Article
Oncology
J. Hammersen, S. Birndt, K. Doehner, P. Reuken, A. Stallmach, P. Sauerbrey, F. La Rosee, M. Pfirrmann, C. Fabisch, M. Weiss, K. Traeger, H. Bremer, S. Russo, G. Illerhaus, D. Droemann, S. Schneider, P. La Rosee, A. Hochhaus
Summary: Dysregulated hyperinflammatory response is a key factor in the development of severe COVID-19. The Janus Kinase 1/2 inhibitor ruxolitinib has shown to be safe and effective in treating COVID-19 patients with defined hyperinflammation, as demonstrated by the reduction in the COVID-19 Inflammation Score (CIS).
Article
Oncology
Alessandro M. Vannucchi, Benedetta Sordi, Alessandro Morettini, Carlo Nozzoli, Loredana Poggesi, Filippo Pieralli, Alessandro Bartoloni, Alessandro Atanasio, Filippo Miselli, Chiara Paoli, Giuseppe G. Loscocco, Andrea Fanelli, Ombretta Para, Andrea Berni, Irene Tassinari, Lorenzo Zammarchi, Laura Maggi, Alessio Mazzoni, Valentina Scotti, Giorgia Falchetti, Danilo Malandrino, Fabio Luise, Giovanni Millotti, Sara Bencini, Manuela Capone, Marie Pierre Piccinni, Francesco Annunziato, Paola Guglielmelli
Summary: In severe cases of COVID-19, treatment with Ruxolitinib may improve pulmonary function and clinical symptoms, with further research needed to determine its efficacy in controlled clinical trials.
Article
Biochemistry & Molecular Biology
Fan Xu, Runnan Chen, Yue Shen, Hanhan Liu, Lijuan Hu, Lei Zhu
Summary: In this study, it was found that circUBXN7 was upregulated in acute respiratory distress syndrome (ARDS) and acted as a sponge for miR-622, regulating IL6ST and activating the JAK1/STAT3 signaling pathway, thereby suppressing cell proliferation and promoting cell apoptosis. CircUBXN7 may serve as a potential biomarker for ARDS.
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Danyu Lin, Han Zhang, Jieli Zhang, Kaixun Huang, Ying Chen, Xiuna Jing, Enxiang Tao
Summary: Our research found that the overexpression of IL6ST-AS induced by exogenous alpha-synuclein could inhibit the expression of IL6ST and the activation of JAK2-STAT3 pathway in HMC3 cells. In addition, a reduction in STAT3 resulted in the transcription inhibition of HIF1A and the acceleration of oxidative stress injury in SH-SY5Y cells co-cultured with alpha-synuclein-induced HMC3 cells. Our findings indicate that IL6ST-AS is an important factor that regulates microglia activation and neuronal necrosis in the progression of PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Zoya Qureshy, Hua Li, Yan Zeng, Jose Rivera, Ning Cheng, Christopher N. Peterson, Mi-Ok Kim, William R. Ryan, Patrick K. Ha, Julie E. Bauman, Steven J. Wang, Steven R. Long, Daniel E. Johnson, Jennifer R. Grandis
Summary: The study found that ruxolitinib has inhibitory effects on the active STAT3 levels, cell growth, and colony formation of HNSCC cell lines. For patient-derived xenografts (PDX) from HNSCC patients who received a short course of neoadjuvant ruxolitinib in a clinical trial, ruxolitinib had an impact on tumor growth and STAT3 activation.
CLINICAL CANCER RESEARCH
(2022)
Article
Cell Biology
Yuechao Sun, Weipeng Gong, Song Zhang
Summary: The study revealed the dual role of METTL3 in colorectal cancer as both an m6A writer and a transcription regulator, working together in the same signaling pathway to drive the malignancy of colorectal cancer.
