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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
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...
February 16, 2018: European Journal of Pharmacology
Seyedmehdi Nourashrafeddin, Batool Hosseini Rashidi
Initiation of spermatogenesis in primates is triggered at puberty by an increase in gonadotropins; i.e., follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Prior to puberty, testis of the monkey contains only undifferentiated germ cells. However, sermatogonial differentiation and spermatogenesis may be initiated prior to puberty after stimulation with exogenous LH and FSH. Retinoic acid (RA) signaling is considered to be a major component that drives spermatogonial differentiation. We were interested in evaluating the relative role of LH and FSH, either alone or in combination, in regulating the retinoic acid signaling in monkey testis...
January 2018: Acta Medica Iranica
Yi-Liang Bi, Min Min, Wei Shen, Yan Liu
BACKGROUND: Genistein is a natural flavonoid that has been reported to exhibit anticancer effects against different types of cancers which include, but are not limited to, breast and oral squamous cell carcinoma. PURPOSE: The present study was designed to evaluate the anticancer effects of the natural flavonoid genistein against pancreatic cancer cell lines and to explore the underlying mechanism. METHODS: Antiproliferative activity was investigated by MTT assay...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Sara M Thomasy, Vijay Krishna Raghunathan, Hidetaka Miyagi, Alexander T Evashenk, Jasmyne C Sermeno, Geneva K Tripp, Joshua T Morgan, Christopher J Murphy
The transformation of keratocytes and fibroblasts to myofibroblasts is important to corneal wound healing as well as formation of stromal haze. The purpose of this study was to determine the effect of latrunculin B, an actin cytoskeleton disruptor in conjunction with a fundamental biophysical cue, substrate stiffness, on myofibroblast transformation in vitro and in vivo. Rabbit corneal fibroblasts were cultured on substrates of differing compliance (1.5, 22, and 71 kPa) and tissue culture plastic (TCP; > 1 GPa) in media containing 0 or 10 ng/ml TGFβ1 for 72 h...
February 5, 2018: Experimental Eye Research
Mohammed Gagaoua, Muriel Bonnet, Marie-Pierre Ellies-Oury, Leanne De Koning, Brigitte Picard
The validation of biomarkers and tools for the prediction of beef texture remains a challenging task. In this study, reverse phase protein arrays (RPPA) quantified 29 protein biomarkers in the m. Longissimus thoracis of Charolais cattle sampled early post-mortem. Myosin heavy chain 1 (MHC1, slow-oxidative fibers) and Retinal dehydrogenase 1 (ALDH1A1, oxidative enzyme) discriminated between tender and juicy vs. tough meat with residues classes and are validated as prime biomarkers of beef texture. Several proteins belonging to energy metabolism, heat shock and oxidative stress, cytoskeletal, cell signaling and apoptosis were related with tenderness...
June 1, 2018: Food Chemistry
Ying-Hui Song, Mei-Zuo Zhong, Qin Chai, Kui-Yu Gong, Xiao-Lang Tan, Jin-Yue Hu, Gui-Hua Wang
Previously we showed that aldehyde dehydrogenase 1A1 (ALDH1A1) is a new mediator for resistance of DLBCL to CHOP and a facility predictor of clinical prognosis. In the present study, knockdown and inhibitor of ALDH1A1 were applied to identify the role of ALDH1A1 in Raji cells. CCK-8 and clone formation assay were applied to determine the CHOP sensitivity and clone formation ability. Caspase colorimetric assay and Annexin V/FITC staining was performed to determine the degree of apoptosis. Western blot analysis was used to detect the NF-κB/STAT3 signaling proteins and apoptotic-associated proteins...
January 18, 2018: Oncology Reports
Qiang Wang, Jun Jiang, Guoguang Ying, Xiao-Qing Xie, Xia Zhang, Wei Xu, Xuemin Zhang, Erwei Song, Hong Bu, Yi-Fang Ping, Xiao-Hong Yao, Bin Wang, Shilei Xu, Ze-Xuan Yan, Yanhong Tai, Baoquan Hu, Xiaowei Qi, Yan-Xia Wang, Zhi-Cheng He, Yan Wang, Ji Ming Wang, You-Hong Cui, Feng Chen, Kun Meng, Zhaoyi Wang, Xiu-Wu Bian
The 66 kDa estrogen receptor alpha (ERα66) is the main molecular target for endocrine therapy such as tamoxifen treatment. However, many patients develop resistance with unclear mechanisms. In a large cohort study of breast cancer patients who underwent surgery followed by tamoxifen treatment, we demonstrate that ERα36, a variant of ERα66, correlates with poor prognosis. Mechanistically, tamoxifen directly binds and activates ERα36 to enhance the stemness and metastasis of breast cancer cells via transcriptional stimulation of aldehyde dehydrogenase 1A1 (ALDH1A1)...
