In vivo and in vitro propagation of intraductal papillary mucinous neoplasms.

Intraductal papillary mucinous neoplasms (IPMNs) are one of the three known curable precursor lesions of invasive pancreatic ductal adenocarcinoma, an almost uniformly fatal disease. Cell lines from IPMNs and their invasive counterparts should be valuable to identify gene mutations critical to IPMN carcinogenesis, and permit high-throughput screening to identify drugs that cause regression of these lesions. To advance the study of the biological features of IPMNs, we attempted in vivo and in vitro growth of selected IPMNs based on the hypothesis that IPMNs could be grown in the most severely immunodeficient mice. We examined 14 cases by implanting them into nude, severe combined immunodeficient (SCID), and NOD/SCID/IL2Rgamma(null) (NOG) mice, in addition to direct culture, to generate tumor xenografts and cell lines. One sample was directly cultured only. Thirteen tumors were implanted into the three types of mice, including 10 tumors implanted into the triple immunodeficient NOG mice, in which the majority (8 of 10) grew. This included five IPMNs lacking an invasive component. One of the explanted IPMNs, with an associated invasive carcinoma, was successfully established as a cell line. Tumorigenicity was confirmed by growth in soft agar, growth in immunodeficient mice, and the homozygous deletion of p16/cdkn2a. Epithelial differentiation of the cell line was documented by cytokeratin expression. Patient origin was confirmed using DNA fingerprinting. Most non-invasive IPMNs grow in NOG mice. We successfully established one IPMN cell line, and plan to use it to clarify the molecular pathogenesis of IPMNs.

Synthesis of bis(sigma-aryl)dirhodium(III) caprolactamates by oxidative arylation with arylboronic acids.

Recently discovered stable bis(sigma-phenyl)dirhodium(III) caprolactamate and its substituted derivatives are conveniently prepared in high yields from dirhodium(II) caprolactamate and commercially available arylboronic acids in a copper-catalyzed process.

Hetero-bis(sigma-aryl)dirhodium(III) caprolactamates. Electronic communication between aryl groups through dirhodium(III).

Fourteen hetero-bis(sigma-aryl)dirhodium(III) caprolactamates that differ by the two aryl groups at the axial positions of dirhodium have been synthesized in good yield and characterized. Copper(II) catalyzed oxidation of dirhodium(II) caprolactamate at room temperature in the presence of two arylboronic acids results in a mixture of a hetero-bis(sigma-aryl)dirhodium(III) caprolactamate and two homo-bis(sigma-aryl)dirhodium(III) caprolactamates for each arylboronic acid combination. The UV-vis lambda(max) values for hetero-bisaryldirhodium(III) caprolactamates fall in between those for the corresponding homo-bisaryldirhodium(III) caprolactamates; electronic interaction between the two aryl groups occurs through dirhodium, but this transmission is probably indirect through the caprolactamate ligands rather than directly between rhodiums. The chemical shift for the carbon bound to Rh shows very limited dependence on the substituent from the aryl group on the adjacent Rh. Bisaryldirhodium(III) caprolactamates with electron-withdrawing substitutions have higher oxidation potentials than those with electron-donating substitutions. A plot of oxidation potentials versus the corresponding UV-visible absorption maxima for the bisaryldirhodium(III) caprolactamates shows a relationship between oxidation potentials and lambda(max) values. The electronic/electrochemical information obtained for hetero-bis(sigma-aryl)dirhodium(III) caprolactamates suggests that communication between aryl substituents occurs.