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Biomedical subjects

D L Morton

Publications and source records attributed to D L Morton.

At least 271 records · Page 15Linked to original sources
PubMed1982

Hepatic resection of metastatic colorectal carcinoma: a ten-year experience.

Nineteen patients have undergone partial hepatectomy for metastatic colorectal carcinoma at UCLA during the past ten years, including five trisegmentectomies (TS), eight lobectomies (L), and six segmentectomies (SG), with only one (5.3%) mortality. Twelve lesions were solitary (S) and seven multiple (M). Mean survival is 27.4 months, with three patients surviving over five years and one nearly eight years. Better mean survival exists for S (33.2 months) compared with M (15.8 months) lesions; for lesser resections: SG (44.7 months), compared with L (24.3 months) and TS (11.0 months); and for those with delayed appearance of hepatic metastases: beyond two years (40.5 months), less than one year (24.8 months), and synchronous (23.1 months). Survival figures should improve, as none of the 12 surviving patients have evidence of recurrent disease and many have short follow-up. This experience defends aggressive surgical treatment of resectable colorectal carcinoma metastatic to liver, because systemic therapy is markedly less effective.

Adult↗
PubMed1982

Clinical correlations with drug sensitivities in the clonogenic assay: a retrospective study.

We tested the ability of the in vitro clonogenic assay (CLAS) to predict clinical response for patients with solid tumors. Patients had objectively measurable disease and received at least one course of chemotherapy. The correlation between clinical responses and in vitro sensitivity was evaluated retrospectively. Tumor types included melanoma (19), sarcoma (five), hepatoma (one), and carcinoma of the stomach (two), colon (three), lung (one), and breast (one). Five patients received two separate courses of chemotherapy with different drugs or drug regimens. In nine of 11 (82%) instances, tumors were sensitive to a particular drug, and the patient had at least 50% regression of tumor following treatment with the tested drug. Two patients whose tumors were sensitive in vitro had no evidence of clinical response. In 25 of 26 assays, the CLAS accurately predicted tumor resistance, and only one patient had evidence of clinical response (96%). Associations of in vitro results with clinical responses were highly significant. The CLAS can accurately predict the chemosensitivity of a variety of solid tumors.

Antineoplastic Agents↗
PubMed1982

Comparison of the techniques used for monitoring humoral immunity in cancer patients.

The humoral immune response to tumor-associated antigens (TAA) in cancer patients undergoing immunotherapy can vary considerably. This variability is inherent from patient to patient and is also dependent on the type of assay used to measure patient antibody response to tumors. In this investigation four serological techniques, complement-dependent antibody-mediated cytotoxicity, immune adherence, complement fixation, and indirect membrane immunofluorescence, were used to assess the humoral immune response in melanoma patients receiving specific immunization with cultured allogeneic melanoma cell vaccine. Two different patterns of antibody response were elicited. One was directed against TAA and oncofetal antigens (OFA) and the other was against HLA antigens. The sensitivity and reactivity varied among the different techniques suggesting that one test or technique may not be sufficient to evaluate critically a patient's response to immunotherapy.

Antibody Formation↗
PubMed1982

Excretion of tumor-associated antigen(s) in the urine of patients with colon carcinoma.

Urine samples collected from patients with colon carcinoma and from normal donors were tested for antigenic activity by the microcomplement-fixation assay. When autologous serum was used as the antibody source, 65.4% (17/26) of the urine samples from patients with colon carcinoma were positive for antigen as opposed to only 10% (2/20) from normal volunteers. Absorption of a representative serum with cultured colon cancer cells completely removed reactivity against its autologous urine. Using this serum to screen urine from colon carcinoma patients, antigenic activity was found in 71.4% (30/46) of the samples; however, only 10% (2/20) of the urine samples from apparently healthy volunteers were positive. Analysis of urine samples collected from three patients before and after resection of their primary colon carcinoma and from nine patients undergoing hyperthermia for liver metastases revealed that two of the patients who had curative surgical procedures had marked decreases in urinary antigen levels by the second postoperative day, while the third patient whose disease was unresectable had no significant decrease. Seven of nine patients with metastatic disease had a greater than fourfold increase in antigen activity after hyperthermia and chemotherapy. These results suggest that tumor-associated antigens were excreted into urine, possibly the result of treatment-caused tumor necrosis. Therefore, assessment of tumor-associated antigen(s) in the urine of patients with colon carcinoma may serve as a marker for response to treatment of this disease.

