Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.12 (chondroitinase)
 2,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tamoxifen is a synthetic nonsteroidal drug with antiestrogenic properties. This report describes the response of patients with metastatic breast cancer to tamoxifen and correlates clinical responses with tumor tissue content of cytoplasmic estrogen binding proteins (EBPs) and other biochemical parameters. Ages of patients ranged from 27 to 82 years. 7 patients were premenopausal, 63 postmenopausal, and 2 had recent endocrine ablaetion. Prior hormone therapy, radiotherapy, or chemotherapy ahd been given to all patients. Tamoxifen was given at a dose of 20 mg orally for a minimum of 4 weeks and continued if an objective remission was shown. Before therapy a biopsy specimen was taken for determination of EBP and for specific enzyme activities. Another biopsy specimen was taken for at least 8 weeks after therapy. A total of 72 patients were treated for at least 4 weeks. The overall response rate was 38%. Most frequent responses were in the over-70 age group. The median duration of response has been 9.5 months. Bony involvement responded to therapy in 21 of 28 patients. No responses were shown in 6 patients with liver metastases. Only 1 of 18 patients who had previous chemotherapy responded. Of 31 who had no prior chemotherapy, 73% achieved a remission. There was a 44% correlation between patients with a positive EBP assay and response to therapy, but none in EBP-negative patients. In this study 20 of 28 patients had normal arylsulfatase B/DNA ratios in their tumor tissue and 11 of the 20 responded to tamoxifen therapy. Patients who responded most favorably to therapy had normal G-6-PD activities. It is concluded that tamoxifen therapy may cancel the need for ablative surgery in postmenopausal patients with positive EBPs and who have had a prior response to additive hormonal treatment.
Cancer Treat Rep 1976 Oct
PMID:Therapeutic use of tamoxifen in advanced breast cancer: correlation with biochemical parameters. 19 Nov 85

Glycosaminoglycans have been characterized from a normal human breast cell line (HBL-100) and two different cell lines from human breast carcinoma (MDA-MB-231 and MCF-7). The glycosaminoglycans were labeled by exposure of cell cultures to [3H]glucosamine and [35S]sulfate and then isolated from both spent media and cells by pronase digestion and cetylpyridinium chloride fractionation. They were further characterized by (a) hexosamine composition, (b) controlled-pore glass exclusion chromatography, (c) reactivity with specific enzymes (hyaluronidase chondroitinase, heparitinase, and heparinase), (d) nitrous acid degradation, and (e) DEAD-Sephadex chromatography. The results indicate that the HBL-100 line synthesizes mainly hyaluronic acid, most of which is secreted into the medium. Chondroitin sulfate and heparan sulfate are the predominant glycosaminoglycans synthesized by the cancer lines; both are found mainly in the spent medium, but the hyaluronic acid synthesized by the MDA-MB-231 line remains cell associated. The cell-associated heparan sulfate had a molecular weight in excess of 13,000 and may contain linkages susceptible to testicular hyaluronidase. The MCF-7 cells produce significantly lower amounts of glycosaminoglycans than do the other two lines.
Cancer Res 1979 Mar
PMID:Glycosaminoglycans of normal and malignant cultured human mammary cells. 42 76

Arylsulfatase B activity has been determined in 24-hour urine samples from 243 patients with colorectal cancer. Elevated activity of the enzyme was obsereved in 172 out of 243 (71%) patients. Employing Dukes' modified classification of colorectal cancer, urine arylsulfatase B activity was elevated in Dukes' A lesions-1/8 (12%), Dukes' B lesions-24/43 (55%). Dukes' C lesions-89/111 (80%), and Dukes' D lesions-66/81 (82%). Arylsulfatase B activity in urine, when elevated, may be used to follow response to therapy since in those patients with elevated urine arylsulfatase B values who subsequently responded to therapy, the enzyme values became or approached normal. Urine arylsulfatase B activity also correlated with plasma carcinoembryonal antigen (CEA) as a diagnostic indicator of colorectal cancer in 33/46 (71%) patients. In contrast to the urinary findings, arylsulfatase B activity in tumor tissue was elevated in only 24% (27/110) of the specimens of colorectal cancer. It was also found that in a group of 55 patients treated with 5-fluorouracil, all of the 13 patients that showed objective response to therapy had activities of arylsulfatase B in the tumor tissue within the normal range for large bowel mucosa. Nevertheless, 22 to 26 of the 43 patients that did not respond also presented values in the normal range. The roles of lysosomal enzymes in colorectal cancer are discussed.
Cancer 1975 Dec
PMID:Arylsulfatse B in colorectal cancer. 121 50

