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)

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

We have attempted to better define host humoral immune response in neoplasia by quantitating serial circulating immune complex values before and after surgery in patients with primary or metastatic colorectal cancer. Circulating immune complex levels were correlated with serial carcinoembryonic antigen values and tumor courses in patients with primary resectable colorectal cancer (four patients), resectable liver metastases (three patients), diffuse liver metastases treated with regional chemotherapy (three patients), and untreated intrahepatic (one patient) and extrahepatic metastases (one patient). Circulating immune complex levels, as measured by an antigen-nonspecific assay, which utilized 4 percent polyethylene glycol insolubilization, were increased in all patients at presentation (734 delta OD450 +/- 381) when compared with normal human control sera (202 +/- 4, p less than 0.05). No particular relation was found between presenting circulating immune complex levels and tumor burden. Progressive circulating immune complex increases were demonstrated only in patients whose tumors were either completely removed or dramatically responded to regional therapy (that is, when the tumor antigen load, as reflected by the carcinoembryonic antigen value, rapidly diminished). Serum samples obtained at times of presumed antibody excess in the patients with gastrointestinal cancers were found to contain unexpectedly high concentrations of IgA. We believe these data demonstrate the kinetics of circulating immune complex change during tumor course and they have allowed us to begin to identify circulating immune complex components in patients with colorectal cancer. The results confirm our earlier findings in patients with gestational tumors and differ from accepted relations between immune complexes and tumor growth.
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PMID:Circulating immune complexes in patients with colorectal cancer. 683 92

B16 mouse melanoma sublines in culture spontaneously shed intact plasma membrane vesicles. These vesicles can be fused with the plasma membrane of cells from homologous and heterologous B16 sublines by using polyethylene glycol and phytohemagglutinin-P. Fusion of vesicles from a highly metastatic subline (F10) that localizes exclusively in the lung with cells from a poorly metastatic subline (F1) significantly increased the ability of F1 cells to become arrested in the lung and form metastases in this organ. In contrast, fusion of F1 vesicles with F10 cells did not alter the ability of vesicle-modified cells to localize in the lung or form lung metastases. F10 vesicle-modified F1 cells reverted to their original arrest behavior and metastatic capacity after removal of F10 vesicle components from the plasma membrane. The changes in the arrest and metastatic behavior of F10 vesicle-modified F1 cells were highly highly specific. Vesicles from other B16 sublines that are poorly metastatic and show limited localization in the lung (F1, FLLr, and F10Lr) did not modify the arrest behavior and metastatic capacity of FU cells. These results suggest that the differences in the abilities of the F1 and F10 sublines to localize in the lung are determined by differences in cell surface properties.
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PMID:Arrest and metastasis of blood-borne tumor cells are modified by fusion of plasma membrane vesicles from highly metastatic cells. 692 31

B16 mouse melanoma sublines cultured in vitro spontaneously shed intact vesicles of plasma membrane. These vesicles can be fused with the plasma membrane of cells from homologous and heterologous B16 sublines using polyethylene glycol (PEG) and phytohemagglutinin (PHA). The ability of FI cells to arrest in the lung and form metastases in this organ is significantly increased by fusion of vesicles from a highly metastatic subline (F10) that localizes exclusively in the lung with cells from another subline (F1) which is poorly metastatic and produce few lung metastases. In contrast, fusion of F1 vesicles with F10 cells does not reduce their ability to localize in the lung of form lung metastases. Vesicle-treated F1 cells revert to their original arrest behavior and metastatic capacity following removal of F10 vesicle components from the plasma membrane. The changes in the arrest and metastatic behavior of F1 cells induced by F10 vesicles are highly specific. Vesicles from other B16 sublines which show limited abilities to localize in the lung (F1, F1(1r) and F10(1r) fail to modify the arrest behavior of F1 cells. These results suggest that the differences in the ability of the F1 and F10 sublines to localize in the lung are determined by differences in surface properties.
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PMID:The influence of cell surface properties on the arrest of circulating melanoma cells. 719 63

