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)

The prognosis of renal cell carcinoma (RCC) is related to the initial staging, assessed by nephrectomy. Metastases are present at the time of diagnosis in 30% of cases. Solitary metastases are rare. The most common metastatic sites include lungs, lymph nodes and bones. Anatomical pathways as well as local events in the secondary sites are responsible for the site specificity of the tumor spread. Patients with disseminated disease have a 5 years survival rate of less than 10%. RCC is intrinsically chemo-resistant. Vinblastine leads to a global response rate (RR) of 15%. In view of the lack of effective chemotherapeutic agents, interest has been directed towards the potential value of biological response modifiers (BRM). Response rates are about 15% with IFN alpha. Significant synergy between IFN alpha and vinblastine has not been proved. Interleukin-2 (IL-2) with or without Lymphokine Activated Killer (LAK) cells leads to a RR of 20%. Some durable complete remissions have been reported. Ideal doses and schedules remain to be determined.
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PMID:[Metastasis of renal cancer]. 179 52

Adoptive immunotherapy in cancer has been essentially restricted to the use of lymphoid effector cells (NK, TIL, LAK) stimulated with IL-2. Differentiated macrophages represent another key effector population even more important for the immune control of cancer. We have shown that activated murine macrophages reduced primary tumors and experimental metastases. Human macrophages differentiated from circulating monocytes and activated with IFN gamma (MAK) were cytotoxic in vitro for a variety of tumor cell and caused regression of human tumors implanted in nude mice. A large scale technology has been developed for the generation of antitumor macrophages. These MAK cells (10(8) to 10(9] were injected in cancer patients in pilot clinical trials and were well tolerated. MAK treatment is technically feasible, clinically safe and presents several advantages compared to other immunotherapies.
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PMID:Adoptive immunotherapy of solid tumors with activated macrophages: experimental and clinical results. 188 50

This study was designed to investigate acute effects of various doses of the cytokines IFN-alpha, IFN-gamma, Interleukin 2 and tumor necrosis factor alpha on white blood cell differential counts. Before initiation of phase II trials, a dose-determination phase was performed, where three different dose levels of each cytokine were applied as a single dose. White blood cell differential counts were assessed immediately before and 2, 12, 24, 48 and 168 h after injection. Patients enrolled suffered from metastatic cancer or chronic active hepatitis. In addition, IFN-alpha was administered to five healthy volunteers. Results indicate that cytokines cause rapid and transient changes in the numbers of leukocyte subsets. Hematologic changes were cell-type- and cytokine-specific: transient lymphopenia was observed after administration of all four cytokines, reaching a nadir 12 to 24 h after subcutaneous injection. Administration of TNF-alpha and IFN-gamma also caused transient monocytopenia. Neutrophilia developed after administration of Interleukin 2, IFN-alpha and TNF-alpha. We conclude that cytokines play a key role in the regulation of peripheral blood cell traffic by their capacity to influence homing patterns of peripheral blood leukocytes.
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PMID:Acute hematologic effects of interferon alpha, interferon gamma, tumor necrosis factor alpha and interleukin 2. 190 9

We analyzed the expression of class-I antigens in ex vivo human tumor cells by isoelectric focusing (IEF) the anti-class-I mAb W6/32 immunoprecipitates prepared from cell lysates. Out of 42 experiments, 27 were technically successful. The patient's blood lymphocytes were used as controls. In vitro exposure of the tumor cells to IFN gamma and TNF alpha elevated class-I antigen expression. In 11 cases, defects in MHC-class-I-antigen expression were observed. In 2 cases the antigens were detected only in the cytokine-treated tumor samples, probably due to a defect in the association between beta 2m and class-I heavy chains. Selective changes in the expression of alleles were seen in 10 cases and might involve HLA A, B and C antigens. Alterations in class-I expression as compared with the lymphocytes were observed in 9 of 13 cases in which the tumor cells were collected from metastases, and only in 2 of 14 primary tumors.
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PMID:Expression of MHC-class-I antigens in human carcinomas and sarcomas analyzed by isoelectric focusing. 206 76

