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https://www.readbyqxmd.com/read/28279624/p21-a-two-faced-genome-guardian
#1
REVIEW
Alexandros G Georgakilas, Olga A Martin, William M Bonner
Upon DNA damage or other stressors, the tumor suppressor p53 is activated, leading to transient expression of the cyclin-dependent kinase inhibitor (CKI) p21. This either triggers momentary G1 cell cycle arrest or leads to a chronic state of senescence or apoptosis, a form of genome guardianship. In the clinic, the presence of p21 has been considered an indicator of wildtype p53 activity. However, recent evidence suggests that p21 also acts as an oncogenic factor in a p53-deficient environment. Here, we discuss the controversial aspects of the two-faced involvement of p21 in cancer and speculate on how this new information may increase our understanding of its role in cancer pathogenesis...
March 6, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28246584/from-targeting-the-tumor-to-targeting-the-immune-system-transversal-challenges-in-oncology-with-the-inhibition-of-the-pd-1-pd-l1-axis
#2
REVIEW
Melissa Bersanelli, Sebastiano Buti
After that the era of chemotherapy in the treatment of solid tumors have been overcome by the "translational era", with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new "immunotherapy era" with the advent of immune checkpoint inhibitors (CKI) antibodies. The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers. The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types...
February 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28169243/efficacy-of-compound-kushen-injection-plus-radiotherapy-on-nonsmall-cell-lungcancer-a-systematic-review-and-meta-analysis
#3
REVIEW
Shanshan Wang, Xiaobo Lian, Miaomiao Sun, Lei Luo, Lizhong Guo
OBJECTIVE: To evaluate the benefits of compound Kushen injection (CKI) combined with radiotherapy for nonsmall cell lung cancer. MATERIALS AND METHODS: We searched nine electronic databases and six gray literature databases comprehensively until June 2015. Two reviewers independently selected and assessed the included trials according to the inclusion and exclusion criteria. The risk of bias tool from the Cochrane Handbook version 5.1.0, the Review Manager 5.3 software was employed for data analysis...
October 2016: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28115244/identification-expression-pattern-and-functional-characterization-of-as-kip2-in-diapause-embryo-restarting-process-of-artemia-sinica
#4
Mengchen Zhang, Feng Yao, Tong Qin, Lin Hou, Xiangyang Zou
Proper control of the cellular processes requires a variety of regulatory proteins that are involved in the cell cycle, proliferation and apoptosis. Cyclin-dependent kinase inhibitor (CKI) negatively regulates transcription and arrests the cell cycle in G1 phase. KIP2 is a member of CKI family, which could inhibit proliferation by tight-binding with several cyclin-CDK complexes. During the embryonic development of the brine shrimp, Artemia sinica, KIP2 plays a key role in the cell cycle regulation, but the specific mechanisms remain unknown...
April 15, 2017: Gene
https://www.readbyqxmd.com/read/28049764/the-scf%C3%AE-trcp-e3-ubiquitin-ligase-complex-targets-lipin1-for-ubiquitination-and-degradation-to-promote-hepatic-lipogenesis
#5
Kouhei Shimizu, Hidefumi Fukushima, Kohei Ogura, Evan C Lien, Naoe Taira Nihira, Jinfang Zhang, Brian J North, Ailan Guo, Katsuyuki Nagashima, Tadashi Nakagawa, Seira Hoshikawa, Asami Watahiki, Koji Okabe, Aya Yamada, Alex Toker, John M Asara, Satoshi Fukumoto, Keiichi I Nakayama, Keiko Nakayama, Hiroyuki Inuzuka, Wenyi Wei
The SCF(β-TRCP) E3 ubiquitin ligase complex plays pivotal roles in normal cellular physiology and in pathophysiological conditions. Identification of β-transducin repeat-containing protein (β-TRCP) substrates is therefore critical to understand SCF(β-TRCP) biology and function. We used a β-TRCP-phosphodegron motif-specific antibody in a β-TRCP substrate screen coupled with tandem mass spectrometry and identified multiple β-TRCP substrates. One of these substrates was Lipin1, an enzyme and suppressor of the family of sterol regulatory element-binding protein (SREBP) transcription factors, which activate genes encoding lipogenic factors...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28042744/influence-of-acute-and-chronic-kidney-failure-in-rats-on-the-disposition-and-pharmacokinetics-of-zyan1-a-novel-prolyl-hydroxylase-inhibitor-for-the-treatment-of-chronic-kidney-disease-induced-anemia
#6
Harilal Patel, Amit Arvind Joharapurkar, Vrajesh Bhaskarbhai Pandya, Vishal Jagjivanbhai Patel, Samadhan Govind Kshirsagar, Prakash Patel, Bhavesh Gevriya, Mukul R Jain, Nuggehally R Srinivas, Pankaj Ramanbhai Patel, Ranjit C Desai
1. ZYAN1 is a prolyl hydroxylase inhibitor in clinical development for treatment of anemia associated with chronic kidney disease (CKD). We evaluated the effect of acute and chronic kidney impairment on the pharmacokinetics of ZYAN1 in rat models. 2. Cisplatin (2.5, 5 and 7.5 mg/kg) was used to induce acute kidney injury (AKI), and five-sixth and total nephrectomy was used to induce chronic kidney injury (CKI) in male Wistar rats. All groups received a single 15 mg/kg oral dose of ZYAN1. Blood/urine samples were analyzed for ZYAN1 to assess peak concentration (Cmax), area under the concentration-time curve (AUCinf), total body clearance (CL/F) and elimination half-life (T1/2)...
