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1.
Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.  相似文献   
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Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose was to ascertain if any relation exists between the elevated intraocular pressure (IOP) in patients with...  相似文献   
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Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.  相似文献   
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Journal of Developmental and Physical Disabilities - Caregiver support is an important contextual factor in the daily functioning of children with cerebral palsy (CP), but few studies have examined...  相似文献   
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Graefe's Archive for Clinical and Experimental Ophthalmology - Ferromagnetic foreign bodies (FFB) present during magnetic resonance imaging (MRI) explorations can lead to tissue injury due to...  相似文献   
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Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz -  相似文献   
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Background: Nanotechnology is receiving greater attention these days as a result of its applications in numerous industrial, medical, and environmental fields. Objective: To synthesize silver nanoparticles with a green alga, Cladophora glomerata, and determine their inhibitory activity against tumor cell (MCF-7) and transgenic mouse cell (L20B) lines. Materials and Methods: Methanol extract was prepared from Cladophora glomerata and used as a safe factory for the synthesis of silver nanoparticles (AgNPs). UV-visible spectrophotometer, X-ray diffraction, scanning electron microscopy, and EDX analyses were used to characterize the biosynthesized AgNPs. The anti-tumor activity of the phycosynthesized AgNPs was tested against the MCF-7 and L20B cell lines. Furthermore, the bioactive compounds in the algal extract were determined by gas chromatography-mass spectroscopy (GC-MS). Results: The phycosynthesis produced clusters of spherical and polydispersed cuboidal pure AgNPs with an average size of 32 nm. The phycosynthesized AgNPs possess anti-cancer and anti-tumor activities on the MCF-7 and L20B cell lines, with significant anti-proliferation percentages of 52.8 and 65.8%, respectively, after 48 hours of treatment with 100 μg/ml AgNPs. Both treated cell lines showed a significant change in cellular shape and tissue detachment. The GC-MS analysis revealed the presence of a high proportion of octadecanoic acid (47.59%) and hexadecanoic acid (14.97%). Conclusion: Cladophora glomerata contains chemicals that improve the stabilization and reduction properties of the nanoparticles. It can be used as a safe, local, and natural source for the synthesis of AgNPs and can also be used as a benign factory for many other metal nanoparticles. The phycosynthesized AgNPs have anti-cancer and anti-tumor activities on the test cell lines and provide an insight into the potential for using them as a trend in cancer nanotherapy.  相似文献   
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Breast Cancer Research and Treatment - The NSABP B-36 compared four cycles of doxorubicin and cyclophosphamide (AC) with six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-100) in...  相似文献   
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