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C M Townsend

Publications and source records attributed to C M Townsend.

At least 271 records · Page 15Linked to original sources

Establishment and characterization of an in vitro model system for human adenocarcinoma of the stomach.

Ten permanent clones derived from a single biopsy specimen of an untreated human adenocarcinoma of the stomach were established and characterized in vitro. Tissue culture growth properties, doubling times, plating efficiencies, growth fractions, cell cycle phase distributions, DNA indices, modal chromosome numbers, and ploidies were determined. Growth fractions were nearly 100%, and doubling times ranged from 23 to 37 hr. The plating efficiencies were generally high for tumor cells in culture, ranging up to 70%. Modal chromosome numbers varied from 45 to 48, with a wider range of variability in about 25% of the cells studied in each clone. In addition, the parent cell line (from which the clones were isolated) was shown to grow in athymic mice and to have the same histochemical and cytological characteristics as the specimen taken from the patient. It is important to characterize human tumor cells in vitro in this detailed manner, since they serve as excellent model systems for other studies involving the heterogeneous responses to drugs and radiation. The identification of mechanisms of drug sensitivity and resistance and the testing of drug and radiation combination treatment schedules in such in vitro systems can provide valuable insight into the design of clinical protocols for treatment of stomach cancer in humans.

Adenocarcinoma↗

Is staging laparotomy for Hodgkin's disease still justified?

The records of 50 consecutive patients who underwent staging laparotomy for Hodgkin's disease were reviewed. Preoperative clinical stages were as follows: stage I, 12 patients; stage II, 20 patients; and stage III, 18 patients. The accuracy of preoperative lymphangiography, confirmed pathologically, was 80 percent. Early experience with computed axial tomographic scanning is promising. The stages of 20 patients (40 percent) were changed by laparotomy, and their treatment was altered as a result. Fourteen patients were upstaged and 6 downstaged. Patient who were upstaged to stage IIIB and IV received chemotherapy; those downstaged to stage I and II received radiotherapy only. Sixty-seven percent of patients with preoperative constitutional symptoms (class B) had positive findings at laparotomy, compared with only 28 percent of patients without such symptoms (class A). Patients with mixed cellularity or lymphocyte-depleted histology were more likely to have positive findings at laparotomy. There were four complications and operative deaths. We conclude that staging laparotomy retains a useful role in the diagnosis and management of Hodgkin's lymphoma.

Adolescent↗

Gastrinoma.

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Adolescent↗

Use of 1,2:5,6-dianhydrogalactitol in studies on cell kinetics-directed chemotherapy schedules in human tumors in vivo.

Recently, it has been shown that 1,2:5,6-dianhydrogalactitol (DAG) can cause reversible alterations in cell cycle kinetics. Following treatment of CHO cells in vitro and Ehrlich ascites tumor cells in vivo, significant increases in the fraction of cells in S phase were observed to occur, and this was followed by an increase in the fractions of cells in G2 and mitosis. Treatments with S or G2-M phase-specific drugs at the peak enrichment times after DAG was given resulted in greater cell kills than when given by any other schedule. We have extended these kinetics-directed drug schedule studies to human tumors in vivo. The first phase was to determine whether DAG could be used to perturb cell kinetics in vivo as effectively in patients as it was in vitro. In 14 of 17 tumors studied, increases in the S-phase fractions were observed (ranging from 30 to 240% increases). The hr at which the S-phase peaks were observed (post-DAG treatment) was variable among the patients and among the tumors studied. However, this points out the value of obtaining actual cell kinetics data from serially biopsied tumors growing on the body surface and illustrates the importance that these data may have in helping to select an optimal time at which to give an S phase-specific drug. If such tumor cell kinetics-directed scheduling is ultimately shown to be effective, it will represent a means of individualizing therapy for a large fraction of tumor patients whose tumors are growing on or near the surface of the body. The tumors utilized in these studies were squamous carcinomas of the head and neck, skin, anus, and cervix; adenocarcinomas of the breast and rectum; and malignant melanoma. The second phase of this study will be to determine the tumor responses in patients treated with such kinetics-directed schedules.

