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11.
Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung 总被引:1,自引:0,他引:1
Prahalad AK; Ross JA; Nelson GB; Roop BC; King LC; Nesnow S; Mass MJ 《Carcinogenesis》1997,18(10):1955-1963
Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic
hydrocarbon, is the most potent carcinogen ever tested in mouse skin and
rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction,
tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in
strain A/J mouse lung. Groups of mice received a single i.p. injection of
0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment,
DNA adducts were measured at times between 1 and 28 days, while tumors were
counted at 250 days and analyzed for the occurrence of point mutations in
codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung
induced six major and four minor DNA adducts. Maximal levels of adduction
occurred between 5 and 10 days after injection followed by a gradual
decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti-
and syn-11,12- dihydroxy-13,14-epoxy-
11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both
deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed
by cochromatography. The major adduct was identified as a product of the
reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced
significant numbers of lung adenomas in a dose- dependent manner, with the
highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In
tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based
on the administered dose, DB[a,l]P was more active than other environmental
carcinogens including benzo[a]pyrene. As a function of time-integrated DNA
adduct levels, DB[a,l]P induced lung adenomas with about the same potency
as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar
in carcinogenic potency to other PAHs in the strain A/J mouse lung model.
Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors
revealed the predominant mutations to be G-->T transversions in the
first base of codon 12, A-->G transitions in the second base of codon
12, and A-->T transversions in the second or third base of codon 61,
concordant with the DNA adduct profile.
相似文献
12.
Dirk De Ruysscher Stofferinus Wanders Andre Minken Aniek Lumens Jacqueline Schiffelers Cissie Stultiens Serve Halders Liesbeth Boersma Angela van Baardwijk Tom Verschueren Monique Hochstenbag Gabriel Snoep Brad Wouters Sebastiaan Nijsten S?ren M Bentzen Marinus van Kroonenburgh Michel Ollers Philippe Lambin 《Radiotherapy and oncology》2005,77(1):5-10
BACKGROUND AND PURPOSE: To investigate the effect of radiotherapy planning with a dedicated combined PET-CT simulator of patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Twenty-one patients underwent a pre-treatment simulation on a dedicated hybrid PET-CT-simulator. For each patient, two 3D conformal treatment plans were made: one with a CT based PTV and one with a PET-CT based PTV, both to deliver 60Gy in 30 fractions. The maximum tolerable prescribed radiation dose for CT versus PET-CT PTV was calculated based on constraints for the lung, the oesophagus, and the spinal cord, and the Tumour Control Probability (TCP) was estimated. RESULTS: For the same toxicity levels of the lung, oesophagus and spinal cord, the dose could be increased from 55.2+/-2.0Gy with CT planning to 68.9+/-3.3Gy with the use of PET-CT (P=0.002), with corresponding TCP's of 6.3+/-1.5% for CT and 24.0+/-5.6% for PET-CT planning (P=0.01). CONCLUSIONS: The use of a combined dedicated PET-CT-simulator reduced radiation exposure of the oesophagus and the lung, and thus allowed significant radiation dose escalation whilst respecting all relevant normal tissue constraints. 相似文献
13.
Vidthiya Menon Rebecca Davis Nick Shackel Bjorn A. Espedido Alicia G. Beukers Slade O. Jensen Sebastiaan J. van Hal 《Diagnostic microbiology and infectious disease》2018,90(2):120-122
Daptomycin β-Lactam combination therapy offers “protection” against daptomycin non-susceptibility (DNS) development in Enterococcus faecium. We report failure of this strategy and the importance of source control. Mutations were detected in the LiaF and cls genes in DNS isolates. A single DNS isolate contained an unrecognized mutation, which requires confirmation. 相似文献
14.
15.
