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Biomedical subjects

C M Sutherland

Publications and source records attributed to C M Sutherland.

At least 55 records · Page 3Linked to original sources

Effect of pregnancy upon malignant melanoma.

Results of this study suggest melanomas diagnosed, initiated or stimulated during pregnancy have worse prognoses than do those of patients not having this history. For those female patients who have had melanomas without a history of the preceding factors, it appears they can become pregnant following the diagnosis and treatment of melanoma without increased hazard. Further biochemical studies on hormone receptors and correlation with the clinical course are needed to clarify the influences of endocrines on malignant melanomas.

Adult↗

Breast cancer as analyzed by the human tumor stem cell assay.

Patients with primary and recurrent carcinomas of the breast were studied by the human tumor stem cell assay to determine if (1) colonies would form from breast cancer specimens, (2) growth in the culture would equate with aggressiveness of disease, (3) the assay would yield specific information on drug responsiveness, and (4) the assay would yield nonspecific information on drug responsiveness. Colony counts ranged from 0 to 363. There was no significant difference in median colony counts by pathologic stage of disease or site. Among stage IV patients presenting for treatment with primary disease, those with colony counts greater than 10 had a mortality rate of 4.7/1000 person-days; there were no deaths among those with colony counts less than or equal to 10 (P = 0.042). Stage IV patients presenting with recurrent disease showed no association between colony counts and survival (P = 0.53). No significant relationship between colony counts and disease-free intervals was observed among stages I, II, and III patients (P = 0.10). Drug sensitivity in vitro was found in 14% of the cultures with colony counts greater than or equal to 30. The only complete clinical responses in stage IV patients occurred in two patients with 0 colony counts. These data demonstrate that colonies grow from breast cancer specimens, that colony formation in vitro may be related to aggressiveness of growth in vivo in patients presenting with stage IV disease, that drug sensitivity is demonstrated in few cultures, and that patients with metastatic disease who have complete response to systemic therapy may be identified by lack of growth in the culture.

Antineoplastic Agents↗

In vivo delayed hypersensitivity reactions to partially purified human melanoma antigens.

Sera from patients receiving autologous cell immunization were shown to contain antibody specific for melanoma cells by immunofluorescence, microcomplement fixation, and mixed hemadsorption. These hyperimmune specific sera were used to define antigens shed into tissue culture media from human malignant melanoma cells. When supernatants from cultured melanoma cells were passed over a Sephadex G-200 column, melanoma antigens were found in Peak 2. The active fraction was further purified by carboxymethylcellulose ion exchanger and found in the 0.4 M NaCl gradient. This fraction has been tested in four immunized patients and in one nonimmunized melanoma patient. All five patients developed lymphocytic vasculitis compatible with delayed hypersensitivity reaction. These antigens should be of benefit in studying delayed hypersensitivity in melanoma patients and as potential agents for specific immunotherapy.

Adult↗

Acral lentiginous melanoma. A clinicopathologic entity.

Acral lentiginous melanoma (ALM) is the fourth clinicopathologic variant of malignant melanoma. It occurs on volar surfaces of hands and feet, subungual sites, and fingers or toes. It is characterized by slow lentiginous radial growth and central plaque-like thickening, heavily pigmented tumor cells, markedly thickened papillary dermis, and diffuse reticular infiltration. Lesions are unusually large and, in most cases, thick and ulcerated. There were 180 patients with acral melanoma (AM), which includes 67 in whom the specific features of ALM could be documented. One hundren sixty had primary lesions on ;the foot, and 20 occurred on the hand. There were 104 men and 76 women. There were 41 black patients and 139 whites. Five-year survivals following all modalities of therapy in 122 patients with Stage I acral melanoma is 63% for planter/palmar lesions, 58% for subungual lesions, and 27% for skin of digits. For the subgroup of Stage I patients with ALM treated by surgery and regional chemotherapy by perfusion, the five-year survival for all sites is 72% and 56% at 10 and 15 years, respectively. Survival in ALM is essentially the same as for all AM lesions.

Adult↗

Recurrence of neuroblastoma following prolonged remission.

A 6-year-old girl with unresectable and metastatic neuroblastoma had a complete remission with irradiation to the primary tumor and systemic administration of cyclophosphamide. The patient was disease-free for 16 years but had an explosive recurrence of tumor six weeks after a hysterectomy. Although no clear cause-and-effect relationship exists between the surgery and the recurrence, this case illustrates that a recurrence is possible after a long disease-free interval. Diagnostic and therapeutic procedures in such patients should be undertaken with caution.

Abdominal Neoplasms↗

Effect of different fixatives on the localization of human melanoma antigens by immunofluorescence.

