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https://www.readbyqxmd.com/read/28081228/resistance-for-genotoxic-damage-in-mesenchymal-stromal-cells-is-increased-by-hypoxia-but-not-generally-dependent-on-p53-regulated-cell-cycle-arrest
#1
Jana Lützkendorf, Elisabeth Wieduwild, Katrin Nerger, Nina Lambrecht, Hans-Joachim Schmoll, Carsten Müller-Tidow, Lutz Peter Müller
Adult stem cells including multipotent mesenchymal stromal cells (MSC) acquire a high amount of DNA-damage due to their prolonged lifespan. MSC may exert specific mechanisms of resistance to avoid loss of functional activity. We have previously shown that resistance of MSC is associated with an induction of p53 and proliferation arrest upon genotoxic damage. Hypoxia may also contribute to resistance in MSC due to the low oxygen tension in the niche. In this study we characterized the role of p53 and contribution of hypoxia in resistance of MSC to genotoxic damage...
2017: PloS One
https://www.readbyqxmd.com/read/28078560/knockdown-of-pycr1-inhibits-cell-proliferation-and-colony-formation-via-cell-cycle-arrest-and-apoptosis-in-prostate-cancer
#2
Tengyue Zeng, Libing Zhu, Min Liao, Wenli Zhuo, Shunliang Yang, Weizhen Wu, Dong Wang
Pyrroline-5-carboxylate reductase 1 (PYCR1) is an enzyme involved in cell metabolism, which has been shown to be up-regulated in cancers. However, the functions of PYCR1 in prostate cancers (PCa) are still largely unknown. In the present study, we found that PYCR1 was highly expressed in prostate cancer tissues and then knocked down PYCR1 in PCa cell lines (DU145, PC-3 and LNCap) via lentivirus-mediated gene delivery and analyzed its biological function. Both qRT-PCR and western blotting indicated that PYCR1 was suppressed efficiently after sh-PYCR1 infection...
February 2017: Medical Oncology
https://www.readbyqxmd.com/read/28062857/positive-feedback-loop-mediated-by-protein-phosphatase-1%C3%AE-mobilization-of-p-tefb-and-basal-cdk1-drives-androgen-receptor-in-prostate-cancer
#3
Xiaming Liu, Yanfei Gao, HuiHui Ye, Sean Gerrin, Fen Ma, Yiming Wu, Tengfei Zhang, Joshua Russo, Changmeng Cai, Xin Yuan, Jihong Liu, Shaoyong Chen, Steven P Balk
P-TEFb (CDK9/cyclin T) plays a central role in androgen receptor (AR)-mediated transactivation by phosphorylating both RNA polymerase 2 complex proteins and AR at S81. CDK9 dephosphorylation mobilizes P-TEFb from an inhibitory 7SK ribonucleoprotein complex, but mechanisms targeting phosphatases to P-TEFb are unclear. We show that AR recruits protein phosphatase 1α (PP1α), resulting in P-TEFb mobilization and CDK9-mediated AR S81 phosphorylation. This increased pS81 enhances p300 recruitment, histone acetylation, BRD4 binding and subsequent further recruitment of P-TEFb, generating a positive feedback loop that sustains transcription...
