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https://www.readbyqxmd.com/read/29330507/uncovering-the-anticancer-mechanism-of-compound-kushen-injection-against-hcc-by-integrating-quantitative-analysis-network-analysis-and-experimental-validation
#1
Li Gao, Ke-Xin Wang, Yu-Zhi Zhou, Jian-Song Fang, Xue-Mei Qin, Guan-Hua Du
Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM) preparation that has been clinically used in China to treat various types of solid tumours. Although several studies have revealed that CKI can inhibit the proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds, potential targets and pathways involved in these effects have not been systematically investigated. Here, we proposed a novel idea of "main active compound-based network pharmacology" to explore the anti-cancer mechanism of CKI...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29291026/can-kushen-injection-combined-with-tace-improve-therapeutic-efficacy-and-safety-in-patients-with-advanced-hcc-a-systematic-review-and-network-meta-analysis
#2
Yingshi Zhang, Fuhai Hui, Yue Yang, Haixiao Chu, Xiaochun Qin, Mingyi Zhao, Qingchun Zhao
Objective: To assess the comparative efficacy and safety of combination treatment with Compound Kushen Injection (CKI) and transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) through a systematic review and network meta-analysis and to identify the best conditions for using CKI. Materials and Methods: We performed a network meta-analysis based on randomized controlled trials. We searched databases for studies published by August 2017...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287584/risk-factors-for-community-acquired-acute-kidney-injury-in-patients-with-and-without-chronic-kidney-injury-and-impact-of-its-initial-management-on-prognosis-a-prospective-observational-study
#3
Fabien Stucker, Belen Ponte, Victoria De la Fuente, Cyrielle Alves, Olivier Rutschmann, Sebastian Carballo, Nicolas Vuilleumier, Pierre-Yves Martin, Thomas Perneger, Patrick Saudan
BACKGROUND: We aimed to describe clinical characteristics of patients with community-acquired acute kidney injury (CA-AKI), the effectiveness of initial management of CA-AKI, its prognosis and the impact of medication on its occurrence in patients with previous chronic kidney injury (CKI). METHODS: We undertook a prospective observational study within the Emergency Department (ED) of a University Hospital, screening for any patient >16 years admitted with an eGFR <60 ml/mn/1...
December 29, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29259647/efficacy-and-safety-of-compound-kushen-injection-on-patients-with-advanced-colon-cancer-a-meta-analysis-of-randomized-controlled-trials
#4
REVIEW
Lixiu Yu, Ying Zhou, Yu Yang, Furong Lu, Yeqin Fan
Objective: The efficacy and safety of Compound Kushen Injection (CKI) on advanced colon cancer remain controversial. We undertook a systematic meta-analysis of randomized controlled clinical studies on this issue. Methods: A comprehensive literature search was conducted by searching the following electronic databases: PubMed, Cochrane, Chinese Biological Medical disc, Chinese National Knowledge Infrastructure, and Wan-Fang Database in China by the end of January 31, 2017, without language restriction...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29200817/evaluation-of-corneal-symmetry-after-uv-corneal-crosslinking-for-keratoconus
#5
Hanan Mofty, Khaled Alzahrani, Fiona Carley, Sophie Harper, Arun Brahma, Leon Au, Debbie Morley, M Chantal Hillarby
Purpose: The purpose of this study was to assess UV corneal crosslinking (CXL) treatment outcomes for keratoconus by evaluating the corneal regularity in patients through follow-up using the Oculus Pentacam. Patients and methods: A total of 18 eyes from CXL patients with keratoconus were studied before and after CXL treatment, and six eyes from six patients who were not treated with CXL served as controls. Treated patients had Pentacam images taken before CXL treatment and regularly 3 months post treatment up to the 12th month...
2017: Clinical Ophthalmology
https://www.readbyqxmd.com/read/29098944/defective-interaction-between-p27-and-cyclin-a-cdk-complex-in-certain-human-cancer-cell-lines-revealed-by-split-yfp-assay-in-living-cells
#6
Taku Chibazakura, Yuichi Asano
Cyclin-cyclin dependent kinase (CDK) complex is negatively regulated by interaction with CDK inhibitors (CKIs). p27 protein is a major CKI in mammals and its down-regulation correlates with malignant transformation. However, some cancer cells express p27 at normal level, suggesting not only quantitative but qualitative control of p27, although little is known about such control. We analyzed the interaction between p27 and cyclin A (CycA)-CDK complex in living human cell lines, using a split yellow fluorescent protein (YFP) system in which the YFP fluorescence solely depends on p27-CycA binding...
November 3, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28982238/carbon-kinetic-isotope-effects-and-the-mechanisms-of-acid-catalyzed-decarboxylation-of-2-4-dimethoxybenzoic-acid-and-co2-incorporation-into-1-3-dimethoxybenzene
#7
Adelle A Vandersteen, Graeme W Howe, Barbara Sherwood Lollar, Ronald Kluger
The rate of decarboxylation of 2,4-dimethoxybenzoic acid (1) is accelerated in parallel to the extent that the carboxyl group acquires a second proton (1H(+)). However, the conjugate acid would resist C-C bond breaking as that would lead to formation of doubly protonated CO2. An alternative via formation of a higher-energy protonated phenyl tautomer (2H(+)) prior to C-C bond breaking would produce protonated CO2, an energetically inaccessible species that can be avoided by transfer of the carboxyl proton to water in the same step...
