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Old 11-30-2011, 06:16 PM   #1
Jackie07
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Johns Hopkins Dr. Sidransky on individualized therapy

An excellent (video) overview by Dr. Sidransky of Johns Hopkins on individualized cancer treatment including tumor grafting, tumor markers, chemo sensitivity tests, ...etc. A must 'watch'!

http://cancerconnect.com/dr-sidransky-archive/
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Old 12-03-2011, 12:20 AM   #2
Rich66
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Re: Johns Hopkins Dr. Sidransky on individualized therapy

Very interesting.
Especially the fact that he mentioned sensitivity testing in terms of old school testing "on plastic" vs mouse tumor grafts. Now..I have been wondering for some time if/when/whether folks like Nagourney at Rational Therapeutics etc would migrate from 3D tumor cluster/sample testing to something that emulates traditional yet impersonal "in vivo" research using tumor grafts in mice...but figured the costs would be prohibitive even if possible. But more importantly, I am surprised..maybe..that he broke things down that way...essentially skipping over a major chunk of the work in that arena. Tumor grafting may have been done..as he said..back in the 60's for a pan ca patient..or currently in some experimental/trial fashion..but I have not come across this as an available approach. I'm happy if it is available..but not happy he skipped over the more readily available 3D culture functional profiling of RT or Weisenthal or the Medicare approved grown out cell approach of Chemofx. What gives? Is JH about to bring tumor grafting to the broader market? Again..love the idea if it is possible..but hate any concealment/distortion of the current options patients actually have now.

Perhaps further insight to be gleaned here:
http://www.personalizedcancertreatme..._June_2011.pdf
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Old 12-03-2011, 12:50 AM   #3
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Re: Johns Hopkins Dr. Sidransky on individualized therapy

As far as I can see it, the translation of tumor graft analysis is a long way off. In general, the problem with these experiments is that they are usually done on SCID (severe combined immunodeficiency) mice - aka, mice with ZERO immune system.

SCID mice are routinely used as model organisms for research into the basic biology of the immune system, cell transplatation strategies and the effects of disease on mammalian systems.

They have been extensively used as hosts for normal and malignant tissue transplants. Hence infecting mice with human breast cancer tumors.

They also use nude mice, which don't have a thymus (and therefore no T cells). T cells mature in the thymus. They do this to eliminate the potential for rejection. T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes and play a central role in cell-mediated immunity.

Promising research or same old grant getter?
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Old 12-03-2011, 12:56 AM   #4
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Re: Johns Hopkins Dr. Sidransky on individualized therapy

Yes..well...floating a 3D cluster of cells in some abstract medium might not exactly duplicate the various factors within a body either. I just resent exclusion of research/clinical developments from a timeline..very fishy...not FISHy.
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Old 12-03-2011, 06:48 AM   #5
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Re: Johns Hopkins Dr. Sidransky on individualized therapy

Cancer is already in 3D conformation. Analyzing cultures of fresh tumor cells in "real life" 3D conformation makes profiling indicative of what willl happen in the body, where cells interact with and support other living cells, both malignant and non-malignant cells. That's why functional profiling studies cancer cells in small clusters or microspheroids.

Real-life cancers grow as a complex organism that includes both malignant and non-malignant components. It may include fibrous tissue, mesothelial cells, fibroblasts, endothelial cells, etc. In order to exhibit its most characteristic behavior patterns, a cancer cell needs to be surrounded by a colony of other cells, both normal and malignant.

Human tumors represent micro-ecosystems composed of transformed cells, stroma, fibroblasts, vascular elements, extra-cellular protein matrices and inflammatory elements. The behavior of human cancers and their reponse to therapy reflect the complex interplay between humoral, vascular, adhesion and cytokine-mediated events acting in concert.

Tumors are very complex organisms. Ignoring this complexity, most studies of human cancer in culture have focused upon individual tumor cells that have been removed from their complex microenvironoment. It needs to be kept intact.

Cells that are routinely broken up by mechanical and enzymatic means, alters their subsequent behavior. Some previous methods of assays limited their analysis only to isolated tumor cells and failed to incorporate the crucial contribution of non-tumorous elements to the cancer phenomenon.

When allowed to grow in vitro, living cancer cells develop into these tiny micro-spheroid clusters that form a complex biosystem in which each malignant cell reacts upon its fellow colonists in subtle but important ways.

Each of these microspheres contains all the complex elements of tumor biosytems that are found in the human body and which can impact clinical reponse.
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Old 12-03-2011, 03:06 PM   #6
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Re: Johns Hopkins Dr. Sidransky on individualized therapy

Well..no doubt tumor behavior is complex.
I guess my thinking is that grafting into even a deficient, less than ideal animal host is a slight step closer to emulating tumor behavior in a human host..as opposed to a cluster of cells in suspension.
That being said, either one strikes me as a better choice than guessing.
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Old 12-03-2011, 04:31 PM   #7
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Re: Johns Hopkins Dr. Sidransky on individualized therapy

Well, not with SCID and nude mice. It willl never emulate tumor behavior in a human being.
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Old 12-03-2011, 04:38 PM   #8
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Re: Johns Hopkins Dr. Sidransky on individualized therapy

That's focusing on the hampered immune aspect of lab mice when a cluster of cells in suspension is exposed to no more immune response. I guess I'm figuring other non immuno aspects (growth factors etc) of grafting into a live animal would give a slight advantage over cells in suspension. Not saying it's perfect..just a step closer.
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