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https://www.readbyqxmd.com/read/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#1
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28314259/mast-cells-in-mammary-carcinogenesis-host-or-tumor-supporters
#2
Ana I Faustino-Rocha, Adelina Gama, Maria J Neuparth, Paula A Oliveira, Rita Ferreira, Mário Ginja
BACKGROUND/AIM: The effects of mast cells on carcinogenesis is not yet fully understood. This work aimed to disclose the role of mast cells in mammary carcinogenesis in a rat model. MATERIALS AND METHODS: Mammary tumors were induced by the administration of N-methyl-N-nitrosourea (MNU) in three groups of rats. Animals from one group were treated with ketotifen immediately after MNU administration, and animals from another only received ketotifen after the development of the first mammary tumor...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28304246/a-mouse-model-for-human-unstable-hemoglobin-santa-ana
#3
Samantha I Miyashiro, Silvia M G Massironi, Claudia M C Mori, Carolina C Cruz, Mitika K Hagiwara, Paulo C Maiorka
In the present study, we described the phenotype, histologic morphology, and molecular etiology of a mouse model of unstable hemoglobin Santa Ana. Hematologic evaluation of anemic mice (Anem/+) discovered after N-ethyl-N-nitrosourea mutagenesis revealed moderate anemia with intense reticulocytosis and polychromasia, followed by anisocytosis, macrocytosis, hypochromia, and intraerythrocytic inclusion and Heinz bodies. The mice also demonstrated hemoglobinuria, bilirubinemia, and erythrocytic populations with differing resistance to osmotic lysis...
December 1, 2016: Comparative Medicine
https://www.readbyqxmd.com/read/28301260/cancer-targeting-potential-of-99m-tc-finasteride-in-experimental-model-of-prostate-carcinogenesis
#4
Gowsia Jan, Neelima D Passi, Devinder Kumar Dhawan, Vijayta Dani Chadha
This study aimed to radiolabel finasteride, a novel 5α-reductase inhibitor, to evaluate its cancer targeting potential in experimental model of prostate carcinogenesis. Finasteride was effectively radiolabeled with (99m)Tc and showed >90% labeling efficiency. The radiopharmaceutical was found to be stable up to 6 hours in rat serum at 37°C. The blood kinetics of the (99m)Tc-finasteride followed a biphasic release pattern, whereby fast-release phase was observed at 15 seconds and a slow-release phase was observed after 30 minutes of administration...
March 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28297563/spermatogenesis-associated-22-is-required-for-dna-repair-and-synapsis-of-homologous-chromosomes-in-mouse-germ-cells
#5
E Hays, N Majchrzak, V Daniel, Z Ferguson, S Brown, K Hathorne, S La Salle
Analysis of the N-ethyl-N-nitrosourea (ENU)-induced repro42 mutation previously identified spermatogenesis associated 22 (Spata22) as a gene required for meiotic progression and fertility in both male and female mice, but its specific contribution to the process was unclear. Here, we report on a novel, null allele of Spata22 (Spata22(Gt) ) and confirm its requirement for germ cell development. Similar to repro42 mutant mice, histological and mating analyses indicate that gametogenesis is profoundly affected in Spata22(Gt/Gt) males and females, resulting in infertility...
March 2017: Andrology
https://www.readbyqxmd.com/read/28292025/design-synthesis-and-anticancer-screening-of-3-3-substituted-phenyl-acryloyl-2h-chromen-2ones-as-selective-anti-breast-cancer-agent
#6
Santosh N Mokale, Afreen Begum, Nikhil S Sakle, Vishakha R Shelke, Swati A Bhavale
By utilizing concept of molecular hybridization, involving combination of various Pharmacophore, novel substituted coumarin-chalcone hybrids was synthesized and evaluated for anti-proliferative activity against estrogen receptor-positive MCF-7 and negative MDA-MB-435 breast cancer cell lines. In-vivo study was carried out by N-methyl nitrosourea (MNU) induced mammary carcinoma in virgin female Spraque Dawly (SD) rats. The compound 5b has highest potential than standard drug Adriamycin, comparable against Tamoxifen against ER-positive MCF-7 breast cancer cell lines...
