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)

Lactose-binding lectins having Mr values of approximately 14,000 (L-14.5) and approximately 35,000 Da have been found in a variety of vertebrate tissues, including normal intestine and colon, and in several types of tumors such as colon carcinomas. To determine the clinical relevance of such lectins in human colon cancer, specimens from 46 patients with colorectal carcinoma of identified Dukes' stages were selected and analyzed for the presence and amount of lactose-binding lectins by immunoblotting using a polyclonal, rabbit anti-lectin antibody followed by binding of 125I-labeled anti-rabbit IgG. The amount of a lectin having an Mr value of approximately 31,000 Da (L-31) varied among the specimens. The levels of L-31 lectin in colorectal cancer specimens from primary tumors of patients with distant metastases (Dukes' stage D) were significantly higher than were those from patients without detectable metastases (Dukes' stages B1 and B2). In contrast, among the various specimens the variation in the level of the L-14.5 lectin was smaller, and there was no correlation between the amount of this lectin and cancer stage. Immunohistochemical staining of thin sections of colorectal tumor specimens using antibodies specific for either L-31 or L-14.5 lectin revealed that the two were located at different places, the L-31 lectin primarily within the cytoplasm of carcinoma cells, and the L-14.5 lectin associated with secreted material. These results indicated that the relative amount of the L-31 lectin increases as the colorectal cancer progresses to a more malignant stage.
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PMID:Lactose-binding lectin expression in human colorectal carcinomas. Relation to tumor progression. 193 52

Chemotherapy does not only affect the viability of the tumor cell. It may also cause alterations in normal organs. Thus, tumor-free areas within human lung parenchyma of 63 surgical specimens of intrapulmonary metastases were analyzed to assess the extent of morphologic changes in response to previous cytostatic therapy. The material included 34 cases of sarcoma, 20 cases of germ cell tumors, 6 cases of hypernephroid carcinoma, two cases of mammary carcinoma and one case of metastatic melanoma. All patients had received cytostatic therapy in generally applied regimens for more than two years. Morphologic analysis was carried out by routine procedures. In addition to conventional staining procedures including HE, PAS, and Sirius stain, further tools were employed to extend the array of determined characteristics. To evaluate any changes in the tissue in order to specifically recognized carbohydrate structures, labeled neoglycoproteins or proteoglycans with specificity for endogenous receptors that bind to mannose, maltose, L-fucose, lactose, N-acetyl-D-glucosamine, and heparin were used. A monoclonal antibody binding the HLA-DR receptor was also included in the study. As a control, sections of 20 cases with intrapulmonary metastases without exposure to previous cytostatic therapy were included. To address the further question whether cytostatic therapy may induces changes in tumor-free lung that show similarities to the organ in question, sections from 18 cases with tuberculosis and from 37 cases suffering from sarcoidosis were similarly examined. Focal interstitial fibrosis was seen in 28/63 (44%) of the patients receiving chemotherapy. In contrast, only 2/20 (10%) patients of the untreated group exhibited this alteration. An active fibrosis with proliferating smooth muscle cells was found in two cases, dysplastic pneumocytes in 10 cases (16%) in the group with cytostatic therapy, but in no cases in the untreated group. Expression of the HLA-DR receptor in the pneumocytes was observed in 27/63 cases (43%) of the cytostatic cohort, in 21/37 (57%) patients of the sarcoidosis cohort, in 15/18 (83%) patients of the tuberculosis cohort, and in 1/20 (5%) of the untreated patients. In contrast to sections from treated patients, binding of neoglycoproteins was low in the untreated cohort. Interestingly, similarities between the tuberculosis cohort and the cytostatic cohort were seen for receptors that are specific for fucose and lactose, respectively. The results suggest that long-lasting cytostatic therapy induces focal fibrosis in 40%-50% of the patients, mainly via unspecific interstitial inflammatory infiltrates. A hypersensitivity reaction or direct toxicity may less frequently lead to pathologic alterations.
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PMID:Alterations in human lung parenchyma after cytostatic therapy. 200 Dec 78

