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)

Five proteins with anticoagulant and antimetastatic activities were isolated from the salivary glands of the Amazon leech, Haementeria ghilianil. These proteins, designated ghilantens, were co-purified on DEAE-cellulose and heparin-agarose, and were purified by microbore C-18 reverse-phase HPLC. Each variant had a similar molecular weight (18,000), amino acid composition, and a blocked amino terminus. Ghilantens caused a dose-dependent prolongation of the prothrombin time of normal human plasma and blocked the factor Xa-mediated hydrolysis of methoxycarbonyl-D-cyclohexylglycyl-glycl-arginine-p-nitro anillide acetate. Ghilantens were quantitatively absorbed to bovine factor Xa-AffiGel-15 and were eluted with 0.1 mol/L benzamidine, an active-site reversible inhibitor of factor Xa. These findings show that ghilantens can form a reversible association with the enzyme. When administered intravenously to mice by tall vein injection, ghilantens potently suppressed lung metastases of B16-F10 melanoma cells. These findings suggest that ghilantens may have therapeutic value in the treatment of metastatic disease.
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PMID:Ghilantens: anticoagulant-antimetastatic proteins from the South American leech, Haementeria ghilianii. 229 60

The Glycosylation inhibitors, glucosamine or tunicamycin induced a marked loss of pigment within melanoma cells in addition to their reduced metastatic ability. Electrophoresis of tyrosinase demonstrated the disappearance of or a marked decrease in membrane-bound tyrosinase, T3 in the small and large-granule fractions. Glycoprotein synthesis in the melanogenic subcellular compartments of pigment cells seems to play an integral role in melanogenesis which is principally enhanced in their carcinogenic status. The effect of interferon (IFN) on melanoma metastasis was investigated using B16-F10 melanoma cells. The inhibitory effect was maximal when given 3 h prior to tumor cell inoculation. IFN given 12 and 24 h prior to, as well as simultaneously with, tumor cell inoculation, also reduced metastases, but to a lesser extent. When given 2 h after the inoculation, no effect was shown. The salutary effect of IFN was abolished by anti-asialo GMI, but NK activity was enhanced equally throughout 3 to 24 hrs. This indicates that the effect is substantially dependent on NK cell activity, although the implication of other factors is not excluded.
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PMID:[Control of melanogenesis by glycosylation inhibitors and the inhibitory effect of interferon on melanoma metastasis]. 240 78

Malignancy in a potential autologous blood donor is considered by some as a relative contraindication for the collection of autologous blood. There is, however little experimental information regarding the safety of transfusion of autologous blood that may contain viable tumor cells. The purpose of this study was to determine if tumor cells seeded into autologous blood retain their metastatic potential and, if so, for how long. A well-established model of the pulmonary metastasis of B16/F10 (F10) melanoma in C57BL/6 mice was used. Equal numbers of F10 cells were seeded into CPDA-1 blood from the mice or into saline, and the number of lung tumors was evaluated 14 days after infusion of blood or saline. The CPDA-1 blood seeded with F10 cells was stored for up to 21 days in transfer packs at 4 to 6 degrees C, and the metastatic potential of F10 cells in the stored blood was ascertained as above. F10 cells seeded into autologous blood that was then transfused without storage gave rise to the same number of metastatic foci (404 +/- 32 metastases) as did those cells transfused in saline (374 +/- 38, p = 0.5). In contrast, the number of metastatic foci resulting from the transfusion of blood containing F10 cells decreased progressively after storage of the blood (7 days = 124 +/- 14 metastases; 14 days = 7 +/- 1; 21 days = 2 +/- 1; all p values less than 0.001 vs fresh blood). Also, the predilection of F10 cells to metastasize to the lung was unchanged by storage in blood.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of storage on the metastatic potential of tumor cells collected in autologous blood. An animal model. 273 21

