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J A Greager

Publications and source records attributed to J A Greager.

At least 19 recordsLinked to original sources
PubMed2000

Female sex hormones modulate the function of LPS-treated macrophages.

PROBLEM: To study the effects of estradiol (E2) or progesterone on macrophage function in the presence of lipopolysaccharide (LPS). METHOD OF STUDY: Male rat peritoneal macrophages were treated in vitro with 0.1 microg/mL of LPS and E2 or progesterone. RESULTS: At 10(-2) ng/mL, E2 significantly (P < 0.05; n = 6) enhanced tumor necrosis factor (TNF) release by LPS-treated macrophages. TNF release was significantly (P < 0.05; n = 6) inhibited by 10(2) ng/mL or 10(3) ng/mL of E2 and by progesterone at less than 10(-3) ng/mL or greater than 10(-1) ng/mL. E2 (10(-4) and 10 ng/mL) and progesterone (10(-6)-10(-4) ng/mL and 10(2) ng/mL) each significantly (P < 0.05, n = 8) enhanced H2O2 release by LPS-treated macrophages. E2 ( < 10(-2) and > 10 ng/mL) and progesterone (10(-7)-10(4) ng/mL) each significantly inhibited (P< 0.05; n = 6) NO2- release by LPS-treated macrophages. CONCLUSIONS: Exposure to LPS tended to diminish the effects of E2 and to enhance the effects of progesterone on the parameters determined here. Such LPS-associated alterations in the dose-response profile of macrophages to female sex hormones may contribute to gender-related differences in the immune response under normal and pathological conditions.

Animals↗
PubMed1997

Experimental pulmonary sarcoma metastases in athymic nude mice.

BACKGROUND: Pulmonary metastases remain a challenging therapeutic problem in the treatment of patients with soft tissue sarcomas. A pulmonary sarcoma metastases animal model might facilitate studying the biology of metastases, diagnosis, and treatment modalities of this disease. Intravenous injection of human tumor cells into nude mice has been reported using human melanoma and colorectal carcinoma to produce pulmonary metastases. Human fibrosarcoma cells were intravenously administered to athymic nude mice to simulate clinical pulmonary metastases. METHODS: HT-1080 human sarcoma cells derived from a poorly differentiated fibrosarcoma were used to prepare inoculant at a concentration of 5 x 10(6) cells per ml. Male athymic nude mice were injected subcutaneously with 1 x 10(6) cells in the right hind flank and sacrificed when the tumors were 1-2 cm in diameter. Age- and weight-matched athymic nude mice were intravenously injected through tail veins with 10(4), 10(5), and 10(6) cells. The mice were sacrificed at 7, 14, and 21 days after intravenous injection of the tumor cells. Tissues were histologically examined for pulmonary metastases. RESULTS: Neither gross nor microscopic spontaneous metastases were found in any of the animals that received subcutaneous xenografts, and no pulmonary metastases were identified in mice intravenously injected with < 10(5). All mice inoculated with 10(6) cells developed tumor colonies in the lungs, which were microscopically evident as early as day 7. No metastases were found in the liver, spleen, heart, or other tissues. In a second experiment, HT-1080 cells were injected at 10(6); all animals developed lung metastases and died of lung tumor involvement, with an average survival of 35 days. CONCLUSIONS: These experiments identify a sarcoma animal pulmonary metastases model that is readily available, relatively inexpensive, easily utilized, and reproducible.

Animals↗
PubMed1997

Binding and internalization of anti-sarcoma IgG and IgM antibodies.

