The Nearby Supernova Factory (SNfactory) is an ambitious project to find and study in detail approximately 300 nearby Type Ia supernovae (SNe Ia) at redshifts 0.03<
z<0.08. This program will provide ...an exceptional data set of well-studied SNe in the nearby smooth Hubble flow that can be used as calibration for the current and future programs designed to use SNe to measure the cosmological parameters. The first key ingredient for this program is a reliable supply of Hubble-flow SNe systematically discovered in unprecedented numbers using the same techniques as those used in distant SNe searches. In 2002, 35 SNe were found using our test-bed pipeline for automated SN search and discovery. The pipeline uses images from the asteroid search conducted by the Near Earth Asteroid Tracking group at JPL. Improvements in our subtraction techniques and analysis have allowed us to increase our effective SN discovery rate to ∼12 SNe/month in 2003.
Bone morphogenetic protein-2 (BMP-2) is an important regulator of osteoblast differentiation. However, the regulation of osteoblast apoptosis by BMP signaling remains poorly understood. Here we ...examined the role of type I BMP receptor (BMP-RI) in osteoblast apoptosis promoted by BMP-2. Despite undetectable BMP-RIB expression in OHS4 cells, BMP-2 or BMP-2 overexpression increased osteoblast differentiation similarly as in SaOS2 cells which express BMP-RIB, as shown by alkaline phosphatase and CBFA1/RUNX2 expression. In contrast to SaOS2 cells, however, BMP-2 or BMP-2 overexpression did not increase caspase-9 and caspases-3, -6, and -7 activity and DNA fragmentation in OHS4 cells. Consistently, BMP-2 increased protein kinase C (PKC) activity, and PKC inhibition suppressed BMP-2-induced caspase activity in SaOS2 but not in OHS4 cells that lack BMP-RIB. A dominant negative BMP-RIB inhibited BMP-2-induced caspase activity, whereas wild-type BMP-RIB promoted caspase activity induced by BMP-2 in SaOS2 and MC3T3-E1 cells. Wild-type BMP-RIB rescued the apoptotic response to BMP-2, and a constitutively active BMP-RIB restored the apoptotic signal in OHS4 cells, supporting an essential role for BMP-RIB in osteoblast apoptosis. We also assessed whether BMP-2-induced apoptosis occurred independently of osteoblast differentiation. General inhibition of caspases did not abolish BMP-2-induced alkaline phosphatase and CBFA1/RUNX2 expression in SaOS2 cells. Furthermore, broad caspases inhibition increased matrix mineralization but did not reverse the BMP-2 effect on mineralization in MC3T3-E1 cells. These results indicate that BMP-2-induced apoptosis was mediated by BMP-RIB in osteoblasts and occurred independently of BMP-2-induced osteoblast differentiation, which provides additional insights into the dual mechanism of BMP-2 action on osteoblast fate.
In this study we aimed to examine the independent effect of baseline QoL and persistent CRT among pts with early BC.
We included data stage I-III BC pts treated with chemotherapy who were included in ...the CANTO prospective cohort study (NCT-01993498) from 03/2012 to 12/2014. The primary outcome was CRT defined as the presence at 3-6 months after the end of treatment, of any of the following toxicities (NCI-CTC-AE): infection, venous or arterial thrombosis, neurological G2-4, digestive G3-4 or pulmonary toxicities G3-4). Treatment deliver including chemotherapy dose reductions were also examined. The independent variable of this study was baseline Qol defined by the EORTC QLQ-C30 subscales of general global health status (GHS) (< or≥70) and physical functioning PF (< or≥90). The defined cutoffs correspond to the average values in the French general population. Clinical relevant adjustment covariates included stage, age, performance status (PS), body mass index (BMI), HR and HER2 status, baseline lymphopenia, albumin, creatinine clearance, alcohol consumption, and smoking status. Multivariable logistic models were performed.
Among 3079 BC pts included in this analysis, 33% received neoadjuvant and 77% adjuvant treatment. Median age at diagnosis was 53 years, median BMI= 25kg/m2, 94% of patients had a PS=0 and 83% stage I-II disease. Pts reported on average a good GHS = 68 (±19) and PF=90 (±14). GHS and PF were higher in women with better performance status PS=0 vs 1+, (68 vs 60 p<0.001) and 91 vs 78 p<0.001) respectively. 952 (31%) BC pts developed ≥1 CRT: 23% had an infection, 7% thrombosis, 0.3% G3-4 diarrhea, nausea or vomiting, 4% G2-4 neurological and 0.2% G3-4 pulmonary toxicities. 16% had chemotherapy dose reduction. Pts with a baseline GHS <70 had 19 % higher odds of CRT vs to those with GHS≥70, OR=1.19 95% CI 1.02-1.41 and similarly those with a PF<90 had a 23% higher odds of CRT when compared to those with PF≥90 (OR=1.23 95% CI 1.03-1.49).
Global and physical QoL before BC treatments are independently associated with CRT. QoL should be assessed before any treatment to identify patients at risk CRT.
NCT01993498.
UNICANCER/Villejuif, France, 94805 Principal Investigator: Fabrice André Gustave Roussy – Villejuif.
Has not received any funding.
All authors have declared no conflicts of interest.
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