Malignant schwannoma of the head and neck.
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Adolescent↗
Biomedical subjects
J A Greager
Publications and source records attributed to J A Greager.
Newcastle disease virus selectively kills human tumor cells.
Newcastle disease virus (NDV), strain 73-T, has previously been shown to be cytolytic to mouse tumor cells. In this study, we have evaluated the ability of NDV to replicate in and kill human tumor cells in culture and in athymic mice. Plaque assays were used to determine the cytolytic activity of NDV on six human tumor cell lines, fibrosarcoma (HT1080), osteosarcoma (KHOS), cervical carcinoma (KB8-5-11), bladder carcinoma (HCV29T), neuroblastoma (IMR32), and Wilm's tumor (G104), and on nine different normal human fibroblast lines. NDV formed plaques on all tumor cells tested as well as on chick embryo cells (CEC), the native host for NDV. Plaques did not form on any of the normal fibroblast lines. To detect NDV replication, virus yield assays were performed which measured virus particles in infected cell culture supernatants. Virus yield increased 10,000-fold within 24 hr in tumor and CEC supernatants. Titers remained near zero in normal fibroblast supernatants. In vivo tumoricidal activity was evaluated in athymic nude Balb-c mice by subcutaneous injection of 9 x 10(6) tumor cells followed by intralesional injection of either live or heat-killed NDV (1.0 x 10(6) plaque forming units [PFU]), or medium. After live NDV treatment, tumor regression occurred in 10 out of 11 mice bearing KB8-5-11 tumors, 8 out of 8 with HT-1080 tumors, and 6 out of 7 with IMR-32 tumors. After treatment with heat-killed NDV no regression occurred (P less than 0.01, Fisher's exact test). Nontumor-bearing mice injected with 1.0 x 10(8) PFU of NDV remained healthy. These results indicate that NDV efficiently and selectively replicates in and kills tumor cells, but not normal cells, and that intralesional NDV causes complete tumor regression in athymic mice with a high therapeutic index.
Animals↗
The extensor carpi radialis longus muscle flap for anterior elbow coverage.
A muscle group resection for treatment of malignant fibrous histiocytoma of the distal arm exposed a 15 cm length of radial nerve. The soft tissue defect and radial nerve were covered with an extensor carpi radialis longus muscle island flap. The proximal dominant vascular pedicle enabled extensive mobilization and transposition of this muscle to cover the defect while preserving normal elbow, radial nerve, and hand function. Because of its ease of elevation, extensive arc of rotation, and its expendability, the extensor carpi radialis longus muscle flap should be considered as an option for reconstruction of defects about the elbow joint.
Elbow↗
Carcinoma of the extrahepatic bile ducts.
Thirty-seven patients with carcinoma of the extrahepatic bile ducts (EHBD), diagnosed over 14 years from 1974 to 1987, were studied retrospectively. The most common presenting complaint was jaundice, followed by abdominal pain, nausea and vomiting, and weight loss. The majority of EHBD carcinomas were located at the middle third of the bile duct (43.2%), followed by upper third bile duct (37.8%), and lower third bile duct (18.9%). The resectability of the surgically managed group was 44.4%. The most common histologic type was adenocarcinoma. The 30-day postoperative mortality was 30.6%. The mean overall survival of the patients with EHBD carcinoma was 11.2 months. Patients with distal third tumors had the best prognosis with a mean overall survival of 16.0 months. The mean overall survival of patients with upper-third and middle-third tumors were 10.9 months and 9.4 months. A high index of suspicion of the disease as well as earlier, aggressive surgery may improve patient survival.
Adenocarcinoma↗
Primary carcinoma of the gallbladder.
Seventy-four patients with primary carcinoma of the gallbladder, diagnosed over 18 years from 1969 to 1987, were studied retrospectively. The most common presenting complaint was abdominal pain, followed by jaundice and weight loss. Surgery was performed in 61 patients and of these patients, only two had accurate preoperative diagnosis which was made by ultrasonography. Twelve of the 13 patients who were treated medically had the disease diagnosed at autopsy. One of the 13 patients had the diagnosis of gallbladder cancer by the findings of ultrasonography and abdominal computed tomography (CT) scanning. The resectability of the surgically managed group was 36.1%, and the majority of patients with advanced tumors (82.2%) were deemed unresectable. The most common histologic type was adenocarcinoma. Liver was the organ most commonly invaded (76.5%) by direct extension and/or metastases, followed by regional lymph nodes (52.9%). The overall 5-year survival rate was 5.4%. A high index of suspicion of the disease, intraoperative examination of gallbladder specimen, and earlier, more aggressive surgical treatment may improve patient survival.
Adenocarcinoma↗
Localization of human sarcoma with radiolabeled monoclonal antibody--a follow-up report.
