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https://www.readbyqxmd.com/read/28340357/ruthenium-complexes-with-phenylterpyridine-derivatives-target-cell-membrane-and-trigger-death-receptors-mediated-apoptosis-in-cancer-cells
#1
Zhiqin Deng, Pan Gao, Lianling Yu, Bin Ma, Yuanyuan You, Leung Chan, Chaoming Mei, Tianfeng Chen
Elucidation of the communication between metal complexes and cell membrane may provide useful information for rational design of metal-based anticancer drugs. Herein we synthesized a novel class of ruthenium (Ru) complexes containing phtpy derivatives (phtpy = phenylterpyridine), analyzed their structure-activity relationship and revealed their action mechanisms. The result showed that, the increase in the planarity of hydrophobic Ru complexes significantly enhanced their lipophilicity and cellular uptake...
March 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28340347/rejuvenation-by-therapeutic-elimination-of-senescent-cells
#2
Paul Krimpenfort, Anton Berns
In this issue of Cell, Baar et al. show how FOXO4 protects senescent cell viability by keeping p53 sequestered in nuclear bodies, preventing it from inducing apoptosis. Disrupting this interaction with an all-D amino acid peptide (FOXO4-DRI) restores p53's apoptotic role and ameliorates the consequences of senescence-associated loss of tissue homeostasis.
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340339/targeted-apoptosis-of-senescent-cells-restores-tissue-homeostasis-in-response-to-chemotoxicity-and-aging
#3
Marjolein P Baar, Renata M C Brandt, Diana A Putavet, Julian D D Klein, Kasper W J Derks, Benjamin R M Bourgeois, Sarah Stryeck, Yvonne Rijksen, Hester van Willigenburg, Danny A Feijtel, Ingrid van der Pluijm, Jeroen Essers, Wiggert A van Cappellen, Wilfred F van IJcken, Adriaan B Houtsmuller, Joris Pothof, Ron W F de Bruin, Tobias Madl, Jan H J Hoeijmakers, Judith Campisi, Peter L J de Keizer
The accumulation of irreparable cellular damage restricts healthspan after acute stress or natural aging. Senescent cells are thought to impair tissue function, and their genetic clearance can delay features of aging. Identifying how senescent cells avoid apoptosis allows for the prospective design of anti-senescence compounds to address whether homeostasis can also be restored. Here, we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28340115/cellular-senescence-in-mouse-hippocampus-after-irradiation-and-the-role-of-p53-and-p21
#4
Zoey Cheng, Yan Zhen Zheng, Yu-Qing Li, C Shun Wong
Diverse stress signals including irradiation may trigger cellular senescence. We asked whether irradiation induced senescence in mouse hippocampus, and whether p53 or p21 played a role in this response. Following whole-brain irradiation, polymerase chain reaction (PCR) arrays for senescence-associated genes showed increased expression of CDKN1A (p21) and CDKN2A (p19ARF) in mouse hippocampus at 9 weeks. Upregulation of p21 and p19ARF was confirmed using real-time PCR, which also demonstrated increased CDKN2A/p16INKa expression after irradiation...
March 14, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28339723/leveraging-molecular-datasets-for-biomarker-based-clinical-trial-design-in-glioblastoma
#5
Shyam K Tanguturi, Lorenzo Trippa, Shakti H Ramkissoon, Kristine Pelton, David Knoff, David Sandak, Neal I Lindeman, Azra H Ligon, Rameen Beroukhim, Giovanni Parmigiani, Patrick Y Wen, Keith L Ligon, Brian M Alexander
Background.: Biomarkers can improve clinical trial efficiency, but designing and interpreting biomarker-driven trials require knowledge of relationships among biomarkers, clinical covariates, and endpoints. We investigated these relationships across genomic subgroups of glioblastoma (GBM) within our institution (DF/BWCC), validated results in The Cancer Genome Atlas (TCGA), and demonstrated potential impacts on clinical trial design and interpretation. Methods.: We identified genotyped patients at DF/BWCC, and clinical associations across 4 common GBM genomic biomarker groups were compared along with overall survival (OS), progression-free survival (PFS), and survival post-progression (SPP)...
