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)

Mucins are large molecular weight glycoproteins characterized by carbohydrate sugars attached via 'O-glycosidic' linkages to serine or threonine. Mucins are synthesized by a variety of epithelial tissues as membrane-bound or secreted proteins, encoded by several distinct mucin genes. Numerous alterations of mucin-associated carbohydrates can be detected in neoplastic epithelial tissues and on circulating mucins in patients with adenocarcinomas. The expression of various sialyosylated-carbohydrate epitopes may correlate with poor prognosis and enhanced metastatic disease in colorectal adenocarcinomas. Mucin-associated carbohydrate and peptide antigens are currently being investigated for their role in cancer diagnosis, monitoring for progression or metastases, immunotherapy and immunosuppression.
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PMID:Carbohydrate antigens on cancer-associated mucin-like molecules. 172 30

Fourteen hormone-producing gastrointestinal tract tumors were tested for their content of somatostatin (SRIH) receptors, using receptor autoradiography and in vitro binding assay with tumor homogenates. All four gastrinomas tested had high levels of SRIH receptors, as did two of five insulinomas and four of five vasoactive intestinal peptide-producing tumors. Receptor visualization was obtained with two different radioligands, either a SRIH-28 analog, [125I]-[Leu8,D-Trp22,Tyr25]SRIH-28, or a SRIH octapeptide, the [125I]Tyr3 derivative of SMS 201-995 [H-DPhe-Cys-Phe-DTrp-Lys-Thr-Cys-Thr(ol)], [125I]204-090. In both cases receptors were localized over the tumor cell area only. Biochemical and pharmacological analyses of one insulinoma and two vipomas revealed saturable, high affinity binding sites with pharmacological specificity for SRIH. However, differences in receptor affinity of selected SRIH analogs, in particular SRIH-28 and SRIH octapeptides, were found between the insulinomas and the two other tumor types, vipoma and gastrinoma. The presence of SRIH receptors on various hormone-producing gastrointestinal tumors suggests that at least part of the beneficial effects of chronic therapy with SRIH analogs may be mediated through such membrane-bound receptors located on the tumor itself. SRIH receptor measurement may be of prognostic value in assessment of the therapeutic efficacy of SRIH analogs. They may also be of diagnostic value, if used as in vivo markers for the localization of small hormone-producing gastrointestinal tumors or their metastases.
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PMID:Hormone-producing gastrointestinal tumors contain a high density of somatostatin receptors. 282 49

Oncogenes encoding serine/threonine or tyrosine kinases were introduced into the established rodent fibroblast cell line NIH 3T3 and tested for tumorigenic and metastatic behavior in T cell-deficient nude mice. Transforming oncogenes of the ras family were capable of converting fibroblast cell lines to fully metastatic tumors. Cell lines transformed by the kinase oncogenes mos, raf, src, fes, and fms formed experimental metastases and (in some cases) these genes were more efficient at metastatic conversion than a mutant ras gene. In contrast, cells transformed by either of two nuclear oncogenes, myc or p53, were tumorigenic when injected subcutaneously but were virtually nonmetastatic after intravenous injection. These data demonstrate that, in addition to ras, a structurally divergent group of kinase oncogenes can induce the metastatic phenotype.
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PMID:Transformation by oncogenes encoding protein kinases induces the metastatic phenotype. 365 11

By means of a radioimmunoassay, which utilized [125I]-epiglycanin and anti-epiglycanin antiserum induced in rabbits by injections of viable TA3-Ha ascites cells with Freund's complete adjuvant, picogram quantities of epiglycanin could be detected. Anti-epiglycanin antiserum was similarly produced in allogeneic mice. Unlabeled epiglycanin lost the capacity to compete with [125I]epiglycanin in the radioimmunoassay as a result of periodate oxidation or incubation with endo-alpha-N-acetyl-D-galactosaminidase (Diplococcus pneumoniae), an enzyme found to cleave only the disaccharide beta-D-galactopyranosyl-(1----3)-2-acetamido-2-deoxy-D-galactose chain from serine or threonine residues in epiglycanin. Glycosylhydrolases known to cleave alpha-D-mannose, beta-D-galactose (1,4-linked), beta-N-acetyl-D-glucosamine, and alpha-N-acetyl-D-galactosamine did not reduce the activity of epiglycanin. Neuraminidase enhanced the activity twofold to fivefold. The finding that little or no activity was demonstrated by the disaccharide, the reduced disaccharide, or other glycoproteins containing the same disaccharide chain suggested that the antigenic determinant probably involved the disaccharide and a unique amino acid sequence at the site of its attachment. By means of the radioimmunoassay epiglycanin cross-reactive antigens were detected in the peritoneal or pleural fluid and in the sera of patients with metastatic cancer. Lower concentrations of epiglycanin-like antigen(s) were found in the peritoneal fluid of patients with hepatitis or liver cirrhosis but not in normal serum.
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PMID:Antibody to epiglycanin and radioimmunoassay to detect epiglycanin-related glycoproteins in body fluids of cancer patients. 620 3

