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Yesol Bak, Hui-Joo Jang, Jong-Woon Shin, Soo-Jin Kim, Hyun Woo Chun, Ji-Hye Seo, Su-Hyun No, Jung-Il Chae, Dong Hee Son, Seung Yeoun Lee, Jintae Hong, Do-Young Yoon
The carcinogenicity of chemicalsin the environment is a major concern. Recently, numerous studies have attempted to develop methods for predicting carcinogenicity including rodent and cell-based approaches. However, rodent carcinogenicity tests for evaluating the carcinogenic potential of a chemical to humans are time-consuming and costly. This study focused on the development of an alternative method for predicting carcinogenicity using quantitative PCR (qPCR) and colon cancer stem cells.A toxicogenomic method,mRNA profiling, is useful for predicting carcinogenicity...
March 15, 2018: Journal of Microbiology and Biotechnology
Katsuya Komatsu, Masahiko Wanibuchi, Takeshi Mikami, Yukinori Akiyama, Satoshi Iihoshi, Kei Miyata, Toshiya Sugino, Kengo Suzuki, Aya Kanno, Shouhei Noshiro, Shunya Ohtaki, Nobuhiro Mikuni
BACKGROUND: Preoperative evaluation of malignancy in gliomas is important for surgical planning, particularly to determine if a 1,3-bis-2-chloroethyl-1-nitrosourea wafer should be placed into the tumor cavity. In some cases, the intraoperative pathological diagnosis of World Health Organization grade differs from the final diagnosis. Supplemental methods in addition to the routine contrast tomography or magnetic resonance imaging sequences may provide a more accurate preoperative diagnosis...
March 9, 2018: World Neurosurgery
Miriam E Szurman-Zubrzycka, Justyna Zbieszczyk, Marek Marzec, Janusz Jelonek, Beata Chmielewska, Marzena M Kurowska, Milena Krok, Agata Daszkowska-Golec, Justyna Guzy-Wrobelska, Damian Gruszka, Monika Gajecka, Patrycja Gajewska, Magdalena Stolarek, Piotr Tylec, Paweł Sega, Sabina Lip, Monika Kudełko, Magdalena Lorek, Małgorzata Gorniak-Walas, Anna Malolepszy, Nina Podsiadlo, Katarzyna P Szyrajew, Anete Keisa, Zodwa Mbambo, Elena Todorowska, Marek Gaj, Zygmunt Nita, Wanda Orlowska-Job, Miroslaw Maluszynski, Iwona Szarejko
TILLING (Targeting Induced Local Lesions IN Genomes) is a strategy used for functional analysis of genes that combines the classical mutagenesis and a rapid, high-throughput identification of mutations within a gene of interest. TILLING has been initially developed as a discovery platform for functional genomics, but soon it has become a valuable tool in development of desired alleles for crop breeding, alternative to transgenic approach. Here we present the Hor TILLUS ( Hor deum - TILL ING- U niversity of S ilesia) population created for spring barley cultivar "Sebastian" after double-treatment of seeds with two chemical mutagens: sodium azide (NaN3 ) and N-methyl-N-nitrosourea (MNU)...
2018: Frontiers in Plant Science
Caroline M Gorvin, Angela Rogers, Michelle Stewart, Anju Paudyal, Tertius A Hough, Lydia Teboul, Sara Wells, Steve Dm Brown, Roger D Cox, Rajesh V Thakker
The adaptor protein-2 sigma subunit (AP2σ), encoded by AP2S1 , forms a heterotetrameric complex, with AP2α, AP2β, and AP2μ subunits, that is pivotal for clathrin-mediated endocytosis, and AP2σ loss-of-function mutations impair internalization of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor, and cause familial hypocalciuric hypercalcemia type-3 (FHH3). Mice with AP2σ mutations that would facilitate investigations of the in vivo role of AP2σ, are not available, and we therefore embarked on establishing such mice...
