Global Medical Discovery features paper: Professor Randy Mrsny

About The Author

Randy Mrsny currently holds a Professor’s chair of Epithelial Cell Biology at the University of Bath in the Department of Pharmacy and Pharmacology where he studies biological principles associated with normal epithelia cell function and how these are affected in disease states. His work in drug delivery is internationally recognized as evidenced by his election as president of the Controlled Release Society and to co-organize a Gordon Conference on Drug Delivery.

Global Medical Discovery featured article: Enhanced paracellular transport of insulin can be achieved via transient induction of myosin light chain phosphorylation 

 

 

Global Medical Discovery features paper: Prof. Yoshifumi Nishimura

About The Author

Prof. Yoshifumi Nishimura received his Ph. D degree in 1976 from Faculty of Pharmaceutical Sciences of the University of Tokyo on UV resonance Raman spectroscopy of biological molecules, and then worked as an instructor and Associate Professor in the Faculty. In 1989, he moved into Graduate School of Yokohama City University as a Professor and worked on NMR spectroscopy of several transcription factors. Professor Nishimura has been working on structural epi-genomics by NMR, and now is an Adviser to the President of Yokohama City University and also a Project Leader of NMR Platform, which contains 950 MHz, 800 MHz, 700 MHz, 600 MHz, and 500 MHz NMR spectrometers, in the Graduate School of Medical Life Science of Yokohama City University.

Global Medical Discovery featured article: Structural Insight into the Mechanism of TFIIH Recognition by the Acidic String of the Nucleotide Excision Repair Factor XPC  

 

 

Global Medical Discovery features paper: Prof. Markus Raderer, M.D.

About The Author

Prof. Markus Raderer, M.D.

Medical University of Vienna, Vienna, Austria

Markus Raderer undertook his early medical studies at the Medical University of Vienna, completing his residency in internal medicine between 1993 and 1999, specialising in haematology and oncology in 2001. He received the venia docendi for ‘Applied and Experimental Oncology’ and ‘Internal Medicine’ in 1999 and 2002, respectively.  Professor Raderer is currently the Programme Director for Extranodal Lymphomas and for Endocrine Tumours at the Medical University of Vienna. He has been responsible for the management and conduct of phase II and III clinical trials at his institution since 1992.

Professor Raderer is on the Editorial Board of a number of journals including the Journal of Clinical Oncology, World Journal of Gastroenterology, and Middle European Journal of Medical Oncology. He has participated on consensus panels for the European Gastrointestinal Lymphoma Study Group (EGILS) on the topic of B-cell lymphoma of mucosa-associated lymphoid tissue, and the European Society of Medical Oncology (ESMO) on the subject of the management of lymphoid malignancies.

For a list of publications see http://ift.tt/1Pbi5V2

Global Medical Discovery featured article: Long-term safety and activity of cladribine in patients with extranodal B-cell marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) lymphoma 

 

Oncolytic adenovirus targeting cyclin E overexpression repressed tumor growth in syngeneic immunocompetent mice

Significance Statement

Induction of cyclin E by adenoviral E1B55K protein is required for productive virus replication in normal cells. However this viral protein is not required in cancer cells, allowing E1B55K-deleted adenoviruses to conduct oncolytic replication (Fig. A). In many cancer cells cyclin E expression is already deregulated, likely because that the cellular factors targeted by E1B55K may already be activated or there are E1B55K-like factors to relax cyclin E regulation. As the cyclin E promoter is highly active in many types of cancer cells and is further stimulated after adenovirus infection, Cheng and colleagues first applied this unique property of cyclin E promoter into the design of a novel tumor-specific oncolytic adenoviral vector Ad-cycE, in which the cyclin E promoter was used to control the critical regulatory viral E1a gene. Significant and selective antitumor efficacy can be achieved with Ad-cycE (Fig. B). In this study, Cheng et al. further present an interesting new model for the study in an immunocompetent preclinical model of lung cancer. This new model could be of great value in the preclinical development of the new anticancer agents and allow researchers to better evaluate oncolytic adenoviral vectors in a more patient-like setting.

About The Author

Dr. Pei-Hsin Cheng received her Ph.D. degree in Pharmacology and Toxicology from the University of Louisville, in 2013. With the motivation to find innovative biotherapeutics and to develop rational combination strategies for cancer treatments, she joined the St. Jude Children’s Research Hospital as a Postdoctoral Research Associate since 2014. Her research interests include oncolytic virotherapy, gene therapy, miRNA replacement therapy and immunotherapy.

Journal Reference

BMC Cancer. 2015;15:716.

Cheng PH¹, Rao XM², Wechman SL^3,4, Li XF⁵, McMasters KM^6,7, Zhou HS^8,9,10. 

Show Affiliations

1. Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. paisin.paisin@gmail.com.
2. James Graham Brown Cancer Center, University of Louisville Medical School, 505 South Hancock Street, CTR Building, Room 306, Louisville, KY, 40202, USA. x0rao001@louisville.edu.
3. Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. slwech01@exchange.louisville.edu.
4. Hiram C. Polk Jr MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA. slwech01@exchange.louisville.edu.
5. Department of Diagnostic Radiology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. x0li0027@exchange.louisville.edu.
6. Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. mcmasters@louisville.edu.
7. Hiram C. Polk Jr MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA. mcmasters@louisville.edu.
8. James Graham Brown Cancer Center, University of Louisville Medical School, 505 South Hancock Street, CTR Building, Room 306, Louisville, KY, 40202, USA. hszhou01@louisville.edu.
9. Hiram C. Polk Jr MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40292, USA. hszhou01@louisville.edu.
10. ⁰Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, 40292, USA. hszhou01@louisville.edu.

Abstract

BACKGROUND:

Clinical trials have indicated that preclinical results obtained with human tumor xenografts in mouse models may overstate the potential of adenovirus (Ad)-mediated oncolytic therapies. We have previously demonstrated that the replication of human Ads depends on cyclin E dysregulation or overexpression in cancer cells. ED-1 cell derived from mouse lung adenocarcinomas triggered by transgenic overexpression of human cyclin E may be applied to investigate the antitumor efficacy of oncolytic Ads.

METHODS:

Ad-cycE was used to target cyclin E overexpression in ED-1 cells and repress tumor growth in a syngeneic mouse model for investigation of oncolytic virotherapies.

RESULTS:

Murine ED-1 cells were permissive for human Ad replication and Ad-cycE repressed ED-1 tumor growth in immunocompetent FVB mice. ED-1 cells destroyed by oncolytic Ads in tumors were encircled in capsule-like structures, while cells outside the capsules were not infected and survived the treatment.

CONCLUSION:

Ad-cycE can target cyclin E overexpression in cancer cells and repress tumor growth in syngeneic mouse models. The capsule structures formed after Ad intratumoral injection may prevent viral particles from spreading to the entire tumor.

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