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Peter D Inskip, Lene H S Veiga, Alina V Brenner, Alice J Sigurdson, Evgenia Ostroumova, Eric J Chow, Marilyn Stovall, Susan A Smith, Rita E Weathers, Wendy Leisenring, Leslie L Robison, Gregory T Armstrong, Charles A Sklar, Jay H Lubin
While thyroid cancer risks from exposure to ionizing radiation early in life are well characterized quantitatively, the association of radiation with nonmalignant, functional thyroid disorders has been less studied. Here, we report on a risk analysis study of hypothyroidism with radiation dose to the thyroid gland and the hypothalamic-pituitary axis among survivors of childhood cancer. Utilizing data from the Childhood Cancer Survivor Study, a cohort of 14,364 five-year survivors of childhood cancer diagnosed at 26 hospitals in the U...
May 15, 2018: Radiation Research
Enrico Franceschi, Giuseppe Lamberti, Michela Visani, Alexandro Paccapelo, Antonella Mura, Giovanni Tallini, Annalisa Pession, Dario De Biase, Santino Minichillo, Alicia Tosoni, Monica Di Battista, Alessio Cubeddu, Stefania Bartolini, Alba A Brandes
AIM: To identify patients with recurrent glioblastoma after temozolomide (TMZ) concurrent with and adjuvant to radiotherapy who could benefit from TMZ rechallenge at the time of disease progression. METHODS: We retrospectively evaluated 106 glioblastoma patients who had nonprogressive disease at first magnetic resonance imaging after completion of TMZ concurrent with and adjuvant to radiotherapy, a treatment-free interval (TFI) of at least 8 weeks and received TMZ rechallenge or a nitrosourea at the time of progression...
May 9, 2018: Future Oncology
Ayako Furukawa, Kayo Sugitani, Yoshiki Koriyama
Retinal degenerative diseases, such as retinitis pigmentosa, are characterized by night blindness and peripheral vision loss caused by the slowly progressive loss of photoreceptor cells. A comprehensive molecular mechanism of the photoreceptor cell death remains unclear. We previously reported that heat shock protein 70 (HSP70), which has a protective effect on neuronal cells, was cleaved by a calcium-dependent protease, calpain, in N-methyl-N-nitrosourea (MNU)-treated mice retina. Carbonylated HSP70 is much more vulnerable than noncarbonylated HSP70 to calpain cleavage...
2018: Advances in Experimental Medicine and Biology
Javier R Revollo, Azra Dad, Lea P McDaniel, Mason G Pearce, Vasily N Dobrovolsky
Genetic toxicology assays estimate mutation frequencies by phenotypically screening for the activation or inactivation of endogenous or exogenous reporter genes. These reporters can only detect mutations in narrow areas of the genome and their use is often restricted to certain in vitro and in vivo models. Here, we show that Interclonal Genetic Variation (ICGV) can directly identify mutations genome-wide by comparing sequencing data of single-cell clones derived from the same source or organism. Upon ethyl methanesulfonate (EMS) exposure, ICGV detected greater levels of mutation in a dose- and time-dependent manner in E...
May 2018: Mutation Research
Ken Uchibori, Naohiko Inase, Makoto Nishio, Naoya Fujita, Ryohei Katayama
INTRODUCTION: The survival of patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer has dramatically improved since the introduction of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Recently, osimertinib demonstrated significantly prolonged progression-free survival than 1st-generation EGFR-TKI in first-line treatment, suggesting that a paradigm change that would move osimetinib to first-line treatment is indicated. We performed N-ethyl-N-nitrosourea (ENU) mutagenesis screening to uncover the resistant mechanism in first- and second-line osimertinib treatment...
April 24, 2018: Journal of Thoracic Oncology
Yusaku Mori, Eunhyoung Ko, Rudolf Furrer, Linda C Qu, Stuart C Wiber, George I Fantus, Mario Thevis, Alan Medline, Adria Giacca
It is not fully clarified whether insulin glargine, an analogue with a high affinity for insulin-like growth factor 1 receptor (IGF-1R), increases the risk for cancers that abundantly express IGF-1R such as breast cancer or some types of breast cancer. To gain insight into this issue, female Sprague-Dawley rats fed a high-fat diet were given the carcinogen N-Methyl-N-nitrosourea and randomly assigned to vehicle (control), NPH (unmodified human insulin), glargine, or detemir (n=30 per treatment). Insulins were given subcutaneously (15 U kg-1 day-1) 5 days a week...
