scholarly journals Organotypic three-dimensional cancer cell cultures mirror drug responses in vivo: lessons learned from the inhibition of EGFR signaling

Oncotarget ◽  
2017 ◽  
Vol 8 (64) ◽  
pp. 107423-107440 ◽  
Author(s):  
Nico Jacobi ◽  
Rita Seeboeck ◽  
Elisabeth Hofmann ◽  
Helmut Schweiger ◽  
Veronika Smolinska ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Lessons Learned ◽  
Egfr Signaling ◽  
Drug Responses

Mapping chemotherapeutic drug distribution in cancer cell spheroids using 2D-TOF-SIMS and LESA-TIMS-MS

The Analyst ◽  
2020 ◽  
Vol 145 (21) ◽  
pp. 7056-7062
Author(s):  
Yarixa L. Cintron-Diaz ◽  
Arlet M. Acanda de la Rocha ◽  
Anthony Castellanos ◽  
Jeremy M. Chambers ◽  
Francisco Fernandez-Lima
Keyword(s):  
Cancer Cell ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Drug Distribution ◽  
Chemotherapeutic Drug ◽  
Cell Spheroids ◽  
Tof Sims ◽  
Cancer Tumor ◽  
Effective Models

Three-dimensional (3D) cancer cell cultures grown in the form of spheroids are effective models for the study of in vivo-like processes simulating cancer tumor pharmacological dynamics and morphology.

scholarly journals Visual pH Sensors: From a Chemical Perspective to New Bioengineered Materials

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2952
Author(s):  
Luigi Di Costanzo ◽  
Barbara Panunzi
Keyword(s):  
Ph Monitoring ◽  
Three Dimensional ◽  
Lessons Learned ◽  
Background Information ◽  
Biological Macromolecules ◽  
Ph Sensing ◽  
Ph Sensors ◽  
Cellular Functions ◽  
Metal Organic

Many human activities and cellular functions depend upon precise pH values, and pH monitoring is considered a fundamental task. Colorimetric and fluorescence sensors for pH measurements are chemical and biochemical tools able to sense protons and produce a visible signal. These pH sensors are gaining widespread attention as non-destructive tools, visible to the human eye, that are capable of a real-time and in-situ response. Optical “visual” sensors are expanding researchers’ interests in many chemical contexts and are routinely used for biological, environmental, and medical applications. In this review we provide an overview of trending colorimetric, fluorescent, or dual-mode responsive visual pH sensors. These sensors include molecular synthetic organic sensors, metal organic frameworks (MOF), engineered sensing nanomaterials, and bioengineered sensors. We review different typological chemical entities of visual pH sensors, three-dimensional structures, and signaling mechanisms for pH sensing and applications; developed in the past five years. The progression of this review from simple organic molecules to biological macromolecules seeks to benefit beginners and scientists embarking on a project of pH sensing development, who needs background information and a quick update on advances in the field. Lessons learned from these tools will aid pH determination projects and provide new ways of thinking for cell bioimaging or other cutting-edge in vivo applications.

scholarly journals Impedance Study of Dopamine Effects after Application on 2D and 3D Neuroblastoma Cell Cultures Developed on a 3D-Printed Well

Chemosensors ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 6 ◽  
Author(s):  
Georgia Paivana ◽  
Theofylaktos Apostolou ◽  
Sophie Mavrikou ◽  
Dimitris Barmpakos ◽  
Grigoris Kaltsas ◽  
...  
Keyword(s):  
Cell Cultures ◽  
Immobilized Cells ◽  
Neuroblastoma Cell ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Impedance Analysis ◽  
Neural Cells ◽  
Opposite Behavior ◽  
2D And 3D

