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Casein cancer

Ferda Hoşgörler, Didem Keleş, Serpil Tanrıverdi-Akhisaroğlu, Şeniz İnanç, Mustafa Akhisaroğlu, Ülker Cankurt, Zekiye Aydoğdu, Ahmet Deniz Uçar, Oğuz Çetinayak, Gülgün Oktay, Sevil Gönenç Arda
BACKGROUND: Matrix metalloproteinase (MMP) inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA) and doxycycline (DX) are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date. AIMS: The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition...
September 2016: Balkan Medical Journal
Jun Sang Bae, See-Hyoung Park, Urangoo Jamiyandorj, Kyoung Min Kim, Sang Jae Noh, Jung Ryul Kim, Hye Jeong Park, Keun Sang Kwon, Sung Hoo Jung, Ho Sung Park, Byung-Hyun Park, Ho Lee, Woo Sung Moon, Karl G Sylvester, Kyu Yun Jang
Recently, the roles of sirtuins (SIRTs) in tumorigenesis have been of interest to oncologists, and casein kinase 2 α1 (CSNK2A1) has been shown to be involved in tumorigenesis by phosphorylating various proteins, including SIRT1. Therefore, we evaluated the roles of CSNK2A1, SIRT6, and phosphorylated SIRT6 and their relationships in breast carcinoma. Nuclear expression of CSNK2A1 and SIRT6 predicted shorter overall survival and relapse-free survival by multivariate analysis. Inhibition of CSNK2A1 decreased the proliferative and invasive activity of cancer cells...
October 13, 2016: American Journal of Pathology
Chandrika Gowda, Mansi Sachdev, Sunil Muthisami, Malika Kapadia, Lidija Petrovic-Dovat, Melanie Hartman, Yali Ding, Chunhua Song, Jonathon L Payne, Bi-Hua Tan, Sinisa Dovat
BACKGROUND: Casein kinase II (CK2) is a pro-oncogenic protein, which is emerging as a promising therapeutic target in cancer. Recent studies have revealed an important role for CK2 in tumorigenesis. High levels of CK2 are noted in many malignancies including leukemia. Use of CK2 inhibitors in various malignancies including breast, prostate, and lung cancer are being tested. Although many CK2 inhibitors exist, only a few have emerged as selective inhibitors that are potent and effective...
October 6, 2016: Current Pharmaceutical Design
Evanthia Pangou, Christina Befani, Ilias Mylonis, Martina Samiotaki, George Panayotou, George Simos, Panagiotis Liakos
Hypoxia Inducible Factor 2 (HIF-2) is a transcriptional activator implicated in the cellular response to hypoxia. Regulation of its inducible subunit, HIF-2α, involves post-translational modifications. Here, we demonstrate that casein kinase 1δ (CK1δ) phosphorylates HIF-2α at Ser383 and Thr528 in vitro Disruption of these phosphorylation sites and silencing or chemical inhibition of CK1δ reduced the expression of HIF-2 target genes and the secretion of erythropoietin (EPO) in two hepatic cancer cell lines, Huh7 and HepG2, without affecting levels of HIF-2α protein expression...
September 29, 2016: Journal of Cell Science
Takahisa Kuga, Hideaki Kume, Jun Adachi, Naoko Kawasaki, Maiko Shimizu, Isamu Hoshino, Hisahiro Matsubara, Youhei Saito, Yuji Nakayama, Takeshi Tomonaga
In some fibroblasts, casein kinase 1α (CK1α) is localized to nuclear speckles, which are sub-nuclear compartments supplying splicing factors, whereas it is recruited on keratin filaments in colorectal cancer cells such as DLD1 cells. In order to obtain a deeper understanding of why CK1α is localized to these different subcellular sites, we herein elucidated the mechanisms underlying its localization to nuclear speckles. CK1α and FAM83H were localized to nuclear speckles in RKO and WiDr colorectal cancer cells, which do not express simple epithelial keratins, and in DLD1 cells transfected with siRNAs for type I keratins...
September 29, 2016: Scientific Reports
F Linke, M Harenberg, M M Nietert, S Zaunig, F von Bonin, A Arlt, M Szczepanowski, H A Weich, S Lutz, C Dullin, P Janovská, M Krafčíková, L Trantírek, P Ovesná, W Klapper, T Beissbarth, F Alves, V Bryja, L Trümper, J Wilting, D Kube
The interaction between vascular endothelial cells (ECs) and cancer cells is of vital importance to understand tumor dissemination. A paradigmatic cancer to study cell-cell interactions is classical Hodgkin Lymphoma (cHL) owing to its complex microenvironment. The role of the interplay between cHL and ECs remains poorly understood. Here we identify canonical WNT pathway activity as important for the mutual interactions between cHL cells and ECs. We demonstrate that local canonical WNT signaling activates cHL cell chemotaxis toward ECs, adhesion to EC layers and cell invasion using not only the Wnt-inhibitor Dickkopf, tankyrases and casein kinase 1 inhibitors but also knockdown of the lymphocyte enhancer binding-factor 1 (LEF-1) and β-catenin in cHL cells...
