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)

The quantity and localization of two lactose-binding lectins with molecular weights of 31,000 and 14,500 in human colorectal carcinoma tissue specimens obtained by surgical resection have been studied using specific polyclonal antibodies. Electrophoretic separation and blotting of detergent extracts of tumor tissues (48 specimens), followed by the binding of an antibody that recognizes both of these lectins, demonstrated that the contents of Mr 31,000 and 14,500 lectins vary from one specimen to another. The Mr 31,000 lectin content was higher in tumor specimens classified as Dukes' stage D than in those from other stages. A significant correlation was found between Mr 31,000 lectin levels and the levels of carcinoembryonic antigen in the patients' sera at the time of surgery. Immunohistochemical staining with antibodies specific for each lectin was performed with 20 colon carcinoma tissues and 5 colonic adenoma tissues. The results showed that the Mr 31,000 lectin localizes in the cytoplasm of colorectal carcinoma cells and normal epithelial cells, whereas antibody binding to Mr 14,500 lectin is observed in a limited number of carcinoma specimens and is mainly associated with luminal surfaces and secretory products. Adenoma cells were reactive with Mr 14,500 anti-lectin antibody at their luminal surfaces or cytoplasms, but they did not stain with Mr 31,000 anti-lectin antibody. These results suggest that a correlation exists among the level of the Mr 31,000 lectin, the serum level of carcinoembryonic antigen, and the stage of progression of colorectal carcinomas.
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PMID:Increased content of an endogenous lactose-binding lectin in human colorectal carcinoma progressed to metastatic stages. 198 99

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

Toxicology and carcinogenesis studies of pentaerythritol tetranitrate (PETN), an organic nitrate used in explosives and as a therapeutic agent for angina pectoris, were conducted by administering diets containing PETN,NF (National Formulary Grade, a 1:4 mixture of PETN and lactose) to both sexes of F344 rats and B6C3F1 mice in 14-day, 13-week and 2-year studies. PETN was found to be essentially non-toxic in 14-day and 13-week studies at dietary concentrations as high as 10,000 ppm; the weight gain of female rats was lower than that of controls at 5000 and 10,000 ppm in the 13-week study. In the 13-week studies, one in ten high-dose female rats had an adenoma of the Zymbal gland and one in ten high-dose female mice had a hepatocellular adenoma. Dietary concentrations chosen for the 2-year studies were 5000 and 10,000 ppm for male rats and male and female mice, and 1240 and 2500 ppm for female rats. In the 2-year studies, there were no adverse effects on survival or body weight gains in either sex of rats or mice. No neoplastic or non-neoplastic lesions were considered to be related clearly to PETN administration. Neoplasms of the Zymbal gland occurred at low incidences in PETN-exposed groups of both sexes of rats in the 2-year study.
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PMID:No evidence of toxicity or carcinogenicity of pentaerythritol tetranitrate given in the diet to F344 rats and B6C3F1 mice for up to two years. 225 87

Endogenous lectins may augment the panel of tumor markers. Specific protein-carbohydrate interactions especially involve carbohydrate moieties that are located at sequence termini, e.g. D-galactose and N-acetyl-D-galactosamine. Respective endogenous lectins can be detected by suitably constructed neoglycoproteins. In order to evaluate the influence of sugar and label density as well as coupling mode of the carbohydrate moiety to the carrier protein for lectin localization in histopathology, four different types of neoglycoproteins, carrying beta-galactosides or alpha- and beta-anomers of N-acetyl-D-galactosamine were employed to reveal the presence of specific receptors in invasive ductal mammary carcinomas with propensity for metastasis formation. Staining of tumor cells was more intense than staining of normal cell types. Coupling of the diazo derivatives of p-aminophenyl glycosides led in most cases to the relatively highest extent of staining in terms of number of stained cells and staining intensity. Classified next according to these categories attachment of sugars via p-isothiocyanato derivatives or via an aliphatic linker after his reaction with the C6-hydroxyl group of the sugar moiety was rather equally well effective, whereas reductive amination with concomitant ring opening at the reducing end of the disaccharide lactose resulted in neoglycoproteins, yielding the lowest extent of staining. The alpha-anomer is preferred as a ligand to endogenous lectins of tumor cells to the beta-anomer of N-acetyl-D-galactosamine. To reduce the number of steps in glycohistochemical processing, glycosylated enzymes were successfully employed. They also allowed to measure the lectin density on breast carcinoma cells, leading to rational selection for demonstrated lectin-mediated targeting of neoglycoprotein-hematoporphyrin conjugates. Immobilization of ligands as an approach to prepare histochemically valuable reagents to localize respective receptors is not confined to tumor lectinology, as emphasized by additional application of hormone-protein conjugates, termed neohormoproteins.
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PMID:Endogenous lectins with specificity to beta-galactosides and alpha- or beta-N-acetyl-galactosaminides in human breast cancer. Their glycohistochemical detection in tissue sections by synthetically different types of neoglycoproteins, their quantitation on cultured cells by neoglycoenzymes and their usefulness as targets in lectin-mediated phototherapy in vitro. 228 87

