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Biomedical subjects

D L Morton

Publications and source records attributed to D L Morton.

At least 253 records · Page 14Linked to original sources
PubMed1983

Blood flow in human tumors during hyperthermia therapy: demonstration of vasoregulation and an applicable physiological model.

A quantitative assessment of the effect of localized magnetic-loop hyperthermia on blood flow was performed in 12 human tumors using the 133Xe clearance method. Because blood flow in these tumors changed in response to needle injection, a physiologically based, one-compartment model was developed that included both a hyperemic and a steady-state component. In six tumors, changes in blood flow induced by heat were also observed. The ability of tumor vessels to respond dynamically to stress and the degree of response may be predictive of tumor heating capacity and subsequent therapeutic response.

Abdominal Neoplasms↗
PubMed1983

Humoral response of melanoma patients to two different tumor-associated antigens.

Sera of 8 stage II melanoma patients undergoing surgical adjunctive immunotherapy with bacille Calmette Guérin (BCG) plus melanoma cell vaccine (MCV) were assayed for humoral response by the complement-dependent antibody cytotoxicity (CDAC) assay and by the microcomplement fixation (MCF) test. The patients developed high levels of cytotoxic (CTX) and complement-fixing (CF) antibodies to the UCLA-SO-M14 (M14) cells, one of the three melanoma cell lines in the MCV. Significant rises in CTX and CF antibodies occurred one month post-immunotherapy. While the level of CTX antibodies was maintained for 11 months thereafter, the titer of CF antibodies was sustained for seven months, then gradually declined. When the sera were absorbed with lymphoblastoid (ML14) cells which are autologous to the M14 cells, two residual peaks of CTX antibodies, one and four months postimmunotherapy and two peaks of CF antibodies, one and seven months postimmunotherapy, emerged. Two sera that exhibited high levels of CTX and CF antibodies one month postimmunotherapy were absorbed with ML14 cells and human fetal brain tissue. The reactivity of one serum in both the CDAC and MCF assays were abolished, whereas the reactivity of the other serum was not significantly diminished in either assay. These data indicate that the stage II post-surgical melanoma patients developed a humoral immune response to at least two distinct tumor antigens on the membrane of the M14 cells. One of these antigens appeared to be of fetal origin (OFA), the other M14-associated (TAA). Both antigens, OFA and TAA, were involved in complement-dependent antibody cytotoxic and complement fixation reactions in vitro.

Animals↗
PubMed1983

The pharmacologic manipulation of blood flow in hyperthermia therapy.

Many human tumors treated by hyperthermia do not reach therapeutic temperatures (42 degrees C). The explanation for this difference may be that some tumors react to thermal stress in a manner similar to normal tissues; ie, they increase blood flow during hyperthermia in order to dissipate the heat. Higher temperatures might be achieved in these heat-resistant tumors by administering vasoconstrictive agents in an effort to reduce blood flow. In this preliminary study, we determined the extent to which pharmacologic inhibition of local blood flow might allow higher temperatures to develop in normal muscles exposed to localized radiofrequency hyperthermia. We found that the local muscle temperature rise could be increased by at least 90% in two dogs and six rabbits with the use of a local vasoconstrictive drug.

Animals↗
PubMed1983

Nature of antigens and antibodies in immune complexes isolated by staphylococcal protein A from plasma of melanoma patients.

Immune complexes (IC) were isolated from plasma of melanoma patients by absorption to staphylococcal protein A and subsequent elution with MgCl2. The isolated ICs were purified by precipitation with polyethylene glycol and sucrose density gradient ultracentrifugation after radioiodination with 125I. The purified ICs were dissociated and radiolabeled antigen/antibody components were separated by ultracentrifugation at low pH (2.6). Under these conditions, about 72% radioactivity of the purified IC remained in the light-density region as a wide band. After neutralization, 26%-60% radioactivity in the region of 5S sedimentation bound to immobilized autologous immunoglobulins, as opposed to a maximum of 23% to immobilized immunoglobulins from human normal serum. Significant levels (73%-77%) of radioactivity in 7S region bound to rabbit anti-human IgG immunobeads. Immunoprecipitation of the antigen fraction by allogeneic anti-melanoma and rabbit anti-melanoma antibodies followed by SDS-polyacrylamide gel electrophoresis revealed the presence of a fetal antigen (FA) and a melanoma tumor-associated antigen (TAA). In addition, the presence of auto-antigen(s) was indicated by using autologous antibody in immunoprecipitation. Immunoglobulins (IgG) isolated from purified IC bound to cultured melanoma, sarcoma, and normal fibroblasts, although the binding to sarcoma and normal fibroblasts could be inhibited by preincubation of isolated IgG with soluble FA but not with soluble melanoma TAA. Thus, results of this investigation provide evidence that circulating IC in melanoma patients are composed of at least IgG and different antigens, and some of these antigens are produced by their tumor.

