Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of recombinant tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on B16 mouse melanoma experimental metastatic ability and major histocompatibility complex (H-2b) antigens expression were studied. B16 cells exposed in vitro to TNF-alpha had an increased H-2 expression and were more metastatic than untreated cells. The simultaneous treatment with TNF-alpha and IFN-gamma amplified the enhancement of experimental metastasis and all other effects obtained with TNF-alpha alone. The B16 clone B78H1, selectively resistant to H-2 induction and to enhancement of metastatic ability by IFN-gamma, was not affected by treatment with TNF-alpha and with TNF-alpha + IFN-gamma. These findings contribute to a better understanding of the pleiotropic effects of TNF, some of which can have opposing actions in the complex tumor-host relationships.
Clin Exp Metastasis
PMID:Enhancement of experimental metastatic ability by tumor necrosis factor-alpha alone or in combination with interferon-gamma. 210 93

Tumor-infiltrating lymphocytes (TILs) are T cells that can be grown from enzyme-digested murine or human tumors. When adoptively transferred to tumor-bearing hosts concurrent with the administration of recombinant interleukin-2 (rIL-2), TILs can mediate significant regression of tumor. To examine whether expression of class I major histocompatibility complex on tumor cells influenced the generation and antitumor activity of TILs, we used clones of murine B16BL6 melanoma either transfected with or lacking the class I gene Kb to generate TILs at a high dose (1,000 U/mL) or at a low dose (20 U/mL) of human rIL-2. TILs grew from both tumors in high-dose rIL-2, but they grew from the class I-expressing tumor only in low-dose rIL-2. TILs from the class I-deficient tumor did not lyse any target tested in vitro, nor did they demonstrate any therapeutic effect in vivo on established tumors that lacked or expressed class I. In contrast, TILs from the class I-expressing tumor specifically lysed the tumor of origin in vitro and caused it to regress in vivo. Further, these TILs demonstrated activity in vitro against the non-class I-expressing melanoma treated with the combination of murine recombinant interferon gamma and human recombinant tumor necrosis factor alpha; in vivo, when administered with recombinant interferon gamma and recombinant tumor necrosis factor alpha, TILs from the class I-expressing tumor mediated regression of non-class I-expressing pulmonary metastases, presumably by augmenting class I expression.
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PMID:Effects of murine tumor class I major histocompatibility complex expression on antitumor activity of tumor-infiltrating lymphocytes. 210 92

We have investigated the relationship between in vitro cultivation of autologous melanoma metastases derived from different patients and their levels of expression of class-I and -II major histocompatibility complex (MHC) antigens and melanoma-associated antigens (MAAs). Cell cultures were established from 23 individual metastatic melanoma lesions from 10 patients and were tested early after isolation (between 3rd and 10th passages) for both constitutive expression and modulation by recombinant human leukocyte (IFN-alpha), fibroblast (IFN-beta) or immune (IFN-gamma) interferon of MHC antigens and MAA. All of the melanoma cell lines displayed altered antigen expression following IFN treatment. While in vitro cultures derived from different individuals varied in both constitutive and IFN-modified antigenic expression, cultures of autologous metastases derived from the same patient were very similar. In addition, differences in antigenic profile were apparent when early-passage in vitro cultures were compared with the same melanoma lesion, not established in culture, from which they were derived. The unique de novo and IFN-modified antigenic phenotype of cultures derived from different patients indicates that the antigenic phenotype displayed by melanoma cultures grown in vitro is genetically determined. The differences found between in vitro cultures and their corresponding in vivo lesions, as well as the antigenic heterogeneity displayed by multiple autologous melanoma lesions in vivo, suggest that the in vivo antigenic phenotype may be determined, at least in part, at an epigenetic level.
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PMID:Modulation of the antigenic phenotype of early-passage human melanoma cells derived from multiple autologous metastases by recombinant human leukocyte, fibroblast and immune interferon. 211 85

Tumor cell variants were derived from an AKR T-cell lymphoma cell line (BW5147, H-2k haplotype). These variants differed in their malignant potential and in their membrane expression of class I MHC antigens. High tumorigenic and spontaneous metastatic capacity was found to be predominantly associated with a decrease of H-2Kk class I major histocompatibility complex (MHC) antigen expression. In contrast, high experimental metastatic capacity correlated strongly with an increased H-2Dk antigen expression. The in vitro invasive potential and the LFA-1 expression of the BW variants showed no correlation with the differential MHC antigen expression and the differential metastatic and tumorigenic capacity of the BW variants. Furthermore, the susceptibility of the BW 5147 variants to TNF and NK-mediated cytotoxicity was not related to the differential metastatic potential and the expression of the class I MHC antigens.
Invasion Metastasis 1990
PMID:Association between MHC class I antigen expression and malignancy of murine T lymphoma variants. 230 62

Leu-19 antigen is a 200-220 kDa surface glycoprotein, initially detected on natural killer (NK) cells exhibiting non-major histocompatibility complex-restricted cytotoxicity. Using a monoclonal antibody (mAb) directed against the Leu-19 molecule, we were unable to identify NK cells immunohistologically in cryostat sections of neuroectodermal tumors. Instead, mAb Leu-19 cross-reacted with the surfaces of the tumor cells, except for melanomas. It stained mesodermal tumor cells less intensely and did not stain those of carcinoma metastases. In three plasmacytomas, cells were observed, most likely NK cells, which extend Leu-19-positive cell processes towards to the unstained tumor cells. Furthermore, the Leu-19 antigen was identified on physiological tissues, especially on all neuroendocrine cells analyzed. The cross-reactions observed with Leu-19 mAb were confirmed using mAb NKH-1, which is also directed against the Leu-19 molecule. Thus, the expression of Leu-19 on neuroectodermal cells is another example of antigen sharing between specialized immune cells and the nervous system.
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PMID:Cross-reactivity of monoclonal antibody Leu-19 with some neuroectodermal and other non-immune tissues. 232 52

