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)

In a murine pulmonary metastases model, interleukin-2 (IL-2), a lymphokine capable of expanding all classes of T lymphocytes, synergizes with interferon-alpha (IFN-alpha) to reduce established metastases and prolong survival. We tested whether indomethacin (INDO), which inhibits synthesis of prostaglandin E2 (a potent immunosuppressor), could further augment the antitumor efficacy of these lymphokines. Age-matched C57BL/6 mice bearing pulmonary micrometastases of a weakly immunogenic fibrosarcoma MCA-106 were treated intraperitoneally for 6 consecutive days, starting on day 3 with (1) saline solution, (2) IL-2 (50,000 units twice a day), (3) IFN-alpha A/D (50,000 units per day), and (4) IL-2 and IFN-alpha A/D. Half of each treatment group was given plain water and the rest INDO-treated (14 micrograms/cc) drinking water throughout the duration of the experiment. Pulmonary metastases were enumerated on day 21. IFN or INDO alone had little effect, whereas IL-2 reduced metastases and prolonged survival. All combination treatments, including INDO/IFN, decreased metastases and prolonged survival except INDO/IL-2/IFN in which several early deaths negated any significant survival prolongation. Early mortality (less than 21 days) was seen with IFN/INDO (8.3%), IL-2/IFN (7.7%), and IL-2/IFN/INDO (8.3%) indicating toxicity of these treatments. Spontaneous proliferation of splenocytes from non-tumor-bearing mice treated for 5 days showed that INDO combined with IL-2 or IFN enhanced proliferation measured 3 days after cessation or treatments. A striking reduction in T-cell marker (Thy 1.2+) in groups treated with IL-2/IFN, INDO/IL-2, INDO/IFN, and INDO/IL-2/IFN 3 days after cessation of IL-2 and IFN suggests that a non-T-cell is amplified when INDO is combined with IL-2 or IFN. These results show that INDO can enhance efficacy of IL-2 or IL-2/IFN. Furthermore, INDO/IFN offers an equi-efficacious, albeit similarly toxic, alternative to IL-2 treatment of tumors and may be useful clinically.
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PMID:Indomethacin-enhanced immunotherapy of pulmonary metastases using IL-2 and IFN-alpha. 278 16

The influence of combination of local hyperthermia and radiation on tumor growth and metastases was studied using Lewis lung carcinoma. Tumors growing intramuscularly in the right hind legs of C57BL/6 mice were irradiated at 10 Gy of radiation dose and immersed in a water bath. Time and number of development of metastases were determined according to size and number of lung colonies at 19 days after tumor implantation. Local hyperthermia at 42.8, 43.3 or 43.5 degrees C for 30 min immediately after or before irradiation enhanced the growth delay of tumor with irradiation or with hyperthermia alone. Development of metastases several days after heating was also inhibited by the combination of heating and irradiation. These effects were diminished with hyperthermia applied 3 hr or more after irradiation. Promotion of metastases around the time of heating by severe hyperthermia with above 43.3 degrees C alone was not inhibited by combination with radiation, regardless of their sequence. Radiation had no effect on the number of metastases developed by the heating. However, irradiation 48 hr or more before severe heating reduced the number of metastases developed by the heating.
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PMID:[Influence of local hyperthermia combined with radiation on tumor growth and lung metastases of transplantable Lewis lung carcinoma growing in hind legs]. 279 49

Adult sarcoma-bearing mice were used to demonstrate whether hypoglycemia was the immediate cause of death in experimental animals with rapidly growing tumors without metastases. This kind of tumor model is representative of the majority of animal models used in experimental cancer research. Tumor-bearing animals died with severe hypoglycemia under all experimental conditions, while pair-killed controls were normoglycemic. Anorexia prevented tumor-bearing animals from attenuating the hypoglycemia by drinking glucose-containing water while completely starved control animals survived more than 14 days with glucose-containing water as the only energy source. Adrenalectomy shortened survival in tumor-bearing animals, but survival of adrenalectomized tumor-bearing animals could be normalized by daily injections of pharmacologic doses of hydrocortisone (25 mg/25 g body wt/day) but not by physiologic replacement (20 micrograms/25 g body wt/day). Injections of pharmacologic doses of hydrocortisone did not influence on survival or body composition in tumor-bearing animals with intact adrenals. Glucagon was without effect on either survival, tumor growth or body composition. Based on the results in this study and in our previous reports we conclude that hypoglycemia is the cause of death in the majority of murine tumor models. This hypoglycemic theory is important, since any treatment modality in animal experiments that influences glucose metabolism in the host may indirectly change tumor growth and may thus be misinterpreted as a direct tumor effect.
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PMID:The cause of death in non-metastasizing sarcoma-bearing mice. A study with relevance for tumor treatment experiments in mice. 280 52

