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https://www.readbyqxmd.com/read/29458017/synergistic-and-additive-effects-of-atra-in-combination-with-different-anti-tumor-compounds
#1
REVIEW
Eduarda Schultze, Tiago Collares, Caroline Lucas, Fabiana K Seixas
All-trans retinoic acid (ATRA), a derivative of vitamin A, has been shown to potentiate cancer chemotherapy due to its ability to induce signals for cell differentiation or death, and inhibit cell proliferation. The combination of ATRA with taxoids, kinase inhibitors, natural compounds, retinoids, ER or HER2 inhibitors, chemotherapeutic drugs, proteasome inhibitors and nanoformulations of tretinoin have demonstrated additive or synergistic effects in anti-cancer activities. The mechanisms by which the compounds exert their synergistic effects depend on the tumor and the cell type...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29454094/synergistic-activity-of-bet-inhibitor-bi-894999-with-plk-inhibitor-volasertib-in-aml-in-vitro-and-in-vivo
#2
Ulrike Tontsch-Grunt, Dorothea Rudolph, Irene Waizenegger, Anke Baum, Daniel Gerlach, Harald Engelhardt, Melanie Wurm, Fabio Savarese, Norbert Schweifer, Norbert Kraut
Interactions between a new potent Bromodomain and extraterminal domain (BET) inhibitor BI 894999 and the polo-like kinase (PLK) inhibitor volasertib were studied in acute myeloid leukemia cell lines in vitro and in vivo. We provide data for the distinct mechanisms of action of these two compounds with a potential utility in AML based on gene expression, cell cycle profile and modulation of PD biomarkers such as MYC and HEXIM1. In contrast to BI 894999, volasertib treatment neither affects MYC nor HEXIM1 expression, but augments and prolongs the decrease of MYC expression caused by BI 894999 treatment...
February 14, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29449541/long-noncoding-rna-meg3-suppresses-liver-cancer-cells-growth-through-inhibiting-%C3%AE-catenin-by-activating-pkm2-and-inactivating-pten
#3
Qidi Zheng, Zhuojia Lin, Jie Xu, Yanan Lu, Qiuyu Meng, Chen Wang, Yuxin Yang, Xiaoru Xin, Xiaonan Li, Hu Pu, Xin Gui, Tianming Li, Wujun Xiong, Dongdong Lu
Maternally expressed gene 3 (MEG3) encodes an lncRNA which is suggested to function as a tumor suppressor and has been showed to involve in a variety of cancers. Herein, our findings demonstrate that MEG3 inhibits the malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, MEG3 promotes the expression and maturition of miR122 which targets PKM2. Therefore, MEG3 decreases the expression and nuclear location of PKM2 dependent on miR122. Furthermore, MEG3 also inhibits CyclinD1 and C-Myc via PKM2 in liver cancer cells...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449271/targeted-therapies-for-targeted-populations-anti-egfr-treatment-for-egfr-amplified-gastroesophageal-adenocarcinoma
#4
Steven B Maron, Lindsay Alpert, Heewon A Kwak, Samantha Lomnicki, Leah Chase, David Xu, Emily O'Day, Rebecca J Nagy, Richard B Lanman, Fabiola Cecchi, Todd Hembrough, Alexa Schrock, John Hart, Shu-Yuan Xiao, Namrata Setia, Daniel V T Catenacci
Previous anti-EGFR trials in unselected gastroesophageal adenocarcinoma (GEA) patients were resoundingly negative. We identified EGFR amplification in 5% (19/363) of patients at the University of Chicago, including 6% (8/140) who were prospectively screened with intention-to-treat using anti-EGFR therapy. Seven pts received >1 dose of treatment: three first line FOLFOX plus ABT-806, one second line FOLFIRI plus cetuximab, and three third/fourth line cetuximab alone. Treatment achieved objective response in 58% (4/7) and disease control in 100% (7/7) with a median progression-free survival of 10 months...
February 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29449053/genetic-and-epigenetic-alterations-in-the-tumour-tumour-margins-and-normal-buccal-mucosa-of-patients-with-oral-cancer
#5
N Eljabo, N Nikolic, J Carkic, D Jelovac, M Lazarevic, N Tanic, J Milasin
Despite adequate surgical resection, oral squamous cell carcinoma (OSCC) shows a high rate of recurrence and metastasis, which could be explained by the presence of molecular alterations in seemingly normal tumour margins and the entire oral mucosa. The aims of this study were (1) to assess the presence of gene amplification (c-Myc and HER2) and promoter methylation (p14 and p16) in the tumours, tumour margins, and unaffected oral mucosa of 40 OSCC patients, and (2) to evaluate the possibility of using these alterations as prognostic markers...