Intraperitoneal (i.p.) injection of crocidolite asbestos was used to induce mesotheliomas in rats. The morphological changes of the mesothelial cells were studied by light and electron microscopy and by cytologic examination of peritoneal washings. After injection, the asbestos fibres stimulated an acute inflammatory response and were rapidly phagocytosed by the mesothelial cells and incorporated into the submesothelial tissues. At 7 days, the normal microvillous surface of the mesothelium was replaced with a syncytium of proliferating mesothelial cells showing extensive loss of microvilli. Nine months or so later, multifocal mesothelial tumours arose within the peritoneal cavity. The surface thermodynamic properties of normal, asbestos-stimulated mesothelial cells and of mesothelial tumour cells in culture were studied using an aqueous two-phase system containing 4% Dextran T-2000 and 4% poly (ethylene glycol) (PEG) w/w. After asbestos stimulation, there was a significant (P < 0.01) increase in contact angle between the dextran-rich phase and the mesothelial cell surface. These changes were even greater for the mesothelial tumours. The results indicate that the work of adhesion for asbestos-stimulated mesothelial cells and mesothelial tumours is lower than in normal tissue. These findings may be relevant to the process of tumour spread in the serosal cavities and to the development of distant metastases.
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PMID:A study of surface property changes in rat mesothelial cells induced by asbestos using aqueous two-phase polymer solutions. 768 99

The efficacy of tumor therapy using polyethylene-glycol-modified interleukin-2 (PEG-IL-2), alone or in combination with cyclophosphamide, was studied in advanced metastatic disease in the guinea pig. Line 10 (L10) tumor cells appeared in the axillary lymph node only 7 days after intradermal tumor-cell inoculation, and lymph-node leukocytes were almost completely replaced by tumor cells on day 28. Local treatment of the intradermally growing L10 hepatocarcinoma in the guinea pig with a relatively low dose of PEG-IL-2 resulted in regression of the primary tumor and prevention of lymph-node metastases. Therapy was completely curative (4 out of 5 animals) when started on day 7 or 14 after tumor-cell inoculation. When started on day 21, therapy was effective in only some (2 out of 5 cured) of the treated animals. Anti-tumor effects against the primary tumor and against lymph-node metastases were observed only after intratumoral (i.t.) administration of PEG-IL-2. Injection of the agent into or near lymph-node metastases in the absence of the primary tumor had no curative effect. In PBS/BSA-treated control animals the primary tumor and metastases grew progressively. In the treatment of far advanced metastatic disease, the combination of i.t. administration of PEG-IL-2 and i.p. injection of cyclophosphamide (Cy) resulted in improved anti-tumoral effects (5/5 guinea pigs were cured) when compared with monotherapy using either agent (one and none out of 5 animals cured, respectively). PBS/BSA heated controls showed progressive tumor-growth. We conclude that large primary tumors and lymph-node metastases can be treated effectively with PEG-IL-2. The i.t. route of administration is of major importance in the treatment of metastases, since administration of PEG-IL-2 near or into the lymph node had no therapeutic effect. Combination of PEG-IL-2 therapy with systemic injections of Cy significantly improved the curative effects of the treatment of advanced metastatic cancer.
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PMID:PEG-IL-2 therapy of advanced cancer in the guinea pig. Impact of the primary tumor and beneficial effect of cyclophosphamide. 792 81

We show here that in contrast to BALB/c mice bearing a late-stage, large MOPC-315 plasmacytoma, BALB/c mice bearing a late-stage, large RPC-5 plasmacytoma were not cured by cyclophosphamide therapy (15, 50, 100 or 200 mg/kg). However, most BALB/c mice bearing a late-stage RPC-5 tumor were cured by cyclophosphamide therapy (100 mg/kg) in conjunction with adoptive immunotherapy using tumor-infiltrated spleen cells (TISpC) that had been cultured with inactivated RPC-5 tumor cells plus polyethylene glycol 6000, even though this protocol was not effective for the therapy of mice bearing a barely palpable, early-stage RPC-5 tumor. Only a few of the mice that were cured of a late-stage RPC-5 tumor following adoptive chemoimmunotherapy (ACIT) were resistant to a subsequent challenge with RPC-5 tumor cells. However, the challenged mice that had developed progressively growing tumors could then be cured by cyclophosphamide alone when the tumor became large, even though this treatment was not curative for mice bearing a tumor of similar size but not previously treated by ACIT. Thus, the cure by ACIT of BALB/c mice bearing a lethal, late-stage RPC-5 tumor with extensive metastases provides a novel experimental tumor model for investigating the mechanisms by which a chemotherapeutic drug and adoptive cellular immunotherapy can cooperate in causing the complete regression of a large tumor load.
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PMID:Cure of mice bearing a late-stage, highly metastatic, drug-resistant tumor by adoptive chemoimmunotherapy. 843 86

