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https://www.readbyqxmd.com/read/27908290/bile-acid-a-potential-inducer-of-colon-cancer-stem-cells
#1
Lulu Farhana, Pratima Nangia-Makker, Evan Arbit, Kathren Shango, Sarah Sarkar, Hamidah Mahmud, Timothy Hadden, Yingjie Yu, Adhip P N Majumdar
BACKGROUND: Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promote stemness in colonic epithelial cells leading to generation of cancer stem cells (CSCs) that play a role in the development and progression of colon cancer. METHODS: Normal human colonic epithelial cells (HCoEpiC) were used to study bile acid DCA/LCA-mediated induction of CSCs...
December 1, 2016: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27908206/the-role-of-mesenchymal-stem-cells-in-oncology-and-regenerative-medicine
#2
Maliha Khan, Syeda Ezze Rukhshan Adil, Amanda L Olson
Mesenchymal stem cells (MSCs) have long been used as therapeutic agents in disease affecting various organ systems. However, MSCs are fast emerging as promising anticancer agents which have the potential to treat a number of different cancer types, including glioblastoma and metastatic breast, ovarian and hepatic carcinoma. The ability of MSC to migrate directly into the tumor microenvironment and to produce IFN-α and -β makes this possible. However, the possibility of MSC undergoing either malignant transformation or transformation into protumorigenic fibroblasts currently limits their role in clinical use...
December 2, 2016: Future Oncology
https://www.readbyqxmd.com/read/27905066/a-multiscale-approach-to-the-migration-of-cancer-stem-cells-mathematical-modelling-and-simulations
#3
Nikolaos Sfakianakis, Niklas Kolbe, Nadja Hellmann, Mária Lukáčová-Medvid'ová
We propose a multiscale model for the invasion of the extracellular matrix by two types of cancer cells, the differentiated cancer cells and the cancer stem cells. We investigate the epithelial mesenchymal-like transition between them being driven primarily by the epidermal growth factors. We moreover take into account the transdifferentiation program of the cancer stem cells towards the cancer-associated fibroblast cells as well as the fibroblast-driven remodelling of the extracellular matrix. The proposed haptotaxis model combines the macroscopic phenomenon of the invasion of the extracellular matrix by both types of cancer cells with the microscopic dynamics of the epidermal growth factors...
November 30, 2016: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/27902484/depletion-of-mitochondrial-reactive-oxygen-species-downregulates-epithelial-to-mesenchymal-transition-in-cervical-cancer-cells
#4
Galina Shagieva, Lidiya Domnina, Olga Makarevich, Boris Chernyak, Vladimir Skulachev, Vera Dugina
In the course of cancer progression, epithelial cells often acquire morphological and functional characteristics of mesenchymal cells, a process known as epithelial-to-mesenchymal transition (EMT). EMT provides epithelial cells with migratory, invasive, and stem cell capabilities. Reactive oxygen species produced by mitochondria (mtROS) could be of special importance for pro-tumorigenic signaling and EMT.In our study, we used mitochondria-targeted antioxidant SkQ1 to lower the mtROS level and analyze their role in the regulation of the actin cytoskeleton, adhesion junctions, and signaling pathways critical for tumorigenesis of cervical carcinomas...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27901498/targeting-the-vegf-c-vegfr3-axis-suppresses-slug-mediated-cancer-metastasis-and-stemness-via-inhibition-of-kras-yap1-signaling
#5
REVIEW
Yu-Wen Yeh, Ching-Chia Cheng, Shu-Ting Yang, Chi-Feng Tseng, Ting-Yu Chang, Sin-Ying Tsai, Earl Fu, Chien-Ping Chiang, Li-Chuan Liao, Pei-Wen Tsai, Yung-Luen Yu, Jen-Liang Su
Vascular endothelial growth factor-C (VEGF-C) has been implicated in epithelial-mesenchymal transition (EMT) processes and various human cancers, including skin cancer. Skin cancer is an aggressive human malignancy with increasing incidence worldwide; however, the underlying mechanisms involved in VEGF-C-induced skin cancer stemness and metastasis remain unclear. Here, we report that VEGF-C enhances skin cancer migration, invasion and stemness through Slug up-regulation. Oncomine database analysis indicated that the KRAS/MAPK (mitogen-activated protein kinases) pathway and YAP1 (yes-associated protein 1) expression are positively correlated with metastatic skin cancer...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899964/radiation-induces-the-generation-of-cancer-stem-cells-a-novel-mechanism-for-cancer-radioresistance