January 19, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27923179/structural-dynamics-of-casein-kinase-i-cki-from-malarial-parasite-plasmodium-falciparum-isolate-3d7-insights-from-theoretical-modelling-and-molecular-simulations
#7
Budheswar Dehury, Santosh Kumar Behera, Namita Mahapatra
The protein kinases (PKs), belonging to serine/threonine kinase (STKs), are important drug targets for a wide spectrum of diseases in human. Among protein kinases, the Casein Kinases (CKs) are vastly expanded in various organisms, where, the malarial parasite Plasmodium falciparum possesses a single member i.e., PfCKI, which can phosphorylate various proteins in parasite extracts in vitro condition. But, the structure-function relationship of PfCKI and dynamics of ATP binding is yet to be understood. Henceforth, an attempt was made to study the dynamics, stability, and ATP binding mechanisms of PfCKI through computational modelling, docking, molecular dynamics (MD) simulations, and MM/PBSA binding free energy estimation...
January 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/27821587/activation-proliferation-associated-protein-2-caprin-2-positively-regulates-cdk14-cyclin-y-mediated-lipoprotein-receptor-related-protein-5-and-6-lrp5-6-constitutive-phosphorylation
#8
Xin Wang, Yingying Jia, Cong Fei, Xiaomin Song, Lin Li
Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) are co-receptors for Wnt ligands. Upon ligand binding, LRP5/6 undergo glycogen synthase kinase 3 (GSK3)/casein kinase I (CKI)-mediated phosphorylation at multiple PPP(S/T)P motifs in the intracellular domain, which is essential for canonical Wnt signal transduction. On the other hand, in the Wnt-off state, the mitosis-specific CDK14-Cyclin Y kinase complex phosphorylates Ser-1490 of LRP5/6 at G2/M, thereby priming the receptor for Wnt-induced phosphorylation...
December 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27738720/efficient-multi-enzyme-catalyzed-cdp-choline-production-driven-by-an-atp-donor-module
#9
Yingmiao Liu, Junzhi Wang, Chongmao Xu, Yong Chen, Junjie Yang, Dong Liu, Huanqing Niu, Yu Jiang, Sheng Yang, Hanjie Ying
Cytidine diphosphate choline (CDP-choline) has been applied for treating acute craniocerebral injury and allowing recovery of consciousness after brain surgery. In this study, an acetate kinase (ACK)/acetyl phosphate system was used to supply ATP and combined with Escherichia coli-overexpressed CMP kinase (CMK), NDP kinase (NDK), choline phosphate cytidylyltransferase (CCT), and choline kinase (CKI) to produce CDP-choline from CMP and choline chloride. Within 1 h, 49 mM CDP-choline was produced, for a molar yield of 89...
February 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27738441/efficacy-of-compound-kushen-injection-in-combination-with-induction-chemotherapy-for-treating-adult-patients-newly-diagnosed-with-acute-leukemia
#10
Honglei Tu, Bo Lei, Shan Meng, Hailing Liu, Yongchang Wei, Aili He, Wanggang Zhang, Fuling Zhou
We assessed the clinical effectiveness and safety of CKI (compound Kushen injection) plus standard induction chemotherapy for treating adult acute leukemia (AL). We randomly assigned 332 patients with newly diagnosed AL to control (n = 165, receiving DA (daunorubicin and cytarabine) or hyper-CVAD (fractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone)) or treatment (n = 167, receiving CKI and DA or hyper-CVAD) groups. Posttreatment, treatment group CD3+, CD4+, CD4+/CD8+, natural killer (NK) cell, and immunoglobulin (IgG, IgA, and IgM) levels were significantly higher than those of the control group (p < 0...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27669459/sustained-erk-inhibition-maximizes-responses-of-brafv600e-thyroid-cancers-to-radioiodine
#11
James Nagarajah, Mina Le, Jeffrey A Knauf, Giuseppe Ferrandino, Cristina Montero-Conde, Nagavarakishore Pillarsetty, Alexander Bolaender, Christopher Irwin, Gnana Prakasam Krishnamoorthy, Mahesh Saqcena, Steven M Larson, Alan L Ho, Venkatraman Seshan, Nobuya Ishii, Nancy Carrasco, Neal Rosen, Wolfgang A Weber, James A Fagin
Radioiodide (RAI) therapy of thyroid cancer exploits the relatively selective ability of thyroid cells to transport and accumulate iodide. Iodide uptake requires expression of critical genes that are involved in various steps of thyroid hormone biosynthesis. ERK signaling, which is markedly increased in thyroid cancer cells driven by oncogenic BRAF, represses the genetic program that enables iodide transport. Here, we determined that a critical threshold for inhibition of MAPK signaling is required to optimally restore expression of thyroid differentiation genes in thyroid cells and in mice with BrafV600E-induced thyroid cancer...
