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https://www.readbyqxmd.com/read/29735299/discontinuation-of-tyrosine-kinase-inhibitor-therapy-in-chronic-myeloid-leukaemia-euro-ski-a-prespecified-interim-analysis-of-a-prospective-multicentre-non-randomised-trial
#1
Susanne Saussele, Johan Richter, Joelle Guilhot, Franz X Gruber, Henrik Hjorth-Hansen, Antonio Almeida, Jeroen J W M Janssen, Jiri Mayer, Perttu Koskenvesa, Panayiotis Panayiotidis, Ulla Olsson-Strömberg, Joaquin Martinez-Lopez, Philippe Rousselot, Hanne Vestergaard, Hans Ehrencrona, Veli Kairisto, Katerina Machová Poláková, Martin C Müller, Satu Mustjoki, Marc G Berger, Alice Fabarius, Wolf-Karsten Hofmann, Andreas Hochhaus, Markus Pfirrmann, Francois-Xavier Mahon
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have improved the survival of patients with chronic myeloid leukaemia. Many patients have deep molecular responses, a prerequisite for TKI therapy discontinuation. We aimed to define precise conditions for stopping treatment. METHODS: In this prospective, non-randomised trial, we enrolled patients with chronic myeloid leukaemia at 61 European centres in 11 countries. Eligible patients had chronic-phase chronic myeloid leukaemia, had received any TKI for at least 3 years (without treatment failure according to European LeukemiaNet [ELN] recommendations), and had a confirmed deep molecular response for at least 1 year...
May 4, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29734252/are-ski-and-snon-involved-in-the-tumorigenesis-of-oral-squamous-cell-carcinoma-through-smad4
#2
Mojgan Alaeddini, Shahroo Etemad-Moghadam
Transforming growth factor-β has been implicated in the tumorigenesis of oral squamous cell carcinoma (OSCC). Ski and SnoN are negative regulators of transforming growth factor-β/Smad pathway with both prooncogenic and antioncogenic functions in different cancers. The aim of this study was to assess the expression of Ski and SnoN in OSCC for the first time. Smad4 was also evaluated in these tumors. Clinical data on 61 primary OSCCs were gathered, and the specimens were subjected to immunohistochemical staining with monoclonal antibodies against SKI, SnoN, and Smad4 and scored semiquantitatively...
May 4, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29630164/comprehensive-outreach-prevention-education-and-skin-cancer-screening-for-utah-ski-resorts
#3
Amir Varedi, Aaron M Secrest, Garrett Harding, Lori Maness, Donna Branson, Kristi Smith, Christopher M Hull
Outdoor recreation can lead to substantial sun exposure. Employees of outdoor recreation establishments with extended time outdoors have amplified cumulative exposure to ultraviolet (UV) radiation and an increased risk of skin cancer. The "Sun Safe on the Slopes" program was created by Huntsman Cancer Institute at the University of Utah and the Utah Cancer Action Network to address increased UV exposure and skin cancer risk with free skin cancer screenings, outreach, and prevention education to local ski resorts...
February 15, 2018: Dermatology Online Journal
https://www.readbyqxmd.com/read/29588413/hydrophobic-patches-on-smad2-and-smad3-determine-selective-binding-to-cofactors
#4
Ken-Ichi Miyazono, Saho Moriwaki, Tomoko Ito, Akira Kurisaki, Makoto Asashima, Masaru Tanokura
The transforming growth factor-β (TGF-β) superfamily of cytokines regulates various biological processes, including cell proliferation, immune responses, autophagy, and senescence. Dysregulation of TGF-β signaling causes various diseases, such as cancer and fibrosis. SMAD2 and SMAD3 are core transcription factors involved in TGF-β signaling, and they form heterotrimeric complexes with SMAD4 (SMAD2-SMAD2-SMAD4, SMAD3-SMAD3-SMAD4, and SMAD2-SMAD3-SMAD4) in response to TGF-β signaling. These heterotrimeric complexes interact with cofactors to control the expression of TGF-β-dependent genes...
