In the present study, we have shown that Z-360 combined with gemcitabine can inhibit pancreatic tumor growth and prolong survival in a pancreatic carcinoma xenograft model, on a possible mode of action being the inhibition of gastrin-induced PKB/Akt phosphorylation through blockade of the CCK-2 receptor. Our results suggest that Z-360 may be a useful adjunct to gemcitabine for the treatment of pancreatic carcinoma and a therapeutic option for patients with advanced pancreatic cancer.
The effect of polaprezinc, a chelate compound consisting of zinc ion and L-carnosine, on abnormalities of taste sensation induced by feeding a zinc-deficient diet to rats was examined by using the two-bottle preference test (quinine hydrochloride as a bitter taste and sodium chloride as a salty taste). Rats were fed either a zinc-deficient or a zinc-sufficient diet. The zinc-deficient diet increased the preference for both taste solutions, while polaprezinc (at doses of 3 and 10 mg/kg) restored the altered taste preferences. We also evaluated the proliferation of taste bud cells using 5-bromo-2'-deoxyuridine (BrdU). The BrdU incorporation into taste bud cells was significantly reduced in rats fed a zinc-deficient diet compared with rats fed a zinc-sufficient diet (from 50.8% to 45.0%, p<0.05) and this reduction was reversed by polaprezinc at doses of 1, 3, and 10 mg/kg, increasing to 50.2%, 53.5%, and 52.5%, respectively. These findings indicate that zinc deficiency induces the delayed of proliferation of taste bud cells, while polaprezinc improves cell proliferation. In conclusion, polaprezinc had a therapeutic effect in a rat model of abnormal taste sensation. Its mechanism of action was suggested to involve improvement of the decrease in taste bud cell proliferation caused by zinc deficiency.
We examined the delayed induction of telomere instability in hTERT-immortalized normal human fibroblast (BJ1-hTERT) cells exposed to X-rays. BJ1-hTERT cells were irradiated with 2 Gy of X-rays, and chromosome aberrations were analyzed 24 hours after irradiation and in the surviving cells 14 days after X-ray exposure. We found that the X-ray-surviving cells showed an increased frequency of chromatid gaps and breaks and chromosome fragments compared to the control cells. Furthermore, centromere- and telomere-FISH revealed that the frequency of telomere loss and duplication significantly increased in surviving cells compared to the control level. Because no induction of telomere abnormality was observed in cells 24 hours after irradiation, X-irradiation might not affect telomeres directly, but it specifically induces delayed telomere instability in normal human fibroblast cells.
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