scholarly journals Cooperation of partially transformed clones: an invisible force behind the early stages of carcinogenesis

2021 ◽  
Vol 8 (2) ◽  
pp. 201532
Author(s):  
Alessandro Esposito
Keyword(s):  
Tumour Progression ◽  
Three Dimensional ◽  
Cell Communication ◽  
Significant Heterogeneity ◽  
Early Stages ◽  
Dna Mutations ◽  
A Cell ◽  
Mechanisms Of Carcinogenesis ◽  
Fundamental Forces ◽  
Mutational Process

Most tumours exhibit significant heterogeneity and are best described as communities of cellular populations competing for resources. Growing experimental evidence also suggests that cooperation between cancer clones is important as well for the maintenance of tumour heterogeneity and tumour progression. However, a role for cell communication during the earliest steps in oncogenesis is not well characterized despite its vital importance in normal tissue and clinically manifest tumours. Here, we present a simple analytical model and stochastic lattice-based simulations to study how the interaction between the mutational process and cell-to-cell communication in three-dimensional tissue architecture might contribute to shape early oncogenesis. We show that non-cell-autonomous mechanisms of carcinogenesis could support and accelerate pre-cancerous clonal expansion through the cooperation of different, non- or partially transformed mutants. We predict the existence of a ‘cell-autonomous time horizon', a time before which cooperation between cell-to-cell communication and DNA mutations might be one of the most fundamental forces shaping the early stages of oncogenesis. The understanding of this process could shed new light on the mechanisms leading to clinically manifest cancers.

scholarly journals Cooperation of partially-transformed clones: an invisible force behind the early stages of carcinogenesis

2018 ◽  
Author(s):  
Alessandro Esposito
Keyword(s):  
Tumour Progression ◽  
Three Dimensional ◽  
Cell Communication ◽  
Significant Heterogeneity ◽  
Early Stages ◽  
Dna Mutations ◽  
A Cell ◽  
Mechanisms Of Carcinogenesis ◽  
Fundamental Forces ◽  
Mutational Process

AbstractMost tumours exhibit significant heterogeneity and are best described as communities of cellular populations competing for resources. Growing experimental evidence also suggests, however, that cooperation between cancer clones is important as well for the maintenance of tumour heterogeneity and tumour progression. However, a role for cell communication during the earliest steps in oncogenesis is not well characterised despite its vital importance in normal tissue and clinically manifest tumours. By modelling the interaction between the mutational process and cell-to-cell communication in three-dimensional tissue architecture, we show that non-cell-autonomous mechanisms of carcinogenesis could support and accelerate pre-cancerous clonal expansion through the cooperation of different, non- or partially- transformed mutants. We predict the existence of a ‘cell-autonomous time-horizon’, a time before which cooperation between cell-to-cell communication and DNA mutations might be one of the most fundamental forces shaping the early stages of oncogenesis. The understanding of this process could shed new light on the mechanisms leading to clinically manifest cancers.

scholarly journals A structural perspective on the mechanisms of quorum sensing activation in bacteria

2015 ◽  
Vol 87 (4) ◽  
pp. 2189-2203 ◽  
Author(s):  
CAROLINA LIXA ◽  
AMANDA MUJO ◽  
CRISTIANE D. ANOBOM ◽  
ANDERSON S. PINHEIRO
Keyword(s):  
Gene Expression ◽  
Quorum Sensing ◽  
Rational Design ◽  
Three Dimensional ◽  
Cell Communication ◽  
Dependent Manner ◽  
Regulate Gene Expression ◽  
Wide Range ◽  
A Cell ◽  
Regulate Gene

Bacteria are able to synchronize the population behavior in order to regulate gene expression through a cell-to-cell communication mechanism called quorum sensing. This phenomenon involves the production, detection and the response to extracellular signaling molecules named autoinducers, which directly or indirectly regulate gene expression in a cell density-dependent manner. Quorum sensing may control a wide range of biological processes in bacteria, such as bioluminescence, virulence factor production, biofilm formation and antibiotic resistance. The autoinducers are recognized by specific receptors that can either be membrane-bound histidine kinase receptors, which work by activating cognate cytoplasmic response regulators, or cytoplasmic receptors acting as transcription factors. In this review, we focused on the cytosolic quorum sensing regulators whose three-dimensional structures helped elucidate their mechanisms of action. Structural studies of quorum sensing receptors may enable the rational design of inhibitor molecules. Ultimately, this approach may represent an effective alternative to treat infections where classical antimicrobial therapy fails to overcome the microorganism virulence.

