Whole-body molecular imaging is able to directly map spatial distribution of molecules and monitor its biotransformation in intact biological tissue sections. Imaging mass spectrometry (IMS), a label-free molecular imaging method, can be used to image multiple molecules in a single measurement with high specificity. Herein, a novel easy-toimplement, whole-body IMS method was developed with air flow-assisted ionization in a desorption electrospray ionization mode. The developed IMS method can effectively image molecules in a large whole-body section in open air without sample pretreatment, such as chemical labeling, section division, or matrix deposition. Moreover, the signal levels were improved, and the spatial assignment errors were eliminated; thus, high-quality whole-body images were obtained. With this novel IMS method, in situ mapping analysis of molecules was performed in adult rat sections with picomolar sensitivity under ambient conditions, and the dynamic information of molecule distribution and its biotransformation was provided to uncover molecular events at the whole-animal level. A global view of the differential distribution of an anticancer agent and its metabolites was simultaneously acquired in whole-body rat and model mouse bearing neuroglioma along the administration time. The obtained drug distribution provided rich information for identifying the targeted organs and predicting possible tumor spectrum, pharmacological activity, and potential toxicity of drug candidates.
Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane receptor that is activated by insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors and plays an important role in colorectal cancer etiology and progression. In this study, we used bioinformatic analyses to search for miRNAs that potentially target IGF1R. We identified specific target sites for miR-143 and miR-145 (miR-143/145) in the 3′-untranslated region (3′-UTR) of the IGF1R gene. These miRNAs are members of a cluster of miRNAs that have been reported to exhibit tumor suppressor activity. Consistent with the bioinformatic analyses, we identified an inverse correlation between miR-143/145 levels and IGF1R protein levels in colorectal cancer tissues. By overexpressing miR-143/145 in Caco2, HT29 and SW480 colorectal cancer cells, we experimentally validated that miR-143/145 directly recognizes the 3′-UTR of the IGF1R transcript and regulates IGF1R expression. Furthermore, the biological consequences of the targeting of IGF1R by miR-143/145 were examined by cell proliferation assays in
vitro. We demonstrated that the repression of IGF1R by miR-143/145 suppressed the proliferation of Caco2 cells. Taken together, our findings provide evidence for a role of the miR-143/145 cluster as a tumor suppressor in colorectal cancer through the inhibition of IGF1R translation.
Computational models of embedded control systems often combine continuous-time with discrete-event behavior, mathematically representing hybrid dynamic systems. An essential element of numerical simulation of a hybrid dynamic system is the generation of discrete events from continuous variables that exceed thresholds. In particular, the occurrence of such an event has to be detected and the point in time where the threshold is first exceeded has to be located. This paper presents a number of problems that are encountered in event detection and location when using existing techniques. Solution strategies that balance efficiency and robustness are presented to address: (i) repeated detection of a zero-crossing event at consecutive time steps, (ii) masked zero-crossing events because of multiple zero-crossing functions, and (iii) chattering and Zeno behavior.
Resveratrol (3,4',5-trihydroxy-trans-stilbene), a naturally occurring phytoalexin found in grapes and wine, possesses cancer-preventive activity. Angiogenesis is a crucial step in the growth and metastasis of cancers. We have investigated the effect of resveratrol on angiogenesis in vitro and ex vivo, and found that resveratrol directly inhibited human umbilical vein endothelial cell growth and decreased the gelatinolytic activities of matrix metalloproteinase-2. Tube formation was inhibited by treatment with resveratrol after plating endothelial cells on Matrigel. Resveratrol treatment also inhibited endothelial cell attachment to basement membrane components fibronectin and laminin, and displays similar behavior on cell chemotaxis. In addition, resveratrol has been found to be an angiogenesis inhibitor in the rat aorta matrix culture model. Therefore, inhibition of angiogenesis associated with cancer may be a novel mechanism for the anticancer activity of resveratrol.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.