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)

Hematogenous metastasis requires the arrest and extravasation of blood-borne tumor cells, possibly involving direct adhesive interactions with vascular endothelium. Cytokine activation of cultured human endothelium increases adhesion of melanoma and carcinoma cell lines. An inducible 110-kD endothelial cell surface glycoprotein, designated INCAM-110, appears to mediate adhesion of melanoma cells. In addition, an inducible endothelial receptor for neutrophils, ELAM-1, supports the adhesion of a human colon carcinoma cell line. Thus, activation of vascular endothelium in vivo that results in increased expression of INCAM-110 and ELAM-1 may promote tumor cell adhesion and affect the incidence and distribution of metastases.
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PMID:An inducible endothelial cell surface glycoprotein mediates melanoma adhesion. 258 7

Cytokine therapy of metastatic renal cell carcinoma reveals a remission rate of about 25% regarding to the different patients selection criteria, i.e. age, performance status, site of metastasis, tumour load. Remission is not correlated to patient's survival. Adjuvant or neoadjuvant immunotherapy is not a treatment option. Nephrectomy has no influence on distant metastases and should be limited to symptomatic primary tumours. In conclusion, cytokine therapy is not a standard treatment. Its value has to be evaluated in randomized trials.
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PMID:[Cytokine therapy of metastatic renal cell carcinoma]. 761 May 12

To determine whether IL-1 alpha and/or IL-1 beta protein is expressed by human melanoma tumor in vivo, we first analyzed nine human melanoma cell lines and optimized the in situ detection of these proteins. Three of the melanoma cell lines stained positively for both IL-1 alpha and IL-1 beta using immunohistochemistry (IHC). THe specificity of IHC was confirmed by the ability of purified recombinant IL-1 alpha and IL-1 beta protein to abolish the staining after being adsorbed by their respective antibodies before use in IHC. The three positively staining cell lines were also the only lines to demonstrate IL-1 production by western blot analysis as well as IL-1 secretion by ELISA. Next we examined 29 surgically obtained melanoma tumor specimens (6 primary and 23 metastases) that had been formalin fixed and paraffin embedded. Using the same anti-IL-1 antibodies, 5 of 23 metastatic tumors stained positively. None of the 6 primary lesions stained for either IL-1 alpha or IL-1 beta. Comparison of staining pattern performed on serially sectioned tissue using preimmune serum and antibodies against S-100 protein, melanoma-associated antigen (HMB-45), and CD68 (kappa P1), which recognizes monocyte-macrophage cell lineage, demonstrates for the first time that IL-1 protein is produced by human melanoma tumor cells in vivo. These findings provide the basis for examination of what may be a previously unrecognized biologically distinct subset of patients.
J Interferon Cytokine Res 1995 Apr
PMID:Interleukin-1 production in tumor cells of human melanoma surgical specimens. 762 8

The purpose of this study was to determine the mRNA expression level of multiple cytokine and growth factor genes in human malignant melanoma. Melanoma cells were isolated from several surgical specimens, adapted to growth in culture, characterized for their ability to produce experimental metastases in nude mice, and assessed for cytokine and growth factor steady-state gene expression. Highly metastatic in vivo- and in vitro-derived variants isolated from a single melanoma, A375, were also analyzed. Northern blot analyses revealed that all melanomas analyzed constitutively expressed steady-state mRNA transcripts for the growth and angiogenic factors, basic fibroblast growth factor (bFGF), and transforming growth factor alpha (TGF-alpha), which correlated with metastatic propensity. Only one highly metastatic melanoma, TXM-1, originally isolated from a lymph node metastasis, expressed mRNA transcripts specific for monocyte chemotactic and activating factor (MCAF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, of the nine melanomas examined, only TXM-1 expressed interleukin (IL)-1 alpha, IL-1 beta, and IL-6, important immunomodulatory cytokines. These data demonstrate the differential and heterogeneous expression of cytokine and growth factor genes in human malignant melanoma.
J Interferon Cytokine Res 1995 Jan
PMID:Heterogeneity of cytokine and growth factor gene expression in human melanoma cells with different metastatic potentials. 764 37

