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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three modes of receptor-mediated cancer therapy were reviewed presenting our own data. Employment of tumoricidal cytokines (IFN, TNF, LT) to this type of therapy has been expected to be the most promising approach. However, preclinical and clinical results so far obtained, revealed that they were useful only for the very limited diseases including renal cancer or some hematological malignancies. Second approach is to utilize growth factors conjugated with toxin or carzinostatin which are readily internalized into tumor cells. In this context, transferrin-neocarzinostatin was examined in our laboratory both in vitro and in vivo for its anticancer activity and was found to suppress tumor growth more significantly than neocarzinostatin alone on the basis of molar ratio. Thus this approach may be worthy to be clinically investigated. Adoptive therapy of lymphokine activated killer (LAK) or tumor infiltrating lymphocyte (TIL) may also be categorized into receptor mediated cancer treatment since both are activated by signals through IL-2 receptor. Although clinical evaluation is still on going, the therapy appears to be effective only when effector cells are administered locally to tumors.
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PMID:[Receptor-mediated cancer therapy--tumoricidal cytokines, adoptive therapy of LAK, TIL]. 169 87

Deterioration in nutritional status occurs late in the progress of cancers at certain sites, but at all stages in patients with gastrointestinal cancer. Weight loss with decrease in body fat and muscle wastage, occurs to a varying degree. Superficially, the clinical condition resembles simple food deprivation. However, the derangements in metabolism are often and some patients show an elevated resting energy expenditure, disturbances of carbohydrate, fat and protein metabolism and generally, a failure to adapt to reduced food intake, which is characteristic of cachexia. Cancer cachexia then becomes characterized by signs of marked negative energy and protein balance, including hypoalbuminemia, weight loss, and anemia. On the other hand, toxohormone extracted from tumor tissues was considered as the main cause to produce cancer cachexia. However, it has become clearer that cytokines, e.g. cachectin/TNF, IL-1, LT and IFN gamma play an important role to produce cachexia. Patients who are malnourished have an incidence of postoperative complications double that seen in adequately nourished patients. The effectiveness of cancer-chemotherapy is also different in nutritional status of patients. Although in patients requiring hyperalimentation, enteral nutritional support may feasible and enteral feeding has a distinct metabolic advantage compared with parenteral feeding, there is a definite role for total parenteral nutrition in patients who have severe chronic radiation enteritis, side effect of chemotherapy, weight loss and malabsorption. Tentative weight gain and correction of hypoalbuminemia without improving patient survival may be expected by this intravenous hyperalimentation.
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PMID:[Palliative therapy in cancer 2. Nutrition control]. 169 91

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.
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PMID:In vitro natural killer and lymphokine-activated killer activity in patients with bronchogenic carcinoma. 169 27

Guanine ribonucleosides, substituted at the C8 position with either a bromine or a thiol group, have recently been shown to regulate several immunologic responses. We have previously shown that 8-mercaptoguanosine (8MG) can replace the requirement for cytokines in the generation of MHC-restricted CTL. In this paper, we examined the ability of 8MG to induce MHC-nonrestricted killer cells. We found that 8MG did not induce significant lytic activity from normal resting lymphocytes. However, 8MG was able to synergize with minimal amounts of IL-2 in inducing lytic activity similar to lymphokine-activated killers (LAK) in that both NK-sensitive and NK-resistant tumor cells were killed. Both the precursors and effectors of 8MG-LAK activity were similar to NK cells and were CD4- CD8- asialo-GM1+ NK1.1+. Similar to IL-2-induced LAK, 8MG-LAK were B220+. 8MG appeared to "stage" these precursor lymphocytes to become more responsive to IL-2 because optimal induction of 8MG-LAK required preincubation with 8MG before the addition of IL-2. This "staging" appeared to be due to the release of a "second signal" since it was readily inhibited by cyclosporine A. Anti-IFN-alpha beta was as efficient as cyclosporine A in inhibiting 8MG-LAK generation, whereas anti-IFN-gamma and anti-IL-1 did not exhibit significant inhibition. These findings suggest that 8MG can be of possible utility as an IL-2-sparing agent in LAK generation from NK cells.
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PMID:Lymphokine-activated killer (LAK) cells. V. 8-Mercaptoguanosine as an IL-2-sparing agent in LAK generation. 170 14

