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)

Mobilization of the capillary endothelium is one of the first events observed during angiogenesis, and the study of conditions that control or influence the mobilization of the endothelium in vitro has been assumed to offer information relevant to the understanding of angiogenesis in vivo. In vitro mobilization of the bovine capillary endothelium was substantially enhanced by addition of gangliosides to the culture medium. Optimal mobilization was obtained when the endothelium incorporated the gangliosides first and was then seeded on fibronectin anchored to collagen type I. Preincubation of the capillary endothelium with gangliosides, trisialoganglioside in particular, doubled the amount of fibronectin bound to the cells and enhanced the migration about 5-fold. 'Blockage' of ganglioside binding with cholera toxin or gamma-interferon substantially reduced migration. Rabbit corneas, treated in vivo with a variety of angiogenesis effectors to induce neovascularization, consistently showed an increase in sialic acid content just prior to the time the tissue would be penetrated by the capillaries. This finding was interpreted to indicate that an increment of the ganglioside content of the capillary endothelial cell membranes may play a determinant role in the mobilization of the capillary endothelium in vivo as shown here to take place in vitro. Since the formation of a tumor from a micrometastasis requires formation of new capillaries and highly metastasizing tumors very frequently have high levels of sialic acid on the cell surface, it is hypothesized that production and shedding of gangliosides from the surface of neoplastic cells may be a factor in promoting angiogenesis and metastatic growth.
Invasion Metastasis 1986
PMID:Interaction of gangliosides with fibronectin in the mobilization of capillary endothelium. Possible influence on the growth of metastasis. 242 14

The heptanoyl tripeptide, FK-565 is a biological response modifier with potent therapeutic properties for the treatment of experimental and spontaneous metastases. Doses of FK-565 greater than 5 mg/kg are required for in vivo augmentation of natural killer cells, macrophages, and for therapeutic activity, presumably because FK-565 is a peptide small molecular mass which is rapidly degraded and excreted. Optimal therapeutic activity is observed at approximately 25-50 mg/kg FK-565, administered i.v. three times per week for 4 weeks. In addition to its therapeutic properties, which were consistently greater than the positive control at optimal doses, FK-565 had significant immunoaugmentary properties for natural killer cells, macrophages, and T cells both in vitro and in vivo, suggesting that its therapeutic activity is due to immune augmentation.
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PMID:Immunomodulatory and therapeutic properties of FK-565 in mice. 252 14

Three elderly females are reported who presented with high-grade lymphoma of the thyroid and subsequently were found to have extensive gastrointestinal (GI) lymphoma that dominated their clinical courses. One of the patients remains free of disease 30+ months after extensive resection of involved bowel and combination chemotherapy. Two died from disseminated lymphoma. Optimal delivery of therapy in both of the latter patients was impeded by massive gastrointestinal hemorrhage. A review of previously reported cases of thyroid lymphoma, plus those described here, suggests a predilection for these tumors to involve the GI tract independent of other organ metastases.
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PMID:Thyroid lymphoma with gastrointestinal involvement: report of three cases. 300 77

