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  • Chemical Engineering  (22)
  • Analytical Chemistry and Spectroscopy  (21)
  • Organic Chemistry  (10)
  • melanoma  (4)
  • 1
    ISSN: 1573-7373
    Keywords: melanoma ; metastasis ; proteases ; endoglycosidases ; growth factors ; growth factor receptors ; basement membrane ; blood brain barrier ; neurotrophins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mouse and human melanoma cells metastatic to the brain express degradative enzyme activities that are used for invasion of brain basement membrane and parenchyma. Compared to poorly metastatic or lung- or ovary-metastatic murine melanoma lines, the brain-metastatic sublines secreted higher levels of a variety of degradative enzymes. Brain-metastatic murine and human melanoma cells also degraded subendothelial basement membrane and reconstituted basement membrane at rates higher than other metastatic melanoma cells. In some cases these degradative activities in mouse and human melanoma cells can be induced by paracrine factors known to be present in the brain parenchyma, such as nerve growth factor (NGF). NGF stimulates the expression of degradative enzymes, such as the endo-Β-glucuronidase heparanase, that are important in basement membrane penetration but this factor does not stimulate melanoma cell growth. The growth of brain-metastasizing melanoma cells appears to be stimulated by other paracrine growth factors, such as paracrine transferrin. Melanoma cells metastatic to brain express higher numbers of transferrin receptors and respond and proliferate at lower concentrations of transferrin than do melanoma cells metastatic to other sites or poorly metastatic melanoma cells. The results suggest that degradation and invasion of brain basement membrane and responses to paracrine neurotrophins and paracrine transferrins are important properties in brain metastasis of murine and human malignant melanoma cells.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Clinical & experimental metastasis 13 (1995), S. 67-88 
    ISSN: 1573-7276
    Keywords: brain metastasis ; growth factors ; melanoma ; melanotropins ; nerve growth factor ; neurotrophins ; signal transduction ; tumor progression ; tyrosine receptor kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: The brain is a unique microenvironment enclosed by the skull, lacking lymphatic drainage and maintaining i highly regulated vascular transport barrier. To metastasize to the brain malignant tumor cells must attach to microvessel endothelial cells, respond to brain-derived invasion factors, invade the blood-brain barrier and respond to survival and growth factors. Trophic factors are important in brain invasion because they can act to stimulate this process. In responsive malignant cells trophic factors such as neurotrophins can promote invasion by enhancing the production of basement membrane-degradative enzymes (such as type IV collagenase/gelatinase and heparanase) capable of locally destroying the basement membrane and the blood-brain barrier. We examined human melanoma cell lines that exhibit varying abilities to form brain metastases. These melanoma lines express low-affinity neurotrophin receptor p75NTR in relation to their brain-metastatic potentials but the variants do not express trkA, the gene encoding a high affinity nerve growth factor (NGF) tyrosine kinase receptor p140 trkA . Melanoma cells metastatic to brain also respond to paracrine factors made by brain cells. We have found that a paracrine form of transferrin is important in brain metastasis, and brain-metastatic cells respond to low levels of transferrin and express high levels of transferrin receptors. Brain-metastatic tumor cells can also produce autocrine factors any inhibitors that influence their growth, invasion and survival in the brain. We found that brain-metastatic melanoma cells synthesize transcripts for the following autocrine growth factors: TGFβ, bFGF, TGFα and IL-1β. Synthesis of these factors may influence the production of neurotrophins by adjacent brain cells, such as oligodendrocytes and astrocytes. Increased amounts of NGF were found in tumor-adjacent tissues at the invasion front of human melanoma tumors in brain biopsies. Trophic factors, autocrine growth factors, paracrine growth factors and other factors may determine whether metastatic cells can successfully invade, colonize and grow in the central nervous system.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cancer and metastasis reviews 14 (1995), S. 303-321 
    ISSN: 1573-7233
    Keywords: brain metastasis ; melanoma ; tumor progression ; growth factors ; neurotrophins ; nerve growth factor ; melanotropins ; signal transduction ; tyrosine receptor kinase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To metastasize to the central nervous system (CNS) malignant cells must attach to brain microvessel endothelial cells, respond to brain endothelial cell-derived motility factors, respond to CNS-derived invasion factors and invade the blood-brain barrier (BBB), and finally, respond to CNS survival and growth factors. Trophic factors such as the neurotrophins play an important role in tumor cell invasion into the CNS and in the survival of small numbers of malignant cells under stress conditions. Trophic factors promote BBB invasion by enhancing the production of basement membrane-degrading enzymes in neurotrophin-responsive cells. The expression of certain neurotrophin receptors on brain-metastasic neuroendrocrine cells occurs in relation to their invasive and survival properties. For example, CNS-metastatic melanoma cells respond to particular neurotrophins (nerve growth factor, neurotrophin-2) that can be secreted by normal cells within the CNS. In addition, a paracrine form of transferrin is important in CNS metastasis, and brain-metastatic cells respond to low levels of transferrin and express high levels of transferrin receptors. CNS-metastatic tumor cells can also produce autocrine factors and inhibitors that influence their growth, invasion and survival in the brain. Synthesis of paracrine factors and cytokines may influence the production of trophic factors by normal brain cells adjacent to tumor cells. Moreover, we found increased amounts of neurotrophins in brain tissue at the invasion front of human melanoma tumors in CNS biopsies. Thus the ability to form metastatic colonies in the CNS is dependent on tumor cell responses to trophic factors as well as autocrine and paracrine growth factors and probably other underdescribed factors.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0886-1544
