Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperthermia treatment has been shown to enhance the in vitro antiproliferative effects of IFN-alpha, IFN-beta, and IFN-gamma, with IFN-gamma being more strongly enhanced than IFN-alpha. The comparative effects of hyperthermia on the in vivo antitumor activities of IFN-alpha and IFN-gamma were evaluated in the murine system using both subcutaneous and intraperitoneal B16 melanoma tumor model systems. Heat-induced whole body hyperthermia, resulting in a 2 degree C rise in body temperature, was administered by incubating the mice for 8 hours in a dry incubator at 37.1 degrees C. Whole body hyperthermia was found to enhance the antitumor activity of IFN-alpha by approximately 1.0 fold and 1.2 fold for the subcutaneous and intraperitoneal tumor models, respectively. This represented an additive effect of hyperthermia and IFN-alpha. Hyperthermia was found to enhance the antitumor activity of IFN-gamma by approximately 2.9 fold and 2.2 fold for the subcutaneous and intraperitoneal tumor models, respectively. This represented a synergistic effect of hyperthermia and IFN-gamma. The results of this in vivo study confirm and extend the in vitro observation that hyperthermia more strongly enhances the antitumor action of IFN-gamma than IFN-alpha. These results may have clinical importance because they suggest that hyperthermia may be used in combination with IFN-gamma to provide a synergistically enhanced antitumor action.
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PMID:Effect of hyperthermia on the antitumor actions of interferons. 128 87

Tumor cells often display alterations in their normal program of cellular differentiation. A promising approach for the treatment of cancer involves the induction of terminal differentiation and a loss of proliferative capacity in cancer cells. In human melanoma cells, the combination of mezerein (MEZ) and fibroblast interferon (IFN-beta), results in a rapid and irreversible suppression of cell growth with a concomitant increase in the synthesis of melanin. The induction of terminal differentiation is associated with alterations in the expression of several cellular genes, including fibronectin, ISG-15 and ISG-54, and changes in the expression of specific cell surface antigens, including intercellular adhesion molecule-1 (ICAM-1) and HLA Class I antigens. In the HO-1 human melanoma cell line, induction of terminal differentiation by MEZ plus IFN-beta results in an induction and/or increased expression of ICAM-1, HLA Class I antigens and HLA Class II antigens. IFN-beta and MEZ alone can modulate expression of these antigens to a lower extent than does the combination of compounds. Induction of terminal differentiation and the irreversible suppression of cell growth is not a prerequisite for antigenic modulation in HO-1 cells. This is indicated by the inability of immune interferon (IFN-gamma), a strong inducer of ICAM-1, HLA Class I antigens and HLA Class II antigens synthesis, or the combination of IFN-beta plus IFN-gamma which synergistically but reversibly suppresses HO-1 growth, to induce melanin synthesis or terminal differentiation in HO-1 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of the antigenic phenotype of human melanoma cells by differentiation-inducing and growth-suppressing agents. 135 50

The clinical tolerance of and the effects recombinant human interferon-beta (rHuIFN-beta) obtained from mammalian cells (Chinese hamster ovary cells) exerts on 2',5'-oligoadenyl (2-5A) synthetase activity, human-Mx protein, neopterin, beta 2-microglobulin, interleukin-1 (IL-1) alpha and beta synthesis were compared to those of natural IFN-beta in 12 healthy volunteers. Each subject received a single i.m. injection of 6 x 10(6) IU rHuIFN-beta and natural IFN-beta according to a randomized double-blind cross-over study design. Both were well tolerated and provoked similar changes in clinical indices. Moreover, rHuIFN-beta and natural IFN-beta induced significant and similar increases in 2'-5' adenylates, human Mx protein, and neopterin levels, but neither modulated beta 2-microglobulin, IL-1 alpha or beta synthesis. The sum of these findings indicates that rHuIFN-beta and natural IFN-beta are biologically equivalent. In view of these results, we are of the opinion that these two types of IFN are probably also therapeutically equivalent and, in consequence, that trials to evaluate the response of viral and neoplastic disease patients to rHuIFN-beta are fully justified.
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PMID:Double-blind randomized phase I study on the clinical tolerance and biological effects of natural and recombinant interferon-beta. 143 12

