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Published by: anon_219287102 on Mar 13, 2012
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 A Perspective Suggested by Peer-Reviewed Literature
of How Glycosaminoglycans May Mediate Cellular Activities Including  Proliferation and Transformation
D. Grant, Ph.D., Turriff AB53 Scotland UK A topic which is believed to continue to be of public interest was thesubject of a presentation made at Marischal College Aberdeen in 1982 by Nancy E. Woodhead (a member of the W.F. Long, F.B. WilliamsonPolysaccharide Research Group).This document contains an edited transcript of my shorthand notes madeat the time to which I now append an update of selected peer-reviewedliterature in this field and also an edited version of a hypothesis which isthought to be of related interest (“Ascorbate and Nitric Oxide in RedoxControl of Heparan Sulphate…” which was originally posted on theinternet [dg4,5,8] in 2000 on a now-discontinued server.=====================================================================“Glycosaminoglycans and Cellular Transformation”Prior to 1982 literature reports were classified by Nancy Woodhead asfollows:1.Experiments directly relating glycosaminoglycans (GAGs) to cellgrowth control andtransformation.2.Alterations in GAG contents of cultured cells after transformation.3.Alterations of GAG contents of mammalian tumors compared tonormal tissue; [this provides more material than is available from cellsin culture].4.Changes in complex composition of certain cell surface GAGs;[especially of HS)]5.Searches for a specific changes in function of cell surface GAGs;[possible functional change due to regional alterations in GAGstructure].
Includes reports of experiments relating GAGs to cell growth control andcellular transformation; starting from 1932:Year Author 1932 Zakrezewski Reported that heparin suppresses the growthof normal embryonic tissue andJensen sarcoma tissue.1957 Sister M. Lippman Reported experimental evidence that heparincan act as a mitotic inhibitor.[This was an
in vivo
study of the effect of howadministration of subcutaneous heparinaffected the measured size of Ehrlich Ascitestumors in rats. It was shown that heparin,under the conditions studied, produced a 40-50% regression of these tumors]. 1960 Ozzello
et al 
. Umbilical cord extracted hyaluronate (HA) or chondroitin sulfate(CS) promoted the growth of humanmammary carcinoma cells in culture.Any of these substance taken singly promotedtumor growth.
et al 
. Heparin prevented mitosis. Evidence for intracellular action of heparin.Heparin also caused formation of microvilion cell surfaces.(Is this an abnormal effect of heparin or is atan apparent normalintracellular function of heparin-likemolecules?)It was apparent that the phenomenon was probably not a unique property of EDTA (a high affinity Ca
chelator) which had been previouslyknown to produce microvilli formation.This outcome may simply be caused by theremoval of Ca
fromthe cell surface. (Heparin-like moleculesmay have this function
in vivo
1966 Takeuchi CS enhanced of tumor growth.Hydrocortisone inhibited the growth of tumors, but this inhibition was prevented bythe presence of CS.1974 Takeuchi
et al 
. Heparin CS and HA : maintained cells inculture after they degenerated in normalculture medium.Some effect of CS and HA on cell surfaceswas suggested toincrease their potential for affecting cellgrowth.1975 Olin in
et al 
. ? Salt effects ? (and related sources of salt
.) can apparently[link to this document lost] can exert a concentration-dependent controleffect on tumor cell growth. Large doses – inhibited epithelial cell growth but low cellsurface doses accelerated growth. 
. 50-100
g/ml level (at) cell surfaceinhibited cell growth while0.5
g/ml promoted growth.Summary of the pre-1975 findings1. Polyanions can enhance tumor growth by protecting cell surfaceantigenic sites.2. The production of new connective tissue giving GAGs is favorable tocancer cell growthMore GAGs (if present)… they can be chosen for cancers to (allowcells to stick?)3. Effect of heparin on nucleoproteins.Evidence shows that heparin interacts with proteins in thenucleus (and thereby affects DNA) and so (affects) protein synthesis.4. Heparin removes Ca from cell surfaces.Cellular proliferation might be affected by this mechanism.Studies which report an

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