Characterizing the Phenotypic Response of Endothelial Cells Cultured on Pro-Angiogenic In Vitro Tumor Mimics

2012 ◽  
Author(s):  
Christopher S. Szot ◽  
Cara F. Buchanan ◽  
Joseph W. Freeman ◽  
Marissa Nichole Rylander
Keyword(s):  
Cancer Research ◽  
Cancer Progression ◽  
Tumor Development ◽  
New Drugs ◽  
Preclinical Models ◽  
Fda Approval ◽  
Culture Models ◽  
Cell Culture Models

Despite the 200 billion dollars invested in cancer therapy research and development since 1971, only 5% of new drugs entering clinical trials successfully obtain FDA approval [1, 2]. There is a growing concern in the cancer research community that this slow movement in progress stems from the need for improved preclinical models for testing new therapeutic agents [1]. A burgeoning interface between cancer research and tissue engineering is transforming how tumor development is being studied in vitro. As a result, complex 3D cancer cell culture models are beginning to be developed with phenotypes representative of in vivo cancer progression [3].

scholarly journals Engineering Breast Cancer On-chip—Moving Toward Subtype Specific Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Carmen Moccia ◽  
Kristina Haase
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Triple Negative ◽  
New Drugs ◽  
Patient Specific ◽  
Preclinical Models ◽  
Cancer Subtypes ◽  
On Chip

Breast cancer is the second leading cause of death among women worldwide, and while hormone receptor positive subtypes have a clear and effective treatment strategy, other subtypes, such as triple negative breast cancers, do not. Development of new drugs, antibodies, or immune targets requires significant re-consideration of current preclinical models, which frequently fail to mimic the nuances of patient-specific breast cancer subtypes. Each subtype, together with the expression of different markers, genetic and epigenetic profiles, presents a unique tumor microenvironment, which promotes tumor development and progression. For this reason, personalized treatments targeting components of the tumor microenvironment have been proposed to mitigate breast cancer progression, particularly for aggressive triple negative subtypes. To-date, animal models remain the gold standard for examining new therapeutic targets; however, there is room for in vitro tools to bridge the biological gap with humans. Tumor-on-chip technologies allow for precise control and examination of the tumor microenvironment and may add to the toolbox of current preclinical models. These new models include key aspects of the tumor microenvironment (stroma, vasculature and immune cells) which have been employed to understand metastases, multi-organ interactions, and, importantly, to evaluate drug efficacy and toxicity in humanized physiologic systems. This review provides insight into advanced in vitro tumor models specific to breast cancer, and discusses their potential and limitations for use as future preclinical patient-specific tools.

scholarly journals CircZNF609 Promotes Bladder Cancer Progression and Inhibits Cisplatin Sensitivity via miR-1200/CDC25B Pathway

2021 ◽  
Author(s):  
Dexiang Feng ◽  
Jiancheng Lv ◽  
Kai Li ◽  
Qiang Cao ◽  
Jie Han ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Tumor Development ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Online Databases ◽  
Cisplatin Sensitivity ◽  
Cisplatin Chemoresistance

Abstract Circular RNAs (circRNAs) have been extensively studied in tumor development and treatment. CircZNF609 has been shown to act as an oncogene in a variety of solid tumors and may serve as a novel biomarker for tumor diagnosis and treatment. However, the underlying role and mechanism of circZNF609 in bladder cancer (BCa) development and cisplatin chemosensitivity were unknown. Quantitative real-time PCR (qRT-PCR) was applied to determine the expression of circZNF609, microRNA 1200 (miR-1200) and CDC25B in BCa cells and tissues. Western blot was used to detect the protein level of CDC25B. Functional assays in vitro and in vivo were conducted to investigate the effects of circZNF609 on tumor development and cisplatin chemosensitivity in BCa. RNA sequencing and online databases were used to predict the interactions among circZNF609, miR-1200 and CDC25B. Dual luciferase reporter assay, RNA pull-down assay and RNA fluorescence in situ hybridization (FISH) were applied to confirm the mechanism. CircZNF609 expression was significantly up-regulated in BCa cell lines and tissues. Increased expression of circZNF609 was related to a worse survival in BCa patients. In vitro and in vivo, enforced-expression of circZNF609 enhanced BCa cells proliferation, migration and cisplatin chemoresistance. Mechanistically, circZNF609 alleviated the inhibition effect on target CDC25B expression by sponging miR-1200. CircZNF609 promoted tumor growth through novel circZNF609/miR-1200/CDC25B axis, implying that circZNF609 has significant potential to serve as a new diagnostic biomarker and therapeutic target for BCa patients.