In this work, the assessment of the interactions of a bioactive substance applied to immobilized cells in either a two-dimensional (2D) or three-dimensional (3D) arrangement mimicking in vivo tissue conditions is presented. In particular, dopamine (DA) was selected as a stimulant for the implementation of an impedance analysis with a specific type of neural cells (murine neuroblastoma). The aim of this study was the extraction of calibration curves at various frequencies with different known dopamine concentrations for the description of the behavior of dopamine applied to 2D and 3D cell cultures. The results present the evaluation of the mean impedance value for each immobilization technique in each frequency. The differential responses showed the importance of the impedance when frequency is applied in both 2D and 3D immobilization cases. More specifically, in 2D immobilization matrix impedance shows higher values in comparison with the 3D cell culture. Additionally, in the 3D case, the impedance decreases with increasing concentration, while in the 2D case, an opposite behavior was observed.

scholarly journals The Effective Combination between 3D Cancer Models and Stimuli-Responsive Nanoscale Drug Delivery Systems

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3295
Author(s):  
Federica Foglietta ◽  
Loredana Serpe ◽  
Roberto Canaparo
Keyword(s):  
Drug Delivery ◽  
Cancer Cell ◽  
Cell Cultures ◽  
Drug Delivery Systems ◽  
In Vitro Models ◽  
Delivery Systems ◽  
Stimuli Responsive ◽  
Cancer Models

Stimuli-responsive drug-delivery systems (DDSs) have emerged as a potential tool for applications in healthcare, mainly in the treatment of cancer where versatile nanocarriers are co-triggered by endogenous and exogenous stimuli. Two-dimensional (2D) cell cultures are the most important in vitro model used to evaluate the anticancer activity of these stimuli-responsive DDSs due to their easy manipulation and versatility. However, some limitations suggest that these in vitro models poorly predict the outcome of in vivo studies. One of the main drawbacks of 2D cell cultures is their inadequate representation of the 3D environment’s physiological complexity, which sees cells interact with each other and the extracellular matrix (ECM) according to their specific cellular organization. In this regard, 3D cancer models are a promising approach that can overcome the main shortcomings of 2D cancer cell cultures, as these in vitro models possess many peculiarities by which they mimic in vivo tumors, including physiologically relevant cell–cell and cell–ECM interactions. This is, in our opinion, even more relevant when a stimuli-responsive DDS is being investigated. In this review, we therefore report and discuss endogenous and exogenous stimuli-responsive DDSs whose effectiveness has been tested using 3D cancer cell cultures.

scholarly journals The CCL2-CCR2 astrocyte-cancer cell axis in tumor extravasation at the brain

2021 ◽  
Vol 7 (26) ◽  
pp. eabg8139
Author(s):  
Cynthia Hajal ◽  
Yoojin Shin ◽  
Leanne Li ◽  
Jean Carlos Serrano ◽  
Tyler Jacks ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Three Dimensional ◽  
Brain Parenchyma ◽  
Cell Axis ◽  
Chemokine Ligand ◽  
Chemokine Ligand 2 ◽  
The Brain

Although brain metastases are common in cancer patients, little is known about the mechanisms of cancer extravasation across the blood-brain barrier (BBB), a key step in the metastatic cascade that regulates the entry of cancer cells into the brain parenchyma. Here, we show, in a three-dimensional in vitro BBB microvascular model, that astrocytes promote cancer cell transmigration via their secretion of C-C motif chemokine ligand 2 (CCL2). We found that this chemokine, produced primarily by astrocytes, promoted the chemotaxis and chemokinesis of cancer cells via their C-C chemokine receptor type 2 (CCR2), with no notable changes in vascular permeability. These findings were validated in vivo, where CCR2-deficient cancer cells exhibited significantly reduced rates of arrest and transmigration in mouse brain capillaries. Our results reveal that the CCL2-CCR2 astrocyte-cancer cell axis plays a fundamental role in extravasation and, consequently, metastasis to the brain.

