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https://www.readbyqxmd.com/read/27926488/blocking-ezh2-methylation-transferase-activity-by-gsk126-decreases-stem-cell-like-myeloma-cells
#1
Delong Zeng, Maoxing Liu, Jingxuan Pan
EZH2 is a critical epigenetic regulator that is deregulated in various types of cancers including multiple myeloma (MM). In the present study, we hypothesized that targeting EZH2 might induce apoptosis in myeloma cells including stem cell-like cells (CSCs). We investigated the effect of EZH2 inhibition on MM cells using a potent inhibitor (GSK126). The results showed that GSK126 effectively abrogated the methylated histone 3 (H3K27me3) level in MM.1S and LP1 cells, and inhibited the number of live cells and colony formation in soft agar of six MM cell lines...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27919680/aldh1a1-induces-resistance-to-chop-in-diffuse-large-b-cell-lymphoma-through-activation-of-the-jak2-stat3-pathway
#2
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/27917791/investigation-of-the-expression-of-rif1-gene-on-head-and-neck-pancreatic-and-brain-cancer-and-cancer-stem-cells
#3
Hacer E GursesCila, Muradiye Acar, Furkan B Barut, Mehmet Gunduz, Reidar Grenman, Esra Gunduz
PURPOSE: Recent studies have shown that cancer stem cells are resistant to chemotherapy. The aim of this study was to compare RIF1 gene expression in head and neck, pancreatic cancer and glioma cell lines and the cancer stem cells isolated from these cell lines. METHODS: UT-SCC-74 from Turku University and UT-SCC-74B primary tumor metastasis and neck cancer cell lines, YKG-1 glioma cancer cell line from RIKEN, pancreatic cancer cell lines and ASPC-1 cells from ATCC were grown in cell culture...
December 1, 2016: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/27910892/dynamic-microenvironment-induces-phenotypic-plasticity-of-esophageal-cancer-cells-under-flow
#4
Gizem Calibasi Kocal, Sinan Güven, Kira Foygel, Aaron Goldman, Pu Chen, Shiladitya Sengupta, Ramasamy Paulmurugan, Yasemin Baskin, Utkan Demirci
Cancer microenvironment is a remarkably heterogeneous composition of cellular and non-cellular components, regulated by both external and intrinsic physical and chemical stimuli. Physical alterations driven by increased proliferation of neoplastic cells and angiogenesis in the cancer microenvironment result in the exposure of the cancer cells to elevated levels of flow-based shear stress. We developed a dynamic microfluidic cell culture platform utilizing eshopagael cancer cells as model cells to investigate the phenotypic changes of cancer cells upon exposure to fluid shear stress...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27904609/deciphering-biological-characteristics-of-tumorigenic-subpopulations-in-human-colorectal-cancer-reveals-cellular-plasticity
#5
Hamed Mirzaei, Hossein Salehi, Amirhossein Sahebkar, Amir Avan, Mahmoud Reza Jaafari, Afshin Namdar, Abbas Rezaei, Hamid Reza Mirzaei
BACKGROUND: It is supposed that human colorectal cancer consists of a phenotypically distinct population of tumorigenic cancer cells known as cancer stem cells (CSCs) which play a pivotal role in cancer progression, maintenance, metastasis, and the relapse. The aim of this effort was to investigate and compare biological characterizations of CD133(+) with CD133(-) cell subsets isolated from both primary and metastatic human colorectal tumors. MATERIALS AND METHODS: Using our optimized protocols, unfixed colorectal tumors were enzymatically and mechanically dissociated into single cells followed by evaluation of postdigestion viability...
