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stem cell carcinogenic

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https://www.readbyqxmd.com/read/28927044/isolation-and-characterization-of-adult-mammary-stem-cells-from-breast-cancer-adjacent-tissues
#1
Ai-Ping Shi, Zhi-Min Fan, Ke-Wei Ma, Yan-Fang Jiang, Lei Wang, Ke-Wei Zhang, Shi-Bo Fu, Ning Xu, Zhi-Ru Zhang
Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28912540/sox9-regulates-cancer-stem-like-properties-and-metastatic-potential-of-single-walled-carbon-nanotube-exposed-cells
#2
Maria A Voronkova, Sudjit Luanpitpong, Liying Wang Rojanasakul, Vincent Castranova, Cerasela Zoica Dinu, Heimo Riedel, Yon Rojanasakul
Engineered nanomaterials hold great promise for the future development of innovative products but their adverse health effects are a major concern. Recent studies have indicated that certain nanomaterials, including carbon nanotubes (CNTs), may be carcinogenic. However, the underlying mechanisms behind their potential malignant properties remain unclear. In this study, we linked SOX9, a stem cell associated transcription factor, to the neoplastic-like properties of human lung epithelial cells chronically exposed to a low-dose of single-walled carbon nanotubes (SWCNTs)...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28904060/early-exposure-to-a-high-fat-high-sugar-diet-increases-the-mammary-stem-cell-compartment-and-mammary-tumor-risk-in-female-mice
#3
Isabel U Lambertz, Linjie Luo, Thomas R Berton, Scott L Schwartz, Stephen D Hursting, Claudio J Conti, Robin Fuchs-Young
Obesity and alterations in metabolic programming from early diet exposures can affect the propensity to disease in later life. Through dietary manipulation, developing mouse pups were exposed to a hyperinsulinemic, hyperglycemic milieu during three developmental phases: gestation, lactation and post-weaning. Analyses showed that a post-weaning high fat/high sugar (HF/HS) diet had the main negative effect on adult body weight, glucose tolerance and insulin resistance. However, dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis revealed that animals born to a mother fed a HF/HS gestation diet, nursed by a mother on a mildly diet-restricted, low fat/low sugar diet (DR) and weaned onto a HF/HS diet (HF/DR/HF) had the highest mammary tumor incidence, while HF/HF/DR had the lowest tumor incidence...
September 13, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28881733/positive-regulation-of-taz-expression-by-ebv-lmp1-contributes-to-cell-proliferation-and-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#4
Jiang He, Feiyu Tang, Liyu Liu, Lin Chen, Jiang Li, Danming Ou, Lu Zhang, Zhi Li, Deyun Feng, Wenzheng Li, Lun-Quan Sun
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28869601/role-of-smad-proteins-in-colitis-associated-cancer-from-known-to-the-unknown
#5
REVIEW
P Chandrasinghe, B Cereser, M Moorghen, I Al Bakir, N Tabassum, A Hart, J Stebbing, J Warusavitarne
Small mothers against decapentaplegic (SMAD) proteins are a family of signal transduction molecules in transforming growth factor β (TGFβ) ligand pathways that have been found to have a key role in the pathogenesis of inflammatory bowel disease (IBD). Long standing IBD predisposes individuals to colitis-associated colorectal cancer (CAC), an entity that possess unique characteristics compared to hereditary and sporadic cancer. The ligands of the TGFβ super family along with SMADs have also been implicated in several aspects of colorectal cancer formation...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28851689/the-second-generation-pgi2-analogue-treprostinil-fails-to-chemoprevent-tumors-in-a-murine-lung-adenocarcinoma-model
#6
Lori D Dwyer-Nield, Gregory A Hickey, Micah Friedman, Kevin Choo, Debbie G McArthur, Meredith A Tennis, Melissa L New, Mark Geraci, Robert L Keith
Prostacyclin (prostaglandin I2, PGI2) over-production in FVB/N mice prevents the formation of carcinogen and tobacco smoke induced adenomas, and administration of the oral prostacyclin analog iloprost to wild type mice also prevented carcinogen-induced mouse lung adenoma formation. Former smokers taking oral iloprost showed improved bronchial dysplasia histology compared to placebo. Next generation oral prostacyclin analogues, like treprostinil, were developed for treatment of pulmonary arterial hypertension (PAH)...
