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)

The ruthenium-dimethylsulfoxide complex Na(trans-RuCl4(DMSO)Im] was given i.v. to mice bearing MCa mammary carcinoma and its effects on tumor growth and on healthy host tissues were studied by macroscopic examination of primary tumor growth, by survival time, and by histological analysis using light microscopy and SEM. Either by means of vivo-vivo bioassays or by microscopic examination it appeared that the growth of lung tumors was markedly reduced, whereas the growth of the i.m. primary tumor was much less affected. These effects account for the prolongation of survival time and for the cure rate observed. The favourable effect on survival time was also influenced by the lack of significant cytotoxicity for normal tissues such as lung and kidney epithelia, muscle and liver cells, splenocytes and bone marrow. It thus appears that the selective interaction with tumor cells in the lungs cannot simply be attributed to a selectively higher localization of the compound at this site, nor to a modification of the histological structure of primary tumor. These results highlight the pharmacologic properties of this compound for the control of solid tumor metastases, an effect that was shown to be similarly exerted on advanced tumor metastases.
Clin Exp Metastasis 1994 Mar
PMID:Antimetastatic action and toxicity on healthy tissues of Na[trans-RuCl4(DMSO)Im] in the mouse. 830 32

Gastrin and pancreastatin-like immunoreactivity were determined by radioimmunoassay methods and chromogranin A was determined by enzyme-linked immunoassay in sera from 18 patients with gastrinomas (Zollinger-Ellison syndrome) and in 20 age and sex matched controls. Gastrin serum levels in the gastrinoma patients were in the range 26-80,000 pmol/l, and in the controls 5-31 pmol/l. Chromogranin A serum levels in the gastrinoma group were in the range 6-2,700 ng/ml (mean +/- SEM: 400 +/- 147 ng/ml). The mean value of chromogranin A was significantly higher than in the control group (8 +/- 2 ng/ml, p = 0.008). The serum levels of pancreastatin-like immunoreactivity in the gastrinoma patients were in the range 23-1,994 pg/ml (597 +/- 123 pg/ml). The mean value of pancreastatin-like immunoreactivity in the gastrinoma group was significantly higher than in the control group (104 +/- 25 pg/ml, p = 0.0002). The levels of chromogranin A and pancreastatin-like immunoreactivity were significantly higher in patients with verified metastatic disease (p = 0.04, p = 0.01 respectively). There was a significantly positive correlation between levels of gastrin and pancreastatin-like immunoreactivity (r = 0.7, p = 0.002), while no correlation was found between gastrin and chromogranin A levels or between levels of chromogranin A and pancreastatin-like immunoreactivity. The study demonstrates an elevation of both chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. The lack of correlation between gastrin and chromogranin A, however, gives an indication that the gastrinoma cells are not the main source of serum chromogranin A elevation.
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PMID:Chromogranin A and pancreastatin-like immunoreactivity in serum of gastrinoma patients. 832 58

Interleukin-2 (IL-2) therapy is dose limited by a severe vascular leak with resulting systemic and pulmonary toxicity. Although recognized as a mediator of septic shock and vascular leak, the relative role of IL-1 in IL-2 toxicity is unclear. We evaluated the effect of IL-1 receptor antagonist (IL-1ra) on IL-2 lethality, pulmonary vascular leak, and treatment of pulmonary metastases in a murine model. In vivo induction of mRNA for IL-1 alpha was evaluated in liver by Northern blots after 0, 5, 8, and 11 doses of IL-2 in C3H/HEN mice. The expression index for the IL-1 alpha gene increased from 0.16 to 0.74 after 5 doses of IL-2, and further increased to 1.04 after 11 doses of IL-2. C3H/HEN mice (n = 56) were randomized to receive phosphate-buffered saline (PBS), IL-1ra high dose (HD), or IL-1ra low dose (LD) by continuous subcutaneous infusion via Alzet mini-pumps. The biologic effectiveness of the dose and administration of IL-1ra was determined by the ability to block IL-1-induced IL-6 production in vivo. Mean serum IL-6 levels 3 hr after intraperitoneal IL-1 alpha (10 micrograms/kg) were: PBS, 3730 +/- 526 (mean +/- SEM pg/ml); IL-1ra (LD), 1156 +/- 398; and IL-1ra (HD), 594 +/- 30 (P < 0.01, IL-1ra HD or LD vs PBS). Pulmonary vascular leak was measured by iv I125 albumin after 8 doses of IL-2 (100,000 U ip q 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IL-1 receptor antagonist (IL-1ra) augments IL-2-induced pulmonary vascular leak. 833 27

