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)

We have evaluated in a homologous system the mechanisms of platelet activation by cells isolated from fresh human tumor tissues and the role of thromboxane B2 (TxB2) generation in this process. Thirty-eight of the 46 tumor tissues considered showed a high platelet-aggregating activity, with no particular distribution in any specific tumor type. Apyrase caused a nonsignificant reduction in the aggregation response, hirudin did not change it, while iodoacetic acid or p-hydroxymercuriphenylsulfonate, specific cysteine proteinase inhibitors, significantly reduced the platelet-aggregating capacity of these tumor cells. In 9 colon carcinomas and in 8 breast carcinomas the levels of TxB2 produced by platelets after addition of tumor cells were measured: tumor cell-induced platelet aggregation was accompanied by a significant production of the metabolite; indobufen, a cyclooxygenase inhibitor, significantly reduced aggregation and particularly TxB2 production, while the drug had no effect on both parameters if preincubated with tumor cells only. These data suggest that cells isolated from different human tumor tissues activate platelets through the activity of tumor-associated cysteine proteinase(s); platelet aggregation by tumor cells is largely dependent on arachidonic acid metabolism in platelets, while such metabolism in tumor cells does not play a significant role.
Invasion Metastasis 1991
PMID:Thromboxane production by platelets during tumor cell-induced platelet activation. 191 83

Using an in vitro monolayer assay (MIA) we analyzed the invasive behaviour of a panel of B-cell hybridomas prepared by the fusion of non-invasive, non-metastatic NSO plasmacytoma cells and normal murine B-cells. Interaction of these hybridomas with fibroblast-like monolayers consisted mostly of adhesion on top of the monolayers, whereas only a fraction of these cells penetrated through the monolayer. This is in sharp contrast with the highly invasive properties displayed by T-cell hybridomas. Whereas T-cell hybridomas highly infiltrated monolayers of rat hepatocyte in vitro, B-cell hybridomas neither adhered to nor infiltrated hepatocyte monolayers. We found a good correlation between the degree of adhesion of B-cell hybridomas to fibroblast-like monolayers and their metastatic capabilities upon i.v. injection into syngeneic animals. Unlike T-cell hybridomas which formed diffuse metastasis in liver and spleen, B-cell hybridomas generated nodular metastatic lesions. . When normal LPS-stimulated B-lymphocytes were tested in the fibroblast-MIA, only part of the population infiltrated the monolayers. This again contrasts with T-lymphocytes where a majority of the cells penetrated through the monolayers. These results suggest that (i) B-lymphocytes express invasive properties, albeit to a lesser extent than T-lymphocytes, (ii) non-invasive B-lymphoma cells can acquire invasiveness following cell fusion with a normal B-cell, (iii) these invasive properties contribute to the malignancy of the hybridomas when tested in recipient animals.
Clin Exp Metastasis
PMID:Interaction of B-cell hybridomas with fibroblast or hepatocyte monolayers in vitro and their metastatic behaviour in vivo. 203 16

The purpose of this study was to characterize an in vivo model of human pancreatic cancer suitable for chemotherapy and immunotherapy studies. In this study we report a 2-year experience in growing the MIA PaCa-2 (CRL 1420) human pancreatic cancer cell line in 92 adult (8 weeks old) and 256 young (3-6 weeks old) nude mice. Ten million tumor cells were transplanted into orthotopic (duodenal lobe of the pancreas) and/or heterotopic positions (hepatic and subcutaneous) and data on operative mortality, effect of total body irradiation (TBI), tumor growth kinetics, and survival are presented comparing the two age groups. Operative mortality was due to anesthetic intolerance which was higher in the young mouse population (13.4% versus 5.7%). Adult mice withstood TBI (500 rad) without mortality but young mice were highly sensitive to radiation damage and their maximum tolerated dose (LD50) was 425-450 rad. Subcutaneous tumors grew significantly more often in young compared to adult animals (97.9% versus 69%) and this finding was not affected by TBI (96.9% versus 75%), though tumors did appear more quickly after TBI. An average of 14.7 +/- 2.8 days was required for the subcutaneous tumors to become macroscopically apparent in the adult population compared with 3.1 +/- 0.8 days in the young mice. The largest subcutaneous tumor diameter 28 days following tumor implant averaged 9.3 +/- 0.6 mm in the young animals and 5.5 +/- 1.7 mm in the adult population (P less than 0.01). Treatment of young mice with human recombinant interleukin-2 (IL-2) (10,000 Units twice a day for 28 days) produced a 27% decrease in tumor growth. This effect was abolished by prior irradiation of the young mice with 375 rad TBI. Pancreatic tumor growth also occurred more consistently in young than in adult animals (91.2% versus 64.3%) and irradiation did not affect pancreatic tumor take in either group. Occasionally intrapancreatic tumor growth was associated with liver metastases in animals that were killed after 28 days (17.8% in young and 22.2% in adult animals). However, when more than 45 days elapsed before sacrificing the animals, the incidence of hepatic metastases increased to 57.1%. This was slightly less than the incidence of hepatic lesions found after direct injection of cancer cells into the liver by portal vein injection (71.4%). Direct extension of tumor into surrounding tissues was common with frequent involvement of the duodenum (83.7%), kidneys (30.6%), and other intraabdominal organs (43.9%). Survival was significantly longer in adult compared to young mice.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The nude mouse as a model for the study of human pancreatic cancer. 258 1

