Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00216 (ABC)
 8,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To contribute to the investigation of the composition of the extracellular matrix in epithelial tumours, mammary gland tissues of dogs (including tumours, hyperplasias and normal tissue as well as metastatic lesions in lymph nodes and lung) were studied histochemically and immunohistochemically for distribution of sulphated glycosaminoglycans (s-GAGs). The formaline-fixed tissue was stained by alcian blue at pH 5.8, using the 'critical electrolyte concentration' to study the degree of sulphation of s-GAGs. s-GAGs were characterized by degradation with enzymes and nitrous acid and by immunohistochemistry with two anti-chondroitin sulphate monoclonal antibodies. The light microscopic investigation of s-GAG deposits revealed a limited number of patterns of their distribution. The main s-GAGs found in the mammary gland tumours of dogs and in metastatic lesions were chondroitin sulphate (CS) and heparin/heparan sulphate (HEP/HS). CS accumulated in diffuse structures between epithelial cells as well as around clusters of tumour cells. The latter pattern, possibly representing a mesenchymal reaction to the tumour, was present in 74% of the tumours, and in 67% of these, highly sulphated CS was present. A diffuse accumulation of CS was present almost exclusively in complex and mixed tumours; because of the expression of the 3B3 epitope for CS in immature cartilage the spindle cells of complex tumours are argued to be the precursors of the cartilage in mixed tumours. HEP/HS was stored mainly in mast cells that were found in increased numbers in hyperplasias and tumours. By pretreatment of microscopic slides with chondroitinase AC or ABC immunostaining of fibronectin could be made possible in areas in which CS was abundantly present, suggesting that CS may mask fibronectin epitopes. It is concluded that CS with different degrees of sulphation is the most important s-GAG in the extracellular matrix of mammary tumours of dogs. CS and other s-GAGs accumulate at different sites and may have a different pathogenetic significance.
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PMID:Stromal accumulation of chondroitin sulphate in mammary tumours of dogs. 1042 36

By using ligands with various affinities for the T-cell receptor (TCR) and by altering the contribution of the CD45 tyrosine phosphatase, the effects of the potency of TCR-induced signals on the function of small GTPases Ras and Rap1 were studied. T cells expressing low-molecular-weight CD45 isoforms (e.g., CD45RO) exhibited the strongest activation of the Ras-dependent Elk-1 transcription factor and the highest sensitivity to the inhibitory action of dominant negative mutant Ras compared to T cells expressing high-molecular-weight CD45 isoforms (ABC). Moreover, stimulation of CD45RO(+), but not CD45ABC(+), T cells with a high-affinity TCR ligand induced suboptimal Elk-1 activation compared with the stimulation induced by an intermediate-affinity TCR-ligand interaction. This observation suggested that the Ras-dependent signaling pathway is safeguarded in CD45RO(+) expressors by a negative regulatory mechanism(s) which prohibits maximal activation of the Ras-dependent signaling events following high-avidity TCR-ligand engagement. Interestingly, the biochemical activity of another small GTPase, the Ras-like protein Rap1, which has been implicated in the functional suppression of Ras signaling, was inversely correlated with the extent of Elk-1 activation induced by different-affinity TCR ligands. Consistently, overexpression of putative Rap dominant negative mutant RapN17 or the physiologic inhibitor of Rap1, the Rap GTPase-activating protein RapGAP, augmented the Elk-1 response in CD45RO(+) T cells. This is in contrast to the suppressive effect of RapN17 and RapGAP on CD45ABC(+) T cells, underscoring the possibility that Rap1 can act as either a repressor or a potentiator of Ras effector signals, depending on CD45 isoform expression. These observations suggest that cells expressing distinct isoforms of CD45 employ different signal transduction schemes to optimize Ras-mediated signal transduction in activated T lymphocytes.
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PMID:Combinatorial effect of T-cell receptor ligation and CD45 isoform expression on the signaling contribution of the small GTPases Ras and Rap1. 1107 75

