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Colon cancer prevention currently relies on colonoscopy using white light to detect and remove polyps, but small and flat polyps are difficult to detect and frequently missed when using this technique. Fluorescence colonoscopy combined with a fluorescent probe specific for a polyp biomarker may improve polyp detection. Here we describe GE-137, a water-soluble probe consisting of a 26-amino acid cyclic peptide that binds the human tyrosine kinase c-Met conjugated to a fluorescent cyanine dye. Intravenous administration of GE-137 leads to its accumulation specifically in c-Met-expressing tumors in mice, and it is safe and well tolerated in humans. Fluorescence colonoscopy in patients receiving intravenous GE-137 enabled visualization of all neoplastic polyps that were visible with white light (38), as well as an additional nine polyps that were not visible with white light. This first-in-human pilot study shows that molecular imaging using an intravenous fluorescent agent specific for c-Met is feasible and safe, and that it may enable the detection of polyps missed by other techniques., Colorectal cancer (CRC) is a major cause of cancer death (1), and colonoscopy is firmly established as the mainstay of CRC prevention. Evidence that CRC can be prevented by the [...]

We have studied in vivo responses of 'spontaneous' Brca1- and p53-deficient mammary tumors arising in conditional mouse mutants to treatment with doxorubicin, docetaxel, or cisplatin. Like human tumors, the response of individual mouse tumors varies, but eventually they all become resistant to the maximum tolerable dose of doxorubicin or docetaxel. The tumors also respond well to cisplatin but do not become resistant, even after multiple treatments in which tumors appear to regrow from a small fraction of surviving cells. Classical biochemical resistance mechanisms, such as up-regulated drug transporters, appear to be responsible for doxorubicin resistance, rather than alterations in drug-damage effector pathways. Our results underline the promise of these mouse tumors for the study of tumor-initiating cells and of drug therapy of human cancer. multidrug resistance | P-glycoprotein I cancer stem cells

The [sup.226][Ra.sup.2+] selectivity of the ionizable (thia)calix[4]-crowns 1-4 was determined in the presence of a large excess of the most common alkali and alkaline earth cations. Selective [sup.226][Ra.sup.2+] (2.9 x [10.sup.-8] M) extraction occurs even at extremely high [M.sup.n+]/[sup.226][Ra.sup.2+] ratios of 3.5 x [10.sup.7] [[M.sup.n+] = [Na.sup.+], [K.sup.+], [Rb.sup.+], [Cs.sup.+], [Mg.sup.2+], [Ca.sup.2+], and [Sr.sup.2+] (1 M)] and an ionophore concentration of [10.sup.-4] M. The selectivity coefficients log([K.sup.Ra.sub.ex]/[K.sup.M.sub.ex]) are ~3.5 for [Mg.sup.2+], [Ca.sup.2+], and [Sr.sup.2+]. In the presence of [Ba.sup.2+], which has very similar chemical properties, only the thiacalix[4]crown-6 derivative 4 showed a selectivity for [sup.226][Ra.sup.2+]. In addition to the remarkable [sup.226][Ra.sup.2+] selectivities, the effective pH range (pH 8-13) of the thiacalix[4]crown dicarboxylic acids (3 and 4) allows for full regeneration of the ionophores at lower pH values (pH

A systematic study on the formation and conformations of p-tert-butylthiacalix[4]arene-(bis)crowns-4, -5 and -6 was made. Temperature-dependent studies revealed that the conformationally flexible 1,3-dimethoxythiacalix-[4] arene-crowns exclusively occupy the 1,3-alternate conformation.