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)

Investigations on mechanisms of metastatic tumour spread revealed a role for compounds that inhibit tumour dissemination at the time of hematogenous dissemination. The platelet aggregation inhibitor prostacyclin and its stable analogues were shown to inhibit tumour-cell-induced platelet interaction as well as tumour cell adhesive mechanisms. This study concentrates on the effect of the stable prostacyclin analogue cicaprost: 5-[(E)-(1S,5S,6S,7R)-7-hydroxy-6-[(3S,4S)-3-hydroxy-4-methylnona-1 ,6- diinyl]-bicyclo[3,3,0]octan-3-ylidene]-3-oxapentanoic acid (Schering AG), as cyclodextrin clathrate, on spontaneous tumour metastases of two different carcinomas of the rat. In Cop rats bearing spontaneously metastasizing R 3327 MAT Lu prostate carcinomas, cicaprost (1.0 mg/kg p.o. daily) inhibited the number of lung metastases by about 80%, whereas the lower doses (0.1 and 0.5 mg/kg) exhibited borderline efficacy. In female Wistar-Furth rats bearing s.c. implanted SMT 2A mammary carcinomas, spontaneously metastasizing into regional lymph nodes and lungs, cicaprost (0.1, 0.5 and 1 mg/kg) p.o. daily exhibited a dose-dependent inhibition of the number of lung metastases. Five out of ten animals treated by 1 mg/kg were free of visible lung metastases. The weight of the axillary lymph node was significantly reduced by the 1 mg/kg dose of cicaprost, whereas lower doses had no effect on the weight of the lymph nodes. The growth of the primary tumour was not influenced by cicaprost in the R 3327 MAT Lu prostate carcinoma nor in the SMT 2A mammary carcinoma in the dose range tested. In conclusion, the stable prostacyclin analogue cicaprost exhibits a strong antimetastatic action in two metastasizing tumours of the rat and interferes with the steps not only of haematogenous, but also of lymphogenous metastasis.
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PMID:The prostacyclin analogue cicaprost inhibits metastasis of tumours of R 3327 MAT Lu prostate carcinoma and SMT 2A mammary carcinoma. 162 41

Much attention has recently focused on the role of tumor cell-platelet interaction in the metastatic cascade. Prostacyclin and stable prostacyclin analogues have been shown to inhibit specifically the formation of metastases in experimental tumor models. This action is based on their ability to reduce the attachment of tumor cells to platelets and to inhibit adhesion of tumor cells-platelet aggregates to the endothelial lining. To investigate the antimetastatic potential of two prostacyclin analogues (Iloprost and Eptaloprost, Schering AG), we have tested these compounds in the spontaneously metastasizing R 3327 MAT Lu prostate carcinoma of the Cop rat in two types of experiments. Treatment was performed for 33 days, starting one day before s.c. implantation of the tumor. The primary s.c.-implanted tumor remained in situ throughout the experiment. In the first test, Iloprost (0.3 micrograms/kg/min) and Eptaloprost (0.1 micrograms/kg/min) were administered via Alzet mini pumps s.c.. There was a considerable reduction of the number of visible lung metastases by Eptaloprost. In the second test, Eptaloprost was administered p.o. in doses of 0.1 and 0.5 mg/kg daily. The number of lung metastases was significantly reduced. Both compounds had no effect on the growth of the primary tumor in the first as well as in the second test. These data show that the prostacyclin analogue Eptaloprost has a significant antimetastatic activity in a spontaneously metastasizing tumor model and thus merits further investigation.
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PMID:Effects of prostacyclin analogues in in vivo tumor models. 170 84

Since an involvement of platelet aggregation in the metastatic process has been found, platelet activation inhibitors were investigated for their potential to reduce tumor metastases. Recent in-vitro and in-vivo investigations showed an antimetastatic effect of prostacyclin (PGI2) and stable prostacyclin analogues. This study concentrates on the effect of the stable prostacyclin analogue Cicaprost (Schering AG) on tumor metastases in two metastasizing tumors of rodents. C57BL/6 mice bearing s.c.-implanted M5076 reticulum sarcoma were treated with Cicaprost in doses of 0.1-1.0 mg/kg throughout the experiment. Cicaprost in all doses tested reduced the number of liver metastases in a statistically significant manner. The 1.0 mg/kg dose, which decreases the median number of liver metastases to more than 93% compared to the control, was most effective. Cicaprost in the 0.5 mg/kg dose reduced the number of liver metastases in mice bearing i.v.-implanted M5076 reticulum sarcoma. In Cop-Fisher rats bearing s.c.-implanted spontaneously metastasizing R3327 MAT Lu prostate carcinoma, Cicaprost in a dose of 1.0 mg/kg p.o. daily strongly reduced the number of lung metastases. These results indicate that Cicaprost is a potent inhibitor of tumor metastases in different tumor models in rodents.
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PMID:Cicaprost inhibits metastases of animal tumors. 176 1

