Biomedical subjects

C Donawho

Publications and source records attributed to C Donawho.

6 recordsLinked to original sources

PubMed1998

Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma.

Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 10(7) UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.

Adjuvants, Immunologic↗

PubMed1996

Sunburn, sunscreen, and melanoma.

This paper reviews the current epidemiologic and experimental evidence regarding the effect of sunburns on cutaneous malignant melanoma and the possible effectiveness of sunscreens in preventing those effects. Although there is growing agreement that sunlight exposure, particularly the ultraviolet wavelengths in solar radiation, contributes to the etiology of cutaneous malignant melanoma, there are at present insufficient data on the effective ultraviolet waveband and whether the use of sunscreens may be useful in preventing melanoma. The main obstacle in answering this question is that the exact role of sunlight in the pathogenesis of melanoma still remains undefined. However, new experimental animal models are now available that will assist in determining and defining the mechanism of initiation and promotion of melanoma by sunlight and, particularly, ultraviolet radiation in sunlight. While we await more definitive data, it is reasonable to recommend an overall "safe sun strategy" in which the use of sunscreens certainly must be accompanied by other protective measures of overall reduction of sunlight exposure.

Basal Cell Carcinoma↗

PubMed1996

The immune system in ultraviolet carcinogenesis.

The immune system plays an important role in ultraviolet (UV) carcinogenesis by contributing to host resistance against skin cancer development. UV radiation, however, circumvents immune surveillance against skin cancers by modulating the immune response in a way that favors tumor development. Studies addressing the cellular mechanisms by which UV radiation modifies immune function are summarized. These studies demonstrate that UV irradiation of the skin produces both local, nonspecific immune suppression that inhibits immune effector functions within irradiated skin, as well as systemic, specific immune suppression against antigens introduced at a critical time after exposure to UV radiation. Evidence is presented suggesting that the production of cytokines by epidermal cells in response to UV-induced DNA damage is an important component of UV-induced specific immune suppression.

Animals↗

PubMed1992

Immunobiology of primary murine melanomas.

Primary cutaneous melanomas can be induced in inbred mice by applying a dose of dimethylbenz[a]anthracene to the skin of 4-day-old mice, and then applying repeated doses of a tumor promoter to the same site over a long period of time. Preliminary experiments suggest that the final incidence of melanomas is strongly influenced by the age at which the initiating dose of carcinogen is applied. Melanomas induced by this method in C3H mice are immunogenic and exhibit a high degree of cross-reactivity when tested by immunization and challenge in vivo. Exposing the mice to ultraviolet (UV) radiation during carcinogenesis dramatically accelerates the appearance of melanoma. We are attempting to determine how UV radiation potentiates melanoma induction by studying the growth of melanoma cells transplanted into UV-irradiated skin. Our studies suggest that UV irradiation accelerates the outgrowth of melanoma cells by means of a local, immunosuppressive effect on the skin. However, this effect is distinct from the ability of UV irradiation to alter epidermal Langerhans cells and interfere with the induction of contact hypersensitivity responses. We postulate that UV irradiation augments melanoma development by interfering with the efferent arm of the immune response in the UV-irradiated site.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1990

Immunogenicity and cross-reactivity of syngeneic murine melanomas.

Non-melanoma skin cancers induced in mice by chemical carcinogens or ultraviolet radiation are often antigenic but rarely induce cross-protective immunity when tested by in vivo transplantation methods. We wished to determine whether melanocytic skin tumors behave similarly or whether they exhibit cross-reactive antigens in vivo. Three melanomas induced in C3H/HeNCr(MTV-) mice by initiation with ultraviolet radiation and promotion with croton oil or initiation with 7,12-dimethyl-benz[a]anthracene and promotion with 12-O-tetradecanoyl-phorbol-13-acetate or croton oil plus ultraviolet radiation were tested for immunogenicity and cross-reactivity in vivo. The three melanomas were highly immunogenic, and all induced some degree of protection against the other melanomas. Non-melanoma skin cancers induced by the same carcinogens were less immunogenic and did not immunize against the melanomas. We conclude that unlike other skin cancers, melanocytic tumors induced by chemical carcinogens and ultraviolet radiation are highly cross-reactive in vivo and thus represent a unique subset of murine skin cancers.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1988

Effect of ultraviolet-B radiation on the in vivo growth of murine melanoma cells.

The role of UV radiation in the development of malignant melanoma has yet to be clearly defined. The purpose of these studies was to determine whether UV irradiation of mice produces local or systemic alterations that increase the in vivo growth of transplanted melanoma cells. K-1735 melanoma cells were injected into the external ears of syngeneic C3H mice. UV irradiation of the mice before or at the time of injection of the melanoma cells accelerated the appearance of the tumors. The effect was observed when melanoma cells were transplanted directly into the site of UV irradiation, but not when they were injected into an unirradiated site. The initial survival of radiolabeled melanoma cells at the site of inoculation was not altered by UV irradiation of the host, suggesting that the accelerated appearance of tumors was due to an increase in the clonogenic potential of cells injected into UV-irradiated skin. The effect of UV irradiation on the development of other syngeneic tumors was also investigated. The outgrowth of a second melanoma was also accelerated in UV-irradiated mice, whereas the growth of a UV-induced fibrosarcoma, a methylcholanthrene-induced fibrosarcoma, and a spontaneous hepatocarcinoma was not affected. These results suggest that, in addition to its carcinogenic activity, UV radiation may contribute to the incidence of cutaneous melanoma because of a local effect on the skin that stimulates melanoma development.

Animals↗