Treatment of the metastatic melanoma cell lines B16-F1 and B16-F10 with 1.5-2 per cent butanol elevates their experimental metastatic potential, whereas reconstitution of butanol-extracted B16 cells with crude butanol extracts decreases the number of experimentally induced lung foci. We partially purified the biologically active components from crude butanol extracts of B16-F1 by high-performance liquid chromatography and isoelectric focusing, and found the inhibitory activity (i) was in the low-molecular-weight (5-10 kDa) fraction of the chromatogram, (ii) had an isoelectric pH between 5.6 and 5.8, (iii) was distinct from a thiol-protease activity eluted from the isoelectric focusing bed at pH 4.9-5.3 and (iv) was not itself an inhibitor of serine or thiol proteases. Incubation of butanol-extracted B16-F10 cells with known inhibitors of serine, acid and thiol protease inhibitors had no effect on the experimental metastatic phenotype. Although the apparent molecular weight was low, the inhibitor(s) tended to aggregate after focusing, probably owing to the presence of carrier ampholines. Using two-dimensional gel electrophoresis, we observed slight differences between intact and butanol-extracted cells, most of them in the low-molecular-weight region. These results suggest that butanol treatment may reversibly release certain inhibitors of cell surface enzymes other than proteases, which might be involved in invasion and metastasis.
Clin Exp Metastasis
PMID:Low-molecular-weight membrane component inhibits the metastatic phenotype of B16-F10 melanoma. 292 48

The effects of local tumor hyperthermia on regional lymph node metastases are inconclusive. We studied the effects of hyperthermia on the incidence of popliteal, femoral, and abdominal lymph node metastases in C57BL/6 mice with primary B16 melanomas (F10 variant) growing subcutaneously in the left foot. Tumors were heated to 42.3, 43.5, and 44.2 degrees C for 90 minutes either 7 days after inoculation of 5 X 10(4) viable cells (microscopic tumor = mic) or when the tumors were approximately 3 mm in diameter (macroscopic tumor = mac). Femoral lymph node metastases occurred in 0/21 control animals and in 8/22 (36%), 11/19 (58%), and 11/17 (65%) animals whose primary tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively. For all three treatments, the increase in metastases as compared to controls was statistically significant (p less than 0.004, Fisher's exact test). The incidence of abdominal lymph node metastasis was slightly higher in the treated groups than controls. Twenty of 21 (95%) control mice developed popliteal lymph node metastases and hyperthermia-induced increases could not be demonstrated. Fifteen of 21 control mice killed 3 weeks after amputation of tumor-containing leg had pulmonary metastases with an average of 6 +/- 4 (standard deviation) lesions per affected mouse. Pulmonary metastases occurred in 22/22 (100%), 17/19 (89%), and 13/17 (76%) of mice whose tumors were heated to 42.3, 43.5, and 44.2 degrees C, respectively. The numbers of metastases for affected mice were significantly increased compared to controls for tumors heated to 43.5 and 44.2 degrees C (28 +/- 43, 43 +/- 52, 119 +/- 121, p greater than 0.02, p less than 0.006, p less than 0.002, for two sample T-test). While 0/8 mic tumors were cured 5/9 mac tumors heated to 44.2 degrees C disappeared (p less than 0.03, Fisher's exact test) and there was a growth delay in the remaining mice. Mic tumors, heated to 43.5 degrees C, had an accelerated onset of growth while mac tumors heated to this temperature had a slight growth delay. Growth of both mic and mac primary tumors heated to 42.3 degrees C was similar to controls. These results show that therapeutic and subtherapeutic local hyperthermia increases metastases to regional lymph nodes and to lungs even when primary tumor growth rate is partially or totally controlled.
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PMID:Regional lymph node and pulmonary metastases after local hyperthermia of melanomas in C57BL/6 mice. 295 71

