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https://www.readbyqxmd.com/read/28615297/disruption-of-aneuploidy-and-senescence-induced-by-aurora-inhibition-promotes-intrinsic-apoptosis-in-double-hit-or-double-expressor-diffuse-large-b-cell-lymphomas
#1
Daruka Mahadevan, Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings
Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ~30%, while ~70% are aneuploid and senescent cells (AASCs), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28599419/a-conditionally-replicating-adenovirus-expressing-il-24-acts-synergistically-with-temozolomide-to-enhance-apoptosis-in-melanoma-cells-in-vitro
#2
Zhen Liang, Chun-Sheng Yang, Feng Gu, Lan-Sheng Zhang
Malignant melanoma is characterized by suppressed apoptosis in tumor cells and high levels of invasion. Temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and frequently. Therapeutic cytokines such as interleukin-24 (IL-24) and conditionally replicating adenoviruses have exhibited promising results as complementary therapies. Thus, the present study hypothesized that a conditionally replicating adenovirus expressing IL-24 combined with TMZ may exhibit increased antitumor activity compared with either treatment alone in melanoma A375 and M14 cell lines in vitro...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28596365/pcgf3-5-prc1-initiates-polycomb-recruitment-in-x-chromosome-inactivation
#3
Mafalda Almeida, Greta Pintacuda, Osamu Masui, Yoko Koseki, Michal Gdula, Andrea Cerase, David Brown, Arne Mould, Cassandravictoria Innocent, Manabu Nakayama, Lothar Schermelleh, Tatyana B Nesterova, Haruhiko Koseki, Neil Brockdorff
Recruitment of the Polycomb repressive complexes PRC1 and PRC2 by Xist RNA is an important paradigm for chromatin regulation by long noncoding RNAs. Here, we show that the noncanonical Polycomb group RING finger 3/5 (PCGF3/5)-PRC1 complex initiates recruitment of both PRC1 and PRC2 in response to Xist RNA expression. PCGF3/5-PRC1-mediated ubiquitylation of histone H2A signals recruitment of other noncanonical PRC1 complexes and of PRC2, the latter leading to deposition of histone H3 lysine 27 methylation chromosome-wide...
June 9, 2017: Science
https://www.readbyqxmd.com/read/28590415/the-dual-roles-of-myc-in-genomic-instability-and-cancer-chemoresistance
#4
REVIEW
Alpana Kumari, Watson P Folk, Daitoku Sakamuro
Cancer is associated with genomic instability and aging. Genomic instability stimulates tumorigenesis, whereas deregulation of oncogenes accelerates DNA replication and increases genomic instability. It is therefore reasonable to assume a positive feedback loop between genomic instability and oncogenic stress. Consistent with this premise, overexpression of the MYC transcription factor increases the phosphorylation of serine 139 in histone H2AX (member X of the core histone H2A family), which forms so-called γH2AX, the most widely recognized surrogate biomarker of double-stranded DNA breaks (DSBs)...
June 7, 2017: Genes
https://www.readbyqxmd.com/read/28583816/tert-butylhydroquinone-protects-pc12%C3%A2-cells-against-ferrous-sulfate-induced-oxidative-and-inflammatory-injury-via-the-nrf2-are-pathway
#5
Wenzhe Xu, Feng Li, Zhenkuan Xu, Bin Sun, Jingwei Cao, Yuguang Liu
Increasing evidence had proved the critical role of iron in the pathogenesis of numerous neurodegenerative diseases because of its capacity to promote the formation of reactive oxygen species (ROS). Tert-butylhydroquinone (tBHQ) was a metabolite of butylated hydroxyanisole, a widely used food antioxidant. This study was aimed to investigate the protective effects of tBHQ on a cellular model of neurodegenerative disease, which was established in PC12 cells by exposure to ferrous sulfate (FS), and elucidate the potential protective mechanisms...
