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)

Twelve patients with Zollinger-Ellison syndrome and one patient with WDHA syndrome are reviewed. Three of the Z-E patients exhibited MEA, two having hyperinsulinism and one hyperparathyroidism. Ages ranged from nine to 71 years. Diagnosis of Z-E syndrome was established from history, gastric acid secretion, radiologic studies, serum gastrin measurements and from actual tissue biopsy in 10 of the 12 patients. Total gastrectomy was performed in 8 of the 12 Z-E patients, with abolition of the ulcer diathesis in all. However, in none of our patients was there objective evidence of subsequent tumor regression. Three patients remain alive. Four died of tumor, one from post-total gastrectomy complications, one from post-subtotal gastrectomy in another hospital, two from ulcer hemorrhage, and one from electrolyte imbalance with autopsy diagnosis of Z-E tumor. A patient is recorded in detail who exhibited both hyperinsulinemia and hypergastrinemia from a malignant islet cell tumor, had the tumor "debulked" four times over a 14 year period and whose hepatic metastases were temporarily abolished by streptozotocin infusion. The question is raised regarding relationships between chronic organic hyperinsulinism and subsequent hypergastrinemia.
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PMID:Zollinger-Ellison syndrome: special considerations. 14 Jun 31

Thirty-two patients with medullary carcinoma of the thyroid (MCT) were studied before and after therapy. Sixteen patients had familial and 16 had the sporadic type of disease. The groups differed in several features: Patients with sporadic disease were older at diagnosis and presented with enlargements in the thyroid or lymph nodes, and one patient had neuromata; in the familial group the disease was more often bilateral and was associated at times with the MEA syndrome (parathyroid adenoma or pheochromocytomas, or both). The immunoreactive serum calcitonin (CT) level was measured before and after some form of therapy in all 32 patients. Our investigations showed: 1) Delaying treatment was clearly detrimental in this progressive disease; 2) The most effective therapy was surgery, while radiotherapy and chemotherapy were less effective; 3) Postoperatively, the CT level usually fell sharply, when the disease was thought extirpated, but the lowest nadir might be reached at from 1 month to 6 years; 4) In all such patients the CT level eventually rose from the postoperative nadir; 5) Patients with no clinical or radiological evidence of disease, had high CT levels for a mean of 3 years of observation; 6) A marked rise of CT levels in three patients preceded metastases and death; 7) Patients with abdominal, particularly liver disease had the highest CT levels; and 8) Patients who died had relatively high CT levels, corresponding in general with the extent of disease.
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PMID:Medullary thyroid carcinoma: importance of serial serum calcitonin measurement. 42 24

In 82 patients, a preoperative diagnosis of primary hyperparathyroidism has been established by means of transfemoral neck vein catheterization and measurement of serum immunoreactive parathyroid hormone (iPTH). Twenty-five of these patients have had cancer in other parts of the body but with no evidence of recurrence or metastasis. One patient had carcinoma of the colon with metastases, and four were members of families with multiple endocrine adenomatosis (MEA, Types I and II). In six other hypercalcemic patients, high levels of iPTH were found also in the effluent blood from cancer sites other than the parathyroid gland, secondary to ectopic hormone production or pseudohyperparathyroidism. In addition, a high serum level of iPTH was found in the superior vena cava of a seventh patient who had carcinoma of the breast but no clinical or radiological signs of recurrence or metastasis with the exception of an enlarged liver. This iPTH finding was interpreted as being, probably, the result of parathyroid adenoma in either the neck or the mediastinum. At the time of operation, a transcervical mediastinal search was made. Four normal cervical parathyroid glands were found; three were removed. Hypercalcemia persisted after operation, and the patient died. At postmortem examination, microscopic study revealed that the disease had metastasized to lungs and hilar lymph nodes. There was massive metastasis in the liver; the liver contained a large amount of iPTH. The results of these investigations suggest that (1) venous catheterization of the neck veins and the effluent blood from extraparathyroid tumors aid in identifying and localizing iPTH production; (2) primary benign hyperparathyroidism is not uncommon in patients with cancer, and its co-existence must be recognized; (3) high serum iPTH level in the superior vena cava may be found in patients with metastatic or primary cancer of the thoracic cavity; and (4) hyperparathyroidism may be the first hint of a familial multiple endocrine syndrome.
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PMID:Hypercalcemia in patients with known malignent disease. 96 5