February 12, 2018: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/29445860/origin-and-initiation-mechanisms-of-neuroblastoma
#6
REVIEW
Shoma Tsubota, Kenji Kadomatsu
Neuroblastoma is an embryonal malignancy that affects normal development of the adrenal medulla and paravertebral sympathetic ganglia in early childhood. Extensive studies have revealed the molecular characteristics of human neuroblastomas, including abnormalities at genome, epigenome and transcriptome levels. However, neuroblastoma initiation mechanisms and even its origin are long-standing mysteries. In this review article, we summarize the current knowledge about normal development of putative neuroblastoma sources, namely sympathoadrenal lineage of neural crest cells and Schwann cell precursors that were recently identified as the source of adrenal chromaffin cells...
February 14, 2018: Cell and Tissue Research
https://www.readbyqxmd.com/read/29445227/novel-ubiquitin-independent-nucleolar-c-myc-degradation-pathway-mediated-by-antizyme-2
#7
Noriyuki Murai, Yasuko Murakami, Ayasa Tajima, Senya Matsufuji
The proto-oncogene c-Myc encodes a short-lived protein c-Myc that regulates various cellular processes including cell growth, differentiation and apoptosis. Degradation of c-Myc is catalyzed by the proteasome and requires phosphorylation of Thr-58 for ubiquitination by E3 ubiquitin ligase, Fbxw7/ FBW7. Here we show that a polyamine regulatory protein, antizyme 2 (AZ2), interacts with c-Myc in the nucleus and nucleolus, to accelerate proteasome-mediated c-Myc degradation without ubiquitination or Thr-58 phosphorylation...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29445162/mycn-drives-glutaminolysis-in-neuroblastoma-and-confers-sensitivity-to-an-ros-augmenting-agent
#8
Tingting Wang, Lingling Liu, Xuyong Chen, Yuqing Shen, Gaojian Lian, Nilay Shah, Andrew M Davidoff, Jun Yang, Ruoning Wang
Heightened aerobic glycolysis and glutaminolysis are characteristic metabolic phenotypes in cancer cells. Neuroblastoma (NBL), a devastating pediatric cancer, is featured by frequent genomic amplification of MYCN, a member of the Myc oncogene family that is primarily expressed in the early stage of embryonic development and required for neural crest development. Here we report that an enriched glutaminolysis gene signature is associated with MYCN amplification in children with NBL. The partial knockdown of MYCN suppresses glutaminolysis in NBL cells...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445150/loss-of-ndrg2-in-liver-microenvironment-inhibits-cancer-liver-metastasis-by-regulating-tumor-associate-macrophages-polarization
#9
Mengyang Li, Xiaofeng Lai, Ying Zhao, Yuan Zhang, Minghui Li, Danxiu Li, Jing Kong, Yong Zhang, Pengyu Jing, Huichen Li, Hongyan Qin, Liangliang Shen, Libo Yao, Jipeng Li, Kefeng Dou, Jian Zhang
The liver is the predominant metastatic site for several types of malignancies. Tumor-associated macrophages (TAMs) in the liver play crucial roles in the metastasis process. Shifting tumor-promoting M2-like TAMs toward the M1-like phenotype, which exerts tumor suppressor functions via phagocytosis and the secretion of inhibitory factors, may be a potential therapeutic strategy for liver cancer metastasis treatment.We first cloned NDRG2 (N-myc downstream-regulated gene 2) and verified its tumor suppressor role in multiple solid tumors, including colorectal cancer and hepatocellular carcinoma...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445127/cripto-1-contributes-to-stemness-in-hepatocellular-carcinoma-by-stabilizing-dishevelled-3-and-activating-wnt-%C3%AE-catenin-pathway
#10
Regina Cheuk-Lam Lo, Carmen Oi-Ning Leung, Kristy Kwan-Shuen Chan, Daniel Wai-Hung Ho, Chun-Ming Wong, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness...