March 27, 2018: Science Signaling
https://www.readbyqxmd.com/read/29510895/effect-of-abcg2-oct1-and-abcb1-mdr1-gene-expression-on-treatment-free-remission-in-a-euro-ski-subtrial
#5
Sébastien Rinaldetti, Markus Pfirrmann, Kirsi Manz, Joelle Guilhot, Christian Dietz, Panayiotidis Panagiotidis, Birgit Spiess, Wolfgang Seifarth, Alice Fabarius, Martin Müller, Maria Pagoni, Maria Dimou, Jolanta Dengler, Cornelius F Waller, Tim H Brümmendorf, Regina Herbst, Andreas Burchert, Carsten Janβen, Maria Elisabeth Goebeler, Philipp J Jost, Stefan Hanzel, Philippe Schafhausen, Gabriele Prange-Krex, Thomas Illmer, Viktor Janzen, Martine Klausmann, Robert Eckert, Gerd Büschel, Alexander Kiani, Wolf-Karsten Hofmann, François-Xavier Mahon, Susanne Saussele
INTRODUCTION: Tyrosine kinase inhibitors (TKIs) can safely be discontinued in chronic myeloid leukemia (CML) patients with sustained deep molecular response. ABCG2 (breast cancer resistance protein), OCT1 (organic cation transporter 1), and ABCB1 (multidrug resistance protein 1) gene products are known to play a crucial role in acquired pharmacogenetic TKI resistance. Their influence on treatment-free remission (TFR) has not yet been investigated. MATERIALS AND METHODS: RNA was isolated on the last day of TKI intake from peripheral blood leukocytes of 132 chronic phase CML patients who discontinued TKI treatment within the European Stop Tyrosine Kinase Inhibitor Study trial...
April 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29358619/novel-therapeutic-strategy-for-cervical-cancer-harboring-fgfr3-tacc3-fusions
#6
Ryo Tamura, Kosuke Yoshihara, Tetsuya Saito, Ryosuke Ishimura, Juan Emmanuel Martínez-Ledesma, Hu Xin, Tatsuya Ishiguro, Yutaro Mori, Kaoru Yamawaki, Kazuaki Suda, Seiya Sato, Hiroaki Itamochi, Teiichi Motoyama, Yoichi Aoki, Shujiro Okuda, Cristine R Casingal, Hirofumi Nakaoka, Ituro Inoue, Roel G W Verhaak, Masaaki Komatsu, Takayuki Enomoto
We previously found that therapeutic targetable fusions are detected across various cancers. To identify therapeutic targetable fusion in uterine cervical cancer, for which no effective gene targeted therapy has yet been clinically applied, we analyzed RNA sequencing data from 306 cervical cancer samples. We detected 445 high confidence fusion transcripts and identified four samples that harbored FGFR3-TACC3 fusion as an attractive therapeutic target. The frequency of FGFR3-TACC3-fusion-positive cervical cancer is also 1...
January 23, 2018: Oncogenesis
https://www.readbyqxmd.com/read/29344185/downregulation-of-mir-30a-is-associated-with-proliferation-and-invasion-via-targeting-mef2d-in-cervical-cancer
#7
Jing Zhao, Bo Li, Chuqiang Shu, Yun Ma, Yingping Gong
Accumulating studies have revealed that microRNAs serve crucial roles in cancer development and progression. MicroRNA-30a (miR-30a) has been implicated in various cancer types. However, the role of miR-30a in cervical cancer remains unclear. In the current study, a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed that miR-30a was significantly downregulated in cervical cancer tissues compared with adjacent normal tissues, and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329 normal cervical epithelial cells...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343462/a-tailored-web-based-advice-tool-for-skiers-and-snowboarders-protocol-for-a-randomized-controlled-trial
#8
Ellen Kemler, Vincent Gouttebarge
BACKGROUND: Being active in sports has many positive health effects. The direct effects of engaging in regular physical activity are particularly apparent in the prevention of several chronic diseases, including cardiovascular disease, diabetes, cancer, hypertension, obesity, depression, and osteoporosis. Besides the beneficial health effects of being active, sports participation is unfortunately also associated with a risk of injuries. In the case of many sports injuries (eg, winter sports) preventive measures are not compulsory, which means that a behavioral change in sports participants is necessary to increase the use of effective measures, and subsequently prevent or reduce injuries in sports...
