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https://www.readbyqxmd.com/read/29658601/silencing-of-casein-kinase-2-inhibits-pkc%C3%A2-induced-cell-invasion-by-targeting-mmp%C3%A2-9-in-mcf%C3%A2-7-cells
#1
Jeong-Mi Kim, Eun-Mi Noh, Hyun-Kyung Song, Yong-Ouk You, Sung Hoo Jung, Jong-Suk Kim, Kang-Beom Kwon, Young-Rae Lee, Hyun Jo Youn
Casein kinase 2 (CK2) is a serine/threonine protein kinase that has been considered to represent an important factor in mammary tumorigenesis. Increased expression of matrix metalloproteinase‑9 (MMP‑9) via nuclear factor‑κB (NF‑κB) activation has been demonstrated to promote breast cancer cell invasion. In the present study, the involvement of CK2 in protein kinase C (PKC) induced cell invasion in MCF‑7 breast cancer cells was investigated as well as the underlying molecular mechanisms. The mRNA and protein levels of MMP‑9 in MCF‑7 cells were investigated using reverse transcription‑quantitative polymerase chain reaction, western blot analyses and a zymography assay...
April 13, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29619377/roles-of-nucks1-in-diseases-susceptibility-potential-biomarker-and-regulatory-mechanisms
#2
REVIEW
Pengru Huang, Yujie Cai, Bin Zhao, Lili Cui
Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) is a 27 kD chromosomal, highly conserved, and vertebrate-specific protein. NUCKS1 gene encodes a nuclear protein and the conserved regions of NUCKS1 contain several consensus phosphorylation sites for casein kinase II (CK2) and cyclin-dependent kinases (Cdk) and a basic DNA-binding domain. NUCKS1 is similar to the high mobility group (HMG) family which dominates chromatin remodeling and regulates gene transcription. Meanwhile, NUCKS1 is a RAD51 associated protein 1 (RAD51AP1) paralog that is significant for homologous recombination (HR) and genome stability and also a transcriptional regulator of the insulin signaling components...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29606502/a-positive-feed-forward-loop-between-lncrna-cytor-and-wnt-%C3%AE-catenin-signaling-promotes-metastasis-of-colon-cancer
#3
Ben Yue, Chenchen Liu, Huimin Sun, Mengru Liu, Chenlong Song, Ran Cui, Shenglong Qiu, Ming Zhong
We previously demonstrated that long non-coding RNA cytoskeleton regulator RNA (CYTOR), also known as Linc00152, was significantly overexpressed in colon cancer and conferred resistance to oxaliplatin-induced apoptosis. At the same time, elevated CYTOR expression was also reported in gastric cancer and exerted influences on epithelial-mesenchymal transition (EMT) markers. However, the precise mechanism by which CYTOR promotes the EMT phenotype and cancer metastasis remains poorly understood. Here, we showed that loss of epithelial characteristics and simultaneous gain of mesenchymal features correlated with CYTOR expression...
March 6, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29593330/ck1%C3%AE-suppresses-lung-tumour-growth-by-stabilizing-pten-and-inducing-autophagy
#4
Junchao Cai, Rong Li, Xiaonan Xu, Le Zhang, Rong Lian, Lishan Fang, Yongbo Huang, Xianming Feng, Ximeng Liu, Xu Li, Xun Zhu, Heng Zhang, Jueheng Wu, Musheng Zeng, Erwei Song, Yukai He, Yuxin Yin, Jun Li, Mengfeng Li
The contribution of autophagy to cancer development remains controversial, largely owing to the fact that autophagy can be tumour suppressive or oncogenic in different biological contexts. Here, we show that in non-small-cell lung cancer (NSCLC), casein kinase 1 alpha 1 (CK1α) suppresses tumour growth by functioning as an autophagy inducer to activate an autophagy-regulating, tumour-suppressive PTEN/AKT/FOXO3a/Atg7 axis. Specifically, CK1α bound the C-terminal tail of PTEN and enhanced both PTEN stability and activity by competitively antagonizing NEDD4-1-induced PTEN polyubiquitination and abrogating PTEN phosphorylation, thereby inhibiting AKT activity and activating FOXO3a-induced transcription of Atg7...