The deficits in plasma amino acids and serum unesterified fatty acids of cancer patients undergoing chemotherapy and/or radiation therapy were studied to delineate the special requirements of the patients and efficacy of our nutritional therapy. Seven general surgery patients and 13 patients treated by the Head-Neck Service had baseline levels measured as part of their nutritional evaluation prior to surgical treatment of their cancers. Fifteen chemotherapy outpatients maintained on their regular diets had fasting levels analyzed. Twenty-six patients who were admitted for their therapy had their intake of the regular hospital diet supplemented with a low-residue enteral diet formula (Vivonex High Nitrogen Diet); parenteral nutrition was used only if their oral intake was totally inadequate. Baseline and sequential measurements were made of plasma amino acid and serum unesterified fatty acid levels by gas liquid chromatographic techniques. Before operation the patients had normal levels of amino acids except for a significant deficiency of threonine and glycine observed in patients with head-neck tumors. Outpatients with and without hepatic metastases had significantly depressed levels of the essential amino acids valine, leucine, threonine, and methionine and the nonessential amino acids serine, glycine, and proline. The baseline levels of the patients admitted for treatment had similar deficiencies except for more evidence of lysine deficiency. Patients supported with total parenteral nutrition had rapid elevation of the amino acid levels. The patients whose intake was supplemented with the oral diets had improvement in their amino acid levels, but the deficiency in the leucine and threonine fractions persisted up to 4 weeks of therapy. Although the lysine levels were normal when first analyzed, significant differences developed in the patients without hepatic metastases after the start of chemotherapy with return to normal only after chemotherapy was discontinued. Fatty acid levels were not significantly different between the cancer groups except for preoperative elevated oleic acid levels noted in the general surgery tumor group; there were no deficiencies in the essential fatty acids. These studies indicate a need for enteral formulas with adequate branched-chain amino acids and enrichment with threonine and lysine for supplementing the nutrition of the cancer patient who is undergoing chemotherapy.
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PMID:Plasma amino acid and serum unesterified fatty acid deficits and the effect of nutritional support in chemotherapy treatment. 642 62

Our previous study revealed that mutations of the p53 gene were detected by cDNA sequencing in one of four (25%) primary gastric tumors and in five of six (83%) gastric cancer cell lines. It was of interest that all five cell lines established from metastatic lesions had p53 gene mutations, while the single cell line established from a primary tumor lacked an abnormality. Thus, the current study was initiated to determine the frequency of p53 mutations in 10 pairs of samples from primary gastric carcinomas and their lymph node metastases, in addition to morphologically normal gastric mucosa. In addition, we correlated the findings with other relevant molecular markers including the metastasis associated nm23-H1 gene and loss of heterozygosity (LOH) using multiple polymorphic markers for chromosome 17p and sequencing the entire open reading frame (ORF) of the p53 gene. Five of ten (50%) patients were constitutionally heterozygous for one or more 17p and/or p53 probes (pYNZ 22, BamHI RFLP; pMct35.1, Mspl RFLP; php53cl, Bg/II RFLP), while none had LOH at the 17p and/or p53. A Bg/II RFLP for analysis of possible nm23-H1 somatic allelic deletion revealed no LOH out of four informative cases. One paired sample demonstrated the substitution of valine for isoleucine at codon 41 (GTT to ATT) in both primary gastric tumor and metastasis. Another metastatic sample demonstrated the substitution of proline for threonine at codon 278 (CCT to C/ACT) in addition to a non-mutated codon, while only the wild-type p53 sequence was present in the paired primary gastric tumor tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of p53 gene mutations in paired primary and metastatic gastric tumor tissues. 790 5

