Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 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.
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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.
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PMID:[Radiologic characteristics of the thorax during therapy with interleukin-2]. 145 17

Recombinant interleukin-2 (IL-2) produces clinical responses in approximately 20% of adult patients with renal cell carcinoma and melanoma, with both high-dose bolus and continuous infusion regimens. Because of the lower toxicity of continuous infusion, we elected to investigate in a Phase I trial a 5-day continuous infusion repeated for three weeks in children with malignancies refractory to standard therapy. Nineteen children with solid tumors and eight children with hematologic malignancies were entered into the study. The maximum tolerated dose was 3 x 10(6) U/m2/day, with dose-limiting toxicities occurring in five of seven patients treated at the 5 x 10(6) U/m2/day dose level. Dose-limiting toxicities included hypotension, hyperbilirubinemia, thrombocytopenia, pulmonary/pleural effusion, and nephrotoxicity. Serum IL-2 levels were detectable at the higher dose levels and were comparable to those observed in adult patients. Hematologic changes at the higher dose levels included rebound lymphocytosis occurring within 48 h of discontinuation of IL-2, eosinophilia, and decreased platelet counts. No objective responses to therapy were seen. We have identified a dose and schedule of administration for IL-2 in pediatric patients that can be given without intensive care unit support. Pediatric Phase II trials examining the anti-tumor activity of IL-2 given by this schedule are in progress.
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PMID:A phase I study of interleukin-2 in children with cancer. 145 95

Some biologic agents have proven effective in the treatment of lymphoproliferative diseases by stimulating host antitumor immunity or by applying active antitumor properties that specifically or nonspecifically effect tumor growth or tumor survival. These agents include interferons, which regulate cell gene expression, structure, and function; interleukin-2, which has several functions related to lymphoproliferation and mediation of lymphoid cell transport; anti-idiotype antibodies, which appear to cause a specific antiproliferative response against the patient's tumor; anti-idiotype vaccines, which produce cyclic complementary binding sites and idiotypes to induce specific immunity to tumors with resultant antitumor activity; radioisotope labeled monoclonal antibodies, which directly deliver tumoricidal doses of radiation to tumors, sparing normal tissue toxicity; and monoclonal antibody-immunotoxin conjugates, which directly deliver tumoricidal doses of radiation to tumors, sparing normal tissue toxicity. Encouraging results have been seen in clinical studies with these agents and much knowledge has been gained regarding the mechanisms involved. These findings dictate ongoing therapy modifications to produce continuing progress in the therapeutic applications of biologic agents in lymphoproliferative disease processes.
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PMID:Biologic response modifiers: therapeutic approaches to lymphoproliferative diseases. 145 99

Growth of epithelial ovarian cancer is influenced by several factors including transforming growth factor-alpha and transforming growth factor-beta, macrophage colony stimulating factor, tumor necrosis factor-alpha, interleukin-1 and interleukin-6, c-erb B-2 (HER-2/neu), and mutant p53. Continued expression of the epidermal growth factor receptor, new expression of c-fms, and overexpression of HER-2/neu are associated with a poor prognosis. A number of cytokines have been used to treat patients with ovarian cancer, including interferon-alpha, interferon-gamma, tumor necrosis factor-alpha, and interleukin-2. Judging from preclinical models, interferon-gamma may be more active than interferon-alpha against human ovarian cancer. Although tumor necrosis factor-alpha can stimulate proliferation of some ovarian cancers, the cytotoxic activity of tumor necrosis factor-alpha has been amplified ex vivo by inhibitors of protein synthesis. Similar heterogeneity exists with regard to interleukin-1 where stimulation or inhibition of cell proliferation has been observed. Tumor-infiltrating lymphocytes from ascites fluid contain cells capable of major histocompatibility complex-restricted and major histocompatibility complex-nonrestricted cytotoxicity. Tumor-infiltrating lymphocytes and interleukin-2 have been combined with cytotoxic chemotherapy to treat advanced or recurrent disease. Bispecific monoclonal antibodies that react both with T cells and ovarian tumor cells have produced tumor inhibition in human tumor xenografts. Immunotoxins that contain OVB3 and pseudomonas exotoxin have been evaluated in a phase I clinical trial. Dose-limiting central neurotoxicity has been observed without tumor regression. A monoclonal antibody designated OVX1 has been developed against a high-molecular-weight mucinlike molecule associated with ovarian cancers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biology and therapy with biologic agents in gynecologic cancer. 145 11

