Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo anti-tumor activity of 2 recombinant cytokines, interleukin-2 (rIL-2) and human hybrid interferon alpha (rHuIFN-alpha A/D), were tested using the murine reticulum cell sarcoma M5076. Experimental hepatic metastases, following i.v. injection of tumor cells, and tumor growth and spontaneous metastases, following s.c. injection of tumor cells, were inhibited to a greater extent in mice treated with a combination of these cytokines than in animals treated with either one alone. When used in conjunction with surgical removal of the s.c. tumor, treatment of mice with both cytokines significantly prolonged survival of tumor-bearing animals. Injection of normal mice with a combination of cytokines, but not with either cytokine alone, resulted in a marked increase in cytotoxic activity of hepatic effector cells. The effector cells in these mice appeared to be NK cells since this enhanced cytotoxicity was markedly reduced in animals treated in vivo with anti-asialo GM1 or in NK-deficient beige mice. Furthermore, no in vivo efficacy was observed in M5076-bearing beige mice treated with these cytokines. Thus, injection of mice with rIL-2 and rHuIFN-alpha A/D results in the induction of an NK-cell-like population in the liver with enhanced cytotoxic activity that correlates with the observed anti-tumor activity in vivo in this murine model. These results suggest that combinations of cytokines, in particular IFN-alpha and IL-2, can be effectively used in combination for the treatment of tumors and/or metastases.
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PMID:In vivo anti-tumor activity of combinations of interferon alpha and interleukin-2 in a murine model. Correlation of efficacy with the induction of cytotoxic cells resembling natural killer cells. 349 83

The latest treatment of biological response modifiers (BRM) with or without another cancer treatment modalities has been increased. In this paper, radiotherapy combined with some BRM, which were used in systemic administration and intra-arterial infusion, was demonstrated. 1) In experimental study, radiation and IL-2 indicated the synergic effects on the tumor growth inhibition. 2) Radiotherapy and IFN-beta for advanced head and neck and pelvic tumor were successful in tumor effects and tolerable in side effects. 3) The clinical trial showed that pathological effects and clinical tumor response (CR rate) of radiation and LC9018 for cervical cancer stage IIb, III were significantly better than those of radiotherapy alone. These data suggested that the treatment of radiation and BRM was useful and should be considered in multimodal therapy for cancer.
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PMID:[Radiotherapy combined with BRM (biological response modifiers) in the treatment of cancer]. 349 28

The capacity of inbred W/Fu rats bearing syngeneic colon carcinomas to generate interleukin(s) (IL) was studied during primary tumor growth, after tumor resection, and during postresection immunotherapy. During local tumor growth, there was a significant decrease in the capacity of the host's adherent mononuclear cells to generate IL-1 and of peripheral blood mononuclear cells to generate IL-2 (16.6 and 23%, respectively, when compared to control animals; P less than .01). The presence of regional metastases or large primary tumor burden resulted in a further sharp fall in IL generation (0.9 and 10% for IL-1 and IL-2, respectively, when compared to control animals; P less than .01). With the use of three different doses of tumor inoculum, inhibition of IL generation was shown to occur when tumors were barely palpable. Decrease in IL correlated with tumor growth and not with the initial number of tumor cells injected. Tumor resection resulted in a rise in IL-2 generation from 36 to 64% of control animals' levels. Postresection immunotherapy with the use of an active specific immunization protocol successfully modulated IL-2 production to normal in animals protected from tumor recurrence. Animals that developed recurrent tumors despite immunization exhibited a continued inability to generate IL (mean values of IL-2 production compared to controls: 184% in animals free of recurrence after immunotherapy, 1% in animals developing recurrent tumors after immunotherapy; P less than .01). These results suggested that alterations in IL generation may lead to immune unresponsiveness during tumor growth. Active specific immunotherapy protecting animals from recurrence after primary tumor resection may be predicated on the successful modulation of IL level generation by host immunocytes.
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PMID:Interleukin generation in experimental colon cancer of rats: effects of tumor growth and tumor therapy. 387 59

This study delineates the temporal relationship between immune complex formation and tumor growth, and provides one possible explanation for host immunosuppression during tumor growth. The authors have studied serial circulating immune complex (CIC) levels and interleukin (IL) elaboration by peripheral blood cells (IL-1 production by adherent mononuclear cells [AMC]; and IL-2 generation by peripheral blood mononuclear cells [PBMC]) during the growth of syngeneic tumor isografts in an inbred rat model. Male Wistar/Furth (W/Fu) rats were injected, subcutaneously (SC) with 2 X 10(6) W163 ( a dimethylhydrazine [DMH]-induced colon adenocarcinoma) cells into their hind limbs. Serial CIC levels, (measured by the antigen nonspecific polyethylene glycol turbidity assay) and IL-1 and IL-2 production were measured before isografting and weekly thereafter. Progressive local tumor growth occurred for 3 weeks followed by regional lymph node metastases during the fourth week. During local tumor growth, there was a progressive rise in CIC levels (123% rise compared with baseline value; P less than 0.05) which correlated with a fall in both IL-1 and IL-2 generation (r = -0.768). At the time of regional metastasis, the mean CIC levels declined, and there was a further significant decrease in IL production (IL-1 = 0.9% and IL-2 = 10% of controls in tumor bearers). These results show that progressive tumor growth results in decreased IL production by host PBC, and suggest that CIC may be involved in regulating IL generation.
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PMID:Effects of tumor growth on interleukins and circulating immune complexes. Mechanisms of immune unresponsiveness. 660

