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)

A center in Belfast, Northern Ireland, has established a register for tumors of the gastroenteropancreatic endocrine system. Carcinoid tumors occur most frequently. Of the non-carcinoid tumors, insulinomas, gastrinomas, and unknown types have the highest incidence, with other types being extremely rare. The potentially remediable nature of the tumors is stressed, and frequently a good quality of life can be experienced even in the presence of metastatic disease. The syndromes are probably underdiagnosed as they present with clinical features for which there are more common explanations, and appropriate diagnostic methods are therefore not used. The management of the syndromes is reviewed with particular emphasis on the treatment of patients with inoperable disease. Histamine (H2)-receptor antagonist therapy has made an impact in Zollinger-Ellison syndrome, and streptozotocin and somatostatin analogues can control tumor growth and endocrine syndromes, respectively.
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PMID:Neuroendocrine tumors. A European view. 287 46

Four patients with Zollinger-Ellison Syndrome (ZES) are presented to highlight the difficulties in the recognition, diagnosis and management of this rare disease. The presentation of ZES is usually indistinguishable from ordinary peptic ulcer disease and in those patients with symptoms not related to peptic ulcer, i.e., diarrhoea, as their main complaint, the diagnosis is often not even considered. A high index of suspicion is required, however, in patients with recurrent ulcers, multiple ulcers and in those with resistant or rapidly relapsing ulcers after conventional therapy. A presumptive diagnosis can be made by the demonstration of grossly elevated fasting serum gastrin levels combined with a secretin stimulation test in doubtful cases. The main problem is the location of the gastrin-secreting tumour which is usually pancreatic but often too small to be detected by currently available techniques. Histamine H2-receptor antagonists in high doses are effective in controlling the gastric acid hypersecretion which is chiefly responsible for the morbidity and mortality in ZES. They provide the treatment of choice in patients where the tumour cannot be located, though every attempt should be made to do this as surgery is the treatment of choice for this invariably malignant tumour. Total gastrectomy is now reserved for those patients in whom medical therapy has failed. The role of chemotherapy in metastatic disease has yet to be established.
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PMID:Zollinger-Ellison syndrome--report of four cases and review of literature. 614 89

Histamine type-2 receptor antagonists (H-2RA) have been used chronically to prevent dyspepsia in cancer patients subjected to immunotherapy with chronic indomethacin (Indo) and intermittent IL-2 in our cancer centre. We tested the effects of these agents during immunotherapy of C3H/HeJ mice transplanted s.c. with 5 x 10(5) C3L5 mammary adenocarcinoma cells. Tumor-transplanted mice were divided into groups receiving: (1) Indo (14 micrograms/ml); (2) H-2RA, i.e. (a) ranitidine at 28.6 micrograms/ml (Ran-lo) or 143 micrograms/ml (Ran-hi), or (b) famotidine (Fam) at 4.3 micrograms/ml, or (c) cimetidine (Cim) at 107 micrograms/ml, all in the drinking water on days 5-24; (3) IL-2 (1.5 x 10(3) Cetus U i.p. every 8 h on days 10-14 and 20-24); (4) combinations of H-2RA + Indo; or (5) combinations of H-2RA + Indo + IL-2. Animals were killed on day 24 for examination of primary s.c. tumor growth, secondary lung metastasis and splenocyte cytotoxicity against YAC-1 lymphoma cells (51Cr release assay). Results revealed: (1) primary tumor growth was reduced in mice treated with Fam + Indo, Indo + IL-2 and any of the H-2RA + Indo + IL-2 (no difference observed within the last two groups); (2) lung metastases decreased in mice treated with IL-2 alone, Indo + IL-2, and Indo + IL-2 + Ran-hi; (3) splenic cytotoxicity was suppressed in tumor-bearing controls, with partial restoration seen in Ran (both doses), Ran-lo + Indo, Ran-lo + Indo + IL-2, and Cim + Indo + IL-2 treated groups. Nearly complete restoration was seen in Cim, Cim + Indo, Indo + IL-2, Ran-hi + Indo + IL-2, and Fam + Indo + IL-2 groups. Thus, addition of H-2RA did not alter the overall therapeutic efficacy of the standard Indo + IL-2 tumor immunotherapy.
Clin Exp Metastasis 1993 May
PMID:Effects of histamine type-2 receptor antagonists on indomethacin and IL-2 immunotherapy of metastasis. 809 42

Although the majority of colorectal carcinomas express carcino-embryonic antigen (CEA), systemic anti-CEA antibody administration is an ineffective treatment for colorectal liver metastasis. A xenograft model of human colorectal carcinoma in the rat was used to determine anti-CEA antibody uptake into liver metastases. The influence of systemic (iliolumbar vein) or regional (gastroduodenal artery) delivery and effects of regional delivery of histamine, angiotensin II and vasopressin on anti-CEA antibody uptake by metastases were examined. Systemic antibody delivery achieved a median tumour:liver antibody uptake ratio of 1.60 (interquartile range (i.q.r.) 1.02-2.51). Regional delivery resulted in a similar median ratio of 1.61 (i.q.r. 1.22-2.46). Histamine and antibody delivered regionally produced a median tumour:liver ratio of 3.15 (i.q.r. 2.50-4.27), which was significantly greater than that obtained with systemic delivery (P = 0.004). Regional infusion of angiotensin resulted in a median (i.q.r.) ratio of 2.23 (1.58-2.49) and vasopressin in 2.15 (1.41-2.60), values that were not significantly different from those found with systemic or regional delivery alone. When both angiotensin and histamine were infused with antibody, the median tumour:liver ratio was 3.09 (i.q.r. 2.22-4.31), significantly greater than for systemic delivery (P = 0.01) but not significantly different from that obtained following the addition of histamine alone (P = 0.94). Histamine significantly increases antibody uptake in a model of liver metastasis and may improve the effectiveness of targeted immunotherapy in the treatment of colorectal liver metastasis.
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PMID:Histamine but neither angiotensin nor vasopressin increases antibody uptake into xenograft colorectal liver metastases. 842