The function of VEGF in laryngeal carcinoma was studied by observing either the expressions of VEGF and its receptor flk-1 in laryngeal carcinoma, or the effect of anti-VEGF antibody and anti-VEGF receptor antibody on the growth of human laryngeal cancer cell line HEP-2 in vitro. The expression of VEGF and flt in the specimen of laryngeal carcinoma were determined by standardized immunohistochemistry (Elite ABC method). Anti-VEGF antibody and anti-VEGF receptor antibody were also added at various concentrations to the culture medium, respectively, and the growth of HEP-2 was measured by MTT assay. The immunohistochemical staining showed that the expressions of VEGF and flt were detected both in carcinoma cells and endothelial cells. The growth of HEP-2 cell line in vitro was suppressed when adding various concentration of anti-VEGF antibody and anti-VEGF receptor antibody to the culture medium. The laryngeal cancer cells can secret VEGF and there exists VEGF-binding site on laryngeal cancer cell. Both blockading VEGF with anti-VEGF antibody and blockading VEGF-binding site with anti-VEGF receptor antibody could inhibit HEP-2 growth.
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PMID:[The influence of vascular endothelial growth factor and its receptor on the growth of laryngeal cancer cell]. 1126 58

We currently recognize five large ubiquitous superfamilies and one small eukaryotic-specific family in which cellular multidrug efflux pumps occur. One, the ABC superfamily, includes members that use ATP hydrolysis to drive drug efflux, but the MFS, RND, MATE and DMT superfamilies include members that are secondary carriers, functioning by drug:H(+)or drug:Na(+)antiport mechanisms. The small MET family seems to be restricted to endosomal membranes of eukaryotes, and only a single such system has been functionally characterized. In this review article, these families of drug transporters are discussed and evaluated from phylogenetic standpoints.
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PMID:Phylogeny of multidrug transporters. 1142 13

Midkine (MK) is a heparin-binding growth factor that promotes cell migration, cell growth and cell survival. The promotion of migration of inflammatory cells, especially macrophages, by MK is involved in formation of a vascular abnormality, i.e. neointima formation. MK-induced migration of peritoneal exudate macrophages was inhibited by heparin, chondroitin sulfate E and dermatan sulfate, but not by chondroitin sulfate D or chondroitin 6-sulfate. Digestion of macrophages with chondroitinase ABC as well as chondroitinase B decreased the migratory activity. However, heparitinase digestion showed only slight effects. These results indicated that a chondroitin sulfate, i.e. an E-type oversulfated structure with dermatan sulfate domain, is involved in MK-induced migration of macrophages. Although a chondroitin sulfate proteoglycan, receptor-type protein tyrosine phosphatase zeta (PTP zeta), participates in MK-induced migration of neurons and osteoblasts, PTP zeta was not detected in macrophages. The MK-induced migration was inhibited by PP1, wortomanin, PD 98059 and vanadate, indicating that the downstream signaling system, which includes Src, PI3 kinase and ERK as important components, is shared with other MK signaling systems in which PTP zeta is involved.
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PMID:Requirement of chondroitin sulfate/dermatan sulfate recognition in midkine-dependent migration of macrophages. 1192 7

