Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TNF, IFN, LT and IL-1 are well-known biological response modifiers (BRM) with cytocidal activity. Whereas carcinostatic agents generally derive their cytocidal action from their direct mutual reaction with target molecules (e.g., DNA, RNA), the cytocidal action of BRM resides in the enzyme response which ensures upon their binding to receptors. Accordingly, concomitant use of these drug of differing mechanism of action has a rationale. Considering that a certain kind of counteracting protein is present in cancer cells which are refractory or resistant to such cytokines, combination therapy with carcinostatic agents with inhibitive activity against such protein is also justified. In the same context the effects of TIL and LAK activated by IL-2 could be enhanced if the immune system should be modulated by combined use of BRM and carcinostatic agents such as CY. This paper discusses the results obtained with BRM and carcinostatic agents in combination in animal models and clinical cases.
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PMID:[Tumoricidal biological response modifiers (BRM)]. 169 52

Chemoimmunotherapy with anticancer drugs and immunoregulatory drugs and cytokines is a logical combination of 2 forms of therapy that have different mechanisms of action and no overlapping toxicity. Generally, anticancer drugs show rapidly the strong suppressive effect on tumor growth but also on host hemato-immunological functions. On the other hand, immunotherapy demonstrate the potential of restoring the hemato-immunological dysfunction of chemotherapy as well as the gradual antitumor effect through activating host defense mechanisms against cancer, indicating that these therapeutic modalities are complementary. On these biological rationale of chemoimmunotherapy mentioned above, we have demonstrated that immunostimulant, Nocardia-CWS is capable of producing tumoricidal macrophages being different from anticancer drugs in cytotoxic mechanism against cancer, and also that macrophage tumoricidal activity is significantly suppressed by exposure to anticancer drug, mitomycin C. Another beneficial activity of immunostimulant showed in our previous studies is a capability of production of colony stimulating activities. In a cooperative study with lung cancer patients it has been shown that recovery of leucopenia after chemotherapy is accelerated by administration of immunostimulant, MDP-Lys. Recently, immunomodulatory lymphokine, IL-2, has been clinically used for induction of activated killer lymphocytes (LAK cells) with tumoricidal activity. According to our studies, however, anticancer drug, when administered to cancer patients or added directly to culture of lymphocytes with IL-2 for LAK induction, shows significant suppressive effect on LAK induction. Considering these experimental and clinical studies, it can be concluded that immunotherapy, when employed as adjuvant after chemotherapy, play the important roles not only in eradication of tumor cells being escaped from chemotherapy but also in prevention of infections complication by activating host defense mechanisms common to cancer and infection.
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PMID:[Bases on timing of combined modality of chemotherapy and immunotherapy]. 169 53

The authors examined peripheral blood mononuclear cells from 45 patients with bronchogenic carcinoma to determine natural killer (NK) and lymphokine-activated killer (LAK) activity after in vitro incubation with media alone or media plus interferon gamma (IFN, 200 U/ml) and/or interleukin-2 (IL-2, 100 U/ml). Our results show that lymphocytes from patients with bronchogenic carcinoma can acquire LAK activity, but the level of activity acquired was significantly lower compared with lymphocytes from 25 control subjects when IL-2 cultures were supplemented with 10% autologous human serum (AHS) (15.6% +/- 2.1% specific release versus 26.0% +/- 2.9% specific release, P = 0.004). The LAK activity, defined as cytotoxicity of an NK-resistant cell line, of the patients' lymphocytes was augmented when cells were cultured with both IL-2 and IFN compared with IL-2 alone (P = 0.0001, paired t-test). Control subjects were unchanged (P = 0.09). There was no significant difference between groups of patients with different histologic types of tumor or different stages of disease. The NK activity, defined as killing of NK-sensitive K-562 target cells, of the patients' lymphocytes was not significantly different from that of the controls' lymphocytes (42.8% +/- 3.0% specific release versus 49.3% +/- 3.3% specific release, P = 0.16). These studies indicate the feasibility of IL-2 and IFN therapy in patients with bronchogenic carcinoma.
Cancer 1990 Oct 01
PMID:In vitro natural killer and lymphokine-activated killer activity in patients with bronchogenic carcinoma. 169 27