Antibodies, Neoplasm↗
PubMed1983

Chromosomal abnormalities of a mediastinal embryonal cell carcinoma in a patient with 47,XXY Klinefelter syndrome: evidence for the premeiotic origin of a germ cell tumor.

Trypsin-Giemsa banding studies were performed on 30 tumor cells from an embryonal cell carcinoma originating in the mediastinum of an 18-year-old male with the Klinefelter syndrome (47,XXY). All tumor cells revealed an XXY chromosomal pattern with the addition of extra chromosomes. Electrophoretic patterns of the patient's red blood cells and tumor cells were identical. These data suggest that this germ cell tumor originated from a primordial germ cell in which oncogenesis had occurred prior to meiotic division.

Adolescent↗
PubMed1983

Immunochemical characterization of fetal antigen isolated from spent medium of a human melanoma cell line.

A fetal antigen (FA) was isolated from spent culture medium of a melanoma (M14) cell line. Allogeneic serum samples from melanoma patients, previously characterized with respect to anti-FA activity, were used as the source of anti-FA antibody. The FA activity was partially purified by membrane ultrafiltration, gel filtration, and chloroform:methanol extraction. The partially purified FA was then used to develop an enzyme-linked immunosorbent assay (ELISA). By indirect ELISA both the IgG and IgM classes of anti-FA antibodies were detected in the sera of cancer patients and normal volunteers. The incidences of anti-FA antibodies in the sera of cancer patients and normal volunteers were not significantly different. As detected by competitive inhibition in ELISA, FA activity was widely distributed among melanoma, sarcoma, and carcinoma tumor tissues and cultured tumor cells, as well as among fetal brain, skin, and muscle tissues. FA activity was destroyed by treatment with beta-galactosidase and hyaluronidase, but it was not destroyed by proteolytic and lipolytic enzymes. The antigen bound to immobilized ricin, peanut, and soybean lectins. FA activity in material purified by ricin-affinity chromatography was associated with molecules in the 60,000- to 70,000-dalton region as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results suggest a glycoprotein nature for the FA isolated from the spent culture medium of melanoma (M14) cells; this FA apparently elicits formation of natural antibodies in the cancer patients and normal donors.

Antigens↗
PubMed1983

Detection of tumour associated antigen in eluates from protein A columns used for ex vivo immunoadsorption of plasma from melanoma patients by radioimmunoassay.

Tumour associated antigen (TAA) of defined specificity and anti-TAA antibodies were isolated by elution with 0.1 M glycine-HCl buffer (pH 3.5) and 2.5 M MgCl2 from non-viable Staphylococcus aureus used in ex vivo immunoadsorption of plasma from four melanoma patients. The anti-TAA antibody activity in the MgCl2 eluate was determined by its ability to bind a melanoma 125I-TAA. The melanoma 125I-TAA was isolated and purified from the spent culture medium of a human melanoma cell line. The activity and specificity of TAA in the glycine-HCl eluates were determined by competitive inhibition in a radioimmunoassay in which melanoma 125I-TAA and an allogeneic antiserum obtained from a melanoma patient were used as the reagents. Results indicated that 0.04-0.81% of the total protein contained in the glycine-HCl eluates was TAA. The proportion of TAA to total protein in these eluates varied from patient to patient and treatment to treatment. Inhibition by the glycine-HCl eluates in the competitive radioimmunoassay was dose-dependent. Similarly, binding of melanoma 125I-TAA in a direct radioimmunoassay decreased with decreasing amounts of the anti-TAA antibody fraction. Quantitative analysis revealed that the MgCl2 eluates contained anti-TAA protein at levels ranging from 0.15 to 5.78% of total protein. Because both TAA and anti-TAA activities were found in eluates from S. aureus (protein A positive) used for immunoadsorption of plasma from melanoma patients, and because melanoma 125I-TAA isolated and purified from a human melanoma cell line did not bind to protein A directly, the results indicated that TAAs immunologically similar to the melanoma TAA were circulating in the form of immune complexes in plasma of four patients with melanoma and that these complexes could be removed from plasma by ex vivo immunoadsorption.