October 4, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Somdutta Sinha Roy, Shyamali Mukherjee, Billy R Ballard, Salil K Das
Consumption of α-lactalbumin as dietary protein offers a beneficial effect on breast cancer development. Breast cancer was developed by gavage administration of single dose of dimethylbenz(a)anthracene (DMBA) in female rats, maintained on AIN-76A diet with either 20% casein or α-lactalbumin (a component of whey protein). All tumors were detected by palpation. After approximately 130 days of DMBA administration, the animals were euthanized. There was a delay in the development of breast tumor in the α-lactalbumin group in comparison to the casein group...
2016: International Journal of Cancer and Oncology
Chunhui Li, James I S MacDonald, Asghar Talebian, Jennifer Leuenberger, Claudia Seah, Stephen H Pasternak, Stephen W Michnick, Susan O Meakin
Macropinocytosis is a normal cellular process by which cells internalize extracellular fluids and nutrients from their environment and is one strategy that Ras-transformed pancreatic cancer cells use to increase uptake of amino acids to meet the needs of rapid growth. Paradoxically, in non-Ras transformed medulloblastoma brain tumors, we have shown that expression and activation of the receptor tyrosine kinase TrkA overactivates macropinocytosis, resulting in the catastrophic disintegration of the cell membrane and in tumor cell death...
October 15, 2016: Molecular and Cellular Biology
Stefanie Lindner, Jan Krönke
Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells...
August 5, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
H Z Li, Y H Chen, Y L Fang, L Y Zhong, Q Q Yuan, X Y Xu, J G Cao
OBJECTIVE: To investigate whether inhibitory effect of chrysin on sphere formation of ovarian cancer stem-like cells(spheroids derived from human ovarian cancer SKOV3 cell line ) is involved in the down-regulating of the protein expression of casein kinase CK2α. METHODS: SKOV3-derived ovarian cancer stem-like cells obtained by suspension culture in stem cell-condition medium using ultra-low adhesion plate were treated with various concentrations (5.0, 10.0 and 20...
July 5, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Jorunn Litlekalsoy, Kari Rostad, Karl-Henning Kalland, Jens G Hostmark, Ole Didrik Laerum
BACKGROUND: The purpose of this study was to evaluate invasive and metastatic potential of urothelial cancer by investigating differential expression of various clock genes/proteins participating in the 24 h circadian rhythms and to compare these gene expressions with transcription of other cancer-associated genes. METHODS: Twenty seven paired samples of tumour and benign tissue collected from patients who underwent cystectomy were analysed and compared to 15 samples of normal bladder tissue taken from patients who underwent cystoscopy for benign prostate hyperplasia (unrelated donors)...
2016: BMC Cancer
Jing Huang, Weiping Qian, Liya Wang, Hui Wu, Hongyu Zhou, Andrew Yongqiang Wang, Hongbo Chen, Lily Yang, Hui Mao
Engineered nanocarriers have emerged as a promising platform for cancer therapy. However, the therapeutic efficacy is limited by low drug loading efficiency, poor passive targeting to tumors, and severe systemic side effects. Herein, we report a new class of nanoconstructs based on milk protein (casein)-coated magnetic iron oxide (CNIO) nanoparticles for targeted and image-guided pancreatic cancer treatment. The tumor-targeting amino-terminal fragment (ATF) of urokinase plasminogen activator and the antitumor drug cisplatin (CDDP) were engineered on this nanoplatform...
2016: International Journal of Nanomedicine
Afshin Faridi Esfanjani, Seid Mahdi Jafari
Phenolic compounds are major micronutrients in our diet,(1) and evidence for their role in the prevention of degenerative diseases such as cancer, inflammation and neurodegenerative diseases is emerging. The easily destruction against environment stresses and low bioavailability of phenolics are main limitations of their application. Therefore, nano-encapsulated phenolics as a fine delivery system can solve their restrictions. Polymeric nanoparticles and natural nano-carriers are one of the most effective and industrial techniques which can be used for protection and delivery of phenolics...
