Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MEA I and II are two genetically distinct tumor endocrinopathies, both showing autosomal dominant inheritance. Little overlap exists between these conditions, and that which is present can be explained on the basis of two mutually exclusive factors: (1) the secondary consequences of hormone excess on another endocrine gland or (2) the fact that both tumor syndromes appear to result from genetically faulty differentiation of neuroectoderm. A seemingly disproportionate amount of effort has been expended on study of the MEA syndromes. However, there would seen to be ample justification for this interest: 1) The MEA syndromes, unlike most neoplastic conditions, are hereditary and can be readily detected and more expeditiously treated; 2) hormone radioimmunoassay has greatly facilitated diagnosis in asymptomatic individuals; and (3) probably most importantly, study of these syndromes has provided considerable insight into the embryologic origin of the endocrine system. It is conceivable that knowledge gained from these conditions may stimulate further inquiry into the processes whereby neoplasia occurs in endocrine tissue and thus lead the way to the development of effective therapy for a host of hormone-producing tumors.
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PMID:Multiple endocrine adenomatosis syndromes. 0 2

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

A high percentage of human breast and ovarian tumors display amplified c-erbB-2 gene copies, leading to overexpression of the growth factor receptor. Its membrane location and elevated expression make the erbB-2 protein an appropriate target for a directed tumor therapy. We have used recombinant DNA technology to produce a single-chain antibody-exotoxin A (scFv-ETA) fusion protein which specifically binds the human erbB-2 receptor. The scFv portion is composed of the heavy- and light-chain variable domains of a monoclonal antibody which recognizes the extracellular domain of the human erbB-2 receptor. The bacterially produced scFv-ETA protein was shown to bind specifically to cells expressing the human erbB-2 protein. The scFv-ETA inhibits protein synthesis in erbB-2-expressing tumor cells at doses ranging from 2 to 200 ng/ml and is cytotoxic for these cells at equivalent doses. In athymic nude mice, administration of the scFv-ETA inhibited the growth of erbB-2-overexpressing human ovarian carcinoma cells.
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PMID:Selective inhibition of tumor cell growth by a recombinant single-chain antibody-toxin specific for the erbB-2 receptor. 135 32

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

We have outlined the symptoms, diagnostic procedures and operative treatment of "multiple endocrine adenomatosis" (MEA I, IIa und IIb). The priority of the operative procedure whenever two or more clinical syndromes in a patient with MEA are present and the possibility of multiple tumors has to be considered carefully. When there is a tumor of an endocrine organ, it should always bethought about the MEA-syndrome. We report about 9 patients seen in our hospital.
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PMID:[Disease picture and operative therapy in multiple endocrine adenomatoses (MEA sydrome)]. 610 38

The 24 endocrine pancreatic tumors and 14 carcinoids were examined immunohistochemically for cholecystokinin, insulin, gastrin, GIP, glucagon, sercretin, VIP, motilin, neurotensin, pancreatic polypeptide (PP), somatostatin, and ACTH. In 12 tumors of the pancreas more than one peptide-containing cell type was observed. The clinical symptoms showed hypersecretion of only one of the hormones, however. The midgut carcinoids (jejunum, appendix) represented the classical view of the carcinoid as an argentaffin cell tumor secreting 5-hydroxytryptamine. Tumors originating in the foregut (bronchus, stomach, duodenum) and hindgut carcinoids (rectum) were nonargentaffine, containing and secreting various polypeptide hormones. We conclude that light microscopic immunohistochemical methods are useful in distinguishing endocrine from nonendocrine tumors and multihormonal syndromes (MEA) in the classification of predominant hormone-secreting tumors.
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PMID:[Endocrine tumors of the gastrointestinal and pancreatic systems. Multiple endocrine adenoma from another viewpoint]. 610 39

Details of health, with particular reference to endocrinopathy, were acquired on all living and decreased members of a 4 generation family. Five members were found to be affected with MEA-I. Hyperparthyroidism was the most frequently diagnosed endocrinopathy, but pancreatic tumors were also found to be involved. No indications of the involvement of pituitary tumors were observed. A mediastinal tumor accompanied by a thymoma was also observed. None of the children under 18 years of age were affected. Genetic analysis confirmed the concept that the syndrome follows an autosomal dominant mode of inheritance with virtually complete penetrance but variable expressivity. A careful investigation at regular intervals of high risk members of an affected family is recommended for proper medical management of the condition.
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PMID:A kindred with 5 cases of multiple endocrine adenomatosis type I. 611 2