The efficacy of glioma-specific cytotoxic T-lymphocyte for a syngeneic murine malignant glioma (a 20-methylcholanthrene-induced ependymoblastoma, 203-glioma) was investigated. The cytotoxic clone (G-CTLL 1), established and expanded exponentially by T-cell growth factor, has retained target specificity for more than 6 months. In adoptive therapy and Winn assay, the in vivo antitumor activity of G-CTLL 1 was demonstrated against mice inoculated intracranially with 203-glioma cells. The therapeutic effects in adoptive immunotherapy were largely dependent on dose and time of i.v. administration, although the therapy was rather ineffective in condition of increased intracranial pressure due to the tumor growth. The mechanisms responsible for the in vivo protection were probably related to the killing activity of G-CTLL 1 or the tumor-specific production of immune interferon by G-CTLL 1.
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PMID:Specific adoptive immunotherapy with tumor-specific cytotoxic T-lymphocyte clone for murine malignant gliomas. 660 88

The immunoregulatory effects of TCGF (T-cell growth factor) on the generation and growth of syngeneic murine malignant glioma (20-methylcholanthrene-induced 203-glioma)-specific killer T-cell were investigated in C57BL/6 adult mice in order to clarify the immunopotential usefulness for anti-tumor local adoptive immunotherapy against malignant brain tumor. TCGF was prepared and assayed. Briefly, 5 x 10(6) ml mouse spleen cells were cultured with 2 microgram/ml concanavalin A in RPMI-1640 medium supplemented with 2% fetal calf serum for 24 hours. Culture supernatants were concentrated by ammonium sulphate precipitation (55 to 80% saturation) and purified by gel filtration (Sephadex G-100, a molecular weight from 30 to 36,000 daltons) and ion exchange chromatography (DEAE-cellulose, elution with 0.15 M in NaCl at ph 7.4). The purified TCGF had no IFN activity. Assays for TCGF was performed for quantitative analysis using 203-glioma-specific killer T cell clone (G-CTLL), which was obtained by limiting dilution method (0.3 cells/well in 96 well microtiter plate) and maintained for over 6 months in the presence of TCGF. Titer (U/ml) of TCGF was defined as the quantity of TCGF required to obtain one-half of the maximal stimulation of G-CTLL proliferation assay. It was confirmed that the specific killer T-cell against 203-glioma was generated in mice after intracranial as well as subcutaneous inoculation of the tumor cells. The killer T-cell activity of spleen cells, however, began to be severely impaired 2 weeks after intracranial inoculation concurrently with the increased intracranial pressure due to developing the tumor growth. Sensitized lymphocytes obtained from intracranial and subcutaneous tumor-bearing mice were assessed for CTL (cytotoxic T-lymphocyte) activity in MLTC (mixed lymphocyte-tumor cell culture) for 18 hours by microcytotoxicity assay. The specific cytotoxicity against 203-glioma cells was enhanced when sensitized lymphocytes from intracranial and subcutaneous tumor-bearing mice were pre-cultured with optimal TCGF (20 U/ml) for over 5 days. After the treatment of sensitized lymphocytes with anti-Thy-1 monoclonal antibody and complement, however, the specific cytotoxicity of sensitized lymphocytes was eliminated almost completely. Therefore, it was thought that TCGF possesses immunoregulatory effects of enhancement of killer T-cell activity. On the contrary, TCGF had no influence on normal T lymphocytes and the growth of 203-glioma cells in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Effects of TCGF (T-cell growth factor) on experimental malignant glioma-specific killer T-cell]. 660 19