January 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28059702/cdk-regulated-dimerization-of-m18bp1-on-a-mis18-hexamer-is-necessary-for-cenp-a-loading
#4
Dongqing Pan, Kerstin Klare, Arsen Petrovic, Annika Take, Kai Walstein, Priyanka Singh, Arnaud Rondelet, Alex W Bird, Andrea Musacchio
Centromeres are unique chromosomal loci that promote the assembly of kinetochores, macromolecular complexes that bind spindle microtubules during mitosis. In most organisms, centromeres lack defined genetic features. Rather, they are specified epigenetically by a centromere-specific histone H3 variant, CENP-A. The Mis18 complex, comprising the Mis18α:Mis18β subcomplex and M18BP1, is crucial for CENP-A homeostasis. It recruits the CENP-A specific chaperone HJURP to centromeres and primes it for CENP-A loading...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28053959/sorbus-rufopilosa-extract-exhibits-antioxidant-and-anticancer-activities-by-inducing-cell-cycle-arrest-and-apoptosis-in-human-colon-adenocarcinoma-ht29-cells
#5
You Na Oh, Soojung Jin, Hyun-Jin Park, Hyun Ju Kwon, Byung Woo Kim
BACKGROUND: Sorbus rufopilosa, a tsema rowan, is a species of the small ornamental trees in the genus Sorbus and the family Rosaceae found in East Asia. The bioactivities of S. rufopilosa have not yet been fully determined. The objective of this study is to evaluate the antioxidant and anticancer effects of ethanol extract of S. rufopilosa (EESR) and to determine the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. METHODS: To examine the antioxidant activity of EESR, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity assay was performed...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28051275/ratio-of-proliferation-markers-and-hsp90-gene-expression-as-a-predictor-of-pathological-complete-response-in-breast-cancer-neoadjuvant-chemotherapy
#6
Michal Jarzab, Monika Kowal, Wieslaw Bal, Malgorzata Oczko-Wojciechowska, Justyna Rembak-Szynkiewicz, Malgorzata Kowalska, Ewa Stobiecka, Ewa Chmielik, Tomasz Tyszkiewicz, Malgorzata Kaszuba, Elzbieta Nowicka, Barbara Lange, Agnieszka Czarniecka, Jolanta Krajewska, Alicja Dyla, Miroslaw Dobrut, Dariusz Lange, Barbara Jarzab, Barbara Bobek-Billewicz, Rafal Tarnawski
INTRODUCTION: Prediction of response to preoperative breast cancer chemotherapy may offer a substantial optimization of medical management of this disease. The most efficient prediction would be done a priori, before the start of chemotherapy and based on the biological features of patient and tumor. Numerous markers have been proposed but none of them has been applied as a routine. The role of MKI67 and HSP90 expression has been recently suggested to predict treatment sensitivity in HER2-positive breast cancer...
January 4, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28036090/antiproliferative-effects-of-cynara-cardunculus-l-var-altilis-dc-lipophilic-extracts
#7
Patrícia A B Ramos, Ângela R Guerra, Olinda Guerreiro, Sónia A O Santos, Helena Oliveira, Carmen S R Freire, Armando J D Silvestre, Maria F Duarte
Besides being traditionally used to relieve hepatobiliary disorders, Cynara cardunculus L. has evidenced anticancer potential on triple-negative breast cancer (TNBC). This study highlights the antiproliferative effects of lipophilic extracts from C. cardunculus L. var. altilis (DC) leaves and florets, and of their major compounds, namely cynaropicrin and taraxasteryl acetate, against MDA-MB-231 cells. Our results demonstrated that MDA-MB-231 cells were much less resistant to leaves extract (IC50 10.39 µg/mL) than to florets extract (IC50 315...
December 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28035361/korean-byungkyul-citrus-platymamma-hort-et-tanaka-flavonoids-induces-cell-cycle-arrest-and-apoptosis-regulating-mmp-protein-expression-in-hep3b-hepatocellular-carcinoma-cells
#8
Gyeong Eun Hong, Ho Jeong Lee, Jin A Kim, Silvia Yumnam, Suchismita Raha, Venu Venkatarame Gowda Saralamma, Jeong Doo Heo, Sang Joon Lee, Eun Hee Kim, Chun Kil Won, Gon Sup Kim
Citrus platymamma Hort.et Tanaka is an indigenous fruit of Jeju island in Korea. In this study the bioactivity of C. platymamma flavonoids were evaluated on human hepatoma Hep3B cell lines. Eleven flavonoids were identified from the peels of C. platymamma Hort.et Tanaka through high-performance liquid chromatography-Tandem mass spectrometry and the anticancer effect of these C. platymamma flavonoids on human hepatoma Hep3B were studied. Chromatin condensation was observed in Hep3B cells treated with C. platymamma flavonoids...
