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Biomedical subjects

D L Morton

Publications and source records attributed to D L Morton.

At least 325 records · Page 18Linked to original sources

A serologic study of cultured breast cancer cell lines: lack of antibody response to tumour specific membrane antigens in patients.

Humoral antibodies to tumour associated membrane antigens of cultured human breast cancer cell lines were studied using the immune adherence (IA) test. Sera from 353 post-operative breast cancer patients and from twenty-five patients immunized by allogeneic breast cancer cells were tested against the MDA-MB-436 cell line. Fifty-five (15.6%) sera samples from the non-vaccinated group and 131 (77.3%) of 168 sera samples from the immunotherapy group were IA-positive to this cell line after absorption with bovine erythrocytes to exclude antibody to heterologous membrane antigens (HM Ag). Forty-five of the 55 positive-sera from the non-immunized group and 113 of the 131 positive sera from the immunized group became IA-negative after further absorption with lymphoblastoid cells autologous to MDA-MB-436. Subsequently, the twenty-eight positive sera remaining sere tested for oncofetal antigens (OFA). After absorption with OFA rich tissues (fetal brain and M14 melanoma cells), no reactivity remained in the sera samples. In order to identify antibodies specific to breast cancer antigens, the 129 sera samples from non-immunized patients were tested against four other breast cancer cell lines; MDA-MB-157, MDA-MB-231, MCF-7 and UCLASO-B1. Four sera which reacted to more than three of the cell lines were identified. The reactivity of three of the four was due to anti-OFA antibody. The last serum sample was reactive to anti-HLA antibodies. These results indicate that sera of patients with breast cancer contain antibodies to OFA, but do not detect breast histologic type specific antigens as tested by IA using five breast cancer cultured cell lines.

Antibodies, Neoplasm↗

Internal hemipelvectomy--excision of the hemipelvis with limb preservation. An alternative to hemipelvectomy.

Our results indicate that it is technically possible to resect the hemipelvis and maintain a viable extremity. Functional results are remarkably good and tumor control has been equivalent to standard hemipelvectomy. Excision of the ilium with preservation of the extremity in selected cases would appear to be a reasonable alternative to the standard hemipelvectomy, which involves amputation of the extremity.

Adolescent↗

Serum-mediated immunosuppression in lung cancer.

Immunosuppression in 45 patients with lung cancer was studied by examining delayed cutaneous hypersensitivity reactions to DNCB and by analyzing the effect of the patient's serum on the proliferative response of normal donor lymphocytes. Both diminution of DNCB reactivity and inhibition of the proliferative response of normal donor lymphocytes to mitogens were associated with the stage of the disease and the presence of unresected tumor. Suppressive sera were associated with poor prognosis. The suppressive effects of patients' sera on lymphocytes from a normal donor suggest that the immunosuppression seen in lung cancer may be mediated by serum factors. The significant association of clinically evident tumor with this serum-mediated immunosuppression further suggests that the tumor itself could account for the appearance of these factors in the host. The clinical implications of these findings may be useful for designing new clinical trials.

Adult↗

Multiple primary melanoma.

From a series of 712 patients with melanoma, 38 patients (5.3%) had more than one primary melanoma. Twenty-four patients had two primaries, 11 patients had three, 2 patients had four, and 1 patient had eight. Twelve patients (32%) had one or more synchronous primaries. Forty-five percent of all multiple primaries were diagnosed within the first year. Microstaging by level and depth was determined prior to treatment and in patients with nonsynchronous primaries, 83% had a subsequent melanoma equal or less advanced than the original. Twenty-six patients with Stage I primaries were skin-tested with DNCB prior to therapy. No significant differences in delayed cutaneous hypersensitivity reactions were found between multiple primary and matched controls with only a single melanoma. Four of 10 patients with multiple primaries treated with adjuvant BCG or BCG-tumor cell vaccine developed subsequent melanomas suggesting that immunotherapy with BCG will not prevent the development of a new primary melanoma. Survival in patients with Stage I and II multiple primary melanomas was improved compared to Stage I and Stage II patients with a single primary. This study suggests that prognosis in multiple primary melanomas is better reflected by the most advanced primary based on microstaging and the presence or absence of regional lymph node metastases than by multiplicity.

Adult↗

Rheumatoid factor in melanoma patients: alterations of humoral tumor immunity in vitro.