June 2, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28573252/induction-of-cell-cycle-arrest-and-apoptosis-by-ormenis-eriolepis-a-morrocan-endemic-plant-in-various-human-cancer-cell-lines
#6
Lamiae Belayachi, Clara Aceves-Luquero, Nawel Merghoub, Silvia Fernández de Mattos, Saaîd Amzazi, Priam Villalonga, Youssef Bakri
BACKGROUND: Ormenis eriolepis Coss (Asteraceae) is an endemic Moroccan subspecies, traditionally named "Hellala" or "Fergoga". It's usually used for its hypoglycemic effect as well as for the treatment of stomacal pain. As far as we know, there is no scientific exploration of anti tumoral activity of Ormenis eriolepis extracts. MATERIALS AND METHODS: In this regard, we performed a screening of organic extracts and fractions in a panel of both hematological and solid cancer cell lines, to evaluate the potential in vitro anti tumoral activity and to elucidate the respective mechanisms that may be responsible for growth arrest and cell death induction...
2017: African Journal of Traditional, Complementary, and Alternative Medicines: AJTCAM
https://www.readbyqxmd.com/read/28572698/phosphorylation-of-histone-h2a-x-in-peripheral-blood-mononuclear-cells-may-be-a-useful-marker-for-monitoring-cardiometabolic-risk-in-nondiabetic-individuals
#7
So Ra Yoon, Juhyun Song, Jong Hwa Lee, Oh Yoen Kim
Phosphorylation of H2A.X (serine 139) in the histone H2A family located in the downstream of the DNA damage kinase signaling cascade is an important indicator of DNA damage. Recently, phosphorylation of H2A.X was proposed as a sensitive biomarker of aging. This study investigated if phosphorylation of H2A.X in peripheral blood mononuclear cells (PBMCs) is associated with cardiometabolic risk in nondiabetic individuals. Basic parameters and oxidative stress/inflammatory markers were measured in nondiabetic healthy Koreans (n = 119)...
2017: Disease Markers
https://www.readbyqxmd.com/read/28546332/establishing-177-lu-psma-617-radioligand-therapy-in-a-syngeneic-model-of-murine-prostate-cancer
#8
Wolfgang P Fendler, Andreea D Stuparu, Susan Evans-Axelsson, Katharina Lückerath, Liu Wei, Woosuk Kim, Soumya Poddar, Jonathan Said, Caius G Radu, Matthias Eiber, Johannes Czernin, Roger Slavik, Ken Herrmann
Clinical (177)Lu-PSMA-617 radioligand therapy (RLT) is applied in advanced stage prostate cancer. However, to the best of our knowledge murine models to study the biological effects of various activity levels have not been established. AIM: To optimize specific and total activity for (177)Lu-PSMA-617 RLT in a syngeneic model of murine prostate cancer. Methods: 0.1x106 murine reconstituted, oncogene-driven prostate cancer cells (RM1), transduced to express human prostate-specific membrane antigen (PSMA), were injected into the left flank of C57Bl6 immunocompetent mice...
May 25, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28529619/effects-of-prolonged-exposure-to-low-dose-metformin-in-thyroid-cancer-cell-lines
#9
Safar Kheder, Karen Sisley, Sirwan Hadad, Sabapathy P Balasubramanian
Background: Thyroid cancer is generally associated with an excellent prognosis, but there is significant long-term morbidity with standard treatment. Some sub-types however have a poor prognosis. Metformin, an oral anti-diabetic drug is shown to have anti-cancer effects in several types of cancer (breast, lung and ovarian cancer). The proposed mechanisms include activation of the Adenosine Mono-phosphate-activated Protein Kinase (AMPK) pathway and inhibition of the mTOR pathway (which promotes growth and proliferation)...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28526910/expression-and-regulation-of-type-2a-protein-phosphatases-and-alpha4-signalling-in-cardiac-health-and-hypertrophy
#10
Olga Eleftheriadou, Andrii Boguslavskyi, Michael R Longman, Jonathan Cowan, Asvi Francois, Richard J Heads, Brian E Wadzinski, Ali Ryan, Michael J Shattock, Andrew K Snabaitis
Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACβ > PP2ACα > PP4C > PP6C), NRVM (PP2ACβ > PP2ACα = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACα > PP2ACβ > PP6C > PP4C)...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28492345/the-focinator-v2-0-graphical-interface-four-channels-colocalization-analysis-and-cell-phase-identification
#11
Sebastian Oeck, Nathalie M Malewicz, Sebastian Hurst, Klaudia Al-Refae, Adam Krysztofiak, Verena Jendrossek
The quantitative analysis of foci plays an important role in various cell biological methods. In the fields of radiation biology and experimental oncology, the effect of ionizing radiation, chemotherapy or molecularly targeted drugs on DNA damage induction and repair is frequently performed by the analysis of protein clusters or phosphorylated proteins recruited to so called repair foci at DNA damage sites, involving for example γ-H2A.X, 53BP1 or RAD51. We recently developed "The Focinator" as a reliable and fast tool for automated quantitative and qualitative analysis of nuclei and DNA damage foci...
