LIVIVO - Search results -

Search results

Result 1 - 10 of total 16

Search options

Article ; Online: Computational simulations of tumor growth and treatment response

Mohammad R. Nikmaneshi / Rakesh K. Jain / Lance L. Munn

PLoS Computational Biology, Vol 19, Iss

Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization

2023 Volume 6

Abstract: Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three- ... ...

Abstract	Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three-dimensional mathematical model of the TME to simulate tumor growth and angiogenesis and then employed the model to evaluate an array of single and combination therapy approaches. Treatments included maximum tolerated dose or metronomic (i.e., frequent low doses) scheduling of anti-cancer drugs combined with anti-angiogenic therapy. The results show that metronomic therapy normalizes the tumor vasculature to improve drug delivery, modulates cancer metabolism, decreases interstitial fluid pressure and decreases cancer cell invasion. Further, we find that combining an anti-cancer drug with anti-angiogenic treatment enhances tumor killing and reduces drug accumulation in normal tissues. We also show that combined anti-angiogenic and anti-cancer drugs can decrease cancer invasiveness and normalize the cancer metabolic microenvironment leading to reduced hypoxia and hypoglycemia. Our model simulations suggest that vessel normalization combined with metronomic cytotoxic therapy has beneficial effects by enhancing tumor killing and limiting normal tissue toxicity. Author summary Effective treatment of solid tumors with injected drugs requires that sufficient exposure of cancer cells to the cytotoxic drugs. However, non-uniform and poorly functioning blood vessels make this difficult. The amount of drug that reaches a given cancer cells depends on many factors, including the drug chemistry, its lifetime in the blood circulation, its ability to cross the blood vessel wall and enter the tissue, and the schedule of the injections. We present a mathematical model of tumor growth, angiogenesis, metabolism and drug transport that examines how these processes affect the response to treatment. We find that low dose, high frequency (metronomic) therapy normalizes the tumor ...
Keywords	Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The effects of gravity and compression on interstitial fluid transport in the lower limb

James W. Baish / Timothy P. Padera / Lance L. Munn

Scientific Reports, Vol 12, Iss 1, Pp 1-

2022 Volume 16

Abstract: Abstract Edema in the limbs can arise from pathologies such as elevated capillary pressures due to failure of venous valves, elevated capillary permeability from local inflammation, and insufficient fluid clearance by the lymphatic system. The most ... ...

Abstract	Abstract Edema in the limbs can arise from pathologies such as elevated capillary pressures due to failure of venous valves, elevated capillary permeability from local inflammation, and insufficient fluid clearance by the lymphatic system. The most common treatments include elevation of the limb, compression wraps and manual lymphatic drainage therapy. To better understand these clinical situations, we have developed a comprehensive model of the solid and fluid mechanics of a lower limb that includes the effects of gravity. The local fluid balance in the interstitial space includes a source from the capillaries, a sink due to lymphatic clearance, and movement through the interstitial space due to both gravity and gradients in interstitial fluid pressure (IFP). From dimensional analysis and numerical solutions of the governing equations we have identified several parameter groups that determine the essential length and time scales involved. We find that gravity can have dramatic effects on the fluid balance in the limb with the possibility that a positive feedback loop can develop that facilitates chronic edema. This process involves localized tissue swelling which increases the hydraulic conductivity, thus allowing the movement of interstitial fluid vertically throughout the limb due to gravity and causing further swelling. The presence of a compression wrap can interrupt this feedback loop. We find that only by modeling the complex interplay between the solid and fluid mechanics can we adequately investigate edema development and treatment in a gravity dependent limb.
Keywords	Medicine ; R ; Science ; Q
Subject code	532 ; 550
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Glycocalyx mechanotransduction mechanisms are involved in renal cancer metastasis

Heriberto Moran / Limary M. Cancel / Peigen Huang / Sylvie Roberge / Tuoye Xu / John M. Tarbell / Lance L. Munn

Matrix Biology Plus, Vol 13, Iss , Pp 100100- (2022)

2022

Abstract: Mammalian cells, including cancer cells, are covered by a surface layer containing cell bound proteoglycans, glycoproteins, associated glycosaminoglycans and bound proteins that is commonly referred to as the glycocalyx. Solid tumors also have a dynamic ... ...