A variety of monoclonal antibodies directed against tumor cell surface antigens have been employed for tumor detection and delivery of toxins and radioisotopes to tumors in situ. The sequence of events following antibody binding to tumor cells may be critical to the success or failure of tumor imaging or therapy. Using indirect immunofluorescence, we have examined the binding and internalization of two different monoclonal antibodies (19-24 and MFH 4.10) by HT-1080, a cultured human sarcoma cell line. MAb 19-24 (IgG1) and MAb MFH 4.10 (IgM) are directed against surface antigens on cells from human malignant fibrous histiocytoma (MFH). For both of these antibodies, the initial binding on the surface of HT-1080 cells at 4 degrees C was uniform. After binding secondary fluorescent antibody, monoclonal antibodies underwent rapid internalization at 37 degrees C. Surface-bound antigen-antibody complexes were completely cleared from the cell surface in 30-60 min. In the absence of secondary fluorescent antibody, MAb 19-24 remained bound to the cell surface at 37 degrees C for up to 20 hr without being released or internalized. However, under these same conditions MAb MFH 4.10 was internalized completely within 30 min by HT-1080 cells and did not subsequently return to the cell surface. Such differences in the mechanisms of binding and uptake for these two antibodies may have significant implications for their future clinical or therapeutic uses.

Animals↗
PubMed1995

Steroid sex hormones regulate the release of tumor necrosis factor by macrophages.

Generally, females have been found to have a heightened immune response and a concomitantly higher incidence of autoimmune diseases compared to males. We have used male rat peritoneal macrophages (M phi) to study the effect of female sex hormones on tumor necrosis factor (TNF) release. The amount of TNF released by macrophages (M phi) exposed to 10(-2) and 10(-3) ng/ml of 17 beta-estradiol (E2) (35.1 +/- 7.3 and 23.2 +/- 2.5 units/ml, respectively) was significantly (P < 0.05; n = 9) greater than that released by untreated M phi. Progesterone (P) also significantly (P < 0.05; n = 8) stimulated a maximal TNF release (24.4 +/- 2.8 units/ml TNF) at 10(-2) ng/ml. On the other hand, the amount of TNF released by M phi exposed to E2 or P at concentrations greater than 10(-1) or less than 10(-4) ng/ml was significantly (P < 0.05) reduced compared to untreated controls. In contrast, testosterone did not significantly affect TNF release at any concentration. Within the physiological range of E2 and P concentrations, TNF release from M phi is finely regulated and dramatically affected by relatively small changes in hormone concentrations.

Animals↗
PubMed1994

Endoscopically defined treatment strategies in patients with locally advanced esophageal cancer.

Sixty-five consecutive, locally advanced esophageal cancer patients were treated by the West Side Medical Center Esophageal Service at the Cook County and University of Illinois hospitals. Each patient was prospectively evaluated with multiple endoscopies including esophagogastroduodenoscopy, bronchoscopy, nasopharyngoscopy, and laryngoscopy. Twenty-four patients (37%) had endoscopic findings that significantly altered therapeutic regimens. Patients identified as having an obvious or impending esophageal fistula or poor performance status were treated in a palliative fashion. Forty (61.5%) patients were considered candidates for treatment with multimodal therapy which included radiation, chemotherapy, and surgery. There was a response rate of 82.5% and a 1-year disease-free survival of 88.9% which was statistically significant when compared to the other patient treatment groups. These data illustrate the necessity of multiple endoscopic evaluation of locally advanced esophageal cancer patients for stratification into appropriate treatment groups. Aggressive treatment afforded selected patients excellent relief of presenting symptomatology, as well as an improved, more acceptable, disease-free survival.

Adenocarcinoma↗
PubMed1994

Fibrosarcoma of the head and neck.

Fourteen adult patients with fibrosarcoma of the head and neck were treated by the Division of Surgical Oncology at the University of Illinois and Cook County Hospitals. All patients had a mass in the head and neck area, and four patients (29%) had tumors in a burn scar or in a field of irradiation. The 2-, 5-, and 10-year disease-free rates were 57%, 57%, and 50%, respectively, with overall survivals of 79%, 71%, and 57%, respectively. The median survival was significantly higher for patients with low-grade tumors than for patients with high-grade lesions (P < 0.05). Wide surgical excision was the mainstay of therapy, with re-excision considered for some patients with locally recurrent disease. Aggressive treatment can afford fibrosarcoma patients good long-term therapeutic results.