April 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29581866/calpastatin-phosphorylation-regulates-radiation-induced-calpain-activity-in-glioblastoma
#5
Emily A Bassett, Kamalakannan Palanichamy, Mitchell Pearson, Joseph P McElroy, Saikh Jaharul Haque, Erica Hlavin Bell, Arnab Chakravarti
Glioblastoma (GBM) is an aggressive, malignant brain tumor that inevitably develops resistance to conventional chemotherapy and radiation treatments. In order to identify signaling pathways involved in the development of radiation resistance, we performed mass spectrometry-based phospho-proteomic profiling of GBM cell lines and normal human astrocytes before and after radiation treatment. We found radiation induced phosphorylation of a number of proteins including calpastatin, specifically in GBM stem cells (GSCs)...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29564122/potential-signaling-pathways-as-therapeutic-targets-for-overcoming-chemoresistance-in-mucinous-ovarian-cancer
#6
Emiko Niiro, Sachiko Morioka, Kana Iwai, Yuki Yamada, Kenji Ogawa, Naoki Kawahara, Hiroshi Kobayashi
Cases of mucinous ovarian cancer are predominantly resistant to chemotherapies. The present review summarizes current knowledge of the therapeutic potential of targeting the Wingless (WNT) pathway, with particular emphasis on preclinical and clinical studies, for improving the chemoresistance and treatment of mucinous ovarian cancer. A review was conducted of English language literature published between January 2000 and October 2017 that concerned potential signaling pathways associated with the chemoresistance of mucinous ovarian cancer...
March 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29549930/pyrvinium-sensitizes-clear-cell-renal-cell-carcinoma-response-to-chemotherapy-via-casein-kinase-1%C3%AE-dependent-inhibition-of-wnt-%C3%AE-catenin
#7
Long Cui, Juan Zhao, Jingjing Liu
BACKGROUND: Aberrant Wnt/β-catenin activation has been shown to play essential roles in cancer, including renal cell carcinoma (RCC). In this work, we demonstrate that Wnt/β-catenin inhibition by a Food and Drug Administration-approved drug, pyrvinium, effectively targets clear cell RCC and enhances chemotherapy agent's efficacy. MATERIALS AND METHODS: We performed in vitro cell culture assays and in vivo xenograft tumor model to evaluate the effects of pyrvinium alone and its combination with paclitaxel, and analyzed the underlying mechanism(s) of pyrvinium's action in RCC...
March 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29547721/the-dietary-supplement-chondroitin-4-sulfate-exhibits-oncogene-specific-pro-tumor-effects-on-braf-v600e-melanoma-cells
#8
Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29527958/molecular-dynamics-simulations-reveal-structural-insights-into-inhibitor-binding-modes-and-mechanism-of-casein-kinase-ii-inhibitors
#9
Zaheer Ul-Haq, Sajda Ashraf, Majdi M Bkhaitan
Casein kinase-II, a member of protein kinase family, plays significant role in different cellular processes such as cell growth, differentiation, proliferation, gene expression and embryogenesis. Being a potent suppressor of apoptosis, it serves as a significant link for its association with various types of malignancies such as colorectal and breast cancer. To overcome its pathological role in various cancerous diseases, CK-II procures great consideration as a therapeutic target. This study aimed at understanding the binding mechanism and structural properties of benzimidazole derivatives by utilizing various computational tools including docking simulation, 3-dimensional quantitative structure activity relationships and molecular dynamic simulation...
March 12, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29511364/viola-yedoensis-suppresses-cell-invasion-by-targeting-the-protease-and-nf-%C3%AE%C2%BAb-activities-in-a549-and-lewis-lung-carcinoma-cells
#10
She-Fang Huang, Shu-Chen Chu, Yi-Hsien Hsieh, Pei-Ni Chen, Yih-Shou Hsieh
Cancer metastasis is a vital trait in malignancies with complicated early diagnosis and therapeutic management. Therefore, the development of new remedies and the utilization of natural medicines that target metastasis are of great interest and have been studied extensively. Chinese medicinal herbs have various anti-carcinogenesis properties; however, the in vitro effect and mechanism of Viola yedoensis on cancer cell metastasis remains poorly understood. V. yedoensis extracts (VYE) can suppress the invasion of a highly metastatic human lung cancer cell line, A549 cells...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29475723/umbralisib-a-novel-pi3k%C3%AE-and-casein-kinase-1%C3%AE%C2%B5-inhibitor-in-relapsed-or-refractory-chronic-lymphocytic-leukaemia-and-lymphoma-an-open-label-phase-1-dose-escalation-first-in-human-study
#11
Howard A Burris, Ian W Flinn, Manish R Patel, Timothy S Fenske, Changchun Deng, Danielle M Brander, Martin Gutierrez, James H Essell, John G Kuhn, Hari P Miskin, Peter Sportelli, Michael S Weiss, Swaroop Vakkalanka, Michael R Savona, Owen A O'Connor
BACKGROUND: Umbralisib (TGR-1202) is a novel next-generation inhibitor of phosphatidylinositol 3-kinase (PI3K) isoform p110δ (PI3Kδ), which is structurally distinct from other PI3Kδ inhibitors and shows improved isoform selectivity. Umbralisib also uniquely inhibits casein kinase-1ε, a major regulator of protein translation. The aim of this first-in-human phase 1 study was to establish the safety and preliminary activity profile of umbralisib in patients with haematological malignancies...
