Plenary Lecture

Plenary Lecture

Novel Family of Human Hormone-Peptides with
Strong Anti-Cancer Activity

Professor Uziel Sandler
Chair of Computational Biochemistry Department
Jerusalem College of Technology
Jerusalem, Israel

Abstract: In this talk we present the novel human proteins: Thymus Expressed Apoptosis Factor (TEAF) and Natural Killer Colony Activation Factor (NKCAF). TEAF and NKCAF have similar size and second structure. Structure analysis and blood test showed that TEAF and NKCAF are the hormone-peptides.
TEAF was cloned from human thymus cDNA library. RT-PCR and immuno histochemical studies showed that this protein is expressed solely in the medulla and Hassal’s corpuscles of human thymus gland.
We have found that TEAF poses triple anti-cancer activity:
• It kills the cancer cells by inducing both Caspase 8 and Bcl-2 mediated pathways of apoptosis;
• It suppress angiogenesis by inhibiting the expression of the VEGFA and VEGFR1 receptor and by enhancing the expression of IL-10;
• It modulates activity of innate immune response.
It should be noted that TEAF induces apoptosis in proliferating cancer cells like: acute myeloid leukemia cells (U937 pre-meyloid cells), human carcinoma cells, human lung cancer and HeLa cella, while, in contrast, TEAF was unable to induce apoptosis in the healthy cells. The selectivity of TEAF-induced apoptosis is related to the level of T1/ST2 receptor expression. The in vitro results were corroborated by in vivo tumor suppression by TEAF of tumors raised in mice injected with human AML’s cells and human and murine carcinoma cells. It is important that TEAF was able to completely eliminate AML cells from bone marrow.
NKCAF was cloned from human cDNA library and is expressed, mainly, in pancreas, kidney and testis. The activated monocytes and CD8 cells express NKCAF as well. It has been found that NKCAF activates Natural Killer cells and promotes release of the perforin and granzyme B. Application of NKCAF to mice injected with human pancreatic cancer cells drastically decreases the tumor size.

Brief Biography of the Speaker:
Prof. Uziel Sandler, Chair of Department of Computational Biochemistry of Jerusalem College of Technology and Founder, CEO of ISK LTD.
Professor Uziel Sandler is expert in Nonlinear Properties and Critical Behavior of Condensed Matter, DNA Sequence Analysis and Evolutionary Computations. He is one of the founders of the advanced mathematical discipline called “Fuzzy Dynamics”, which describes evolution of complex systems with uncertainty in their dynamics laws. Fuzzy Dynamics has been successfully applied to modeling of the immune system cells’ maturation and to modeling of behavior of a neural cell. Prof. Sandler has published more than 70 academic articles in prestigious scientific journals and 3 books. He is also serving as chair in international conferences and as a member in several worldwide committees in the above-mentioned fields.
At 2005 together with Dr. Yoram Devary he has found Immune System Key Ltd. (ISK LTD), the biotechnology company, which has cloned a novel human hormone-peptide with strong anti-cancer activity. He is also serving as chair of Department of Computational Biochemistry and as Professor at the Department of Applied Mathematics of Jerusalem College of Technology.
Prof. Sandler holds a Ph.D. in Theoretical Physics from L.V. Kirensky Institute of Physics, Academy of Science of former USSR.






WSEAS Unifying the Science