scholarly journals MiR-223 Promotes Tumor Progression via Targeting RhoB in Gastric Cancer

2022 ◽  
Vol 2022 ◽  
pp. 1-10
Author(s):  
You Hu ◽  
Bin Yi ◽  
Xin Chen ◽  
Lu Xu ◽  
Xiaojun Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Progression ◽  
Cancer Progression ◽  
Tumor Development ◽  
Migration And Invasion ◽  
Cellular Mechanisms ◽  
Borrmann Type ◽  
Potential Biomarker

Gastric cancer (GC) is among the most prevalent causes of cancer-related death globally. MiR-223 has been implicated in a variety of cellular mechanisms linked to cancer progression. However, the miR-223 expressions and its function in GC are unknown. We discovered that miR-223 expression was raised in GC tissues in comparison with nearby normal tissues in this investigation. Additionally, multiplied miR-223 expression was strongly linked with TNM stage ( p = 0.022 ), live metastasis ( p = 0.004 ),lymph node metastasis ( p = 0.004 ),and Borrmann type and was associated with an unfavorable prognostic for patients with GC. Furthermore, suppressing miR-223 significantly increased cell death and prevented cell migration and invasion in vitro. Additionally, miR-223 silencing decreased tumor development in vivo. Additionally, we discovered that miR-223 enhanced GC development by specifically targeting RhoB. In summary, our findings reveal that miR-223 increases tumor progression in GC by targeting RhoB, suggesting that it could serve to be a potential biomarker for the prediction of the disease.

scholarly journals PPAR-gamma Fun(gi) With Prostaglandin

2020 ◽  
Vol 17 ◽  
pp. 155076291989964
Author(s):  
Robert J. Evans ◽  
Simon A. Johnston
Keyword(s):  
Partial Agonist ◽  
Ppar Gamma ◽  
Host Cells ◽  
Culture Models ◽  
Important Regulator ◽  
Inflammatory Phenotypes ◽  
First Time ◽  
Cell Culture Models

In our recent publication, we show for the first time that the fungal pathogen Cryptococcus neoformans is able to manipulate host cells by producing eicosanoids that mimic those found in the host. Using complementary in vivo zebrafish and in vitro macrophage cell culture models of Cryptococcus infection, we found that these eicosanoids manipulate host innate immune cells by activating the host receptor PPAR-gamma which is an important regulator of macrophage inflammatory phenotypes. We initially identified PGE2 as the eicosanoid species responsible for this effect; however, we later found that a derivative of PGE2—15-keto-PGE2—was ultimately responsible and that this eicosanoid acted as a partial agonist to PPAR-gamma. In this commentary, we will discuss some of the concepts and conclusions in our original publication and expand on their implications and future directions.

scholarly journals Organotypic Modeling of the Tumor Landscape

2020 ◽  
Vol 8 ◽  
Author(s):  
Maria M. Haykal ◽  
Clara Nahmias ◽  
Christine Varon ◽  
Océane C. B. Martin
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Complex Disease ◽  
Epithelial Tumor ◽  
Stromal Compartment ◽  
Culture Models ◽  
Potential Benefits

Cancer is a complex disease and it is now clear that not only epithelial tumor cells play a role in carcinogenesis. The tumor microenvironment is composed of non-stromal cells, including endothelial cells, adipocytes, immune and nerve cells, and a stromal compartment composed of extracellular matrix, cancer-associated fibroblasts and mesenchymal cells. Tumorigenesis is a dynamic process with constant interactions occurring between the tumor cells and their surroundings. Even though all connections have not yet been discovered, it is now known that crosstalk between actors of the microenvironment drives cancer progression. Taking into account this complexity, it is important to develop relevant models to study carcinogenesis. Conventional 2D culture models fail to represent the entire tumor microenvironment properly and the use of animal models should be decreased with respect to the 3Rs rule. To this aim, in vitro organotypic models have been significantly developed these past few years. These models have different levels of complexity and allow the study of tumor cells alone or in interaction with the microenvironment actors during the multiple stages of carcinogenesis. This review depicts recent insights into organotypic modeling of the tumor and its microenvironment all throughout cancer progression. It offers an overview of the crosstalk between epithelial cancer cells and their microenvironment during the different phases of carcinogenesis, from the early cell autonomous events to the late metastatic stages. The advantages of 3D over classical 2D or in vivo models are presented as well as the most promising organotypic models. A particular focus is made on organotypic models used for studying cancer progression, from the less complex spheroids to the more sophisticated body-on-a-chip. Last but not least, we address the potential benefits of these models in personalized medicine which is undoubtedly a domain paving the path to new hopes in terms of cancer care and cure.