The human interferon-induced intracellular protein homologous to the murine Mx-protein has recently been identified by means of a specific monoclonal antibody. Three of six melanoma cell lines elicited this intracellular human Mx-homolog upon incubation with IFN-alpha or IFN-gamma, yet all six melanoma cell lines tested were susceptible to the antiproliferative effect of IFN-alpha and IFN-gamma. Compared per antiviral unit, IFN-gamma had weaker Mx-inducing but stronger antiproliferative activity than IFN-alpha. These data suggest that the IFN-induced Mx-homologous protein is not involved in the antiproliferative action of IFN on malignant melanoma cell lines. Furthermore, 51 patients with advanced malignant melanoma were treated thrice weekly with 10 x 10(6) IU rIFN-alpha-2b and 6 x 10(6) nIFN-alpha, respectively. Nine of the 51 patients experienced systemic objective tumor responses (3 complete response, 6 partial response), but had Mx concentrations in their mononuclear cells equal to the Mx levels of non-responders during IFN-alpha therapy. Therefore, the level of Mx-homologous protein induced during IFN therapy is not a predictive marker for an antitumor response in malignant melanoma.
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PMID:Correlation of the antiproliferative effect and the Mx-homologous protein induction by IFN in patients with malignant melanoma. 170 9

The mechanism of tumor regression by adoptive immunochemotherapy has been unknown. We examined tumor infiltrating lymphocytes (TILs) and cytokines, using immunohistochemical staining and the histo in situ hybridization (HISH) technique, on Meth A tumor in regression of BALB/c mice. In addition, we examined cytokine activity in the serum of mice with a tumor in regression. The result of immunohistochemical staining showed that the number of Thy-1+ cells, Lyt-1+ cells, OKIa1+ cells all increased in the tumors in regression compared to those in the tumors in non-regression. However, there were no these TILs in the necrotic part of tumor. This result suggested that TILs released substances which might include cytokines. A small number of each cytokine mRNA was observed, using HISH with cytokine DNA probes. TNF-alpha, and -beta mRNA were observed in both he tumors in regression and non-regression; while, IFN-beta and -gamma mRNA were observed only in the tumor in regression. TNF-alpha activity in the serum of tumor in regression group was higher than that of he tumor in non-regression group. IFN activity in the serum of the tumor in regression group started increasing after adoptive immunochemotherapy. These results show that cytokines as well as TILs have important roles in tumor regression.
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PMID:[Study on the mechanism of tumor regression by adoptive immunochemotherapy in mice]. 170 81

Eight patients with metastatic carcinoid tumor, seven of whom had symptoms of the carcinoid syndrome, were treated with either human leukocyte interferon (seven patients) or recombinant alpha-interferon (IFN alpha-2b) (one patient) at doses of 4.5 to 21 x 10(6) IU weekly for 1 to 21 (mean, 8.5) months. Tumor regression on computed tomography (CT) scan was found in one patient, the CT findings remained unchanged in three, and the tumor progressed in four patients. A clearcut and continuing decrease in urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) was observed in one patient and a transient one in four patients. The symptoms improved in only two of seven patients. Four patients had leukopenia develop, which was circumvented by reducing the dose. The authors conclude that interferon therapy of the carcinoid tumor is not as successful as has been suggested in previous reports.
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PMID:Is the treatment of metastatic carcinoid tumor with interferon not as successful as suggested? 185 91