This study was conducted to determine the mechanisms for the enhanced inhibitory effect of cell-adhesive peptides conjugated to polyethylene glycol (PEG) on tumor metastasis. Tyr-Ile-Gly-Ser-Arg (YIGSR), a laminin-derived peptide, conjugated with amino-PEG (YIGSR-aPEG) inhibited lung metastasis of B16-BL6 melanoma cells more effectively than unconjugated YIGSR peptide. [125I]-YIGSR-aPEG and native [125I]-YIGSR showed similar biphasic elimination and profiles after intravenous injection into C57BL/6 mice. Both [125I]-YIGSR and [125I]-YIGSR-aPEG expressed similar plasma half-lives and organ distributions. The radioactivity of both compounds was transported rapidly from the blood to the kidneys, and immediately excreted into the urine. [125I]-YIGSR was almost completely degraded in the urine, but [125I]-YIGSR-aPEG was not. In an in vitro stability assay, [125I]-YIGSR was degraded immediately upon incubation with mouse serum, whereas [125I]-YIGSR-aPEG was not degraded after 180 min incubation in mouse serum. These findings indicate that the enhanced inhibitory effect of YIGSR-aPEG on lung metastasis might be due to its increased stability in the blood.
Invasion Metastasis 1995
PMID:Synthetic cell-adhesive laminin peptide YIGSR conjugated with polyethylene glycol has improved antimetastatic activity due to a longer half-life in blood. 862 Dec 71

Liposomes containing polyethylene glycol-derivatized phospholipids are able to evade the reticuloendothelial system and thereby remain in circulation for prolonged periods. We report here that doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) suppresses the growth of established human lung tumor xenografts in severe combined immunodeficient (SCID) mice and inhibits the spontaneous metastases of these tumors. The enhanced therapeutic efficacy of S-DOX compared to free doxorubicin was demonstrated in two independent human/mouse models. In the first model, S-DOX inhibited the growth of a human non-small cell lung tumor xenograft established orthotopically in the lungs of SCID mice. Treatment of these mice with S-DOX, but not with free drug, suppressed the growth of the tumor in the lung, prevented metastasis from the lung, and enhanced survival percentage. In another model, the human lung tumor is engrafted into gonadal fat pad of SCID mice. Human tumor xenografts grow floridly in this site of engraftment, and the tumor spreads from this primary site into the peritoneal cavity and subsequently reaches the liver and lung. In this model, free drug suppressed the growth of the primary tumor but had no effect upon the subsequent spread of the tumor into the peritoneal cavity, liver, and lung. In contrast, treatment of the tumor-bearing mice with S-DOX (but not with doxorubicin in conventional liposomes) suppressed the tumor spread to the peritoneal cavity, completely arrested metastasis to the liver and lung, and suppressed the growth of the primary tumor xenograft. This report provides the first evidence that antitumor drugs delivered by sterically stabilized liposomes can arrest the metastasis of human tumor xenografts.
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PMID:Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts. 870 18

Cancer is a progressive multigenic disorder characterized by defined changes in the transformed phenotype that culminates in metastatic disease. Determining the molecular basis of progression should lead to new opportunities for improved diagnostic and therapeutic modalities. Through the use of subtraction hybridization, a gene associated with transformation progression in virus- and oncogene-transformed rat embryo cells, progression elevated gene-3 (PEG-3), has been cloned. PEG-3 shares significant nucleotide and amino acid sequence homology with the hamster growth arrest and DNA damage-inducible gene gadd34 and a homologous murine gene, MyD116, that is induced during induction of terminal differentiation by interleukin-6 in murine myeloid leukemia cells. PEG-3 expression is elevated in rodent cells displaying a progressed-transformed phenotype and in rodent cells transformed by various oncogenes, including Ha-ras, v-src, mutant type 5 adenovirus (Ad5), and human papilloma virus type 18. The PEG-3 gene is transcriptionally activated in rodent cells, as is gadd34 and MyD116, after treatment with DNA damaging agents, including methyl methanesulfonate and gamma-irradiation. In contrast, only PEG-3 is transcriptionally active in rodent cells displaying a progressed phenotype. Although transfection of PEG-3 into normal and Ad5-transformed cells only marginally suppresses colony formation, stable overexpression of PEG-3 in Ad5-transformed rat embryo cells elicits the progression phenotype. These results indicate that PEG-3 is a new member of the gadd and MyD gene family with similar yet distinct properties and this gene may directly contribute to the transformation progression phenotype. Moreover, these studies support the hypothesis that constitutive expression of a DNA damage response may mediate cancer progression.
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PMID:Subtraction hybridization identifies a transformation progression-associated gene PEG-3 with sequence homology to a growth arrest and DNA damage-inducible gene. 925 46


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