2016: Journal of Research in Medical Sciences: the Official Journal of Isfahan University of Medical Sciences
https://www.readbyqxmd.com/read/27903987/mapping-heterogeneity-in-patient-derived-melanoma-cultures-by-single-cell-rna-seq
#6
Tobias Gerber, Edith Willscher, Henry Loeffler-Wirth, Lydia Hopp, Dirk Schadendorf, Manfred Schartl, Ulf Anderegg, Gray Camp, Barbara Treutlein, Hans Binder, Manfred Kunz
Recent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27897208/beta-1-integrin-ligation-and-tlr-ligation-enhance-gm-csf-induced-aldh1a2-expression-in-dendritic-cells-but-differentially-regulate-their-anti-inflammatory-properties
#7
Aya Yokota-Nakatsuma, Yoshiharu Ohoka, Hajime Takeuchi, Si-Young Song, Makoto Iwata
Retinoic acid (RA)-producing CD103(+) mature dendritic cells (DCs) in mesenteric lymph nodes (MLNs) play crucial roles in gut immunity. GM-CSF and RA contribute to the expression of the RA-producing enzyme ALDH1A2. However, additional signals appeared to be required for inducing ALDH1A2(high) mature DCs from immature DCs. We found here that TLR ligands (Ls) and immobilized E-cadherin could provide such signals in FLT3-L-generated bone marrow (BM)-derived DCs after treatment with GM-CSF and the RA receptor agonist Am80...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27895670/wnt5a-increases-properties-of-lung-cancer-stem-cells-and-resistance-to-cisplatin-through-activation-of-wnt5a-pkc-signaling-pathway
#8
Jiali Yang, Kangjian Zhang, Jing Wu, Juan Shi, Jing Xue, Jing Li, Juan Chen, Yongzhao Zhu, Jun Wei, Jinxi He, Xiaoming Liu
The development of chemoresistance to cisplatin regimens causes a poor prognosis in patients with advanced NSCLC. The role of noncanonical Wnt signaling in the regulation of properties of lung cancer stem cells and chemoresistance was interrogated, by accessing capacities of cell proliferation, migration, invasion, and clonogenicity as well as the apoptosis in A549 cell lines and cisplatin-resistant A549 cells treated with Wnt5a conditional medium or protein kinase C (PKC) inhibitor GF109203X. Results showed that the noncanonical Wnt signaling ligand, Wnt5a, could promote the proliferation, migration, invasion, and colony formation in A549 lung adenocarcinoma cells and cisplatin-resistant A549/DDP cells and increase the fraction of ALDH-positive cell in A549/DDP cells...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27895076/mesothelial-cells-create-a-novel-tissue-niche-that-facilitates-gastric-cancer-invasion
#9
Masamitsu Tanaka, Sei Kuriyama, Go Itoh, Daichi Maeda, Akiteru Goto, Yutaro Tamiya, Kazuyoshi Yanagihara, Masakazu Yashiro, Namiko Aiba
Peritoneal mesothelial cells (PMC) cover organ surfaces in the abdominal cavity. In this study, lineage tracing revealed that PMC guide cancer cell invasion in the gastric wall and in peritoneal metastatic lesions. Serosal PMC covering the stomach surface entered the gastric wall to create a novel niche that favored gastric cancer cell invasion. PMC infiltration was induced by incorporation of cancer cell-derived, Wnt3a-containing extracellular vesicles (EV). Infiltrated PMC in turn promoted subserosal invasion of cancer cells...
November 28, 2016: Cancer Research
https://www.readbyqxmd.com/read/27894093/new-use-of-an-old-drug-inhibition-of-breast-cancer-stem-cells-by-benztropine-mesylate
#10
Jihong Cui, Maija Hollmén, Lina Li, Yong Chen, Steven T Proulx, Daniel Reker, Gisbert Schneider, Michael Detmar
Cancer stem cells (CSCs) play major roles in cancer initiation, metastasis, recurrence and therapeutic resistance. Targeting CSCs represents a promising strategy for cancer treatment. The purpose of this study was to identify selective inhibitors of breast CSCs (BCSCs). We carried out a cell-based phenotypic screening with cell viability as a primary endpoint, using a collection of 2,546 FDA-approved drugs and drug-like molecules in spheres formed by malignant human breast gland-derived cells (HMLER-shEcad cells, representing BCSCs) and control immortalized non-tumorigenic human mammary cells (HMLE cells, representing normal stem cells)...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885254/aldehyde-dehydrogenase-is-used-by-cancer-cells-for-energy-metabolism
#11
Joon Hee Kang, Seon-Hyeong Lee, Dongwan Hong, Jae-Seon Lee, Hee-Sung Ahn, Ju-Hyun Ahn, Tae Wha Seong, Chang-Hun Lee, Hyonchol Jang, Kyeong Man Hong, Cheolju Lee, Jae-Ho Lee, Soo-Youl Kim
We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid...