Prognosis of gastrinoma patients with metastases to lymph nodes only is uncertain, and the true nature of isolated nodal gastrinomas remains controversial. The purpose of this study was to determine the outcome of such patients and whether nodal gastrinomas may occur as primary lesions. Eleven patients with nodal involvement but without hepatic metastases are reported (mean follow-up of 129 months). Primary gastrinomas were located in the duodenum in seven (Group 1) and not identified in four (Group 2). In Group 1, five patients remained eugastrinemic after excision of all gross tumors and gastrectomy (n = 4) or pancreaticoduodenectomy (n = 1), one patient had residual disease and died of other causes (survival of 88 months), and one patient had MEA-I syndrome with multiple gastrinomas (follow-up of 126 months). In Group 2, three patients became eugastrinemic after nodal excision and total gastrectomy (mean follow-up of 212 months) and may represent primary nodal gastrinomas, and in one patient, liver metastases developed and the patient died. Four deaths occurred in a 27-year period, but only one was tumor-related. There was no significant difference in 20-year survival rates between the two groups (85% vs. 75%). It is concluded that 1) lymph node gastrinomas are usually metastatic from primary duodenal lesions, 2) although rare, nodal gastrinomas may occur as primary lesions, and 3) in the absence of hepatic metastases, lymph node gastrinomas, whether primary or metastatic, have a good prognosis and should not deter aggressive surgical treatment.
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PMID:Outcome of lymph node involvement in patients with the Zollinger-Ellison syndrome. 342 54

A double tumor model (3LL and EAT) was established in C57BL/6 mice. The primary 3LL tumor was growth-inhibited by EAT inoculated into the same host. Growth inhibition of the 3LL primary tumor depended on the number of EAT cells injected. Inhibition of the growth of the primary 3LL tumor was also observed after injection of the optimal number (10(7)) of EAT cells 24 h to 7 days before or after inoculation of 3LL cells. In contrast, metastasis of the 3LL tumor was only inhibited after simultaneous inoculation of 3LL and ETA cells. Moreover, EAT cells inhibited the growth of preformed 3LL-derived metastases after resection of the primary 3LL tumor. Although the EAT-induced stimulation of a host defense system is not excluded, the results are consisted with the continued release of growth inhibition factors from EAT cells acting on 3LL cells in the primary tumor and in lung metastases.
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PMID:Inhibition of Lewis lung tumor growth and metastasis by Ehrlich ascites tumor growing in the same host. 370 Apr 61

The secretion of calcitonin (CT) by thyroid C cells has been reported to be reduced by dopamine in vitro and by L-dopa in patients with medullary thyroid carcinoma (MTC). These results have suggested that dopa uptake ad decarboxylation to dopamine may play an inhibitory role in the control of CT secretion. We studied the effects of either L-dopa or bromocriptine, a dopamine agonist, on CT secretion in 11 patients with MTC. Seven patients had multiple endocrine adenomatosis type II (MEA II), 1 had MEA III, and 3 had sporadic MTC. Metastatic disease was confirmed in 8, was probable in 2, and was absent in 1. L-Dopa (500 mg orally) was given to 10 patients in 12 trials. Serum obtained serially for CT measurement RIA over a 4-h period showed a fall in 4 instances in 3 patients; there was no decrease in 7 patients. Absorption of L-dopa was confirmed by the finding of the expected rise in serum GH concentration in all nonresponders except 1. Bromocriptine administered in increasing doses (7.5-50 mg/day) for periods from 4-18 weeks in 5 patients with metastatic disease failed to lower the serum CT concentration in any patient. In 2 of 4 cases, pentagastrin-induced CT release was augmented during bromocriptine administration. These results show L-dopa suppression of CT secretion only in a minority of patients with MTC; the lack of response to bromocriptine suggessts that dopamine receptor stimulation by dopaminergic ergots does not inhibit CT secretion in this same group of patients.
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PMID:Effects of L-dopa and bromocriptine on calcitonin secretion in medullary thyroid carcinoma. 741 66

The potent vasoconstrictor endothelin-1 (ET-1) is at its highest concentration in the normal human ejaculate and is associated with the progression of metastatic prostate cancer. ET-1 protein expression is detected in situ in 14 of 14 primary cancers and 14 of 16 metastatic sites of human prostatic carcinoma. Exogenous ET-1 induces prostate cancer proliferation directly and enhances the mitogenic effects of insulin-like growth factor I, insulin-like growth factor II, platelet-derived growth factor, basic fibroblast growth factor, and epidermal growth factor in serum-free conditions in vitro. The ETA-selective receptor antagonist A-127722 inhibits ET-1-stimulated growth, but the ETB-selective receptor antagonist BQ-788 does not. ET-3, an ETB-selective agonist, also had no effect on prostate cancer growth. No specific ETB-binding sites could be demonstrated in any established human prostate cancer cell line tested, and ETB mRNA, detected by reverse transcription PCR, was reduced. The predominance of ETB binding on human benign prostatic epithelial tissue is not present in metastatic prostate cancer by autoradiography. In human prostate cancer progression to metastases, ET-1 and ETA expression are retained, whereas ETB receptor expression is reduced.
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PMID:Endothelin-1 production and decreased endothelin B receptor expression in advanced prostate cancer. 863 Sep 91

