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)

For a large number of N-nitroso compounds a comparison of their carcinogenic effects in rats and Syrian golden hamsters has been made. Nitrosamines, which require metabolic activation, and nitrosoalkylamides, which do not, produce quite different tumor responses. There are also large differences in the types of tumor induced in rats and in hamsters. In all the studies doses of the various compounds, equimolar to the extent that was possible, are administered orally. Continuous doses (in drinking water or food) often produce a response different from that after administration of the same compound in pulsed doses (by gavage), even though the same total dose is delivered. Continuous doses of nitrosamines are usually more effective than pulsed doses, but with the nitrosoalkylureas, the reverse is more generally the case. Rat and hamster liver is a common target of many nitrosamines, but rarely of nitrosamides. The most common site of tumor induction in rats by N-nitroso compounds is the esophagus, but the hamster esophagus never responds. The pancreas duct of the hamster is a common target of nitrosamines containing a beta-oxygenated propyl group, but pancreas duct tumors are never seen in rats. Nitrosomethyl-n-alkylamines (with an even numbered carbon chain) induce bladder tumors in rats and hamsters. Many nitrosoalkylureas induce tumors of the nervous system in rats, as well as a great variety of other tumors. In hamsters, nitrosoalkylureas give rise only to tumors of the forestomach and spleen, but no tumors of the nervous system. The similar carcinogenic actions of certain groups of N-nitroso compounds can be related to their generation, directly or by metabolism, of similar simple moieties having certain organs as their target.
Cancer Metastasis Rev 1987
PMID:Structure-activity relations in carcinogenesis by N-nitroso compounds. 331 73

Indirect mammo-lymphography with serial radiograms was made on rats bearing three established rat mammary carcinomas (SMT-2A, TMT-50, MT-W9B), with the water-soluble contrast medium, Iotasul. In the lymphogenously metastasizing SMT-2A, fine lymphatic sprouts from the tumor were seen converging into an afferent lymph vessel that was extending toward a metastatic regional lymph node, in 15-30 min. For 45 min, the dye remained localized in the primary tumor with no other vascular structures or viscera visible until it emerged in the urinary bladder, indicating that Iotasul was absorbed slowly into the systemic circulation via lymphatics and diluted beyond recognition by lymph and blood, and then reconcentrated in urine. In contrast, in the hematogenously metastasizing TMT-50, Iotasul was rapidly diffused into the blood stream, revealing the inferior caval vein within 5 min, and by 15 min the heart, aorta, common carotid arteries, kidney and ureter were all clearly revealed. In the non-metastasizing MT-W9B host, several small vascular markings around the tumor were seen by 10 min and the outline of kidneys and urinary bladder in 15 min, suggesting that the dye was also absorbed through blood capillaries but somewhat slowly. Thus, the differential vascular permeability in rat mammary tumors revealed by Iotasul has not only helped to distinguish lymphatics from blood vessels, but also to correlate it with their metastatic potential.
Clin Exp Metastasis
PMID:Differential permeability of lymphatic and blood vessels in determining the route of metastasis as demonstrated by indirect lymphography. 335 12

Ten patients with debilitating hip or knee pain were examined with magnetic resonance (MR) imaging. All had conventional radiographs that were either normal or showed nonspecific osteopenia. Nine patients had bone scintigrams that showed focal increased radionuclide uptake in the region of the painful joint. In each case, MR images of the affected joint showed regional decreased signal intensity of the bone marrow on T1-weighted images and increased signal intensity on T2-weighted images. Biopsy results of four patients excluded ischemic necrosis and metastases. The symptoms resolved spontaneously in all cases. The ten patients were followed up for 12-36 months, and there were no recurrences. The authors believe that the findings on MR images represent a transient increase in bone marrow water content. The focal findings on scintigrams confirmed the periarticular distribution of the process and provided evidence of accompanying hyperemia and increased bone mineral metabolism. For lack of a better term and to emphasize the generic character of the condition, the authors termed this condition "the transient marrow edema syndrome."
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PMID:Transient osteoporosis: transient bone marrow edema? 336 36

