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Francesco Crea, Antonello Di Paolo, Hui Hsuan Liu, Marialuisa Polillo, Pier-Luc Clermont, Francesca Guerrini, Elena Ciabatti, Federica Ricci, Claudia Baratè, Giulia Fontanelli, Sara Barsotti, Riccardo Morganti, Romano Danesi, Yuzhuo Wang, Mario Petrini, Sara Galimberti, Cheryl D Helgason
AIM: Imatinib is a tyrosine kinase inhibitor that has revolutionized the treatment of chronic myeloid leukemia (CML). Despite its efficacy, about a third of patients discontinue the treatment due to therapy failure or intolerance. The rational identification of patients less likely to respond to imatinib would be of paramount clinical relevance. We have shown that transmembrane transporter hOCT1 genotyping predicts imatinib activity. In parallel, Polycomb group genes (PcGs) are epigenetic repressors implicated in CML progression and in therapy resistance...
August 2015: Epigenomics
David R Nanyes, Sarah E Junco, Alexander B Taylor, Angela K Robinson, Nicolle L Patterson, Ambika Shivarajpur, Jonathan Halloran, Seth M Hale, Yogeet Kaur, P John Hart, Chongwoo A Kim
The self-association of sterile alpha motifs (SAMs) into a helical polymer architecture is a critical functional component of many different and diverse array of proteins. For the Drosophila Polycomb group (PcG) protein Polyhomeotic (Ph), its SAM polymerization serves as the structural foundation to cluster multiple PcG complexes, helping to maintain a silenced chromatin state. Ph SAM shares 64% sequence identity with its human ortholog, PHC3 SAM, and both SAMs polymerize. However, in the context of their larger protein regions, PHC3 SAM forms longer polymers compared with Ph SAM...
October 2014: Proteins
Dennis U Nielsen, Camille Lescot, Thomas M Gøgsig, Anders T Lindhardt, Troels Skrydstrup
Reaction conditions for the three-component synthesis of aryl 1,3-diketones are reported applying the palladium-catalyzed carbonylative α-arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)2] (dba=dibenzylideneacetone) as the palladium source and 1,3-bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two-chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO-releasing compound, 9-methylfluorene-9-carbonyl chloride (COgen)...
December 23, 2013: Chemistry: a European Journal
F Crea, L Sun, L Pikor, P Frumento, W L Lam, C D Helgason
BACKGROUND: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. METHODS: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. RESULTS: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8-35%)...
September 17, 2013: British Journal of Cancer
Angela K Robinson, Belinda Z Leal, David R Nanyes, Yogeet Kaur, Udayar Ilangovan, Virgil Schirf, Andrew P Hinck, Borries Demeler, Chongwoo A Kim
Sterile alpha motifs (SAMs) are frequently found in eukaryotic genomes. An intriguing property of many SAMs is their ability to self-associate, forming an open-ended polymer structure whose formation has been shown to be essential for the function of the protein. What remains largely unresolved is how polymerization is controlled. Previously, we had determined that the stretch of unstructured residues N-terminal to the SAM of a Drosophila protein called polyhomeotic (Ph), a member of the polycomb group (PcG) of gene silencers, plays a key role in controlling Ph SAM polymerization...
July 10, 2012: Biochemistry
Haya H Al-Balool, David Weber, Yilei Liu, Mark Wade, Kamlesh Guleria, Pitsien Lang Ping Nam, Jake Clayton, William Rowe, Jonathan Coxhead, Julie Irving, David J Elliott, Andrew G Hall, Mauro Santibanez-Koref, Michael S Jackson
In silico analyses have established that transcripts from some genes can be processed into RNAs with rearranged exon order relative to genomic structure (post-transcriptional exon shuffling, or PTES). Although known to contribute to transcriptome diversity in some species, to date the structure, distribution, abundance, and functional significance of human PTES transcripts remains largely unknown. Here, using high-throughput transcriptome sequencing, we identify 205 putative human PTES products from 176 genes...
November 2011: Genome Research
Shuang-shuang He, Chun-shui Lin, Miao-ning Gu, Dong-ting Chen, Shi-lan Zong, Ying Chen
OBJECTIVE: To investigate the effect of penehyclidine hydrochloride (PHC) in a rat model of renal injury induced by hemorrhagic shock and lipopolysaccharides (LPS). METHODS: Forty-five healthy Wistar rats were randomized into sham operated group, model group, and 3 penehyclidine hydrochloride (PHC) dose (1, 2 and 3 mg/kg) groups (PHC1, PHC2, and PHC3 groups, respectively). The arterial blood samples were collected to determine the concentrations of serum tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interleukin-1 (IL-1), urine creatinine (Cr) and blood urine nitrogen (BUN), and the renal tissues were collected to measure the expressions of ICAM-1 and nuclear factor-κB (NF-κB) and observe the pathological changes...
May 2011: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Perrine Le Faou, Pamela Völkel, Pierre-Olivier Angrand
Polycomb repression controls regulation of hundreds of genes involved in development, signalling or cancer and is mediated by essentially two classes of chromatin-associated protein complexes, the Polycomb repressive complexes 1 and 2 (PRC1 and PRC2). PRC2 trimethylates histone H3 at Lysine 27 and this H3K27me3 epigenetic mark serves as a docking site for the PRC1 protein complex. Drosophila core PRC1 is composed of four subunits, Polycomb (Pc), Posterior sex combs (Psc), Polyhomeotic (Ph), and Sex combs extra (Sce)...
