scholarly journals The Revolutionary Roads to Study Cell–Cell Interactions in 3D In Vitro Pancreatic Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Response ◽  
Three Dimensional ◽  
Cellular Models ◽  
Common Cancer ◽  
Cancer Models ◽  
Anti Cancer ◽  
Tumor Environment

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.

Fabrication of Micro Organs Using a Digital Micro-Mirroring Microfabrication System

2012 ◽  
Author(s):  
Qudus Hamid ◽  
Chengyang Wang ◽  
Wei Sun
Keyword(s):  
Three Dimensional ◽  
Biologically Inspired ◽  
Micro Electro Mechanical Systems ◽  
Cancer Models ◽  
Anti Cancer ◽  
Magnetic Resonance Imaging Mri ◽  
Three Dimensional Models ◽  
Microfabrication Techniques

Micro-Electro-Mechanical Systems (MEMS) technologies have been very attractive and demonstrate the potential for many applications in the field of tissue engineering, regenerative medicine, and life sciences. These fields bring together the multidisciplinary field of engineering and integrated sciences to fabricate three-dimensional models that aides the exploration, generation or regeneration of organic tissues and organs. Presently, monolayer cell cultures are frequently used to investigate potential anti-cancer agents. The issues at hand are that these models give very little in terms of feedback on the effects of the microenvironment on chemotherapeutic and the heterogeneity of the tumor. Three-dimensional tumor and cancer models that mimic the actual disease are developed for in vitro investigations. These models create an environment that enables diseases to have an enhanced evaluation (compared to two dimensional) and eliminate the limitations of the traditional mainstays of cancer research. Three-dimensional Cancer models are economic, allow for biological characterizations. Cancer models are developed from investigations of the actual disease; computer tomography (CT) and magnetic resonance imaging (MRI) allow for biomodeling of the disease’s environmental conditions. Unlike many traditional microfabrication techniques, the Digitial Micro-mirror Microfabrication (DMM) System eliminates the need for mask by incorporating a dynamic mask-less fabrication technique. The DMM is specifically designed for the developments of biologically inspired devices, whether it’s a multicellular spheroid, hollow fiber, or multicellular layer (MCL) models; the DMM has the potential to utilize its dynamic micro mirrors to build the tissue model according to its desired design and characteristics. Each model is specifically designed to mimic the in vivo conditions of the tissue of interest.

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 Berberine inhibits the proliferation of pancreatic cancer targeting pancreatic cancer stem cells

2021 ◽  
Author(s):  
Mengmeng Liu ◽  
Yue Pan ◽  
Xufeng Tao ◽  
Ning Li ◽  
Kun Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Effectiveness ◽  
The Novel ◽  
Migration Assay ◽  
Medicinal Value ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Pancreatic Cancer Stem Cells

Abstract BackgroundPDAC is universally acknowledged to be one of the highest mortality rate of cancer-related deaths. PCSCs, regulated by EMT, could promote the proliferation of PDAC. Berberine with high medicinal value has usually been used as an anti-cancer agent. Hence the purpose of this study is to investigate the anti-cancer effect of berberine in PDAC. MethodsMTT assay was used to verify berberine inhibiting the proliferation of PDAC. Immunofluorescence staining, stem cell sphere, wound healing and transwell migration assay were demonstrated the anti-proliferation and anti-stemness of PCSCs in vitro . PANC-02 cells were injected in C57BL/6 mice to establish the orthotopic pancreatic-cancer model in vivo . H&E and Ki67 immunohistogical staining assay were used to evaluated the effect of berberine in PDAC in vivo. q-PCR and Western blot methods were applied to detect the expression of EMT procedure.ResultsIn this study, berberine has selective anti-cancer effect in PDAC in vitro . Moreover, berberine suppressed the proliferation and stemness of PCSCs in PDAC. In vivo , berberine reduced the tumor size and decreased the expression of Ki67 in orthotopic pancreatic-cancer pancreases. In addition, berberine inhibit the EMT signaling pathway both in vitro and in vivo . ConclusionsOur study indicates that berberine inhibit the proliferation of PDAC in vivo and vitro . The mechanism of anti-cancer effect on berberine may suppress the PCSCs through inhibiting EMT procedure. Therefore, berberine may be the novel antineoplastic drug with clinical effectiveness in PDAC. Keywords: Berberine, PDAC, PCSCs, EMT, berberine

scholarly journals A Novel Assay for Profiling GBM Cancer Model Heterogeneity and Drug Screening

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 702 ◽  
Author(s):  
Christian T. Stackhouse ◽  
James R. Rowland ◽  
Rachael S. Shevin ◽  
Raj Singh ◽  
G. Yancey Gillespie ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Therapeutic Response ◽  
Specific Gene ◽  
Cancer Model ◽  
In Vivo Models ◽  
Cancer Models ◽  
Model Independent ◽  
Orthotopic Xenografts

Accurate patient-derived models of cancer are needed for profiling the disease and for testing therapeutics. These models must not only be accurate, but also suitable for high-throughput screening and analysis. Here we compare two derivative cancer models, microtumors and spheroids, to the gold standard model of patient-derived orthotopic xenografts (PDX) in glioblastoma multiforme (GBM). To compare these models, we constructed a custom NanoString panel of 350 genes relevant to GBM biology. This custom assay includes 16 GBM-specific gene signatures including a novel GBM subtyping signature. We profiled 11 GBM-PDX with matched orthotopic cells, derived microtumors, and derived spheroids using the custom NanoString assay. In parallel, these derivative models underwent drug sensitivity screening. We found that expression of certain genes were dependent on the cancer model while others were model-independent. These model-independent genes can be used in profiling tumor-specific biology and in gauging therapeutic response. It remains to be seen whether or not cancer model-specific genes may be directly or indirectly, through changes to tumor microenvironment, manipulated to improve the concordance of in vitro derivative models with in vivo models yielding better prediction of therapeutic response.