Almost all of anti-cancer drugs developed, injured not only the tumor cells but also the normal cells. For this reason, immunotherapy which injures specifically the tumor cells, has been developed. However, the clinical studies conducted in the past 20 years tend to indicate that even though the immunotherapy does not produce any serious side effect, the anti-tumor effect are not totally satisfactory in spite of marked prolongation of survivals. In recent years, various fields of cancer therapy have seen the development and application of treatment modalities which take into account the quality of the patients. Several patient's self-assessment questionnaires are widely used practical at the aims to assess what happens in the cancer-patients and to improve the cancer treatment. The measurements of quality of life have been performed on both immunochemotherapy group and chemotherapy group. The results showed the remarkable improvement of QOL in the immunochemotherapy group. The biotechnological advances have been made in the last 10 years. Various cytokines which participate in the immunological response between cancer and host. Many of these biologicals that will be called as biological response modifiers (BRM) are cell products of lymphocytes or macrophage. Systemic administration of exogenous cytokines to act against a tumor at a distant site may not be as successful as more localized therapy in situation. In most circumstances, cytokines are produced transiently at a local site acting in an autocrine or paracrine manner. Cytokines, whether naturally produced, or administered therapeutically, are rapidly clear from the circulation, both as a result of finding to often ubiquitous cell surface receptors, and by active excretion. So, the local injections of TNF and LAK cells are effective to decrease tumor size without the side effects. Finally, the serum level of IL-2 and TNF-alpha were determined for 24 healthy volunteers and 42 patients with advanced or terminal cancer, and the relationship between these levels and the QOL was investigated. In the cancer-patients who showed a higher serum level of IL-2 than the healthy volunteers, it was elucidated that there was an inverse correlation between the serum IL-2 level and the QOL. This finding cannot be explained at present, but it is surmised that, for this subpopulation of cancer-patients, the serum IL-2 level can probably serve as an objective biochemical index for use in evaluating the QOL.
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PMID:[Palliative therapy in cancer. 6. Quality of life and BRM therapy in cancer-patients]. 169 99

The cytotoxicity mediated by the CD2+ CD3- lymphocyte subset, either NK or LAK, is puzzling since no specific antigen recognition structures, equivalent to the CD3-associated heterodimer T-cell receptor, have been recognized on these cells so far. The possibility exists that the CD3- cytotoxic effectors recognize their targets through non-specific adhesion mechanisms. The goal of this study was: (a) to examine the correlation between binding properties and susceptibility to lysis of 6 informative target cell lines; (b) to evaluate the role, as ligands on these targets, of adhesion molecules such as LFA-1, LFA-3 and ICAM-1. The effectors used in this study were IL-2-activated LGL, predominantly CD3-, or highly purified CD3- lymphocytes from normal human donors. The 6 target lines studied included 2 pairs of EBV-transformed B-cell lines (721 LCL vs. 721.134, and MM vs. MM-10F2) in which the parental lines were resistant to lysis while HLA variants were susceptible. A third pair was the Daudi Burkitt cell line, susceptible to LAK lysis, and an HLA-positive transfected Daudi line which was more resistant to lysis. The binding properties of these targets to LAK effectors (conjugate formation) were evaluated using a sensitive double fluorescence flow cytometry method. In each pair examined, the susceptible targets formed more conjugates and were surrounded by more cytotoxic LAK effectors than their resistant counterparts, indicating that the conjugation properties of targets are closely correlated with their susceptibility to LAK lysis. The expression of adhesion molecules on the informative targets was examined by indirect immunofluorescence and their role was evaluated by inhibition of lysis after pre-coating the targets with the relevant antibodies. The differences in the expression of the classical cell-cell adhesion molecules LFA-1, LFA-3 and ICAM-1 on the target surfaces were only marginal, insufficient to explain the striking differences in susceptibility to lysis and in binding properties. Coating the target cells with antibodies directed against these adhesion determinants had no effects on the lysis of susceptible target cells. The same antibodies reacting with the LAK effectors did inhibit lysis. Taken together, these results suggest that, on the targets, presently undefined membrane adhesion structures may have a major role in conjugate formation between target and CD3- effectors and determine the susceptibility of the targets to lysis.
Int J Cancer 1991 Feb 01
PMID:Target lysis by human LAK cells is critically dependent upon target binding properties, but LFA-1, LFA-3 and ICAM-1 are not the major adhesion ligands on targets. 170 56

