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

A total of 29 patients with advanced renal cell carcinoma entered a pilot study of combination therapy with interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma). IFN-alpha (HLBI: 3 x 10(6) IU, BALL 1:5 x 10(6) IU, IFN-alpha-2a: 9 x 10(6) IU or IFN-alpha-2b: 6 x 10(6) IU) was given intramuscularly every day and IFN-gamma (IFN-gamma-1a: 3 x 10(6) JRU) was given intravenously by drip infusion 3 times a week (every 2-3 days). The treatment was continued for 3 months as the induction therapy, and then the tumor response was evaluated. Of the 22 evaluable patients, 4 achieved a partial response (PR), 10 showed no change (NC), and in 8 the disease had progressed (PD) during the therapy. Thus, the overall response rate was 18.2% [95% confidence interval (CI) 2.1-34.3%]. A favorable response tended to be obtained in patients with good performance status or small pulmonary metastases, or in those who had no prior therapy with IFN-alpha, who received this treatment immediately subsequent to radical nephrectomy, or who received IFN-gamma as much as possible according to this regimen. Toxicity was evaluated in 28 patients: fever, general fatigue, anorexia, leukocytopenia and impaired liver function were frequently noted, and 3 patients were withdrawn from the study because of such adverse effects. In patients who had a PR or NC, the same dosage of IFN-alpha was continued to be given intramuscularly 2-3 times a week (every 2-4 days) as the maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of advanced renal cell carcinoma with a combination of interferon alpha and gamma]. 747 18

Thirteen patients with renal cell carcinoma who had proven bony metastases were treated with multimodal treatment including surgery, radiotherapy and immunotherapy in the form of subcutaneous continuous injection of by natural type interferon-alpha (INF). The mode of administration of IFN was as follows: IFN, 2,5000 x 10(4) unit dissolved in 60 ml saline, was continuously injected (0.5 ml/hr) via a subcutaneous route as one course of the treatment and was given two courses in two weeks preoperatively. Postoperatively, IFN was given every week and the number of courses totally amounted to 15. In some cases IFN was given thereafter either every week or every other week. In four patients whose serum concentration of IFN was measured during and after administration of continuous IFN, the concentration of IFN rose after injection and showed 40.5 IU/ml in average 24 hours later. The concentration was kept measurable in six to eight days long and the maximum concentration was 167 IU/ml. In IFN-treated patients nine survived including two CRs, two NCs, five PDs and four deaths. The five year survival rate was 53%. Continuous subcutaneous injection of IFN in combination with surgery and/or radiotherapy is effective in the treatment of bony metastasis from renal cell carcinoma.
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PMID:[Continuous subcutaneous injection therapy with interferon-alpha for renal cell carcinoma patients with bone metastasis]. 747 39

The IFNs, alpha and gamma, have been shown to enhance the tumor-associated glycoprotein (TAG-72) on adenocarcinoma cells in vitro and in mice with human breast cancer xenografts, resulting in improved targeting of monoclonal antibody CC49. To determine the effect of IFN-alpha on biodistribution and tumor uptake of 131I-labeled CC49, patients with metastatic breast cancer were randomized to either receive or not receive IFN-alpha (3 million units daily for 14 days) by s.c. injection. Three days after beginning IFN-alpha, all patients received 10-20 mCi of 131I-CC49 (specific activity, 16.7 mCi/mg) i.v. Total-body Anger camera scans, along with total-body blood and plasma pharmacokinetics, were performed. Tumor biopsies were taken in all patients before and 48 h after IFN-alpha treatment. There were no significant differences in number of metastases imaged or whole-body, blood and plasma pharmacokinetics between IFN-alpha-treated and untreated patients. Quantitative immunohistochemistry on biopsy specimens from IFN-alpha-treated patients demonstrated a significant increase in mean +/- SEM TAG-72 expression (45.7 +/- 19.4%) compared to patients that were not given IFN-alpha (1.3 +/- 0.95%; P < 0.05). Although slight increases in the percent injected dose of 131I-CC49 in tumor occurred after IFN-alpha-treatment, the changes were not significant at the P < 0.05 level. These data suggest that IFN-alpha may be useful in enhancing TAG-72 antigen expression in vivo in humans, despite modest improvement in tumor uptake of CC49, possibly because of limited tumor access or other unknown factors.
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PMID:Enhanced TAG-72 expression and tumor uptake of radiolabeled monoclonal antibody CC49 in metastatic breast cancer patients following alpha-interferon treatment. 749 72

