Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antimetastatic activity of the prostacyclin analog Iloprost has been examined in mice bearing Lewis lung carcinoma. An inhibition of lung colony formation is observed when 100 or 200 micrograms/kg Iloprost are administered i.v. 1 h before i.v. injection of tumor cells, which is dependent on the size of tumor inoculum. The effects of 200 micrograms/kg Iloprost persist for 24 h, and are of the same magnitude as those obtained with 10 mg/kg prostacyclin, which last only for 30 min. When treatment with Iloprost is followed by surgical removal of primary tumor, spontaneous metastasis formation is reduced, and the survival time of the treated animals is significantly increased over controls treated with surgery only. The antimetastatic effects of Iloprost appear dissociated from drug's effects on the hemostatic system of the host as indicated by the clot retraction assay, performed after in vivo treatment, using ADP or tumor cells as platelet aggregating agents. Iloprost thus appears to reduce spontaneous metastasis formation and intraoperative tumor cell dissemination, with pharmacological properties more favourable to therapeutic use than those of prostacyclin.
Clin Exp Metastasis
PMID:Antimetastatic action of the prostacyclin analog iloprost in the mouse. 247 73

Coagulation system and platelets play an important role in the stage of lodgement of tumor cells. We examined abilities of human and hamster pancreatic cancer cell lines to aggregate platelets in vitro, and investigated the effect of prostaglandin E1, I2, on artificial liver metastases of pancreatic cancer in Syrian golden hamster. Platelet aggregating activities were found in five out of six human pancreatic cancer cell line and thromboplastin likes activity in five cell lines. Diisopropanolnitrosamine induced hamster pancreatic cancer cells (HPK-1) were able to aggregate platelets both in vitro and in vivo and these activities were inhibited by prostaglandin I2. Hamster was inoculated intraportally with 1 X 10(6) HPK-1 cells. After two weeks autopsy of these hamsters revealed multiple metastatic nodules on liver surface. In this model we administered prostaglandin E1, I2 into the portal vein five minutes before cell inoculation. Number of liver surface nodules were significantly decreased to 33.1 + 7.0, 11.0 + 9.6 in hamster given 100g PGE1 PGI2 before cell inoculation, compared with control group of hamsters (62.0 + 6.6 PH9.3, 66.1 + 13.9 PH7.4). But administration of prostaglandin after cell injection was not effective. In all cases none of extrahepatic metastases were noted. Inhibitory action of PGE1 PGI2 on liver metastasis is suspected to be related to inhibition of platelet aggregation.
 ...
PMID:[Inhibitory effect of anti-platelet prostaglandin on liver metastasis of hamster pancreatic cancer]. 250 99

Hemostatic diffusion is mediated in part by platelet activation. Prostacyclin (PGI2) is known to be a powerful inhibitor of the aggregation of human platelets in vitro. In this study exogenous PGI2 was incubated in plasma of patients with bone and soft tissue cancer and its inhibiting activity of platelet aggregation was evaluated. Inhibition was found to be significantly lower and of shorter duration in the plasma of the 10 cancer patients tested as compared to the activity in the plasma of the healthy controls. Mechanisms of decreased prostacyclin activity are discussed in relation to the platelets in tumor cell metastases.
 ...
PMID:[Biologic activity of prostacyclin in patients with malignant tumors of the bones and soft tissues]. 250 50

Prostanoids are substances which are of great regulatory importance for the organism. Recently not only their active participation in the metabolism of malignant tissue is discussed, but also the possibility of their use in the comprehensive treatment of malignant diseases. At present the effect on a reduction of metastases after prostaglandin I2 administration (= prostacycline) as well as of prostaglandin E2 is tested experimentally as they inhibit the capacity of primary tumours to form metastases. The possibility is also considered of using quantitative estimation of some prostanoids for evaluation of the severity of invasion of the organism by a malignant process.
 ...
PMID:[The role of prostanoids in malignant diseases]. 272 Jul 34

