Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effect of high dose iv bolus interleukin-2 (IL-2) therapy on sex hormone and adrenal steroid concentrations in six men treated for metastatic renal cell carcinoma or malignant melanoma. Blood concentrations of testosterone, 17 beta-estradiol, LH, FSH, cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEA-S) were measured before and after a 5-day course of IL-2 therapy. Cortisol levels rose and DHEA-S decreased insignificantly. DHEA declined, reaching a nadir (P less than 0.001) on day 6, and testosterone decreased significantly on day 2 and reached a nadir on day 6 (P less than 0.0001). Concentrations of both steroids then gradually rose. Estradiol rose on day 4 (P less than 0.001) and then declined. Neither LH nor FSH was affected significantly, although there was a rise in the mean level of LH after IL-2 therapy. Our results suggest that high dose IL-2 therapy in men affects both adrenal and testicular androgen production without inhibiting pituitary trophic hormone secretion. These effects of IL-2 on plasma sex steroids may be the result of cytokines stimulated by IL-2 therapy, rather than direct responses to IL-2.
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PMID:Reduction of testosterone synthesis after high dose interleukin-2 therapy of metastatic cancer. 183 90

The suppressor and cytotoxic activities of mononuclear blood cells (MNC) were studied in 70 cancer patients (melanoma, renal carcinoma) undergoing adoptive immunotherapy (AIT). In the course of AIT the patients' MNC were treated in vitro with the recombinant interleukin-2 (RIL-2) in order to generate the lymphokine-activated killer (LAK) cells. Then patients received i/v 2.5-13.6 10(9) autologous LAK cells and RIL-2 (75000 u). Each course included 2-3 repeated infusions; the patients received 1-5 courses according to their clinical conditions. The cytotoxic activity of MNC was assessed by a routine method; but for evaluation of the suppressor activity we used a new technique based on separation of MNS populations in the Percoll gradient. Twenty-four hours after the completion of each AIT course the suppressor activity of MNC decreased drastically up to the zero level in some patients. The decrease in the suppressor activity inversely correlated with the rise in the cytotoxic activity on Mel-I (LAK-sensitive) and K-562 (natural killer-sensitive) target cells. The level of cytotoxicity in some patients reached 51.2%.
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PMID:[A comparison of the suppressor and cytotoxic activities of the blood mononuclear cells during the adoptive immunotherapy of cancer patients using lymphokine-activated killers with a low dose of recombinant interleukin-2]. 183 73

An HLA-A2-specific cytotoxic T lymphocyte (CTL) clone (CTL49), capable of killing the HLA-A2-negative autologous melanoma (Me665/2) in a T cell receptor and MHC-independent fashion, lysed six of 16 Me665/2 tumour clones in short-term (4 and 18 hour) 51Cr-release assays. In long-term (96 hour) lytic assays, CTL49 could lyse all the 16 tumour clones. The lysis observed in the 96 hour assay could be enhanced by stimulating CTL49 with anti-CD3 monoclonal antibodies (MAb) and interleukin-2 (IL-2). Supernatants of anti-CD3- or antigen-stimulated CTL49, known to contain tumour necrosis factor (TNF) alpha and interferon (IFN)gamma, were also able to lyse all but one (665/2/51) of the tumour clones in 96 hour assays. Absence of lysis of tumour clone 2/51 by supernatants correlated with resistance of the same tumour clone to lysis by recombinant IFN-gamma plus TNF-alpha. Antibodies to TNF-alpha and, to a lesser extent, to IFN-gamma, reduced significantly the 96 hour lysis of Me2/9 and Me2/10, two of the tumour clones killed in long term but not in short term assays. Winn assays in nude mice revealed that CTL49, stimulated with anti-CD3-MAb plus IL-2, could abolish tumour cell growth when injected together with clones 2/9 or 2/10. These results indicate that intra-tumour heterogeneity for susceptibility to lysis can be overcome even by a single CTL clone providing that appropriate signals (i.e. anti-CD3-MAb and IL-2) are supplied to an effector able to mediate tumour cell lysis by multiple mechanisms.
Melanoma Res
PMID:An autologous T cell clone overcomes intra-melanoma heterogeneity for susceptibility to cell-mediated lysis by using multiple lytic mechanisms: in vitro and in vivo analysis. 184 13

Recent papers dealing with the effect of biologic response modifiers on the therapeutic activity of anticancer drugs are reviewed. Preclinical findings indicate that both interferons and tumor necrosis factor-alpha are able to synergize with different cytotoxic drugs in increasing both tumor cytotoxicity or cytostasis in vitro and the therapeutic effect in animal models in vivo. The mechanism of such a synergy, however, has not been definitively worked out. Several clinical phase I and II trials have assessed the interactions of biologic response modifiers (mainly interferons and interleukin-2) with anticancer drugs, particularly in melanoma and renal cancer patients. Evidence of a therapeutic synergism is limited with most of the studies, indicating a lack of synergic or additive effects of the combination compared with single agents. Few phase III studies provided conflicting results. It is concluded that further studies on the combination of biologic response modifiers and chemotherapy both at preclinical and clinical levels are necessary to establish the possible synergistic or additive therapeutic effect of such a therapeutic approach.
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PMID:Biologic agents as modifiers of chemotherapeutic effects. 184 10