Fifty-three evaluable patients with metastatic malignant melanoma were enrolled in a phase II prospective study designed to assess the response rate, time to progression and survival after dacarbazine (DTIC) and interferon-alpha 2a (IFN-alpha 2a) treatment in patients with local metastatic disease compared with patients with distant metastases. Patients received intravenous DTIC from day 1 at a dosage of 400-500 mg/m2, repeated every 21 days (in the case of good tolerance--25 patients--the dose was increased to 600-800 mg/m2) combined with subcutaneous IFN-alpha 2a (9 x 10(6) U three times/week, increased in the case of good tolerance to 15 x 10(6) U three times/week). Forty-two patients with distant metastases were compared with 11 patients who had local metastatic disease. Three complete (6%) and six partial (11%) responses were seen, with an overall response rate of 17% (95% confidence interval 8-29). Patients with local metastases had a higher response rate (50%) compared with patients with distant metastases (visceral involvement, mediastinal and para-aortic lymph node metastases) (10%; p = 0.01). The median overall survival was 4.5 months. The progression-free interval for responders with distant metastases was significantly longer (11 months), than for responders with local metastases (4.5 months) (p = 0.004). These results may suggest that the combination treatment DTIC/IFN-alpha has a greater benefit in terms of longer progression-free interval in responders with distant metastases.
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PMID:Dacarbazine and interferon-alpha 2a in advanced malignant melanoma: high response rate and prolongation of response duration occur in different patient subpopulations. 749 65

We screened a panel of 8 primary and 21 metastatic melanoma cell lines for constitutive secretion of cytokines. Melanomas expressed bioactivity for TGF-beta (8/25 lines) and IFN (7/12), but not IL-2. Immunoassays detected IL-1 alpha (4/25), IL-1 beta (12/25), IL-6 (13/29), IL-8 (29/29), TGF-beta 2 (5/12) and GM-CSF (11/29), but not IL-3, IL-4, TNF-alpha, or IFN-gamma. There was no preferential association of cytokine production with cells cultured from primary versus metastatic disease, and only IL-8 was produced by all lines tested. These data demonstrate that cultured melanomas produce a variety of cytokines which are potentially capable of influencing tumor growth in vivo.
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PMID:Production of multiple cytokines by cultured human melanomas. 751 80

We have reported that patients with metastatic melanoma treated with an autologous, dinitrophenol-modified vaccine develop inflammatory responses at tumor sites. Histologically, these inflamed lesions are characterized by T cell infiltration, which is sometimes associated with tumor cell destruction. We tested biopsy specimens of eight subcutaneous metastases that had developed inflammation following vaccine treatment for expression of mRNA for interferon gamma (IFN gamma), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF alpha), and IL-10. Post-vaccine, inflamed biopsies contained mRNA for IFN gamma (5/8), IL-4 (4/8) or both (3/8), and for TNF alpha (4/7). In contrast, IFN gamma mRNA was detected in only 1/17 and TNF alpha mRNA in 2/16 control specimens (pre-treatment lymph node metastases or non-inflamed subcutaneous metastases). mRNA for IL-10, a cytokine with anti-inflammatory properties, was detected in 24/25 melanoma metastases and was independent of lymphoid content; in situ the reverse transcriptase/polymerase chain reaction confirmed that melanoma cells were the major source. These findings may provide a new parameter by which to measure the effects of cancer immunotherapy.
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PMID:Expression of cytokine mRNA in human melanoma tissues. 755 83

A wide range of immunological abnormalities have been described in renal-cell carcinoma (RCC). The only constant one was the decrease of CD4/CD8 ratio, reversible following radical nephrectomy in the absence of metastases. Alpha-interferon was administered with variable benefit to patients with metastatic RCC. The aim of this study was to document whether the treatment of patients with metastatic RCC, with unpurified human alpha-interferon, induced any change in the number and functional properties of peripheral blood T lymphocytes and monocytes. Fifteen patients were included in the study; all were treated with IFN 2,000,000 IJ/24h x 15 days, with an intercycle interval of 15 days during at least 4 cycles. The immunological analyses included the percentage and absolute number of E-rosette forming cells, CD3+, CD4+, CD8+ and CD4/CD8 ratio as well as the percentage and absolute number of monocytes and their phagocytic index toward the yeast particles. The analyses were done before the treatment and after the 4th cycle of the IFN therapy and compared toward the same analyses done in 22 healthy controls. Following IFN treatment two significant changes were noted: a decrease in CD4/CD8 ratio (mean 1.050 fall for 19% to 44%, mean 27.25% from the initial value) as well as a marked decrease in monocyte phagocytic index (p < 0.005). These data point to either disease-related or treatment-related decrease in the phagocytic properties of monocytes and the decrease of CD4/CD8 ratio.
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PMID:[Effect of interferon alpha on immunologic parameters in patients with carcinoma of the renal parenchyma]. 759 Apr 6

