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)

Polyglutamylation of (anti)folates catalyzed by folylpolyglutamate synthetase (FPGS) determines the retention of these compounds in the cell. This feature is essential for the activity of folates (e.g., folinic acid) and antifolates (e.g., methotrexate) in the treatment of cancer. A FPGS assay was developed using murine liver and was based on published methods, but had a novel analytic procedure. Tritiated glutamate and aminopterin served as substrates for FPGS, and after the reaction the mixture of substrates and products was separated by thin-layer chromatography. Results were verified by standard anion-exchange high performance liquid chromatography for folates. The assay was applied to measure the activity of FPGS in several cancer cell lines and human and murine (tumor) tissues. Cancer cell lines had a much higher activity (varying from 82 to 656 pmol diglutamate formed per hour per 10(6) cells) than murine bone marrow cells (35 pmol/h/10(6) cells). Murine gut mucosa had a very low FPGS activity compared to murine liver (7 vs. 24 pmol diglutamate/h/g wet weight), but the activity in murine colon tumors was comparable to or higher than that in liver (28-52 pmol diglutamate/h/g wet weight). A screening of 11 human colon tumors or metastases demonstrated that there was a large variation in FPGS activity in this tumor type, but overall the activity was higher in tumor tissue than in normal colon mucosa. The latter feature may increase the selectivity of antifolate-based chemotherapy of colon tumors. The FPGS assay described in this paper allows large-scale screening of cell lines and tissues, because of its rapid separation procedure by thin-layer chromatography.
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PMID:Screening of colon tumor cells and tissues for folylpolyglutamate synthetase activity. 852 66

We report the histological, immunohistochemical and ultrastructural changes in mice containing a chimeric glucagon-simian virus 40 T antigen (SV40Tag) gene. Transgene expression was detected in endocrine cells of pancreas, small and large intestine. Hyperplasia of glucagon-containing cells developed in pancreas and large bowel by gestational day 19. In large bowel, hyperplastic cells increased in number postnatally and invasive carcinomas were identified at 4 weeks; several animals had lymph node metastases. In contrast, no pathology was detected in the small bowel in any of the transgenic mice. Colonic tumours expressed SV40Tag, proglucagon-derived peptides and peptide YY (PYY); scattered cells contained cholecystokinin or glycoprotein hormone alpha-subunit. Somatostatin or serotonin was also detected in some tumours. By electron microscopy, the colonic tumours retained features of endocrine differentiation, but secretory granules were smaller than those of non-tumorous intestinal glucagon-producing L cells. In postnatal pancreas, atypical cells containing SV40Tag and glucagon were initially clustered at the periphery of islets; this atypical hyperplasia progressed to neoplasia by 11-12 weeks. Some neoplastic pancreatic cells contained glucagon, PYY or vasoactive intestinal peptide immunopositivity, but most were negative for all peptides; they contained immunoreactivity for tyrosine hydroxylase and by electron microscopy, pancreatic tumour cells had neuronal features. Pancreatic polypeptide was not detected in the non-tumorous islets of transgenic animals. This line of transgenic mice provides a model for the analysis of endocrine tumour progression in the gut and pancreas.
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PMID:Development of colonic and pancreatic endocrine tumours in mice expressing a glucagon-SV40 T antigen transgene. 860 71

Malignant melanoma, a common malignancy whose prevalence is increasing, represents 1-3% of cancers in the United States [1]. At autopsy, metastatic deposits to the gut are frequently found, but less than 9% of melanoma patients are diagnosed with gastrointestinal metastases while living [2]. Modern management includes aggressive surgical therapy to prolong survival and to palliate the disease [3]. Therefore, imaging of metastatic melanoma is clinically important to detect extent and determine whether the patient would benefit by surgery. Gastrointestinal metastases may manifest as mucosal or submucosal masses, serosal implants, or carcinomatosis [4]. They arise more commonly in the mesentery or distal small bowel than the proximal gastrointestinal tract or colon. The purpose of this essay is to illustrate the appearance of melanoma metastatic to the gastrointestinal tract on luminal contrast studies and on CT and to emphasize the importance of early investigation of gastrointestinal symptoms in a patient with a history of malignant melanoma.
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PMID:Malignant melanoma metastatic to the gastrointestinal tract. 861 May 55

nma, a novel gene, was isolated by using a subtractive hybridization technique in which the gene expression was compared in a panel of human melanoma cell lines with different metastatic potential. nma mRNA expression (1.5 kb) is high in poorly metastatic human melanoma cell lines and xenografts and completely absent in highly metastatic human melanoma cell lines. Fluorescence in situ hybridization combined with the analysis of a panel of human-rodent somatic cell hybrids indicated that the nma gene is located on human chromosome 10, in the region p11.2-p12.3. Sequence analysis of nma showed no homologies with other known genes or proteins, except for several partially sequenced cDNAs. The predicted amino acid sequence suggests that the protein encoded by nma contains a transmembrane domain. Expression of nma is high in human kidney medulla, placenta and spleen, low in kidney cortex, liver, prostate and gut and absent in lung and muscle. Whereas nma is not expressed in normal skin tissue, expression is high in melanocytes and in 3 out of 11 melanoma metastases tested.
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PMID:Expression of nma, a novel gene, inversely correlates with the metastatic potential of human melanoma cell lines and xenografts. 862 Dec 28

