Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DAB486IL-2 is a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with human interleukin-2 (IL-2). It selectively binds and intoxicates only cells that bear the high-affinity receptor for IL-2. In the first clinical trial of a genetically engineered ligand fusion-toxin, we have treated 18 patients with chemotherapy-resistant IL-2 receptor expressing hematologic malignancies with escalating doses of DAB486IL-2. The maximal tolerated dose of a daily intravenous bolus of DAB486IL-2 was 0.1 mg/kg per day for 10 doses, established by asymptomatic, reversible elevations of hepatic transaminases without changes in other tests of liver function. Other mild reversible side effects noted were rash, nausea, elevated creatinine, chest tightness, and fever. Pharmacokinetic analysis showed a monophasic clearance of 5.8 +/- 0.7 minutes with peak levels of 3,549 +/- 1,041 mg/mL at the 0.1 mg/kg dose. Approximately 50% of patients developed an antibody response to diphtheria toxin or DAB486IL-2. The presence of such antibodies did not preclude patients from experiencing an antitumor response as four of the six patients with antitumor effect had detectable antibody titers. Although this was a phase I trial designed to define the safety of DAB486IL-2, remissions were observed in three patients lasting from 5 to over 18 months. The ability to achieve significant tumor reductions in this group of heavily treated patients is encouraging and suggests additional trials are warranted in hematologic malignancies.
 ...
PMID:Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologic malignancies expressing the IL-2 receptor. 158 7

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B-derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.
 ...
PMID:Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia. 633 57

The disialoganglioside GD3 is expressed on the surface of soft tissue sarcoma, malignant melanoma, and other malignant cells and is, therefore, a potential target for therapeutic monoclonal antibodies. Intravenously administered R24, a murine IgG3 monoclonal antibody to GD3, induces inflammation and tumor regression at sites of metastatic malignant melanoma. R24 5 mg/m2 was given intravenously every other day for six doses to 10 patients with pulmonary metastases from a primary soft tissue sarcoma of the extremity for whom thoracotomy was planned. Resected tissue was available from 7 patients. All metastases expressed GD3; however, expression was heterogeneous within tumors, and in no tumor were more than 80% of the cells GD3 positive. A mild to moderate infiltrate consisting of mononuclear cells with T-cell markers was identified around or within pulmonary metastases in 6 patients. Tolerable acute allergic reactions occurred in all patients, but 3 patients had severe chest tightness and bronchospasm that limited the planned therapy. The setting of thoracotomy for metastatic disease provides an ideal system for studies on the pharmacology and biological effects of monoclonal antibodies that target soft tissue sarcoma antigens.
 ...
PMID:Biological study of R24 mouse monoclonal antibody in patients undergoing thoracotomy for pulmonary metastases from soft tissue sarcoma. 828 62

XOMAZYME-Mel (XMMME-001-RTA) is an immunoconjugate comprised of ricin A chain conjugated to a murine monoclonal antibody directed against high molecular weight melanoma antigens. Although not necessarily related to increased toxicity or decreased efficacy, the development of anti-immunoconjugate antibodies may limit repetitive dosing with an immunoconjugate. We evaluated the role of cyclosporine A in blocking the antibody response in patients with melanoma treated with XMMME-001-RTA. Patients received cyclosporine in divided daily doses to achieve serum levels by HPLC of 150-200 ng/ml on days 1-22. On day 3, XMMME-001-RTA was begun at dosages 0.2-0.6 mg/kg daily for 5 days. Treatment was repeated every 35 days. Three patients were treated in each dosage tier (0.2, 0.4, 0.6 mg/kg). Nine patients were entered and all nine were evaluable. Patients had histologically confirmed melanoma. Metastatic sites included skin, soft tissue, and lymph nodes (seven), lung (two), liver (one), and spleen (one). There were four men and five women aged 46-75 years. Toxicities included myalgia, arthralgia, hypoalbuminemia, fatigue, elevations in liver function tests, and increased peripheral edema. Four patients received two to five repeated dosages of XMMME-001-RTA. One wheal-and-flare reaction from an immunotoxin test dose of XMMME-001-RTA was noted after five cycles. After a test dose subsequent to one cycle, two patients experienced chest tightness without ECG changes and were removed from the study. All toxicities resolved without sequelae. One patient experienced partial lymph node remission for 9 months. A second patient had stable mediastinal disease for 20 months. XMMME-001-RTA is safe when given repeatedly with cyclosporine.
J Immunother Emphasis Tumor Immunol 1993 Apr
PMID:Phase I/II study of murine monoclonal antibody-ricin A chain (XOMAZYME-Mel) immunoconjugate plus cyclosporine A in patients with metastatic melanoma. 847 94

