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)

Our earlier studies indicated a role for polyamines (namely, putrescine, spermidine, and spermine) not only in tumor growth but also in tumor metastases. We have observed that administration of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, resulted in significant inhibition of visually detectable pulmonary metastases in mice implanted with Lewis lung carcinoma. The objective of the present study is to investigate the effect of DFMO on other spontaneous and experimental metastatic models and also to determine which step(s) in the tumor metastatic cascade is sensitive to DFMO. The results presented in this study with malignant mouse B16 amelanotic melanoma (B16a) showed a dose-dependent effect of DFMO on the inhibition of both tumor growth and grossly detectable pulmonary metastases. DFMO, when administered as 0.5, 1, and 2% solution in drinking water, resulted in 0, 24.5, and 60% inhibition of tumor growth, respectively, whereas at the same doses an inhibition of 55, 83, and 96% of visible metastases was observed. At treatment levels of 1 and 2% DFMO, 30 and 65% of the animals were free of metastases. DFMO, at 0.5%, did not show any effect on tumor growth, while a significant 55% inhibition of visible pulmonary metastasis was observed, suggesting a specific role for polyamines in tumor metastasis. DFMO treatment also resulted in a significant reduction of putrescine and spermidine levels with a slight increase in spermine concentration in the tumor tissue. DFMO administration did not inhibit the experimental metastases induced as a result of i.v. injection of B16 melanoma (line F10) tumor and Lewis lung carcinoma cells into the tail vein. These results provide preliminary evidence to indicate that tumor cell polyamine depletion by DFMO might affect the first step in the metastatic cascade, intravasation (i.e., prevent the invasion of metastatic tumor cells into lymphatics or blood vessels), although the effect of DFMO on other steps in the metastatic cascade cannot be ruled out.
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PMID:Antimetastatic activity of DL-alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, in mice. 310 31

Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected. Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines. A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice, yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca fractions and monokines might be mediated by activated peritoneal macrophages.
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PMID:Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by these fractions. 311 66

The anti-metastatic effect of two chemotherapeutic agents was analyzed in a murine melanoma model. Difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, was administered as a 2% aqueous solution in the drinking water. A second drug, dacarbazine (DTIC) was administered intravenously in single bolus injections. Each drug produced significant anti-metastatic effects that were manifested by a reduction in the number of pulmonary metastases and in the prolongation of host survival times. Maximal chemotherapy was achieved when both drugs were combined. The specificity, low toxicity, ease of administration, infrequent side effects, and therapeutic effectiveness of DFMO make it an attractive candidate for clinical use in human subjects being treated for uveal melanoma. The effectiveness of DTIC against blood-borne melanoma cells suggests that this drug may prove useful as a prophylactic adjunct in patients undergoing enucleation of a melanoma-containing eye.
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PMID:Suicide enzyme inhibition as a chemotherapeutic strategy for controlling metastases derived from intraocular melanomas. 311 18

At the Finsen Institute, Copenhagen, from 1971 to 1981, 134 patients were treated for lymph node metastases from primary cutaneous malignant melanoma of axial localization (e.g., in the head and neck and trunk), where metastases to regional lymph node groups were the first sign of dissemination. Due to the lack of sufficient clinical data, 27 patients were excluded from the study. Median time from excision of primary tumor to diagnosis of node metastases was 11 months. In 42 of 85 (49%) patients with truncal melanoma, the primary tumor was placed in the lymphatic water-shed areas. Two patients among this group showed bilateral simultaneous metastases to two different node groups. In the remaining 43 patients with truncal tumors located outside water-shed areas, node metastases developed in unexpected groups in seven (16%) patients. Of 22 patients with head and neck tumors, two (9%) patients demonstrated metastases to distant lymph node groups without metastases to the regional node basins.
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PMID:Patterns of the first lymph node metastases in patients with cutaneous malignant melanoma of axial localization. 316 20

In experiments using cultured cells, LS2616 has been shown to decrease growth of primary tumors and pulmonary metastasis of murine melanoma. In the current study, we examine the efficacy of LS2616 for the prophylactic and therapeutic treatment of metastases from ocular and flank inoculations of the highly aggressive in vivo derived B16F10 melanoma in C57BL/6J mice. Experimental animals were treated with 160 mg/kg/day of this drug in drinking water, until they became moribund or died. When mice were pretreated for 7 days and inoculated subcutaneously (sc) or intracamerally (ic) with 10(5) in vivo derived B16F10 tumor cells, the mean number of pulmonary metastases was significantly reduced, and the incidence of pulmonary metastases decreased. In ocular experiments, when pretreatment with drug was combined with enucleation at day 7, the mean number of lung nodules was significantly reduced, the incidence of metastasis to the lung and lymph nodes decreased and survival increased. An apparent cure rate of 31% was observed. Treatment beginning on the day of enucleation (day 7) resulted in a reduction of pulmonary metastases, a decrease in metastasis to the lungs and lymph nodes and no change in survival. LS2616 did not alter tumorigenicity of either sc or ic inoculations. In an in vivo neutralization assay, spleen cells of mice treated for 7 days with LS2616 demonstrated an increase in cytostatic or cytotoxic activity when incubated with B16F10 melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A treatment for metastasis of murine ocular melanoma. 317 Jan 23

