c-Met

C - MET
  • 文章类型: Case Reports
    BACKGROUND: Recently, tooth deformities have been frequently encountered by pediatric dentists. Severe enamel hypomineralization sometimes induces pain such as hyperesthesia, but composite resin restoration is difficult because it often detaches without any cavity preparation. Resin-based hypersensitivity inhibitors for tooth physically seal the dentinal tubules. It was reported that hypersensitivity inhibitor containing novel adhesive monomers forms apatite and induces remineralization in vitro. Therefore, these case series assessed the clinical effects of remineralization and the suppression of hypersensitivity by Bio Coat Ca (Sun Medical, Shiga, Japan).
    METHODS: After mechanical tooth cleaning was performed, the hypersensitivity inhibitors were applied and cured by light exposure. Changes in hypersensitivity were determined by visual analog scale (VAS). The improvement of hypomineralization was evaluated by the change in color tone based on the digital images of intraoral photographs.
    RESULTS: After repeated monthly treatments, these cases showed decreased hypersensitivity after the fourth application, while the opaque white and brownish color improved on the seventh application.
    CONCLUSIONS: This novel hypersensitivity inhibitor with calcium salt of 4-methacryloxyethyl trimellitic acid (C-MET) and 10-methacryloyloxydecyl dihydrogen calcium phosphate (MDCP) not only suppressed hypersensitivity but also improved cloudiness and brown spots in recently erupted permanent teeth in presented cases.
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  • 文章类型: Case Reports
    Gastric cancer is one of the most common gastrointestinal tumors. Most patients have been in advanced stage at diagnosis and lack effective treatment. Molecular targeted drugs have become new therapeutic strategies. MET is an important driving gene for the development of gastric cancer. MET gene amplification and protein over-expression are closely related to the invasion and metastasis, late stage and poor prognosis of gastric cancer. Crizotinib is a small molecule inhibitor against MET. There are few reports of crizotinib in gastric cancer patients with c-MET amplification. This article reports a case of c-MET gene amplification in advanced gastric cancer with liver metastases. After 2 months of treatment with crizotinib, liver lesions were completely relieved and progression-free survival lasted for up to 20 months.
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  • 文章类型: Journal Article
    在过去的二十年中,蛋白水解靶向嵌合体(PROTAC)技术已成为靶向降解内源性蛋白质的强大工具。在这里,我们描述了受体酪氨酸激酶的PROTACs的发展,尚未针对诱导蛋白质降解的蛋白质家族。使用VHL招募PROTACs对抗该蛋白质家族揭示了降解优于单独抑制的几个优点:完全功能的直接比较,含有失活E3连接酶募集配体的靶抑制变体的靶降解PROTACs显示降解导致更有效的细胞增殖抑制和更持久和持续的下游信号应答。从而解决了许多受体酪氨酸激酶抑制剂所看到的kinome重新布线挑战。合并,这些发现证明了使用PROTAC技术靶向受体酪氨酸激酶进行降解的能力,并概述了这种基于降解的方法的优势。
    Proteolysis targeting chimera (PROTAC) technology has emerged over the last two decades as a powerful tool for targeted degradation of endogenous proteins. Herein we describe the development of PROTACs for receptor tyrosine kinases, a protein family yet to be targeted for induced protein degradation. The use of VHL-recruiting PROTACs against this protein family reveals several advantages of degradation over inhibition alone: direct comparisons of fully functional, target-degrading PROTACs with target-inhibiting variants that contain an inactivated E3 ligase-recruiting ligand show that degradation leads to more potent inhibition of cell proliferation and a more durable and sustained downstream signaling response, and thus addresses the kinome rewiring challenge seen with many receptor tyrosine kinase inhibitors. Combined, these findings demonstrate the ability to target receptor tyrosine kinases for degradation using the PROTAC technology and outline the advantages of this degradation-based approach.
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    文章类型: Case Reports
    Metformin has been proposed as a novel anti-cancer drug for adrenocortical carcinoma (ACC) based upon Poli\'s recent preclinical studies that 1. \"in vitro\" metformin modulates the ACC cell model H295R and 2. \"in vivo\" metformin inhibits tumor growth in a xenograft model as confirmed by a significant reduction of Ki67 [1]. Here we report on our prior clinical case study that provides proof of concept for Poli\'s studies. We were requested to perform morphoproteomic analysis to further define the biology of, and raise targeted therapeutic options, for a case of post-treatment and chemoresistant ACC metastatic to the liver and the lung. Profiling the patient\'s ACC from the liver resulted in the recommendation of metformin as a maintenance therapy, which was supported by biomedical data analysis. The patient remains on maintenance therapy with metformin and melatonin and is free of disease some 7 years post diagnosis, thus underscoring the recommendation for clinical trials employing these therapeutic agents.
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  • 文章类型: Case Reports
    肝细胞癌(HCC)是原发性肝癌的一种主要病理类型。索拉非尼在肝癌的靶向治疗中显示出明确的疗效。然而,当索拉非尼治疗失败时,必须找到合适的药物进行进一步治疗。本文报道了一例HCC患者在索拉非尼治疗后接受血管生成抑制剂阿西替尼和c-Met抑制剂卡博替尼治疗。该报告侧重于临床治疗和毒性。还探讨了靶向治疗的合理应用。
    Hepatocellular carcinoma (HCC) is a major pathological type of primary liver cancer. Sorafenib has demonstrated definite efficacy in targeted therapy for HCC. However, when treatment with sorafenib fails, suitable drugs must be found for further treatment. This article reports a case of an HCC patient who was treated with angiogenesis inhibitor axitinib and c-Met inhibitor cabozantinib following treatment with sorafenib. The report focuses on clinical treatment and toxicity. Rational application of targeted therapy is also explored.
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