Injection of ethyl alcohol in high concentrations into tissues produces coagulative necrosis. The benefits of direct injection of 98% ethanol into hepatic metastases from 1,2-dimethylhydrazine (DMH)-induced colonic cancer was investigated in groups of 20 Sprague-Dawley rats of either sex. At 10 weeks of age, rats were subcutaneously injected every week with 10 mg/kg DMH for 28 weeks. They were then housed for 3 months. At the end of this period all the animals had developed colonic carcinoma with multiple hepatic metastases. Total colectomy and the fashioning of an ileostomy coupled with direct injection of 0.1-0.2 ml of ethanol into each of the hepatic metastases, after mobilizing the liver by dividing its fascial attachments to facilitate easier tumour detection by inspection and palpation, afforded a significant survival advantage relative to colectomy alone (20.1 +/- 0.2 months of age, vs, 12.8 +/- 0.2 months of age, mean +/- SEM, n = 20, p < 0.01 by the Mann-Whitney U test). The clinical implications of these observations were, therefore, examined in a pilot study carried out on 6 patients (2 women and 4 men with an age range of 43-71 years, mean 56) who had adenocarcinoma of the sigmoid colon with multiple hepatic secondaries. The colonic tumour was resected and an end-to-end anastomosis effected, then all palpable hepatic metastases were slowly injected with 1-1.5 ml of 98% ethanol. Two weeks post-operatively and thereafter once every 2 months any hepatic lesions detected ultrasonically were similarly treated percutaneously. This treatment produced no adverse effects of any significance. None of the patients died during the first post-operative year. Death was due to disease spread in all the patients. The mean survival measured from the time of tumour resection until death from any cause was 20 months (range 17-26 months). It thus appears that chemonecrosis for the treatment of liver metastases from colonic cancer is a simple and safe therapeutic modality which offers a survival gain.
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PMID:Chemonecrosis for localized dynamic destruction of hepatic metastases of colonic cancer. A new approach. 842 95

The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 +/- 1.5 years (x +/- SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 +/- 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 +/- 0.22 vs. -0.12 +/- 0.25, +0.03 +/- 0.19 vs. -0.54 +/- 0.24, and +0.08 +/- 0.14 vs. -0.02 +/- 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 +/- 0.04 vs. 0.40 +/- 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (-2.1 +/- 1.1 vs. +7.0 +/- 3.3 micrograms/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 +/- 2.5% vs. -0.3 +/- 1.4%, and +8.1 +/- 4.7 vs. -0.9 +/- 1.7, after 10.3 +/- 0.4 and 17.3 +/- 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.
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PMID:Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer. 880 93

1H MR spectroscopy was used to correlate the metabolite signals in 66 untreated metastatic brain tumors with the results of Gd-DTPA enhanced MRI. Cubic volumes containing brain metastases of lung cancer (n = 17), mammary carcinoma (n = 24), melanoma (n = 12) and those originating from other tumors (n = 13) were examined using the double spin echo technique with CHESS pulses for water suppression and TE = 135 ms. Apart from trends toward reduced signals of choline-containing compounds (Cho) and reduced post-Gd MRI contrast in lung cancer compared with the other pathology groups, the four tumor groups had similar MRI and MRS characteristics. Metastases without lipid or lactate (Lact) signal in the 1H MR spectra were comparatively small in size with homogeneous post-Gd MRI enhancement (33 +/- 5%, means +/- SEM; n = 24) and elevated Cho signals compared with normal contralateral brain tissue (70 +/- 5% of contralateral N-acetyl aspartate signal; p < 0.001). The other metastases showed either unambiguous lipid signals (n = 30) or MRS detectable Lact (n = 12) and were heterogeneous on MRI with divergent signals of Gd-enhancement (49 +/- 5% vs 14 +/- 8%, p < 0.001) and Cho (88 +/- 10 vs 47 +/- 8% of contralateral NAA; p = 0.02). Those with Lact were significantly larger compared with both other groups (p < 0.02, both). It is concluded that brain metastases can be categorized into early stage (Cho), intermediate stage (lipid, higher Cho) and late stage metastases (Lact, lower Cho).
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PMID:1H MR spectroscopy detection of lipids and lactate in metastatic brain tumors. 888 70

The Boyden chamber assay is widely used for in vitro measurement of the invasive capacity of cells. However, results can be affected significantly if certain precautions are not taken. Using the Boyden chamber assay we investigated in vitro the invasive potential of a variety of human gynecological tumor cell lines to degrade and migrate through the artificial basement membrane matrix Matrigel. However, in the absence of this Matrigel layer large differences were observed in the ability of cells to adhere to, migrate through and attach to the lower side of the filter membranes. These differences were influenced by cell density, degree of directional locomotion, and the size of the filter pores. To adjust for these influences (which are not directly correlated to the capacity of cells to traverse the Matrigel layer), invasion results were corrected for the ability of cells to migrate through the filter membrane. In addition, the invasion of MDA-MB-231 cells was used as an internal standard to compensate for variations in the Matrigel layer between different experiments. Overall, in our experimental set up, the five human breast cancer cell lines were the most invasive (mean invasion +/- SEM relative to MDA-MB-231 invasion: 104.7 +/- 6.1%), the five human ovarian cancer cell lines the least invasive (60.2 +/- 2.2%) and the six human endometrial cancer cell lines showed an intermediate capacity (79.1 +/- 3.5%). In conclusion, the Boyden chamber assay can be used reliably for studying the invasive potential of cells in vitro, if the ability of the cells to migrate through the filter is taken into account, and a reference cell line is included to enable comparison of the data obtained from independently performed experiments on different cell lines.
Clin Exp Metastasis 1997 Jan
PMID:Assessment of the invasive potential of human gynecological tumor cell lines with the in vitro Boyden chamber assay: influences of the ability of cells to migrate through the filter membrane. 900 6

