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Article ; Online: Toward a science of tumor forecasting for clinical oncology.

Yankeelov, Thomas E / Quaranta, Vito / Evans, Katherine J / Rericha, Erin C

2015 Volume 75, Issue 6, Page(s) 918–923

Abstract: We propose that the quantitative cancer biology community makes a concerted effort to apply lessons from weather forecasting to develop an analogous methodology for predicting and evaluating tumor growth and treatment response. Currently, the time course ...

Abstract	We propose that the quantitative cancer biology community makes a concerted effort to apply lessons from weather forecasting to develop an analogous methodology for predicting and evaluating tumor growth and treatment response. Currently, the time course of tumor response is not predicted; instead, response is only assessed post hoc by physical examination or imaging methods. This fundamental practice within clinical oncology limits optimization of a treatment regimen for an individual patient, as well as to determine in real time whether the choice was in fact appropriate. This is especially frustrating at a time when a panoply of molecularly targeted therapies is available, and precision genetic or proteomic analyses of tumors are an established reality. By learning from the methods of weather and climate modeling, we submit that the forecasting power of biophysical and biomathematical modeling can be harnessed to hasten the arrival of a field of predictive oncology. With a successful methodology toward tumor forecasting, it should be possible to integrate large tumor-specific datasets of varied types and effectively defeat one cancer patient at a time.
MeSH term(s)	Forecasting ; Humans ; Medical Oncology/trends ; Meteorology ; Models, Theoretical
Language	English
Publishing date	2015-03-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-14-2233
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Article ; Online: Steering in quadruplet: the complex signaling pathways directing chemotaxis.

Rericha, Erin C / Parent, Carole A

Science signaling

2008 Volume 1, Issue 22, Page(s) pe26

Abstract: Studies in the social amoeba Dictyostelium discoideum reveal that signaling cascades coordinating chemotactic directional sensing and migration are complex, with redundant pathways emerging as cells differentiate. Lack of accumulation of the leading-edge ...

Abstract	Studies in the social amoeba Dictyostelium discoideum reveal that signaling cascades coordinating chemotactic directional sensing and migration are complex, with redundant pathways emerging as cells differentiate. Lack of accumulation of the leading-edge marker phosphatidylinositol-3,4,5-trisphosphate can be compensated by a pathway containing phospholipase A2 (PLA2) in early developed cells and guanylyl cyclase (GC) in later developed, polarized cells. Because numerous signaling networks operational during Dictyostelium chemotaxis are conserved in mammalian cells, PLA2 and GC pathways may also be effective in higher eukaryotes, providing avenues for future research.
MeSH term(s)	Animals ; Chemotaxis ; Dictyostelium ; Guanylate Cyclase/metabolism ; Phospholipases A2/metabolism ; Signal Transduction/physiology
Chemical Substances	Phospholipases A2 (EC 3.1.1.4) ; Guanylate Cyclase (EC 4.6.1.2)
Language	English
Publishing date	2008-06-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.122pe26
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Article ; Online: A mechanically coupled reaction-diffusion model that incorporates intra-tumoural heterogeneity to predict

Hormuth, David A / Weis, Jared A / Barnes, Stephanie L / Miga, Michael I / Rericha, Erin C / Quaranta, Vito / Yankeelov, Thomas E

Journal of the Royal Society, Interface

2017 Volume 14, Issue 128

Abstract: While gliomas have been extensively modelled with a reaction-diffusion (RD) type equation it is most likely an oversimplification. In this study, three mathematical models of glioma growth are developed and systematically investigated to establish a ... ...

Abstract	While gliomas have been extensively modelled with a reaction-diffusion (RD) type equation it is most likely an oversimplification. In this study, three mathematical models of glioma growth are developed and systematically investigated to establish a framework for accurate prediction of changes in tumour volume as well as intra-tumoural heterogeneity. Tumour cell movement was described by coupling movement to tissue stress, leading to a mechanically coupled (MC) RD model. Intra-tumour heterogeneity was described by including a voxel-specific carrying capacity (CC) to the RD model. The MC and CC models were also combined in a third model. To evaluate these models, rats (
MeSH term(s)	Animals ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/physiopathology ; Female ; Glioma/diagnostic imaging ; Glioma/physiopathology ; Magnetic Resonance Imaging ; Models, Biological ; Neoplasms, Experimental/diagnostic imaging ; Neoplasms, Experimental/physiopathology ; Rats ; Rats, Wistar
Language	English
Publishing date	2017-03-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2156283-0
ISSN	1742-5662 ; 1742-5689
ISSN (online)	1742-5662
ISSN	1742-5689
DOI	10.1098/rsif.2016.1010
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Article ; Online: Dictyostelium cells migrate similarly on surfaces of varying chemical composition.

