[Galactosylceramide (KRN7000) -- Kirin]
>>Published online before print July 16, 2003
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.1630663100
Immunology
-Galactosylceramide (KRN7000) suppression of chemical- and oncogene-dependent carcinogenesis
Yoshihiro Hayakawa *, Stefania Rovero , Guido Forni , and Mark J. Smyth *¶
*Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett Street, Melbourne 8006, Australia; Department of Clinical and Biological Sciences, University of Turin, I-10043 Orbassano, Italy; and Center for Experimental Research and Medical Studies, St. Giovanni Battista Hospital, I-10126 Turin, Italy
Edited by Lloyd J. Old, Ludwig Institute for Cancer Research, New York, NY, and approved June 3, 2003 (received for review February 3, 2003)
Recent studies have revealed significant efficacy of the marine sponge glycolipid, -galactosylceramide (-GalCer), in treatment of experimental metastatic cancers, infections, and autoimmune diseases. However, the capacity of -GalCer to prevent tumor development had never, to our knowledge, been evaluated in mouse models of chemical- and oncogene-dependent carcinogenesis. In this study, we demonstrate that long-term administration of soluble -GalCer, spanning the time of tumor initiation, inhibits primary tumor formation in three different models: methylcholanthrene-induced sarcomas, mammary carcinomas in Her-2/neu transgenic mice, and spontaneous sarcomas in p53-/- mice. Weekly treatment of mice with -GalCer maintained lymphoid tissue natural killer cell and T cell activation and elevated serum IFN- and IL-4 concentrations. Consistent with the antimetastatic activity of -GalCer, prevention of methylcholanthrene-induced sarcoma was IFN-- and tumor necrosis factor-related apoptosis-inducing ligand dependent, but not perforin-dependent. Taken together, our results demonstrate that NK1.1+TCR+ cell-based immune therapy can inhibit primary tumorigenesis.<<
Those guys flunk the literature search test . . .
>>Asian Pac J Cancer Prev. 2003 Jan-Mar;4(1):45-50.
No inhibition of urinary bladder carcinogenesis in rats with intravesical instillation of alpha-galactosylceramide.
Mitsuhashi M, Wanibuchi H, Wei M, Doi K, Morimura K, Masuda C, Wada S, Nakatani T, Kakizoe T, Fukushima S.
Department of Pathology, Osaka City University Medical School, Osaka 545-8585, Japan. fukuchan@med.osaka-cu.ac.jp
The immunostimulatory a-galactosylceramide, KRN 7000 ((2S,3S,4R)-1-O-(a-D-galactopyranosyl)-2-(N-hexacosnoylamino)-1,3,4-octadecatrienol), may be anticipated to have antitumor activity in vivo apart from any direct toxicity to cancer cells. In this experiment, inhibition of rat bladder carcinogenesis by intravesically instillated KRN7000 was investigated. Male Fischer 344 rats, 6-weeks-old at the start, were divided into 4 groups, all first receiving the carcinogen, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine, in their drinking water for 12 weeks. Then groups 1 and 2 respectively were administered 500 and 50 mg/kg of KRN7000 intravesically once weekly for 17 weeks. Group 3 similarly received only 0.3 micro/l of saline (vehicle control). Group 4 did not undergo bladder catheterization. On macroscopic examination at 30 weeks, multiplicities and sizes of bladder tumors in the KRN 7000 high and low-dose groups were not significantly different from those of the vehicle control group. Histologic examination confirmed no significant variation in incidences of carcinomas or preneoplastic lesions in the bladder among groups 1 to 4. Thus the results indicate that intravesical instillation of KRN7000 does not inhibit bladder carcinogenesis in rats.<<
It looks as though KRN7000's ability to inhibit carcinogenesis depends on the type of tumor. There's plenty of literature out there on this compound.
Cheers, Tuck |
