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)

Patients with metastatic cancer have a permanent shortening of platelet survival and increased platelet consumption. Acetylsalicylic acid or dipyridamole in doses known to inhibit platelet aggregation, had no effect on platelet consumption.
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PMID:Platelet turnover in metastatic cancer and the effect of platelet aggregation inhibitors. 13 24

The characteristics of bone pain in metastatic cancer of the prostate were studied in 23 patients. The pain may be continuous or intermittent, show diurnal variations, and be migratory. The effects of activity, rest, and alcohol vary in different individuals. Relief of bone pain by analgesic medications is unsatisfactory. Aspirin-containing compounds are often more effective than narcotics for pain relief. The effects of external beam irradiation for palliation of pain are unpredictable.
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PMID:Bone pain in metastatic cancer of prostate. 43 19

The major cause of failure in the treatment of patients with solid malignancies is failure to prevent or control the spread of metastases. The metastatic process is a series of interrelated steps that must be accomplished before distant tumour foci can be established. Tumour cell motility is a complex process, which is involved in many of these steps. The mechanisms by which motility is stimulated and physically generated are complex and as yet poorly understood. Viewing the cell as a chemomechanical engine that relies on a tension based system for movement allows us to design chemotherapeutic strategies to inhibit tumour cell motility directly. Chemotherapeutic agents that block stimulation, interfere with cell-ECM interactions and interfere with cytoskeletal mechanics are already being tested. Further studies will be needed to define their efficacy.
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PMID:Cell motility as a chemotherapeutic target. 168 57

In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine.
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PMID:High-dose cisplatin with dacarbazine and tamoxifen in the treatment of metastatic melanoma. 164 25

For suppression of primary tumor growth and metastatic spread, aspirin and theophylline, either alone or combined, were given daily to inbred female BN rats after sc implantation of a syngeneic nonimmunogenic tumor. Treatment with 200 mg aspirin/kg (body wt) resulted in a statistically significant regression of tumor growth as well as of the number of metastases in the lungs. Aspirin given in a lower dose (20 mg/kg) did not show significant difference from the vehicle group. Theophylline (75 mg/kg) significantly increased primary tumor growth as well as lung metastases. Inhibition of in vitro platelet aggregation, determined in whole blood taken from non-tumor-bearing animals treated with the same therapeutic regimen, was most pronounced in those groups in which tumor growth and spread were significantly retarded. However, this positive correlation between inhibition of tumor spread and platelet aggregation was not associated with a favorable balance of prostacyclin and thromboxane A2 in these animals.
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PMID:Reductive effect of aspirin treatment on primary tumor growth and metastasis of implanted fibrosarcoma in rats. 351 10

Monocytes are thought to play a role in host resistance to tumor cell growth in animals and humans. In addition, platelets are known to be involved in tumor metastases. To investigate the interaction of these two cell types and their effect on tumor cells, human monocytes and platelets were examined using an in vitro monocyte-tumor cell cytotoxicity assay. Monocytes alone resulted in 32% +/- 1.5 (mean +/- SEM) tumor cell kill. When platelets were added to monocytes in a 1:1 ratio, an increase in cytotoxicity to 61% +/- 3.2 was observed. The cytotoxicity noted when platelets were added to a fixed number of monocytes and tumor cells was dependent on the number of platelets added. A decrease in cytotoxicity from 32% +/- 1.5 to 12% +/- 2.3 was observed when contaminating platelets were removed from monocyte preparations. Platelets added to tumor cells in the absence of any monocytes were also toxic, resulting in a maximum kill of 95% at a 4:1 platelet/tumor cell ratio. Secreted products of freshly isolated platelets may be responsible for much of the observed cytotoxicity, since supernatants from the platelets were toxic for tumor cells. Platelets pretreated with a cyclooxygenase inhibitor (ASA) or a lipoxygenase inhibitor had decreased cytotoxicity compared with untreated platelets. Our results indicate that products of platelet arachidonate metabolism are toxic for tumor cell lines. They also suggest that the role of the platelet must be considered when studying monocyte-tumor cell cytotoxicity.
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PMID:Human platelets exert cytotoxic effects on tumor cells. 392 50