December 22, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/28028462/network-based-analysis-of-differentially-expressed-genes-in-cerebrospinal-fluid-csf-and-blood-reveals-new-candidate-genes-for-multiple-sclerosis
#9
Nahid Safari-Alighiarloo, Mostafa Rezaei-Tavirani, Mohammad Taghizadeh, Seyyed Mohammad Tabatabaei, Saeed Namaki
BACKGROUND: The involvement of multiple genes and missing heritability, which are dominant in complex diseases such as multiple sclerosis (MS), entail using network biology to better elucidate their molecular basis and genetic factors. We therefore aimed to integrate interactome (protein-protein interaction (PPI)) and transcriptomes data to construct and analyze PPI networks for MS disease. METHODS: Gene expression profiles in paired cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMCs) samples from MS patients, sampled in relapse or remission and controls, were analyzed...
2016: PeerJ
https://www.readbyqxmd.com/read/28024945/mc37-a-new-mono-carbonyl-curcumin-analog-induces-g2-m-cell-cycle-arrest-and-mitochondria-mediated-apoptosis-in-human-colorectal-cancer-cells
#10
Baoxia Liang, Ziyi Liu, Yingnan Cao, Cuige Zhu, Yinglin Zuo, Lei Huang, Gesi Wen, Nana Shang, Yu Chen, Xin Yue, Jun Du, Baojian Li, Binhua Zhou, Xianzhang Bu
(E)-1-(3'-fluoro-[1,1'-biphenyl-3-yl)-3-(3-hydroxy-4-methoxyphenyl)prop-2-en-1-one) (MC37), a novel mono-carbonyl curcumin analog, was previously synthesized in our laboratory as a nuclear factor kappa B (NF-κB) inhibitor with excellent cytotoxicity against several cancer cell lines. In this study, our further investigations showed that the potent growth inhibitory activity of MC37 in human colorectal cancer cells was associated with the arrest of cell cycle progression and the induction of apoptosis. As a multi-targeted agent, MC37 inhibited the intracellular microtubule assembly, altered the expression of cyclin-dependent kinase 1 (CDK1), and ultimately induced G2/M cell cycle arrest...
December 23, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28017591/a-dual-inhibitory-mechanism-sufficient-to-maintain-cell-cycle-restricted-cenp-a-assembly
#11
Ana Stankovic, Lucie Y Guo, João F Mata, Dani L Bodor, Xing-Jun Cao, Aaron O Bailey, Jeffrey Shabanowitz, Donald F Hunt, Benjamin A Garcia, Ben E Black, Lars E T Jansen
Chromatin featuring the H3 variant CENP-A at the centromere is critical for its mitotic function and epigenetic maintenance. Assembly of centromeric chromatin is restricted to G1 phase through inhibitory action of Cdk1/2 kinases in other phases of the cell cycle. Here, we identify the two key targets sufficient to maintain cell-cycle control of CENP-A assembly. We uncovered a single phosphorylation site in the licensing factor M18BP1 and a cyclin A binding site in the CENP-A chaperone, HJURP, that mediated specific inhibitory phosphorylation...
December 21, 2016: Molecular Cell
https://www.readbyqxmd.com/read/28012276/molecular-basis-of-outer-kinetochore-assembly-on-cenp-t
#12
Pim J Huis In 't Veld, Sadasivam Jeganathan, Arsen Petrovic, Priyanka Singh, Juliane John, Veronica Krenn, Florian Weissmann, Tanja Bange, Andrea Musacchio
Stable kinetochore-microtubule attachment is essential for cell division. It requires recruitment of outer kinetochore microtubule binders by centromere proteins C and T (CENP-C and CENP-T). To study the molecular requirements of kinetochore formation, we reconstituted the binding of the MIS12 and NDC80 outer kinetochore subcomplexes to CENP-C and CENP-T. Whereas CENP-C recruits a single MIS12:NDC80 complex, we show here that CENP-T binds one MIS12:NDC80 and two NDC80 complexes upon phosphorylation by the mitotic CDK1:Cyclin B complex at three distinct CENP-T sites...