A retrospective study was performed to evaluate and compare preoperative computed tomography (CT) scanning with less expensive tests that are used to identify hepatic metastases in patients with colorectal carcinoma. Thirty-three patients treated for colorectal carcinoma from January 1985 to December 1986 had preoperative CT scans performed as well as serum levels of lactose dehydrogenase (LDH), and carcinoembryonic antigen (CEA) measured. All patients underwent intraoperative evaluation of the liver. Only one patient had metastases found by CT exam that was not apparent at laparotomy. The sensitivity and specificity of the CT scan for detecting hepatic metastases were 1.00 and 0.96, respectively. The sensitivity and specificity of elevations in LDH or CEA when used in combination for detecting liver involvement was 1.00 and 0.54, respectively. Although the CT scan is effective in detecting hepatic metastases in patients with colorectal carcinoma we found that its routine use is unnecessary and expensive.
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PMID:The efficacy of preoperative computed tomography in patients with colorectal carcinoma. 235 Jan 6

A 7 year study of megestrol and chlormadinone in female dogs is in progress. This report characterized histopathologically 60 mammary nodules during the first 4 years of the study. 100 purebred female beagles, 6-12 months of age, were randomly assigned to 5 equal groups. One group was used as a control. Oral doses were .01, .10, and .25 mg/kg/day of megestrol acetate in coconut oil in capsules and of chlormadinone acetate .25 mg/kg/day in lactose tablets. These doses were 1, 10, and 25 times the projected dose of megestrol for humans and about 25 times the human dose of chlormadinone. After 2 years 4 dogs from each group were necropsied. One high-dose megestrol-treated and 1 chlormadinone-treated dog had benign mixed mammary tumors. Palpable nodules were first observed at 16 months in the chlormadinone-treated dogs, at 18 months in dogs given the high dose megestrol and at 27 months in the dogs treated with middle-dose megestrol. Transitory nodules were found in 4 control dogs after 21 months and in low dose megestrol-treated dogs at 26 months. Of 38 grossly detected nodules evaluated microscopically from the megestrol-treated dogs 27 were nodular hyperplasia, 5 were benign mixed mammary tumors, 3 were ductal dialatations, 1 was a lymph node, 1 was fat necrosis and 1 was the umbilicus. Of 22 nodules from the chlormadinone-treated dogs 12 were nodular hyperplasia, 4 benign mixed mammary tumors, 1 chondromucoid degeneration and 1 adenocarcinoma with widespread metastases. 3 nodules were lymph nodes and 1 other had no mammary tissue. Involutions, regression and sclerosis of many areas of nodular hyperplasia were evident at 4 years. Thus of the 60 nodules evaluated during the first 4 years of the study 50 were non-neoplastic and 10 were neoplastic. It is considered that the 1 adenocarcinoma may have been spontaneous and not a treatment-related neoplasm. A precursor stage through nodular hyperplasia apparently did not occur.
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PMID:Mammary nodules in dogs during four years' treatment with megestrol acetate or chlormadinone acetate. 412 57

Recognition of the carbohydrate part of cellular glycoconjugates by sugar receptors like lectins may contribute to biosignaling and interactions between normal and transformed cells. Such recognitions may be essential for establishing phenotypic characteristics in neoplastic cells, including metastasis-associated properties. To evaluate various glycoconjugates in tumor diagnosis and clinical therapy, a panel of 18 biotinylated neoglycoproteins was prepared. This included conjugates of a histochemically inert carrier protein and crucial sugar moieties such as D-glucuronic acid, alpha- and beta-N-acetyl-galactosamine, beta-N-acetyl-glucosamine, melibiose, lactose, maltose, cellobiose, mannose, mannose-6-phosphate, fucose, rhamnose, and xylose. In so doing the diazo derivative of the respective p-aminophenyl glycosides was coupled with galactose, beta-N-acetyl-galactosamine or beta-N-acetyl-glucosamine via an epoxy group-containing aliphatic spacer. Other glycoconjugates used were the proteoglycan heparin and the sulfated fucan fucoidan. Labeling was effected with cyanogen bromide activation and aminoalkylation for specific detection of endogeneous sugar receptors, especially lectins. Tissues studied were paraformaldehyde-fixed, paraffin-embedded surgical biopsies from patients with different stages of squamous cell carcinomas (SCCs) of the oral cavity (n = 16) and oropharynx (n = 17), including three lymph node metastases from oropharyngeal primary tumors. Semiquantitative binding differences of probes to tumor stages were evaluated statistically by the Mann-Whitney U-Wilcoxon rank sum W test. Specific binding of a probe to cytoplasmic and nuclear structures was detected with apparent quantitative differences. Overall, the cytoplasmic compartment revealed a higher intensity of histochemical reaction than did nuclear structures, indicating a comparatively higher density of specific carbohydrate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of sugar receptor expression by neoglycoproteins in oral and oropharyngeal squamous cell carcinomas. 757 87