The antimetastatic effect of a new water-soluble derivative of camptothecin, 7-ethyl-10-(4-(1-piperidino)-1-piperidino) carbonyloxy-camptothecin (CPT-11), were examined in several metastatic murine tumor systems. Intravenous (i.v.) injection of CPT-11 into BALB/c mice inhibited lung metastasis by i.v. inoculated, metastatic colonic adenocarcinoma 26 (C26) cells, C26NL-17, in BALB/c mice. This treatment was also effective in C57BL/6 mice against lung metastasis by i.v. inoculated B16-F10 and B16-BL6 cells, highly metastatic variants of the B16 melanoma. Furthermore, intraperitoneal (i.p.) injection of CPT-11 significantly inhibited the growth of C26NL-22 cells, a highly metastatic variant of C26, inoculated subcutaneously (s.c.) into the left front footpads of BALB/c mice. Also, i.p. or i.v. injection of CPT-11 effectively inhibited the growth of 3LL tumors inoculated s.c. into the hind footpads of C57BL/6 mice. Moreover, following s.c. inoculation of either C26NL-22 or 3LL cells, combined surgical excision of the primary tumor and either i.p. or i.v. CPT-11 injections given before or after surgery markedly inhibited the formation of pulmonary metastases. These results show that a new derivative of camptothecin, CPT-11, has a potent inhibitory effect against both spontaneous and experimental lung metastasis.
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PMID:Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice. 337 Jul 38

J82 monolayer cell cultures and 647 V multicellular tumor spheroids were incubated in Resectal, urine (pH 5.5; 7.5) and distilled water for 5-30 min. In the case of both monolayers and tumor spheroids inhibition of tumor cell growth was achieved by incubation in distilled water. Transurethral resection (TUR) of a primary superficial bladder cancer was performed in 133 patients (Ta, T1). In 60 of these patients selected biopsies of apparently normal bladder mucosa were taken at the same time. There was no significant difference in tumor recurrence between the groups with biopsy and without biopsy. However, all patients with dysplasia in the selected mucosal biopsies developed a tumor recurrence. Between 1969 and 1984 bladder wall perforation occurred in 12 patients during TUR of Ta, T1 bladder cancer. None of the patients who experienced bladder wall perforation developed extraperitoneal or intraperitoneal metastases. Although our clinical results suggest that iatrogenic tumor cell implantation during TUR of a bladder cancer is rather unlikely, this event could be prevented by the use of distilled water during and after TUR.
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PMID:[Iatrogenic tumor cell implantation in bladder cancer]. 337 73

There are two strategies for evaluating the antitumor effect of IL-2. In the first approach IL-2 has been used to support the proliferation of T-effector cells or LAK cells in vitro in the hope that large quantities of these effector cells can be used therapeutically. This approach has shown some efficacy in animal models if LAK cells are administered in combination with IL-2. However, it is extremely difficult to standardize the numbers of lymphocytes and the biological activity of effector cells for clinical use. Recently the cloning of IL-2 has made available large quantities of purified recombinant IL-2 (rIL-2) for preclinical and clinical trials. Accordingly there have been recent attempts at injecting rIL-2 directly to stimulate effector cells in vivo. In this study, in vivo and in vitro augmentation of the cytotoxicity of spleen lymphocytes against syngeneic B-16 melanoma cells (induction of LAK cells) and the suppression of artificial pulmonary and liver metastases of B-16 melanoma in C57BL/6 mice was tried by subcutaneous multiple injections of high-dose human rIL-2. In addition, the immunosuppressive effect of a water-soluble nitrosourea derivative (ACNU) was determined 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 were examined in ACNU-treated C57 BL/6 mice. It was also tested whether the administration of LAK cells and/or rIL-2 could reduce the increased numbers of pulmonary metastases in ACNU-treated mice. The cytotoxicity of spleen lymphocytes against YAC-1 cells as well as against syngeneic B-16 and F-10 melanoma cells was augmented not only by incubation of spleen lymphocytes with human recombinant interleukin-2 (rIL-2) in vitro but also by injecting high-dose rIL-2 into C57BL/6 mice for more than 3 consecutive days. In animals injected with multiple high doses of rIL-2 subcutaneously, the numbers of tumor nodules in the lung were significantly decreased 21 days after intravenous tumor inoculation. In addition, in these groups of animals no liver metastases were observed although liver metastases were detected in 6/11 of control mice. The maximum effective dose of ACNU suppressed the cytotoxicity of spleen lymphocytes and pretreatment with ACNU enhanced the induction of artificial pulmonary metastases.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Strategy of cancer treatment using human recombinant interleukin 2 and lymphokine activated killer cells]. 348 26