October 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28913509/effects-of-single-segment-intacs-implantation-on-visual-acuity-and-corneal-topographic-indices-of-keratoconus
#8
Kazem Amanzadeh, Roghiyeh Elham, Ebrahim Jafarzadepur
PURPOSE: To assess the changes in visual acuity and topographic indices after implantation of single-segment Intacs. METHODS: Forty-two keratoconic eyes received Femtosecond-assisted single-segment Intacs. Uncorrected distance visual acuity (UDVA) and best spectacle corrected visual acuity (BSCVA), refractive error, keratometry (K1, K2, Km, and KMax.), and seven Pentacam measured topographical indices; index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), central keratoconus index (CKI), index of height asymmetry (IHA), index of height decentration (IHD), and minimum radius of curvature (R Min) were assessed 4 months after surgery...
September 2017: Journal of Current Ophthalmology
https://www.readbyqxmd.com/read/28886336/temperature-sensitive-substrate-and-product-binding-underlie-temperature-compensated-phosphorylation-in-the-clock
#9
Yuta Shinohara, Yohei M Koyama, Maki Ukai-Tadenuma, Takatsugu Hirokawa, Masaki Kikuchi, Rikuhiro G Yamada, Hideki Ukai, Hiroshi Fujishima, Takashi Umehara, Kazuki Tainaka, Hiroki R Ueda
Temperature compensation is a striking feature of the circadian clock. Here we investigate biochemical mechanisms underlying temperature-compensated, CKIδ-dependent multi-site phosphorylation in mammals. We identify two mechanisms for temperature-insensitive phosphorylation at higher temperature: lower substrate affinity to CKIδ-ATP complex and higher product affinity to CKIδ-ADP complex. Inhibitor screening of ADP-dependent phosphatase activity of CKIδ identified aurintricarboxylic acid (ATA) as a temperature-sensitive kinase activator...
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28844736/structure-and-binding-studies-of-proliferating-cell-nuclear-antigen-from-leishmania-donovani
#10
Satya Prakash Yadav, Prashant Kumar Singh, Pradeep Sharma, Naseer Iqbal, Punit Kaur, Sujata Sharma, Tej P Singh
Proliferating cell nuclear antigen (PCNA) acts as a sliding clamp to support DNA replication and repair. The structure of PCNA from Leishmania donovani (LdPCNA) has been determined at 2.73Å resolution. Structure consists of six crystallographically independent molecules which form two trimeric rings. The pore diameter of the individual trimeric ring is of the order of 37Å. The two rings are stacked through their front to front faces. In order to gain a stable packing, the rings are rotated by 42° about the pore axis and shifted by 7Å and tilted by 16° along the perpendicular direction to pore axis...
August 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28771906/cdk1-interacting-protein-cip1-is-regulated-by-the-s%C3%A2-phase-checkpoint-in-response-to-genotoxic-stress
#11
Ze Zhang, Ping Ren, Ajay A Vashisht, James A Wohlschlegel, David G Quintana, Fanli Zeng
In eukaryotic cells, a surveillance mechanism, the S phase checkpoint, detects and responds to insults that challenge chromosomal replication, arresting cell cycle progression and triggering appropriate events to prevent genomic instability. In the budding yeast Saccharomyces cerevisiae, Mec1/ATM/ATR, and its downstream kinase, Rad53/Chk2, mediate the response to genotoxic stress. In this study, we place Cip1, a recently identified Cdk1 inhibitor (CKI), under the regulation of Mec1 and Rad53 in response to genotoxic stress...
October 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28706580/risk-factors-for-acute-kidney-injury-after-partial-hepatectomy
#12
Luis Cesar Bredt, Luis Alberto Batista Peres
AIM: To identify risk factors for the occurrence of acute kidney injury (AKI) in the postoperative period of partial hepatectomies. METHODS: Retrospective analysis of 446 consecutive resections in 405 patients, analyzing clinical characteristics, preoperative laboratory data, intraoperative data, and postoperative laboratory data and clinical evolution. Adopting the International Club of Ascites criteria for the definition of AKI, potential predictors of AKI by logistic regression were identified...
