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stem cell carcinogenic

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https://www.readbyqxmd.com/read/28478815/tumors-arise-from-the-excessive-repair-of-damaged-stem-cells
#1
Jun-Wen Li, Dong Yang, Danfeng Yang, Zhaoli Chen, Jing Miao, Weili Liu, Xinxing Wang, Zhigang Qiu, Min Jin, Zhiqiang Shen
Although many hypotheses for tumorigenesis have been proposed, none can explain the occurrence and development of tumors comprehensively until now. We put forward a new hypothesis: tumors arise from the excessive repair of damaged stem cells. There are stem cells in all tissues and organs, and the stem cells have perfect damage repair mechanisms, including damage repair systems and repair-inhibiting systems. Tumors arise from the excessive repair of damaged stem cells, i.e., carcinogens induce stem cell damage, leading to overexpression of damage repair systems, and simultaneous inactivation of repair-inhibiting systems through genetic or non-genetic mechanisms, finally forming tumors...
May 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28476168/dioxins-and-related-environmental-contaminants-increase-tdp-43-levels
#2
Peter E A Ash, Elizabeth A Stanford, Ali Al Abdulatif, Alejandra Ramirez-Cardenas, Heather I Ballance, Samantha Boudeau, Amanda Jeh, James M Murithi, Yorghos Tripodis, George J Murphy, David H Sherr, Benjamin Wolozin
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition that is characterized by progressive loss of motor neurons and the accumulation of aggregated TAR DNA Binding Protein-43 (TDP-43, gene: TARDBP). Increasing evidence indicates that environmental factors contribute to the risk of ALS. Dioxins, related planar polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that activate the aryl hydrocarbon receptor (AHR), a ligand-activated, PAS family transcription factor...
May 5, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28466856/stem-cell-proliferation-patterns-as-an-alternative-for-in-vivo-prediction-and-discrimination-of-carcinogenic-compounds
#3
An-Sofie Stevens, Maxime Willems, Michelle Plusquin, Jan-Pieter Ploem, Ellen Winckelmans, Tom Artois, Karen Smeets
One of the major challenges in the development of alternative carcinogenicity assays is the prediction of non-genotoxic carcinogens. The variety of non-genotoxic cancer pathways complicates the search for reliable parameters expressing their carcinogenicity. As non-genotoxic and genotoxic carcinogens have different cancer risks, the objective of this study was to develop a concept for an in vivo test, based on flatworm stem cell dynamics, to detect and classify carcinogenic compounds. Our methodology entails an exposure to carcinogenic compounds during the animal's regeneration process, which revealed differences in proliferative responses between non-genotoxic and genotoxic carcinogens during the initial stages of the regeneration process...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28448110/heavy-metals-induce-decline-of-derivatives-of-5-methycytosine-in-both-dna-and-rna-of-stem-cells
#4
Jun Xiong, Xiaona Liu, Qing-Yun Cheng, Shan Xiao, Lai-Xin Xia, Bi-Feng Yuan, Yu-Qi Feng
Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC)...
