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)

Using the murine monoclonal antibody (MoAb) B1.1 we have analyzed the immunochemical profile and the tissue distribution of a human melanoma associated antigen (MAA) carrying an epitope shared by the 180 kd CEA. Results of this study have demonstrated that the epitope expressed by the MAA is carried by a distinct set of molecules of 110-140 kd. Similarly to the 180 kd CEA molecules synthesized by carcinomas, the expression of the melanoma associated CEA like components (MA-CEA) is upregulated by IFN-alpha. The tissue distribution of MA-CEA is not restricted to malignant primary and metastatic melanocytic lesions but is found also at low levels in 64% of benign nevi. No circulating CEA was found in patients bearing widespread metastatic disease of MA-CEA positive lesions. Preliminary clinical evaluation of stage I melanoma patients bearing MoAb B1.1 positive lesions has not shown a significative prognostic association of this phenotypic marker with clinical course of the disease.
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PMID:Molecular profile, tissue distribution and prognostic evaluation of a human melanoma-carcinoma antigen recognized by the murine monoclonal antibody B1.1. 323 49

Attempts have been made to design optimal strategies for the immunotherapy of established tumors. In mice bearing pulmonary metastases from sarcomas, a substantial therapeutic synergy was seen when both interleukin-2 (IL-2) and alfa interferon (alpha-IFN) were administered compared with the effect of either agent given alone. This synergy was dependent on Lyt-2+ T cells, since therapeutic effects were abrogated in Lyt-2-depleted mice. The alpha-IFN and IL-2 combination was also synergistic with tumor-infiltrating lymphocytes in mediating the reduction of established lung metastases. These experiments demonstrate that combination immunotherapy can result in substantial reduction of established metastatic deposits and provide a rationale for the application of this treatment to patients with advanced cancer.
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PMID:Combination immunotherapy for cancer: synergistic antitumor interactions of interleukin-2, alfa interferon, and tumor-infiltrating lymphocytes. 326 72

A recombinant human hybrid alpha interferon (rIFN-alpha A/D) with antiviral, immunomodulating and cell-growth-inhibitory activity on murine cells strongly inhibited the development of experimental pulmonary metastases of the Colo 26 adenocarcinoma in BALB/c mice. Twenty-one days after i.v. injection of 5 X 10(4) cells, 8/8 control mice had greater than 200 lung tumour nodules whereas 1/6 mice receiving 500 ng rIFN-alpha A/D had one lung tumour nodule and the other 5 mice were tumour-free. Equally strong inhibition was seen in immunodeficient BALB/c nu/nu (athymic) and beige nu/nu (athymic and NK-deficient) mice. Scheduling experiments in vivo showed that the most important time of IFN treatment was from the day of tumour cell injection to day 5, although statistically significant reductions in lung tumour nodule number and lung weight were seen even when IFN treatment was started 7 days after cell injection. rIFN-alpha A/D was cytostatic to Colo 26 in vitro, causing 50% or more inhibition of cell growth or colony number at IFN levels that could be achieved in the sera of IFN-treated mice. Although rIFN-alpha A/D stimulated NK-cell activity in BALB/c mice, Colo 26 cells were resistant in vitro to such cells whether from control or IFN treated mice.
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PMID:The effect of interferon on experimental metastases in immunocompetent and immunodeficient mice. 348 83

The in vivo anti-tumor activity of 2 recombinant cytokines, interleukin-2 (rIL-2) and human hybrid interferon alpha (rHuIFN-alpha A/D), were tested using the murine reticulum cell sarcoma M5076. Experimental hepatic metastases, following i.v. injection of tumor cells, and tumor growth and spontaneous metastases, following s.c. injection of tumor cells, were inhibited to a greater extent in mice treated with a combination of these cytokines than in animals treated with either one alone. When used in conjunction with surgical removal of the s.c. tumor, treatment of mice with both cytokines significantly prolonged survival of tumor-bearing animals. Injection of normal mice with a combination of cytokines, but not with either cytokine alone, resulted in a marked increase in cytotoxic activity of hepatic effector cells. The effector cells in these mice appeared to be NK cells since this enhanced cytotoxicity was markedly reduced in animals treated in vivo with anti-asialo GM1 or in NK-deficient beige mice. Furthermore, no in vivo efficacy was observed in M5076-bearing beige mice treated with these cytokines. Thus, injection of mice with rIL-2 and rHuIFN-alpha A/D results in the induction of an NK-cell-like population in the liver with enhanced cytotoxic activity that correlates with the observed anti-tumor activity in vivo in this murine model. These results suggest that combinations of cytokines, in particular IFN-alpha and IL-2, can be effectively used in combination for the treatment of tumors and/or metastases.
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PMID:In vivo anti-tumor activity of combinations of interferon alpha and interleukin-2 in a murine model. Correlation of efficacy with the induction of cytotoxic cells resembling natural killer cells. 349 83

