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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nude mice bearing bilateral xenografts of human breast carcinoma cells (MCF-7 and BT20) were treated with 2 or 45-day cycles of intralesional (i.l.) injections of human natural interferon beta (nIFN-beta) alone or in combination with human natural interferon gamma (nIFN-gamma). The injections were administered to only 1 of the 2 tumors in each animal, thus making it possible to assess at the same time local therapeutic effects in the injected tumors and systemic effects in the contralateral ones. When n-IFN-beta was used as a single agent only mild local antitumor effects and virtually no systemic effects were observed. In contrast, the combined administration of nIFN-beta/nIFN-gamma produced marked antiproliferative effects, presumably as a result of the synergistic action of type I and type II IFNs. These effects ranged from complete regression documented histologically in 2 MCF-7 tumors to varying degrees of growth inhibition with persistence of residual microscopic or grossly detectable tumor. Local effects were more pronounced than systemic effects. The therapeutic efficacy of nIFN-beta proved to be greater than that of recombinant interferon beta (rIFN-beta). In MCF-7 tumors nIFN-beta appeared to be less effective than nIFN-alpha, whereas the opposite was true for BT20 tumors.
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PMID:Antiproliferative effects of natural interferon beta alone and in combination with natural interferon gamma on human breast carcinomas in nude mice. 212 36

We administered doses of 5 to 180 x 10(6) IU of beta-serine-interferon (IFN-beta ser17) twice weekly to 20 patients with recurrent malignant gliomas in a Phase I study. Interferon was given through an Ommaya reservoir connected by a catheter to the tumor cavity. Side effects of interferon therapy occurred in only one patient and consisted of nausea, vomiting, fever, and chills after each treatment, presumably due to rapid diffusion of interferon into ventricular cerebrospinal fluid (CSF). Problems with the Ommaya reservoir (obstruction in two patients and infection in four patients) led to six patients being terminated from the study, and represent the major difficulty with this form of therapy. Although this was primarily a study of interferon toxicity, of 12 evaluable patients, 3 had stable disease for 148, 192, and 539 days; 9 had progressive disease. In addition, we tested the effect of IFN-beta ser17 on the growth of early passage in vitro cultures of malignant gliomas established from patients. Growth inhibition varied from 0% to more than 50%. In all cultures evaluated, the combination of recombinant gamma-interferon plus IFN-beta ser17 enhanced growth inhibition. Further clinical and laboratory study is necessary to better define the therapeutic efficacy of IFN-beta ser17 and the role of combinations of interferons in the treatment of malignant gliomas.
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PMID:Intratumor administration of beta-interferon in recurrent malignant gliomas. A phase I clinical and laboratory study. 229 73

Alveolar II pulmonary tumor cells (A549 cells) maintained in continuous tridimensional organotypic culture were used to test the effects of recombinant human interferons -alpha 2, -beta and -gamma on growth inhibition and survival of the tumor nodules. The organotypic culture method has several advantages: the three-dimensional structures of the cells as well as some cell differentiation are maintained and the extremely low traumatizing culture conditions offer injured cells the maximum chance of survival. A continuous treatment lasting 65 days (three weekly interferon changes) with 10, 10(2), 10(3) and 10(4) U/ml doses of the three interferons led to growth inhibition and necrosis only in the presence of the two highest doses (10(3) and 10(4) U/ml) of IFN-alpha 2 and -gamma. IFN-beta had no inhibitory effect. Some nodules, especially at the lower dose levels (10(2) U/ml), showed enhanced growth in presence of the three types of interferons. After stopping the treatments, all the necrotic and disintegrating nodules resumed growth. Growth of the recovered nodules was followed in the absence of interferon for another period of 70 days. The growth rate of IFN-beta and -gamma-treated nodules was similar to that of the controls, but was slowed down for the regenerated IFN-alpha 2-treated nodules. Hence, in A549 organotypic cancer nodules and under our experimental conditions, only high doses of IFN-alpha 2 and -gamma appeared to have a partial cytolytic, but finally no tumoricidal action; IFN-beta was inactive. At the lower doses growth stimulation was found during the treatments with the three interferons.
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PMID:Effects of human recombinant interferons-alpha 2, -beta and -gamma on growth and survival of human cancer nodules maintained in continuous organotypic culture. 242 38

The mechanisms of the direct and indirect antitumor effects of human interferon-beta (IFN-beta, MR-21) were examined. IFN-beta suppressed DNA, RNA and protein synthesis in cells derived from human tumor. The expression of cellular oncogenes (c-Ha-ras and c-myc) in tumor-originated cells was also suppressed by IFN-beta. These results suggest that such suppression is one possible mechanism of the direct anticellular effect induced by IFN-beta. IFN-beta augmented NK cell activity and the ADCC activity of human peripheral blood lymphocytes. It is also suggested that these are two of the immune system-mediated mechanisms responsible for the indirect antitumor effect of IFN-beta in vivo.
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PMID:[Basic study on human interferon-beta: Part III. The mechanisms of its antitumor effect]. 242 73

