Biomedical subjects

D L Morton

Publications and source records attributed to D L Morton.

At least 235 records · Page 13Linked to original sources

PubMed1984

Limb salvage for skeletal and soft tissue sarcomas. Multidisciplinary preoperative therapy.

One hundred eighty-three patients with malignant skeletal (83) or soft tissue sarcoma (100) were entered into the multimodality preoperative limb salvage protocol. Local recurrences were observed in 5 of 183 (2.7%). Six patients required amputation because of complications, and 13 patients died within 1 year from metastatic disease. There was no statistical difference in survival rates between a series of patients who had amputation and adjuvant therapy and patients treated by limb salvage and adjuvant therapy. Overall survival rates for patients with soft tissue sarcoma were 76%. Although the exact reason for the improved local control is not known, it is our belief that it is the result of the multidisciplinary therapy that destroys microscopic disease at the periphery of the primary tumor.

Adolescent↗

PubMed1984

Selective effects of insulin and hydrocortisone on colony formation and chemosensitivity of human tumors in soft agar.

Because low plating efficiencies of most human cancers severely limit the number of successful chemosensitivity tests that can be performed, we studied the growth-enhancing effects of insulin and hydrocortisone on a variety of solid tumors. Colony formation in soft agar was significantly increased in 23/49 (47%) tumors treated with 3 U/ml insulin, whereas fewer colonies were observed in 7 (14%). These effects were highly selective for tumor type. Colony growth for ovarian, lung, and colon carcinomas increased by 123%, 37% and 28%, respectively. In contrast, insulin inhibited the growth of melanoma, kidney, and breast tumors. Hydrocortisone at 0.05 microgram/ml increased colony numbers in 23/45 (51%) tumors, while in 7 (16%) colony numbers were decreased. Growth of ovarian, lung, breast, and kidney carcinomas was increased by 136%, 126%, 78% and 69%, respectively, whereas melanomas, sarcomas, and colon tumors were inhibited by hydrocortisone. In vitro chemosensitivities were relatively unchanged by the hormones. In 168 (134 paired) drug/tumor tests, sensitivity to standard antineoplastic drugs in the presence or absence of hormones was concordant 82% of the time (correlation coefficient, 0.71). However, in 20 tests (15%), significant enhancement of chemosensitivity was observed. We concluded that cloning efficiencies of many common human tumor types can be improved with hormones, and that these growth-enhancing effects are selective for tumor type.

Cells, Cultured↗

PubMed1984

A prospective postoperative evaluation of urinary tumor-associated antigens in sarcoma patients. Correlation with disease recurrence.

Tumor-associated antigens (TAA) excreted into the urine of sarcoma patients can be detected by the complement-fixation assay. The authors prospectively measured TAA levels in the urine of 50 sarcoma patients postoperatively to determine whether reappearance of antigen in the urine would be predictive of disease recurrence. Twenty-five patients developed recurrence of their disease in the postoperative period, and 24 (96%) had reappearance of antigen in the urine 10.1 +/- 9.2 months prior to clinical evidence of recurrence. Of the 25 patients who remained disease free (mean follow-up, 48 months), 23 of 25 (92%) were urinary-antigen negative at last follow-up, although 8 patients had transient elevations of urinary TAA early in the postoperative period. Results indicate that postoperative measurement of urinary TAA in sarcoma patients permits selection of a subset of individuals at high risk for the development of recurrence. This knowledge can be of assistance in the postoperative management of these patients.

Adolescent↗

PubMed1984

Clinical thermochemotherapy. A controlled trial in advanced cancer patients.

In vitro and in vivo animal studies and some clinical trials have shown apparent benefit from thermochemotherapy; however, this treatment modality has not been adequately tested in humans. This investigation evaluated response to and toxicity of secondary thermochemotherapy, using each patient as his own control. Patients with advanced cancer who had documented disease progression while receiving chemotherapy alone were subsequently treated with the same drug, by the same dose and route, combined with localized hyperthermia. Thirty-four patients whose diseases included metastatic colon carcinoma, melanoma, sarcoma and hepatoma in viscera (29) or surface tissues (5) were treated with combination thermochemotherapy for 1 hour daily for 5 days/month. Effective heating from 41 to 45 degrees C minimum tumor temperature was possible in 17/19 (89%) tumors in which temperatures could be measured safely. The authors observed 5 (15%) tumor regressions for 1 to 5 months (median, 2 months), and 19 (56%) tumor stabilizations (growth arrest of previously progressive disease) for 1 to 9 months (median, 4 months). Subjective improvement in activity and/or pain control occurred in 6 (18%) patients and 20 (59%) had no progression of symptoms during treatment. Moreover, there was no detectable morbidity from localized hyperthermia, and no evidence of increased chemotherapy toxicity. While the mechanism(s) of response is poorly understood, the documented disease regressions and stabilizations of previously progressive disease in 24 (71%) patients during secondary combination thermochemotherapy indicates that the addition of hyperthermia may have useful anticancer activity. Expanded trials are warranted.