April 1, 2011: Gene
Shintaro Iwata, Hisanori Takenobu, Hajime Kageyama, Haruhiko Koseki, Takeshi Ishii, Atsuko Nakazawa, Shin-ichiro Tatezaki, Akira Nakagawara, Takehiko Kamijo
Polyhomeotic homolog 3 (PHC 3) is a member of the human polycomb complex and has been regarded as a candidate tumor suppressor of osteosarcoma. In the present paper, we performed a mutation survey and PHC3 expression analysis by quantitative real-time PCR using 10 osteosarcoma cell lines and 42 primary osteosarcoma samples. Relative PHC3 expression values of clinical samples were analyzed with clinical outcomes, and it was suggested that lower PHC3-expressing patients had significantly worse overall survival...
July 2010: Cancer Science
L S Moreira, T G de Andrade, D M Albuquerque, A F Cunha, A Fattori, S T O Saad, F F Costa
1. The major effect associated with hydroxyurea (HU) treatment of sickle cell anaemia (SCA) patients is an increase in fetal haemoglobin (HbF) synthesis, which inhibits the polymerization of haemoglobin S. 2. Hydroxyurea improves clinical symptoms by reducing the frequency of pain and vaso-occlusive crises, acute chest syndrome, transfusion requirements and hospitalization. 3. The molecular mechanisms responsible for HU-mediated induction of fetal globin transcription are not completely understood. Therefore, the aim of the present study was to identify differentially expressed genes participating in these mechanisms...
May 2008: Clinical and Experimental Pharmacology & Physiology
A M Deshpande, J D Akunowicz, X T Reveles, B B Patel, E A Saria, R G Gorlick, S L Naylor, R J Leach, M F Hansen
Polyhomeotic-like 3 (PHC3) is a ubiquitously expressed member of the polycomb gene family and part of the human polycomb complex hPRC-H. We found that in normal cells PHC3 associated with both hPRC-H complex components and with the transcription factor E2F6. In differentiating and confluent cells, PHC3 and E2F6 showed nuclear colocalization in a punctate pattern that resembled the binding of polycomb bodies to heterochromatin. This punctate pattern was not seen in proliferating cells suggesting that PHC3 may be part of an E2F6-polycomb complex that has been shown to occupy and silence target promoters in G(0)...
March 15, 2007: Oncogene
Kyo-Ichi Isono, Yu-Ichi Fujimura, Jun Shinga, Makoto Yamaki, Jiyang O-Wang, Yoshihiro Takihara, Yasuaki Murahashi, Yuki Takada, Yoko Mizutani-Koseki, Haruhiko Koseki
The Polycomb group (PcG) gene products form multimeric protein complexes and contribute to anterior-posterior (A-P) specification via the transcriptional regulation of Hox cluster genes. The Drosophila polyhomeotic genes and their mammalian orthologues, Phc1, Phc2, and Phc3, encode nuclear proteins that are constituents of evolutionarily conserved protein complexes designated class II PcG complexes. In this study, we describe the generation and phenotypes of Phc2-deficient mice. We show posterior transformations of the axial skeleton and premature senescence of mouse embryonic fibroblasts associated with derepression of Hox cluster genes and Cdkn2a genes, respectively...
August 2005: Molecular and Cellular Biology
H Shang, Q Wang, L Sun
OBJECTIVE: To investigate whether all-trans retinoic acid (RA) has antitumor effect in vivo. METHODS: Sixteen nude mice were transplanted with human laryngeal cell carcinoma PHC3. Eight of them were injected with RA intraperitoneally and others with solvent as the control. Response was measured and tumor histopathological features were studied. RESULTS: The growth and weight of RA-treated tumors were significantly reduced in comparison with those of the control...
August 1999: Zhonghua Er Bi Yan Hou Ke za Zhi
Emma Tonkin, Donna-Marie Hagan, Weiping Li, Tom Strachan
We have identified and characterised novel members of the mammalian polyhomeotic gene family, comprising a third human homologue, PHC3, and its mouse counterpart, Phc3. The two new genes have essentially the same genomic organisation, with 15 exons specifying proteins of 983 (PHC3) or 981 (Phc3) amino acids, with an overall sequence identity of 93%. Northern blot hybridisations have identified a single large transcript in a variety of adult mouse tissues and in situ hybridisation analyses indicate apparently ubiquitous expression during early human and mouse development...
October 2002: Human Genetics
Y Wu, M Guo
In order to know whether laryngeal cancer draining lymph node lymphocytes (INL) have antitumor effects in vivo, we transfered IL-2 activated LNL to nude mice with human laryngeal squamous cell carcinoma line PHC3 xenografts, and observed a suppressive effect on tumor growth. It was also found in the epitype changes of LNL by indirect immunofluorencence method the major composition of freshly isolated LNL was CD3+ T cells in which there were more Th/i cells than Ts/c cells, CD4+/CD8+ ratio was 3.30 +/- 0.653...
1996: Zhonghua Er Bi Yan Hou Ke za Zhi
Y Wu, M Guo
The distribution of 3H-TdR labeled human laryngeal cancer drained lymph node lymphocytes (LNL) to human laryngeal squamous cell carcinoma were traced in PHC3 bearing nude mice, and the radioactivity in tissues was detected. 30.7% labeled cells were localized in live in first day after transfer, and a few in lung, spleen and kidney. Labeled cells were reduced weekly and by the end of the fourth week there were still 4.3% in live, but very few were detected in the tumor site. This indicated that cancer drained LNL had no specificity to tumor, and could not infiltrate into tumor sites...
1995: Zhonghua Er Bi Yan Hou Ke za Zhi
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