January 17, 2018: JMIR Research Protocols
https://www.readbyqxmd.com/read/29303970/cytotoxic-effects-and-anti-angiogenesis-potential-of-pistachio-pistacia-vera-l-hulls-against-mcf-7-human-breast-cancer-cells
#9
Maryam Seifaddinipour, Reyhaneh Farghadani, Farideh Namvar, Jamaludin Mohamad, Habsah Abdul Kadir
Pistachio ( Pistacia vera L.) hulls (PVLH) represents a significant by-product of industrial pistachio processing that contains high amounta of phenolic and flavonoid compounds known to act as antioxidants. The current study was designed to evaluate the anti-tumor and anti-angiogenic potentials of PVLH extracts. The cytotoxic effects of hexane, ethyl acetate, methanol, and water PVLH extracts toward human colon cancer (HT-29 and HCT-116), breast adenocarcinoma (MCF-7), lung adenocarcinoma (H23), liver hepatocellular carcinoma (HepG2), cervical cancer (Ca Ski), and normal fibroblast (BJ-5ta) cells were assessed using a MTT cell viability assay...
January 5, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29296202/cell-death-and-restoration-of-trail-sensitivity-by-ciglitazone-in-resistant-cervical-cancer-cells
#10
Marie-Laure Plissonnier, Sylvie Fauconnet, Hugues Bittard, Christiane Mougin, Jean Rommelaere, Isabelle Lascombe
Known activators of the Peroxisome Proliferator-Activated Receptor γ (PPARγ), thiazolidinediones (TZD) induce apoptosis in a variety of cancer cells through dependent and/or independent mechanisms of the receptor. We tested a panel of TZD (Rosiglitazone, Pioglitazone, Ciglitazone) to shed light on their potential therapeutic effects on three cervical cancer cell lines (HeLa, Ca Ski, C-33 A). In these cells, only ciglitazone triggered apoptosis through PPARγ-independent mechanisms and in particular via both extrinsic and intrinsic pathways in Ca Ski cells containing Human PapillomaVirus (HPV) type 16...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227283/sharpin-mediated-regulation-of-protein-arginine-methyltransferase-5-controls-melanoma-growth
#11
Hironari Tamiya, Hyungsoo Kim, Oleksiy Klymenko, Heejung Kim, Yongmei Feng, Tongwu Zhang, Ji Yun Han, Ayako Murao, Scott J Snipas, Lucia Jilaveanu, Kevin Brown, Harriet Kluger, Hao Zhang, Kazuhiro Iwai, Ze'ev A Ronai
SHARPIN, an adaptor for the linear ubiquitin chain assembly complex (LUBAC), plays important roles in NF-κB signaling and inflammation. Here, we have demonstrated a LUBAC-independent role for SHARPIN in regulating melanoma growth. We observed that SHARPIN interacted with PRMT5, a type II protein arginine methyltransferase, and increased its multiprotein complex and methyltransferase activity. Activated PRMT5 controlled the expression of the transcription factors SOX10 and MITF by SHARPIN-dependent arginine dimethylation and inhibition of the transcriptional corepressor SKI...