These studies were designed to examine the immunodulatory and immunotherapeutic properties of recombinant murine interferon gamma (rM IFN-gamma) and recombinant human tumor necrosis factor (rH TNF). We report that rM IFN-gamma activated murine natural killer cells and macrophages in a dose-dependent manner in vivo. The rM IFN-gamma, which demonstrated a bell-shaped therapeutic response curve, must be administered at specific doses and schedules to produce optimal therapeutic activity. Optimal activity was observed after i.v. administration of 50,000 U/animal rM IFN-gamma three times per week. In contrast, rH TNF produced its major therapeutic activity in the treatment of metastatic disease after i.v. but not i.p. administration. The therapeutic effects of rH TNF were as great in these in vivo systems as those of rM IFN-gamma. Furthermore, rH TNF had additive therapeutic activity when administered in conjunction with suboptimal doses of rM IFN-gamma. Unlike rM IFN-gamma, rH TNF did not activate natural killer cells in vivo or in vitro but did augment in vivo and in vitro macrophage tumoricidal activity. It also had synergistic cytostatic properties with rM IFN-gamma for some murine tumor cell lines in vitro. High levels of rH TNF were readily detected in the serum with a half-life of approximately 30 min after i.v. administration. In contrast, only minimal serum TNF activity occurred after i.p. administration, suggesting that i.v. administration may more efficiently facilitate systemic therapeutic activity. In summary, rH TNF and rM IFN-gamma have therapeutic activity for metastatic disease as individual agents and additive therapeutic activity when used in combination. Furthermore, it appears that in addition to therapeutic potential as cytostatic agents, the immunomodulatory properties of rH TNF have a role in its therapeutic properties.
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PMID:Immunomodulatory and immunotherapeutic properties of recombinant gamma-interferon and recombinant tumor necrosis factor in mice. 310 65

The treatment of lymphatic metastasis depends on an understanding of its basic biology. We are still uncertain as to how human cancer cells enter lymphatic vessels and as to what reactions if any in the draining lymph node inhibit metastasis. We are uncertain as to whether lymphatic metastasis is an indicator or a governor of rapid dissemination, and poor prognosis. We are uncertain as to whether it is worth attempting to treat lymphatic metastases by means supplementary to those used in treating systemic tumour dissemination. It may be possible to obtain local cure of a local lesion by local lymphatic therapy and to concentrate therapy locally by intralymphatic infusion of a chemotherapeutic agent or encapsulation in liposomes. This is at best accessory to obtaining systemic cure of systemically disseminated neoplasm. Optimal results could be expected from appropriate combinations of local and systemic immunotherapy, chemotherapy and radiotherapy, after appropriate surgical reduction in tumour bulk.
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PMID:Lymphatic metastasis and its treatment. 329 22

Nutritional antioxidants support prostacyclin synthesis by preventing lipid hydroperoxide-mediated inhibition of prostacyclin synthetase. Recent preliminary clinical studies indicate that supplementary antioxidants exert antithrombotic effects in vivo that are most likely attributable to enhanced prostacyclin production. Optimal antioxidant nutrition may thus have preventive and therapeutic value for disorders in which inappropriate platelet aggregation plays an etiologic role, including MI, stroke, atherogenesis, pre-eclampsia, and the vascular complications of diabetes. In light of evidence that platelet aggregation encourages the implantation of hematogenous tumor metastases, supplemental antioxidants should also impede tumor dissemination--an effect which will be complemented by the immunostimulant actions of these nutrients. By exerting anticarcinogenic, immunostimulant and anti-metastatic effects, nutritional antioxidants should act to inhibit neoplasia at each stage of its development.
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PMID:An antithrombotic role for nutritional antioxidants: implications for tumor metastasis and other pathologies. 352 Feb 53

The purpose of these studies was to determine the optimal conditions and limitations for the eradication of spontaneous melanoma metastases by the systemic administration of liposomes containing MTP-PE. Mice whose primary melanoma had been excised were given i.v. injections of liposomes at various schedules. Optimal treatment was achieved by twice weekly administration for 4 weeks (eight i.v. injections). Bioassays failed to reveal the presence of melanoma cells in lungs of mice surviving to day 250 of the experiment. The success of liposome treatment of metastases diminished when the first i.v. injection of liposomes-MTP-PE commenced on day 10 after surgical excision of the local melanoma, as compared with day 3 or day 7 after surgery. We conclude that the major limitation for macrophage-mediated destruction of metastases is the number of tumor cells in the lesions. Because of this limitation, it is unlikely that the systemic activation of macrophages could be used as a single modality for treatment of advanced metastases.
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PMID:Optimization and limitations of systemic treatment of murine melanoma metastases with liposomes containing muramyl tripeptide phosphatidylethanolamine. 369 58