1. We characterized specific 125I-endothelin-1 (125I-ET-1) binding sites in microvessels isolated from human meningiomas, using an in vitro quantitative receptor autoradiographic technique coupled to a radioluminographic imaging plate system. 2. This newly developed and highly sensitive method revealed high-affinity ET receptors present in pellet sections of the microvessels from all the meningiomas studied, regardless of histological subtypes (dissociation constant, 1.2 +/- 0.3 nM; maximum binding capacity, 185 +/- 56 fmol/mg; means +/- SE for nine tumors). 3. In five cases of meningiomas, ET-3 competed for 125I-ET-1 binding to microvessels from those tumors with a low affinity [50% inhibiting concentration (IC50) of 1.6 +/- 0.4 x 10(-6) M], and a selective ETB receptor agonist, sarafotoxin S6c, up to 10(-6) M, did not displace ET binding from the sections. 4. In the sections of microvessels from four other tumors, biphasic competition curves were obtained in the case of incubation in the presence of increasing concentrations of ET-3, with an IC50 of 1.1 +/- 0.2 x 10(-9) M for the high-affinity component and 1.6 +/- 0.3 x 10(-6) M for the low-affinity component, respectively. In addition, S6c competed for ET binding to those sections (IC50 = 2.3 +/- 0.2 x 10(-10) M) and 10(-6) M S6c displaced 30% of the control, corresponding to the high-affinity component of competition curves obtained in the presence of ET-3. 5. Our results suggest that (a) capillaries in human meningiomas express a large number of high-affinity ETA (non-ETB) receptors with a small proportion of ETB receptors, and (b) ET may have a role in neovascularization, tumor blood flow, and/or function of the blood-tumor barrier in meningioma tissues by interacting with specific receptors present on the surface of the endothelium.
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PMID:Endothelin receptor in microvessels isolated from human meningiomas: quantification with radioluminography. 755 32

Many human tumors over-express erbB-2 and EGF receptors. The membrane localization of these receptor tyrosine kinases make them appropriate targets for directed tumor therapy. We have used recombinant DNA technology to produce single-chain antibody exotoxin A (scFv-ETA) fusion proteins which specifically bind the erbB-2 and EGF receptors. The scFv portion is composed of the heavy- and light-chain variable domains of monoclonal antibodies which recognize the extracellular portion of each receptor. We have previously described the anti-tumor activity of the bacterially produced scFv(FRP5)-ETA directed to the erbB-2 receptor. In this paper we describe the characteristics of scFv(225)-ETA, a protein which binds the EGF receptor. The bacterially produced recombinant protein binds to the receptor with high affinity and inhibits the in vitro growth of the EGF receptor over-expressing tumor cell lines A431 and MDA-MB468. Combination treatment with scFv-(FRP5)-ETA and scFv(225)-ETA led to an additive inhibitory effect on the in vitro growth of A431 cells. SKBR3 cells expressing low levels of EGF receptor but high levels of p185erbB-2 were not affected by scFv(225)-ETA treatment but were sensitive to scFv(FRP5)-ETA. Stimulation of SKBR3 cells and HCII RI#11 mouse mammary epithelial cells expressing the human erbB-2 with EGF led to an increase in scFv(FRP5)-ETA activity, showing that the EGF-induced activation of erbB-2 can potentiate the action of the erbB-2-directed toxin. Treatment of athymic nude mice with scFv(FRP5)-ETA and the combination of both scFv-ETA proteins led to the transient arrest of growth of established A431 tumors. scFv(225)-ETA treatment alone was the most effective, leading to tumor shrinkage during the course of treatment, whereas treatment with the parental monoclonal antibody 225 led to retarded tumor growth.
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PMID:EGF receptor and p185erbB-2-specific single-chain antibody toxins differ in their cell-killing activity on tumor cells expressing both receptor proteins. 781 46


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