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)

An ion exchange automatic chromatographic analysis of the free amino acid concentrations of 18 human glial tumours and of 4 human fetal brains was carried out and the concentrations were compared to those of 13 biopsy specimens of normal adult brain. In addition, the concentrations of the amino acids of the glial tumours were compared to those of 7 intracerebral metastases of various origin. The chromatograms of several tumour specimens showed an unidentified peak overlapping proline. As far as the amino acid concentrations are concerned they varied depending upon the origin of the sample. The concentrations of most amino acids were higher in fetal brain than in adult brain with the exception of aspartic acid, glutamic acid, glutamine, cystathionine and GABA. Two peptides: glutathione and homocarnosine were absent in fetal brain and were present in adult brain. In glial tumours, homocarnosine and some amino acids, namely aspartic acid, glutamic acid and GABA, showed lower concentrations than in normal brain. Some amino acids were in the same concentration as in normal brain: taurine, phosphoethanolamine, glutamine and cystathionine. Most of the others were in higher concentrations than in normal brain, mainly proline. The results suggest that the concentrations of 5 compounds: taurine, proline, cystathionine, GABA and homocarnosine, taken as a whole, provide information on the origin of the sample.
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PMID:Free amino acids and related substances in human glial tumours and in fetal brain: comparison with normal adult brain. 18 55

Cohorts of 4- to 5-wk-old female Fischer 344 rats received four biweekly 1.5-mg doses of N-methyl-N-nitrosourea (MNU) intravesically and were sacrificed at various intervals. By 13 wk after initiation of the carcinogen, all animals have flat epithelial atypia and/or papillary transitional cell bladder carcinomas, and 67% of the lesions are histological Grade II or III. By 20 wk, 83% have gross bladder wall muscle-invasive tumors that eventually kill the host. There was no gross evidence of visceral metastases in any animal. This rat model of transitional cell carcinoma of the bladder is useful because: (a) all animals develop progressive neoplastic changes in situ within 4 mo after initiation of MNU treatment; (b) these lesions progress to grossly detectable bladder tumors which invade the bladder wall and kill the host; (c) this full progression of bladder epithelial cells from atypical hyperplasia through flat carcinoma in situ to transitional cell carcinoma occurs at discrete time points; (d) the histology of the grossly detectable tumors is that of invasive transitional cell carcinomas; and (e) no leukemias, breast cancers, lymphomas, or other non-bladder tumors are induced. Six MNU-induced bladder wall-invasive tumors were karyotyped, and all tumors were diploid with 42 chromosomes. Three of the tumors had apparently normal karyotypes, while three tumors had karyotypes containing one or more cytogenetic structural markers. One of these markers (i.e., 8p+) was observed in two of the three tumors. The level of expression of total ras p21 (N-, Ki-, and Ha-ras p21) and codon 12-mutated c-Ha-ras p21 (i.e., glycine to glutamic acid mutation in codon 12) in a series of these MNU-induced bladder tumors was determined by Western blot analysis. No increase in the total ras p21 nor any expression of codon 12-mutated c-Ha-ras p21 was detected in any of these tumors.
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PMID:Characterization of an N-methyl-N-nitrosourea-induced autochthonous rat bladder cancer model. 220 31

Laminin-1, a major basement membrane glycoprotein, promotes tumor cell malignancy. Incubation of B16-F10 melanoma cells with a peptide containing an active sequence in laminin-1, designated AG-73 (leu-glu-val-glu-leu-ser-ile-arg; LQVQLSIR), enhances in vitro adhesion, migration, invasion and gelatinase production and in vivo lung colonization and metastases to the liver. In the current study, we have tried to define the mechanism of enhancement of liver metastases induced by AG-73 using B16-F10 murine melanoma cells selected for adhesion on AG-73-coated dishes. Cells were sequentially selected for adhesion more than 30 times and then characterized. AG-73 selected cells had much longer cytoplasmic processes and occasionally formed nodular aggregates. AG-73 selected cells attached 1.2- to 1.5-fold better to both AG-73 and laminin-1, were able to invade through the Matrigel-coated filter up to 6-fold more, grew s.c. 1.5-2 times faster, produced twice the number of lung colonies, and showed more liver nodules (12 of 28 vs. 1 of 27) than parental cells. Our data demonstrate that the enhanced malignant phenotype of B16-F10 cells can be observed in the absence of added peptide with the adhesion-selected cells.
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PMID:Liver metastasis formation by laminin-1 peptide (LQVQLSIR)-adhesion selected B16-F10 melanoma cells. 913 81