Adoptive transfer of splenic T lymphocytes from DBA/2 mice immunized against Friend erythroleukemia cells (FLC) inhibited the development of visceral metastases and increased the survival time of DBA/2 mice challenged i.v. with parental FLC 24 hr to 2 months later. Immune spleen cells were ineffective in mice pre-treated with potent neutralizing antibody to mouse IFN alpha/beta (but not to IFN gamma), demonstrating the essential participation of endogenous IFN alpha/beta in the inhibitory action of immune T lymphocytes against FLC metastases. These findings suggest that the reported inability of immune T lymphocytes to exert an anti-FLC effect in immunodeficient DBA/2 mutant beige (bg/bg) mice (unless these mice had also been treated with IFN alpha/beta), may have been due to lower levels of endogenous IFN alpha/beta in DBA/2 bg/bg mice than in normal DBA/2+/bg mice. Experimental results in support of this hypothesis are presented.
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PMID:The essential role of endogenous IFN alpha/beta in the anti-metastatic action of sensitized T lymphocytes in mice injected with Friend erythroleukemia cells. 759 Dec 92

The goal of any treatment strategy for cancer is to improve not only patient survival but also quality of that survival. Between March 1990 and February 1993, we treated 10 patients with advanced RCC (9 men and 1 woman) by combined immunotherapy using natural interferon-alpha (IFN-alpha), recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells, and resulting the quality of life (QOL) issues examined. The ages of the patients ranged from 36 to 78 years (mean: 60.2) and the performance status (PS) ranged from 30 to 100% (mean: 77%). There were 8 lung, 3 bone, 2 brain and 1 neck and para-aortic lymph node metastases. We could evaluate 8 patients, 2 patients dropped out because of bone fracture and acute pneumonia. The protocol was as follows; 1 x 10(6) IU of rIL-2 as an intravenous infusion and 6 x 10(6) IU of IFN-alpha intramuscularly on days 1-7 and 15-21. In additions LAK cells obtained from the patients were given on days 14, 21, 28, and 35 intravenously. This protocol was repeated for more than three cycles (mean: 4.13 cycles) in each patient. The maintenance therapy on outpatient basis were performed in 4 patients after confirmation of the safety of the combined immunotherapy. This outpatient regimen was composed of 1 x 10(6) IU of rIL-2 intravenously, 6 x 10(6) IU of IFN-alpha intramuscularly on days, 1, 8, 15, 22, and 29, plus LAK cells on days 15 and 29. We repeated this protocol for 3-5 cycles (mean: 4.25 cycles).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Combined immunotherapy using interferon-alpha, interleukin-2 and lymphokine-activated killer cells--improvement of quality of life in patients with advanced renal cell carcinoma]. 760 59

We examined various prognostic factors of metastatic renal cell carcinoma. Patients who had metastasis at nephrectomy (A group, 38 cases) and those who had metastasis as recurrent tumors after nephrectomy (B group, 38 cases) entered in this study. Five-year survival rate of total cases after confirmation of metastatic foci was 15% and there was no statistical significant difference between A and B groups. Several pathological factors were related to poorer prognosis and included large diameters of original tumors, positive lymph nodes, higher grade tumors and non-clear cell type tumors. Patients who have a solitary lung metastasis showed better prognosis compared to those with multiple lung metastases or metastases of other organs. Two factors related to treatment were shown to contribute to better prognosis. These were the response to interferon alfa (IFN alpha) and the possibility of total resection of visible metastatic tumors. Patients who belong to A group were shown to achieve markedly better therapeutic benefit from IFN alpha or IFN alpha plus anticancer drugs. Five-year survival rate for the responders was 40%, as compared to less than 5% for the non-responders. Ten-year survival rate for patients with metastasis who had undergone complete resection of visible tumor was 50%, and the for patients belonging to B group Showed 80%. We concluded that these prognostic factors should be considered to decide how to select patients with metastatic renal cell cancer.
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PMID:[Prognostic factors for metastatic renal cell cancer]. 763 45


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