The authors reviewed their experiences to date with chemosensitivity testing of 629 tumors by human tumor clonogenic assay (HTCA) and of 199 tumors by scintillation assay (SA). HTCA and SA were both performed using a double-layer-soft-agar system with continuous exposure of cells to one concentration of standard anticancer drugs. Overall, 60% of specimens in HTCA and 58% in SA produced significant growth in vitro. HTCA was 52% (13/25) reliable for predicting in vivo sensitivity, and 95% (36/38) reliable for in vivo resistance, whereas SA was 40% (8/20) reliable for in vivo sensitivity and 88% (21/24) for in vivo resistance. The current results indicate that there is no particular difference in the success rate and in the predictive accuracy for in vivo sensitivity and resistance between HTCA and SA. Therefore, it is doubtful whether only clonogenic tumor cells among whole tumor cell populations should be selected in assessing the chemosensitivities of human tumors. In vitro success rates were variable, depending on the tumor histology. In vitro growth of gastric cancer specimens was characteristically lower than that of colon cancer specimens (48% and 60% in HTCA, and 46% and 68% in SA, respectively). (p less than 0.005). Optimal in vitro-in vivo drug concentrations and culture conditions are still being defined. Correlation studies of in vitro-in vivo responses of gastrointestinal cancers suggested that in vitro concentrations of 5-fluorouracil and mitomycin C used in this study were considerably higher than their optimal doses. Tumor cell heterogeneity poses significant problems in the clinical use of chemosensitivity assays. The question arises as to whether a single biopsy specimen is representative of a patient's disease. In this last study, we sought evidence of tumor heterogeneity by comparing chemosensitivity responses between: 1) different portions of a single tumor, 2) a primary and a metastatic biopsy taken from a patient on the same day, and 3) different metastases from a patient taken on the same day. The results demonstrated the presence of considerable heterogeneity of response to chemotherapy among different tumors from the same patient, and even within the same tumor. The reported discrepancies of in vitro and in vivo sensitivity may be due to such therapeutic heterogeneity among tumors.
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PMID:[Results of in vitro chemosensitivity assays: human tumor clonogenic and scintillation assay]. 372 39

The charts of 67 patients treated for epidermoid carcinoma of the surgical anal canal were reviewed. The clinical presentation, type of surgical procedure performed, lymph node status of the pararectal and inguinal nodes, time of recurrence, site of recurrence, and median survival from the date of primary surgery and from the date of recurrence were determined. There were 55 patients (82%) who had a minimum of 5 years' follow-up since initial treatment. Optimal surgical treatment requires an abdominoperineal resection with wide dissection of the ischiorectal fossa and perineum in all patients, as well as an en bloc excision of the posterior vaginal wall in women. Although excision of the posterior vaginal wall improves the disease-free interval, median survival is not altered, compared with the group without vaginectomy. The predominant sites of local recurrence in men are the pelvis and perineum, and in women, the pelvis and posterior vaginal wall. The status of the pararectal lymph nodes from the operative specimen can give accurate information about the relative risk of recurrence. The presence of inguinal lymph node metastases represents a poor prognosis because of a close association with systemic metastases.
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PMID:Epidermoid carcinoma of the anal canal. 394 74

Clinicians frequently perform tests to determine whether patients have liver metastases. Optimal use of a laboratory test requires that the clinician know the test's operating characteristics (its sensitivity and specificity) and have an estimate of the pretest probability that disease is present. We have surveyed studies that examined the value of four biochemical and three imaging tests in establishing a diagnosis of hepatic metastases in patients who underwent an invasive procedure to establish the presence or absence of disease. We have pooled the data from these studies to arrive at values for the sensitivity and specificity of each of these tests, and calculated the predictive values for these tests over a wide range of pretest probabilities of disease. Several examples illustrate how this information may be used clinically. We provide a framework for the optimal interpretation of these commonly ordered tests and indicate the data needed for their complete analysis.
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PMID:Diagnosing liver metastases: a Bayesian analysis. 395 Jun 77


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