October 1, 2016: Colloids and Surfaces. B, Biointerfaces
Christian Nienberg, Anika Retterath, Kira-Sophie Becher, Thorsten Saenger, Henning D Mootz, Joachim Jose
Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI) of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF) could be incorporated into CK2α...
2016: Pharmaceuticals
Zheng Ge, Yan Gu, Lichan Xiao, Qi Han, Jianyong Li, Baoan Chen, James Yu, Yuka Imamura Kawasawa, Kimberly J Payne, Sinisa Dovat, Chunhua Song
Acute lymphoblastic leukemia (ALL) remains the leading cause of cancer-related death in children and young adults. Compared to ALL in children, adult ALL has a much lower cure rate. Therefore, it is important to understand the molecular mechanisms underlying high-risk ALL and to develop therapeutic strategies that specifically target genes or pathways in ALL. Here, we explored the IL7R and SH2B3 expression in adult ALL and found that IL7R is significantly higher and Sh2B3 lower expressed in B-ALL compared to normal bone marrow control, and the IL7RhighSH2B3low is associated with high-risk factors, and with high relapse rate and low disease-free survival rate in the patients...
June 14, 2016: Oncotarget
Fernando Benavent, Carla S Capobianco, Juan Garona, Stéfano M Cirigliano, Yasser Perera, Alejandro J Urtreger, Silvio E Perea, Daniel F Alonso, Hernan G Farina
OBJECTIVES: Casein kinase 2 (CK2) is overexpressed in several types of cancer. It has more than 300 substrates mainly involved in DNA reparation and replication, chromatin remodeling and cellular growth. In recent years CK2 became an interesting target for anticancer drug development. CIGB-300 is a peptidic inhibitor of CK2 activity, designed to bind to the phospho-acceptor domain of CK2 substrates, impairing the correct phosphorylation by the enzyme. The aim of this work was to explore the antitumor effects of this inhibitor in preclinical lung cancer models...
June 1, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Jit Kong Cheong, David M Virshup
Mutant RAS-driven cancer cells cope with proliferative stress by increasing basal autophagy to maintain protein/organelle and energy homeostasis. We recently demonstrated that casein kinase 1 alpha (CK1α), a therapeutically tractable enzyme, is critical for fine-tuning the transcriptional regulation of mutant RAS-induced autophagy and the development of mutant RAS-driven cancers.
May 2016: Molecular & Cellular Oncology
Pradip De, Jennifer H Carlson, Hui Wu, Adam Marcus, Brian Leyland-Jones, Nandini Dey
Tumor cells acquire metastasis-associated (MA) phenotypes following genetic alterations in them which cause deregulation of different signaling pathways. Earlier, we reported that an upregulation of the Wnt-beta-catenin pathway (WP) is one of the genetic salient features of triple-negative breast cancer (TNBC), and WP signaling is associated with metastasis in TNBC. Using cBioPortal, here we found that collective % of alteration(s) in WP genes, CTNNB1, APC and DVL1 among breast-invasive-carcinomas was 21% as compared to 56% in PAM50 Basal...
April 26, 2016: Oncotarget
Takahisa Kuga, Mitsuho Sasaki, Toshinari Mikami, Yasuo Miake, Jun Adachi, Maiko Shimizu, Youhei Saito, Minako Koura, Yasunori Takeda, Junichiro Matsuda, Takeshi Tomonaga, Yuji Nakayama
FAM83H is essential for the formation of dental enamel because a mutation in the FAM83H gene causes amelogenesis imperfecta (AI). We previously reported that the overexpression of FAM83H often occurs and disorganizes the keratin cytoskeleton in colorectal cancer cells. We herein show that FAM83H regulates the organization of the keratin cytoskeleton and maintains the formation of desmosomes in ameloblastoma cells. FAM83H is expressed and localized on keratin filaments in human ameloblastoma cell lines and in mouse ameloblasts and epidermal germinative cells in vivo...
2016: Scientific Reports
Y Zhou, S Zhang, K Li, X R Dong, L Liu, G Wu, R Meng
Nowadays, EGFR-TKIs are important treatment strategy in lung cancer, but the resistance to EGFR-TKIs remains an unsolved issue preventing the patients from further benefits. Recent studies have shown that casein kinase (CK2) plays an important role in carcinogenesis and development of cancer. CK2 inhibitor has also demonstrated anti-tumor effects. Here we reviewed the mechanism of EGFR-TKIs and the potential reasons of resistance. Interestingly, there is a crosstalk between CK2 and EGFR downstream signaling pathways, therefore, it may be possible that CK2 inhibitor can overcome the EGFR-TKIs resistance...
May 23, 2016: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
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