The human tumor colony-forming assay (HTCFA) is an in vitro test that has been used to predict the activity of anticancer drugs against a patient's tumor. We utilized the assay to analyze the antiproliferative effects of seven interferons (IFNs) against 40 human melanomas to determine which IFN had the greatest antiproliferative activity in this drug-resistant tumor. IFNs studied included recombinant IFN-alpha 2; human lymphoblastoid IFN; IFN-alpha Cantell; native beta RPMI; two recombinant IFNs-beta; and recombinant IFN-gamma. Growth was sufficient [greater than 30 tumor colony-forming units (TCFU)/well] for assessing the antiproliferative effects of at least one IFN in 25 tumors (63%). A dose-response relationship was demonstrated by all IFNs in tumors in which some activity was observed (p less than or equal to 0.01). Individual melanomas differed in their sensitivities to the various IFNs. Overall, however, none of the IFNs was markedly more effective in antiproliferative effects than any other, although there was a trend toward IFN-beta ser having more potent antiproliferative properties when compared to IFN-alpha 2 (p = 0.055). Twelve of 13 tumors exposed to combinations of IFN-beta ser and IFN-gamma demonstrated a synergistic antiproliferative effect. In all but two of these, low concentrations of each IFN (less than or equal to 50 U/ml), when combined, resulted in 85-95% inhibition. As prolonged exposure to high concentrations of IFN are often not clinically tolerable, these data suggest that IFN combinations may be one way of achieving more clinically meaningful IFN doses, schedules, and regimens, provided antiproliferative effects are of importance in vivo.
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PMID:Antiproliferative effects of interferons on human melanoma cells in the human tumor colony-forming assay. 243 22

We examined the sensitivity of four human germ-cell-tumor cell lines exhibiting different stages of differentiation to human interferons (IFNs) in vitro. The cell lines were derived from two embryonal carcinomas (NEC 8 and NEC 14), a choriocarcinoma (IMa), and a yolk-sac tumor (HUOT). Treatment with poly I:C induced IFN production in IMa and HUOT cells, but not in NEC-8 and NEC-14 cells. In the two embryonal-carcinoma cell lines, the addition of IFN-alpha, IFN-beta, and IFN-gamma did not prevent infection by vesicular stomatitis virus and encephalomyocarditis virus. Also, in these two lines, 2-5A synthetase was not induced by the addition of IFN-alpha. In contrast, both IMa and HUOT showed sensitivity to the antiviral action of IFN-alpha and IFN-beta against the two viruses, and 2-5A synthetase was induced by IFN-alpha. IFNs added at doses of up to 1000 IU/ml had no antiproliferative effect on NEC 8, NEC 14, and HUOT, whereas colony formation by IMa cells was greatly suppressed by all three forms of IFN. These results indicate that the production of and sensitivity to IFN are developmentally regulated and are related to the level of differentiation of human germ-cell stem cells.
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PMID:Sensitivity of human germ-cell-tumor cell lines to human interferons. 243 4

The mouse fibroblast-like transformed cell line C-243 adapted to growth in suspension was used as a source of virus-induced interferons (MulFN-alpha, beta), and spontaneously produced active growth factors. These factors were purified from C-243 cells grown as tumors in BALB/c mice, and had properties identical to those of TGF-alpha or TGF-beta isolated by others from different tissues. Exogenous TGF-alpha, beta stimulated colony formation by C-243 cells in soft agar, whereas MulFN-alpha, beta inhibited it. Clonal growth of human lung adenocarcinoma A549 cells in soft agar was inhibited as well by human interferons (types alpha, beta, or gamma) as by TGF-beta. Inhibition was dose-related. Pure EGF, which is an analogue of TGF-alpha, diminished the antiproliferative activity of interferons alpha, beta, and gamma in A549 cells. On the other hand, the anti-mitogenic action of IFN-beta and TGF-beta was clearly synergistic. In mice bearing C-243 cell tumors, TGF-alpha, beta stimulated growth, whereas MulFN-alpha, beta inhibited it. Stimulation of tumor growth was also observed after administration of anti-IFN serum that could neutralize endogenous IFN-alpha, beta. The simultaneous administration of MulFN-alpha, beta and TGF-alpha, beta diminished anti-tumor effects of IFN in mice. Our results suggest that both TGFs and IFNs are autocrine, positive or negative growth factors modulating the rate of proliferation and the neoplastic behavior of the cells. The final effects depend on the target-cell sensitivity and on the relative concentration of the various hormone-like factors. Cancer cells overstimulated by TGF-alpha, beta or by EGF may not respond to IFNs.
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PMID:Interactions of interferons and transforming growth factors during clonal growth of mouse or human cells in soft agar and in mice. 243 65

