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https://www.readbyqxmd.com/read/28288821/reversal-of-cisplatin-resistance-in-human-gastric-cancer-cells-by-a-wogonin-conjugated-pt-iv-prodrug-via-attenuating-casein-kinase-2-mediated-nuclear-factor-%C3%AE%C2%BAb-pathways
#1
Feihong Chen, Xiaodong Qin, Gang Xu, Shaohua Gou, Xiufeng Jin
Pt(IV) prodrugs, with two additional coordination sites in contrast to Pt(II) drugs, have been actively studied nowadays, for they can perform well in enhancing the accumulation and retention of the corresponding Pt(II) drugs in cancer cells. Our designed Pt(II) drug, DN604, was recently found to exhibit significant anticancer activity and low toxicity. While, wogonin, a naturally O-methylated flavones, has been widely investigated for its tumor therapeutic potential. Thus, two Pt(IV)-based prodrugs were derived by addition of a wogonin unit to the axial position of DN604 and its analogue DN603 via a linker group...
March 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28236970/ck1-in-developmental-signaling-hedgehog-and-wnt
#2
Jin Jiang
The casein kinase 1 (CK1) family of serine (Ser)/threonine (Thr) protein kinases participates in a myriad of cellular processes including developmental signaling. Hedgehog (Hh) and Wnt pathways are two major and evolutionarily conserved signaling pathways that control embryonic development and adult tissue homeostasis. Deregulation of these pathways leads to many human disorders including birth defects and cancer. Here, I review the role of CK1 in the regulation of Hh and Wnt signal transduction cascades from the membrane reception systems to the transcriptional effectors...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28230762/the-development-of-ck2-inhibitors-from-traditional-pharmacology-to-in-silico-rational-drug-design
#3
REVIEW
Giorgio Cozza
Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by "trial and error testing". In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range...
February 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28196025/autophagy-induced-by-cx-4945-a-casein-kinase-2-inhibitor-enhances-apoptosis-in-pancreatic-cancer-cell-lines
#4
Dae Wook Hwang, Kwang Sup So, Song Cheol Kim, Kwang-Min Park, Young-Joo Lee, Sun-Whe Kim, Chang-Min Choi, Jin Kyung Rho, Yun Jung Choi, Jae Cheol Lee
OBJECTIVES: Pancreatic cancer is the most lethal malignancy with only a few effective chemotherapeutic drugs. Because the inhibition of casein kinase 2 (CK2) has been reported as a novel therapeutic strategy for many cancers, we investigated the effects of CK2 inhibitors in pancreatic cancer cell lines. METHODS: The BxPC3, 8902, MIA PaCa-2 human pancreatic cancer cell lines, and CX-4945, a novel CK2 inhibitor, were used. Autophagy was analyzed by acridine orange staining, fluorescence microscope detection of punctuate patterns of GFP-tagged LC3 and immunoblotting for LC3...
April 2017: Pancreas
https://www.readbyqxmd.com/read/28178627/fundamentals-of-protein-and-cell-interactions-in-biomaterials
#5
REVIEW
Hammed Tanimowo Aiyelabegan, Esmaeil Sadroddiny
The extracellular matrix (ECM) is an active and complex microenvironment with outstanding biomechanical, biophysical, and biochemical characteristics, which can indirectly or directly controls cell adhesion, migration, proliferation, and differentiation, as well as partaking in regeneration and homeostasis of organs and tissues. The ECM has captivated a great deal of attention with the rapid progress of tissue engineering (TE) in the field of regenerative medicine (RM). Approaches to TE, RM and cancer therapy center on the necessity to deliver cell signals to direct cell proliferation and differentiation...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28152014/apigenin-selective-ck2-inhibitor-increases-ikaros-expression-and-improves-t-cell-homeostasis-and-function-in-murine-pancreatic-cancer
#6
Nadine Nelson, Karoly Szekeres, Cristina Iclozan, Ivannie Ortiz Rivera, Andrew McGill, Gbemisola Johnson, Onyekachi Nwogu, Tomar Ghansah
Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model...
