Article
Pharmacology & Pharmacy
Chung-Pu Wu, Sung-Han Hsiao, Yu-Shan Wu
Summary: The overexpression of human ATP-binding cassette (ABC) transporters in cancer cells can lead to multidrug resistance (MDR), which poses a significant obstacle to chemotherapy. Currently, there are no approved drugs specifically designed to treat multidrug-resistant cancers. However, drug repurposing has emerged as a practical approach to discover effective modulators of drug transporters.
DRUG RESISTANCE UPDATES
(2023)
Article
Biochemistry & Molecular Biology
Chung-Pu Wu, Yen-Ching Li, Megumi Murakami, Sung-Han Hsiao, Yun-Chieh Lee, Yang-Hui Huang, Yu-Tzu Chang, Tai-Ho Hung, Yu-Shan Wu, Suresh V. Ambudkar
Summary: This study aims to evaluate whether furmonertinib overcomes drug resistance mediated by ABCB1 and ABCG2 transporters, and explore its interaction mechanisms with these proteins. The results suggest that furmonertinib holds potential as a candidate for combination therapy, enhancing the efficacy of conventional anticancer drugs and overcoming MDR in cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Ingrid Fatima Zattoni, Leticia Carani Delabio, Julia de Paula Dutra, Diogo Henrique Kita, Gustavo Scheiffer, Marina Hembecker, Giovana da Silva Pereira, Vivian Rotuno Moure, Glaucio Valdameri
Summary: The primary source of failure in cancer therapies is multidrug resistance (MDR) caused by overexpression of ABC transporters, particularly the breast cancer resistance protein (BCRP/ABCG2). Inhibiting ABCG2 function and modulating its expression are promising strategies to overcome MDR. This review provides an overview of various ABCG2 inhibitors and discusses their chemical aspects, experimental methods used for identification and characterization, as well as the biological requirements for preclinical tests. Additionally, the potential use of ABCG2 inhibitors in cancer stem cells (CSC) to improve treatment response and the mechanism of ABCG2 modulators at the transcriptional and protein expression levels are discussed.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Yu Zhang, Dimitrios Vagiannis, Youssif Budagaga, Ziba Sabet, Ivo Hanke, Tomas Rozkos, Jakub Hofman
Summary: Sonidegib has the potential to act as a perpetrator of drug-drug interactions (DDIs) and modulator of transporter- and enzyme-mediated multidrug resistance (MDR). It effectively inhibits transport functions of ABCB1 and ABCG2, and enhances the cytotoxicity of specific drugs in cells and tumor cultures. Furthermore, it does not hamper the anticancer effects of ABC transporters associated with MDR and has no significant influence on the activity of the CYP3A4 enzyme.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Nicolas Tournier, Sebastien Goutal, Severin Mairinger, Irene Hernandez-Lozano, Thomas Filip, Michael Sauberer, Fabien Caille, Louise Breuil, Johann Stanek, Anna F. Freeman, Gaia Novarino, Charles Truillet, Thomas Wanek, Oliver Langer
Summary: This study investigated the feasibility of simultaneous inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar. The combination led to increased brain distribution of the model substrate in mice and macaques, potentially enhancing brain delivery of molecularly targeted anticancer drugs for the treatment of brain tumors. Additionally, tolerability and induction of apoptosis were assessed in human cerebral organoids, showing promising results for future applications.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Multidisciplinary Sciences
Wang Yin, Dongxi Xiang, Tao Wang, Yumei Zhang, Cuong Pham, Shufeng Zhou, Guoqin Jiang, Yingchun Hou, Yimin Zhu, Yinglu Han, Liang Qiao, Phuong H-L Tran, Wei Duan
Summary: Inhibiting MDR1 or ABCG2 was found to increase the sensitivity of liver cancer stem cells to doxorubicin, leading to elevated intracellular concentration of the drug and increased apoptosis. This approach effectively reversed chemoresistance in liver cancer stem cells, demonstrating a promising strategy for enhancing the therapeutic efficacy of doxorubicin.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Simon Heumos, Sandra Dehn, Konstantin Braeutigam, Marius C. Codrea, Christian M. Schuerch, Ulrich M. Lauer, Sven Nahnsen, Michael Schindler
Summary: This study identified specific cell surface receptor biomarkers for colon and renal cancer through analyzing the surface receptors of tumor cells, with CD106 (VCAM1) identified as a promising novel immunotherapeutic target for renal cancer treatment.