Adult↗

PubMed1984

Melanoma metastatic to "lipomata".

Three patients presented with solitary melanoma metastases that mimicked a simple "lipomata." On further investigation each patient had a discrete fatty tissue tumor mass surrounding a melanoma metastasis. The presence of an enlarging mass in patients with a history of melanoma should be viewed with suspicion and a biopsy should be performed.

Aged↗

PubMed1984

Failure of subcutaneous mastectomy to prevent the development of breast cancer.

Three patients treated with bilateral subcutaneous mastectomies and implants for fibrocystic disease or carcinoma in situ subsequently developed invasive breast carcinoma. These cases emphasize that subcutaneous mastectomy does not prevent the development of breast cancer. If the circumstances in an individual patient justify prophylactic mastectomy, then the appropriate procedure would seem to be total mastectomy, which would accomplish thorough removal of all breast tissue, the subareolar region, and the nipple. Subcutaneous mastectomy for the patient who is likely to harbor occult invasive disease seems particularly inappropriate. As a means to reduce the risk of breast cancer, the procedure is unproved and must be considered an experimental therapeutic approach.

Adenocarcinoma↗

PubMed1984

Combination radiofrequency hyperthermia and chemotherapy (BCNU) for brain malignancy. Animal experience and two case reports.

Patients with high-grade primary and metastatic brain malignancies have a median survival time of 3-8 months, regardless of therapy. Because MagnetrodeTM hyperthermia provides safe, deep internal heating without normal-tissue injury, we studied its effects first on the brain and surrounding tissues of rabbits. The normal rabbit brain (n = 26) could be heated to potentially tumoricidal temperatures (42-43 degrees C) without apparent histopathologic or clinical damage to the brain, skull, external eye, subcutaneous tissue or skin. Intracranial pressure did not rise significantly. Using transplanted VX-2 carcinoma, we showed both the safety and potential efficacy of thermochemotherapy (IV BCNU: 14 mg/kg) in the presence of a solid brain tumor. The average maximum brain temperature achieved was 43.06 degrees C. Mean survival from the time of tumor implantation in the treated group (n = 16) was 18.56 days, compared to 9.3 days for untreated controls (n = 30) (p less than .0001). Two patients have been treated with localized brain hyperthermia combined with intravenous BCNU (80 mg/m2) for a total of eight treatments. Maximum normal brain temperature achieved was 40.0 degrees C in Patient #1 and 41.5 degrees C in Patient #2. A tumor temperature of 42.9 degrees C was achieved in Patient #2. Intracranial pressure remained within the upper limits of normal. Swan-Ganz monitoring in Patient #1 revealed a stable cardiac index and mean pulmonary artery pressure with mild fluctuations in the CVP, PAD, and PCW. No increase in chemotherapy toxicity was observed and no normal tissue injury occurred in either patient. We conclude that non-invasive localized radiofrequency hyperthermia to the brain is feasible and can be performed safely in the presence of a solid brain tumor.

Animals↗

PubMed1984

Breast cancers: estrogen and progesterone receptor status as a predictor of in vitro chemotherapeutic response.