CELL DEATH & DISEASE
(2023)
Article
Pharmacology & Pharmacy
Eduardo Huarte, Michael T. Peel, Katherine Verbist, Brittany L. Fay, Rachel Bassett, Sabrin Albeituni, Kim E. Nichols, Paul A. Smith
Summary: Hyperinflammatory syndromes are characterized by severe inflammation, multiple organ dysfunction, and potential death. Oral ruxolitinib dosing effectively reduces the harmful consequences of immune overactivation in various hyperinflammatory models without causing broad immunosuppression.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maxim Kondratyev, Vladimir R. Rudnev, Kirill S. Nikolsky, Alexander A. Stepanov, Denis Petrovsky, Liudmila Kulikova, Arthur T. Kopylov, Kristina A. Malsagova, Anna L. Kaysheva
Summary: Rheumatoid arthritis is a chronic autoimmune disease characterized by destructive synovitis and extra-articular manifestations. Cytokines play a role in the pathogenesis of rheumatoid arthritis by regulating inflammatory processes and inducing autoimmunity and chronic inflammation. Janus-associated kinase (JAK) and signal transducer and activator of transcription (STAT) proteins are involved in the development of autoimmune and inflammatory diseases. Small-molecule drugs that target JAK proteins are used for the treatment of rheumatoid arthritis. In this study, we investigated the interactions between the small-molecule drug ruxolitinib and JAK1 and JAK2 isoforms using molecular docking. Our results show that ruxolitinib selectively binds to JAK1 and JAK2 isoforms with high affinity, primarily through hydrophobic interactions. The specific amino acid residues responsible for the binding and retention of ruxolitinib were identified.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Shiqi Li, Xinxin Wang, Zhongtao Yuan, Lin Liu, Le Luo, Yu Li, Kun Wu, Jia Liu, Chunhui Yang, Zhimin Li, Duanpeng Wang, Lianjun Shen, Xun Ye, Jiaping He, Cong Han, Youcheng Wang, Dingsong Zhang, Yancheng Dong, Lihua Fang, Yingnian Chen, Martina Sersch, Wei William Cao, Sanbin Wang
Summary: The study reports two cases of patients with relapsed/refractory T-ALL treated with GC027, showing robust expansion of CAR-T cells and rapid eradication of CD7(+) T lymphoblasts. Both patients achieved complete remission with no minimal residual disease. One patient remained in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome occurred in both patients and was managed with a novel approach using ruxolitinib. No graft-versus-host disease was observed. These findings suggest that GC027 may be a promising new approach for treating refractory/relapsed T-ALL. Further studies are needed.
CLINICAL CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ping Tang, Yushan Xu, Jingrong Zhang, Juanli Nan, Ruxian Zhong, Jingmei Luo, Dazhi Xu, Shaoqing Shi, Lihua Zhang
Summary: Diabetic kidney disease (DKD) is a common complication in diabetic patients that poses a major health threat to the aging population. A dysregulated miRNA, hsa-miR-223-3p, has been identified as a potential biomarker for DKD diagnosis. However, the specific mechanism of miR-223-3p in DKD pathogenesis is still unknown.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Xin Zhang, Bo Hu, Yun-Fan Sun, Xiao-Wu Huang, Jian-Wen Cheng, Ao Huang, Hai-Ying Zeng, Shuang-Jian Qiu, Ya Cao, Jia Fan, Jian Zhou, Xin-Rong Yang
Summary: Differentiation-inducing therapy using arsenic trioxide (ATO) was shown to effectively induce differentiation of hepatocellular carcinoma (HCC) cancer stem cells (CSCs) by downregulating CSC-related genes and suppressing tumorigenicity. Combinatorial treatment with ATO and 5-fluorouracil/cisplatin enhanced therapeutic effects through synergistic inhibition of the LIF/JAK1/STAT3 and NF-kB signaling pathways in HCC cells. These findings provide new insights for clinical treatment of HCC.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Wenbiao Li, Xinni Qu, Xiangping Kang, Haiyin Zhang, Xueli Zhang, Haiyan Hu, Lingai Yao, Lina Zhang, Jing Zheng, Yuejuan Zheng, Jianghong Zhang, Yanwu Xu
Summary: Growing evidence suggests that silibinin (SLB), extracted from Chinese herb Silybum marianum, can effectively counteract doxorubicin (DOX)-induced myocardial injury (DIMI) by activating IL6ST/JAK2/STAT3 signaling pathway and restoring autophagy.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Paul Smith, Wenqing Yao, Stacey Shepard, Maryanne Covington, Jim Lee, Jennifer Lofland, Ahmad Naim, Trupti Sheth, Bhavnish Parikh, Swamy Yeleswaram
Summary: The JAK signaling pathway is crucial for the downstream signaling of inflammatory cytokines, and the development of a localized, selective JAK inhibitor, ruxolitinib cream, offers a novel therapy for treating various immune-mediated dermatologic diseases.