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.
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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

Cancer immunotherapy is based on the idea that anti-tumor immunity in its various aspects can usefully complement the effect of conventional treatments (surgery, chemotherapy, radiotherapy). Immunotherapy can be active when one stimulates the function of cells capable to contribute to tumor regression, notably by using interleukin-2 or immunomodulators. It can be adoptive when patients' lymphocytes are collected and incubated in vitro in the presence of cytokines to enhance their function and reinjected in the patients. It can be passive when one administers anti-tumor monoclonal antibodies.
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PMID:[Cancer immunotherapy: from fundamental concepts to clinical applications]. 146 32

Cytokines are soluble mediators involved in cell-cell regulations in the immunological and the hematopoietic systems-genetic engineering now allows the characterization and the availability of recombinant molecules, some of them being recently introduced in clinical trials. Interleukin-2 (IL-2) is the first factor having demonstrated a reproducible therapeutic effect on human metastatic solid tumors, mainly chemo-resistant. High-dose IL-2 alone could achieve about 25% objective responses in metastatic renal cancers, with a low but significant number of complete, relatively long-lasting complete responses. Similar data are obtained in metastatic melanoma. IL-2 is probably acting through the activation of cytotoxic lymphocytes (LAK: lymphokine activated killers). The interest for simultaneous administration of autologous LAK cells generated through in vitro culture with IL-2 is discussed. Cytokine therapy is currently limited by important systemic toxicities, including mainly general symptoms with fever, and a capillary leak syndrome with weight gain, edema and functional renal failure-cardiac are respiratory troubles can be life-threatening. Future trends for cytokine therapy will be: The discovery of new cytokines, and a better knowledge of their synergies, allowing the design of rational associations. A letter understanding of the mechanisms of toxicities, allowing specific prevention of adverse effects not needed for efficient anti-tumor action. Gene therapy, which will lead to important and prolonged release of cytokines by the tumor cells themselves, or by infiltrating peri-tumoral cells, in order to achieve local efficacy and to circumvent systemic toxicities.
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PMID:[Immunotherapy: current problems and outlook]. 146 35

The soluble Interleukin-2 Receptor (sIL-2R) serum levels were assessed in 42 patients with Hairy-Cell Leukemia (HCL) at diagnosis and after alpha-Interferon therapy and correlated with spleen size, peripheral hematological values, hairy cell index (HCI) and clinical response. Serum sIL-2R levels were significantly increased in all HCL patients, particularly in those with a higher HCI (> 0.50) and in non-splenectomized patients. Among the 26 HCL patients who were studied before and after 12 months of alpha-IFN treatment, 16 normalized the sIL-2R level and 10 did not. Our findings suggest that sIL-2R levels in HCL patients correlate with the splenic and bone marrow tumor burden as assessed by HCI. In addition patients with low levels of sIL-2R at diagnosis appear to have a better chance of achieving a good clinical response.
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PMID:Serum soluble interleukin-2 receptor levels in hairy cell leukemia: correlation with clinical and hematological parameters and with alpha-interferon treatment. 147 20

The effects of glioma culture supernatant (GCS) and interleukin-2(IL-2) on the motility of autologous stimulated lymphocytes (ASL) were studied by using collagen gel system, chemotaxic chamber system and flow cytometric analysis. GCS inhibited the migration of ASL into collagen gel. It enhanced the ASL motility and the expression of CD 26 antigen on the cell surface. IL-2 inhibited the migration of ASL into collagen gel and had no influence on the motility of ASL, but enhanced the expression of CD 26 antigen. On the other hand, a clinical glioma specimen showed limited depth of ASL migration when injected into the tumor cavity in addition to the formation of fibrin like membrane on its surface and a layer of degenerated ASL under it. To make ASL therapy more effective to malignant glioma, the following measures should be recommended; 1) inject adequate volume of IL-2 into tumor cavity, 2) reduce the frequency of ASL administration, 3) wash out of glioma secreting factors, degenerated ASL and glioma cells in addition to reduce the volume of tumor tissue.
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PMID:[The motility of IL-2 activated lymphocytes into malignant glioma]. 147 10


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