We have examined the effects on platelet function of two sublines (M4 and M9) derived from spontaneous lung nodules of a benzopyrene-induced murine fibrosarcoma (m FS6). The subline M4 was more metastatic and the subline M9 less metastatic than the primary tumour. Only the more malignant cells were able to induce irreversible aggregation of human platelets; this effect was concentration-dependent and was associated with the release of serotonin by platelets. Both aggregation and release were inhibited by preincubation of platelets with ASA, not by preincubation of the cells. The supernatants of cell suspensions had no aggregating activity. However, the neoplastic cells in culture media released an activity directly stimulating platelet aggregation and potentiating the platelet response to ADP; again, this activity was higher for the more malignant cells and the effects were inhibited by preincubation of platelets with ASA. These results suggest a role for platelets in the development of tumour metastases.
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PMID:Interactions between neoplastic cells with different metastasizing capacity and platelet function. 668 86

Adenocarcinoma of the appendix is a rare entity with a reported incidence of .03 to .08 per cent. A review of all appendectomies performed at St. Joseph Mercy Hospital (a private community hospital) between 1963 and 1979 was undertaken to assess the efficacy of preoperative diagnosis. Six adenocarcinomas were found, consisting of five male patients and one female patient with a mean age of 65 years. Symptoms were present for 24 hours or greater in all cases. A preoperative diagnosis was not made in any patient. Three patients later required a definitive therapeutic procedure, and two patients died from metastatic disease during their initial hospitalization. The literature was reviewed to evaluate methods of preoperative and intraoperative diagnosis of appendical adenocarcinoma. A suspicion of carcinoma of the appendix should be entertained for patients over the age of 50 years who present with signs and symptoms of appendicitis for greater than 24 hours. A barium enema performed preoperatively and especially a frozen section at the time of surgery of any suspicious appendiceal lesions may improve the diagnostic accuracy and survival of patients with this disease entity. If preoperative or intraoperative diagnosis is made, the patient can be better prepared and definitive surgical therapy carried out. This avoids delay in treatment and a second operative procedure.
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PMID:Primary adenocarcinoma of the appendix. Can preoperative or intraoperative diagnosis be made? 684 61

Sixty-six patients with Duke's B2 or C colon or rectal cancer were randomized for treatment with aspirin (ASA), 600 mg, p.o., twice daily x 2 years or placebo (P). Compliance was checked in both groups by random measurement of blood salicylate levels. Fifty-seven patients are currently evaluable. No difference in disease-free (p = .66) or overall survival (p = .90) is present between ASA and P groups. The time at which ASA therapy is started (within 2 or within 4 weeks) following surgery does not affect these results. Aspirin at conventional dosage is ineffective in preventing the appearance of metastases in patients with colo-rectal cancer.
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PMID:Adjuvant antiplatelet therapy with aspirin in colo-rectal cancer. 696 32

The influence on transpulmonary passage by an inhibitor of platelet aggregation, aspirin, and/or anabolic steroid, (Nandrolone decanoate), was investigated in syngeneic CBA mice. An increase of extrapulmonary metastases was used as a measure of increased redistribution of tumor cells from lungs to other organs. Aspirin alone did not reduce metastasis formation in lungs and did not significantly increase transpulmonary passage of tumor cells. The anabolic steroid increased the metastasis crop only in the lungs. However, treatment with the two compounds together increased the metastases in lungs and extrapulmonary organs. The results disclosed that in this system inhibition of platelet aggregation did not reduce metastasis formation but in combination with another drug, an anabolic steroid, it increased the number of experimental metastases.
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PMID:Influence of aspirin and/or anabolic steroid (nandrolone decanoate) on experimental metastasis formation. 734 91


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