Abstract	Mammalian cells, including cancer cells, are covered by a surface layer containing cell bound proteoglycans, glycoproteins, associated glycosaminoglycans and bound proteins that is commonly referred to as the glycocalyx. Solid tumors also have a dynamic fluid microenvironment with elevated interstitial flow. In the present work we further investigate the hypothesis that interstitial flow is sensed by the tumor glycocalyx leading to activation of cell motility and metastasis. Using a highly metastatic renal carcinoma cell line (SN12L1) and its low metastatic counterpart (SN12C) we demonstrate in vitro that the small molecule Suberoylanilide Hydroxamic Acid (SAHA) inhibits the heparan sulfate synthesis enzyme N-deacetylase-N-sulfotransferase-1, reduces heparan sulfate in the glycocalyx and suppresses SN12L1 motility in response to interstitial flow. SN12L1 cells implanted in the kidney capsule of SCID mice formed large primary tumors and metastasized to distant organs, but when treated with SAHA metastases were not detected. In another set of experiments, the role of hyaluronic acid was investigated. Hyaluronan synthase 1, a critical enzyme in the synthetic pathway for hyaluronic acid, was knocked down in SN12L1 cells and in vitro experiments revealed inhibition of interstitial flow induced migration. Subsequently these cells were implanted in mouse kidneys and no distant metastases were detected. These findings suggest new therapeutic approaches to the treatment of kidney carcinoma metastasis.
Keywords	Glycocalyx ; Metastasis ; Mechanotransduction ; Renal carcinoma ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Effects of Low Intensity Continuous Ultrasound (LICU) on Mouse Pancreatic Tumor Explants

Despina Bazou / Nir Maimon / Lance L. Munn / Iciar Gonzalez

Applied Sciences, Vol 7, Iss 12, p

2017 Volume 1275

Abstract: This paper describes the effects of low intensity continuous ultrasound (LICU) on the inflammatory response of mouse pancreatic tumor explants. While there are many reports focusing on the application of low-intensity pulsed ultrasound (LIPUS) on cell ... ...

Abstract	This paper describes the effects of low intensity continuous ultrasound (LICU) on the inflammatory response of mouse pancreatic tumor explants. While there are many reports focusing on the application of low-intensity pulsed ultrasound (LIPUS) on cell cultures and tissues, the effects of continuous oscillations on biological tissues have never been investigated. Here we present an exploratory study of the effects induced by LICU on mouse pancreatic tumor explants. We show that LICU causes significant upregulation of IFN-γ, IL-1β, and TNF-α on tumor explants. No detectable effects were observed on tumor vasculature or collagen I deposition, while thermal and mechanical effects were not apparent. Tumor explants responded as a single unit to acoustic waves, with spatial pressure variations smaller than their size.
Keywords	low-intensity continuous ultrasound ; bioeffects ; inflammation ; tumor ; interferon-γ interleukins ; tumor necrosis factor-α (TNF-α) ; collagen I ; vasculature ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
Subject code	500
Language	English
Publishing date	2017-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Towards principled design of cancer nanomedicine to accelerate clinical translation

Mohammad Souri / M. Soltani / Farshad Moradi Kashkooli / Mohammad Kiani Shahvandi / Mohsen Chiani / Fatemeh Sadat Shariati / Mohammad Reza Mehrabi / Lance L. Munn

Materials Today Bio, Vol 13, Iss , Pp 100208- (2022)

2022

Abstract: Nanotechnology in medical applications, especially in oncology as drug delivery systems, has recently shown promising results. However, although these advances have been promising in the pre-clinical stages, the clinical translation of this technology is ...

Abstract	Nanotechnology in medical applications, especially in oncology as drug delivery systems, has recently shown promising results. However, although these advances have been promising in the pre-clinical stages, the clinical translation of this technology is challenging. To create drug delivery systems with increased treatment efficacy for clinical translation, the physicochemical characteristics of nanoparticles such as size, shape, elasticity (flexibility/rigidity), surface chemistry, and surface charge can be specified to optimize efficiency for a given application. Consequently, interdisciplinary researchers have focused on producing biocompatible materials, production technologies, or new formulations for efficient loading, and high stability. The effects of design parameters can be studied in vitro, in vivo, or using computational models, with the goal of understanding how they affect nanoparticle biophysics and their interactions with cells. The present review summarizes the advances and technologies in the production and design of cancer nanomedicines to achieve clinical translation and commercialization. We also highlight existing challenges and opportunities in the field.
Keywords	Tumor microenvironment ; Nanomedicine ; Drug delivery ; Nanoparticle design ; Drug loading ; Clinical translation ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Strategies to minimize heterogeneity and optimize clinical trials in Acute Respiratory Distress Syndrome (ARDS)

Sonu Subudhi / Chrysovalantis Voutouri / C. Corey Hardin / Mohammad Reza Nikmaneshi / Ankit B. Patel / Ashish Verma / Melin J. Khandekar / Sayon Dutta / Triantafyllos Stylianopoulos / Rakesh K. Jain / Lance L. Munn

EBioMedicine, Vol 75, Iss , Pp 103809- (2022)

Insights from mathematical modelling

2022

Abstract: Summary: Background: Mathematical modelling may aid in understanding the complex interactions between injury and immune response in critical illness. Methods: We utilize a system biology model of COVID-19 to analyze the effect of altering baseline ... ...

