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https://www.readbyqxmd.com/read/28231559/prostate-cancer-heterogeneity-discovering-novel-molecular-targets-for-therapy
#1
REVIEW
Chiara Ciccarese, Francesco Massari, Roberto Iacovelli, Michelangelo Fiorentino, Rodolfo Montironi, Vincenzo Di Nunno, Francesca Giunchi, Matteo Brunelli, Giampaolo Tortora
Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies...
February 11, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28228392/idh-mutant-tumors-vulnerable-to-parp-inhibition
#2
(no author information available yet)
Several cancers, including glioma and acute myeloid leukemia, carry mutations in IDH1 or IDH2 Researchers have found that these mutations impair homologous recombination, making the tumors sensitive to PARP inhibition. They showed that one such inhibitor, olaparib, killed IDH1/2-mutant cancer cells in culture and slowed tumor growth in mice.
February 22, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28228218/-thioridazine-sensitizes-apoptotic-effect-of-trail-in-human-lung-cancer-pc9-cells-through-er-stress-mediated-up-regulation-of-dr5
#3
Juan Li, Yi Wang, Liu Liu, Yuan Yuan, Yangyi Bao
BACKGROUND: Tumor necrosis factor-related apoptosis-inducting ligand (TRAIL) can induce apoptosis of tumor cells, however, various of tumor cells may survive because of resistance to TRAIL-mediated apoptosis. This study is to observe the proliferation inhibition effect of TRAIL sensitized by thioridazine on PC9 cells through endoplasmic reticulum (ER) stress mediated up-regulation of death receptor 5 (DR5) and investigate its mechanism. METHODS: PC9 cells were treated with different concentrations of thioridazine and TRAIL alone or in combination...
February 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28224182/parp-inhibition-ameliorates-nephropathy-in-an-animal-model-of-type-2-diabetes-focus-on-oxidative-stress-inflammation-and-fibrosis
#4
Esraa M Zakaria, Nabila N El-Maraghy, Ahmed F Ahmed, Abdelmonim A Ali, Hany M El-Bassossy
Poly(ADP-ribose) polymerase (PARP) enzyme contributes to nephropathy, a serious diabetic complication which may lead to end-stage renal disease. The study aims to investigate the effect of PARP over-activation on kidney functions in a type 2 diabetic rat model. The study also tests the therapeutic use of PARP inhibitors in diabetic nephropathy. Type 2 diabetes was induced in adult male rats by high-fructose/high-fat diet and low streptozotocin dose. Then, the PARP inhibitor 4-aminobenzamide (4-AB) was administered daily for 10 weeks...
February 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28223667/-molecular-diagnosis-and-treatment-of-hboc-syndrome
#5
Yoshio Miki
Hereditary breast and ovarian cancer(HBOC)is an inherited cancer caused by mutations of the BRCA1 or BRCA2 genes. BRCA genetic testing is used for HBOC diagnosis and continues to progress such as the annotation of VUS. In HBOC clinical practice, surveillance methods have been established through collaboration between genetic medicine and cancer medicine, and treatment, including options based on genetic diagnosis, has advanced significantly. Furthermore, the analysis of BRCA1 and BRCA2 function has progressed, and a novel therapeutic method based on synthetic lethality, such as a PARP inhibitor use, has been developed...
February 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28223140/reduced-cell-viability-and-apoptosis-induction-in-human-thyroid-carcinoma-and-mesothelioma-cells-exposed-to-cidofovir
#6
Simona Catalani, Francesco Palma, Serafina Battistelli, Barbara Nuvoli, Rossella Galati, Serena Benedetti
Besides its well-recognized antiviral activity, Cidofovir (CDV) has been shown to exert anticancer properties both within in vitro and in vivo models. The aim of this study was to evaluate the effects of CDV on still unexplored cultured cancer cells from human mesothelioma as well as breast, colon, liver, lung, prostate, and thyroid carcinomas. Overall, a dose- and time-dependent inhibition of cell viability was observed after CDV exposure. To clarify the mechanisms underlying CDV action, apoptotic cell death was investigated in two infected cell lines [Ist-Mes1 and Ist-Mes2 mesothelioma cells (SV40+)] and in two uninfected cell lines (NCI-H2425 mesothelioma cells and FTC-133 thyroid cancer cells), which resulted the most sensitive to CDV treatment...