We have identified and characterized a 55 kDa nuclear protein (referred to as nmt55) from human breast tumors and MCF-7, human adenocarcinoma breast cell line, using site-directed monoclonal antibodies. Measurements of estrogen receptors (ER) and progesterone receptors (PR), by ligand binding assays, in cytosols of 63 human breast tumors permitted classifications of these tumors into four phenotypes (ER+/PR+, ER+/ PR-, ER-/PR-, ER-/PR+). Nuclear protein (nmt55) expression in these tumors, as determined from Western blot analyses, showed a statistically significant association (p = 0.001) with tumor hormonal phenotype. Review of the pathologic characteristics of tumors analyzed suggested that lack of nmt55 expression was significantly associated with mean tumor size (p < 0.03), mean ER (p = 0.001) and mean PR (p < 0.002), but was not associated with tumor stage, grade, or type. To further study this protein, we cloned and sequenced a 2.5 kb cDNA using a monoclonal antibody to nmt55. The complete predicted open reading frame encodes a protein with 471 amino acids and a calculated molecular mass of 54,169 Da. The deduced amino acid sequence exhibited unique regions rich in glutamine, histidine, arginine, and glutamic acid. Northern blot analysis of RNA from MCF-7 cells and ER+/PR+ human breast tumors showed a 2.6 kb mRNA. Southern blot analysis suggested the presence of a single copy of this gene. Chromosomal mapping, using fluorescent in situ hybridization (FISH), located nmt55 gene to the X chromosome, region q13. The extensive homology between nmt55 and RNA binding proteins suggested that nmt55 may be involved in hnRNA splicing. The strong association observed between expression of nmt55, tumor hormonal phenotype, mean tumor size, mean ER, and mean PR content suggests that loss of nmt55 expression may be related to events involved in hormone insensitivity, tumor differentiation, and unregulated tumor cell growth and metastases.
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PMID:Loss of expression of a 55 kDa nuclear protein (nmt55) in estrogen receptor-negative human breast cancer. 936 Aug 42

Of the rare pancreatic endocrinomas, glu-cagonomas, either with or without diabetico-dermatogenic syndrome (DDS), are probably third in frequency after insulinomas and gastrinomas. This study was carried out to evaluate the present status of glucagonoma/DDS in a statistically reliable number of cases and to provide precise information to investigators actively working in this particular field of research. A total of 407 cases of glucagonoma were collected from the international literature and evaluated according to characteristic clinicopathologic features. Findings were: (1) The incidence of DDS was 57.2% (233/407). (2) The tail of the pancreas was predominantly involved, in 53.7% (213/397). (3) One-third of the tumors (80 of 276 for whom size was recorded; 29.0%) measured 20 mm or less. (4) Metastases occurred in 51.4% (209/407) and malignant tumors in 60.7% (247/407). (5) Multiplicity occurred in 11.8% (48/407), and associated multiple endocrine neoplasia type 1 in 13. 0% (53/407). (6) In the patients with DDS, the rates of hyperglucagonemia, necrolytic migratory erythema, diabetes mellitus, loss of weight, hypo-aminoacidemia, or anemia, as representative constituents of DDS, were all higher than rates in the overall series (P < 0.01). (7) The 10-year survival rate in the 233 patients with DDS was 51.6% in those with metastases and 64.3% in those without metastases (P < 0.001).
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PMID:Glucagonomas/diabetico-dermatogenic syndrome (DDS): a statistical evaluation of 407 reported cases. 988 Jul 81

We have carried out a genetic screen designed to isolate regulators of teashirt expression. One of these regulators is the Grunge gene, which encodes a protein with motifs found in human arginine-glutamic acid dipeptide repeat, Metastasis-associated-like and Atrophin-1 proteins. Grunge is the only Atrophin-like protein in Drosophila, whereas several exist in humans. We provide evidence that Grunge is required for the proper regulation of teashirt but also has multiple activities in fly development. First, Grunge is crucial for correct segmentation during embryogenesis via a failure in the repression of at least four segmentation genes known to regulate teashirt. Second, Grunge acts positively to regulate teashirt expression in proximoventral parts of the leg. Grunge has other regulatory functions in the leg, including the patterning of ventral parts along the entire proximodistal axis and the proper spacing of bristles in all regions.
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PMID:Grunge, related to human Atrophin-like proteins, has multiple functions in Drosophila development. 1187 8

Chemokines have pleiotropic effects in regulating immunity, angiogenesis, stem cell trafficking, and mediating organ-specific metastases of cancer. In the context of angiogenesis, the CXC chemokine family is a unique group of cytokines known for their ability to behave in a disparate manner in the regulation of angiogenesis. The glutamic acid-leucine-arginine (ELR+) CXC chemokines are potent promoters of angiogenesis, and mediate their angiogenic activity via signal-coupling of CXCR2 on endothelium. By contrast, members of the CXC chemokine family, such as platelet factor-4 (PF4; CXCL4) and interferon-inducible CXC chemokines are potent inhibitors of angiogenesis, and use CXCR3 on endothelium to mediate their angiostatic activity. This review will discuss the biology of CXC chemokines in the context of angiogenesis related to cancer.
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PMID:Cancer CXC chemokine networks and tumour angiogenesis. 1651 Feb 80

