Mouse monoclonal antibody to a melanoma-carcinoma-associated antigen synthesized by a human melanoma cell line propagated in serum-free medium.

A monoclonal antibody, F11, was produced against a tumor-associated antigen from the spent medium of the M14 human malignant melanoma cell line which was grown continuously in serum-free medium. Ouchterlony double-diffusion study revealed that the F11 monoclonal antibody is an immunoglobulin G1. The F11 monoclonal antibody reacted positively with seven of eight (88%) melanoma, five of five (100%) carcinoma, zero to five normal, and zero of two lymphoblastoid cell lines by indirect immunofluorescence test. Also, by indirect immunofluorescence test, F11 monoclonal antibody reacted with cryostat sections from four of five (80%) melanomas, six of seven (86%) carcinomas, zero of one benign nevus, and zero of two benign breast diseases. By the indirect avidin:biotin:peroxidase complex immunoperoxidase method, the F11 monoclonal antibody reacted positively with cryostat sections from five of five (100%) melanomas, five of five (100%) breast cancers, two of two (100%) colon cancers, zero of one benign nevus, and zero of one Hodgkin's disease spleen. Thus, the tumor-associated antigen that the F11 monoclonal antibody recognizes appears to be expressed by melanomas and carcinomas, hence the designation melanoma-carcinoma-associated antigen. Microscopic observations disclosed that the melanoma-carcinoma-associated antigen is present in the cytoplasm, on the membrane of melanoma and carcinoma cells, and in the lumen of glandular structures of breast and colon carcinomas. The molecular weight of the melanoma-carcinoma-associated antigen in spent medium from the M14 CEM cell line is 100,000 as determined by sodium dodecyl sulfate:polyacrylamide gel electrophoretic analysis of indirect immunoprecipitates obtained with the F11 monoclonal antibody.

Automation of the leukocyte adherence inhibition assay. Counting live mononuclear cells with an automated light microscope system.

Adaptation of an automated light microscope system to the leukocyte adherence inhibition assay provides a rapid automated assay of cell mediated immunity. Comparison between the numbers of live mononuclear cells counted by eye and by machine yields no statistical differences in the per cent adherence or in the standard errors when performing either 10 or 20 replicate counts per antigen-cell mixture. Using the cell counter in a semi-automated mode, the counting is performed 10 times as fast in comparison to the manual method. A semi-automated system is described. The procedure requires from 4-6 X 10(5) mononuclear cells and from 2-3 micrograms crude KCl extract using a standard hemocytometer. The value of the technique lies in its availability as a rapid assay for both research applications and immunologic monitoring in the clinical laboratory.

Bilateral adrenalectomy for advanced breast cancer: a 21 year experience.

Of 680 patients who had bilateral adrenalectomies for metastatic breast cancer, 583 were evaluable. Two hundred and nine patients (36 percent) responded (180 objective, 29 subjective responders) for at least 6 months. Age, menstrual status, prior response to oophorectomy, disease-free interval, involved organ systems, and incidental splenectomy were correlated with adrenalectomy response. Patients aged 21 to 35 years did poorly (23 percent response rate), whereas 41 percent of patients aged 51 to 65 responded. Menstrual status appeared to have no effect upon whether or not a patient responded to adrenalectomy. Oophorectomy responders benefited from adrenalectomy 40 percent of the time and oophorectomy failures responded in 27 percent of the cases. Patients with a disease-free interval of zero to 2.5 years responded to adrenalectomy at a rate of 31 percent whereas patients with a free interval greater than 2.5 years responded at a rate of 50 percent. When a single visceral organ or any combination of bone and soft tissue was involved, the average response rate was 39 percent. However, when multiple visceral organs or a single visceral organ with any combination of bone or soft tissue was involved, the response rate dropped to 26 percent. Sixty-six patients had splenectomies at the time of adrenalectomy with a 44 percent response rate, whereas nonsplenectomized patients had a 35 percent response rate. The median survival rate of 209 adrenalectomy responders was 26 months; it was 10 months for 374 nonresponders. The 5 and 10 year survival rates for adrenalectomy responders were 18 and 7 percent, respectively, and zero percent for adrenalectomy nonresponders. The patients who received greatest benefit from adrenalectomy in this series were aged 51 to 65 years, had a disease-free interval greater than 2.5 years and had metastases limited to a single visceral organ or any combination of bone and soft tissues.