February 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28339300/genetic-manipulation-by-zinc-finger-nucleases-in-rat-induced-pluripotent-stem-cells
#6
Sheng Yang, Shufang Ding, Qianhua Xu, Xiong Li, Qiong Xiong
Induced pluripotent stem cells (iPSCs) have an extensive application in regenerative medicine, pharmaceutical discovery, and basic research. With the recent derivation of rat iPSCs, it is now feasible to apply genetic manipulation in this species. But such tools do not yet exist for many rat strains, especially for disease model rat. The Sprague Dawley (SD) rat is an inbred disease model for hypertension, nephropathy, pulmonary hypertension, depression, and alcohol consumption. In this study, the SD rat iPSCs were generated using lentiviral method...
March 24, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28339172/maternal-high-fat-diet-consumption-enhances-offspring-susceptibility-to-dss-induced-colitis-in-mice
#7
Shima Bibi, Yifei Kang, Min Du, Mei-Jun Zhu
OBJECTIVE: Maternal high-fat diet (HFD) may alter the offspring intestinal immune system, thereby enhancing susceptibility toward inflammatory bowel disease. The objective of the current study was to investigate the impact of maternal HFD on offspring intestinal health using a mouse model of dextran sulfate sodium (DSS)-induced colitis. METHODS: Dams were provided with either HFD (60%) or control diet. After weaning, female offspring from both groups were kept on 45% HFD...
March 24, 2017: Obesity
https://www.readbyqxmd.com/read/28339093/rock-inhibition-as-a-potential-therapeutic-target-involved-in-apoptosis-in-hemangioma
#8
Ming-Ke Qiu, Shu-Qing Wang, Chang Pan, Yang Wang, Zhi-Wei Quan, Ying-Bin Liu, Jing-Min Ou
Gene expression was examined in hemangiomas (HA), benign, birthmark-like tumors occurring in infancy, and confirmed in HA-derived endothelial cells (HDEC), for which cell proliferation and apoptosis were also assessed. Protein and mRNA accumulation of Rho-associated protein kinase (ROCK), vascular endothelial growth factor (VEGF), Ki-67 and proliferating cell nuclear antigen was significantly higher in proliferating phase HAs than in involuting phase HAs. In contrast, p53 and caspase-3 exhibited higher levels of accumulation in involuting than proliferating HAs...
March 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28339062/p53-microrna-374b-akt1-regulates-colorectal-cancer-cell-apoptosis-in-response-to-dna-damage
#9
Hangjun Gong, Yu Cao, Gang Han, Yun Zhang, Qing You, Yidong Wang, Yamin Pan
Colorectal cancer (CRC) has a rising morbidity worldwide and its resistance to chemotherapy has been observed in clinical treatment. Tumor suppressor p53 is well-studied in CRC, but little is known about its effects during DNA damage of CRC cells. This study was aimed at uncovering potential mechanisms of p53 regarding microRNA-374b and v-akt murine thymoma viral oncogene homolog 1 (AKT1) during DNA damage of CRC cells. CRC cells HCT116 and HT29 were transfected with p53-specific small interfering RNA (siRNA), p53 overexpression vector or miR-374b inhibitor, and then treated with 10 µM bleomycin (BLM) for 24 h to induce DNA damage...
March 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28339050/p53-mutation-status-is-a-primary-determinant-of-placenta-specific-protein-1-expression-in-serous-ovarian-cancers
#10
Eric J Devor, Jesus Gonzalez-Bosquet, Akshaya Warrier, Henry D Reyes, Nonye V Ibik, Brandon M Schickling, Andreea Newtson, Michael J Goodheart, Kimberly K Leslie
Placenta-specific protein 1 (PLAC1) expression is co-opted in numerous human cancers. As a consequence of PLAC1 expression, tumor cells exhibit enhanced proliferation and invasiveness. This characteristic is associated with increased aggressiveness and worse patient outcomes. Recently, the presence of the tumor suppressor p53 was shown in vitro to inhibit PLAC1 transcription by compromising the P1, or distal/cancer, promoter. We sought to determine if this phenomenon occurs in primary patient tumors as well...