February 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28222632/cryptotanshinone-potentiates-the-antitumor-effects-of-doxorubicin-on-gastric-cancer-cells-via-inhibition-of-stat3-activity
#7
Jiye Wang, Guangji Zhang, Chunyan Dai, Xiufei Gao, Jianbin Wu, Li Shen, Zhe Chen, Pei Liu
Objective To investigate the synergistic effects of cryptotanshinone (CPT) and doxorubicin (DOXO) on induction of apoptosis in human gastric cancer cells and the mechanisms. Methods Cell proliferation and apoptosis were detected using the CCK8 assay and AnnexinV/PI staining, respectively. Western blotting was used to determine the levels and phosphorylation of proteins encoded by STAT3-regulated genes and the cleaved forms of caspases and PARP. Results CPT significantly potentiated the antiproliferative effect of DOXO in gastric cancer cell lines...
February 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28220271/anandamide-oxidative-metabolism-induced-endoplasmic-reticulum-stress-and-apoptosis
#8
M Almada, B M Fonseca, C Amaral, M Diniz-da-Costa, G Correia-da-Silva, N Teixeira
The Endocannabinoid System (ECS) has been recognized as a crucial player in human reproduction. Changes in the levels of anandamide (AEA), the main endocannabinoid (eCB), negatively affect reproductive events, such as implantation, decidualization and placentation. Cyclooxygenase-2 (COX-2) is a major enzyme expressed in the endometrium and its involvement in female reproductive system has evolved over the last few years. Currently, COX-2 oxidative metabolism is emerging as a key mediator of AEA-induced actions...
February 20, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28220129/no-silver-bullet-canonical-poly-adp-ribose-polymerases-parps-are-no-universal-factors-of-abiotic-and-biotic-stress-resistance-of-arabidopsis-thaliana
#9
Dagmar Rissel, Peter P Heym, Kathrin Thor, Wolfgang Brandt, Ludger A Wessjohann, Edgar Peiter
Abiotic and biotic stress can have a detrimental impact on plant growth and productivity. Hence, there is a substantial demand for key factors of stress responses to improve yield stability of crops. Members of the poly(ADP-ribose)polymerase (PARP) protein family, which post-translationally modify (PARylate) nuclear proteins, have been suggested as such universal determinants of plant stress responses. A role under abiotic stress has been inferred from studies in which a genetic or, more commonly, pharmacological inhibition of PARP activity improved the performance of stressed plants...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28219892/an-infectious-disease-associated-il12b-polymorphism-regulates-il-12-23-p40-transcription-involving-poly-adp-ribose-polymerase-1
#10
Quanju Zhao, Qinglin Du, Fang Wei, Jianping Xie, Xiaojing Ma
IL-12 and IL-23 are important host defense factors produced by APCs against certain intracellular and extracellular pathogens. Their dysregulation has also been implicated in several autoimmune diseases. The nucleotide polymorphism in the promoter region of Il12b (rs41292470 consisting of the long or short allele) encoding the shared subunit of IL-12 and IL-23, p40, has been reported to associate with susceptibility to infectious diseases and autoimmune disorders. How these genetic variants impact Il12b expression at the molecular level was unclear...
February 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28219770/silencing-of-the-mrna-binding-protein-hur-increases-the-sensitivity-of-colorectal-cancer-cells-to-ionizing-radiation-through-upregulation-of-caspase-2
#11
Amel Badawi, Stephanie Hehlgans, Josef Pfeilschifter, Franz Rödel, Wolfgang Eberhardt
Increased abundance of the mRNA-binding protein human antigen R (HuR) is a characteristic feature of many cancers and frequently associated with a high grade malignancy and therapy resistance. HuR elicits a broad cell survival program mainly by stabilizing or increasing the translation of mRNAs coding for anti-apoptotic effector proteins. Conversally, we previously identified the pro-apoptotic caspase-2 as a novel HuR target which is mainly regulated at the level of translation. In this study, we investigated whether siRNA-mediated HuR knockdown interferes with cell survival and radiation sensitivity by monitoring apoptosis, DNA repair and three-dimensional (3D) clonogenic survival...
February 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28219700/inhibition-of-ros-production-autophagy-or-apoptosis-signaling-reversed-the-anticancer-properties-of-antrodia-salmonea-in-triple-negative-breast-cancer-mda-mb-231-cells
#12
Chia-Ting Chang, Mallikarjuna Korivi, Hui-Chi Huang, Varadharajan Thiyagarajan, Kai-Yuan Lin, Pei-Jane Huang, Jer-Yuh Liu, You-Cheng Hseu, Hsin-Ling Yang
We investigated the in vitro and in vivo anticancer properties of Antrodia salmonea (AS), a well-known edible/medicinal mushroom in Taiwan, on human triple-negative breast cancer (MDA-MB-231) cells and xenografted nude mice; and revealed the underlying molecular mechanisms involved in autophagic- and apoptotic-cell death. Treatment of MDA-MB-231 cells with fermented culture broth of AS (0-200 μg/mL) inhibited cell viability/growth. AS-induced autophagy was evidenced via increased LC3-II accumulation, GFP-LC3 puncta and AVOs formation in MDA-MB-231 cells...