Although clinical observations have shown that estrogen receptor-positive (ER+) breast tumors are more responsive to hormonal therapy than ER-negative (ER-) tumors, it remains controversial whether ER status can predict chemotherapeutic response. To determine if there was any correlation between estrogen and progesterone values and in vitro chemosensitivity to various anticancer drugs, clonogenic (CA), estrogen (ERA), and progesterone (PRA) assays on breast cancers were performed on 100 patients. Clonogenic assays were performed using the double-layer soft agar technique with continuous drug exposures. ERAs and PRAs were performed using the charcoal-coated dextran method. Chemosensitivity was defined as 50% inhibition of colony formation. ERA was considered positive if greater than or equal to 5 fmole/mg cytosol and PRA positive if greater than or equal to 10 fmole/mg cytosol. Significant tumor growth (greater than 30 colonies/plate) was achieved in 81/100 assays. ERA and PRA values were not predictive of colony formation in vitro. Of all agents or combinations of agents tested (L-PAM, 5-FU, MTX, adriamycin, vinblastine, cis-plat, FAC, CMF), only the response to 5-FU correlated significantly with ERA. Eight of 11 (73%) of the ER- tumors were sensitive to 5-FU, whereas only 6/20 (30%) of ER+ tumors were sensitive (P less than 0.05). ER- tumors were also more likely to be sensitive to CMF (P = 0.09) and adriamycin (P = 0.07) than ER+ tumors. PRA values were not predictive of chemosensitivity, nor did combining PRA and ERA enhance the predictive value of ERA alone.

Antineoplastic Agents↗

PubMed1984

Studies of a melanoma tumor-associated antigen detected in the spent culture medium of a human melanoma cell line by allogeneic antibody. I. Purification and development of a radioimmunoassay.

A tumor-associated antigen (TAA) was isolated from spent culture medium (chemically defined serum-free medium) of human melanoma cell line UCLA-SO-M14 (M14). The isolation procedures included concentration, ultrafiltration, gel filtration chromatography, and chloroform:methanol (C:M) extraction. The melanoma TAA activity recovered from the organic phase of the C:M extract was subsequently fractionated by gel filtration and radiolabeled with Na125I. The radioiodinated antigen was further purified by Sephacryl S-200 gel filtration and allogeneic antibody affinity chromatography. With the use of previously characterized anti-TAA allogeneic sera from melanoma patients and 125I-labeled TAA, a radioimmunoassay (RIA) was developed. Protein A-bearing Staphylococcus aureus was used to separate bound and unbound 125I-labeled TAA. The coefficient of variation between experiments and within experiments with unlabeled melanoma TAA as the competitor in the competitive RIA ranged from 8.9 to 20.4%. These variations were consistently lower (8.9-13.6%) at high levels (6 micrograms melanoma TAA/ml) of the competitor than they were (17.3-20.5%) at low levels (0.5 microgram melanoma TAA/ml), suggesting reasonable reproducibility of the assay. A logit versus log plot of the competitive RIA data and analysis by linear regression yielded a straight line. This line represented a 5- to 1,000-ng detection range for melanoma TAA. Analysis of C:M-extracted and Sephacryl S-200-purified melanoma TAA by the competitive RIA revealed a 695-fold purification of the antigen that represented a 37.5% recovery from the spent culture medium. The greatest enrichment of the melanoma TAA was achieved by the C:M extraction step. This step separated the melanoma TAA from other antigens, e.g., fetal antigen and human leukocyte antigens.

Antigens, Neoplasm↗

PubMed1984

Studies of a melanoma tumor-associated antigen detected in the spent culture medium of a human melanoma cell line by allogeneic antibody. II. Immunobiologic characterization.

A tumor-associated antigen (TAA) was isolated from spent culture medium of human melanoma cell line UCLA-SO-M14 (M14). After radioiodination and further purification, it was used in a radioimmunoassay (RIA). When tested in RIA for anti-TAA activity, 56% (111/200) of sera from melanoma patients, 21% (21/100) of sera from sarcoma patients, and 19% (19/100) of sera from carcinoma patients, as well as 12% (6/50) sera from pregnant women and 10% (10/100) apparently normal sera, were positive. The variations (0.25-3.8 micrograms/mg total protein) in specific TAA activity in 20 different batches of spent media collected for 18 months exhibited patterns of gradual increases and decreases, suggesting a cell growth cycle-related phenomenon. Binding between the allogeneic antibody and 125I-labeled TAA was inhibited by 70% (32/47) of melanoma spent media and cells (from culture or biopsy). Conversely, only 7% (3/33) spent medium or membrane extracts of other tumor cells and 0% (1/69) of human normal, fetal, or placental cells were positive in competitive RIA. The TAA was immunologically different from normal tissue antigens, blood-group antigens, human leukocyte antigens, and microbial antigens. These immunobiologic properties of the TAA isolated from M14 spent culture medium and used in the RIA suggested that such TAA was melanoma associated.

