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)

Peritumoral injection of relatively low doses of either mouse interferon (IFN)-alpha/beta (10,000-20,000 units/injection) or of recombinant human interleukin-1 (IL-1) beta (125-250 ng/injection) in mice transplanted s.c. with Friend erythroleukemia cells (FLC) resulted in some inhibition of primary tumor growth, inhibition of liver and splenic metastases and increased survival time. A synergistic anti-tumor effect was observed in mice injected with both IL-1 and IFN-alpha/beta. Highly purified mouse IFN-beta also exerted a synergistic anti-tumor effect when combined with IL-1-beta in mice injected with FLC. The anti-tumor action of IL-1/IFN was markedly reduced in mice treated with antibodies to CD4 antigens. Antibodies to asialo-GM1 also diminished the anti-tumor effect by the combined cytokine treatment. The combined IL-1/IFN therapy was effective in NK-deficient bg/bg mice, although the extent of the anti-tumor response in these mice was less than that observed in bg/+mice.
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PMID:Synergistic anti-tumor effects of combined IL-1/IFN-alpha/beta therapy in mice injected with metastatic Friend erythroleukemia cells. 187 71

In an adjuvant clinical trial, 34 high-risk malignant melanoma patients were treated with natural interferon (IFN)-beta and recombinant IFN-gamma. Patients with tumor location on head, neck, and trunk received 3 million IU IFN-beta intravenously (IV) three times weekly for 24 weeks. Patients with tumor location on the extremities received subcutaneous (SC) injection of 2 million IU of IFN-beta distal the locoregional lymph nodes instead. All patients were given 50 micrograms IFN-gamma SC on 3 consecutive days every 4 weeks. Antibody formation was detected by coincubation of IFN and patients' serum and assessment of the inhibition of the cytopathic effect by a virus suspension. Soluble interleukin-2 receptors (sIL-2R) were determined by enzyme-linked immunosorbent assay (ELISA) technique. No antibodies against IFN-gamma were observed. The overall incidence of antibody formation to IFN-beta was 55.8% (19/34). Ninety-two percent of the SC-treated patients (13/14) and 30% (six of 20) of the IV-treated patients developed antibodies. Soluble interleukin-2 receptors were found to be significantly lower in antibody-positive patients than in antibody-negative patients. The authors conclude that IFN-beta antibody formation is frequent and might influence IFN induced sIL-2R elevation in vivo.
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PMID:Formation of neutralizing antibodies against natural interferon-beta, but not against recombinant interferon-gamma during adjuvant therapy for high-risk malignant melanoma patients. 190 14

High-titered spontaneous interferon (IFN) antibodies were detected in a patient with pure red cell aplasia (PRCA), a benign mediastinal tumor, and recurrent cutaneous carcinomas. The circulating IFN antibodies reacted broadly with various human IFN-alpha subtypes (20-140 x 10(3) neutralizing units/ml serum) but not with IFN-beta or IFN-gamma, and they neutralized the antiviral activity of the patient's endogenous IFN-alpha. The IFN-alpha-binding activity was restricted to the IgG1 subclass in a nonmonoclonal manner. Whereas the PRCA repeatedly responded to immunosuppression with high-dose cyclosporin A (CSA) and CSA plus plasmapheresis, IFN antibody production continued during treatment with cyclophosphamide and CSA. Serological analysis revealed past infection with parvovirus B19 and persistent B19 IgM titers. Antibody-mediated impairment of the IFN-alpha system might have favored the development of both PRCA and the various cutaneous carcinomas in this patient.
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PMID:Spontaneous interferon-alpha antibodies in a patient with pure red cell aplasia and recurrent cutaneous carcinomas. 190 12

Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-gamma or IFN-beta ser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.g., hairy cell leukemia, melanoma) had positive titers of TAG-72 or CEA, and interferon neither increased nor resulted in the appearance of either tumor antigen in those sera. In contrast, 59.2% and 75.4% of the patients with adenocarcinoma had positive serum levels of TAG-72 and CEA, respectively, prior to interferon. IFN-gamma and IFN-beta ser alone or in combination significantly increased serum TAG-72 or CEA in approximately 65% of those patients. The results suggest that interferon administration to patients with adenocarcinoma can result in increased serum levels of selected tumor-associated antigens used in the diagnosis of malignancy. These preliminary findings may be important in the development of new strategies to obtain more sensitive tumor antigen serum assays for the diagnosis and monitoring for disease progression of adenocarcinoma.
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PMID:Evidence for the elevation of serum carcinoembryonic antigen and tumor-associated glycoprotein-72 levels in patients administered interferons. 190 81