Adult↗
PubMed1982

Surgical management and reconstruction of extensive chest wall malignancies.

Seven patients aged 8 to 77 years underwent massive resection for chest wall malignancies. Two had chondrosarcoma, one recurrent breast cancer, one malignant hemangioepithelioma, one embryonal cell sarcoma, one metastatic osteogenic sarcoma, and one lymphangiosarcoma. The smallest surgical defect was 17 by 19 cm, the largest 35 by 45 cm. Closure was done with Marlex mesh, full-thickness muscle flaps, or free island pectoralis or latissimus dorsi flaps. The rotation of myocutaneous island flaps (bilateral in two patients) greatly facilitated reconstruction. No infection, pulmonary compromise, or operative morbidity or mortality was encountered. The age of the patients and the location or size of the lesions were not significant factors. Designing a surgical strategy which provides adequate full-thickness margins and immediate reconstruction is critically important. Massive chest wall resection for malignancy should be pursued aggressively whenever these lesions are encountered. The operations can be performed safely and can be curative, and the benefits to patients in terms of comfort and prolonged survival justify this extensive surgery.

Adolescent↗
PubMed1982

Thermal distribution of magnetic-loop induction hyperthermia in phantoms and animals: effect of the living state and velocity of heating.

Hyperthermia has shown promise for the treatment of cancer. The magnetrode radio-frequency magnetic-loop induction applicator was recently introduced and is being evaluated at many centers with encouraging initial results. This investigation was undertaken to delineate the thermal distribution patterns of magnetrode hyperthermia in both normal tissue phantoms and healthy dogs. Temperatures on homogeneous and heterogeneous tissue equivalents and animal tissue phantoms, a dead animal extremity, a dead dog and a live dog subjected to rapid high-dose heating showed preferential and potentially injurious peripheral heating with a central "cold spot." However, sequential moderate-dose heating in live dogs showed virtually uniform (less than 1 degree C) and potentially tumoricidal temperatures greater than or equal to 42 degrees C in both peripheral and central internal organs without injury to surface tissues. These data indicate that magnetic-loop induction can produce potentially safe and effective deep central heat in living, normal animals, but that safety and effectiveness are significantly influenced by the velocity of heat deposition. Furthermore, normal tissue phantom models and dead animals are unreliable predictors of magnetrode heat patterns in living systems.

Animals↗
PubMed1982

Monoclonal antibodies to 125 kd and 95 kd proteins on human melanoma cells: comparison with other monoclonal-defined melanoma antigens.

Two monoclonal antibodies produced by hybridomas were identified by an indirect 125I-protein A binding assay that define cell surface antigens expressed on cultured human melanoma cells but not on autologous lymphoblastoid cells. The first antibody, 705F6 (an IgG2b immunoglobulin), bound to 14/14 melanoma lines, 6/9 carcinomas and sarcomas, 7/7 gliomas and neuroblastomas, 2/2 fetal cell lines, 0/8 lymphoblastoid cell lines, and weakly to 2/4 leukemia lines. The second monoclonal antibody, 436G10 (IgG1), reacted with 10/14 melanomas 5/13 carcinomas and sarcomas, 2/7 gliomas and neuroblastomas, and weakly with the fetal cells, but not with the leukemic or lymphoblastoid cell lines. Comparison of 705F6 and 436G10 with 28 other monoclonal antibodies from different laboratories identified several with similar binding patterns to a panel of tumor and nontumor cell lines. Crossblocking of 125I-labeled 436G10 was not observed by R23, I12 or L10 antibodies. However, 705F6 was completely blocked by monoclonal 376.96S, showing that these two antibodies bind to the same antigenic determinant. The 705F6 antibody immunoprecipitated a 95 kd (kilodalton) membrane protein and the 436G10 antibody bound a 125 kd protein from 125I-labeled melanoma cells. The broad distribution of these two proteins on melanomas and other solid tumors suggests that they define common oncodevelopmental antigens expressed on proliferating cells.