June 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28676626/yeast-cip1-is-activated-by-environmental-stress-to-inhibit-cdk1-g1-cyclins-via-mcm1-and-msn2-4
#13
Ya-Lan Chang, Shun-Fu Tseng, Yu-Ching Huang, Zih-Jie Shen, Pang-Hung Hsu, Meng-Hsun Hsieh, Chia-Wei Yang, Silvia Tognetti, Berta Canal, Laia Subirana, Chien-Wei Wang, Hsiao-Tan Chen, Chi-Ying Lin, Francesc Posas, Shu-Chun Teng
Upon environmental changes, proliferating cells delay cell cycle to prevent further damage accumulation. Yeast Cip1 is a Cdk1 and Cln2-associated protein. However, the function and regulation of Cip1 are still poorly understood. Here we report that Cip1 expression is co-regulated by the cell-cycle-mediated factor Mcm1 and the stress-mediated factors Msn2/4. Overexpression of Cip1 arrests cell cycle through inhibition of Cdk1-G1 cyclin complexes at G1 stage and the stress-activated protein kinase-dependent Cip1 T65, T69, and T73 phosphorylation may strengthen the Cip1and Cdk1-G1 cyclin interaction...
July 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28652280/immune-related-adverse-events-as-a-biomarker-in-non-melanoma-patients-treated-with-programmed-cell-death-1-inhibitors
#14
Julia Judd, Matthew Zibelman, Elizabeth Handorf, John O'Neill, Chethan Ramamurthy, Sasini Bentota, Jamie Doyle, Robert G Uzzo, Jessica Bauman, Hossein Borghaei, Elizabeth R Plimack, Ranee Mehra, Daniel M Geynisman
BACKGROUND: The programmed death 1 (PD-1) checkpoint inhibitors (CKIs) can lead to immune-related adverse events (irAEs). We sought to evaluate whether the development of irAEs correlates with treatment response in non-melanoma malignancies. MATERIALS AND METHODS: We conducted a retrospective study of patients who received anti-PD-1 CKI monotherapy at Fox Chase Cancer Center. Endpoints included overall response rate (ORR), time to next therapy or death (TTNTD), and overall survival (OS)...
October 2017: Oncologist
https://www.readbyqxmd.com/read/28644159/investigation-of-the-rosenbaum-concussion-knowledge-and-attitudes-survey-in-collegiate-athletes
#15
Erin B Chapman, Alan Nasypany, Jim May, Timothy Henry, Chris Hummel, Hyung-Pil Jun
OBJECTIVE: The purpose of this study is to determine whether the Rosenbaum Concussion Knowledge and Attitudes Survey (RoCKAS) is an appropriate outcome measure to assess knowledge and attitudes toward concussion in collegiate student-athletes as determined through validity and reliability testing. STUDY DESIGN: Convenience study. SETTING: The researcher recruited all athletic teams at a Division III National Collegiate Athletic Association institution...
June 14, 2017: Clinical Journal of Sport Medicine: Official Journal of the Canadian Academy of Sport Medicine
https://www.readbyqxmd.com/read/28560460/synthetic-lethal-interaction-of-cdk-inhibition-and-autophagy-inhibition-in-human-solid-cancer-cell-lines
#16
Yoshinari Okada, Shunsuke Kato, Yasuhiro Sakamoto, Takayuki Oishi, Chikashi Ishioka
Cell cycle control is a promising target in cancer treatments, and some small-molecule cyclin-dependent kinase (CDK) inhibitors have exhibited clinical effectiveness. However, no biomarkers predictive of efficacy have been developed. Recent studies have revealed that CDK inhibitor (CKI) proteins, such as p27 and p16, also induced cytoprotective autophagy in cancer cells. However, it is unclear whether small-molecule CKIs also induce autophagy in solid tumors, as induced autophagy promotes cancer cell survival...
July 2017: Oncology Reports
https://www.readbyqxmd.com/read/28378189/cleavage-and-phosphorylation-important-post-translational-modifications-of-galectin-3
#17
REVIEW
Xiaoge Gao, Jingjie Liu, Xiangye Liu, Liantao Li, Junnian Zheng
As the unique chimeric member of the β-galactoside-binding protein family, galectin-3 is a multivalent and multifunctional oncogenic protein involved in multiple physiological and pathological processes, including cell growth, cell differentiation, cell adhesion, RNA splicing, cell apoptosis, and malignant transformation. Post-translational modifications can effectively increase a protein's functional diversity, either by degradation or adding chemical modifications, thus regulating activity, localization, and ligand interaction...
April 4, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28360132/dose-dependent-transduction-of-hedgehog-relies-on-phosphorylation-based-feedback-between-the-g-protein-coupled-receptor-smoothened-and-the-kinase-fused
#18
Matthieu Sanial, Isabelle Bécam, Line Hofmann, Julien Behague, Camilla Argüelles, Vanessa Gourhand, Lucia Bruzzone, Robert A Holmgren, Anne Plessis
Smoothened (SMO) is a G-protein-coupled receptor-related protein required for the transduction of Hedgehog (HH). The HH gradient leads to graded phosphorylation of SMO, mainly by the PKA and CKI kinases. How thresholds in HH morphogen regulate SMO to promote switch-like transcriptional responses is a central unsolved issue. Using the wing imaginal disc model in Drosophila, we identified new SMO phosphosites that enhance the effects of the PKA/CKI kinases on SMO accumulation, its localization at the plasma membrane and its activity...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28279624/p21-a-two-faced-genome-guardian
#19
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...
April 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
#20
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
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