May 3, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28445992/interaction-between-the-estrogen-receptor-and-fibroblast-growth-factor-receptor-pathways-in-non-small-cell-lung-cancer
#5
Jill M Siegfried, Mariya Farooqui, Natalie J Rothenberger, Sanja Dacic, Laura P Stabile
The estrogen receptor (ER) promotes non-small cell lung cancer (NSCLC) proliferation. Since fibroblast growth factors (FGFs) are known regulators of stem cell markers in ER positive breast cancer, we investigated whether a link between the ER, FGFs, and stem cell markers exists in NSCLC. In lung preneoplasias and adenomas of tobacco carcinogen exposed mice, the anti-estrogen fulvestrant and/or the aromatase inhibitor anastrozole blocked FGF2 and FGF9 secretion, and reduced expression of the stem cell markers SOX2 and nanog...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439013/biliary-epithelial-injury-induced-regenerative-response-by-il-33-promotes-cholangiocarcinogenesis-from-peribiliary-glands
#6
Hayato Nakagawa, Nobumi Suzuki, Yoshihiro Hirata, Yohko Hikiba, Yoku Hayakawa, Hiroto Kinoshita, Sozaburo Ihara, Koji Uchino, Yuji Nishikawa, Hideaki Ijichi, Motoyuki Otsuka, Junichi Arita, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Norihiro Kokudo, Keisuke Tateishi, Kazuhiko Koike
The carcinogenic mechanism of extrahepatic cholangiocarcinoma (ECC) is unclear, due at least in part to the lack of an appropriate mouse model. Because human studies have reported frequent genetic alterations in the Ras- and TGFβ/SMAD-signaling pathways in ECC, mice with tamoxifen-inducible, duct-cell-specific Kras activation and a TGFβ receptor type 2 (TGFβR2) deletion were first generated by crossing LSL-Kras(G12D) , Tgfbr2(flox/flox) , and K19(CreERT) mice (KT-K19(CreERT) ). However, KT-K19(CreERT) mice showed only mild hyperplasia of biliary epithelial cells (BECs) in the extrahepatic bile duct (EHBD) and died within 7 wk, probably a result of lung adenocarcinomas...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28304347/plausible-roles-for-rage-in-conditions-exacerbated-by-direct-and-indirect-secondhand-smoke-exposure
#7
REVIEW
Joshua B Lewis, Kelsey M Hirschi, Juan A Arroyo, Benjamin T Bikman, David L Kooyman, Paul R Reynolds
Approximately 1 billion people smoke worldwide, and the burden placed on society by primary and secondhand smokers is expected to increase. Smoking is the leading risk factor for myriad health complications stemming from diverse pathogenic programs. First- and second-hand cigarette smoke contains thousands of constituents, including several carcinogens and cytotoxic chemicals that orchestrate chronic inflammatory responses and destructive remodeling events. In the current review, we outline details related to compromised pulmonary and systemic conditions related to smoke exposure...
March 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28266526/elf-mf-exposure-affects-the-robustness-of-epigenetic-programming-during-granulopoiesis
#8
Melissa Manser, Mohamad R Abdul Sater, Christoph D Schmid, Faiza Noreen, Manuel Murbach, Niels Kuster, David Schuermann, Primo Schär
Extremely-low-frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic" to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216675/extracellular-superoxide-dismutase-expression-in-papillary-thyroid-cancer-mesenchymal-stem-stromal-cells-modulates-cancer-cell-growth-and-migration
#9
Alessia Parascandolo, Francesca Rappa, Francesco Cappello, Jaehyup Kim, David A Cantu, Herbert Chen, Gianluigi Mazzoccoli, Peiman Hematti, Maria Domenica Castellone, Marco Salvatore, Mikko O Laukkanen
Tumor stroma-secreted growth factors, cytokines, and reactive oxygen species (ROS) influence tumor development from early stages to the metastasis phase. Previous studies have demonstrated downregulation of ROS-producing extracellular superoxide dismutase (SOD3) in thyroid cancer cell lines although according to recent data, the expression of SOD3 at physiological levels stimulates normal and cancer cell proliferation. Therefore, to analyze the expression of SOD3 in tumor stroma, we characterized stromal cells from the thyroid...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209158/gene-regulatory-network-underlying-the-immortalization-of-epithelial-cells
#10
Luis Fernando Méndez-López, Jose Davila-Velderrain, Elisa Domínguez-Hüttinger, Christian Enríquez-Olguín, Juan Carlos Martínez-García, Elena R Alvarez-Buylla
BACKGROUND: Tumorigenic transformation of human epithelial cells in vitro has been described experimentally as the potential result of spontaneous immortalization. This process is characterized by a series of cell-state transitions, in which normal epithelial cells acquire first a senescent state which is later surpassed to attain a mesenchymal stem-like phenotype with a potentially tumorigenic behavior. In this paper we aim to provide a system-level mechanistic explanation to the emergence of these cell types, and to the time-ordered transition patterns that are common to neoplasias of epithelial origin...