February 20, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29462394/nondysplastic-ulcerative-colitis-has-high-levels-of-the-homologous-recombination-repair-protein-nucks1-and-low-levels-of-the-dna-damage-marker-gamma-h2ax
#12
Paula M De Angelis, Aasa R Schjølberg, Juliana B Hughes, Henrik S Huitfeldt, Solveig Norheim Andersen, Anne Carine Østvold
Background: The colon and rectum are continuously exposed to oxidative stress that generates reactive oxygen species, which are a major cause of DNA double-strand breaks (DSB). Furthermore, chronic inflammatory diseases such as ulcerative colitis (UC) are characterized by an excess of reactive nitrogen species that can also lead to DNA double-strand breakage and genomic instability. We investigated the expression of the nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) protein in UC and sporadic colorectal cancer (CRC) due to its involvement in both DNA double-strand break repair and inflammatory signaling...
February 15, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29423390/dual-effects-of-high-protein-diet-on-mouse-skin-and-colonic-inflammation
#13
Xuelei Cui, Eunjung Kim
Chronic inflammation is a major etiology of cancer. Accumulating epidemiological and experimental evidences suggest that intake of high protein diet (HPD) is associated with colitis-associated colon cancer, however, most of the studies were confined in colon. Systemic influence of HPD on inflammation indices in different tissues of an organism has never been studied. We therefore investigated the effect of HPD on mouse skin and colonic inflammation using the well characterized inflammation induction protocol in both tissues (12- O -tetradecanoylphorbol-13-acetate [TPA] for skin and dextran sodium sulfate [DSS] for colon)...
January 2018: Clinical Nutrition Research
https://www.readbyqxmd.com/read/29413610/genipin-stabilized-caseinate-chitosan-nanoparticles-for-enhanced-stability-and-anti-cancer-activity-of-curcumin
#14
Muhamad Alif Razi, Rie Wakabayashi, Yoshiro Tahara, Masahiro Goto, Noriho Kamiya
Nanoparticles formed by the assembly of protein and polysaccharides are of great interest for the delivery of hydrophobic molecules. Herein, the formation of genipin-crosslinked nanoparticles from caseinate (CS) and chitosan (CH) is reported for the delivery of curcumin, a polyphenolic compound from turmeric, to cells. Genipin-crosslinked CS-CH nanoparticles (G-CCNPs) having a diameter of ∼250 nm and a low polydispersity index showed excellent stability over a wide pH range, as indicated by dynamic light scattering and transmission electron microscopic measurements...
January 31, 2018: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29384474/targeting-posttranslational-modifications-of-riok1-inhibits-the-progression-of-colorectal-and-gastric-cancers
#15
Xuehui Hong, He Huang, Xingfeng Qiu, Zhijie Ding, Xing Feng, Yuekun Zhu, Huiqin Zhuo, Jingjing Hou, Jiabao Zhao, Wangyu Cai, Ruihua Sha, Xinya Hong, Yongxiang Li, Hongjiang Song, Zhiyong Zhang
RIOK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that RIOK1 is methylated at K411 by SETD7 methyltransferase and that lysine-specific demethylase 1 (LSD1) reverses its methylation. The mutated RIOK1 (K411R) that cannot be methylated exhibits a longer half-life than does the methylated RIOK1. FBXO6 specifically interacts with K411-methylated RIOK1 through its FBA domain to induce RIOK1 ubiquitination. Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1...
January 31, 2018: ELife
https://www.readbyqxmd.com/read/29382046/how-do-we-study-the-dynamic-structure-of-unstructured-proteins-a-case-study-on-nopp140-as-an-example-of-a-large-intrinsically-disordered-protein
#16
REVIEW
Jung-Hyun Na, Won-Kyu Lee, Yeon Gyu Yu
Intrinsically disordered proteins (IDPs) represent approximately 30% of the human genome and play key roles in cell proliferation and cellular signaling by modulating the function of target proteins via protein-protein interactions. In addition, IDPs are involved in various human disorders, such as cancer, neurodegenerative diseases, and amyloidosis. To understand the underlying molecular mechanism of IDPs, it is important to study their structural features during their interactions with target proteins. However, conventional biochemical and biophysical methods for analyzing proteins, such as X-ray crystallography, have difficulty in characterizing the features of IDPs because they lack an ordered three-dimensional structure...
