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https://www.readbyqxmd.com/read/28821904/developmentally-regulated-signaling-pathways-in-glioma-invasion
#1
REVIEW
Shwetal Mehta, Costanza Lo Cascio
Malignant gliomas are the most common, infiltrative, and lethal primary brain tumors affecting the adult population. The grim prognosis for this disease is due to a combination of the presence of highly invasive tumor cells that escape surgical resection and the presence of a population of therapy-resistant cancer stem cells found within these tumors. Several studies suggest that glioma cells have cleverly hijacked the normal developmental program of neural progenitor cells, including their transcriptional programs, to enhance gliomagenesis...
August 18, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28821543/airway-basal-cell-heterogeneity-and-lung-squamous-cell-carcinoma
#2
EDITORIAL
Robert E Hynds, Sam M Janes
Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution...
August 18, 2017: Cancer Prevention Research
https://www.readbyqxmd.com/read/28818454/the-anti-tumor-effect-of-intravesical-administration-of-normal-urothelial-cells-on-bladder-cancer
#3
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need...
August 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28815441/pluripotent-stem-cells-in-adult-tissues-struggling-to-be-acknowledged-over-two-decades
#4
REVIEW
Deepa Bhartiya
Stem cells have fascinated scientists for a long time and huge research efforts have been put into them as they have the potential to regenerate diseased organs. Besides embryonic stem cells (ES) and induced pluripotent stem cells (iPS), it has been postulated that pluripotent stem cells (PSCs) may also exist in various adult tissues. They are thought to be more primitive than the adult stem cells (ASCs), serve as a backup pool to give rise to ASCs and thus play a crucial role in maintaining life-long homeostasis...
August 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28814980/cooperative-effect-of-chidamide-and-chemotherapeutic-drugs-induce-apoptosis-by-dna-damage-accumulation-and-repair-defects-in-acute-myeloid-leukemia-stem-and-progenitor-cells
#5
Yin Li, Yan Wang, Yong Zhou, Jie Li, Kai Chen, Leisi Zhang, Manman Deng, Suqi Deng, Peng Li, Bing Xu
BACKGROUND: Many conventional chemotherapeutic drugs are known to be involved in DNA damage, thus ultimately leading to apoptosis of leukemic cells. However, they fail to completely eliminate leukemia stem cells (LSCs) due to their higher DNA repair capacity of cancer stem cells than that of bulk cancer cells, which becomes the root of drug resistance and leukemia recurrence. A new strategy to eliminate LSCs in acute myeloid leukemia (AML) is therefore urgently needed. RESULTS: We report that a low-dose chidamide, a novel orally active benzamide-type histone deacetylase (HDAC) inhibitor, which selectively targets HDACs 1, 2, 3, and 10, could enhance the cytotoxicity of DNA-damaging agents (daunorubicin, idarubicin, and cytarabine) in CD34(+)CD38(-) KG1α cells, CD34(+)CD38(-) Kasumi cells, and primary refractory or relapsed AML CD34(+) cells, reflected by the inhibition of cell proliferation, induction of apoptosis, and increase of cell cycle arrest in vitro...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28807057/inhibitory-effects-of-hnf4%C3%AE-on-migration-maltransformation-of-hepatic-progenitors-hnf4%C3%AE-overexpressing-hepatic-progenitors-for-liver-repopulation
#6
Ping Wang, Min Cong, Tianhui Liu, Hufeng Xu, Lin Wang, Guangyong Sun, Aiting Yang, Dong Zhang, Jian Huang, Yameng Sun, Wenshan Zhao, Hong Ma, Jidong Jia, Hong You
BACKGROUND: Although they are expandable in vitro, hepatic progenitors are immature cells and share many immunomarkers with hepatocellular carcinoma, raising potential concerns regarding maltransformation after transplantation. This study investigated the effects of hepatic nuclear factor (HNF) 4α on the proliferation, migration, and maltransformation of hepatic progenitors and determined the feasibility of using these manipulated cells for transplantation. METHODS: The effects of HNF4α on rat hepatic progenitors (i...