May 2, 2017: JBMR Plus
Hiroyuki Kuroda, Toshiko Kinomoto, Shuji Ogawa, Mayumi Kawabe, Mayuko Suguro, Hitoshi Naraoka, Kazuhiko Takamatsu, Yuji Oishi
Although acotiamide hydrochloride hydrate (acotiamide-HH) has not been reported to have genotoxic findings in any of the genotoxicity studies or treatment-related toxicological findings in reproductive and developmental studies, suspicious uterine tumorigenesis was observed in the results of a long-term rat carcinogenicity study. To clarify the uterine tumorigenesis of acotiamide-HH, we performed a 2-stage uterine carcinogenicity model in the transgenic rasH2 mouse initiated by N-Ethyl-N-nitrosourea (ENU). This model facilitated the short-term detection of uterine carcinogenic potential, and it appears to be a very useful testing method for assessing the safety of chemicals that may affect uterine tumorigenesis...
January 2018: Journal of Toxicologic Pathology
Katarzyna Siewierska, Iwona Malicka, Christopher Kobierzycki, Urszula Paslawska, Marek Cegielski, Jedrzej Grzegrzolka, Aleksandra Piotrowska, Marzenna Podhorska-Okolow, Piotr Dziegiel, Marek Wozniewski
BACKGROUND/AIM: Physical exercise is increasingly considered by many authors to be a factor reducing the risk of cancer development and premature cancer-related death. Data indicate higher cure rates and longer times of survival in cancer patients who regularly exercise. MATERIALS AND METHODS: A total of 50 female Sprague-Dawley rats were used in the experiment. Animals at 1 month of age were intraperitoneally injected with N-methyl-N-nitrosourea. Three months following drug administration, rats underwent supervised physical training...
March 2018: In Vivo
Ichiyo Shibahara, Mitsuto Hanihara, Takashi Watanabe, Mitsuru Dan, Sumito Sato, Hiroki Kuroda, Akinori Inamura, Madoka Inukai, Atsuko Hara, Yoshie Yasui, Toshihiro Kumabe
Biomaterials to treat cancers hold therapeutic potential; however, their translation to bedside treatment requires further study. The carmustine (1,3-bis (2-chloroethyl)-1-nitrosourea; BCNU) wafer, a biodegradable polymer, currently is the only drug that is able to be placed at the surgical site to treat malignant tumors. However, how this wafer affects the surrounding tumor microenvironment is not well understood to date. We retrospectively reviewed all patients with glioblastoma treated with and without BCNU wafers who underwent repeat resection at tumor recurrence...
February 21, 2018: Journal of Neuro-oncology
Pierre Bourdillon, Tanguy Boissenot, Lauriane Goldwirt, Julien Nicolas, Caroline Apra, Alexandre Carpentier
In situ carmustine wafers containing 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) are commonly used for the treatment of recurrent glioblastoma to overcome the brain-blood barrier. In theory, this chemotherapy diffuses into the adjacent parenchyma and the excipient degrades in maximum 8 weeks but no clinical data confirms this evolution, because patients are rarely operated again. A 75-year-old patient was operated twice for recurrent glioblastoma, and a carmustine wafer was implanted during the second surgery...
February 17, 2018: Journal of Materials Science. Materials in Medicine
Shao-Feng Yang, Ran Ma, Li-Li Pan, Jing Cao, Nan Sheng
Gastric cancer is associated with a high mortality rate, with the development of gastric cancer stem cells underlying this. Gastric cancer stem cells are responsible for tumor initiation, progression and recurrence. However, the link between gastric cancer and gastric cancer stem cells remains to be fully understood. Murine models mimic a human microenvironment more accurately than in vitro studies and are useful models for understanding the behavior of different markers. The present study compared the expression of cluster of differentiation 44 (CD44), a stem cell marker, with the expression of other cancer-associated markers, including Raf kinase inhibitor protein (RKIP) and peroxiredoxin 2, in different pathological conditions of gastric cancer development using histological, immunohistological and western blot analyses...
March 2018: Oncology Letters
Arif N Ali, Peixin Zhang, W K Alfred Yung, Yuhchyau Chen, Benjamin Movsas, Raul C Urtasun, Christopher U Jones, Kwang N Choi, Jeff M Michalski, A Jennifer Fischbach, Arnold M Markoe, Christopher J Schultz, Marta Penas-Prado, Madhur K Garg, Alan C Hartford, Harold E Kim, Minhee Won, Walter J Curran
From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1-3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity...
