Summary 2-Chlorodeoxyadenosine (2-CDA) is an adenosine deaminase resistant analogue of deoxyadenosine which has shown clinical activity in human hematologic neoplasms. The exact mode of action of this drug remains the subject of investigation. We applied the Differential Staining Cytotoxicity (DiSC) assay to 50 human tumour specimens obtained from patients with a variety of hematologic malignancies to characterise the activity spectrum of 2-CDA. We evaluated the disease-specific activity of al., 1992). The mode of action of this drug remains the subject of investigation, however its ability to kill resting as well as proliferating lymphocytes (Seto et al., 1985;Carson et al., 1983), toxicity to peripheral blood monocytes (Carrera et al., 1989;Carrera et al., 1990) and relative non-cross resistance with other nucleoside analogues in cell lines (Seto et al., 1985;Carrera et al., 1990) has intensified interest in the drugs clinical potential. To characterise the activity spectrum of 2-CDA, we utilised the Differential Staining Cytotoxicity (DiSC) assay in 50 fresh human tumour specimens obtained from patients with a variety of hematologic malignancies. The DiSC assay, originally described by Weisenthal et al. (1983) has previously been shown to correlate with both response and survival in solid and hematologic neoplasms (Tidefelt et al., 1989;Lathan et al., 1990;Bosanquet, 1991; Gazdar et al., 1990 (Bosanquet, 1985). Sample preparationFresh human tumour specimens were placed in Roswell Park Memorial Institute-1640 media (Irvine Scientific, Irvine, Ca.) containing 15% heat-inactivated foetal bovine serum or 40% heat-inactivated horse serum (Irvine Scientific, Irvine, Ca.) penicillin (100 IU ml'), streptomycin (100 jig ml'), 2 mM glutamine, and 15 units ml-' preservative-free heparin for transport to the laboratory. Tumour

Although rare, adrenocortical carcinoma is among the most common tumors found in children with Li-Fraumeni syndrome and Li-Fraumeni-like syndrome, associated with germ-line mutations in the TP53 gene. In southern Brazil, one form of Li-Fraumeni syndrome, associated with childhood adrenocortical carcinoma, is caused by a mutation in the R337H TP53 tetramerisation domain and is attributed to a familial founder effect. Adrenocortical carcinoma is considered an aggressive neoplasm, usually of poor prognosis and is generally unresponsive to systemic chemotherapy. Optimal treatment regimens remain to be established. We report the case of a young woman with metastatic adrenocortical carcinoma, who achieved stable disease with mitotane, cisplatin, doxorubicin, and etoposide as first-line therapy, but then had an objective response to oral metformin that lasted 9 months. The presence of the R337H TP53 mutation suggests a mechanism for the observed response to metformin.

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