2017: PloS One
https://www.readbyqxmd.com/read/28125685/lack-of-casein-kinase-1-delta-promotes-genomic-instability-the-accumulation-of-dna-damage-and-down-regulation-of-checkpoint-kinase-1
#7
Yoshimi Endo Greer, Bo Gao, Yingzi Yang, Andre Nussenzweig, Jeffrey S Rubin
Casein kinase 1 delta (CK1δ) is a conserved serine/threonine protein kinase that regulates diverse cellular processes. Mice lacking CK1δ have a perinatal lethal phenotype and typically weigh 30% less than their wild type littermates. However, the causes of death and small size are unknown. We observed cells with abnormally large nuclei in tissue from Csnk1d null embryos, and multiple centrosomes in mouse embryo fibroblasts (MEFs) deficient in CK1δ (MEFCsnk1d null). Results from γ-H2AX staining and the comet assay demonstrated significant DNA damage in MEFCsnk1d null cells...
2017: PloS One
https://www.readbyqxmd.com/read/28117670/exploring-the-ck2-paradox-restless-dangerous-dispensable
#8
REVIEW
Cinzia Franchin, Christian Borgo, Silvia Zaramella, Luca Cesaro, Giorgio Arrigoni, Mauro Salvi, Lorenzo A Pinna
The history of protein kinase CK2 is crowded with paradoxes and unanticipated findings. Named after a protein (casein) that is not among its physiological substrates, CK2 remained in search of its targets for more than two decades after its discovery in 1954, but it later came to be one of the most pleiotropic protein kinases. Being active in the absence of phosphorylation and/or specific stimuli, it looks unsuitable to participate in signaling cascades, but its "lateral" implication in a variety of signaling pathways is now soundly documented...
January 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28105499/cx4945-suppresses-the-growth-of-castration-resistant-prostate-cancer-cells-by-reducing-ar-v7-expression
#9
Chuangzhong Deng, Jieping Chen, Shengjie Guo, Yanjun Wang, Qianghua Zhou, Zaishang Li, Xingping Yang, Xingsu Yu, Zhenfeng Zhang, Fangjian Zhou, Hui Han, Kai Yao
PURPOSE: The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. METHODS: A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay...
January 19, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28105163/selection-of-antitumor-displayed-peptides-for-the-specific-delivery-of-the-anticancer-drug-lactaptin
#10
Anna Andreevna Nemudraya, Elena Vladimirovna Kuligina, Alexandr Alexeevich Ilyichev, Alexandr Sergeevich Fomin, Grigory Alexandrovich Stepanov, Anna Valentinovna Savelyeva, Olga Alexandrovna Koval, Vladimir Alexandrovich Richter
It has been previously demonstrated that lactaptin, the proteolytic fragment of human milk protein κ-casein, induces the death of various cultured cancer cells. The recombinant analog of lactaptin, RL2, effectively induces the apoptosis of mouse hepatocarcinoma-1 (HA-1) tumor cells in vitro and suppress the growth of HA-1 tumors and metastases in vivo. The antitumor drug Lactaptin developed on the basis of RL2 has been successful in preclinical trials. Lactaptin shows its efficiency in relation to mouse and human cancer cells and tumors...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28092746/supranutritional-selenium-intake-from-enriched-milk-casein-impairs-hepatic-insulin-sensitivity-via-attenuated-irs-pi3k-akt-signaling-and-decreased-pgc-1%C3%AE-expression-in-male-sprague-dawley-rats
#11
Priska Stahel, Julie J Kim, Scott R L Cieslar, Jenny M Warrington, Changting Xiao, John P Cant
Selenium (Se)-enriched milk provides antioxidant benefits and has therapeutic potential against cancer. However, both antidiabetic and prodiabetic effects have been attributed to Se. Our objective was to evaluate the effect of Se-enriched milk casein on insulin sensitivity in rats when given at the requirement of 0.25 ppm Se and supranutritionally on both low- and high-fat diets. Two hundred sixteen male Sprague-Dawley rats were fed low- or high-fat diets containing one, two or eight times the Se requirement in a randomized block design...
