ESHAP is an active regimen for relapsing Hodgkin's disease, with myelosuppression as its dose-limiting toxicity. An increased risk of treatment-related mortality when it is combined with high-dose chemotherapy can not be ruled out.
(E)-2-alkenals are aldehydes containing an unsaturated bond between the alpha and beta carbons. 2-alkenals are produced by many organisms for defense against predators and secretions containing (E)-2-alkenals cause predators to stop attacking and allow the prey to escape. Chemical ecologists have described many alkenal compounds with 3-20 carbons common, having varied positions of double bonds and substitutions. How do these defensive alkenals act to deter predators? We have tested the effects of (E)-2-alkenals with 6-12 carbons on transient receptor potential channels (TRP) commonly found in sensory neurons. We find that (E)-2-alkenals activate transient receptor potential ankyrin subtype 1 (TRPA1) at low concentrations-EC50s 10-100 µM (in 0 added Ca(2+) external solutions). Other TRP channels were either weakly activated (TRPV1, TRPV3) or insensitive (TRPV2, TRPV4, TRPM8). (E)-2-alkenals may activate TRPA1 by modifying cysteine side chains. However, target cysteines include others beyond the 3 in the amino-terminus implicated in activation, as a channel with cysteines at 621, 641, 665 mutated to serine responded robustly. Related chemicals, including the aldehydes hexanal and decanal, and (E)-2-hexen-1-ol also activated TRPA1, but with weaker potency. Rat trigeminal nerve recordings and behavioral experiments showed (E)-2-hexenal was aversive. Our results suggest that TRPA1 is likely a major target of these commonly used defensive chemicals.
Obesity is the cause of up to one-third of all cancers affecting women today, most notably endometrial, colon and breast cancer. Women’s health providers are poised to advise women on obesity’s link to cancer development, but often lack resources or training to provide appropriate counseling. Here, we review obesity’s role in increasing the risk of several common reproductive system conditions faced by women, including polycystic ovarian syndrome, infertility, gynecologic surgical complications, and pregnancy complications. These events can be used as teachable moments to help frame the discussion of weight management and promote cancer prevention. We also review national guidelines and existing tangible weight-loss strategies that can be employed within the outpatient women’s health setting to help women achieve weight loss goals and affect cancer prevention.
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