August 14, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28794285/preventing-chemotherapy-induced-myelosuppression-by-repurposing-the-flt3-inhibitor-quizartinib
#7
Samuel J Taylor, Johanna M Duyvestyn, Samantha A Dagger, Emma J Dishington, Catherine A Rinaldi, Oliver M Dovey, George S Vassiliou, Carolyn S Grove, Wallace Y Langdon
We describe an approach to inhibit chemotherapy-induced myelosuppression. We found that short-term exposure of mice to the FLT3 inhibitor quizartinib induced the transient quiescence of multipotent progenitors (MPPs). This property of quizartinib conferred marked protection to MPPs in mice receiving fluorouracil or gemcitabine. The protection resulted in the rapid recovery of bone marrow and blood cellularity, thus preventing otherwise lethal myelosuppression. A treatment strategy involving quizartinib priming that protected wild-type bone marrow progenitors, but not leukemic cells, from fluorouracil provided a more effective treatment than conventional induction therapy in mouse models of acute myeloid leukemia...
August 9, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28793923/concurrent-antitumor-and-bone-protective-effects-of-everolimus-in-osteotropic-breast-cancer
#8
Andrew J Browne, Marie L Kubasch, Andy Göbel, Peyman Hadji, David Chen, Martina Rauner, Friedrich Stölzel, Lorenz C Hofbauer, Tilman D Rachner
BACKGROUND: The mammalian target of rapamycin inhibitor everolimus is approved as an antitumor agent in advanced estrogen receptor-positive breast cancer. Surrogate bone marker data from clinical trials suggest effects on bone metabolism, but the mode of action of everolimus in bone biology remains unclear. In this study, we assessed potential bone-protective effects of everolimus in the context of osteotropic tumors. METHODS: The effects of everolimus on cancer cell viability in vitro and on tumor growth in vivo were assessed...
August 9, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28791287/bidirectional-mast-cell-eosinophil-interactions-in-inflammatory-disorders-and-cancer
#9
REVIEW
Maria Rosaria Galdiero, Gilda Varricchi, Mansour Seaf, Giancarlo Marone, Francesca Levi-Schaffer, Gianni Marone
Human mast cells (MCs) and eosinophils were first described and named by Paul Ehrlich. These cells have distinct myeloid progenitors and differ morphologically, ultrastructurally, immunologically, biochemically, and pharmacologically. However, MCs and eosinophils play a pivotal role in several allergic disorders. In addition, these cells are involved in autoimmune disorders, cardiovascular diseases, and cancer. MCs are distributed throughout all normal human tissues, whereas eosinophils are present only in gastrointestinal tract, secondary lymphoid tissues, and adipose tissue, thymus, mammary gland, and uterus...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28782836/histone-deacetylase-3-deletion-in-mesenchymal-progenitor-cells-hinders-long-bone-development
#10
Marina Feigenson, Lomeli Carpio Shull, Earnest L Taylor, Emily T Camilleri, Scott M Reister, Andre J van Wijnen, Elizabeth W Bradley, Jennifer J Westendorf
Long bone formation is a complex process that requires precise transcriptional control of gene expression programs in mesenchymal progenitor cells. Histone deacetylases (Hdacs) coordinate chromatin structure and gene expression by enzymatically removing acetyl groups from histones and other proteins. Hdac inhibitors are used clinically to manage mood disorders, cancers and other conditions, but are teratogenic to the developing skeleton and increase fracture risk in adults. In this study, the functions of Hdac3, one of the enzymes blocked by current Hdac inhibitor therapies, in skeletal mesenchymal progenitor cells were determined...