January 7, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28057520/molecular-basis-for-the-regulation-of-the-circadian-clock-kinases-ck1%C3%AE-and-ck1%C3%AE%C2%B5
#12
REVIEW
Yu Yang, Tingting Xu, Yunfei Zhang, Ximing Qin
CK1δ and CK1ε are unique in the casein kinase 1 family and play critical roles in a number of physiological intracellular pathways. In particular, these kinases are involved in composing the mammalian circadian clock by phosphorylating core clock proteins. Considering that CK1δ/ε phosphorylate other key biological molecules, such as β-catenin and p53, understanding how the kinase activity is regulated would be greatly significant, since they are potential targets to develop pharmacological agents against cancer, pain, and circadian disorders...
February 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28056552/soy-protein-isolate-inhibits-hepatic-tumor-promotion-in-mice-fed-a-high-fat-liquid-diet
#13
Kelly E Mercer, Casey F Pulliam, Kim B Pedersen, Leah Hennings, Martin Jj Ronis
Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28039480/nutrient-induced-fnip-degradation-by-scf%C3%AE-trcp-regulates-flcn-complex-localization-and-promotes-renal-cancer-progression
#14
Katsuyuki Nagashima, Hidefumi Fukushima, Kouhei Shimizu, Aya Yamada, Masumi Hidaka, Hisashi Hasumi, Tetsuro Ikebe, Satoshi Fukumoto, Koji Okabe, Hiroyuki Inuzuka
Folliculin-interacting protein 1 and 2 (FNIP1 and FNIP2) play critical roles in preventing renal malignancy through their association with the tumor suppressor FLCN. Mutations in FLCN are associated with Birt-Hogg-Dubé (BHD) syndrome, a rare disorder with increased risk of renal cancer. Recent studies indicated that FNIP1/FNIP2 double knockout mice display enlarged polycystic kidneys and renal carcinoma, which phenocopies FLCN knockout mice, suggesting that these two proteins function together to suppress renal cancer...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/27981451/bromelain-functionalized-multiple-wall-lipid-core-nanocapsules-formulation-chemical-structure-and-antiproliferative-effect-against-human-breast-cancer-cells-mcf-7
#15
Catiúscia P Oliveira, Willian A Prado, Vladimir Lavayen, Sabrina L Büttenbender, Aline Beckenkamp, Bruna S Martins, Diogo S Lüdtke, Leandra F Campo, Fabiano S Rodembusch, Andréia Buffon, Adalberto Pessoa, Silvia S Guterres, Adriana R Pohlmann
PURPOSE: This study was conducted a promising approach to surface functionalization developed for lipid-core nanocapsules and the merit to pursue new strategies to treat solid tumors. METHODS: Bromelain-functionalized multiple-wall lipid-core nanocapsules (Bro-MLNC-Zn) were produced by self-assembling following three steps of interfacial reactions. Physicochemical and structural characteristics, in vitro proteolytic activity (casein substrate) and antiproliferative activity (breast cancer cells, MCF-7) were determined...
December 15, 2016: Pharmaceutical Research
https://www.readbyqxmd.com/read/27929731/autophagic-homeostasis-is-required-for-the-pluripotency-of-cancer-stem-cells
#16
Tanveer Sharif, Emma Martell, Cathleen Dai, Barry E Kennedy, Patrick Murphy, Derek R Clements, Youra Kim, Patrick W K Lee, Shashi A Gujar
Pluripotency is an important feature of cancer stem cells (CSCs) that contributes to self-renewal and chemoresistance. The maintenance of pluripotency of CSCs under various pathophysiological conditions requires a complex interaction between various cellular pathways including those involved in homeostasis and energy metabolism. However, the exact mechanisms that maintain the CSC pluripotency remain poorly understood. In this report, using both human and murine models of CSCs, we demonstrate that basal levels of autophagy are required to maintain the pluripotency of CSCs, and that this process is differentially regulated by the rate-limiting enzyme in the NAD(+) synthesis pathway NAMPT (nicotinamide phosphoribosyltransferase) and the transcription factor POU5F1/OCT4 (POU class 5 homeobox 1)...
