Tips on using my ppt.
1. You can freely download, edit, modify and put your
2. Don’t be concerned about number of slides. Half the
slides are blanks except for the title.
3. First show the blank slides (eg. Aetiology ) > Ask
students what they already know about ethology of
today's topic. > Then show next slide which enumerates
4. At the end rerun the show – show blank> ask questions >
show next slide.
5. This will be an ACTIVE LEARNING SESSION x
6. Good for self study also.
7. See notes for bibliography.
Introduction & History.
• The surgical portal to the eradication of
diseases, especially malignant diseases, has
played a role in longevity.
• The surgical incision, our entryway into the
body, has allowed for the extirpation of
• In recent times, the length of the incision
has decreased tremendously, allowing for a
more effective recovery period. Shorter
seems to be better. -
Etiology of Cancer
• Genetic mutations, whether inherited or
sporadic, drive cells toward malignant
transformation and degeneration.
• The central dogma of genetics, so aptly
coined and oversimplified by Francis Crick,
is: “DNA makes RNA. RNA makes
• Proteins are the workhorses of the body,
providing cellular structure, facilitating
enzymatic activity, helping with molecular
transport, and playing critical roles in DNA
replication and cellular signaling between
cells. In essence, proteins are the
locomotives of life.
The Genome, the Proteome
• The entire set of our genes is the genome.
Genes code for the production of proteins.
The entire set of our proteins is our
proteome, and the study of proteins is
• Researchers in the proteomic field study
the form and function of our proteins on a
• Often, protein research is combined with
the research in genetics, as it is our genes
that make our proteins.
• Working backward, researchers can identify
abnormal proteins and attempt to match
them with their DNA parent.
• It is as if Crick’s central dogma is being
reversed: “Protein comes from RNA. RNA
comes from DNA.”
• First, find the abnormal proteins, and then
work toward the mutant parent DNA.
• The protein product is the signature of the
• Normal proteins perform the body’s work.
Abnormal proteins perform cancer’s work.
• Genetically reengineered DNA and
modified proteins might perform the
• It was recently announced that several
unique protein signatures of colorectal
cancer have been identified, possibly setting
the stage for the eventual early diagnosis
and totally noninvasive eradication of
colorectal cancer, and by extension, other
cancers (Nature 2014;513:382-387).
• Proteomics enabled researchers to isolate
abnormal proteins associated with certain
subtypes of colorectal cancer.
• Further understanding and manipulation of
these proteins might enable the IV
therapeutic approach, and replace the
scalpel in the curative treatment of
• Or, the therapy could be performed at the
DNA level by modifying or repairing
The Proteomics of Colon Cancer
• Beginning in 2005, researchers began
cataloging the genetic mutations of those
tumors responsible for many of the common
cancers. These were published in “The
Cancer Genome Atlas” (TCGA). Samples
of malignant tumors were collected and
their DNA was sequenced, yielding a vast
library of tumor DNA genetic sequences.
• Researchers at Vanderbilt University, in
Nashville, Tenn., and six other institutions
identified five colorectal cancer protein
subtypes in the TCGA group (Nature
• Genomic data were integrated with
• Some of the amplified chromosomes in the
tumor samples correlated with amplified
and abnormal proteins. This suggested that
proteomics might yield clues to the most
important and common genetic
abnormalities, which might be targeted by
new “designer” drugs or other therapeutic
• Working backward, researchers identified a
single chromosome that might contain the
responsible colon cancer “driver” genes.
For purists, chromosome 20q.
• Chromosome 20, long arm seemed to be
associated with three abnormal protein
quantities and was associated with
corresponding abnormal mRNA.
• The genes on chromosome 20q that are
thought to be “driver” gene candidates
are: HNF4A (hepatocyte nuclear factor 4
); TOMM34 (translocase of mitochondrial
membrane 34); and SRC (SRC proto-
oncogene, nonreceptor tyrosine kinase).
• Studies have shown that 20q aberrations do
not exist in normal colonic mucosa, appear
in some (but not all) of benign adenomas,
become more prevalent as colorectal cancer
advances and are present in almost all
samples of metastatic colorectal cancers.
• The hope is that understanding the structure
and functioning of these abnormal proteins
will help researchers work backward to find
the exact piece of mutated gene responsible
for the protein malfunction, and possibly
repair the faulty DNA in patients and their
at-risk family members.
• Barring identification at the DNA level,
these proteins might allow for early
identification of the dysfunction of our
MMR genes or the early identification of
• With constant inspection of our genomic
DNA and its protein products, researchers
may be on the verge of unlocking the
heretofore opaque functioning of our cells
and our cellular machinery.
• Perhaps incisionless cures will follow soon.
• The surgeon of tomorrow, after confirming
the diagnosis, will don sterile surgical
gloves, place an IV line, administer a
genetically engineered protein, step away
from the patient, grab a cup of coffee and
return an hour later to remove the IV line,
sending the patient home to recover on the
golf course or in a movie theater.
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