#6
Fengsheng Li, Kunming Zhou, Ling Gao, Bin Zhang, Wei Li, Weijuan Yan, Xiujun Song, Huijie Yu, Sinian Wang, Nan Yu, Qisheng Jiang
Radioresistance remains a major obstacle for the radiotherapy treatment of cancer. Previous studies have demonstrated that the radioresistance of cancer is due to the existence of intrinsic cancer stem cells (CSCs), which represent a small, but radioresistant cell subpopulation that exist in heterogeneous tumors. By contrast, non-stem cancer cells are considered to be radiosensitive and thus, easy to kill. However, recent studies have revealed that under conditions of radiation-induced stress, theoretically radiosensitive non-stem cancer cells may undergo dedifferentiation subsequently obtaining the phenotypes and functions of CSCs, including high resistance to radiotherapy, which indicates that radiation may directly result in the generation of novel CSCs from non-stem cancer cells...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27898034/emerging-non-canonical-functions-and-regulation-by-p53-p53-and-stemness
#7
REVIEW
David J Olivos, Lindsey D Mayo
Since its discovery nearly 40 years ago, p53 has ascended to the forefront of investigated genes and proteins across diverse research disciplines and is recognized most exclusively for its role in cancer as a tumor suppressor. Levine and Oren (2009) reviewed the evolution of p53 detailing the significant discoveries of each decade since its first report in 1979. In this review, we will highlight the emerging non-canonical functions and regulation of p53 in stem cells. We will focus on general themes shared among p53's functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27895787/runx2-expression-a-mesenchymal-stem-marker-for-cancer
#8
Maria Teresa Valenti, Paola Serafini, Giulio Innamorati, Anna Gili, Samuele Cheri, Claudio Bassi, Luca Dalle Carbonare
The transcription factor runt-related transcription factor 2 (Runx2) is a master gene implicated in the osteogenic differentiation of mesenchymal stem cells, and thus serves a determinant function in bone remodelling and skeletal integrity. Various signalling pathways regulate Runx2 abundance, which requires a number of molecules to finely modulate its expression. Furthermore, this gene may be ectopically-expressed in cancer cells. Recent studies have reported the involvement of Runx2 in cell proliferation, epithelial-mesenchymal transition, apoptosis and metastatic processes, suggesting it may represent a useful therapeutic target in cancer treatment...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895151/high-fat-diet-promotes-mammary-gland-myofibroblast-differentiation-through-mir-140-downregulation
#9
Benjamin Wolfson, Yongshu Zhang, Ramkishore Gernapudi, Nadire Duru, Yuan Yao, Pang-Kuo Lo, Qun Zhou
Human breast adipose tissue is a heterogonous cell population consisting of mature white adipocytes, multipotent mesenchymal stem cells, committed progenitor cells, fibroblasts, endothelial cells, and immune cells. Dependent on external stimulation, adipose derived stem cells differentiate along diverse lineages into adipocytes, chondrocytes, osteoblasts, fibroblasts, and myofibroblasts. It is currently not fully understood how high-fat diet reprograms adipose-derived stem cells into myofibroblasts. In our study, we use regular-diet and high-fat diet induced obesity mouse models to investigate the role of dietary fat on myofibroblast differentiation in the mammary stromal microenvironment...
November 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27892545/erythrocyte-membrane-based-cationic-polymer-mcdna-complexes-as-an-efficient-gene-delivery-system
#10
Ping Huang, Jing Zhao, Chiju Wei, Xiaohu Hou, Pingzhang Chen, Yan Tan, Cheng-Yi He, Zhiyong Wang, Zhi-Ying Chen
Gene therapy has great promise for the treatment of obtained and inherited serious diseases. However, the lack of safe and efficient gene delivery systems remains a barrier for their clinical application. Here, we reported a potential gene delivery vehicle composed of the erythrocyte membrane and cationic polymers, for example the XtremeGENE from Roche and the ε-caprolactone modified polyethylenimine. In addition to high efficiency, this system showed negligible cytotoxicity compared to the two cationic polymers alone in various cell lines, including human embryonic kidney cells (293T), human liver cancer cells (Huh7 and HepG2), murine dendritic cells (DC2...
