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Effects of U0126 on growth and activation of mitogen-activated protein kinases in Aspergillus fumigatus

Chinese Medical Journal 2013年第2期126卷 220-225页

作者： MA Dong-mei JI Ya-juan YANG Fang LIU Wei WAN Zhe LI Ruo-yu Department of Dermatology Peking University First HospitalResearch Center for Medical Mycology Peking University Beijing100034 China

Background Invasive aspergillosis （IA）, which is mainly caused by Aspergillus fumigatus （A. fumigatus）, is a major cause of morbidity and mortality in immunocompromised patients. Despite considerable progress in currently available antifungals the mortality still remains high in critically ill patients. U0126 which is a highly selective inhibitor of MEK1 and MEK2 in the RAF/MEK/ERK pathway in mammalian cells has been demonstrated to have an anti-proliferative role in cancer cells. The purpose of this study was to explore the role of U0126 on growth inhibition and activation of mitogen-activated protein kinases （MAPKs） in A. fumigatus. Methods Germination percentage and hyphae growth in A. fumigatus treated with U0126 were observed and compared with untreated controls. Western blotting analysis was used to detect changes in activation of SakA, MpkA and MpkB. Results U0126 inhibited germination and hyphae growth in A. fumigatus and enhanced the phosphorylation of SakA and MpkA under oxidative stress. U0126 at 10 pmol/L did not block the activation of MpkB during nitrogen starvation stress. Conclusion U0126 shows promise as an antifungal candidate and the MAPK pathway may be a possible antifungal drug target for A. fumigatus.

关键词： Aspergillus fumigatus protein kinase inhibitors mitogen-activated protein kinases

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Targeting MET in cancer therapy

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Chronic Diseases and Translational Medicine 2017年第3期3卷 148-153页

作者： Hong-Nan Mo Peng Liu Department of Medical Oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China

MET encodes a receptor tyrosine kinase c-MET for hepatocyte growth factor (HGF). The specific combination of c-MET and HGF activates downstream signaling pathways to trigger cell migration, proliferation, and angiogenesis. MET exon 14 alterations and MET gene amplification play a critical role in the origin of cancer. Several monoclonal antibodies and small-molecule inhibitors of c-MET have been evaluated in clinical trials. In patients with advanced non-small cell lung cancer, cabozantinib and crizotinib showed clear efficacy with a generally tolerable adverse events profile. In gastrointestinal cancers, most phase III trials of MET inhibitors showed negative results. In hepatocellular carcinoma, based on the encouraging results of some phase II studies, a series of phase III trials are currently recruiting patients to access the efficacy and safety of MET inhibitors.

关键词： Proto-oncogene protein c-MET Antineoplastic agents protein kinase inhibitors Molecular targeted therapy

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Lenvatinib-induced multiorgan adverse events in Hurthle cell thyroid cancer: A case report

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World Journal of Clinical Oncology 2021年第4期12卷 272-281页

作者： Muhammad Imran Butt Abdulmohsen Mohammed Khalid Bakhsh Quaid Johar Nadri Department of Medicine King Faisal Specialist HospitalResearch CentreAl Faisal UniversityRiyadh 12713Saudi Arabia

BACKGROUND The management of metastatic progressive radioiodine-resistant differentiated thyroid cancer remains challenging for *** availability of tyrosine kinase inhibitors(TKIs),sorafenib and lenvatinib,within the last decade has expanded treatment options;however,these lead to significant adverse effects,which may curtail their *** SUMMARY We report the case of a 47-year-old female with Hurthle cell thyroid cancer who underwent total thyroidectomy followed by radioiodine *** followup,she developed noniodine-avid renal and pulmonary *** respect to her pre-existing diabetes,hypertension,and polycystic kidney disease,the tumor board decided against performing renal metastasectomy because of the risk of future renal decline requiring *** were treated using sorafenib,which provided stability followed by progression within a *** switched to lenvatinib,which led to disease ***,the patient experienced severe adverse effects,including cardiomyopathy,bicytopenia,renal impairment,and the rarely reported nephrotic *** metastasis is a rare manifestation of Hurthle cell thyroid cancer with only two reported cases in *** report the experience of our first case of renal metastasis and its treatment with *** case serves as a reminder of the adverse drug reactions associated with TKI *** We advocate close monitoring of patients’hematological and renal profiles as well as their cardiac status using an echocardiogram.

关键词： Hurthle cell thyroid cancer Lenvatinib Nephrotic syndrome Vascular endothelial growth factor protein kinase inhibitors Kidney neoplasms/secondary neoplasm Case report

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Immunotherapy in hepatocellular carcinoma: Combination strategies

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World Journal of Meta-Analysis 2020年第3期8卷 190-209页

作者： Alexander Claudius Jordan Jennifer Wu Department of Internal Medicine New York University School of MedicineNew YorkNY 10016United States Division of Hematology and Oncology Perlmutter Cancer CenterNew York University Langone Medical CenterNew YorkNY 10016United States

Liver cancer is one of the most common causes of cancer death globally,and its incidence in the United States is *** with advanced hepatocellular carcinoma(HCC)who are not candidates for surgical resection,liver transplant,or locoregional therapies can be treated with systemic *** agents,including sorafenib,lenvatinib,and regorafenib are approved for use as either first-or second-line therapy in this patient population,but all have relatively modest survival *** is potentially susceptible to therapy with checkpoint inhibitors,including agents such as nivolumab and pembrolizumab,which are both approved by the Food and Drug Administration for patients previously treated with sorafenib but have not demonstrated superior overall survival in phase III *** is clear that more effective approaches are needed to potentiate the effects of checkpoint inhibitors in patients with *** review will outline and appraise the current literature on the use of checkpoint inhibitors in HCC as part of a combination treatment involving an additional mode of *** list of agents that can be paired with checkpoint inhibitors includes an additional checkpoint inhibitor,vascular endothelial growth factor or vascular endothelial growth factor receptor inhibitors,tyrosine kinase inhibitors,OX-40 agonists,and PT-112 *** main non-pharmacologic therapies currently being studied for inclusion in a combination strategy include radiation therapy,trans-arterial chemoembolization,and ablation.

关键词： Hepatocellular carcinoma Liver neoplasms Antineoplastic agents Immunological protein kinase inhibitors Angiogenesis inhibitors

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