Rheumatoid factors (RF) were associated with alterations of antibody reactions to melanoma cells in vitro by two serologic assays. Removal of RF from melanoma patients' sera by absorption with Cohn's Fraction II coated latex particles enhanced seroreactivity in the Immune Adherence (IA) assay and diminished IgM detection by the Indirect Membrane Immunofluorescence (IMI) assay. The addition of serum with high titers of RF to these assay systems led to diminution of IA reactivity and enhancement of IgM detection by IMI. Since these factors are found in cancer patients' sera and can alter humoral immune reactions directed against antigens on the membranes of tumor cells, their presence should be recognized when performing assays with tumor target cells. RF may be of significance in the host-tumor relationship in vivo.

Antibodies, Neoplasm↗

Detection of cancer-associated antigen(s) in urine of sarcoma patients.

Tumor-associated antigens were demonstrated in concentrated and dialyzed urine of several sarcoma patients with large tumor burden. The antigens were detected by complement fixation using autologous and allogeneic sera from sarcoma patients. The antigenic activity in three patients who were studied sequentially disappeared after surgical ablation of tumor. In two of these three patients, the antigenic activity reappeared before tumor recurrence. The reactivity of the sarcoma sera to the urine could be abolished by absorption of the sera with human sarcoma cells but not by normal human liver cells, which indicates that the same antigen was present in the urine and on biopsy-obtained sarcoma cells. Urine from cancer patients with high tumor burden may be useful as a source of tumor-associated antigen. Further studies on the presence of these antigens in urine of sarcoma patients may lead to a method for detecting subclinical tumor recurrence.

Adult↗

Human hyperthermic therapy: relation between tumor type and capacity to induce hyperthermia by radiofrequency.

There is mounting evidence that hyperthermia of 42 degrees C or greater is tumoricidal to cell cultures and to animal and human tumors. However, temperatures of 45 degrees C or greater may have greater potential therapeutic benefit. The ability to selectively achieve such highintratratumor temperatures without injury to normal tissue may be due to the relatively poor blood flow in tumors compared with that in normal tissues. While vascularity and blood flow are known to vary significantly among tumors, we found that of 52 tumors evaluated, temperatures of 42 degrees C or greater in 42 tumors (81 per cent) and of 45 degrees C or greater in 23 tumors (44 per cent) appeared to be independent of the histologic type of tumor. Therefore, therapeutic hyperthermia may be possible for most varieties of human solid cancer.

Adenocarcinoma↗

Growth and metastasis of human melanoma xenografts in the hamster host.

Cells from three human melanoma cell culture lines (UCLASO-M-12, UCLASO-M-7, and WEG-1) were transplanted into the cheek pouches of immunosuppressed hamsters. Tumor nodules were found in the cheek pouches of hamsters receiving any one of these lines, and by 90--100 days after transplantation, nearly all hamsters had grossly visible lung metastases. Metastases were noted only in hamsters receiving continuous immunosuppression during the transplant period.

Animals↗

Isolation and immunochemical characterization of antibodies from the sera of cancer patients which are reactive against human melanoma cell membranes by affinity chromatography.

Immunoglobulins were isolated by affinity chromatography from sera of two patients with melanoma, one with sarcoma, and one with carcinoma. The affinity columns were prepared by covalently linking the membrane-rich fraction of biopsied melanoma cells to cyanogen bromide-activated agarose beads. The membrane-rich fractions were prepared by two methods: (a) hypotonic cell lysis, and (b) homogenization and differential centrifugation. Melanoma sera were autologous to melanoma membrane preparations. The isolated immunoglobulins showed immunoreactivity against antigens prepared from melanoma, sarcoma, and carcinoma cells by complement fixation but not against antigens prepared from normal human liver and lung tissues. Absorption of the isolated immunoglobulins with rabbit anti-human immunoglobulin immunobeads resulted in complete elimination of the complement-fixing antibody titer in one instance, whereas reduction occurred in other samples. Similar absorption with rabbit anti-human immunoglobulin M immunobeads resulted in reduction, but not complete elimination, of the antibody titers against target tumor cell preparations. These results suggest the presence of immunoreactive immunoglobulin G in all immunoglobulins and immunoglobulin M in some. Absorption of the isolated immunoglobulins with cultured sarcoma cells reduced but did not completely abolish antibody activity against autologous or allogeneic melanoma target antigen, whereas it did completely abolish activity against sarcoma target antigen. However, absorption with cultured allogeneic melanoma cells abolished the antibody activity against melanoma as well as sarcoma target antigens. The antibody titers of the isolated immunoglobulins were not affected by absorption with cultured lymphoblastoid cells. Since cultured melanoma and sarcoma cells were known to contain oncofetal antigen(s), these results suggest that the isolated immunoglobulins from cancer sera by melanoma membrane affinity chromatography were of at least two specificities: (a) antioncofetal; and (b) antitumor associated. The former group may be comprised of antibody to cross-reactive antigens associated with different histological types of tumors. However, it was apparent that a portion of the antibody activity was against common tumor-associated antigen(s). These results provide further evidence for the presence of common antigen(s) associated with biopsy specimens of human malignant melanoma.