August 7, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28781954/mammalian-enabled-mena-protein-enhances-oncogenic-potential-and-cancer-stem-cell-like-phenotype-in-hepatocellular-carcinoma-cells
#11
Kunpeng Hu, Pinzhu Huang, Hui Luo, Zhicheng Yao, Qingliang Wang, Zhiyong Xiong, Jizong Lin, He Huang, Shilei Xu, Peng Zhang, Bo Liu
Mammalian-enabled (MENA) protein is an actin-regulatory protein that influences cell motility and adhesion. It is known to play a role in tumorigenicity of hepatocellular carcinoma (HCC) but the underlying molecular mechanism remains unknown. This study aimed to investigate the oncogenic potential of MENA and its capacity to regulate cancer stem cell (CSC)-like phenotypes in HCC cells. Real-time-PCR and western blot were used to assess mRNA and protein levels of target genes in human HCC tissue specimens and HCC cell lines, respectively...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28777795/regulation-of-gli-ciliary-localization-and-hedgehog-signaling-by-the-py-nls-karyopherin-%C3%AE-2-nuclear-import-system
#12
Yuhong Han, Yue Xiong, Xuanming Shi, Jiang Wu, Yun Zhao, Jin Jiang
Hedgehog (Hh) signaling in vertebrates depends on primary cilia. Upon stimulation, Hh pathway components, including Gli transcription factors, accumulate at primary cilia to transduce the Hh signal, but the mechanisms underlying their ciliary targeting remains largely unknown. Here, we show that the PY-type nuclear localization signal (PY-NLS)/karyopherinβ2 (Kapβ2) nuclear import system regulates Gli ciliary localization and Hh pathway activation. Mutating the PY-NLS in Gli or knockdown of Kapβ2 diminished Gli ciliary localization...
August 2017: PLoS Biology
https://www.readbyqxmd.com/read/28777465/basal-progenitor-cells-bridge-the-development-malignant-cancers-and-multiple-diseases-of-esophagus
#13
REVIEW
Baoshun Lin, Fuan Xie, Zhangwu Xiao, Xiaoqian Hong, Liming Tian, Kuancan Liu
The esophagus is a pivotal organ originating from anterior foregut that links the mouth and stomach. Moreover, its development involves precise regulation of multiple signal molecules and signal transduction pathways. After abnormal regulation of these molecules in the basal cells of the esophagus occurs, multiple diseases, including esophageal atresia with or without tracheoesophageal fistula, Barrett esophagus, gastroesophageal reflux, and eosinophilic esophagitis, will take place as a result. Furthermore, expression changes of signal molecules or signal pathways in basal cells and the microenvironment around basal cells both can initiate the switch of malignant transformation...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28775207/development-of-aggressive-pancreatic-ductal-adenocarcinomas-depends-on-granulocyte-colony-stimulating-factor-secretion-in-carcinoma-cells
#14
Michael W Pickup, Philip Owens, Agnieszka E Gorska, Anna Chytil, Fei Ye, Chanjuan Shi, Valerie M Weaver, Raghu Kalluri, Harold L Moses, Sergey V Novitskiy
The survival rate for pancreatic ductal adenocarcinoma (PDAC) remains low. More therapeutic options to treat this disease are needed, for the current standard of care is ineffective. Using an animal model of aggressive PDAC (Kras/p48(TGFβRIIKO)), we discovered an effect of TGFβ signaling in regulation of G-CSF secretion in pancreatic epithelium. Elevated concentrations of G-CSF in PDAC promoted differentiation of Ly6G(+) cells from progenitors, stimulated IL10 secretion from myeloid cells, and decreased T-cell proliferation via upregulation of Arg, iNOS, VEGF, IL6, IL1b from CD11b(+) cells...
August 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28768192/time-restricted-feeding-shifts-the-skin-circadian-clock-and-alters-uvb-induced-dna-damage
#15
Hong Wang, Elyse van Spyk, Qiang Liu, Mikhail Geyfman, Michael L Salmans, Vivek Kumar, Alexander Ihler, Ning Li, Joseph S Takahashi, Bogi Andersen
The epidermis is a highly regenerative barrier protecting organisms from environmental insults, including UV radiation, the main cause of skin cancer and skin aging. Here, we show that time-restricted feeding (RF) shifts the phase and alters the amplitude of the skin circadian clock and affects the expression of approximately 10% of the skin transcriptome. Furthermore, a large number of skin-expressed genes are acutely regulated by food intake. Although the circadian clock is required for daily rhythms in DNA synthesis in epidermal progenitor cells, RF-induced shifts in clock phase do not alter the phase of DNA synthesis...
