A 77-year-old white man with 64 intracutaneous melanoma metastases and a pulmonary metastatic deposit was treated with immunotherapy. Over an 8-month period, 17 intracutaneous lesions were inoculated with BCG. All 17 injected lesions and all 47 uninjected intracutaneous lesions resolved; no new nodules appeared and the pulmonary metastasis regressed (greater than 50%). This is the first documented case of a pulmonary metastatic focus responding to intralesional BCG therapy of intracutaneous metastases.

A patient with biopsy-proven dermal recurrent malignant melanoma who refused therapy, and who was observed to undergo clinical regression during the period of November 1972 through June 1974 was studied to define the histologic features of spontaneous remission, and to evaluate the immune response as measured by in vitro assays of lymphocyte cytotoxicity and serum effects during the course of regression. Biopsy of regressed areas showed the following histologic features: 1) absence of malignant melanoma cells in basal layers of epidermis with relative increase in basal layer clear cells; 2) dermal inflammatory reaction with lymphocytic infiltrate, melanophages, and degenerate malignant melanocytes; and 3) dermal reactive vascular proliferation and interstitial edema progressing to reparative dermal fibrosis. Using a microcytotoxicity assay with two established allogeneic melanoma cell cultures as target cells, a statistically significant (p less than 0.01) increase in lymphocyte cytotoxicity values was observed over the clinical time course of regression. No significant serum cytotoxic or serum blocking effects were detectable. These findings are consistent with an immunologic basis for the spontaneous remission of the dermal melanoma metastases present in this patient.

A microcytotoxicity technique was used to determine the sequential in vitro reactivity against melanoma cells of lymphocytes from melanoma patients receiving immunotherapy and from healthy donors. Lymphocytes were collected 2 weeks for 2-3 months and were stored in liquid nitrogen until use. Preliminary studies had indicated that freezing did not effect the reactivity of lymphocytes. Lymphocytes from 10 healthy donors tested against melanoma cells exhibited substantial reactivity which showed no consistent pattern over time. Lymphocytes from 9 melanoma patients exhibited increased reactivity after immunotherapy. Patterns of reactivity against melanoma cells and against bladder carcinoma cells were similar, indicating lack of specificity for melanoma antigens. Correlations with clinical course of the disease were not apparent.

Certain phenolic phytochemicals can kill cancer cells. Possible interference from antioxidants is a concern, and this issue has not been studied appreciably. Therefore, the effect of ascorbate and N-acetylcysteine on the ability of epigallocatechin gallate (EGCG) and curcumin to kill HCT116 colon cancer cells was examined. EGCG and curcumin each caused DNA damage in the cells. The DNA-damaging ability of EGCG, but not curcumin, was hindered by either ascorbate or NAC, which was also shown in HT29 and SW480 colon cancer cells. Also, iron chelators (deferoxamine and 2,2'-dipyridyl) inhibited the ability of EGCG, but not curcumin, to cause damage to the DNA in HCT116 cells. Interestingly, curcumin, but not EGCG, increased the expression of growth arrest and DNA damage-inducible gene 153 and also heme oxygenase-1, and this stress gene upregulation by curcumin was antioxidant-insensitive. With prolonged incubation of HCT116 cells with either EGCG or curcumin, cell shrinkage, membrane blebbing, apoptotic bodies, and chromatin condensation/fragmentation were observed. These morphological changes were not apparent in EGCG-treated cells that had been pretreated with either ascorbate or NAC. However, the ascorbate and NAC pretreatments did not prevent the occurrence of the morphological changes in curcumin-treated cells. Thus, these findings suggest that ascorbate and NAC interfere with the ability of EGCG, but not curcumin, to kill HCT116 cells. This basic knowledge may help to better plan and optimize strategies for chemoprevention or chemotherapy.