A new human urachal adenocarcinoma cell line (KO-BT-1) was established and characterized. It consisted of cuboidal, spindle, and polymorphic giant cells and continued to grow for more than 27 months without contact inhibition. Doubling time was about 15.5 h at the 70th passage. In nude mice the cells produced tumors, the histologies of which were similar to the original patient-derived tumor. Moreover, serum carcinoembryonic antigen level was elevated in the patient and the histological section of tumor formed in nude mice was stained with an antibody to carcinoembryonic antigen by peroxidase-antiperoxidase method. Electron microscopically, the cells covered with microvilli had cell-junction complexes. The chromosome number was aneuploid with a modal number of 60. At clinically achievable concentrations, doxorubicin, cis-platinum, mitomycin C, and 40487S which was an in vitro-active type of cyclophosphamide did not reduce colony formation to 30% or less of the control value; likewise in this patient chemotherapy had not been effective. In addition, among human recombinant tumor necrosis factor, alpha-interferon, and recombinant beta- and gamma-interferon, recombinant IFN-beta was most effective against this tumor. These results indicated that KO-BT-1 cells showed the similar chemosensitivity and properties to those of the original tumor, and might be useful in basic studies for the diagnosis, treatment, and etiology of urachal tumors.
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PMID:Establishment of a human urachal adenocarcinoma cell line (KO-BT-1) and its chemosensitivity. 244 57

Interferons (IFNs) have established antitumor action; the mechanism underlying this effect is, however, not yet clear. To probe the possible contribution of inhibition of angiogenesis, we have assessed angiogenesis in the mouse initiated by either human or murine tumor cell lines. Whether test cells were inoculated in the dermis or tumor fragments were grafted onto the cornea, tumor-induced angiogenesis (TIA) was inhibited by IFNs. TIA was also inhibited by the potent IFN inducer polyriboinosinic-polyribocytidylic acid. The effect of IFN was species specific; human IFNs inhibited human tumors and mouse IFNs inhibited murine tumors. This effect suggested that in contrast to other angiogenesis inhibitors, IFNs modulated the signal for angiogenesis produced by the tumor cells. Tumor cells treated in vitro with homologous IFN were significantly (P less than 0.005) less competent to initiate angiogenesis than were untreated cells. Inhibition of angiogenesis was achieved whether vascular response was assessed 1 or 3 days after tumor cell inoculation, suggesting that antiangiogenesis activity was independent of the antiproliferative effects of IFNs. To further substantiate this, L1210 leukemia cells, resistant to the antiproliferative effects of IFNs, were treated with 500 units/ml IFN-beta. IFN had no effect on their proliferation, but in four separate experiments, L1210R cells were impaired in their ability to induce angiogenesis. Thus, inhibition of TIA by IFNs was species specific, occurred at least partly by modulation of the signal inducing angiogenesis, and was expressed in the absence of antiproliferative effects. IFNs also inhibited immunologically induced angiogenesis, whether initiated by allogeneic lymphocytes (LIA) or by the mouse's own T-cells in response to an exogenous antigen (sheep RBC). LIA was markedly suppressed by treatment of host mice with homologous IFN-beta. For example, mean vessel counts induced by allogeneic mouse lymphocytes were decreased from 22.8 +/- 1.4 (SE) to 12.5 +/- 0.8 (P less than 0.0001); mouse IFN-beta had no corresponding effect on xenogeneic human lymphocytes (mean vessel counts decreased to 21.7 +/- 2.6 from 22.7 +/- 2.0). Treatment with human IFN-alpha, -beta, or -gamma in vitro or host mice in vivo reduced the ability of inoculated human peripheral blood lymphocytes to initiate xenogeneic LIA. Inhibition of LIA required a lower dose and/or a shorter incubation period than that needed to modulate TIA. Treatment of the donor of the allogeneic spleen cells in vivo with murine IFN or inducers also resulted in lesser LIA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibition of angiogenesis by interferons: effects on tumor- and lymphocyte-induced vascular responses. 244 62

Hairy cell leukemia (HCL) is a pre-plasma B cell tumor which responds to interferon (IFN)-alpha therapy. In vitro, B cell growth factor (BCGF) can induce proliferation of hairy cells. We have investigated the effect of in vitro and in vivo treatments with different recombinant IFN on the capacity of hairy cells to proliferate in response to human BCGF. In vitro treatment of leukemic cells from HCL patients with recombinant IFN-alpha-2 (5/5 cases) or IFN-beta (4/5 cases) resulted in a marked inhibition of the BCGF-dependent response. This suppressive effect was obtained with IFN concentrations of 1000, 100 IU/ml, and even occasionally 10 IU/ml. In contrast, no such inhibition was observed with IFN-gamma, despite the presence of specific IFN-gamma receptors on hairy cells at densities similar to receptors for IFN-alpha/beta. The IFN-alpha-induced suppression of the proliferative response of hairy cells to BCGF was also observed in vivo in two patients within 6-12 hr after administration of single doses of IFN-alpha. When hairy cells were maintained in culture for 1 week, they recovered their capacity to be stimulated by BCGF. This reversion was also shown in vivo in hairy cells isolated 1 week after IFN administration. Since in vivo growth of hairy cells could possibly result from the autocrine secretion of BCGF, we propose that the therapeutic effect of IFN-alpha on HCL may be due in part to an inhibition of such autocrine loop.
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PMID:Proliferative response of hairy cells to B cell growth factor (BCGF): in vivo inhibition by interferon-alpha and in vitro effects of interferon-alpha, -beta, and -gamma. 244 36


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