Gene array identification of Ipf1/Pdx1-/- regulated genes in pancreatic progenitor cells

<p>Abstract</p> <p>Background</p> <p>The homeodomain transcription factor IPF1/PDX1 exerts a dual role in the pancreas; <it>Ipf1/Pdx1 </it>global null mutants fail to develop a pancreas whereas conditional inactivation of <it>Ipf1/Pdx1 </it>in β-cells leads to impaired β-cell function and diabetes. Although several putative target genes have been linked to the β-cell function of <it>Ipf1/Pdx1</it>, relatively little is known with respect to genes regulated by IPF1/PDX1 in early pancreatic progenitor cells.</p> <p>Results</p> <p>Microarray analyses identified a total of 111 genes that were differentially expressed in e10.5 pancreatic buds of <it>Ipf1/Pdx1</it>^-/-embryos. The expression of one of these, <it>Spondin 1</it>, which encodes an extracellular matrix protein, has not previously been described in the pancreas. Quantitative real-time RT-PCR analyses and immunohistochemical analyses also revealed that the expression of <it>FgfR2IIIb</it>, that encodes the receptor for FGF10, was down-regulated in <it>Ipf1/Pdx1</it>^-/-pancreatic progenitor cells.</p> <p>Conclusion</p> <p>This microarray analysis has identified a number of candidate genes that are differentially expressed in <it>Ipf1/Pdx1</it>^-/-pancreatic buds. Several of the differentially expressed genes were known to be important for pancreatic progenitor cell proliferation and differentiation whereas others have not previously been associated with pancreatic development.</p

Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study

PrefHer revealed compelling and consistent patient preference for subcutaneous (s.c.) trastuzumab, regardless of delivery by single-use injection device or hand-held syringe. s.c. trastuzumab was well-tolerated and safety data, including immunogenicity, were consistent with previous reports. No new safety signals were identified compared with the known intravenous trastuzumab profile in early breast cance

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer, and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. Cancer Res; 76(17); 5103-14. ©2016 AACR

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis

Disposition eller röd tråd? : En praktiknära studie av svensklärares bruk av ämnesspecifik terminologi

Ett mått på hur väl ett skolämne definierar sig i förhållande till de övriga är klassifikation. Den ämnesdidaktiska forskningen tyder på att svenskämnet, bland annat genom en låg tillämpning av ämnesspecifik terminologi, kännetecknas av en svag klassifikation. Tre svensklärare vid gymnasiet intervjuades angående deras uppfattning om sitt eget ämnes­relaterade språkbruk och observerades vid två lektionstillfällen var. Resultaten ger vid handen ett språkbruk som till största del präglas av termer som är ämnesrelaterade men inte hämtade från språk- eller litteraturvetenskapen. Detta indikerar en klassifikation av varken alltigenom svag eller stark grad. De uppfattningar som lärarna ger uttryck för i intervjuerna motsvaras endast delvis av den observerade undervisningen

Disposition eller röd tråd? : En praktiknära studie av svensklärares bruk av ämnesspecifik terminologi

Ett mått på hur väl ett skolämne definierar sig i förhållande till de övriga är klassifikation. Den ämnesdidaktiska forskningen tyder på att svenskämnet, bland annat genom en låg tillämpning av ämnesspecifik terminologi, kännetecknas av en svag klassifikation. Tre svensklärare vid gymnasiet intervjuades angående deras uppfattning om sitt eget ämnes­relaterade språkbruk och observerades vid två lektionstillfällen var. Resultaten ger vid handen ett språkbruk som till största del präglas av termer som är ämnesrelaterade men inte hämtade från språk- eller litteraturvetenskapen. Detta indikerar en klassifikation av varken alltigenom svag eller stark grad. De uppfattningar som lärarna ger uttryck för i intervjuerna motsvaras endast delvis av den observerade undervisningen