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Francesco Pasqualetti, Alessandra Gonnelli, Martina Cantarella, Durim Delishaj, Alessandro Molinari, Valerio Ortenzi, Francesco Carbone, Sabrina Montrone, Stefano Ursino, Sara Franceschi, Riccardo Morganti, Paola Orlandi, Teresa Di Desidero, Chiara Maria Mazzanti, Katia Zavaglia, Antonio Giuseppe Naccarato, Guido Bocci, Fabiola Paiar
Glioblastoma (GBM) is the most frequent malignant primary brain tumor in adults and, despite recent advances, the prognosis for this cancer remains dismal. The aims of this study were to test the influence of XRCC1 rs25487, XRCC3 rs861539, XRCC3 rs1799794, RAD51 rs1801320 and GSTP-1 rs1695 single nucleotide polymorphisms on progression free survival (PFS) and overall survival (OS) in GBM patients treated with radiotherapy (RT) and temozolomide (TMZ). Fifty GBM patients treated with upfront radio-chemotherapy (RT 60 Gy/30 sessions; TMZ 75 mg/m(2) during RT and 200 mg/m(2) days 1 → 5 every 28 days) were enrolled...
September 30, 2017: Investigational New Drugs
Shinichiro Kashiwagi, Wakaba Fukushima, Yuka Asano, Wataru Goto, Koji Takada, Satoru Noda, Tsutomu Takashima, Naoyoshi Onoda, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The recently developed reagent, eribulin mesylate (eribulin), is a microtubule dynamics inhibitor with a mechanism of action that differs from those of taxanes and vinca alkaloids. This drug is considered to be a promising chemotherapeutic agent for the treatment of locally advanced or metastatic breast cancer (MBC). In this study, we investigated if variables such as tumor expression of β-tubulin class III, glutathione S-transferase pi (GSTP) 1 or transducin-like enhancer of split (TLE) 3 might act as predictive factors on the therapeutic effect of eribulin chemotherapy...
August 31, 2017: BMC Cancer
Vincent L M Yip, Xiaoli Meng, James L Maggs, Rosalind E Jenkins, Philippe T Marlot, Anthony G Marson, B Kevin Park, Munir Pirmohamed
Carbamazepine (CBZ) is an effective antiepileptic drug that has been associated with hypersensitivity reactions. The pathogenesis of those reactions is incompletely understood but is postulated to involve a complex interplay between the drug's metabolism, genetic variation in human leukocyte antigens, and adverse activation of the immune system. Multiple T-cell activation mechanisms have been hypothesized including activation by drug-peptide conjugates derived from proteins haptenated by reactive metabolites...
July 17, 2017: Chemical Research in Toxicology
Chia-Yuan Lin, Ru-Huei Fu, Ruey-Hwang Chou, Jing-Hsien Chen, Chi-Rei Wu, Shu-Wei Chang, Chia-Wen Tsai
Pi class of glutathione S-transferase (GST) is known to suppress c-Jun N-terminal kinase (JNK)-related apoptosis through protein-protein interactions. Moreover, signaling by PKA/cAMP response element binding protein (CREB) is necessary for GSTP up-regulation. This study explored whether carnosic acid (CA) from rosemary prevents 6-hydroxydopamine (6-OHDA)-induced neurotoxicity by inhibition of JNK through GSTP via PKA/CREB signaling. Results indicated that the GSTP protein was increased in SH-SY5Y cells treated with CA for 18 and 24 h...
May 2017: Food and Chemical Toxicology
Theodossis A Theodossiou, Cathrine E Olsen, Marte Jonsson, Andreas Kubin, John S Hothersall, Kristian Berg
The diverse responses of different cancers to treatments such as photodynamic therapy of cancer (PDT) have fueled a growing need for reliable predictive markers for treatment outcome. In the present work we have studied the differential response of two phenotypically and genotypically different breast adenocarcinoma cell lines, MCF7 and MDA-MB-231, to hypericin PDT (HYP-PDT). MDA-MB-231 cells were 70% more sensitive to HYP PDT than MCF7 cells at LD50. MCF7 were found to express a substantially higher level of glutathione peroxidase (GPX4) than MDA-MB-231, while MDA-MB-231 differentially expressed glutathione-S-transferase (GSTP1), mainly used for xenobiotic detoxification...
August 2017: Redox Biology
Yongli Hua, Wangling Yao, Peng Ji, Yanming Wei
CONTEXT: Angelica sinensis (Oliv.) Diels (Umbelliferae) (AS) is a well-known Traditional Chinese Medicine (TCM) that enriches and regulates the blood. OBJECTIVE: An integrated metabonomic and proteomic method was developed and applied to study the blood enrichment effects and mechanisms of AS on blood deficiency (BD) mouse model. MATERIALS AND METHODS: Forty mice were randomly divided into the control, BD, High-dose of AS (ASH), Middle-dose of AS (ASM), and Low-dose of AS (ASL) groups...