The synthesis and secretion of mucin-like high-molecular glycoprotein was studied in 2 human colon cancer cell lines that spontaneously differentiate in culture (Caco-2 and T84) and in 2 cell lines that do not spontaneously differentiate (LS174T and HT29). Mucin, quantitated by 3H-glucosamine labelling and chromatography on Sepharose CL-4B was found to be produced by all 4 cell lines. The mucinous nature of the labelled high-molecular glycoprotein was verified by enzymatic degradation treatments (heparinase, hyaluronidase, chondroitinase ABC, and N-glycanase), alkaline-borohydride treatment, inhibition of labelling by the glycosylation inhibitor benzyl-alpha-GalNAc, and by CsCl-density-gradient centrifugation. In all 4 cell lines, an inverse correlation of mucin synthesis with cell density was demonstrated. In Caco-2 cells, the spontaneous post-confluent enterocytic differentiation with increased brush-border enzyme expression was associated with a decrease in mucin synthesis and in the activities of polypeptidyl GalNAc transferase and beta 1,3-galactosyltransferase activity. Using cDNA probes for 2 distinct human intestinal mucins (MUC2 and MUC3), we found that all 4 colon cancer cell lines expressed mucin message, but the types of mucin mRNA expressed differed. These data indicate that mucin-like glycoproteins can be synthesized by cell lines derived from non-mucinous colon cancer, whether or not they undergo spontaneous differentiation in culture. These cell lines may serve as in vitro models for studying apomucin heterogeneity and control of mucin gene expression.
Int J Cancer 1992 Jan 02
PMID:Mucin synthesis and secretion in relation to spontaneous differentiation of colon cancer cells in vitro. 172 5

The isolation and partial characterization of a novel anticoagulant from the plasma of a patient with metastatic prostate cancer is described. The patient had a prolonged activated partial thromboplastic time, prothrombin time and thrombin time which did not correct by mixing with normal plasma. The reptilase time was normal and the prolonged thrombin time was corrected with protamine sulfate suggesting a heparin-like anticoagulant. A glycosaminoglycan anticoagulant (GAC) was isolated from the patient's plasma. The inhibitory activity of the GAC was destroyed by treatment with chondroitinase ABC. The GAC migrated on agarose gel electrophoresis between keratin sulfate and heparan sulfate. Purified GAC possessed only 2% (W/W) of the antithrombin III cofactor activity of porcine heparin. In assays using purified fibrinogen, the GAC was shown to directly inhibit fibrinogen proteolysis by thrombin. It is concluded that this glycosaminoglycan anticoagulant directly inhibits thrombin clotting of fibrinogen and is a new mechanism for abnormal hemostatic assays in cancer.
 ...
PMID:A glycosaminoglycan inhibitor of thrombin: a new mechanism for abnormal hemostatic assays in cancer. 189 11

Since the 1960s, the loss of sulfomucin from colonic epithelium has been considered to be an indicator of an early stage of carcinogenesis; yet, the biochemical basis for this phenomenon has never been elucidated. We recently prepared a monoclonal antibody (mAb) 91.9H that immunoprecipitates the normal colonic mucins metabolically incorporating [35S]-sulfate. This mouse IgG1 antibody did not cross-react with colon carcinoma mucins that lack sulfate groups. Using normal colonic epithelia unlabeled or radiolabeled with [35S]sulfate and [3H]glucosamine, we purified a high molecular weight glycoprotein that reacts with mAb 91.9H. This was achieved by a combination of DEAE-cellulose anion-exchange chromatography, consecutive treatments with chondroitinase ABC plus heparitinase and with sodium dodecyl sulfate plus 2-mercaptoethanol, and gel filtration on Sepharose CL-2B in the presence of 8 M urea. Antibody reactivity was found in acidic but not neutral high molecular weight glycoproteins. After Sepharose CL-2B fractionation, the mAb 91.9H-reactive fractions consisted of a component with an approximate molecular weight of 500,000-900,000. A purified sulfomucin contained protein, neutral sugar, amino sugar, sialic acid, and sulfate in an approximate ratio of 2.5:1.0:1.1:0.4:0.5. The polypeptide portion was rich in hydrophilic amino acids, particularly threonine. Binding of mAb 91.9H in solid-phase assays was inhibited to 50% by purified normal colon acidic mucin at doses of 5-50 micrograms/ml, depending on different preparations. Various glycosaminoglycans or sulfatides did not show inhibitory activity. Sulfomucin reactivity with mAb 91.9H, as determined by solid-phase-binding inhibition and by dot blot assays, was significantly reduced by chemical desulfation of sulfomucins with anhydrous hydrochloric acid, suggesting that sulfate groups served as a portion of the immunochemical determinant for this antibody. Sulfate residues were apparently linked to alkaline-sensitive carbohydrate chains, but alkaline-released carbohydrate chains did not react with mAb 91.9H. Immunohistochemical examinations showed that mAb 91.9H bound normal colonic epithelial cells, which also stained with high-iron diamine, more strongly than it bound colon carcinoma cells.
Cancer Res 1991 Oct 15
PMID:Human colonic sulfomucin identified by a specific monoclonal antibody. 191 91