CANCER CELL INTERNATIONAL
(2022)
Article
Cell Biology
Chung-Pu Wu, Cheng-Yu Hung, Ya-Ju Hsieh, Megumi Murakami, Yang-Hui Huang, Tsung-Yao Su, Tai-Ho Hung, Jau-Song Yu, Yu-Shan Wu, Suresh V. Ambudkar
Summary: The phosphoinositide-3-kinase (PI3K)/Akt signaling pathway plays a crucial role in tumor growth, and the drug HS-173, a PI3K inhibitor, has shown potential in halting cancer cell proliferation. However, this study found that the multidrug efflux transporters ABCB1 and ABCG2 can reduce the efficacy of HS-173 through drug-efflux processes. Inhibiting the drug-efflux function of ABCB1 and ABCG2 can restore the effectiveness of HS-173 in multidrug-resistant cancer cells.
Article
Multidisciplinary Sciences
Tomoka Gose, Heather M. Aitken, Yao Wang, John Lynch, Evadnie Rampersaud, Yu Fukuda, Medb Wills, Stefanie A. Baril, Robert C. Ford, Anang Shelat, Megan L. O' Mara, John D. Schuetz
Summary: This research reveals the mechanism of substrate selection by ABCG2, identifying a crucial residue N436 that acts as a discriminator for substrate recognition and is required for optimal inhibitor action.
NATURE COMMUNICATIONS
(2023)
Article
Environmental Sciences
Andre C. Pereira, Ana Tenreiro, Monica Cunha
Summary: The combination of FISH and FLOW techniques allows for high-throughput evaluation and sorting of single cells within microbial communities in environmental microbiology, providing a key tool for studying their heterogeneity.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Cell Biology
Sundeep Singh Nimisha, Sundeep Singh Saluja, Abhay Kumar Sharma, Phani Kumar Nekarakanti, Real Sumayya Abdul Apurva, Arun Kumar, Real Sumayya Abdul Sattar, Hasib Anjum, Vineeta Vijay Batra, Syed Akhtar Husain
Summary: The function of ABC transporters in the body is diverse and includes maintaining homeostasis, affecting multi-drug resistance, and playing a role in tumor initiation and progression. The research investigated the methylation status and expression pattern of ABCB1 and ABCG2 in gallbladder cancer. The study found that hypomethylation of ABCB1 and ABCG2 was associated with cancer development and that overexpression of these genes may contribute to gallbladder cancer tumorigenesis.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Oncology
Miwako Omori, Rintaro Noro, Masahiro Seike, Kuniko Matsuda, Mariko Hirao, Aya Fukuizumi, Natsuki Takano, Akihiko Miyanaga, Akihiko Gemma
Summary: This study identified key factors in the chemoresistance of SCLC, including drug efflux proteins ABCB1 and ABCG2. Inhibiting these proteins can restore drug sensitivity and promote apoptotic activity in SCLC cells. ABC transporter inhibitors may be a promising therapeutic strategy for overcoming resistance to topoisomerase inhibitors in SCLC patients.
Article
Oncology
Milica Nedeljkovic, Nasta Tanic, Mirjana Prvanovic, Zorka Milovanovic, Nikola Tanic
Summary: ABC transporters play a key role in chemoresistance of solid tumors, with higher expression in TNBC compared to ER+ breast cancer. Among the three transporters studied, ABCG2 and ABCC1 showed significantly higher levels of expression in TNBC compared to ABCB1, with ABCB1 associated with metastatic spread in TNBC patients. Surprisingly, high expression of ABCG2 was correlated with longer disease-free interval and overall survival in TNBC patients.