McCann, Colin P / Rericha, Erin C / Wang, Chenlu / Losert, Wolfgang / Parent, Carole A

PloS one

2014 Volume 9, Issue 2, Page(s) e87981

Abstract: During cell migration, cell-substrate binding is required for pseudopod anchoring to move the cell forward, yet the interactions with the substrate must be sufficiently weak to allow parts of the cell to de-adhere in a controlled manner during typical ... ...

Abstract	During cell migration, cell-substrate binding is required for pseudopod anchoring to move the cell forward, yet the interactions with the substrate must be sufficiently weak to allow parts of the cell to de-adhere in a controlled manner during typical protrusion/retraction cycles. Mammalian cells actively control cell-substrate binding and respond to extracellular conditions with localized integrin-containing focal adhesions mediating mechanotransduction. We asked whether mechanotransduction also occurs during non-integrin mediated migration by examining the motion of the social amoeba Dictyostelium discoideum, which is thought to bind non-specifically to surfaces. We discovered that Dictyostelium cells are able to regulate forces generated by the actomyosin cortex to maintain optimal cell-surface contact area and adhesion on surfaces of various chemical composition and that individual cells migrate with similar speed and contact area on the different surfaces. In contrast, during collective migration, as observed in wound healing and metastasis, the balance between surface forces and protrusive forces is altered. We found that Dictyostelium collective migration dynamics are strongly affected when cells are plated on different surfaces. These results suggest that the presence of cell-cell contacts, which appear as Dictyostelium cells enter development, alter the mechanism cells use to migrate on surfaces of varying composition.
MeSH term(s)	Alkanes/pharmacology ; Cell Adhesion/drug effects ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cell Movement/drug effects ; Cell Polarity/drug effects ; Dictyostelium/cytology ; Dictyostelium/drug effects ; Glass/chemistry ; Myosin Type II/metabolism ; Polylysine/pharmacology ; Serum Albumin, Bovine/pharmacology ; Silanes/pharmacology ; Surface Properties ; Talin/metabolism
Chemical Substances	Alkanes ; Silanes ; Talin ; tridecafluoro-1,1,2,2-tetrahydrooctyl-1-dimethylchlorosilane ; Polylysine (25104-18-1) ; Serum Albumin, Bovine (27432CM55Q) ; Myosin Type II (EC 3.6.1.-)
Language	English
Publishing date	2014-02-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0087981
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Article ; Online: Direct biochemical measurements of signal relay during Dictyostelium development.

Das, Satarupa / Rericha, Erin C / Bagorda, Anna / Parent, Carole A

The Journal of biological chemistry

2011 Volume 286, Issue 44, Page(s) 38649–38658

Abstract: Upon starvation, individual Dictyostelium discoideum cells enter a developmental program that leads to collective migration and the formation of a multicellular organism. The process is mediated by extracellular cAMP binding to the G protein-coupled cAMP ...

Abstract	Upon starvation, individual Dictyostelium discoideum cells enter a developmental program that leads to collective migration and the formation of a multicellular organism. The process is mediated by extracellular cAMP binding to the G protein-coupled cAMP receptor 1, which initiates a signaling cascade leading to the activation of adenylyl cyclase A (ACA), the synthesis and secretion of additional cAMP, and an autocrine and paracrine activation loop. The release of cAMP allows neighboring cells to polarize and migrate directionally and form characteristic chains of cells called streams. We now report that cAMP relay can be measured biochemically by assessing ACA, ERK2, and TORC2 activities at successive time points in development after stimulating cells with subsaturating concentrations of cAMP. We also find that the activation profiles of ACA, ERK2, and TORC2 change in the course of development, with later developed cells showing a loss of sensitivity to the relayed signal. We examined mutants in PKA activity that have been associated with precocious development and find that this loss in responsiveness occurs earlier in these mutants. Remarkably, we show that this loss in sensitivity correlates with a switch in migration patterns as cells transition from streams to aggregates. We propose that as cells proceed through development, the cAMP-induced desensitization and down-regulation of cAMP receptor 1 impacts the sensitivities of chemotactic signaling cascades leading to changes in migration patterns.
MeSH term(s)	Adenylyl Cyclases/metabolism ; Biochemistry/methods ; Chemotaxis/physiology ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Dictyostelium/growth & development ; Fluorescence Resonance Energy Transfer/methods ; MAP Kinase Signaling System ; Models, Biological ; Mutation ; Phosphorylation ; Receptors, Cyclic AMP/metabolism ; Signal Transduction
Chemical Substances	Receptors, Cyclic AMP ; Cyclic AMP (E0399OZS9N) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Adenylyl Cyclases (EC 4.6.1.1)
Language	English
Publishing date	2011-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.M111.284182
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Article ; Online: Predicting in vivo glioma growth with the reaction diffusion equation constrained by quantitative magnetic resonance imaging data.