The present study was conducted to evaluate the current status of rectal carcinoids from multiple systemic aspects, based on extensive information provided by 1271 cases cited in 465 international articles published since 1912. Each case report was carefully read, computerized, and analyzed by the gut-pancreatic endocrinoma analysis system (Niigata Registry). To avoid case duplication, cases without individual identification, such as the age and sex of the patient, and those with identical clinical and laboratory data and institutes of source, were excluded. Where appropriate, selected cases from an overall gastrointestinal (GI) series consisting of 4461 cases similarly documented in the same Registry were referred to for comparison. The representative characteristics of rectal carcinoids consisted of a male preponderance, small-sized tumors of 10 mm or less at detection, predominant submucosal invasion with a relatively high incidence of metastases, a high incidence of hematogenous spread, a predominant histology of the B-type growth pattern, a low rate of silver reactivity, the infrequent association of carcinoid syndrome, and a relatively high rate of mortality within 5 years after removal of the lesions.
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PMID:Carcinoids of the rectum: an evaluation of 1271 reported cases. 901 86

Because SRS identifies 90% of hepatic metastatic disease and the addition of other studies (ultrasonography, C.T. MRI, and selective mesenteric angiography) identities only 4% more, the identification of a primary lesion with SRS obviates for the most part the use of further investigations. If SRS is negative, additional studies should only be undertaken if surgery is contemplated. Because SRS may only localize 60%-70% of primary gut NETs, an additional 10%-15% may be identified by undertaking additional studies. The most sensitive test, STIR-MRI, should be undertaken next, but because it is not widely available, pancreatic protocol CT scan is almost as effective in identification of a primary lesion. If a primary gastrinoma cannot be identified by SRS or STIR-MRI, endoscopic ultrasonography should be undertaken because duodenal gastrinomas are often minute and multicentric. A similar strategy applies for insulinomas because up to 40% cannot be located by SRS and the majority are located in the pancreatic head. Thus, STIR-MRI followed by endoscopic ultrasonography is the most appropriate course. Although calcium provocation-angiography is highly effective in the identification of insulinomas, it is significantly more invasive and should be used only as a last resort. Of particular interest is the observation that in the study of gastrinomas, SRS altered clinical management in almost 50% of patients. This reflected the ability of SRS not only to identify the primary tumor location but clarify equivocal localization results generated by conventional imaging studies. It thus seems that the simplicity, superior sensitivity, high specificity, and cost-effectiveness of SRS mandate that it be the imaging modality in patients with gastrinomas. Because the cost of an SRS is $1800 and may obviate the need for multiple other topographic studies that are at least as expensive, the fiscal dictates further warrant the use of this study as the initial topographic investigation. These observations are probably applicable to all gut NETs, although the likelihood of primary identification in the instance of insulinoma patients may be somewhat less. The timely and cost-effective establishment of the type of NET, its primary site, and the detection metastatic spread will enable determination of the appropriate management strategy.
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PMID:Approaches to the diagnosis of gut neuroendocrine tumors: the last word (today). 902 13

Echinococcosis is a human disease caused by the larval form of Taenia echinococcus, which lives in the gut of the dog, wild canides and other carnivorous animals which represent the definitive hosts and involves as intermediate hosts both domestic and wild animals. Humans become accidental intermediate hosts by ingesting Taenia eggs. The main species pathogenic for man are E granulosus causing cystic echinococcosis with worldwide distribution and endemic in sheep and cattle breeding countries, and E multilocularis causing alveolar echinococcosis, with preferential distribution in the northern hemisphere. After ingestion of contaminated food, hexacanth embryos migrate by the portal system to liver and later lung, brain and other tissues. Symptoms are related to both cyst location and size. E granulosus infection of the central nervous system (CNS) may be primary or secondary and has been estimated to be low (2%). Sharply demarcated, spherical and intraparenchymal, cysts may reach a large size causing neurological symptoms. Spilling of cyst fluid due to trauma or surgery may trigger anaphylaxis as well as disseminated infection. Host reaction is minimal in the brain but a foreign giant cell reaction may develop. E multilocularis develops within the liver as a rapid invasive pseudomalignant growth and may metastasize to the CNS, where estimated incidence reaches 5%. Hydatid antigens induce an immune reaction in the host which is helpful for the diagnosis. DNA probes and PCR may be applied to differentiate between Echinococcus spp. Although the host develops an immunological protection from reinfection, the parasite evades host immune attack. A wide range of evasion mechanisms have been advanced, including a barrier for host cells due to hydatid cyst laminated cuticle, polyclonal activation of lymphocytes by parasite soluble antigens, and depression of host cell immune responses. Chronic stimulation of the host by cyst fluid antigens leads to increased specific IgG4 production, which might act as blocking antibodies against anaphlaxis suggestive of host response immunomodulation.
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PMID:Echinococcosis. 903 73