December 2017: Pharmaceutical Biology
Jiao Meng, Zhenyu Lv, Xinhua Qiao, Xiaopeng Li, Yazi Li, Yuying Zhang, Chang Chen
Aging is tightly associated with redox events. The free radical theory of aging indicates that redox imbalance may be an important factor in the aging process. Most studies about redox and aging focused on the static status of oxidative stress levels, there has been little research investigating differential responses to redox challenge during aging. In this study, we used Caenorhabditis elegans and human fibroblasts as models to compare differential responses to oxidative stress challenge in young and old individuals...
April 2017: Redox Biology
Xinsheng Lai, Yuren Zhou, Xiaoyun Xia, Qingfu Zhang
The Steiner tree problem (STP) aims to determine some Steiner nodes such that the minimum spanning tree over these Steiner nodes and a given set of special nodes has the minimum weight, which is NP-hard. STP includes several important cases. The Steiner tree problem in graphs (GSTP) is one of them. Many heuristics have been proposed for STP, and some of them have proved to be performance guarantee approximation algorithms for this problem. Since evolutionary algorithms (EAs) are general and popular randomized heuristics, it is significant to investigate the performance of EAs for STP...
December 13, 2016: Evolutionary Computation
K Başak, P Y Başak, D K Doğuç, F Aylak, S Oğuztüzün, B M Bozer, F Gültekin
Glutathione-S-transferase (GST) and cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) metabolize and detoxify carcinogens, drugs, environmental pollutants, and reactive oxygen species. Changes of GST expression in tissues and gene mutations have been reported in association with many neoplastic skin diseases and dermatoses. Widely used artificial food coloring additives (AFCAs) also reported to effect primarily behavioral and cognitive function and cause neoplastic diseases and several inflammatory skin diseases...
November 16, 2016: Human & Experimental Toxicology
Jing Zhou, Lianping Ge, Changkai Jia, Xiling Zheng, Huixia Cui, Rongrong Zong, Xiaorui Bao, Yuanyuan Yin, Jian-Xing Ma, Wei Li, Zuguo Liu, Yueping Zhou
The role of ROS in stem cell biology has not been fully illustrated and understood. Here we compared the different responses and investigated the mechanism underlying oxidative stress induced by hydrogen peroxide (H2O2) between murine corneal epithelial progenitor cell line (TKE2) and mature murine corneal epithelial cells (MCE). TKE2 showed a different homeostasis and strong resistance to H2O2. TKE2 reduced the production of ROS, inhibited ROS generation enzyme NADPH oxidase 4 (NOX4), and increased dual specificity phosphatase 6 (DUSP6)...
November 2, 2016: Scientific Reports
A V Ivanov, A G Dedul, Y N Fedotov, E V Komlichenko
BACKGROUND: At present, the patient preparation for IVF needs to undergo a series of planned tests, including the genotyping of single nucleotide polymorphism (SNP) alleles of some genes. In former USSR countries, such investigation was not included in overwhelming majority of health insurance programs and paid by patient. In common, there are prerequisites to the study of more than 50 polymorphisms. An important faced task is to determine the optimal panel for SNP genotyping in terms of price/number of SNP...
October 2016: Gynecological Endocrinology
Fang Yang, Hong Yang, Aramandla Ramesh, J Shawn Goodwin, Emmanuel U Okoro, ZhongMao Guo
UNLABELLED: We previously reported that overexpression of catalase upregulated xenobiotic- metabolizing enzyme (XME) expression and diminished benzo(a)pyrene (BaP) intermediate accumulation in mouse aortic endothelial cells (MAECs). Endoplasmic reticulum (ER) is the most active organelle involved in BaP metabolism. To examine the involvement of ER in catalase-induced BaP detoxification, we compared the level and distribution of XMEs, and the profile of BaP intermediates in the microsomes of wild-type and catalase transgenic endothelial cells...
2016: PloS One
Richard Ramsden, Evan P Gallagher
The transcription factor NFE2L2 (Nuclear Factor, Erythroid 2-Like 2, or NRF2) plays a key role in maintaining the redox state within cells. Characterization of this pathway has extended to fish, most notably zebrafish (Danio rerio), in which two paralogs of the transcription factor exist: Nrf2a, an activator, and Nrf2b, a negative regulator during embryogenesis. Only one ARE target has been thoroughly delineated in zebrafish, and this deviated from the canonical sequence derived from studies in mammals. In general, the mechanistic pathway has not been characterized in non-model aquatic organisms that are commonly exposed to environmental pollutants...