Hormuth, David A / Weis, Jared A / Barnes, Stephanie L / Miga, Michael I / Rericha, Erin C / Quaranta, Vito / Yankeelov, Thomas E

Physical biology

2015 Volume 12, Issue 4, Page(s) 46006

Abstract: Reaction-diffusion models have been widely used to model glioma growth. However, it has not been shown how accurately this model can predict future tumor status using model parameters (i.e., tumor cell diffusion and proliferation) estimated from ... ...

Abstract	Reaction-diffusion models have been widely used to model glioma growth. However, it has not been shown how accurately this model can predict future tumor status using model parameters (i.e., tumor cell diffusion and proliferation) estimated from quantitative in vivo imaging data. To this end, we used in silico studies to develop the methods needed to accurately estimate tumor specific reaction-diffusion model parameters, and then tested the accuracy with which these parameters can predict future growth. The analogous study was then performed in a murine model of glioma growth. The parameter estimation approach was tested using an in silico tumor 'grown' for ten days as dictated by the reaction-diffusion equation. Parameters were estimated from early time points and used to predict subsequent growth. Prediction accuracy was assessed at global (total volume and Dice value) and local (concordance correlation coefficient, CCC) levels. Guided by the in silico study, rats (n = 9) with C6 gliomas, imaged with diffusion weighted magnetic resonance imaging, were used to evaluate the model's accuracy for predicting in vivo tumor growth. The in silico study resulted in low global (tumor volume error <8.8%, Dice >0.92) and local (CCC values >0.80) level errors for predictions up to six days into the future. The in vivo study showed higher global (tumor volume error >11.7%, Dice <0.81) and higher local (CCC <0.33) level errors over the same time period. The in silico study shows that model parameters can be accurately estimated and used to accurately predict future tumor growth at both the global and local scale. However, the poor predictive accuracy in the experimental study suggests the reaction-diffusion equation is an incomplete description of in vivo C6 glioma biology and may require further modeling of intra-tumor interactions including segmentation of (for example) proliferative and necrotic regions.
MeSH term(s)	Animals ; Brain Neoplasms/physiopathology ; Computer Simulation ; Diffusion ; Female ; Glioma/physiopathology ; Magnetic Resonance Imaging ; Models, Theoretical ; Rats ; Rats, Wistar
Language	English
Publishing date	2015-06-04
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2133216-2
ISSN	1478-3975 ; 1478-3967
ISSN (online)	1478-3975
ISSN	1478-3967
DOI	10.1088/1478-3975/12/4/046006
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Article ; Online: Shear stress induces noncanonical autophagy in intestinal epithelial monolayers.

Kim, Sun Wook / Ehrman, Jonathan / Ahn, Mok-Ryeon / Kondo, Jumpei / Lopez, Andrea A Mancheno / Oh, Yun Sik / Kim, Xander H / Crawley, Scott W / Goldenring, James R / Tyska, Matthew J / Rericha, Erin C / Lau, Ken S

Molecular biology of the cell

2017 Volume 28, Issue 22, Page(s) 3043–3056

Abstract: Flow of fluids through the gut, such as milk from a neonatal diet, generates a shear stress on the unilaminar epithelium lining the lumen. We report that exposure to physiological levels of fluid shear stress leads to the formation of large vacuoles, ... ...

Abstract	Flow of fluids through the gut, such as milk from a neonatal diet, generates a shear stress on the unilaminar epithelium lining the lumen. We report that exposure to physiological levels of fluid shear stress leads to the formation of large vacuoles, containing extracellular contents within polarizing intestinal epithelial cell monolayers. These observations lead to two questions: how can cells lacking primary cilia transduce shear stress, and what molecular pathways support the formation of vacuoles that can exceed 80% of the cell volume? We find that shear forces are sensed by actin-rich microvilli that eventually generate the apical brush border, providing evidence that these structures possess mechanosensing ability. Importantly, we identified the molecular pathway that regulates large vacuole formation downstream from mechanostimulation to involve central components of the autophagy pathway, including ATG5 and LC3, but not Beclin. Together our results establish a novel link between the actin-rich microvilli, the macroscopic transport of fluids across cells, and the noncanonical autophagy pathway in organized epithelial monolayers.
MeSH term(s)	Actins/metabolism ; Autophagy/physiology ; Caco-2 Cells ; Cell Culture Techniques ; Epithelium/physiology ; Humans ; Intestinal Mucosa/physiology ; Intestines/physiology ; Microvilli/metabolism ; Stress, Physiological/physiology ; Vacuoles/physiology
Chemical Substances	Actins
Language	English
Publishing date	2017-08-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	1098979-1
ISSN	1939-4586 ; 1059-1524
ISSN (online)	1939-4586
ISSN	1059-1524
DOI	10.1091/mbc.E17-01-0021
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Article: Real-time measurements of cAMP production in live Dictyostelium cells

Bagorda, Anna / Das, Satarupa / Rericha, Erin C / Chen, David / Davidson, Jean / Parent, Carole A

Journal of cell science. 2009 Nov. 1, v. 122, no. 21

2009

Abstract: Cyclic AMP has a crucial role during the entire developmental program of the social amoebae Dictyostelium, acting both as an intracellular second messenger and, when secreted, as a directional cue that is relayed to neighboring cells during chemotaxis. ... ...

