Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study the efficacy of treatment of two cyclo-oxygenase inhibitors, ibuprofen (Ibu) and indomethacin (Indo), are compared in the immunotherapy of metastasis designed to reverse prostaglandin E2 (PGE2)-mediated inactivation of interleukin-2 (IL-2)-dependent host killer cell lineages. These agents were tested either alone for the prevention of metastasis or in combination with IL-2 for the eradication of established metastasis. C3H/HeN mice were placed on chronic oral Ibu (CIbT; 200 and 600 micrograms/ml of water) or Indo (CIT; 10 micrograms/ml) 5 days after s.c. transplantation of 5 x 10(5) metastatic C3L5 mammary carcinoma for the prevention of spontaneous lung metastases. They showed intolerance to Indo at a dosage of 14 micrograms/ml, which was well tolerated by other mouse strains in previous studies, but tolerated the Ibu dosages used. Control and treated mice were killed on day 30 to score metastatic lung colonies, to evaluate killer activity in splenocytes against natural killer (NK)-sensitive YAC-1 lymphoma or NK-resistant C3L5 adenocarcinoma and 8911 lymphoma targets, and to phenotype the surface markers of killer cells. CIbT and CIT alone at the above dosage significantly reduced the number of lung colonies, retarded local tumor growth and restored NK activity of splenic killer cells expressing AGM-1+, Thy-1-, Lyt-2- phenotype. To treat established lung metastasis, mice bearing 15-day C3L5 transplants were given CIbT or CIT alone or in combination with two 4-day rounds (days 20-23, 31-34) of IL-2 (15,000 Cetus units, i.p. every 8 h) and were killed on day 35 to score lung colonies and characterize splenic killer cells. CIbT or CIT alone reduced the number of spontaneous lung metastases and restored anti-YAC-1 killer function of splenocytes with NK-like phenotype (AGM-1+, Thy-1-, Lyt-2-); some anti-C3L5 killer function was also generated in the high dose Ibu group and the killer cell showed AGM-1+, Thy-1+ and Lyt-2+ phenotype. Combined therapies with CIbT or CIT plus IL-2 were more effective in reducing metastases and promoting killer cell function, the best results being achieved with high dose Ibu+IL-2. All killer cells expressed AGM-1 and Thy-1. In addition, C3L5 killer cells also expressed Lyt-2, suggesting T-cell stimulation. PGE2 synthesis in the host was inhibited by at least 50% in mice subjected to CIbT or CIT.(ABSTRACT TRUNCATED AT 400 WORDS)
Clin Exp Metastasis 1992 Jul
PMID:Immunotherapy of mammary adenocarcinoma metastases in C3H/HeN mice with chronic administration of cyclo-oxygenase inhibitors alone or in combination with IL-2. 161 32

Thirty two human livers were removed at autopsy. These included 7 with space-occupying or tumour-like lesions, namely one with multiple cysts, three with haemangiomas, a lobated liver with multiple nodules of focal nodular hyperplasia, one with a metastasis which also had a small haemangioma and one with a hepatocellular carcinoma. Fine particle barium diluted 2:1 with water was injected by hand to fill the arterial system. In the lobated liver, the portal system was also filled. High definition radiographs of liver slices showed arteriographic detail not visible on angiography. The arteriographic appearances were correlated with the macroscopic and microscopic pathology. Liver cysts compress the arteries and arterioles but an apparent halo on the whole liver radiograph was shown to be spurious on a 1 cm thick high definition film. The small vessel pattern of haemangiomas is well demonstrated accounting for the hyperechoic sonograms but hypoechoic areas may also occur due to involution of or haemorrhage into tumours. The small lesions of focal nodular hyperplasia had a poor arterial supply but filled from a portal venous injection. Metastases had a peripheral network of small vessels, central necrosis and normal sized peripheral arteries with no large artery entering the tumour. In hepatocellular carcinoma, a large artery was demonstrated entering the tumour which was considerably more vascular than the metastases. These features should aid in distinguishing these lesions on sonography.
 ...
PMID:Radiological-pathological correlation of mass lesions in the liver. 166 81

Twenty patients with known malignancies, back pain, abnormal roentgenograms of the spine, and normal neurological examinations were evaluated by outpatient computed tomographic (CT) myelography to determine the presence and extent of epidural tumor. Spinal CT following the intrathecal administration of low doses of water soluble contrast agents provided high quality diagnostic information. Three patients experienced adverse effects from this procedure which were mild and easily managed in the outpatient setting. Epidural tumor was identified in 15 of 20 (75%) patients. Patients were followed for 9-27 months following myelography. The 14 patients with epidural tumor treated with local radiation experienced pain relief and only one of these patients developed signs or symptoms of recurrent epidural tumor in the treated site. This study documents the high incidence of epidural tumor in selected patients without neurological deficits and the excellent palliative results of non-emergent, carefully planned radiation therapy. It also demonstrates that high resolution CT myelography can be performed safely in an outpatient setting in patients at high risk for epidural tumor. Outpatient myelography facilitates the early diagnosis of epidural tumor and provides needed information on the extent of the tumor for radiation treatment planning while conserving health care resources. For these reasons, outpatient CT myelography should be considered in selected patients with cancer who are at high risk for epidural metastases.
 ...
PMID:Early diagnosis of spinal epidural metastases using out-patient computed tomographic myelography. 169 89