Biochemical and cytochemical analysis of Lewis lung tumor variants revealed that the low metastatic cells contained more galactose/N-acetylgalactosamine residues in a high-molecular-mass (15-20 kDa) mixed N- and O-glycan fraction than the highly metastatic ones. It was also found that the highly metastatic variant was less sensitive to macrophage cytotoxicity in vitro. The cytotoxicity against the low metastatic target cells was inhibited by asialofetuin (10-20 microM), and, to a small degree--and at much higher concentration--by lactose, while galactose and other monosaccharides were ineffective. We suppose that complex galactosylated tumor cell membrane glycans could play a role in the antitumoral cytotoxicity of macrophages.
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PMID:Galactosylated glycan expression and macrophage sensitivity of Lewis lung tumor cells with different metastatic phenotype. 237 Feb 52

Incubation of the human monoblastoid tumor cell line U937 with 5 x 10(-9) M 12-O-tetradecanoylphorbol-13-acetate (TPA) for 3 days was associated with marked morphological and functional changes including adherence of the cells and cessation of proliferation. While growth arrest and the viability of the cells were not influenced, the TPA-induced adherence of U937 cells could be totally blocked by incubation with tunicamycin, suggesting an involvement of N-linked carbohydrates in these cell attachment processes. The isolation and characterization of endogenous lectins with specificities for lactose, L-fucose, and D-mannose from U937 controls and TPA-differentiated U937 cells demonstrated marked differences in either the pattern and the distribution of these sugar-specific carbohydrate-binding proteins. Our results indicate that alterations in cell-surface carbohydrates are of central importance for the attachment of the differentiating U937 tumor cells.
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PMID:Alterations in glycosylation and lectin pattern during phorbol ester-induced differentiation of U937 cells. 240 39

DF3 is an IgG1 monoclonal antibody (MAb) generated against a Mr 350,000-400,000 glycoprotein expressed by approximately 80% of human breast cancers. We have coupled MAb DF3 to ricin. Purification of the immunotoxin (DF3-IT) was obtained by affinity and size exclusion chromatography. DF3 antigen-positive breast cancer cell lines (ZR-75-1, BT-20, and MCF-7) and DF3 antigen-negative lung cancer cell lines (A549 and CALU6) were tested for cytotoxicity with metabolic labeling and clonogenic assays. The cells were exposed for 3 h to different concentrations of DF3-IT, MAb DF3, ricin, and a combination of unconjugated MAb DF3 and ricin. In the presence of 100 mM lactose, DF3-IT specifically inhibited protein synthesis of lines expressing DF3 antigen on their cell surface. Moreover, clonogenic survival experiments demonstrated that DF3-IT at a concentration of 1 x 10(-9) M specifically kills 2.6-2.8 log of ZR-75-1 and BT-20 cells and 1.6 log of MCF-7 cells. At the same concentration, nonspecific toxicity of DF3-IT resulted in a 30% reduction of bone marrow granulocyte and macrophage colony formation. In bone marrow-purging experiments, tumor cells were mixed with an excess of bone marrow cells and treated with DF3-IT or ricin. Tumor cell clonogenic survival assays demonstrated that the presence of bone marrow cells had no detectable effect on activity or specificity of the DF3-IT. These results thus indicate that MAb DF3 is an effective vehicle to specifically deliver toxins to cancer cells which express DF3 antigen on their surface and that DF3-IT may be useful for in vitro purging of bone marrow.
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PMID:Evaluation of monoclonal antibody DF3 conjugated with ricin as a specific immunotoxin for in vitro purging of human bone marrow. 240 89

