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)

Honn et al. [Science (Wash. DC), 212: 1270, 1981] have recently reported a 93% reduction in the development of metastases of B16 amelanotic tumor cells given i.v. following a single dose of prostacyclin (PGI2) (100 micrograms) and theophylline (100 micrograms) 30 min prior to the injection of tumor cells. We have been unable to reduce pulmonary metastases induced by the i.v. injection of CT26 colon adenocarcinoma, Lewis lung carcinoma, or B16 amelanotic melanoma cells with a similar regimen. Thus, PGI2 and theophylline given prior to injection of tumor cells and 2 hr postinjection had no effect on the number or volume of pulmonary tumor nodules for CT26 cells, using 15 experimental and 14 control animals; Lewis lung cells, using 14 experimental and 13 control animals; or B16 amelanotic cells, using 26 experimental and 12 control animals. The PGI2 used was shown to be active in vitro, inhibiting tumor-induced platelet aggregation by all three tumors at 10(-9)M; and in vivo by inhibition of Lewis lung-induced thrombocytopenia at 1 hr, using 100 micrograms PGI2 prior to the injection of tumor cells.
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PMID:Lack of effect of in vivo prostacyclin on the development of pulmonary metastases in mice following intravenous injection of CT26 colon carcinoma, Lewis lung carcinoma, or B16 amelanotic melanoma cells. 637 76

Combination of dibutyryl adenosine 3', 5'-cyclic monophosphate or prostaglandin E1 (PGE1) and papaverine effectively induced differentiation of neuroblastoma in mice. Two cases of human neuroblastoma with stage III and IV were administered intraaortic PGE1 infusion combined with oral papaverine and conventional chemotherapy. There were no noticeable side effects and the treatment was effective in decreasing tumor size and promoting tumor maturation in the infused area. However, distant osseous metastases were developed in both cases, during and after the PGE1 administration. They survived 30 and 17 months, respectively, from the initiation of therapy. (Jpn J Cancer Chemother 10(9): 1936-1943, 1983) These results prompted us to study the metastatic potentials of neuroblastoma. In vitro studies demonstrated that cultured human neuroblastoma cells (NB-1, GOTO, SK-N-DZ, SJ-N-KP, SJ-N-CG and SK-N-FI) aggregate human platelets with maximum aggregation ranging from 28% to 51%. Addition of PGE1 or PGD2 to PRP effectively inhibited the tumor-cell-platelet interaction, with IC50 approximately 100 nM for PGE1 and 10 nM for PGD2, respectively. In addition, 50 microM PGE1 or PGD2, 5 microM PGI2 reversed neuroblastoma-induced platelet aggregation in 4 out of 5 cell lines were studied. These findings indicate a the possible role of PGs in effective inhibition of neuroblastoma metastases in vivo. However, two cell lines (SK-N-DZ and SJ-N-CG), which had been exposed to 8.5 microM PGE1 or PGD2 for 90 min and 72 hr, respectively, retained the platelet aggregating activity which was not significantly different from that of untreated cells. We conclude that clinical application of intraaortic PGE1 in the treatment of advanced neuroblastoma has advantage in potentiation of tumor cell kill and in inducing maturation. Administered PGE1 may exert its action in two ways: in preventing tumor metastasis or possibly in enhancing the metastatic potential of neuroblastoma cells. Further refinement of these modalities including other PGs such as PGD2 or PGI2 and more detailed studies on optimal PG administration to prevent metastasis should be evaluated in future.
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PMID:[Differentiation induction and potentiation of chemotherapy by PGE1 infusion in patients with neuroblastoma--effect of PGE1 on metastatic potential of neuroblastoma]. 658 82

The study of cardiac output (CO) distribution to tumors and metastases is of interest for a better understanding of tumor biology and for pharmacological approaches. A radioactive microsphere method was developed to asses CO distribution in C57BL/6J mice bearing syngeneic 3LL or BALB/c mice with JWS. At the initial stages of cancer growth, the CO relative fractions per g of tissue (%CO/g) to 3LL and JWS were similar to those in surrounding tissues. In both tumors a positive, significant correlation was found between tumor weight and tumor CO fraction, but %CO/g was lower in 3LL 2 and 3 weeks after transplantation, whereas it did not change in JWS. Indeed, much larger necrotic areas developed in 3LL than in JWS. The %CO/g to the lungs increased in both models when metastases were not yet visible; subsequently, the appearance of lung nodules was accompanied by a decrease of %CO/g in JWS and a further increase in 3LL. This corresponded to the much higher ratio of metastatic to intact lung tissue in JWS than in 3LL. In fact, isolated lung metastases had a significantly lower blood supply than the surrounding tissue. This might be due to a different vascularization pattern and/or smaller amounts of vasodilator substances being produced by metastatic nodules; the latter is suggested by lower generation of prostacyclin activity in isolated lung metastases than in intact pulmonary tissue.
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PMID:Distribution of cardiac output during development of two metastasizing murine tumors. 668 42