Combined Modality Therapy↗
PubMed1994

The esophageal mucosal resistance: structure and function of an unique gastrointestinal epithelial barrier.

The purpose of this review is to delineate the factors that contribute to the innate epithelial resistance of the esophageal mucosa when challenged with potentially damaging intraluminal aggressive factors that are present as a result of gastroesophageal reflux. The ability of this mucosa to act as an effective barrier is dependent on the structural complexity of its 20 to 30 cell layer-thick stratified squamous epithelia, its convoluted intercellular spaces (paracellular resistance), and the cellular ion transport mechanisms that maintain intracellular homoestasis (cellular resistance). Because H+ ion is the most important damaging agent in the gastroesophageal refluxate, we have primarily focused on mechanisms that impede or prevent H+ ion entry into the mucosa ("pre-epithelial" and "mucosal factors"), cellular mechanisms that allow cells to maintain their intracellular pH in the presence of an external acid environment ("cellular factors"), mechanisms that limit continued mucosal and cellular injury ("submucosal factors") and reparative processes that come into play after damage has occurred.

Animals↗
PubMed1993

Squamous cell carcinoma of the tongue: experience with 86 consecutive cases.

Charts from 86 patients treated for carcinoma of the tongue were reviewed to identify strategies that might improve patient outcome. Seventy-one patients (83%) were black and 69 patients (80%) were male. Overall 2- and 5-year survival rates were 20% and 12%, with stage-specific 2-year survivals of 71% (I and II, n = 7), 33% (III, n = 15), and 11% (IV, n = 64) (P < 0.01). Patients with well-differentiated tumors (n = 27) had a higher 2-year survival than that of the others (n = 53, 30% vs. 11%, P = 0.05). Six were unclassified. Twenty-three (27%) patients underwent primary surgical resection and lymphadenectomy with or without adjuvant therapy. Two-year overall and disease-free survivals were 43% and 26%, respectively. Fifty (58%) patients received radiotherapy with or without chemotherapy, achieving 2-year overall and disease-free survivals of 12% and 6% (P < 0.01). The remaining 13 patients received chemotherapy alone or no treatment and survived an average of 6 months. Distant metastasis were diagnosed in 14 patients (16%). Tongue carcinoma in this socioeconomic setting was characterized by late diagnosis and poor prognosis. Degree of tumor differentiation, disease stage, and treatment modality seemed to correlate with prognosis. Surgery, when possible, achieved superior results for disease control and survival. While cancer prevention efforts are critical, steps to identify high-risk groups to implement early detection programs may help improve outcome for these patients.

Adult↗
PubMed1993

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

A labeling method utilizing modified carbohydrate moieties in antibody heavy chains as radionucleotide binding sites was evaluated. Murine anti-sarcoma monoclonal antibody (MAb 19-24) was labeled with Indium-111 (111In) using this technique and subcutaneous human sarcoma xenografts were successfully localized in nude mice. A nonspecific monoclonal antibody BL-3 was used as a negative control. Tumor-to-blood ratios of radioactivity in the mice injected with 111In-labeled MAb 19-24 were significantly (P < 0.05) higher than those obtained with nonspecific MAb BL-3. Calculations of percentage injected dose of radioactivity per gram tissue showed relatively high specific uptake of MAb 19-24 in sarcoma xenografts. Radioactivity cleared from the blood rapidly and hepatic uptake of 111In-labeled antibodies was found to be relatively low. Biodistribution studies in normal mice with 111In-labeled antibodies showed only blood pool activity with no significant concentration of activity into organs. Therefore, immunoreactivity of the antibodies was retained after 111In-labeling utilizing this new technique, allowing specific binding of radiolabeled MAb to tumor xenografts with relatively low hepatic uptake.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