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J u n e 1 1 - 1 3 , 2 0 1 8 | D u b l i n , I r e l a n d

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Page 25

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.edu

BIOGRAPHY