Constituents of the bone marrow microenvironment have the capacity to influence both normal and malignant hematopoietic cell behavior. For example, HL-60 human promyelocytic leukemia cells in vitro display a more mature phenotype when grown on a bone marrow stroma-derived matrix. To elucidate which component(s) of the stromal matrix is capable of modulating HL-60 cell phenotype, matrices were treated with a variety of chemicals and enzymes prior to being used in the differentiation assay. Treatment of matrices with collagenase, pronase, chondroitinase, or chloroform:methanol:ether could not abolish the differentiation-promoting activity of bone marrow stroma. In contrast, the activity was destroyed by alkali treatment (0.5 M NaOH for 18 h) or heparinase/heparitinase enzymes. Heparin added to cultures increased maturation of HL-60 cells as determined by esterase production, Fc rosette formation, and morphological appearance. Other stromal components such as laminin, fibronectin, collagen I, collagen IV, or chondroitin sulfate did not alter the HL-60 leukemia cell phenotype. Stroma-derived matrix material which labeled with [35S]sulfate and eluted on a DEAE ion-exchange column as a high ionic fraction in 1.5 M LiCl and 7.5% sodium dodecyl sulfate contained the active fraction. A heparan sulfate proteoglycan component isolated by polyacrylamide-agarose gel electrophoresis induced a more mature HL-60 phenotype, and digestion with heparinase/heparitinase in the presence of protease inhibitors abrogated the effects on HL-60 phenotype. We conclude that a heparan sulfate-associated fraction of the bone marrow matrix plays a key role in the regulation of leukemic cell maturation.
Cancer Res 1990 Jun 15
PMID:A heparan sulfate-containing fraction of bone marrow stroma induces maturation of HL-60 cells in vitro. 214 Feb 91

The antigenic determinant recognized by monoclonal antibody SPan-1 is greatly elevated in sera of patients with pancreatic cancer but not in sera of normal individuals. Here we describe the mucin-like characteristics of the SPan-1 antigen isolated from culture medium and xenografts of the human pancreatic cancer cell line SW-1990. YPan-1, another pancreatic cancer associated monoclonal antibody, also reacts with the SPan-1 antigen. The SPan-1/YPan-1 antigens have densities of 1.4-1.5 g/ml and elute in the void volume of Sepharose CL-2B columns. They are resistant to degradation by chondroitinase ABC, nitrous acid, and hyaluronidase but susceptible to protease digestion and reductive beta-elimination. All these characteristics suggest that the SPan-1 and YPan-1 determinants are carried on mucinous antigens. Both SPan-1 and YPan-1 immunoreactivities are unaffected by boiling or by alkylation and reduction of the mucins while they are abolished by mild periodate oxidation or neuraminidase and are markedly decreased by wheat germ agglutinin. Thus, their antigenic determinants are composed principally of carbohydrates with sialic acid, an absolute requirement for reactivity. However, the epitope specificities of SPan-1 and YPan-1 are different since YPan-1 does not compete with SPan-1 for binding to antigen. Moreover, YPan-1 and SPan-1 can be distinguished from several other sialic acid requiring, cancer associated antibodies such as B72.3, CSLEX-1, DU-PAN-2, OC-125, and 19-9 by either their epitope characteristics or their tissue reactivity patterns.
Cancer Res 1988 Jul 15
PMID:Mucin-like antigens in a human pancreatic cancer cell line identified by murine monoclonal antibodies SPan-1 and YPan-1. 245 32