November 28, 2016: Biomaterials Science
https://www.readbyqxmd.com/read/27889319/cell-type-specific-chromatin-states-differentially-prime-squamous-cell-carcinoma-tumor-initiating-cells-for-epithelial-to-mesenchymal-transition
#11
Mathilde Latil, Dany Nassar, Benjamin Beck, Soufiane Boumahdi, Li Wang, Audrey Brisebarre, Christine Dubois, Erwin Nkusi, Sandrine Lenglez, Agnieszka Checinska, Alizée Vercauteren Drubbel, Michael Devos, Wim Declercq, Rui Yi, Cédric Blanpain
Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential...
November 16, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27888618/involvement-of-inflammation-and-its-related-micrornas-in-hepatocellular-carcinoma
#12
REVIEW
Ke Jin, Tong Li, Gonzalo Sánchez-Duffhues, Fangfang Zhou, Long Zhang
Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed type of cancer. The tumor inflammatory microenvironment regulates almost every step towards liver tumorigenesis and subsequent progression, and regulation of the inflammation-related signaling pathways, cytokines, chemokines and non-coding RNAs influences the proliferation, migration and metastasis of liver tumor cells. Inflammation fine-tunes the cancer microenvironment to favor epithelial-mesenchymal transition, in which cancer stem cells maintain tumorigenic potential...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27888521/cancer-associated-mesenchymal-stroma-fosters-the-stemness-of-osteosarcoma-cells-in-response-to-intratumoral-acidosis-via-nf-%C3%AE%C2%BAb-acivation
#13
Sofia Avnet, Gemma Di Pompo, Tokuhiro Chano, Costantino Errani, Arig Ibrahim-Hashim, Robert J Gillies, Davide Maria Donati, Nicola Baldini
The role of mesenchymal stem cells (MSC) in osteosarcoma (OS), the most common primary tumor of bone, has not been extensively elucidated. We have recently shown that OS is characterized by interstitial acidosis, a microenvironmental condition that is similar to a wound setting, in which mesenchymal reactive cells are activated to release mitogenic and chemotactic factors. We therefore intended to test the hypothesis that, in OS, acid-activated MSC influence tumor cell behavior. Conditioned media or co-culture with normal MSC previously incubated with short-term acidosis (pH 6...
November 26, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27882459/analysis-of-proliferation-of-melanoma-cells-and-mesenchymal-stem-cells-in-co-culture-and-contribution-of-experimental-conditions-into-interpretation-of-the-results
#14
O F Kandarakov, E E Kopantseva, A V Belyavsky
A series of experiments on co-culturing of Mel IL melanoma cells and mesenhymal stem cells showed that these cells do not influence proliferation of each other, but we observed weaker adhesion of stromal stem cells to plastic in cocultures where with melanoma cells were grown on mesenhymal stem cells feeder. Cell proliferation was also considerably influenced by experimental conditions, which should be taken into account for correct interpretation of obtained results. The principles of experiments on co-culturing of cancer and stromal cells are formulated that take into account the most important factors influencing cell behavior and minimize the probability of artifact results...
November 23, 2016: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27878307/hmga2-regulates-epithelial-mesenchymal-transition-and-the-acquisition-of-tumor-stem-cell-properties-through-twist1-in-gastric-cancer
#15
Wei Li, Ziwei Wang, Lang Zha, Dequan Kong, Gang Liao, Hui Li
High expression of high mobility group protein A2 (HMGA2) is correlated with the invasiveness of gastric cancer and is an independent prognostic factor. The reason may be that HMGA2 promotes epithelial-mesenchymal transition (EMT) and the acquisition of tumor stem cell properties, yet the mechanism remains unclear. In this study, immunohistochemistry and western blot analysis revealed that the expression of HMGA2 and Twist-related protein 1 (TWIST1) in gastric carcinoma tissues was higher than that in the peritumoral tissues and that the expression levels of these two proteins were positively correlated...
