HSP27 is highly expressed in, and supports oncogene addiction of, many cancers. HSP27 phosphorylation is a limiting step for activation of this protein and a target for inhibition, but its highly disordered structure challenges rational structure-guided drug discovery. We performed multistep biochemical, structural, and computational experiments to define a spherical 24-monomer complex composed of 12 HSP27 dimers with a phosphorylation pocket flanked by serine residues between their N-terminal domains. Ivermectin directly binds this pocket to inhibit MAPKAP2-mediated HSP27 phosphorylation and depolymerization, thereby blocking HSP27-regulated survival signaling and client-oncoprotein interactions. Ivermectin potentiated activity of anti–androgen receptor and anti-EGFR drugs in prostate and EGFR/HER2-driven tumor models, respectively, identifying a repurposing approach for cotargeting stress-adaptive responses to overcome resistance to inhibitors of oncogenic pathway signaling.
Prostate Problems
If urination is not complete, so you must soon go again, especially in the night, it is suggestive of pressure on the urethra from an enlarged prostate gland. Keeping a little urine from being voided is conducive to bladder and kidney infection, too, because bacteria soon find this “free food.”
The prostate collects toxins as if it were a designated dump site, especially for nickel. Urinary tract bacteria quickly find “their” metal, nickel. Any supply of nickel will attract bacteria as quickly as crumbs and cheese attract mice. Urinary tract bacteria are making use of your urea as their food. To digest it, they first break the urea molecule apart into two ammonia molecules. It is the ammonia smell of the urine that gives away their presence. The urine should have no ammonia smell. Our bodies do not make ammonia. Only bacteria can do this! Their digestive enzyme is called urease. In order to do its job, this enzyme requires the element nickel.
Nickel is plentiful in the soil which is undoubtedly where these bacteria belong, breaking up and utilizing the urine and droppings left there by animals. They perform an essential task in our environment, destroying animal excrement and thereby cleaning-up the soil around us. What folly it is to load ourselves up with nickel so that in one short hop from the earth they are residing in us! Bacteria are all around us doing their valuable jobs. We cannot stop associating with bacteria. We were not meant to feed them, however. If we did not supply them with nickel, as if we were just another patch of earth, they could not gain a foothold in our urinary tract and then to the prostate.
How can we rid our bodies of nickel? This is the challenge. Are we eating dirt? A small amount of dirt can't be avoided on our food. But we can stop sucking on nickel as if it were a lollipop. Our spoons, forks and knives are made of nickel! Stainless steel is 8% nickel! Does it really come off as you eat? When you stick a knife into the mayonnaise jar, it is stained in a few minutes. Try it. The mayonnaise has reacted with the metal loosening the nickel. When you smear the knife over your bread, this film comes off and you eat it. If you were to put the knife in your mouth, now, you could taste the metal. You will later wash the knife but not before you have eaten enough nickel to supply all the bacteria in your body with the daily allowance of their essential element, nickel. Nickel is not our essential mineral.
Even plants keep their nickel levels very low. But due to pollution of animal feed with it, even a hen's egg now has 3mcg/100 gm of nickel in it.12 To produce a nickel-polluted egg, the chicken must be polluted.
Especially infants and children should never be given metal cups or cutlery. They need all their immune power to combat the barrage of new bacteria and viruses that is emerging in this age of AIDS. Nickel is part of dirt and belongs there, not in our pots and cutlery.
Another large source of nickel is metal dentalware. It is used to harden gold! If you suffer from prostate problems, remove metal from your dentalware. Nickel is used to make bridges, gold crowns, retainers, amalgams. Exchange it all for plastic ware and composite buildups (see Sources for more dental information).
Stop eating and cooking with metal utensils; use old fashioned wooden or sturdy plastic cutlery instead. Always use a plastic knife for butter or mayonnaise. Never buy foil-wrapped butter.
Nickel is fat soluble and is stored in your skin fat temporarily when a surge of it enters the body. Your skin oils may be loaded with nickel causing “allergies” in the skin. Male pattern baldness is such an allergy. The sweat tries to excrete it for you. Always wash off your scalp sweat to help with this excretion. The skin oils dissolve nickel from metal jewelry (sometimes leaving your skin with a greenish black color) and transport it into your body. Don't wear metal jewelry. Earring posts should be plastic. Metal watches and metal rimmed glasses should be replaced with all plastic types. Metal rings should be replaced. After lowering your total body nickel levels and your prostate disease is only a memory, you might notice scalp hair returning to sparse areas. Search around the edge of the hair line for the first returnees.
Bacteria cannot live in the prostate without nickel being present. You can cure your prostate problems with the simple tactic of stopping nickel pollution of your body. Notice that you get a fresh attack after accidentally using metal cutlery in a restaurant or eating mayonnaise-style salad with a metal spoon stuck in it. It might be wise to take a histidine capsule (about 500 mg., one a day for three weeks, see Sources) when this happens.
Histidine is a nickel chelator. Taking zinc is helpful too (60 mg. two times a day for a month). Possibly, the nickel was poisoning zinc enzymes. Read about the benefits of flaxseed, too, but remember to test every product for pollutants before accepting it as a supplement.
Prostate problems of all kinds clear up when bacteria are zapped, the Kidney Cleanse is done, dental cleanup is done, and the Bowel Program is followed.
more at the link below...
Objective: To analyze the relationship between onion and garlic intake and benign prostatic hyperplasia (BPH), using data from a multicenter case-control study conducted in Italy.
Methods: A multicenter case-control study of 1369 patients with BPH and 1451 controls, admitted to the same hospitals for a wide spectrum of acute, non-neoplastic conditions, was conducted in Italy between 1991 and 2002. Information was collected by trained interviewers using a validated and reproducible food frequency questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were obtained after allowance for recognized confounding factors and energy intake.
Results: Compared with nonusers, the multivariate ORs for the highest category of onion and garlic intake were 0.41 (95% CI 0.24 to 0.72) and 0.72 (95% CI 0.57 to 0.91), respectively. The combined OR for frequent users versus nonusers of both onion and garlic was 0.65 (95% CI 0.49 to 0.86). The inverse relationships were consistent across age strata.
Conclusions: This uniquely large data set from European populations showed an inverse association between allium vegetable consumption and BPH.
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