Chorioangiomas are benign angiomatous tumours of the placenta occurring with a frequency of approximately one per cent of all examined placentae. Hypoxia and genetic factors are discussed to be predisposing factors for chorioangiomas. However, not much is known about the tumorigenesis of these benign tumours. Screening with various antibodies in a rare case of chorangiomatosis, we found disseminated spindle cells coexpressing vascular epithelial growth factor (VEGF), neutral endopeptidase 24.11 (NEP/CD10), and KIT protein (CD117) within the tumour stroma. A possible involvement of such factors in angiogenesis and tumorigenesis of chorioangiomas/chorangiomatosis has not been studied so far.Seven placentae with chorioangiomas (n=6) or chorangiomatosis (n=1), six normal placentae, and four cutaneous haemangiomas were analysed immunohistochemically (ABC and APAAP methods) using antibodies against VEGF, NEP, KIT protein, as well as endothelial markers like PECAM-1 (CD31), CD34, v. Willebrand factor (factor VIII), and ulex europaeus. In addition, analysis of c-kit 'gain of function' mutation Asp 816 to Val by means of Hinfl digestion and direct sequencing of semi-nested polymerase chain reaction products was performed. All chorioangiomas and haemangiomas strongly expressed the endothelial markers CD34, CD31, and FVIII, while only weak expression of ulex lectin was noted. Disseminated groups of VEGF-, NEP-, and KIT protein-positive spindle cells, which coexpressed vimentin and smooth-muscle actin were identified as myofibroblasts in the stroma of four chorioangiomas. These spindle cells were quantified as numerous in two and as rare in two other cases. No VEGF-positive myofibroblasts, however, were detected in the villous stroma of normal control placentae and haemangiomas. Only scattered perivascular myofibroblasts expressing KIT protein and NEP were detected in early gestational placenta controls. In all chorioangiomas and chorangiomatosis PCR analysis failed to unveil c-kit 'gain of function' mutation Asp 816 to Val in KIT protein-positive spindle cells. Moreover, a significant increase in mast cells was observed only in the haemangiomas. As expected, endothelial origin of chorioangiomas/chorangiomatosis was verified by CD31, CD34, FVIII expression. Myofibroblastic spindle cells expressing VEGF and NEP may be precursor cells in these peculiar angiomatous tumours. Although activating c-kit mutation Asp 816 to Val was not detected by PCR, the presence of KIT protein (CD117)-positive intratumoral myofibroblastic spindle cells in chorioangiomas and chorangiomatosis might suggest involvement of the stem cell factor (SCF)-receptor in pathologically enhanced angiogenesis.
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PMID:VEGF-, KIT protein- and neutral endopeptidase (NEP/CD10)-positive myofibroblasts-precursors of angiogenesis in chorioangiomas? 1285 66

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase-2, -9 (MMP-2, MMP-9), tissue inhibitor-1 of matrix metalloproteinase (TIMP-1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP-2, MMP-9, TIMP-1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship (P<0.05) between the expression of MMP-2 and MMP-9, TIMP-1 and CD44v6, HER2/neu and MMP-9, MMP-2 and p53. Up-regulation of MMP-2 was accompanied by advanced T stage (P<0.01). There was also a trend of MMP-2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence(P<0.05). The expression of TIMP-1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non-keratinizing SCC than that in basaloid SCC(P<0.05). These findings suggested that MMP-2 and MMP-9, HER2/neu and MMP-9, MMP-2 and p53 had a coordinate function in aggression of tumor; that MMP-2 had a more important function than MMP-9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.
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PMID:Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis. 1286 29

We report the isolation and characterization of a phototrophic ferrous iron [Fe(II)]-oxidizing bacterium named TIE-1 that differs from other Fe(II)-oxidizing phototrophs in that it is genetically tractable. Under anaerobic conditions, TIE-1 grows photoautotrophically with Fe(II), H2, or thiosulfate as the electron donor and photoheterotrophically with a variety of organic carbon sources. TIE-1 also grows chemoheterotrophically in the dark. This isolate appears to be a new strain of the purple nonsulfur bacterial species Rhodopseudomonas palustris, based on physiological and phylogenetic analysis. Fe(II) oxidation is optimal at pH 6.5 to 6.9. The mineral products of Fe(II) oxidation are pH dependent: below pH 7.0 goethite (alpha-FeOOH) forms, and above pH 7.2 magnetite (Fe3O4) forms. TIE-1 forms colonies on agar plates and is sensitive to a variety of antibiotics. A hyperactive mariner transposon is capable of random insertion into the chromosome with a transposition frequency of approximately 10(-5). To identify components involved in phototrophic Fe(II) oxidation, mutants of TIE-1 were generated by transposon mutagenesis and screened for defects in Fe(II) oxidation in a cell suspension assay. Among approximately 12,000 mutants screened, 6 were identified that are specifically impaired in Fe(II) oxidation. Five of these mutants have independent disruptions in a gene that is predicted to encode an integral membrane protein that appears to be part of an ABC transport system; the sixth mutant has an insertion in a gene that is a homolog of CobS, an enzyme involved in cobalamin (vitamin B12) biosynthesis.
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PMID:Isolation and characterization of a genetically tractable photoautotrophic Fe(II)-oxidizing bacterium, Rhodopseudomonas palustris strain TIE-1. 1608 40