Patient-derived organoids for personalized drug screening in intrahepatic cholangiocarcinoma.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 581-581
Author(s):  
Ricardo J. Antonia ◽  
Kan Toriguchi ◽  
Eveliina Karelehto ◽  
Dania Annuar ◽  
Luika Timmerman ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Intrahepatic Cholangiocarcinoma ◽  
Three Dimensional ◽  
Small Samples ◽  
Patient Specific ◽  
Mtor Inhibition ◽  
Drug Responses

581 Background: Despite standard treatment with gemcitabine and cisplatin, median survival for unresectable Intrahepatic Cholangiocarcinoma (ICC) is < 1 year. Clearly, novel therapeutic strategies are urgently needed. The paucity of targetable mutations in ICC and the as yet unproven benefit of genetically targeted drugs led us to ask whether a reliable clinical benefit may be revealed by patient-specific therapeutic testing in novel models of ICC. Here we describe our ability to establish patient-derived three-dimensional organoid cultures (PDO) that enable individualized identification of active single agents or drug combinations in surrogate models of ICC. Methods: To model patient-specific drug responses, we used the freshly resected ICCs from small samples of single patient tumors to generate PDXs and PDOs, small spheroidal clusters of tumor cells grown in vitro. We have employed a high-throughput drug screening platform using AI-enhanced robotics (Yamaha Motor Corporation) to identify and distribute single, uniformly sized PDOs into 384-well ultra-low adherent plates. This is coupled with a TECAN D300e drug dispenser that rapidly delivers nanoliter volumes of a 34-drug panel, thereby facilitating rapid, reliable drug response analyses. Results: Our data show that PDOs retain characteristic genomic and histological features of the patients’ tumors. Drug responses were specific to each patient tumor, but PDOs from all patients responded to a greater or lesser degree to mTOR inhibition, suggesting that this pathway is important in ICC. The responses of PDO to the mTOR inhibitor Sapanisertib (INK128), was recapitulated in the same patient’s PDX. Further, INK128 was synergistic with gemcitabine in patient 970 PDOs as well as in vivo in PDX also from patient 970. Conclusions: As it is believed that PDX can predict patient responses to drugs, our results suggest that PDO may also predict patient drug responses. The establishment of PDO may allow economical patient-specific, high throughput drug screens that could ultimately inform clinical practice. [Table: see text]

scholarly journals In vivo-like drug responses of human tumors growing in three-dimensional gel-supported primary culture.

1987 ◽  
Vol 84 (14) ◽  
pp. 5029-5033 ◽  
Author(s):  
R. A. Vescio ◽  
C. H. Redfern ◽  
T. J. Nelson ◽  
S. Ugoretz ◽  
P. H. Stern ◽  
...  
Keyword(s):  
Primary Culture ◽  
Three Dimensional ◽  
Human Tumors ◽  
Drug Responses

scholarly journals A Novel 3D Scaffold for Cell Growth to Asses Electroporation Efficacy

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1470 ◽  
Author(s):  
Dettin ◽  
Sieni ◽  
Zamuner ◽  
Marino ◽  
Sgarbossa ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Cultures ◽  
Three Dimensional ◽  
Cell Interaction ◽  
Growth Patterns ◽  
3D Scaffold ◽  
Electric Pulses ◽  
Breast Carcinoma Cell Lines ◽  
Cell Cell

Tumor electroporation (EP) refers to the permeabilization of the cell membrane by means of short electric pulses thus allowing the potentiation of chemotherapeutic drugs. Standard plate adhesion 2D cell cultures can simulate the in vivo environment only partially due to lack of cell–cell interaction and extracellular matrix (ECM). In this study, we assessed a novel 3D scaffold for cell cultures based on hyaluronic acid and ionic-complementary self-assembling peptides (SAPs), by studying the growth patterns of two different breast carcinoma cell lines (HCC1569 and MDA-MB231). This 3D scaffold modulates cell shape and induces extracellular matrix deposit around cells. In the MDA-MB 231 cell line, it allows three-dimensional growth of structures known as spheroids, while in HCC1569 it achieves a cell organization similar to that observed in vivo. Interestingly, we were able to visualize the electroporation effect on the cells seeded in the new scaffold by means of standard propidium iodide assay and fluorescence microscopy. Thanks to the presence of cell–cell and cell–ECM interactions, the new 3D scaffold may represent a more reliable support for EP studies than 2D cancer cell cultures and may be used to test new EP-delivered drugs and novel EP protocols.

