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https://www.readbyqxmd.com/read/28212569/mir-124-acts-as-a-tumor-suppressor-by-inhibiting-the-expression-of-sphingosine-kinase-1-and-its-downstream-signaling-in-head-and-neck-squamous-cell-carcinoma
#1
Yuan Zhao, Zhiqiang Ling, Yubin Hao, Xiaowu Pang, Xianlin Han, Joseph A Califano, Liang Shan, Xinbin Gu
By analyzing the expression profile of microRNAs in head and neck squamous cell carcinomas (HNSCC), we found that the expression level of miR-124 was 4.59-fold lower in tumors than in normal tissues. To understand its functions, we generated a miR-124-expressing subline (JHU-22miR124) and a mock vector-transfected subline (JHU-22vec) by transfecting the mimic of miR-124 into JHU-22 cancer cells. Restored expression of miR-124 in JHU-22miR124 cells led to reduced cell proliferation, delayed colony formation, and decreased tumor growth, indicating a tumor-suppressive effect of miR-124...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212547/resveratrol-induces-cell-cycle-arrest-and-apoptosis-with-docetaxel-in-prostate-cancer-cells-via-a-p53-p21waf1-cip1-and-p27kip1-pathway
#2
Santosh Kumar Singh, Saswati Banerjee, Edward P Acosta, James W Lillard, Rajesh Singh
Resveratrol (RES) is the most effective natural products used for the treatment of a variety of cancers. In this study, we tested the effect of RES in enhancing the efficacy of docetaxel (DTX) treatment in prostate cancer (PCa) cells. The C4-2B and DU-145 cell lines were treated with RES, DTX and combination followed by evaluating the apoptosis and cell cycle progression. The combined drug treatment up-regulates the pro-apoptotic genes (BAX, BID, and BAK), cleaved PARP and down regulates the anti-apoptotic genes (MCL-1, BCL-2, BCL-XL) promoting apoptosis...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212434/prognostic-and-clinicopathological-value-of-poly-adenosine-diphosphate-ribose-polymerase-expression-in-breast-cancer-a-meta-analysis
#3
Weiqiang Qiao, Linlin Pan, Changgui Kou, Ke Li, Ming Yang
BACKGROUND: Previous studies have shown that the poly (adenosine diphosphate-ribose) polymerase (PARP) level is a promising indicator of breast cancer. However, its prognostic value remains controversial. The present meta-analysis evaluated the prognostic value of PARP expression in breast cancer. MATERIALS AND METHODS: Eligible studies were retrieved from the PubMed, Web of Science, Embase, and Cochrane Library databases through July 20, 2016. Studies investigating PARP expression as well as reporting survival data in breast cancer were included...
2017: PloS One
https://www.readbyqxmd.com/read/28212373/poly-adp-ribose-polymerase-1-mrna-levels-strongly-correlate-with-the-prognosis-of-myelodysplastic-syndromes
#4
P Diamantopoulos, K Zervakis, P Zervakis, M Sofotasiou, T Vassilakopoulos, I Kotsianidis, A Symeonidis, V Pappa, A Galanopoulos, E Solomou, E Kodandreopoulou, V Papadopoulou, P Korkolopoulou, M Mantzourani, G Kyriakakis, N-A Viniou
Poly (ADP-ribose) polymerase 1 (PARP-1) has a central role in the repair of DNA breaks and is a promising treatment target in malignancy. We measured PARP1 mRNA levels by a SYBR-green-based PCR in the bone marrow of 74 patients with myelodysplastic syndrome (MDS) and correlated them to their demographic, hematologic and prognostic characteristics. The median PARP1 mRNA levels were correlated to the type of MDS (2008/2016 WHO classification, P=0.005) and to the IPSS score (P=0.002). A correlation was also found with the IPSS-R score (P=0...
