Inhibiting Aromatase (to Lower Estrogen) May Treat Gastric (stomach) Cancer

Discussion in 'Scientific Studies' started by haidut, Dec 4, 2019.

  1. haidut

    haidut Member

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    Yet another study demonstrating the causative link between estrogen and a cancer considered to be hormone-independent. Gastric cancer is one of the leading causes of cancer-deaths worldwide, and especially Asian countries. It is considered very hard to treat and most patients are diagnosed at stages when surgery is not a viable option. As such, the 5-year survival rate is truly abysmal and by some measures "rivals" the one for pancreatic cancer. Some older studies demonstrated a strong decrease in the androgen index, and increase in estrogen/cortisol in patients with gastric cancer from both sexes. Unfortunately, for some reason this discovery did not seem to have follow up studies done on it and did not change/inform clinical practice.

    [Sex hormone excretion in stomach cancer patients]. - PubMed - NCBI
    [Hormonal correlations in stomach cancer patients]. - PubMed - NCBI

    Now, more than 40 years after those initial studies linking steroid imbalance to the gastric cancer pathology, a new study demonstrates that aromatase inhibition may be a viable treatment approach for this type of cancer. The study used both in-virto and in-vivo methods, and the chemical of choice was the steroidal, suicidal aromatase inhibitor (AI) exemestane (EXE). The doses used in the in-vivo portion correspond to about the 25mg daily dose currently approved for prevention/treatment of breast cancer. Interestingly, of all the AI tested only EXE had therapeutic effects. According to the authors, it is due to the fact that EXE not only inhibits the activity of aromatase but lowers its expression too, so much less of it is produced by cells. Aromatase expression increases robustly with aging, obesity, stress, high-PUFA diet, lack of sunlight exposure, vitamin D deficiency, etc. As such, we can once again point the finger to environmental/metabolic/dietary factors in causing this disease.

    Preclinical evaluation of exemestane as a novel chemotherapy for gastric cancer. - PubMed - NCBI

    "...As mentioned, two MOAs of ARIs were considered to test whether ARIs can be used for GCa therapy. Three ARIs (ARI‐I: anastrozole and letrozole, reversible inhibitor; and ARI‐II: exemestane, irreversible inhibitor) were introduced. Cytotoxicity (Figure (Figure22A,A,2B)2B) and colony formation capacity (Figure (Figure2C)2C) were measured, and the results revealed that exemestane had excellent cytotoxic against GCa cells. By contrast, we did not observe a significant cytotoxic effect of anastrozole or letrozole on GCa cells, implying that ARIs have a different mode of action in GCa. In addition, exemestane could suppress Ar expression at the transcriptional level (Figure (Figure2D).2D). The discrepancy in cytotoxic efficacy between ARI‐I and ARI‐II raised the question whether Ar expression but not enzymatic activity (concerting androgens to oestrogens) may be crucial for cytotoxic efficacy against GCa cells."

    "...The tumour size decreased with exemestane treatment in a dose‐dependent manner (Figure (Figure5A).5A). A low dose (10 mg/kg/mouse) of exemestane could reduce the tumour size by approximately 50%, and a medium dose (20 mg/kg) of exemestane could reduce the tumour size by approximately 70%. Furthermore, a low dose (5 mg/kg) of 5‐FU slightly reduced the tumour size (65%), but add‐on treatment with exemestane could suppress the tumour size by approximately 90% (Figure (Figure5B).5B). Notably, the bodyweights were comparable among all groups. Tumour weight was significantly reduced in mice treated with exemestane (P = .0002), but mice receiving a low dose of 5‐FU alone did not show significant tumour growth inhibition (P = .3895). In addition, exemestane and 5‐FU could synergistically promote anticancer efficacy (from P = .0263 to P = .007). Considering the effects of the treatments on the general wellness of the experimental mice, we divided tumour weight by bodyweight (Figure (Figure5C).5C). We used it as the basis to compare within the treatment groups. We determined that combination treatment was the best scheme for therapy."

    "...In this study, we observed that Ar is a crucial GCa prognostic biomarker. Suppressing Ar expression by using ARI‐II could be an excellent therapeutic strategy, particularly when ARI‐II is used in combination with 5‐FU. Additional pharmaceutical studies and human trials are encouraged."
     
  2. Literally

    Literally Member

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    Thanks, @haidut. Off the top of your head do you know of any significant aromatase inhibitors that are available in whole foods or OTC supplements?
     
  3. Adrenaline

    Adrenaline Member

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    Letrozole had great effects on me.
     
  4. Lokzo

    Lokzo Member

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    White button mushrooms, Raw Shredded Carrots, Tongkat Ali.
     
  5. Literally

    Literally Member

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  6. boris

    boris Member

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    @Literally Guavas, orange juice and orange skin (as in marmelade) and bamboo shoots, too.

    OTC: Aspirin, Vitamins AEDK2 (Estroban)

     
  7. Kunstruct

    Kunstruct Member

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    @Literally, Letrozole is not over the counter.
     
  8. Adrenaline

    Adrenaline Member

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    It was not answer for him. Just said I had good results from Letrozole.
     
  9. OP
    haidut

    haidut Member

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    Naringenin and apigenin are pretty decent. Mushrooms are also a great one, in pills (as extract) or as food. Aspirin and the fat soluble vitamins (especially A and E) are also pretty good.
     
  10. raypeatclips

    raypeatclips Member

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    Do you think the apigenin content of a cup of chamomile tea is enough to make a difference?

    Do you think the mushroom water should be consumed as well as the meat?
     
  11. ecstatichamster

    ecstatichamster Member

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    I think mushroom water may have a lot of AI in it.
     
  12. boris

    boris Member

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    Peat said the water is beneficial too. I just cook it down long enough so a little water stays to make it grind easier in the blender.
     
  13. raypeatclips

    raypeatclips Member

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    @haidut do you think the apigenin in a cup of chamomile tea would be enough to make a difference?
     
  14. OP
    haidut

    haidut Member

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    It depends on how much is in one cup. The animal studies use a widely varying amounts of apigenin/naringenin and the lowest doses I have seen used correspond to a human dose of 50mg-75mg daily. Interestingly, combining apigenin and naringenin seems to increase their effects over 10-200 times, so maybe doing one cup of chamomile tea and a glass of OJ would be enough to elicit therapeutic effect.
    Enhanced action of apigenin and naringenin combination on estrogen receptor activation in non-malignant colonocytes: implications on sorghum-derive... - PubMed - NCBI
    "...Apigenin reduced ER-mediated YAMC cell growth comparable to physiological levels of estradiol (E₂, 1 nM) at 1 μM; naringenin had similar effect at 10 μM. However, when combined, 0.1 μM apigenin plus 0.05 μM naringenin produced similar effect as 1 nM E₂; these concentrations represented 1/10th and 1/200th, respectively, of the active concentrations of apigenin and naringenin, demonstrating a strong enhanced action. A sorghum extract higher in flavones (apigenin and luteolin) (4.8 mg g(-1)) was more effective (5 μg mL(-1)) at activating ER in YAMC than a higher flavanone (naringenin and eriodictyol) (28.1 mg g(-1)) sorghum extract (10 μg mL(-1))."
     
  15. raypeatclips

    raypeatclips Member

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    Interesting, thank you.
     
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