Fluid and electrolyte homeostasis is impaired in patients suffering from hypothyroidism and myxedema because myxedema induces retention of salt and water. We have measured plasma levels of human atrial natriuretic peptide (hANP) in 8 female patients who had been totally thyroidectomized because of thyroid carcinoma. Estimations of the hormone were done 4 weeks after diagnostic withdrawal (searching for iodine retaining metastases) and after 2 weeks and 4 weeks of reinitiation of thyroid suppressive therapy by L-thyroxine. hANP levels, although within the normal range (10-80 ng/l) throughout the study, were positively linked to the amount of pericardial effusion (determined by echocardiography), which was highest initially and decreased or vanished with duration of L-thyroxine therapy. Additionally, a positive correlation between thyroid hormone levels and hANP was obtained when the counteracting effect of pericardial effusion was allowed for by partial correlation analysis. Our findings might facilitate explanation of mild polyuria in hyperthyroidism and impaired water excretion in hypothyroidism.
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PMID:Thyroid hormones and pericardial effusion may influence plasma levels of atrial natriuretic peptide (ANP) in humans. 294 72

Mesenteric panniculitis is an inflammatory condition of mesenteric fat which may result in peritoneal space occupying lesions. Only two previously reported cases in the English literature have been evaluated by computed tomography (CT). We present 2 additional cases and emphasize that CT patterns are not specific, but suggest the diagnosis in the presence of a well-defined fibrous wall circumscribing a fatty mass containing regions with attenuation near that of water. Lymphoma and mesenteric metastases should be considered the most frequent radiologic, clinical and surgical differential diagnosis.
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PMID:Mesenteric panniculitis. 296 8

The quantity of water, lipid and some metals was measured in autopsy specimens of 8 normal livers, 9 livers with fatty change, and in 12 livers with metastases of various origins. These parameters contribute to the CT number measured in the liver. Water played a major role in demonstration of liver metastases as a low-density area on CT. Other contributory factors include iron, magnesium and zinc. Lipid and calcium had no influence in this respect. Heavy accumulation of calcium in a metastatic lesion gives a high-density area on CT. However, even when a metastatic lesion was perceived on CT as a low-density area, the calcium content of the lesion was not always lower than that of the non-tumour region.
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PMID:Distribution of water, fat, and metals in normal liver and in liver metastases influencing attenuation on computed tomography. 296 41

Proton MR relaxation times T1 and T2 were determined in vitro in 136 small specimens of astrocytomas grades I-IV, of oligodendrogliomas, metastases of adenocarcinomas, meningiomas and acoustic neuromas. In addition, 7 samples of peritumoural white matter were analysed. The analysed specimens were studied microscopically in their entirety regarding tumour type and occurrence of necrosis and non-tumour tissue admixture, such as fibrosis and haemorrhage. Most of the gliomas had longer relaxation times than normal white matter and T2 was significantly longer than in the other three tumour groups. The metastases had longer T1 than normal white matter, while T2 varied. The astrocytomas tended to show shorter relaxation times with increasing degree of malignancy, and shortening of T1 and T2 correlating with the proportion of tissue necrosis. Similarly, the metastases with tissue necrosis had shorter T1 and T2 than non-necrotic samples. The meningiomas had T1 values comparable with normal cortex, while the T2 values varied. Tumours containing a large proportion of fibrous tissue had shorter relaxation times than the others. Acoustic neuromas had only slightly longer T1 than normal white matter, while T2 was not prolonged. Both T1 and T2 were significantly shorter than in all other tumours studied. Peritumoural white matter had prolonged relaxation times compared with normal white matter, correlating to increased water content. These in vitro differences regarding relaxation times in various types of tumours of the central nervous system, dependent on various types of tissue alterations, should be of interest for the interpretation of in vivo images.
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PMID:Tumours of the central nervous system. Proton magnetic resonance relaxation times T1 and T2 and histopathologic correlates. 302 46