February 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28193239/buformin-inhibits-the-stemness-of-erbb-2-overexpressing-breast-cancer-cells-and-premalignant-mammary-tissues-of-mmtv-erbb-2-transgenic-mice
#11
Amanda B Parris, Qingxia Zhao, Erin W Howard, Ming Zhao, Zhikun Ma, Xiaohe Yang
BACKGROUND: Metformin, an FDA-approved drug for the treatment of Type II diabetes, has emerged as a promising anti-cancer agent. Other biguanide analogs, including buformin and phenformin, are suggested to have similar properties. Although buformin was shown to reduce mammary tumor burden in carcinogen models, the anti-cancer effects of buformin on different breast cancer subtypes and the underlying mechanisms remain unclear. Therefore, we aimed to investigate the effects of buformin on erbB-2-overexpressing breast cancer with in vitro and in vivo models...
February 13, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28167050/changing-mutational-and-adaptive-landscapes-and-the-genesis-of-cancer
#12
L Alexander Liggett, James DeGregori
By the time the process of oncogenesis has produced an advanced cancer, tumor cells have undergone extensive evolution. The cellular phenotypes resulting from this evolution have been well studied, and include accelerated growth rates, apoptosis resistance, immortality, invasiveness, and immune evasion. Yet with all of our current knowledge of tumor biology, the details of early oncogenesis have been difficult to observe and understand. Where different oncogenic mutations may work together to enhance the survival of a tumor cell, in isolation they are often pro-apoptotic, pro-differentiative or pro-senescent, and therefore often, somewhat paradoxically, disadvantageous to a cell...
February 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28163802/nitrative-and-oxidative-dna-damage-in-infection-related-carcinogenesis-in-relation-to-cancer-stem-cells
#13
REVIEW
Shosuke Kawanishi, Shiho Ohnishi, Ning Ma, Yusuke Hiraku, Shinji Oikawa, Mariko Murata
Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells, and result in the formation of oxidative and nitrative DNA lesions, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1), including bacterium Helicobacter pylori (H...
2017: Genes and Environment: the Official Journal of the Japanese Environmental Mutagen Society
https://www.readbyqxmd.com/read/28154735/preventing-aging-with-stem-cell-rejuvenation-feasible-or-infeasible
#14
EDITORIAL
Kanya Honoki
Characterized by dysfunction of tissues, organs, organ systems and the whole organism, aging results from the reduced function of effective stem cell populations. Recent advances in aging research have demonstrated that old tissue stem cells can be rejuvenated for the purpose of maintaining the old-organ function by youthful re-calibration of the environment where stem cells reside. Biochemical cues regulating tissue stem cell function include molecular signaling pathways that interact between stem cells themselves and their niches...
January 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28137721/transcriptional-functional-and-mechanistic-comparisons-of-stem-cell-derived-hepatocytes-heparg-cells-and-three-dimensional-human-hepatocyte-spheroids-as-predictive-in-vitro-systems-for-drug-induced-liver-injury
#15
Catherine C Bell, Volker M Lauschke, Sabine U Vorrink, Henrik Palmgren, Rodger Duffin, Tommy B Andersson, Magnus Ingelman-Sundberg
Reliable and versatile hepatic in vitro systems for the prediction of drug pharmacokinetics and toxicity are essential constituents of preclinical safety assessment pipelines for new medicines. Here, we compared three emerging cell systems-hepatocytes derived from induced pluripotent stem cells, HepaRG cells, and three-dimensional primary human hepatocyte (PHH) spheroids-at transcriptional and functional levels in a multicenter study to evaluate their potential as predictive models for drug-induced hepatotoxicity...
April 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28100039/low-dose-radiation-causes-skin-cancer-in-mice-and-has-a-differential-effect-on-distinct-epidermal-stem-cells
#16
Tatiana Revenco, Gaelle Lapouge, Virginie Moers, Sylvain Brohée, Panagiota A Sotiropoulou
The carcinogenic effect of ionizing radiation has been evaluated based on limited populations accidently exposed to high dose radiation. In contrast, insufficient data are available on the effect of low dose radiation (LDR), such as radiation deriving from medical investigations and interventions, as well as occupational exposure that concern a large fraction of western populations. Using mouse skin epidermis as a model, we showed that LDR results in DNA damage in sebaceous gland (SG) and bulge epidermal stem cells (SCs)...
