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https://www.readbyqxmd.com/read/28928900/dihydroorotate-dehydrogenase-inhibitors-target-c-myc-and-arrest-melanoma-myeloma-and-lymphoma-cells-at-s-phase
#1
Mathura Subangari Dorasamy, Bhavesh Choudhary, Kavitha Nellore, Hosahalli Subramanya, Pooi-Fong Wong
Dihydroorotate dehydrogenase (DHODH) is a rate-limiting enzyme in the de novo biosynthesis pathway of pyrimidines. Inhibition of this enzyme impedes cancer cell proliferation but the exact mechanisms of action of these inhibitors in cancer cells are poorly understood. In this study, we showed that cancer cells, namely melanoma, myeloma and lymphoma overexpressed DHODH protein and treatment with A771726 and Brequinar sodium resulted in cell cycle arrest at S-phase. Transfection with DHODH shRNA depleted DHODH protein expression and impeded the proliferation of melanoma cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928827/inhibition-of-c-myc-expression-accounts-for-an-increase-in-the-number-of-multinucleated-cells-in-human-cervical-epithelial-cells
#2
Feng Mei Cui, Xiu Jin Sun, Cheng Cheng Huang, Qiu Chen, Yong Ming He, Shi Meng Zhang, Hua Guan, Man Song, Ping Kun Zhou, Jun Hou
The present study aimed to explore the mechanisms by which c-Myc is involved in mitotic catastrophe. HeLa-630 is a cell line stably silenced for c-Myc expression that was established in the laboratory of the School of Radiation Medicine and Protection. Multinucleated cells were observed in this line, and gene expression analysis was utilized to examine differences in gene expression in these cells compared with in the control cells transfected with the control plasmid. Gene ontology analysis was performed for differentially expressed genes...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927089/chronic-radiation-exposure-of-neuroblastoma-cells-reduces-nmyc-copy-number
#3
Manu Gnanamony, Reuben Antony, Karen S Fernández, Libes Jaime, Julian Lin, Pushpa A Joseph, Christopher S Gondi
Neuroblastoma accounts for >15% of cancer-associated mortalities of children in the USA. Despite aggressive treatment regimens, the long-term survival for these children remains <40%. The identification of v-Myc avian myelocytomatosis viral oncogene neuroblastoma-derived homolog (nMYC) gene amplification during diagnosis is associated with poor prognosis in neuroblastoma. There are limited studies examining changes in nMYC copy numbers in response to therapy and its biological effect on cancer cells. The aim of the present study was to evaluate the effect of radiation on nMYC expression and amplification status in high-risk neuroblastoma...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927069/overexpression-of-reic-dkk-3-suppresses-the-expression-of-cd147-and-inhibits-the-proliferation-of-human-bladder-cancer-cells
#4
Yuhei Horikawa, Masami Watanabe, Takuya Sadahira, Yuichi Ariyoshi, Yasuyuki Kobayashi, Motoo Araki, Koichiro Wada, Kazuhiko Ochiai, Shun-Ai Li, Yasutomo Nasu
Our group previously developed an adenoviral vector encoding the REIC/Dkk-3 gene (Ad-REIC), a tumor suppressor, for cancer gene therapy. The Ad-REIC agent induces apoptosis and inhibits invasion in a number of cancer cell lines; however, the molecular mechanisms underlying its effects remain unclear. Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer (EMMPRIN), is a key molecule that promotes cancer proliferation and invasion. In order to elucidate the therapeutic mechanism of Ad-REIC, its effect on the expression of CD147 in human bladder cancer KK47 cells was investigated...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28925366/establishment-of-a-human-ipsc-line-iishdoi001-a-from-a-patient-with-mcardle-disease
#5
María Del Carmen Ortuño-Costela, Nathalie Rodríguez-Mancera, Marta García-López, Francisco Zurita-Díaz, Ana Moreno-Izquierdo, Alejandro Lucía, Miguel Ángel Martín, Rafael Garesse, M Esther Gallardo
Human iPSC line IISHDOi001-A was generated from fibroblasts of a patient with McArdle disease harbouring the mutation, c.148C>T; p.Arg50Ter, in the PYGM gene. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using Sendai virus.