scholarly journals Development of a tunable 3D wrinkled platfom for designing cellular three-dimensional communication networks

2021 ◽  
Author(s):  
Bethany R. Hughes
Keyword(s):  
Communication Networks ◽  
Three Dimensional ◽  
Cell Communication ◽  
Cellular Growth ◽  
Clinical Aspects ◽  
Wide Range ◽  
Cellular Communication Network ◽  
Potential Applications ◽  
A Cell ◽  
Washing Method

The study of cell-cell communication is hindered by the absence of a platform which is capable of specifically directing cellular growth while allowing examination of the communication between cells. In this thesis, a tuneable micro-to-nano scale wrinkled nonplanar platform was developed and optimized through the use of photolithography and a microfluidic washing method. The platform demonstrated the ability to create micro and nanowrinkled structures in a wide range of flow conditions. The developed platform was then used as a cell culture platform to investigate the spacing dependence of bovine fibroblasts. The identification of a critical bridging distance for bovine fibroblasts provided a means to optimized the platform for culturing a cellular communication network between bovine fibroblasts. The cellular network which resulted demonstrated, via FRAP (Fluorescence-recovery-after-photobleaching), the capacity for communication between cells. Creating multilevel length scaled structures on a tunable platform which directed cellular growth while maintaining communication presents potential applications in research, industry and clinical aspects.

scholarly journals Development of a tunable 3D wrinkled platfom for designing cellular three-dimensional communication networks

2021 ◽  
Author(s):  
Bethany R. Hughes
Keyword(s):  
Communication Networks ◽  
Three Dimensional ◽  
Cell Communication ◽  
Cellular Growth ◽  
Clinical Aspects ◽  
Wide Range ◽  
Cellular Communication Network ◽  
Potential Applications ◽  
A Cell ◽  
Washing Method

The study of cell-cell communication is hindered by the absence of a platform which is capable of specifically directing cellular growth while allowing examination of the communication between cells. In this thesis, a tuneable micro-to-nano scale wrinkled nonplanar platform was developed and optimized through the use of photolithography and a microfluidic washing method. The platform demonstrated the ability to create micro and nanowrinkled structures in a wide range of flow conditions. The developed platform was then used as a cell culture platform to investigate the spacing dependence of bovine fibroblasts. The identification of a critical bridging distance for bovine fibroblasts provided a means to optimized the platform for culturing a cellular communication network between bovine fibroblasts. The cellular network which resulted demonstrated, via FRAP (Fluorescence-recovery-after-photobleaching), the capacity for communication between cells. Creating multilevel length scaled structures on a tunable platform which directed cellular growth while maintaining communication presents potential applications in research, industry and clinical aspects.

A Three-Dimensional Viscous Transonic Inverse Design Method

2000 ◽  
Author(s):  
W. T. Tiow ◽  
M. Zangeneh
Keyword(s):  
Design Method ◽  
Flow Analysis ◽  
Three Dimensional ◽  
Viscous Effects ◽  
Flow Equations ◽  
Flow Solution ◽  
Turbomachinery Blades ◽  
A Cell ◽  
Inverse Design Method ◽  
Euler Solver

The development and application of a three-dimensional inverse methodology is presented for the design of turbomachinery blades. The method is based on the mass-averaged swirl, rV~θ distribution and computes the necessary blade changes directly from the discrepancies between the target and initial distributions. The flow solution and blade modification converge simultaneously giving the final blade geometry and the corresponding steady state flow solution. The flow analysis is performed using a cell-vertex finite volume time-marching algorithm employing the multistage Runge-Kutta integrator in conjunction with accelerating techniques (local time stepping and grid sequencing). To account for viscous effects, dissipative forces are included in the Euler solver using the log-law and mixing length models. The design method can be used with any existing solver solving the same flow equations without any modifications to the blade surface wall boundary condition. Validation of the method has been carried out using a transonic annular turbine nozzle and NASA rotor 67. Finally, the method is demonstrated on the re-design of the blades.

scholarly journals Titanium oral implants: surface characteristics, interface biology and clinical outcome

2010 ◽  
Vol 7 (suppl_5) ◽  
Author(s):  
Anders Palmquist ◽  
Omar M. Omar ◽  
Marco Esposito ◽  
Jukka Lausmaa ◽  
Peter Thomsen
Keyword(s):  
Surface Properties ◽  
Cellular Response ◽  
Randomized Clinical Trials ◽  
Three Dimensional ◽  
Cell Communication ◽  
Surface Characteristics ◽  
Titanium Implants ◽  
Material Surface ◽  
Oral Implants