Adenosine 5'-triphosphate (ATP) has antineoplastic activity in vitro and in murine tumor systems, but there are no data in humans defining its potential use as an antineoplastic agent. We conducted a phase I study to determine the spectrum of toxicity, maximum safely tolerated dose (MTD), and pharmacokinetics of intravenous ATP. Fourteen men with advanced cancer received 96-hour infusions of ATP once monthly in doses ranging from 50 to 100 micrograms/kg/minute. Toxicity was assessed by standard National Cancer Institute (NCI) criteria, cardiac function was monitored serially by two-dimensional echocardiography, and whole blood ATP was measured serially in a subset of patients. ATP was generally well tolerated and no significant hematologic toxicity was noted. The dose-limiting toxicity was a cardiopulmonary reaction characterized by chest tightness and dyspnea that resolved within seconds of discontinuing ATP. Dose-limiting cardiopulmonary toxicity occurred in 3 of 3 patients at 100 micrograms/kg/minute, in 3 of 6 patients at 75 micrograms/kg/minute, and 4 of 11 patients at 50 micrograms/kg/minute. Whole blood ATP levels significantly increased with treatment, reaching a steady state by 24 hours and returning to or near baseline by 1 week after treatment. Plateau levels were 63%, 67%, and 116% above base-line at 50, 75, and 100 micrograms/kg/min, respectively. We conclude that prolonged infusions of ATP are feasible with acceptable toxicity and that 50 micrograms/kg/minute is both the MTD and the most appropriate dose rate for subsequent Phase II testing of 96-hour infusions of ATP in patients with advanced cancer.
 ...
PMID:Phase I trial of extracellular adenosine 5'-triphosphate in patients with advanced cancer. 869 94

Two case reports of primary cardiac sarcoma, which is uncommon, are presented. The first case, a 38-year-old male, complained of chest tightness. Chest roentgenograms showed enlargement of the cardiac shadow and left pleural effusion. Transthoracic echocardiography and chest magnetic resonance imaging showed a tumor in the right atrium, and pericardial effusion. The tumor involved the right atrial wall and interatrial septum, and was partially resected. Pathohistological examination revealed angiosarcoma. He died 1 month later. The second case, a 19-year-old male complained of dyspnea and orthopnea. Chest roentgenograms showed pulmonary congestion. Transthoracic echocardiography showed a large mobile mass in the left atrium. An emergency operation was performed and the tumor was totally resected. Pathohistological examination demonstrated leiomyosarcoma. The postoperative course was uneventful, but the tumor rapidly recurred. Second and third operations were performed at intervals of 2 months. After the third operation, he was treated with radiotherapy. Local recurrence was not found but multiple distant metastases were found 2 months after completion of radiation therapy.
 ...
PMID:Primary cardiac sarcoma: two case reports. 1823 85

We present a case of mediastinal mesenchymal tumor in a 53-year-old woman with a 1-month history of chest tightness. A histological diagnosis of lymphangiohemangioma was obtained by excisional biopsy. CT findings are reported with emphasis on its association with intratumoral superior vena cava ectasia.
 ...
PMID:CT features of mediastinal lymphangiohemangioma associated with superior vena cava ectasia. A case report. 1101 60

Angiosarcomas of the pleura are very rare tumors and it is difficult to differentiate them from other common pleural tumors such as mesothelioma and metastasic carcinoma clinically and pathologically. We report a case of a young Korean woman with angiosarcoma arising in the pleura. A 34-yr-old woman presented with dyspnea and chest tightness and pain for several months. A computed tomographic scan of the chest showed diffuse thickening of the left pleura and effusion with passive atelectasis. At thoracotomy the left pleura was thick and indurated. Histologically, the decorticated pleura revealed infiltration of sheets or cords of polygonal and epithelioid tumor cells showing rudimentary vascular differentiation. Immunohistochemically, the tumor cells were strongly positive for CD31, CD34, and vimentin, whereas weakly positive for factor VIII, and negative for cytokeratin, which are characteristic and specific findings of angiosarcoma.
 ...
PMID:Epithelioid angiosarcoma of the pleura: a case report. 1174 65