Our earlier work revealed that PGE-mediated inactivation of NK cells in tumor-bearing mice by host macrophages promoted spontaneous lung metastasis that could be prevented or ameliorated by chronic indomethacin therapy. Since PGE was found to suppress the in vitro development and/or activation of a family of tumoricidal lymphocytes such as CTL, NK, and LAK cells by one or both of two mechanisms, that is to say, a down regulation of IL-2-R and an inhibition of IL-2 production, the present study tested whether a combined therapy with indomethacin and IL-2 was more effective than one with indomethacin or IL-2 alone in ameliorating established experimental lung metastasis. B6 mice injected intravenously with 10(6) highly metastatic B16F10 melanoma cells showed profuse micrometastases in the lungs by day 5, and macrometastases by day 10 which were confluent on day 21. Chronic indomethacin therapy by the oral route (14 micrograms/ml in drinking water) starting on day 0 or day 5, or a single round of IL-2 therapy (25,000 U rIL-2, every 8 h for 5 d on days 10-14) reduced the number of metastatic nodules by two-thirds (from a median of 473 in control mice receiving vehicles alone) by day 21. A single round of IL-2 as above, combined with either protocol of indomethacin therapy, completely or nearly completely irradicated the lung metastases, corroborated by a histological examination. An evaluation of splenic killer cell activity measured with a 4-h 51Cr-release assay against NK-sensitive YAC-1 lymphoma and B16F10 melanoma or NK-resistant thymic lymphoma 9705 targets revealed negligible activity in control tumor-bearing mice, and a good restoration of activity against NK-sensitive targets with either protocols of indomethacin therapy. IL-2 alone or a combination of IL-2 and indomethacin given by either protocol generated strong killer activity against all these targets, most marked with the combination therapy. Splenic killer cell phenotype in normal as well as all treated animals was ASGM1+, Thy-1-, and Lyt-2-. The combination therapy resulted in the strongest mononuclear cell infiltration in the lungs, with areas of young granulation tissue suggestive of repair sites of original metastases.
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PMID:Amelioration of B16F10 melanoma lung metastasis in mice by a combination therapy with indomethacin and interleukin 2. 349 67

Adoptive immunotherapy with lymphokine-activated killer cells and recombinant interleukin 2 (IL 2) can produce significant reduction of visceral metastases in tumor-bearing mice and, as shown recently, in humans with disseminated cancer. Because further dose escalations of IL 2 have been prevented by the development of a vascular leak syndrome (VLS) in both mice and humans, we investigated this VLS in mice undergoing the systemic administration of high-dose IL 2. A model for quantitating capillary permeability was used in which 125I-bovine serum albumin was injected i.v., and 2 hr later, tissues were counted in a gamma analyzer. A permeability index (PI) was calculated by dividing the mean counts per minute (cpm) of tissues from IL 2-treated mice by those from control animals. The injection of IL 2 produced increases in vascular permeability that were most pronounced in the thymus, spleen, lungs, liver, and kidneys (PI = 18.0, 10.0, 9.7, 6.7, and 6.3, respectively, on day 6). The development of the VLS was highly dependent on the number of days of IL 2 treatment (for example, the lungs contained 638, 1382, 3350, and 6187 cpm after 0, 1, 3, and 6 days of IL 2, respectively). Moreover, the degree of the VLS was directly related to the dose of IL 2 administered. Measurement of the wet and dry weights of lungs from IL 2-treated mice demonstrated that IL 2 produced a dramatic increase in their water weight (from 0.10 g at base line to 0.22 g after 200,000 U of IL 2 for 6 days). The injection of the IL 2 excipient failed to induce capillary leakage in tissues. Immunosuppression of mice by pretreatment irradiation (500 rad) or by injection of cyclophosphamide or by concurrent use of cortisone acetate markedly reduced or eliminated the development of the VLS. Similarly, the VLS was not observed in nude mice receiving IL 2. Thus, the administration of IL 2 produces a dose-limiting VLS that may be mediated, directly or indirectly, by host lymphoid elements.
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PMID:Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2. 352 89