January 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29207959/insulin-like-growth-factor-receptor-and-sphingosine-kinase-are-prognostic-and-therapeutic-targets-in-breast-cancer
#12
Aleksandra M Ochnik, Robert C Baxter
BACKGROUND: Targeting the type 1 insulin-like growth factor receptor (IGF1R) in breast cancer remains an ongoing clinical challenge. Oncogenic IGF1R-signaling occurs via activation of PI3K/AKT/MAPK downstream mediators which regulate cell proliferation and protein synthesis. To further understand IGF1R signaling we have investigated the involvement of the oncogenic IGF1R-related sphingosine kinase (SphK) pathway. METHODS: The prognostic (overall survival, OS) and therapeutic (anti-endocrine therapy) co-contribution of IGF1R and SphK1 were investigated using breast cancer patient samples (n = 236) for immunohistochemistry to measure total and phosphorylated IGF1R and SphK1...
December 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29200721/helichrysetin-induces-dna-damage-that-triggers-jnk-mediated-apoptosis-in-ca-ski-cells
#13
Ho Yen Fong, Sri Nurestri Abd Malek, Hui Shin Yee, Saiful Anuar Karsani
Background: Cervical cancer has become one of the most common cancers in women and currently available treatment options for cervical cancer are very limited. Naturally occurring chalcones and its derivatives have been studied extensively as a potential anticancer agent in different types of cancer and helichrysetin is naturally occurring chalcone that possess potent antiproliferative activity toward human cancer cells. Materials and Methods: Inhibitory activity of helichrysetin was evaluated at different concentrations...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29191063/changes-in-dna-methylation-induced-by-multi-walled-carbon-nanotube-exposure-in-the-workplace
#14
Manosij Ghosh, Deniz Öner, Katrien Poels, Ali M Tabish, Jelle Vlaanderen, Anjoeka Pronk, Eelco Kuijpers, Qing Lan, Roel Vermeulen, Bram Bekaert, Peter Hm Hoet, Lode Godderis
This study was designed to assess the epigenetic alterations in blood cells, induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The study population comprised of MWCNT-exposed workers (n=24) and unexposed controls (n=43) from the same workplace. We measured global DNA methylation/hydroxymethylation levels on the 5th cytosine residues using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. Sequence-specific methylation of LINE1 retrotransposable element 1 (L1RE1) elements, and promoter regions of functionally important genes associated with epigenetic regulation [DNA methyltransferase-1 (DNMT1) and histone deacetylase 4 (HDAC4)], DNA damage/repair and cell cycle pathways [nuclear protein, coactivator of histone transcription/ATM serine/threonine kinase (NPAT/ATM)], and a potential transforming growth factor beta (TGF-β) repressor [SKI proto-oncogene (SKI)] were studied using bisulfite pyrosequencing...
November 2017: Nanotoxicology
https://www.readbyqxmd.com/read/29118270/upregulation-of-pir-gene-expression-induced-by-human-papillomavirus-e6-and-e7-in-epithelial-oral-and-cervical-cells
#15
Diego Carrillo, Juan P Muñoz, Hernán Huerta, Gabriel Leal, Alejandro Corvalán, Oscar León, Gloria M Calaf, Ulises Urzúa, Enrique Boccardo, Julio C Tapia, Francisco Aguayo
The hallmark of high-risk human papillomavirus (HR-HPV)-related carcinogenesis is E6 and E7 oncogene overexpression. The aim of this work was to characterize epithelial oral and cervical cancer cells that express HR-HPV E6 and E7 oncoproteins. Transcriptomic assay using DNA microarrays revealed that PIR gene expression was detected in oral cells in an HR-HPV E6/E7-dependent manner. In addition, PIR was overexpressed in HPV-positive SiHa and Ca Ski cells, whereas it was undetectable in HPV-negative C33A cells...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29028945/sphingosine-kinase-1-expression-in-peritoneal-macrophages-is-required-for-colon-carcinogenesis
#16
Hideki Furuya, Paulette M Tamashiro, Yoshiko Shimizu, Kayoko Iino, Rafael Peres, Runpu Chen, Yijun Sun, Yusuf A Hannun, Lina M Obeid, Toshihiko Kawamori
Accumulating evidence suggests that the sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate (S1P) pathway plays a pivotal role in colon carcinogenesis. Our previous studies indicate that the SphK1/S1P pathway mediates colon carcinogenesis at least by regulating COX-2 expression and prostaglandin E2 (PGE2) production. However, the mechanisms by which this pathway regulates colon carcinogenesis are still unclear. First, we show that SphK1 deficient mice significantly attenuated azoxymethane (AOM)-induced colon carcinogenesis as measured by colon tumor incidence, multiplicity, and volume...
