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https://www.readbyqxmd.com/read/28650468/mkp-1-suppresses-parp-1-degradation-to-mediate-cisplatin-resistance
#1
J Wang, D H Kho, J-Y Zhou, R J Davis, G S Wu
Understanding the mechanisms of platinum compound resistance, including cisplatin resistance, has important implications for improving cancer treatments. Previous studies identified a potential role for mitogen-activated protein kinase phosphatase-1 (MKP-1) in cisplatin resistance. This work focuses on the regulation of poly(ADP-ribose) polymerase-1 (PARP-1) expression by MKP-1. We found that MKP-1 overexpression stimulates PARP-1 and poly(ADP-ribose) (PAR) protein expression and cisplatin resistance while its downregulation suppresses PARP-1 and PAR protein expression and cisplatin resistance...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28644128/intraductal-cisplatin-treatment-in-a-brca-associated-breast-cancer-mouse-model-attenuates-tumor-development-but-leads-to-systemic-tumors-in-aged-female-mice
#2
Jolien S de Groot, Paul J van Diest, Miranda van Amersfoort, Eva J Vlug, Xiaojuan Pan, Natalie D Ter Hoeve, Hilde Rosing, Jos H Beijnen, Sameh A Youssef, Alain de Bruin, Jos Jonkers, Elsken van der Wall, Patrick W B Derksen
BRCA deficiency predisposes to the development of invasive breast cancer. In BRCA mutation carriers this risk can increase up to 80%. Currently, bilateral prophylactic mastectomy and prophylactic bilateral salpingo-oophorectomy are the only preventive, albeit radical invasive strategies to prevent breast cancer in BRCA mutation carriers. An alternative non-invasive way to prevent BRCA1-associated breast cancer may be local prophylactic treatment via the nipple.Using a non-invasive intraductal (ID) preclinical intervention strategy, we explored the use of combined cisplatin and poly (ADP)-ribose polymerase 1 (PARP1) inhibition to prevent the development of hereditary breast cancer...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642874/combination-treatment-with-ppar%C3%AE-ligand-and-its-specific-inhibitor-gw9662-downregulates-bis-and-14-3-3-gamma-inhibiting-stem-like-properties-in-glioblastoma-cells
#3
Chang-Nim Im
PPARγ is a nuclear receptor that regulates differentiation and proliferation and is highly expressed in many cancer cells. Its synthetic ligands, such as rosiglitazone and ciglitazone, and its inhibitor GW9662, were shown to induce cellular differentiation, inhibit proliferation, and lead to apoptosis. Glioblastoma is a common brain tumor with poor survival prospects. Recently, glioblastoma stem cells (GSCs) have been examined as a potential target for anticancer therapy; however, little is known about the combined effect of various agents on GSCs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28642177/protective-functions-of-pj34-a-parp-inhibitor-is-related-to-down-regulation-of-calpain-and-nf-%C3%AE%C2%BAb-in-a-mouse-model-of-tbi
#4
Xiaogang Tao, Xuetao Chen, Zonggang Hou, Shuyu Hao, Baiyun Liu
OBJECTIVES: Poly(ADP-ribose) polymerase (PARP), calpain, and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathological conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participated in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI). METHODS: PJ34 (10 mg/kg), a selective PARP inhibitor, was administered intraperitoneally 5 min and 8 h after experimental CCI...
