Monday, February 16, 2015

Weird letter on cancer carcinogenesis

Also from this week's C&EN, a really odd letter on cancer and chemistry (emphasis mine):
...This letter is to point out that chemistry plays the central role in the ­etiology and prevention of the most ­prevalent types of human cancer. The chemical agents responsible for the initiation of cancer are the estrogens. They become carcinogenic when their unbalanced metabolism in our bodies generates excessive amounts of estrogen-3,4-quinones. 
When that happens, the estrogen-3,4-quinones react with DNA, forming depurinating estrogen-DNA adducts that generate the mutations leading to the initiation of cancer. We have demonstrated this for five different types of human cancer: breast, ovarian, and thyroid for women and prostate and non-Hodgkin lymphoma for men. We also think that other prevalent types of cancer are initiated by the same mechanism. This mechanism can be prevented by use of natural compounds such as resveratrol and N-acetylcysteine to block formation of estrogen-DNA ­adducts. 
When we began conducting cancer research in the 1970s, chemical carcinogenesis played a relevant role in cancer research, supported by the National Cancer Institute. Unfortunately, appreciation of the role of chemistry in carcinogenesis was lost, and NCI dissolved the chemical carcinogenesis branch. 
Meanwhile, we discovered that the potent polycyclic aromatic hydrocarbon carcinogens formed predominantly depurinating PAH-DNA adducts that generate cancer-initiating mutations (Proc. Natl. Acad. Sci. USA 10422), and then we found that the depurinating estrogen-DNA adducts are also responsible for cancer-initiating mutations. The discovery of the importance of these depurinating DNA adducts has been neglected for the past 20 years. The final tragedy of this neglect is that chemistry also provides the pathway to cancer prevention. By using natural compounds such as resveratrol and N-acetylcysteine to prevent the formation of estrogen-DNA adducts, the transformation of cells to malignancy is also prevented. 
With all of the great advances chemistry has provided for humankind, cancer research is one more area in which chemistry can enhance life and remove misery—if this is recognized by scientists. 
Ercole Cavalieri
Eleanor Rogan
Eppley Institute for Research in Cancer & Allied Diseases
Omaha
This seems like something with a real backstory. I don't know much about carcinogenesis and prevention of such, but it sure seems like to me that this resveratrol/N-acetylcysteine stuff surely must have been proven correct or falsified in the literature by now. Anyone have any understanding of what's going on here?

UPDATE: Oh, man, this is no good. Anon504p nails it, with a link to these authors selling something? that "Keeps Your Body in Balance" and "Blocks DNA Damage." $69/bottle on Amazon.
"Prevennia® is based on the pioneering work of Dr. Ercole Cavalieri and Dr. Eleanor Rogan who led the team that identified the initial step in the mutation – initiation – promoter - tumor formation, namely the formation of a reactive estrogen metabolite."
Ugh.

UPDATE 2: An anonymous commenter writes in to give a wise word of caution:
I have some thoughts on Anon@5:04PM's point. 
- It's not unheard of for snake oil hucksters to cite published, peer-reviewed research in their sales material.
- Neither Cavalieri nor Rogan are listed anywhere in the executive team; the founder is someone else.
- Although Google reveals that the web site has a bio for Cavalieri, Rogan and another academic scientist, the end of the bio document is a disclaimer which suggests that none of the three had anything to do with the bio. 
It seems possible (to me, at least) that neither Cavalieri nor Rogan have any connection to Prevennia.
I think that's a fair point, so I think I am going to contact Drs. Cavalieri and Rogan and see if that is or is not the case. 

12 comments:

  1. Are they saying estrogen is the root of all evil?

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  2. He might be onto something but the tone sure sounds bitter and deranged. I do not know the specifics of the research in question, I just did a thesis work for people who started as scientists and in their zeal they gradually made a transition into questionable alternative medicine, and they blamed the medical establishment and pharma industry for keeping them down... Over the four years that I worked with my old advisors I had many repetitive discussions and I thing I can tell - I used to be the true believer myself...

