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
E-mail:
sandler@jct.ac.il
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.
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