Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were designed to investigate the therapeutic efficacy of interleukin-2 (IL-2) combined with radiotherapy. The effect of IL-2 and local thoracic irradiation (LTI) was determined on 4-day-old lung micrometastases, generated by i.v. injection of tumor cells into mice. IL-2 alone reduced the number of lung nodules more effectively when given from 1 to 4 than 4 to 7 days after tumor cell injection. The combination of IL-2 and LTI reduced the number of lung nodules more than did the individual treatments alone. When IL-2 therapy was combined with local irradiation of 8-mm leg tumors, there was no change in the TCD50 (radiation dose yielding 50% local tumor control). However, the combination of IL-2 treatment on days 1-4 with irradiation of tumor-bearing legs on day 1 after inoculation of tumor cells reduced the TCD50 by a factor of 1.3. These results show that IL-2 improves tumor radiotherapy, but that the improvement depends on anatomic localization and tumor size at the time of treatment.
Clin Exp Metastasis 1992 Nov
PMID:Combination of interleukin-2 and irradiation in therapy of murine tumors. 145 53

Interleukin-2 is a glycoprotein physiologically produced by human lymphocytes which is capable of mediating some still unknown immunologic reactions. In vitro, interleukin-2 was seen to induce a lytic reaction against tumor cells through the activation of a cytolytic system of natural killer cells. If administered to man in heavy doses, it causes a clinical response in the treatment of metastases from melanoma and renal cell carcinoma in 20-40% of cases. However, the clinical use of the drug, in therapeutic doses, is prevented by the occurrence of several side-effects, the major one being increased permeability of alveolar vessels with capillary leak and interstitial pulmonary edema (Vascular Leak Syndrome in the English literature). Thus, this work was aimed at evaluating chest radiographs during interleukin-2 treatment to detect, in the pulmonary district, the early stages of the vascular leak syndrome--i.e., pulmonary edema, pleural and pericardial effusions. Forty-three patients had been treated for metastases from renal cell carcinoma and melanoma November 1989 through September 1991: standard chest radiographs demonstrated 26 cases (60%) of pulmonary edema, 14 cases (32%) of bilateral pleural effusions and 12 cases (27%) of pericardial effusions. Daily chest films of the patients undergoing interleukin-2 therapy allowed the early stage of the vascular leak syndrome to be depicted, thus enabling the physician to use the highest tolerated doses and eventually to stop infusion before marked respiratory distress develops.
 ...
PMID:[Radiologic characteristics of the thorax during therapy with interleukin-2]. 145 17

Fifty-one cervical nodes from 19 patients with advanced head and neck cancer were stimulated with phorbol dibutyrate and ionomycin (PDBu + Io) to determine the effect of such stimulation on the generation of cytotoxic T cells and whether this stimulation could bypass the need for autologous tumor stimulation. Lymphocytes stimulated with PDBu + Io demonstrated a sixfold greater in vitro expansion and significantly increased DNA synthesis. Whereas fresh lymphocytes displayed no cytotoxicity, stimulation with PDBu + Io and culture in interleukin-2 (IL-2) led to significant cytotoxicity equivalent to that of lymphocytes stimulated with autologous tumor and IL-2. T cells with the greatest cytotoxicity were generated from patients with nodal metastases. In patients with stage IV tumors, effector cells demonstrating greater lysis of natural killer-resistant targets (Daudi cells) were associated with higher rates of recurrence (50% versus 12%, respectively, p < 0.001). Stimulation with PDBu + Io augments growth and proliferation of lymphocytes from draining lymph nodes and preserves cytotoxicity without the need for autologous tumor. Excluding the need for antigenic stimulation by autologous tumor may prove useful in adoptive immunotherapy procedures.
 ...
PMID:Phorbol dibutyrate plus ionomycin improves the generation of cytotoxic T cells from draining lymph nodes of patients with advanced head and neck cancer. 146 10

Fifteen patients with metastatic renal cell carcinoma (RCC) were treated by administration of autologous lymphokine-activated killer (LAK) cells given together with systemic administration of interleukin-2 (IL-2). Pulmonary metastases alone were found in 10 cases, pulmonary and mediastinal nodal metastases in 3, and pulmonary and bone metastases in 2. LAK cells, generated by incubation in 700 units/ml of IL-2 for 3-4 days, were intravenously administered once a week. In addition, beginning on the day of the first LAK cell infusion, 3.5 x 10(5) units of IL-2 were intravenously infused once or twice a day with occasional supplementation of 3.5 x 10(5) units of IL-2 on each day of LAK cell infusion. The total number of LAK cells and total amount of IL-2 administered per patient in this study ranged from 0.8 x 10(10) to 6.9 x 10(10) cells and from 10.2 x 10(6) to 74.9 x 10(6) units, respectively. As toxic effects caused by the infusion of LAK cells, headache, shaking chills, fever and leukocytosis were found in all cases. Side effects possibly induced by IL-2 infusion were tolerable fever, fluid retention (body weight gain of 2-3 kg) and eosinophilia. Out of 15 patients, a partial response was observed in 4 patients who had pulmonary metastases alone. One of the 4 patients with a partial response was clinically free of disease after undergoing a thoracotomy for resection of residual lesions, but a brain metastasis was detected 10 months after the thoracotomy. The remaining 3 patients are being closely followed up at present.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Lymphokine-activated killer (LAK) therapy for metastatic renal cell carcinoma]. 148 86