February 14, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29445088/cancer-cell-responses-to-hsp70-inhibitor-jg-98-comparison-with-hsp90-inhibitors-and-finding-synergistic-drug-combinations
#11
Julia A Yaglom, Yongmei Wang, Amy Li, Zhenghu Li, Stephano Monti, Ilya Alexandrov, Xiongbin Lu, Michael Y Sherman
Hsp70 is a promising anti-cancer target. Our JG-98 series of Hsp70 inhibitors show anti-cancer activities affecting both cancer cells and tumor-associated macrophages. They disrupt Hsp70 interaction with a co-chaperone Bag3 and affect signaling pathways important for cancer development. Due to a prior report that depletion of Hsp70 causes similar responses as depletion of Hsp90, interest to Hsp70 inhibitors as drug prototypes is hampered by potential similarity of their effects to effects of Hsp90 inhibitors...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29442041/the-interaction-between-atrip-and-mcm-complex-is-essential-for-atrip-chromatin-loading-and-its-phosphorylation-in-mantle-cell-lymphoma-cells
#12
Yuling Nie, Tao Lang
AIM: The ATR-interacting protein (ATRIP) is responsible for the recognition of DNA damage-induced structure and regulation of cellular responses to DNA damage and replication stress. The purpose of our study was to identify the underlying mechanism with respect to chromatin loading and phosphorylation of ATRIP in mantle cell lymphoma (MCL). METHODS: JeKo cells were used in our study. Differently tagged ATRIP (Myc-, hemaglutinin (HA) or Flag) and minichromosome maintenance (MCM) complex (MCM2, MCM3, MCM5, and MCM6) were transfected into 293T cells...
November 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29442023/mir-122-5p-inhibits-tumor-cell-proliferation-and-induces-apoptosis-by-targeting-myc-in-gastric-cancer-cells
#13
Z J Pei, Z G Zhang, A X Hu, F Yang, Y Gai
MicroRNAs (miRNAs) play crucial roles in the development and progression of human cancers, including Gastric cancer (GC). In this study, we investigated the correlation of miR-122-5p expression with cell proliferation, and apoptosis in a GC cell line. GC cells SCG 7901 were transfected with control, miR-122-5p or miR-122-5p inhibitor and MTT assay, western blot, and BrdU staining were respectively used to investigate the effect of miR-122-5p on GC cell cycle. The overexpression of miR-122-5p could reduce cell proliferation in SCG7901 cells, and BrdU staining finally verified miR-122-5p induced cell growth arrest by upregulation p27 expression in SCG7901cells...
June 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441950/long-noncoding-rna-ccal-promotes-gastric-cancer-cell-proliferation-and-migration-in-a-myc-dependent-way
#14
Yuqiang Shan, Wencheng Kong, Akao Zhu, Panpan Yu, Qi Xie, Sixin Zheng, Huicheng Jin
AIMS: Long non-coding RNAs (lncRNAs) play key roles in cancers, yet their potential molecular mechanisms are not well understood. The objective of this study is to examine the expression, biological functions and mechanism of lncRNA CCAL in gastric cancer (GC). METHODS: MTT and Colony formation assay were used to detect cell proliferation and the colony formation ability of gastric cancer cells. Wound healing, Migration, and invasion assay were respectively used to explore the migration, and invasion in gastric cancer cell lines...
January 2, 2018: Die Pharmazie
https://www.readbyqxmd.com/read/29441887/effect-of-npm1-type-b-mutation-on-the-proliferation-invasion-and-chemosensitivity-of-thp-1-leukemia-cells
#15
Jie Peng, Bin Fu, Gan Fu, Xielan Zhao, Xiaolin Li, Fangping Chen
Acute myeloid leukemia (AML) is the most malignant myeloid disorder in adults. AML with mutated nucleophosmin (NPM1) is regarded as an independent leukemia subtype. According to previous studies, the role of NPM1 gene A mutation in AML has been well established; however, another major type, NPM1 gene B type mutation (NPM1 MutB) has been rarely reported. In the present study, we found that overexpression of NPM1 MutB enhanced the proliferation and invasion of THP-1 AML cells through the regulation of TIMP-2, MMP-2, Ang-1, c-myc and CCND1; led to no significant change of apoptosis rate with the absence of chemotherapy agents, while enhanced the chemosensitivity of THP-1 AML cells to chemotherapy agents DNR and Ara-C through the regulation of Bax, Bcl-2 and caspase-3...