April 24, 2018: Endocrine Connections
Nickolay K Isaev, Elisaveta E Genrikhs, Dmitriy N Voronkov, Marina R Kapkaeva, Elena V Stelmashook
Streptozotocin (STZ) is a glucosamine-nitrosourea compound that is particularly toxic to the insulin-producing beta-cells of the pancreas in mammals; it is used for experimental simulation of sporadic Alzheimer's disease by means of intracerebroventricular administration in vivo. Here we show that the application of 3-4 mM STZ to primary culture for 48 h induces neuronal death in immature (2-3 days in vitro) cultures of rat cerebellar granule cells. Mature cultures (7-8 days in vitro) were poorly sensitive to this toxic treatment...
April 20, 2018: Toxicology and Applied Pharmacology
Swetlana Gautam, Atul K Rawat, Shreesh R Sammi, Subhadeep Roy, Manjari Singh, Uma Devi, Rajnish K Yadav, Lakhveer Singh, Jitendra K Rawat, Mohd N Ansari, Abdulaziz S Saeedan, Dinesh Kumar, Rakesh Pandey, Gaurav Kaithwas
The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) (DuCLOX-2/5) inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor) and zileuton (5-LOX inhibitor) were validated for their effect against methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control...
2018: Frontiers in Pharmacology
Swetlana Gautam, Soniya Rani, Gaurav Kaithwas
The present study was designed to evaluate the effects of Phenidone (Dual inhibitor of COX-2 and 5-LOX, DuCLOX-2/5) on various aspects of cancer chemoprevention against MNU induced mammary gland carcinoma. MNU treated rat showed altered heart rate variability (HRV), increased alveolar bud count, differentiation score, up regulated inflammatory enzyme markers (COX, LOX, NO and H2S) and distorted oxidative stress markers (TBARs, protein carbonyl, SOD, catalase and GSH). The mammary gland surface architecture was studied using carmine staining and H&E staining...
April 18, 2018: Toxicology and Applied Pharmacology
Enrico Franceschi, Giuseppe Lamberti, Alexandro Paccapelo, Monica Di Battista, Giovenzio Genestreti, Santino Minichillo, Antonella Mura, Stefania Bartolini, Raffaele Agati, Alba A Brandes
BACKGROUND: Standard glioblastoma therapy is long-lasting. Among second-line therapy, choices could be bevacizumab and nitrosoureas depending on National Agencies approval. There is no consensus on 3rd line therapy or clinical trials specifically designed for this setting. METHODS: We reviewed our institutional database on all consecutive patients who received 3rd line therapy for glioblastoma. RESULTS: Data on 168 out of 1337 (12.6%) glioblastoma patients who underwent 3rd line therapy treatment were collected...
April 18, 2018: Journal of Neuro-oncology
Danielle P LeBlanc, Nathalie A Behan, Jason M O'Brien, Francesco Marchetti, Amanda J MacFarlane
Folate deficiency causes megaloblastic anemia and neural tube defects, and is also associated with some cancers. In vitro, folate deficiency increases mutation frequency and genome instability, as well as exacerbates the mutagenic potential of known environmental mutagens. Conversely, it remains unclear whether or not elevated folic acid (FA) intakes are beneficial or detrimental to the induction of DNA mutations and by proxy human health. We used the MutaMouse transgenic model to examine the in vivo effects of FA deficient, control, and supplemented diets on somatic DNA mutant frequency (MF) and genome instability in hematopoietic cells...
April 18, 2018: Environmental and Molecular Mutagenesis
Thomas Christoph, Babette Kögel, Klaus Schiene, Thomas Peters, Wolfgang Schröder
N-ethyl-N-nitrosourea (ENU) random mutagenesis was used to generate a mouse model for the analysis of the transient receptor potential vanilloid 1 (TRPV1) cation channel. A transversion from T→A in exon 4 led to a Leu206Stop mutation generating a loss-of-function mutant. The TRPV1 agonist capsaicin was used to analyze functional and nociceptive parameters in vitro and in vivo in TRPV1 Leu206Stop mice and congenic C3HeB/FeJ controls. Capsaicin-induced [Ca2+ ]i changes in small diameter DRG neurons were significantly diminished in TRPV1 Leu206Stop mice and administration of capsaicin induced neither hypothermia nor nocifensive behaviour in vivo...