A total of 18 patients with advanced metastatic renal cell cancer were treated with recombinant interferon alpha-2C (rIFN alpha-2C) at daily doses of 10 X 10(6) IU by intramuscular injection. All patients had evaluable metastatic lung, liver, or abdominal disease as measured by radiographic or computerized tomographic scans. In 2 of the 18 patients an objective response (1 CR, 1 PR) with a duration of +28 and 12 months, respectively was achieved. A 25$ to 50$ decrease in tumor measurements (MR) was seen in 2 additional patients; in 3 cases a stabilisation of the disease (SD) was observed, whereas it progressed in 11. 3/4 responding patients (including MR) and all 3 cases with SD had measurable disease in the lungs as predominant site of metastatic disease. Additional clinical characteristics of patients exhibiting response or SD to IFN therapy included prior nephrectomy, favourable initial performance status and limited metastatic disease. No serious haematologic or irreversible organ toxic effects were attributed to interferon. Several patients, however, had constitutional symptoms, and major dose reductions due to CNS toxicity became necessary in two. Further studies are warranted to evaluate the use of interferons in combination with cytotoxic drugs or other biologic response modifiers.
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PMID:Phase II trial of recombinant interferon alpha-2C in metastatic renal cell carcinoma. 350 86

Human recombinant interferon alpha A/D (alpha A/D) was examined for its antitumor activity in several mouse tumor models using metastatic tumors, such as B16 melanoma F1, BL6 and F10, UV2237m fibrosarcoma, and K1735m melanoma. Therapeutic treatment with alpha A/D reduced the incidence of pulmonary metastasis and inhibited the tumor growth resulting in an increase of the mean survival time. Since alpha A/D also showed a prophylactic activity against the metastasis, its antitumor activity was suggested to be due to augmentation of the host defense systems. This was confirmed by the fact that alpha A/D inhibited the in vivo growth and incidence of pulmonary metastasis of B16 F1 sublines regardless of their sensitivity to the direct antiproliferative activity of the IFN in vitro.
Clin Exp Metastasis
PMID:Antitumor and antimetastatic activities of human recombinant interferon alpha A/D. 384 Oct 37

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.
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PMID:Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report. 402 Apr 10

The authors report a case of anaplastic oligodendroglioma, in which multiple bone metastases developed about 6 years after the first craniotomy. A 32-year-old woman was admitted because of an apathetic state. CT scan and angiography suggested right frontal glioma. On August 15, 1977, a right frontal lobectomy was performed and histological sections showed anaplastic oligodendroglioma. Postoperative course was uneventful and she was discharged after chemoradiotherapy. In January, 1982, CT scan suggested recurrence of the right frontal tumor. On February 8, 1982, the second craniotomy was performed and this time, local radiation therapy by the afterloading technique (192Ir seed assembly) was given after the operation. In March, 1983, she began to complain of low back pains and multiple bone metastases were found by bone X-Ps and scintigrams. Biopsy of bone metastases was performed and at the same time, the whole body was surveyed for malignant tumors. But no primary cancer other than the right frontal brain tumor was found. In spite of therapy such as IFN, her condition gradually deteriorated and she died in December, 1983. Histological bone biopsy sections showed anaplastic oligodendroglioma much like the histology of the first operation. As the progress of curative means has increased, so has also the number of long-time survivors of malignant brain tumors. And in proportion to the increase in long-time survivors, cases of extracranial metastases may also increase. The etiology, diagnosis and therapy of extracranial metastases from the literature was also studied.
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PMID:[Diffuse bone marrow metastasis of an anaplastic oligodendroglioma]. 405 67

Patients with metastatic cancer were given single intramuscular injections of 10(7) units of partially purified preparations of either leukocyte or fibroblast IFN. Serum levels of inteferon, of beta 2-microglobulin and of carcino-embryonic antigen (CEA), as well as NK activity of circulating lymphocyte, were followed over a period of 96 hr post injection. In confirmation of previous studies, levels of circulating IFN were lower after injection of fibroblast IFN than after injection of leukocyte IFN. Despite this difference in pharmacokinetics, the natural killer activity of circulating lymphocytes was enhanced with both IFNs. Levels of DEA were not influenced by the IFN injections. Leukocyte but not fibroblast IFN caused an increase in serum levels of beta 2-microglobulin in the circulation. A similar difference between leukocyte and fibroblast IFN in their ability to influence the beta 2-microglubulin system was observed in experiments on cell cultures. Only leukocyte IFN was able to cause release of beta 2-microglobulin by either leukocytes or fibroblasts.
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PMID:Comparison of effects of leukocyte and fibroblast interferon on immunological parameters in cancer patients. 617 92

The influence of tumor load, surgical trauma, and bacterial sepsis upon the ability of patient's peripheral leukocytes to produce interferon-alpha (IFN-alpha), the detectable serum IFN levels and circulating serum IFN inactivators were studied. Peripheral blood leukocytes of patients with solid tumors had significantly reduced ability to produce IFN-alpha. Complete resectional surgery resulted in restoration of their ability to produce normal IFN-alpha levels. Circulating IFN levels were detectable in 70% of patients with localized disease while only in 20% of patients with metastatic disease. Interferon-alpha activators were detected in 45% of all patients. Both circulating interferon and IFN-alpha inactivators became undetectable upon tumor resection. Surgical trauma is accompanied by a transient but definite decrease in IFN-alpha production capability. Bacterial sepsis during postoperative days, in patients who successfully recovered, was definitely accompanied by increase in IFN-alpha production capability. Our findings suggest that advanced malignant epithelial tumors have an adverse effect upon the patient's ability to produce interferon and are often accompanied by the presence of circulating serum interferon inactivators. These effects can be reversed by surgical resection of the malignant neoplasm.
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PMID:The effect of malignant epithelial tumors, surgical therapy, and bacterial sepsis upon various parameters of interferon system. 672 84


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