May 11, 2017: Radiation Research
https://www.readbyqxmd.com/read/28491095/angelica-sinensis-polysaccharide-prevents-hematopoietic-stem-cells-senescence-in-d-galactose-induced-aging-mouse-model
#12
Xinyi Mu, Yanyan Zhang, Jing Li, Jieyu Xia, Xiongbin Chen, Pengwei Jing, Xiaoying Song, Lu Wang, Yaping Wang
Age-related regression in hematopoietic stem/progenitor cells (HSC/HPCs) limits replenishment of the blood and immune system and hence contributes to hematopoietic diseases and declined immunity. In this study, we employed D-gal-induced aging mouse model and observed the antiaging effects of Angelica Sinensis Polysaccharide (ASP), a major active ingredient in dong quai (Chinese Angelica Sinensis), on the Sca-1(+) HSC/HPCs in vivo. ASP treatment prevents HSC/HPCs senescence with decreased AGEs levels in the serum, reduced SA-β-Gal positive cells, and promoted CFU-Mix formation in the D-gal administrated mouse...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28487971/azidothymidine-inhibits-cell-growth-and-telomerase-activity-and-induces-dna-damage-in-human-esophageal-cancer
#13
Haoli Wang, Jianwen Zhou, Qiong He, Yu Dong, Yanhui Liu
Esophageal cancer is one of the most common type of malignancies. Telomerase activity, which is absent or weakly detected in the majority of human somatic cells, is elevated in esophageal cancer. Although azidothymidine (AZT), a reverse transcriptase inhibitor, has been utilized as a treatment for tumors, its role in treating esophageal cancer has not been confirmed. The aim of the present study was to determine the effect of AZT on telomerase activity and the proliferation of the human esophageal cancer cell line TE‑11...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28454371/synergistic-effects-of-a-novel-lipid-soluble-extract-from-pinellia-pedatisecta-schott-and-cisplatin-on-human-cervical-carcinoma-cell-lines-through-the-regulation-of-dna-damage-response-signaling-pathway
#14
Mingxing Zhang, Hongwei Zhang, Yi Yu, Haixia Huang, Guiling Li, Congjian Xu
Herbal medicines have been recognized as an attractive approach for cancer therapy with minimal side effects. The present study investigated the type of interaction between a novel lipid-soluble extract from Pinellia pedatisecta Schott (PE) and cisplatin (CDDP) on human cervical cancer SiHa and CaSki cell lines in vitro. The mechanism of this combination was studied using cell proliferation, invasion and apoptosis assays, and by analyzing cell cycle distribution and protein expression, with a focus on DNA damage response (DDR) activation...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28442502/ribonucleotide-reductase-large-subunit-rrm1-as-a-novel-therapeutic-target-in-multiple-myeloma
#15
Morihiko Sagawa, Hiroto Ohguchi, Takeshi Harada, Mehmet K Samur, Yu-Tzu Tai, Nikhil C Munshi, Masahiro Kizaki, Teru Hideshima, Kenneth C Anderson
Purpose: To investigate the biologic and clinical significance of ribonucleotide reductase (RR) in multiple myeloma (MM). <p>Experimental Design: We assessed the impact of RR expression on patient outcome in MM. We then characterized the effect of genetic and pharmacological inhibition of RRM1 on MM growth and survival using siRNA and clofarabine (CLO), respectively, both in vitro and in vivo mouse xenograft model.</p> <p>Results: Newly diagnosed MM patients with higher RRM1 expression have shortened survival...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28436335/localization-of-the-werner-protein-together-with-h2ax-in-%C3%AE-irradiation-induced-neoplastic-transformed-human-mesenchymal-stem-cells
#16
Nedime Serakinci, Tufan Cankaya, Steen Kølvraa
The H2A histone family, member X (H2AX), and Werner (WRN) are important proteins for genome and telomere maintenance. WRN has a major role in genome stability, particularly during DNA replication, transcription, recombination, and repair of DNA double-stranded breaks (DSBs) via base excision repair, homologous recombination, or nonhomologous end joining. H2AX plays a part in the rapid, sensitive, cellular response to the ionizing radiation or DNA-damaging chemotherapeutic agents that cause DSBs. This occurs when radiation-induced DSBs trigger the activation of H2AX and begin the damage-repair process...
