Combined treatment of gemcitabine with indole-3-carbinol or metformin on drug efficacy in pancreatic cancer cell lines: The role of human equilibrative nucleoside transporters

Joseph, Sarah; Word, Beverly; Lyn‐Cook, Beverly

doi:10.14312/2052-4994.2018-2

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…The single-agent chemotherapy treatment that has been widely used since the 1990s is gemcitabine, a nucleoside analogue. To exert its cytotoxic effects, it must enter cells via the human equilibrative nucleoside transporter (hENT1) that is usually expressed on the surface of the cells 20,21 . Alternative chemotherapeutic agents that can be administrated single or combined are 5-Fluorouracil (5-FU), oxaliplatin, irinotecan, SN38 (active analogue of irinotecan via a nanocarrier), fludarabine, abraxane (albumin-bound paclitaxel), paclitaxel, cisplatin and docetaxel.…”

Section: Current Treatment Optionsmentioning

confidence: 99%

Evaluation of synergistic hybrid nanoparticles for improved diagnosis and treatment of pancreatic cancer

Ischyropoulou

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Here I declare that my doctoral thesis entitled has been written independently with no other sources and aids than quoted. Myrto IschyropoulouGöttingen, May 2023 Above all else, I would like to convey my appreciation to my supervisor, PD. Dr. Joanna Napp, for granting me the invaluable opportunity of being selected as a DFG fellow in her research grant. Additionally, I am grateful to her for effectively inspiring, motivating, directing me throughout my doctoral studies and helping a lot with bureaucracy. Additionally, I am grateful to Prof. Dr. med. Frauke Alves for accepting me into her research group and providing me with abundant resources for my PhD. I am particularly thankful for the opportunity to pursue diverse projects and collaborate with various research teams under her guidance. Lastly, I extend my appreciation for the exceptional level of critical support she has offered for this thesis, which undoubtedly contributes to my growth as a researcher. I also would like to acknowledge the members of my Thesis Committee, Prof. Dr. Susann Boretius and Prof. Dr. Ralf Dressel, for advising me during the thesis committees, and together with Prof. Dr. Luis Pardo and Prof. Dr. Heidi Hahn for participating at my PhD thesis committee.The endeavor of such a study would certainly not have been possible without the practical help of many people for whose support I am very grateful, Sarah Garbode, Sabine Wolfgramm, Bettina Jeep and Regine Kruse for helping with immunohistochemistry. However, most significantly, the individual who played an instrumental role in enabling these achievements is Bärbel Heidrich. Throughout the entirety of my three-year project, she provided immense assistance and support. Her contributions extended beyond professional matters, as she became not only a valued colleague but also a genuine friend. Herzliches Dankeschön, Bärbel! Together with them, I would also like to thank all the members of the AG Alves, especially Dr. Fernanda Ramos Gomes for helping with all kind of microscopes whenever I faced a problem, Dr. Andrea Markus for correcting my English, Dr. Christian Dullin for helping me the in vivo fluorescence imaging and their data processing, Dr. Dolma Choezom for helping me with the Cell Titer Glo experiment, Dr Diana Pinkert-Leetsch and Dr. Jeannine Mißbach-Güntner for helping with the LSFM appointments coordination.I would also like to thank the AG Feldmann group, especially Dr. Kristina Sabljo and Dr. David Rudolph for doing excellent work synthesizing and providing me with the nanoparticles for the project and being in a continuous communication and feedback. Herzliches Dankeschön Prof. Dr. Claus Feldmann for everything! It has been an honor collaborating with you.Additionally, a big thank you to Dr. Miso Mitkovski and Heiko Röhse, for the introductions and the technical support of the microscopy in the Max Planck Microscopy Facility that they provided. I would also like to thank...

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Section: Current Treatment Optionsmentioning

confidence: 99%

Evaluation of synergistic hybrid nanoparticles for improved diagnosis and treatment of pancreatic cancer

Ischyropoulou

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High‐Load Gemcitabine Inorganic–Organic Hybrid Nanoparticles as an Image‐Guided Tumor‐Selective Drug‐Delivery System to Treat Pancreatic Cancer

Ischyropoulou,

Sabljo,

Schneider

et al. 2023

Advanced Materials

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Pancreatic ductal adenocarcinoma (PDAC) has a devastating prognosis without effective treatment options. Thus, there is an urgent need for more effective and safe therapies. Here, we present inorganic‐organic hybrid nanoparticles (GMP‐IOH‐NPs) as novel drug‐delivery system for the selective delivery of extraordinarily high concentrations of gemcitabine monophosphate (GMP) not only to the primary tumor but also to metastatic sites. GMP‐IOH‐NPs have a composition [ZrO]2+[GMP]2– with GMP as drug anion (76% of total IOH‐NP mass). Multiscale fluorescence imaging confirms an efficient uptake in tumor cells, independent of the activity of the human‐equilibrative‐nucleoside transporter (hENT1), being responsible for gemcitabine (GEM) transport into cells and a key factor for GEM resistance. Delivering already phosphorylated GMP via GMP‐IOH‐NPs into tumor cells also allows to overcome cellular resistance induced by the down‐regulation of deoxycytidine kinase. GMP‐IOH‐NPs show high accumulation in tumor lesions and only minor liver trapping when given intraperitoneally. GMP‐IOH‐NPs result in a higher anti‐tumor efficacy compared to free GEM and is further enhanced applying cetuximab‐functionalized GMP‐CTX‐IOH‐NPs. By maximizing the therapeutic benefits with high drug load, tumor‐specific delivery, minimizing undesired side effects, overcoming mechanisms of chemoresistance, and preventing systemic GEM inactivation, we anticipate GMP‐IOH‐NPs to have a high chance to significantly improve current PDAC‐patient outcome.This article is protected by copyright. All rights reserved

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Protective effect of Indole-3-carbinol, an NF-κB inhibitor in experimental paradigm of Parkinson’s disease: In silico and in vivo studies

Saini

Akhtar

Chauhan

et al. 2020

Brain, Behavior, and Immunity

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Combined treatment of gemcitabine with indole-3-carbinol or metformin on drug efficacy in pancreatic cancer cell lines: The role of human equilibrative nucleoside transporters

Cited by 3 publications

References 53 publications

Evaluation of synergistic hybrid nanoparticles for improved diagnosis and treatment of pancreatic cancer

Evaluation of synergistic hybrid nanoparticles for improved diagnosis and treatment of pancreatic cancer

High‐Load Gemcitabine Inorganic–Organic Hybrid Nanoparticles as an Image‐Guided Tumor‐Selective Drug‐Delivery System to Treat Pancreatic Cancer

Protective effect of Indole-3-carbinol, an NF-κB inhibitor in experimental paradigm of Parkinson’s disease: In silico and in vivo studies

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