Switching from tacrolimus to sirolimus halts the appearance of new sebaceous neoplasms in Muir-Torre syndrome.

Little is known about the effects of immunosuppression on patients with hereditary nonpolyposis colorectal cancer (HNPCC). We describe a kidney transplant recipient with unrecognized Muir-Torre syndrome in whom the administration of a tacrolimus-based regimen led to the eruption of multiple sebaceous tumors. The patient was later found to harbor an MSH2 mutation. Switching to a sirolimus-based regimen resulted in arrest of the disease. When the patient was switched back to tacrolimus, new facial lesions rapidly appeared. Switching again to sirolimus resulted again in halting the appearance of new lesions. This finding is in line with the known antiangiogenic activity of sirolimus and reports on the regression of cutaneous Kaposi's sarcoma in kidney transplant recipients switched from another immunosuppressive regimen to sirolimus. Further studies on the potential use of sirolimus for the treatment of de novo tumors in immunosuppressed kidney transplant recipients with HNPCC are warranted.

Effects of aminothiols in 2-acetylaminofluorene-treated rats. I. Damage and repair of liver DNA, hyperplastic foci, and Zymbal gland tumors.

One hundred and seventy-nine male Wistar rats were divided into 6 groups and fed with a standard diet supplemented with 0.05% 2-acetylaminofluorene (2AAF) and/or 0.1% glutathione (GSH) or N-acetyl-L-cysteine (NAC). Each treatment cycle lasted for 3 weeks, followed by 1 week of standard meal. After 4 cycles, survival was 100% in the 3 control groups, and 86.0, 100 and 91.7%, in the groups receiving 2AAF, 2AAF plus GSH, and 2AAF plus NAC, respectively. After an additional 4-8 weeks, all the 5 surviving rats fed with 2AAF exhibited deforming ear tumors, which on histological examination were classified as sebaceous squamocellular carcinomas of Zymbal glands. No such tumors were detectable in control groups, nor in the 16 surviving rats fed with 2AAF plus GSH or NAC. In the liver, 2AAF produced significant DNA damage at the 3rd week of each cycle, which was partially repaired during the week of standard meal feeding. Moreover, 2AAF determined the appearance of gamma-glutamyl transpeptidase-positive foci, which tended to increase with time both in number and in size. GSH and NAC exerted similar protective effects on these phenomena, but only at early stages of the experimental model used.

[Inhibition of the growth of 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced mammary gland neoplasms by methionine in rats]. / Tormozhenie metioninom razvitiia raka molochnoi zhelezy, indutsirovannogo 7,12-dimetilbenz(a)antratsenom i N-nitrozometilmochevinoi u krys.

The diets supplemented with 0.5% methionine inhibited the development of mammary adenocarcinomas induced in female rats with 7,12-dimethylbenz(a)anthracene and N-nitrosomethylurea by 3.8 and 2.3 times, respectively. Methionine produced no effect on the incidence of other new-growths. It is suggested that the mechanism by which methionine exerts an antineoplastic effect on mammary carcinomas is a consequence of its hypolipidemic and neurotropic activity.