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)

Nine patients with metastatic breast cancer received 30 x 10(6) I.U. of Interferon - Betaser (Betaseron) intravenously daily times five for two consecutive weeks followed by a two week rest period. Only one patient received more than one such cycle of Betaseron. The drug was well tolerated in eight of these patients. One patient, with liver metastases and liver dysfunction, developed hepatic decompensation during therapy. Toxicity consisted of anorexia, chills, fever, fatigue and nausea with an occasional patient having emesis. One patient developed severe thrombocytopenia, two, significant leukopenia and nine, mild elevations of serum transaminase. Two patients developed beta interferon binding antibodies but none developed neutralizing antibodies. No anti-tumor responses were seen and disease progression occurred rapidly during the four week cycle in eight of nine patients.
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PMID:Phase II trial of recombinant beta (IFN-betaser) interferon in the treatment of metastatic breast cancer. 319 87

A capillary cloning system for primary human tumor colony-forming units was applied to a total of 286 tumors, and 226 (79%) provided satisfactory cultures. These were used to study the in vitro anti-proliferative effects of a recombinant DNA human interferon-beta (rIFN-beta ser). Growth inhibition was somewhat greater when relatively high IFN concentrations were used, but continuous exposure to the IFN was not more effective than exposure for only 1 h. The tumors inhibited included breast, kidney, lung (non-small-cell), head and neck cancers, melanoma, and, especially, mesothelioma. This spectrum of activity differs from that of the IFNs-alpha so far examined. The IFN-beta ser did not differ significantly in activity from native IFN-beta. When tested in combination with five cytotoxic anticancer agents, it did not increase their effects. Future correlation of these in vitro data with clinical results will show whether this capillary cell cloning method is a useful predictor of antitumor activity in patients.
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PMID:Effect of recombinant interferon-beta ser on primary human tumor colony-forming units. 323 Mar 32

Recent evidence has demonstrated a protein kinase C (PKC)-dependent step in cytotoxic T lymphocyte activation. Here, we examined the influence of PKC in the lytic response of human NK cells to K562, an NK-sensitive tumor target cell. We used the known protein kinase inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and HA1004. H-7 caused a dose-related inhibition of NK cell-mediated cytolysis (CMC) when the inhibitor was present throughout the course of the 3-h chromium release assay. The 50% inhibitory concentration for H-7 was 7 microM. In contrast, HA1004, which exerts a greater inhibitory effect on cyclic nucleotide-dependent protein kinases than PKC, had no effect on NK-CMC. The suppression of NK-CMC by H-7 was not due to inhibition of binding of the effector cells to target cells and could be reversed by the addition of PMA. H-7 was most effective in abrogating NK-CMC when added to the assay within the first 30 min and treatment of the effector and target cells with H-7 resulted in no loss of NK-CMC. Because nearly 50% of the normal NK lytic activity had taken place by 30 min, this suggested that H-7 inhibited an early event. H-7 exerted a dose-related suppression of antibody-dependent cell-mediated cytotoxicity (ADCC) suggesting that NK-CMC and ADCC share the utilization of PKC, however, HA1004 did not inhibit ADCC. Treating NK cells with IL-2 or IFN-beta did not overcome the inhibition of NK-CMC by H-7. In this study, we have thus demonstrated the presence of a PKC-dependent step in NK-CMC and ADCC.
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PMID:Inhibition of human natural killer cell activity by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine is an early but post-binding event. 326 83

IFN is known to enhance NK activity against cultured cell lines such as K562, but not against frozen autologous tumor cells. In order to obtain increased NK cytotoxicity using IFN-beta, various modifications were performed on autologous tumor cells. IFN-beta induced more enhanced NK cytotoxicity of normal lymphocytes when frozen tumor target cells were cultured for 4-5 days in the medium, or when these cells were treated with Vibrio cholerae neuraminidase (VCN). However, in an autologous setting, IFN-beta did not enhance NK cytotoxicity against either cultured autologous tumor cells or VCN-treated tumor cells. Also, IFN-beta did not enhance cytotoxic T cell activity against autologous tumor cells induced by mixed lymphocyte-tumor cell culture, although IFN-beta was able to induce enhancement of allospecific cytotoxic T cells mediated by mixed lymphocyte culture.
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PMID:[Lymphocyte cytotoxicity against autologous tumor cells and the effect of interferon-beta on their activities. (1) Evaluation by modification of target tumor cells]. 349 40

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

Interferon-beta-serine (IFN-beta ser) is a recombinant genetically altered interferon with extensive in vitro antiproliferative, antiviral, and immunological effects. We undertook a Phase I/II trial of this agent in patients with untreated metastatic renal cell carcinoma with good performance status. IFN-beta ser was given twice weekly (Monday/Thursday) by a 4-h i.v. infusion. Three patients were entered at increasing drug levels until the maximum tolerated dose was determined. Moreover, if individual patients tolerated the initial IFN treatment, the dose was escalated one level at the next treatment. Preliminary studies with normal donor cells demonstrated that IFN-beta ser in vitro enhanced activity in a mononuclear-MBL-2 growth inhibition, NK-cell, and monocyte antibody-dependent cellular cytotoxicity assay. Therefore, prior to therapy these in vitro tests were performed utilizing each patient's mononuclear cells in an attempt to predict tumor response with in vitro immunological response to IFN. In general, there was no difference in IFN responsiveness in vitro between patients who developed tumor response (3) and those who did not (12). After initiation of treatment blood was taken from patients at frequent intervals for assessment of biological response. The following parameters were not altered at any dose or time interval: T-cell number, T-H/S ratio, % Leu 11a-positive cells, percentage or intensity of staining with anti-HLA-DR, and concanavalin A driven T-cell proliferation. Monocyte antibody-dependent cellular cytotoxicity was significantly depressed 4 h after doses of 30-150 million units/m2 but returned to base line at 24 h. Activity in three assays was significantly increased in patients receiving therapy: MBL-2/growth inhibition assay, NK-cell, and 2',5' oligonucleotide synthetase activity. In general changes in these assays were observed at low levels of IFN-beta ser, increased at 4-48 h, then returned toward base line. We conclude that IFN-beta ser is an active biological agent in vitro and significantly modulated the biological responses in patients with renal cell carcinoma.
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PMID:Phase I/II trial of interferon-beta-serine in patients with renal cell carcinoma: immunological and biological effects. 356 33

