3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

Nonfiction, Health & Well Being, Medical, Medical Science, Biotechnology
Cover of the book 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions by Carsten Wenzel, GRIN Verlag
View on Amazon View on AbeBooks View on Kobo View on B.Depository View on eBay View on Walmart
Author: Carsten Wenzel ISBN: 9783668259133
Publisher: GRIN Verlag Publication: July 13, 2016
Imprint: GRIN Verlag Language: English
Author: Carsten Wenzel
ISBN: 9783668259133
Publisher: GRIN Verlag
Publication: July 13, 2016
Imprint: GRIN Verlag
Language: English

Research Paper (postgraduate) from the year 2014 in the subject Medicine - Biomedical Engineering, , language: English, abstract: Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions.

View on Amazon View on AbeBooks View on Kobo View on B.Depository View on eBay View on Walmart

Research Paper (postgraduate) from the year 2014 in the subject Medicine - Biomedical Engineering, , language: English, abstract: Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions.

More books from GRIN Verlag

Cover of the book Die internationale Regulierung des Arzneimittelsektors zwischen gewerblichem Rechtsschutz und öffentlichem Gesundheitsschutz by Carsten Wenzel
Cover of the book Die freie Reichsstadt Mühlhausen: Kultur im Zeichen von Reformation und Machtpolitik by Carsten Wenzel
Cover of the book Irish Migration to North America - From the 1810s until the 1850s by Carsten Wenzel
Cover of the book Transfer von EDV-gestützten Qualitätssicherungskonzepten im arabischen Raum by Carsten Wenzel
Cover of the book Der Kalte Krieg aus der Sicht Willy Brandt's 1945 - 1953 by Carsten Wenzel
Cover of the book Bestimmung und Anwendung von Preisgrenzen by Carsten Wenzel
Cover of the book Discuss the interplay of religious themes and ideas in Chaucer's 'Troilus and Criseyde' by Carsten Wenzel
Cover of the book Metafiktionalität in Calderòn de la Barcas Drama 'La vida es sueno' by Carsten Wenzel
Cover of the book Odradek: eine Leerstelle. Genaues Lesen von Franz Kafkas` 'Die Sorge des Hausvaters' und sich daraus ergebende Möglichkeiten für den Unterricht by Carsten Wenzel
Cover of the book Interpretation, Interaktion, Illustration zu Martial VI 39 by Carsten Wenzel
Cover of the book Die Entwicklung vom Ereigniskino zum postmodernen Kino am Beispiel 'Star Wars' by Carsten Wenzel
Cover of the book Innovation Clusters by Carsten Wenzel
Cover of the book The Ukraine Crisis and Russia's Attitude towards the Organization for Security and Co-operation in Europa by Carsten Wenzel
Cover of the book Die 'Initiative Neue Soziale Marktwirtschaft' by Carsten Wenzel
Cover of the book Die Rolle des Toskanischen am Beispiel Brunetto Latinis 'Tesoretto' by Carsten Wenzel
We use our own "cookies" and third party cookies to improve services and to see statistical information. By using this website, you agree to our Privacy Policy