February 2, 2018: Cell Research
Xiaoting Li, Xiaoqian Wang, Chunfeng Xie, Jianyun Zhu, Yu Meng, Yue Chen, Yuan Li, Ye Jiang, Xue Yang, Shijia Wang, Jiaqi Chen, Qi Zhang, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Yu Zhao
Cancer stem cells (CSCs) play an essential role in the progression of many tumors. Sonic hedgehog (Shh) and Wnt/β-catenin pathways are crucial in maintaining the stemness of CSCs. Curcumin has been shown to possess anticancer activity. However, the interventional effect of curcumin on breast CSCs has not been elucidated. In the present study, we investigated the role of Shh and Wnt/β-catenin pathway in curcumin inhibition of breast CSCs. We showed that the levels of breast CSCs markers were significantly elevated in SUM159 and MCF7 sphere-forming cells...
January 22, 2018: Anti-cancer Drugs
Rong Wang, Laixiu Yang, Shen Li, Dongmei Ye, Lihong Yang, Qingyan Liu, Zibo Zhao, Qing Cai, Junzhen Tan, Xiuli Li
BACKGROUND Quercetin, nature's most common flavonoid, possesses anticarcinogenic properties against various forms of cancer. The aim of this study was to investigate the effect of quercetin on breast cancer stem cells in the MDA-MB-231 cell line, and to elucidate the possible mechanisms for those effects. MATERIAL AND METHODS We evaluated breast cancer stem cell proliferation, clone generation, and mammosphere formation to determine the effect of quercetin treatment on breast cancer stem cells. RESULTS In our study, quercetin suppressed breast cancer stem cell proliferation, self-renewal, and invasiveness...
January 21, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Hilla Solomon, Nathan Dinowitz, Ioannis S Pateras, Tomer Cooks, Yoav Shetzer, Alina Molchadsky, Meital Charni, Stav Rabani, Gabriela Koifman, Ohad Tarcic, Ziv Porat, Ira Kogan-Sakin, Naomi Goldfinger, Moshe Oren, Curtis C Harris, Vassilis G Gorgoulis, Varda Rotter
Emerging notion in carcinogenesis ascribes tumor initiation and aggressiveness to cancer stem cells (CSCs). Specifically, colorectal cancer (CRC) development was shown to be compatible with CSCs hypothesis. Mutations in p53 are highly frequent in CRC, and are known to facilitate tumor development and aggressiveness. Yet, the link between mutant p53 and colorectal CSCs is not well-established. In the present study, we set to examine whether oncogenic mutant p53 proteins may augment colorectal CSCs phenotype...
January 18, 2018: Oncogene
Letizia Astrologo, Eugenio Zoni, Sofia Karkampouna, Peter C Gray, Irena Klima, Joël Grosjean, Marie J Goumans, Lukas J A C Hawinkels, Gabri van der Pluijm, Martin Spahn, George N Thalmann, Peter Ten Dijke, Marianna Kruithof-de Julio
Prostate cancer is the second most common cancer in men and lethality is normally associated with the consequences of metastasis rather than the primary tumor. Therefore, targeting the molecular pathways that underlie dissemination of primary tumor cells and the formation of metastases has a great clinical value. Bone morphogenetic proteins (BMPs) play a critical role in tumor progression and this study focuses on the role of BMP9- Activin receptor-Like Kinase 1 and 2 (ALK1 and ALK2) axis in prostate cancer...
2017: Frontiers in Cell and Developmental Biology
Bo Wang, Faya Zhang, Hui Zhang, Zhixiu Wang, Yan-Nan Ma, Mei-Jun Zhu, Min Du
Cancer is commonly associated with cachexia, a paraneoplastic syndrome characterized by body weight loss, muscle wasting, adipose tissue atrophy and inflammation. Chronic alcohol consumption increases the risk of multiple types of cancer, and enhances cancer-associated cachexia (CAC), but the underlying mechanisms remain poorly defined. To test, C57BL/6 mice were fed with 0% or 20% (w/v) alcohol for 3 months, then inoculated with B16BL6 melanoma cells subcutaneously in the right side of the hip and continued to feed with/without alcohol for 3 or 4 weeks...
November 21, 2017: Oncotarget
Jin Won Park, Kyung-Ho Jung, Jin Hee Lee, Seung Hwan Moon, Young Seok Cho, Kyung-Han Lee
We hypothesized that aldehyde dehydrogenase1 (ALDH1) protects cancer cells from retinaldehyde-induced cytotoxicity, and that targeting this enzyme would enhance the therapeutic effect of retinaldehyde. ALDEFLUOR™ assays showed high ALDH activity in A549 and H522 cancer cells and low activity in H1666 and T47D cancer cells. Immunoblots showed that expression of ALDH1A1 and ALDH1A3 was high in A549 and H522 cells, but low in H1666 cells. HPLC confirmed that N, N-diethylaminobenzaldehyde (DEAB) inhibits ALDH-mediated disposal of retinaldehyde in A549 cells and lysates...
