🚀 go-pugleaf

On Nov 14, 8:44 am, PiLS <p...@invalid.ca> wrote:
> If you're going to target chromatids (as you would be doing in the
> <repeat><repeat><repeat><END> example, it's worth noting that you'd
> kill any dividing cell. Chemotherapy does that to a certain extent,
> but for very limited periods of time (and it makes the patients
> VERY sick). For any prolonged period of time it would simply kill
> the patient.
> In addition, terminally ill patients may be willing to sacrifice gametes,
> but killing the megacaryocytes would be a BAD thing (not that it would
> matter if you killed the dividing cells to begin with of course, as the
> patient would be dead before the platelet count dropped so low as to
> cause massive,letal haemorrhage).
> When you say that harnessing the immune system to target surface antigens
> failed, what are you referring to? We just started trying!
> Or is there some precedent that I am not aware of? (entirely possible).
> Targetting chromosomes is a bad idea. Nature plays to much with them,
> and they already have their own very fine regulatory mechanisms.
> (most cells do't survive accidental aneuplo dy already).
> In addition, not all cancer cells are aneuplo d. In fact, in most cases
> aneuplo dy is probably only a side-effect of the cancer cells being
> "immortal" already (so accidental aneuploidy is not eliminated as it
> usually is). So my opinion is that targetting aneuploid cells would
> NOT cure cancer (arguably the most important flaw in the system).
>
> --
> PiLS
> Everything is worth discussing

Greetings,

I envision the harmless precursor interacting with a drain feature on
or associated with the chromosome, such as the end of the chromosome.
The drain feature acts as a catalyst with respect to the harmless
precursor, breaking it apart or transforming it into a toxin.  This
would not necessarilly kill the dividing cell.  Indeed, if the drain
feature changes geometry during cell division, it may be possible to
engineer the reaction to occur only when the cell is not dividing.

I don't know about surface antigens specifically but there have been
many many attempts to harness the immune system at least since the
1970s with consistently disappointing results.

The relationship between cancer and aneuploidy is not well understood.
Yes, I agree this is the most serious issue with the approach, as I
state in the article.

If, for example, aneuploidy only causes the rapid mutation and thus
adaptation of the cancer cells, then killing the aneuploid cells by
itself would only reduce the malginanacy without curing the disease.
However, the surviving cells would not adapt to anti-cancer agents as
is currently believed to be the case.  So a combination of a system
that kills the aneuploid cells and something else, perhaps even a
currently known drug, might cure the disease.

For the purpose of the successful treatment or cure of cancer, whether
aneuploidy is a cause or consequence of cancer may be an academic
question. If we can find a feature that is always or frequently
present in cancer cells or even predictably associated with highly
malignant cancer cells and never or rarely present in normal cells,
this feature can be used to selectively kill cancer cells or, at
least, highly malignant cancer cells, curing or effectively treating
the disease.

If cancer has a single unified cause, it is logical to seek this
single cause. If cancer has many specific causes, it may be more
effective to seek some common trait shared by the many variants of
cancer, something that is a consequence rather than a cause.

Penicillin and many other antibiotics are effective because they
attack a feature shared by the many different bacteria that cause
bacterial pneumonias and other diseases, even though the specific
causes of bacterial pneumonia and other diseases are many different
kinds of bacteria — which differ at the genetic level.

Some scientific references on aneuploidy and cancer

URL: http://www.sciencemag.org/content/333/6045/942.summary

Science 19 August 2011:
Vol. 333 no. 6045 pp. 942-943
DOI: 10.1126/science.1211154

Aneuploidy Drives a Mutator Phenotype in Cancer

Richard D. Kolodner, Don W. Cleveland, Christopher D. Putnam
+ Author Affiliations
Ludwig Institute for Cancer Research, University of California San
Diego School of Medicine, La Jolla, CA 92093-0660, USA.
E-mail: rkolodner@ucsd.edu, dcleveland@ucsd.edu, cdputnam@ucsd.edu

