What are they?
Cancers arise from maturation arrest in the hierarchy of a cell lineage due
to failure of cells to diff
erentiate. Properties of cancer stem cells include: self renewal, ability to
grow in vitro indefi
nitely (transformation), translatability (tumor initiation) and resistance to
Where do the come from?
In each of the major causes of cancer arises from stem cells. 1.
Field defect: Teratocarcinoma arises from germinal stem cells due to a fi
eld or niche eff
Chemical Carcinogenesis. Th
e cellular reactions of the liver exposed to chemical carcinogens
shows that liver cancers arise from maturation arrest of liver stem and progenitor cells. 3. Virus
infections: Viruses that cause cancer infect tissue stem cells (for example basal epithelial cells)
with resultant continued proliferation of immature cells. 4. Mutations: Leukemias are caused
by of specifi
c gene rearrangements (mutations) that produce constitutive signaling lesions at
various stages of diff
erentiation (maturation arrest). Specifi
c reversal of the molecular lesions
ective in restoring maturation. 5. Epigenetic changes: In gastric cancers associated with
infection, hypermethylation of the gastric epithelial cells leads to fi
which is maintained by long-lived gastric stem cells.
What can we do about them?
Conventional therapies are directed toward the proliferating
transit amplifying cells. When these therapies are discontinued, the cancer will re-grow from
the cancer stem cells, which are not proliferating at the time therapy is administered. In order
to prevent re-growth new therapies must be developed that are directed to the cancer stem cells
Dr. Sell received an MD from the University of Pittsburgh in 1960, residency in pathology at Massachusetts
General Hospital, and fellowship training at NIH and U. Birmingham in England. He served on the faculty at Pitt;
USCD; UT Houston; and Albany Medical College. He has published 265 research papers, 83 invited papers,
36 book chapters and 14 books. He has a paper listed as a ?Citation Classic? by Current Contents and another
as a ?Scienti
c Landmark? by AACR. Awards include: Distinguished Scientist Award, IATMO; Virchow Award,
LeadershipMedica; Legacy Laureate, Pitt (Highest Award for Alumni); and the Abbott Award of ISOBM.
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