Animals↗
PubMed1982

Factors prognostic for survival in patients with malignant melanoma spread to the regional lymph nodes.

To establish clinical and histologic determinants of survival, records of all UCLA patients with resectable melanoma metastatic to the lymph nodes during the years 1954-1976 were reviewed. These 150 patients were treated first with wide excision, lymphadenectomy, and with radiation/chemotherapy and/or additional surgery only if further recurrences developed. None received adjuvant immunotherapy or chemotherapy. In 97 of 139 patients with identified primary tumors, slides of the primary lesion were reviewed. Putative prognostic factors included age, sex, parity, site of primary tumor, presence of satellitosis, clinical status of nodes, histologic characteristics of primary lesion (Clark's level, thickness of tumor, presence/width of ulceration, and number of mitoses/HPF), time from biopsy of primary tumor to lymphadenectomy, and number of positive nodes. kaplan-Meier estimates of survival for the entire group at one, two, five, and ten years were 73, 55, 37, and 33%, respectively. Median follow-up period of survivors was four years. Univariate analyses using the log-rank test showed that thickness of the primary lesion (p less than 0.001), width of ulceration (p = 0.003), absence of ulceration (p = 0.024), and number of positive nodes (p = 0,.033) were prognostic for survival. In multivariate analysis by the Cox procedure, thickness of the primary (p = 0.001) and number of melanoma-containing nodes (p = 0.043) were prognostic for survival. Location of the primary tumor became marginally significant (p = 0.12) in the multrivariate model. These findings demonstrate the prognostic importance of characteristics of both the primary lesion and extent of regional dissemination. Future prospective randomized trials for (adjuvant) therapy of Stage II melanoma should be stratified by these variables.

Adolescent↗
PubMed1982

The management of locally recurrent soft-tissue sarcoma.

Thirty-eight patients with locally recurrent soft-tissue sarcomas of various histologic types and grades but with no evidence of distant metastases were studied. Twenty-five patients had more than one local recurrence. Most primary lesions had been initially treated by simple or "wide local" excision with removal of little or no surrounding normal tissue. The most common site for recurrence was the extremity. Sixteen patients received preoperative intra-arterial Adriamycin (30 mg/day X three days) and radiation therapy (3500 R over ten days) followed by wide resection of the recurrence and the previous operative field. Tumor-free margins were confirmed microscopically. There were no subsequent local recurrences in this group. In five patients, no preoperative therapy was used, and the resection was incomplete because of proximity to vital structures. In these patients, postoperative radiation therapy and chemotherapy could not prevent continued local tumor progression. Amputation for control of local recurrence was necessary in only three patients. the remaining patients underwent either resection alone or resection in combination with postoperative radiation and/or chemotherapy. Life-table analysis of these 38 patients shows an unexpectedly high predicted five-year survival of 76% (87% for patients whose local recurrence could be completely resected). This high salvage rate clearly justifies aggressive treatment of patients with local recurrences alone and warrants attempts to salvage functional extremities.

Abdomen↗
PubMed1982

Results of ilioinguinal dissection for stage II melanoma.

Eighty-two Stage II melanoma patients with inguinal lymph node metastases have undergone ilioinguinal node dissections at UCLA during the past 10 years. Twenty-four (29.3%) patients had involvement of both inguinal and iliac nodes, whereas 58 (70.7%) patients had only inguinal metastases. The frequency of iliac metastases did not relate to location, Clark's level or thickness of the primary tumor or interval from diagnosis of primary tumor to lymphadenectomy, but was related to the number of inguinal nodes involved with metastases, rising from 14.6% with one positive inguinal node to 50% with four or more inguinal node metastases. Twenty of 24 (83.3%) patients with inguinal and iliac node metastases developed recurrent disease, whereas 32/58 (55.2%) patients with only inguinal node metastases and no tumor in the iliac nodes recurred. The time to recurrence was much shorter if iliac nodes were diseased (median disease-free interval 5.8 months versus 25.6 months). Three of five patients with clinically negative but histologically positive inguinal and iliac nodes survived 5 years, while only 1/18 patients with clinically positive inguinal nodes and diseased iliac nodes lived 5 years. Those with clinically negative but histologically positive inguinal nodes and iliac metastases had recurrence and survival rates similar to those with clinically negative but histologically positive inguinal nodes and no iliac metastases. Ilioinguinal lymphadenectomy provides significant prognostic information for Stage II patients with inguinal metastases and may be therapeutic for those with iliac metastases. Therefore, ilioinguinal dissection is the operation of choice for melanoma patients with regional metastases to the inguinal area.