February 2017: Autophagy
https://www.readbyqxmd.com/read/27899804/casein-kinase-2-controls-the-survival-of-normal-thymic-and-leukemic-%C3%AE-%C3%AE-t-cells-via-promotion-of-akt-signaling
#17
S T Ribeiro, M Tesio, J C Ribot, E Macintyre, J T Barata, B Silva-Santos
The thymus is the major site for normal and leukemic T-cell development. The dissection of the molecular determinants of T-cell survival and differentiation is paramount for the manipulation of healthy or transformed T cells in cancer (immuno)therapy. Casein kinase 2 (CK2) is a serine/threonine protein kinase whose anti-apoptotic functions have been described in various hematological and solid tumors. Here we disclose an unanticipated role of CK2 in healthy human thymocytes that is selective to the γδ T-cell lineage...
December 16, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888634/targeting-protein-kinase-ck2-suppresses-bladder-cancer-cell-survival-via-the-glucose-metabolic-pathway
#18
Xiaolei Zhang, Xiao Yang, Chengdi Yang, Peng Li, Wenbo Yuan, Xiaheng Deng, Yidong Cheng, Pengchao Li, Haiwei Yang, Jun Tao, Qiang Lu
Casein kinase 2 (CK2) is a constitutively active serine/threonine kinase that promotes cell proliferation and resists apoptosis. Elevated CK2 expression has been demonstrated in several solid tumors. The expression of CK2α in bladder cancer was elevated in tumor tissues compared with that in adjacent normal tissues. Amplified expression of CK2α was highly correlated with histological grade in bladder cancer(P = 0.024). Knockdown of CK2α in bladder cancer cell lines resulted in a reduction in tumor aerobic glycolysis, accompanied with lower phosphorylated AKT...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27874833/a-herpesviral-induction-of-rae-1-nkg2d-ligand-expression-occurs-through-release-of-hdac-mediated-repression
#19
Trever T Greene, Maria Tokuyama, Giselle M Knudsen, Michele Kunz, James Lin, Alexander L Greninger, Victor R DeFilippis, Joseph L DeRisi, David H Raulet, Laurent Coscoy
Natural Killer (NK) cells are essential for control of viral infection and cancer. NK cells express NKG2D, an activating receptor that directly recognizes NKG2D ligands. These are expressed at low level on healthy cells, but are induced by stresses like infection and transformation. The physiological events that drive NKG2D ligand expression during infection are still poorly understood. We observed that the mouse cytomegalovirus encoded protein m18 is necessary and sufficient to drive expression of the RAE-1 family of NKG2D ligands...
November 22, 2016: ELife
https://www.readbyqxmd.com/read/27829216/ern1-and-alpk1-inhibit-differentiation-of-bi-potential-tumor-initiating-cells-in-human-breast-cancer
#20
Juliane Strietz, Stella S Stepputtis, Bogdan-Tiberius Preca, Corinne Vannier, Mihee M Kim, David J Castro, Qingyan Au, Melanie Boerries, Hauke Busch, Pedro Aza-Blanc, Susanne Heynen-Genel, Peter Bronsert, Bernhard Kuster, Elmar Stickeler, Thomas Brabletz, Robert G Oshima, Jochen Maurer
Cancers are heterogeneous by nature. While traditional oncology screens commonly use a single endpoint of cell viability, altering the phenotype of tumor-initiating cells may reveal alternative targets that regulate cellular growth by processes other than apoptosis or cell division. We evaluated the impact of knocking down expression of 420 kinases in bi-lineage triple-negative breast cancer (TNBC) cells that express characteristics of both myoepithelial and luminal cells. Knockdown of ERN1 or ALPK1 induces bi-lineage MDA-MB-468 cells to lose the myoepithelial marker keratin 5 but not the luminal markers keratin 8 and GATA3...
December 13, 2016: Oncotarget
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