scholarly journals Pterostilbene inhibits gallbladder cancer progression by suppressing the PI3K/Akt pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chenhao Tong ◽  
Yali Wang ◽  
Jiandong Li ◽  
Wenda Cen ◽  
Weiguang Zhang ◽  
...  
Keyword(s):  
Gallbladder Cancer ◽  
Cancer Progression ◽  
New Drugs ◽  
Tumor Xenograft ◽  
Migration And Invasion ◽  
Akt Activation ◽  
Degree Of Malignancy ◽  
High Degree

AbstractGallbladder cancer is the most common malignant tumor of the biliary system and is characterized by difficulty to diagnose in early stages, a high degree of malignancy, and poor prognosis. Finding new drugs may improve the prognosis for this dismal cancer. Herein, we investigated the potential application of pterostilbene (PTS) against gallbladder cancer in vivo and in vitro. PTS potently inhibited cell proliferation, migration and invasion of gallbladder cancer cells. Moreover, PTS also had a function of inducing apoptosis in vitro. Meanwhile, PTS reversed EMT with a correlated inhibition of PI3K/Akt activation. Tumor xenograft models showed that PTS inhibited tumor growth and had low toxicity in vivo, which were consistent with the in vitro data. These findings indicate that PTS arrests cell growth through inhibition of PI3K/AKT signaling and is a potential drug for the therapy of gallbladder cancer.

scholarly journals Optimizations of In Vitro Mucus and Cell Culture Models to Better Predict In Vivo Gene Transfer in Pathological Lung Respiratory Airways: Cystic Fibrosis as an Example

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 47
Author(s):  
Rosy Ghanem ◽  
Véronique Laurent ◽  
Philippe Roquefort ◽  
Tanguy Haute ◽  
Sophie Ramel ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Gene Therapy ◽  
Cell Culture ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Culture Models ◽  
Transfer Strategies ◽  
Cell Culture Models

The respiratory epithelium can be affected by many diseases that could be treated using aerosol gene therapy. Among these, cystic fibrosis (CF) is a lethal inherited disease characterized by airways complications, which determine the life expectancy and the effectiveness of aerosolized treatments. Beside evaluations performed under in vivo settings, cell culture models mimicking in vivo pathophysiological conditions can provide complementary insights into the potential of gene transfer strategies. Such models must consider multiple parameters, following the rationale that proper gene transfer evaluations depend on whether they are performed under experimental conditions close to pathophysiological settings. In addition, the mucus layer, which covers the epithelial cells, constitutes a physical barrier for gene delivery, especially in diseases such as CF. Artificial mucus models featuring physical and biological properties similar to CF mucus allow determining the ability of gene transfer systems to effectively reach the underlying epithelium. In this review, we describe mucus and cellular models relevant for CF aerosol gene therapy, with a particular emphasis on mucus rheology. We strongly believe that combining multiple pathophysiological features in single complex cell culture models could help bridge the gaps between in vitro and in vivo settings, as well as viral and non-viral gene delivery strategies.

scholarly journals Selenomethionine-Dominated Selenium-Enriched Peanut Protein Ameliorates Alcohol-Induced Liver Disease in Mice by Suppressing Oxidative Stress

Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 2979
Author(s):  
Lin Gao ◽  
Jiawei Yuan ◽  
Yuhuan Cheng ◽  
Mengling Chen ◽  
Genhua Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Therapeutic Agents ◽  
Peanut Protein ◽  
Culture Models ◽  
Therapeutic Properties ◽  
Cell Culture Models ◽  
Dependent Mechanism