The uterine artery and its branches are the most important vessels that supply the uterus with blood, nutrients and active substances. Epidermal growth factor (EGF) and its receptor (EGFR) are expressed in many tissues, including reproductive organs, and is involved in angiogenesis, embryo implantation and development as well as in proliferation and differentiation of various cells. The aim of our study was to determine EGF and EGFR immunoexpression in the uterine artery and its branches during the estrous cycle in the pig. The experiment was performed on cryostat sections of the uterine artery and its branches stained immunohistochemically by ABC method. Light microscopic observations revealed the phase-related immunoreactivity of EGF and EGFR in the endothelial cells of the uterine artery and its branches. The highest intensity of EGF and EGFR immunoreaction in endothelial cells of the uterine artery was observed in the follicular phase. A significant decrease in the intensity of EGF and EGFR immunoreactivity was found in the middle luteal phase. Similar results of the immunostaining were found with regard to EGFR. In the endothelium of the uterine arterial branches, a significant increase in the intensity of EGF and EGFR-immunoreactivity was observed in the middle luteal phase. A decrease in the intensity of EGF immunostaining was observed in the late luteal phase. The phase-related expression of EGF and EGFR in the endothelium of the uterine artery and its branches suggest the modulatory effect of EGF and its receptor on the uterine artery and the region supplying these vessels.
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PMID:Epidermal growth factor and epidermal growth factor receptor immunoreactivity in the endothelial cells of the uterine artery and its branches during different stages of the estrous cycle in the pig. 1702 10

Accumulating evidence suggests the involvement of chondroitin sulfate (CS) and dermatan sulfate (DS) hybrid chains in the brain's development and critical roles for oversulfated disaccharides and IdoUA residues in the growth factor-binding and neuritogenic activities of these chains. In the pursuit of sources of CS/DS with unique structures, neuritogenic activity, and therapeutic potential, two novel CS/DS preparations were isolated from shark liver by anion exchange chromatography. The major (80%) low sulfated and minor (20%) highly sulfated fractions had an average molecular mass of 3.8-38.9 and 75.7 kDa, respectively. Digestion with various chondroitinases (CSases) revealed a large panel of disaccharides with either GlcUA or IdoUA scattered along the polysaccharide chains in both of the fractions. The higher M(r) fraction, richer in IdoUA(2-O-sulfate)alpha1-3GalNAc(4-O-sulfate) and GlcUAbeta/IdoUAalpha1-3GalNAc(4,6-O-disulfate) units, exerted greater neurite outgrowth-promoting (NOP) activity and better promoted the binding of various heparin-binding growth factors, including pleiotrophin (PTN), midkine, recombinant human heparin-binding epidermal growth factor-like growth factor, VEGF(165), fibroblast growth factor-2, fibroblast growth factor-7, and hepatocyte growth factor (HGF). These activities were largely abolished by digestion with CSase ABC or B but only moderately affected by a mixture of CSases AC-I and AC-II. In addition, the NOP activity of the larger fraction was markedly reduced by desulfation with alkali, suggesting a role for the 2-O-sulfate of IdoUA(2-O-sulfate)alpha1-3GalNAc(4-O-sulfate). The NOP activity of the higher molecular weight fraction and that of the embryonic pig brain-derived CS/DS fraction were also sup pressed to a large extent by antibodies against HGF, PTN, and their individual receptors cMet and anaplastic lymphoma kinase, revealing the involvement of the HGF and PTN signaling pathways in the activity.
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PMID:Neuritogenic activity of chondroitin/dermatan sulfate hybrid chains of embryonic pig brain and their mimicry from shark liver. Involvement of the pleiotrophin and hepatocyte growth factor signaling pathways. 1714 50


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