The MAT-Lu subline of the Dunning R3327 system of rat prostatic adenocarcinomas universally metastasizes to the lungs of untreated recipient hosts. The MAT-Lu cancer was implanted into the hind leg of animals and the primary tumor was allowed to grow to various sizes before the tumor bearing leg was surgically removed. These studies demonstrated that there is a direct relationship between the size of the primary tumor at the time of surgical removal and the number of metastases already established in the lungs. Once the primary MAT-Lu reaches a size of greater than or equal to 0.5 cc, greater than or equal to 50% of all inoculated animals already have established lung metastases and are thus not cured by surgery alone. In an attempt to increase the cure rates, adjuvant chemotherapy (cytoxan given at a dose of 90 mg./kg. body weight) was used in combination with surgery. These studies demonstrated that if chemotherapy was given by itself to animals bearing macroscopically established (greater than or equal to 0.5 cc) MAT-Lu cancers, no animals could be cured. In direct contrast, by combining the same intensity of adjuvant chemotherapy with the removal of the primary MAT-Lu cancer, cures could be produced in high (greater than 90%) frequency, but only if this combinational approach was simultaneously initiated when the primary tumor was less than 2 cc in size. If the primary MAT-Lu cancer was allowed to grow to too large a size before surgery (greater than 2 cc) or if the chemotherapy was delayed following surgery (both processes allowing the metastatic tumor burden to increase before initiating adjuvant chemotherapy), the ability of the adjuvant chemotherapy to cure the host of its metastatic tumor burden is lost. These results demonstrate that the MAT-Lu rat prostatic cancer, like human prostatic cancer, is not effectively treated by chemotherapy alone or by adjuvant chemotherapy combined with surgery if the treatment is given too late in the course of the disease. These studies emphasize the critical requirement of combining surgery and adjuvant chemotherapy as early as possible in the treatment of metastatic prostatic cancer in order to minimize the total metastatic tumor burden and maximize the possibility of cure.
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PMID:Relationship between tumor size and the curability of metastatic prostatic cancer by surgery alone or in combination with adjuvant chemotherapy. 336 56

The transplantable Dunning R-3327 rat prostatic adenocarcinoma model has provided a series of tumor variants with broad ranges of metastatic potential. We tested whether cell surface charge might be related to metastatic potential by measuring the electrophoretic mobility of live tumor cells obtained by needle aspiration. Cells were aspirated from tumors with low metastatic potential (following subcutaneous inoculation of 10(6) tumor cells the H, G and AT-1 variants had less than 5% metastases; AT-2 had 5-20%) and were compared to the electrophoretic mobility of cells aspirated from highly metastatic tumors (MAT-LyLu, MAT-Lu, AT-3 had greater than 90% metastases). Electrophoretic mobility expressed in mu/sec/volt/cm. was measured on 100 cells from each tumor subline, and the cell surface charge expressed as a zeta potential was calculated from electrophoretic mobility using the Helmholtz-Smoluchowski equation. The average zeta potential (+/- S.E.M.) for the four sublines with low metastatic potential was (-17.4 +/- 0.4 mV) compared to the three sublines with high metastatic potential (-26.5 +/- 0.7 mV), and the differences were significant (p less than .01) using the Mann-Whitney Wilcoxon test. Using a zeta potential of -20.5 mV as the cutoff between high and low metastatic potential, the sensitivity and specificity of zeta potential in predicting metastatic potential in 140 determinations on seven tumor lines were 92% and 82.5%, respectively. The predictive value of a positive test (value greater than -20.5 mV) was 80% and the predictive value of a negative test (value less than -20.5 mV) was 93%. The results support a difference in the cell surface charge between these metastatic and nonmetastatic tumors with increasing negativity at the cell surface correlating with increased metastatic potential, but not with tumor growth rates.
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PMID:Cell surface charge in predicting metastatic potential of aspirated cells from the Dunning rat prostatic adenocarcinoma model. 337 85

Normal Copenhagen rat bone marrow was assayed for growth inhibition of cultured MAT LyLu rat prostate tumor cells. A marrow-derived factor was identified that had significant growth inhibitory activity in vitro against MAT LyLu as well as against DU-145 human prostate tumor and MBT-2 mouse bladder tumor cells but that was noninhibitory to normal rat fibroblasts. The factor was stable to degradation by acid, heat, freezing, trypsin, and carboxypeptidase B. The factor was nonreactive with Coomassie blue, and the molecular weight was estimated as less than 620 daltons. A similar factor was identified in normal human and normal rat sera. The presence of this factor in bone marrow may explain the absence of osseous metastases in the Dunning rat prostate tumor model.
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PMID:In vitro growth inhibition of Dunning rat prostate tumor by bone marrow factor. 356 48