September 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28890935/ski-178-a-multitargeted-inhibitor-of-sphingosine-kinase-and-microtubule-dynamics-demonstrating-therapeutic-efficacy-in-acute-myeloid-leukemia-models
#17
Jeremy A Hengst, Taryn E Dick, Arati Sharma, Kenichiro Doi, Shailaja Hegde, Su-Fern Tan, Laura M Geffert, Todd E Fox, Arun K Sharma, Dhimant Desai, Shantu Amin, Mark Kester, Thomas P Loughran, Robert F Paulson, David F Claxton, Hong-Gang Wang, Jong K Yun
AIM: To further characterize the selectivity, mechanism-of-action and therapeutic efficacy of the novel small molecule inhibitor, SKI-178. METHODS: Using the state-of-the-art Cellular Thermal Shift Assay (CETSA) technique to detect "direct target engagement" of proteins intact cells, in vitro and in vivo assays, pharmacological assays and multiple mouse models of acute myeloid leukemia (AML). RESULTS: Herein, we demonstrate that SKI-178 directly target engages both Sphingosine Kinase 1 and 2...
July 2017: Cancer Translational Medicine
https://www.readbyqxmd.com/read/28681918/microrna-137-is-negatively-associated-with-clinical-outcome-and-regulates-tumor-development-through-ezh2-in-cervical-cancer
#18
Huimin Zhang, Ting Yan, Zhijun Liu, Jun Wang, Yu Lu, Donglin Li, Wentong Liang
We intend to evaluate the expression, clinical relevance, and functional role of microRNA-137 (miR-137) in human cervical cancer (CC). MiR-137 expressions were assessed by qPCR in CC cell lines and human CC tumors. The correlation between endogenous miR-137 expression and CC patients' postoperative overall survival was examined statistically. CC cell lines, Ca-Ski, and SiHa cells were transduced with lentivirus to ectopically upregulate endogenous miR-137 expressions. Possible inhibitory effects of miR-137 upregulation on CC in vitro proliferation and migration, as well as in vivo transplantation were evaluated...
January 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28627406/multi-omics-facilitated-variable-selection-in-cox-regression-model-for-cancer-prognosis-prediction
#19
Cong Liu, Xujun Wang, Georgi Z Genchev, Hui Lu
MOTIVATION: New developments in high-throughput genomic technologies have enabled the measurement of diverse types of omics biomarkers in a cost-efficient and clinically-feasible manner. Developing computational methods and tools for analysis and translation of such genomic data into clinically-relevant information is an ongoing and active area of investigation. For example, several studies have utilized an unsupervised learning framework to cluster patients by integrating omics data...
July 15, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28611495/antibacterial-anticancer-and-neuroprotective-activities-of-rare-actinobacteria-from-mangrove-forest-soils
#20
Adzzie-Shazleen Azman, Iekhsan Othman, Chee-Mun Fang, Kok-Gan Chan, Bey-Hing Goh, Learn-Han Lee
Mangrove is a complex ecosystem that contains diverse microbial communities, including rare actinobacteria with great potential to produce bioactive compounds. To date, bioactive compounds extracted from mangrove rare actinobacteria have demonstrated diverse biological activities. The discovery of three novel rare actinobacteria by polyphasic approach, namely Microbacterium mangrovi MUSC 115(T), Sinomonas humi MUSC 117(T) and Monashia flava MUSC 78(T) from mangrove soils at Tanjung Lumpur, Peninsular Malaysia have led to the screening on antibacterial, anticancer and neuroprotective activities...
June 2017: Indian Journal of Microbiology
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