November 25, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27882330/aldh2-inhibition-potentiates-high-glucose-stress-induced-injury-in-cultured-cardiomyocytes
#12
Guodong Pan, Mandar Deshpande, Rajarajan A Thandavarayan, Suresh Selvaraj Palaniyandi
Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27876836/nf-kappa%C3%AE-inducing-kinase-regulates-stem-cell-phenotype-in-breast-cancer
#13
Karla Vazquez-Santillan, Jorge Melendez-Zajgla, Luis Enrique Jimenez-Hernandez, Javier Gaytan-Cervantes, Laura Muñoz-Galindo, Patricia Piña-Sanchez, Gustavo Martinez-Ruiz, Javier Torres, Patricia Garcia-Lopez, Carolina Gonzalez-Torres, Victor Ruiz, Federico Avila-Moreno, Marco Velasco-Velazquez, Mayra Perez-Tapia, Vilma Maldonado
Breast cancer stem cells (BCSCs) overexpress components of the Nuclear factor-kappa B (NF-κB) signaling cascade and consequently display high NF-κB activity levels. Breast cancer cell lines with high proportion of CSCs exhibit high NF-κB-inducing kinase (NIK) expression. The role of NIK in the phenotype of cancer stem cell regulation is poorly understood. Expression of NIK was analyzed by quantitative RT-PCR in BCSCs. NIK levels were manipulated through transfection of specific shRNAs or an expression vector...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871335/aldehyde-dehydrogenase-expression-in-metaphire-posthuma-as-a-bioindicator-to-monitor-heavy-metal-pollution-in-soil
#14
Raju Panday, Padam Shekhar Bhatt, Tribikram Bhattarai, Kumudini Shakya, Lakshmaiah Sreerama
BACKGROUND: Soil contamination and associated pollution plays a detrimental role in soil flora and fauna. Soil is processed and remodeled by subterranean earthworms, accordingly are referred to as soil chemical engineers. These worms, besides processing carbon and nitrogen, serve as minors for processing metals. In heavy metal contaminated soils, they accumulate heavy metals, which in turn cause altered gene expression, including aldehyde dehydrogenase (ALDH) enzymes. This study explores the possibility of ALDH expression in earthworms as a novel biomarker for the heavy metal contamination of soil...
November 21, 2016: BMC Research Notes
https://www.readbyqxmd.com/read/27857231/quantitative-proteomic-analysis-of-age-related-subventricular-zone-proteins-associated-with-neurodegenerative-disease
#15
Xianli Wang, Chuanming Dong, Lixin Sun, Liang Zhu, Chenxi Sun, Rongjie Ma, Ke Ning, Bing Lu, Jinfu Zhang, Jun Xu
Aging is characterized by a progressive decline in the function of adult tissues which can lead to neurodegenerative disorders. However, little is known about the correlation between protein changes in the subventricular zone (SVZ) and neurodegenerative diseases with age. In the present study, neural stem cells (NSCs) were derived from the SVZ on postnatal 7 d, 1 m, and 12 m-old mice. With age, NSCs exhibited increased SA-β-gal activity and decreased proliferation and pool size in the SVZ zone, and were associated with elevated inflammatory chemokines and cytokines...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27842518/mir-199a-5p-confers-tumor-suppressive-role-in-triple-negative-breast-cancer
#16
Jiawei Chen, Vivian Y Shin, Man T Siu, John C W Ho, Isabella Cheuk, Ava Kwong
BACKGROUND: Triple-negative breast cancer (TNBC) remains a poor prognostic factor for breast cancer since no effective targeted therapy is readily available. Our previous studies confirmed miR-199a-5p is a TNBC-specific circulating biomarker, however, its functional roles in breast cancer is largely unknown. Thus, we investigated the functional implication of miR-199a-5p in TNBC and its potential underlying mechanisms. METHODS: MTT assay was performed to investigate the cell proliferation after transient transfection of miR-199a-5p in MDA-MB-231 cell line, followed by cell cycle analysis...