scholarly journals Anti-Tumor Effects of Exosomes Derived from Drug-Incubated Permanently Growing Human MSC

2020 ◽  
Vol 21 (19) ◽  
pp. 7311 ◽  
Author(s):  
Catharina Melzer ◽  
Juliane von der Ohe ◽  
Ralf Hass
Keyword(s):  
Breast Cancer ◽  
Cancer Cell ◽  
Cell Cultures ◽  
Large Scale ◽  
Primary Cultures ◽  
Cancer Model ◽  
Oral Gavage ◽  
Cytotoxic Effects ◽  
Breast Cancer Model

Similar to growth-limited human primary cultures of mesenchymal stroma/stem-like cells (MSC), the continuously proliferating human MSC544 cell line produced extracellular vesicles as characterized by expression of the tetraspanin molecules CD9, CD63, and CD81. Release of these particles was predominantly detectable during continuous cell growth of MSC544 in contrast to confluency-mediated transient growth arrest. For therapeutic use, these particles were isolated from proliferating MSC544 after taxol treatment and applied to different cancer cell cultures. A pronounced cytotoxicity of lung, ovarian, and breast cancer cells was observed primarily with taxol-loaded exosomes, similar to the effects displayed by application of taxol substance. While these findings suggested pronounced cancer cell targeting of MSC544 exosomes, a tumor therapeutic approach was performed using a mouse in vivo breast cancer model. Thus, intravenous injection of taxol-loaded MSC544 exosomes displayed superior tumor-reducing capabilities as compared to application of taxol exosomes by oral gavage. To broaden this therapeutic spectrum, epirubicin was applied to MSC544, and the derived exosomes likewise exhibited significant cytotoxic effects in different cancer cell cultures. These findings suggest an unlimited source for large-scale exosome production with reproducible quality to enable variable drug targeting of tumors or other diseases.

scholarly journals Non-Invasive Quantification of the Growth of Cancer Cell Colonies by a Portable Optical Coherence Tomography

Micromachines ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 35 ◽  
Author(s):  
Meng-Tsan Tsai ◽  
Bo-Huei Huang ◽  
Chun-Chih Yeh ◽  
Kin Fong Lei ◽  
Ngan-Ming Tsang
Keyword(s):  
Optical Coherence Tomography ◽  
Cancer Cell ◽  
Cellular Response ◽  
Tumor Development ◽  
Three Dimensional ◽  
Cancer Cell Line ◽  
Optical Coherence ◽  
Non Invasive

Investigation of tumor development is essential in cancer research. In the laboratory, living cell culture is a standard bio-technology for studying cellular response under tested conditions to predict in vivo cellular response. In particular, the colony formation assay has become a standard experiment for characterizing the tumor development in vitro. However, quantification of the growth of cell colonies under a microscope is difficult because they are suspended in a three-dimensional environment. Thus, optical coherence tomography (OCT) imaging was develop in this study to monitor the growth of cell colonies. Cancer cell line of Huh 7 was used and the cells were applied on a layer of agarose hydrogel, i.e., a non-adherent surface. Then, cell colonies were gradually formed on the surface. The OCT technique was used to scan the cell colonies every day to obtain quantitative data for describing their growth. The results revealed the average volume increased with time due to the formation of cell colonies day-by-day. Additionally, the distribution of cell colony volume was analyzed to show the detailed information of the growth of the cell colonies. In summary, the OCT provides a non-invasive quantification technique for monitoring the growth of the cell colonies. From the OCT images, objective and precise information is obtained for higher prediction of the in vivo tumor development.

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