Article
Physiology
Faping Wang, Shaohua Wang, Chujie Zhang, Xue Tian, Yongfang Zhou, Weixia Xuan, Eric L. Matteson, Fengming Luo, Daniel Tschumperlin, Robert Vassallo
Summary: This study revealed the role of JAK1/STAT3 pathway in pulmonary fibrosis. JAK1 directly interacts with the TGF-beta receptor, and its silencing promotes myofibroblast transdifferentiation. STAT3 is constitutively active and represses myofibroblast transdifferentiation. Modulation of JAK1/STAT3 signaling represents a potential novel approach to treat pulmonary fibrosis.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Cell Biology
Hao Wang, Wei Hou, Aldeb Perera, Carlee Bettler, Jordan R. Beach, Xianzhong Ding, Jun Li, Mitchell F. Denning, Asha Dhanarajan, Scott J. Cotler, Cara Joyce, Jun Yin, Fowsiyo Ahmed, Lewis R. Roberts, Wei Qiu
Summary: EphA2 expression is enriched in human HCC and loss of EphA2 can suppress the initiation and growth of HCC. Targeting EphA2 inhibits both AKT and JAK1/STAT3 signaling pathways in HCC, and a small molecule kinase inhibitor of EphA2 shows promising results in suppressing tumor progression in a murine model.
Article
Gastroenterology & Hepatology
Jihyun An, Deokhoon Kim, Bora Oh, Yoo-Jin Oh, Jihyun Song, Naomi Park, Ha Il Kim, Hyo Jeong Kang, Ji-Hye Oh, Wonkyung Kim, Eunjung Lee, Chang Ohk Sung, Gi-Won Song, Dae-Ghon Kim, Eunsil Yu, Eric Letouze, Jessica Zucman-Rossi, Han Chu Lee, Ju Hyun Shim
Summary: This study identified the landscape and mechanisms of HBV integration in iCCA tumors, revealing recurrent viral integration breakpoints at multiple sites including TERT and FAT2, and oncogenic effects through intergenic insertions activating the mTOR pathway. The mutational profiles of HBV-iCCA were found to be more similar to nonviral conventional iCCA, rather than HBV-related liver cancers like HBV-HCC and HBV-cHCC/CCA.
Article
Oncology
Cong Trung Nguyen, Stefano Caruso, Pascale Maille, Aurelie Beaufrere, Jeremy Augustin, Loetitia Favre, Anais Pujals, Camille Boulagnon-Rombi, Rami Rhaiem, Giuliana Amaddeo, Luca di Tommaso, Alain Luciani, Helene Regnault, Raffaele Brustia, Olivier Scatton, Frederic Charlotte, Isabelle Brocheriou, Daniele Sommacale, Patrick Soussan, Vincent Leroy, Alexis Laurent, Van Ky Le, Van To Ta, Hong Son Trinh, Thi Lan Tran, David Gentien, Audrey Rapinat, Jean Charles Nault, Manon Allaire, Sebastien Mule, Jessica Zucman-Rossi, Jean-Michel Pawlotsky, Christophe Tournigand, Fouad Lafdil, Valerie Paradis, Julien Calderaro
Summary: This study identified two immune subtypes of combined hepatocellular-cholangiocarcinoma (cHCC-CCA): an immune-high subtype characterized by higher densities of immune cells and activation of gene signatures related to immune response and immunotherapy in hepatocellular carcinoma (HCC), and an immune-low subtype. The immune-high subtype was associated with improved overall survival. These findings suggest that a subset of cHCC-CCA patients may benefit from immunomodulating therapeutic approaches.