The staging system of limited disease (LD) and extensive disease (ED) is widely used and has been shown to provide useful prognostic information in cases of small cell lung cancer (SCLC). However, accurate examinations are necessary for correct staging. In this report, we evaluated the clinical usefulness of magnetic resonance imaging (MRI) of bone marrow in SCLC. 37 patients with LD by standard staging and 41 with ED were examined with bone marrow MRI. Results of bone marrow MRI did not influence the choice of treatment in patients with LD. For subsequent analysis, patients with LD were divided into two groups: patients in whom bone marrow infiltration was detected with MRI (MRI-positive LD group) and those in whom it was not (MRI-negative LD group). Focal or diffuse metastases to bone marrow were detected with MRI in 46% (36/78) of all patients and 35% (13/37) of LD patients. The response rates to treatment in patients with MRI-positive LD were lower than those in patients with MRI-negative LD (P = 0.006). The survival of patients with MRI-positive LD was worse than that of MRI-negative LD (generalised Wilcoxon test: P = 0.0157), and closer to that of ED. Multivariate analyses using a Cox model that included the result of bone marrow MRI, performance status, chemotherapy regimen, radiotherapy and serum lactose dehydrogenase (LDH) level showed that the result of bone marrow MRI remained a prognostic factor in SCLC patients with limited disease. Bone marrow examination with MRI is useful for better staging of SCLC. According to our analysis of response rates and survival, MRI-positive LD should be considered a type of ED.
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PMID:Effect on prognosis of bone marrow infiltration detected by magnetic resonance imaging in small cell lung cancer. 961 77

Soluble kappa-elastin peptides were shown to stimulate the expression of MMP-2 (but not MMP-9) by human fibrosarcoma HT-1080 cells, both at the protein and mRNA levels; maximal effect being observed at a concentration of 25 microg/ml of kappa-elastin. The stimulatory effect could be reproduced using Val-Gly-Val-Ala-Pro-Gly (VGVAPG) peptide, an elastin-derived hydrophobic hexapeptide which represented the elastin receptor binding sequence of tropoelastin. Furthermore, treatment of cells with lactose (30 mM), which dissociated 67-kDa elastin binding protein (EBP) from cell surfaces, completely abolished this effect, suggesting that the elastin receptor could mediate such a response. Using a specific monoclonal antibody, 67-kDa EBP was detected in HT-1080 membrane preparations by Western immunoblotting. Following treatment with 25 microg/ml kappa-elastin or 200 microg/ml VGVAPG, increased levels of the active 62-kDa form of MMP-2 were found in HT-1080 cell extracts. Stimulation of MT1-MMP mRNA expression by treatment with elastin-derived peptides (EDPs) was shown by competitive polymerase chain reaction (PCR). A reverse zymography analysis revealed that EDPs also stimulated TIMP-2 (but not TIMP-1) production by HT-1080 cells. Competitive PCR confirmed increased TIMP-2 mRNA expression by such treatment. These results suggest that occupancy of the 67-kDa elastin receptor by elastin-derived peptides enhanced both expression and activation of proMMP-2 and consequently, could promote the invasive/metastatic ability of tumor cells expressing this receptor.
Clin Exp Metastasis 1998 Aug
PMID:Regulation of matrix metalloproteinase-2 (gelatinase A, MMP-2), membrane-type matrix metalloproteinase-1 (MT1-MMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2) expression by elastin-derived peptides in human HT-1080 fibrosarcoma cell line. 987 97