Cytotoxic strategies which are directed to tumor-associated antigens might be most beneficial for cancer patients with minimal tumor load such as in an adjuvant setting after initial therapy. We have recently described a highly potent single chain antibody-toxin, scFv(14E1)-ETA, which consists of the variable domains of the antibody 14E1 genetically fused to a truncated form of Pseudomonas exotoxin A. ScFv(14E1)-ETA specifically recognizes the human epidermal growth factor receptor (EGFR) and the oncogenically activated receptor variant EGFRvIII, which have been implicated in the development of various human malignancies. Here we have investigated the antimetastatic activity of bacterially expressed scFv(14E1)-ETA and its disulfide-stabilized derivative ds-scFv(14E1)-ETA in a novel model for disseminated disease which is based on murine renal carcinoma cells subsequently transfected with the E. coli beta-galactosidase gene, and human full-length or variant EGFR cDNAs. Intravenous injection of these Renca-lacZ/EGFR and Renca-lacZ/EGFRvIII cells in syngenic Balb/c mice led to the formation of pulmonary metastases which were readily detectable upon excision of the lungs and X-gal staining. Systemic treatment of mice with scFv(14E1)-ETA resulted in the complete suppression of Renca-lacZ/EGFRvIII metastasis formation and drastically reduced the number of pulmonary Renca-lacZ/EGFR tumor nodules. The ds-scFv(14E1)-ETA derivative where the antibody variable regions are connected by an artificial disulfide bond displayed improved thermal stability at physiological temperature but due to reduced cytotoxic activity was less potent than the original scFv(14E1)-ETA in metastasis suppression.
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PMID:Suppression of metastasis formation by a recombinant single chain antibody-toxin targeted to full-length and oncogenic variant EGF receptors. 1020 32

Pancreatic carcinoma still has the highest mortality rate in comparison to any other malignancy. Major reasons are late detection of disease, highly aggressive tumor growth and the early formation of metastases. Thus, novel effective therapies are urgently needed to improve the outcome of the patients. Overexpression of the epidermal growth factor receptor (EGFR) and its ligands has been implicated in the oncogenesis of pancreatic carcinoma and associated with an unfavorable prognosis. Consequently, the EGFR represents a specific target antigen suitable for immunotherapy. We generated a recombinant immunotoxin by fusing the anti-EGFR single chain fragment 425(scFv) to a truncated mutant of Pseudomonas Exotoxin A (ETA'). Using the expression vector pBM1.1, functional 425(scFv)-ETA' was periplasmically expressed under osmotic stress conditions in the presence of compatible solutes. The 72 kDa His10-tagged fusion protein was purified by a combination of metal-ion affinity and molecular size chromatography. Binding activity and specificity of the immunotoxin to the EGFR-positive pancreatic carcinoma cell line L3.6pl was confirmed by flow cytometry and ELISA. Finally, 425(scFv)-ETA' showed significant toxicity toward this cell line reaching 50% inhibition of cell proliferation at a concentration (IC50) of 7.5 ng/ml. This is the first report documenting the specific cytotoxicity of a recombinant immunotoxin towards metastatic pancreatic carcinoma cells, suggesting that EGFR-specific antibody toxins may become valuable therapeutic reagents for the treatment of pancreatic carcinoma.
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PMID:The recombinant anti-EGF receptor immunotoxin 425(scFv)-ETA' suppresses growth of a highly metastatic pancreatic carcinoma cell line. 1296 2

The essential fatty acid deficiency (EFAD) is a metabolic condition related to cancer development. We studied the effect of eicosapentaenoic acid (EPA, 20:5 n-3) and eicosatrienoic acid (ETA, 20:3 n-9), an essential fatty acid (EFA) and non-EFA respectively, on tumour cells parameters linked to tumour progression and metastases. Human tumour cell lines (T-24 from urothelium, MCF-7 from breast and HRT-18 from colon) were used. EPA showed an anti-proliferative effect on the three lines. ETA showed the following effects: in T-24, the lipid peroxidation was decreased and E-cadherin was undetectable; in MCF-7, increased E-cadherin expression enhanced the lipid peroxidation and decreased cell proliferation; on HRT-18, the E-cadherin expression and lipid peroxidation diminished, whereas cell proliferation was increased. In conclusion, EFA (20:5 n-3) exhibited beneficial effects, whereas unusual ETA showed an opposite effect on some tumour parameters. The possible riskiness of EFA-deprivation, along with the potential of EFA as natural nutrapeutic products for human tumour prevention and treatment, makes EFA worthy of further consideration.
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PMID:Effects of eicosatrienoic acid (20:3 n-9, Mead's acid) on some promalignant-related properties of three human cancer cell lines. 1451 60


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