Numerous natural compounds are considered as potential therapeutic agents against alcohol-induced liver disease (ALD). Research shows that selenium (Se) has a variety of bioactivities, including liver protecting ability. The present study based on in vitro cell culture models and in vivo mouse models was aimed at examining the contribution of selenomethionine (SeMet)-dominated Se-enriched peanut protein (SePP) to liver protection. SeMet and especially SePP reversed cell viability and cell death, inhibited ethanol induced CYP2E1 activation, decreased reactive oxygen species level, and restored GSH level. Hence, SeMet-dominated SePP alleviates alcohol-induced AML-12 cytotoxicity by suppressing oxidative stress. The p38-dependent mechanism was found to be responsible for SePP-induced Nrf-2 activation. Furthermore, supplementation with SePP and SeMet regulated lipid metabolism and reduced oxidative stress, minimizing liver damage in mice. Selenomethionine-dominated SePP possesses potential therapeutic properties and can be used to treat ALD through the suppression of oxidative stress.

scholarly journals Tissue Engineering of Oral Mucosa and Salivary Gland: Disease Modeling and Clinical Applications

Micromachines ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1066
Author(s):  
Akram Abdo Almansoori ◽  
Bongju Kim ◽  
Jong-Ho Lee ◽  
Simon D. Tran
Keyword(s):  
Cell Culture ◽  
Salivary Gland ◽  
Oral Mucosa ◽  
Disease Modeling ◽  
Clinical Applications ◽  
New Drugs ◽  
Human Organ ◽  
Culture Models ◽  
Cell Culture Models

Oral mucosa and salivary gland are composed of complex and dynamic networks of extracellular matrix, multiple cell types, vasculature, and various biochemical agents. Two-dimensional (2D) cell culture is commonly used in testing new drugs and experimental therapies. However, 2D cell culture cannot fully replicate the architecture, physiological, and pathological microenvironment of living human oral mucosa and salivary glands. Recent microengineering techniques offer state of the science cell culture models that can recapitulate human organ structures and functions. This narrative review describes emerging in vitro models of oral and salivary gland tissue such as 3D cell culture models, spheroid and organoid models, tissue-on-a-chip, and functional decellularized scaffolds. Clinical applications of these models are also discussed in this review.

scholarly journals In Vivo Airway Surface Liquid Cl− Analysis with Solid-State Electrodes

2001 ◽  
Vol 119 (1) ◽  
pp. 3-14 ◽  
Author(s):  
Ray A. Caldwell ◽  
Barbara R. Grubb ◽  
Robert Tarran ◽  
Richard C. Boucher ◽  
Michael R. Knowles ◽  
...  
Keyword(s):  
Solid State ◽  
Airway Surface Liquid ◽  
Culture Models ◽  
Normal Human ◽  
Surface Liquid ◽  
Multiple Species ◽  
Cell Culture Models ◽  
Made In

The pathogenesis of cystic fibrosis (CF) airways disease remains controversial. Hypotheses that link mutations in CFTR and defects in ion transport to CF lung disease predict that alterations in airway surface liquid (ASL) isotonic volume, or ion composition, are critically important. ASL [Cl−] is pivotal in discriminating between these hypotheses, but there is no consensus on this value given the difficulty in measuring [Cl−] in the “thin” ASL (∼30 μm) in vivo. Consequently, a miniaturized solid-state electrode with a shallow depth of immersion was constructed to measure ASL [Cl−] in vivo. In initial experiments, the electrode measured [Cl−] in physiologic salt solutions, small volume (7.6 μl) test solutions, and in in vitro cell culture models, with ≥93% accuracy. Based on discrepancies in reported values and/or absence of data, ASL Cl− measurements were made in the following airway regions and species. First, ASL [Cl−] was measured in normal human nasal cavity and averaged 117.3 ± 11.2 mM (n = 6). Second, ASL [Cl−] measured in large airway (tracheobronchial) regions were as follows: rabbit trachea and bronchus = 114.3 ± 1.8 mM; (n = 6) and 126.9 ± 1.7 mM; (n = 3), respectively; mouse trachea = 112.8 ± 4.2 mM (n = 13); and monkey bronchus = 112.3 ± 10.9 mM (n = 3). Third, Cl− measurements were made in small (1–2 mm) diameter airways of the rabbit (108.3 ± 7.1 mM, n = 5) and monkey (128.5 ± 6.8 mM, n = 3). The measured [Cl−], in excess of 100 mM throughout all airway regions tested in multiple species, is consistent with the isotonic volume hypothesis to describe ASL physiology.

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