November 21, 2017: Oncotarget
Xiaoting Li, Yu Meng, Chunfeng Xie, Jianyun Zhu, Xiaoqian Wang, Yuan Li, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Min Li
Cancer stem cells (CSCs) play a central role in the development of breast cancer. The canonical Wnt/β-catenin signal pathway is critical for maintaining CSCs characteristics. Diallyl trisulfide (DATS), a natural organosulfur compound from the garlic, exhibits effective antitumor properties. However, the role of DATS in regulating breast CSCs activity and the underlying molecular mechanisms remain obscure. In the present study, we reported that DATS efficiently inhibited the viability of breast CSCs as evidenced by reducing turmorspheres formation, decreasing the expression of breast CSCs markers (CD44, ALDH1A1, Nanog and Oct4), as well as inhibiting proliferation and inducing apoptosis...
December 15, 2017: Journal of Cellular Biochemistry
Rahul Metri, Abhilash Mohan, Jérémie Nsengimana, Joanna Pozniak, Carmen Molina-Paris, Julia Newton-Bishop, David Bishop, Nagasuma Chandra
Understanding the biological factors that are characteristic of metastasis in melanoma remains a key approach to improving treatment. In this study, we seek to identify a gene signature of metastatic melanoma. We configured a new network-based computational pipeline, combined with a machine learning method, to mine publicly available transcriptomic data from melanoma patient samples. Our method is unbiased and scans a genome-wide protein-protein interaction network using a novel formulation for network scoring...
December 11, 2017: Scientific Reports
Edna Grünblatt, Josefine Ruder, Camelia Maria Monoranu, Peter Riederer, Moussa Bh Youdim, Silvia A Mandel
Parkinson's disease is the most common neurodegenerative disorder after Alzheimer's disease, with the majority of cases being sporadic or "idiopathic". The aetiology of the sporadic form is still unknown, but there is a broad consensus that Parkinson's disease involves multiple pathways. In previous human post-mortem studies investigating substantia nigra of parkinsonian subjects, gene expression alterations in various metabolic pathways including protein folding, trafficking, aggregation, ubiquitination and oxidative stress were found...
December 7, 2017: Neurotoxicity Research
Richárd Nagymihály, Zoltán Veréb, Andrea Facskó, Morten C Moe, Goran Petrovski
Purpose: To determine the effect of the isolation technique and location upon the phenotype of human corneal stroma-derived cells (CSCs). Methods: CSCs were isolated from the corneal stroma center and periphery using the explant or enzymatic digestion technique. The native tissue was stained for functional markers, while cultured cells were analysed by FACS. PCR was used to determine gene expression in the cultured versus native cells. Results: The native stroma was positive for α -actinin, ALDH1A1, CD31, CD34, Collagen I, and Vimentin...
2017: Stem Cells International
Wan-Jing Chen, Rwei-Fen S Huang
Low-folate (LF) nutritional status is associated with increased risks of lung cancer. It has unexplored effects on lung cancer malignancy, a cancer stem cell (CSC) disease. We hypothesized that LF may reprogram CSC-like potential and bioenergetics metabolism to increase metastasis potential of lung cancers. Cultivation of human non-small-cell lung cancer cells (H23) in an LF medium enhanced CSC-like properties signified by increased expressions of the CSC surface marker CD44 and pluripotency markers Sox2, Oct4 and ALDH1A1, and promoted self-renewal ability of anchorage-independent oncospheroid formation...
March 2018: Journal of Nutritional Biochemistry
Zhiyu Xia, Kathy B Baumgartner, Richard N Baumgartner, Stephanie D Boone, Lisa M Hines, Esther M John, Roger Wolff, Martha L Slattery, Avonne E Connor
PURPOSE: ALDH1A1, one of the main isotopes of aldehyde dehydrogenase-1 is involved in the differentiation and protection of normal hematopoietic stem cells and functions in alcohol sensitivity and dependence. We evaluated the associations between ALDH1A1 polymorphisms, alcohol consumption, and mortality among Hispanic and non-Hispanic white (NHW) breast cancer (BC) cases from the Breast Cancer Health Disparities Study. METHODS: Nine SNPs in ALDH1A1 were evaluated in 920 Hispanic and 1372 NHW women diagnosed with incident invasive BC...
November 30, 2017: Breast Cancer Research and Treatment
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