Ole A. Holtermann

Treatment of kaposi's sarcoma with vinblastine

Fourteen patients with Kaposis sarcoma (KS) were treated systemically with vinblastine sulfate in a low‐dose regimen and compared with 23 patients reported in the medical literature. The therapeutic results in our series were excellent in terms of regression of cutaneous lesions. Vinblastine appears to be a drug that is well suited for the management of KS in an outpatient setting. Intravenous therapy may be supplemented with intralesional or intraarterial vinblastine.

Selective cytotoxicity of peritoneal leucocytes for neoplastic cells

Abstract Peritoneal leucocytes of nonspecifically stimulated rats (about 70% large mononuclear cells) were found to display a high degree of cytotoxicity in vitro . This cytotoxicity appeared to be exerted through a selective mechanism. Growth inhibition and cell destruction were observed when peritoneal leucocytes were cultivated with syngeneic or allogeneic neoplastic cells. Less or no cytotoxicity was observed when peritoneal leucocytes were cultivated with syngeneic or allogeneic normal kidney cells or normal embryo cells. Lymph node cells of stimulated rats were not cytotoxic towards syngeneic or allogeneic normal kidney cells. These findings may reflect a mechanism for surveillance of neoplastic cells more primitive than that ascribed to specifically committed T cells. This mechanism may be relevant to tumor regression occurring at sites of induced delayed hypersensitivity reactions.

Preliminary observations on tumor regressions induced by local administration of a lymphoid cell culture supernatant fraction in patients with cutaneous metastatic lesions

Abstract A fraction with lymphokine properties was isolated from supernatant medium of the continuous cultured human lymphoblast cell line, 1788. Culture medium containing 2% human serum was used for cell growth in order to minimize antigenicity of isolated supernatant fractions. The culture medium was passed through an Amicon XM-100 membrane, concentrated over a PM-10 membrane, lyophilized and reconstituted to a final concentration of approximately 40:1. Studies in vivo showed that the active fraction contained skin reactive factor which, when injected intradermally into normal skin, produced skin lesions in humans resembling delayed-type hypersensitivity reactions but peaking between 10 and 12 hr. This same preparation, when injected intralesionally into cutaneous tumors, induced an inflammatory reaction followed by tumor regression. Only the fraction confined between membranes of pore size 10,000–100,000 daltons was active in promoting tumor regression. Patients with skin lesions from metastatic carcinoma of the breast and other malignancies were studied, and 16 out of 30 treated lesions were judged to have undergone either complete or greater than 50% regression. Of these, 9 were biopsied before and after lymphokine injection and 6 out of 9 were negative for tumor cells.

Lymphokine properties of a lymphoid cultured cell supernatant fraction active in promoting tumor regression

Abstract In the present study supernatant culture medium from a cultured human lymphoid cell line, which was shown to have inflammation-inducing and tumor-regressing properties in man, was tested for lymphokine properties. Skin reactive factor, lymphotoxin, macrophage activation factor, and chemotactic factor were assayed and found to be present in the crude, active fraction that was confined to a size of 104–105 daltons and was active in producing clinical tumor lesion regression. These results suggest that the in vivo antitumor effect is related to lymphokines present in the active preparation.

In Vitro Destruction of Tumor Cells by Human Monocyte

Summary Human blood monocytes were cytotoxic towards cells of a human osteosarcoma and a reticulum cell sarcoma in vitro. Activation of the monocytes by supernatant fluids of mitogen stimulated human lymphocytes markedly increased their cytotoxicity towards the neoplastic cells. Intradermal injection of these supernatant fluids into human skin induced an inflammatory infiltrate consisting predominantly of large mononuclear cells. The role of large mononuclear cells in cancer surveillance is discussed.

The effects of nucleoside analogs on cutaneous neoplasms.

Antitumor effects of cytotoxic agents have been demonstrated following their local administration to neoplastic lesions involving the Subsequent studies indicated that local chemotherapy provided effective therapy for primary epidermal t ~ m o r s ~ . ~ . ’ and palliation for some types of secondary neoplastic lesions in the skin and other accessible site^.^,^. Whereas 5-fluorouracil is now widely employed in topical chemotherapy, its use has limitations. In order to extend the potential of local chemotherapy, and with a view toward further exploring cutaneous tumors as model systems in tumor therapy, local administration of a number of nucleosides was investigated.

Discussion paper: effect of supernatants from long-term lymphoid cell lines on metastatic cutaneous tumors following local injection.

A fraction with lymphokine properties was isolated from supernatant medium of the continuous cultured human lymphoblast cell line, 1788. Culture medium containing 2% human serum was used for cell growth in order to minimize antigenicity of supernatant fractions isolated from the medium. The culture medium was passed through an Amicon XM-100 membrane, concentrated over a PM-10 membrane, lyophilized, and reconstituted to a final concentration of approximately 40:1. Studies in vivo and in vitro showed that the active fraction contained skin reactive factor (when injected intradermally into guinea pigs and humans), lymphotoxin, migration inhibition factor, chemotactic factor, and macrophage activation factor. This same preparation, when injected intralesionally into cutaneous tumors, induced an inflammatory reaction followed by tumor regression. The fraction confined between membranes of pore size 10,000-100,000 daltons was active in promoting tumor regression, while the fraction less than 10,000 daltons was inactive. Patients with skin lesions from metastatic carcinoma of the breast and other malignancies were studied, and 16 out of 30 treated lesions were judged to have undergone either complete or greater than 50% regression. Of these, 8 were biopsied before and after lymphokine injection, and 6 out of 9 were negative for tumor cells. Additional studies in vitro with material fractionated on Sephadex G-200 indicated that the macrophage-activating component binds to alpha-2 macroglobulin in the culture medium.