Inhibition of coagulation,fibrinolysis, and endothelial cell activation by a p38 mitogen-activated protein kinase inhibitor during human endotoxemia 总被引:7,自引:2,他引:7
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Branger J van den Blink B Weijer S Gupta A van Deventer SJ Hack CE Peppelenbosch MP van der Poll T 《Blood》2003,101(11):4446-4448
P38 mitogen-activated protein kinase (MAPK) is an important component of intracellular signaling cascades that initiate various inflammatory cellular responses. To determine the role of p38 MAPK in the procoagulant response to lipopolysaccharide (LPS), 24 healthy subjects were exposed to an intravenous dose of LPS (4 ng/kg), preceded 3 hours earlier by orally administered 600 or 50 mg BIRB 796 BS (a specific p38 MAPK inhibitor), or placebo. The 600-mg dose of BIRB 796 BS strongly inhibited LPS-induced coagulation activation, as measured by plasma concentrations of the prothrombin fragment F1 + 2. BIRB 796 BS also dose dependently attenuated the activation and subsequent inhibition of the fibrinolytic system (plasma tissue-type plasminogen activator, plasmin-alpha2-antiplasmin complexes, and plasminogen activator inhibitor type 1) and endothelial cell activation (plasma soluble E-selectin and von Willebrand factor). Activation of p38 MAPK plays an important role in the procoagulant and endothelial cell response after in vivo exposure to LPS. 相似文献
16.
Sebastiaan C Goulooze Adam F Cohen Robert Rissmann 《British journal of clinical pharmacology》2015,80(4):762-764
Mirabegron is used for the treatment of symptoms associated with overactive bladder syndrome. It selectively stimulates the β3-adrenoreceptor, which relaxes the detrusor muscle. This improves urine storage by distension of the bladder body.In this series we draw attention to medicines that have entered the European market with an entirely new mechanism of action. Publication is not to be confused with endorsement of use in clinical practice. Copyright to the images belongs to Leiden University, but use of the images (also available at http://coo.lumc.nl/trc and in the app stores) is free. 相似文献
17.
MS Anglesio Y Wang W Yang J Senz A Wan A Heravi‐Moussavi C Salamanca S Maines‐Bandiera DG Huntsman GB Morin 《The Journal of pathology》2013,229(3):400-409
Our group recently described recurrent somatic mutations of the miRNA processing gene DICER1 in non‐epithelial ovarian cancer. Mutations appeared to be clustered around each of four critical metal‐binding residues in the RNase IIIB domain of DICER1. This domain is responsible for cleavage of the 3′ end of the 5p miRNA strand of a pre‐mRNA hairpin. To investigate the effects of these cancer‐associated 'hotspot' mutations, we engineered mouse DICER1‐deficient ES cells to express wild‐type and an allelic series of the mutant DICER1 variants. Global miRNA and mRNA profiles from cells carrying the metal‐binding site mutations were compared to each other and to wild‐type DICER1. The miRNA and mRNA profiles generated through the expression of the hotspot mutations were virtually identical, and the DICER1 hotspot mutation‐carrying cells were distinct from both wild‐type and DICER1‐deficient cells. Further, miRNA profiles showed that mutant DICER1 results in a dramatic loss in processing of mature 5p miRNA strands but were still able to create 3p strand miRNAs. Messenger RNA (mRNA) profile changes were consistent with the loss of 5p strand miRNAs and showed enriched expression for predicted targets of the lost 5p‐derived miRNAs. We therefore conclude that cancer‐associated somatic hotspot mutations of DICER1, affecting any one of four metal‐binding residues in the RNase IIIB domain, are functionally equivalent with respect to miRNA processing and are hypomorphic alleles, yielding a global loss in processing of mature 5p strand miRNA. We further propose that this resulting 3p strand bias in mature miRNA expression likely underpins the oncogenic potential of these hotspot mutations. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
18.
Hiroux Charlotte Dalle Sebastiaan Koppo Katrien Hespel Peter 《Journal of muscle research and cell motility》2021,42(2):169-181
Journal of Muscle Research and Cell Motility - Exercise training is considered as a potential intervention to counteract muscle degeneration in cancer cachexia. However, evidence to support such... 相似文献
19.
Steinkamp Pieter Jan Voskuil Floris Jan van der Vegt Bert Doff Jan Johannes Schepman Kees-Pieter de Visscher Sebastiaan Antonius Hendrik Johannes Kelder Wendy Jayalakshmi Yalia Gao Jinming Sumer Baran Devrim van Dam Gooitzen Michell Witjes Max Johannes Hendrikus 《Molecular imaging and biology》2021,23(6):809-817
Molecular Imaging and Biology - Intra-operative management of the surgical margin in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) remains challenging as surgeons still have... 相似文献
20.