Estradiol (E2) and estrogen receptor (ER) signaling have been implicated in the development and progression of several cancers. Emerging evidence suggests that the status of ER coregulators in tumor cells plays an important role in hormonal responsiveness and tumor progression. Proline, glutamic acid, and leucine-rich protein-1 (PELP1/MNAR)-a novel ER coactivator that plays an essential role in the ER's actions and its expression-is deregulated in several hormonal responsive cancers. The precise function of PELP1/MNAR in cancer progression remains unclear, but PELP1 appears to function as a scaffolding protein, coupling ER with several proteins that are implicated in oncogenesis. Emerging evidence suggests that PELP1/MNAR increases E2-mediated cell proliferation and participates in E2-mediated tumorigenesis and metastasis.
Clin Exp Metastasis 2006
PMID:Comprehensive analysis of recent biochemical and biologic findings regarding a newly discovered protein-PELP1/MNAR. 1682 28

Polymeric micelles are promising nanocarriers, which might enhance the efficacy of antitumor drugs. Herein, polymeric micelles incorporating dichloro(1,2-diamino-cyclohexane)platinum(II) (DACHPt), the oxaliplatin parent complex, were prepared through the polymer-metal complex formation of DACHPt with poly(ethylene glycol)-b-poly(glutamic acid) [PEG-b-P(Glu)] block copolymer having different lengths of the poly(glutamic acid) block [p(Glu): 20, 40, and 70 U]. The resulting micelles were studied with the aim of optimizing the system's biological performance. DACHPt-loaded micelles (DACHPt/m) were approximately 40 nm in diameter and had a narrow size distribution. In vivo biodistribution and antitumor activity experiments (CDF1 mice bearing the murine colon adenocarcinoma C-26 inoculated subcutaneously) showed 20-fold greater accumulation of DACHPt/m at the tumor site than free oxaliplatin to achieve substantially higher antitumor efficacy. Moreover, the micelles prepared from PEG-b-P(Glu) with 20 U of P(Glu) exhibited the lowest non-specific accumulation in the liver and spleen to critically reduce non-specific accumulation, resulting in higher specificity to solid tumors. The antitumor effect of DACHPt/m was also evaluated on multiple metastases generated from intraperitoneally injected bioluminescent HeLa (HeLa-Luc) cells. The in vivo bioluminescent data indicated that DACHPt/m decreased the signal 10-to 50-fold compared to the control indicating a very strong antitumor activity. These results suggest that DACHPt/m could be an outstanding drug delivery system for oxaliplatin in the treatment of solid tumors.
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PMID:Optimization of (1,2-diamino-cyclohexane)platinum(II)-loaded polymeric micelles directed to improved tumor targeting and enhanced antitumor activity. 1762 62

Detection of HER2-overexpression in tumors and metastases is important for the selection of patients who will benefit from trastuzumab treatment. Earlier investigations showed successful imaging of HER2-positive tumors in patients using indium- or gallium-labeled Affibody molecules. The goal of this study was to evaluate the use of (99m)Tc-labeled Affibody molecules for the detection of HER2 expression. The Affibody molecule Z(HER2:342) with the chelator sequences mercaptoacetyl-Gly-Glu-Gly (maGEG) and mercaptoacetyl-Glu-Glu-Glu (maEEE) was synthesized by peptide synthesis and labeled with technetium-99m. Binding specificity, cellular retention, and in vitro stability were investigated. The biodistribution of (99m)Tc-maGEG-Z(HER2:342) and (99m)Tc-maEEE-Z(HER2:342) was compared with (99m)Tc-maGGG-Z(HER2:342) in normal mice, and the tumor targeting properties of (99m)Tc-maEEE-Z(HER2:342) were determined in SKOV-3 xenografted nude mice. The results showed that the Affibody molecules were efficiently labeled with technetium-99m. The labeled conjugates were highly stable in vitro with preserved HER2-binding capacity. The use of glutamic acid in the chelator sequences for (99m)Tc-labeling of Z(HER2:342) reduced the hepatobiliary excretion 3-fold with a single Gly-to-Glu substitution and 10-fold with three Gly-to-Glu substitutions. (99m)Tc-maEEE-Z(HER2:342) showed a receptor-specific tumor uptake of 7.9 +/- 1.0 %IA/g and a tumor-to-blood ratio of 38 at 4 h pi. Gamma-camera imaging with (99m)Tc-maEEE-Z(HER2:342) could detect HER2-expressing tumors in xenografts already at 1 h pi. It was concluded that peptide synthesis for the coupling of chelator sequences to Affibody molecules for (99m)Tc labeling is an efficient way to modify the in vivo kinetics. Increased hydrophilicity, combined with improved stability of the mercaptoacetyl-triglutamyl chelator, resulted in favorable biodistribution, making (99m)Tc-maEEE-Z(HER2:342) a promising tracer for clinical imaging of HER2 overexpression in tumors.
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PMID:(99m)Tc-maEEE-Z(HER2:342), an Affibody molecule-based tracer for the detection of HER2 expression in malignant tumors. 1794 27


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