Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-Histidinol, a protein synthesis inhibitor and structural analogue of L-histidine, has been demonstrated in chemotherapy-treated mice to be cytoprotective to normal stem cells but to enhance cytotoxicity to tumor cells. N,N-Diethyl-2-[4-(phenylmethyl) phenoxy]ethanamine.HCl (DPPE) is an antagonist of recently described microsomal and nuclear intracellular histamine receptors implicated in the mediation of proliferation and modulation of prostaglandin synthesis. DPPE is cytotoxic to tumor cells in vitro and cytoprotective to the gut in vivo. Noting the similar pharmacologic profiles for histidinol and DPPE and the structural resemblance between histidinol and histamine, we tested 1) whether binding to intracellular histamine receptors may be important to the action of histidinol, 2) whether there exists a differential effect of DPPE and histidinol on proliferating normal and transformed or malignant cells, and 3) whether DPPE, like histidinol, protects host cells from the effects of chemotherapy while augmenting tumor cell kill in vivo. It was observed that histidinol does compete at intracellular histamine receptors in isolated microsomes and nuclei, but with significantly lower affinity than DPPE. Nevertheless, for each agent, potency at intracellular histamine receptors correlates with potency to inhibit DNA and protein synthesis, without cytotoxicity, in normal mitogen-stimulated murine lymphocytes and to kill transformed mouse lymphocytes or MCF-7 human breast cancer cells. As demonstrated previously for histidinol (1-2 g/kg), DPPE (4 mg/kg) protected murine bone marrow progenitors from doxorubicin or fluorouracil, while doses of 4-50 mg/kg significantly enhanced the antitumor activity of doxorubicin and daunorubicin in murine models of early cancer. One postulate to explain the effects of intracellular histamine receptor ligands is that intracellular histamine mediates DNA and protein synthesis, possibly through a downward modulation of growth-inhibitory prostaglandin levels. Antagonism of the intracellular action of histamine at intracellular histamine receptors by DPPE or histidinol may result in differential perturbations of growth/eicosanoid metabolism in normal and malignant cells, thus forming the basis of a new approach to chemotherapy.
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PMID:Increased therapeutic index of antineoplastic drugs in combination with intracellular histamine antagonists. 188 59

The biochemical composition of proteoglycans was investigated in human breast tissues of different age either with invasive mammary carcinoma or with benign lesions of the breast. Proteoglycans were extracted from tissues under dissociative conditions (4 M guanidine-HCl), isolated by CsCl gradient ultracentrifugation, and purified by gel exclusion and ion exchange chromatography. Glycosaminoglycan side chain compositions of proteoglycans were evaluated by enzymatic analysis (chondroitinases ABC and AC) and nitrous acid degradation. Biochemical data indicated that proteoglycans of high density and molecular size were increased (per wet weight of tissue) in neoplastic compared to nonneoplastic tissues. Overall proteoglycan content was increased almost 2-fold in tumors. Furthermore, enzymatic data revealed a change in the proportions of glycosaminoglycan chains in neoplastic and nonneoplastic tissues. In particular, an increase in chondroitin sulfate (63% versus 35%, respectively) together with a decrease of dermatan sulfate (12% versus 45%, respectively) characterized tumors in comparison to mammary tissues with benign lesions, while the relative content of heparan sulfate side chains remained similar in both tissues. However, morphometric analyses revealed that heparan sulfate content per epithelial cell volume was in fact decreased in neoplastic tissue. These differences in proteoglycans indicate that there are significant changes in the extracellular matrix and surface properties of cells in breast cancer tissue.
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PMID:Partial characterization of proteoglycans isolated from neoplastic and nonneoplastic human breast tissues. 199 83

An one-step procedure using a nuclear isolation medium containing propidium iodide has been found to be a suitable preparation technique for flow cytometric DNA analysis in breast cancer samples. In the case of cervical squamous carcinoma, a pretreatment with HCl seems to be a methodological improvement. One advantage with the HCl modification is that some "false" near-diploid cell populations are abolished. These "false" G0/G1 peaks may represent diploid nuclei with a different stainability for propidium iodide compared to normal diploid nuclei. The HCl treatment has, furthermore, the advantage of increasing the elution of nuclei (mean factor of 4.0), especially non-diploid nuclei from higher differentiated squamous carcinomas.
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PMID:Improved preparation technique of cervical carcinoma for flow cytometric DNA analysis with tissue disintegration in hydrochloric acid. 210 64

N,N-diethyl-2-[(4 phenylmethyl)-phenoxy]-ethanamine X HCl (DPPE), a compound selective for the antiestrogen binding site, is structurally similar to the aminoethyl ether group of antihistamines. Our studies now reveal that H1-, but not H2-antagonists, also compete for this site in the order: DPPE = hydroxyzine = perchlorperazine greater than phenyltoloxamine greater than pyrilamine greater than diphenhydramine. The affinity of these compounds for the antiestrogen binding site correlates with their in vitro cytotoxicity against MCF-7 and EVSA-T human breast cancer cells. Tamoxifen, DPPE and hydroxyzine also bind to H1 receptors present in digitonin-solubilized rat liver microsomes, but with less affinity than pyrilamine, which is selective for this site; the ratio of H1 to antiestrogen binding sites in this preparation is 4:1. The data suggest that the antiestrogen binding site may be, in whole or in part, a receptor for histamine different from H1 and H2.
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PMID:Evidence that the antiestrogen binding site is a histamine or histamine-like receptor. 285 5