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925364/generation-and-characterization-of-a-human-ipsc-line-from-a-patient-with-propionic-acidemia-due-to-defects-in-the-pcca-gene
#6
Esmeralda Alonso-Barroso, Sandra Brasil, Álvaro Briso-Montiano, Rosa Navarrete, Celia Pérez-Cerdá, Magdalena Ugarte, Belén Pérez, Lourdes R Desviat, Eva Richard
Human induced pluripotent stem cell (iPSC) line was generated from fibroblasts of a patient with propionic acidemia carrying mutations in the PCCA gene: c.1899+4_1899+7delAGTA; p.(Cys616_Val633del) and c.1430--?_1643+?del; p.(Gly477Glufs*9). Reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC were delivered using a non-integrative method based on the Sendai virus. Once established, iPSCs have shown full pluripotency, differentiation capacity and genetic stability.
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28924385/dna-methylation-mediated-downregulation-of-mir-449c-controls-osteosarcoma-cell-cycle-progression-by-directly-targeting-oncogene-c-myc
#7
Qing Li, Hua Li, Xueling Zhao, Bing Wang, Lin Zhang, Caiguo Zhang, Fan Zhang
MicroRNAs (miRNAs) are critical regulators of gene expression, and they have broad roles in the pathogenesis of different diseases including cancer. Limited studies and expression profiles of miRNAs are available in human osteosarcoma cells. By applying a miRNA microarray analysis, we observed a number of miRNAs with abnormal expression in cancerous tissues from osteosarcoma patients. Of particular interest in this study was miR-449c, which was significantly downregulated in osteosarcoma cells and patients, and its expression was negatively correlated with tumor size and tumor MSTS stages...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28924376/verteporfin-inhibits-cell-proliferation-and-induces-apoptosis-in-human-leukemia-nb4-cells-without-light-activation
#8
Min Chen, Liang Zhong, Shi-Fei Yao, Yi Zhao, Lu Liu, Lian-Wen Li, Ting Xu, Liu-Gen Gan, Chun-Lan Xiao, Zhi-Ling Shan, Bei-Zhong Liu
Background and Aims: Verteporfin (VP), clinically used in photodynamic therapy for neovascular macular degeneration, has recently been proven a suppressor of yes-associated protein (YAP) and has shown potential in anticancer treatment. However, its anti-human leukemia effects in NB4 cells remain unclear. In this study, we investigated the effects of VP on proliferation and apoptosis in human leukemia NB4 cells. Methods: NB4 cells were treated with VP for 24 h. The effects of VP on cell proliferation were determined using a Cell-Counting Kit-8 assay (CCK-8) assay and colony forming assay...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28922143/leukocyte-reduced-platelet-rich-plasma-stimulates-the-in-vitro-proliferation-of-adipose-tissue-derived-mesenchymal-stem-cells-depending-on-pdgf-signaling
#9
Siegmund Lang, Marietta Herrmann, Christian Pfeifer, Gero Brockhoff, Johannes Zellner, Michael Nerlich, Peter Angele, Lukas Prantl, Sebastian Gehmert, Markus Loibl
BACKGROUND: Platelet-rich Plasma (PRP) is suggested as xenoprotein-free cell-culture medium replacement for animal-derived supplements. OBJECTIVE: The aim of this study was to investigate PRP-triggered signaling in adipose derived mesenchymal stem cells (ASCs). METHODS: PRP was obtained from 4 male patients. We incubated ASCs in α-MEM with different Platelet derived growth factor (PDGF) subtypes or 10% or 20% pooled PRP or 20% fetal calf serum (FCS) prior to determination of the S-phase fraction (SPF)...
