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)

Monocytes and macrophages play an important role in host defense against neoplasia. Studies from our and other laboratories have demonstrated that patients with a variety of cancers have a defect in monocyte chemotactic responses. Tumor-bearing mice are also inhibited in their ability to accumulate macrophages to inflammatory foci. We have shown that extracts prepared from murine tumors, as well as the plasma and urine of tumor-bearing mice, contain anti-inflammatory proteins which are antigenically and physicochemically related to the immunosuppressive retroviral envelope protein p15E. Similarly, proteins capable of inhibiting monocyte chemotactic responses are present in human cancerous effusions and can be specifically absorbed by monoclonal antibodies to p15E. Furthermore, we have demonstrated that human malignant and mitogen-transformed cells contain p15E-related antigens. These findings led us to propose a two stage model of tumorigenesis: the first stage involves neoplastic transformation of a cell while the second stage involves activation of a gene coding for a p15E-like protein which allows the transformed cell to escape immune surveillance and go on to become a tumor. Support for this model has come from recent studies which have identified within the human genome an endogenous retrovirus sequence whose envelope gene is partially homologous to a highly conserved region of p15E. Using a synthetic peptide, termed CKS-17, we have shown that this region may be responsible for many of the biological activities of p15E and is capable of suppressing lymphocyte and natural killer cell immune functions as well as those of monocytes and macrophages. Thus tumors may be capable of evading host defense mechanisms by activation of a normal gene related to the immunosuppressive retroviral protein p15E.
Cancer Metastasis Rev 1986
PMID:Effects of tumor growth on host defenses. 352 88

An evaluation of natural killer cell activity was performed in 42 patients with pharyngeal carcinoma. Compared with age- and sex-matched control subjects, the cancer patients expressed significantly lower cytotoxicity against K562 target cells (68 +/- 8 lytic units versus 99 +/- 8 lytic units, p less than 0.01), with 52 percent of the patients expressing deficient activity (below 1 standard deviation of the mean activity of the control population). The probability of deficient activity was greater in these patients than observed in patients with cancer of other head and neck sites. Although natural killer cell activity was lower in patients who drank alcohol or had nodal metastases, no single clinical factor was predictive of deficient cytotoxic response. Prospective longitudinal evaluation (mean = 12 months) of these pharyngeal cancer patients demonstrated that deficient natural killer cell activity measured before treatment identified a population with a significantly increased risk for the development of distant metastases. Distant metastases developed in 7 of 18 patients (39 percent) with deficient natural killer cell activity. In contrast, none of the 16 patients with normal natural killer cell function had evidence of distant disease at last follow-up (p less than 0.01). Deficient natural killer cell activity exists in patients with pharyngeal cancer and is an independent marker for the subsequent development of distant metastases.
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PMID:Pharyngeal carcinoma and natural killer cell activity. 376 83

A determination of natural killer cell activity was performed in 67 individuals with advanced head and neck cancer. The mean activity of 28 patients clinically staged T3 NO or T4 NO was 81 +/- 11 lytic units (LU), significantly higher than 39 patients with palpable lymph node metastases (54 +/- 5 LU). Assessing patients by extent of nodal disease revealed that activity actually increased, though not significantly, with progressive N-staging. A major determinate of increased natural killer cell cytotoxicity in patients with lymph node metastases was extranodal cancer within the neck. The mean activity of nine patients whose tumor was fixed to underlying structures or adherent to skin was 87 +/- 15 LU, significantly higher than the 45 +/- 4 LU mean value of the remaining patients with clinically determined regional nodal disease. The potential clinical implications of these findings are discussed.
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PMID:Natural killer cell response to regional lymph node metastases. 395 96

