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https://www.readbyqxmd.com/read/28324784/an-in%C3%A2-vivo-active-1-2-5-oxadiazole-pt-ii-complex-a-promising-anticancer-agent-endowed-with-stat3-inhibitory-properties
#1
Federica Porta, Giorgio Facchetti, Nicola Ferri, Arianna Gelain, Fiorella Meneghetti, Stefania Villa, Daniela Barlocco, Daniela Masciocchi, Akira Asai, Nao Miyoshi, Silvia Marchianò, Byoung-Mog Kwon, Yena Jin, Valentina Gandin, Cristina Marzano, Isabella Rimoldi
New Pt(II) complexes (Pt-1-3) bearing 1,2,5-oxadiazole ligands (1-3) were synthesized, characterized and evaluated for their ability to disrupt STAT3 dimerization. Ligand 3·HCl showed cytotoxic effects on HCT-116 cells (IC50 = 95.2 μM) and a selective ability to interact with STAT3 (IC50 = 8.2 μM) versus STAT1 (IC50 > 30 μM). Its corresponding platinum complex Pt-3 exhibited an increased cytotoxicity (IC50 = 18.4 μM) and a stronger interaction with STAT3 (IC50 = 1.4 μM), leading to inhibition of its signaling pathway...
March 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28324749/a-phase-i-study-of-sar405838-a-novel-human-double-minute-2-hdm2-antagonist-in-patients-with-solid-tumours
#2
Maja de Jonge, Vincent A de Weger, Mark A Dickson, Marlies Langenberg, Axel Le Cesne, Andrew J Wagner, Karl Hsu, Wei Zheng, Sandrine Macé, Gilles Tuffal, Koruth Thomas, Jan H M Schellens
PURPOSE: In tumours with wild-type TP53, the tumour-suppressive function of p53 is frequently inhibited by HDM2. This phase I, dose-escalating study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics and pharmacodynamics of SAR405838, an HDM2 inhibitor, in patients with advanced solid tumours (NCT01636479). METHODS: In dose escalation, patients with any locally advanced/metastatic solid tumour with TP53 mutation prevalence below 40%, or documented as TP53 wild-type, were eligible...
March 16, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28324744/centrosomes-piddosome-joins-the-counting-game
#3
Susana Godinho
Centrosome numbers are tightly regulated during the cell cycle. A new study shows that the PIDDosome prevents the propagation of cells carrying amplified centrosomes via p53 stabilisation and p21-mediated cell-cycle arrest, thus ensuring the maintenance of normal centrosome numbers.
March 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28324505/probing-the-telomere-damage-response
#4
Rekha Rai, Sandy Chang
Telomere dysfunctions, rendered through replicative attrition of telomeric DNA or due to the removal of shelterin components, are recognized as DNA double-stranded breaks (DSBs) by the DNA damage repair (DDR) pathway. This leads to the activation of DNA damage checkpoint sensors, including the Mre11-Rad50-Nbs1 (MRN) complex, γ-H2AX and 53BP1, the ATM and ATR signal-transducing kinases, and downstream effectors, including Chk1, Chk2, and p53. Robust DNA damage response signals at dysfunctional telomeres, achieved by the complete deletion of TRF2 or by expressing dominant-negative mutant TPP1ΔRD, can be detected by their association with γ-H2AX and 53BP1 forming "telomere dysfunction induced foci (TIFs)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28319526/anaplastic-variant-of-diffuse-large-b-cell-lymphoma-displays-intricate-genetic-alterations-and-distinct-biological-features
#5
Mingyang Li, Yixiong Liu, Yingmei Wang, Gang Chen, Qiongrong Chen, Hualiang Xiao, Fang Liu, Chubo Qi, Zhou Yu, Xia Li, Linni Fan, Ying Guo, Qingguo Yan, Shuangping Guo, Zhe Wang
Anaplastic diffuse large B-cell lymphoma (A-DLBCL) is a rare morphologic variant characterized by the presence of polygonal, bizarre-shaped tumor cells. However, the clinicopathologic and genetic features of this variant are largely unknown. In this study, we investigated 35 cases of A-DLBCL with regard to their clinical, pathologic, and genetic characteristics. The age of the patients ranged from 23 to 89 years (median age, 62 y) with a male to female ratio of 23:12. Twenty-two of 26 (85%) patients had Ann Arbor stage III or IV disease, and 17/26 (65%) patients had a high-intermediate or high International Prognostic Index score...