February 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28216291/ovarian-tumor-domain-containing-protein-1-deubiquitinates-and-stabilizes-p53
#13
Shudong Piao, Han Zhong Pei, Bin Huang, Suk-Hwan Baek
Ubiquitination and deubiquitination pathways play important roles in the regulation of p53 stability and activity. p53 is ubiquitinated and destabilized by E3 ubiquitin ligases and is deubiquitinated and stabilized by deubiquitinases (DUBs). We screened ovarian tumor (OTU) subfamily proteins to identify novel DUBs that stabilized p53. OTU domain-containing protein 1 (OTUD1) is a DUB belonging to the OTU family; however, its substrates and its role in cells are unknown. Here, we used an overexpression and knockdown system to show that OTUD1 is a novel regulator of p53 stability...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28216025/pi3k-akt-mtor-inhibitors-in-breast-cancers-from-tumor-cell-signaling-to-clinical-trials
#14
REVIEW
Dey Nandini, De Pradip, Leyland-Jones Brian
Breast cancer (BC) is the most common women cancer and second most common cause of cancer death in women. A woman living in the Unites States has 12.3% lifetime risk of being diagnosed with BC. From the genomics point of view, the most common three subtypes of BC encountered in clinics are HR+, HER2+, and TNBC or basal-like BC. Estrogen receptor (ER) status or HER2 amplification or chemotherapy is not sufficient to understand the underlying mechanisms of disease progression and resistance (de novo or acquire)...
February 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28215644/from-molecular-insight-to-therapeutic-strategy-the-holistic-approach-for-treating-triple-negative-breast-cancer
#15
REVIEW
Rittwika Bhattacharya, Koyel Banerjee, Nupur Mukherjee, Minakshi Sen, Ashis Mukhopadhyay
Aim of the present study was to analyze the molecular pathogenesis of TNBC, therapeutic practice, challenges, and future goals in treatment strategies. Based on the alterations of distinct pathways, Lehmann's subgroups of TNBCs were further categorized. Those with defective DNA damage repair and replication pathways, viz. Basal Like 1 & 2 (BL1, BL2) were found susceptible to DNA intercalating drugs while those with upregulated cell signalling & motility (mesenchymal (M), mesemchymal stem like (MSL)), cell survival (BL2, M, MSL), angiogenesis (BL2, MSL), T cell signalling (Immunomodulatory/IM) pathways required targeted therapies...
January 19, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28214344/neferine-potentiates-the-antitumor-effect-of-cisplatin-in-human-lung-adenocarcinoma-cells-via-a-mitochondria-mediated-apoptosis-pathway
#16
Kalai Selvi Sivalingam, Poornima Paramasivan, Ching Feng Weng, Viswanadha Vijaya Padma
Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G0/G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes as well as loss of mitochondrial membrane potential (ΔΨM)...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28214329/-p-clphse-2-reduces-hepatotoxicity-induced-by-monosodium-glutamate-by-improving-mitochondrial-function-in-rats
#17
Caroline B Quines, Pietro M Chagas, Diane Hartmann, Nélson R Carvalho, Félix A Soares, Cristina W Nogueira
It is has been demonstrated that mitochondrial dysfunction, oxidative stress and chronic inflammatory process are associated with progress of morbid obesity in human patients. For this reason, the searching for safe and effective antiobesity drugs has been the subject of intense research. In this context, the organic selenium compounds have attracted much attention due to their pharmacological properties, such as antihyperglycemic, antioxidant and anti-inflammatory. The aim of this study was to evaluate the hepatoprotective action of p-chloro-diphenyl diselenide (p-ClPhSe)2 , an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#18
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28212747/catalytic-independent-functions-of-parp-1-determine-sox2-pioneer-activity-at-intractable-genomic-loci
#19
Ziying Liu, W Lee Kraus
Pioneer transcription factors (TFs) function as genomic first responders, binding to inaccessible regions of chromatin to promote enhancer formation. The mechanism by which pioneer TFs gain access to chromatin remains an important unanswered question. Here we show that PARP-1, a nucleosome-binding protein, cooperates with intrinsic properties of the pioneer TF Sox2 to facilitate its binding to intractable genomic loci in embryonic stem cells. These actions of PARP-1 occur independently of its poly(ADP-ribosyl) transferase activity...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#20
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
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