The antitumor activity of interferon against Dunn osteogenic sarcoma in C3H/HeN mice was studied. The administration of murine interferon prolonged the mean survival days, and reduced pulmonary metastases after the excision of the primary tumor. The administration of interferon augmented natural killer cell activity in vitro, and eliminated tumor cells from the lung rapidly. This rapid cytolysis of tumor cells occurring in vivo correlated well with NK activity in the spleens measured in vitro. These findings suggest that NK cells augmented by interferon have a major effect during the early period of pulmonary metastases.
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PMID:The antitumor effect of interferon against murine osteogenic sarcoma. 618 27

The biology of the natural killer cell system is being investigated by many different laboratories using multiple approaches. The rationale for these investigations is the experimental evidence that NK cells play some role in inhibiting tumor growth and metastasis, convey some protective immunity and may be operative in control of differentiation from fetal life to adulthood. Thus, a survey of the literature reveals a multiplicity of studies examining many of these potential roles for NK cells. This review will attempt to summarize some of the findings critical to an understanding of the role NK cells play in immunophysiology and in immune reactions to various diseases. Even after ten years of study, the whole system of 'natural' reactivity remains difficult to define. The evidence available would indicate that the NK system while incompletely understood, may be manipulated in favor of the host when threatened by infectious or neoplastic disorders.
Cancer Metastasis Rev 1983
PMID:Natural killer cells: artifact to reality: an odyssey in biology. 637 59

A series of investigations was employed to determine if metastases of intraocular melanomas could be induced by experimental manipulations. Syngeneic B16F10 melanoma cells transplanted intracamerally into C57BL/6 mice produced progressively growing intraocular tumors, yet formed only occasional pulmonary metastases. Neither enucleation nor mechanical manipulation of the melanoma-containing eye promoted a significant increase in the incidence of metastases. Likewise, immunologic impairment in the form of natural killer cell deficiency, T-lymphocyte deficiency, or gamma-irradiation-induced lymphopenia failed to produce spontaneous metastases in intraocular melanoma-bearing mice. However, enucleation in consort with immune impairment (T-cell deficiency) produced a sharp increase in the incidence and number of pulmonary metastases in intraocular melanoma-bearing mice. Further studies showed that external pressure to the tumor-containing globe (without enucleation) produced extensive metastases in athymic, nude mice. By contrast, atraumatic enucleation of rapidly frozen eyes prevented metastasis of intraocular melanomas in similar hosts. Collectively, the results indicate that induction of distant metastases in hosts harboring intraocular melanomas requires two simultaneous processes: (1) mechanical manipulation of the melanoma-containing eye, and (2) concomitant impairment of T-cell-dependent immune processes. The data strongly suggest that mechanical manipulation of melanoma-containing eyes produces intravascular showers of melanoma cells that are rejected by T-cell-dependent immune processes in the immunocompetent host. In the absence of these normal T-cell-dependent immune mechanisms, enucleation-induced showers of blood-borne melanoma cells gain a foothold in the lung and form progressive metastases.
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PMID:Enucleation in consort with immunologic impairment promotes metastasis of intraocular melanomas in mice. 638 75

Certain "membrane-mutant," lectin-resistant (Lecr) variants derived from the highly metastatic and poorly immunogenic DBA/2 mouse tumor MDAY-D2 previously were found to differ substantially in their ability to grow and to metastasize. In the present study, the parental MDAY-D2 tumor and several wheat germ agglutinin-resistant (WGAr) variants were examined for alterations in sensitivity to activated macrophage (M phi)- and natural killer cell (NK)-mediated lysis. The results indicated that selection in WGA after mutagenic treatment of a metastatic parental tumor cell line (MDAY-D2), which was M phi-sensitive (M phi S) and NK-resistant (NKR), can result in the isolation of a significantly M phi-resistant (M phi R) and NK-sensitive (NKS) tumor variant, MDW4. The in vivo hybridization of the M phi R, NKS, Lecr MDW4 variant with a normal host-derived cell within a primary subcutaneous tumor, previously demonstrated to result in the progressive and selective outgrowth and metastasis of hybrid products, was found to be associated directly with reversion to the M phi S, NKR phenotype of the metastatic parental MDAY-D2 cell line. DMA/2 mice given iv injections of 10(5) M phi R, NKS cells (MDW4 or MDW4-110c1, a cloned line isolated from a subcutaneous primary tumor of an MDW4-injected animal) survived for a significantly prolonged period as compared to animals given injections of either the parental tumor or M phi S, NKR hybrid products isolated from a MDW4 subcutaneous primary tumor (MDW4-110c2) or visceral metastases (MDW4-24a, MDW4-24b, and MDW4-24c). The results clearly indicate an inverse relationship among the tumor variants in their ability to be lysed by either M phi or NK and suggest a central role for NK rather than M phi surveillance in this tumor system.
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PMID:Alterations in sensitivity to nonspecific cell-mediated lysis associated with tumor progression: characterization of activated macrophage- and natural killer cell-resistant tumor variants. 658 40