Gastrointestinal stromal tumors (GISTs), as currently defined, are mesenchymal tumors of the gastrointestinal tract composed of spindled and/or epithelioid stromal cells that are neither mature Schwann cells nor smooth muscle cells. Many studies have lumped GISTs from all gut sites, when in fact these tumors differ histologically by location. In this study, we evaluated a set of parameters by both univariate and multivariate analysis to determine which parameters correlated with metastases in 36 GISTs from the jejunum and ileum, exclusively. The parameters included organoid architecture, cellularity, mitotic counts, epithelioid cell shape, mucosal invasion, tumor size, skeinoid fibers, nuclear pleomorphism, ischemic necrosis, immunohistochemical differentiation, and proliferating cell nuclear antigen labeling. We evaluated these retrospectively without knowledge as to the metastatic outcome of the tumors. By univariate analysis, dense cellularity, mitotic counts, epithelioid cell shape, mucosal invasion, and size were statistically significant correlates with metastases. By multivariate analysis, only dense cellularity and mitotic counts were independent correlates with metastases. Whether these features are useful predictors of behavior remains to be tested.
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PMID:Stromal tumors of the jejunum and ileum. 907 27

A great number of gut endocrine tumours show high expression of receptors for neuropeptides, such as SRIF and VIP. The expression of ssts is essential for the control of hormonal hypersecretion and tumour growth by octapeptide somatostatin analogues. Five different sst subtypes, named sst1-5, have been cloned and characterized. The therapeutic efficacy of the octapeptide analogues is determined by the expression of sst2 (sst3) and sst5 on the tumour. In general, there is a predominant expression of sst1 and sst2 mRNA in gut endocrine tumours. In vivo sst scintigraphy, after injection of [111In]pentetreotide, provides a useful tool for the diagnostic work-up of patients with these tumours. This technique can be used for the localization of the primary tumour(s), for the determination of the extent of metastatic spread and for the selection of potential candidates for therapy with (radiolabelled) octapeptide analogues. Differentiated gut endocrine tumours also show a high expression of VIP-Rs. However, undifferentiated tumours show VIP-R expression to a smaller degree. In vivo scintigraphy with 123I-labelled VIP is a sensitive technique for the in vivo identification of gut endocrine tumours and their metastases. The functional role of the tumoral VIP-Rs is still unclear and at present there are no known therapeutic applications for VIP-R agonists or antagonists in humans.
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PMID:Peptide receptors in gut endocrine tumours. 911 13

This study aimed at obtaining a better understanding of the malignant characteristics of carcinoids (gut endocrinomas) of the digestive system. After excluding cases with no possible individual identification as for age and sex, 2001 carcinoid cases with metastases among 5647 of the digestive system computerized in the Niigata Registry were thus subject to the present analysis. These cases were divided into two groups: [A] 1719 with ordinary carcinoid histology and [B] 282 with atypical varieties including argyrophil (endocrine) cell carcinomas, small/oat cell carcinomas of endocrine type, composite carcinoid-adenocarcinoma varieties and other neuroendocrine tumors. In many aspects, a comparative analysis demonstrated statistical differences between [A] and [B]: average age (55.7 vs 60.1), the rates of metastases (34.4% vs 55.6%), the association of carcinoid syndrome (21.4% vs 2.8%), tumor size 20mm or less (42.2% vs 22.5%), depth of invasion down to the submucosa (21.6% vs 11.7%) and transmural invasion (34.3% vs 47.7%), immunohistochemistry of neuron-specific enolase (86.5% vs 66.7%), chromogranin (86.1% vs 67.6%), vasointestinal polypeptides, ACTH and alpha-fetoprotein, and the 5-year survival rate (61.4% vs 17.9%). No statistical differences between these two groups were found in the male to female ratio, serotonin activities and Grimelius argyrophilia. Although no generally acceptable definite criteria and definition for atypical carcinoid varieties have yet established, neoplasias of this category seem to have a wide range of histological, histochemical, immunohistochemical, ultrastructural and biochemical features that may mostly be placed in between ordinary carcinoids and ordinary carcinomas.
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PMID:Statistical evaluation of 2001 carcinoid cases with metastases, collected from literature: a comparative study between ordinary carcinoids and atypical varieties. 964 27


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