Immunoregulatory factor (IRF) is a 70,000 molecular weight glycoprotein produced by human tumors that suppresses lymphocyte function including mitogen-stimulated tritiated leucine (3H-leu) and tritiated thymidine (3H-Tdr) uptake, in vitro immunoglobulin synthesis, induction of allospecific cell-mediated cytotoxicity, and proliferation of T-cell growth factor-dependent lymphocyte cultures. Antisera to IRF were produced by immunization of goats and rabbits with IRF purified by diethylaminoethyl (DEAE)-anion exchange and affinity chromatography. Antisera specificity was demonstrated by binding to IRF but not control muscle extract in an ELISA test and by specific removal of IRF activity by antibody coupled to acrylamide beads. Using these antisera, a double antibody-binding assay was developed to measure circulating levels of IRF and to determine its relationship to tumor growth and relevance for monitoring the clinical course of cancer patients. Quantitative autologous as well as allogeneic binding of sarcoma patients' sera to anti-IRF antibody was demonstrated. Of five tumor extracts tested, two had immunosuppressive activity, and IRF was detected in the preoperative sera of both patients. These extracts were not suppressive and IRF was not detected in the preoperative sera of these patients. In a double-blind study, analysis of serial serum samples from 26 sarcoma patients, 11 normal volunteers, and eight noncancer patients, demonstrated four patterns of circulating IRF: sustained high levels, increasing levels, decreasing levels, and no detectable IRF. Seven of 14 patients who eventually developed metastatic disease demonstrated sustained high or increasing levels of IRF. Eleven of 12 patients clinically free of tumor for five years or more, ten of 11 normal volunteers, and eight of eight noncancer patients had either a pattern of decreasing levels or no detectable IRF. Circulating IRF levels are correlated with the presence of tumor and may be useful in monitoring the clinical course of cancer patients.
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PMID:Detection of a suppressive immunoregulatory factor (IRF) in the sera of sarcoma patients by enzyme-linked immunoassay (ELISA) and correlation with clinical course. 687 4

A human monoclonal anti-idiotypic antibody, 105AD7, which mimics a colorectal tumor associated antigen, 791Tgp72, has been developed. A Phase I trial in advanced colorectal cancer patients showed that 105AD7 therapy was nontoxic and that immunised patients had prolonged survival when compared to a contemporary group of patients treated in the same center. There is accumulating clinical evidence that 105AD7 delays tumor growth by stimulating anti-tumor T-cell responses. Stimulation of helper T-cells was exemplified in the phase I study as 105AD7 immunized patients showed antigen specific T-cell blastogenesis responses and enhanced IL-2 production. Further evidence was obtained from a new clinical study in which colorectal cancer patients were immunized prior to tumor resection. Immune infiltrating cells were analysed by immunohistochemistry and effector cell function was studied in immune cells from peripheral blood and tumor draining lymph nodes. Both activated CD4 and natural killer (NK) cells were observed at the tumor site, which is of interest as NK cells are rarely found in colorectal tumors. Effector studies confirmed that NK activity was enhanced in 3/6 patients. Increased autologous tumor killing was also found in 3/4 patients and accumulation of CD8RO cells following 105AD7 immunization also suggested that CD8 T cells were being stimulated.
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PMID:Clinical evidence that the human monoclonal anti-idiotypic antibody 105AD7, delays tumor growth by stimulating anti-tumor T-cell responses. 749 53

We screened a panel of 8 primary and 21 metastatic melanoma cell lines for constitutive secretion of cytokines. Melanomas expressed bioactivity for TGF-beta (8/25 lines) and IFN (7/12), but not IL-2. Immunoassays detected IL-1 alpha (4/25), IL-1 beta (12/25), IL-6 (13/29), IL-8 (29/29), TGF-beta 2 (5/12) and GM-CSF (11/29), but not IL-3, IL-4, TNF-alpha, or IFN-gamma. There was no preferential association of cytokine production with cells cultured from primary versus metastatic disease, and only IL-8 was produced by all lines tested. These data demonstrate that cultured melanomas produce a variety of cytokines which are potentially capable of influencing tumor growth in vivo.
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PMID:Production of multiple cytokines by cultured human melanomas. 751 80

We have previously demonstrated that local tumor irradiation effectively enhanced the therapeutic effect of IL-2 therapy on pulmonary metastases from a murine renal adenocarcinoma, Renca. Irradiation with 300 rad to the left lung only, followed by systemic IL-2 therapy, results in increased tumor reduction in both lungs, suggesting that radiation enhances the systemic effect of immunotherapy. In this study, we show that irradiation of the tumor-bearing organ is essential for the combined effect of both modalities. This effect is radiation dose-dependent as increases in the radiation dosage result in greater tumor reduction in the irradiated field as well as systemically in nonirradiated fields when combined with immunotherapy. We find that irradiation has a direct inhibitory effect on Renca cell growth in vitro. Irradiation of Renca cells also causes an upregulation in H-2Kd class I MHC antigen detectable at 300 rad and more pronounced with 800 rad. By in vivo selective depletion of lymphocyte subsets, we demonstrate the involvement of Lyt-2+ and L3T4+ T cell subsets and AsGM1+ cells, including NK cells, in the antitumor effect mediated by tumor irradiation and IL-2 therapy. Immunohistochemistry studies, performed on lung sections, showed a significant infiltration of CD3+ T cells and macrophages in the tumor nodules following treatment with tumor irradiation and IL-2 therapy. Our studies indicate that the mechanism of interaction between tumor irradiation and immunotherapy may include radiation-induced alterations in the tumor growth and antigenicity which may enhance or trigger an anti-tumor response elicited by IL-2 and mediated by T cells, AsGM1+ cells, and macrophages.
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PMID:Local tumor irradiation augments the response to IL-2 therapy in a murine renal adenocarcinoma. 755 89


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