May 2017: Stem Cells
https://www.readbyqxmd.com/read/28049045/in-vitro-models-reveal-differences-in-the-developmental-neurotoxicity-of-an-environmental-polycylic-aromatic-hydrocarbon-mixture-compared-to-benzo-a-pyrene-neuronotypic-pc12-cells-and-embryonic-neural-stem-cells
#17
Theodore A Slotkin, Samantha Skavicus, Jennifer Card, Richard T Di Giulio, Frederic J Seidler
In addition to their carcinogenic activity, polycyclic aromatic hydrocarbons (PAHs) are suspected to be developmental neurotoxicants. We evaluated the effects of PAHs with two in vitro models that assess distinct "decision nodes" in neurodifferentiation: neuronotypic PC12 cells, which characterize the transition from cell replication to neurodifferentiation, neurite outgrowth and neurotransmitter specification; and embryonic neural stem cells (NSCs), which evaluate the origination of neurons and glia from precursors...
February 15, 2017: Toxicology
https://www.readbyqxmd.com/read/27996035/induction-of-cancer-associated-fibroblast-like-cells-by-carbon-nanotubes-dictates-its-tumorigenicity
#18
Sudjit Luanpitpong, Liying Wang, Vincent Castranova, Cerasela Zoica Dinu, Surapol Issaragrisil, Yi Charlie Chen, Yon Rojanasakul
Tumor microenvironment has been recognized as a key determinant of tumor formation and metastasis, but how tumor microenvironment is affected by nanomaterials is essentially unknown. Here, we investigated whether carbon nanotubes (CNTs), a widely used nanomaterial with known carcinogenic potential, can affect cancer-associated fibroblasts (CAFs), which are a key component of tumor microenvironment that provides necessary support for tumor growth. We show for the first time that single-walled CNT and to a lesser extent multi-walled and its COOH-functionalized form induced CAF-like cells, which are non-tumorigenic in animals, but promote tumor growth of human lung carcinoma and CNT-transformed lung epithelial cells...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27991910/establishment-and-characterization-of-bhd-f59rsvt-an-immortalized-cell-line-derived-from-a-renal-cell-carcinoma-in-a-patient-with-birt-hogg-dub%C3%A3-syndrome
#19
Mitsuko Furuya, Hisashi Hasumi, Masaya Baba, Reiko Tanaka, Yasuhiro Iribe, Takahiro Onishi, Yoji Nagashima, Yukio Nakatani, Yasuhiro Isono, Masahiro Yao
Hereditary renal cell carcinomas (RCCs) are life-threatening disorders not only for the patients but also for their relatives. Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN). The protein product, FLCN, functions as a tumor suppressor, and the affected patients have high risks of developing multiple RCCs. The carcinogenic mechanisms stemming from FLCN dysfunction have been investigated using rodent models and human RCC tissues. However, very limited information has been available about in vitro signaling of human renal cells with genetically mutant FLCN...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27981389/pro-differentiating-effects-of-a-synthetic-flavagline-on-human-teratocarcinomal-cancer-stem-like-cells
#20
Fathi Emhemmed, Sarah Ali Azouaou, Qian Zhao, Aline Appert-Collin, Amar Bennasroune, Valérie B Schini-Kerth, Christian D Muller, Laurent Désaubry, Guy Fuhrmann
As initiators of the carcinogenic process, cancer stem cells (CSCs) are considered as new targets for anti-cancer therapies. However, these cells are hidden in the cancer bulk and remain relatively insensitive to chemotherapy, which targets their proliferative capacities. Alternatively, growing evidences have pointed out that a differentiation therapy could adversely affect these cells, which consequently should lose their self-renewal properties and become less aggressive. In order to evaluate the differentiation potential of an emerging class of anti-cancer drugs, we used the poorly differentiated teratocarcinomal cell as a model of Oct4-expressing CSC and determined the molecular mechanisms induced by the highly active flavagline FL3...
June 2017: Cell Biology and Toxicology
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