June 19, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28639907/ferrichrome-identified-from-lactobacillus-casei-atcc334-induces-apoptosis-through-its-iron-binding-site-in-gastric-cancer-cells
#5
Masami Ijiri, Mikihiro Fujiya, Hiroaki Konishi, Hiroki Tanaka, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Junpei Sasajima, Katsuya Ikuta, Toshikatsu Okumura
Ferrichrome is known to be a siderophore, but it was recently identified as a tumor-suppressive molecule derived from Lactobacillus casei ATCC334 ( L. casei). In the present study, we investigated the effects of ferrichrome in gastric cancer cells. Cell lines and xenograft models treated with ferrichrome demonstrated growth suppression. The expression levels of cleaved poly (adenosine diphosphate-ribose) polymerase, and cleaved caspase-9 were increased by ferrichrome treatment. Although the tumor-suppressive effects of ferrichrome were almost completely diminished by the iron chelation, the reduction in the intracellular iron by ferrichrome did not correlate with its tumor-suppressive effects...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639887/microrna-138-enhances-trail-induced-apoptosis-through-interferon-stimulated-gene-15-downregulation-in-hepatocellular-carcinoma-cells
#6
Chaohui Zuo, Xinyi Sheng, Zhuo Liu, Min Ma, Shuhan Xiong, Hongyu Deng, Sha Li, Darong Yang, Xiaohong Wang, Hua Xiao, Hu Quan, Man Xia
Hepatocellular carcinoma is a leading cause of cancer-related mortality worldwide. TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) is a potential target for cancer therapy. However, many cancer cells are resistant to TRAIL-induced apoptosis and its mechanism is not well understood. In this study, to identify potential therapeutic targets for TRAIL-resistant cancer cells, we compared the expression levels of interferon-stimulated gene 15 in TRAIL-sensitive and TRAIL-resistant hepatocellular carcinoma cell lines...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28636950/structural-evidence-of-quercetin-multi-target-bioactivity-a-reverse-virtual-screening-strategy
#7
Diego Carvalho, Margot Paulino, Fabio Polticelli, Florencia Arredondo, Robert J Williams, Juan A Abin-Carriquiry
The ubiquitous flavonoid quercetin is broadly recognized for showing diverse biological and health-promoting effects, such as anti-cancer, anti-inflammatory and cytoprotective activities. The therapeutic potential of quercetin and similar compounds for preventing such diverse oxidative stress-related pathologies has been generally attributed to their direct antioxidant properties. Nevertheless, accumulated evidence indicates that quercetin is also able to interact with multiple cellular targets influencing the activity of diverse signaling pathways...
June 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28636652/integrative-analysis-of-genomic-alterations-in-triple-negative-breast-cancer-in-association-with-homologous-recombination-deficiency
#8
Masahito Kawazu, Shinya Kojima, Toshihide Ueno, Yasushi Totoki, Hiromi Nakamura, Akiko Kunita, Wei Qu, Jun Yoshimura, Manabu Soda, Takahiko Yasuda, Natsuko Hama, Mihoko Saito-Adachi, Kazuhito Sato, Shinji Kohsaka, Eirin Sai, Masako Ikemura, Shigeru Yamamoto, Tomoko Ogawa, Masashi Fukayama, Keiichiro Tada, Yasuyuki Seto, Shinichi Morishita, Shoichi Hazama, Tatsuhiro Shibata, Yoshihiro Yamashita, Hiroyuki Mano
Triple-negative breast cancer (TNBC) cells do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2. Currently, apart from poly ADP-ribose polymerase inhibitors, there are few effective therapeutic options for this type of cancer. Here, we present comprehensive characterization of the genetic alterations in TNBC performed by high coverage whole genome sequencing together with transcriptome and whole exome sequencing. Silencing of the BRCA1 gene impaired the homologous recombination pathway in a subset of TNBCs, which exhibited similar phenotypes to tumors with BRCA1 mutations; they harbored many structural variations (SVs) with relative enrichment for tandem duplication...
June 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28636622/inhibition-of-hepatitis-b-viral-entry-by-nucleic-acid-polymers-in-heparg-cells-and-primary-human-hepatocytes
#9
Clément Guillot, Nora Martel, Françoise Berby, Isabelle Bordes, Olivier Hantz, Matthieu Blanchet, Camille Sureau, Andrew Vaillant, Isabelle Chemin
Hepatitis B virus (HBV) infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV drugs. Nucleic acid polymers (NAPs) are phosphorothioated oligonucleotides that have demonstrated a great potential to inhibit infection with several viruses. In chronically infected human patients, NAPs administration lead to a decline of blood HBsAg and HBV DNA and to HBsAg seroconversion, the expected signs of functional cure...