August 29, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28846189/the-mechanisms-for-lung-cancer-risk-of-pm2-5-induction-of-epithelial-mesenchymal-transition-and-cancer-stem-cell-properties-in-human-non-small-cell-lung-cancer-cells
#7
Hongying Wei, Fan Liang, Wei Cheng, Ren Zhou, Xiaomeng Wu, Yan Feng, Yan Wang
Fine particulate matter (PM2.5 ) is a major component of air pollutions that are closely associated with increased risk of lung cancer. However, the role of PM2.5 in the etiology of lung cancer is largely unknown. In this study, we performed acute (24 hours) and chronic (five passages) exposure models to investigate the carcinogenetic mechanisms of PM2.5 by targeting the induction of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) properties in human non-small cell lung cancer cell line A549...
August 28, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28747557/%C3%AE-h2ax-53bp1-and-rad51-protein-foci-changes-in-mesenchymal-stem-cells-during-prolonged-x-ray-irradiation
#8
Anastasia Tsvetkova, Ivan V Ozerov, Margarita Pustovalova, Anna Grekhova, Petr Eremin, Natalia Vorobyeva, Ilya Eremin, Andrey Pulin, Vadim Zorin, Pavel Kopnin, Sergey Leonov, Alex Zhavoronkov, Dmitry Klokov, Andreyan N Osipov
At high exposure levels ionizing radiation is a carcinogen. Little is known about how human stem cells, which are known to contribute to tumorigenesis, respond to prolonged radiation exposures. We studied formation of DNA double strand breaks, accessed as γH2AX and 53BP1 foci, in human mesenchymal stem cells (MSCs) exposed to either acute (5400 mGy/h) or prolonged (270 mGy/h) X-irradiation. We show a linear γH2AX and 53BP1 dose response for acute exposures. In contrast, prolonged exposure resulted in a dose-response curve that had an initial linear portion followed by a plateau...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28670377/mesenchymal-stem-cells-inhibited-development-of-lung-cancer-induced-by-chemical-carcinogens-in-a-rat-model
#9
Tonggang Liu, Kai Zhu, Changkang Ke, Sanhu Yang, Feng Yang, Zongfang Li, Zhipei Zhang
Mesenchymal stem cells (MSCs) may play a significant role in carcinogenesis; however, data have shown that MSCs can both promote and inhibit tumor growth. We investigated the effect of MSCs on the development of lung cancer in a rat model. Bone marrow-derived MSCs were isolated from male Wistar rats and fluorescently labeled. Genotoxic carcinogens 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) were instilled into the left lung lobes of female rats to induce tumors. Labeled male MSCs were infused into the female rats via tail vein, and the rats were sacrificed on days 3 and 7...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28642169/a-novel-method-to-quantify-base-substitution-mutations-at-the-10-6-per-bp-level-in-dna-samples
#10
Satoshi Yamashita, Naoko Iida, Hideyuki Takeshima, Naoko Hattori, Masahiro Maeda, Takayoshi Kishino, Reiko Nagano, Taichi Shimazu, Shoichiro Tsugane, Toshikazu Ushijima
Somatic base substitution mutations of frequencies at the 10(-6)/bp level are expected to be present in many biomedical samples, such as tissues exposed to carcinogenic factors and exhausted stem cells. However, measurement of such rare mutations has been very difficult in human DNA samples. Here, we invented the use of 100 copies of genomic DNA as a template for amplicon deep sequencing so that a real mutation in a single DNA molecule would be detected at a variant allele frequency of 1% while sequencing errors have less frequency...