March 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28286973/curcumin-inhibits-urothelial-tumor-development-by-suppressing-igf2-and-igf2-mediated-pi3k-akt-mtor-signaling-pathway
#7
Binqiang Tian, Yingmei Zhao, Tao Liang, Xuxiao Ye, Zuowei Li, Dongliang Yan, Qiang Fu, Yonghui Li
We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin...
March 11, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28285967/prognostic-factors-in-mnu-and-dmba-induced-mammary-tumors-in-female-rats
#8
Antonieta Alvarado, Ana C Lopes, Ana I Faustino-Rocha, António M S Cabrita, Rita Ferreira, Paula A Oliveira, Bruno Colaço
Chemically-induced mammary tumors in rats by the carcinogens 1-methyl-1-nitrosourea- (MNU) and 7,12-dimethylbenz[a]anthracene (DMBA) are the most widely used models for studies related with human breast cancer. This study aimed to evaluate the immunoexpression of the prognostic factors estrogen receptor α (ERα), progesterone receptor (PR) and Ki-67, in MNU and DMBA-induced rat mammary tumors, in order to know the model that best suits to woman breast cancer. Twenty-eight MNU-induced and 16 DMBA-induced mammary tumors in virgin female Sprague-Dawley rats were analyzed...
February 24, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28272691/the-effect-of-curcumin-on-bladder-tumor-in-rat-model
#9
Z-J Pan, N Deng, Z-H Zou, G-X Chen
OBJECTIVE: Bladder cancer is the most commonly malignant tumor in the urogenital tract, only next to prostate cancer with a higher incidence in China. Curcumin is the major component of curcuma longa and has multiple biological effects including anti-tumor. This study aimed to investigate the effect of curcumin on bladder cancer. MATERIALS AND METHODS: SPF-grade Wistar rats were used for establishing bladder cancer model through injection of N-methyl-N-nitrosourea (MNU)...
February 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28247160/convection-enhanced-delivery-of-a-hydrophilic-nitrosourea-ameliorates-deficits-and-suppresses-tumor-growth-in-experimental-spinal-cord-glioma-models
#10
Shogo Ogita, Toshiki Endo, Shinichiro Sugiyama, Ryuta Saito, Tomoo Inoue, Akira Sumiyoshi, Hiroi Nonaka, Ryuta Kawashima, Yukihiko Sonoda, Teiji Tominaga
BACKGROUND: Convection-enhanced delivery (CED) is a technique allowing local infusion of therapeutic agents into the central nervous system, circumventing the blood-brain or spinal cord barrier. OBJECTIVE: To evaluate the utility of nimustine hydrochloride (ACNU) CED in controlling tumor progression in an experimental spinal cord glioma model. METHODS: Toxicity studies were performed in 42 rats following the administration of 4 μl of ACNU CED into the mid-thoracic spinal cord at concentrations ranging from 0...
February 28, 2017: Acta Neurochirurgica
https://www.readbyqxmd.com/read/28245158/alternative-multiorgan-initiation-promotion-assay-for-chemical-carcinogenesis-in-the-wistar-rat
#11
Marize de Lourdes Marzo Solano, Noeme Souza Rocha, Luis Fernando Barbisan, Carla Adriene da Silva Franchi, Ana Lúcia Tozzi Spinardi-Barbisan, Maria Luiza Cotrim Sartor de Oliveira, Daisy Maria Fávero Salvadori, Lúcia Regina Ribeiro, João Lauro Viana de Camargo
The medium-term multiorgan initiation-promotion chemical bioassay (diethylnitrosamine, methyl-nitrosourea, butyl-hydroxybutylnitrosamine, dihydroxypropylnitrosamine, dimethylhydrazine [DMBDD]) with the Fischer 344 rat was proposed as an alternative to the conventional 2-year carcinogenesis bioassay for regulatory purposes. The acronym DMBDD stands for the names of five genotoxic agents used for initiation of multiorgan carcinogenesis. The Brazilian Agency for the Environment officially recognized a variation of this assay (DMBDD(b)) as a valid method to assess the carcinogenic potential of agrochemicals...
