Fritz Sieber, PhD
Professor (with tenure), Pediatrics (Hematology/Oncology/BMT) and Microbiology & Immunology
MS, (Dipl Natw ETH ), Developmental Biology/Biochemistry, Swiss Federal Institute of Technology, Zurich, 1971
- anti-cancer agents
- Antineoplastic Agents, Alkylating
- Bone Marrow Purging
- Bone Marrow Transplantation
- Cell Line, Transformed
- Cell Line, Tumor
- clonal assay
- cytotoxic photoproducts
- cytotoxic subnano selenium
- experimental therapeutics
- autologous hematopoietic stem cell transplantation
- ex vivo purging
- photochemical purging
1) Development of second-generation merocyanine photosensitizers with improved antineoplastic, antiviral, and anti-protozoan activities. Of particular interest are selone analogs that are characterized by extremely high singlet oxygen quantum yields and the photochemical generation of cytotoxic photoproducts. One merocyanine-based application has made the transition from bench to clinic and is showing promising results in a phase I/II trial in adult patients with high-risk acute myelogenous leukemia.
2) Proteinated subnanoparticles of elemental selenium as a novel class of anti-cancer agents. When selenomerocyanine dyes are exposed to light in the presence of oxygen, they generate subnanoparticles of elemental selenium that combine with serum albumin or lipoproteins to form conjugates that are highly cytotoxic to tumor cells but well tolerated by normal cells. A 1-hour exposure to micromolar concentrations of proteinated selenium is sufficient to reduce clonogenic tumor cells by ≥5 orders of magnitude while preserving virtually all normal pluripotent hematopoietic stem cells.
Figure 1: Photochemical generation of proteinated subnanoparticles of elemental selenium and their effects on leukemia and normal hematopoietic stem cells. The protein component acts as a Trojan horse that exploits the enhanced capacity of tumor cells to bind and internalize serum albumin and lipoproteins. The cytotoxic entity (elemental selenium) is preferentially delivered to tumor cells as part of a physiological process.
3) High-dose selenium for the mitigation of therapy-induced toxicities. This project grew out of an effort to develop medical countermeasures against radiation injuries caused by nuclear accidents or acts of radiological terrorism. We could show that very high (supranutritional) doses of dietary selenium are surprisingly effective at reducing radiation injury to kidney, liver, heart, and lung even if the intervention is initiated after radiation exposure. We are now in the process of extending this approach to the mitigation of therapy-induced toxicities in animal models of radiation- and chemotherapy.
(Traul DL, Sieber F.) J Photochem Photobiol B. 2015 Dec;153:153-63 PMID: 26410039 PMCID: PMC4674338 SCOPUS ID: 2-s2.0-84942320153 09/28/2015
(Daziano JP, Günther WH, Krieg M, Tsujino I, Miyagi K, Anderson GS, Sampson RW, Ostrowski MD, Muir SA, Bula RJ, Sieber F.) Photochem Photobiol. 2012 Mar-Apr;88(2):448-60 PMID: 22211823 PMCID: PMC3292634 SCOPUS ID: 2-s2.0-84857995774 01/04/2012
(Sieber F, Muir SA, Cohen EP, Fish BL, Mäder M, Schock AM, Althouse BJ, Moulder JE.) Radiat Res. 2011 Sep;176(3):366-74 PMID: 21867430 PMCID: PMC3237945 SCOPUS ID: 2-s2.0-80052159464 08/27/2011
(Čunderlíková B, Vasovič V, Sieber F, Furre T, Borgen E, Nesland JM, Peng Q.) Bone Marrow Transplant. 2011 Aug;46(8):1118-27 PMID: 21057550 SCOPUS ID: 2-s2.0-80051703773 11/09/2010
(Čunderlíková B, Vasovič V, Sieber F, Furre T, Nesland JM, Peng Q.) Bone Marrow Transplant. 2010 Oct;45(10):1553-61 PMID: 20118993 SCOPUS ID: 2-s2.0-77957932322 02/02/2010
(Sieber F, Muir SA, Cohen EP, North PE, Fish BL, Irving AA, Mäder M, Moulder JE.) Radiat Res. 2009 Mar;171(3):368-73 PMID: 19267564 PMCID: PMC2679178 SCOPUS ID: 2-s2.0-61849152902 03/10/2009
(Tsujino I, Miyagi K, Sampson RW, Sieber F.) Photochem Photobiol. 2006 Mar-Apr;82(2):458-65 PMID: 16613499 PMCID: PMC1626648 SCOPUS ID: 2-s2.0-33646232010 04/15/2006
(Sieber F, Daziano JP, Günther WH, Krieg M, Miyagi K, Sampson RW, Ostrowski MD, Anderson GS, Tsujino I, Bula RJ.) Phosphorus Sulfur Silicon Relat Elem. 2005;180(3-4):647-657 PMID: 16491141 PMCID: PMC1373681 02/24/2006
(Sieber F, Daziano JP, Sampson RW, Tsujino I, Miyagi K, Ostrowski MD, Anderson GS, Günther WHH, Krieg M.) Progress in Biomedical Optics and Imaging - Proceedings of SPIE. 2005;5689:56-65 SCOPUS ID: 2-s2.0-21844436783 07/21/2005
(Miyagi K, Sampson RW, Sieber-Blum M, Sieber F.) J Photochem Photobiol B. 2003 Jul;70(3):133-44 PMID: 12962637 SCOPUS ID: 2-s2.0-0141792990 09/10/2003
Preferential inactivation of paediatric solid tumour cells by sequential exposure to Merocyanine 540-mediated photodynamic therapy and Edelfosine: implications for the ex vivo purging of autologous haematopoietic stem cell grafts.
(Anderson GS, Tsujino I, Miyagi K, Sampson R, Sieber F.) J Photochem Photobiol B. 2003 Feb;69(2):87-95 PMID: 12633981 SCOPUS ID: 2-s2.0-0037295931 03/14/2003
(Anderson GS, Miyagi K, Sampson RW, Sieber F.) J Photochem Photobiol B. 2002 Nov;68(2-3):101-8 PMID: 12468204 SCOPUS ID: 2-s2.0-1842854337 12/07/2002