Changes in motochondrial calcium metabolism after treating mastocytoma cells with N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate.

Comparison of Ca2+ uptake by isolated mouse liver mitochondria, and mitochondria prepared from mastocytoma cells grown with and without N6,O2'-dibutyryladenosine 3',5' cyclic monophosphate (DB cyclic AMP) and theophylline showed several differences in their capacity to take up and retain calcium. In particular mitochondria from DB cyclic AMP-treated mastocytoma cells took up more Ca2+ than mitochondria from untreated mastocytoma cells. Ca2+ uptake by mitochondria from DB cyclic AMP-treated cells was also increased in the presence of oxalate whereas oxalate did not affect Ca2+ uptake by mitochondria from untreated mastocytoma cells and it reduced Ca2+ uptake by mouse liver mitochrondria. The results suggest that inhibiting the growth of mastocytoma cells with DB cyclic AMP alters their mitochondrial Ca2+ metabolism.

Active specific immunotherapy for ovarian cancer.

Ten patients with advanced or recurrent ovarian cancer were treated with a combination of chemotherapy and active specific immunotherapy after tumour stasis had been induced. They were inoculated with irradiated allogeneic cryopreserved tumour cells and B.C.G. once monthly in addition to receiving conventional chemotherapy. The overall duration of "remission", median survival, and projected 24-month actuarial survival in the patients receiving immunotherapy were apparently better than in a retrospectively matched control group treated by chemotherapy alone.

Tumour associated immunity and immunocompetence in ovarian cancer.

Cell-free extracts of autologous ovarian cancer cells evoked a delayed hypersensitivity response (DHR) in skin in four out of six patients in remission from disease and none of seven patients in relapse. These initial results appear to be consistent with in vitro blastogenic assay using the same autologous extracts. To assess whether diminished tumour-associated immunity was due to impaired cell-mediated immunocompetence, blastogenic responses to purified protein derivative of tuberculin (PPD), a secondary recall antigen, and phytohaemagglutinin (PHA) were assessed. Impaired responses to PHA were seen in the relapse group of patients, but responses to PPD did not appear to be impaired in this group.

Tumour-associated immune responses and isolated carcinoembryonic antigen and alpha feto-protein levels related to survival in ovarian cancer patients.

The presence of a tumour-associated immune response in 37 patients with ovarian cancer as assessed by blastogenesis (lymphocyte transformation) evoked by ovarian cancer cell extracts, has been correlated with survival following the test. The difference in these responses is unlikely to be accounted for on the basis of general impairment of cell-mediated immuno-competence. Serum carcinoembryonic antigen (CEA) was also determined in 27 ovarian cancer patients to assess its prognostic significance. Raised CEA levels and absence of blastogenic response to tumour cell extract during relapse are associated with a worse prognosis but neither of these parameters are significant in remission. Possible applications of these findings to the clinical management of ovarian cancer patients are discussed. Serum alpha feto-protein levels measured by radioimmunoassay were not found to be raised in any of the 32 ovarian cancer patients in whom it was measured.

Tumour antigenicity in ovarian cancer.

The blastogenic response to a crude cell extract of ovarian cancer cells has been studied in 48 patients with ovarian cancer (9, autologous, 39 allogeneic), in 26 female controls matched for age and in 18 female patients with other types of cancer in remission from disease. The responses in ovarian cancer patients in remission and relapse were considered separately. The blastogenic responses to cell extracts of foetal ovary, foetal lung, foetal liver and normal adult ovary were also assessed in a proportion of all 3 groups. The blastogenic responses to ovarian cancer and foetal ovary cell extracts were found to be significantly greater in the ovarian cancer patients in remission than in the controls, but the responses to ovarian cancer extract were not greater in the relapse group or in patients with other cancers. As a blastogenic response to normal ovarian extract was also present in some of these patients, the data so far do not support the hypothesis of a tumour specific antigen. This tumour associated response may be occurring to determinants in foetal or adult ovarian tissue to which the patient becomes sensitized in malignant disease. The response is complex and the nature of the antigen requires further analysis.