March 23, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28339038/lncrna%C3%A2-mediated-sirt1-foxo3a-and-sirt1-p53-signaling-pathways-regulate-type-ii-alveolar-epithelial-cell-senescence-in-patients-with-chronic-obstructive-pulmonary-disease
#11
Chao Gu, Yaqing Li, Jialiang Liu, Xiwang Ying, Yuanshun Liu, Jianping Yan, Chun Chen, Hongbin Zhou, Liming Cao, Yingyu Ma
The loss of alveolar structure and airspace enlargement are major pathological changes in chronic obstructive pulmonary disease (COPD). Type II alveolar epithelial cells (AECII) are involved in maintaining lung tissue repair and alveolar homeostasis. Long non‑coding RNAs (lncRNAs) are involved in multi‑regulating gene transcription, affecting processes including embryonic development, cell differentiation and cellular senescence. The primary aim of the present study was to explore the mechanisms of AECII senescence regulated by lncRNA‑mediated sirtuin 1 (SIRT1) and forkhead box O 3a (FoxO3a) signaling pathways in patients with COPD...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28339031/p53-inducible-long-non-coding-rna-picart1-mediates-cancer-cell-proliferation-and-migration
#12
Yu Cao, Minglin Lin, Yiwen Bu, Hongyan Ling, Yingchun He, Chenfei Huang, Yi Shen, Bob Song, Deliang Cao
Long non-coding RNAs (lncRNAs) function in the development and progression of cancer, but only a small portion of lncRNAs have been characterized to date. A novel lncRNA transcript, 2.53 kb in length, was identified by transcriptome sequencing analysis, and was named p53-inducible cancer-associated RNA transcript 1 (PICART1). PICART1 was found to be upregulated by p53 through a p53-binding site at -1808 to -1783 bp. In breast and colorectal cancer cells and tissues, PICART1 expression was found to be decreased...
March 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28338770/response-of-human-non-small-cell-lung-cancer-cells-to-the-influence-of-wogonin-with-sgk1-dynamics
#13
Guanglin Shi, Qian Wang, Xiaoyu Zhou, Jun Li, Hua Liu, Jun Gu, Haiying Wang, Yi Wu, Liang Ding, Songshi Ni, Zhiyuan Tang
A number of significant studies in the field of cell biology have revealed another pattern of intracellular signal transduction in which cells transmit information through the dynamics of key signaling molecules. Dynamical properties of p53 have been demonstrated to be the key factor in dictating cell fate, including cell cycle arrest, permanent cell cycle arrest, and cell death. Previous studies showed a negative feedback regulation pathway between SGK1 and p53, but the dynamics of SGK1 have never been reported before...
February 18, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28338656/focal-adhesion-kinase-depletion-reduces-human-hepatocellular-carcinoma-growth-by-repressing-enhancer-of-zeste-homolog-2
#14
Daniela Gnani, Ilaria Romito, Simona Artuso, Marco Chierici, Cristiano De Stefanis, Nadia Panera, Annalisa Crudele, Sara Ceccarelli, Elena Carcarino, Valentina D'Oria, Manuela Porru, Ezio Giorda, Karin Ferrari, Luca Miele, Erica Villa, Clara Balsano, Diego Pasini, Cesare Furlanello, Franco Locatelli, Valerio Nobili, Rossella Rota, Carlo Leonetti, Anna Alisi
Hepatocellular carcinoma (HCC) is the most common type of liver cancer in humans. The focal adhesion tyrosine kinase (FAK) is often over-expressed in human HCC and FAK inhibition may reduce HCC cell invasiveness. However, the anti-oncogenic effect of FAK knockdown in HCC cells remains to be clarified. We found that FAK depletion in HCC cells reduced in vitro and in vivo tumorigenicity, by inducing G2/M arrest and apoptosis, decreasing anchorage-independent growth, and modulating the expression of several cancer-related genes...
March 24, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28338653/breast-ductal-carcinoma-in-situ-carry-mutational-driver-events-representative-of-invasive-breast-cancer
#15
Jia-Min B Pang, Peter Savas, Andrew P Fellowes, Gisela Mir Arnau, Tanjina Kader, Ravikiran Vedururu, Chelsee Hewitt, Elena A Takano, David J Byrne, David Yh Choong, Ewan Ka Millar, C Soon Lee, Sandra A O'Toole, Sunil R Lakhani, Margaret C Cummings, G Bruce Mann, Ian G Campbell, Alexander Dobrovic, Sherene Loi, Kylie L Gorringe, Stephen B Fox
The spectrum of genomic alterations in ductal carcinoma in situ (DCIS) is relatively unexplored, but is likely to provide useful insights into its biology, its progression to invasive carcinoma and the risk of recurrence. DCIS (n=20) with a range of phenotypes was assessed by massively parallel sequencing for mutations and copy number alterations and variants validated by Sanger sequencing. PIK3CA mutations were identified in 11/20 (55%), TP53 mutations in 6/20 (30%), and GATA3 mutations in 9/20 (45%). Screening an additional 91 cases for GATA3 mutations identified a final frequency of 27% (30/111), with a high proportion of missense variants (8/30)...