October 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29441884/mir-204-14-3-3%C3%AE-axis-regulates-osteosarcoma-cell-proliferation-through-sata3-pathway
#16
Ruibo Zhao, Hongbo He, Yong Zhu, Jun Wan, Yusheng Li, Shuguang Gao, Can Zhang
Hyperproliferation of cells is a major problem is osteosarcoma (OS). So, further elucidation of the molecular mechanisms underlying hyperproliferation of OS is needed. Western blots results showed that 14-3-3ζ protein was upregulated in OS cell lines; 14-3-3ζ knockdown significantly suppressed OS cell proliferation, as well as the protein levels of p-STAT3, c-Myc and Cyclin D1. MicroRNA-204 (miR-204) has been regarded as an essential regulator in cancer carcinogenesis, including OS. Here, we revealed that miR-204 directly targets the 3'UTR of 14-3-3ζ to inhibit its expression, thus to suppress 14-3-3ζ -induced OS cell hyperproliferation...
October 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29440228/ampk-promotes-survival-of-c-myc-positive-melanoma-cells-by-suppressing-oxidative-stress
#17
Alain Kfoury, Marzia Armaro, Caterina Collodet, Jessica Sordet-Dessimoz, Maria Pilar Giner, Stefan Christen, Sofia Moco, Marion Leleu, Laurence de Leval, Ute Koch, Andreas Trumpp, Kei Sakamoto, Friedrich Beermann, Freddy Radtke
Although c-Myc is essential for melanocyte development, its role in cutaneous melanoma, the most aggressive skin cancer, is only partly understood. Here we used the Nras Q61K INK4a -/- mouse melanoma model to show that c-Myc is essential for tumor initiation, maintenance, and metastasis. c-Myc-expressing melanoma cells were preferentially found at metastatic sites, correlated with increased tumor aggressiveness and high tumor initiation potential. Abrogation of c-Myc caused apoptosis in primary murine and human melanoma cells...
February 12, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29438089/stable-accumulation-of-photosystem-ii-requires-one-helix-protein1-ohp1-of-the-light-harvesting-like-family
#18
Fumiyoshi Myouga, Kaori Takahashi, Ryouichi Tanaka, Noriko Nagata, Anett Z Kiss, Christiane Funk, Yuko Nomura, Hirofumi Nakagami, Stefan Jansson, Kazuo Shinozaki
The cellular functions of two Arabidopsis one-helix proteins, OHP1 and OHP2 [also named light-harvesting-like Lil2 and Lil6, respectively, because they have sequence similarity to light-harvesting chlorophyll a/b-binding (LHC) proteins] remain unclear. Tagged null mutants of OHP1 and OHP2 (ohp1 and ohp2) showed stunted growth with pale-green leaves on agar plates, and these mutants were unable to grow on soil. Leaf chlorophyll fluorescence and the composition of thylakoid membrane proteins revealed that ohp1 deletion significantly affected photosystem II (PSII) core protein function and led to reduced levels of PSI core proteins; however, it did not affect LHC accumulation...
February 1, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29436642/synergistic-anticancer-effects-of-ruxolitinib-and-calcitriol-in-estrogen-receptor%C3%A2-positive-human-epidermal-growth-factor-receptor-2%C3%A2-positive-breast-cancer-cells
#19
Seung Taek Lim, Ye Won Jeon, Hongki Gwak, Se Young Kim, Young Jin Suh
The Janus kinase (JAK)1 and JAK2 inhibitor, ruxolitinib, and the active form of vitamin D (calcitriol) were previously reported to possess anticancer effects in breast cancer. The present study investigated the combined effects of ruxolitinib and calcitriol on an estrogen receptor (ER)‑positive, human epidermal growth factor receptor 2 (HER2)‑positive, breast cancer cell line. The ER and HER2‑positive MCF7‑HER18 breast cancer cell line was used to investigate the combination effect of ruxolitinib and calcitriol...
February 8, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436633/microarray-analysis-for-the-identification-of-specific-proteins-and-functional-modules-involved-in-the-process-of-hepatocellular-carcinoma-originating-from-cirrhotic-liver
#20
Wufeng Fan, Guangming Ye
In order to identify the potential pathogenesis of hepatocellular carcinoma (HCC) developing from cirrhosis, a microarray‑based transcriptome profile was analyzed. The GSE63898 expression profile was downloaded from the Gene Expression Omnibus database, which included data from 228 HCC tissue samples and 168 cirrhotic tissue samples. The Robust Multi‑array Average in the Affy package of R was used for raw data processing and Student's t‑test was used to screen differentially expressed genes (DEGs). An enrichment analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery online tool, and the protein‑protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape...
February 2, 2018: Molecular Medicine Reports
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