Patients suffering from malignant disease will probably develop some metabolic abnormality of electrolytes. Hypernatremia is defined as an elevation of serum natrium over 150 mEq/l and caused by decrease of water intake, low level of ADH secretion and impaired response of kidney to ADH. Hyponatremia below 135 mEq/l of serum natrium is caused by SI-DAH, sick cell syndrome and increased loss of natrium from the kidney. On the other hand, hyperkalemia is defined as an elevation of serum kalium over 5.0 mEq/l and caused by acute tumor cell lysis syndrome, adrenal and renal insufficiency. Hypokalemia is caused by kalium loss from kidney and hypersecretion of mineral corticoid. Hypercalcemia is found in the high frequency among patients with malignant disease. Hypercalcemia is defined as an elevation of serum calcium over 11.0 mg/dl, although the most important aspect is the level of ionized calcium. The excess calcium causes defective urinary concentration with polydipsia, nausea and vomiting leading to volume depletion. At serum calcium levels about 13.8 mg/dl, there may be rapid deterioration or renal function, dehydration, coma and cardiac arrhythmias. Hypercalcemia is rarely the first manifestation of cancer. There are three principle pathogenic causes of malignant hypercalcemia, 1) hypercalcemia is a feature of several hematological cancers, including Burkitt's lymphoma, T cell leukemia, but most commonly with myeloma. The hypercalcemia in these myeloma patients is due to the secretion of an osteoclast activator, a lymphokine by the myeloma cells. 2) all patients with bony metastases have biochemical evidence of increased bone resorption. However, not all patients with bony metastases develop hypercalcemia. Probably the hypercalcemia is due partially to increased renal tubular reabsorption of calcium, mediated by a humoral factor, with activity similar to that of parathormone. 3) hypercalcemia in the patients without bony metastases is due to increased bone resorption caused by the ectopic secretion by the tumor. Mildly symptomatic patients will benefit from modest salt loading. They are dehydrated and replacement of the extracellular fluid is the first line of treatment. This may require 4-10 l normal saline/24 h. In addition, frusemide will increase calcium excretion. Calcitonin may be given subcutaneously or intravenously to refuse the mobilisation of calcium from bone. Glucocorticoids are unhelpful, but will prolong the effect of calcitonin. A diphosphonate is also useful.
 ...
PMID:[Palliative therapy in cancer. 4. Palliation of the symptoms from a malignant tumor. (2)]. 169 56

Microvascular proliferation, a hallmark of malignant brain tumors, represents an attractive target of anticancer research, especially because of the quiescent nonproliferative endothelium of the normal brain. Cerebral neoplasms sequester copper, a trace metal that modulates angiogenesis. Using a rabbit brain tumor model, normocupremic animals developed large vascularized VX2 carcinomas. By contrast, small, circumscribed, relatively avascular tumors were found in the brains of rabbits copper-depleted by diet and penicillamine treatment (CDPT). The CDPT rabbits showed a significant decrease in serum copper, copper staining of tumor cell nuclei, microvascular density, the tumor volume, endothelial cell turnover, and an increase in the vascular permeability (breakdown of the blood-brain barrier), as well as peritumoral brain edema. In non-tumor-bearing animals, CDPT did not alter the vascular permeability or the brain water content. CDPT also inhibited the intracerebral growth of the 9L gliosarcoma in F-344 rats, with a similar increase of the peritumoral vascular permeability and the brain water content. CDPT failed to inhibit tumor growth and the vascularization of the VX2 carcinoma in the thigh muscle or the metastases to the lung, findings that may reflect regional differences in the responsiveness of the endothelium, the distribution of copper, or the activity of cuproenzymes. Metabolic and pharmacologic withdrawal of copper suppresses intracerebral tumor angiogenesis; angiosuppression is a novel biologic response modifier for the in situ control of tumor growth in the brain.
 ...
PMID:Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor. 170 Jun 17

The role of Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) in the treatment evaluation of retroperitoneal lymph-node metastases of non-seminomatous testicular tumors (NSTT) was prospectively studied in 10 consecutive patients before, during and after chemotherapy. The results thus obtained were compared with laparotomy findings before and after chemotherapy, the histology of the primary testicular tumor, and that of retroperitoneal residual lesions after chemotherapy. MRI and CT proved to be equivalent in detection and in determining the anatomical localization and size of the retroperitoneal lymph node metastases. Unlike CT, MRI revealed unmistakable changes in the structure of the retroperitoneal lymph-node metastases during chemotherapy, for which no histological cause was found except in mature teratoma. In mature teratoma a high T2 signal was found within the metastases, corresponding with a high water content. On the basis of tumor consistency and signal intensity in the T1- and T2-weighted images, MRI cannot yet warrant any conclusion about the ultimate effect of chemotherapy.
 ...
PMID:The role of magnetic resonance imaging and computed tomography in the treatment evaluation of retroperitoneal lymph-node metastases of non-seminomatous testicular tumors. 171 4

