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EVA-PCD (Ex Vivo Analysis of Programmed Cell Death)

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timmur
(@timmur)
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I'm not sure if you've read about this assay or not, but here's the link to it so you can check it out. This is a quote directly from their website:

Nagourney Cancer Institute has developed a human tumor primary culture platform (called EVA-PCD) for the study of drugs, biologic agents, radiation and drug combinations.

Cells isolated from surgical biopsies, peripheral blood, fluids and bone marrow aspirates are examined for drug-induced programmed cell death. Incorporating the complexity of cell death, this platform measures both apoptotic and non-apoptotic events.

Our laboratory has the capacity to obtain fresh, viable specimens for the isolation of micro-spheroids that have proven reflective of the clinical behavior of human tumors.

Nagourney Cancer Institute has experience in drug development and drug synergy analysis, and has successfully applied these platforms to study the disease-specific efficacy of novel molecules.

So given all of this, I sent them this message asking some specific questions about the assay testing. Here's what I said:

I would like to know how many drugs can be tested utilizing EVA-PCD simultaneously and what particular drugs can be tested. I'm not interested in the normal drugs currently used in the treatment of CLL, but I am interested in multiple off-label drugs and their potential efficacy with regard to CLL. I'm basically looking to test a custom list of drugs that are not likely to be normally tested in this manner but are easy to acquire. All of the drugs show some efficacy in the literature but are not typically tested in a more realistic way (EVA-PCD) and rarely in combination. Thanks.

Bizarrely, to me at any rate, this was the reply:

Thank you for your interest in the work of Nagourney Cancer Institute and the work of Dr. Robert Nagourney. I am sorry to hear of your diagnosis of leukemia. I showed Dr. Nagourney your email and this was his response to your question.

 

“We test many compounds, both conventional and developmental. In order to provide clinically relevant and useful information, we need to examine compounds over time to develop a database usually between 15 and 20 studies. This allows us to compare a given individual with their cohort. Using statistical tools we develop mean, median, and standard deviations to assess relative activity. We cannot do this for a patient unless we have tested the compound or something like it before.“

Um, I think I'm missing something here, lol. I didn't ask about a cohort, I asked about me. Nor did I ask for relative activity with anyone else's treatment, just relative activity amongst the various compounds being tested (or combinations thereof). No mention of the actual items that can be tested (we only test what has been previously tested or something like it, lol?). Also no idea how many drugs or compounds can be tested and in how many combinations. I thought that was the point of the testing; to find those drugs that most effectively cause cell death in your particular cancer? I'm hoping that I'm just missing something here. Has anyone used this testing or can anyone explain why I would want it given the answer I received?


   
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Daniel
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This response shows the complexity behind such tests, that often involve many assumptions. I think most of these labs performing such analysis, in their marketing material try to make it simple and as a result are misleading and create wrong expectations.

To be more specific, I am not sure if there is any chemossensitivity analysis lab that really tests directly a specific tumor or circulating tumor cells against various drugs and supplements. Instead, in most cases, in the best case, they analyze the tumor cells profile and match that with a database of drugs and supplements that can target the specific over expressions and down regulations. 

That makes us wonder about the added value.

Kind regards,
Daniel


   
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timmur
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Hi Daniel,

 

Please take a minute and follow this link for a better explanation of EVA-PCD. This testing should have immense value. All of your protocols are rational-based approaches that are general in nature (out of necessity). Something like this ought to tell a person how well particular rational protocols perform against specific tumor tissue in a semi-realistic fashion.

I'm not trying to "beat a dead horse", I just think perhaps I didn't explain the technology very well?

Tim


   
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johan
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@timmur There are probably different reasons why you got that reply and my guess is they need to operate within the field of oncology and drugs that are FDA-approved for cancer treatment. They are creative and apparently quite successful within these boundaries, and even then it doesn't always seem easy to use a cancer drug they identify as useful for a type of cancer it is not used for, as insurance companies will often not pay for it.