Review
Pharmacology & Pharmacy
Fengjun Sun, Zhuo Chen, Pu Yao, Bangbi Weng, Zhirui Liu, Lin Cheng
Summary: The ABCG2 gene variant rs2231142 A allele was associated with an increased risk of sunitinib-induced thrombocytopenia and hand-foot syndrome in Asians. The ABCB1 gene variant rs1128503 T allele was associated with a decreased risk of sunitinib-induced hypertension but worse progression-free survival. The ABCB1 gene variant rs2032582 T allele was associated with worse progression-free survival.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Youssif Budagaga, Ziba Sabet, Yu Zhang, Eva Novotna, Ivo Hanke, Tomas Rozkos, Jakub Hofman
Summary: Tazemetostat is a unique multispecific chemosensitizer that can inhibit multiple ABC transporters and enhance the synergistic effect of chemotherapy by inducing apoptosis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Neurosciences
Pia Koudouovoh-Tripp, Katharina Huefner, Jonas Egeter, Christina Kandler, Johannes M. Giesinger, Sieghart Sopper, Christian Humpel, Barbara Sperner-Unterweger
Summary: Chronic mental stress is associated with increased state anxiety, depressive symptoms, and perceived stress, as well as enhanced proinflammatory platelet activity. Acute mental stress can alter platelet bioactivity and aggregation. Both chronic and acute mental stress have significant impacts on platelets, potentially linking mental and somatic disorders.
JOURNAL OF NEUROIMMUNE PHARMACOLOGY
(2021)
Review
Oncology
Maximilian Boesch, Florent Baty, Sacha Rothschild, Michael Tamm, Markus Joerger, Martin Frueh, Martin H. Brutsche
Summary: Tumour neoantigens from cancer-specific mutations distinguish cancer from healthy cells, but microbial species can produce epitopes resembling tumour neoantigens, leading to tumour molecular mimicry. Microbiome-mediated tumour neoantigen mimicry may impact the efficacy of immune therapy.
BRITISH JOURNAL OF CANCER
(2021)
Article
Biochemical Research Methods
Maximilian Boesch, Martina Sykora, Silvia Gasteiger, Florent Baty, Martin H. Brutsche, Sieghart Sopper
Summary: This optimized multicolor immunofluorescence panel is designed to efficiently identify and quantify various leukocyte populations in human blood with minimal markers. It offers high performance, is suitable for whole blood, and widely applicable for immune cell identification, quantification, and characterization.
Article
Immunology
Sandra Scheiblhofer, Stephan Drothler, Werner Braun, Reinhard Braun, Maximilian Boesch, Richard Weiss
Summary: This study demonstrates that laser-facilitated epicutaneous immunization with the S1 subunit of the Spike protein of SARS-CoV-2 induces antibody responses that can be boosted by co-administration of adjuvants, representing a potential alternative route for Covid-19 vaccines.
Article
Immunology
Sandra Scheiblhofer, Stephan Drothler, Werner Braun, Reinhard Braun, Maximilian Boesch, Richard Weiss
Summary: The skin has been intensively studied as a target tissue for immunization, with direct targeting of dendritic cells or Langerhans cells in vivo showing potential for inducing T cell responses in cancer immunotherapy. Fractional laser ablation has been investigated as a novel method for efficient delivery of macromolecules to the skin with the adjuvant effect of laser illumination. The study demonstrates the feasibility of peptide delivery to the skin using a specific laser and patches, showing potent cytotoxic T cell responses that can be further enhanced by co-delivery of a helper T cell epitope.
Review
Oncology
Erin Naismith, Janine Steichen, Sieghart Sopper, Dominik Wolf
Summary: NK cells play a crucial role in managing Ph+ and Ph- MPNs, contributing significantly to tumor control. However, their functionality may be altered during MPN treatment, highlighting the importance of further research on their role and associated changes in therapy.