February 17, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28208804/hazelnut-corylus-avellana-l-shells-extract-phenolic-composition-antioxidant-effect-and-cytotoxic-activity-on-human-cancer-cell-lines
#5
Tiziana Esposito, Francesca Sansone, Silvia Franceschelli, Pasquale Del Gaudio, Patrizia Picerno, Rita Patrizia Aquino, Teresa Mencherini
Hazelnut shells, a by-product of the kernel industry processing, are reported to contain high amount of polyphenols. However, studies on the chemical composition and potential effects on human health are lacking. A methanol hazelnut shells extract was prepared and dried. Our investigation allowed the isolation and characterization of different classes of phenolic compounds, including neolignans, and a diarylheptanoid, which contribute to a high total polyphenol content (193.8 ± 3.6 mg of gallic acid equivalents (GAE)/g of extract)...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207569/poly-adp-ribose-polymerase-inhibition-suppresses-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#6
Ling-Yi Xiao, Wai-Ming Kan
Cancer cells may acquire drug resistance by activating DNA repair signaling. Poly ADP-ribose polymerase (PARP) plays an important role in DNA repair and it is overexpressed in many cancers including chronic myeloid leukemia (CML). PARP inhibitors have been used either alone or with other drugs to augment cancer cell death. However, whether PARP inhibitors may also augment cell death induced by chemotherapeutic agents in CML cells has not been studied. K562 cells with or without PARP-1 knockdown were treated with cisplatin alone or together with olaparib...
March 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28207246/aspartate-glycosylation-triggers-isomerization-to-isoaspartate
#7
John Janetzko, Suzanne Walker
O-linked β-N-acetylglucosamine transferase (OGT) is an essential human enzyme that glycosylates numerous nuclear and cytoplasmic proteins on serine and threonine. It also cleaves Host cell factor 1 (HCF-1) by a mechanism in which the first step involves glycosylation on glutamate. Replacing glutamate with aspartate in an HCF-1 proteolytic repeat was shown to prevent peptide backbone cleavage, but whether aspartate glycosylation occurred was not examined. We report here that OGT glycosylates aspartate much faster than it glycosylates glutamate in an otherwise identical model peptide substrate; moreover, once formed, the glycosyl aspartate reacts further to form a succinimide intermediate that hydrolyzes to produce the corresponding isoaspartyl peptide...
February 16, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28205583/flavichalasines-a-m-cytochalasan-alkaloids-from-aspergillus-flavipes
#8
Guangzheng Wei, Dongdong Tan, Chunmei Chen, Qingyi Tong, Xiao-Nian Li, Jinfeng Huang, Junjun Liu, Yongbo Xue, Jianping Wang, Zengwei Luo, Hucheng Zhu, Yonghui Zhang
Two new tetracyclic cytochalasans, flavichalasines A and B (1 and 2), three new pentacyclic cytochalasans, flavichalasines C-E (3-5), and eight new tricyclic cytochalasans, flavichalasines F-M (6-13), together with eight known analogues (14-21), were isolated from the solid culture of Aspergillus flavipes. Structures of these new compounds were elucidated on the basis of extensive spectroscopic analyses including 1D, 2D NMR and HRESIMS data. Their absolute configurations were determined by comparison of their experimental ECD with either computed ECD or experimental ECD spectrum of known compound...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202539/parps-and-adp-ribosylation-recent-advances-linking-molecular-functions-to-biological-outcomes
#9
REVIEW
Rebecca Gupte, Ziying Liu, W Lee Kraus
The discovery of poly(ADP-ribose) >50 years ago opened a new field, leading the way for the discovery of the poly(ADP-ribose) polymerase (PARP) family of enzymes and the ADP-ribosylation reactions that they catalyze. Although the field was initially focused primarily on the biochemistry and molecular biology of PARP-1 in DNA damage detection and repair, the mechanistic and functional understanding of the role of PARPs in different biological processes has grown considerably of late. This has been accompanied by a shift of focus from enzymology to a search for substrates as well as the first attempts to determine the functional consequences of site-specific ADP-ribosylation on those substrates...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28190768/serine-adp-ribosylation-depends-on-hpf1
#10
Juan José Bonfiglio, Pietro Fontana, Qi Zhang, Thomas Colby, Ian Gibbs-Seymour, Ilian Atanassov, Edward Bartlett, Roko Zaja, Ivan Ahel, Ivan Matic
ADP-ribosylation (ADPr) regulates important patho-physiological processes through its attachment to different amino acids in proteins. Recently, by precision mapping on all possible amino acid residues, we identified histone serine ADPr marks in the DNA damage response. However, the biochemical basis underlying this serine modification remained unknown. Here we report that serine ADPr is strictly dependent on histone PARylation factor 1 (HPF1), a recently identified regulator of PARP-1. Quantitative proteomics revealed that serine ADPr does not occur in cells lacking HPF1...
