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Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival rate of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, including data from primary tumor, metastatic and normal samples. By digitally separating tumor, stromal and normal gene expression, we have identified and validated two tumor subtypes, including a 'basal-like' subtype that has worse outcome and is molecularly similar to basal tumors in bladder and breast cancers. Furthermore, we define 'normal' and 'activated' stromal subtypes, which are independently prognostic. Our results provide new insights into the molecular composition of PDAC, which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies are critical. [ABSTRACT FROM AUTHOR]

Objective--To assess kinetic 2-([18F]fluoro)-2-deoxy-D-glucose (18FDG) uptake in the brain of anesthetized healthy adult dogs by use of positron emission tomography (PET) and to determine whether 18FDG uptake differs among anatomic regions of the brain. Animals--5 healthy Beagles. Procedures--Each isoflurane-anesthetized dog was administered 18FDG IV (dose range, 3.0 to 5.2 mCi), and PET data were acquired for 2 hours. A CT scan (without contrast agent administration) was performed to allow more precise neuroanatomic localization. Defined regions of interest within the brain were drawn on reconstructed image data. Standard uptake values (SUVs) for 18FDG were calculated to generate time-activity curves and determine time to peak uptake. Results--Time-activity curve analysis identified 4 regional uptake patterns: olfactory, gray matter, white matter, and other (brainstem, cerebellum, and occipital and frontal regions). The highest maximum SUVs were identified in the olfactory bulbs and cerebral gray matter, and the lowest maximum SUV was identified in cerebral white matter. Mean time to peak uptake ranged from 37.8 minutes in white matter to 82.7 minutes in the olfactory bulbs. Conclusions and Clinical Relevance--Kinetic analysis of 18FDG uptake revealed differences in uptake values among anatomic areas of the brain in dogs. These data provide a baseline for further investigation of 18FDG uptake in dogs with immune-mediated inflammatory brain disease and suggest that 18FDG-PET scanning has potential use for antemortem diagnosis without histologie analysis and for monitoring response to treatment. In clinical cases, a 1-hour period of PET scanning should provide sufficient pertinent data. [ABSTRACT FROM AUTHOR]

The article focuses on some analytical skills to highlight the evaluative language used by media in relation to the behavior of Prince Harry. It also discusses two articles entitled "Prince Harry Faces Racism Investigation" and "Prince Harry 'Shocked' by Riots," which are helpful in teaching different grammatical forms including noun, adjective and clause.

Background: Bispecific T-cell engaging antibodies (BiTES), comprising dual anti-CD3 and anti-tumor antigen scFv fragments, are important therapeutic agents for the treatment of cancer. The dual scFv construct for BiTES requires proper protein folding while their small molecular size leads to rapid kidney clearance.Methods: An intact (150 kDa) anti-tumor antigen antibody to CEA was joined in high yield (ca. 30%) to intact (150 kDa) anti-murine and anti-human CD3 antibodies using hinge region specific Click chemistry to form dual-specific, bivalent BiTES (dbBiTES, 300 kDa). dbBiTEs were tested in vitro by EM, flow cytometry and cell cytoxicity and in vivo by PET tumor imaging and redirected T-cell therapy.Results: The interlocked hinge regions are compatible with a structural model that fits the electron micrographs of 300 kDa particles. Compared to intact anti-CEA antibody, dbBiTES exhibit high in vitro cytotoxicity, high in vivo tumor targeting as demonstrated by PET imaging, and redirected dbBiTE coated T-cells (1 microgram/10 million cells) that kill CEA+ target cells in vivo in CEA transgenic mice.Conclusion: dbBiTE redirected T-cell therapy is a promising, efficient approach for targeting and killing cancer cells. [ABSTRACT FROM AUTHOR]

Carcinoembryonic antigen cell adhesion molecule-1 (CEACAM1), a homotypic cell adhesion molecule glycoprotein with apical expression on normal epithelial cells and activated lymphocytes, is overexpressed on many tumors and acts as an inhibitory receptor on NK cells, preventing their killing of CEACAM1 positive tumors. Production of humanized anti-CEACAM1 antibodies to block the inhibitory activity of CEACAM1 for immunotherapy and immunoimaging. Starting from a scFv, a fully human intact anti-CEACAM1 (DIA 12.3) that recognizes the N-terminal domain of CEACAM1 was developed and shown to bind CEACAM1 positive tumor cells and enhanced NK cell killing of CEACAM1 positive targets. DIA 12.3 bound to human neutrophils without activation, indicating they would be safe for human use. DIA 12.3 exhibited some cross-reactivity to CEACAM5, a tumor marker with high sequence homology to the N-terminal domain of CEACAM1. CEACAM1 PET imaging with 64Cu-COTA-DIA 12.3 showed excellent imaging of CEACAM1 positive tumors with reduced binding to CEACAM5 tumors. Based on its immunoinhibitory an immunoimaging activities, DIA 12.3 shows promise for therapeutic studies in man. [ABSTRACT FROM AUTHOR]