KRAS mutation and epithelial-macrophage interplay in pancreatic neoplastic transformation.

Pancreatic ductal adenocarcinoma (PDA) is characterized by epithelial mutations in KRAS and prominent tumor-associated inflammation, including macrophage infiltration. But knowledge of early interactions between neoplastic epithelium and macrophages in PDA carcinogenesis is limited. Using a pancreatic organoid model, we found that the expression of mutant KRAS in organoids increased (i) ductal to acinar gene expression ratios, (ii) epithelial cells proliferation and (iii) colony formation capacity in vitro, and endowed pancreatic cells with the ability to generate neoplastic tumors in vivo.

Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota.

Background: Colorectal cancer (CRC) is associated with the modern lifestyle. Chronic alcohol consumption-a frequent habit of majority of modern societies-increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC.

PEDF inhibits pancreatic tumorigenesis by attenuating the fibro-inflammatory reaction.

Pancreatic cancer is characterized by a pronounced fibro-inflammatory reaction that has been shown to contribute to cancer progression. Previous reports have demonstrated that pigment epithelium-derived factor (PEDF) has potent tumor suppressive effects in pancreatic cancer, though little is known about the mechanisms by which PEDF limits pancreatic tumorigenesis. We therefore employed human specimens, as well as mouse and in vitro models, to explore the effects of PEDF upon the pancreatic microenvironment.

Rhabdoid carcinoma of anal canal: role of electron microscopy and immunohistochemistry in establishing lineage.

ABSTRACT Rhabdoid carcinoma is a high-grade carcinoma with rhabdoid features and it is different from rhabdoid tumors that are broadly defined as malignant neoplasms with rhabdoid cellular appearance found primarily in the pediatric population, but adult cases have been reported in many anatomic locations. To date, no cases of anal canal rhabdoid carcinoma have been reported in the adult or pediatric population. We are reporting the first case of anal canal rhabdoid carcinoma, found in a 75-year-old male.

Stereoselectivity control by oxaspiro rings during Diels-Alder cycloadditions to cross-conjugated cyclohexadienones: the syn oxygen phenomenon.

The diastereofacial selectivity operating in Diels-Alder additions involving spirocyclic cross-conjugated cyclohexadienones with dienes of varying reactivity has been investigated. The study has included the ether series 1a-c as well as the lactone/ketone pair 2a/2b. In all cases, the preferred [4+2] cycloaddition pathway consisted of bonding from that pi-surface syn to the oxygen atom.

pi-Facial stereoselectivity in Diels-Alder cycloadditions to 1-oxaspiro[4.5]deca-6,9-dien-8-one. The strong directive effect of ether oxygen in a cross-conjugated ketone setting.

[reaction: see text] The title compound 1, prepared from 1,4-cyclohexanedione monoethylene ketal, was treated with several reactive dienes, including diphenylisobenzofuran and 9,10-dihydro-11,12-dimethylene-9,10-ethanoanthracene. These [4 + 2] cycloadditions proceed with a strong kinetic bias for bonding to the dienophile from the direction syn to the tetrahydrofuranyl oxygen and consequently hold value in stereoselective synthesis.