2017: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/28392109/compartmentalization-of-dna-damage-response-between-heterochromatin-and-euchromatin-is-mediated-by-distinct-h2a-histone-variants
#17
Zdravko J Lorković, Chulmin Park, Malgorzata Goiser, Danhua Jiang, Marie-Therese Kurzbauer, Peter Schlögelhofer, Frédéric Berger
DNA double-strand break (DSB) repair depends on the ataxia telangiectasia mutated (ATM) kinase that phosphorylates the conserved C-terminal SQ motif present in the histone variant H2A.X [1-7]. In constitutive heterochromatin of mammals, DSB repair is delayed and relies on phosphorylation of the proteins HP1 and KAP1 by ATM [2, 8-14]. However, KAP1 is not conserved in plants and the HP1-related protein Like-HP1 (LHP1) is not localized at constitutive heterochromatin [15], suggesting that in plants, alternative mechanisms could be responsible for repair of DSBs in heterochromatin...
April 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28356983/tcn-an-akt-inhibitor-exhibits-potent-antitumor-activity-and-enhances-radiosensitivity-in-hypoxic-esophageal-squamous-cell-carcinoma-in-vitro-and-in-vivo
#18
Qing Guo, Jia He, Feng Shen, Wei Zhang, Xi Yang, Chi Zhang, Qu Zhang, Jun-Xing Huang, Zheng-Dong Wu, Xin-Chen Sun, Sheng-Bin Dai
The aim of the present study was to investigate the radiosensitization effect of triciribine (TCN) on human esophageal squamous cell carcinoma (ESCC) in normoxia or hypoxia and its mechanism. The cytotoxicity and radiosensitization mechanism of TCN were investigated by Cell Counting Kit 8, clonogenic assay, flow cytometry, western blotting (WB) and immunofluorescence staining of phospho-histone H2A.X, Ser139 (γ-H2AX) in ESCC in vitro, while the protein expression levels of AKT, phosphorylated (p)-AKT, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were evaluated by WB in vivo...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351316/novel-tetrahydroacridine-and-cyclopentaquinoline-derivatives-with-fluorobenzoic-acid-moiety-induce-cell-cycle-arrest-and-apoptosis-in-lung-cancer-cells-by-activation-of-dna-damage-signaling
#19
Paweł Szymański, Paulina Olszewska, Elżbieta Mikiciuk-Olasik, Antoni Różalski, Agnieszka Maszewska, Łukasz Markiewicz, Magda Cuchra, Ireneusz Majsterek
Lung cancer is still the leading cause of cancer-related death worldwide, indicating a necessity to develop more effective therapy. Acridine derivatives are potential anticancer agents due to their ability to intercalate DNA as well as inhibit enzymes involved in replication and transcription. Recently, we have evaluated anticancer activity of 32 novel acridine-based compounds. We found that the most effective were tetrahydroacridine and cyclopentaquinoline derivatives with fluorobenzoic acid containing eight and nine carbon atoms in the aliphatic chain...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28350066/dna-damage-response-defect-in-williams-beuren-syndrome
#20
David Guenat, Giuseppe Merla, Eric Deconinck, Christophe Borg, Pierre-Simon Rohrlich
Williams-Beuren syndrome (WBS, no. OMIM 194050) is a rare multisystem genetic disorder caused by a microdeletion on chromosome 7q11.23 and characterized by cardiovascular malformations, mental retardation, and a specific facial dysmorphism. Recently, we reported that a series of non‑Hodgkin's lymphoma occurs in children with WBS and thus hypothesized that a predisposition to cancer may be associated with this genetic disorder. The aim of the present study was to ascertain the role played by three genes hemizygously deleted in WBS (RFC2, GTF2I and BAZ1B) in DNA damage response pathways...
January 17, 2017: International Journal of Molecular Medicine
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