An AIN-76A diet supplemented with miso (Japanese soybean paste) reduced the incidence (p = 0.05, Fishers exact test) and delayed the appearance (p = 0.04, log rank test) of dimethylbenz[a]anthracene (DMBA)-induced mammary adenocarcinomas in female Sprague-Dawley rats. A NaCl-supplemented AIN-76A diet (containing the same amount of NaCl as in the miso-supplemented diet) also delayed the appearance of tumors (p = 0.02, log rank test) compared with the AIN-76A control diet. The miso- and NaCl-supplemented diet treatment groups showed a trend toward a lower number of cancers per animal, a trend toward a higher number of benign tumors per animal, and a trend toward a lower growth rate of cancers compared with controls. However, no statistical differences in the total number of tumors per animal or growth rate of the cancers were observed in the miso, NaCl, and control groups. Both miso and NaCl supplementation resulted in increased water intake and urine output but no change in the growth of the animals. These data suggest that miso consumption may be a factor producing a lower breast cancer incidence in Japanese women.
Oxothiazolidine carboxylic acid is a prodrug of cysteine that acts as an anti-diabetic agent via insulin secretion and the formation of the Ca2+-mobilizing second messenger, cyclic ADP-ribose (cADPR). Here we show that a hybrid compound, arginine thiazolidine carboxylate (ATC), increases cytoplasmic Ca2+ in pancreatic β-cells, and that the ATC-induced Ca2+ signals result from the sequential formation of two Ca2+-mobilizing second messengers: nicotinic acid adenine dinucleotide phosphate (NAADP) and cADPR. Our data demonstrate that ATC has potent insulin-releasing properties, due to the additive action of its two components; thiazolidine carboxylate (TC) and L-arginine. TC increases glutathione (GSH) levels, resulting in cAMP production, followed by a cascade pathway of NAADP/nitric oxide (NO)/cGMP/cADPR synthesis. L-arginine serves as the substrate for NO synthase (NOS), which results in cADPR synthesis via cGMP formation. Neuronal NOS is specifically activated in pancreatic β-cells upon ATC treatment. These results suggest that ATC is an ideal candidate as an anti-diabetic, capable of modulating the physiological Ca2+ signalling pathway to stimulate insulin secretion.
The role of heat shock protein (HSP90 kD) has been investigated in regard to its association with steroid receptors. HSP90 kD may play a role in steroid receptor stabilization and activation. Oophorectomized Sprague-Dawley rats (n = 25) were placed into five groups and injected subcutaneously with 30 microg beta-estradiol 17-benzoate in sesame oil, with one group injected with carrier oil (control). After estrogen administration, the rats were killed, and their bladders removed for immunostaining, immunoblotting and enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis demonstrated a 90-kD band in bladder homogenates, even in the absence of estrogen. However, the bands were more intense 12 and 24 h after administering estrogen. ELISA showed significant differences in HSP90 kD synthesis as early as 6 h compared to controls (P< 0.05). After 48 h the estrogen-treated rats and controls were identical. The above results were confirmed by immunostaining for HSP90 kD. HSP90 kD synthesis in the rat urinary bladder is under estrogenic regulation. These findings may be relevant in the etiology and pathobiology of interstitial cystitis and menopausal voiding dysfunctions since the bladder is enriched with estrogenic receptors and is under estrogenic influence.
<p>The absolute risk of developing breast cancer was estimated using data from 20,434 Korean women. The absolute risk of breast cancer was estimated by PRS38_ASN+PRS190_EB for women in different percentiles and age categories. The dotted lines represent the average risks. (A) Lifetime absolute risk (B) 5-year absolute risk</p>
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