Fifty patients suffering from histologically proven metastatic melanoma were treated with a combination of DTIC (400 mg/m2 i.v. every 28 days) and recombinant alpha 2A interferon (Roferon-A) 10 x 10(6) U/m2 daily, administered intramuscularly or subcutaneously for 2 months followed by 7 x 10(6) U/m2 3 times a week. Treatment was carried out for a period of 12 months unless progressive disease was noted after 3 months. Among the 49 evaluable patients, 6 achieved a complete response (CR) and 4 a partial response (PR) (response rate, 20%) at 2 months, 8 CR and 3 PR (25%) and 8 CR and 2 PR (23%; 95% confidence limits, 13-40%) occurred at month 6 and 12 respectively These responses occurred notably in patients with cutaneous (3 cases) or lymph node metastases (4 cases), but 3 responses included visceral sites: lung (1 CR), liver (1CR and 1PR). Average response duration was 16.5 months (range 4-29 + months). The time required for objective response can be up to 6 months, which suggest that treatment should receive a reasonable trial period (at least 3 months). Clinical toxicity consisted mainly of a flu-like syndrome, anorexia and fever, and occurred in more than 50% of patients; hematologic and hepatic toxicities required a dose reduction in 54% of patients but in only one case did treatment have to be terminated because of this. Seventeen (35%) of the patients are still alive, 4 with metastases (follow-up period: 18-34 + months) and 13 without metastases (follow-up period: 13-32 + months). A combined regimen of r-IFN alpha 2A and dacarbazine is effective in treating patients with metastatic melanoma, with acceptable toxicities and a reasonable quality of life (out-patient treatment or district nurse care). The objective response rate (23% at 12 months) compares favourably with those of earlier trials using the same combination of drugs, and occurred not only in cutaneous and lymph node metastases but also in visceral metastases.
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PMID:[Treatment of metastatic melanoma with dacarbazine recombinant interferon alfa 2A combination: results of multicentric study]. 208 Dec 78

We have examined the metastatic capacity of different clones of a chemically induced fibrosarcoma GR9. These clones have previously been characterized for their H-2 class-I and class-II phenotype, NK sensitivity and local tumor growth. Our present data show that clones which express low amounts of H-2 class-I antigens are poorly metastatic in a post-surgical spontaneous metastasis assay, while those expressing high levels of class-I antigens possess a high metastatic capacity. These results correlate inversely with local growth patterns of the clones. High metastatic capacity was associated with resistance to NK cells. In an experimental metastasis assay, based on intravenous administration of in vitro carried GR9 clones to syngeneic BALB/c mice, an opposite result to the post-surgical assay was obtained. Gamma-IFN treatment of B9 clones (H-2-deficient) enhanced H-2 class-I expression and diminished experimentally induced metastases. Metastatic colonies, from the spontaneous metastasis assay, obtained from different organs, showed changes in the ratio H-2K/H-2D. There was a tendency for down-regulation of the expression of H-2K molecules in H-2-positive clones and for up-regulation of H-2D expression in H-2-negative clones.
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PMID:A weakly tumorigenic phenotype with high MHC class-I expression is associated with high metastatic potential after surgical removal of the primary murine fibrosarcoma. 211 97

We have investigated the relationship between in vitro cultivation of autologous melanoma metastases derived from different patients and their levels of expression of class-I and -II major histocompatibility complex (MHC) antigens and melanoma-associated antigens (MAAs). Cell cultures were established from 23 individual metastatic melanoma lesions from 10 patients and were tested early after isolation (between 3rd and 10th passages) for both constitutive expression and modulation by recombinant human leukocyte (IFN-alpha), fibroblast (IFN-beta) or immune (IFN-gamma) interferon of MHC antigens and MAA. All of the melanoma cell lines displayed altered antigen expression following IFN treatment. While in vitro cultures derived from different individuals varied in both constitutive and IFN-modified antigenic expression, cultures of autologous metastases derived from the same patient were very similar. In addition, differences in antigenic profile were apparent when early-passage in vitro cultures were compared with the same melanoma lesion, not established in culture, from which they were derived. The unique de novo and IFN-modified antigenic phenotype of cultures derived from different patients indicates that the antigenic phenotype displayed by melanoma cultures grown in vitro is genetically determined. The differences found between in vitro cultures and their corresponding in vivo lesions, as well as the antigenic heterogeneity displayed by multiple autologous melanoma lesions in vivo, suggest that the in vivo antigenic phenotype may be determined, at least in part, at an epigenetic level.
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PMID:Modulation of the antigenic phenotype of early-passage human melanoma cells derived from multiple autologous metastases by recombinant human leukocyte, fibroblast and immune interferon. 211 85