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  3. They sounds like some bitter academics who may have lost their NIH funding in recent years. They should be grateful that they got as far as they did on the taxpayer dollar.

    There are a lot of people in academia, including non-tenured grunts like myself, who could write similar letters. Why wont the taxpayer fund my super important research? Its the competition and movement of dollars (shifts of money out of certain area of cancer research into other sexy areas like patient specific treatment), stupid.

    Reducing agents detoxifying carcinogens? (I'm assuming that is the mechanism he proposes) If I had to guess, in vitro work with tissue culture and and cell lines supports the idea, but interventional trials with resveratrol, vitamin E, and vitamin C in animals and humans do not.

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  4. I wonder if this helps explain it...

    http://www.prevennia.com/Proven.aspx

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    Replies
    1. My god. This is shameless. They even got Fred Thompson as their shill.

      Delete
    2. An anonymous commenter writes in to say:

      "I have some thoughts on Anon@5:04PM's point.

      - It's not unheard of for snake oil hucksters to cite published, peer-reviewed research in their sales material.
      - Neither Cavalieri nor Rogan are listed anywhere in the executive team; the founder is someone else.
      - Although Google reveals that the web site has a bio for Cavalieri, Rogan and another academic scientist, the end of the bio document is a disclaimer which suggests that none of the three had anything to do with the bio.

      It seems possible (to me, at least) that neither Cavalieri nor Rogan have any connection to Prevennia."

      Delete
  5. It's no wonder my BS alarm was ringing as soon as I read the original posting. I think it was mention of resveratrol that was the first clue.

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  6. Apparently Letters to the Editor are not well-vetted in C&EN.

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  7. It also overlooks the multiple other ways that DNA can be damaged (and potentially lead to cancer). Hell, DNA copy errors occur without the need to introduce any outside agent.

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  8. I've collaborated with someone who came out of their labs. Cavalieri is apparently retired and his lab shut down from lack of funding, and Rogan has continued what she can of it.

    Their letter does summarize their research as i understand it and maybe add a hypothesized but unsubstantiated next step that the reductants would therefore be beneficial... but i don't understand why anyone would write (or publish) such a letter in CEN.

    Also, taking a quick look at their last couple of papers i don't see a Conflict of Interest statement for anything, let alone a supplement company.

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  9. Regarding update 2: I find it hard to believe that promotional literature could use an image of anyone without his or her permission.

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  10. And, unfortunately, there's more.

    "Dr. Ercole Cavalieri and Dr. Eleanor Rogen of the University of Nebraska Medical Center, Eppley Institute for Research in Cancer, located in Omaha, Nebraska, have identified the triggering mechanism by which breast and prostate cancer cells begin. Preventium™ http://www.preventium.org is a recently developed dietary supplement that promises to reduce people's risk for breast and prostate cancer. Ercole Cavalieri, D.Sc. and research collaborator Eleanor Rogen, Ph.D. say: "We have found the first step that starts a cell down the road to becoming a cancer cell. By blocking this first step from happening, we feel we can stop the development of breast and prostate cancer." "

    http://www.businesswire.com/news/home/20090219006085/en/Preventium-Prevention-Breast-Prostate-Cancer-Begins#.VOTzI7d0w3E

    "We are doing further research into the likelihood that Prevennia(R) has a positive effect on hot flashes," stated John Raffanti, CEO of EQ Biosciences, Inc. "Our scientists have spent 40 years in research developing Prevennia(R) and this new information is very exciting."

    http://inpublic.globenewswire.com/releaseDetails.faces?rId=1748542

    Prevennia was the life work of Dr. Ercole Cavalieri, whose team has developed an estrogen metabolism regulating mix that prevents estrogen-adducts from disfiguring DNA.

    http://www.examiner.com/article/health-technologies-at-the-holistic-living-expo

    "Our scientists...", "...was the life work of..."

    There is a very long history here.

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