The physiological performance of an organ depends on an interplay between changes in cellular function and organ size, determined by cell growth, proliferation and death. Nowhere is this more evident than in the endocrine pancreas, where disturbances in function or mass result in severe disease. Recently, the insulin signal-transduction pathway has been implicated in both the regulation of hormone secretion from beta cells in mammals as well as the determination of cell and organ size in Drosophila melanogaster. A prominent mediator of the actions of insulin and insulin-like growth factor 1 (IGF-1) is the 3'-phosphoinositide-dependent protein kinase Akt, also known as protein kinase B (PKB). Here we report that overexpression of active Akt1 in the mouse beta cell substantially affects compartment size and function. There was a significant increase in both beta-cell size and total islet mass, accompanied by improved glucose tolerance and complete resistance to experimental diabetes.

Corynebacterium propinquum is a Gram-positive rod occasionally recovered from clinical infections which, according to 16S rRNA gene sequencing, is most closely related (>99 % sequence similarity) to Corynebacterium pseudodiphtheriticum . The two species are very similar biochemically, commonly differentiated by a single test, the detection of urease, where strains of C. propinquum are described as being urease-non-producing and strains of C. pseudodiphtheriticum are described as urease-producing. In this study, historical and contemporary strains of C. propinquum and C. pseudodiphtheriticum from this laboratory were definitively characterized, which included use of rpoB sequencing. Urease-producing strains of C. propinquum as well as typical urease-non-producing isolates were identified after rpoB sequencing, with six of these being originally identified as C. pseudodiphtheriticum . Based on these observations, we propose emendation of the description of C. propinquum to include strains which produce urease. MALDI-TOF analysis may be a useful tool to differentiate these taxa. Existing commercial databases should be updated to include urease-positive strains of C. propinquum .

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Lymphoid hyperplasia of the stomach is characterized by distinctive findings on double-contrast upper gastrointestinal tract barium examinations; all five patients had innumerable tiny (1--3 mm in diameter) round frequently umbilicated nodules that carpeted the mucosa of the gastric antrum or antrum and body. Three of these five patients had associated Helicobacter pylori gastritis. The diagnosis of gastric lymphoid hyperplasia, therefore, can be suggested on the basis of the radiographic findings.

Introduction: Colorectal cancer is a common cancer that accounts for ∼10% of cancer cell deaths in North America. There are numerous in vivo xenograft models for colorectal cancer available, but in general, these are derived from immortalized cell lines and fail to capture the complexities and heterogeneity of tumors seen in the clinic. Our group has developed a series of orthotopic, primary tumors from samples of human colorectal cancer tissue obtained during surgical resection that maintain the characteristics of the original sample. The effects of Irinophore C™, (a liposomal formulation of irinotecan that is more efficacious and less toxic than the parent drug) on the microenvironment and vascular function of these primary colorectal tumors were examined in the present study. Materials and Methods: Primary tumor tissues, obtained from colorectal cancer patients, were validated by a reference pathologist and implanted subcutaneously in SCID mice. Small pieces of subcutaneous tumors that grew successfully were then passaged orthotopically on the ascending colon of new mice. When these tumors reached ∼200mm3, groups of mice were treated with vehicle control (0.9% saline), irinotecan (50mg/kg), or Irinophore C™ (25mg/kg) once a week for 6 weeks. Separate groups of tumors were harvested on days 3 and 42 after treatment started. Immunofluorescence staining was performed on tumor cryosections followed by computerized image analysis to determine levels of cell proliferation, apoptosis, hypoxia, and vessel density. Results: 4 of 14 samples were successfully propagated orthotopically and were characterized by a reference pathologist. The tumors maintain their original morphology, and one is a highly mucinous adenocarcinoma whereas the others are typical colorectal adenocarcinomas. Treatment with irinotecan and Irinophore C™ reduced tumor volumes by 54% and 92%, respectively, compared to the vehicle control. No toxic effects were seen with Irinophore C™. Immunostaining data showed that the distance between blood vessels remained the same for Irinotecan when compared to control, but increased with Irinophore C™ treatment (+30%; P<0.01). However, perfusion was not significantly different between the three treatment groups. Furthermore, compared to the vehicle treatment group, tumors treated with irinotecan are 42% (P<0.05) more necrotic and tumors treated with Irinophore C™ are 97% less hypoxic. Conclusion: An orthotopic model of colorectal cancer was successfully developed using patient tumor materials that retained the morphology of the primary tumor. Irinophore C™ was more effective in controlling tumor growth than irinotecan despite being delivered at a lower dose. In addition, treatment with Irinophore C™ appeared to improve overall vascular function in the tumor. Based on these data, it is clear that Irinophore C™ has different mechanisms of action and is more efficacious than irinotecan against primary models of colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B12.