Breast cancer in Japan and United States: epidemiology, hormone receptors, pathology, and survival.

Breast cancer is the most common cancer among American women, whereas in Japan it ranks third behind gastric and uterine cancers. In spite of the relatively low incidence of breast cancer in Japan, a sharp increase in the frequency has been noted since 1966, which is decidedly related to change in dietary patterns in Japanese women. An increase of over 250% in dietary intake of fat has been noted during the past 15 years. Cancer is detected at an earlier stage in Japan as compared with the United States, and consequently the end result is significantly better. But the improved results could not be totally explained on the basis of early detection, since stage-for-stage the Japanese series appears to be consistently better than the US series by 10% in their ten-year survival rates.

Biologic behavior of thin malignant melanomas with regressive changes.

Thin cutaneous malignant melanomas are defined as lesions measuring less than 0.76 mm in maximal thickness. Eight of the 36 thin lesions that we studied metastasized within two to 120 months. Of the 11 lesions with regressive features, five (45.5%) metastasized. Of 25 lesions without regression, only three (12%) metastasized. Thin melanomas with regressive changes need to be reported as a separate category because of their propensity to metastasize. Conventional prognostic guidelines for treatment of thin melanomas are not applicable to this type of lesion. Clinicians need to be cognizant that regressive changes are serious warning signals when they occur in thin melanomas.

Immune responses in the treatment of advanced carcinoma of the breast. Effects of adrenalectomy.

We set out to answer the question, "Is the effect of adrenalectomy associated with or mediated through the immune response?" Eleven patients were studied preoperatively and postoperatively by in vitro immunologic tests. The assay system used included absolute T cell counts, phytohemagglutinin (PHA) blastogenesis, leukocyte adherence inhibition (LAI) after contact with 3M potassium chloride breast antigens, and blocking as measured in the blastogenesis and LAI assays. Good correlation was found between favorable clinical response to adrenalectomy and a rise in the number of absolute T cells, an increase in LAI positivity, and a decrease in blocking as measured by LAI blocking assay, but no correlation was seen in PHA blastogenesis assays. The association of clinical objective responses and improved immune responses is of significance.

In vitro activity of the fatty acyl desaturases of human cancerous and noncancerous tissues.

The microsomal desaturase activity of human cancerous and noncancerous tissues was measured in vitro using 1-14C, -11, 14-eicosadienoic and 1-14C-oliec acids as substrates. Tissues used were a case of ovarian cancer, a urinary bladder cancer, a rectal cancer, and a non-specific colonic ulcer with appropriately normal tissues. When 11, 14-20:2 was used as substrate, radioactive tetraene and triene were produced. The tetraene was identified by radio gas chromatography as arachidonic acid (5, 8, 11, 14-20:4), and the triene had a retention time of 5, 11, 14-20:3. Thus, the possibility arises that a delta8 desaturase was involved. In the delta6 desaturase, with the urinary bladder cancerous tissue, the desaturase activity appeared to be decreased in comparison to neighboring tissue, whereas with the colonic cancer tissue, the desaturase appeared to be relatively increased, though the number of samples was inadequate for confidence.

Is SP1 (pregnancy specific beta 1 glycoprotein) elevated in cancer patients?

Pregnancy-specific beta 1-glycoprotein, SP1, was measured in serum by competitive double antibody radioimmunoassay. Very low levels of SP1 or SP1-like activity were found in only 2 out of 85 sera from patients with cancer of the digestive tract, breast cancer, melanoma, and sarcoma, in 2 out of 11 sera from patients with infectious diseases, and in none out of 15 sera from non-pregnant healthy individuals. SP1 thus does not seem to be ectopically produced in vivo by the types of cancer studied, but is probably highly specific for the normal and malignant trophoblast.