The results described here provided an example of a human IgM monoclonal antibody against a tumor-associated glycolipid and of the unusual properties of its corresponding immunotoxin (IT). The monoclonal antibody referred to as 38-13 has been previously described and reacted with the globotriaosylceramide [Gb3:Gal(alpha 1----4)-Gal(beta 1----4)-Glc(beta 1----1)ceramide] specifically expressed on surface membrane of Burkitt's lymphoma (BL) cells. An immunotoxin (38-13 IT) combined with the pokeweed antiviral protein (PAP) toxin via S-S bridges showed paradoxically a lower cytotoxic effect in BL Ramos cells than in non-BL cells such as leukemic mouse L1210 cells, while these cells appeared not to be involved by flow cytometric analysis and complement-dependent cytotoxicity. Consequently, the inhibitory effect of selective galactose analogs on the binding and the cytotoxicity of 38-13 antibody conjugated or not to PAP toxin was compared on BL and non-BL cells. Only the galactose blocked in alpha configuration provided a fine inhibition of 38-13 binding on BL Ramos cells and both alpha and beta-galactose allowed us to establish a clear distinction between the pathway entry of 38-13 IT in BL and non-BL cells; in close correlation with the 38-13 binding specificity the 38-13 IT cytotoxic effect in Ramos BL cells could also be prevented by alpha-Gal only, suggesting that this toxic action is probably mediated through the IT binding to Gb3 antigenic sites. In contrast, on apparently irrelevant L1210 cells, 38-13 IT showed a cytotoxic effect which was inhibited preferentially by lactose (Gal in beta configuration). It was discussed that IT binding alone to either antigenic sites which are inhibited by the hapten alpha-Gal, or nonspecific sites which can compete with the hapten beta-Gal is unable to induce efficient killing of cells. But cooperation of both bindings might give an attractive explanation of IT cytotoxic effect. It was concluded that the unexpected activity of 38-13 IT in non-BL cells probably could be mediated through an active macromolecular transport process which could implicate a beta-galactoside-binding protein (lectin).
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PMID:Comparison of inhibitory effect of galactose analogs on the binding and cytotoxicity of an anti-globotriaosylceramide monoclonal antibody coupled or not coupled to pokeweed antiviral protein. 243 22

Differentiated and anaplastic oligodendrogliomas revealed intracytoplasmic and nuclear presence of endogenous carbohydrate-binding proteins by application of labelled (neo)glycoproteins in histochemical analysis. The histochemical patterns showed differences between the differentiated and anaplastic forms of the same tumor type. Xylose-, lactose- and asialofetuin-specific carbohydrate-binding proteins could be detected in both types of tumors with the same staining intensity. However, maltose-specific carbohydrate-binding proteins were present only in the differentiated form. An inverse intensity of the histochemical reaction was observed with galactose-6-phosphate-, galactose-beta(1.3)-N-acetylglucosamine-N-acetylglucosamine- and mannose-(BSA-biotin) and fucose-(BSA-biotin) respectively, when the differentiated and anaplastic oligodendrogliomas were compared with each other. These differences document changes in the pattern of histochemically detectable carbohydrate-binding proteins, suggesting a role for endogenous carbohydrate-binding proteins in the tumor cell differentiation. These data indicate the potential usefulness of labelled (neo)glycoproteins as a new type of marker for histopathological diagnosis.
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PMID:Endogenous carbohydrate-binding proteins in oligodendrogliomas. A histochemical study. 245 53

Salt and detergent extracts of xenografted human embryonic carcinoma and a human yolk sac carcinoma were fractionated on different sets of Sepharose columns covalently derivatized with lactose, asialofetuin, melibiose, mannan and fucose. Successive elution by chelating reagent and specific sugar resulted in isolation of endogenous Ca2+-dependent and Ca2+-independent carbohydrate-binding proteins, as analyzed by gel electrophoresis. The salt extracts of the embryonic carcinoma contained a Ca2+-dependent carbohydrate-binding protein at Mr66,000, that was undetectable in yolk sac tumor extracts. Also, a Ca2+-independent fucose-binding protein at Mr62,000 could be purified. In general, the pattern of carbohydrate-binding proteins showed quantitative and qualitative differences as compared to normal tissue. The carbohydrate-binding proteins were assayable as agglutinin and showed no enzymatic activity. They can thus be defined as lectins. Their presence within certain stages of differentiation and developmental regulation may contribute to improvement of the classification, diagnosis and therapy of this tumor class. These new lectins may also be functionally related to the stage-specific embryonic antigens like SSEA-1.
Tumour Biol 1986
PMID:Comparison of endogenous lectins in human embryonic carcinoma and yolk sac carcinoma. 301 Apr 37


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