September 11, 2017: Clinical Hemorheology and Microcirculation
https://www.readbyqxmd.com/read/28921051/fine-particle-matters-induce-dna-damage-and-g2-m-cell-cycle-arrest-in-human-bronchial-epithelial-beas-2b-cells
#10
Jing Wu, Yanfeng Shi, Collins Otieno Asweto, Lin Feng, Xiaozhe Yang, Yannan Zhang, Hejing Hu, Junchao Duan, Zhiwei Sun
There is compelling evidence that exposure to particulate matter (PM) is linked to lung tumorigenesis. However, there is not enough experimental evidence to support the specific mechanisms of PM2.5-induced DNA damage and cell cycle arrest in lung tumorigenesis. In this study, we investigated the toxic effects and molecular mechanisms of PM2.5 on bronchial epithelial (BEAS-2B) cells. PM2.5 exposure reduced cell viability and enhanced LDH activity. The cell growth curves of BEAS-2B cells decreased gradually with the increase in PM2...
September 18, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28920958/the-n-6-methyladenosine-m-6-a-forming-enzyme-mettl3-controls-myeloid-differentiation-of-normal-hematopoietic-and-leukemia-cells
#11
Ly P Vu, Brian F Pickering, Yuanming Cheng, Sara Zaccara, Diu Nguyen, Gerard Minuesa, Timothy Chou, Arthur Chow, Yogesh Saletore, Matthew MacKay, Jessica Schulman, Christopher Famulare, Minal Patel, Virginia M Klimek, Francine E Garrett-Bakelman, Ari Melnick, Martin Carroll, Christopher E Mason, Samie R Jaffrey, Michael G Kharas
N(6)-methyladenosine (m(6)A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m(6)A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m(6)A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28920929/structural-investigation-of-nucleophosmin-interaction-with-the-tumor-suppressor-fbw7%C3%AE
#12
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28919027/macrolactin-f-inhibits-rankl-mediated-osteoclastogenesis-by-suppressing-akt-mapk-and-nfatc1-pathways-and-promotes-osteoblastogenesis-through-a-bmp-2-smad-akt-runx2-signaling-pathway
#13
Liang Li, Mahesh Sapkota, Ming Gao, Hyukjae Choi, Yunjo Soh
The balance between bone formation and bone resorption is maintained by osteoblasts and osteoclasts. In the current study, macrolactin F (MF) was investigated for novel biological activity on the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages (BMMs). We found that RANKL-induced osteoclast formation and differentiation from BMMs was significantly inhibited by MF in a dose-dependent manner without cytotoxicity. RANKL-induced F-actin ring formation and bone resorption activity in BMMs which was attenuated by MF...
September 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28915664/morusin-inhibits-cell-proliferation-and-tumor-growth-by-down-regulating-c-myc-in-human-gastric-cancer
#14
Feng Wang, Dunke Zhang, Jingxin Mao, Xiao-Xue Ke, Rui Zhang, Chao Yin, Ning Gao, Hongjuan Cui
Morusin is a pure extract from the root bark of Morus australis (Moraceae). In recent years, morusin has been reported to exhibit anti-tumor biological activity in some types of human cancers through different mechanisms. Here, we attempted to investigate the inhibitory effect and mechanism of morusin on gastric cancer. Morusin markedly inhibited gastric cancer cell proliferation by down-regulating CDKs and Cyclins, such as CDK2, CDK4, Cyclin D1 and Cyclin E1. Additionally, morusin suppressed tumor growth in vitro and in vivo...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915620/prpf-overexpression-induces-drug-resistance-through-actin-cytoskeleton-rearrangement-and-epithelial-mesenchymal-transition
#15
Salman Ul Islam, Adeeb Shehzad, Jong Kyung Sonn, Young Sup Lee
Pre-mRNA processing factor (PRPF) 4B kinase belongs to the CDK-like kinase family, and is involved in pre-mRNA splicing, and in signal transduction. In this study, we observed that PRPF overexpression decreased the intracellular levels of reactive oxygen species, and inhibited resveratrol-induced apoptosis by activating the cell survival signaling proteins NFκB, ERK, and c-MYC in HCT116 human colon cancer cells. PRPF overexpression altered cellular morphology, and rearranged the actin cytoskeleton, by regulating the activity of Rho family proteins...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914785/hsp90%C3%AE-mediates-bmi1-expression-in-breast-cancer-stem-progenitor-cells-through-facilitating-nuclear-translocation-of-c-myc-and-ezh2
