Letrozole (Femara) early and late responses to treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Miller WR
PROVIDER: S-ECPF-GEOD-20181 | biostudies-other | 2012 Feb
REPOSITORIES: biostudies-other
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2010-07-28 | GSE20181 | GEO
Project description:In the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days or 90 days treatment with letrozole. RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation. Keywords: Timecourse between subjects Biopsies were taken from the same subjects at three timepoints: pretreatment, after 10-14 days Letrozol (2.5 mg/day, oral), and after 90 days Letrozol (2.5 mg/day, oral).
2010-07-28 | E-GEOD-20181 | biostudies-arrayexpress
Project description:In the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days treatment with letrozole. RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation. Keywords: time course
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Project description:Is a short visuomotor associative training sufficient to reverse the visuomotor tuning of mirror neurons in adult humans? We tested the effects of associative training on corticospinal modulation during action observation in the 100-320 ms interval after action onset. In two separate experiments, the acceleration of transcranial magnetic stimulation (TMS)-induced movements was recorded before and after training participants to respond to observed acts with an opposite or similar behavior. Before training, TMS-induced accelerations mirrored the observed action at 250 and 320 ms. After training, responses at 250 ms were unchanged and still mirrored the stimuli, without any effect of training direction. Only at 320 ms, we observed training-dependent changes in evoked responses. A control experiment with non-biological rotational movements as visual stimuli indicated that spatial stimulus-response compatibility is not sufficient to account for the results of the two main experiments. We show that the effects of a short visuomotor associative training are not pervasive on the automatic mirror responses. 'Early' (250 ms) responses were not influenced by training. Conversely only 'late' (320 ms) responses changed according to the training direction. This biphasic time course indicates that two distinct mechanisms produce the automatic mirror responses and the newly learned visuomotor associations.
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Project description:Tumorigenic breast cancer cells characterized by high CD44 and low or undetectable CD24 levels (CD44+/CD24-/low) may be resistant to conventional therapies and responsible for cancer relapse. We defined a “signature” expression pattern of hundreds of genes associated with CD44+/CD24-/low, mammosphere-forming cells. In a panel of patient breast tumors, this tumorigenic gene signature was found exclusively manifested in tumors of the recently identified “claudin-low” molecular profile subtype characterized by overexpression of many mesenchymal-associated genes, suggesting that these tumors have pre-existing higher levels of tumorigenic cells. Furthermore, when comparing the expression profiles of paired breast cancer core biopsies before versus after hormone therapy or chemotherapy, both the tumorigenic and “claudin-low” signatures were more active in about half of tumors after treatment, indicative of a greater enrichment of tumorigenic cells as a result of treatments targeting the bulk tumor cells. Experiment Overall Design: Biopsies were taken from the same subjects both pretreatment and after 10-14 days Letrozol, 2.5 mg/day, oral.
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Project description:The productivity and climate feedbacks of tropical forests depend on tree physiological responses to warmer and, over large areas, seasonally drier conditions. However, knowledge regarding such responses is limited due to data scarcity. We studied the impact of growth temperature on net photosynthesis (An), maximum rates of Rubisco carboxylation at 25 °C (Vcmax25), stomatal conductance (gs) and the slope parameter of the stomatal conductance-photosynthesis model (g1), in 10 early successional (ES) and 8 late-successional (LS) tropical tree species grown at three sites along an elevation gradient in Rwanda, differing by 6.8 °C in daytime ambient air temperature. The effect of seasonal drought on An was also investigated. We found that warm climate decreased wet-season An in LS species, but not in ES species. Values of Vcmax25 were lower at the warmest site across both successional groups, and An and Vcmax25 were higher in ES compared with LS species. Stomatal conductance exhibited no significant site differences and g1 was similar across both sites and successional groups. Drought strongly reduced An at warmer sites but not at the coolest montane site and this response was similar in both ES and LS species. Our results suggest that warming has negative effects on leaf-level photosynthesis in LS species, while both LS and ES species suffer photosynthesis declines in a warmer climate with more pronounced droughts. The contrasting responses of An between successional groups may lead to shifts in species' competitive balance in a warmer world, to the disadvantage of LS trees.
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Project description:BackgroundData suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested.MethodsA total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen.ResultsAfter a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum.ConclusionsOral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.).
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Project description:Tumorigenic breast cancer cells characterized by high CD44 and low or undetectable CD24 levels (CD44+/CD24-/low) may be resistant to conventional therapies and responsible for cancer relapse. We defined a âsignatureâ expression pattern of hundreds of genes associated with CD44+/CD24-/low, mammosphere-forming cells. In a panel of patient breast tumors, this tumorigenic gene signature was found exclusively manifested in tumors of the recently identified âclaudin-lowâ molecular profile subtype characterized by overexpression of many mesenchymal-associated genes, suggesting that these tumors have pre-existing higher levels of tumorigenic cells. Furthermore, when comparing the expression profiles of paired breast cancer core biopsies before versus after hormone therapy or chemotherapy, both the tumorigenic and âclaudin-lowâ signatures were more active in about half of tumors after treatment, indicative of a greater enrichment of tumorigenic cells as a result of treatments targeting the bulk tumor cells. Experiment Overall Design: Biopsies were taken from the same subjects both pretreatment and after 10-14 days Letrozol, 2.5 mg/day, oral.
2009-08-22 | E-GEOD-10281 | biostudies-arrayexpress
Project description:Biopsies were collected from post-menopausal women with ER+ HER2- breast cancer who were subsequently treated with either letrozole or letrozole plus bevacizumab.
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