August 1, 2017: Cell Reports
https://www.readbyqxmd.com/read/28768055/harnessing-cxcr4-antagonists-in-stem-cell-mobilization-hiv-infection-ischemic-diseases-and-oncology
#16
REVIEW
Lun Kelvin Tsou, Ying-Huey Huang, Jen-Shin Song, Yi-Yu Ke, Jing-Kai Huang, Kak-Shan Shia
CXCR4 antagonists (e.g., Plerixafor(TM) ) have been successfully validated as stem cell mobilizers for peripheral blood stem cell transplantation. Applications of the CXCR4 antagonists have heralded the era of cell-based therapy and opened a potential therapeutic horizon for many unmet medical needs such as kidney injury, ischemic stroke, cancer, and myocardial infarction. In this review, we first introduce the central role of CXCR4 in diverse cellular signaling pathways and discuss its involvement in several disease progressions...
August 2, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28765161/the-interplay-between-epigenetic-changes-and-the-p53-protein-in-stem-cells
#17
REVIEW
Arnold J Levine, Shelley L Berger
Epigenetic programs regulate the development and maintenance of organisms over a lifetime. These programs are carried out through chemical modifications of DNA and proteins such as histones and transcription factors. These epigenetic modifications are less stable than genetic alterations and even reversible under a variety of circumstances, such as developmental changes, regeneration of tissues, cell divisions, aging, and pathological conditions observed in many cancers. The p53 protein not only enforces the stability of the genome by the prevention of genetic alterations in cells but also plays a role in regulating the epigenetic changes that can occur in cells...
June 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28761088/shift-of-emt-gradient-in-3d-spheroid-mscs-for-activation-of-mesenchymal-niche-function
#18
Sohee Jeon, Ho-Sun Lee, Ga-Young Lee, Gyeongsin Park, Tae-Min Kim, Jihye Shin, Cheolju Lee, Il-Hoan Oh
Despite the wide use of mesenchymal stromal cells (MSCs) for paracrine support in clinical trials, their variable and heterogeneous supporting activity pose major challenges. While three-dimensional (3D) MSC cultures are emerging as alternative approaches, key changes in cellular characteristics during 3D-spheroid formation remain unclear. Here, we show that MSCs in 3D spheroids undergo further progression towards the epithelial-mesenchymal transition (EMT), driven by upregulation of EMT-promoting microRNAs and suppression of EMT-inhibitory miRNAs...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28758931/tumor-stroma-crosstalk-in-bone-tissue-the-osteoclastogenic-potential-of-a-breast-cancer-cell-line-in-a-co-culture-system-and-the-role-of-egfr-inhibition
#19
Laura Mercatali, Federico La Manna, Giacomo Miserocchi, Chiara Liverani, Alessandro De Vita, Chiara Spadazzi, Alberto Bongiovanni, Federica Recine, Dino Amadori, Martina Ghetti, Toni Ibrahim
Although bone metastases represent a major challenge in the natural history of breast cancer (BC), the complex interactions involved have hindered the development of robust in vitro models. The aim of this work is the development of a preclinical model of cancer and bone stromal cells to mimic the bone microenvironment. We studied the effects on osteoclastogenesis of BC cells and Mesenchymal stem cells (MSC) cultured alone or in combination. We also analyzed: (a) whether the blockade of the Epithelial Growth Factor Receptor (EGFR) pathway modified their influence on monocytes towards differentiation, and (b) the efficacy of bone-targeted therapy on osteoclasts...
July 29, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28757593/sechium-edule-jacq-swartz-a-new-cultivar-with-antiproliferative-potential-in-a-human-cervical-cancer-hela-cell-line
#20
Sandra Salazar-Aguilar, Lucero Del Mar Ruiz-Posadas, Jorge Cadena-Iñiguez, Marcos Soto-Hernández, Edelmiro Santiago-Osorio, Itzen Aguiñiga-Sánchez, Ana Rocío Rivera-Martínez, Juan Francisco Aguirre-Medina
The Sechium edule Perla Negra cultivar is a recently-obtained biological material whose progenitors are S. edule var. nigrum minor and S. edule var. amarus silvestrys, the latter of which has been reported to have antiproliferative activity against the HeLa P-388 and L-929 cancer cell lines. The present study aimed to determine if the methanolic extract of the fruit of the Perla Negra cultivar had the same biological activity. The methanolic extract was phytochemically characterized by thin layer chromatography (TLC) and column chromatography (CC), identifying the terpenes and flavonoids...
July 25, 2017: Nutrients
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