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https://www.readbyqxmd.com/read/28524761/when-dna-damage-is-acceptable
#1
Vicente Planelles
No abstract text is available yet for this article.
May 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28521657/several-inhibitors-of-the-plk1-polo-box-domain-turn-out-to-be-non-specific-protein-alkylators
#2
Vincent Archambault, Karine Normandin
For almost a decade, there has been much interest in the development of chemical inhibitors of Polo-like kinase 1 (Plk1) protein interactions. Plk1 is a master regulator of the cell division cycle that controls numerous substrates. It is a promising target for cancer drug development. Inhibitors of the kinase domain of Plk1 had some success in clinical trials. However, they are not perfectly selective. In principle, Plk1 can also be inhibited by interfering with its protein interaction domain, the Polo-Box Domain (PBD)...
May 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28514186/apc-c-cdc20-mediates-deprotection-of-centromeric-cohesin-at-meiosis-ii-in-yeast
#3
Katarzyna Jonak, Ievgeniia Zagoriy, Tugce Oz, Peter Graf, Julie Rojas, Valentina Mengoli, Wolfgang Zachariae
Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by two rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage...
May 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28494180/intra-arterial-administration-of-tumor-targeting-salmonella-typhimurium-a1-r-regresses-a-cisplatin-resistant-relapsed-osteosarcoma-in-a-patient-derived-orthotopic-xenograft-pdox-mouse-model
#4
Kentaro Igarashi, Kei Kawaguchi, Takashi Murakami, Tasuku Kiyuna, Kentaro Miyake, Scott D Nelson, Sarah M Dry, Yunfeng Li, Jane Yanagawa, Tara A Russell, Arun S Singh, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Hiroyuki Tsuchiya, Fritz C Eilber, Robert M Hoffman
Previously, a patient-derived orthotopic xenograft (PDOX) model was established with a lung metastasis from an osteosarcoma patient which developed after adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared to CDDP. In the previous report, osteosarcoma tissue was implanted orthotopically in the distal femur of mice which were randomized into the following groups when tumor volume reached approximately 100 mm(3): On day 14 after initiation of treatment, all but CDDP treatments significantly inhibited tumor growth compared to untreated control: control (G1): 793...
May 11, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28489985/preclinical-evaluation-of-the-imipridone-family-analogues-of-clinical-stage-anti-cancer-small-molecule-onc201-reveals-potent-anti-cancer-effects-of-onc212
#5
Jessica Wagner, Christina Leah Kline, Marie D Ralff, Avital Lev, Amriti Lulla, Lanlan Zhou, Gary L Olson, Bhaskara Rao Nallaganchu, Cyril H Benes, Joshua E Allen, Varun V Prabhu, Martin Stogniew, Wolfgang Oster, Wafik S El-Deiry
Anti-cancer small molecule ONC201 upregulates the integrated stress response (ISR) and acts as a dual inactivator of Akt/ERK, leading to TRAIL gene activation. ONC201 is under investigation in multiple clinical trials to treat patients with cancer. Given the unique imipridone core chemical structure of ONC201, we synthesized a series of analogues to identify additional compounds with distinct therapeutic properties. Several imipridones with a broad range of in vitro potencies were identified in an exploration of chemical derivatives...
May 10, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28486050/the-cdk4-6-inhibitor-palbociclib-synergizes-with-irinotecan-to-promote-colorectal-cancer-cell-death-under-hypoxia
#6
Jun Zhang, Lanlan Zhou, Shuai Zhao, David T Dicker, Wafik S El-Deiry
Hypoxia is an inherent impediment to cancer therapy. Palbociclib, a highly selective inhibitor for CDK4/6, has been tested in numerous clinical trials and has been approved by the FDA. We previously reported that CDK inhibitors can destabilize HIF1α regardless of the presence of hypoxia and can sensitize tumor cells to TRAIL through dual blockade of CDK1 and GSK3-β. In order to translate this knowledge into a cancer therapeutic strategy, we investigated the therapeutic effects and molecular mechanisms of CDK inhibition against colon cancer cells under normoxia and hypoxia...
