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Circulating cytokines and outcome in metastatic colorectal cancer patients treated with regorafenib

World Journal of Gastrointestinal Oncology 2020年第3期12卷 301-310页

作者： Vincenzo Ricci Cristina Granetto antonella Falletta Matteo Paccagnella Andrea Abbona Elena Fea Teresa Fabozzi Cristiana lo Nigro Marco Carlo Merlano Medical Oncology and Laboratory of Translational Oncology Oncology DepartmentS.Croce and Carle Teaching Hospital CuneoCuneo 12100Italy Arco Cuneo Foundation Cuneo 12100Italy Medical Oncology S.G.Bosco HospitalTorino 10154Italy S.Croce and Carle Teaching Hospital Cuneo Cuneo 12100Italy

BACKGROUND Regorafenib is an oral small-molecule multikinase inhibitor approved in third or later line of treatment for patients with metastatic colorectal cancer(mCRC).Regorafenib has shown significant benefits in overall survival and progression free survival in two phase III trials compared to placebo in patients with mCRC who had progressed on previous *** To identify an immune profile that might specifically correlate with the outcome in patients treated with *** Blood samples were collected from 17 patients before treatment with regorafenib and from 6 healthy *** proteins evaluated(TNF-α,TGF-β,VEGF,CCL-2,CCL-4,and CCL-5)were selected on the basis of their roles in angiogenesis and colorectal cancer *** We found that TNF-αbasal level was significantly higher in mCRC patients compared to healthy *** Responder(NR)patients showing progression of disease(n=12)had higher basal level of TGF-β,TNF-α,VEGF,CCL-2 and CCL-5 compared to Responder(R)patients(complete response CR,n=1;partial response PR,n=1;Stable Disease SD,n=3).On the contrary,plasma basal level of CCL-4 was higher in R compared to NR *** values of TGF-βand TNF-αnegatively correlated with progression free *** These results suggest a cytokine signature potentially able to discriminate between R and NR patients to treatment with regorafenib.

关键词： Colorectal cancer Multikinase inhibitor Cytokines Angiogenesis

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Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses

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Cellular & Molecular Immunology 2021年第6期18卷 1463-1475页

作者： Ryan AAdams Cátia Fernandes-Cerqueira antonella Notarnicola Elisabeth Mertsching Zhiwen Xu Wing-Sze lo Kathleen Ogilvie Kyle PChiang Jeanette Ampudia Sanna Rosengren Andrea Cubitt David JKing John DMendlein Xiang-Lei Yang Leslie ANangle Ingrid ELundberg Per-Johan Jakobsson Paul Schimmel aTyr Pharma 3545 John Hopkins CourtSuite 250San DiegoCA92121USA Division of Rheumatology Department of MedicineSolnaKarolinska InstitutetKarolinska University HospitalSE-17176StockholmSweden IAS HKUST-Scripps R&D Laboratory Institute for Advanced StudyHong Kong University of Science and Technologyand Pangu BiopharmaHong KongChina The Scripps Laboratories for tRNA Synthetase Research 10650 North Torrey Pines RoadLa JollaCA92037USA The Scripps Laboratories for tRNA Synthetase Research Scripps Florida130 Scripps WayJupiterFL33458USA

His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4+ and CD8+ T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome.

关键词： Immunology Autoimmunity Synthetase tRNA HARS

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Pancreatic neuroendocrine tumor with hypoglycemia and elevated insulin-like growth factor II:a case report

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Journal of Cancer Metastasis and Treatment 2016年第1期2卷 345-347页

作者： Roberta Modica antonella Di Sarno Annamaria Colao Antongiulio Faggiano Department of Clinical Medicine and Surgery Federico II University80131 NaplesItaly UOC of Oncology A.O.Dei ColliMonaldi Unit80131 NaplesItaly Thyroid and Parathyroid Surgery Unit Istituto Nazionale per lo studio e la cura dei tumori“Fondazione G.Pascale”-IRCCS80131 NaplesItaly

Pancreatic neuroendocrine tumors(pNETs)can be associated with different clinical *** is the most common functioning pNET characterized by hypoglycemia and *** authors report a case of a man presenting with hypoglycemia and biochemical features of insulinoma.A pancreatic lesion was found and growth hormone(GH)deficiency was also diagnosed associated with an empty sella present on the pituitary magnetic resonance *** disappearance of hypoglycemia and normalization of GH secretion after surgical resection of the pancreatic lesion,revealed a rare pNET secreting insulin-like growth factor II.

关键词： Pancreatic neuroendocrine tumor insulinoma hypoglycemia insulin-like growth factor II

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