ABSTRACT
Efficient transfer of S and chalcophile metals through the Earth's crust in arc systems is paramount for the formation of large magmatic-hydrothermal ore deposits. The formation of sulfide-volatile compound drops has been recognized as a potential key mechanism for such transfer but their fate during dynamic arc magmatism remains cryptic. Combining elemental mapping and in-situ mineral analyzes we reconstruct the evolution of compound drops in the active Christiana-Santorini-Kolumbo volcanic field. The observed compound drops are micrometric sulfide blebs associated with vesicles trapped within silicate phenocrysts. The compound drops accumulate and coalesce at mafic-felsic melt interfaces where larger sulfide ovoids form. These ovoids are subsequently oxidized to magnetite during sulfide-volatile interaction. Comparison of metal concentrations between the sulfide phases and magnetite allows for determination of element mobility during oxidation. The formation and evolution of compound drops may be an efficient mechanism for transferring S and chalcophile metals into shallow magmatic-hydrothermal arc systems.
ABSTRACT
The homeobox transcription factor Cdx2 specifies intestinal development and homeostasis and is considered a tumor suppressor in colorectal carcinogenesis. However, Cdx2 mutations are rarely found. Invasion of colorectal cancer is characterized by a transient loss of differentiation and nuclear accumulation of the oncoprotein beta-catenin in budding tumor cells. Strikingly, this is reversed in growing metastases, indicating that tumor progression is a dynamic process that is not only driven by genetic alterations but also regulated by the tumor environment. Here we describe a transient loss of Cdx2 in budding tumor cells at the tumor host interface, and reexpression of Cdx2 in metastases. Cell culture experiments show that collagen type I, through beta(1) integrin signaling, triggers a transient transcriptional down-regulation of Cdx2 and its intestine-specific target gene sucrase isomaltase, associated with a loss of differentiation. These data indicate an active role for the tumor environment in malignant tumor progression.
Subject(s)
Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Avian Proteins , Collagen Type I/physiology , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Homeodomain Proteins/antagonists & inhibitors , Adenocarcinoma/genetics , Animals , Colorectal Neoplasms/genetics , Cytoskeletal Proteins/biosynthesis , Cytoskeletal Proteins/genetics , Disease Progression , Down-Regulation , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/genetics , Integrin beta1/physiology , Male , Mice , Mice, Nude , Signal Transduction/physiology , Trans-Activators/biosynthesis , Trans-Activators/genetics , beta CateninABSTRACT
BACKGROUND & AIMS: Cancer-protective effects of isoflavones like genistin or genistein are well known. High intakes and an adequate absorption rate of isoflavones are necessary for efficient chemoprevention, though other dietary agents might increase absorption efficacy. The aim of this study was to investigate the effect of phloridzin, an inhibitor of the sodium-dependent glucose transporter (SGLT1), on genistin absorption and metabolism. METHODS: Phloridzin and genistin were luminally administered in an isolated preparation of luminally and vascularly perfused rat small intestine. A synthetic perfusate free from blood components was used as vascular medium, with a perfluorocarbon as oxygen carrier. Luminal media consisted of a bicarbonate buffered sodium chloride solution spiked with genistin (24.5 micromol/l) and phloridzin (1 mmol/l). RESULTS: In previous experiments, genistin absorption rate of 17.2% has been observed. In the present study, phloridzin administered simultaneously with genistin, increased genistin uptake 2.5 fold (44.5%). CONCLUSION: The naturally occurring substance phloridzin, present in apples, thus considerably amplify genistin absorption. These effects might offer a promising novel method in designing functional foods for cancer prevention by combining genistin- and phloridzin-containing foods.