April 13, 2018: Biochemical and Biophysical Research Communications
Natalia Kurhaluk, Bianka Bojková, Pawel J Winklewski
Oxidative stress is involved in the development of various cancers. In the present study the effect of long-term administration of peroral antidiabetic metformin and pineal hormone melatonin on liver antioxidant and aerobic status in female Sprague-Dawley rats carrying mammary tumors induced by N-methyl-N-nitrosourea was evaluated. Both substances were administered in a preventive/curative manner (12 days before and 16 weeks after the carcinogen application). Carcinogen administration induced oxidative stress: the level of thiobarbituric acid reactive products (TBARS) as a marker of reactive oxygen species (ROS) generation in liver increased as well as the level of oxidatively modified protein content (OMP, aldehyde and ketone derivates)...
April 15, 2018: Canadian Journal of Physiology and Pharmacology
Tae Woo Oh, Hyun Ju Do, Kwang-Youn Kim, Kwang Il Park, Jin Yeul Ma
BACKGROUND: In the East Asia, the genus Acer (Aceraceae) is a herbal medicine that is used to treat various diseases, including hemostasis, hepatic disorders, traumatic bleeding and poor eyesight. However, the effects of Acer palmatum thumb. on retinal degeneration are unknown. AIM: In this study, we investigated whether Acer palmatum thumb.ethanol extract (KIOM-2015E) can protect eyes from retinal degeneration. Our research investigated whether KIOM-2015E could have a protective effect in the retinal degenerating mouse model induced by N-ethyl-N-nitrosourea (ENU)...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Kazuyo Sadamoto, Yoshinori Yamagiwa, Hideyuki Sakaki, Masaaki Kurata
In ophthalmological research, the use of zebrafish to investigate visual behaviors has been increasing, but can produce misleading, false-positive results if compounds adversely affect their motor functions or central nervous system. Therefore, histological analysis to identify a target organ is important in zebrafish toxicity assay. We investigated the retinal degeneration in zebrafish, using typical retinal toxicants, mainly sodium iodate and N-methyl-N-nitrosourea. No histopathological changes were found after sodium iodate exposure at 1...
April 11, 2018: Journal of Veterinary Medical Science
Fitsum Getachew, Albert Vandenberg, Judit Smits
BACKGROUND: Faba bean (Vicia faba) vicine/convicine (V-C) aglycones (divicine/isouramil) provoke an acute hemolytic anemia called favism in individuals with a glucose-6-phosphate dehydrogenase (G6PD) enzyme defect in their red blood cells. Geneticists/plant breeders are working with faba bean to decrease V-C levels to improve public acceptance of this high protein pulse crop. Here, we present a fast and simple ex-vivo in vitro bioassay for V-C toxicity testing of faba bean or faba bean food products...
April 2, 2018: Journal of the Science of Food and Agriculture
Suman K Samanta, Joomin Lee, Eun-Ryeong Hahm, Shivendra V Singh
We have reported previously that withaferin A (WA) prevents breast cancer development in mouse mammary tumor virus-neu (MMTV-neu) transgenic mice, but the mechanism is not fully understood. Unbiased proteomics of the mammary tumors from control- and WA-treated MMTV-neu mice revealed downregulation of peptidyl-prolyl cis/trans isomerase (Pin1) protein by WA administration. The present study extends these findings to elucidate the role of Pin1 in cancer chemopreventive mechanisms of WA. The mammary tumor level of Pin1 protein was lower by about 55% in WA-treated rats exposed to N-methyl-N-nitrosourea, compared to control...
March 30, 2018: Molecular Carcinogenesis
T Kiskova, V Demeckova, Z Jendzelovska, M Kiktava, K Venglovska, M Bohmdorfer, W Jager, T Thalhammer
Resveratrol (RES) is well known natural polyphenol with proven antioxidant, antiinflammatory and anticarcinogenic properties. Since mode of application may be important for cancer-preventive effects of RES, the aim of this study was to evaluate a possible delay in the initiation and progression of chemically induced mammary carcinogenesis in female Sprague-Dawley rats after the nocturnal administration of RES. Application of a high dose of RES (100 mg/kg body weight), starting 2 weeks before the first N-methyl-N-nitrosourea dose (NMU) (50 mg/kg body weight), reduced tumor incidence and markedly prolonged latency period (P < 0...
December 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
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
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