The purpose of this study was to test the qualitative and quantitative toxicity of lonidamine (L) and alpha-interferon (IFN alpha) when used together, and to observe any apparent synergistic activity in conventionally untreatable measurable metastatic cancer. Eleven patients (8 males and 3 females) were enrolled. There was one response seen as measured by conventional criteria. There is no evidence that these agents are additive at this dose schedule, nor is their apparent synergistic activity.
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PMID:Lonidamine and human lymphoblastoid alpha interferon in metastatic cancer: a phase I study. 226 73

The distinctive biology of renal cell carcinoma and its low response to conventional therapies have prompted researchers in this field to search for other therapeutic strategies. In this paper we describe the current concepts regarding the biology of this neoplasia and new therapeutic perspectives for this disorder, with particular interest in the use of biological response modifiers, including alpha-interferon (alpha-IFN). In view of the evidence of spontaneous regressions of metastases observed after nephrectomy, a possible role of the immune system has been hypothesized in modulating the natural course of renal cell carcinoma. In this context, several groups have focused their attention on the immunotherapeutic approach to this disease. Major biological characteristics of alpha-IFN are reported here, with particular attention paid to its immunomodulatory properties. As a matter of fact, significant results have been obtained by using this molecule, either alone or in association with chemotherapeutic agents (vinblastine). In this paper we focus on the efficacy of these therapeutic approaches by reporting the data obtained from the major clinical trials in which alpha-IFN has been used, including a personal series of cases.
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PMID:[Treatment of renal carcinoma with alpha-interferon: biological bases and clinical results]. 228 23

Interferon-beta-serine (IFN-beta-ser) is a muteine, recombinant IFN that is tolerated at a dose fivefold to 10-fold higher than IFN-alfa and interacts with the same cell membrane receptor as IFN-alfa. We hypothesized that at high doses IFN-beta-ser might induce a higher response rate than IFN-alfa in metastatic renal cell carcinoma. We undertook a phase II trial of IFN-beta-ser in patients with metastatic renal cell carcinoma. Patients were treated three times each week by a 2-hour intravenous infusion. Doses were escalated weekly (.25 to 5.5 mg, 1 mg = 180,000,000 U) until the maximum-tolerated treatment dose (MTTD) was determined. The MTTD is defined as one dose level less than that which caused grade 3 toxicity and was subsequently administered three times weekly for at least 4 weeks. Twenty-nine patients were entered, and 25 were assessable for response and toxicity. The performance status was 0-1 in all patients and only one patient received previous chemotherapy. The MTTD dose was 2.5 mg (range, 0.5 to 5.5 mg per treatment), although in 10 patients, doses were later deescalated because of cumulative toxicity. Initial dose-limiting toxicity and cumulative toxicity were fatigue, malaise, and fever in most patients. Hepatic transaminitis, neutropenia, and elevation of serum creatinine were also observed but were not dose-limiting. There was one complete response (CR) and four partial responses (PRs). All responses but one occurred in pulmonary metastases. The median time to response was 26 days (range, 17 to 102 days). These data demonstrate that IFN-beta-ser given in high doses exhibits significant antitumor activity in renal cell carcinoma; however, the objective response rate is 20%. This is no higher than previous IFN studies; therefore, we reject the hypothesis than IFN-beta-ser at high doses may induce a greater response rate than IFN-alfa. However, we did observe more responses than were seen in a similar trial undertaken with lower dose IFN-beta serine in renal cell carcinoma.
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PMID:Phase II trial of interferon-beta-serine in metastatic renal cell carcinoma. 233 72


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