We studied the effects on platelet function of cells isolated from freshly dissociated human tumor tissues (11 breast carcinomas, 9 colon carcinomas and 1 lymph node metastasis from melanoma) obtained at surgery as compared with cultured human tumor cells: namely, human melanoma 1402 cell line derived from a primary tumor and two lines derived from lymph node metastases (ME 7110/2 and Me 665/1) as well as a human hepatoma cell line (Hep G2). The three melanoma cell lines activated platelets by producing ADP, as evidenced by the inhibitory effect of apyrase and by the direct measurement of the agonist in the supernatants of tumor cell suspensions; this production was much greater by the cells derived from metastases than by the cells derived from the primary tumor. On the other hand, aggregation induced by Hep G2 hepatoma cells was unaffected by apyrase and was inhibited by hirudin or concanavalin A, suggesting that the cells aggregate platelets by producing thrombin, probably through tissue factor activity of the cells themselves. Cells isolated from 16 of the 21 human tumor tissues possessed a potent platelet-aggregating effect, which was not inhibited by apyrase, hirudin or concanavalin A, but was virtually abolished by the cysteine protease inhibitors iodoacetic acid or p-hydroxymercuri-phenylsulfonate. Collectively, our data demonstrate that cells isolated from freshly dissociated tumor tissues activate platelets through tumor-associated cysteine proteinases rather than by the ADP- or thrombin-dependent mechanisms characteristic of cultured human tumor cell lines.
Invasion Metastasis 1989
PMID:Mechanisms of platelet activation by cultured human cancer cells and cells freshly isolated from tumor tissues. 276 27

The procoagulant activity (PCA) was examined in extracts from primary tumor and metastases of experimental Guerin epithelioma transplanted into Wistar rats. PCA was evaluated by measurement of the level of activation of coagulation factor X using specific chromogenic substrate S-2222. We observed that extracts from both primary tumor and metastases were able to activate factor X in vitro. This activity was not factor VII-dependent, it was inhibited by phenylmethylsulfonyl fluoride (PMSF) and mercuric chloride, and in a smaller degree by p-chloromercuric benzoate (p-CMB) and iodoacetic acid (IAA). No difference between procoagulant activity in extracts from primary tumor and from metastases was observed.
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PMID:Factor X-activating activity from Guerin epithelioma. 340 36

This study was designed to investigate the potential of shark cartilage extracts to inhibit the growth and metastatic spread of a murine solid tumour. The SCCVII carcinoma, implanted in the right rear foot of C3H mice, was used. Following tumour implantation, two different commercially available extracts of shark cartilage (Sharkilage and MIA Shark Powder) were dissolved in water and orally administered to the mice at doses that ranged from 5 to 100 mg per mouse. These injections were repeated on a daily basis for up to 25 days post-implantation of the primary tumour. Compared to non-drug-treated animals, daily administration of the shark cartilage extracts did not show any adverse toxicity (as measured by changes in body weight and lethality). More importantly, none of the shark cartilage doses tested had any retarding effect on the growth of the primary tumour, nor did they inhibit the development of metastases seen in the lungs of the tumour-bearing mice at autopsy. In conclusion, our results offer no support for the proposed use of shark cartilage extracts as an anti-cancer therapy.
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PMID:The effect of shark cartilage extracts on the growth and metastatic spread of the SCCVII carcinoma. 983 72