Metastasis is the principal cause of failures to cure human cancers. Prostacyclin is a powerful antimetastatic agent against B16 amelanotic melanoma cells. This effect, which may result from the platelet antiaggregatory action of prostacyclin, is potentiated by a phosphodiesterase inhibitor. Inhibitors of prostacyclin synthesis increase metastasis. Prostacyclin and agents that may increase endogenous prostacyclin production or prolong its activity are suggested as new antimetastatic agents.
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PMID:Prostacyclin: a potent antimetastatic agent. 701 12

The ability of tumor cells to metastasize may be related to their ability to promote aggregation of host platelets. The use of inhibitors of cysteine proteinases resulted in parallel inhibition of B16 amelanotic melanoma-induced platelet aggregation and of a cathepsin B activity. The antimetastatic agent prostacyclin inhibited platelet aggregation induced by the tumor cells and by papain, a cathepsin B-mimicking agent.
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PMID:Tumor cell-platelet aggregation: induced by cathepsin B-like proteinase and inhibited by prostacyclin. 704 53

Cicaprost, a stable prostacyclin analogue, has been shown to be anti-metastatically active in a series of metastasizing rodent tumors. Start of treatment with cicaprost immediately before tumor implantation was a characteristic feature of our previous investigations. We have reported that in rats bearing mammary-fat-pad-implanted SMT2A mammary carcinoma, cicaprost treatment starting before tumor implantation led to a strong decrease in the number of lung metastases. In order to determine the effect on occult tumor metastasis, the present study examined the effect of starting treatment when tumor metastasis is already present. Cicaprost in daily oral doses of 0.1 mg/kg given from day 10 to day 32 reduced the number of lung metastases by about 75% compared with the control, whereas surgical removal of palpable primary tumors on day 5 or day 10 failed to influence lung metastasis. Using different treatment schedules, a pronounced reduction of the number of lung metastases was achieved by administration of cicaprost until the end of the experiment (from day 5 to day 35), whereas short-term treatments (from day 5 to day 15 or to day 25) were without significant effect. In rats whose SMT2A tumors were surgically removed 10 days after tumor implantation, there was a strong decrease of lung metastases by cicaprost given from day 20 to day 36. In addition to its inhibitory potential in animals with advanced tumor disease, cicaprost showed anti-metastatic action when used in peri-operative treatment of animals whose primary tumors had been removed. In conclusion, the present results demonstrate that cicaprost exhibits strong anti-metastatic activity in the SMT2A rat mammary-carcinoma model with treatment started when occult tumor metastases are already present. Results also indicate that direct effects on tumor cells may contribute to the anti-metastatic action of cicaprost in spontaneously metastasizing tumors.
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PMID:Rodent model of systemic mammary tumor disease by surgical removal of the spontaneously metastasizing SMT2A mammary carcinoma: inhibitory effect of the stable prostacyclin analogue cicaprost on occult metastasis. 762 97

More than a decade ago, prostacyclin, a dienoic bicyclic eicosanoid derived from the metabolism of arachidnoic acid, was found to possess potent inhibitory effects on tumor cell metastasis. Thereafter, several laboratories demonstrated the metastasis-suppressive activity of prostacyclin in a wide spectrum of tumor types. Due to the short half-life of prostacyclin, researchers have focused on looking for stable prostacyclin analogues which have extended half lives and increased bioavailabilities. Cicaprost, among other prostacyclin analogues tested, has been demonstrated, like prostacyclin, to effectively inhibit metastasis in several different animal models (i.e., both experimental and spontaneous metastasis models). Prostacyclin as well as cicaprost prevent not only hematogenous, but also lymphatic metastasis. Furthermore, these compounds also inhibit the growth of established micrometastases after removal of the primary tumors. Mechanistic studies revealed that the antimetastatic effects of prostacyclin and its analogues are more related to their interference with tumor cell-host interactions (such as tumor cell induced platelet aggregation, tumor cell adhesion to endothelial cells and subendothelial matrix, tumor cell induced endothelial cell retraction, etc.) than their direct inhibition of the growth of primary tumors. The potent and widespread metastasis-retarding effects of prostacyclin and its stable analogues in animal tumor models warrant their clinical trial in treating human cancer patients and preventing metastasis.
Cancer Metastasis Rev 1994 Dec
PMID:Prostacyclin and its analogues: antimetastatic effects and mechanisms of action. 771 96