With rabbit antibodies to nuclear 0.01 M Tris-HCl, pH 8, extract or "nucleolar preparations" of human HeLa S3 cells and fluorescein-labeled goat antirabbit antibodies, bright nucleolar immunofluorescence was observed in human adenocarcinomas, squamous cell carcinomas, sarcomas, hematological neoplasms, and other malignant tumors. With these antibodies, nucleolar immunofluorescence was not found in most normal tissue specimens, benign adenomas, hyperplastic tissues, and specimens of inflammatory diseases. A study was made on the presence in benign and malignant breast tumors of a common nucleolar antigen previously found in a broad range of human malignant tumors. Bright nucleolar immunofluorescence was observed in 19/20 (95%) of known breast cancer specimens. In the group of 80 unknown samples in the "blind" study, 75 (94%) were correctly identified as malignant or benign on the basis of the presence and distribution of the nucleolar fluorescence. In a group of 67 samples in which the nucleolar fluorescence was either readily observed or virtually absent, 47/48 (98%) of the malignant tumors were correctly identified. Of the bening lesions or normal breast specimens, 18/19 (95%) were correctly identified as negative for nucleolar fluorescence. These studies extend the results previously reported for a common nucleolar antigen in a broad range of human cancers to a larger series of malignancies of a particular organ. The tumor nucleolar antigen(s) were partially characterized by isoelectric focusing on 4% polyacrylamide gels. One major band had a pI of 6.3 and a minor band had a pI of 6.1. These antigens were not found in the normal human liver nucleoli.
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PMID:Studies on the human tumor nucleolar antigens. 616 43

The administration of perioperative doxorubicin HCl (Adriamycin) had profound effects on wound healing for 5 out of 7 breast cancer patients and 5 of 5 melanoma patients following intravenous and intra-arterial infusional chemotherapy, respectively. The clinical observation of significant reduction in wound tear strength (WTS) and wound tear energy ( WTE ) in the group of patients with cutaneous melanoma initiated this experimental analysis. A study of WTS ( kNm -2) in nontumor-bearing (non-TB) and Morris Hepatoma (MH)-7777 (TB) rats treated with therapeutic doses of Adriamycin (ADR) and methotrexate (MTX) was compared with saline-treated controls. Mean tumor volume (cm3) was unaffected by MTX, while significant tumor inhibition (p less than 0.01) was evident for ADR-treated TB animals. A correlation (r = 0.516, p less than 0.01) was observed for tumor volume and WTS. Separate analysis of TB and non-TB animals identified a significant correlation (r = 0.6259, p less than 0.01) between advancing cachexia in TB rats and WTS. A 21-day analysis was done for 160 animals to determine the effect of MTX and ADR on WTS ( kNm -2) and WTE ( Ncm -1). The presence of MH-7777 significantly (p less than 0.01) reduced WTE for TB animals not treated with chemotherapy. TB animals treated with ADR had significant (p less than 0.01) improvement in WTE at day 21 compared with TB controls. This enhancement in WTE was not observed in rats treated with MTX. These clinical and experimental observations suggest significant retardation of the early phases of wound fibroplasia as determined by WTS and WTE following operative trauma and subsequent administration of therapeutic dosages of cytotoxic agents.
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PMID:Experimental and clinical observations of the effects of cytotoxic chemotherapeutic drugs on wound healing. 673 17

A pancreas cancer-associated antigen (PCAA) was identified and isolated from ascites fluid of human pancreatic cancer. Purified PCAA was homogeneous as determined by polyacrylamide gel electrophoresis. PCAA was a glycoprotein with a molecular weight of approximately 1,000,000 and consisted of 20% carbohydrates and 80% peptides, had an isoelectric point of 4.7, and migrated to alpha 2-beta region. It possessed a sedimentation coefficient of 14S and appeared to be a fibrous or fibroglobular protein. Immunoreactivity of PCAA was sensitive to proteolytic enzymes, perchloric acid, KSCN, glycine-HCl at pH 2.5, urea and lithium diiodosalicylate; and insensitive to neuraminidase or beta-glucosidase. Immunohistochemical technique revealed that PCAA was located in the cytoplasm of ductal epithelial cells of malignant pancreas. Using heteroantiserum raised against purified PCAA, horseradish peroxidase and CNBr-activated Sepharose 4B, an enzyme-immunoassay (EIA) for circulating PCAA has been developed. From a group of 40 healthy blood donors, an upper limit of 16.2 micrograms of PCAA/ml of serum has been tentatively determined. An elevated PCAA was shown in 67% (29/43) of patients with pancreas cancer, as well as in 30% (11/36) of lung cancer patients, 27% (10/37) of colonic cancer patients, and in 16% (6/36) of breast cancer patients. The reactive antigen in sera of these cancers was shown to be immunologically identical. PCAA also was detected in extracts of various human tissues, particularly pancreatic tumors, colonic tumors, and in a normal colon. Further, PCAA exhibited heterogeneity in molecular weight, isoelectric point, and electrophoretic mobility.
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PMID:Isolation, characterization and clinical evaluation of a pancreas cancer-associated antigen. 702 47

