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CANCER STEM CELLS AND
ONCOLOGY RESEARCH
11
th
International Conference on
Journal of Medical Oncology and Therapeutics
|
Volume 3
William G Thilly et al., J Med Oncl Ther 2018, Volume 3
METAKARYOTIC CANCER STEM
CELLS ARE CONSTITUTIVELY
RESISTANT TO X-RAYS AND
CHEMOTHERAPEUTIC AGENTS BUT
SENSITIVE TO MANY COMMON
DRUGS: FIRST CLINICAL TRIAL
SHOWS EFFECTIVENESS OF A
METAKARYOCIDE AGAINST STEM
CELLS IN HUMAN PANCREATIC
TUMORS
William G Thilly
and
Elena V Gostjeva
Massachusetts Institute of Technology, USA
A
fter radio- and chemo-therapy human tumors display many dead
eukaryotic cells with pyknotic nuclei. But amitotic metakaryotic
stem cells with hollow, bell shaped nuclei are unaffected as expected
of treatment-resistant cancer stem cells. These same phenomena
may be observed
in vitro
using any of many tumor or metastasis-
derived cell lines the immortality of which is conferred by the presence
of amitotic, metakaryotic cancer stem cells. About 5% of human
colonic adenocarcinoma-derived HT-29 cells in exponential growth
are immortal metakaryotic stem cells that increase by symmetric
amitoses and continuously create mortal mitotic eukaryotic cells by
asymmetric amitoses. Two assays for agents/conditions specifically
toxic to metakaryotic stem cells have been devised: (a) microscopic
recognition of necrotic metakaryotic nuclei and (b) survival of cells
forming large immortal colonies visibly containing metakaryotic stem
cells
in vitro
. X-rays and chemotherapeutic agents (alkylating agents,
antimetabolites and mitocides) have been found to kill eukaryotic cells
but not metakaryotic cells at doses commonly used in cancer therapy. In
contradistinction, we have shown that multiple classes of common drugs
are preferentially cytotoxic to metakaryotic stem cells including NSAIDS,
antibiotics and drugs used to treat diabetes, hypertension and other
medical conditions. There are reports of the first images demonstrating
killing of the preponderance of metakaryotic cancer stem cells in a series
of pancreatic tumors by an antibiotic metakaryocide in a clinical trial in
progress at the Medical College of Wisconsin (Prof. Susan Tsai, M.D,
Principle Investigator). Research plans to identify effective protocols for
a series of metakaryocidal drugs are outlined.
William G Thilly, Sc.D. was born in Port Rich-
mond NY, USA and is now Professor of Ge-
netics, Toxicology and Biological Engineering
at MIT. With multiple collaborators he and Dr
Gostjeva are exploring the bizarre physiology of
metakaryotic stem cells, growing them in cell
cultures, and devising means to kill them with
drugs and protocols expected to be well tolerat-
ed in patients.
thilly@mit.eduBIOGRAPHY