To study the production and significance of prostacyclin (PGI2) and thromboxane A2 (TxA2) in breast cancer, tissue fragments of breast cancer (n=23) and mastopathy (n=10) were superfused in vitro and the release of 6-keto-PGF1 alpha (a metabolite of PG12) and TxB2 (a metabolite of TxA2) measured by radioimmunoassay. Breast cancer formed more 6-keto-PGF1 alpha (4.5 +/- 0.9 ng min-1 g-1 of tissue dry weight, mean +/- s.e.) and TxB2 (2.5 +/- 0.6 ng min-1 g-1) (P less than 0.01) than did mastopathic breast (1.4 +/- 0.5 and 0.4 +/- 0.1 ng min-1 g-1, respectively). These productions were similar in steroid receptor positive and negative tumours. Breast cancer metastasized in 15 patients during the follow-up time of 3.7 +/- 0.7 years, but the initial prostanoid productions in these patients were not different from those in nonmetastatic patients. Two patients died from metastases, but their initial mammary production of prostanoids was not profoundly different from those in the survivors. In 8 patients (4 with steroid receptor positive and 4 with negative tumour), the cancer tissue was superfused in the presence or absence of medroxyprogesterone acetate (100-5000 ng ml-1), which is commonly used for treatment of breast cancer. This hormone had no effect on mammary PGI2 and TxA2 production. We thus conclude that the PGI2 and TxA2 productions are increased in mammary cancer but that this may not be of primary significance for metastastic spread.
 ...
PMID:Prostacyclin and thromboxane in breast cancer: relationship between steroid receptor status and medroxyprogesterone acetate. 298 66

Arachidonic acid metabolites can act as tumor promoters and can affect growth and metastases of tumors in three ways: (a) Prostacyclin inhibits and thromboxane facilitates platelet-tumor cell interactions and, thereby, tumor cell invasiveness; (b) the cytoprotective action of prostaglandins contributes to epithelial cell integrity and influences tissue response to tumor-promoting agents; and (c) lipoxygenase products may act as tumor promoters.
 ...
PMID:Arachidonic acid metabolism. 311 36

Antimetastatic effect of a stable prostacyclin analogue (PGI2-TEI8153) in combination use with adriamycin (ADM) was investigated. Meth A cell, which had membrane protein of 18,000 daltons specifically bound to platelets, induced platelet aggregation dose-dependently. This platelet aggregation was totally suppressed by PGI2-TEI8153. PGI2-TEI8153 also suppressed the pulmonary arrest as well as pulmonary metastasis of Meth A cells. Combined use of PGI2-TEI8153 and ADM exerted much less antimetastatic effect than that with PGI2-TEI8153 alone, indicating the counteracting effect of ADM against the PGI2-TEI8153. However, this combination use brought about additive antimetastatic effects with 2-fold reduction of pulmonary nodules compared to that of ADM alone. Consequently, even the anticancer drug itself has a negative influence on metastasis, the combined use of PGI2-TEI8153 with it is promising for the prevention of metastasis.
Invasion Metastasis 1988
PMID:Effect of combined administration of a prostacyclin analogue and adriamycin against the artificial metastasis of Meth A cell. 327 21