#16
Yueh-Chun Lee, Wen-Wei Chang, Yi-Ying Chen, Yu-Hung Tsai, Ying-Hsiang Chou, Hsien-Chun Tseng, Hsin-Lin Chen, Chun-Chieh Wu, Ju Chang-Chien, Hsueh-Te Lee, Huei-Fan Yang, Bing-Yen Wang
Heat shock protein 90 (Hsp90) is a molecular chaperone that facilitates the correct folding and functionality of its client protein. Numerous Hsp90-client proteins are involved in cancer development. Thus, Hsp90 inhibitors have potential applications as anti-cancer drugs. We previously discovered that Hsp90α expression increased in breast cancer stem cells (BCSCs), which can initiate tumorigenesis and metastasis and resist treatment. In the present study, we further demonstrated that 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), an inhibitor of Hsp90, could suppress the self-renewal of BCSCs by downregulating B lymphoma Mo-MLV insertion region 1 homolog (BMI1), a polycomb family member with oncogenic activity in breast cancer...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28912885/brusatol-mediated-inhibition-of-c-myc-increases-hif-1%C3%AE-degradation-and-causes-cell-death-in-colorectal-cancer-under-hypoxia
#17
Eun-Taex Oh, Chan Woo Kim, Ha Gyeong Kim, Jae-Seon Lee, Heon Joo Park
HIF-1 (hypoxia-inducible factor-1) regulates the expression of ~100 genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control. In the present study, we investigated the molecular mechanisms underlying brusatol-induced HIF-1α degradation and cell death in colorectal cancer under hypoxia (0.5% O2). Under hypoxia, pretreatment of cancer cells with brusatol increased HIF-1α degradation and cancer cell death in a dose-dependent manner...
2017: Theranostics
https://www.readbyqxmd.com/read/28910957/-effects-of-cell-cycle-regulatory-genes-on-breast-cancer-neo-adjuvant-chemotherapy-by-m-fish
#18
C Y Li, W Su, S Zhang, Y H Hu, J J Liu, J Zhang
Objective: The dysregulation of cell cycle could influence cell proliferation, differentiation and response to medicine. The purpose of this study is to explore the correlation between cell cycle regulatory genes and breast cancer neo-adjuvant chemotherapy (NAC) in patients with local advanced breast cancer, and thus to find some predictors of NAC to provide guidance for clinical treatment. Methods: Ninety five cases of local advanced breast cancer were collected, which were treated with NAC of TAC (Taxanes/Anthracycline/Cyclophosphamide) regimen...
September 12, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28903497/downregulation-of-tmem70-in-rat-liver-cells-after-hepatocarcinogen-treatment-related-to-the-warburg-effect-in-hepatocarcinogenesis-producing-gst-p-expressing-proliferative-lesions
#19
Sayaka Mizukami, Yousuke Watanabe, Kota Nakajima, Yasuko Hasegawa-Baba, Meilan Jin, Toshinori Yoshida, Makoto Shibutani
We previously observed downregulation of mitochondrial oxidative phosphorylation-related protein, TMEM70, which is suggestive of disrupted cellular senescence, in GST-P-expressing (+) proliferative lesions from early hepatocarcinogenesis stages in rats. The present study investigated the immunohistochemical relationship between TMEM70 downregulation and cellular metabolic changes in carcinogenic processes, as well as the onset of the liver cell respiratory changes after repeated hepatocarcinogen treatment in rats...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28903484/novel-role-of-fbxw7-circular-rna-in-repressing-glioma-tumorigenesis
#20
Yibing Yang, Xinya Gao, Maolei Zhang, Sheng Yan, Chengjun Sun, Feizhe Xiao, Nunu Huang, Xuesong Yang, Kun Zhao, Huangkai Zhou, Suyun Huang, Bo Xie, Nu Zhang
Background: Circular RNAs (circRNAs) are RNA transcripts that are widespread in the eukaryotic genome. Recent evidence indicates that circRNAs play important roles in tissue development, gene regulation, and carcinogenesis. However, whether circRNAs encode functional proteins remains elusive, although translation of several circRNAs was recently reported. Methods: CircRNA deep sequencing was performed by using 10 pathologically diagnosed glioblastoma samples and their paired adjacent normal brain tissues...
March 1, 2018: Journal of the National Cancer Institute
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