scholarly journals Development, validation and pilot screening of an in vitro multi-cellular three-dimensional cancer spheroid assay for anti-cancer drug testing

2013 ◽  
Vol 21 (4) ◽  
pp. 922-931 ◽  
Author(s):  
Rati Lama ◽  
Lin Zhang ◽  
Janine M. Naim ◽  
Jennifer Williams ◽  
Aimin Zhou ◽  
...  
Keyword(s):  
Drug Testing ◽  
Three Dimensional ◽  
Cancer Drug ◽  
Anti Cancer

scholarly journals Optimization and Validation of a Novel Three-Dimensional Co-Culture System in Decellularized Human Liver Scaffold for the Study of Liver Fibrosis and Cancer

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4936
Author(s):  
Kessarin Thanapirom ◽  
Elisabetta Caon ◽  
Margarita Papatheodoridi ◽  
Luca Frenguelli ◽  
Walid Al-Akkad ◽  
...  
Keyword(s):  
Protein Expression ◽  
Human Liver ◽  
Drug Testing ◽  
Three Dimensional ◽  
Cancer Drug ◽  
3D Scaffolds ◽  
Stat3 Phosphorylation ◽  
Anti Cancer ◽  
Tgf Β1

The introduction of new preclinical models for in vitro drug discovery and testing based on 3D tissue-specific extracellular matrix (ECM) is very much awaited. This study was aimed at developing and validating a co-culture model using decellularized human liver 3D ECM scaffolds as a platform for anti-fibrotic and anti-cancer drug testing. Decellularized 3D scaffolds obtained from healthy and cirrhotic human livers were bioengineered with LX2 and HEPG2 as single and co-cultures for up to 13 days and validated as a new drug-testing platform. Pro-fibrogenic markers and cancer phenotypic gene/protein expression and secretion were differently affected when single and co-cultures were exposed to TGF-β1 with specific ECM-dependent effects. The anti-fibrotic efficacy of Sorafenib significantly reduced TGF-β1-induced pro-fibrogenic effects, which coincided with a downregulation of STAT3 phosphorylation. The anti-cancer efficacy of Regorafenib was significantly reduced in 3D bioengineered cells when compared to 2D cultures and dose-dependently associated with cell apoptosis by cleaved PARP-1 activation and P-STAT3 inhibition. Regorafenib reversed TGF-β1-induced P-STAT3 and SHP-1 through induction of epithelial mesenchymal marker E-cadherin and downregulation of vimentin protein expression in both co-cultures engrafting healthy and cirrhotic 3D scaffolds. In their complex, the results of the study suggest that this newly proposed 3D co-culture platform is able to reproduce the natural physio-pathological microenvironment and could be employed for anti-fibrotic and anti-HCC drug screening.

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

scholarly journals Patient-Derived Organoids as a Model for Cancer Drug Discovery

2021 ◽  
Vol 22 (7) ◽  
pp. 3483
Author(s):  
Colin Rae ◽  
Francesco Amato ◽  
Chiara Braconi
Keyword(s):  
Drug Testing ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Tumour Microenvironment ◽  
In Vitro Models ◽  
Personalized Therapy ◽  
Cancer Drug ◽  
Patient Response

In the search for the ideal model of tumours, the use of three-dimensional in vitro models is advancing rapidly. These are intended to mimic the in vivo properties of the tumours which affect cancer development, progression and drug sensitivity, and take into account cell–cell interactions, adhesion and invasiveness. Importantly, it is hoped that successful recapitulation of the structure and function of the tissue will predict patient response, permitting the development of personalized therapy in a timely manner applicable to the clinic. Furthermore, the use of co-culture systems will allow the role of the tumour microenvironment and tissue–tissue interactions to be taken into account and should lead to more accurate predictions of tumour development and responses to drugs. In this review, the relative merits and limitations of patient-derived organoids will be discussed compared to other in vitro and ex vivo cancer models. We will focus on their use as models for drug testing and personalized therapy and how these may be improved. Developments in technology will also be considered, including the use of microfluidics, 3D bioprinting, cryopreservation and circulating tumour cell-derived organoids. These have the potential to enhance the consistency, accessibility and availability of these models.

