A fetoacinar pancreatic protein (FAP) associated with the ontogenesis, differentiation and oncogenic transformation of the human exocrine pancreas has been purified from pancreatic juices of patients suffering from pancreatitis or duodenal cancers invading the pancreas [Escribano and Imperial (1989) J. Biol. Chem. 264, 21865-21871]. This protein has striking similarities, i.e. M(r), amino acid composition and N-terminal sequence, to the bile-salt-dependent lipase (BSDL) of normal human pancreatic secretion. The aim of this study was to gain further insight into the nature of the two proteins. Reactivity with the mouse monoclonal antibody J28 (mAb J28), which characterizes FAP, and enzyme activity could not be dissociated during biochemical purification of BSDL. Furthermore, a polyclonal antiserum raised against purified human BSDL reacted completely with FAP in Western-blot analysis giving additional support to the idea of similar molecular structures for BSDL and FAP. However, by the same technique, mAb J28 reacted with a relatively restricted population of BSDL molecules. The classical BSDL preparation could be separated into molecules bearing the J28 epitope and those devoid of it by immunoaffinity on immobilized mAb J28. The two subpopulations had identical N-terminal sequences and some differences in their amino acid compositions. However, they had different carbohydrate compositions. J28-epitope-bearing molecules were active on BSDL substrates, although their specific activity was decreased. These results are consistent with the existence of two closely related polypeptide chains with different glycan counterparts. Therefore, if the name FAP is reserved for molecules bearing the J28 epitope, which is linked to a carbohydrate-dependent structure. FAP could represent an oncofetal-related variant of BSDL. Our result is the first demonstration of the existence of an oncofetal-type subpopulation of an otherwise normally secreted human pancreatic enzyme.

Another star for the Palladium: The discovery of reactions promoted by the ubiquitous Pd0 catalysts is still possible. 1H‐1,2,3‐Triazoles are directly obtained by reaction of alkenyl bromides and sodium azide in the presence of a Pd0–xantphos catalyst (see scheme, xantphos=9,9‐dimethyl‐4,5‐bis(diphenylphosphino)xanthene, dba=trans,trans‐dibenzylideneacetone).

The carbonyl group is probably the most versatile functional group in organic synthesis, owing to its rich and highly developed chemistry. In particular, carbonyl compounds are extraordinary sources of enantiomerically pure compounds, that can be obtained from the chiral pool from terpenes, carbohydrates, and amino acids, and also through asymmetric catalysis [1] and organocatalysis.[2] However, carbonyl compounds bearing chirality at the a carbon can be difficult to manipulate owing to their configurational instability through enolization. Moreover, the typical formation of alkenes by nucleophilic-addition/elimination sequences usually affords the more-substituted olefin, [3] with loss of the chiral information (Figure 1 a), and the reactions that proceed through the formation of enolates, such as cross-coupling reactions through enol sulfonates, require tightly controlled kinetic conditions to avoid the equilibration of the chiral center (Figure 1 c). [4,5] For these reasons, the development of methodologies that allow the manipulation of the carbonyl functionality with preservation of the a chirality are highly desirable.The palladium-catalyzed cross-coupling between tosylhydrazones and aryl halides, recently developed by our group, [6] constitutes an efficient method to manipulate the carbonyl functionality. The overall transformation is equivalent to a nucleophilic addition/elimination sequence. However, as we will show herein, in many cases the reaction gives the lesssubstituted alkene, and importantly, with no erosion of the chirality of the stereogenic center at the a position (Figure 1 d); thus, we report the implementation of this new methodology for the manipulation of a-chiral ketones.The catalytic cycle proposed for the palladium-catalyzed cross-coupling between tosylhydrazones and aryl halides is presented in Figure 2. The characteristic steps are formation of the palladium-carbene complex VII, migratory insertion of the aryl to give the alkylpalladium complex VIII, [7,8] and synb-hydride elimination, that releases the coupling product. For tosylhydrazones derived from ketones with two enolizable positions, such as I, two regioisomers II and III can be obtained that differ in the position of the double bond. [6a,c, 8] Cross-coupling reactions of tosylhydrazones derived from ketones with two enolizable positions and aryl halides: the regioselectivity in the formation of the double bond is determined by the syn-bhydride-elimination step on alkylpalladium complex VIII. xphos = 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl.

The effects of insulin and somatostatin on the growth and the colony formation of two human pancreatic cancer cell lines, BxPC-3 and SOJ-6, were studied. The BxPC-3 cell line (American Type Culture Collection no. CRL 1687) was derived from a moderately differentiated pancreatic adenocarcinoma. The SOJ-6 cell line is a subclone of SOJ that was initiated from ascites of a well-differentiated pancreatic adenocarcinoma. Both cell lines express fetoacinar pancreatic antigen, an antigen that might be associated with early transformation stages. However, these lines have different proliferation and tumoral powers. SOJ-6 cells showed an almost twofold higher division rate over BxPC-3 cells when cultured in RPMI-1640 medium containing 10% fetal bovine serum. The tumorigenic degree of SOJ-6 cells, as assessed by tumor growth in nude mice, was about three times greater than that of BxPC-3. The in vitro growth of BxPC-3 cells was significantly promoted by insulin, and was slightly inhibited by somatostatin, whereas the growth of SOJ-6 cells was not influenced by these hormones. Using a clonogenic assay in soft agar, the average ratio of colony numbers formed by SOJ-6 and BxPC-3 was about 10/1, indicating a good correlation between the colony formation and tumorigenic degree in vivo. In this test, the number of colonies formed by BxPC-3 cells was increased about twofold in insulin-supplemented medium. On the other hand, somatostatin inhibited the colony formation by a factor of four to six. However, no hormonal modulation of the colony formation of SOJ-6 cells was observed. Our data show that pancreatic cancer cell lines respond differently to pancreatic hormones, and suggest that this may be correlated to a tumour stage or a tumour type.