January 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29376765/phytosomal-bilayer-enveloped-casein-micelles-for-codelivery-of-monascus-yellow-pigments-and-resveratrol-to-breast-cancer
#17
Shaymaa W El-Far, Maged W Helmy, Sherine N Khattab, Adnan A Bekhit, Ahmed A Hussein, Ahmed O Elzoghby
AIM: Multireservoir nanocarriers were fabricated for delivering antineoplastic drug cocktail from herbal and fungal origin. Monascus yellow pigments (MYPs), monascin and ankaflavin, were isolated from red-mold rice, and incorporated within casein micelles (CAS MCs) along with the herbal drug, resveratrol (RSV). Both drugs (MYPs and RSV) were simultaneously incorporated into the hydrophobic core of CAS MCs. Alternatively, MYPs-loaded CAS MCs were enveloped within RSV-phytosomal bilayer elaborating multireservoir nanocarriers...
January 29, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29373552/self-assembled-supramolecular-nanoparticles-improve-the-cytotoxic-efficacy-of-ck2-inhibitor-thn7
#18
Abdelhamid Nacereddine, Andre Bollacke, Eszter Róka, Christelle Marminon, Zouhair Bouaziz, Ferenc Fenyvesi, Ildikó Katalin Bácskay, Joachim Jose, Florent Perret, Marc Le Borgne
Since the approval of imatinib in 2001, kinase inhibitors have revolutionized cancer therapies. Inside this family of phosphotransferases, casein kinase 2 (CK2) is of great interest and numerous scaffolds have been investigated to design CK2 inhibitors. Recently, functionalized indeno[1,2-b]indoles have been revealed to have high potency against human cancer cell lines such as MCF-7 breast carcinoma and A-427 lung carcinoma. 4-Methoxy-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (THN7), identified as a potent inhibitor of CK2 (IC50 = 71 nM), was selected for an encapsulation study in order to evaluate its antiproliferative activity as THN7-loaded cyclodextrin nanoparticles...
January 26, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29356905/actinidia-callosa-var-callosa-suppresses-metastatic-potential-of-human-hepatoma-cell-sk-hep1-by-inhibiting-matrix-metalloproteinase-2-through-pi3k-akt-and-mapk-signaling-pathways
#19
Jeng-Shyan Deng, Jui-Shu Chang, Jung-Chun Liao, Wei Chao, Ming-Ming Lee, Chien-Hua Cheng, Guan-Jhong Huang
BACKGROUND: Cancer cell metastasis involving multi-step procedures and cytophysiological property changes may make difficult in the clinical management and death rate increasing. RESULTS: In this study, we first observed that ethyl acetate fraction of Actinidia callosa var. callosa (EAAC) carry out a dose-dependent inhibitory effect without cytotoxicity on the mobility and invasion of highly metastatic SK-Hep1 cells. To investigate the EAAC in cancer metastasis, SK-Hep1 cells were treated with EAAC at various concentrations and then subjected to gelatin zymography, casein zymography and western blot to study the impacts of EAAC on metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1/2 (TIMP-1/2), respectively...
January 22, 2018: Botanical Studies (Taipei, Taiwan)
https://www.readbyqxmd.com/read/29289448/development-of-dual-casein-kinase-1%C3%AE-1%C3%AE%C2%B5-ck1%C3%AE-%C3%AE%C2%B5-inhibitors-for-treatment-of-breast-cancer
#20
Andrii Monastyrskyi, Napon Nilchan, Victor Quereda, Yoshihiko Noguchi, Claudia Ruiz, Wayne Grant, Michael Cameron, Derek Duckett, William Roush
Casein kinase 1δ/ε have been identified as promising therapeutic target for oncology application, including breast and brain cancer. Here, we described our continued efforts in optimization of a lead series of purine scaffold inhibitors that led to identification of two new CK1δ/ε inhibitors 17 and 28 displaying low nanomolar values in antiproliferative assays against the human MDA-MB-231 triple negative breast cancer cell line and have physical, in vitro and in vivo pharmacokinetic properties suitable for use in proof of principle animal xenograft studies against human cancers...
February 1, 2018: Bioorganic & Medicinal Chemistry
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