Phosphorylation/dephosphorylation reactions are one of the dynamic mechanisms through which cells modulate protein activity in response to environmental stimuli. The eukaryotic molecules which are responsible for the phosphorylation of serine, threonine and tyrosine residues appear to have co-ordinately evolved from simple prokaryotic enzymes which primarily respond to nutritional cues. In multicellular eukaryotes the complexity of data transfer greatly exceeds that of simple bacteria. The eukaryotic cell needs to exchange information with neighbouring and distant sister cells. Positional, nutritional and hormonal data are transmitted from the extracellular milieu across the plasma membrane and into the cytoplasm. In certain cases the signal must pass into the nucleus or other subcellular organelles where it is decoded and the proper cellular response initiated. All of these events have been shown to have a protein kinase component and it seems likely that in mammalian cells over 1,000 different kinase molecules have evolved to form the requisite signal transducing networks. In this review we describe a previously unappreciated family of protein kinases, the dual specificity or DSK kinases, which play important roles in the regulation of normal cellular growth and differentiation.
Cancer Metastasis Rev 1994 Mar
PMID:Dual specificity kinases--a new family of signal transducers. 814 41

Considerable progress has been made over the past year in elucidating the mechanisms by which extracellular signals are transduced via cell surface receptors to trigger changes in gene expression which determine the growth and differentiated state of a cell. In particular, Ras proteins have been implicated as key intermediates that mediate the signal from upstream tyrosine kinases to a downstream cascade of serine/threonine kinases, which then activate nuclear factors that control gene expression and protein synthesis. How Ras proteins function is regulated in this role as a molecular switch, and how the signal is transmitted between the various components of the pathway, are now being determined. Finally, the Rho family of Ras-related proteins, which regulate the actin cytoskeleton, have also been implicated as mediators of oncogenic Ras transformation. The brisk pace at which the key components of Ras-mediated signal transduction pathways are being identified hold great promise that new targets for therapeutic intervention in cancer may now be identified.
Cancer Metastasis Rev 1994 Mar
PMID:The Ras signal transduction pathway. 814 46

Molecular mechanisms of pituitary tumorigenesis were studied using Polymerase chain reaction-single stranded conformational polymorphism with DNA sequencing to identify potential mutations in the ras protooncogenes and the tumor suppressor gene p53 in invasive pituitary adenomas and carcinomas. Sequencing of exons 5 through 8 of the p53 gene revealed no mutations, nor were mutations detected in the N- or K-ras protooncogenes in four of the carcinomas and their respective metastatic deposits. Point mutations of H-ras however, were identified in three distant metastatic pituitary tumor secondaries, but not in their respective primary pituitary carcinomas, or in six invasive adenomas. Two of the mutations included a G to C substitution at codon 12, and a G to A substitution at codon 18, resulting in a glycine to arginine, and an alanine to threonine change at these amino acids, respectively. A third mutation involved a single base pair (adenine) deletion in codon 3 of H-ras which causes a frame shift, resulting in a termination signal at codon 19. These results suggest that point mutations in p53 and ras are not associated with pituitary tumorigenesis, however, point mutations of the H-ras gene may be important in the formation and or growth of pituitary metastases. This observed genomic instability will be of value in predicting the potential metastatic behavior of these aggressive pituitary tumors.
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PMID:H-ras mutations in human pituitary carcinoma metastases. 815 9

We have used total hip replacement combined with cemented intramedullary nailing to treat a selected group of nine patients with pathological fractures of the proximal femur and impending fractures of the shaft due to metastases. One patient died from cardiopulmonary failure on the third postoperative day, but the others were able to walk within the first week after operation. Complications included one recurrent dislocation of the THR and one fracture of an osteolytic lesion of the femoral shaft during nail insertion. Both were managed successfully. The hybrid osteosynthesis which we describe is an alternative to the use of tumour or long-stem prostheses; it has the advantage of preserving bone stock and muscle attachments.
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PMID:Pathological fractures of the proximal femur with impending shaft fractures treated by THR and cemented intramedullary nailing: a report of nine cases. 863 74


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