May 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28486014/tissue-tgf-%C3%AE-expression-following-conventional-radiotherapy-and-pulsed-low-dose-rate-radiation
#7
Joshua E Meyer, Niklas K Finnberg, Lili Chen, Dusica Cvetkovic, Bin Wang, Lanlan Zhou, Yanqun Dong, Mark A Hallman, Chang-Ming C Ma, Wafik S El-Deiry
The release of inflammatory cytokines has been implicated in the toxicity of conventional radiotherapy (CRT). Transforming growth factor β (TGF-β) has been suggested to be a risk marker for pulmonary toxicity following radiotherapy. Pulsed low-dose rate radiotherapy (PLDR) is a technique that involves spreading out a conventional radiotherapy dose into short pulses of dose with breaks in between to reduce toxicities. We hypothesized that the more tolerable toxicity profile of PLDR compared with CRT may be related to differential expression of inflammatory cytokines such as TGF-β in normal tissues...
May 9, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28475398/persistent-response-of-fanconi-anemia-haematopoietic-stem-and-progenitor-cells-to-oxidative-stress
#8
Yibo Li, Surya Amarachintha, Andrew F Wilson, Xue Li, Wei Du
Oxidative stress is considered as an important pathogenic factor in many human diseases including Fanconi anemia (FA), an inherited bone marrow failure syndrome with extremely high risk of leukemic transformation. Members of the FA protein family are involved in DNA damage and other cellular stress responses. Loss of FA proteins renders cells hypersensitive to oxidative stress and cancer transformation. However, how FA cells respond to oxidative DNA damage remains unclear. By using an in vivo stress-response mouse strain expressing the Gadd45β-luciferase transgene, we show here that haematopoietic stem and progenitor cells (HSPCs) from mice deficient for the FA gene Fanca or Fancc persistently responded to oxidative stress...
May 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28471715/crossover-maturation-inefficiency-and-aneuploidy-in-human-female-meiosis
#9
Shunxin Wang, Nancy Kleckner, Liangran Zhang
No abstract text is available yet for this article.
May 4, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28471288/hoxc6-loss-of-function-truncates-the-main-body-axis-in-xenopus
#10
Kongju Zhu, Herman P Spaink, Antony J Durston
No abstract text is available yet for this article.
May 4, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28463579/peroxisomal-acbd4-interacts-with-vapb-and-promotes-er-peroxisome-associations
#11
Joseph L Costello, Inês G Castro, Tina A Schrader, Markus Islinger, Michael Schrader
Cooperation between cellular organelles such as mitochondria, peroxisomes and the ER is essential for a variety of important and diverse metabolic processes. Effective communication and metabolite exchange requires physical linkages between the organelles, predominantly in the form of organelle contact sites. At such contact sites organelle membranes are brought into close proximity by the action of molecular tethers, which often consist of specific protein pairs anchored in the membrane of the opposing organelles...
May 2, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28463531/hypoxia-favors-the-generation-of-human-plasma-cells
#12
Matthieu Schoenhals, Michel Jourdan, Angélique Bruyer, Alboukadel Kassambara, Bernard Klein, Jérôme Moreaux
Plasma cells (PCs) generation occurs in hypoxic conditions in vivo, whereas the relevance of O2 pressure in PC differentiation remains unknown. Using our in vitro PC differentiation model, we investigated the role of hypoxia in PC generation. Hypoxia increases the generation of plasmablasts (PBs) starting from memory B cells, by increasing cell cycle and division number. Reactome analysis demonstrated a significant enrichment of genes involved in HIF1α and HIF2α transcription factor network, metabolism and MYC related pathways in hypoxic compared with normoxic PBs...
May 2, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28463527/cytidine-deaminase-deficiency-impairs-sister-chromatid-disjunction-by-decreasing-parp-1-activity
#13
Simon Gemble, Géraldine Buhagiar-Labarchède, Rosine Onclercq-Delic, Christian Jaulin, Mounira Amor-Guéret
Bloom Syndrome (BS) is a rare genetic disease characterized by high levels of chromosomal instability and an increase in cancer risk. Cytidine deaminase (CDA) expression is downregulated in BS cells, leading to an excess of cellular dC and dCTP that reduces basal PARP-1 activity, compromising optimal Chk1 activation and reducing the efficiency of downstream checkpoints. This process leads to the accumulation of unreplicated DNA during mitosis and, ultimately, ultrafine anaphase bridge (UFB) formation. BS cells also display incomplete sister chromatid disjunction when depleted of cohesin...