Adult↗

Double-antibody method and the protein-A-bearing Staphylococcus aureus cells method compared for separating bound and free antigen in radioimmunoassay.

We compared the protein-A-bearing Staphylococcus aureus immunoadsorbent to the double-antibody precipitation method for separating bound and free radiolabeled antigen in a radioimmunoassay. With human albumin (antigen) and rabbit anti-human albumin (antibody) as a model, our results indicate that formalin-fixed, heat-killed S. aureus cells could be substituted for the double-antibody precipitation method. Ease of preparation and high adsorption capacity of protein-A-bearing S. aureus for most mammalian IgG make this method economical and time saving.

Antibodies↗

Normal tissue and solid tumor effects of hyperthermia in animal models and clinical trials.

Localized hyperthermia therapy by high-energy radio-frequency waves was evaluated in malignant and adjacent normal tissue of 30 patients with 10 types of cancer. Hyperthermia was delivered to superficial and deep visceral cancers in awake patients who had refractory disease. Histological and clinical responses were recorded serially. Toxicity tests in dogs, sheep, and pigs showed that progressive necrosis of normal and cancer tissue occurred at temperatures above 45 degrees C (113 degrees F). However, as normal tissues approached this temperature, intrinsic heat dissipation occurred (possibly due to augmented blood flow) so that temperatures below 45 degrees C could be maintained, whereas most solid tumors did not have this adaptive capacity and could be heated to 50 degrees C (122 degrees F) with virtually no injury to normal organs, s.c. tissue, or skin. To date, 69 treatments have been administered to 36 tumors in the 30 patients. Selective heating was observed in both primary and metastatic tumors located in surface tissues and internal organs. Response appeared to be related to tumor size in that differential heating was possible more often in the larger lesions. In tumors successfully heated, moderate to marked necrosis occurred. Radio-frequency hyperthermia appears to be a safe and potentially useful form of therapy for selected cancer patients. While other cancer treatments are more effective for small tumors, hyperthermia may be uniquely beneficial against larger lesions.

Abdominal Neoplasms↗

Intratumor bacillus Calmette-Guerin therapy for chest wall recurrence of carcinoma of the breast.

Intratumor bacillus Calmette-Guerin administration is effective for treating chest wall recurrence from carcinoma of the breast in selected patients. Our results suggest that bacillus Calmette-Guerin therapy can be used alone, with systemic chemotherapy, hormonal therapy or in previously irradiated tissue. It represents local treatment for local disease that is well tolerated. Intratumor bacillus Calmette-Guerin treatment is a useful clinical method for the treatment of local chest wall disease.

Adult↗

Treatment for melanoma of the lower extremity with intralesional injection of bacille Calmette Guérin and hyperthermic perfusion.

Twenty-seven patients with locally recurrent melanoma of the lower extremity were treated during a six year period. Recurrences were noted with primary lesions, at Clark's level II, III, IV or V, greater than 1.7 millimeters in depth of invasion and included intransit metastases, satellitosis, subcutaneous metastases and combinations of the three. Median time to recurrence was 12 to 14 months whether or not lymphadenectomy had been performed or lymph node metastases were present. Local recurrence was treated initially with intratumor bacille Calmette Guérin; 20 of 27 patients had complete or transient disease control and 14 patients were alive at 1.5 to 55.0 months. More responders reacted to dinitrochlorobenzene and purified protein derivative skin tests, although these parameters did not predict response to therapy. If intratumor bacille Calmette Guérin therapy did not control local disease or if the disease progressed toward the upper third of the thigh, patients underwent hyperthermic perfusion with L-phenylalanine mustard. Nine patients underwent ten therapeutic perfusions with objective response in seven of nine, with five being alive at two to 65 months. Intratumor bacille Calmette Guérin therapy and subsequent hyperthermic perfusion in bacille Calmette Guérin failures are rational treatment alternatives for locally recurrent melanomas of the extremity.

Adult↗