IFN proteins are a family of lymphokines with anti-viral effects. Several other effects of IFNs have also been described, including enhancement of natural killer (NK) cell activity, enhancement of cytotoxic T-lymphocyte activity, and enhancement of the expression of major histocompatibility complex (MHC) antigens. The latter effects have been characterized as immunomodulatory, whereas the well-known inhibition of growth of malignant cells has been termed anti-proliferative. This review summarizes the current knowledge of the enhancement of MHC products by IFNs. Whereas the basic methodologies for demonstrating the enhancement are simple and reliable, especially when using flow cytometry (FCM), the biological relevance of this reaction is largely unknown. Based on recent findings, however, we have hypothesized that the above-mentioned diverse effects of IFNs are all - in some way or other - related to the classical anti-viral mechanism. This concept proposes that the MHC-enhancing effect of IFNs is a vital part of the immunological defense against virus infections and an integral part of the anti-viral effects of IFN proteins.
Cancer Metastasis Rev 1988 Nov
PMID:IFN-induced modulation of histocompatibility antigens on human cells. Background, mechanisms and perspectives. 246 42

High metastatic, low immunogenic Lewis lung carcinoma clones express low levels of H-2Kb major histocompatibility complex antigens. These cells metastasize spontaneously in mice with C57BL/6 genetic background possessing the H-2Db locus. Transfection of different H-2K genes abrogates metastasis in H-2K, H-2D compatible mice and in C57BL/6 recipients. The transfected cells are potent inducers of H-2K-restricted and alloreactive cytotoxic lymphocytes that kill H-2K-positive cells and cross-react with parental nontransfected cells.
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PMID:Abolishment of metastasis formation by murine tumor cells transfected with "foreign" H-2K genes. 278 97

In 54 patients with lung and 14 with ovarian carcinomas the quantitative variations of the major histocompatibility complex (MHC)-determined class I and class II antigens of the tumor cells were related to their in vitro interaction with blood lymphocytes, to the lymphoid infiltration of the tumors, and to the metastatic state of the disease. The tumor cell-lymphocyte interaction was measured by the proliferative response in mixed lymphocyte tumor cell culture and by the cytotoxic activity of the lymphocytes. The results showed that (1) none of the 23 tumors from patients with disseminated disease were lysed; (2) class I-negative tumors were not damaged; (3) lymphoid infiltration was present in a higher proportion of class II-positive tumors; and (4) both MHC-positive and -negative tumors were found among the disseminated tumors. The requirement of class I expression in the lytic interaction substantiates our earlier conclusion concerning the cytotoxic T lymphocyte nature of lymphocyte-mediated auto-tumor lysis. The lack of auto-tumor lysis in patients with metastases suggests impairment of lymphocyte function in advanced stages of the disease.
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PMID:Importance of MHC antigen expression on solid tumors in the in vitro interaction with autologous blood lymphocytes. 297 65

Metastasis formation is a multistep process that probably requires a complex interplay of a large and heterogeneous group of genes, including genes involved in cellular resistance to immunorejection and genes controlling the invasive potential of cells. Transfection experiments have shown that oncogenes of the ras gene family as well as oncogenes of the kinase group are able to induce invasive and metastatic properties in non-transformed cells as well as in tumorigenic, but non-metastatic, cells. However, these findings are not in agreement with observations on spontaneous human tumours in which no correlation was found between activation or increased expression of ras genes and the invasive and metastatic properties of these cells. Further studies have indicated that in particular cell types nuclear oncogenes like N-myc and adenovirus derived E1A may influence metastasis formation by trans-regulation of other genes, including class I genes of the major histocompatibility complex and genes coding for proteolytic enzymes. The many efforts to identify additional invasion and metastasis associated genes by transfection of high molecular weight metastatic tumour DNA met with little success. Somatic cell fusion studies, however, indicate that such genes exist and that one or more of them are located on human chromosome 7.
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PMID:Genetic analysis of invasion and metastasis. 307 71

We report the results of a phase I study of the tolerance and biologic activity of intramuscularly (IM)-administered recombinant interferon-gamma (rIFN-gamma). Forty-four patients with metastatic cancer were given rIFN-gamma at doses ranging from 0.01 to 2.5 mg/m2/d for 42 days. The most common side effects were fever, flulike symptoms, night sweats, and granulocytopenia. The maximum tolerated dose was 0.5 mg/m2/d. Administration of rIFN-gamma resulted in modulation of immune system functions, including induction of major histocompatibility complex-associated antigens on blood leukocytes, an increase in blood surface immunoglobulin-bearing B cell and natural killer (NK) cell number, and NK cell cytotoxicity. Serum lysozyme, determined as an estimate of tissue macrophage activity, also increased. Serum assays for anti-interferon antibodies were negative in all patients. Five of eight evaluable patients with lymphoproliferative disorders showed objective evidence of tumor regression consisting of partial responses (two patients), and minor responses (three patients). These data suggest that further phase II studies of IM-administered rIFN-gamma are indicated.
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PMID:Phase I study of multiple dose intramuscularly administered recombinant gamma interferon. 308 21


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