February 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28189061/pbde-209-exposure-damages-learning-and-memory-ability-in-rats-potentially-through-increased-autophagy-and-apoptosis-in-the-hippocampus-neuron
#11
Wen Sun, Lili Du, Wenting Tang, Liyun Kuang, Peili Du, Jingsi Chen, Dunjin Chen
This study is to investigate the neurotoxicity of PBDE-209 during pregnancy through autophagy and apoptosis in the fetal hippocampus neuron. The autophagy protein levels of LC3-II and Beclin-1 were significantly higher in hippocampus tissue and neuron, while P62 protein were lower. Apoptosis protein Cleaved Caspase-3 and Cleaved PARP was significantly higher in PBDE dose groups and BCL-2 levels in high PBDE dose groups were significantly lower. During the Morris water maze task, the escape latency times of high PBDE dose groups were significantly longer...
February 4, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28182994/atm-deficient-colorectal-cancer-cells-are-sensitive-to-the-parp-inhibitor-olaparib
#12
Chen Wang, Nicholas Jette, Daniel Moussienko, D Gwyn Bebb, Susan P Lees-Miller
The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors...
February 6, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28181692/irisin-plays-a-pivotal-role-to-protect-the-heart-against-ischemia-and-reperfusion-injury
#13
Hao Wang, Yu Tina Zhao, Shouyan Zhang, Patrycja M Dubielecka, Jianfeng Du, Naohiro Yano, Y Eugene Chin, Shougang Zhuang, Gangjian Qin, Ting C Zhao
Irisin, a newly identified hormone, is critical to modulating body metabolism, thermogenesis and reducing oxidative stresses. However, whether irisin protects the heart against myocardial ischemia and reperfusion (I/R) injury remains unknown. In this study, we determine the effect of irisin on myocardial I/R injury in the Langendorff perfused heart and cultured myocytes. Adult C57/BL6 mice were treated with irisin (100mg/kg) or vehicle for 30 minutes to elicit preconditioning. The isolated hearts were subjected to 30 min ischemia followed by 30 min reperfusion...
February 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28181578/anti-leukemia-effects-of-the-novel-synthetic-1-benzylindole-derivative-21-900-in-vitro-and-in-vivo
#14
Wei-Chun HuangFu, Min-Wu Chao, Chun-Chun Cheng, Yu-Chieh Wei, Yi-Wen Wu, Jing-Ping Liou, George Hsiao, Yu-Ching Lee, Chia-Ron Yang
Cancers are the major cause of death worldwide. Chemotherapy using cytotoxic drugs and targeted therapy is required when surgery is difficult, ineffective, or impossible. We previously synthesized the novel synthetic 1-benzylindole derivative 21-900 and found that it inhibits histone deacetylase (HDAC) activities and tubulin assembly. Here we tested its effects on the human leukaemia cell lines HL-60 and MOLT-4 in vitro and in vivo. We found that its potent cytotoxic effects were mediated through cell cycle arrest at the G2/M phase, which increased the population of sub-G1 cells, leading to apoptosis...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28181505/parp-1-parp-2-double-deficiency-in-mouse-t-cells-results-in-faulty-immune-responses-and-t-lymphomas
#15
Judith Navarro, Beatriz Gozalbo-López, Andrea C Méndez, Françoise Dantzer, Valérie Schreiber, Carlos Martínez, David M Arana, Jordi Farrés, Beatriz Revilla-Nuin, María F Bueno, Coral Ampurdanés, Miguel A Galindo-Campos, Philip A Knobel, Sandra Segura-Bayona, Juan Martin-Caballero, Travis H Stracker, Pedro Aparicio, Margarita Del Val, José Yélamos
The maintenance of T-cell homeostasis must be tightly regulated. Here, we have identified a coordinated role of Poly(ADP-ribose) polymerase-1 (PARP-1) and PARP-2 in maintaining T-lymphocyte number and function. Mice bearing a T-cell specific deficiency of PARP-2 in a PARP-1-deficient background showed defective thymocyte maturation and diminished numbers of peripheral CD4(+) and CD8(+) T-cells. Meanwhile, peripheral T-cell number was not affected in single PARP-1 or PARP-2-deficient mice. T-cell lymphopenia was associated with dampened in vivo immune responses to synthetic T-dependent antigens and virus, increased DNA damage and T-cell death...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28177666/poly-adp-ribose-polymerase-1-parp-1-in-chinese-patients-with-graves-disease-and-graves-ophthalmopathy
#16
Tong Wu, Dong-Run Tang, Liang Zhao, Feng-Yuan Sun
We aimed to evaluate the genetic variation of poly (ADP-ribose) polymerase-1 (PARP-1) as risk factor in development of Graves' disease (GD) and Graves Ophthalmopathy (GO) among Chinese individuals. Patients with confirmed diagnosis of GD or healthy individuals with no clinical symptoms of hyperthyroiditis were enrolled at department of Ophthalmology, Tianjin First Center Hospital, China. Genetic polymorphism was studied in plasma DNA samples of subjects by polymererase chain reaction of restriction fragment length polymorphism to confirm test our hypothesis...