December 24, 2016: ELife
https://www.readbyqxmd.com/read/28009971/dacomitinib-a-new-pan-egfr-inhibitor-is-effective-in-killing-ovarian-cancer-cells
#13
Lei Xu, Huini Wu, Chao Jiang, Hongcai Wang, Bei Gao, Shumei Yan, Yushu Qi, Shufeng Zhou
OBJECTIVE: Aberrant epidermal growth factor receptor (EGFR) is involved in a variety of cancers and its inhibitors have been studied for over a decade. We aim to investigate the effects of dacomitinib, a second generation pan-EGFR inhibitor, on ovarian cancer cells. METHODS: By immunohistochemistry, we studied the clinical significance of EGFR expression in epithelial ovarian cancer (EOC). The correlations between EGFR expression and the clinicopathological variables of patients with EOC were assessed using Pearson's X2 test...
November 2016: Discovery Medicine
https://www.readbyqxmd.com/read/28005359/cyclin-dependent-kinase-cdk-inhibitors-structure-activity-relationships-and-insights-into-the-cdk-2-selectivity-of-6-substituted-2-arylaminopurines
#14
Christopher R Coxon, Elizabeth Anscombe, Suzannah Jane Harnor, Mathew P Martin, Benoit Jean-Pierre Carbain, Bernard Thomas Golding, Ian Robert Hardcastle, Lisa K Harlow, Svitlana Korolchuk, Christopher J Matheson, David R Newell, Martin E M Noble, Mangaleswaran Sivaprakasam, Susan J Tudhope, David M Turner, Lan-Zhen Wang, Stephen R Wedge, Christopher Wong, Roger John Griffin, Jane A Endicott, Celine Cano
Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favour competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 4-((6-([1,1'-biphenyl]-3-yl)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency towards CDK2 (IC50 0...
December 22, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28004354/systematic-investigation-of-expression-of-g2-m-transition-genes-reveals-cdc25-alteration-in-nonfunctioning-pituitary-adenomas
#15
Henriett Butz, Kinga Németh, Dóra Czenke, István Likó, Sándor Czirják, Vladimir Zivkovic, Kornélia Baghy, Márta Korbonits, Ilona Kovalszky, Péter Igaz, Károly Rácz, Attila Patócs
Dysregulation of G1/S checkpoint of cell cycle has been reported in pituitary adenomas. In addition, our previous finding showing that deregulation of Wee1 kinase by microRNAs together with other studies demonstrating alteration of G2/M transition in nonfunctioning pituitary adenomas (NFPAs) suggest that G2/M transition may also be important in pituitary tumorigenesis. To systematically study the expression of members of the G2/M transition in NFPAs and to investigate potential microRNA (miRNA) involvement...
December 21, 2016: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/27998224/phase-ii-study-of-wee1-inhibitor-azd1775-plus-carboplatin-in-patients-with-tp53-mutated-ovarian-cancer-refractory-or-resistant-to-first-line-therapy-within-3-months
#16
Suzanne Leijen, Robin M J M van Geel, Gabe S Sonke, Daphne de Jong, Efraim H Rosenberg, Serena Marchetti, Dick Pluim, Erik van Werkhoven, Shelonitda Rose, Mark A Lee, Tomoko Freshwater, Jos H Beijnen, Jan H M Schellens
Purpose AZD1775 is a first-in-class, potent, and selective inhibitor of WEE1 with proof of chemopotentiation in p53-deficient tumors in preclinical models. In a phase I study, the maximum tolerated dose of AZD1775 in combination with carboplatin demonstrated target engagement. We conducted a proof-of-principle phase II study in patients with p53 tumor suppressor gene ( TP53)-mutated ovarian cancer refractory or resistant (< 3 months) to first-line platinum-based therapy to determine overall response rate, progression-free and overall survival, pharmacokinetics, and modulation of phosphorylated cyclin-dependent kinase (CDK1) in skin biopsies...