Our earlier studies indicated a role for polyamines (namely, putrescine, spermidine, and spermine) not only in tumor growth but also in tumor metastases. We have observed that administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, resulted in significant inhibition of visually detectable pulmonary metastases in mice implanted with Lewis lung carcinoma. The objective of the present study is to investigate the effect of DFMO on other spontaneous and experimental metastatic models and also to determine which step(s) in the tumor metastatic cascade is sensitive to DFMO. The results presented in this study with malignant mouse B16 amelanotic melanoma (B16a) showed a dose-dependent effect of DFMO on the inhibition of both tumor growth and grossly detectable pulmonary metastases. DFMO, when administered as 0.5, 1, and 2% solution in drinking water, resulted in 0, 24.5, and 60% inhibition of tumor growth, respectively, whereas at the same doses an inhibition of 55, 83, and 96% of visible metastases was observed. At treatment levels of 1 and 2% DFMO, 30 and 65% of the animals were free of metastases. DFMO, at 0.5%, did not show any effect on tumor growth, while a significant 55% inhibition of visible pulmonary metastasis was observed, suggesting a specific role for polyamines in tumor metastasis. DFMO treatment also resulted in a significant reduction of putrescine and spermidine levels with a slight increase in spermine concentration in the tumor tissue. DFMO administration did not inhibit the experimental metastases induced as a result of i.v. injection of B16 melanoma (line F10) tumor and Lewis lung carcinoma cells into the tail vein. These results provide preliminary evidence to indicate that tumor cell polyamine depletion by DFMO might affect the first step in the metastatic cascade, intravasation (i.e., prevent the invasion of metastatic tumor cells into lymphatics or blood vessels), although the effect of DFMO on other steps in the metastatic cascade cannot be ruled out.
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PMID:Antimetastatic activity of DL-alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, in mice. 310 31

A comparative study of the antitumor effect of murine recombinant interferon(beta) less than Mu-rIFN(beta) greater than and murine recombinant interferon(gamma) less than Mu-rIFN(gamma) greater on B16-F10 melanoma was conducted. Administration of Mu-rIFN(gamma) i.p. into C57BL/6 mice on days 1 to 7 produced a higher suppressive effect than Mu-rIFN(beta) both on the growth of s.c. implanted tumor and on the formation of artificial pulmonary metastasis. Pharmacokinetic study of Mu-rIFN(gamma) demonstrated that high plasma levels were retained for a long time. In clonogenic assay, Mu-rIFN(gamma) at 1000 units/ml showed about 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN(beta) hardly inhibited the colonies, even at 1000 units/ml. Augmentation of natural killer (NK) cytotoxicity was much greater with Mu-rIFN(beta) than Mu-rIFN(gamma), whereas Mu-rIFN(gamma) enhanced the cytotoxicity of peritoneal macrophages more strongly than Mu-rIFN(beta). Injection of Mu-rIFN(gamma) i.p. 1 day before tumor challenge also inhibited the formation of pulmonary metastasis of B16-F10 melanoma. However, pretreatment of mice with carrageenan significantly suppressed the inhibitory effect of Mu-rIFN(gamma). From these results, it is suggested that the inhibitory effect of Mu-rIFN(gamma) on the tumor growth and metastases of B16-F10 melanoma is mediated partly by direct antitumor effect and partly by the activation of macrophages, and that the augmentation of NK activity contributes mainly to the antitumor effect of Mu-rIFN(beta).
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PMID:Comparative study of the antitumor effect of two types of murine recombinant interferons, (beta) and (gamma), against B16-F10 melanoma. 312 91