The intercellular adhesion molecule (ICAM-1) has been shown to be important in interactions involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In the present study, we have determined by fluorescence-activated cell sorter (FACS) analysis and the anti-ICAM-1 monoclonal antibody (MAb) CL203.4 the base-line expression of ICAM-1 and its modulation by recombinant IFN-beta, IFN-gamma and TNF-alpha in early passage (less than 15) human central nervous system (CNS) tumor-derived cell cultures. These cultures were established from various malignancies, including glioblastoma multiforme (GBM), astrocytoma (AST), ganglioglioma, medulloblastoma, meningioma and a pineal tumor. ICAM-1 expression was highest in the GBM- and AST-derived cell cultures and was lowest in the ganglioglioma and normal pineal cell cultures. Variable ICAM-1 expression was found, however, in tumors of the same histological group. In several cell cultures the variable expression observed by FACS was substantiated by the intensity of the molecular species immunoprecipitated by the anti-ICAM-1 MAb CL203.4 from these cells. All the cell cultures displayed variable but consistent increases in ICAM-1 expression following treatment with IFN-gamma or TNF-alpha. In general, the degree of increase in ICAM-1 expression was greatest in cultures exposed to TNF-alpha. Upregulation of ICAM-1 expression in an established glioblastoma multiforme cell line was of greater magnitude and more rapid following TNF-alpha treatment (within 2 to 3 hr) than exposure to IFN-gamma (by 24 hr). In several cultures, IFN-beta also increased ICAM-1 expression and enhanced the increase induced by TNF-alpha. The results of the present study indicate that variable expression of ICAM-1 is a common property of early passage cultures of CNS tumors and recombinant interferons and TNF-alpha can differentially upregulate ICAM-1 expression in these CNS tumor cell cultures.
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PMID:Expression and modulation by cytokines of the intercellular adhesion molecule-1 (ICAM-1) in human central nervous system tumor cell cultures. 197 69

A multicenter phase I-II trial of intravenous (IV) human recombinant interferon beta (rIFN-beta; Betaseron; Triton Bioscience Inc, Almeda, CA) was conducted in children with recurrent or progressive primary brain and spinal cord tumors. A total of 29 patients were enrolled: high-grade astrocytoma (12), brainstem glioma (nine), and primitive neuroectadermal tumor (three), ependymoma (two), germ cell (two), and spinal cord astrocytoma (one). Betaseron was given by IV infusion over 30 minutes 3 times per week (Monday-Wednesday-Friday [MWF]). Four dose levels were studied, and at least three patients were entered at each dose level. The treatment plan began with a three-step dose escalation for each patient over 6 weeks (initiation phase). The dose-escalation schema for the four dose levels was: 50-100-200, 100-200-400, 200-300-500, and 300-400-600 x 10(6) (M) IU/m2. Patients experiencing an objective response or stable disease after 6 weeks entered the maintenance phase at the final escalated dose, ie, 200, 400, 500, or 600 mlU/m2 (MWF). Common transient effects included chills, fever, and fatigue. Dose-limiting toxicities were hematologic, hepatic, and CNS. The maintenance maximum-tolerable dose (MTD) was 500 mlU/m2, ie, dose level 3. Response was assessed at completion of the initiation phase and at 2-month intervals during the maintenance phase. Objective partial responses were seen in patients with high-grade astrocytoma (two) and brain-stem glioma (two). Thus, four of 21 (19%) assessable patients had partial responses for a median of 4 months. Eight patients had stable disease for a median of 5+ (2 to 14+) months. Antineoplastic activity has been identified in children with high-grade astrocytomas and brainstem gliomas in a dose-intensive regimen.
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PMID:Recombinant interferon beta: a phase I-II trial in children with recurrent brain tumors. 201 20

Recombinant interferon beta (IFN-beta ser) has been administered by intravenous bolus injection three times weekly at a dose of 90 x 10(6) IU to 14 patients with recurrent malignant glioma in an ongoing study. The treatment period has ranged from 1 to 40 weeks. The most common adverse experiences were fever, chills, malaise, and headache. Fever, chills and headache were worse with the first two doses and were usually relieved with acetaminophen. All patients tolerated subsequent treatments without any difficulties. No neurologic or hematologic toxicities were observed. Of ten evaluable patients, five had progressive disease in 4 to 8 weeks; three had stable disease for 12 to 21 weeks; one has had a minor response for 13 weeks; and one has had a complete resolution of tumor for 150 + weeks. IFN-beta ser appears to have activity in human glioma and is well tolerated at this dosage and schedule.
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PMID:A pilot study of recombinant interferon beta (IFN-beta ser) in patients with recurrent glioma. 208 58