A group of 16 sarcoma patients with suspected advanced disease were studied with a radiolabeled anti-sarcoma monoclonal antibody (mAb 19-24) in an attempt to localize tumor deposits. All 16 patients received 125I-mAb 19-24 and then had external-probe analysis and imaging performed. Confirmation of tumor deposits was done at surgery or by autopsy. Tissues were studied in surgical patients when possible and analyzed for radioactivity, and tumor-to-blood ratios ranged from 0.6 to 36.8. In conjunction with the patients previously studied, probe results had an overall sensitivity of 83.3% and an overall specificity of 100%; scintigraphic results showed an overall sensitivity of 78.9% and an overall specificity of 100%. Radiolabeled mAb 19-24 may be developed into a useful tool for clinical immunodetection of sarcoma deposits.
Adolescent↗
Hypophysectomy inhibits the synthesis of tumor necrosis factor alpha by rat macrophages: partial restoration by exogenous growth hormone or interferon gamma.
We recently demonstrated that GH and interferon-gamma (IFN gamma) act in a similar manner to prime macrophages in vitro and in vivo for enhanced superoxide anion release. In this report we investigated the physiological role of the pituitary gland and GH in in vivo priming of resident peritoneal macrophages for the synthesis of tumor necrosis factor-alpha (TNF alpha) in vitro. Compared to normal rats, hypophysectomized animals had an 83% reduction in macrophage production of TNF alpha after in vitro stimulation with lipopolysaccharide. Sham operation had no significant effect on the ability of macrophages to secrete TNF alpha in response to lipopolysaccharide. Both native pituitary-derived porcine GH (48 micrograms/rat.9 days) and native pituitary-derived rat GH (96 micrograms/rat.9 days) more than tripled the in vitro production of TNF alpha by macrophages from hypophysectomized rats (342 and 358 vs. 112 U/mg protein for placebo-treated rats, respectively). Each of these preparations of GH also increased growth more than 6-fold in hypophysectomized rats (32 and 30 g vs. 5 g in placebo controls). Heat inactivation of native pituitary-derived porcine GH significantly reduced its in vivo ability to augment both TNF alpha synthesis by macrophages and body growth. Recombinant rat IFN gamma (2000 U/rat.9 days) more than tripled the production of TNF alpha by macrophages from hypophysectomized rats (343 vs. 112 U/mg protein). In contrast to its in vivo effects, addition of GH in vitro to macrophages from hypophysectomized rats did not prime these cells for the synthesis of TNF alpha, indicating an indirect mechanism of action for GH. To further test the biological relevancy of GH with respect to synthesis of TNF alpha, hemorrhagic necrosis of TNF alpha-sensitive murine methyl-cholanthrene-induced tumors was assessed in pituitary-intact mice. Native porcine GH (133 micrograms/mouse.7 days) significantly augmented both the necrosis to tumor ratio and the hemorrhage to tumor ratio. These findings establish the physiological relevance of the pituitary gland and GH in the priming of macrophages for TNF alpha synthesis.
Animals↗
Results of treatment of stage I-III breast cancer in black Americans. The Cook County Hospital experience, 1973-1987.
Whether the prognosis for black women with breast cancer differs from that of nonblack women remains controversial. The treatment results of 526 black women who received definitive therapy for Stage I-III breast cancer at Cook County Hospital, 1973 through 1987 are presented. The 5-year and 10-year projected survival rates for 272 node-negative patients (83.9% and 76.6%, respectively) and for 72 node-positive nonadjuvant treated patients (58.1% and 35.2%, respectively) are similar to those reported in the literature for nonblack patients. Adjuvant therapy improved the projected relapse-free (P = 0.0744) and overall survival curves (P = 0.0448) for 182 node-positive patients compared with nonadjuvant patients. The greatest benefit was seen for patients greater than 50 years of age with one to three positive nodes. The incidence of estrogen and progesterone receptors was found to be similar to those reported for nonblack patients. Once breast cancer has been diagnosed and appropriately treated, there appear to be few differences in the natural history of breast cancer between black and nonblack patients.
Adenocarcinoma↗
In vivo effects of recombinant interferon-gamma: augmentation of endotoxin-induced necrosis of tumors and priming of macrophages for tumor necrosis factor-alpha production.
Recombinant interferon-gamma (rIFN-gamma) is currently undergoing clinical trials in cancer patients. In this paper, we assessed the in vivo antitumor effects of this lymphokine in rodents. Recombinant murine IFN-gamma or control medium was injected intraperitoneally for 5 days into mice with subcutaneous Meth A tumors. An injection of a suboptimal dose of endotoxin (2 micrograms) on the fifth treatment day caused significant necrosis of tumors in the IFN-gamma-treated group while causing essentially no necrosis of tumors in the control group. Next, we examined macrophages isolated from rats treated for 9 days with either IFN-gamma or saline. Endotoxin stimulated release of significantly higher amounts of TNF-alpha from macrophages from the IFN-gamma-treated group compared to macrophages from the control group. A polyclonal antiserum against recombinant murine TNF-alpha abrogated all of the TNF cytotoxic activity from these rat macrophage supernatants, while control rabbit serum had no effect. These results provide strong evidence that rIFN-gamma can prime macrophages in vivo for TNF-alpha synthesis.
Animals↗
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↗
Malignant schwannoma (neurofibrosarcoma) metastatic to spine. Surgical decompression and stabilization.
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Adult↗
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↗