Prostate cancer cells metastasize to bone causing a predominantly osteosclerotic response. It has been shown that cells from the human prostate cancer cell line PC3 secrete factors that influence the behavior of osteoblast-like cells. Some of these factors with mitogenic activity have been found to be proteins with molecular weights between 20 and 30 kDa, but the identity of the osteoblastic mitogenic factor or factors produced by prostate cancer cells is still unknown. Therefore, the aim of this study was to characterize the protein profile of conditioned medium (CM) from PC3 cells in the molecular weight range from 5 to 30 kDa using proteome analysis. A protein profile of the CM from PC3 cells was performed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Thirty protein spots with molecular weights ranging from 5 to 30 kDa were analyzed by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). One of these spots was identified as galectin-1. We examined whether PC3 CM, recombinant galectin-1 alone, or combined with insulin-like growth factor-I (IGF-I) had any effects on the proliferation or differentiation of human bone marrow stromal (hBMS) cells. Furthermore, we tested whether adhesion of PC3 cells to plastic, laminin, fibronectin, and collagen type I was influenced by lactose, which inhibits galectin-1. Galectin-1 (1000 ng/ml) inhibited the proliferation of hBMS cells up to 70 +/- 12% (treated/control) of control in contrast to PC3 CM, which induced hBMS cell proliferation by 3-fold. This effect was abolished by IGF-I. PC3 CM and galectin-1 in concentrations of 10 and 1000 ng/ml increased the alkaline phosphatase (ALP) activity of hBMS cells up to 175 +/- 27%, 137 +/- 8%, and 131 +/- 11%, respectively, compared with ALP activity of untreated cells, and inhibited the secretion of osteocalcin (OC) up to 81 +/- 3%, 93 +/- 1%, and 58 +/- 2%, respectively, compared with OC secretion of untreated cells. These effects were affected by IGF-I. Lactose inhibited adhesion of PC3 cells to plastic, fibronectin, laminin, and collagen type I up to 58 +/- 4%, 30 +/- 12, 72 +/- 9%, and 86 +/- 4%. In conclusion, galectin-1 modulated osteoblastic proliferation and differentiation. These effects were affected by IGF-I. Thus, galectin-1 is likely be involved in the osteoblastic response, caused by prostate cancer cells metastasizing into bone, by affecting the matrix mineralization.
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PMID:A proteome study of secreted prostatic factors affecting osteoblastic activity: galectin-1 is involved in differentiation of human bone marrow stromal cells. 1256 96

Disease progression of tumors is accompanied by structural changes of the glycan chains of cellular glycoconjugates. Within the concept of the sugar code the presence of complementary receptors such as lectins translates changes in ligand presentation into biological effects, for example in growth regulation and adhesion. By introducing neoglycoproteins to histopathological colon cancer analysis the questions are addressed as to whether specific binding sites for main N- and O-glycan components are present and whether they harbor potential for prognostic predictions. Synthetic conjugation of fucose, lactose, and mannose derivatives to a carrier protein yielded neoglycoproteins for glycohistochemical analysis. The tumor panel included routinely fixed tissue sections from 67 cancer cases (15 Dukes A, 20 Dukes B, 15 Dukes C, and 17 metastatic tumors) and 6 hepatic metastases as well as 20 normal biopsy specimens as control. Quantitative image analysis determined the labeling index and the mean optical density in each case, separating tumor and peritumoral connective tissue. Specific carbohydrate-dependent binding with inter-individual heterogeneity was observed. The distinct staining profiles were not associated with disease stage or metastasis formation. Strong expression of lactose-binding sites in the peritumoral connective tissue especially in terms of the labeling index was significantly correlated with reduced survival in Dukes B patients (p=0.02). A similar tendency was observed in the Dukes C group. In conclusion, the application of the synthetic markers aimed at lectin detection defines lactose binding as new prognostic marker. It has potential relevance for improving the benefit from adjuvant therapy in Dukes B colorectal cancer patients. Technically, chemical ligand immobilization to an inert carrier can find useful application beyond glycosciences in the quest to extend the panel of tumor markers.
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PMID:Prognostic stratification of Dukes B colon cancer by a neoglycoprotein. 1525 22

Metastasis is a multistep process by which cancer cells, after acquiring several capabilities, spread to distinct sites in the body. It is the major cause of death in individuals suffering from cancer. We have recently identified galectin-7 as a new gene associated with the progression of T cell lymphoma toward a metastatic phenotype, suggesting a possible causal relationship. The present study was designed to investigate the role of galectin-7 in lymphoma. We found that the development of thymic lymphoma was accelerated when induced by lymphoma cells overexpressing galectin-7. Moreover, transfection of an expression vector containing the galectin-7 gene in low metastatic lymphoma cells increased their metastatic behavior and confers these cells with the new ability to overcome the resistance of intercellular adhesion molecule-1-deficient mice to lymphoma dissemination. Finally, we provide data suggesting that galectin-7 modulates the aggressive behavior of lymphoma cells by controlling the expression of metastatic genes, such as MMP-9. This hypothesis is based on the following evidence: (a) galectin-7 transfectants have higher levels of MMP-9 expression, (b) addition of beta-lactose completely inhibits expression of MMP-9 by galectin-7 transfectants, and (c) recombinant forms of galectin-7 induces the expression of MMP-9 in both mouse and human lymphoma cells. Our results have uncovered the existence of a previously undescribed activity, the promotion of cancer cell malignancy, to galectin-7.
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PMID:A novel function for galectin-7: promoting tumorigenesis by up-regulating MMP-9 gene expression. 1595 65


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