Successive coculture of Lewis lung carcinoma (3LL) cells with T cell-derived lymphokines and LPS-activated macrophages has led to the acquisition of 3LL tumor variants (macrophage-resistant 3LL tumor variants (3LL-R)), manifesting a highly reduced sensitivity to the cytotoxic potential of T cell-derived lymphokines and LPS-activated macrophages and TNF-alpha. However, when 3LL-R cells are cocultured with Poly I:C-activated macrophages or with conditioned medium derived from these effector cells a significant lysis is observed. TNF-alpha participates in the cytolytic process of Poly I:C-activated macrophages as anti-TNF-alpha antibodies abolish the cytotoxic effect of these effector cells. In addition, class I IFN is involved because IFN-alpha and IFN-beta act synergistically on TNF-alpha mediated lysis of 3LL-R cells within 18 h. Moreover, anticlass I IFN antibodies abolish the cytolytic capacity of Poly I:C-activated macrophages. Hence, Poly I:C-induced macrophage-mediated cytolysis of 3LL-R cells may result from 1) the induction of macrophages by Poly I:C to secrete high amounts of TNF-alpha and class I IFN and 2) a synergism between IFN-alpha/IFN-beta and TNF-alpha on lysis of 3LL-R cells. This synergism does not result from a class I IFN-mediated enhancement of TNF-alpha receptor expression on 3LL-R cells. Therefore, the sensitivity of 3LL-R cells to TNF-alpha-mediated lysis in the presence of class I IFN is most probably regulated at the post-TNF-alpha receptor level. Furthermore, treatment of mice with Poly I:C strongly reduces the metastatic capacity of 3LL-R tumor cells, suggesting the participation of macrophages in the eradication of the established metastasis. Hence, TNF-alpha-resistant 3LL-R tumor cells may serve as a useful tool for the detection of alternative macrophage-related cytotoxins leading to the destruction of neoplastic cells both in vitro and in vivo.
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PMID:Poly I:C activated macrophages are tumoricidal for TNF-alpha-resistant 3LL tumor cells. 211 50

We employed a tumor-type-specific tissue culture model utilizing three human colon carcinoma cell lines to (i) assess the effects of schedule, sequence, dose, and duration of exposure on the antiproliferative activity of combinations of tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) and to (ii) determine the effects of this combination on the production of a TNF-inducible protein, IFN-beta 2, and an IFN-inducible protein, p78. A statistical model was developed to ascertain the effects of each of three of the variables (sequence, dose, and duration) on the other two. With minor exceptions, the maximal antiproliferative effect in all three cell lines was observed when IFN-gamma and TNF were administered simultaneously, regardless of the doses of each agent and duration of exposure. Exposing the cells to TNF before IFN-gamma resulted in the least inhibition in cell growth. In all three cell lines, the antiproliferative effects of each treatment group were related directly to the duration of exposure. In two of the three cell lines, an intermittent schedule was as effective as a 24-h exposure. No p78 induction was observed in the HCT 116 cell line with IFN-gamma alone, TNF alone, or the combination; p78 was slightly induced in the SKC01 and VACO 9P cell lines with IFN-gamma alone, and was synergistically induced by the combination of TNF and IFN-gamma. Treatment with a neutralizing antibody to IFN-beta did not reverse the antiproliferative effect of any of the three treatment groups in HCT 116 cells. We conclude that the maximum antiproliferative effect in human colon carcinoma can be achieved by the prolonged simultaneous administration of high concentrations of each drug. If clinical toxicity prohibits this schedule, an intermittent schedule of administration may be effective. The mechanism of the synergistic effect is not due to the induction of IFN-beta or the p78 protein.
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PMID:Characterization of the synergistic antiproliferative effects of interferon-gamma and tumor necrosis factor on human colon carcinoma cell lines. 211 52

The possible relationship between the effects of alpha 2-, beta- and gamma-interferons (IFNs) on the growth of alveolar II pulmonary tumor cells (A549) maintained in tridimensional organotypic culture (nodules) and the modulation of epidermal growth factor receptor (EGF-R) expression was investigated. Treatment with rHu IFN-alpha 2 or IFN-gamma which results in the inhibition of the growth of A549 nodules had no effect on the binding of 125I-EGF to these cells. In contrast, treatment with rHu IFN-beta which exhibits no antiproliferative activity on A549 nodules resulted in a reproducible increase of the binding of 125I-EGF. Scatchard analysis of the EGF binding data indicated that a 48-hour exposure period resulted in an increase in the apparent number of cell surface EGF-R but did not significantly alter receptor affinity. Results from Northern blot analysis showed that the enhanced expression of EGF-R on the A549 nodule cells treated with IFN-beta correlates with an increase in mRNA for EGF-R. No modification of the EGF-R mRNA expression was observed in nodules treated with IFN-alpha 2 or IFN-gamma. In this model, our results suggest a relationship between resistance to antiproliferative effect of IFN-beta and modulation of EGF-R.
Tumour Biol 1990
PMID:Increase of epidermal growth factor receptor expression associated with a lack of antiproliferative effect of IFN-beta in human lung cancer nodules in organotypic culture. 211 98


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