scholarly journals Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yafei Wang ◽  
Erik Brodin ◽  
Kenichiro Nishii ◽  
Hermann B. Frieboes ◽  
Shannon M. Mumenthaler ◽  
...  
Keyword(s):  
Time Scales ◽  
Constitutive Relations ◽  
Elastic Tissue ◽  
Metastatic Progression ◽  
Patient Death ◽  
Metastatic Growth ◽  
Tumor Parenchyma ◽  
Short Time ◽  
Model Approach

AbstractColorectal cancer and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors could “reawaken” after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach yields insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, and advances the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer.

scholarly journals Impact of tumor-parenchyma biomechanics on liver metastatic progression: a multi-model approach

2020 ◽  
Author(s):  
Yafei Wang ◽  
Erik Brodin ◽  
Kenichiro Nishii ◽  
Hermann B. Frieboes ◽  
Shannon Mumenthaler ◽  
...  
Keyword(s):  
Time Scales ◽  
Constitutive Relations ◽  
Elastic Tissue ◽  
Metastatic Progression ◽  
Patient Death ◽  
Metastatic Growth ◽  
Tumor Parenchyma ◽  
Short Time ◽  
Model Approach

ABSTRACTColorectal cancer (CRC) and other cancers often metastasize to the liver in later stages of the disease, contributing significantly to patient death. While the biomechanical properties of the liver parenchyma (normal liver tissue) are known to affect tumor cell behavior in primary and metastatic tumors, the role of these properties in driving or inhibiting metastatic inception remains poorly understood, as are the longer-term multicellular dynamics. This study adopts a multi-model approach to study the dynamics of tumor-parenchyma biomechanical interactions during metastatic seeding and growth. We employ a detailed poroviscoelastic (PVE) model of a liver lobule to study how micrometastases disrupt flow and pressure on short time scales. Results from short-time simulations in detailed single hepatic lobules motivate constitutive relations and biological hypotheses for a minimal agent-based model of metastatic growth in centimeter-scale tissue over months-long time scales. After a parameter space investigation, we find that the balance of basic tumor-parenchyma biomechanical interactions on shorter time scales (adhesion, repulsion, and elastic tissue deformation over minutes) and longer time scales (plastic tissue relaxation over hours) can explain a broad range of behaviors of micrometastases, without the need for complex molecular-scale signaling. These interactions may arrest the growth of micrometastases in a dormant state and prevent newly arriving cancer cells from establishing successful metastatic foci. Moreover, the simulations indicate ways in which dormant tumors could “reawaken” after changes in parenchymal tissue mechanical properties, as may arise during aging or following acute liver illness or injury. We conclude that the proposed modeling approach yields insight into the role of tumor-parenchyma biomechanics in promoting liver metastatic growth, and advances the longer term goal of identifying conditions to clinically arrest and reverse the course of late-stage cancer.

scholarly journals Implementasi Model Timmons dalam pembinaan startup berbasis teknologi pada inkubator bisnis

2019 ◽  
Vol 19 (1) ◽  
pp. 35-48
Author(s):  
Cut Irna Setiawati ◽  
Putri Meuthia Pratiwi
Keyword(s):  
Product Development ◽  
Business Model ◽  
Qualitative Method ◽  
Working Hours ◽  
Selling Price ◽  
Market Demand ◽  
Short Time ◽  
Model Approach

In 2013 Indonesia has developed Bandung Techno Park (BTP) as the business incubator and develop Startup Corner (SC) program. SC has four main phrases, such as Registration, Selection through Presentation, Pre Incubation, and Implementing Incubation Process. However, SC has not been maximized in identifying aspects of opportunities, teams and resources. The purpose of this research is to know the role of SC in developing in relation with opportunity, team, and resources aspects. This research used descriptive qualitative method, with Timmons Model approach. The sample of this research is SC members and BTP supervisor by using structural interview with informans. As the results, the role of SC on the dimension of idea has played for product development, business model, and selling price. Market demand dimension is directing customer translation so that can assist in reaching customer opportunity and expanding market reach. Furthermore the role of SC in developing startup of team aspect based on leader dimension and team quality. The SC through training program has purposed to shape the entrepreneurial character during Pre Incubation activities. In creating the quality of the team submitted by setting an advisable work discipline in accordance with the BTP working hours other than that Startup Corner helps in disseminating recruitment information for startup requiring members. The role of SC in developing startup from the aspect of resources has provided physical facilities, then assistance to make the legality of a business entity, patent but there is no funding for the sustainability of a startup, then diverted in incubation or other programs. SC arranges all the sections for startup participants and has a good results but the final maitenance would take effort from the startups itself, because BTP only supports them and building the business model in techonology in short time.

scholarly journals The Capacity and Organization of Gustatory Working Memory

2021 ◽  
Author(s):  
Xue Li Lim ◽  
Richard Höchenberger ◽  
Iryna Ruda ◽  
Gereon Fink ◽  
Shivakumar Viswanathan ◽  
...  
Keyword(s):  
Working Memory ◽  
Food Intake ◽  
Serial Position ◽  
Associative Learning ◽  
Time Scales ◽  
Hybrid Model ◽  
Limited Capacity ◽  
Stimulus Similarity ◽  
Short Time

Abstract Remembering a particular taste is crucial in food intake and associative learning. We investigated whether taste can be dynamically encoded, maintained, and retrieved on short time-scales consistent with working memory (WM). We used novel single and multi-item taste recognition tasks to investigate the organization and capacity of gustatory WM. In Experiment 1, we show that a single taste can be reliably recognized despite multiple oro-sensory interferences suggesting active and resilient maintenance. When multiple tastes were presented, the resolution with which these could be maintained, depended on their serial position implying a role of attention. Participants reliably recognized up to three tastes, compatible with a limited capacity of gustatory WM. Lastly, recognition was better for match than foil trials likely due to increased stimulus similarity in foil trials. Together, the results advocate a hybrid model of gustatory WM with a limited number of slots where items are stored with varying precision.