October 2016: Redox Biology
David H McMillan, Jos L J van der Velden, Karolyn G Lahue, Xi Qian, Robert W Schneider, Martina S Iberg, James D Nolin, Sarah Abdalla, Dylan T Casey, Kenneth D Tew, Danyelle M Townsend, Colin J Henderson, C Roland Wolf, Kelly J Butnor, Douglas J Taatjes, Ralph C Budd, Charles G Irvin, Albert van der Vliet, Stevenson Flemer, Vikas Anathy, Yvonne M W Janssen-Heininger
Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease characterized by excessive collagen production and fibrogenesis. Apoptosis in lung epithelial cells is critical in IPF pathogenesis, as heightened loss of these cells promotes fibroblast activation and remodeling. Changes in glutathione redox status have been reported in IPF patients. S-glutathionylation, the conjugation of glutathione to reactive cysteines, is catalyzed in part by glutathione-S-transferase π (GSTP). To date, no published information exists linking GSTP and IPF to our knowledge...
June 2, 2016: JCI Insight
Olivia J Osborne, Katsuki Mukaigasa, Hitomi Nakajima, Bjorn Stolpe, Isabella Romer, Uzoma Philips, Iseult Lynch, Sulayman Mourabit, Shigehisa Hirose, Jamie R Lead, Makoto Kobayashi, Tetsuhiro Kudoh, Charles R Tyler
Some nanoparticles (NPs) may induce adverse health effects in exposed organisms, but to date the evidence for this in wildlife is very limited. Silver nanoparticles (AgNPs) can be toxic to aquatic organisms, including fish, at concentrations relevant for some environmental exposures. We applied whole mount in-situ hybridisation (WISH) in zebrafish embryos and larvae for a suite of genes involved with detoxifying processes and oxidative stress, including metallothionein (mt2), glutathionine S-transferase pi (gstp), glutathionine S-transferase mu (gstm1), haem oxygenase (hmox1) and ferritin heavy chain 1 (fth1) to identify potential target tissues and effect mechanisms of AgNPs compared with a bulk counterpart and ionic silver (AgNO3)...
November 2016: Nanotoxicology
Shanthi Ganesan, Aileen F Keating
Bisphenol A (BPA) is an endocrine disrupting chemical with ubiquitous human exposure. BPA causes primordial follicle loss and DNA damage in germ cells, thus we hypothesized that BPA induces ovarian DNA damage, thereby precipitating follicle loss. We also anticipated that the ovary activates DNA repair and xenobiotic biotransformation to minimize oocyte damage and/or, activate cell death signaling to deplete follicles. Postnatal day 4 F344 rat ovaries were cultured in medium containing vehicle control (1% dimethylsulfoxide [DMSO]) ± BPA (440 µM) for 2-8 days...
July 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Jane T Jones, Xi Qian, Jos L J van der Velden, Shi Biao Chia, David H McMillan, Stevenson Flemer, Sidra M Hoffman, Karolyn G Lahue, Robert W Schneider, James D Nolin, Vikas Anathy, Albert van der Vliet, Danyelle M Townsend, Kenneth D Tew, Yvonne M W Janssen-Heininger
Nuclear Factor kappa B (NF-κB) is a transcription factor family critical in the activation of pro- inflammatory responses. The NF-κB pathway is regulated by oxidant-induced post-translational modifications. Protein S-glutathionylation, or the conjugation of the antioxidant molecule, glutathione to reactive cysteines inhibits the activity of inhibitory kappa B kinase beta (IKKβ), among other NF-κB proteins. Glutathione S-transferase Pi (GSTP) is an enzyme that has been shown to catalyze protein S-glutathionylation (PSSG) under conditions of oxidative stress...
August 2016: Redox Biology
Aml S Nasr, Rania M Sami, Noha Y Ibrahim, Dalia O Darwish
BACKGROUND: The super family of glutathione S-transferases (GSTs) is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1, and GST P1 affect the body's ability to detoxify a range of potential leukemogens encountered in the environment...
October 2015: Indian Journal of Cancer
Christian Kropf, Helmut Segner, Karl Fent
Embryos of oviparous fish, in contrast to (ovo) viviparous species, develop in the aquatic environment, and therefore need solute transport systems at their body surfaces for maintaining internal homeostasis and defending against potentially harmful substances. We hypothesized that solute transporters undergo changes in tissue distribution from the embryo to the larval stage. We therefore studied the mRNA profiles of eight ABC transporters (abcb1a, abcb1b, abcc1, abcc2, abcc3, abcc4, abcc5, abcg2) and three solute carriers (oatp1d, putative oatp2 putative, mate1) in different body regions (head, yolk sac epithelium, abdominal viscera, skin/muscles) of developing rainbow trout...
July 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Desirée Bartolini, Francesco Galli
Glutathione S-transferase P (GSTP), and possibly other members of the subfamily of cytosolic GSTs, are increasingly proposed to have roles far beyond the classical GSH-dependent enzymatic detoxification of electrophilic metabolites and xenobiotics. Emerging evidence suggests that these are essential components of the redox sensing and signaling platform of cells. GSTP monomers physically interact with cellular proteins, such as other cytosolic GSTs, signaling kinases and the membrane peroxidase peroxiredoxin 6...
April 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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