Establishment and characterization of a human ovarian neoplastic cell line, DO-s.

A permanent human neoplastic cell line, DO-s, was established from ascites of a patient with a well-differentiated mucinous cyst-adenocarcinoma of the ovary. This cell line grew as vermiform, floating colonies of epithelial cells in culture. The karyotype of DO-s was of a human female; the chromosome number ranged from 54 to 66 with several abnormalities, mainly trisomy. Epithelial-like character was confirmed by transmission electron microscopy and by the presence of cytokeratin. Inoculation of DO-s cells i.p. or s.c. in athymic nude mice resulted in, respectively, ascites and xenografts. Light and electron microscopical analysis of cultured cells and xenografts demonstrated that the cell line was derived of a mucinous adenocarcinoma biopsy. Tumor-associated antigens, cancer antigen 125 (CA 125), human milk fat globulin, and human placental alkaline phosphatase were expressed by cells in culture and in xenografts. Modulation of the antigens, CA 125 and human milk fat globulin, occurred in DO-s cells growing in athymic mice. Biochemical, immunohistochemical, and histochemical analysis showed that more than 50% of the alkaline phosphatase isoenzymes present in DO-s cells had the characteristics of human placental alkaline phosphatase and placental alkaline phosphatase-like alkaline phosphatase (AP), but fractions of intestinal AP and nonspecific AP (bone-liver-kidney) were also present. The expression of AP isoenzymes could be induced by an enhancement of the serum supplement in the culture media, and by dexamethasone, sodium butyrate, and bromodeoxyuridine. This line will be a valuable tool in studying the therapeutic effects of antibodies to tumor-associated antigens or other agents for ovarian cancer.

Phase II study of liposomal encapsulated daunorubicin in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma.

OBJECTIVE: To evaluate the efficacy and safety of liposomal encapsulated daunorubicin (DaunoXome) in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of DaunoXome in patients with no prior anthracycline chemotherapy for Kaposi's sarcoma. The response rate, time to disease progression, and the incidence and severity of adverse events were documented. SETTING: Hospital-based HIV units. PATIENTS: Thirty HIV-seropositive patients with mucocutaneous Kaposi's sarcoma were enrolled and treated. INTERVENTIONS: Treatment with DaunoXome at a dose of 40 mg/m2 intravenously once every 2 weeks. Treatment with antiretroviral agents and prophylaxis of opportunistic infections where indicated. RESULTS: Of the 30 evaluable patients, 22 patients (73%) achieved a partial response. Median time to treatment response was 30 days (range, 15-202). For patients with a partial response, median time to treatment failure was 153 days (range, 15-558). Patients received a median of 10 cycles (range, 1-44). Adverse events were minimal. The most common side effect was granulocytopenia in 16 patients (53%). CONCLUSION: DaunoXome is an effective and well-tolerated treatment for AIDS-associated mucocutaneous Kaposi's sarcoma and can be administered for prolonged periods. The myelosuppression can be managed by dose reductions and dose not preclude the concurrent use of antiretroviral therapies.

Once-daily dosing decreases renal accumulation of gentamicin and netilmicin.

The pathogenesis of aminoglycoside nephrotoxicity is intimately related to the extent of drug accumulated in the renal cortex. In the framework of searching for preventive measures of aminoglycoside-induced nephrotoxicity, we investigated the influence of dosage regimen on the renal cortical accumulation of gentamicin and netilmicin in humans. Patients with a tumor partly involving one kidney, with normal renal function, and scheduled for nephrectomy received one dose of either gentamicin (4.5 mg/kg) or netilmicin (5 mg/kg) as a single short-term infusion or as 24-hour continuous infusion. Treatment started 24 hours before surgery. Serum aminoglycoside pharmacokinetics were examined during treatment and renal cortical tissue was sampled at the moment of operation for drug determination. The short-term infusion schedule yielded cortical concentrations of 103.2 +/- 36.3 and 137.4 +/- 34.6 micrograms/gm for gentamicin and netilmicin, respectively. Tissue levels after continuous infusion were 158.1 +/- 52.9 and 178.5 +/- 21.8 micrograms/gm for gentamicin and netilmicin, respectively. For each aminoglycoside, a single short-term infusion resulted in significantly lower renal drug levels than did a continuous infusion of the same dose. From the nephrotoxicity point of view, these data support the administration of gentamicin and netilmicin as once-daily injections. This also supports the appropriateness of further studies to determine clinical efficacy of once-a-day dosing for aminoglycosides.