CLINICAL CANCER RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Aurelie Beaufrere, Stefano Caruso, Julien Calderaro, Nicolas Pote, Jean-Charles Bijot, Gabielle Couchy, Francois Cauchy, Valerie Vilgrain, Jessica Zucman-Rossi, Valerie Paradis
Summary: With the use of transcriptomic signature, we identified a 6-gene expression signature that is associated with microvascular invasion in hepatocellular carcinoma (HCC). This signature can be applied to routine tumor biopsies and is also associated with overall survival.
JOURNAL OF HEPATOLOGY
(2022)
Article
Oncology
Eric Trepo, Stefano Caruso, Jie Yang, Sandrine Imbeaud, Gabrielle Couchy, Quentin Bayard, Eric Letouze, Nathalie Ganne-Carrie, Christophe Moreno, Abderrahim Oussalah, Cyrille Feray, Jean Frederic Blanc, Bruno Clement, Patrick Hillon, Jerome Boursier, Valerie Paradis, Julien Calderaro, Viviane Gnemmi, Jean-Charles Nault, Jean-Louis Gueant, Jacques Deviere, Isabelle Archambeaud, Carole Vitellius, Bruno Turlin, Jean-Pierre Bronowicki, Thierry Gustot, Angela Sutton, Marianne Ziol, Pierre Nahon, Jessica Zucman-Rossi
Summary: This study identified genetic variants associated with alcohol-related hepatocellular carcinoma through a genome-wide association analysis. The researchers found that WNT3A-WNT9A is a susceptibility locus for alcohol-related hepatocellular carcinoma and discovered several other genetic variants associated with the risk of liver cancer.
Article
Gastroenterology & Hepatology
Alix Demory, Jean-Marie Peron, Julien Calderaro, Janick Selves, Fatima-Zohra Mokrane, Giuliana Amaddeo, Valerie Paradis, Marianne Ziol, Olivier Sutter, Lorraine Blaise, Nathalie Ganne-Carrie, Valerie Vilgrain, Francois Cauchy, Jessica Zucman-Rossi, Maxime Ronot, Jean-Charles Nault
Summary: This study aims to describe the natural history of hepatocellular adenomas (HCAs) and identify predictive factors for HCA evolution after discontinuation of estrogen-based contraception. The results show that weight variation is strongly associated with the radiological evolution of HCAs, and an estrogen exposure score can predict the regression of HCAs.
Article
Gastroenterology & Hepatology
Adel Hammoutene, Marion Tanguy, Melanie Calmels, Riccardo Pravisani, Miguel Albuquerque, Christophe Casteleyn, Lotfi Slimani, Jeremy Sadoine, Chantal M. Boulanger, Valerie Paradis, Helene Gilgenkrantz, Pierre-Emmanuel Rautou
Summary: Patients with non-alcoholic fatty liver disease (NAFLD) have impaired liver regeneration due to a defect in autophagy of liver endothelial cells. This study aimed to determine the role of endothelial autophagy in liver regeneration following liver resection in NAFLD.
LIVER INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Kevin Bevant, Matthis Desoteux, Gaelle Angenard, Raphael Pineau, Stefano Caruso, Corentin Louis, Panagiotis Papoutsoglou, Laurent Sulpice, David Gilot, Jessica Zucman-Rossi, Cedric Coulouarn
Summary: FOXS1, a SMAD-dependent transcription factor induced by TGF-beta, regulates genes involved in EMT and is associated with poor prognosis in HCC and other cancers, making it a potential biomarker for targeted therapies.
HEPATOLOGY COMMUNICATIONS
(2022)
Meeting Abstract
Oncology
Jessica Zucman-Rossi
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Jessica Zucman-Rossi
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Jessica Zucman-Rossi
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Jessica Zucman-Rossi
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Jessica Zucman-Rossi
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Jessica Zucman-Rossi
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Jessica Zucman-Rossi
CLINICAL CANCER RESEARCH
(2022)
Meeting Abstract
Oncology
Jessica Zucman-Rossi
CLINICAL CANCER RESEARCH
(2022)