Abstract	Summary: Background: Mathematical modelling may aid in understanding the complex interactions between injury and immune response in critical illness. Methods: We utilize a system biology model of COVID-19 to analyze the effect of altering baseline patient characteristics on the outcome of immunomodulatory therapies. We create example parameter sets meant to mimic diverse patient types. For each patient type, we define the optimal treatment, identify biologic programs responsible for clinical responses, and predict biomarkers of those programs. Findings: Model states representing older and hyperinflamed patients respond better to immunomodulation than those representing obese and diabetic patients. The disparate clinical responses are driven by distinct biologic programs. Optimal treatment initiation time is determined by neutrophil recruitment, systemic cytokine expression, systemic microthrombosis and the renin-angiotensin system (RAS) in older patients, and by RAS, systemic microthrombosis and trans IL6 signalling for hyperinflamed patients. For older and hyperinflamed patients, IL6 modulating therapy is predicted to be optimal when initiated very early (<4th day of infection) and broad immunosuppression therapy (corticosteroids) is predicted to be optimally initiated later in the disease (7th – 9th day of infection). We show that markers of biologic programs identified by the model correspond to clinically identified markers of disease severity. Interpretation: We demonstrate that modelling of COVID-19 pathobiology can suggest biomarkers that predict optimal response to a given immunomodulatory treatment. Mathematical modelling thus constitutes a novel adjunct to predictive enrichment and may aid in the reduction of heterogeneity in critical care trials. Funding: C.V. received a Marie Skłodowska Curie Actions Individual Fellowship (MSCA-IF-GF-2020-101028945). R.K.J.'s research is supported by R01-CA208205, and U01-CA 224348, R35-CA197743 and grants from the National Foundation for Cancer Research, Jane's ...
Keywords	Systems biology ; modelling ; COVID-19 ; heterogeneity of treatment effect ; clustering ; principal component analysis ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Comparing machine learning algorithms for predicting ICU admission and mortality in COVID-19

Sonu Subudhi / Ashish Verma / Ankit B. Patel / C. Corey Hardin / Melin J. Khandekar / Hang Lee / Dustin McEvoy / Triantafyllos Stylianopoulos / Lance L. Munn / Sayon Dutta / Rakesh K. Jain

npj Digital Medicine, Vol 4, Iss 1, Pp 1-

2021 Volume 7

Abstract: Abstract As predicting the trajectory of COVID-19 is challenging, machine learning models could assist physicians in identifying high-risk individuals. This study compares the performance of 18 machine learning algorithms for predicting ICU admission and ...

Abstract	Abstract As predicting the trajectory of COVID-19 is challenging, machine learning models could assist physicians in identifying high-risk individuals. This study compares the performance of 18 machine learning algorithms for predicting ICU admission and mortality among COVID-19 patients. Using COVID-19 patient data from the Mass General Brigham (MGB) Healthcare database, we developed and internally validated models using patients presenting to the Emergency Department (ED) between March-April 2020 (n = 3597) and further validated them using temporally distinct individuals who presented to the ED between May-August 2020 (n = 1711). We show that ensemble-based models perform better than other model types at predicting both 5-day ICU admission and 28-day mortality from COVID-19. CRP, LDH, and O2 saturation were important for ICU admission models whereas eGFR <60 ml/min/1.73 m2, and neutrophil and lymphocyte percentages were the most important variables for predicting mortality. Implementing such models could help in clinical decision-making for future infectious disease outbreaks including COVID-19.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	006
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The effects of valve leaflet mechanics on lymphatic pumping assessed using numerical simulations

Huabing Li / Yumeng Mei / Nir Maimon / Timothy P. Padera / James W. Baish / Lance L. Munn

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 17

Abstract: Abstract The lymphatic system contains intraluminal leaflet valves that function to bias lymph flow back towards the heart. These valves are present in the collecting lymphatic vessels, which generally have lymphatic muscle cells and can spontaneously ... ...