January 29, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28177129/role-of-parp-activity-in-lung-cancer-induced-cachexia-effects-on-muscle-oxidative-stress-proteolysis-anabolic-markers-and-phenotype
#17
Alba Chacon-Cabrera, Mercè Mateu-Jimenez, Klaus Langohr, Clara Fermoselle, Elena García-Arumí, Antoni L Andreu, Jose Yelamos, Esther Barreiro
Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1(-/-) ) and Parp-2(-/-) mice...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28173629/enhanced-dependency-of-kras-mutant-colorectal-cancer-cells-on-rad51-dependent-homologous-recombination-repair-identified-from-genetic-interactions-in-saccharomyces-cerevisiae
#18
Murugan Kalimutho, Amanda L Bain, Bipasha Mukherjee, Purba Nag, Devathri M Nanayakkara, Sarah K Harten, Janelle L Harris, Goutham Narayanan Subramanian, Debottam Sinha, Senji Shirasawa, Sriganesh Srihari, Sandeep Burma, Kum Kum Khanna
Activating KRAS mutations drive colorectal cancer tumorigenesis and influence response to anti-EGFR targeted therapy. Despite recent advances in understanding Ras signaling biology and the revolution in therapies for melanoma using BRAF inhibitors, no targeted agents have been effective in KRAS mutant cancers, mainly due to activation of compensatory pathways. Here, by leveraging the largest synthetic lethal genetic interactome in yeast, we identify that KRAS-mutated colorectal cancer cells have augmented homologous recombination repair (HRR) signaling...
February 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28167507/parp-inhibitor-upregulates-pd-l1-expression-and-enhances-cancer-associated-immunosuppression
#19
Shiping Jiao, Weiya Xia, Hirohito Yamaguchi, Yongkun Wei, Mei-Kuang Chen, Jung-Mao Hsu, Jennifer L Hsu, Wen-Hsuan Yu, Yi Du, Heng-Huan Lee, Chia-Wei Li, Chao-Kai Chou, Seung-Oe Lim, Shih-Shin Chang, Jennifer K Litton, Banu Arun, Gabriel N Hortobagyi, Mien-Chie Hung
PURPOSE: To explore whether a crosstalk exists between PARP inhibition and PD-L1/ PD-1 immune checkpoint axis, and determine if blockade of PD-L1/ PD-1 potentiates PARP inhibitor (PARPi) in tumor suppression. EXPERIMENTAL DESIGN: Breast cancer cell lines, xenograft tumors and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, immunohistochemistry and FACS analyses. The phospho-kinase antibody array screen was used to explore the underlying mechanism of PARPi-induced PD-L1 upregulation...
February 6, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28165468/thy-1-interaction-with-fas-in-lipid-rafts-regulates-fibroblast-apoptosis-and-lung-injury-resolution
#20
Xiaoqiu Liu, Simon S Wong, Carmen A Taype, Jeeyeon Kim, Tzu-Pin Shentu, Celia R Espinoza, J Cameron Finley, John E Bradley, Brian P Head, Hemal H Patel, Emma J Mah, James S Hagood
Thy-1-negative lung fibroblasts are resistant to apoptosis. The mechanisms governing this process and its relevance to fibrotic remodeling remain poorly understood. By using either sorted or transfected lung fibroblasts, we found that Thy-1 expression is associated with downregulation of anti-apoptotic molecules Bcl-2 and Bcl-xL, as well as increased levels of cleaved caspase-9. Addition of rhFasL and staurosporine, well-known apoptosis inducers, caused significantly increased cleaved caspase-3, -8, and PARP in Thy-1-transfected cells...
February 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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