Our goal was to assess the utility of manganese dipyridoxyl diphosphate (MnDPDP) as a negative hepatic contrast agent in short inversion time IR MRI (STIR). Twenty patients with focal liver lesions (15 with metastatic disease, 5 with hemangiomas) underwent MRI (T1-weighted SE, breath-hold GE, and STIR sequences) before and after infusion of MnDPDP (5 mumol/kg). We then compared the results obtained with each sequence for hepatic parenchymal enhancement, lesion-to-liver contrast-to-noise ratio (C/N) measurements, and the number of focal liver lesions observed in pre- and postcontrast images. Hepatic enhancement values of 25.3 +/- 9.7 and 33.6 +/- 2.7% (mean +/- SEM) were obtained for the T1-weighted SE and GE sequences, respectively. The STIR sequence showed 78.9 +/- 2.1% negative enhancement (decrease of parenchymal signal intensity). Although a significant (p < 0.0001) C/N increase was seen after MnDPDP administration for all sequences, STIR showed the highest increase (149.0 +/- 25.5%) compared with T1-weighted SE (58.5 +/- 12.7%) and GE (83.3 +/- 7.2%) sequences. Similarly, more lesions for all sequences were detected, but again STIR showed the greatest postcontrast increase (29.0%). MnDPDP is an effective hepatic contrast agent. As both the negative hepatic enhancement and the increase in lesion-to-liver C/N were superior with the STIR sequence when compared with the positive enhancement and C/N values produced by the T1-weighted sequences, it should be considered for inclusion in the imaging protocol for patients with focal liver disease.
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PMID:MnDPDP as a negative hepatic contrast agent: evaluation of STIR imaging compared with T1-weighted SE and GE techniques. 902 76

Plasma levels of chromogranin A (CgA) were measured by ELISA in 22 patients with pheochromocytoma (18 non-metastatic, 3 metastatic, and 1 mixed neuroendocrine-neural tumor), 9 patients with primary hyperparathyroidism, and 9 patients with pituitary adenoma. The plasma levels of CgA were compared with norepinephrine, epinephrine, parathyroid hormone and pituitary hormones, i.e., growth hormone and prolactin. In pheochromocytoma, CgA in preoperative plasma of the patients without metastasis was 228 +/- 38 U/L (mean +/- SEM) and significantly higher than healthy controls (30 +/- 11 U/L, n = 40). Plasma CgA was decreased after removal of the tumors (28 +/- 6.0 U/L), except in three patients with metastatic pheochromocytoma and a mixed neuroendocrine neural tumor. The concentration of CgA in the patients with non-metastatic pheochromocytoma was significantly correlated with that of plasma norepinephrine (P < 0.005, r = 0.68) and urinary norepinephrine (P < 0.05, r = 0.65), but not with that of epinephrine. There was an exceptional case in which CgA was extremely high, but the CA level was normal. This tumor was a highly malignant pheochromocytoma with extensive metastases composed of small tumor cells which were occasionally positive for tyrosine hydroxylase immunohistochemically. These cells were considered to be poorly differentiated tumor cells and synthesized a very small amount of norepinephrine. Plasma levels of the patients with primary hyperparathyroidism and the patients with pituitary adenoma were 44 +/- 4 U/L and 48 +/- 8 U/L, respectively. Only one patient with a growth hormone-producing pituitary adenoma had a high level of CgA. Plasma CgA is a useful tumor marker for pheochromocytoma, even for malignant pheochromocytoma without elevated CA level, but not for hyperparathyroidism, or pituitary adenoma.
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PMID:Plasma chromogranin A in pheochromocytoma, primary hyperparathyroidism and pituitary adenoma in comparison with catecholamine, parathyroid hormone and pituitary hormones. 922 69

Thyroglobulin (Tg) is a glycoprotein produced exclusively by the thyroid. It can be found in the serum of healthy people as well as of those with various thyroid disorders. Elimination of Tg from the body occurs through the liver. The data on Tg serum half-life in the literature are scarce, and the reported values vary from 6-96 h. The aim of our study was to determine the Tg half-life after surgical removal of the thyroid gland. Knowing the exact half-life of Tg would enable rational timing of sampling serum for determination of Tg after thyroid surgery or chemotherapy and/or irradiation for evaluation of treatment in patients with differentiated thyroid cancer (DTC). In 11 patients (10 females and one male, aged 27-85 years) serum samples were taken 24, 48, 72 and 168 h after a near-total or total thyroidectomy. Serum Tg levels were determined and Tg half-life calculated by the use of a one-compartment kinetic model. Mean Tg half-life was 65.2 h (SEM = 4.3), and Tg levels decrease below 5-10 ng/ml approximately only 25 days after thyroidectomy (7-10 x t1/2). Therefore, earlier determination of Tg cannot be used either for reliable detection of distant metastases or for evaluation of the effect of chemotherapy and/or irradiation.
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PMID:The dynamics of serum thyroglobulin elimination from the body after thyroid surgery. 923 92


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