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Biomedical subjects

J A Greager

Publications and source records attributed to J A Greager.

At least 37 records · Page 2Linked to original sources

Detection of pulmonary metastases in a patient with synovial cell sarcoma using In-111 labeled monoclonal antibody 19-24.

A 35-year-old man was diagnosed in 1984 as having a synovial cell sarcoma of his right wrist without evidence of metastatic spread. The patient underwent regional hyperthermic chemoperfusion, wide-field excision, post-operative radiation therapy and systemic adjuvant chemotherapy. In 1986 and in 1987, because of new lesions found on chest radiographs, the patient underwent bilateral staging thoracotomies with resection of pulmonary metastases, followed by chemotherapy and radiotherapy. Later in 1987, a chest radiograph showed a large left hilar mass and multiple bilateral pulmonary nodules. Computerized tomography of the chest demonstrated a left hilar mass and two nodules in the right lower lung, raising the possibility of recurrent pulmonary metastatic cancer. As a diagnostic procedure, In-111 labeled monoclonal antibody (Mab) 19-24, produced against a human malignant fibrous histiocytoma, was infused intravenously, and 48-hour images revealed focal areas of increased uptake corresponding to the lesions seen on CT. At surgery, the lesions were confirmed to be synovial cell sarcoma. Imaging with Mabs specific for sarcoma may be particularly useful in sarcoma patients in whom there is clinical uncertainty regarding the nature of pulmonary lesions. In this case, the Mab was useful in distinguishing tumor deposits from postsurgical scarring and helped to guide subsequent surgery and treatment.

Adult↗

Leiomyoblastoma of the jejunum.

A 35-year-old male with the symptoms of acute abdomen proved to have a jejunal leiomyoblastoma. We renew recommendations for treatment by wide excision and regional lymphadenectomy.

Abdomen, Acute↗

Merkel cell tumor of the back detected during pregnancy.

Merkel cell tumor is an unusual, aggressive malignancy of skin that has been considered to be derived from cutaneous Merkel cells. We are reporting a case of Merkel cell tumor overlying the left scapula with metastases to the thoracic spine and pleura. The tumor was found incidentally in a 23-year-old pregnant black woman. The tumor recurred locally 5 months after initial wide excision. Subsequently, a second wide excision of the recurrent tumor with ipsilateral axillary dissection was performed. The course of the disease was complicated by local recurrence and formation of distant metastases to pleura and spine. At the end-stage of the disease, the patient was found to have a cardiac murmur, and echocardiography revealed a mass in the anterior wall of the right ventricle that was suspicious for a metastatic lesion. The patient expired from extensive distant metastases 23 months after diagnosis.

Adult↗

Localization of pulmonary human sarcoma xenografts in athymic nude mice with indium-111-labeled monoclonal antibodies.

In order to study localization of metastatic tumors with a radiolabeled monoclonal antibody, a pulmonary metastases model was devised in athymic mice. Metastatic pulmonary sarcoma colonies were verified by histological examination. A murine monoclonal antibody (MAb 19-24) directed against a human sarcoma antigen was labeled with indium-111 (111In) by use of the linker 1-(p-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (SCN-Bz-DTPA). MAb P3 was similarly labeled as a negative control. In the group given MAb 19-24, the percent injected dose per gram lung tissue bearing tumor colonies (30.1%, 29.6%, and 27.7% on Days 1, 2, and 3, respectively) was significantly (p less than 0.05) higher than in those receiving MAb P3. Hepatic activities of both 111In-MAb 19-24 and 111In-MAb P3 were low. The lungs with tumor colonies demonstrated clearest images on Day 3. The specific binding of 111In-SCN-Bz-DTPA-labeled MAb 19-24 to pulmonary xenografts without appreciable liver uptake indicates that it may be useful in the clinical localization of pulmonic metastatic lesions.

Animals↗

Breast cancer screening in an urban black population. A preliminary report.