Summary

The association of chromosomal abnormalities with cancer—including
chromosome translocations, deletions, amplifications, and
inappropriate numbers of chromosomes (aneuploidy)—has been known for
more than a century. Even karyotypically stable cancers are
genetically abnormal because of high frequencies of point mutations.
Despite our current understanding of cancer genomes, it has been
difficult to determine whether many genetic abnormalities are a cause
or consequence of carcinogenesis. Increased missegregation of whole
chromosomes prior to the final steps of cell division (mitosis)
generates aneuploidy and can promote tumorigenesis in some genetic
contexts in mice (1), as the German biologist Theodor Boveri initially
proposed more than 100 years ago. Two papers in this issue, by
Sheltzer et al. (2) on page 1026 and Solomon et al. (3) on page 1039,
show that aneuploidy enhances genetic recombination and defective DNA
damage repair, thereby providing a mechanistic link between aneuploidy
and genomic instability.
The editors suggest the following Related Resources on Science sites
In Science Magazine

Aneuploidy Drives Genomic Instability in Yeast

Jason M. Sheltzer, Heidi M. Blank, Sarah J. Pfau, Yoshie Tange, Benson
M. George, Timothy J. Humpton, Ilana L. Brito, Yasushi Hiraoka, Osami
Niwa, and Angelika Amon
Science 19 August 2011: 1026-1030.
Mutational Inactivation of STAG2 Causes Aneuploidy in Human Cancer
David A. Solomon, Taeyeon Kim, Laura A. Diaz-Martinez, Joshlean Fair,
Abdel G. Elkahloun, Brent T. Harris, Jeffrey A. Toretsky, Steven A.
Rosenberg, Neerav Shukla, Marc Ladanyi, Yardena Samuels, C. David
James, Hongtao Yu, Jung-Sik Kim, and Todd Waldman
Science 19 August 2011: 1039-1043.

URL: http://www.nature.com/nature/journal/v446/n7131/full/446038a.html

Nature 446, 38-39 (1 March 2007) | doi:10.1038/446038a; Published
online 28 February 2007
Cell biology: Aneuploidy and cancer
By David Pellman (1)

Abstract

Aneuploidy is the condition in which a cell has extra or missing
chromosomes, and is often associated with tumours. But whether it is a
cause or a consequence of cancer remains a vexed question.
Aneuploid cancers are like Tolstoy’s unhappy families: each aneuploid
cancer has its own particular abnormal chromosome content, and thus
its own abnormal characteristics. This variability has long frustrated
biologists trying to establish whether aneuploidy is a cause or a
consequence of malignant transformation.

1.David Pellman is at the Dana-Farber Cancer Institute, Children’s
Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Email: david_pellman@dfci.harvard.edu

URL: http://www.ncbi.nlm.nih.gov/pubmed/10687734

Curr Opin Oncol. 2000 Jan;12(1):82-8.
Aneuploidy and cancer.
Sen S.

SourceUniversity of Texas, M.D. Anderson Cancer Center, Department of
Laboratory Medicine, Houston 77030, USA. ssen@mdanderson.org

Abstract

Numeric aberrations in chromosomes, referred to as aneuploidy, is
commonly observed in human cancer. Whether aneuploidy is a cause or
consequence of cancer has long been debated. Three lines of evidence
now make a compelling case for aneuploidy being a discrete chromosome
mutation event that contributes to malignant transformation and
progression process. First, precise assay of chromosome aneuploidy in
several primary tumors with in situ hybridization and comparative
genomic hybridization techniques have revealed that specific
chromosome aneusomies correlate with distinct tumor phenotypes.
Second, aneuploid tumor cell lines and in vitro transformed rodent
cells have been reported to display an elevated rate of chromosome
instability, thereby indicating that aneuploidy is a dynamic
chromosome mutation event associated with transformation of cells.
Third, and most important, a number of mitotic genes regulating
chromosome segregation have been found mutated in human cancer cells,
implicating such mutations in induction of aneuploidy in tumors. Some
of these gene mutations, possibly allowing unequal segregations of
chromosomes, also cause tumorigenic transformation of cells in vitro.
In this review, the recent publications investigating aneuploidy in
human cancers, rate of chromosome instability in aneuploidy tumor
cells, and genes implicated in regulating chromosome segregation found
mutated in cancer cells are discussed.
PMID:10687734[PubMed - indexed for MEDLINE] Publication Types, MeSH
TermsPublication TypesResearch Support, Non-U.S. Gov’tResearch
Support, U.S. Gov’t, P.H.S.ReviewMeSH TermsAneuploidy*Cell
Transformation, Neoplastic*HumansMitosisNeoplasms/
genetics*PhenotypePoint Mutation