Plasma membranes were prepared from the P-glycoprotein expressing human breast cancer cell line MCF-7 ADR. [3H]Vinblastine bound to these membranes saturably with a Bmax of 24 pmol/mg of protein and KD of 23 nM. In contrast, membranes from the parent cells MCF-7 WT, which do not express P-glycoprotein, did not bind [3H]vinblastine with high affinity. Cytotoxics known to be transported by P-glycoprotein inhibited the binding of [3H]vinblastine, as did multidrug reversing agents including the 1,4-dihydropyridine, dexniguldipine-HCl (Ki, 15 nM). In dissociation kinetic experiments, dexniguldipine-HCl accelerated the dissociation of [3H]vinblastine from P-glycoprotein, indicating a negative heterotropic allosteric mechanism of action through a drug binding site distinct from that of vinblastine. Other 1,4-dihydropyridines tested also accelerated [3H]vinblastine dissociation from P-glycoprotein, however, multidrug reversing drugs of different chemical classes, including quinidine, verapamil and cyclosporin A did not. These results suggest that P-glycoprotein of MCF-7 ADR cell membranes possesses at least two drug acceptor sites which are allosterically coupled: receptor site-1 which binds vinca alkaloids, and receptor site-2 which binds 1,4-dihydropyridines such as dexniguldipine-HCl, which had the highest affinity of the tested derivatives.
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PMID:Allosteric regulation of [3H]vinblastine binding to P-glycoprotein of MCF-7 ADR cells by dexniguldipine. 759 47

Matrix proteins were extracted from bovine cortical bone with EDTA/Tris-HCl under non-dissociative conditions at neutral pH. Four distinct bone resorptive proteins with molecular masses of 14, 25, 29 and 40 kDa were purified and partially characterized using an in vitro neonatal mouse calvarial assay and a growth factor assay using BALB/c/3T3 cells. The 14 kDa protein was purified by anion exchange chromatography (Mono Q) and gel filtration (Superdex 75HR) using FPLC (fast protein liquid chromatography); this factor stimulated the proliferation of MCF-7 human breast cancer cells, a bioassay which is specific for the insulin-like growth factors (IGFs). The 25, 29 and 40 kDa proteins were purified by sequential chromatography as follows: anion-exchange (Mono Q), heparin-Sepharose, hydroxyapatite, concanavalin A-Sepharose, phenyl-Superose, reversed phase high performance liquid chromatography (HPLC) and sodium dodecylsulfate polyacrylamide gelelectrophoresis (SDS-PAGE). The 25 kDa protein was identified as TGF-beta by its inhibitory effect on the proliferation of mink lung cells. The 40 kDa protein enhanced the formation of multinucleate tartrate-resistant acid phosphatase positive cells in a murine bone marrow differentiation assay, but was without effect in an isolated osteoclast assay and had no growth factor activity; this protein is likely to be a colony stimulating factor. The 29 kDa protein was also without growth factor activity; it was, however, able to stimulate bone resorption in the isolated osteoclast assay, suggesting a direct action in osteoclast function. The 29 and 40 kDa proteins may be osteoblast gene products that have been sequestrated by the bone matrix in a similar fashion to TGF-beta and the IGFs. This is the first report of proteins isolated from bone matrix which directly stimulate osteoclast differentiation and activity.
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PMID:The purification and partial characterization of bone resorptive polypeptides from bovine bone matrix. 794 32

The suitability of commercial and pure aluminum-hematein for quantitative DNA image cytometry was investigated. Cervical smears, breast cancer aspiration biopsies, and rabbit liver tissue imprints were stained with Mayer's and Harris' al-hematein with variable staining times and dye concentrations. Pure and commercial hematoxylin was used. Nucleic acids were removed by enzyme digestion or by HCl-hydrolysis. A standard Feulgen stain served as control. DNA-polyacrylamide films were used as staining models. Absorption was measured using a VIDAS image analyzer. DNA in liver cell nuclei was not stained in a stoichiometric dye-DNA ratio. Sequential staining of cervical smears with hematein followed by the Feulgen reaction gave a covariance between 0.77 and 0.88 for IOD. Photometric errors due to unspecific RNA or protein staining were remarkable. Harris' and Mayer's hematein gave comparable results. Pure hematein gave slightly better results than commercial batches. DNA staining in model films was not quantitative with hematein. Al-hematein should therefore not be used for quantitative DNA cytometry.
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PMID:Hematoxylin staining in quantitative DNA cytometry: an image analysis study. 861 2


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