The nature of the fibrosis associated with mammary carcinomas MC2 and MC3 was investigated in syngeneic C3H mice. Accelerated and enhanced peri-tumor cellular and fibrotic responses and retarded tumor growth were observed in actively immunized and in adoptively immunized mice, and in mice treated with IL-2. T lymphocytes and, particularly, macrophages were closely associated with collagen deposition at the tumors. The collagen deposition frequently resulted in the encapsulation and regression of the less invasive tumor MC2. A cellular fibrous response was not observed at tumors implanted into athymic C3Hnu/nu mice. The results suggest that tumor fibrosis may in some circumstances be promoted by an immune response.
Int J Cancer 1992 Jan 02
PMID:Immunologic aspects of fibrosis in mouse mammary carcinomas. 172 15

Soluble inhibitory factors (SIF) have been demonstrated in the sera of cancer patients, which interfere with the T-cell activation process. We have shown that the major contributory factor to the inhibitory effect of sera from patients with Hodgkin's disease (HD) could be the soluble form of Interleukin-2 receptors (sIL-2R). The parameters studied to show the presence of SIF include (i) inhibiton of mitogen-induced proliferation; (ii) status of high- and low-affinity IL-2R; and (iii) internalization of IL-2-IL-2R complex, by lymphocytes from healthy donors activated with mitogen in presence of HD sera. Parameters studied to show the inhibitory role of sIL2R include (i) quantitation of sIL-2R in HD sera; (ii) effect of high-sIL-2R-containing sera on mitogen-induced proliferation and detection of IL-2 in activated lymphocyte culture supernatants; (iii) effect of exogenous IL-2 supplementation; and (iv) abrogation of inhibitory activity of sIL-2R-containing sera after passing them through IL-2 affinity columns. Our results show that 6/23 HD sera tested had high inhibitory activity (greater than 50% inhibition of mitogen-induced proliferation). The SIF did not affect expression of high- and low-affinity IL-2 receptors, or internalization of the complex by activated lymphocytes. Ten of the 15 sera tested showed significantly high levels of sIL-2R. Pooled sera with high sIL-2R content inhibited mitogen-induced proliferation of normal lymphocytes with a concomitant reduction in IL-2 activity in the lymphocyte culture supernatants. When supplemented with exogenous IL-2, there was a partial recovery of the inhibitory effect. When sIL-2R containing serum pool was passed on IL-2 affinity columns, the inhibitory effect was reduced. The eluted "sIL-2R" adsorbed on the IL-2 column showed anti-proliferative effect.
Int J Cancer 1992 Jan 21
PMID:Analysis of regulation of T-cell responses by soluble inhibitory factors from the sera of patients with Hodgkin's disease. 173 May 12