Experimental and clinical studies were conducted on lymphokine-activated killer (LAK) cell therapy for advanced renal cell carcinoma (RCC). The traffic assay using radiolabeled LAK cells indicated short-term but appreciable accumulation of LAK cells in the tumor site when trans-arterially infused. By contrast, systemically infused LAK cells were localized not to the tumor tissue but to the lung. Therefore, we began treatment of the patients with extrapulmonary metastases by means of regional arterial administration of LAK cells and those who had pulmonary metastases by a systemic LAK therapy. Regimen of Interleukin-2 (IL-2) administration was bolus infusion of 5 x 10 U IL-2 twice daily. Frequency of LAK cell administration varied from one to three times a week depending upon the patient's condition. Eight out of 16 metastases, such as bone, muscle, and lymph node metastases, in 9 patients treated by arterial LAK therapy showed regression. Side effects during LAK therapy were not serious. Past history of having chemotherapy was an unfavorable factor that could reduce the sensitivity to LAK therapy. Our laboratory study showed the production of Interferon (IFN)-gamma and Tumor Necrosis Factor (TNF)-alpha by LAK cells when preincubated with RCC cells, which may indicate the mechanism of LAK cell-mediated antitumor activity in vivo. The study also showed that LAK cells as well as monocytes preincubated with the supernatant of LAK cells damaged normal endothelial cells in vitro, which suggested the possibility that LAK therapy risks increasing the frequency of brain metastasis by damaging the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Lymphokine-activated killer (LAK) therapy for advanced renal cell carcinoma: clinical study on arterial LAK therapy and experimental study on LAK cell activity]. 148 87

Chemoresistant melanoma cells are known to be susceptible in vitro to lymphokine activated killer (LAK) cells. To obtain a high LAK/tumour cell ratio in vivo and avoid systemic toxicity due to interleukin-2 (IL-2), we used IL-2 plus LAK cells in the treatment of in transit melanoma metastases of the limbs by isolation perfusion (IP). In vivo immunological modifications induced by this immunotherapeutic approach were also analysed. Six patients previously treated with IP in extracorporeal circulation with tumour cytotoxic drugs and presently relapsing or not responding, were submitted to locoregional adoptive therapy consisting of 5 days systemic administration of IL-2 (Proleukin, EuroCetus) (9-12 x 10(6) IU/m2/day c.i.). Autologous LAK cells were derived from leukapheresis and subsequent in vitro stimulation with IL-2; LAK cells were then given along with IL-2 (120-2400 IU/ml of perfusion priming) to the affected limb by IP. In addition, 7-16 x 10(9) LAK cells were administered by systemic infusion the day after together with IL-2 (9-12 x 10(6) IU/m2/day) by c.i. for 5 days. All patients concluded the treatment without major toxicity. The analysis of circulating lymphocytes obtained from extracorporeal circuit at different times revealed rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. Clinical responses included four partial and one complete response; another patient had stable disease. All patients are presently alive. Follow-up after IP ranges from 8 to 22 months.
 ...
PMID:Treatment of recurrent in transit metastases from cutaneous melanoma by isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine activated killer cells. A pilot study. 149 Jan 14

Twenty-seven patients with evaluable metastatic cancer were treated with recombinant interleukin-2 (rIL-2) and escalating doses of interferon gamma (IFN-gamma). rIL-2 was infused over a 15 min period at a constant dose (8 x 10(6) IU/m2/8 h x 5 days first cycle, and 8 x 10(6) IU/m2/12 h x 5 days second and third cycles, with 9 days rest between each cycle). IFN-gamma was started 4 days before each cycle of rIL-2 and was given every other day at a dosage of 1 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 3/cycle (four patients), 5 x 10(6) U/m2 x 5/cycle (four patients) and 10 x 10(6) U/m2 x 5/cycle (15 patients). Common side effects were fluid retention and hepatic toxicity (27 and 15% grade greater than or equal to 2); one ischemic chest pains and one acute respiratory distress occurred. Toxicities were not greater than those described with high dose rIL-2 alone and were similar in each dose level of IFN-gamma. No patient died from the procedure. Four patients responded, one complete response and three partial responses; all were treated with 25 or 50 x 10(6) U/m2/cycle of IFN-gamma (melanoma, two patients; renal cell carcinoma, one patient; lymphoma, one patient). Further phase II studies at these dosages are justified to precisely define the antitumoral efficacy of this association.
 ...
PMID:Interleukin-2 in association with increasing doses of interferon-gamma in patients with advanced cancer. 151 26