Antibodies, Neoplasm↗

PubMed1984

Studies of a melanoma tumor-associated antigen detected in the spent culture medium of a human melanoma cell line by allogeneic antibody. III. Physicochemical properties.

A melanoma tumor-associated antigen (TAA), isolated from spent culture medium of human melanoma cell line UCLA-SO-M14, was purified to mean homogeneity to determine its physical and biochemical nature. Gel filtration and native polyacrylamide gel electrophoretic analyses of the 125I-labeled melanoma TAA revealed that the antigen had a molecular weight in the range of 180,000-190,000. However, ultracentrifugation of melanoma 125I-labeled TAA in a 5-20% sucrose density gradient revealed a sedimentation coefficient to be 4.96 +/- 0.24. Melanoma 125I-labeled TAA focused at a pH of 6.5 by isoelectric focusing. No carbohydrates were detectable by various colorometric methods in the highly purified melanoma TAA fraction, and melanoma TAA failed to bind with several lectins. Its antigenic activity was destroyed by the proteolytic enzymes but was not affected by the glycosidic enzymes or phospholipase A2. The results suggested that the melanoma TAA was most likely a lipoprotein that had a molecular weight of 180,000-190,000, a sedimentation coefficient of approximately 5, and a pl value of 6.5. The protein portion apparently formed the antibody binding site(s).

Antigens, Neoplasm↗

PubMed1984

Clinical correlations with chemosensitivities measured in a rapid thymidine incorporation assay.

A rapid assay for in vitro chemosensitivity testing measuring [3H]thymidine incorporation has been developed. Results of this assay correlate highly with chemosensitivities determined by the soft-agar clonogenic assay. A correlative study was carried out on 219 solid tumor specimens to assess the ability of the rapid assay to predict clinical response to antineoplastic therapy. One hundred forty-two of 219 tumors (65%) yielded chemosensitivity data. Of these, 33 were evaluable for in vitro-in vivo correlations. In vitro sensitivity (greater than or equal to 80% inhibition of thymidine uptake) was associated with clinical response in 6 of 13 patients. In vitro resistance was associated with progressive disease in 20 of 20 patients. The rapid assay offers several advantages over the soft-agar clonogenic assay, including higher success rate, avoidance of clumping artifact, shorter time course (5 days), and very low false-negative rate. Further refinement may be necessary, but the rapid assay appears to have potential for individualizing solid tumor chemotherapy.

Antineoplastic Agents↗

PubMed1984

Human leukocyte (alpha) interferon in metastatic malignant melanoma: the American Cancer Society phase II trial.

Forty-four evaluable patients with metastatic malignant melanoma confined to the skin, subcutaneous tissues, lymph nodes, and/or lung were randomly assigned to receive either 1 X 10(6), 3 X 10(6), or 9 X 10(6) units of partially purified human leukocyte (alpha) interferon by daily im injection for 42 days. One patient achieved a partial response, two had minor responses, and three others had mixed responses. The only partial response was observed at the lowest dose of interferon. Toxicity increased in frequency and intensity with increasing interferon dose. This preparation of interferon at the doses, route, and schedule used appears to have little efficacy in metastatic malignant melanoma.

Adolescent↗

PubMed1983

Predictability of response to clinical thermochemotherapy by the clonogenic assay.

In order to assess the value of the clonogenic assay for predicting clinical response to dimethyl-triazeno-imidazole-carboxamide (DTIC) plus hyperthermia (42 degrees C), the responses of patients with measurable disease, who received combined therapy, were compared with assay results. The clonogenic assay was used independently to determine in vitro sensitivities of 53 melanomas to DTIC, with and without hyperthermia. Separate cell suspensions were incubated for 1 hour with DTIC at 37 degrees C and at 42 degrees C. In vitro sensitivity was determined by inhibition of colony formation in a double-layer agar system. Three of the 53 (6%) melanomas were sensitive to DTIC at 37 degrees C, 13 of the 53 (25%) were sensitive to 42 degrees C hyperthermia alone, and 22 of the 53 (42%) were sensitive to DTIC at 42 degrees C. Nine patients were treated with DTIC, plus hyperthermia, to the areas of their melanoma metastases (one pulmonary, four hepatic, and four subcutaneous). In five patients, the clonogenic assay results predicted positive tumor sensitivity to combined therapy, and 4 of the 5 had objective tumor regression. Tumors were resistant in vitro for four patients, and all had disease progression during treatment. Statistical analysis suggested that some responses were due to synergism of the combination of heat and drug, whereas others were due to an additive effect. The apparent direct correlation between in vitro tumor cell sensitivity to DTIC at 42 degrees C and actual clinical response to chemotherapy, plus hyperthermia, in this limited trial, has been encouraging. The clonogenic assay and in vitro evaluation of drug-heat interaction may prove helpful for selecting those patients in whom hyperthermia should be used as an adjunct to chemotherapy, and may help determine the most effective drug/heat scheduling. Further trials with other malignancies and other chemotherapeutic agents are warranted.