Breast cancer is a major cause of death among black women. At Cook County Hospital in Chicago, a hospital serving a predominantly black population, only 31% of breast cancers were localized at the time of diagnosis in the years 1980-1983. A survey of patient records in the largest primary care clinic in the hospital revealed that only 2% of eligible patients had received mammograms in 1982. A nurse-run breast cancer detection program was begun in mid-1983. Since that time the proportion of women who have received periodic breast examinations has increased from 26% to 46% (P less than 0.001) and periodic mammograms have increased from 2% to 41% (P less than 0.001). The proportion of women having received breast self-examination teaching increased from 10% to 58% (P less than 0.001). The proportion of localized breast cancer was significantly greater for those women whose cancer was diagnosed through the screening program (44 of 72, 61%) compared to other clinical areas (71 of 213, 33%) in the years 1984 through 1986 (P less than 0.001). There has been a significant increase in the percentage of localized breast cancer at Cook County Hospital comparing 1980-1983 statistics (31%), before the Breast Cancer Detection Program was fully established, with 1984-1986 statistics (40%) (P less than 0.02).

Black or African American↗

Improved sarcoma imaging and reduced hepatic activity with indium-111-SCN-Bz-DTPA linked to MoAb 19-24.

A murine monoclonal antibody (MoAb 19-24) directed against a human sarcoma antigen was prepared and labeled with 111In by use of the linker 1-(p-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid (SCN-Bz-DTPA). Imaging and biodistribution of this radioimmunocomplex were evaluated. MoAb P3 was similarly labeled as a negative control. Of 24 athymic mice bearing s.c. human fibrosarcoma, 12 received 10 microCi of [111In]MoAb 19-24 and 12 received 10 microCi of [111In]MoAb P3. The mice were imaged at 24, 48, 68, or 168 hr, after i.p. injection. Region of interest and biodistribution analysis showed maximum localization of MoAb 19-24 in the tumor at 72 hr with maximum liver localization of 24 hr. Analysis of MoAb P3 showed maximum tumor and liver activity at 24 hr. Tumor specificity studies were also conducted in three nude mice bearing a sarcoma in the left flank and a Burkitt's lymphoma in the right flank. Selective uptake was seen in the sarcoma but not in the lymphoma. The excellent uptake of [111In]SCN-Bz-DTPA-MoAb 19-24 in sarcoma without appreciable liver activity indicates that it may be a useful tumor imaging agent in man.

Animals↗

Soft tissue sarcomas of the adult thoracic wall.

Forty-nine adult patients with soft tissue sarcomas of the thoracic wall have been treated by the Division of Surgical Oncology at the University of Illinois. Fibrosarcoma was the most common histologic type (20%). Patients with dermatofibrosarcoma protuberans had the longest mean overall survival time (150.8 months). The mean overall survival time for all patients was 98.2 months, and the disease-free 2-, 5-, and 10-year survival rates were 68%, 51%, and 34%, respectively. Wide excision was the treatment of choice; selected patients also received adjuvant radiotherapy, chemotherapy, or both. In all 10-year survivors, the sarcomas were low grade and well differentiated, or were less than or equal to 5.0 cm in diameter. Aggressive treatment afforded these patients good long-term results.

Adult↗

Localization of human sarcoma with radiolabeled monoclonal antibody. A preliminary study.

The early localization of recurrent or metastatic sarcoma remains a challenging clinical problem. 125I-labeled monoclonal antibody (Mab) 19-24, produced in our laboratories against a human malignant fibrous histiocytoma, has been evaluated for detection of locally recurrent or metastatic disease in selected sarcoma patients. In vitro testing indicated various degrees of positive Mab reactivity with most sarcoma types, and low but significant reactivity with some nonsarcoma tumors and several normal tissues, including liver. The iodine-labeled Mab had an immunoreactivity of 90% and a high binding constant (8.1 X 10(9) M-1). Biodistribution studies of radioisotope in sarcoma patients showed rapid clearance of radiolabeled from the blood and uptake in tumor deposits, liver, and spleen. A differential in radioactivity kinetics between liver and tumor was also found. Serial patient scanning determined optimal imaging time to be between 24 and 48 h after i.v. infusion of the radiolabeled Mab. Analysis of tissues obtained during surgery (including a dual antibody-label study using a nonspecific Mab) showed selective localization of the Mab into the sarcoma deposits. Radiolabeled Mab shows potential as a clinically useful tool for localization of sarcoma deposits.