Oligoclonality was investigated in interleukin-2 (IL-2)-activated T cells (tumor-infiltrating lymphocytes, TILs) residing in metastatic melanomas using seven different monoclonal antibodies (mAbs) specific for T-cell receptor (TCR) V alpha or V beta regions and flow cytometry. IL-2-activated TILs from 25 of 42 metastatic melanomas (60%) displayed oligoclonal expansion, whereas IL-2-activated peripheral bllod mononuclear cells (PBMCs) from only 2 of 20 patients (10%) did so during 2-5 weeks in culture. Skin-derived lymphocytes from 20 patients were cultured; only four samples proliferated and none showed oligoclonal expansion. Preferential oligoclonal expansion of TILs was observed in V beta 8+ cells (10/42, P less than 0.05), V beta 6.7+ cells (7/42, P less than 0.05), and V alpha 2+ cells (7/42, not significant). Oligoclonal expansion of V beta 8+ cells was primarily found in T cells from subcutaneous metastases (8/20 cases, P less than 0.05), whereas that of V beta 6.7+ cells and V alpha 2+ cells was also found in T cells from lymph node or organ metastases. These mAbs to TCR V regions stimulated effector TILs to produce interferon-gamma, but not IL-2 or IL-4. Subcutaneous tumor-specific (V beta 8+ cells) and non-specific (V beta 6.7+ cells and V alpha 2+ cells) oligoclonalities were observed in IL-2-activated melanoma TILs, suggesting different immune responses among different sites of metastases.
Clin Exp Metastasis 1992 Jan
PMID:Oligoclonal expansion of V beta 8+ cells in interleukin-2-activated T cells residing in subcutaneous metastatic melanoma. 153 Nov 24

The chest roentgenograms of 54 patients receiving high dose interleukin-2 with or without lymphokine-activated killer cell therapy for advanced cancer were retrospectively reviewed. Thirty-nine patients (72 percent) developed chest roentgenographic abnormalities consisting of pleural effusions, 28 (52 percent); diffuse infiltrates (pulmonary edema), 22 (41 percent); and focal infiltrates, 12 (22 percent). These abnormalities resolved in 30 of 39 (77 percent) patients by four weeks after therapy. Simple pleural effusions were the only residual roentgenographic abnormalities seen and were present primarily in patients receiving IL-2 by bolus intravenous injection (8 of 28) (29 percent) as compared to continuous intravenous infusion (1 of 24) (4 percent) (p = 0.03). Only roentgenographic evidence of pulmonary edema appeared to correlate with the degree of clinical pulmonary toxicity (p = 0.001). The development of chest roentgenographic abnormalities correlated with the administration of IL-2 solely by bolus intravenous injection (p = 0.04), a pretreatment FEV1 of less than 3 L (p = 0.04), and treatment associated bacteremia (p = 0.09), but not with prior therapy, the presence of pulmonary metastases or the degree of systemic capillary leak as measured by percentage of weight gain during therapy. Although the roentgenographic abnormalities did not relate to the number of LAK cells received, two patients developed sudden onset of dyspnea and chest roentgenographic evidence of pulmonary edema shortly after the first LAK cell administration, implying that a direct cause-and-effect relationship exists in some patients. Possible mechanisms for these IL-2 related chest roentgenographic abnormalities and pulmonary toxicity in general are discussed.
 ...
PMID:Chest roentgenographic abnormalities in IL-2 recipients. Incidence and correlation with clinical parameters. 154 Nov 42

A patient with liver metastases of human lymphocyte antigen (HLA) class II-negative malignant melanoma was treated with several cycles of adoptive immunotherapy with interleukin-2 and lymphokine-activated killer (LAK) cells. The authors evaluated the efficacy of regional transfer of LAK cells versus systemic intravenous administration. Initially, the patient was treated according to a regional treatment protocol, consisting of perfusion of the spleen with interleukin-2 and transfer of LAK cells into the portal vein; a partial remission was observed. Because of technical problems, interleukin-2 and LAK cells were administered intravenously in a second treatment cycle. This systemic treatment course resulted only in a minor mixed response of the hepatic metastases. A third treatment course was administered with the use of intravenous interleukin-2 infusion and arterial perfusion of the liver with LAK cells. The patient had separate hepatic arteries to both lobes of the liver as an anatomic variation. Because most of the tumor mass was present in the right lobe of the liver, a third of the LAK cells were injected into the right hepatic artery and the remaining cells were administered intravenously. The lesions in the right lobe of the liver regressed, but disease progression occurred in the left lobe. A fourth treatment cycle, consisting of intravenous infusion of interleukin-2 and arterial perfusion of both lobes of the liver with LAK cells, resulted in a complete response of all hepatic lesions, which has lasted 18 months to date. Because, in this patient, tumor regression was observed only in anatomic areas of the liver, which were perfused with LAK cells, it is suggested that the regional administration of LAK cells was essential for successful treatment.
 ...
PMID:Regional administration of lymphokine-activated killer cells can be superior to intravenous application. 154 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>