November 14, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27829238/combining-a-gsi-and-bcl-2-inhibitor-to-overcome-melanoma-s-resistance-to-current-treatments
#17
Nabanita Mukherjee, Adam Almeida, Katie A Partyka, Yan Lu, Josianna V Schwan, Karoline Lambert, Madison Rogers, William A Robinson, Steven E Robinson, Allison J Applegate, Carol M Amato, Yuchun Luo, Mayumi Fujita, David A Norris, Yiqun G Shellman
Major limitations of current melanoma treatments are for instances of relapse and the lack of therapeutic options for BRAF wild-type patients who do not respond to immunotherapy. Many studies therefore focus on killing resistant subpopulations, such as Melanoma Initiating Cells (MICs) to prevent relapse. Here we examined whether combining a GSI (γ-Secretase Inhibitor) with ABT-737 (a small molecule BCL-2/BCL-XL/BCL-W inhibitor) can kill both the non-MICs (bulk of melanoma) and MICs. To address the limitations of melanoma therapies, we included multiple tumor samples of patients relapsed from current treatments, with a diverse genetic background (with or without the common BRAF, NRAS or NF1 mutations) in these studies...
November 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27826122/variable-aldehyde-dehydrogenase-activity-and-effects-on-chemosensitivity-of-primitive-human-leukemic-cells
#18
A Bogen, C Buske, W Hiddemann, S K Bohlander, O Christ
Aldehyde dehydrogenase (ALDH) activity is an established feature of primitive normal human hematopoietic cells in which it has been associated with a high expression of the 1A1 isoform of ALDH. High ALDH1A1 activity has been reported to also characterize cells that propagate malignant populations arising in other tissues, but the regulation and basis of ALDH activity in primary human leukemic cells has not been well studied. We obtained samples from patients with newly diagnosed AML (n=21) and CML (n=8) and analyzed different phenotypically and functionally defined subsets for their ALDH activity using the ALDEFLUOR(®) kit and expression of the ALDH1A1 gene...
November 5, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27803106/egfl6-regulates-the-asymmetric-division-maintenance-and-metastasis-of-aldh-ovarian-cancer-cells
#19
Shoumei Bai, Patrick Ingram, Yu-Chih Chen, Ning Deng, Alex Pearson, Yashar Niknafs, Patrick O'Hayer, Yun Wang, Zhong-Yin Zhang, Elisa Boscolo, Joyce Bischoff, Euisik Yoon, Ronald J Buckanovich
Little is known about the factors that regulate the asymmetric division of cancer stem-like cells (CSC). Here, we demonstrate that EGFL6, a stem cell regulatory factor expressed in ovarian tumor cells and vasculature, regulates ALDH(+) ovarian CSC. EGFL6 signaled at least in part via the oncoprotein SHP2 with concomitant activation of ERK. EGFL6 signaling promoted the migration and asymmetric division of ALDH(+) ovarian CSC. As such, EGFL6 increased not only tumor growth but also metastasis. Silencing of EGFL6 or SHP2 limited numbers of ALDH(+) cells and reduced tumor growth, supporting a critical role for EGFL6/SHP2 in ALDH(+) cell maintenance...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27803105/bet-inhibitors-suppress-aldh-activity-by-targeting-aldh1a1-super-enhancer-in-ovarian-cancer
#20
Yuhki Yokoyama, Hengrui Zhu, Jeong Heon Lee, Andrew V Kossenkov, Sherry Y Wu, Jayamanna M Wickramasinghe, Xiangfan Yin, Katherine C Palozola, Alessandro Gardini, Louise C Showe, Kenneth S Zaret, Qin Liu, David Speicher, Jose R Conejo-Garcia, James E Bradner, Zhiguo Zhang, Anil K Sood, Tamas Ordog, Benjamin G Bitler, Rugang Zhang
The emergence of tumor cells with certain stem-like characteristics, such as high aldehyde dehydrogenase (ALDH) activity due to ALDH1A1 expression, contributes to chemotherapy resistance and tumor relapse. However, clinically applicable inhibitors of ALDH activity have not been reported. There is evidence to suggest that epigenetic regulation of stem-related genes contributes to chemotherapy efficacy. Here, we show that bromodomain and extraterminal (BET) inhibitors suppress ALDH activity by abrogating BRD4-mediated ALDH1A1 expression through a super-enhancer element and its associated enhancer RNA...
November 1, 2016: Cancer Research
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