scholarly journals Three-Dimensional (3D) Culture Models in Cancer Investigation, Drug Testing and Immune Response Evaluation

2020 ◽  
Vol 22 (1) ◽  
pp. 150
Author(s):  
Roberto Benelli ◽  
Maria Raffaella Zocchi ◽  
Alessandro Poggi
Keyword(s):  
Drug Testing ◽  
Three Dimensional ◽  
3D Culture ◽  
Cancer Drug ◽  
Response Evaluation ◽  
Preclinical Models ◽  
Safety And Efficacy ◽  
Anti Cancer ◽  
Culture Models ◽  
Definition Of

Preclinical models for the definition of anti-cancer drug safety and efficacy are constantly evolving [...]

scholarly journals Patient-Derived Tumor Organoids for Drug Repositioning in Cancer Care: A Promising Approach in the Era of Tailored Treatment

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3636
Author(s):  
Silvia Vivarelli ◽  
Saverio Candido ◽  
Giuseppe Caruso ◽  
Luca Falzone ◽  
Massimo Libra
Keyword(s):  
Cancer Care ◽  
Drug Testing ◽  
Drug Repositioning ◽  
Therapy Resistance ◽  
Cancer Drug ◽  
Cancer Resistance ◽  
Off Label ◽  
Anti Cancer ◽  
Tumor Organoids

Malignancies heterogeneity represents a critical issue in cancer care, as it often causes therapy resistance and tumor relapse. Organoids are three-dimensional (3D) miniaturized representations of selected tissues within a dish. Lately, organoid technology has been applied to oncology with growing success and Patients Derived Tumor Organoids (PDTOs) constitute a novel available tool which fastens cancer research. PDTOs are in vitro models of cancer, and importantly, they can be used as a platform to validate the efficacy of anti-cancer drugs. For that reason, they are currently utilized in clinics as emerging in vitro screening technology to tailor the therapy around the patient, with the final goal of beating cancer resistance and recurrence. In this sense, PDTOs biobanking is widely used and PDTO-libraries are helping the discovery of novel anticancer molecules. Moreover, they represent a good model to screen and validate compounds employed for other pathologies as off-label drugs potentially repurposed for the treatment of tumors. This will open up novel avenues of care thus ameliorating the life expectancy of cancer patients. This review discusses the present advancements in organoids research applied to oncology, with special attention to PDTOs and their translational potential, especially for anti-cancer drug testing, including off-label molecules.

scholarly journals Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 3930
Author(s):  
Sangun Park ◽  
Tae Kim ◽  
Soo Kim ◽  
Seungkwon You ◽  
Youngmee Jung
Keyword(s):  
Lung Cancer ◽  
Extracellular Matrix ◽  
Three Dimensional ◽  
A549 Cells ◽  
Circulatory System ◽  
Lung Fibroblasts ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microenvironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool.

scholarly journals Tumour-on-a-chip: microfluidic models of tumour morphology, growth and microenvironment

2017 ◽  
Vol 14 (131) ◽  
pp. 20170137 ◽  
Author(s):  
Hsieh-Fu Tsai ◽  
Alen Trubelja ◽  
Amy Q. Shen ◽  
Gang Bao
Keyword(s):  
Effective Means ◽  
Three Dimensional ◽  
Tumour Microenvironment ◽  
Cancer Drug ◽  
Oncology Research ◽  
Chip Technology ◽  
Anti Cancer ◽  
Microscopic Studies ◽  
Drug Leads

Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening. In particular, tumour-on-a-chip microdevices allow well-controlled microscopic studies of the interaction among tumour cells, immune cells and cells in the TME, of which simple tissue cultures and animal models are not amenable to do. The challenges in developing the next-generation tumour-on-a-chip technology are also discussed.