March 2018: Journal of Neuro-oncology
Naoko Sogame, Rebecca Risbon, Kristine E Burgess
OBJECTIVE To describe signalment, clinicopathologic features, and outcomes of dogs with confirmed primary intestinal lymphoma and assess factors associated with survival times in these patients. DESIGN Retrospective case series. ANIMALS 84 client-owned dogs. PROCEDURES Medical records from 7 veterinary institutions were retrospectively reviewed to identify dogs with primary intestinal lymphoma. Data collected included signalment, clinical signs, anatomic location of tumors, diagnostic procedures, treatment, outcome, and dates of diagnosis and death...
February 15, 2018: Journal of the American Veterinary Medical Association
Victor A Levin, Sandra E Ictech, Kenneth R Hess
This review covers the literature between 1989 and 2007 on studies relevant to the neuro-oncology usage of eflornithine (α-difluoromethylornithine), an oral agent that irreversibly inhibits the enzyme ornithine decarboxylase. It covers the use of eflornithine, alone or in combination, to treat high-grade gliomas. In addition, we provide an update on overall survival from The University of Texas MD Anderson Cancer Center Community Clinical Oncology Program and Clinical Trials Data Office that demonstrates a meaningful benefit in overall survival for eflornithine as a single agent and in combination with nitrosourea-based therapies for anaplastic gliomas...
January 30, 2018: CNS Oncology
Tugce Dalli, Merve Beker, Sule Terzioglu-Usak, Fahri Akbas, Birsen Elibol
Streptozotocin (STZ), a glucosamine-nitrosourea compound, produces deficiencies in learning, memory, and cognitive functions when it was administered intracerebroventricularly (i.c.v). In molecular level, increase in neuroinflammation and oxidative stress in brain, and decrease in the number of surviving neurons are the outcomes of STZ administration. Herein, we aimed to investigate the effect of thymoquinone (TQ), an anti-inflammatory, immunomodulatory and neuroprotective agent, on STZ-induced neurodegeneration in rats...
January 20, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Rhiannon David, Emily Talbot, Bethany Allen, Amy Wilson, Usman Arshad, Ann Doherty
A recent flow cytometry-based in vivo mutagenicity assay involves the hemizygous phosphatidylinositol class A (Pig-a) gene. Pig-a forms the catalytic subunit of N-acetylglucosaminyltransferase required for glycophosphatidylinositol (GPI) anchor biosynthesis. Mutations in Pig-a prevent GPI-anchor synthesis resulting in loss of cell-surface GPI-linked proteins. The aim of the current study was to develop and validate an in vitro Pig-a assay in L5178Y mouse lymphoma cells. Ethyl methanesulfonate (EMS)-treated cells (186...
January 23, 2018: Archives of Toxicology
Youming Zhang, Thanushiyan Poobalasingam, Laura L Yates, Simone A Walker, Martin S Taylor, Lauren Chessum, Jackie Harrison, Loukia Tsaprouni, Ian M Adcock, Clare M Lloyd, William O Cookson, Miriam F Moffatt, Charlotte H Dean
We previously identified dipeptidyl-peptidase 10 (DPP10) on chromosome 2 as a human asthma susceptibility gene, through positional cloning. Initial association results were confirmed in many subsequent association studies but the functional role of DPP10 in asthma remains unclear. Using the MRC Harwell N-ethyl-N-nitrosourea (ENU) DNA archive, we identified a point mutation in Dpp10 that caused an amino acid change from valine to aspartic acid in the β propeller region of the protein. Mice carrying this point mutation were recovered and a congenic line was established (Dpp10145D )...
December 28, 2017: Disease Models & Mechanisms
Mathilde Doyard, Séverine Bacrot, Céline Huber, Maja Di Rocco, Alice Goldenberg, Mona S Aglan, Perrine Brunelle, Samia Temtamy, Caroline Michot, Ghada A Otaify, Coralie Haudry, Mireille Castanet, Julien Leroux, Jean-Paul Bonnefont, Arnold Munnich, Geneviève Baujat, Pablo Lapunzina, Sophie Monnot, Victor L Ruiz-Perez, Valérie Cormier-Daire
BACKGROUND: Stüve-Wiedemann syndrome (SWS) is characterised by bowing of the lower limbs, respiratory distress and hyperthermia that are often responsible for early death. Survivors develop progressive scoliosis and spontaneous fractures. We previously identified LIFR mutations in most SWS cases, but absence of LIFR pathogenic changes in five patients led us to perform exome sequencing and to identify homozygosity for a FAM46A mutation in one case [p.Ser205Tyrfs*13]. The follow-up of this case supported a final diagnosis of osteogenesis imperfecta (OI), based on vertebral collapses and blue sclerae...