March 17, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28317845/dna-damage-during-s-phase-mediates-the-proliferation-quiescence-decision-in-the-subsequent-g1-via-p21-expression
#6
Alexis R Barr, Samuel Cooper, Frank S Heldt, Francesca Butera, Henriette Stoy, Jörg Mansfeld, Béla Novák, Chris Bakal
Following DNA damage caused by exogenous sources, such as ionizing radiation, the tumour suppressor p53 mediates cell cycle arrest via expression of the CDK inhibitor, p21. However, the role of p21 in maintaining genomic stability in the absence of exogenous DNA-damaging agents is unclear. Here, using live single-cell measurements of p21 protein in proliferating cultures, we show that naturally occurring DNA damage incurred over S-phase causes p53-dependent accumulation of p21 during mother G2- and daughter G1-phases...
March 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28316065/identification-of-key-genes-and-construction-of-microrna-mrna-regulatory-networks-in-multiple-myeloma-by-integrated-multiple-geo-datasets-using-bioinformatics-analysis
#7
Hongyu Gao, Huihan Wang, Wei Yang
Multiple myeloma (MM) is a common hematological malignancy. To identify key genes and microRNAs in MM, we downloaded two gene expression profiles (GSE16558 and GSE47552) and two microRNA expression profiles (GSE17498 and GSE16558) from the Gene Expression Omnibus (GEO) database. A total of 596 differentially expressed genes (DEGs) and 39 differentially expressed microRNAs (DEMs) were screened out. Pathway analysis showed that upregulated genes were mainly enriched in the "B cell receptor signaling pathway", "Cell cycle" and "NF-kappa B signaling pathway", whereas downregulated genes were mainly enriched in the "Ribosome", "FoxO signaling pathway" and "p53 signaling pathway"...
March 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28315428/p53-modulates-the-effect-of-ribosomal-protein-s6-kinase1-s6k1-on-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#8
Ling-Yi Xiao, Wai-Ming Kan
Chronic myeloid leukemia (CML) is characterized by the expression of the oncoprotein, BCR-ABL. BCR-ABL inhibitors revolutionized CML chemotherapy while blast crisis (BC) CML patients are less responsive. Since suppression of ribosomal protein S6 kinase1 (S6K1) phosphorylation reverses the resistance to BCR-ABL inhibitor in CML cells and S6K1 inhibitors augment cisplatin toxicity in lung cancer cells, we speculated that combination of S6K1 inhibitor and cisplatin may be beneficial for eliminating BC CML cells...
March 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28315337/p53-signaling-pathway-polymorphisms-associated-with-emphysematous-changes-in-copd-patients
#9
Shiro Mizuno, Takeshi Ishizaki, Maiko Kadowaki, Masaya Akai, Kohei Shiozaki, Masaharu Iguchi, Taku Oikawa, Ken Nakagawa, Kazuhiro Osanai, Hirohisa Toga, Jose Gomez-Arroyo, Donatas Kraskauskas, Carlyne D Cool, Herman J Bogaard, Norbert F Voelkel
BACKGROUND: The p53 signaling pathway may be important for the pathogenesis of emphysematous changes in the lungs of smokers. Polymorphism of p53 at codon 72 is known to affect apoptotic effector proteins, and the polymorphism of mouse double minute 2 homolog (MDM2) SNP309 is known to increase MDM2 expression. The aim of this study was to assess polymorphisms of the p53 and MDM2 genes in smokers and confirm the role of SNPs in these genes in the pathogenesis of pulmonary emphysema. METHODS: 365 patients with a smoking history were included in this study, and the polymorphisms of p53 and MDM2 genes were identified...
March 14, 2017: Chest
https://www.readbyqxmd.com/read/28315203/adc-histogram-analysis-of-cervical-cancer-aids-detecting-lymphatic-metastases-a-preliminary-study
#10
Stefan Schob, Hans Jonas Meyer, Nikolaos Pazaitis, Dominik Schramm, Kristina Bremicker, Marc Exner, Anne Kathrin Höhn, Nikita Garnov, Alexey Surov
PURPOSE: Apparent diffusion coefficient (ADC) histogram analysis has been used to some extent in cervical cancer (CC) to distinguish between low-grade and high-grade tumors. Although this differentiation is undoubtedly helpful, it would be even more crucial in the presurgical setting to determine whether a tumor already gained the potential to metastasize via the lymphatic system. So far, no studies investigated the potential of 3T ADC histogram analysis in CC to differentiate between nodal-positive and nodal-negative entities...