Adenocarcinoma↗

Development of a transplantable model of pancreatic duct adenocarcinoma.

We report here the first development of a continuous cell line in tissue culture of an animal pancreatic duct adenocarcinoma that is histologically similar to human pancreatic duct adenocarcinoma. A primary pancreatic duct adenocarcinoma, induced in a male Syrian golden hamster after 23 weeks of weekly subcutaneous injection of N-nitrobis (2-hydroxypropyl)amine, was minced and injected subcutaneously into three hamsters. After 8 weeks, a single tumor was apparent. Subsequent passages of fragments into the cheek pouches were performed at 3- to 4-week intervals. After five passages, minced fragments of a tumor were placed in tissue culture. Colonies appeared by 7 days; an epitheloid cell line, without fibroblasts, was established by 60 days. Single-cell suspensions, injected into hamster cheek pouches or subcutaneously, produced tumors in a dose-dependent fashion. Spent culture medium of tissue culture cells and saline extracts of freshly excised tumors contained pancreatic oncofetal antigen-like activity.

Adenocarcinoma↗

Renal transplantation after thoracic duct drainage.

Forty-seven patients treated by at least 28 days of thoracic duct drainage (TDD) before cadaveric renal transplant are compared with 63 patients treated with standard immunosuppression. The TDD patients were begun on half the dosage of steroids, and at 30 days were receiving approximately two-thirds the dose that the non-TDD patients received. Acute rejection occurred in 35% of the TDD group, as compared with 61% of the non-TDD group. Graft survival in the TDD patients was twice as good as the non-TDD patients at all time intervals. The patient survival rates were not significantly different between the two groups. TDD pretransplant favorably affects cadaveric renal allograft survival for at least five years.

Adult↗

Infiltrating (intramuscular) lipomas and angiolipomas. A clinicopathologic study of six cases.

Infiltrating (intramuscular) lipomas and angiolipomas are benign mesenchymal tumors that usually appear as a deep, nontender mass within soft tissue, particularly in the extremities. The average tumor size in six cases studied was 11.2 cm (range, 2.0 to 22.0 cm). On gross examination, these tumors are circumscribed but unencapsulated, with infiltration of adjacent skeletal muscle. The correct preoperative diagnosis is seldom made, and the characteristic infiltrating pattern seen microscopically can lead to a mistaken diagnosis of sarcoma. Soft-tissue roentgenograms can be helpful in diagnosis and localization. The recommended mode of therapy is complete local excision with tumor-free soft-tissue margins. None of the six patients described here have experienced recurrence of tumor an average of two years after surgical resection. Prolonged follow-up is recommended, however, since inadequate resection can result in late tumor recurrence.

Adult↗

Breast lumps.

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Adenofibroma↗

Limb salvage using preoperative intraarterial adriamycin and radiation therapy for extremity soft tissue sarcomas.

Surgical therapy has been the accepted method for management of most soft tissue sarcomas of the extremities, although it has been associated frequently with local treatment failure. Even when local control was achieved, over 50% of the patients with soft tissue sarcomas eventually developed and succumbed to distant metastases of their disease. Therefore, single modality therapy for soft tissue sarcomas by operation alone results in an unacceptably high incidence of treatment failure. Fortunately, new adjuvant treatment techniques have been developed that seem to have activity against these neoplasms. It is the purpose of this article to discuss our experience with a number of these techniques.

Doxorubicin↗

Selective reduction of human tumor cell populations by human granulocytes in vitro.

Human peripheral blood granulocytes at a 10:1 effector cell:target cell ratio were shown by an in vitro semiquantitative staining procedure to reduce the number of human tumor cells, but not that of normal cells. Microscopic observations revealed that this selective reduction of tumor cells by granulocytes was a function of both detachment and cytolysis. The cytotoxic effect of granulocytes on the tumor cells was confirmed by a quantitative 5-[125I]iodo-2-deoxyuridine release assay. The data indicate that human granulocytes at a relatively low effector:target cell ratio (10:1) have the capacity to recognize and destroy human tumor cells in vitro.