We have achieved efficient transduction of tumour metastases in vivo by the vascular delivery of retroviral producer cells. Experimental liver metastases in mice were created by intrasplenic injection of tumour cells into the portal venous circulation. Following the establishment of micrometastases, delivery of retroviral producer cells by the same route with a vector containing the Escherichia coli beta-galactosidase (lacZ) gene demonstrated selective in vivo gene transfer to tumour deposits. By this approach, two retroviral producer cell lines encoding cytokines (IL-4 and IL-2) directed tumoricidal inflammatory responses to established metastases. Cytokine gene targeting inhibited metastasis formation and caused significant overall reduction in tumour burden. These results suggest a novel therapeutic approach for the treatment of disseminated cancer.
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PMID:Gene therapy of metastatic cancer by in vivo retroviral gene targeting. 767 Apr 93

The anti-tumour properties of interleukin 1 beta (IL-1 beta) were examined using an intradermal B16 murine melanoma surgical model. B16 cells were injected intradermally on the right ventral side and surgery was performed on days 10-20 to remove the primary tumours. IL-1 beta or vehicle was administered prior to surgery for 5-7 consecutive days. In mice which received only injections of vehicle, survival ranged between 0 and 30% when measured on day 120 after implantation of B16 cells. Mice died of metastases and growth of B16 cells in the thoracic lymph nodes. When mice without metastases were rechallenged with viable B16 cells, only one out of 22 mice (5%) failed to develop tumours. No significant immunity to B16 cells was detected in this group of mice. In contrast, in mice which received injections of IL-1 beta, survival ranged between 70-100% on day 120 after implantation of B16 cells. When IL-1 beta treated mice were rechallenged with viable B16 cells on day 120, 20 out of 32 (63%) mice failed to develop B16 tumours suggesting that some of these mice had immunity to B16 melanoma cells. Moreover, mice with immunity to B16 cells did develop tumours when injected with another syngeneic tumour, MCA 105. In vitro specific immune responses were also demonstrated in spleen cells and sera from mice treated with IL-1 beta, but not in the spleen cells or sera of mice that received only vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
Cytokine 1994 May
PMID:Anti-tumour effects of interleukin 1 beta: in vivo induction of immunity to B16 melanoma, a non-immunogenic tumour. 805 88

Expression of an extended panel of cytokine genes was investigated by reverse polymerase chain reaction (PCR) in 10 freshly excised melanoma metastases infiltrated by lymphocytes (TIL). cDNA encoding for CD3-delta and tyrosinase could be amplified in all samples, confirming the presence of T lymphocytes and melanoma cells. Cytokine genes possibly transcribed by both cell types, such as GM-CSF, IL-6 and IL-10 could be amplified from 5, 2 and 2 samples respectively. In contrast, IL-1 beta and TNF-alpha mRNA were never detectable, IL-1 alpha, IL-3 and IL-7 mRNA could be observed only in one case each. Transcripts encoding for TGF-beta 1 were observed in 8 samples, while TGF-beta 2 and 3 mRNA were detectable in only 2 specimens. mRNA encoding for cytokine genes typically transcribed by antigen-stimulated T lymphocytes, such as IL-2, IL-4 and IFN-gamma were rarely or never detectable (none, none and 1 of the samples respectively). In one case, where no cytokine gene transcription was detectable at the time of surgery, we addressed the question of the antigenicity of the tumor and of the functional competence of TIL. A primary tumor cell line was generated and cultured TIL were induced to transcribe IL-2 and IFN-gamma genes by incubation with the autologous irradiated tumor cell line, but not with autologous EBV-transformed cells. In these conditions, tumor-specific cytotoxic T lymphocytes (CTL) could be generated only after 3 weekly re-stimulations. In contrast, if autologous irradiated EBV-transformed cells were added to the cultures, specific CTL could be detected after one single tumor stimulation. Thus, signs of active responsiveness in terms of lymphokine gene mRNA are seldom detectable in melanoma metastases. Tumor-specific responses, however, including IL-2 and IFN-gamma gene expression and generation of CTL can be produced in vitro from specimens in which no cytokine gene mRNA is detectable ex vivo.
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PMID:The pattern of cytokine gene expression in freshly excised human metastatic melanoma suggests a state of reversible anergy of tumor-infiltrating lymphocytes. 818 65