Adult↗

Adult head and neck soft-tissue sarcomas.

Adult soft tissue sarcomas of the head and neck are so rare that an accurate diagnosis and appropriate therapy are frequently delayed. A retrospective study of such patients seen at the University of Illinois over the last 15 years has helped to better characterize this disease entity. Patients with sarcoma of the neck, the most common anatomic location (37 per cent), had the highest 5-year disease-free survival rate (67 per cent). Fibrosarcoma was the most common histologic type (25 per cent). Aggressive fibromatosis patients experienced the longest mean survival time (93 months). The disease-free 2-year, 5-year, and 10-year survival rates were found to be 68, 54, and 28 per cent, respectively. Wide excision was the treatment of choice, with adjuvant radiotherapy or chemotherapy, or both, used in selected patients. The sarcomas of all long-term survivors were either well-differentiated or 5.0 cm or less in diameter. It is evident that aggressive therapy of adult head and neck sarcomas can provide good long-term results.

Adult↗

Soft tissue sarcomas of the distal extremities.

Multimodality therapy and limb salvage procedures constitute a significant advance in the treatment of soft tissue sarcoma of the extremity. The applicability of these procedures to soft tissue sarcoma of the distal extremities was evaluated in a retrospective study of 159 such cases treated during a 10-year period. Thirty-seven patients were treated by operation alone, 57 had operation and adjuvant chemotherapy, and 65 had multimodal therapy. The distal extremities are unusual sites for soft tissue sarcomas and accounted for only 20% of our patients with sarcoma. The majority of patients were younger than 50 years and the sex distribution was approximately equal. The major histologic types were synovial cell sarcoma (18.2%), fibrosarcoma (15%), liposarcoma (13.8%), and rhabdomyosarcoma (13.8%). The 5-year survival rate was 72% with multimodality therapy, 72% for operation and chemotherapy, and 51% for operation alone. The local recurrence rate was 13% with operation alone, 9% with operation and adjuvant chemotherapy, and 12% with multimodality therapy. Based on our review, wide local excision and adjuvant chemotherapy proved to be as effective as multimodal therapy.

Adult↗

Soft tissue sarcomas of the adult head and neck.

From 1969 to 1983, 53 adult patients with head and neck soft tissue sarcomas were evaluated and treated by the Division of Surgical Oncology at the University of Illinois. The most common anatomic location was the neck (36%), and these patients had the highest 5-year disease-free survival rate (67%). Fibrosarcoma was the most common histologic type (26%); patients with aggressive fibromatosis had the longest mean survival time (93 months). The mean overall survival time was 58.7 months, and the disease-free 2-year, 5-year, and 10-year survival rates were 68%, 54%, and 28%, respectively. Wide excision was the treatment of choice, with adjuvant radiotherapy or chemotherapy, or both, used in selected patients. In all of the long-term survivors, the tumors were either well-differentiated or less than or equal to 5.0 cm in diameter. It is apparent that aggressive therapy of such tumors can provide good long-term results.

Adolescent↗

Pelvic exenteration.

Sixty-eight patients at the University of Illinois, Cook County, and the West Side Veterans Administration hospitals underwent pelvic exenteration for advanced pelvic malignancies during the 15-year period from 1969 to 1984. Thirty-two had colorectal cancers, eleven cervical, seven bladder, and six vulvar; in twelve the cancers were in miscellaneous pelvic sites. Forty-five exenterations were done with intent to cure, and twenty-three for palliation of patients with bulky, necrotic tumors that had caused symptomatic fistulae, local sepsis, chronic bleeding, or severe localized pain. The total 30-day postoperative mortality was 4.4% (3/68). The 5-year survival rate of patients who underwent curative exenteration was 33% (median 27 months). Pelvic exenteration appears to be a feasible surgical procedure for a variety of advanced malignancies as well as for palliation of severely symptomatic patients.