2017: PloS One
https://www.readbyqxmd.com/read/28636353/synthesis-of-8-substituted-analogues-of-cyclic-adp-4-thioribose-and-their-unexpected-identification-as-ca2-mobilizing-full-agonists
#10
Satoshi Takano, Takayoshi Tsuzuki, Takashi Murayama, Tomoshi Kameda, Yasuhiro Kumaki, Takashi Sakurai, Hayato Fukuda, Mizuki Watanabe, Mitsuhiro Arisawa, Satoshi Shuto
A series of 8-substituted analogues of cyclic ADP-4-thioribose (cADPtR, 3), which is a stable equivalent of Ca2+-mobilizing second messenger cyclic ADP-ribose (cADPR, 1), were designed as potential pharmacological tools for the studies on cADPR-modulated Ca2+ signaling pathways. These 8-amino analogue (8-NH2-cADPtR, 4), 8-azido analogue (8-N3-cADPtR, 5), and 8-chloro analogue (8-Cl-cADPtR, 6) were efficiently synthesized, where the stereoselective N1-β-thioribosyladenine-ring closure reaction via an α/β-equilibrium of the 1-aminothioribose derivative and construction of the characteristic 18-membered pyrophosphate ring by Ag+-promoted activation of a phenyl phosphorothioate-type substrate were the two key steps...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28634224/igh-myc-translocation-associates-with-brca2-deficiency-and-synthetic-lethality-to-parp1-inhibitors
#11
Silvia Maifrede, Kayla Martin, Paulina Podszywalow-Bartnicka, Katherine Sullivan, Samantha K Langer, Reza Nejadi, Yashodhara Dasgupta, Michael Hulse, Daniel Gritsyuk, Margaret Nieborowska-Skorska, Lena N Lupey-Green, Huaqing Zhao, Katarzyna Piwocka, Mariusz A Wasik, Italo Tempera, Tomasz Skorski
Burkitt lymphoma/leukemia (BL) cells carry t(8;14)(q24;q32) chromosomal translocation encoding IGH/MYC, which results in the constitutive expression of the MYC oncogene. Here, it is demonstrated that untreated and cytarabine (AraC)-treated IGH/MYC-positive BL cells accumulate a high number of potentially lethal DNA double-strand breaks (DSBs) and display low levels of the BRCA2 tumor suppressor protein, which is a key element of homologous recombination (HR)-mediated DSB repair. BRCA2 deficiency in IGH/MYC-positive cells was associated with diminished HR activity and hypersensitivity to poly (ADP-ribose) polymerase-1 (PARP1) inhibitors (olaparib, talazoparib) used alone or in combination with cytarabine in vitro...
June 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28631564/indole-3-carbinol-induces-apoptosis-of-chronic-myelogenous-leukemia-cells-through-suppression-of-stat5-and-akt-signaling-pathways
#12
Majid Safa, Leila Jafari, Fatemeh Alikarami, Rima Manafi Shabestari, Ahmad Kazemi
Signal transducer and activator of transcription 5 and Akt pathways, implicated in signaling transduction downstream of BCR-ABL, play critical roles in the pathogenesis of chronic myeloid leukemia. Therefore, idenication of novel compounds that modulate the activity of such pathways could be a new approach in the treatment of chronic myeloid leukemia. Previous studies have demonstrated that indole-3-carbinol inhibits the proliferation and induces apoptosis of various tumor cells. However, its anticancer activity against chronic myeloid leukemia cells and the underlying mechanism remain unclear...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28630443/chemical-chaperone-tudca-unlike-pba-mitigates-protein-aggregation-efficiently-and-resists-er-and-non-er-stress-induced-hepg2-cell-death
#13
Jagadeesh Kumar Uppala, Amina R Gani, Kolluru V A Ramaiah
Stress induced BSA (bovine serum albumin) protein aggregation is effectively mitigated in vitro by TUDCA (tauroursodeoxycholic acid) than by PBA (4- phenylbutyric acid), chemical chaperones approved by FDA for the treatment of biliary cirrhosis and urea cycle disorders respectively. TUDCA, unlike PBA, enhances trypsin mediated digestion of BSA. TUDCA activates PERK, an ER-resident kinase that phosphorylates the alpha-subunit of eukaryotic initiation factor2 (eIF2α) and promotes the expression of activated transcription factor 4 (ATF4) in HepG2 cells...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630126/a-key-enzyme-of-the-nad-salvage-pathway-in-thermus-thermophilus-characterization-of-nicotinamidase-and-the-impact-of-its-gene-deletion-at-high-temperatures
#14
Hironori Taniguchi, Sathidaphorn Sungwallek, Phatcharin Chotchuang, Kenji Okano, Kohsuke Honda
Nicotinamide adenine dinucleotide (NAD(+)) is a cofactor related to many cellular processes. This cofactor is known to be unstable, especially at high temperatures, where it chemically decomposes to nicotinamide and ADP-ribose. Bacteria, yeast, and higher organisms possess the salvage pathway for reconstructing NAD(+) from these decomposition products; however, the importance of the salvage pathway for survival is not well elucidated, except for in pathogens lacking the NAD(+)de novo synthesis pathway. Herein, we report the importance of the NAD(+) salvage pathway in the thermophilic bacterium Thermus thermophilus HB8 at high temperatures...