December 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/28243914/the-thymus-in-experimental-mammary-carcinogenesis-and-polychemotherapy
#12
O V Kazakov, A V Kabakov, I Yu Ishchenko, A F Poveshchenko, T V Raiter, D N Strunkin, S V Michurina, V I Konenkov
Histological study of structural transformations in the thymus of Wistar females in induced carcinogenesis (N-methyl-N-nitrosourea injection in the right 2-nd mamma) and polychemotherapy (6 months after tumor growth initiation; cyclophosphamide, methotrexate, and 5-fluorouracyl) was carried out. The area of the cortical matter in the thymus decreased 6 months after carcinogenesis induction, the percentage of connective tissue elements and glandular tissue and the counts of immunoblasts and cells with pyknotic nuclei increased, this indicating the development of accidental involution of the thymus...
February 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28230087/nardilysin-regulates-inflammation-metaplasia-and-tumors-in-murine-stomach
#13
Yuto Kimura, Kozo Ikuta, Takeshi Kimura, Tsutomu Chiba, Hiroko Oshima, Masanobu Oshima, Eiichiro Nishi, Hiroshi Seno
Chronic inflammation contributes to a wide variety of human disorders. In the stomach, longstanding gastritis often results in structural alterations in the gastric mucosa, including metaplastic changes and gastric cancers. Therefore, it is important to elucidate factors that are involved in gastric inflammation. Nardilysin (N-arginine dibasic convertase; Nrdc) is a metalloendopeptidase of the M16 family that promotes ectodomain shedding of the precursor forms of various growth factors and cytokines by enhancing the protease activities of a disintegrin and metalloproteinase (ADAM) proteins...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228618/preventive-effect-of-intravesical-ozone-supplementation-on-n-methyl-n-nitrosourea-induced-non-muscle-invasive-bladder-cancer-in-male-rats
#14
Kerem Teke, Tayyar A Ozkan, Oguz O Cebeci, Hasan Yilmaz, Muhammed E Keles, Levend Ozkan, Meltem O Dillioglugil, Demir K Yildiz, Ozdal Dillioglugil
Although non-muscle invasive bladder cancer (NMIBC) is widely seen in men, most laboratory studies of new intravesical therapies to prevent NMIBC have been conducted on female animals. In addition, ozone (O3) has been shown to be a beneficial agent as an intravesical application in the treatment of various disorders. In the current study, we evaluated the immunohistopathological oxidative-antioxidative effects of intravesical O3 treatment on n-methyl-n-nitrosourea (MNU)-induced NMIBC. Male Wistar-Albino rats (n=51) were divided into four groups: sham (n=6), O3 only (n=15), MNU only (n=15), and MNU+O3 (n=15)...
February 22, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28216882/anticancer-potential-of-nutraceutical-formulations-in-mnu-induced-mammary-cancer-in-sprague-dawley-rats
#15
Gummalla Pitchaiah, Annapurna Akula, Vishala Chandi
BACKGROUND: Nutraceuticals help in combating some of the major health problems of the century including cancer, and 'nutraceutical formulations' have led to the new era of medicine and health. OBJECTIVE: To develop different nutraceutical formulations and to assess the anticancer potential of nutraceutical formulations in N-methyl-N-nitrosourea (MNU)-induced mammary cancer in Sprague Dawley rats. MATERIALS AND METHODS: Different nutraceutical formulations were prepared using fine powders of amla, apple, garlic, onion, papaya, turmeric, and wheat grass with and without cow urine distillate...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28214545/potential-of-amphiphilic-graft-copolymer-%C3%AE-tocopherol-succinate-g-carboxymethyl-chitosan-in-modulating-the-permeability-and-anticancer-efficacy-of-tamoxifen
#16
Sunil K Jena, Sanjaya K Samal, Shamandeep Kaur, Mahesh Chand, Abhay T Sangamwar
Recent studies showed an enhanced oral bioavailability of tamoxifen (TMX) by hydrophobically modified α-tocopherol succinate-g-carboxymethyl chitosan (Cmc-TS) micelles. As a continued effort, here we evaluated TMX-loaded polymeric micelles (TMX-PMs) for its enhanced permeability with increased anticancer efficacy and decreased hepatotoxicity. We employed co-solvent evaporation technique to encapsulate TMX into Cmc-TS. Apparent permeability assay of TMX-PMs was performed on Caco-2 cell line. The absorptive transport of TMX increased significantly about 3...