Thirty-six deep hepatic lesions of localized photocoagulation were induced in 11 pigs by means of a neodymium-YAG laser. Laser applications of 80 W/10 sec (10.190 W/cm2) were transmitted through a handpiece coupled to a water-cooling circulation system to protect the quartz fiber and positioned through an echo-guided trocar. During irradiation, temperature was sufficient for vaporization up to 5 mm from the laser source and high enough for tumor cell kill at a 10-mm distance (54 degrees C/60 sec). Intraoperative ultrasound visualized increasing photocoagulation (12-18 mm), and further controls demonstrated an echo-free core of vaporization progressively covered by increasing fibrosis, well demarcated from normal parenchyma. Microscopy revealed central coagulative necrosis marginated from the third day by a growing fibrosis. By day 20 immunoblasts and mast cells were in profusion in the lesion border, and by day 120 a fibrotic network had invaded the scar and confirmed healing free of complication. This technique is proposed for deep vaporization of disseminated hepatic metastases.
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PMID:Deep localized neodymium (Nd)-YAG laser photocoagulation in liver using a new water cooled and echoguided handpiece. 306 50

The immunosuppressive effect of a water-soluble nitrosourea derivative, 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), was evaluated in terms of the cytotoxicity of spleen lymphocytes, and the restoring effect of lymphokine-activated killer (LAK) cells and/or human recombinant interleukin-2 (rIL-2) on the cytotoxicities of spleen lymphocytes was examined in ACNU-treated C57BL/6 mice. In addition, we tested whether the administration of LAK cells and/or rIL-2 could reduce the increased numbers of pulmonary metastases in ACNU-treated mice. The maximum effective dose of ACNU suppressed the cytotoxicity of spleen lymphocytes and pretreatment with ACNU enhanced the induction of artificial pulmonary metastases. The administration of LAK cells and/or human rIL-2 restored the cytotoxicity of spleen lymphocytes against YAC-1 and syngeneic B-16 melanoma cells in ACNU-treated mice, and these treatments partially suppressed the increased numbers of artificial pulmonary metastases of B-16 melanoma cells in ACNU-treated mice. These results are extremely important in providing a rationale for the introduction of adoptive immunotherapy using LAK cells and rIL-2 in patients with advanced cancer who are being treated with anticancer agent(s).
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PMID:Reduction of pulmonary metastases of B16 melanoma by human recombinant interleukin 2 and lymphokine-activated killer cells in immunosuppressed C57BL/6 mice receiving anticancer agent. 308 80

Increased sialylation and branching of asparagine-linked oligosaccharides have recently been associated with both neoplastic transformation and the metastatic phenotype. Swainsonine, an inhibitor of Golgi alpha-mannosidase II blocks the synthesis of sialylated tri- and tetraantennary asparagine-linked oligosaccharides and results in the expression of hybrid-type oligosaccharides at the cell surface. Both the lymphoid tumor line MDAY-D2 and B16F10 melanoma cells were less metastatic when grown in swainsonine (0.3 micrograms/ml) for 48 h prior to injection of the cells into the lateral tail veins of mice. The addition of swainsonine (2.5 micrograms/ml) to the drinking water of the mice further reduced the incidence of lung colonization by B16F10 melanoma cells. MDAY-D2 tumors removed from mice on swainsonine-supplemented drinking water showed a loss of leukoagglutinin-binding complex-type oligosaccharides similar to that of tumor cells cultured in medium containing swainsonine. The growth rate of s.c. MDAY-D2 tumors was not reduced by the addition of swainsonine to the drinking water of the host; however, when mice were given two i.p. injections of the interferon-inducing agent polyinosinic:polycytidylic acid in addition to swainsonine, the primary tumor grew at a reduced rate compared to either treatment alone. Swainsonine alone did not inhibit tumor cell growth in vitro; however, the drug enhanced the antiproliferative effect of interferon. The survival time of mice bearing established MDAY-D2 metastases was extended by treating the animals with swainsonine and polyinosinic:polycytidylic acid; however, the number of long-term survival was unchanged. Swainsonine-treated tumor cells appeared to be compromised in two ways: reduced organ colonization potential; and drug-treated MDAY-D2 cells were more sensitive to the antiproliferative effects of interferon in vitro and in vivo.
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PMID:Effects of swainsonine and polyinosinic:polycytidylic acid on murine tumor cell growth and metastasis. 309 60


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