June 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28624442/loss-of-fructose-1-6-bisphosphatase-induces-glycolysis-and-promotes-apoptosis-resistance-of-cancer-stem-like-cells-an-important-role-in-hexavalent-chromium-induced-carcinogenesis
#11
Jin Dai, Yanli Ji, Wei Wang, Donghern Kim, Leonard Yenwong Fai, Lei Wang, Jia Luo, Zhuo Zhang
Hexavalent chromium (Cr(VI)) compounds are confirmed human carcinogens for lung cancer. Our previous studies has demonstrated that chronic exposure of human bronchial epithelial BEAS-2B cells to low dose of Cr(VI) causes malignant cell transformation. The acquisition of cancer stem cell-like properties is involved in the initiation of cancers. The present study has observed that a small population of cancer stem-like cells (BEAS-2B-Cr-CSC) exists in the Cr(VI)-transformed cells (BEAS-2B-Cr). Those BEAS-2B-Cr-CSC exhibit extremely reduced capability of generating reactive oxygen species (ROS) and apoptosis resistance...
September 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28618017/curcumin-and-metformin-mediated-chemoprevention-of-oral-cancer-is-associated-with-inhibition-of-cancer-stem-cells
#12
Gangotri Siddappa, Safeena Kulsum, Doddathimmasandra Ramanjanappa Ravindra, Vinay V Kumar, Nalini Raju, Nisheena Raghavan, Holalugunda Vittalamurthy Sudheendra, Anupam Sharma, Sumsum P Sunny, Tina Jacob, Binu T Kuruvilla, Merina Benny, Benny Antony, Mukund Seshadri, Padma Lakshminarayan, Wesley Hicks, Amritha Suresh, Moni A Kuriakose
Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin, are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4NQO (4-nitro-quinoline-oxide) induced, mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven, oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40 to 100 fold) and protein levels (p≤0...
June 15, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28578586/origin-of-somatic-mutations-in-%C3%AE-catenin-versus-adenomatous-polyposis-coli-in-colon-cancer-random-mutagenesis-in-animal-models-versus-nonrandom-mutagenesis-in-humans
#13
Da Yang, Min Zhang, Barry Gold
Wnt signaling is compromised early in the development of human colorectal cancer (CRC) due to truncating nonsense mutations in adenomatous polyposis coli (APC). CRC induced by chemical carcinogens, such as heterocyclic aromatic amines and azoxymethane, in mice also involves dysregulation of Wnt signaling but via activating missense mutations in the β-catenin oncogene despite the fact that genetically modified mice harboring an inactive APC allele efficiently develop CRC. In contrast, activating mutations in β-catenin are rarely observed in human CRC...
June 15, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28566211/carcinogenicity-efficiency-and-biosafety-analysis-in-xeno-free-human-amniotic-stem-cells-for-regenerative-medical-therapies
#14
Tatsanee Phermthai, Sasiprapa Thongbopit, Puttachart Pokathikorn, Suparat Wichitwiengrat, Suphakde Julavijitphong, Nednapis Tirawanchai
BACKGROUND AIMS: Human amniotic mesenchymal stromal cells (hAMSCs) are a potent and attractive stem cell source for use in regenerative medicine. However, the safe uses of therapeutic-grade MSCs are equally as important as the efficiency of MSCs. To provide efficient, clinic-compliant (safe for therapeutic use) MSCs, hAMSC lines that completely eliminate the use of animal products and have been characterized for carcinogenicity and biosafety are required. METHODS: Here, we have efficiently generated 10 hAMSC lines under human umbilical cord blood serum (hUCS)-supplemented medium (xeno-free culture) and fetal bovine serum (FBS)-supplemented medium (standard culture) and investigated carcinogenicity and immunosuppressive properties in the resultant hAMSC lines...
May 26, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28478815/tumors-arise-from-the-excessive-repair-of-damaged-stem-cells
#15
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
#16
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
#17
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
#18
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)...
June 16, 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
#19
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
#20
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
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