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Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma
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作者 Sirish Dharmapuri UmutÖzbek +34 位作者 Hiren Jethra Tomi Jun Thomas U Marron Anwaar Saeed Yi-Hsiang Huang Mahvish Muzaffar Matthias Pinter Lorenz Balcar Claudia Fulgenzi Suneetha Amara Arndt Weinmann Nicola Personeni Bernhard Scheiner Tiziana Pressiani Musharraf Navaid Bertram Bengsch Sonal Paul Uqba Khan Dominik Bettinger Naoshi Nishida Yehia Ibrahim Mohamed Arndt Vogel Anuhya Gampa James Korolewicz Antonella Cammarota Ahmed Kaseb Peter R Galle Anjana Pillai Ying-Hong Wan Alessio Cortellini Masatoshi Kudo Antonio D’Alessio Lorenza Rimassa David James Pinato Celina Ang 《World Journal of Gastrointestinal Oncology》 SCIE 2023年第11期1900-1912,共13页
BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontin... BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs. 展开更多
关键词 Neutrophil-lymphocyte ratio Platelet-lymphocyte ratio Inflammatory biomarkers Immunotherapy Immune toxicity
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Targeting glutamine metabolism enhances responses to platinum-based chemotherapy in triple-negative breast cancers(TNBC) 被引量:1
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作者 Jiaxin Hong Yao-An Shen +6 位作者 Chih-Yi Hsu Peng Huang Alicja Tomaszewski Edward Gabrielson Ie-Ming Shih Stephanie Gaillard Tian-Li Wang 《Genes & Diseases》 SCIE 2022年第6期1408-1411,共4页
Reprogramming of metabolic pathways,a hallmark of human cancer,results from a process in which cancer cells become dependent on specific metabolic pathways such as glutamine catabolism or glutaminolysis for growth and... Reprogramming of metabolic pathways,a hallmark of human cancer,results from a process in which cancer cells become dependent on specific metabolic pathways such as glutamine catabolism or glutaminolysis for growth and survival.Previous studies have demonstrated that triplenegative breast cancers(TNBC)may use glutamine as an extracellular nutrient source to generate lipids,proteins,and nucleic acids.1 Glutamine catabolism in cancer cells also contributes to the production of the antioxidant,glutathione(GSH),which is critical for redox homeostasis and for protection of cells from oxidative stress elicited by reactive oxygen species(ROS).2 Considering TNBC cell lines are often dependent on glutamine for growth and survival,we sought to determine whether targeting glutaminolysis with a small molecule inhibitor,CB-839,in combination with platinum-based chemotherapy drug,would elicit significant anti-tumor activity. 展开更多
关键词 METABOLISM TNBC CHEMOTHERAPY
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