Computational modeling of therapy on pancreatic cancer in its early stages.

Computational modeling of therapy on pancreatic cancer in its early stages. Biomech Model Mechanobiol. 2019 Sep 09;: Authors: Chen J, Weihs D, Vermolen FJ Abstract More than eighty percent of pancreatic cancer involves ductal adenocarcinoma with an abundant desmoplastic extracellular matrix surrounding the solid tumor entity. This aberrant tumor microenvironment facilitates a strong resistance of pancreatic cancer to medication. Although various therapeutic strategies have been reported to be effective in mice with pancreatic cancer, they still need to be tested quantitatively in wider animal-based experiments before being applied as therapies. To aid the design of experiments, we develop a cell-based mathematical model to describe cancer progression under therapy with a specific application to pancreatic cancer. The displacement of cells is simulated by solving a large system of stochastic differential equations with the Euler-Maruyama method. We consider treatment with the PEGylated drug PEGPH20 that breaks down hyaluronan in desmoplastic stroma followed by administration of the chemotherapy drug gemcitabine to inhibit the proliferation of cancer cells. Modeling the effects of PEGPH20 + gemcitabine concentrations is based on Green's fundamental solutions of the reaction-diffusion equation. Moreover, Monte Carlo simulations are performed to quantitatively investigate uncertainties in the input parameters as well as predictions for the likelihood of succ...
Source: Biomechanics and Modeling in Mechanobiology - Category: Biomedical Science Authors: Tags: Biomech Model Mechanobiol Source Type: research

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Authors: Burkhardt C, Bühler L, Tihy M, Morel P, Forni M Abstract Experimental studies have shown that the IL6/GP130/STAT3 pathway is involved in pancreatic cancer tumorigenesis and progression as well as in the development of other tumors. Bazedoxifene, a selective estrogene receptor modulator clinically available for the treatment of osteoporosis, has been shown to be an effective GP130/STAT3 signaling inhibitor through in vitro and small animal studies. Our aim was to investigate the effect of bazedoxifene on tumor progression in patients with advanced pancreatic and gastric tumors. We analyzed the data of ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer. Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal cancer, is an uncommon but challenging disease. Its incidence has recently increased highly worldwide (1). The risk factors for GBC include sex, aging, obesity, chronic cholecystitis, and cholelithiasis (2, 3). Because of the lack of an effective early diagnostic method, the disease often is not diagnosed ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Michal Yalon1†, Amos Toren1,2†, Dina Jabarin2, Edna Fadida3, Shlomi Constantini3 and Ruty Mehrian-Shai1* 1Pediatric Hemato-Oncology, Edmond and Lilly Safra Children's Hospital and Cancer Research Center, Sheba Medical Center, Ramat Gan, Israel 2The Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel 3Department of Pediatric Neurosurgery, Dana Children's Hospital, Tel-Aviv-Sourasky Medical Center, Tel Aviv, Israel Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important r...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Saeed Nourmohammadi1†, Thazin Nwe Aung2†, Jian Cui2, Jinxin V. Pei1, Michael Lucio De Ieso1, Yuka Harata-Lee2, Zhipeng Qu2, David L. Adelson2* and Andrea J. Yool1* 1Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia 2Department of Molecular and Biomedical Science, School of Biological Sciences, The University of Adelaide, Adelaide, SA, Australia Traditional Chinese Medicines are promising sources of new agents for controlling cancer metastasis. Compound Kushen Injection (CKI), prepared from medicinal plants Sophora flavescens and Heterosmilax chinensis, disrupts cell cycle...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusion Several TISC-based immunotherapeutic approaches are under development in various stages of preclinical studies. As outlined in this review article, a careful and more exhaustive genetic and metabolic understanding of TISC-associated phenotypes is critical to develop novel TISC based immunotherapies. Various components within the tumor microenvironment such as tumor cells, infiltrating immune cells, and supporting stromal cells impact the TISC metabolism. This unique metabolic profile leads to upregulation of certain enzymes and proteins such as ALDH1, CEP55, IDO COA1 etc., which can be utilized for development ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Ginevra Doglioni1,2†, Sweta Parik1,2† and Sarah-Maria Fendt1,2* 1Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium 2Laboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology, KU Leuven and Leuven Cancer Institute, Leuven, Belgium Metastasis formation is the leading cause of death in cancer patients. Thus, understanding and targeting this process is an unmet need. Crucial steps during the establishment of metastases include the (pre)metastatic niche formation. This process relies on the interaction of th...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
This study highlights how the use of in vitro 3D model can allow rapid screening and selection of new and safer drugs. Introduction Angiogenesis is a complex and finely regulated process that consists of the growth of new capillary blood vessels from pre-existing vessels to create communication pathways among tissues. The coordination of different activities such as endothelial cell proliferation and migration, metalloproteinase function, integrin expression and pericyte stabilization is essential for angiogenesis (Folkman, 1984). The “angiogenic switch” is “on” when the balance between pro-...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
In this study, T cells deficient in TRAF6 display enhanced T cell activation, CD28-indpendent stimulation and resistance to Treg cell-mediated suppression (176). Although TLR signaling can promote T cell resistance to Treg cells, the precise molecular mechanism remains yet to be elucidated. It is worth noting that TLR stimulation of T cells increases cytokine production (173, 177), thus future studies should delineate the effect of TLR-MyD88 signaling vs. subsequently induced cytokines in generating resistance to Treg cells. Lastly, it is also crucial to evaluate the effect of TLR signaling on regulatory T cells which also...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusion In this article, we use the amphiphilic copolymer DSPE-SS-mPEG, which is connected by disulfide bonds. Afterward, the magnetic Fe3O4 nanoparticles and the hydrophobic drug are made by the self-assembly of the amphiphilic copolymer. DOX is encapsulated in the amphiphilic copolymer to form a magnetic nano drug controlled release system which is sensitive and responds to a reducing environment. This controlled release system can dissociate the disulfide bonds in the presence of dithiothreitol, thereby triggering the release system to disintegrate and expel the drug. When the DOX-loaded nanocarrier is transported ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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