84 research outputs found
Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2
Anti-oestrogen is effective for the treatment of oestrogen receptor (ER)-positive breast carcinomas, butmost of these tumours become resistant to anti-oestrogen. It has been suggested that anti-oestrogen therapy may induce a HER2signalling pathway in breast cancer cells and this may cause resistance to anti-oestrogen. Thus, it is conceivable that combinedtherapy with anti-oestrogen and anti-HER2 antibody might be more effective. In the present study, we investigated the effect ofcombined treatment with a humanized anti-HER2 monoclonal antibody, rhumAbHER2 (trastuzumab), and an anti-oestrogen, ICI 182,780, onthe cell growth of three human breast cancer cell lines which respectively express different levels of ER and HER2. The combinedtreatment enhanced the growth inhibitory effect on ML-20 cells, which express a high level of ER and a moderate level of HER2, butshowed no additive effect on either KPL-4 cells, which express no ER and a moderate level of HER2, or MDA-MB-231 cells, whichexpress no ER and a low level of HER2. It is also suggested that both the antibody and anti-oestrogen induce a G1–S blockadeand apoptosis. These findings indicate that combined treatment with anti-HER2 antibody and anti-oestrogen may be useful for thetreatment of patients with breast cancer expressing both ER and HER2. © 2000 Cancer Research Campaig
Identification of major dioxin-like compounds and androgen receptor antagonist in acid-treated tissue extracts of high trophic-level animals
We evaluated the applicability of combining in vitro bioassays with instrument analyses to identify potential endocrine disrupting pollutants in sulfuric acid-treated extracts of liver and/or blubber of high trophic-level animals. Dioxin-like and androgen receptor (AR) antagonistic activities were observed in Baikal seals, common cormorants, raccoon dogs, and finless porpoises by using a panel of rat and human cell-based chemical-activated luciferase gene expression (CALUX) reporter gene bioassays. On the other hand, no activity was detected in estrogen receptor α (ERα)-, glucocorticoid receptor (GR)-, progesterone receptor (PR)-, and peroxisome proliferator-activated receptor γ2 (PPARγ2)-CALUX assays with the sample amount applied. All individual samples (n = 66) showed dioxin-like activity, with values ranging from 21 to 5500 pg CALUX-2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ)/g-lipid. Because dioxins are expected to be strong contributors to CALUX-TEQs, the median theoretical contribution of dioxins calculated from the result of chemical analysis to the experimental CALUX-TEQs was estimated to explain up to 130% for all the tested samples (n = 54). Baikal seal extracts (n = 31), but not other extracts, induced AR antagonistic activities that were 8-150 μg CALUX-flutamide equivalent (FluEQ)/g-lipid. p,p′-DDE was identified as an important causative compound for the activity, and its median theoretical contribution to the experimental CALUX-FluEQs was 59% for the tested Baikal seal tissues (n = 25). Our results demonstrate that combining in vitro CALUX assays with instrument analysis is useful for identifying persistent organic pollutant-like compounds in the tissue of wild animals on the basis of in vitro endocrine disruption toxicity. © 2011 American Chemical Society
New hydroxylated metabolites of 4-monochlorobiphenyl in whole poplar plants
Two new monohydroxy metabolites of 4-monochlorobiphenyl (CB3) were positively identified using three newly synthesized monohydroxy compounds of CB3: 2-hydroxy-4-chlorobiphenyl (2OH-CB3), 3-hydroxy-4-chlorobiphenyl (3OH-CB3) and 4-hydroxy-3-chlorobiphenyl (4OH-CB2). New metabolites of CB3, including 2OH-CB3 and 3OH-CB3, were confirmed in whole poplars (Populus deltoides × nigra, DN34), a model plant in the application of phytoremediation. Furthermore, the concentrations and masses of 2OH-CB3 and 3OH-CB3 formed in various tissues of whole poplar plants and controls were measured. Results showed that 2OH-CB3 was the major product in these two OH-CB3s with chlorine and hydroxyl moieties in the same phenyl ring of CB3. Masses of 2OH-CB3 and 3OH-CB3 in tissues of whole poplar plants were much higher than those in the hydroponic solution, strongly indicating that the poplar plant itself metabolizes CB3 to both 2OH-CB3 and 3OH-CB3. The total yield of 2OH-CB3 and 3OH-CB3, with chlorine and hydroxyl in the same phenyl ring of CB3, was less than that of three previously found OH-CB3s with chlorine and hydroxyl in the opposite phenyl rings of CB3 (2'OH-CB3, 3'OH-CB3, and 4'OH-CB3). Finally, these two newly detected OH-CB3s from CB3 in this work also suggests that the metabolic pathway was via epoxide intermediates. These five OH-CB3s clearly showed the complete metabolism profile from CB3 to monohydroxylated CB3. More importantly, it's the first report and confirmation of 2OH-CB3 and 3OH-CB3 (new metabolites of CB3) in a living organism
The role of Herceptin in early breast cancer
Herceptin is widely regarded as the most important development in the treatment of breast cancer since Tamoxifen and the development of the multidisciplinary team (MDT). It is particularly exciting from an oncological polint of view as it represents success in the emerging field of specific targeted therapies to specific molecular abnormalities in tumour cells. This review will focus on the nature of the Her2 overexpression and the role of herceptin in the treatment of early breast cancer
Apoptosis Induced by the UV Filter Benzophenone-3 in Mouse Neuronal Cells Is Mediated via Attenuation of Erα/Pparγ and Stimulation of Erβ/Gpr30 Signaling
Spatial and temporal trends of the Stockholm Convention POPs in mothers’ milk — a global review
In-situ formation compaction monitoring in deep reservoirs by use of fiber optics
We have devised a new in situ monitoring method for the amount of stratified
compaction in borehole drilled several hundred meters underground. This
newly developed epoch-making monitoring system differs from conventional
monitoring methods for land subsidence in that it is designed to
continuously monitor the amounts of displacement in several intervals
separately, using optical fibers fitted in the sensor assembly. This report
presents results from a deep observation well. This is a continued report
from the previous one on EISOLS 2010
Contamination status and accumulation features of dioxins and related compounds in terrestrial mammals from Japan
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