scholarly journals Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer

Medicines ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. 17 ◽  
Author(s):  
Maryam Nakhjavani ◽  
Jennifer E Hardingham ◽  
Helen M Palethorpe ◽  
Yoko Tomita ◽  
Eric Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Metastatic Breast ◽  
Therapeutic Agents ◽  
Ginsenoside Rg3 ◽  
Cancer Models ◽  
Anti Cancer ◽  
Ginseng Plant

Breast cancer is still one of the most prevalent cancers and a leading cause of cancer death worldwide. The key challenge with cancer treatment is the choice of the best therapeutic agents with the least possible toxicities on the patient. Recently, attention has been drawn to herbal compounds, in particular ginsenosides, extracted from the root of the Ginseng plant. In various studies, significant anti-cancer properties of ginsenosides have been reported in different cancers. The mode of action of ginsenoside Rg3 (Rg3) in in vitro and in vivo breast cancer models and its value as an anti-cancer treatment for breast cancer will be reviewed.

Therapeutic and preventive properties of honey and its bioactive compounds in cancer: an evidence-based review

2019 ◽  
Vol 33 (1) ◽  
pp. 50-76 ◽  
Author(s):  
Sadia Afrin ◽  
Shoja M. Haneefa ◽  
Maria J. Fernandez-Cabezudo ◽  
Francesca Giampieri ◽  
Basel K. al-Ramadi ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Bioactive Compounds ◽  
Clinical Studies ◽  
Natural Antioxidants ◽  
Cancer Models ◽  
Increased Risk ◽  
Anti Cancer ◽  
Preclinical Animal Models

AbstractDespite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.

scholarly journals Engineered Resistant-Starch (ERS) Diet Shapes Colon Microbiota Profile in Parallel with the Retardation of Tumor Growth in In Vitro and In Vivo Pancreatic Cancer Models

Nutrients ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 331 ◽  
Author(s):  
Concetta Panebianco ◽  
Kaarel Adamberg ◽  
Signe Adamberg ◽  
Chiara Saracino ◽  
Madis Jaagura ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Resistant Starch ◽  
Cancer Models

scholarly journals Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce In Vitro the Human Body Complexity

2021 ◽  
Vol 22 (3) ◽  
pp. 1195
Author(s):  
Giada Bassi ◽  
Maria Aurora Grimaudo ◽  
Silvia Panseri ◽  
Monica Montesi
Keyword(s):  
Three Dimensional ◽  
Chemical Properties ◽  
Basic Research ◽  
Biomedical Science ◽  
Specific Cell ◽  
Multicellular Spheroids ◽  
Physiological Models ◽  
Cellular Models

A hot topic in biomedical science is the implementation of more predictive in vitro models of human tissues to significantly improve the knowledge of physiological or pathological process, drugs discovery and screening. Bidimensional (2D) culture systems still represent good high-throughput options for basic research. Unfortunately, these systems are not able to recapitulate the in vivo three-dimensional (3D) environment of native tissues, resulting in a poor in vitro–in vivo translation. In addition, intra-species differences limited the use of animal data for predicting human responses, increasing in vivo preclinical failures and ethical concerns. Dealing with these challenges, in vitro 3D technological approaches were recently bioengineered as promising platforms able to closely capture the complexity of in vivo normal/pathological tissues. Potentially, such systems could resemble tissue-specific extracellular matrix (ECM), cell–cell and cell–ECM interactions and specific cell biological responses to mechanical and physical/chemical properties of the matrix. In this context, this review presents the state of the art of the most advanced progresses of the last years. A special attention to the emerging technologies for the development of human 3D disease-relevant and physiological models, varying from cell self-assembly (i.e., multicellular spheroids and organoids) to the use of biomaterials and microfluidic devices has been given.

scholarly journals Mesenchymal-like glioma cells are enriched in the gelatin methacrylate hydrogels

2021 ◽  
Author(s):  
Nameeta Shah ◽  
Pavan M. Hallur ◽  
Raksha A. Ganesh ◽  
Pranali Sonpatki ◽  
Divya Naik ◽  
...  
Keyword(s):  
Therapeutic Response ◽  
Immune Cell ◽  
Three Dimensional ◽  
Glioma Cells ◽  
Cellular Phenotype ◽  
3D Scaffold ◽  
Promising Alternative ◽  
Cells Cultured

AbstractGlioblastoma is the most lethal primary malignant brain tumor in adults. Simplified two-dimensional (2D) cell culture and neurospheres in vitro models fail to recapitulate the complexity of the tumor microenvironment, limiting its ability to predict therapeutic response. Three-dimensional (3D) scaffold-based models have emerged as a promising alternative for addressing these concerns. One such 3D system is gelatin methacrylate (GelMA) hydrogels, which can be used for modeling the glioblastoma microenvironment. We characterized the phenotype of patient-derived glioma cells cultured in GelMA hydrogels (3D-GMH) for their tumorigenic properties using invasion and chemoresponse assays. In addition, we used integrated single-cell and spatial transcriptome analysis to compare cells cultured in 3D-GMH to cells in vivo. Finally, we assessed tumor-immune cell interactions with a macrophage infiltration assay and a cytokine array. We show that cells cultured in 3D-GMH develop a mesenchymal-like cellular phenotype found in perivascular and hypoxic regions present in the core of the tumor, and recruit macrophages by secreting cytokines in contrast to the cells grown as neurospheres that match the phenotype of cells of the infiltrative edge of the tumor.

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