In a serum-free culture system, the release of TNF, lI-1, lI-6, IFN-alpha, and IFN-beta during interaction of elutriated human monocytes (MO) with human tumor cells (TC) was studied by ELISA-technique. Contributions of these cytokines to inhibition of TC-growth and to induction of TC-death by supernatants (SU) gained from such MO/TC-interaction cultures were investigated using affinity chromatography for removal of individual cytokines. Although the TC used are relatively insensitive to recombinant human TNF, withdrawal of TNF causes 50% to 75% reduction of SU-induced TC-death rates, suggesting that susceptibility to TNF is raised during MO/TC-interaction by the other cytokines. Individual removal of other cytokines does not cause reduction of SU-mediated TC-death. However, combined withdrawal of lI-1 and IFN-alpha/beta causes in 2 of 4 TC-lines significant reduction of TC-death. Combined removal of TNF, IFN-alpha/beta, lI-1, and lI-6 leads to complete prevention of SU-mediated growth inhibitory and lytic effects, suggesting that besides these cytokines other signals are not involved significantly. SU-effects can be mimicked by appropriate combinations of authentic cytokines. The response of TC to SU- or cytokine-exposure is strikingly dependent on TC-density, leading at subconfluent TC-density exclusively to inhibition of growth and at postconfluent TC-density to induction of cell death. The principal effect of SU or cytokine combinations in this context seems to be the activation of growth inhibitory signal transduction pathways leading to TC-death in postconfluent TC-populations exclusively if growth stimulatory pathways are activated at the same time. Mouse L cells do not follow this reaction pattern: Their death is exclusively dependent on the presence of TNF in SU and they die upon SU-exposure at postconfluent as well as at subconfluent cell density.
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PMID:Cytokines involved in monocyte mediated tumor cell death and growth inhibition in serum-free medium. 150 17

To investigate a possible role of cytokines in parvovirus-mediated suppression of tumorigenesis, we tested in cell culture whether parvoviruses are able to induce interferon (IFN)-beta, tumor necrosis factor (TNF)-alpha or interleukin-6 (IL-6). Infection of rodent or human cells with the parvoviruses minute virus of mice (MVM), H-1 or adeno-associated virus (AAV) types 2 or 5 failed to induce expression of the luciferase or beta-galactosidase reporter genes transfected into these cells as constructs containing an IFN-beta promoter. Parvoviruses did weakly induce synthesis of TNF-alpha and of IL-6 in cell culture and could slightly enhance synthesis of these cytokines when induced by other agents. These in vitro data suggest that the rather unspecific tumor-suppressive properties of parvoviruses are unlikely to be attributable to stimulation of the synthesis of IFN, TNF or IL-6.
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PMID:Parvoviruses are inefficient in inducing interferon-beta, tumor necrosis factor-alpha, or interleukin-6 in mammalian cells. 152 25

Class I antigens are necessary for the recognition of tumor cells by cytotoxic T lymphocytes (CTL). The line 1 lung carcinoma is a spontaneous murine tumor deficient in class I antigen expression. Consistent with this, line 1 cells are highly metastatic in vivo. We investigated whether increasing class I antigen expression on line 1 cells could alter the metastatic potential of these tumor cells using an in vivo lung metastasis model. We used three methods to induce class I antigen expression on line 1 cells: gene transfection, treatment with dimethyl sulfoxide (DMSO), or treatment with interferon (IFN)-beta or -gamma. We found that line 1 cells expressing a transfected class I gene were significantly less metastatic than parental line 1 cells. DMSO-treated line 1 cells also formed significantly fewer metastases than parental line 1 cells. These results indicate that increased class I antigen expression decreases the metastatic potential of line 1 cells in vivo. However, we did not observe a significant decrease in the number of lung metastases in mice receiving line 1 cells treated with IFN-beta or -gamma, despite high levels of class I antigen expression. Thus, increasing class I antigen expression with IFN has an opposite effect on metastasis from class I antigen expression induced by transfection or DMSO. These results show that the method used to increase class I antigen expression is critical in terms of the in vivo effect observed. To investigate a possible mechanism for the differences observed in vivo between these class I expressing cells, we tested whether IFN alters or blocks susceptibility of line 1 cells to immune effector cells. We found IFN treatment increased the ability of line 1 cells to be recognized by CTL but concomitantly decreased the susceptibility of line 1 cells to NK cell lysis by a non-class I antigen-related mechanism. In contrast, transfected or DMSO-treated line 1 cells which were less metastatic in vivo were susceptible to both CTL and NK-mediated lysis. Taken together, these results suggest that immune intervention against metastasizing line 1 cells may involve NK cells and CTL.
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PMID:Alteration of the metastatic potential of line 1 lung carcinoma cells: opposite effects of class I antigen induction by interferons versus DMSO or gene transfection. 169 90