   
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timmur
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@johan Yeah I assumed all of that, but I'll pay out of pocket for the test and I just want the drugs/compounds that show the most promise (from a rational perspective) to be tested.

I'm stage 0 CLL on wait/watch. From my perspective, an early effective treatment protocol could be curative. By effective treatment protocol, I mean a combination of off-label drugs and natural compounds, taken in the right combinations along with lifestyle changes. Having the ability to screen potential protocols without the actual trial and error of taking them is obviously incredibly helpful. The fact that this isn't readily available and standard practice says a whole bunch about how hard the industry is trying to "solve cancer".  This is just another example of why the so-called war on cancer is a joke. Utilized correctly, testing like this could make large clinical differences at very low cost. Of course that could be said of most everything on this site, lol.

Thanks for the response, btw!


   
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johan
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@timmur 

I admire Dr. Nagourney and understand why he can't pursue what you're asking, but I understand your frustration. Best of luck!


   
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johan
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@timmur 

you've probably seen this but just in case...

Phase 2 trial of daily, oral Polyphenon E in patients with asymptomatic, Rai stage 0 to II chronic lymphocytic leukemia

https://pubmed.ncbi.nlm.nih.gov/22760587/


   
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timmur
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@j Saw that! My protocol includes slightly more than that, lol! But that certainly is essential! Thanks for looking out!


   
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Daniel
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@timmur Hi Tim,

Thank you for sharing the links. The technology is clear indeed. It is just that I was very enthusiastic about such tests many years ago, and I became less enthusiastic every year as I realize that many of the labs are not performing the direct test of the substances against the cancer cells but instead just due the analysis of the up regulations and down regulations of the cancer cells and match that with drugs and supplements known to modulate those targets. However, looking at the tests performed at Robert A. Nagourney which I also like based on his talks and results, they claim to do exactly what others don't (but claim or imply they do). Given his professionalism and position, I woudl indeed trust Rational Therapeutics do the test right, as we all want, i.e. direct exposure of the cancer cells to the drugs.

However, even in this case, they need a "context" (a database with drug info) in which the results can be integrated and analyzed, so that they can conclude if a drug works e.g. at realistic doses. And I guess that is what they don't have when someone asks them to test a tumor against new substances not available in their database. (as they state, "LC50 values interpolated from dose response curves are compared with the Rational Therapeutics database to assess drug response probability and drug synergy.")

Kind regards,
Daniel

 

 


   
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timmur
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Posted by: @daniel

@timmur Hi Tim,

-snip-

However, even in this case, they need a "context" (a database with drug info) in which the results can be integrated and analyzed, so that they can conclude if a drug works e.g. at realistic doses. And I guess that is what they don't have when someone asks them to test a tumor against new substances not available in their database. (as they state, "LC50 values interpolated from dose response curves are compared with the Rational Therapeutics database to assess drug response probability and drug synergy.")

Kind regards,
Daniel

 

 

I guess I don't understand this. Cell death is measurable, yes? Methyl Jasmonate, as an example, has been tested in vitro for its ability to cause apoptosis, necrosis, or some other form of cell death? Some sort of assay was used to measure this, correct? So I'm still not clear why EVA-PCD can't be applied to this compound. If you say that this has to be an item that's previously been tested, then you could never test anything new or at all! The dilemma, from my perspective, is this: I can measure and report cell death in a journal for a particular substance, but Rational Therapeutics can't perform EVA-PCD analysis on this studied substance? That just doesn't make sense so clearly, I'm missing something. Sorry for being so obtuse, but I still don't get it.


   
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johan
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@timmur I think they can but they likely have their own criteria that they apply to establish a hypothesis of a drug worth testing.


   
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timmur
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Topic starter  

@j Seems like they might need some better criteria then. I know they've looked at methyl jasmonate. I wonder why they just wouldn't answer the question. What have you tested? The list isn't that big.


   
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johan
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@timmur 

We should get Dr. Nagourney on the forum 🙂


   
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