Antibodies, Neoplasm↗
PubMed1983

Prognostic significance of urinary antigen analysis by enzyme-linked immunosorbent assay in melanoma patients.

Urine samples collected from normal donors and melanoma patients were analyzed for the presence of tumor-associated antigen by competitive inhibition in the enzyme-linked immunosorbent assay (ELISA) using an allogeneic melanoma serum as the source of antibody and partially purified urine from the same donor as the target antigen. The results were expressed as antigen units (ng antigen protein/mg creatinine). The antigen levels in urine of melanoma patients (median = 56.5, N = 56) were significantly higher (P less than 0.05) than those of normal donors (median = 1.9, N = 56). The 90th percentile for the normal group was 34.3 antigen units. Using this value as the criterion for positivity, 36 of 56 (64%) urine samples of melanoma group were positive for the antigen as opposed to only 6 of 56 (11%) of normal donors. Subsequently, a retrospective analysis of 58 melanoma patients paired on the basis of disease recurrence and no recurrence after lymphadenectomy revealed a median antigen level of 68 units for the recurrent group and 18.9 for the nonrecurrent group. Eighteen of 29 (62%) melanoma patients who had recurrence of their disease and 9 of 29 (31%) patients who remained disease free were urinary antigen positive. These incidences were significantly different (P less than 0.005). The results of this investigation suggest that assessment of urinary antigen in stage I and II melanoma patients may prognosticate recurrence of the disease.

Antigens, Neoplasm↗
PubMed1983

Natural thermal resistance of human tumor cells and the role of prostaglandin.

We found that human malignant melanoma cells had varying thermal sensitivity and that some exhibited natural thermal resistance, a heretofore unrecognized phenomenon. Samples of 73 melanoma cell suspensions were heated at 42 degrees C for 1 hour before plating in the soft agar clonogenic assay or the thymidine assay for proliferating cells. We observed greater than 75% cell kill after hyperthermia in 39 (53%) tumors. Native thermal resistance was apparent in 17 (23%) tumors and growth enhancement in 17 (23%) at this temperature and exposure time. We postulated that prostaglandin, known to protect stomach mucosa against thermal injury, has a role in stabilizing the tumor cell membrane exposed to heat. Three melanoma cell lines known to be thermosensitive were heated to 42 degrees C without and with exogenous prostaglandin E2 (PGE2). The survival of colony-forming cells was increased in all three lines in the presence of 30 microM PGE2. A naturally thermoresistant cell line was exposed to 1 microgram/ml indomethacin for 24 hours before hyperthermic treatment. The survival of colony-forming cells was significantly decreased compared to cells not treated with indomethacin. The addition of 30 microM of exogenous PGE2 to indomethacin-treated cells reestablished thermal resistance. These preliminary data suggest that some tumor cells synthesize prostaglandins to render the cell thermoresistant. Treatment with indomethacin blocks prostaglandin synthesis and induces thermosensitivity. These discoveries may have important clinical applications for hyperthermia treatment of human cancers.

Cell Line↗
PubMed1983

Definition of human melanoma-associated cell surface antigens by hybridoma monoclonal antibodies.

Many human melanoma cell lines express HLA-D antigens in addition to HLA-A, -B, and -C specificities. Hybridoma antibodies produced after sensitization with melanoma cells are directed not only against tumor-associated antigens but against HLA and Ia-like specificities. Paired human melanoma cell lines and autologous lymphoblast lines were used to identify those monoclonal hybridoma antibodies that define human melanoma-associated antigens. Autologous lymphoblast lines were used to exclude hybridoma antibodies directed against HLA and Ia-like specificities. Using this method, we have identified several cell surface antigens that are expressed on the majority of human melanoma cell lines tested.

Animals↗
PubMed1982

Cloning of human solid tumors in soft agar.

