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胰岛素样生长因子结合蛋白7(IGFBP7)属于胰岛素样生长因子结合蛋白超家族成员,参与细胞内信号转导、细胞生长及细胞代谢,在人类多种组织中均有表达。IGFBP7在银屑病患者表皮中表达显著降低,其参与银屑病发病的机制可能为通过胰岛素及IGFs等信号途径抑制角质形成细胞增殖、诱导其分化及凋亡,下调VEGF的表达从而抑制新生血管生成。维A酸类药物治疗银屑病取得较好疗效,可能与其直接或间接调节IGFs的活性,上调IGFBP7及其mRNA的表达相关。 相似文献
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Julian Hellmann‐Regen Irmelin Herzog Norina Fischer Isabella Heuser Francesca Regen 《Experimental dermatology》2014,23(4):290-293
For decades, retinoic acid (RA) is known as the most potent therapeutic option in the therapy of acne and altered homeostasis of endogenous retinoids has been discussed in the context of acne pathogenesis. Besides retinoids, antibiotics such as tetracyclines or erythromycin are well established in acne pharmacotherapy. Accumulating evidence points towards common molecular pathways being targeted by both RA and anti‐acne antibiotics; however, a precise ‘common denominator’ connecting these chemically diverse anti‐acne agents has not yet been identified. Interestingly, tetracyclines are associated with the occurrence of pseudotumor cerebri, a rare neurological side effect otherwise associated with retinoid intoxication or RA exposure. This association at the clinical level suggests an interaction between tetracyclines and endogenous RA signalling. As erythromycin does not cross the blood brain barrier, CNS side effects are not to be expected, yet not precluding a possible local interaction of erythromycin with endogenous RA metabolism in the skin. We hypothesize tetracyclines and erythromycin to locally inhibit endogenous RA metabolism in the skin and thus mimic therapeutic action of RA. This readily testable hypothesis suggests inhibition of endogenous RA metabolism and amplification of endogenous RA signalling as a mechanism underlying the biochemical actions of antibiotics in acne therapy. Elucidation of such interactions may ultimately enhance our understanding of acne therapy and pathogenesis and may yield a sound, scientific basis for hypothesis‐driven development of novel therapeutic compounds. 相似文献
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The novel atypical retinoid ST1926 is active in ATRA resistant neuroblastoma cells acting by a different mechanism 总被引:1,自引:0,他引:1
Di Francesco AM Meco D Torella AR Barone G D'Incalci M Pisano C Carminati P Riccardi R 《Biochemical pharmacology》2007,73(5):643-655
E-3-(4'-Hydroxy-3'-adamantylbiphenyl-4-yl)acrylic acid (ST1926) is a novel orally available compound belonging to the class of synthetic atypical retinoids. These agents are attracting growing attention because of their unique mechanism of antitumor action that appears different from that of classical retinoic acid. This study aims at investigating the antitumor activity of ST1926 in neuroblastoma (NB) preclinical models. In vitro, ST1926 was more cytotoxic than both its prototype, CD437 and all-trans-retinoic acid (ATRA) and it was active in the SK-N-AS cell line, which is refractory to ATRA. We showed that unlike ATRA, ST1926 does not induce morphological differentiation in NB cells where it produces indirect DNA damage, cell cycle arrest in late S-G2 phases and p53-independent programmed cell death. DNA damage was not mediated by oxidative stress and was repaired by 24h after drug removal. The SK-N-DZ cell line appeared the most sensitive to the proapoptotic activity of ST1926, probably because both the extrinsic and intrinsic pathways appear involved in the process. Studies with Z-VAD-FMK, suggested that ST1926 might also mediate caspase-independent apoptosis in NB cells. In vivo, orally administered ST1926, appeared to inhibit tumor growth of NB xenografts with tolerable toxicity. Overall, our results support the view that ST1926 might represent a good drug candidate in this pediatric tumor. 相似文献