for other diseases.In the Hisayama Study, hypertension increased the risk of vascular dementia, but were not associated with an increased risk of Alzheimer disease, and that subjects with hypertension in midlife and normotension and hypertension in late-life increased risks of incident vascular dementia...
September 2016: Journal of Hypertension
Stephen B Keysar, Phuong N Le, Bettina Miller, Brian C Jackson, Justin R Eagles, Cera Nieto, Jihye Kim, Binwu Tang, Magdalena J Glogowska, J Jason Morton, Nuria Padilla-Just, Karina Gomez, Emily Warnock, Julie Reisinger, John J Arcaroli, Wells A Messersmith, Lalage M Wakefield, Dexiang Gao, Aik-Choon Tan, Hilary Serracino, Antonio Jimeno
BACKGROUND: We have an incomplete understanding of the differences between cancer stem cells (CSCs) in human papillomavirus-positive (HPV-positive) and -negative (HPV-negative) head and neck squamous cell cancer (HNSCC). The PI3K pathway has the most frequent activating genetic events in HNSCC (especially HPV-positive driven), but the differential signaling between CSCs and non-CSCs is also unknown. METHODS: We addressed these unresolved questions using CSCs identified from 10 HNSCC patient-derived xenografts (PDXs)...
January 2017: Journal of the National Cancer Institute
Wei-Ching Chen, Hui-Ping Hsu, Chung-Yen Li, Ya-Ju Yang, Yu-Hsuan Hung, Chien-Yu Cho, Chih-Yang Wang, Tzu-Yang Weng, Ming-Derg Lai
Cancer stem cell (CSC) markers have been identified for CSC isolation and proposed as therapeutic targets in various types of cancers. CD90, one of the characterized markers in liver and gastric cancer, is shown to promote cancer formation. However, the underexpression level of CD90 in ovarian cancer cells and the evidence supporting the cellular mechanism have not been investigated. In the present study, we found that the DNA copy number of CD90 is correlated with mRNA expression in ovarian cancer tissue and the ovarian cancer patients with higher CD90 have good prognosis compared to the patients with lower CD90...
September 15, 2016: International Journal of Oncology
Oula El Atat, Diane Antonios, George Hilal, Nabil Hokayem, Joelle Abou-Ghoch, Hussein Hashim, Rim Serhal, Clara Hebbo, Mayssam Moussa, Nada Alaaeddine
The use of adipose-derived stem cells (ADSC) in regenerative medicine is rising due to their plasticity, capacity of differentiation and paracrine and trophic effects. Despite the large number of cells obtained from adipose tissue, it is usually not enough for therapeutic purposes for many diseases or cosmetic procedures. Thus, there is the need for culturing and expanding cells in-vitro for several weeks remain. Our aim is to investigate if long- term proliferation with minimal passaging will affect the stemness, paracrine secretions and carcinogenesis markers of ADSC...
2016: PloS One
Syn Kok Yeo, Jun-Lin Guan
Intra-tumor heterogeneity can be attributed in part to the ability of tumor cells to acquire traits associated with less differentiated cells. In MMTV-PyMT mammary tumors, this hierarchical heterogeneity can be illustrated with the use of ITGB1/CD29(hi) ITGB3/CD61(+) markers to enrich for mammary stem-like cells and ALDH(+) to identify luminal progenitor-like cells. Macroautophagy/autophagy appears to be important for maintaining the cancer stem-like traits of both these populations. Interestingly, the regulation of these distinct cancer stem-like cells by autophagy occurs through EGFR-STAT3 and TGFB/TGF-β-SMAD pathways, respectively...
October 2, 2016: Autophagy
Phu Hung Nguyen, Julie Giraud, Lucie Chambonnier, Pierre Dubus, Linda Wittkop, Genevieve Belleannée, Denis Collet, Isabelle Soubeyran, Serge Evrard, Benoit Rousseau, Nathalie Dugot-Senant, Francis Mégraud, Frédéric Mazurier, Christine Varon
PURPOSE: Gastric carcinomas (GC) are heterogeneous, and the current therapy remains essentially based on surgery with conventional chemo- and radiotherapy. This study aimed to characterize biomarkers allowing the detection of cancer stem cells (CSC) in human GC of different histological types. EXPERIMENTAL DESIGN: The primary tumors from thirty-seven patients with intestinal or diffuse type non-cardia GC were studied, and patient's derived tumor xenograft (PDX) models in immunodeficient mice were developed...
September 12, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Masahito Naito, Keiju Aokage, Kouichi Saruwatari, Kakeru Hisakane, Tomohiro Miyoshi, Tomoyuki Hishida, Junji Yoshida, Sugano Masato, Motohiro Kojima, Takeshi Kuwata, Satoshi Fujii, Atsushi Ochiai, Yukitoshi Sato, Masahiro Tsuboi, Genichiro Ishii
OBJECTIVES: Invasive lepidic predominant adenocarcinoma (LPA) of the lung is thought to progress in a stepwise fashion from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). The aim of this study was to investigate the microenvironmental changes during the development from AIS to LPA. MATERIALS AND METHODS: Clinicopathological characteristics of AIS (n=51), MIA (n=59), LPA smaller than 3cm (LPA-S, n=113), and LPA larger than 3cm (LPA-L, n=47) were analyzed...
October 2016: Lung Cancer: Journal of the International Association for the Study of Lung 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
Lisa Ramirez, Jason I Herschkowitz, Jun Wang
Cellular heterogeneity in function and response to therapeutics has been a major challenge in cancer treatment. The complex nature of tumor systems calls for the development of advanced multiplexed single-cell tools that can address the heterogeneity issue. However, to date such tools are only available in a laboratory setting and don't have the portability to meet the needs in point-of-care cancer diagnostics. Towards that application, we have developed a portable single-cell system that is comprised of a microchip and an adjustable clamp, so on-chip operation only needs pipetting and adjusting of clamping force...
2016: Scientific Reports
Nadia Lobello, Flavia Biamonte, Maria Elena Pisanu, Maria Concetta Faniello, Žiga Jakopin, Emanuela Chiarella, Emilia Dora Giovannone, Rita Mancini, Gennaro Ciliberto, Giovanni Cuda, Francesco Costanzo
OBJECTIVES: Ferritin is the major intracellular iron storage protein essential for maintaining the cellular redox status. In recent years ferritin heavy chain (FHC) has been shown to be involved also in the control of cancer cell growth. Analysis of public microarray databases in ovarian cancer revealed a correlation between low FHC expression levels and shorter survival. To better understand the role of FHC in cancer, we have silenced the FHC gene in SKOV3 cells. RESULTS: FHC-KO significantly enhanced cell viability and induced a more aggressive behaviour...
August 22, 2016: Oncotarget
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