January 22, 2018: Journal of Medical Genetics
Thomas Gstrein, Andrew Edwards, Anna Přistoupilová, Ines Leca, Martin Breuss, Sandra Pilat-Carotta, Andi H Hansen, Ratna Tripathy, Anna K Traunbauer, Tobias Hochstoeger, Gavril Rosoklija, Marco Repic, Lukas Landler, Viktor Stránecký, Gerhard Dürnberger, Thomas M Keane, Johannes Zuber, David J Adams, Jonathan Flint, Tomas Honzik, Marta Gut, Sergi Beltran, Karl Mechtler, Elliott Sherr, Stanislav Kmoch, Ivo Gut, David A Keays
The formation of the vertebrate brain requires the generation, migration, differentiation and survival of neurons. Genetic mutations that perturb these critical cellular events can result in malformations of the telencephalon, providing a molecular window into brain development. Here we report the identification of an N-ethyl-N-nitrosourea-induced mouse mutant characterized by a fractured hippocampal pyramidal cell layer, attributable to defects in neuronal migration. We show that this is caused by a hypomorphic mutation in Vps15 that perturbs endosomal-lysosomal trafficking and autophagy, resulting in an upregulation of Nischarin, which inhibits Pak1 signaling...
January 8, 2018: Nature Neuroscience
Patrick M Lelliott, Hong Ming Huang, Matthew W Dixon, Arman Namvar, Adam J Blanch, Vijay Rajagopal, Leann Tilley, Cevayir Coban, Brendan J McMorran, Simon J Foote, Gaetan Burgio
The malaria parasite hijacks host erythrocytes to shield itself from the immune system and proliferate. Red blood cell abnormalities can provide protection from malaria by impeding parasite invasion and growth within the cell or by compromising the ability of parasites to avoid host clearance. Here, we describe 2 N-ethyl-N-nitrosourea-induced mouse lines, SptbMRI26194 and SptbMRI53426 , containing single-point mutations in the erythrocyte membrane skeleton gene, β spectrin (Sptb), which exhibit microcytosis but retain a relatively normal ratio of erythrocyte surface area to volume and are highly resistant to rodent malaria...
December 12, 2017: Blood Advances
Takahiro Yoshida, Max Kates, Nikolai A Sopko, Xiaopu Liu, Alok K Singh, William R Bishai, Gregory Joice, David J McConkey, Trinity J Bivalacqua
OBJECTIVE: We ex vivo cultured primary tumor cells from N-methyl-N-nitrosourea (MNU)-induced bladder tumors in rats and established an immortalized cell line from them. MATERIALS AND METHODS: Bladder tumors in rats were induced by instillation of MNU into the murine bladder. Primary tumor cells were prepared by the cancer-tissue originated spheroid method. An immortalized cell line was established by co-culture with fibroblasts. The cultured tumor cells were molecularly and functionally characterized by quantitative real-time polymerase chain reaction, Western blot, growth assay, and transwell migration assay...
December 26, 2017: Urologic Oncology
Sonal Wankhede, Nitesh Kumar, Lalitha Simon, Subhankar Biswas, Karthik Gourishetti, Grandhi Venkata Ramalingayya, Mit Joshi, C Mallikarjuna Rao
Two 5'acetamido chalcones, C1 and C2 were synthesized by Claisen-Schmidt condensation method and characterized by IR, LC-MS, 1H NMR and 13C NMR. These compounds were evaluated for anticancer activity in vitro in breast cancer cell lines (MCF-7 and MDA-MB-231) using MTT assay, anti-metastatic assay, apoptotic screening by AO/EB staining and in vivo in N-Methyl-N-nitrosourea (MNU) induced breast carcinoma model. Sprague-Dawley rats with developed tumors (50 mg/kg MNU i.p.) were grouped in four, namely MNU control (0...
2017: EXCLI Journal
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