The metastatic behavior of seven human tumor cell lines grown in young (3- to 4-week-old) nude mice was studied. Two cell lines were derived from malignant melanomas, one from a colon carcinoma, two from prostate adenocarcinomas, and two from renal adenocarcinomas. Many of the cell lines produced metastases after i.v. injection (experimental metastasis) and after s.c. transplantation (spontaneous metastasis) into young nude mice. The incidence of metastasis seemed dependent primarily on the biological characteristics of the individual tumor cell line. However, the incidence of metastasis of some tumor cell lines could be increased by isolation and establishment of variant sublines from secondary tumor deposits, by prolonged systemic administration of 17 beta-estradiol to suppress natural killer cell activity, and/or by use of an advantageous site of tumor implantation. Intrasplenic injection of tumor cells allowed the most dramatic overall expression of metastatic capacity in these cell lines, resulting in frequent and large metastases to liver, lungs, and the mesenteric, omental, and mediastinal lymph nodes.
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PMID:Metastatic behavior of human tumor cell lines grown in the nude mouse. 674 77

The purpose of these studies was to investigate whether young (3-wk-old) nude mice, which lack functional T-lymphocytes and demonstrate low natural killer cell activity, could serve as in vivo models for the selection of metastatic subpopulations of cells from heterogeneous allogeneic melanomas. Three-week-old BALB/cAnN or N:NIH(S) nude mice received iv injections of single cells harvested from either the B16 or K-1735 melanoma. Individual pulmonary metastases were harvested 4 weeks later and implanted sc into nude mice to expand the population. Cells from each of these metastases colonized in the lungs of 3-week-old nude mice and 6-week-old normal syngeneic mice with significantly higher efficiency than did cells from the parent tumors. It was concluded that, in addition to being a useful in vivo model for ascertaining the metastatic potential of neoplasms, the healthy young nude mouse could be used for selecting and maintaining tumor cell variants of high metastatic potential room heterogeneous allogeneic tumors.
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PMID:Use of young nude mice for selection of subpopulations of cells with increased metastatic potential from nonsyngeneic neoplasms. 695 6

Partially purified human beta interferon (HuIFN-beta) was administered to six patients with metastatic breast carcinoma by the intramuscular route at doses of 3 X 10(6) and 6 X 10(6) units on a daily schedule. Objective antitumor effects were observed in three patients (one partial remission, two minor responses) in soft tissue and lymph node metastases. Systemic side effects (fatigue, fever, pruritus, nausea, etc.) attributable to the treatment occurred in all patients. Augmenting effects by IFN-beta on cell-mediated immunity in vivo (delayed-type hypersensitivity) and in vitro natural killer cell and antibody-dependent cell-mediated cytotoxicity were observed in several patients. The clinical and immunological effects were considered evidence of systemic biological activity despite very low or undetectable serum antiviral activity following administration of this agent.
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PMID:Clinical and immunological study of beta interferon by intramuscular route in patients with metastatic breast cancer. 714 62


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