Animals↗

A new in vivo assay of human lymphocyte-mediated immunity to melanoma.

Lymphocytes from melanoma patients more frequently inhibited the growth of human melanoma cells in the hamster cheek pouch than did lymphocytes from normal donors. Growth inhibition was accomplished with a much lower ratio of target cells to lymphocytes than in in vitro assays. The hamster cheek pouch assay can be used to study the relationship of blocking factors and humoral antibodies to cell-mediated immunity against human cancers.

Animals↗

In vitro evidence for increased cellular immunity to lung cancer antigen during Levamisole immunotherapy.

Levamisole, a potentiator of cell-mediated immunity, has been reported to increase survival in patients with resectable carcinoma of the lung. Cell-mediated immunity can be measured in vitro by the leukocyte migration inhibition test. We have previously reported that this test detects cell-mediated immunity to human lung tumor antigens. In the present studies, patients with lung cancer were treated with Levamisole. Their leukocytes were evaluated in the leukocyte migration inhibition assay before, during, and following Levamisole therapy. Small increases in cell-mediated immunity were observed when patients had a high pre-existing tumor immunity. When tumor-associated reactivity was absent prior to therapy, larger increases were measured. Although Levamisole is a nonspecific immunostimulant, these data indicate that in vitro anti-tumor immune responses are enhanced by Levamisole therapy. Augmentation of cell-mediated immunity to tumor antigens may explain the clinical benefits of Levamisole therapy.

Adenocarcinoma↗

Skeletal and soft tissue sarcomas. Treatment with adjuvant immunotherapy.

Because there is evidence for an active immunologic response against sarcoma, a clinical trial of adjuvant immunotherapy using bacillus Calmette-Guérin (BCG) and tumor cell vaccine was begun. Eleven of 18 patients with localized soft tissue sarcoma who received immunotherapy are free of disease, compared to only 5 of 15 treated by operation alone who are free of disease. Furthermore, immunotherapy also prolonged the median disease-free interval from 7.3 months to 15 months in the patients who experienced recurrence of their disease.

BCG Vaccine↗

High dose methotrexate therapy of solid tumors: observations relating to clinical toxicity.

In clinical studies performed during 111 infusions of high dose methotrexate (MTX) we have evolved a clinical and laboratory protocol which permits such therapy without prohibitive risk to the patient. The plasma MTX data obtained indicate that pharmacokinetic disposition is dose related during these infusions and that such data are useful in identifying patients at risk from serious toxicity.

Adolescent↗

Results of BCG adjuvant immunotherapy for melanoma of the head and neck.

The present study was performed to determine if postoperative systemic BCG adjuvant immunotherapy would improve survival in patients with pathologic stage II melanoma of the head and neck. Seventeen of twenty-five (68 per cent) patients treated with BCG are free of disease, whereas only seven of seventeen (40 per cent) patients treated by radical neck dissection alone are free of disease. Clark's technic for determining the level of invasion of the primary lesion was used to predict the presence of metastatic tumor in regional lymph nodes. Results indicate that patients with pathologically confirmed lymph node metastases from melanoma of the head and neck benefit from postoperative BCG adjuvant immunotherapy.

BCG Vaccine↗

Limb salvage from a multidisciplinary treatment approach for skeletal and soft tissue sarcomas of the extremity.

Multimodality management of extremity skeletal and soft tissue sarcomas with preoperative intra-arterial Adriamycin and radiation therapy, radical surgical resection and postoperative chemotherapy or chemo-immunotherapy has resulted in preservation of a functional extremity in 13 or 14 patients. Seven of 8 patients with Stage IIIA and IIIB soft tissue sarcomas, managed with preoperative intra-arterial Adriamycin and radiation therapy, followed by en bloc soft tissue resection and 6 patients with bone sarcomas managed by preoperative treatment, followed by bone resection and replacement with cadaver bone allografts, remained free of disease from 4 to 34 months. The results of the combined modality approach were significantly better than the results obtained in patients managed by surgical resection alone, or by combination of operation with another single modality, both in terms of short term-recurrence free survival and salvage of a functional extremity.

Bone Neoplasms↗