Adult↗

Localization of radiolabeled monoclonal antibody in a human soft tissue sarcoma xenograft.

125I-labeled monoclonal antibody 19-24 (mouse isotype IgG1) was evaluated for its potential usefulness in the clinical radioimmunodetection of sarcoma. The antibody reacts with a cell surface antigen preferentially expressed in many human soft tissue and bone sarcomas. Chromatographic and electrophoretic analyses indicated that the labeled preparation was relatively pure. Binding studies in vitro demonstrated that specificity for antigen was retained after iodination and indicated that the labeled antibody possessed an immunoreactivity in excess of 90% and a binding constant of 8.1 X 10(9) M-1. When administered to athymic NCr-nu/nu mice bearing 1-cm diameter human fibrosarcoma HT-1080 xenografts, the labeled antibody preferentially localized in tumor deposits. Maximum tumor-to-blood radioactivity ratios (2.2-3.4) were obtained 7 days after antibody injection. Specificity of the localization was confirmed with a control mouse IgG1 antibody and by using a nonreactive xenograft. Distinct tumor images were obtained by gamma camera without the use of subtraction techniques, demonstrating the possible clinical utility of the labeled antibody.

Animals↗

Metastatic cancer from an undetermined primary site.

The charts of 285 patients diagnosed as metastatic cancer from an undetermined primary site were reviewed. An attempt was made to characterize this disease entity more specifically, and to evaluate the various modes of therapy utilized in such patients. Adenocarcinoma is the most common histologic type overall; squamous cell carcinoma is most common in 5-year survivors. Lymph nodes are the most common metastatic site overall and in 5-year survivors. The mean overall survival is 8.69 months with 8.7% 2-year survivors and 2.8% 5-year survivors. Surgery alone, radiation alone or in combination, and chemotherapy alone or in combination were utilized in these patients with 5-year survivals of 11, 3.7, and 1.1%, respectively. The 5-year survivors all had therapy initiated immediately after histologic diagnosis and medical workup, and all of their tumors were less than 8 cm in diameter. In view of this data, patients with metastatic cancer from an undetermined primary site should always be considered for early, aggressive therapy.

Adenocarcinoma↗

Antitumour effects of tilorone hydrochloride on the in vivo growth of chemically induced and spontaneously arising rat tumours.

Inhibition of subcutaneous tumour growth, following treatment with tilorone hydrochloride, was observed with two transplantable methylcholanthrene-induced rat sarcomas (Mc7, Mc4), but similar drug treatment was ineffective against two rat hepatomas induced by dimethylaminoazobenzene (D23, D30). Successful therapy of sarcoma Mc7 and Mc4 subcutaneous growth was not accompanied by the development of specific antitumour immunity, although with hepatoma D30, which grew out following tilorone hydrochloride treatment, specific immunity was demonstrated, indicating that drug treatment does not prevent the initiation of an antitumour response during progressive tumour development. Under defined experimental conditions tilorone hydrochloride also prevented pulmonary metastases from a subcutaneous tumour graft of epithelioma SP1 and mammary carcinoma SP22, as measured by an increased survival or treated rats.

Adenoma↗

Chemotherapy, BCG, and serum from tumor-bearing mice: comparative effects on growth and spread of mouse Lewis lung cancer.

In 101 mice, Lewis lung tumor (25 mg apiece) was implanted subcutaneously in the right hind limb and the mice separated into various groups and protocols to test treatment with immunotherapeutic and chemotherapeutic agents. In those treated intralesionally with BCG, the growth of primary tumor was retarded (P smaller than or equal to .05). Tumor growth in animals treated with systemic BCG and serum from tumor-bearing mice was not different from controls. In 14 of 20 mice treated with chemotherapy (semustine and cyclophosphamide), there was no primary or metastatic growth (P smaller than or equal to .01). The observations show that this sort of systemic immunotherapy had no effect on mouse Lewis lung tumor, that intralesionally there was a retarding effect of BCG (although it did not influence metastases), and that this protocol of chemotherapy was strikingly effective.

Animals↗