Hairy cell leukemia (HCL) is a B cell tumor affecting the pre-plasma stage of B cell differentiation. Hairy cells produce B cell growth factor (BCGF)-related growth factor(s) and we have previously shown that low mol wt (LMW)-BCGF-induced proliferation of hairy cells is inhibited in vitro and in vivo by IFN-alpha. We therefore suggested that this effect might contribute to the exquisite sensitivity of HCL to IFN-alpha therapy. To elucidate the mechanism involved in the therapeutic effect of IFN-alpha, we have analyzed the pattern of phosphorylated proteins in hairy cells. We detected the presence of a hyperphosphorylated protein with a molecular mass of about 35 kDa. This protein was identified as the CD20 molecule (B1), which is a structurally unique phosphoprotein exclusively detected on B cells and expressed during most stages of B cell development. Incubation of hairy cells with mitogenic concentrations of LMW-BCGF induces an additional increase in CD20 protein phosphorylation. In contrast, preincubation of cells with IFN-alpha, but not IFN-gamma, decreases both basal and LMW-BCGF-induced CD20 phosphorylation. CD20 phosphorylation in hairy cells is also reduced after in vivo IFN-alpha administration. In contrast, in one case of a patient unresponsive to IFN-alpha therapy, CD20 phosphorylation is not altered by in vitro IFN-alpha treatment, whereas LMW-BCGF still elicits CD20 phosphorylation stimulation. Our results suggest that IFN-alpha may act in HCL, at least in part, by inhibiting leukemic cell proliferation via regulation of phosphorylation, since CD20 phosphorylation is thought to be associated with cellular proliferation. A model involving dysregulation of CD20 is discussed.
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PMID:Hyperphosphorylation of CD20 in hairy cells. Alteration by low molecular weight B cell growth factor and IFN-alpha. 170 83

A human monoclonal antibody with specificity for breast and colorectal carcinoma has been isolated after hybridoma formation between regional lymph node lymphocytes from a patient with breast carcinoma and a mouse x human heteromyeloma (SPAZ-4). The monoclonal, MAB 15.2.3, is an IgM, kappa, which binds to an epitope found on at least four glycoproteins with approximate molecular weights of 37, 39, 43 and 56 kilodaltons (kD). These antigens are expressed intracellularly and on the surface of breast and colorectal carcinoma cells and their level of expression is increased by treatment with recombinant human leukocyte (IFN-alpha A) or immune (IFN-gamma) interferon. Analysis of formalin-fixed tumor cell lines indicates specificity for carcinomas. Similarly, immunostaining of paraffin-embedded tissue indicates both cell membrane and intracytoplasmic reactivity with breast (8 of 12), colorectal (3 of 4) and prostate (1 of 3) carcinomas. By employing a series of enzymes which specifically cleave sugar residues on proteins, it was demonstrated that the binding of MAB 15.2.3 could be increased. These observations suggest that the epitope recognized by MAB 15.2.3. is protein in nature and expressed on a series of glycoproteins. Pretreatment of Colo 205 (human colorectal carcinoma) cells with MAB 15.2.3 prior to implantation into nude mice, results in a reduction in the size and weight of tumors. With appropriate genetic engineering, resulting in the conversion of this antibody to an IgG, MAB 15.2.3. could prove of value for the diagnosis and ultimately the therapy of human breast and colorectal carcinomas.
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PMID:Isolation and characterization of a human monoclonal antibody which reacts with breast and colorectal carcinoma. 170 93

Macrophages in varying states of activation differ in their ability to perform antibody-dependent cellular cytotoxicity (ADCC) and antibody-independent macrophage-mediated tumor cytotoxicity (MTC). To define further the activation requirements for macrophages to perform various cytolytic functions, we stimulated peptone-elicited peritoneal macrophages, which are only poorly cytolytic, with one of a panel of cytokines and then quantified three distinct cytolytic capacities. The peptone-elicited macrophages, after stimulation with IFN-alpha/beta, IL-4, or TNF, had increased ability to perform both the rapid and slow variants of ADCC but not to perform MTC. Stimulation with high doses of IFN-gamma, however, increased the macrophages' ability to perform all three cytolytic functions. GM-CSF had no effects on any cytolytic capacity. The effects of IL-4, TNF, IFN-gamma, and IFN-alpha/beta on the macrophages' capacity for both forms of ADCC were dose-dependent. IFN-gamma and IFN-alpha/beta increased the macrophages' capacity for both variants of ADCC within 4 hr of treatment, whereas IL-4 and TNF did so only after prolonged treatment. These results suggest that three forms of macrophage cytolytic capacity can be enhanced by cytokine treatment but that the requirements for enhancing each of the three forms of macrophage cytolytic capacity differ.
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PMID:Activation of macrophages for ADCC in vitro: effects of IL-4, TNF, interferons-alpha/beta, interferon-gamma, and GM-CSF. 170 10


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