Article
Medicine, General & Internal
Martin Bauer, Edith Lackner, Peter Matzneller, Valentin Al Jalali, Sahra Pajenda, Vincent Ling, Christof Bohler, Werner Braun, Reinhard Braun, Maximilian Boesch, Patrick M. Brunner, Markus Zeitlinger
Summary: This study investigated the safety and tolerability of ablative fractional laser treatment in patients with plaque-type psoriasis, showing a favorable safety profile. Topical administration of ETA to psoriatic plaques via AFL-generated micropores was generally well-tolerated.
FRONTIERS IN MEDICINE
(2021)
Editorial Material
Immunology
Florian Hornsteiner, Martina M. Sykora, Christoph H. Tripp, Sieghart Sopper, Patrizia Stoitzner
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Editorial Material
Oncology
Maximilian Boesch, Florent Baty, Tobias Kowatsch, Dominik Wolf, Martin Frueh, Martin H. Brutsche
Review
Oncology
Maximilian Boesch, Lena Horvath, Florent Baty, Andreas Pircher, Dominik Wolf, Stephan Spahn, Ravid Straussman, Herbert Tilg, Martin H. Brutsche
Summary: This article reviews the latest research on the tumor-associated microbiome, highlighting its impact on anticancer immunity and checkpoint immunotherapy outcome. It emphasizes the need to study the tumor-associated microbiome in addition to the gut microbiome and calls for further research to understand the mechanisms involved and develop therapeutic strategies. A better understanding of the tumor microbiome can improve cancer immunotherapy and advance precision medicine for solid tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Respiratory System
Maximilian Boesch, Frank Rassouli, Florent Baty, Anja Schwarzler, Sandra Widmer, Peter Tinschert, Iris Shih, David Cleres, Filipe Barata, Elgar Fleisch, Martin H. Brutsche
Summary: This study demonstrates that cough frequency can serve as a digital biomarker for disease activity in COVID-19 and other lower respiratory tract infections. Using smartphone-based audio recordings and convolutional neural networks, automated cough detection correlated with clinical and laboratory markers of inflammation. This approach allows for real-time telemonitoring and personalized treatment.
Article
Health Care Sciences & Services
Filipe Barata, David Cleres, Peter Tinschert, Chen-Hsuan Iris Shih, Frank Rassouli, Maximilian Boesch, Martin Brutsche, Elgar Fleisch
Summary: This study validated an automated smartphone-based cough counting system for continuous monitoring of coughs in hospital wards. The system showed high sensitivity and specificity in detecting coughs compared to manual counting. Therefore, it can be used for continuous hourly assessment of cough frequency in the ward.
JMIR FORMATIVE RESEARCH
(2023)
Proceedings Paper
Engineering, Biomedical
Fabian Braun, Guillaume Bonnier, Patrick Theurillat, Martin Proenca, Yara-Maria Proust, Florent Baty, Maximilian Boesch, Simon Annaheim, Martin Brutsche, Damien Ferrario, Mathieu Lemay
Summary: The study found that placing the reflectance pulse oximetry device on the upper arm was more accurate in measuring SpO(2) compared to the wrist, with a lower rate of data rejection. The accuracies obtained at both measurement locations complied with the ISO standard and FDA guidance.
2021 43RD ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE & BIOLOGY SOCIETY (EMBC)
(2021)
Article
Oncology
Maximilian Boesch, Florent Baty, Werner C. Albrich, Lukas Flatz, Regulo Rodriguez, Sacha Rothschild, Markus Joerger, Martin Fruh, Martin H. Brutsche
Summary: The study revealed a significant association between the diversity of the local tumor microbiome in non-small cell lung cancer patients and patient survival rates, as well as the presence of Gammaproteobacteria potentially leading to poor response to immunotherapy. It suggests novel microbiome-specific biomarkers for predicting and prognosticating response to checkpoint-based immunotherapy in lung cancer, drawing attention to the importance of the local tumor microbial habitat as an addition to the gut compartment microbiome.