November 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27668869/visual-topographic-and-pachymetric-effects-of-pediatric-corneal-collagen-cross-linking
#12
Ibrahim Toprak, Volkan Yaylali, Cem Yildirim
PURPOSE: To evaluate the effects of pediatric corneal collagen cross-linking (CXL) on corrected distance visual acuity (CDVA), maximum keratometry (Kmax), and other Scheimpflug imaging system parameters during 2 years of follow-up. METHODS: The records of 29 eyes of 29 pediatric patients who underwent unilateral CXL treatment for progressive keratoconus were reviewed. Changes in CDVA, Kmax, anterior chamber depth, anterior chamber volume, anterior chamber angle, pupil-center pachymetry, apical pachymetry, thinnest pachymetry, corneal volume, and topographic indices (index of surface variance [ISV], index of vertical asymmetry [IVA], index of height asymmetry [IHA], keratoconus index [KI], center keratoconus index [CKI], index of height decentration [IHD], and minimum radius of curvature [Rmin]) were analyzed among baseline and 1 and 2 years after the CXL treatment...
September 26, 2016: Journal of Pediatric Ophthalmology and Strabismus
https://www.readbyqxmd.com/read/27649746/a-new-layer-of-degradation-mechanism-for-pr-set7-set8-during-cell-cycle
#13
Nana Zheng, Xiangpeng Dai, Zhiwei Wang, Wenyi Wei
Set8 is critically involved in transcription regulation, cell cycle progression and genomic stability. Emerging evidence has revealed that E3 ubiquitin ligases such as CRL4(cdt2) and SCF(Skp2) regulate Set8 protein abundance. However, it is unclear whether other E3 ligase(s) could govern Set8 level for proper cell cycle progression in response to genotoxic stress such as UV irradiation. Recently, we report that the SCF(β-TRCP) complex regulates Set8 protein stability by targeting it for ubiquitination and subsequent degradation...
November 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27602759/identification-of-candidate-anti-cancer-molecular-mechanisms-of-compound-kushen-injection-using-functional-genomics
#14
Zhipeng Qu, Jian Cui, Yuka Harata-Lee, Thazin Nwe Aung, Qianjin Feng, Joy M Raison, Robert Daniel Kortschak, David L Adelson
Compound Kushen Injection (CKI) has been clinically used in China for over 15 years to treat various types of solid tumours. However, because such Traditional Chinese Medicine (TCM) preparations are complex mixtures of plant secondary metabolites, it is essential to explore their underlying molecular mechanisms in a systematic fashion. We have used the MCF-7 human breast cancer cell line as an initial in vitro model to identify CKI induced changes in gene expression. Cells were treated with CKI for 24 and 48 hours at two concentrations (1 and 2 mg/mL total alkaloids), and the effect of CKI on cell proliferation and apoptosis were measured using XTT and Annexin V/Propidium Iodide staining assays respectively...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27569911/nuclear-pore-permeabilization-is-a-convergent-signaling-event-in-effector-triggered-immunity
#15
Yangnan Gu, Sophia G Zebell, Zizhen Liang, Shui Wang, Byung-Ho Kang, Xinnian Dong
Nuclear transport of immune receptors, signal transducers, and transcription factors is an essential regulatory mechanism for immune activation. Whether and how this process is regulated at the level of the nuclear pore complex (NPC) remains unclear. Here, we report that CPR5, which plays a key inhibitory role in effector-triggered immunity (ETI) and programmed cell death (PCD) in plants, is a novel transmembrane nucleoporin. CPR5 associates with anchors of the NPC selective barrier to constrain nuclear access of signaling cargos and sequesters cyclin-dependent kinase inhibitors (CKIs) involved in ETI signal transduction...
