Highly purified melanoma TAA which induce melanoma-related cellmediated immune responses have been further characterized using hyperimmune TAA antisera after affinity chromatography for double immunodiffusion-imrnunoelectrophoresis and indirect immunofluorescence studies. An additional study of antigenic modulation was performed in 23 nonanergic and seven anergic melanoma patients, tested simultaneously with melanoma TAA prepared from primary and metastatic tumors, which had been obtained from one patient a t different time periods. The results of pilot clinical trials are reported, including toxicity, timing and dosage studies in 20 patients and subsequent studies of patients with metastatic melanoma treated a t three separate centers, using a single lot of purified, allogeneic melanoma TAA. The results of these latter studies in 51 patients with Stage 111 (distantly metastatic) melanoma and in five patients with earlier stages of disease indicate that: (1) when the interval from primary therapy to recurrence is greater than one year and when liver, bone and brain are not involved, partial or total clinical regression may be noted in up to 25% of patients with metastatic disease receiving immunochemotherapy; (2) when total regression does occur, the effect usually lasts from one to three years; (3) cytoreductive (debulking) surgery, when possible, in cutaneous, nodal retroperitoneal, and visceral regions may enhance the response to specific active immunochemotherapy, although some debulked patients had less tumor burden and this factor alone may lead to an improved prognosis in patients undergoing any subsequent treatment; (4) when circulating inhibitory factors are modified through preimmunization chemotherapy, an enhanced host response may be seen; and (5) Cancer Serum Indices (CSI) may be useful in predicting recurrence and in following tumor load and response to therapy. Information obtained from these studies suggests the need for further trials to determine the effect of immunization on patients with earlier stages of disease where recurrence rates remain high, and to evaluate the mechanisms of tumor rejection or tumor progression in the face of immune stimulation.Cancer 49:1387-1404, 1982.OR several years, we have worked to identify sep-F arated cell membrane components which produce cell-mediated immune reactivrty. We have studied the separated soluble membrane components from malig- nant tissues and counterpart fetal, and benign and normal adult tissues. Our studies differed from those of others in that we started with carefully washed membrane preparations from washed, counted, viable cells for all of our initial work; and we attempted to find antigens appropriate for immunotherapy rather than immunodiagnosis by identifying only those separated components which induce cell-mediated immune responses in vivo and then in vitro.New advancements in technology have permitted us to perform experiments with a view to helping those who are interested in developing diagnostic or monitoring tests for melanoma. S...
Recently, a simple noninvasive screening test for colorectal cancer was proposed, based on a hypothesis involving galactose-containing carbohydrate moieties such as the ThomsenFriedenreich antigen. According to the hypothesis, such carbohydrate moieties, present in the human rectal mucous of patients with colorectal cancer, can be specifically oxidized with galactose oxidase to form substances that, upon reaction with Schiff reagent, yield purple (magenta) coloured compounds. While evaluating this proposed test, we discovered that the colour formation is not due to the proposed reaction between oxidized galactose moieties present in rectal mucous and Schiff reagent. We found instead that the mucous from colorectal cancer patients contains compounds that form purple (magenta) adducts with the Schiff reagent directly, i.e., they do not require oxidation by galactose oxidase. We have identified these compounds as long-chain aliphatic aldehydes, mainly palmitic aldehyde C15H31CH=O and stearic aldehyde C17H35CH=O. We have further found that the aldehydes originate from plasmalogens present in the phospholipid fraction of the mucous obtained from colorectal cancer patients. The aldehydes, present in plasmalogens as enol ethers, are released by the acidity of the Schiff reagent and in turn react with the Schiff reagent to form the coloured adducts. Correct identification of these markers could lead to the development of a more accurate colorectal cancer screening tool and to a deeper understanding of colorectal carcinogenesis.Key words: T-antigen, plasmalogen-derived aldehydes, colorectal cancer marker.
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