To study the production of antiaggregatory prostacyclin (PGI2) and proaggregatory thromboxane (TxA2) by ovarian tumors, we incubated pieces of benign and malignant ovarian tissue in vitro, and measured by radioimmunoassay the release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (a hydration product of PGI2) and thromboxane B2 (TxB2) (a hydration product of TxA2). Healthy ovary (n = 10) produced both 6-keto-PGF1 alpha [mean, 8.9; 95% confidence interval (CI) from 5.4 to 15.2 ng/mg protein/min] and TxB2 (mean, 1.9 ng/mg protein/min; 95% CI from 1.0 to 3.7 ng/mg protein/min). The production of 6-keto-PGF1 alpha (mean, 12.2; 95% CI from 7.7 to 19.3 ng/mg protein/min) and that of TxB2 (mean, 4.8; 95% CI from 2.1 to 11.9 ng/mg protein/min) by benign cystic tumors (n = 12) was normal. Ovarian anaplastic cancer and adenocarcinoma (n = 12) produced 6-keto-PGF1 alpha on average 11.6-fold (95% CI from 5.2 to 26.0) 6-keto-PGF1 alpha and TxB2 on average 30.0-fold (95% CI from 13.5 to 66.7) over production by healthy ovaries, and the ratio of 6-keto-PGF1 alpha to TxB2 shifted to the dominance of TxB2. Similarly ovarian metastases of breast cancer, tubal cancer, and colon cancer produced increasingly 6-keto-PGF1 alpha (mean, 20.7 ng/mg protein/min) and TxB2 (5.1 ng/mg protein/min). The dominance of TxA2 in human ovarian cancer may contribute to the aggressing growth and spreading of this tumor.
 ...
PMID:Increased synthesis of prostacyclin and thromboxane in human ovarian malignancy. 328 48

Circulating prostaglandins, including thromboxane A2 and prostacyclin, have been implicated as possible facilitative agents in the growth and dissemination of squamous cell carcinomas of the head and neck. The purpose of this study was to evaluate the relationship of plasma concentrations of these compounds to tumor stage and the effect of surgical resection on plasma prostaglandin levels. Blood samples were obtained from 40 patients with head and neck cancer. Ten treated patients were clinically disease-free (NED), and 30 patients with active disease were previously untreated at the time of this study. Plasma concentrations of thromboxane A2 and prostacyclin were measured by radioimmunoassay of their stable metabolites thromboxane B2 (TxB) and prostaglandin 6-keto-F1 (PGI). Platelet aggregation was performed with normal donor platelets (PRP) and normal control or patient plasma (PPP). TxB and TxB/PGI ratios were increased in T1N0M0 patients, compared with NED and with T4N0M0 primary lesions versus all other groups. With lymphatic and hematogenous metastases, TxB and TxB/PGI ratios fell to NED levels. ADP-induced platelet aggregation was significantly increased in head and neck cancer patients, compared with normal controls, and with T4N0M0 lesions, compared with NED. There were no significant differences in PGI levels. TxB, PGI, TxB/PGI, and platelet aggregometry did not change significantly with curative surgery. TxB and TxB/PGI interactions are involved in head and neck cancer. Changes in TxB and TxB/PGI may be related to increased platelet aggregation.
 ...
PMID:Plasma thromboxane A2 and prostacyclin concentrations in squamous cell carcinoma of the head and neck. 328 5

Prostacyclin and its synthetic analog carbacyclin were compared as to their abilities to inhibit tumor cell-platelet interactions. Aggregation of rat platelets was induced in vitro by homologous rat Walker 256 carcinosarcoma cells. The extent of cellular interactions was examined ultrastructurally. The ultrastructural data presented here indicate that the tumor cell-platelet interactions began with individual platelets which initiated platelet chain formation in focal association with tumor cell surfaces. By mid-phase aggregation large homotypic platelet aggregates had formed with tumor cells positioned on the external surfaces of the emboli. Tumor cell-platelet interactions became progressively more extensive as tumor cells became enmeshed with growing platelet aggregates. Prostacyclin and carbacyclin inhibited tumor cell platelet interactions in a dose-dependent manner. Carbacyclin inhibition of tumor cell induced platelet aggregation was longer in duration but carbacyclin was 10-fold less effective than was prostacyclin. We report here that prostacyclin and carbacyclin inhibit both aggregation and the ultrastructural changes associated with tumor cell-platelet interactions.
Invasion Metastasis 1987
PMID:Inhibition of tumor cell induced platelet aggregation by prostacyclin and carbacyclin: an ultrastructural study. 329 27


<< Previous 1 2 3 4 5 Next >>