Cytokine gene therapy for cancer could involve either the direct delivery of cytokine genes to established tumours to stimulate their rejection or the injection of cytokine-secreting tumour cells to stimulate an immune response that could reduce metastatic disease. To assess the feasibility of the first approach, we have compared the ability of different cytokine-secreting tumour cells to induce the rejection of admixed, unmodified cells. While interleukin (IL)-2- or interleukin-4-secreting tumour cells were ineffective, interferon-gamma (IFN-gamma)-secreting cells could induce rejection of 10% admixed, unmodified cells. Because direct gene delivery to tumours is unlikely to be 100% efficient, these data suggest that IFN-gamma may be the most suitable of these cytokines for this approach. However, we have demonstrated that injection of IL-2-secreting tumour cells, following primary tumour excision, can prevent the development of metastases and prolong survival of rats. This suggests that IL-2-secreting tumour cells can be effective in the treatment of metastatic disease.
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PMID:Cytokine gene transfer as a therapeutic strategy. 828 Jul 13

Very little is known about factors influencing the migration of highly activated T-lymphocytes. One such lymphocyte population is the IL-2 expanded population of T cells infiltrating tumors. These tumor-infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic cancer and in murine tumor models when given in adoptive transfer. In patients with melanoma, these TIL have been shown to migrate to sites of tumor and this may be a critical factor in their antitumor activity. In this study, a 48-well microchemotaxis chamber and a 5 microns pore nitrocellulose filter membrane system was utilized to study the motility of murine TIL. A chemotactic response was observed to supernatants from freshly explanted, autologous, and nonautologous tumor cultured for 24 h. Serially passaged autologous and nonautologous tumors also produced supernatants with chemotactic activity. Supernatants from single cell suspensions of normal tissues prepared and cultured identically did not elicit chemotaxis. Chemotactic activity for TIL was not removed by dialysis (2000 MW exclusion limit), its activity was undiminished by heat treatment at 60 degrees C for up to 60 min, and it was trypsin sensitive. Tumor supernatants were also chemotactic for two IL-2-dependent specifically alloreactive CTL lines (CTL-TIM and OE-4), but not two helper T cell lines (D-10 and D-1.5) or normal resting lymphocytes. This is the first demonstration of a chemotactic effect on IL-2-dependent, activated T cells. Characterization and purification of factors from tumor responsible for this directed migration are in progress.
Lymphokine Cytokine Res 1993 Feb
PMID:A tumor-elaborated supernatant factor chemotactic for IL-2 expanded tumor infiltrating T-lymphocytes. 845 27

The role of cytokines was intensively discussed over the course of a two and a half day meeting sponsored by the US-JAPAN Cancer Cooperative Research Program of the Office of International Affairs, National Cancer Institute and held at The National Institutes of Health, Bethesda, Maryland on 15-17 January 1996. Most of the first day was devoted to a discussion of the role of cytokines in modulating angiogenesis and the consequent effect of this on tumor growth and metastases. This was followed by sessions on the effect of various cytokines in enhancing or suppressing immunological responses to tumors. Several presentations focused on the direct inhibitory or growth promoting effects of cytokines on tumor growth. The final session consisted of a comparison of the efficacy of different approaches to tumor vaccination including gene therapy, enhanced antigen presentation, use of polymeric carriers or of DNA vectors. For background information the reader is referred to appropriate chapters on the role of cytokines in neoplastic diseases (Oppenheim JJ, Rossio JL, Gearing AJH, eds. In Clinical Application of Cytokines: Role of Pathogenesis, Diagnosis and Therapy. Oxford University Press, New York, 1993 [1]).
Cytokine Growth Factor Rev 1996 Oct
PMID:The role of cytokines in cancer. 897 83


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