The anticellular effect of human interferon-beta (IFN-beta, MR-21) was examined in vitro. IFN-beta had a wide anticellular spectrum in proliferation inhibition assay. Of 67 human cell lines including 62 tumor-originated cell lines, 51 were sensitive to IFN-beta (IC50 less than 1,000 IU/ml) while 16 including normal diploid cells were resistant (IC50 greater than or equal to 1,000 IU/ml). These anticellular effects were reversible and there was no relationship between the origins of tumor cell lines and their sensitivity to IFN-beta. IFN-beta induced not only proliferation inhibition but also cytotoxicity in several cell lines. It was suggested that the mode of anticellular effects of IFN-beta was mainly time-dependent.
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PMID:[Basic study on human interferon-beta: Part II. Anticellular effect]. 371 58

The effects of human interferon-beta (IFN-beta, MR-21) on the growth of xenografted human tumors in nude mice were examined. IFN-beta was administered to mice with malignant melanoma (SK-MEL-28 and Sk-14) intratumorally at a dose of 1 X 10(5)-3 X 10(5) IU/mouse, with acute leukemia (CCRF-HSB-2) intratumorally at a dose of 3 X 10(5) IU/mouse, with glioblastoma (U-373 MG) intravenously or intratumorally at a dose of 1 X 10(5)-6 X 10(5) IU/mouse, or with uterine cervical tumor (HeLa S3) intravenously at a dose of 0.3 X 10(5)-1 X 10(5) IU/mouse. IFN-beta inhibited the growth of all of these tumors in a dose-dependent manner.
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PMID:[Basic study on interferon-beta: Part IV. Antitumor effect on nude mouse-transplanted human tumors]. 371 59

Two H-2 negative variants of the YAC-1 lymphoma were selected by mutagenization and sequential in vitro selections and compared with wild-type cells for changes in NK sensitivity and H-2 expression after interferon treatment or in vivo passage. The H-2 negative variants and the low H-2 expressor YAC-1 wild-type cells had similar NK sensitivity. However, IFN-beta or recombinant IFN-gamma pretreatments increased the H-2 expression of YAC-1 and protected them from NK lysis, whereas the H-2 variants, which remained H-2 negative, were not protected and often more sensitive to NK lysis. The H-2 variants were similarly susceptible as wild-type cells to three other cellular effects of interferon: protection from virus infection, modulation of Con A capping, and inhibition of cell proliferation. Thus, the only interferon-mediated effect that distinguished the H-2 negative variants from wild-type cells was the inability of the former to increase their H-2 expression and decrease their NK sensitivity. The wild-type YAC-1 line showed increased H-2 expression and decreased NK sensitivity after in vivo passage. In contrast, in vivo passaged H-2 variants showed no reexpression of H-2, and remained NK sensitive. The altered responses to interferon and in vivo passage were specific for loss or down-regulation of H-2, because Thy-1 loss (H-2 positive) YAC-1 variants behaved as the wild-type cells in all respects. This study supports the hypothesis that NK cells may function in vivo to eliminate host cells that fail to express H-2 after interferon stimulation during an immune response; such cells are a potential threat because they may escape recognition by T lymphocytes despite the expression of viral or tumor-associated antigens.
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PMID:YAC-1 MHC class I variants reveal an association between decreased NK sensitivity and increased H-2 expression after interferon treatment or in vivo passage. 390 67

De novo synthesis of major histocompatibility complex (MHC) class II antigens was induced by affinity-purified preparations of interferon (IFN)-gamma, but not by IFN-beta (as judged by the criteria of cell surface expression and protein synthesis) in human osteogenic sarcoma, colorectal carcinoma, and melanoma cell lines that were not constitutive producers of these antigens. The synthesis of heavy-chain and light-chain (beta 2-microglobulin) components of MHC class I antigens was enhanced by both IFN-gamma and IFN-beta; IFN-gamma showed the greater activity. IFN-gamma and IFN-beta also enhanced the expression of class I antigens on the plasma membrane in a dose-dependent manner; IFN-gamma was again the more active agent. Only IFN-gamma induced the membrane appearance of class II antigens in cell lines that appeared negative for HLA-DR expression by all criteria. However, in SW480 cells, which spontaneously express low levels of HLA-DR, IFN-gamma and IFN-beta both enhanced the expression of class II antigens. These results suggest that IFN of both types amplify the products of actively transcribed genes, but that type II IFN is unique in its capacity to induce HLA-DR expression in nonconstitutive cell lines. Kinetic studies showed that enhancement of class I membrane expression preceded the induction of class II expression and peaked earlier. The specificity of these responses was underlined by the inability of either IFN to enhance the synthesis or expression of the tumor-associated membrane glycoprotein gp22. The data indicate that tumor cell lines of diverse tissue origin that do not synthesize or express class II antigens by the criteria of immunoprecipitation or monoclonal antibody binding can be induced to do so by IFN-gamma and may therefore be subject to therapeutic and immunoregulatory modulation.
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PMID:HLA-DR synthesis induction and expression in HLA-DR-negative carcinoma cell lines of diverse origins by interferon-gamma but not by interferon-beta. 392 46


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