April 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28205273/in-vitro-responses-to-known-in-vivo-genotoxic-agents-in-mouse-germ-cells
#17
Khaled Habas, Martin H Brinkworth, Diana Anderson
Genotoxic compounds have induced DNA damage in male germ cells and have been associated with adverse clinical outcomes including enhanced risks for maternal, paternal and offspring health. DNA strand breaks represent a great threat to the genomic integrity of germ cells. Such integrity is essential to maintain spermatogenesis and prevent reproduction failure. The Comet assay results revealed that the incubation of isolated germ cells with n-ethyl-n-nitrosourea (ENU), 6-mercaptopurine (6-MP) and methyl methanesulphonate (MMS) led to increase in length of Olive tail moment and % tail DNA when compared with the untreated control cells and these effects were concentration-dependent...
March 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28197307/synthesis-and-antitumor-activity-evaluation-of-a-novel-combi-nitrosourea-prodrug-bgcnu
#18
Yameng Wang, Ting Ren, Xinxin Lai, Guohui Sun, Lijiao Zhao, Na Zhang, Rugang Zhong
Chloroethylnitrosoureas (CENUs) are an important type of alkylating agent employed in the clinical treatment of cancer. However, the anticancer efficacy of CENUs is greatly decreased by a DNA repairing enzyme, O(6)-alkylguanine-DNA alkyltransferase (AGT), by preventing the formation of interstrand cross-links (ICLs). In this study, a combi-nitrosourea prodrug, namely, N-(2-chloroethyl)-N'-2-(O(6)-benzyl-9-guanine)ethyl-N-nitrosourea (BGCNU), which possesses an O(6)-benzylguanine (O(6)-BG) derivative and CENU pharmacophores simultaneously, was synthesized and evaluated for its ability to induce ICLs...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28190923/diphenylarsinic-acid-exerts-promotion-effects-on-hepatobiliary-carcinogenesis-in-a-rat-medium-term-multiorgan-carcinogenicity-bioassay
#19
Naomi Ishii, Min Gi, Masaki Fujioka, Shotaro Yamano, Mai Okumura, Anna Kakehashi, Hideki Wanibuchi
We have previously demonstrated that diphenylarsinic acid (DPAA) promotes liver carcinogenesis in rats in a medium-term liver carcinogenicity bioassay. However, the effects of DPAA on other organs have not been determined. In the present study, the effects of DPAA on carcinogenesis were investigated using a rat multiorgan carcinogenicity bioassay. A total of 60 six-week-old male F344 rats were treated with the carcinogens diethylnitrosamine, N-butyl-N-(4-hydroxybutyl) nitrosamine, N-methyl-N-nitrosourea, N-bis (2-hydroxypropyl) nitrosamine, and 1,2-dimethylhydrazine dihydrochloride to initiate carcinogenesis in multiple organs...
January 2017: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/28154203/metformin-accumulation-correlates-with-organic-cation-transporter-2-protein-expression-and-predicts-mammary-tumor-regression-in-vivo
#20
L Allyson Checkley, Michael C Rudolph, Elizabeth A Wellberg, Erin D Giles, Reema S Wahdan-Alaswad, Julie A Houck, Susan M Edgerton, Ann D Thor, Pepper Schedin, Steven M Anderson, Paul S MacLean
Several epidemiologic studies have associated metformin treatment with a reduction in breast cancer incidence in prediabetic and type II diabetic populations. Uncertainty exists regarding which patient populations and/or tumor subtypes will benefit from metformin treatment, and most preclinical in vivo studies have given little attention to the cellular pharmacology of intratumoral metformin uptake. Epidemiologic reports consistently link western-style high fat diets (HFD), which drive overweight and obesity, with increased risk of breast cancer...
February 2, 2017: Cancer Prevention Research
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