Simulation of the Protein-Shedding Kinetics of a Fully Vascularized Tumor

Cancer Informatics - Tập 14 - Trang CIN.S35374 - 2015
Hermann B. Frieboes1,2, Louis T. Curtis1, Min Wu3, Kian Kani4, Parag Mallick5
1Department of Bioengineering, University of Louisville, Louisville, KY, USA
2James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA
3Department of Engineering Sciences and Applied Mathematics, Northwestern University, Chicago, IL, USA
4Center for Applied Molecular Medicine, University of Southern California, Los Angeles, CA, USA.
5Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA, USA.

Tóm tắt

Circulating biomarkers are of significant interest for cancer detection and treatment personalization. However, the biophysical processes that determine how proteins are shed from cancer cells or their microenvironment, diffuse through tissue, enter blood vasculature, and persist in circulation remain poorly understood. Since approaches primarily focused on experimental evaluation are incapable of measuring the shedding and persistence for every possible marker candidate, we propose an interdisciplinary computational/experimental approach that includes computational modeling of tumor tissue heterogeneity. The model implements protein production, transport, and shedding based on tumor vascularization, cell proliferation, hypoxia, and necrosis, thus quantitatively relating the tumor and circulating proteomes. The results highlight the dynamics of shedding as a function of protein diffusivity and production. Linking the simulated tumor parameters to clinical tumor and vascularization measurements could potentially enable this approach to reveal the tumor-specific conditions based on the protein detected in circulation and thus help to more accurately manage cancer diagnosis and treatment.

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Tài liệu tham khảo

Stewart B.W., 2014, World Cancer Report.

10.1016/j.bbcan.2009.04.004

10.1016/j.drudis.2014.07.006

10.1158/2159-8274.CD-10-0010

10.1038/nrc1041

10.1056/NEJMoa1102873

10.1126/science.1101637

10.1158/0008-5472.CAN-10-2676

10.1038/nrc2329

10.1038/ncponc1237

10.1007/s00285-010-0369-1

10.1258/ebm.2009.009230

10.1002/wsbm.102

10.1093/carcin/bgq087

10.1002/wsbm.75

10.1088/0951-7715/23/1/R01

Byrne H.M., 2010, Cancer., 10, 221

Michor F., 2011, Cancer., 11, 657

10.1146/annurev-bioeng-071910-124729

10.1098/rsta.2010.0173

10.1016/j.jtbi.2010.02.036

10.1016/j.jtbi.2012.11.031

10.1007/s11538-008-9349-7

10.1186/1742-4682-4-50

10.1016/j.jtbi.2008.03.027

10.1016/j.mcm.2008.05.011

10.1093/imamat/hxr025

10.1098/rsif.2012.0030

10.1158/0008-5472.CAN-11-1399

10.1016/j.neuroimage.2007.03.008

10.1371/journal.pcbi.1003008

10.1158/0008-5472.CAN-05-3166

Frieboes H., 2014, PLoS One., 10, e0129433, 10.1371/journal.pone.0129433

10.1158/0008-5472.CAN-08-3740

10.1371/journal.pcbi.1003231

10.1007/s00285-008-0214-y

10.1016/j.jtbi.2014.04.012

10.1007/s10928-015-9403-7

10.1016/j.drudis.2013.06.015

10.1016/j.mcm.2007.02.028

10.1504/IJNBM.2011.042131

10.1007/s13346-013-0162-y

10.1021/nn1018818

Li M., 2012, Int J Nanomedicine., 7, 1345

10.2217/nnm.13.117

10.1371/journal.pone.0056876

10.1088/1367-2630/15/5/055004

10.1063/1.3699060

10.1007/s11095-008-9697-x

10.1016/S0065-2660(10)69009-8

10.1208/s12248-013-9478-2

10.1007/978-0-387-25842-3_15

10.1093/carcin/bgp261

10.1111/j.1365-2796.2011.02492.x

10.1016/j.cell.2011.03.001

10.1016/j.jtbi.2006.06.034

10.1101/sqb.2005.70.022

10.1016/j.cbpa.2005.12.016

10.1016/j.semcancer.2014.04.003

10.1371/journal.pmed.0050170

10.1371/journal.pone.0023090

10.1126/scitranslmed.3003110

10.1007/s00285-008-0216-9

10.1016/j.jtbi.2005.12.022

10.1021/pr060102+

10.1002/pmic.200300563

10.1021/pr070233q

10.1371/journal.pmed.0050123

10.1021/pr7007994

10.1074/mcp.M400126-MCP200

10.1021/pr0503533

10.1021/ac025747h

10.1021/ac0341261

10.1074/mcp.M500084-MCP200

10.1074/mcp.M800231-MCP200

10.1093/jnci/92.2.143

10.1158/1535-7163.MCT-11-0852

10.1089/dna.2011.1240

10.1038/nm1101

Nugent L.J., 1984, Cancer Res., 44, 238

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Cancer Informatics

Tập 14

CIN.S35374

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