The authors report on 14 patients in whom cerebral tissue pressure was recorded after operation for brain tumours. Cerebral tissue pressure was recorded by a 5 French catheter with two microtransducers. The transducers were placed intraoperatively in the wall of the tumour cavity and in a distance of approximately 2.5 cm. Differences between both pressures from 4 to 28 mmHg were observed. They were higher in patients with glioblastomas and meningiomas than in patients with intracranial metastases. In 7 patients proximal tissue pressure was higher than distal. In 4 patients the contrary was observed. Discussing the literature the authors think intrahemispheric changes of brain water content, blood flow, and brain tissue elastance to be responsible for this phenomenon.
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PMID:Intrahemispheric gradients of brain tissue pressure in patients with brain tumours. 317 28

The components of vasogenic oedema associated with brain tumours were investigated in human biopsy material sampled from tumour and peritumoural tissue intraoperatively. Sixty patients with glioblastomas, gliomas, meningiomas and metastases, which had been treated with dexamethasone prior to surgery were employed for tissue measurements of water, electrolyte, haemoglobin, serum protein and dexamethasone concentrations. The quantification of serum proteins was achieved with the method described by Bodsch et al. Accordingly, serum proteins in the brain tissue and the blood were determined with 125J labelled antihuman antibody. Taking into account brain haematocrit and blood-volume, quantitative measurements of the so-called oedema proteins as a measure of tumour oedema were performed. With the exception of metastases positive correlations were obtained between water and both serum proteins and sodium contents in tumours and peritumoural tissue. The serum protein content varied considerably being high in glioblastomas and low in peritumoural tissue surrounding metastases. However water and serum protein contents decreased with increasing dexamethasone concentrations in glioblastomas, while this effect was virtually absent in gliomas and meningiomas. Our results suggest a previously unknown selectivity among tumour types for the reduction of water content and serum proteins in corticosteroid treated oedematous tissue.
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PMID:Glucocorticosteroid treatment of vasogenic oedema. 321 42

Treatment with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) or N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) in the drinking water induces bladder cancer of rats or mice with high incidence. Induced bladder cancers of rats are mostly papillary, non-invasive type, whereas those of mice are non-papillary, invasive type. Histologically, most of BBN-induced bladder cancers are transitional cell carcinoma in both rats and mice. On the other hand, the incidences of squamous cell carcinoma increased in cases of mice, especially in mice treated with EHBN. Metastases and invasions of bladder cancers are more common in mice than in rats. There are strain and species differences in the bladder response to BBN and EHBN. In addition, a putative preneoplastic lesion, papillary or nodular hyperplasia of the epithelium is a good marker for early detection of bladder cancer development.
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PMID:[Animal models of bladder cancer]. 324 66

Previous studies have indicated the efficacy of adoptive immunotherapy utilizing recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in the treatment of advanced neoplastic disease. However, this therapeutic approach is associated with considerable toxicity, primarily due to the systemic administration of rIL-2. The present study was undertaken to determine the efficacy of a newly developed water-soluble glucan, when administered in combination with LAK cells, in the therapy of experimental hepatic metastases. Mice were challenged subcutaneously (1 X 10(4) cells) with reticulum cell sarcoma M5076 on day 0. Therapy was initiated on day 15, when a palpable primary tumor mass and hepatic micrometastases were evident, and continued at 3-day intervals up to day 54. Sarcoma-bearing mice received glucan (250 mg/kg) intravenously, either alone or in combination with LAK cells (1 X 10(7)/mouse). Control mice received 5% (wt/vol) dextrose in water. Glucan-LAK cell therapy significantly suppressed primary tumor growth, inhibited the progression of hepatic metastases and prolonged survival in sarcoma-bearing mice. Splenocytes, incubated with rIL-2 for 72 h, exhibited significant natural killer (NK) cell activity and were cytotoxic to sarcoma cells in vitro. Glucan-LAK cell administration resulted in significant increases in splenic NK cell activity and Kupffer cell-mediated tumoricidal activity. In addition, bone marrow proliferation was enhanced following the co-administration of glucan and LAK cells. Due to its nontoxic nature and immunostimulating properties, soluble glucan may prove to be an attractive biological response modifying agent for utilization in adoptive immunotherapy of advanced neoplastic disease.
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PMID:Soluble glucan and lymphokine-activated killer (LAK) cells in the therapy of experimental hepatic metastases. 328 99

Thirty six hepatic lesions (12-18 mm) of localized hyperthermia are induced in eleven pigs by means of a Nd-YAG laser. Laser shots of 80 W/10 sec. are transmitted through a stereotaxic handpiece coupled to a water cooling circulation protecting the optic fibre. The handpiece placement is performed through an ultrasound-guided trocar. The efficiency of the irradiation is visualized by immediate temperature increasing, by ultrasonographic imaging and by anatomical verifications from operating time to four months. The center of lesion initially occupied by coagulative necrosis is rapidly marginated by a gaining ground fibrosis. At long term a fibrotic network invades the scar and confirms healing free of complications. This ultrasonographically assisted technique is proposed for deep vaporisation of disseminated hepatic metastases.
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PMID:[Deep and localized hyperthermia of the liver induced by stereotaxic Nd-YAG laser irradiation]. 328 62


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