The molecular species of gastrin in the circulation and in tumor extracts were studied in two groups of patients: (1) with benign gastrinoma and (2) with gastrinoma with liver metastases. Radioimmunoassays (RIAs) and immunoaffinity chromatography for the amino (NH2)- and amidated COOH-terminus of gastrin-17 (antiserum G17) and the NH2-terminus of gastrin-34 (antiserum G34) were employed. In both benign and metastatic tumors the molecular forms of gastrin in boiling water extracts measured by the gastrin-17 NH2- and COOH-terminal assays were similar. In addition to a molecular component resembling the amidated gastrin-17, there were also significant amounts of larger molecular weight (mol. wt.) forms. The larger mol. wt. forms absorbed by the NH2-terminus of G17 antiserum corresponded to the COOH-terminus-extended forms of gastrin-17. Furthermore, larger mol. wt. gastrins immunopurified by antiserum to the NH2-terminus of gastrin-34 corresponded to gastrin-34 extended molecules. Sera of patients with liver metastases had higher concentrations of the NH2-terminal of gastrin-17 whereas sera of patients with benign gastrinoma contained predominantly gastrins detected by the COOH-terminal assay. These results suggest that: (a) there are differences in the molecular pattern of gastrin in the circulation of patients with benign and metastatic gastrinomas; (b) gastrins which are fully processed with carboxy-terminal amidation predominate in the circulation of patients with benign gastrinoma; and (c) gastrins containing the gastrin-17 and COOH-terminally extended gastrin-17 and gastrin-34 precursor molecules occur in high concentration in the circulation of gastrinoma patients with metastases to the liver.
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PMID:Identification of gastrin molecular variants in gastrinoma syndrome. 355 1

Possible prophylactic antitumor and/or antimetastatic effects of long-term oral administration of a potent inhibitor of platelet aggregation, the pyrimido-pyrimidine derivative RA233, were assessed using four phenotypically distinct clones of the mouse B16 melanoma. The clones tested included: a poorly tumorigenic, very slowly growing and poorly metastatic population (G3.15); a moderately tumorigenic and slowly growing population that frequently metastasizes to the lungs (G3.5); a highly tumorigenic, moderately growing and highly metastatic population (G3.12); and a highly tumorigenic and rapidly growing population that is generally nonmetastatic but can be slightly metastatic when tumors are initiated by very small numbers of cells (G3.26). Addition of 0.5 mg/ml RA233 to the drinking water continuously from the time of subcutaneous injection of cultured tumor cells until death from tumor growth, which resulted in a daily uptake of 80-100 mg/kg of drug per mouse, failed to significantly influence the tumorigenicities, tumor growth rates, metastatic incidences, or metastatic burdens of any of these clones. RA233 at doses equivalent to those delivered daily to experimental animals strongly inhibited ADP-induced aggregation of homologous C57BL/6 mouse platelets and exhibited selective anti-proliferative effects on cultured cells. Although RA233 prolonged bleeding times, pharmacokinetic analysis indicated that clearance of RA233 from mice was so rapid that achievement of sustained circulating levels sufficient to influence tumor cells or platelet-tumor cell interactions by oral administration was unlikely.
Clin Exp Metastasis
PMID:Failure of orally administered RA233 to influence B16 melanoma growth or metastasis. 359 74


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