Lectin-binding characteristics of a previously described highly metastatic variant (clone 4), derived in vivo from a poorly metastatic rat mammary adenocarcinoma (DMBA-8), have been investigated. of the lectins studied clone 4 cells, unlike the parent cells, bound Ulex europaeus agglutinin (UEA-1; specificity alpha-L-fucose) and peanut agglutinin (PNA; specificity D-galactose). These differences may be related to the greatly enhanced ability of clone 4 cells to form lung foci after intravenous injection. After neuraminidase treatment the differential binding of PNA, as shown by flow cytofluorography, was abrogated whereas that of UEA was unchanged. After separation by SDS-PAGE, four proteins in total cell extracts of clone 4 cells bound 125I-UEA applied to the gels. These had subunit molecular weights greater than 100,000 daltons and were also found in cellular extracts of another highly metastatic rat mammary adenocarcinoma (MAT 13762-B), but were missing from DMBA-8 cell extracts. In clone 4 and MAT 13762-B cells exogenous 3H-fucose was mainly incorporated into four fucoproteins of similar molecular weights to those which bound 125I-UEA. DMBA-8 cells, which incorporated slightly less exogenous fucose, showed a different pattern of fucoprotein labelling, which would seem to explain why DMBA-8 cells failed to bind UEA. Differences in cell surface protein iodination patterns were also noted between DMBA-8 and clone 4 cells.
Invasion Metastasis 1987
PMID:Lectin-binding characteristics of related high- and low-metastatic rat mammary adenocarcinoma cell lines. 367 43

Studies carried out by the authors on the rat mammary adenocarcinoma cell lines MAT 13762 and DMBA-8 are summarized. A series of variants and somatic cell hybrids have been prepared and partially characterized in terms of phenotypic properties which may correlate with metastatic potential. These include measurement of in vitro migration, lectin binding properties, expression of procoagulant activity and shedding of cell surface components. Particular emphasis has been placed on the production of enzymically-active plasminogen activator, as this seems to correlate with the ability of cells to metastasize. The finding has also been made that several of the cell types studied produce, in vitro, an inhibitor of plasminogen activator which may influence the metastatic behaviour of tumor cells. Results obtained are discussed in the context of the usefulness of these tumor systems for the study of spontaneous and experimental metastasis and the factors involved in these processes. Preliminary results of cloning and fluctuation analysis of metastatic potential together with discussion of the role of the metastatic heterogeneity and the formation of metastatic variants by mutation events are included.
Cancer Metastasis Rev 1985
PMID:Studies on rat mammary adenocarcinomas: a model for metastasis. 390 19

The spontaneous capillary tube migration of metastatic MAT 13762 rat mammary adenocarcinoma cells has been measured and compared with that of a non-metastatic variant, TGR. MAT 13762 cells migrated to a greater extent in the presence than in the absence of serum, and in both cases migration areas were considerably greater than for TGR cells. Different clones of hybrids, formed by fusing metastatic and non-metastatic variants, showed migration areas ranging from those of the metastatic to those of the non-metastatic parent cells. Despite their differing migrations, all of these clones were either non or only slightly metastatic. Treatment of TGR cells with trypsin enhanced their migration to that of MAT 13762 cells, whereas trypsin-treated MAT 13762 cells showed a slightly decreased migration. Although MAT 13762 cells, unlike TGR cells, produced large amounts of plasminogen activator (PA), no evidence was obtained for the direct involvement of PA in the high migration rate of MAT 13762 cells.
Invasion Metastasis 1984
PMID:Spontaneous capillary tube migration of metastatic rat mammary adenocarcinoma cells. 653 58

The Dunning R 3327 AT tumor is a rapidly growing, androgen insensitive, serially transplantable rat tumor of prostatic origin. In early passages, the AT tumor had a very low rate of distant metastases (less than 1 per cent); however, after 60 serial subcutaneous passages, the AT tumor has given rise to a new tumor line which has an extremely high metastatic rate. Greater then 75 per cent of all animals inoculated with this late passage tumor develop lymph node metastases alone or in combination with lung metastases. This high passage tumor seems to be distinct from the original AT tumor since it has a substantially faster doubling time and a massively increased metastatic potential; it has therefore been named the Dunning R 3327 MAT LyLu tumor (metastatic AT tumor able to disseminate to lymph nodes and lung). The MAT LyLu tumor, like the parent nonmetastatic AT tumor, is androgen insensitive with regard to its growth rate, rate of distant metastases and mean survival time. This newly characterized MAT LyLu tumor provides an appropriate animal model system for testing the potential effectiveness of a variety of therapeutic approaches specifically aimed at limiting the metastatic spread of prostatic cancer.
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PMID:The characterization of a newly identified, highly metastatic variety of Dunning R 3327 rat prostatic adenocarcinoma system: the MAT LyLu tumor. 725 19


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