March 17, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28314679/an-analysis-of-the-rewarding-and-aversive-associative-properties-of-nicotine-in-the-neonatal-quinpirole-model-effects-on-glial-cell-line-derived-neurotrophic-factor-gdnf
#11
Russell W Brown, Seth L Kirby, Adam R Denton, John M Dose, Elizabeth D Cummins, Wesley Drew Gill, Katherine C Burgess
This study analyzed the associative properties of nicotine in a conditioned place preference (CPP) paradigm in adolescent rats neonatally treated with quinpirole (NQ) or saline (NS). NQ produces dopamine D2 receptor supersensitivity that persists throughout the animal's lifetime, and therefore has relevance towards schizophrenia. In two experiments, rats were ip administered quinpirole (1mg/kg) or saline from postnatal day (P)1-21. After an initial preference test at P42-43, animals were conditioned for eight consecutive days with saline or nicotine (0...
March 14, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28314511/novel-platinum-iv-complexes-conjugated-with-a-wogonin-derivative-as-multi-targeted-anticancer-agents
#12
Xiaodong Qin, Gang Xu, Feihong Chen, Lei Fang, Shaohua Gou
Platinum-based complexes like cisplatin and oxaliplatin are well known the mainstay of chemotherapy regimens on clinic. Wogonin, a natural product that possesses wide biological activities, is now in phase I clinical test as an anticancer agent in China. Herein reported are a series of novel Pt(IV) complexes that conjugated a wogonin derivative (compound 3) to the axial position via a linker group. After being tethered to the platinum(IV) complexes, the wogonin derivative provided multiple anticancer effects, especially in compound 10, a fusion containing wogonin and cisplatin units...
March 7, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28303973/e6-e7-p53-pou2f1-cthrc1-axis-promotes-cervical-cancer-metastasis-and-activates-wnt-pcp-pathway
#13
Rong Zhang, Huan Lu, Yuan-Yuan Lyu, Xiao-Mei Yang, Lin-Yan Zhu, Guang-Dong Yang, Peng-Cheng Jiang, Yuan Re, Wei-Wei Song, Jin-Hao Wang, Can-Can Zhang, Fei Gu, Tian-Jiao Luo, Zhi-Yong Wu, Cong-Jian Xu
Cervical cancer is an infectious cancer and the most common gynecologic cancer worldwide. E6/E7, the early genes of the high-risk mucosal human papillomavirus type, play key roles in the carcinogenic process of cervical cancer. However, little was known about its roles in modulating tumor microenvironment, particular extracellular matrix (ECM). In this study, we found that E6/E7 could regulate multiple ECM proteins, especially collagen triple helix repeat containing 1 (CTHRC1). CTHRC1 is highly expressed in cervical cancer tissue and serum and closely correlated with clinicopathological parameters...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28303890/baf60b-mediated-atm-p53-activation-blocks-cell-identity-conversion-by-sensing-chromatin-opening
#14
Shuyi Ji, Linying Zhu, Yimeng Gao, Xiaoran Zhang, Yupeng Yan, Jin Cen, Rongxia Li, Rong Zeng, Lujian Liao, Chunhui Hou, Yawei Gao, Shaorong Gao, Gang Wei, Lijian Hui
Lineage conversion by expression of lineage-specific transcription factors is a process of epigenetic remodeling that has low efficiency. The mechanism by which a cell resists lineage conversion is largely unknown. Using hepatic-specific transcription factors Foxa3, Hnf1α and Gata4 (3TF) to induce hepatic conversion in mouse fibroblasts, we showed that 3TF induced strong activation of the ATM-p53 pathway, which led to proliferation arrest and cell death, and it further prevented hepatic conversion. Notably, ATM activation, independent of DNA damage, responded to chromatin opening during hepatic conversion...
March 17, 2017: Cell Research
https://www.readbyqxmd.com/read/28303539/p53-induction-and-cell-viability-modulation-by-genotoxic-individual-chemicals-and-mixtures
#15
Carolina Di Paolo, Yvonne Müller, Beat Thalmann, Henner Hollert, Thomas-Benjamin Seiler
The binding of the p53 tumor suppression protein to DNA response elements after genotoxic stress can be quantified by cell-based reporter gene assays as a DNA damage endpoint. Currently, bioassay evaluation of environmental samples requires further knowledge on p53 induction by chemical mixtures and on cytotoxicity interference with p53 induction analysis for proper interpretation of results. We investigated the effects of genotoxic pharmaceuticals (actinomycin D, cyclophosphamide) and nitroaromatic compounds (4-nitroquinoline 1-oxide, 3-nitrobenzanthrone) on p53 induction and cell viability using a reporter gene and a colorimetric assay, respectively...