November 18, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27878251/glyceraldehyde-3-phosphate-dehydrogenase-promotes-cancer-growth-and-metastasis-through-upregulation-of-snail-expression
#16
Kaiyan Liu, Zhenjie Tang, Amin Huang, Ping Chen, Panpan Liu, Jing Yang, Wenhua Lu, Jianwei Liao, Yicheng Sun, Shijun Wen, Yumin Hu, Peng Huang
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in multiple cellular functions including metabolism and gene transcription. Our previous study showed that GAPDH expression was elevated in colon cancer and further upregulated in liver metastatic tissues, suggesting a possilbe role of GAPDH in promoting cancer metastasis. The present study was designed to investigate the underlying mechanism, using multiple experimental approaches including genetic silencing of GAPDH expression by short hairpin RNA (shRNA) and biochemcial/molecular analyses of the key events involved in glycolytic metabolism and epithelial-mesenchymal transition (EMT)...
November 18, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/27875275/histone-chaperone-aplf-regulates-induction-of-pluripotency-in-murine-fibroblasts
#17
Khaja Mohieddin Syed, Sunu Joseph, Ananda Mukherjee, Aditi Majumder, Jose M Teixeira, Debasree Dutta, Madhavan Radhakrishna Pillai
Induction of pluripotency in differentiated cells by the exogenous expression of transcription factors, Oct4, Sox2, Klf4 and cMyc, involves reprogramming at the epigenetic level. Histones and their metabolism governed by histone chaperones constitute a significant aspect of epigenetics. We hypothesized that histone chaperones might facilitate or inhibit the course of reprogramming. For the first time, we report here that the downregulation of histone chaperone Aprataxin PNK-like factor (APLF) promotes reprogramming by augmenting the expression of E-cadherin (Cdh1), implicated in mesenchymal-to-epithelial transition (MET) involved in the generation of induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblasts (MEFs)...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27873362/influence-of-mesenchymal-stem-cells-conditioned-media-on-proliferation-of-urinary-tract-cancer-cell-lines-and-their-sensitivity-to-ciprofloxacin
#18
Malgorzata Maj, Anna Bajek, Ewelina Nalejska, Dorota Porowinska, Tomasz Kloskowski, Lidia Gackowska, Tomasz Drewa
Mesenchymal stem cells (MSCs) are known to interact with cancer cells through direct cell-to-cell contact and secretion of paracrine factors, although their exact influence on tumor progression in vivo remains unclear. To better understand how fetal and adult stem cells affect tumors, we analyzed viability of human renal (786-0) and bladder (T24) carcinoma cell lines cultured in conditioned media harvested from amniotic fluid-derived stem cells (AFSCs) and adipose-derived stem cells (ASCs). Both media reduced metabolic activity of 786-0 cells, however, decreased viability of T24 cells was noted only after incubation with conditioned medium from ASCs...
November 22, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27872098/systematic-drug-screening-identifies-tractable-targeted-combination-therapies-in-triple-negative-breast-cancer
#19
Vikram B Wali, Casey G Langdon, Matthew A Held, James T Platt, Gauri A Patwardhan, Anton Safonov, Bilge Aktas, Lajos Pusztai, David F Stern, Christos Hatzis
Triple-negative breast cancer (TNBC) remains an aggressive disease without effective targeted therapies. In this study, we addressed this challenge by testing 128 FDA-approved or investigational drugs as either single agents or in 768 pairwise drug combinations in TNBC cell lines to identify synergistic combinations tractable to clinical translation. Medium-throughput results were scrutinized and extensively analyzed for sensitivity patterns, synergy, anticancer activity and validation in low-throughput experiments...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27871860/in%C3%A2-vitro-reconstitution-of-breast-cancer-heterogeneity-with-multipotent-cancer-stem-cells-using-small-molecules
#20
Masaki Kawamata, Takeshi Katsuda, Yasuhiro Yamada, Takahiro Ochiya
A small fraction of tumor cells are thought to possess the potential for both multiple-lineage differentiation and self-renewal, which underlies the cancer stem cell hypothesis. However, the differentiation mechanisms of these cells have not been elucidated due to a lack of appropriate culture methods. Here, we established a culture condition for maintaining multipotent tumor cells from rat breast tumors using 4 small molecules. Cultured tumor cells in this condition retained their intrinsic myoepithelial features, expressing p63 and CK14 and vimentin...
November 18, 2016: Biochemical and Biophysical Research Communications
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