March 24, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28338201/the-clinical-relationship-between-the-slug-mediated-puma-p53-signaling-pathway-and-radiotherapy-resistance-in-nasopharyngeal-carcinoma
#16
T Xu, Y Yuan, D-J Xiao
OBJECTIVE: To explore the clinical relationship between the Slug-mediated Puma/p53 signaling pathway and radiotherapy resistance in nasopharyngeal carcinoma. PATIENTS AND METHODS: Forty surgical specimens were collected from nasopharyngeal carcinoma patients treated at our hospital between February 2010 and February 2015. Twenty patients with poorly differentiated nasopharyngeal carcinoma with and without radiotherapy resistance were included in the experimental and control groups, respectively...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28338198/the-expression-of-sirt3-in-primary-hepatocellular-carcinoma-and-the-mechanism-of-its-tumor-suppressing-effects
#17
Y Liu, Y-L Liu, W Cheng, X-M Yin, B Jiang
OBJECTIVE: To observe the SIRT 3 expression in primary hepatocellular carcinoma (HCC), and then establish the eukaryotic expression vector of SIRT3 to observe the proliferation and apoptosis of pZsGreen-c1-SIRT3 HepG2 cells. Furthermore, we explored the mechanism of SIRT3 in inhibiting HCC. PATIENTS AND METHODS: Immunohistochemistry was used to detect the expression of SIRT3 in the tumor tissue and para-tumor tissue in 32 patients with HCC and the normal liver tissue in 10 patients...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28338113/antiproliferative-and-apoptotic-effects-of-lidocaine-on-human-hepatocarcinoma-cells-a-preliminary-study
#18
Ancuta Jurj, Ciprian Tomuleasa, Tiberiu T Tat, Ioana Berindan-Neagoe, Stefan V Vesa, Daniela C Ionescu
BACKGROUND AND AIMS: It is now well documented that certain anesthetic techniques may influence long term outcome in cancer patients undergoing surgery. More recently, local anesthetics proved certain antiproliferative effects in cancer cells. In our study, we aimed to investigate if lidocaine has antiproliferative effects in human hepatocarcinoma cells and to identify possible mechanisms of these effects. METHODS: We investigated the inhibitory effect of different concentrations of lidocaine on the proliferation of cultured HepG2 human hepatocarcinoma cells and LX2 normal liver fibroblasts...
March 2017: Journal of Gastrointestinal and Liver Diseases: JGLD
https://www.readbyqxmd.com/read/28337887/up-regulation-of-mir-888-5p-in-hepatocellular-carcinoma-cell-lines-and-its-effect-on-malignant-characteristics-of-cells
#19
E Hao, J Yu, S Xie, W Zhang, G Wang
MicroRNA (miRNA) expression has been linked to the molecular pathogenesis of hepatocellular carcinoma (HCC). The aberrant expression of miRNA is involved in the processes of tumorigenesis and cancer progression. According to the latest research, miR-888-5p is associated with strong cancer-promoting effect. For instance, miR-888-5p is up-regulated in prostate cancer and breast cancer. Nevertheless, the role of miR-888-5p in HCC has not been investigated to date. In this study, we found that miR-888-5p levels in four HCC cell lines (SMMC7721, HepG2, Huh-7 and Bel7402) were significantly up-regulated compared with human hepatocyte cell line (HHL-5)...
January 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28337870/jak2-tyrosine-kinase-inhibitor-ag490-suppresses-cell-growth-and-invasion-of-gallbladder-cancer-cells-via-inhibition-of-jak2-stat3-signaling
#20
L X Fu, Q W Lian, J D Pan, Z L Xu, T M Zhou, B Ye
The Janus kinase-signal transducers and activators of transcription signaling pathway (JAK/STAT pathway) have displayed a critical role in tumor development and progression in multiple malignancies. Previous studies showed that inhibition of JAK/STAT signaling blocked cell growth and metastasis in cancer cells, however, the antitumor effects of JAK inhibitor AG490 on gallbladder cancer (GBC) have not been reported. Our present study aimed to investigate the effects and associated mechanisms of JAK inhibitor AG490 on cell growth, invasive potential and apoptosis in GBC cells (GBC-SD and SGC-996) indicated by MTT, cell colony formation, Transwell and flow cytometry...
January 2017: Journal of Biological Regulators and Homeostatic Agents
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