    Keywords: transglutaminase ; melanoma ; digital image analysis ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The importance of cell adhesion in a variety of physiological phenomena requires development of an understanding of the factors and molecular mechanisms underlying these behaviors. Cell adhesion is a multistep process involving primary receptor-ligand interactions followed by secondary events that may lead to the formation of focal contacts. Due to the lack of well-defined assays to study adhesion stabilization, little is known about this process, except that it may involve signaling events, receptor recruitment, and, as we have demonstrated, covalent peptide cross-linking by cell membrane-associated transglutaminase [Menter et al.: Cell Biophys. 18:123-143, 1992]. To study the stabilization process we have developed a dynamic assay employing a parallel plate flow chamber coupled with video microscopy and digital image processing. Our studies utilize wheat germ agglutinin-selected human metastatic melanoma cell variants that exhibit differences in their experimental metastatic potential and expression of transglutaminase. Using this assay, quantifying cell-substrate stabilization was found to be quick, reliable, reproducible, and useful in evaluating agents that block this process. © 1993 Wiley-Liss, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Biological Mass Spectrometry 14 (1987), S. 603-607 
    ISSN: 0887-6134
    Keywords: Chemistry ; Analytical Chemistry and Spectroscopy
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Fractional dietary Ca absorption, ‘a’, is measured by determining the ratio of two stable isotopic tracers, one of them orally (44Ca @ 0.2-0.5 mg/kg) and the other intravenously (42Ca @ 0.02-0.1 mg/kg). Thermal ionization mass spectrometry (TIMS) is used to measure the perturbation of natural abundance isotope ratios (delta % excess). Typical sensitivity of the TIMS permits detection of a 2.5 delta % excess change from the natural Ca isotope ratio with relative standard deviations of about 0.5%. At sufficiently long times absorption becomes constant so that ‘a’ is determined by a product of constants and a measured ratio.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 41 (1995), S. 415-425 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A 1-D model, which neglects radial variations, describes the hydrodynamics of cell-free ultrafiltration hollow-fiber bioreactors (HFBRs) and the transport of highmolecular-weight proteins trapped in the extracapillary space (ECS). The profiles of radially-averaged protein concentrations predicted by this model are identical to those obtained using a model with radial variations. The model predictions agree well with axial profiles of bovine serum albumin (BSA) and human transferrin concentrations measured in transient and steady-state experiments. The validated model explores the influence of cell culture operating conditions on HFBR protein transport. Increasing protein loading decreases BSA and transferrin polarization in HFBRs operated with unidirectional lumen flow. A relationship developed predicts the protein loading needed to ensure a nonzero steady-state protein concentration throughout the ECS. This critical protein loading depends only on the lumen pressure drop and the ECS protein osmotic pressure. Periodic reversal of the lumen flow direction also decreases protein polarization. The influence of the flow-direction switching time and membrane permeability on the ECS protein distribution is investigated.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 39 (1993), S. 904-907 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Hoboken, NJ : Wiley-Blackwell
    AIChE Journal 41 (1995), S. 805-811 
    ISSN: 0001-1541
    Keywords: Chemistry ; Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A mathematical model of mass transport through dispersed-phase networks to be used for the sustained release of drugs or other solutes at steady rates is presented. The drug is assumed to be encapsulated within the dispersed microdomains and transported to the bulk by diffusion across the interface. A drug is released to the surroundings by diffusion through the bulk. The results show that the desired steady flux of a drug to the surroundings may be obtained given appropriate values of structural properties of the network. These properties may be manipulated easily in the fabrication of dispersed-phase networks reported previously.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 6 (1994), S. 239-244 
    ISSN: 0899-0042
    Keywords: HPLC ; reverse-phase additive ; β-cyclodextrin ; methylphenobarbitone ; molecular mechanics ; complex stability ; chiral separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Molecular modelling of β-cyclodextrin and optimisation of its potential energy suggests that a favoured conformation is that distorted from a symmetrical torus. The inclusion of water molecules into the torus cavity simulates the increased stability in an aqueous solvent. Complexes of β-cyclodextrin with (R)- and (S)-enantiomers of methylphenobarbitone have been modelled and energetically optimised by the application of molecular mechanics. The simulations suggests that the guest molecules adopt an orientation in which the phenyl ring is projected into the torus cavity, with in each case the plane of the ring parallel to a longer axis of the distorted torus and slightly displaced from the axis through the torus cavity. It is suggested that the asymmetry in the macrocyclic ring contributes to chiral recognition as a result of additional discriminatory binding to the barbiturate ring residue of each enantiomer, which occupy different 3D geometries. The enantiomers form complexes of different minimum potential energies. The resulting difference in complex stability can be related to the behaviour of β-cyclodextrin, as a mobile phase additive in reverse-phase HPLC to effect chiral separation of rac-medthylphenobarbitone during chromatography. © 1994 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0899-0042
    Keywords: receptor-operated calcium channel antagonist ; 1H NMR ; chiral HPLC ; calmodulin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 1H nuclear magnetic resonance at 360 MHz shows that SK&F 96365 (1-{β-[3-(p-methoxyphenyl)-propyloxy]-p-methoxyphenethyl}-1H- imidazole hydrochloride), an antagonist of mammalian receptor-operated calcium channels, interacts with the calcium-binding regulatory protein calmodulin (CaM). This may be inferred by a number of chemical shift changes in the spectrum of the calcium-saturated protein induced by addition of the compound. Moreover, two well-resolved singlets corresponding to the 2-proton of the SK&F 96365 imidazolium moiety are observed in the spectrum over a wide range of protein:compound ratios. Separation of rac SK&F 96365 into its two enantiomers by high-performance liquid chromatography on a cellulose tris (4-methylbenzoate) column enabled us to show that the doubling of this NMR signal in the presence of CaM is due to a propensity of the protein to distinguish between the two optical isomers of the compound.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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