Metastatic tumor spread is regarded as the highest degree of malignancy of tumors and generally determines the prognosis. Before clinically detectable metastases are evident in distant organs, tumor cells interact with cellular and non-cellular components of the host as they complete the multistep process referred to as the metastatic cascade. Many investigational drugs acting at different levels of the metastatic process were tested for beneficial effects on metastasis. Because of the influence of prostaglandins on host components essential for tumor metastasis, this group of a compounds was tested in model of tumor growth and metastasis. Prostaglandins of the E, D and J series inhibit growth of variety of tumor cells and cause a reduction of primary tumor growth in vivo. The antiproliferative action of prostaglandins of the E series seems to be related to an induction of differentiation, whereas prostaglandins of the D and J series mediate growth inhibition by a blockade of the cell cycle and an inhibition of RNA and DNA synthesis. There is no conclusive evidence that prostaglandins of the E, D and J series may specifically interfere with mechanisms of tumor metastasis. In contrast to the prostaglandins of the E, D and J series, prostacyclin has been shown to inhibit several processes involved in tumor metastasis, but without exerting a direct cytotoxic effect on tumor cells. Our own studies have shown that Cicaprost, a stable prostacyclin analogue, prevents metastasis if given continuously from the day of tumor implantation, and is also effective in reducing metastasis if treatment is begun following surgical removal of the primary tumor, when micrometastases are already present.
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PMID:[Prostaglandins and prostaglandin analogs: experimental studies on their effect of tumor metastasis]. 777 16

Prostacyclin and its stable analogues have been shown to interfere specifically with certain steps of the metastatic cascade. The antimetastatic activity of the stable prostacyclin analogue Cicaprost (Schering AG) on haematogenous metastasis in a series of tumours in rats and mice has been well established. In order to test the effect of Cicaprost on lymphogenous metastasis we chose the metastatic cell clone MTLn3 derived from the 13762NF rat mammary carcinoma. The effect of Cicaprost on prevention of lung metastasis, lymph node metastasis and primary tumour growth was investigated. Cicaprost given in daily doses of 0.01, 0.03 and 0.1 mg/kg orally, reduced the number of lung metastases in a dose-dependent manner. Whereas the median number of lung metastases in the controls was greater than 1000, Cicaprost at a dose of 0.1 mg/kg reduced the number of lung metastases to between 11 and 100. The weight of the ipsilateral axillary lymph nodes was diminished by Cicaprost to 30-50% of controls. Moreover, metastasis to the contralateral axillary lymph node was completely inhibited by Cicaprost at all three doses tested. Cicaprost did not influence the growth rate of the MTLn3 cell clone implanted into the mammary fat pad or the weight of the primary tumour at the end of treatment. In conclusion, in addition to its dose-dependent effect on haematogenous metastasis, Cicaprost strongly inhibits lymph node metastasis.
Clin Exp Metastasis 1994 Jan
PMID:The stable prostacyclin analogue Cicaprost inhibits metastasis to lungs and lymph nodes in the 13762NF MTLn3 rat mammary carcinoma. 828 16

Prostacyclins have long been shown to have anti-metastatic activity. One hypothesis is their modulation of cell adhesion molecule (CAM) expression by target organ endothelial cells. We have postulated that prostacyclin, its analogs, and mechanistic mimics decrease colon carcinoma adhesion to cytokine-stimulated endothelial cells by blocking endothelial expression of the adhesion molecule E-selectin, but not the vascular cell adhesion molecule-1 (VCAM-1). Cultured human microvascular endothelial cells (HDMEC) were pre-incubated with prostacyclin (PGI2), dibutyrl-cAMP (dbcAMP), forskolin (FOR), and/or iso-methylbutylxanthine (IBMX) for 15 min, then co-incubated with the cytokine tumor necrosis factor (TNF) for 4 h. HDMEC surface expression of E-selectin and VCAM-1 was evaluated by flow cytometry and ELISA. Adherence of 51Cr-labeled colon carcinoma cells to HDMEC monolayers was then determined. In parallel assays, HDMECs were incubated with anti-E-selectin and anti-VCAM-1 monoclonal antibody (1:100) prior to the addition of tumor cells. Prostacyclins, its analogs, and mimics significantly reduced E-selectin expression by HDMEC, while the reduction of VCAM-1 expression was much less pronounced. Prostacyclins also significantly decreased colon carcinoma adherence to stimulated HDMECs. The inhibition of E-selectin expression, but not VCAM-1 expression, corresponded to the reduction of tumor cell adherence. Prostacyclin's effects on tumor adhesion were nullified by pre-incubation with E-selectin antibody. The inhibition of colon carcinoma adherence to cytokine-stimulated endothelial cells treated with prostacyclin, its analogs, and mimics appears to result from blocking endothelial E-selectin, but not VCAM-1, expression. These data support the hypothesis that prostacyclins may exert their anti-metastatic effect, in part, by inhibiting CAM-mediated adherence of colon carcinoma to endothelial cells in metastatic target organs.
Clin Exp Metastasis 1996 May
PMID:Anti-metastatic prostacyclins inhibit the adhesion of colon carcinoma to endothelial cells by blocking E-selectin expression. 867 77


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