Sera from BDIX rats inoculated with 2 tumor clones derived from a single syngeneic colon carcinoma were assayed by Western blotting for the presence of antibodies against the grafted tumor. The PROb clone is progressive and produces metastases. We observed that rats bearing this tumor developed antibodies against an unglycosylated water-soluble protein of 105 kDa. The magnitude of this humoral response, as assessed by the intensity of the signal on immunoblots, was inversely correlated with survival of the rats. Furthermore, rats inoculated with the REGb clone, which is immunologically rejected, never developed detectable antibodies against the tumor. Antisera from rats injected with PROb tumor detected p105 antigen in cellular extracts from the REGb clone and from a series of rat and human cell lines. This protein was also detected in variable amounts in some normal adult and fetal tissues. Treatment of PROb or REGb cells by either interferon-gamma or heat shock did not significantly alter the expression of the p105 auto-antigen.
 ...
PMID:Identification and characterization of a rat protein (p 105) auto-antigenic in rats bearing a progressive syngeneic colon carcinoma. 173 May 26

Fotemustine is a highly reactive chloroethyl-nitrosourea anti-tumor drug that is currently undergoing phase III clinical trials in stage IV metastatic malignant melanoma. The drug is a potent alkylating agent and rapidly chloroethylates the active sites of the important thioproteins thioredoxin reductase (TR), glutathione reductase (GR) and ribonucleotide reductase (RR). These enzymes control ribonucleotide reduction and, consequently, DNA synthesis in the S phase of the cell cycle. Side effects are minor due to the rapid metabolism of the drug. [14C]Fotemustine exhibited a half-life of 90 min in the vascular system after the administration of 100 mg/m2. Fotemustine was shown to yield the volatile degradation product acetylene (a) in distilled water (4.1%/h), (b) in melanoma cell culture medium (MCDB) supplemented with 10% fetal calf serum (33%/h) and (c) in fotemustine-sensitive human melanoma cells in culture medium (70.5%/h). Due to its rapid metabolism and its low toxicity, high concentrations of fotemustine (55 x 10(-3) M) were injected directly into cutaneous and subcutaneous melanoma metastases (n = 36) of seven patients, resulting in minor necrosis followed by total remission of the metastases. Untreated metastases adjacent to the treated tumors were not affected by fotemustine, confirming that rapid local metabolism of this drug occurs only in the vicinity of injected tumors without producing any systemic effects.
 ...
PMID:Local treatment of cutaneous and subcutaneous metastatic malignant melanoma with fotemustine. 176 Aug 62

Seven patients suffering from carcinoma of the lower portion of duodenum were examined by means of CT. Water was used as oral contrast medium. In all patients CT showed parietal thickening in the lesion site, with hyperdense (4 cases) or isodense (3 cases) patterns with respect to adjacent normal walls; irregularities on the inner surface were also demonstrated. CT correctly staged the tumor in 5/7 patients (70%), showing pancreatic infiltration in 5 cases--in 1 case associated with hepatic metastases--, vena caval infiltration in 1 patient, and right anterior pararenal fascia involvement in 1 case. In 2 patients the relationship between duodenal carcinoma and pancreas could not be evaluated. CT is suggested for the patients with suspected neoplastic pathologic conditions of the duodenum thanks to its capabilities of showing extraparietal lesion spread, as well as adjacent organs infiltration, adjacent vessels involvement, and distant metastases.
 ...
PMID:[The role of computerized tomography in the study of duodenal carcinoma]. 176 51

Renal pelvic carcinoma was induced in mice by giving N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Initially, differences in renal pelvic carcinogenesis by BBN were examined in three male mouse strains: NON/Shi, which demonstrate spontaneous hydronephrosis with incidences of 10-30%, and DS/Shi and B6C3F1, which do not exhibit hydronephrosis. When mice of these strains were given 0.05% BBN in the drinking water for 12 weeks followed by water without BBN for 8 weeks, renal pelvic carcinoma morphologically similar to human carcinomas developed in 8 of 23 NON/Shi mice (35%). Metastasis to the lung was found in one of them (13%). B6C3F1 and DS/Shi mice had no pelvic tumors, but the response to urinary bladder carcinogenesis in NON/Shi mice was nearly equal to that in DS/Shi and B6C3F1 mice. These results suggest that renal pelvic carcinogenesis is related to the presence of stagnant urine containing carcinogen in the renal pelvis. In a second experiment, we examined renal pelvic carcinogenesis in NON/Shi mice given BBN for 4 weeks followed by water without BBN for 32 weeks. The incidence of renal pelvic carcinoma (28%) was similar to that in the first experiment, but the incidence of metastasis was markedly elevated to 60%. These results indicate that BBN treatment can induce renal pelvic carcinoma which often metastasizes to the lung in NON/Shi mice.
 ...
PMID:Renal pelvic carcinoma which shows metastatic potential to distant organs, induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice. 177 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>