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

Interferon-alpha is an effective treatment for a subset of patients with AIDS-associated Kaposi's sarcoma. When given at high doses to patients who lack systemic signs, symptoms, and opportunistic infections associated with advanced HIV infection and who maintain some degree of cell-mediated immune function, tumor regression may be observed in a high proportion of patients. Although the addition of chemotherapy to IFN-alpha appears to confer no added benefits, the combination of IFN-alpha with zidovudine has induced high tumor response rates in preliminary studies, including responses in some patients considered unlikely to respond to IFN-alpha alone. IFN-alpha-induced tumor regression has also been associated with suppression of HIV, as measured by serum p24 antigen concentrations and peripheral blood virus cultures. Other biologic agents, including interferons beta and gamma, tumor necrosis factor, and IL-2, have also been tested, to a lesser extent, in patients with Kaposi's sarcoma. Although systemically administered IFN-beta and intralesional TNF injections have led to tumor regression in some cases, the role of these biologics has been incompletely defined. Additional studies of these agents in combination with nucleoside reverse transcriptase inhibitors such as zidovudine will be required to fully assess their role in the treatment of Kaposi's sarcoma and HIV infection. It can also be anticipated that newer biologic agents, which specifically inhibit the production or action of angiogenic factors believed to be involved in the genesis of Kaposi's sarcoma, will be studied in the near future.
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PMID:Interferon and other biologic agents for the treatment of Kaposi's sarcoma. 170 60

We compared the regulatory effects of interferon (IFN)-beta and IFN-gamma on the susceptibility of a human gliosarcoma line GI-1 to the attack of autologous cloned tumor-specific cytotoxic T-lymphocytes (CTL) and lymphokine-activated killer (LAK) cells. Preincubation of GI-1 cells with IFN-gamma caused augmented susceptibility to the cytotoxic attack of two autologous CTL clones, whereas IFN-beta exhibited no such marked effect. On the other hand, preincubation with either IFN-beta or IFN-gamma made the GI-1 cells resistant to the attack of autologous LAK cells. Both IFNs augmented the surface expression of HLA class-I molecules on GI-1 cells. A monoclonal anti-HLA class-I antibody blocked the cytolysis by one CTL clone, but not by the other one. These results suggest that IFN-gamma exerts some different effect (s) from that of IFN-beta on the target GI-1 cells in their susceptibility to the CTL-mediated cytolysis, and that recognition mechanisms of target cells by the CTL are different from those by LAK cells. This draws our attention to IFN administration in adoptive immunotherapy against brain tumors using CTLs and LAK cells.
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PMID:[Immunomodulatory effects of interferons on target human gliosarcoma cells in the tumor-specific CTL- and LAK-mediated cytolysis]. 176 55

We previously showed that the in vivo invasion of a squamous cell carcinoma induced by the intradermal injection of tumor cells was significantly delayed after the IFN-gamma-producing gene transfer to tumor cells. With respect to the mechanism of the delayed invasion, it was suggested that the IFN-gamma might inhibit the adhesion of the cells to extracellular matrices (ECM) and the subsequent locomotion. Thus, we examined the effect of IFN-gamma on the adhesion of Pam-T cells to ECM. The attachment of Pam-T cells to fibronectin (FN) was significantly higher than that to laminin (LN), collagen type I (COL I) or collagen type IV (COL IV) substrata. The attachment to FN was significantly enhanced specifically by the IFN-gamma-treatment of the cells, although the attachment to LN, COL I or COL IV was not altered by IFN-gamma. Neither IFN-alpha nor IFN-beta had any effect on the attachment of Pam-T cells to FN. When Pam-T cells were treated with IFN-gamma together with a neutralizable anti-IFN-gamma antibody, this enhancement was completely abolished. Moreover, the attachment of IFN-gamma-treated Pam-T cells as well as non-treated cells to FN was blocked by the synthetic peptide Arg-Gly-Asp-Ser (RGDS), but not by the control peptide Arg-Gly-Glu-Ser. Based on these results, we conclude that IFN-gamma specifically enhances the adhesiveness of Pam-T cells to FN substrata by the modulation of integrin activity.
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PMID:Modulatory effects of interferon-gamma on the fibronectin receptor function of squamous cell carcinoma cells in vitro. 183 57


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