Adult↗
PubMed1982

Systemic administration of human leukocyte interferon to melanoma patients. I. Effects on natural killer function and cell population.

Natural killer (NK) cytotoxicity was assessed against K562 targets in 14 melanoma patients who received daily im doses of human leukocyte interferon (IFN) for 42 consecutive days. The most common pattern of NK activity was a decline from pretreatment levels 1 day after initiation of treatment, followed by increasing cytotoxicity with peak activity at day 7 and a subsequent gradual decline to pretreatment levels during the remaining weeks of treatment. This pattern was particularly apparent in patients who received 3 x 10(6) or 9 x 10(6) U IFN/day, while patients who received 1 X 10(6) U IFN/day tended to lack the decline at day 1 and maintained the elevated NK activity past day 7. Changes in NK activity could not be related to changes in absolute lymphocyte counts; to proportions of cells bearing membrane receptors for erythrocyte-antibody-complement, of cells bearing FC gamma receptor; or to clinical response to IFN.

Cytotoxicity, Immunologic↗
PubMed1982

Monoclonal antibody against A1 Lewis d antigen produced by the hybridoma immunized with a pulmonary carcinoma.

A monoclonal antibody (CALed) against a human pulmonary squamous cell carcinoma line was cytotoxic to the line but did not react to an autologous B-lymphoblastoid line. Although the antibody was thought to be cancer specific, principally on the basis of this evidence, the antibody actually had the A1 Lewis d (Led) specificity. It reacted with approximately 2% of the random donor T-lymphocytes and with all six lymphocytes from donors who were A1 Led type without reacting to lymphocytes of any other type. The monoclonal antibody reactivity was also absorbed out by A1 Led red blood cells but not by red cells of other types. We conclude that the A1 Led antigen had been synthesized by the pulmonary carcinoma lines but not by the autologous lymphoblastoid line, resulting in disparity for this antigen. Since the combination A1 Led only occurs in 2% of the population, it is difficult to distinguish this type of antibody from tumor-specific antibodies.

Antibodies, Monoclonal↗
PubMed1982

Humoral immune response to intralymphatic immunotherapy for disseminated melanoma: correlation with clinical response.

Since September 1979, 44 stage III melanoma patients treated with intralymphatic immunotherapy (ILI) with an oncofetal antigen (OFA-I)--enriched tumor cell vaccine (TCV) had evaluable humoral immune responses and clinical follow-up. Fourteen patients (32%) had stabilization or regression of tumors or remained free of resected disease. The median survival was 17 months, compared with 6 months for controls (P less than 0.001). Humoral immune responses were monitored by immune adherence using an OFA-positive human melanoma cell line, M14, as target. Alloantibodies were removed by absorption with L14 lymphoblasts autologous to M14. Twenty-two patients (50%) developed elevated antibody titers within 4 months, and 12 of the 22 (55%) had no disease progression. In contrast, 20 of 22 patients (91%) who failed to develop elevated titers had disease progression (P less than 0.01). The median titer was significantly higher during the first 4 months in the group whose disease did not progress (P less than 0.04). This study demonstrated that ILI with allogeneic OFA-I-enriched TCV can induce objective tumor regression and prolonged survival in patients with disseminated melanoma. Furthermore, because the specific humoral immune response correlates with clinical results, immunization efficacy can be monitored within a short period of time, which should aid future efforts to achieve optimal immunotherapy.

Adult↗