?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=Complex+Systems+Analysis+of+Arrested+Neural+Cell+Differentiation+during+Development+and+Analogous+Cell+Cycling+Models+in+Carcinogenesis%0A%0A&rft.creator=Baianu%2C+Professor+I.C.&rft.creator=Prisecaru%2C+M.S.+V&rft.subject=Dynamical+Systems&rft.subject=Complexity+Theory&rft.subject=MEO+PrePrint&rft.subject=Theoretical+Biology&rft.description=A+new+approach+to+the+modular%2C+complex+systems+analysis+of+nonlinear+dynamics+of+arrested+neural+cell+Differentiation--induced+cell+proliferation++during+organismic+development+and+the+analogous+cell+cycling+network+transformations+involved+in+carcinogenesis+is+proposed.+Neural+tissue+arrested+differentiation+that+induces+cell+proliferation+during+perturbed+development+and+Carcinogenesis+are+complex+processes+that+involve+dynamically+inter-connected+biomolecules+in+the+intercellular%2C+membrane%2C+cytosolic%2C+nuclear+and+nucleolar+compartments.+Such+'dynamically+inter-connected'+biomolecules+form+numerous+inter-related+pathways+referred+to+as+'molecular+networks'.+One+such+family+of+signaling+pathways+contains+the+cell+cyclins.+Cyclins+are+proteins+that+link+several+critical+pro-apoptotic+and+other+cell+cycling%2Fdivision+components%2C+including+the+tumor+suppressor+gene+TP53+and+its+product%2C+the+Thomsen-Friedenreich+antigen+(T+antigen)%2C+Rb%2C+mdm2%2C+c-Myc%2C+p21%2C+p27%2C+Bax%2C+Bad+and+Bcl-2%2C+which+play+major+roles+in+various+neoplastic+transformations+of+many+tissues.+The+novel+theoretical+analysis+presented+here+is+based+on+recently+published+studies+of+arrested+cell+differentiation+that+normally+leads+to+neural+system+formation+during+early+developmental+stages%3B+the+perturbed+development+may+involve+cyclin+signaling+and+cell+cycling+responsible+for+rapidly+induced+cell+proliferation+without+differentiation+into+neural+cells+in+such+experimental+studies%3B+special+emphasis+in+this+modular+model+is+placed+upon+the+roles+of+cyclins+D1+and+E%2C+and+does+suggest+novel+clinical+trials+as+well+as+rational+therapies+of+cancer+through+re-establishment+of+cell+cycling+inhibition+in+metastatic+cancer+cells.+Cyclins+are+proteins+that+are+often+over-expressed+in+cancerous+cells+(Dobashi+et+al.%2C+2004).+They+may+also+be+over-expressed+in+cells+whose+differentiation+is+arrested+during+the+early+stages+of+organismic+development%2C+leading+to+increased+cell+proliferation+instead+of+differentiation+into+specialized+tissues+such+as+those+forming+the+neural+system.+Cyclin-dependent+kinases+(CDK)%2C+their+respective+cyclins%2C+and+inhibitors+of+CDKs+(CKIs)+were+identified+as+instrumental+components+of+the+cell+cycle-regulating+machinery.+In+mammalian+cells+the+complexes+of+cyclins+D1%2C+D2%2C+D3%2C+A+and+E+with+CDKs+are+considered+motors+that+drive+cells+to+enter+and+pass+through+the+%E2%80%9CS%E2%80%9D+phase.+Cell+cycle+regulation+is+a+critical+mechanism+governing+cell+division+and+proliferation%2C+and+it+is+finely+regulated+by+the+interaction+of+cyclins+with+CDKs+and+CKIs%2C+among+other+molecules+(Morgan+et+al.%2C+1995).+A+categorical+and+Topos+framework+for+%C5%81ukasiewicz+Algebraic+Logic+models+of+nonlinear+dynamics+in+complex+functional+genomes+and+cell+interactomes+is+also+proposed.+%C5%81ukasiewicz+Algebraic+Logic+models+of+genetic+networks+and+signaling+pathways+in+cells+are+formulated+in+terms+of+nonlinear+dynamic+systems+with+n-state+components+that+allow+for+the+generalization+of+previous+logical+models+of+both+genetic+activities+and+neural+networks.+An+algebraic+formulation+of+varying+'next-state'+functions+is+extended+in+a+%C5%81ukasiewicz-Topos+with+an+n-valued+%C5%81ukasiewicz+Algebraic+Logic+subobject+classifier+description+that+represents+non-random+and+nonlinear+network+activities+as+well+as+their+transformations+in+developmental+processes+and+carcinogenesis.+%0A++Important+aspects+of+Cell+Cycling%2C+the+Control+of+Cell+Division%2Cand+the+Neoplastic+Transformation+in+Carcinogenesis+are+being+considered+and+subjected+to+algebraic-logico-+relational%2C+and+computer-aided+investigations.+The+essential+roles+of+various+levels+of+%0Ac-Myc%2C+p27+quasi-complete+inhibition%2Fblocking%2C+TP53+and%2For+p53+inactivation%2C+as+well+as+the+perpetual+hTERT+activation+of+Telomerase+biosynthesis+are+pointed+out+as+key+conditions+for+Malignant+Cell+transformations+and+partial+re-differentiation+leading+to+various+types+of+cancer+such+as+lung%2C+breast%2Cskin%2C+prostate+and+colon.+Rational+Clinical+trials%2C+Individualized+Medicine+and+the+potential+for+optimized+Radio-%2C+Chemo-%2C+Gene-%2C+and+Immuno-+therapies+of+Cancers+are+suggested+on+the+basis+of+integrated+complex+systems+biology+modeling+of+oncogenesis%2C+coupled+with+extensive+genomic%2Fproteomic+and+interactomic+High-throughput%2Fhigh-sensitivity+measurements+of+identified%2C+sorted+cell+lines+that+are+being+isolated+from+malignant+tumors+of+patients+undergoing+clinical+trials+with+adjuvant+signaling+drug+therapies.+The+implications+of+the+cyclin+model+for+abnormal+neural+development+during+early+development+are+being+considered+in+this+model+that+may+lead+to+explanations+of+subsequent+cognitive+changes+associated+with+abnormal+neural+cell+differentiation+in+environmentally-affected+embryos.+This+new+model+may+also+be+relevant+to+detecting+the+onset+of+senescing+neuron+transformations+in+Alzheimer's+and+related+diseases+of+the+human+brain+in+ageing+populations+at+risk.+++%0A%0A&rft.date=2004-06&rft.type=Preprint&rft.type=NonPeerReviewed&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F3703%2F6%2FCancersignaling_ICBval.pdf&rft.identifier=++Baianu%2C+Professor+I.C.+and+Prisecaru%2C+M.S.+V++(2004)+Complex+Systems+Analysis+of+Arrested+Neural+Cell+Differentiation+during+Development+and+Analogous+Cell+Cycling+Models+in+Carcinogenesis.++%5BPreprint%5D+++++&rft.relation=http%3A%2F%2Fcogprints.org%2F3703%2F