Mitotic arrest-deficient protein 1 (MAD1) is a component of the mitotic spindle assembly checkpoint. We have created a knockout mouse model to examine the physiologic consequence of reduced MAD1 function. Mad1 +/À mice were successfully generated, but repeated paired mating of Mad1 +/À with Mad1 +/À mice failed to produce a single Mad1 À/À animal, suggesting that the latter genotype is embryonic lethal. In aging studies conducted for >18 months, Mad1 +/À mice compared with control wild-type (wt) littermates showed a 2-fold higher incidence of constitutive tumors. Moreover, 42% of Mad1 +/À (P < 0.03), but 0% of wt, mice developed neoplasia after treatment with vincristine, a microtubule depolymerization agent. Mad1 +/À mouse embryonic fibroblasts (MEF) were found to be more prone than wt cells to become aneuploid; Mad1 +/À , but not wt, MEFs produced fibrosarcomas when explanted into nude mice. Our results indicate an essential MAD1 function in mouse development and correlate Mad1 haploinsufficiency with increased constitutive tumors. [Cancer Res 2007;67(1):160-6]

PDT with chlorin e(6) for skin metastases from melanoma is effective and well tolerated. Further clinical investigation of PDT with chlorin e(6) is warranted.

Here we present a case of a coincidence of addiction to "Kratom" (botanically known as Mitragyna speciosa Korth) and developed severe primary hypothyroidism. We are discussing a possibility that high dose of indole alkaloid mitragynine (the major alkaloid identified from "Kratom") might reduce the normal response of the thyroid gland to thyroid-stimulating hormone resulting in primary hypothyroidism. Further experimental investigations of mitragynine as a possible suppressor of thyroid gland function would be a matter of interest.

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein can repress the transcriptional activity of the tumor suppressor protein p53. However, it remains controversial whether Tax requires NF-B factors/ activity and/or p300/CBP in order to inactivate p53 function. To address this issue, we have investigated Tax