Visiopharm would like thank all our attendees and Dr. Rebecca Hull, of the University of Washington, for a wonderful webinar this morning. We had a great audience, with wonderful participation during our Q&A session. If you missed it, please enjoy our webinar below. If you have any questions, or would like to request a copy of Dr. Hull’s presentation, please email us.
Tag Archive for Webinars
Quantitative Analysis of Pancreas Immunostaining – Insight into Islet Pathology in Type 2 Diabetes
Speaker: Rebecca Hull, PhD, University of Washington
Thursday, April 18, 2013
9 AM PST/ 12 PM EST / 6 PM CET
Register at: https://www1.gotomeeting.com/register/329213176
Type 2 diabetes is characterized by loss of ?-cell mass and function. Islet amyloid deposition occurs in the vast majority subjects with type 2 diabetes. The extent of islet amyloid deposition is associated with decreased islet ?-cell area and increased ?-cell apoptosis, suggesting that islet amyloid contributes to ?-cell loss. To better understand the detrimental effects of amyloid deposition in islets, we developed a transgenic mouse model that expresses the human, amyloidogenic form of islet amyloid polypeptide (hIAPP) in its ? cells. In vivo studies demonstrated that increased dietary fat intake increases islet amyloid deposition in these mice, resulting in ?-cell loss. Anti-diabetic therapies, including rosiglitazone and metformin are highly effective in inhibiting islet amyloid deposition and its detrimental effects on the ? cell. Islet transplantation is another setting in which amyloid deposition likely has detrimental effects. Indeed, transplantation of hIAPP transgenic islets into diabetic mice results in amyloid deposition, leading to increased ?-cell apoptosis, with no corresponding increase in ?-cell replication and ultimately leading to ?-cell loss. Amyloid deposition can also be induced in isolated islets from these mice, with culture at elevated glucose levels. This in vitro model has allowed us to demonstrate roles for oxidative stress and JNK signaling, but not ER stress, in mediating amyloid-induced ?-cell apoptosis. Recently, we have been working to identify strategies to inhibit islet amyloid deposition, with the goal of developing novel therapeutic strategies to limit amyloid-induced ?-cell loss in diabetes.
About our Speaker
Dr. Rebecca L. Hull received her PhD in Biochemistry from the University of Nottingham, and undertook her postdoctoral training at the University of Washington prior to joining the faculty there. Her research focuses on the mechanisms of pancreatic islet b-cell failure in type 2 diabetes. Dr. Hull is currently a Research Associate Professor in the Division of Metabolism, Endocrinology and Nutrition at the Veterans Affairs Puget Sound Health Care System and University of Washington School of Medicine. She is Associate Director of the University of Washington Diabetes Research Center’s Cellular and Molecular Imaging Core and is an editorial board member for the Journal of Histochemistry and Cytochemistry. She has extensive expertise in specimen collection and immunostaining in pancreas, cultured islets and islet transplant grafts from humans and rodents. She has expertise in morphometric analysis and has used these data to obtain sensitive measures of beta-cell mass, replication and apoptosis, and amyloid deposition for many of her studies.
On February 28, 2013 at 9 AM EST / 3 PM CET Visiopharm will host a webinar titled “Progression Markers in Non-Muscle Invasive Bladder Cancer” presented by Dr. Niels Fristrup from Aarhus University Hospital, Denmark. This webinar coordinates with Visiopharm’s Cancer Research APPs for Bladder Cancer. Our current six Bladder Cancer APPs include:
- Bladder, Annexin 10, Biomarker Expression
- Bladder, MCM7, Biomarker expression
- Bladder, UBE2C, Biomarker expression
- Bladder, TRIM29, Biomarker expression
- Bladder, Survivin, Biomarker expression
- Bladder, CyclinD1, Biomarker expression
Transcripts from the four genes encoding cyclin D1, MCM7, TRIM29, and UBE2C have previously been included in gene expression signatures for outcome prediction in stage Ta/T1 urothelial carcinomas. Here, we investigated the prognostic value of the protein expressions in patients with stage Ta/T1 urothelial carcinomas. We used four different tissue microarrays with a total of 859 Ta/T1 urothelial carcinomas from Danish, Swedish, Spanish, and Taiwanese patient cohorts with long-term follow-up. Protein expression was measured by immunohistochemistry, and antibody specificity was validated by Western blotting.We found the expression of cyclin D1, MCM7, TRIM29, and UBE2C to be significantly associated with progression to muscle-invasive bladder cancer (log-rank test; p<0.001) in the Danish training cohort (n=283). Multivariate Cox regression analysis identified cyclin D1 (p=0.003), TRIM29 (p=0.001), and UBE2C (p<0.001) as independent prognostic markers. The prognostic value of the four proteins was validated in a joint validation cohort from Sweden, Spain, and Taiwan (n=576). We applied computer-assisted image analysis of the prognostic markers and produced results comparable to those obtained by manual scoring. Finally, a four-protein maximum-likelihood classifier was trained on the Danish training cohort; and applied to the validation cohort. The four protein markers may help optimize treatment of patients with Ta/T1 bladder cancer. Additional prospective studies are needed for further validation of their clinical relevance.
Niels Fristrup was educated as medical doctor from the University of Aarhus in 2010. His research started in 2008, primarily concerning prognostic protein markers in non-muscle invasive bladder cancer, now also focusing on predictive markers of Bacillus Calmette Guérin (BCG) treatment response. In his research Niels works to correlate advanced molecular analyses of cancer tissues from patients suffering from bladder cancer with extensive long-term follow-up of large patient cohorts. The goal is to create new, precise ways of identifying the aggressiveness of the cancers as early as possible, or the responsiveness towards BCG immunotherapy. This resarch could potentially lead to a more precise prognostication, again leading towards personalized medicine; the right treatment for each patient. Niels publication list encompasses 10 peer-reviewed articles in renowned journals as The American Journal of Pathology, Oncogene, and Cancer Research.
Our webinar earlier this week, “Can Chromogenic Immunohistochemistry Quantify Intensity?” presented by Diana Fahrer of Biogen Idec, was a great success! If you missed it, it is available on our YouTube channel or for download on our website. To request a copy of the presentation, please email us.
Thank you to all who participated!
Diana Fahrer, a Scientist in the Translational Pathology Laboratory at Biogen Idec, will present on this topic during our webinar next Tuesday, January 15th at 9:00 AM EST/ 3 PM CET.
Do you have a schedule conflict? No problem! Just register and we’ll send an email with information on how to download the recorded webinar.
The ‘holy grail’ of quantitative image analysis is to use intensity measurements of cells stained by immunohistochemistry (IHC) to accurately represent the amount of antigen bound by the primary antibody. Ideally, confidence in such an assay would be defined by using the same rigorous qualification standards as other ligand binding assays and would use chromogenic staining because of the contextural information brightfield staining provides. However, little is written about qualifying brightfield IHC assays and for the most part, intensity quantitation by IHC has relied on fluorophores due to the larger dynamic range they offer. This study represents an initial attempt to qualify a chromogenic IHC assay and to determine what situations, if any, chromogenic staining can be used to quantify intensity.
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