Abstract	Cyclic AMP has a crucial role during the entire developmental program of the social amoebae Dictyostelium, acting both as an intracellular second messenger and, when secreted, as a directional cue that is relayed to neighboring cells during chemotaxis. Although significant knowledge about cAMP production in chemotaxing cells has been derived from studies performed on cell populations, cAMP dynamics at the single cell level have not been investigated. To examine this, we used a FRET-based cAMP sensor that possesses high cAMP sensitivity and great temporal resolution. We show the transient profile of cAMP accumulation in live Dictyostelium cells and establish that chemoattractants control intracellular cAMP dynamics by regulating synthesis via the adenylyl cyclase ACA. aca⁻ cells show no significant change in FRET response following chemoattractant addition. Furthermore, cells lacking ACB, the other adenylyl cyclase expressed in chemotaxing cells, behave similarly to wild-type cells. We also establish that the RegA is the major phosphodiesterase that degrades intracellular cAMP in chemotaxis-competent cells. Interestingly, we failed to measure intracellular cAMP compartmentalization in actively chemotaxing cells. We conclude that cytosolic cAMP, which is destined to activate PKA, is regulated by ACA and RegA and does not compartmentalize during chemotaxis.
Language	English
Dates of publication	2009-1101
Size	p. 3907-3914.
Publishing place	The Company of Biologists Limited
Document type	Article
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Clinically relevant modeling of tumor growth and treatment response.

Yankeelov, Thomas E / Atuegwu, Nkiruka / Hormuth, David / Weis, Jared A / Barnes, Stephanie L / Miga, Michael I / Rericha, Erin C / Quaranta, Vito

Science translational medicine

2013 Volume 5, Issue 187, Page(s) 187ps9

Abstract: Current mathematical models of tumor growth are limited in their clinical application because they require input data that are nearly impossible to obtain with sufficient spatial resolution in patients even at a single time point--for example, extent of ... ...

Abstract	Current mathematical models of tumor growth are limited in their clinical application because they require input data that are nearly impossible to obtain with sufficient spatial resolution in patients even at a single time point--for example, extent of vascularization, immune infiltrate, ratio of tumor-to-normal cells, or extracellular matrix status. Here we propose the use of emerging, quantitative tumor imaging methods to initialize a new generation of predictive models. In the near future, these models could be able to forecast clinical outputs, such as overall response to treatment and time to progression, which will provide opportunities for guided intervention and improved patient care.
MeSH term(s)	Cell Division ; Humans ; Models, Biological ; Neoplasms/pathology ; Neoplasms/therapy
Language	English
Publishing date	2013-05-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.3005686
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Article: Collective cell migration requires vesicular trafficking for chemoattractant delivery at the trailing edge

Kriebel, Paul W / Barr, Valarie A / Rericha, Erin C / Zhang, Guofeng / Parent, Carole A

Journal of cell biology. 2008 Dec. 1, v. 183, no. 5

2008

Abstract: Chemoattractant signaling induces the polarization and directed movement of cells secondary to the activation of multiple effector pathways. In addition, chemotactic signals can be amplified and relayed to proximal cells via the synthesis and secretion ... ...

Abstract	Chemoattractant signaling induces the polarization and directed movement of cells secondary to the activation of multiple effector pathways. In addition, chemotactic signals can be amplified and relayed to proximal cells via the synthesis and secretion of additional chemoattractant. The mechanisms underlying such remarkable features remain ill defined. We show that the asymmetrical distribution of adenylyl cyclase (ACA) at the back of Dictyostelium discoideum cells, an essential determinant of their ability to migrate in a head-to-tail fashion, requires vesicular trafficking. This trafficking results in a local accumulation of ACA-containing intracellular vesicles and involves intact actin, microtubule networks, and de novo protein synthesis. We also show that migrating cells leave behind ACA-containing vesicles, likely secreted as multivesicular bodies and presumably involved in the formation of head-to-tail arrays of migrating cells. We propose that similar compartmentalization and shedding mechanisms exist in mammalian cells during embryogenesis, wound healing, neuron growth, and metastasis.
Language	English
Dates of publication	2008-1201
Size	p. 949-961.
Publishing place	The Rockefeller University Press
Document type	Article
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
Database	NAL-Catalogue (AGRICOLA)

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