Treatment of tumor cells with interferon-gamma (IFN) frequently reduces their susceptibility towards NK cells and results in augmented expression of MHC antigens, which may increase immunogenicity of tumor cells. Depending on the relative strength of these opposing effects, i.e. escape from non-adaptive immune defense versus facilitated activation of T-cell-mediated defense, IFN-treatment may be beneficial or disadvantageous for the tumor-bearing host. This is demonstrated for the variants F1 and F10 of the B16 melanoma, which differ in metastasizing capacity. IFN-treatment of B16-F1 melanoma cells significantly reduced susceptibility towards non-adaptive immune defense, and increased metastasizing potential. On the other hand, H2K antigen expression was augmented by a factor of 50; concomitantly, lysability by CTL was increased, together with the number and expansion rate of cytotoxic T-cell precursors (CTLp) recruited after immunization with IFN-treated B16-F1. The benefit of increased antigenicity and immunogenicity outweighed the disadvantage or reduced susceptibility towards non-adaptive immune defense. B16-F10 cells were less susceptible to NK cells, expression of MHC antigens was found to be stronger and they were more immunogenic than B16-F1 cells. After IFN-treatment, susceptibility to non-adaptive immune defense was further reduced. Expression of MHC antigens as well as antigenicity and immunogenicity were only moderately augmented. As a consequence, the decreased susceptibility to non-adaptive immune defense was dominating in the tumor bearing host and could not be counterbalanced by immunization with IFN-treated B16-F10 cells. We interpret these data to show that a precise knowledge of the relative decrease in susceptibility to non-adaptive immune defense, the relative increase in MHC antigen expression, antigenicity and immunogenicity may allow a more precise prognosis of the influence of IFN on metastatic capacity in the B16 system, and eventually also in a clinical therapeutic regimen.
Clin Exp Metastasis
PMID:IFN-treatment of B16-F1 versus B16-F10: relative impact on non-adaptive and T-cell-mediated immune defense in metastatic spread. 313 43

Three metastatic variants, BL6 (high metastasis), F1 (nonmalignant) and F10 (intermediate malignancy) of the B16 murine melanoma, and a pulmonary metastatic line BL6-ML8 of the BL6 primary tumour have been examined for spontaneous sister chromatid exchange (SCE). Two human astrocytoma cell lines were also examined. SCE was encountered in 29 and 13% of second division metaphases of BL6 and F10. In contrast, only 3% of second division metaphases of the F1 showed SCE. In BL6-ML8, 40% of the metaphases showed SCE. Approximately 2-4% of the human astrocytoma second division cells showed SCE. The variant lines were karyotypically heterogeneous. The pattern of cell distribution according to chromosome number showed an overall similar profile in the melanoma variants. However, the metastatic BL6-ML lines showed a marked shift to a hypertriploid state. SCEs occurred with higher frequency in this hypertriploid subpopulation of BL6 and F10 cells than in F1. SCE incidence in the hypertriploid subpopulation was twofold higher in the metastatic line than in the primary BL6 line. The number of SCEs per chromosome was twice as high in F10, BL6 and BL6-ML8 as in the F1 cells. This hypertriploid subpopulation showed a marked increase of SCEs on exposure to mitomycin C and ethyl methane sulphonate, indicating their mutability. It is suggested that the parallelism between SCE and metastatic potential may be relevant in the context of the generation of the metastatic phenotype.
Invasion Metastasis 1988
PMID:Spontaneous sister chromatid exchange in metastatic variants of the murine B16 melanoma and human astrocytomas in culture. 313 79

We analyzed mechanisms responsible for organ-specific metastasis by using two melanoma sublines derived from the same mouse tumor, of which one colonizes the lungs (F10) and the other colonizes the liver (L8) after intravenous injection. Both lines were obtained by selective growth in lung or liver after injection of tumor cells into a tail vein or portal vein. Contrary to common concepts, the cells of the liver-colonizing melanoma line do not accumulate preferentially in the liver after intravenous administration in vivo. However, the selective survival and proliferation of these melanoma cells in the target organ (liver) may be explained by the unexpected observation that they can be specifically stimulated to proliferate in the presence of hepatocytes, whereas the cells of the lung-colonizing line cannot. Growth promotion under coculture conditions in vitro was monitored both by thymidine incorporation into DNA and by increase in cell numbers. The proliferative stimulus is not mediated by an easily diffusible factor but rather depends upon direct contact between liver cells and those tumor cells that metastasize to that particular organ.
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PMID:Growth regulation of cancer metastases by their host organ. 317 31


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