Did this paper about D + Q and tumorigenesis concern anyone here?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218402/
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, which develops in the context of fibrosis and cirrhosis caused by chronic inflammation, in turn due to non-alcoholic fatty liver disease (NAFLD), alcohol consumption and/or hepatitis viral infection. An increased number of senescent cells are associated with age-related tissue degeneration during NAFLD-induced HCC, or during chemotherapeutic treatment. Senolytic agents target selectively senescent cells. A combination of the senolytic drugs dasatinib and quercetin (D+Q) reduced hepatic lipid accumulation and alleviated age-associated physical dysfunction in mice. However, whether D+Q can impact the treatment of HCC, at the end-stage of the NAFLD inflammatory spectrum, is unknown. Here, using two well-established HCC cell lines (HepG2, Huh-7), we demonstrate that the maximal cytostatic doses for D and/or Q (1 + 1 μM) lacked efficacy in removing doxorubicin-induced β-gal-positive senescent cells. Moreover, D+Q did not affect doxorubicin-dependent induction of flattened morphology, activation of p16, expression of SASP-associated genes or formation of γH2AX foci. We then investigated the antitumor efficacy of doxorubicin, D+Q, or the combination, in xenograft studies conducted with HCC cells inoculated in athymic nude mice. Doxorubicin reduced tumor growth by 30% compared to control mice, while D+Q was ineffective in synergizing with doxorubicin and in clearing doxorubicin-induced HCC senescent cells. Unexpectedly, D+Q alone appeared to have acute pro-tumorigenic effects in control mice. While our data need to be confirmed in animal models that fully recapitulate NAFLD, we demonstrate that these compounds are ineffective, alone or in synergy with senescence-inducing chemotherapy, against experimental HCC.
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Thanks for posting this.
After reading, YES.
Its conflicting data. Darn!
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In general no, the nature of science is to have conflicting data. That's why it's science. In this case they're examining a specific use case and found it not to work. Assuming the results are valid (they haven't been independently repeated yet) I wouldn't be surprised to find that D&Q isn't a magic bullet. The supposition here is that D&Q is effective for otherwise healthy individuals (though there is the study showing it working for the osteoarthritis patients). In this case the mice had some serious health issues. Also, what works for mice doesn't always work for men, and vice versa, not to mention what dosage did they use?
I suspect that D&Q is good for healthy individuals to reduce general age induced senescent cells. But past some sure, no surprise they can become ineffective. Our previously known senolytic, namely fasting, doesn't work against all cancers either. Some are fasting resistant.
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Dan
Agree.
As I pondered this further, I had a few thoughts about their conclusions as well.
Sample size was quite small (40). Dosing was varied from low to high, but resulting comments did not address this. Ratio of D an Q was not addressed. More than one tumor type was not addressed.
One raw data chart:
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BobM Yeah agree. I think it's a mistake to dismiss research out of hand, and also to accept it unconditionally. To come to the truth you have to synthesize all of the research and data. Not easy, it takes a certain mind and lots of time. So what I do is outsource it. Bill Faloon is one of my experts, I use the information on the LE site and his Disease Prevention and Treatment. He's spent his life doing this, and has a team working with him so is much better at this than I can be.
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