Bioprinting of patient-derived in vitro intrahepatic cholangiocarcinoma tumor model: establishment, evaluation and anti-cancer drug testing

2020 ◽  
Vol 12 (4) ◽  
pp. 045014
Author(s):  
Shuangshuang Mao ◽  
Jianyu He ◽  
Yu Zhao ◽  
Tiankun Liu ◽  
Feihu Xie ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Drug Testing ◽  
Tumor Model ◽  
Cancer Drug ◽  
Anti Cancer

Microdfluidic Based 3-Dimensional Cell Culture Platform

2008 ◽  
Author(s):  
Song-Bin Huang ◽  
Min-Hsien Wu ◽  
Zhanfeng Cui ◽  
Zheng Cui ◽  
Gwo-Bin Lee
Keyword(s):  
Cell Culture ◽  
Drug Testing ◽  
Research Work ◽  
Three Dimensional ◽  
Cancer Drug ◽  
Pulsation Frequency ◽  
3 Dimensional ◽  
Anti Cancer ◽  
D Cell ◽  
One Step

This study reports a new perfusion-based, micro three-dimensional (3-D) cell culture platform for drug testing using enabling microfluidic technologies. In this work, a perfusion-based, micro 3-D cell culture platform is designed and is fabricated based on SU-8 lithography and polydimethylsiloxane (PDMS) replication processes. One of the key features of the system is that the incorporation of a multiple medium pumping mechanism, consisting of 15 membrane-based pneumatic micropumps with serpentine-shape (S-shape) layout, coupled with a pneumatic tank, into the micro 3-D cell culture platform to provide efficient and economical culture medium delivery. Moreover, a “smart cell/agarose (scaffold) loading mechanism” was proposed, allowing the cell/3-D scaffold loading process in one step and avoiding too much laborious works and manual error. The results show that in all of the 15 S-shape pneumatic micropumps studied, the medium delivery mechanism is able to provide a uniform flow output ranging from 5.5 to 131 μl/hr depending on the applied pulsation frequency of the micropumps. In addition, the cell/agarose (scaffold) loading mechanism was proved to be able to perform sample loading tasks precisely and accurately in all of the 15 microbioreactors integrated. Furthermore, anti-cancer drug testing was successfully demonstrated using the proposed culture platform and fluorescent microscopic observation. As a whole, because of miniaturization, not only does this perfusion 3-D cell culture platform provide a homogenous and steady cell culture environment, but it also reduces the need for human intervention. Moreover, due to the integrated pumping of the medium and the cell/agarose (scaffold) loading mechanisms, time efficient and economical research work can be achieved. These characteristics are found particularly useful for high-precision and high-throughput 3-D cell culture-based drug testing.

scholarly journals 3D Bioprinted Vascularized Tumour for Drug Testing

2020 ◽  
Vol 21 (8) ◽  
pp. 2993 ◽  
Author(s):  
Seokgyu Han ◽  
Sein Kim ◽  
Zhenzhong Chen ◽  
Hwa Kyoung Shin ◽  
Seo-Yeon Lee ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Blood Vessels ◽  
Drug Testing ◽  
Tumour Size ◽  
Combined Treatment ◽  
Cancer Drug ◽  
Angiogenic Inhibitor ◽  
Anti Cancer

An in vitro screening system for anti-cancer drugs cannot exactly reflect the efficacy of drugs in vivo, without mimicking the tumour microenvironment (TME), which comprises cancer cells interacting with blood vessels and fibroblasts. Additionally, the tumour size should be controlled to obtain reliable and quantitative drug responses. Herein, we report a bioprinting method for recapitulating the TME with a controllable spheroid size. The TME was constructed by printing a blood vessel layer consisting of fibroblasts and endothelial cells in gelatine, alginate, and fibrinogen, followed by seeding multicellular tumour spheroids (MCTSs) of glioblastoma cells (U87 MG) onto the blood vessel layer. Under MCTSs, sprouts of blood vessels were generated and surrounding MCTSs thereby increasing the spheroid size. The combined treatment involving the anti-cancer drug temozolomide (TMZ) and the angiogenic inhibitor sunitinib was more effective than TMZ alone for MCTSs surrounded by blood vessels, which indicates the feasibility of the TME for in vitro testing of drug efficacy. These results suggest that the bioprinted vascularized tumour is highly useful for understanding tumour biology, as well as for in vitro drug testing.

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