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As the method for the diagnosis of metastasis of breast cancer to internal mammary nodes, 198Au colloid was used in parasternal scintigram. In the internal mammary nodes, the rate of correct diagnosis was 90% in the cases where diagnosis of positive metastasis was obtained, 44. 5% in whom metastasis was suspected, and 100% in whom diagnosis of negative metastasis was made. In the subclavian nodes, corresponding values were 69.0%, 34.5%, and 100% indicating poorer diagnostic rate. Examination on the relationship between metastasis to the lymph nodes and scintigram revealed more intense spots in the lymph nodes with very small metastasis than on normal side. As the metastatic portion increases in size, spots become less intense until finally the spots are cold as the whole lymph nodes are occupied by the cancer tissue. As the site of the tumor not only the medial side but also lateral side are involved in Stage I in a high rate of lymph node metastasis. Need of complete removal of internal mammary nodes was urgently suggested.

The mode of lymph flow from the breast to the regional lymph node was studied using 1llSAu colloid, to ascertain the concept of lymph node of Groups 1, 2, and 3. Lymph flow through the internal mammary nodes was found to be abundant. Especially so when 1llSAu colloid was injected into the lower half of the breast, there was observed more abundant flow than that to axillary lymph nodes. Therefore, it was concluded that regardless of the site of occupation of a tumor, internal mammary nodes should be con· sidered to be of Group 1. Lymph flow through the subclavian nodes proved to be always less than that to the axillary nodes or internal mammary nodes. The rate of the lymph flow appearance on the scintigram was about 20%. Whether the subclavian nodes should be classified as Group 1 or 2 should be further studied. The rate of supraclavicular node visualization was below 3%. Therefore, the supraclavicular nodes should be considered to be Group 2. When these results are applied to the current rule of handling of breast cancer, discrepancy occurs in the Stage number and R-numer.

Synergistic enhancement of anti-tumor effects through the combined use of natural human interferon-alpha (nHuIFN-alpha) and natural human tumor necrosis factor-alpha (nHuTNF-alpha) enabled us to decrease the effective dose of each cytokine and consequently to reduce side effects. One hundred and twenty patients with advanced or recurrent solid cancer were entered in the trial from April 1985 to January 1988, of whom 112 patients were evaluable. A mixture of nHuINF-alpha and nHuTNF-alpha was injected intravenously as the maintenance dose 1 x 10(6)U or more/day for over 8 weeks. There was no response in 40 patients injected with the maintenance dose of 1 x 10(6)U/day, but of 72 patients receiving more than 2 x 10(6)U/day (10 micrograms of nHuIFN-alpha and 3 micrograms of nHuTNF-alpha), 4 had complete responses, 10 had partial responses, and 4 had minor responses. The overall response rate was 12.5% (14/112) and the rate was 19.5% in 72 patients with more than 2 x 10(6)U/day. Positive responses were as follows: hepatoma 3/8), renal cell cancer (4/11), breast cancer (4/17), ovarian cancer (1/2), malignant thymoma (1/1) and liposarcoma (1/1). Serious adverse effects like hypotension, oliguria and severe hepatobiliary toxicity were never experienced. The effective and adequate dose of the mixed preparation was considered 2 to 4 x 10(6)U/day/body.

Constitutional lipid peroxidation in randomly selected 32 cases of clinically advanced carcinoma from human gastrointestinal tract (20 cases), breast (8 cases) and kidney (4 cases) was examined histochemically in frozen sections using cold Schiff's reagent. Only two cases of gastrointestinal carcinoma were positive by the reagent. Non-cancerous parenchymal cells were negative. These findings suggest that detectable constitutional lipid peroxidation seldom occurs in either cancerous or normal tissues. The capacity for normal and neoplastic tissues to undergo lipid peroxidation was also studied by incubation with an iron-NADPH pro-oxidant system. Normal parenchymal cells showed, to various degrees, a positive reactivity. In gastrointestinal carcinoma, 6 out of 7 cases of well differentiated adenocarcinoma reacted positively, whereas 2 out of 8 cases of moderately to poorly differentiated adenocarcinoma disclosed weakly positive reactions. Mucinous adenocarcinomas (4 cases) were all negative. Signet-ring cell carcinoma (1 case) was positive. One out of 8 cases of breast cancer also showed positive reaction. Four renal cell carcinomas were all negative. Cancer cells have lower capacity to undergo lipid peroxidation than normal cells, when the iron-NADPH pro-oxidant system was employed. In gastrointestinal carcinoma, the ability to undergo lipid peroxidation by the iron-NADPH pro-oxidant seems to be correlated with their histological differentiation. This fact may suggest that differences in lipid composition or the NADPH enzyme system exist between well differentiated and poorly differentiated gastrointestinal malignancies.