The purpose of this study was to evaluate the efficacy of treatment with recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells in patients with advanced bladder cancer and to study the induced changes in the distribution of leukocyte subsets in blood and tumor. Nine patients with metastatic transitional cell cancer of the bladder were treated with a continuous infusion of rIL-2 combined with lymphocytes stimulated in vitro with rIL-2. None of the patients responded to the therapy despite substantial changes observed in the immunological cells, both in tumor and blood. The rIL-2 infusion induced migration of leukocytes to the tumors, which was related to increased expression of the adhesion molecule VLA-1 on both peripheral blood mononuclear cells and the endothelial cells of small tumor vessels. Only T-cells, predominately expressing IL-2 receptors, and macrophages infiltrated the tumors. Natural killer cells remained few or absent in the tumors, even though the natural killer cells in peripheral blood were activated by the treatment. This study shows that the present technique of rIL-2 and lymphokine-activated killer cell therapy is able to induce substantial changes in the immune system of patients with metastatic bladder cancer. However, this treatment did not induce tumor regression, which may be due to the advanced stage of disease.
Cancer Res 1992 Feb 01
PMID:Recombinant interleukin-2 and lymphokine-activated killer cell treatment of advanced bladder cancer: clinical results and immunological effects. 173 60

Conventional therapy of pancreatic exocrine cancer is disappointing. The poor prognosis of the disease challenges development of novel therapeutic strategies. We report the results of clinical trials of the monoclonal antibody (Mab) 17-1A in patients with histologically verified unresectable pancreatic exocrine cancer. No antitumor response was seen in 18 patients treated with Mab 17-1A (500 mg) admixed with 10(9) autologous mononuclear cells, and 81% of the patients developed antimouse antibody response. Combination of recombinant gamma interferon and Mab 17-1A mixed with autologous mononuclear white cells resulted in complete response of 4-mo duration in 1 out of 25 evaluable patients and unusually stable disease from 4 to 48+ mo in another 6 patients. High intermittent doses of infused Mab 17-1A did not show any objective antitumor response and caused serious anaphylaxis in two of the patients in the trial. Because examination of six pancreatic adenocarcinoma cell lines with different doses of Mab 17-1A and IL-2 failed to augment lytic activity of mononuclear effector cells against all cancer cell lines tested, there seemed to be no rationale for pursuing clinical studies with IL-2 and Mab 17-1A in either the murine or chimeric form. Attractive therapeutic approaches include active immunotherapy with immunization using idiotypic antibodies or targeted toxicity with the use of radioimmunoconjugates, particularly 125I-labeled chimeric Mab 17-1A.
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PMID:Immunotherapy with monoclonal antibody (Mab) in pancreatic adenocarcinoma. 174 38

To date, the results concerning the prognostic importance of parameters of cell-mediated immunity in breast cancer patients are very contradictory; moreover, in most of them the results are hardly comparable due to methodological differences and heterogeneous groups of patients. In 123 patients with nonmetastatic breast carcinoma TNF alpha, INF alpha, IL 2 and reactivity in the leucocyte migration inhibition test (LMI-Test) against autologous tumor tissue were determined and the results correlated with the clinical course of the disease up to a maximum of 108 months. In breast cancer patients TNF alpha-serum levels were significantly (p less than 0.05) elevated compared to healthy controls. We also found that patients with progressive disease had higher levels than patients without recurrences. There were no differences concerning the IL-2 and IFN alpha serum levels between cancer patients and controls, nor did we find a correlation with the clinical course of the disease. In 38% of all breast cancer patients examined, a MIF production against tumor tissue could be demonstrated in the LMI-test. There was no difference concerning the LMI-reactivity between the groups of lymph-node negative and positive patients, but the observation that those patients with an unfavourable clinical course respond more frequently with an enhanced macrophage migration and rarely with migration inhibition was considered of notable prognostic significance. According to these results, it is possible that determination of TNF alpha and delayed type hypersensitivity reaction against tumor tissue in the LMI-test is of clinical value for the determination of risk groups.
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PMID:Determination of TNF alpha, interferon alpha, interleukin 2 and reactivity in the leucocyte migration inhibition test in breast cancer patients. 174 7


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