MIA was isolated previously as a small soluble protein secreted from malignant melanoma cell lines in vitro. Highly restricted expression patterns in melanocytic tumors were identified in vivo. We therefore quantitated serum levels of MIA protein by means of a non-radioactive ELISA and investigated whether MIA provides clinically relevant parameters in patients with malignant melanomas. Here we report enhanced MIA serum levels in 13% and 23% of patients with stage I and II disease, respectively, and in 100% with stage III or IV disease. Response to therapy in stage IV disease correlated with changes in MIA serum levels and surgical removal of metastases led to normalization of serum values. Repeated measuring of sera from 350 patients with a history of stage I or II melanoma during follow-up, we detected 32 patients developing positive MIA values. At the time of serum analysis 15 of them had developed metastases and one presented with metastatic disease 6 months later. In conclusion, MIA represents a novel serum marker for systemic malignant melanoma revealing the highest sensitivity and specificity among currently available markers.
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PMID:MIA, a novel serum marker for progression of malignant melanoma. 1047 Feb 21

It has recently been shown that the serum level of melanoma-inhibitory protein (MIA) provides useful information for the therapy and follow-up of patients with malignant melanoma. Previously, S100 beta has been described as a useful tumor marker for malignant melanoma. In this study, we compare the significance of the two markers in follow-up, therapy outcome and prognosis by measuring MIA and S100 beta serum levels in 50 melanoma patients. Serum levels were measured in patients with malignant melanomas of stages I-IV with at least 3 time points of measurement. Serial MIA and S100 beta measurements were obtained from 32 patients with stage IV disease in parallel to chemotherapy and from 18 patients with a history of stage I and stage II disease during follow-up. The response to chemotherapy in stage IV disease and relapse of melanoma during follow-up correlated with changes in MIA and S100 beta serum levels. In comparison, MIA revealed slightly higher specificity and sensitivity. In conclusion, both markers are useful for detection of progression from localized to metastatic disease during follow-up and for monitoring therapy of advanced melanomas.
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PMID:Comparison of two prognostic markers for malignant melanoma: MIA and S100 beta. 1105 27

Pancreatic cancer is a highly metastatic disease that responds poorly to currently-available treatment. In order to better visualize and understand the chronology and specificity of metastatic targeting of pancreatic cancer, two human pancreatic cancer cell lines, expressing green fluorescent protein (GFP), were studied in orthotopic models. MIA-PaCa2-GFP and BxPC-3-GFP tumor fragments were transplanted by surgical orthotopic implantation (SOI) to the nude mouse pancreas for fluorescence visualization of the chronology of pancreatic tumor growth and metastatic targeting. BxPC-3-GFP tumors developed rapidly in the pancreas and spread regionally to the spleen and retroperitoneum as early as six weeks. Distant metastases in BxPC-3-GFP were rare. In contrast, MIA-PaCa-2-GFP grew more slowly in the pancreas but rapidly metastasized to distant sites including liver and portal lymph nodes. Regional metastases in MIA-PaCa-2-GFP were rare. These studies demonstrate that pancreatic cancers have highly specific and individual 'seed-soil' interactions governing the chronology and sites of metastatic targeting.
Clin Exp Metastasis 2000
PMID:Chronologically-specific metastatic targeting of human pancreatic tumors in orthotopic models. 1131 94

As the majority of primary malignant melanomas can be cured by surgical excision, the prognosis of melanomas is dependent on whether tumor cells have disseminated orare capable of doing so at the time of surgery. A prospective and valid detection of this minimal residual disease is not currently possible. The most important known so-called markers of melanoma disease, tyrosinase, S100 and MIA, all are more likely to be present in patients with more advanced disease. A valid prognostic effect has only been shown for S100 in patients with already identified metastatic disease. Further prospective studies are required to determine the potential gain of information by routine determination of these markers in melanoma patients.
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PMID:[Disseminated melanoma cells in blood and bone marrow. Significance and detection by potential tumor markers]. 1138 19


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