Photoluminescence decay dynamics in γ-Ga2O3 nanocrystals: The role of exclusion distance at short time scales

2017 ◽  
Vol 684 ◽  
pp. 135-140 ◽  
Author(s):  
Brian Fernandes ◽  
Manu Hegde ◽  
Paul C. Stanish ◽  
Zoran L. Mišković ◽  
Pavle V. Radovanovic
Keyword(s):  
Time Scales ◽  
Photoluminescence Decay ◽  
Short Time

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

410: Cleavage of E-Cadherin and the Role of an 80KDa Fragment in the Metastatic Progression of Prostate Cancer

2004 ◽  
Vol 171 (4S) ◽  
pp. 108-108
Author(s):  
Rainer Kuefer ◽  
Kathleen Day ◽  
Jonathan Rios-Doria ◽  
Matthias Hofer ◽  
Arul Chinnaiyan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Progression ◽  
E Cadherin

The Spread of Pollutants from Harbour Sludge Depots

1984 ◽  
Vol 16 (3-4) ◽  
pp. 623-633
Author(s):  
M Loxham ◽  
F Weststrate
Keyword(s):  
Time Scales ◽  
Molecular Diffusion ◽  
Near Field ◽  
Parameter Analysis ◽  
Migration Patterns ◽  
Long Time ◽  
Dilution Effects ◽  
Short Time ◽  
Harbour Sludge

It is generally agreed that both the landfill option, or the civil techniques option for the final disposal of contaminated harbour sludge involves the isolation of the sludge from the environment. For short time scales, engineered barriers such as a bentonite screen, plastic sheets, pumping strategies etc. can be used. However for long time scales the effectiveness of such measures cannot be counted upon. It is thus necessary to be able to predict the long term environmenttal spread of contaminants from a mature landfill. A model is presented that considers diffusion and adsorption in the landfill site and convection and adsorption in the underlaying aquifer. From a parameter analysis starting form practical values it is shown that the adsorption behaviour and the molecular diffusion coefficient of the sludge, are the key parameters involved in the near field. The dilution effects of the far field migration patterns are also illustrated.

scholarly journals Inhibition of CCL7 derived from Mo-MDSCs prevents metastatic progression from latency in colorectal cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Xiaoli Ren ◽  
Jianbiao Xiao ◽  
Wanning Zhang ◽  
Feifei Wang ◽  
Yongrong Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Suppressor Cells ◽  
Metastatic Progression ◽  
Ht29 Cells ◽  
Metastatic Cells ◽  
Long Time ◽  
Mice Liver ◽  
Short Time ◽  
Related Proteins

AbstractIn colorectal cancer (CRC), overt metastases often appear after years of latency. But the signals that cause micro-metastatic cells to remain indolent, thereby enabling them to survive for extended periods of time, are unclear. Immunofluorescence and co-immunoprecipitation assays were used to explore the co-localization of CCL7 and CCR2. Immunohistochemical (IHC) assays were employed to detect the characters of metastatic HT29 cells in mice liver. Flow cytometry assays were performed to detect the immune cells. Bruberin vivo MS FX Pro Imager was used to observe the liver metastasis of CRC in mice. Quantitative real-time PCR (qRT-PCR) and western blot were employed to detect the expressions of related proteins. Trace RNA sequencing was employed to identify differentially expressed genes in MDSCs from liver micro-M and macro-M of CRC in mice. Here, we firstly constructed the vitro dormant cell models and metastatic dormant animal models of colorectal cancer. Then we found that myeloid-derived suppressor cells (MDSCs) were increased significantly from liver micro-metastases to macro-metastases of CRC in mice. Moreover, monocytic MDSCs (Mo-MDSC) significantly promoted the dormant activation of micro-metastatic cells compared to polymorphonuclear MDSCs (PMN-MDSC). Mechanistically, CCL7 secreted by Mo-MDSCs bound with membrane protein CCR2 of micro-metastatic cells and then stimulated the JAK/STAT3 pathway to activate the dormant cells. Low-dose administration of CCL7 and MDSCs inhibitors in vivo could significantly maintain the CRC metastatic cells dormant status for a long time to reduce metastasis or recurrence after radical operation. Clinically, the level of CCL7 in blood was positively related to the number of Mo-MDSCs in CCR patients, and highly linked with the short-time recurrence and distant metastasis. CCL7 secreted by Mo-MDSCs plays an important role in initiating the outgrowth of metastatic latent CRC cells. Inhibition of CCL7 might provide a potential therapeutic strategy for the prevention of metastasis recurrence.

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