June 19, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28629998/aloe-emodin-ae-nanoparticles-suppresses-proliferation-and-induces-apoptosis-in-human-lung-squamous-carcinoma-via-ros-generation-in-vitro-and-in-vivo
#15
Yuan-Yuan Wu, Jing-Hua Zhang, Jing-Hua Gao, Yong-Sheng Li
Human lung squamous cell carcinoma is a deadly cancer for which present therapeutic strategies are inadequate. And traditional chemotherapy results in severe systemic toxicity. Compounds from living organisms often exert a biological activity, triggering several targets, which may be useful for the improvement of novel pharmaceuticals. Aloe-emodin (AE), a well-known natural compound, is a primary component of anthraquinones in Aloe vera and exhibits anti-proliferative and apoptotic effects on various tumor cells...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28629498/rodentibacter-gen-nov-including-rodentibacter-pneumotropicus-comb-nov-rodentibacter-heylii-sp-nov-rodentibacter-myodis-sp-nov-rodentibacter-ratti-sp-nov-rodentibacter-heidelbergensis-sp-nov-rodentibacter-trehalosifermentans-sp-nov-rodentibacter-rarus-sp-nov
#16
Sadhana Adhikary, Werner Nicklas, Magne Bisgaard, Ron Boot, Peter Kuhnert, Torsten Waberschek, Bent Aalbæk, Bozena Korczak, Henrik Christensen
Rodentibacter gen. nov. is proposed based on isolation and phenotypic characterization of strains, predominantly from rodents. The strains showed 86 % or higher rpoB gene sequence similarity and indicated a genus-level relationship within Pasteurellaceae. The strains compared at 16S rRNA gene sequence level showed 93.8 % or higher similarity, and their genus-level relationship within Pasteurellaceae was confirmed by phenotypic analysis. The type species Rodentibacter pneumotropicus comb. nov. is reclassified from [Pasteurella] pneumotropica with type strain NCTC 8141T (=CCUG 12398T)...
June 20, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28629492/calidifontibacter-terrae-sp-nov-an-actinomycete-isolated-from-soil-with-potential-applications-in-cosmetics
#17
Ram Hari Dahal, Dong Seop Shim, Joon Young Kim, Jaisoo Kim
An aerobic, Gram-stain-positive, oxidase- and catalase-positive, non-motile, non-spore-forming, coccoid, creamish-white-coloured bacterium, designated strain R161T, was isolated from soil in Hwaseong, South Korea. The cell-wall peptidoglycan contained glycine, glutamic acid, alanine, aspartic acid, serine and lysine, and whole-cell sugars were galactose, rhamnose, glucose and ribose. Strain R161T showed antibacterial and enzyme inhibitory activities. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain R161T formed a lineage within the family Dermacoccaceae, and showed highest sequence similarity with type strains of Calidifontibacter indicus PC IW02T (97...
June 20, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/28628644/targeting-multiple-pro-apoptotic-signaling-pathways-with-curcumin-in-prostate-cancer-cells
#18
Mariela Rivera, Yanilda Ramos, Madeline Rodríguez-Valentín, Sheila López-Acevedo, Luis A Cubano, Jin Zou, Qiang Zhang, Guangdi Wang, Nawal M Boukli
Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28628309/dissecting-orthosteric-contacts-for-a-reverse-fragment-based-ligand-design
#19
Arun Chandramohan, Nikhil Kumar Tulsian, Ganesh Srinivasan Anand
Orthosteric sites on proteins are formed typically from non-contiguous interacting sites in three dimensional space where the composite binding interaction of a biological ligand is mediated by multiple synergistic interactions of its constituent functional groups. Through these multiple interactions, ligands stabilize both the ligand binding site and the protein fold. However, relative energetic contributions of the individual contacts in these protein-ligand interactions are difficult to resolve. Deconvolution of the contributions of these various functional groups in natural inhibitors/ligand would greatly aid in iterative fragment-based drug discovery (FBDD)...
June 19, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28628205/stereoselective-synthesis-of-4-selenonucleosides-via-the-seleno-michael-reaction
#20
Pramod K Sahu, Dnyandev B Jarhad, Gyudong Kim, Lak Shin Jeong
5'-Homo-4'-selenonucleosides, a class of next-generation nucleosides, are synthesized from D-ribose via a 4-selenosugar intermediate. The key step in synthesizing this intermediate is a seleno-Michael reaction. 5'-Homo-4'-selenouridine and -adenosine are prepared using Pummerer-type and Vorbrüggen condensation, respectively. © 2017 by John Wiley & Sons, Inc.
June 19, 2017: Current Protocols in Nucleic Acid Chemistry
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