This study was designed to study the effect of different fixatives on melanoma antigens by immunofluorescence. Two postautoimmune antimelanoma sera were tested on two human malignant melanoma cell lines fixed with different fixatives by indirect immunofluorescence. Ethanol, methanol, formalin, trichloroacetic acid and acetone gave sharp membrane fluorescence. Minimal to moderate cytoplasmic fluorescence was seen with acetone but none with the others. Formalin gave the highest membrane fluorescent antibody titers at 1/512. Isopentane and isooctane yielded bright cytoplasmic fluorescence. Weak diffuse cytoplasmic fluorescence was seen with glutaraldehyde. Fluorescence was completely abrogated by paraformaldehyde. No fluorescence was seen with four nonimmunized melanoma sera and phosphate-buffered saline when used as controls. It can be concluded that different fluorescent patterns were seen on melanoma cells when different fixatives were used.

Antibodies, Neoplasm↗

Antibody-induced movement of common melanoma membrane antigens on the surface of unfixed human melanoma cells.

Antisera to common human melanoma antigens were obtained from melanoma patients receiving autologous immunization with their own irradiated cultured melanoma cells and Bacillus Calmette-Guérin. The antibody thus derived was used to detect common antigens on the plasma membrane of three different human melanoma cell lines by membrane immunofluorescence. The antigen-antibody complexes on the surface of melanoma cells would move to a pole (capping) and would subsequently be extruded into the extracellular milieu at room temperature. Approximately 25 to 30% of viable cells were positive by immunofluorescence. However, when the cells were fixed with methanol, 60 to 70% of cells demonstrated membrane binding. Capping was inhibited at 0 degrees or when the cells were pretreated with vinblastine sulfate. It can be concluded that common tumor antigens exist on the surface of viable human melanoma cells and that the redistribution of antigen-antibody complexes is an active process. The extrusion of antigen-antibody complexes in vitro may represent a mechanism of antigenic modulation in vivo and could indicate a basic method of tumor survival since presumably the antigen-denuded cell is viable and capable of replication but not of recognition by subsequent effector immune events.

Antibodies, Neoplasm↗

Chemotherapy of sarcomas of the limbs by regional perfusion.

From 1957 to 1975, 113 patients with sarcoma of the extremities have been treated with chemotherapy by regional perfusion, either alone or as an adjunct to excisional surgery. Perfusion alone in 54 patients was associated with an early response rate of 83%, but only four patients had complete regression of tumor for longer than three months. When perfusion was followed by immediate or delayed excision, better results were obtained. In 49 Stage I patients and in 24 Stage II patients, cumulative survivals of 66% and 59% were obtained at five years and 66% and 51% at 10 years. The procedure has also been useful in saving functional limbs by converting tumors to operability, and in the palliation of pain and ulceration.

Adolescent↗

Changes in distribution of human malignant melanoma membrane antigens in the presence of human antibody by immunofluorescence.

Four viable human melanoma cell lines demonstrated full-surface fluorescence (FSF) after incubation at room temperature with antisera from three melanoma patients receiving autologous or homologous immunization with irradiated cultured melanoma cells and Bacillus Calmette-Guérin. By sequential immuno-fluorescent staining, it had been shown that FSF was followed by capping and extrusion of antigen-antibody complexes. One melanoma cell line was tested against its autologous antiserum. In the presence of excess antigen, FSF cells peaked to 25% of the total cell population at 30 min. Maximum capping (20%) was noted at 3 hr. When excess antibody was present, FSF cells were 30% at 2 min and capped cells peaked to 25% at 1.5 hr. Capping ceased at 4 degrees under both conditions. When the serum-treated cells were reincubated after fixation with methanol, 80 to 85% of the cells showed FSF at 2 min to 13.5 hr. Negative controls were preimmune sera and skin fibroblasts. These experimental data suggest the presence of embedded and protruding melanoma membrane antigens in the phospholipid layer. Methanol amy dissolve the lipid layer and expose the embedded antigens. The extrusion of melanoma antigen-human antibody complexes in vitro seems to be a possible mechanism of antigen shedding by melanoma cells in vivo.

Antibodies, Neoplasm↗

Malignant melanoma in the American Black.

Malignant melanoma in the American Black is an uncommon disease. Scattered reports have appeared in the literature indicating a somewhat different behavior and distribution from melanoma in the White patient. The last published report prior to the organization of the Tumor Registry at Charity Hospital of Louisiana on melanoma in the Black was in 1948 by Muelling when 28 cases were reported. From 1948 through 1974, 96 additional patients have been recorded in the Charity Hospital Registry which represents the largest reported experience in the American Literature. The average age at diagnosis is 57.8 years as opposed to 53 years for White patients observed over the same time period. The ratio by sex is essentially equal in Blacks. The disease usually presents on the palmar or plantar surfaces of the hands or feet in the Black. In the registry data 51% occurred on the lower limb, 11% on the upper limb, 6% on the trunk, 6% on the genitalia, 1% on the head or neck, 13% were of extradermal origin, and 10% had unknown primary sites. The 5-year cumulative survival for all Black patients in this series is 27%. In contrast to the poor overall survival, a 78% 5-year survival has been achieved in Stage I patients treated with perfusion, wide excision, and regional lymph node dissection.

Adolescent↗