March 16, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28303455/duodenal-cancer-in-a-young-patient-with-peuts-jeghers-syndrome-harboring-an-entire-deletion-of-the-stk11-gene
#16
Satoshi Teramae, Koichi Okamoto, Kumiko Tanaka, Reika Matsumoto, Shinji Kitamura, Tetsuo Kimura, Masahiro Sogabe, Hiroshi Miyamoto, Naoki Muguruma, Yoshimi Bando, Mitsuo Shimada, Tetsuji Takayama
A 21-year-old woman with Peuts-Jeghers syndrome (PJS) was referred to our hospital for gastrointestinal surveillance. She had been diagnosed as having PJS from a young age based on her family history and the presence of mucocutaneous pigmentation on her lips and oral mucosa. Her mother and brother had PJS harboring an entire deletion of the STK11 gene. She had tetralogy of Fallot, atrial tachycardia, sick sinus syndrome, and mental retardation in her past history. Esophagogastroduodenoscopy identified a protruded lesion with a depressed area that occupied the lumen half-circumferentially in the duodenal second portion and also showed a 10-mm protruded lesion on the anterior wall of the lower gastric body...
March 16, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28302063/epigenetic-and-genetic-alterations-and-their-influence-on-gene-regulation-in-chronic-lymphocytic-leukemia
#17
Di Huang, Ivan Ovcharenko
BACKGROUND: To understand the changes of gene regulation in carcinogenesis, we explored signals of DNA methylation - a stable epigenetic mark of gene regulatory elements - and designed a computational model to profile loss and gain of regulatory elements (REs) during carcinogenesis. We also utilized sequencing data to analyze the allele frequency of single nucleotide polymorphisms (SNPs) and detected the cancer-associated SNPs, i.e., the SNPs displaying the significant allele frequency difference between cancer and normal samples...
March 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28300573/concomitant-expression-of-ezrin-and-her2-predicts-distant-metastasis-and-poor-prognosis-of-patients-with-salivary-gland-carcinomas
#18
Kazuki Hashimoto, Ryuichi Hayashi, Takashi Mukaigawa, Manabu Yamazaki, Satoshi Fujii
Salivary gland carcinomas (SGCs) exhibit heterogeneous biological behaviors, including the formation of distant metastases, which is a critical event associated with poor prognosis. Ezrin, which is a member of the ezrin-radixin-moesin family of plasma membrane-cytoskeleton linker proteins, may provide a marker for metastasis and poor survival of patients with cancer. The aim of the present study was to investigate the relationship between ezrin expression and the expression of HER2, p53, and Ki-67 as well as clinicopathological factors in SGCs...
March 11, 2017: Human Pathology
https://www.readbyqxmd.com/read/28299675/a-regulatory-role-for-runx1-runx3-in-the-maintenance-of-genomic-integrity
#19
Vaidehi Krishnan, Yoshiaki Ito
All human cells are constantly attacked by endogenous and exogenous agents that damage the integrity of their genomes. Yet, the ensuing damage is mostly fixed and very rarely gives rise to genomic defects that promote cancer formation. This is due to the co-ordinated functioning of DNA repair proteins and checkpoint mechanisms that accurately detect and repair DNA damage to ensure genomic fitness. According to accumulating evidence, the RUNX family of transcription factors participate in the maintenance of genomic stability through transcriptional and non-transcriptional mechanisms...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299666/runx3-and-p53-how-two-tumor-suppressors-cooperate-against-oncogenic-ras
#20
Jung-Won Lee, Andre van Wijnen, Suk-Chul Bae
RUNX family members play pivotal roles in both normal development and neoplasia. In particular, RUNX1 and RUNX2 are essential for determination of the hematopoietic and osteogenic lineages, respectively. RUNX3 is involved in lineage determination of various types of epithelial cells. Analysis of mouse models and human cancer specimens revealed that RUNX3 acts as a tumor suppressor via multiple mechanisms. p53-related pathways play central roles in tumor suppression through the DNA damage response and oncogene surveillance, and RUNX3 is involved in both processes...
2017: Advances in Experimental Medicine and Biology
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