Abstract	Abstract The lymphatic system contains intraluminal leaflet valves that function to bias lymph flow back towards the heart. These valves are present in the collecting lymphatic vessels, which generally have lymphatic muscle cells and can spontaneously pump fluid. Recent studies have shown that the valves are open at rest, can allow some backflow, and are a source of nitric oxide (NO). To investigate how these valves function as a mechanical valve and source of vasoactive species to optimize throughput, we developed a mathematical model that explicitly includes Ca2+ -modulated contractions, NO production and valve structures. The 2D lattice Boltzmann model includes an initial lymphatic vessel and a collecting lymphangion embedded in a porous tissue. The lymphangion segment has mechanically-active vessel walls and is flanked by deformable valves. Vessel wall motion is passively affected by fluid pressure, while active contractions are driven by intracellular Ca2+ fluxes. The model reproduces NO and Ca2+ dynamics, valve motion and fluid drainage from tissue. We find that valve structural properties have dramatic effects on performance, and that valves with a stiffer base and flexible tips produce more stable cycling. In agreement with experimental observations, the valves are a major source of NO. Once initiated, the contractions are spontaneous and self-sustained, and the system exhibits interesting non-linear dynamics. For example, increased fluid pressure in the tissue or decreased lymph pressure at the outlet of the system produces high shear stress and high levels of NO, which inhibits contractions. On the other hand, a high outlet pressure opposes the flow, increasing the luminal pressure and the radius of the vessel, which results in strong contractions in response to mechanical stretch of the wall. We also find that the location of contraction initiation is affected by the extent of backflow through the valves.
Keywords	Medicine ; R ; Science ; Q
Subject code	621
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Determinants of leukocyte margination in rectangular microchannels.

Abhishek Jain / Lance L Munn

PLoS ONE, Vol 4, Iss 9, p e

2009 Volume 7104

Abstract: Microfabrication of polydimethylsiloxane (PDMS) devices has provided a new set of tools for studying fluid dynamics of blood at the scale of real microvessels. However, we are only starting to understand the power and limitations of this technology. To ... ...

Abstract	Microfabrication of polydimethylsiloxane (PDMS) devices has provided a new set of tools for studying fluid dynamics of blood at the scale of real microvessels. However, we are only starting to understand the power and limitations of this technology. To determine the applicability of PDMS microchannels for blood flow analysis, we studied white blood cell (WBC) margination in channels of various geometries and blood compositions. We found that WBCs prefer to marginate downstream of sudden expansions, and that red blood cell (RBC) aggregation facilitates the process. In contrast to tubes, WBC margination was restricted to the sidewalls in our low aspect ratio, pseudo-2D rectangular channels and consequently, margination efficiencies of more than 95% were achieved in a variety of channel geometries. In these pseudo-2D channels blood rheology and cell integrity were preserved over a range of flow rates, with the upper range limited by the shear in the vertical direction. We conclude that, with certain limitations, rectangular PDMS microfluidic channels are useful tools for quantitative studies of blood rheology.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2009-09-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Synchronization and Random Triggering of Lymphatic Vessel Contractions.

James W Baish / Christian Kunert / Timothy P Padera / Lance L Munn

PLoS Computational Biology, Vol 12, Iss 12, p e

2016 Volume 1005231

Abstract: The lymphatic system is responsible for transporting interstitial fluid back to the bloodstream, but unlike the cardiovascular system, lacks a centralized pump-the heart-to drive flow. Instead, each collecting lymphatic vessel can individually contract ... ...

Abstract	The lymphatic system is responsible for transporting interstitial fluid back to the bloodstream, but unlike the cardiovascular system, lacks a centralized pump-the heart-to drive flow. Instead, each collecting lymphatic vessel can individually contract and dilate producing unidirectional flow enforced by intraluminal check valves. Due to the large number and spatial distribution of such pumps, high-level coordination would be unwieldy. This leads to the question of how each segment of lymphatic vessel responds to local signals that can contribute to the coordination of pumping on a network basis. Beginning with elementary fluid mechanics and known cellular behaviors, we show that two complementary oscillators emerge from i) mechanical stretch with calcium ion transport and ii) fluid shear stress induced nitric oxide production (NO). Using numerical simulation and linear stability analysis we show that the newly identified shear-NO oscillator shares similarities with the well-known Van der Pol oscillator, but has unique characteristics. Depending on the operating conditions, the shear-NO process may i) be inherently stable, ii) oscillate spontaneously in response to random disturbances or iii) synchronize with weak periodic stimuli. When the complementary shear-driven and stretch-driven oscillators interact, either may dominate, producing a rich family of behaviors similar to those observed in vivo.
Keywords	Biology (General) ; QH301-705.5
Subject code	532
Language	English
Publishing date	2016-12-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED