Université libre de Bruxelles

About: Université libre de Bruxelles is a education organization based out in Brussels, Belgium. It is known for research contribution in the topics: Population & Breast cancer. The organization has 24974 authors who have published 56969 publications receiving 2084303 citations. The organization is also known as: ULB.

Molecular packing of high-mobility diketo pyrrolo-pyrrole polymer semiconductors with branched alkyl side chains

Abstract: We describe a series of highly soluble diketo pyrrolo-pyrrole (DPP)-bithiophene copolymers exhibiting field effect hole mobilities up to 0.74 cm2 V–1 s–1, with a common synthetic motif of bulky 2-octyldodecyl side groups on the conjugated backbone. Spectroscopy, diffraction, and microscopy measurements reveal a transition in molecular packing behavior from a preferentially edge-on orientation of the conjugated plane to a preferentially face-on orientation as the attachment density of the side chains increases. Thermal annealing generally reduces both the face-on population and the misoriented edge-on domains. The highest hole mobilities of this series were obtained from edge-on molecular packing and in-plane liquid-crystalline texture, but films with a bimodal orientation distribution and no discernible in-plane texture exhibited surprisingly comparable mobilities. The high hole mobility may therefore arise from the molecular packing feature common to the entire polymer series: backbones that are strictly...

The basic helix-loop-helix protein family: comparative genomics and phylogenetic analysis.

Abstract: The basic Helix-Loop-Helix (bHLH) proteins are transcription factors that play important roles during the development of various metazoans including fly, nematode, and vertebrates. They are also involved in human diseases, particularly in cancerogenesis. We made an extensive search for bHLH sequences in the completely sequenced genomes of Caenorhabditis elegans and of Drosophila melanogaster. We found 35 and 56 different genes, respectively, which may represent the complete set of bHLH of these organisms. A phylogenetic analysis of these genes, together with a large number (>350) of bHLH from other sources, led us to define 44 orthologous families among which 36 include bHLH from animals only, and two have representatives in both yeasts and animals. In addition, we identified two bHLH motifs present only in yeast, and four that are present only in plants; however, the latter number is certainly an underestimate. Most animal families (35/38) comprise fly, nematode, and vertebrate genes, suggesting that their common ancestor, which lived in pre-Cambrian times (600 million years ago) already owned as many as 35 different bHLH genes.

Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response

Abstract: Summary Background Findings from the randomised phase 3 NeoALTTO trial in women with HER2-positive early breast cancer showed that the combination of lapatinib and trastuzumab significantly improved rates of pathological complete response compared with either drug alone. Here, we report data for the prespecified secondary endpoints of event-free and overall survival, and assess the association between these outcomes and pathological complete response. Methods We enrolled women with HER2-positive early breast cancer and randomly assigned them to receive oral lapatinib (1500 mg), intravenous trastuzumab (4 mg/kg loading dose followed by 2 mg/kg), or lapatinib (1000 mg) plus trastuzumab (same dose as for single agent) in combination for 6 weeks, followed by an additional 12 weeks of the assigned anti-HER2 therapy in combination with weekly paclitaxel (80 mg/m 2 ). Definitive surgery was done 4 weeks after the last dose of paclitaxel. After surgery, women received three cycles of FEC (fluorouracil 500 mg/m 2 plus epirubicin 100 mg/m 2 plus cyclophosphamide 500 mg/m 2 ) given intravenously every 3 weeks, followed by 34 weeks of the same assigned neoadjuvant anti-HER2 therapy. The primary endpoint was pathological complete response. Secondary endpoints included event-free and overall survival (intention-to-treat analysis), and the association between pathological complete response and event-free or overall survival (analysed by landmark analysis at 30 weeks after randomisation). Follow-up is ongoing, and the trial is registered with ClinicalTrials.gov, number NCT00553358. Findings 455 patients were enrolled: 154 (34%) were assigned to the lapatinib group, 149 (33%) to the trastuzumab group, and 152 (33%) to the lapatinib plus trastuzumab group. At an event follow-up of 3·77 years (IQR 3·50–4·22), 3-year event-free survival was 78% (95% CI 70–84) in the lapatinib group, 76% (68–82) in the trastuzumab group, and 84% (77–89) in the combination group. Event-free survival did not differ between the lapatinib and trastuzumab groups (HR 1·06, 95% CI 0·66–1·69, p=0·81), nor between the combination and trastuzumab groups (0·78, 0·47–1·28, p=0·33). Median survival follow-up was 3·84 years (IQR 3·60–4·24), and 3-year overall survival was 93% (95% CI 87–96) for lapatinib, 90% (84–94) for trastuzumab, and 95% (90–98) for combination therapy. Overall survival did not significantly differ between the lapatinib and trastuzumab groups (HR 0·86, 95% CI 0·45–1·63, p=0·65), nor between the combination and trastuzumab groups (0·62, 0·30–1·25, p=0·19). Landmark analyses showed that 3-year event-free survival was significantly improved for women who achieved pathological complete response compared with those who did not (HR 0·38, 95% CI 0·22–0·63, p=0·0003), as was 3-year overall survival (0·35, 0·15–0·70, p=0·005). Adverse events occurred in 149 (99%) patients receiving lapatinib, 142 (96%) patients receiving trastuzumab, and 147 (99%) patients receiving combination therapy. The most common adverse events were diarrhoea, rash or erythema, hepatic adverse events, and neutropenia (not related to FEC administration), and were consistent with known safety profiles of lapatinib and trastuzumab. Three primary and eight secondary cardiac events occurred, with no significant difference in incidence between treatment groups for primary or any cardiac events. Interpretation Although event-free survival or overall survival did not differ between treatment groups, findings from our study confirm that patients who achieve pathological complete response after neoadjuvant anti-HER2 therapy have longer event-free and overall survival than do patients without pathological complete response. Funding GlaxoSmithKline.

The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients.

Abstract: Pancreatic beta cells have highly developed endoplasmic reticulum (ER) due to their role in insulin secretion. Since ER stress has been associated with beta cell dysfunction, we studied several features of beta cell ER in human type 2 diabetes. Pancreatic samples and/or isolated islets from non-diabetic controls (ND) and type 2 diabetes patients were evaluated for insulin secretion, apoptosis (electron microscopy and ELISA), morphometric ER assessment (electron microscopy), and expression of ER stress markers in beta cell prepared by laser capture microdissection and in isolated islets. Insulin release was lower and beta cell apoptosis higher in type 2 diabetes than ND islets. ER density volume was significantly increased in type 2 diabetes beta cells. Expression of alpha-mannosidase (also known as mannosidase, alpha, class 1A, member 1) and UDP-glucose glycoprotein glucosyl transferase like 2 (UGCGL2), assessed by microarray and/or real-time reverse transcriptase polymerase chain reaction (RT-PCR), differed between ND and type 2 diabetes beta cells. Expression of immunoglobulin heavy chain binding protein (BiP, also known as heat shock 70 kDa protein 5 [glucose-regulated protein, 78 kDa] [HSPA5]), X-box binding protein 1 (XBP-1, also known as XBP1) and C/EBP homologous protein (CHOP, also known as damage-inducible transcript 3 [DDIT3]) was not higher in type 2 diabetes beta cell or isolated islets cultured at 5.5 mmol/l glucose (microarray and real-time RT-PCR) than in ND samples. When islets were cultured for 24 h at 11.1 mmol/l glucose, there was induction of BiP and XBP-1 in type 2 diabetes islets but not in ND islets. Beta cell in type 2 diabetes showed modest signs of ER stress when studied in pancreatic samples or isolated islets maintained at physiological glucose concentration. However, exposure to increased glucose levels induced ER stress markers in type 2 diabetes islet cells, which therefore may be more susceptible to ER stress induced by metabolic perturbations.