Of 1,014 human solid tumors of various histologic types, 690 (68%) showed evidence of colony formation within 2 to 4 weeks. Tumors which grew particularly well were colon carcinoma (104/175), melanoma (134/155), lung carcinoma (62/85), breast cancer (100/140), ovarian carcinoma (50/67), and sarcoma (72/122). Histologic examination indicated that the colony-forming cells retained functional and morphologic features similar to those of the original tumor. Plating efficiencies varied between 0.01% and 0.2%, and the numbers of colonies observed formed a direct linear correlation with the number of cells plated. Recovery of viable tumor cells was increased when enzymatic tumor dissociation was used rather than a mechanical method. A simplified, supplemented medium resulted in improved cloning efficiencies when compared to previously reported methods (Hamburger and Salmon, 1977 b).

Clone Cells↗
PubMed1982

Relationship between circulating immune complexes and urinary antigens in human malignancy.

Urine samples obtained from patients with histologically proved melanoma and sarcoma were analyzed for the presence of tumor-associated antigens by complement fixation and enzyme immunoassay. Also, serum samples obtained during 24-hour urine collection from these patients were analyzed for circulating immune complexes by the complement consumption method and by the K562 radiometric assay. Of 36 cancer patients who were positive for urinary antigen (UA) by both assays, 28 (78%) were also positive for CIC in the two assays, six (17%) were positive in one of the two CIC-detection assays, and two (5%) were negative in both assays. Of 24 patients that were negative for CIC in both assays, ten (42%) were also negative for UA in both assays, i.e., complement fixation and enzyme immunoassay; 12 (50%) were negative by one of the two assays; and only two (8%) exhibited UA by both assays. This relationship was more striking for melanoma than sarcoma patients. In a melanoma patient whose samples were studied sequentially during his thermochemotherapy, the fluctuations in CIC and UA were parallel. These results suggest that excretion of tumor-associated antigen into urine is not an isolated phenomenon; rather, immune complex deposition in kidneys appears to cause glomerular damage which may allow the passage of the antigens into the urine.

Antigen-Antibody Complex↗
PubMed1982

Thermochemotherapy for melanoma metastases in liver.

Metastatic melanoma in the liver has carried an extremely poor prognosis regardless of therapy. Because transient responses (1/6 disease regressions and 2/6 disease stabilizations for four months) in selected patients treated with intraarterial (IA) DTIC infusion were encouraging and because localized hyperthermia may be both tumoricidal and synergistic with chemotherapy, these modalities were combined for treatment of patients with advanced liver metastases. Of 10 patients treated with IA-DTIC plus heat, three (30%) had disease-regression and five (50%) had disease stabilization for 3-14 months (median 6.5 months) and survived 3.5-18 months (median 8.5 months). During treatment, 4/5 patients had pain relief and 7/10 retained or acquired normal activities. Myelosuppression was minimal and no hyperthermia toxicity occurred. A retrospective review of 10 patients with similar disease levels who were treated with conventional intravenous (IV)-DTIC indicated no responses, and no responses were seen in five patients treated with IV-DTIC plus heat. However, this latter group may have been selected patients due to the inability to place a percutaneous hepatic artery infusion catheter. This pilot study suggests that combination IA-DTIC and hyperthermia has a high response rate, is safe, and can provide quality survival for many patients.

Adult↗
PubMed1982

Granulomas in melanoma patients treated with BCG immunotherapy.

Autopsy slides from 22 melanoma patients who received bacille Calmette-Guérin BCG immunotherapy and who had a postmortem examination at the UCLA Center for the Health Sciences were examined for the presence of granulomas. Granulomas were found in six patients (29%) who received BCG but not in a group of 25 melanoma patients who did not have BCG immunotherapy. A number of factors were tested for correlation with the presence of granulomas in the autopsy material. Fifty-five percent of the patients who received BCG by both intralesional and time technique developed granulomas. No patients given BCG by the tine technique alone developed granulomas. No correlation was found between granulomas and the presence of symptoms after the administration of BCG, the duration of BCG immunotherapy, the patient's age, the number of BCG administrations, treatment with immunosuppressive agents, the length of survival after the last BCG administration, the presence of a positive PPD reaction, a positive history for granuloma-forming diseases and tests for immunocompetence. However, these results provide evidence that the route of BCG administration strongly influences the frequency of granulomas in melanoma patients who received BCG immunotherapy.

BCG Vaccine↗