Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application.

Aim The Enhanced Liver Fibrosis (ELF) test comprises a logarithmic algorithm combining three serum markers of hepatic extracellular matrix metabolism. We aimed to evaluate the performance of ELF for the diagnosis of liver fibrosis and to compare it with that of liver stiffness measurement (LSM) by FibroScan in non‐alcoholic fatty liver disease. Methods ELF cut‐off values for the diagnosis of advanced fibrosis were obtained using receiver operating characteristic analysis in patients with biopsy‐confirmed non‐alcoholic fatty liver disease (training set; n = 200). Diagnostic performance was analyzed in the training set and in a validation set (n = 166), and compared with that of LSM in the FibroScan cohort (n = 224). Results The area under receiver operating characteristic curve was 0.81 for the diagnosis of advanced fibrosis, and the ELF cut‐off values were 9.34 with 90.4% sensitivity and 10.83 with 90.6% specificity in the training set, and 89.8% sensitivity and 85.5% specificity in the validation set. There was no significant difference in the area under the receiver operating characteristic curve between ELF and LSM (0.812 and 0.839). A combination of ELF (cut‐off 10.83) and LSM (cut‐off 11.45) increased the specificity to 97.9% and the positive predictive value, versus ELF alone. Sequential use of the Fibrosis‐4 index (cut‐off 2.67) and ELF (cut‐off 9.34) increased the sensitivity to 95.9%. Conclusions ELF can identify advanced liver fibrosis in non‐alcoholic fatty liver disease, and its diagnostic accuracy is comparable to that of FibroScan. According to the clinical setting, combinations or sequential procedures using other non‐invasive tests complement the diagnostic performance of ELF for the identification of advanced fibrosis.

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Ten kinds of monoglycosylceramides (MonoCers), having the same ceramide portion and different sugar moieties, were synthesized and their immunostimulatory and antitumor activities were examined. The manner of combination between sugar and ceramide has been demonstrated to affect the manifestation of immunostimulatory and resultant antitumor activities of MonoCers, and in the case of D-MonoCers having the D-sugar, alpha-D-MonoCers (sugar combined to ceramide in an alpha-configuration) show stronger activities than beta-D-MonoCers. Furthermore, the form of sugar, not the furanose-form but the pyranose-form, and the 2"- and 4"-hydroxyl groups of the pyranose-form of sugar, seemed to play an important role in the manifestation of the activities of alpha-D-MonoCers.

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