Cells, Cultured↗

PubMed1983

LDH and melanoma.

The histories of 121 Stage II melanoma patients were reviewed to determine the value of monitoring serum LDH in postoperative follow-up examinations. Charts of 58 Stage III patients who had autopsies at UCLA also were reviewed to define the relationship between an elevated LDH and liver metastases. The sensitivity and specificity of LDH as an indicator of disease recurrence were 72.1% and 97.0%, respectively. As an indicator of liver metastases, LDH had a sensitivity and specificity of 95.1% and 82.8% in the Stage II patient group and 86.5% and 57.1% in the Stage III autopsied group. An elevated LDH was the first indication of recurrent disease in 11/88 (12.5%) Stage II patients and was almost as frequent an indicator of recurrent disease as pulmonary metastases found on chest x-ray. Mean survival following elevation of LDH was 5.9 months whether or not liver metastases were present. Monitoring of serum LDH can provide useful information in the postoperative follow-up of patients with melanoma.

Adolescent↗

PubMed1983

Delayed diagnosis of breast cancer as a result of normal mammograms.

Review of the effects of a normal mammogram on the treatment of 36 women with palpable breast carcinomas during a two-year period showed that 17 patients had biopsies performed within two months of their normal mammograms and 19 patients had biopsies delayed for three to 24 months. Of the 17 who had biopsies within one month of a normal mammogram, three (17.6%) had extension of disease to axillary nodes. Of 19 patients whose biopsy was delayed, cancer was found in axillary nodes of 11 (57.9%). Normal mammograms should not preclude biopsy of a breast mass.

Adult↗

PubMed1983

Biopsy of thoracic neoplasms for assay of chemosensitivity. New indication for thoracotomy.

Eighty-six thoracic neoplasms, both primary and metastatic, were removed at thoracotomy from 86 patients and were tested for chemosensitivity in the clonogenic assay. Substantial tumor growth was achieved in 79% (67/86). Fifty-two percent (16/31) of the primary lung tumors and 45% (15/33) of the metastatic tumors were sensitive to at least one tested drug. Clinical correlations between in vitro chemosensitivity and in vivo response were possible in 20 patients. The assay was 83% accurate for predicting in vivo sensitivity and 86% accurate for predicting in vivo resistance. The value of the assay as it pertains to lung cancer has been demonstrated. On the basis of the results, thoracotomy is indicated in selected patients as a diagnostic procedure to obtain tissue for chemosensitivity testing.

Antineoplastic Agents↗

PubMed1983

Heterogeneity of human metastatic clones by in vitro chemosensitivity testing. Implications for the clinical application of the clonogenic assay.

To determine whether in vitro chemosensitivities of clones from metastases of human tumors varied, biopsy specimens of two separate metastatic lesions were obtained from 75 patients. Significant tumor growth (greater than 30 colonies per plate) occurred in both specimens in 49 of the 75 patients. Biopsies were performed simultaneously in 22 patients (synchronous) and sequentially in 27 patients (metachronous). Tumor samples were scored as being resistant (less than 50% inhibition of colony formation) or sensitive (greater than 50% inhibition) to each drug. The two tumor samples from each patient were compared for differences in sensitivity after exposure with standard panels of chemotherapeutic agents. A total of 272 individual drug comparisons were possible. Variations were evident in 49 (40%) of 121 metachronous drug comparisons and in 42 (28%) of 151 synchronous drug comparisons. We concluded that multiple metastases of human tumors can vary in chemosensitivity in vitro; this finding seemed to reflect the heterogeneity of metastatic clones.

Antineoplastic Agents↗