May 2, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28463091/curcumin-increases-efficiency-of-%C3%AE-irradiation-in-gliomas-by-inhibiting-hedgehog-signaling-pathway
#14
Xiangqi Meng, Jinquan Cai, Jichao Liu, Bo Han, Fei Gao, Weida Gao, Yao Zhang, Jinwei Zhang, Zhefeng Zhao, Chuanlu Jiang
It was reported that γ-irradiation had a controversial therapeutic effect on glioma cells. We aimed to investigate the cytotoxic effect on the glioma cells induced by γ-irradiation and explore the treatment to rescue the phenotype alteration of remaining cells. We used transwell assay to detect the glioma cell invasion and migration capacity. Cell proliferation and apoptosis were tested by the CCK-8 assay and flow cytometry respectively. Western Blot was used to detect the activity of Hedgehog signaling pathway and Epithelial-to-Mesenchymal Transition (EMT) status...
May 2, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28459381/arsenic-and-sumo-wrestling-in-protein-modification
#15
Lingzhi Li, Fei Chen
No abstract text is available yet for this article.
May 1, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28459356/integrins-in-senescence-and-aging
#16
Michela Borghesan, Ana O'Loghlen
No abstract text is available yet for this article.
May 1, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28453388/susceptibility-of-atm-deficient-pancreatic-cancer-cells-to-radiation
#17
Michael Ayars, James Eshleman, Michael Goggins
Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay...
April 28, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28441108/novel-clades-of-the-hu-ihf-superfamily-point-to-unexpected-roles-in-the-eukaryotic-centrosome-chromosome-partitioning-and-biologic-conflicts
#18
A Maxwell Burroughs, Gurmeet Kaur, Dapeng Zhang, L Aravind
The HU superfamily of proteins, with a unique DNA-binding mode, has been extensively studied as the primary chromosome-packaging protein of the bacterial superkingdom. Representatives also play a role in DNA-structuring during recombination events and in eukaryotic organellar genome maintenance. However, beyond these well-studied roles, little is understood of the functional diversification of this large superfamily. Using sensitive sequence and structure analysis methods we identify multiple novel clades of the HU superfamily...
April 25, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28441080/color-coded-intravital-imaging-demonstrates-a-transforming-growth-factor-%C3%AE-tgf-%C3%AE-antagonist-selectively-targets-stromal-cells-in-a-human-pancreatic-cancer-orthotopic-mouse-model
#19
Takashi Murakami, Yukihiko Hiroshima, Kentaro Miyake, Ho Kyoung Hwang, Tasuku Kiyuna, Jonathan C DeLong, Thinzar M Lwin, Ryusei Matsuyama, Ryutaro Mori, Takafumi Kumamoto, Takashi Chishima, Kuniya Tanaka, Yasushi Ichikawa, Michael Bouvet, Itaru Endo, Robert M Hoffman
Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma which stimulates tumor growth, invasion, and metastasis, and inhibits chemotherapeutic drug delivery. Transforming growth factor-β (TGF-β) has an important role in the formation of stromal desmoplasia. The present study describes the ability of color-coded intravital imaging to demonstrate the efficacy of a TGF-β inhibitor to target stroma in an orthotopic mouse model of pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line expressing green fluorescent protein (GFP), which also has a high TGF-β expression level, was used in an orthotopic model in transgenic nude mice ubiquitously expressing red fluorescent protein (RFP)...
April 25, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28437168/regulation-of-pten-degradation-and-nedd4-1-e3-ligase-activity-by-numb
#20
Chen Shao, Zhiguo Li, Nihal Ahmad, Xiaoqi Liu
The critical tumor suppressor PTEN is regulated by numerous post-translational modifications including phosphorylation, acetylation and ubiquitination. Ubiquitination of PTEN was reported to control both PTEN stability and nuclear localization. Notably, the HECT E3-ligase NEDD4-1 was identified as the ubiquitin ligase for PTEN, mediating its degradation and down-stream events. However, the mechanisms how NEDD4-1 is regulated by up-stream signaling pathways or interaction with other proteins in promoting PTEN degradation remain largely unclear...
April 24, 2017: Cell Cycle
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