Interleukin-2 (IL-2) plus lymphokine-activated killer (LAK) cell therapy has antineoplastic activity in renal cancer and malignant melanoma. In order to explore the activity of this therapy in Hodgkin's disease and non-Hodgkin's lymphoma, the Extramural IL-2/LAK Working Group (ILWG) treated 27 patients on two protocols using high-dose IL-2 and autologous LAK cells. Two of 12 patients with Hodgkin's disease experienced partial responses lasting 6 and 12 weeks. No patient with non-Hodgkin's lymphoma responded (p = NS). The toxicities of therapy were similar to those reported by the ILWG from trials of IL-2/LAK in solid tumors, consisting of transient hemodynamic, cardiopulmonary, renal and hepatic dysfunction, skin rash, fever, and flu-like symptoms. In view of the low response rate and the brief duration of these responses, we do not recommend the regimens reported here for further investigation in Hodgkin's disease or non-Hodgkin's lymphomas.
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PMID:Phase II trial of high-dose interleukin-2 and lymphokine-activated killer cells in Hodgkin's disease and non-Hodgkin's lymphoma. 186 45

The effect of immunosuppressive factors (ISF) derived from tumor cell lines (mastocytoma P-815, leukosis EL-4 and melanoma B16) on the production of interleukin-1 (IL-1) by macrophages and of interleukin-2 (IL-2) by splenocytes of BALB/C mice was investigated. We could show that treatment of above cells by the tumor products resulted in strong decrease of IL-2 production but did not affect IL-1 secretion. ISF inhibited the proliferation of BALB/C lymphoblasts caused by recombinant IL-2. Thus, one of the significant mechanisms of ISF action seems to be disturbance of monolymphokine cascade of lymphocyte activation.
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PMID:[Study of the action of tumor cell immunosuppressive factors on the production of cytokines by lymphocytes and macrophages and the mitogenic activity of interleukin-2]. 187 70

Interleukin-2 (IL2), as a modifier of the biological response, has been intravenously used in patients with advanced cancer associated or not to LAK cells or tumor infiltrating lymphocytes. In different neoplasias positive results have been obtained, being effective in melanoma and renal cancer. There are still, at present, many questions to be answered and multiple research lines are currently open. The association with other cytokines and new chemotherapy protocols grant new therapeutic possibilities.
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PMID:[Interleukin-2 and adoptive immunotherapy: their biological aspects and clinical application in oncology]. 189 96

Lymphokine-activated killer (LAK) cells are generated by the incubation of lymphocytes with high levels of interleukin-2 (IL-2). We report here that interferon-gamma (IFN-gamma) acts synergistically with low levels of IL-2 to promote LAK differentiation in peripheral blood lymphocytes as well as in homogeneous T acute lymphocytic leukemic cells exhibiting LAK precursor reactivity. No augmentation of LAK response was observed with IFN-alpha-2, IFN-beta-1, and IFN-beta-2/IL-6. The synergism between IL-2 and IFN-gamma was expressed in the ability of activated lymphocytes to lyse natural killer resistant cell line targets and surgically removed melanoma cells. The augmented LAK response due to IFN-gamma does not reflect up-regulation of the high-affinity IL-2 receptors consisting both of alpha and beta subunits, since expression of the alpha (Tac) subunit on the responding leukemic cells was not increased by IFN-gamma. The observed IFN-gamma/IL-2 synergism in the induction of monoclonal LAK precursors suggests that a single precursor cell responds to both IFN-gamma and IL-2 and that different mechanisms underlie the basal IL-2-mediated LAK response and its enhancement by IFN-gamma.
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PMID:Lymphokine-activated killer (LAK) cells: interferon-gamma synergizes with interleukin-2 to induce LAK cytotoxicity in homogeneous leukemic preparations. 189 16

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

Cytotoxic T lymphocytes (CTL) specific for autologous human melanoma have been successfully generated in vitro from tumor bearing lymph nodes without any stimulation by the autologous tumor. Tumor-involved lymph node cells (LNC) were cultured in serum free medium (AIM-V) containing 1,000 U/ml of recombinant interleukin-2. The best expansion and specific cytotoxicity of CTL were achieved in 4 to 6 weeks of culture. The predominant populations in cultured LNC-derived CTL were CD2+, CD3+, CD4-, CD8+, CD56-, and HLA-DR+ T cells. These data suggested that tumor-involved LNC may provide an alternative source for the generation of tumor-specific CTL in adoptive immunotherapy.
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PMID:Generation of human autologous melanoma-specific cytotoxic T cells from tumor-involved lymph nodes. 191 Jun 25


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