Bone-anchored titanium implants have revolutionized oral healthcare. Surface properties of oral titanium implants play decisive roles for molecular interactions, cellular response and bone regeneration. Nevertheless, the role of specific surface properties, such as chemical and phase composition and nanoscale features, for the biological in vivo performance remains to be established. Partly, this is due to limited transfer of state-of-the-art preparation techniques to complex three-dimensional geometries, analytical tools and access to minute, intact interfacial layers. As judged by the available results of a few randomized clinical trials, there is no evidence that any particular type of oral implant has superior long-term success. Important insights into the recruitment of mesenchymal stem cells, cell–cell communication at the interface and high-resolution imaging of the interface between the surface oxide and the biological host are prerequisites for the understanding of the mechanisms of osseointegration. Strategies for development of the next generation of material surface modifications for compromised tissue are likely to include time and functionally programmed properties, pharmacological modulation and incorporation of cellular components.

scholarly journals Regional Distribution and Kinetics of Three Sites on the GABAA Receptor: Lack of Effect of Portacaval Shunting

1992 ◽  
Vol 12 (2) ◽  
pp. 334-346 ◽  
Author(s):  
Anke M. Mans ◽  
Kelli M. Kukulka ◽  
Keith J. McAvoy ◽  
Norman C. Rokosz
Keyword(s):  
Kinetic Parameters ◽  
Regional Distribution ◽  
Three Dimensional ◽  
Portacaval Shunt ◽  
Brain Regions ◽  
Significant Heterogeneity ◽  
Heterogeneous Distribution ◽  
Dimensional Reconstruction ◽  
Benzodiazepine Site ◽  
Gaba Neurotransmission

The regional distribution of binding sites on the GABAA receptor and their kinetic parameters were measured by quantitative autoradiography in brains from normal rats and rats with a portacaval shunt, a model of portal systemic encephalopathy in which GABA neurotransmission may be altered. The ligands used were [3H]flunitrazepam (a benzodiazepine-site agonist), [3H]-Ro 15-1788 (a benzodiazepine-site antagonist), [3H]muscimol (a GABA-site agonist), and [35S] t-butylbicyclo-phosphorothionate (35S-TBPS, a convulsant that binds to a site near the chloride channel). Some brains were analyzed by computerized image analysis and three-dimensional reconstruction. The regional distribution of binding of the benzodiazepines was very similar, but the patterns obtained with [3H]muscimol and [35S]TBPS were different in many areas, suggesting a heterogeneous distribution of several subtypes of the GABAA receptor. The kinetic parameters were determined in brain regions for [3H]flunitrazepam, [3H]Ro15-1788, and [3H]muscimol. For each ligand, the Kd showed a significant heterogeneity among brain regions (at least threefold), contrary to conclusions drawn from earlier studies. In portacaval shunted rats, binding of all four ligands was essentially unchanged from that in control rats, indicating that, if there was an abnormality in GABA neurotransmission during portal systemic shunting, it was not reflected by altered binding to the main sites on the GABAA receptor.

scholarly journals Analysis of the RNA content of the exosomes derived from blood serum and urine and its potential as biomarkers

2014 ◽  
Vol 369 (1652) ◽  
pp. 20130502 ◽  
Author(s):  
Mu Li ◽  
Emily Zeringer ◽  
Timothy Barta ◽  
Jeoffrey Schageman ◽  
Angie Cheng ◽  
...  
Keyword(s):  
Blood Serum ◽  
Cell Communication ◽  
Cell Culture Model ◽  
Culture Model ◽  
Wide Range ◽  
Abnormal Cells ◽  
A Cell ◽  
Invasive Diagnostics ◽  
Serum And Urine

Exosomes are tiny vesicles (30–150 nm) constantly secreted by all healthy and abnormal cells, and found in abundance in all body fluids. These vesicles, loaded with unique RNA and protein cargo, have a wide range of biological functions, including cell-to-cell communication and signalling. As such, exosomes hold tremendous potential as biomarkers and could lead to the development of minimally invasive diagnostics and next generation therapies within the next few years. Here, we describe the strategies for isolation of exosomes from human blood serum and urine, characterization of their RNA cargo by sequencing, and present the initial data on exosome labelling and uptake tracing in a cell culture model. The value of exosomes for clinical applications is discussed with an emphasis on their potential for diagnosing and treating neurodegenerative diseases and brain cancer.

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