September 8, 2016: Cell
https://www.readbyqxmd.com/read/27430269/disease-and-carrier-isolates-of-neisseria-meningitidis-cause-g1-cell-cycle-arrest-in-human-epithelial-cells
#16
Michael von Papen, Wilhelm F Oosthuysen, Jérôme Becam, Heike Claus, Alexandra Schubert-Unkmeir
Microbial pathogens have developed several mechanisms to modulate and interfere with host cell cycle progression. In this study, we analyzed the effect of the human pathogen Neisseria meningitidis on the cell cycle of epithelial cells. Two pathogenic isolates, as well as two carrier isolates, were tested for their ability to adhere to and invade into the epithelial cell lines Detroit 562 and NP69 and to modulate the cell cycle. We found that all isolates adhered equally well to both Detroit 562 and NP69 cells, whereas the carrier isolates were significantly less invasive...
October 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27143919/the-important-tumor-suppressor-role-of-per1-in-regulating-the-cyclin-cdk-cki-network-in-scc15-human-oral-squamous-cell-carcinoma-cells
#17
Xiao-Juan Fu, Han-Xue Li, Kai Yang, Dan Chen, Hong Tang
BACKGROUND: Accumulating evidence suggests that the abnormal expression of the circadian clock gene PER1 is closely related to the development and progression of cancer. However, the exact molecular mechanism by which the abnormal expression of PER1 induces carcinogenesis is unclear. This study was conducted to investigate the alterations in downstream cell cycle genes, cell cycle distribution, cell proliferation, apoptosis, and in vivo tumorigenicity in SCC15 oral squamous cell carcinoma cells after PER1 downregulation...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27099469/comparison-of-scheimpflug-imaging-parameters-between-steep-and-keratoconic-corneas-of-caucasian-eyes
#18
Tukezban Huseynova, Farah Abdulaliyeva, Michele Lanza
PURPOSE: To compare the keratometric and pachymetric parameters of healthy eyes with those affected by steep cornea and keratoconus (KC) using Scheimpflug camera. SETTING: Briz-L Eye Clinic, Baku, Azerbaijan. DESIGN: A cross-sectional study. METHODS: In this study, 49 KC (Amsler-Krumeich stage 1) eyes and 36 healthy eyes were enrolled. A complete ophthalmic evaluation and a Scheimpflug camera scan were performed in every eye included in the study...
2016: Clinical Ophthalmology
https://www.readbyqxmd.com/read/27088431/identification-of-cooperative-genes-for-e2a-pbx1-to-develop-acute-lymphoblastic-leukemia
#19
Yasuyuki Sera, Norimasa Yamasaki, Hideaki Oda, Akiko Nagamachi, Linda Wolff, Takeshi Inukai, Toshiya Inaba, Hiroaki Honda
E2A-PBX1 is a chimeric gene product detected in t(1;19)-bearing acute lymphoblastic leukemia (ALL) with B-cell lineage. To investigate the leukemogenic process, we generated conditional knock-in (cKI) mice for E2A-PBX1, in which E2A-PBX1 is inducibly expressed under the control of the endogenous E2A promoter. Despite the induced expression of E2A-PBX1, no hematopoietic disease was observed, strongly suggesting that additional genetic alterations are required to develop leukemia. To address this possibility, retroviral insertional mutagenesis was used...
July 2016: Cancer Science
https://www.readbyqxmd.com/read/27065861/the-therapeutic-efficacy-and-safety-of-compound-kushen-injection-combined-with-transarterial-chemoembolization-in-unresectable-hepatocellular-carcinoma-an-update-systematic-review-and-meta-analysis
#20
REVIEW
Xiao Ma, Rui-Sheng Li, Jian Wang, Yin-Qiu Huang, Peng-Yan Li, Ji Wang, Hai-Bin Su, Rui-Lin Wang, Ya-Ming Zhang, Hong-Hong Liu, Cong-En Zhang, Zhi-Jie Ma, Jia-Bo Wang, Yan-Ling Zhao, Xiao-He Xiao
BACKGROUND: Compound Kushen Injection (CKI) is a Chinese patent medicine approved by the China Food and Drug Administration for the treatment of various types of solid tumors. CKI, combined with transarterial chemoembolization (TACE), is believed to increase the therapeutic efficacy of unresectable hepatocellular carcinoma (HCC). We report an updated and extended meta-analysis with detailed outcomes of both the efficacy and adverse events (AEs) of CKI combined with TACE therapy. MATERIALS AND METHODS: Electronic databases, including PubMed, Embase, the Cochrane Library, the Chinese Biomedical Database (CBM), Wanfang, the VIP medicine information system (VMIS) and the China National Knowledge Infrastructure (CNKI), were examined for relevant articles before November 13, 2015...
2016: Frontiers in Pharmacology
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