We previously demonstrated that an acidic variant form of lysosomal arylsulfatase B accumulated in chronic myelogenous leukemia (CML) cells was highly phosphorylated at its carbohydrate moiety (Uehara Y, et al, Cancer Res 43:5618, 1983). Since lysosomal hydrolases including the sulfatase underwent the posttranslational phosphorylation processing at the carbohydrate moiety, we investigated two enzymes acting on the processing in peripheral leukocytes from leukemia patients. The activity level of the first enzyme in the processing, an N-acetylglucosamine-1-phosphotransferase to form phosphodiester at the carbohydrates, was significantly higher in CML cells than in normal control. The transferase level in CML cells was also higher compared with that in normal bone marrow cells, which include myeloid progenitor cells. However, the activity of the second processing enzyme, a phosphodiester glycosidase that converts a phosphodiester to a phosphomonoester, showed no consistent change in CML cells. Thus, increment of the sulfatase variant containing phosphomonoesters and diesters in CML cells is most probably associated with elevated activities of the phosphotransferase. In two cases of CML in blastic crisis and a case of acute myelogenous leukemia (AML), activity of the processing enzyme was considerably decreased concomitant with reduction of peripheral blastic cells by chemotherapy.
 ...
PMID:Processing enzymes acting on carbohydrate moiety of lysosomal hydrolases in leukemic cells: elevated activity of N-acetylglucosamine-1-phosphotransferase. 254 Aug 59

Seventy five prostatic specimens from cancer, BPH and normal controls were studied by light microscopic histochemical methods for the demonstration of complex carbohydrates and some proteins: 1) alcian blue (AB) (pH 1.0), 2) alcian blue (AB) (pH 2.5), 3) Periodic Acid-Schiff (PAS), 4) peroxidase labelled-Ricinus communis agglutinin-diaminobenzidine (PO-RCA-DAB), 5) Concanavalin A-peroxidase-diaminobenzidine (ConA-PO-DAB), 6) ConA-PO-DAB-periodic acid-m-aminophenol Fast black salt K (ConA-PO-DAB-PA-AP-FBK). For identifying individual acidic and neutral carbohydrates, following procedures of enzyme digestion were performed upon some tissue sections prior to the above histochemical staining: a) sialidase (prior to staining with AB at pH 2.5), b) streptomyces hyaluronidase (prior to staining with AB at pH 2.5), c) testicular hyaluronidase (prior to staining with AB at pH 1.0 or pH 2.5), d) chondroitinase ABC (prior to staining with AB at pH 1.0 or pH 2.5), e) chondroitinase AC (prior to staining with AB at pH 1.0 or pH 2.5), f) alpha-amylase (prior to staining with PAS). In addition, the tissue specimens from prostatic cancer were stained immunohistochemically for demonstration of prostatic acid phosphatase (PAP) and the serum PAP levels were also measured by radioimmunoassay. The histochemical differences in the prostatic tissue among normal control, BPH and cancer as follows. In the tissue of prostatic cancer, chondroitin sulfate A, C and hyaluronic acid were present in the interstitium. Chondroitin sulfate, hyaluronic acid and sialic acid were present in the cytoplasm of cancer cells. In the tissue of BPH chondroitin sulfate B and hyaluronic acid was present in the interstitium and hyaluronic acid was present in the cytoplasm of epitherial cells. In the epithelial basement membrane of the tissue from BPH, chondroitin B and hyaluronic acid were present. 1,2-Glycol groups of neutral complex carbohydrates in the interstitium of prostatic cancer were shown to exist in smaller amounts than in that of BPH. In the cytoplasm of cancer cells the intensity of both PO-RCA-DAB and ConA-PO-DAB staining could be divided into three groups: strong, moderate and weak. In the prostatic cancer there was a good correlation between the intensity of PO-RCA-DAB staining and tumor grade, and intensity of ConA-PO-DAB staining was correlated well with serum PAP level. The cytoplasm of cancer cells showed a positive reaction to PAP immunostaining and no appreciable difference was observed according to tumor grade.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[The histochemistry of complex carbohydrates in the prostatic tumor]. 258 29


1 2 3 4 5 Next >>