Metal working fluids (MWFs) have been widely known to cause asthma and neoplasia of the larynx, pancreas, rectum, skin and urinary bladder (Textbook of Clinical Occupational and Environmental Medicine (1994) 814; Am. J. Ind. Med. 32 (1997) 240; Am. J. Ind. Med. 33 (1997) 282; Am. J. Ind. Med. 22 (1994) 185). Other non-neoplastic respiratory effects in industrial workers attributed to MWFs include increased rates of cough, phlegm production, wheeze, chronic bronchitis and chest tightness (Eur. J. Resir. Dis. 63(118) (1982), 79; J. Occup. Med. 24 (1982) 473; Am. J. Ind. Med. 32 (1997) 450). The epidemic and endemic nature of immune mediated lung morbidity commonly known as hypersensitivity pneumonitis in workers from several different industries using MWFs has been well documented (J. Allergy clin. Immunol. 91 (1993) 311; Chest 108 (1995) 636; MMWR45 (1996) 606; Am. J. Ind. Med. 32 (1997) 423). We studied morphological/functional and antioxidant outcomes in lungs after inhalation exposure of vitamin E deficient mice to MWF (27 mg m(-3) 17 weeks, 5 days a week, 6 h a day). Mice were given vitamin E deficient (<10 IU kg(-1) vitamin E) or basal diets (50 IU kg(-1) vitamin E) for 35 weeks. Inhalation exposure to MWF started after 18 weeks on diet. Microscopic observation of lungs from mice given vitamin E deficient or sufficient diets revealed no inflammation or morphological alteration after exposure to MWF. Mice given vitamin E deficient diet exhibited a significant decrease (P<0.05) in breathing rate, peak inspiratory/expiratory flow, minute ventilation, and tidal volume compared with sufficient controls. However, no differences were found after exposure to MWF in pulmonary function, with the exception of tidal volume which also significantly decreased (P<0.05). Exposure to MWF reduced vitamin E, protein thiol and ascorbate level in lungs. Exposure to MWF in combination with a vitamin E deficient diet resulted in significantly enhanced accumulation of peroxidative products compared with vitamin E deficient controls. This is the first report that describes the increase of oxidative stress in the lungs after MWF exposure.
 ...
PMID:Metal working fluids: sub-chronic effects on pulmonary functions in B6C3F1 mice given vitamin E deficient and sufficient diets. 1213 30

Based on the activity of menadione (M) in the human tumor stem cell assay, we conducted a phase I trial of M in patients with advanced cancer. Forty patients (19 men, 21 women) were treated with 90 courses of M; 82 treatment courses are evaluable for toxicity. The median patient age, Karnofsky performance status, and number of prior chemotherapy regimens were 61 years (range 32-74 years), 80% (range 50-100%), and two, respectively. M was given by a short (1-5 h) intravenous infusion every 3 weeks, starting at 40 mg/m2 and escalating by modified Fibonacci scheme to 1360 mg/m2. Toxicity was graded according to the Southwest Oncology Group toxicity scale with defined hypersensitivity reaction (HSR) scales. No grade > or =2 hematologic toxicity was observed. Non-hematologic toxicity consisted of a HSR syndrome of paresthesiae of the extremities, facial flushing, burning of the eyes and mucous membranes, chest pain and dyspnea. HSR was defined as Grade I toxicity by the presence of facial numbness, flushing, and/or a tingling sensation or burning of the eyes and mucous membranes. Grade II toxicity was defined as the presence of the same above symptoms plus chest tightness, paresthesiae of extremities and/or dyspnea and chest pain. These toxicities were grade 1 in 3 of 4 patients at a dose of 840 mg/m2. At 1360 mg/m2, 2 of 13 patients suffered grade 1 HSR and 7 of 13 grade 2 HSR. No objective partial or complete responses were observed. Plasma menadione concentrations peaked at 1.9-7.4 microM during the infusion in 3 patients receiving 1360 mg/m2. Further phase 1 and 2 combination trials using longer infusion durations have resulted from this trial.
 ...
PMID:Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy. 1586 79


1 2 3 4 Next >>