December 20, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27997828/a-mechanism-for-controlled-breakage-of-under-replicated-chromosomes-during-mitosis
#17
Heike Duda, Meret Arter, Jiradet Gloggnitzer, Federico Teloni, Philipp Wild, Miguel G Blanco, Matthias Altmeyer, Joao Matos
While DNA replication and mitosis occur in a sequential manner, precisely how cells maintain their temporal separation and order remains elusive. Here, we unveil a double-negative feedback loop between replication intermediates and an M-phase-specific structure-selective endonuclease, MUS81-SLX4, which renders DNA replication and mitosis mutually exclusive. MUS81 nuclease is constitutively active throughout the cell cycle but requires association with SLX4 for efficient substrate targeting. To preclude toxic processing of replicating chromosomes, WEE1 kinase restrains CDK1 and PLK1-mediated MUS81-SLX4 assembly during S phase...
December 19, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27997336/transcriptional-signatures-of-somatic-neoblasts-and-germline-cells-in-macrostomum-lignano
#18
Magda Grudniewska, Stijn Mouton, Daniil Simanov, Frank Beltman, Margriet Grelling, Katrien de Mulder, Wibowo Arindrarto, Philipp M Weissert, Stefan van der Elst, Eugene Berezikov
The regeneration-capable flatworm Macrostomum lignano is a powerful model organism to study the biology of stem cells in vivo. As a flatworm amenable to transgenesis, it complements the historically used planarian flatworm models, such as Schmidtea mediterranea. However, information on the transcriptome and markers of stem cells in M. lignano is limited. We generated a de novo transcriptome assembly and performed the first comprehensive characterization of gene expression in the proliferating cells of M. lignano, represented by somatic stem cells, called neoblasts, and germline cells...
December 20, 2016: ELife
https://www.readbyqxmd.com/read/27994737/scaffold-hopping-of-aurones-2-arylideneimidazo-1-2-a-pyridinones-as-topoisomerase-ii%C3%AE-inhibiting-anticancer-agents
#19
Garima Priyadarshani, Anmada Nayak, Suyog M Amrutkar, Sarita Das, Sankar K Guchhait, Chanakya N Kundu, Uttam C Banerjee
Scaffold-hopping of bioactive natural product aurones has been studied for the first time. 2-Arylideneimidazo[1,2-a]pyridinones as potential topoisomerase IIα (hTopoIIα)-targeting anticancer compounds were considered. A multifunctional activator, polyphosphoric acid, enabled to realize a cascade reaction of 2-aminopyridine with 2,3-epoxyesters toward synthesis of 2-arylideneimidazo[1,2-a]pyridinones. Most of the compounds exhibited hTopoIIα-selective poison activity with efficiency more than etoposide and DNA-binding property, while not interacting with hTopo I...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27991932/egf-mediated-inhibition-of-ubiquitin-specific-peptidase-24-expression-has-a-crucial-role-in-tumorigenesis
#20
S-A Wang, Y-C Wang, Y-P Chuang, Y-H Huang, W-C Su, W-C Chang, J-J Hung
In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. Silencing USP24 increases the cancer formation by inhibiting cellular apoptosis and increasing cellular proliferation. Epidermal growth factor (EGF) treatment, and the Kras(G12D) and EGFR(L858R) mutations decrease USP24 protein stability via EGF- or CDK1-mediated phosphorylation at Ser1616, Ser2047 and Ser2604...
December 19, 2016: Oncogene
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