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Targeted therapy or immunotherapy? Optimal treatment in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2018年第5期10卷 108-114页

作者： Merly Contratto jennifer wu Division of Hematology and Oncology Perlmutter Cancer Center New York University School of Medicine

Hepatocellular carcinoma(HCC) is the fifth leading cause of cancer mortality in the United States and the second leading cause of cancer mortality worldwide. Sorafenib is the only food and drug administration(FDA) approved as first line systemic treatment in HCC. Regorafenib and nivolumab are the only FDA approved second line treatment after progression on sorafenib. We will discuss all potential first and second line options in HCC. In addition, we also will explore sequencing treatment options in HCC, and examine biomarkers that can potentially predict benefits from treatments such as immune checkpoint inhibitor. This minireview summarizes potential treatments in HCC based on clinical trials that have been published in manuscript or abstract format from 1994-2018.

关键词： Sequencing treatment Sorafenib Hepatocellular carcinoma treatments Nivolumab Regorafenib Lenvatinib Cabozantinib Immunotherapy Biomarker Pembrolizumab Ramucirumab Alpha-fetoprotein Neoantigen Tumor mutational burden Interferon-gamma

Up to seven criteria in selection of systemic therapy for hepatocellular carcinoma

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World Journal of Gastroenterology 2022年第23期28卷 2561-2568页

作者： Tarik Silk Mikhail Silk jennifer wu Department of Internal Medicine NYU Grossman School of MedicineNew YorkNY 10016United States Department of Interventional Radiology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065United States Division of Hematology and Oncology Perlmutter Cancer Center of NYU Langone HealthNYU School of MedicineNew YorkNY 10016United States

Barcelona clinic liver cancer(BCLC)intermediate stage hepatocellular carcinoma is a heterogenous *** chemoembolization is offered as the first line therapy in this disease *** advances in systemic therapy have markedly improved outcomes even in advanced stage *** use of systemic therapy in BCLC intermediate stage disease may now be of therapeutic benefit in selected *** will focus on“the up to seven”criteria and its utility in selecting systemic therapy.

关键词： Chemoembolization Hepatocellular carcinoma Immunotherapy Drug combinations Review Medical oncology

Cutaneous toxicities of targeted therapies in the treatment of hepatocellular carcinoma

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Hepatoma Research 2020年第10期6卷 88-103页

作者： Tarik Silk jennifer wu Internal Medicine New York University School of MedicineNew YorkNY 10016USA Hematology and Medical Oncology Perlmutter Cancer CenterNew York University School of MedicineNew YorkNY 10016USA

Liver cancer accounts for 4.7%of all newly diagnosed cancers and 8.2%of cancer deaths *** carcinoma(HCC)accounts for the majority of primary liver *** are 2 curative strategies in HCC:resection and ***,50%of patients who undergo resection will relapse in 2 years and many patients on transplant lists become ineligible for transplant due to disease *** majority of patients still require systemic *** kinase inhibitors have successfully extended the overall survival in patients with hepa-tocellular ***,these treatments have been noted to cause severe side effects in-cluding liver toxicity,hypertension,gastrointestinal toxicity and cutaneous adverse *** article will focus on the adverse skin reactions seen during the treatment of hepatocellular carci-noma by various tyrosine kinase *** focus will be symptomatology,management,and whether the development of cutaneous toxicities can be prognostic.

关键词： Hepatocellular cancer tyrosine kinase inhibitors cutaneous toxicity hand foot reaction syndrome

Immunotherapy in pancreatic cancer:Unleash its potential through novel combinations

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World Journal of Clinical Oncology 2017年第3期8卷 230-240页

作者： Songchuan Guo Merly Contratto George Miller Lawrence Leichman jennifer wu Division of Hematology and Oncology Perlmutter Cancer CenterNew York University School of Medicine

Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall *** that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell ***,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive *** this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted *** combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.

关键词： Immunotherapy Pancreatic cancer Antiprogrammed cell death protein-1 Anti-programmed cell death protein-ligand1 Anti-cytotoxic T lymphocyte antigen-4 Single therapy Combination therapies Radiation therapy GVAX CRS-207 CD40 agonist

Anaphylaxis and Undiagnosed Aspirin Exacerbated Respiratory Disease in the Ambulatory Surgery Center: A Case Report

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Open Journal of Anesthesiology 2015年第12期5卷 242-244页

作者： jennifer wu Department of Anesthesiology University of Texas Health Science Center Houston Houston Texas

Severe bronchospasm and anaphylaxis are unanticipated emergencies that may occur in the ambulatory surgery setting. I present a case in which an asthmatic male with nasal congestion has anaphylaxis after induction, with severe bronchospasm as the primary manifestation. During the course of hospitalization, he was exposed to aspirin and a second episode of severe bronchospasm occurred. He was diagnosed with both anaphylaxis to an anesthetic medication and Aspirin Exacerbated Respiratory Disease, or Samter’s Triad.

关键词： Ambulatory Anesthesia Bronchospasm Anaphylaxis Anaphylactoid Samter’s Triad Aspirin Exacerbated Respiratory Disease

Hypoxia inducible factor in hepatocellular carcinoma:A therapeutic target

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World Journal of Gastroenterology 2015年第42期21卷 12171-12178页

作者： Daniel Lin jennifer wu Fellow Hematology and Medical Oncology Program NYU School of Medicine Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology NYU School of Medicine Subdivision of GI Oncology Perlmutter Cancer Center NYU Langone Medical Center Division of Hematology and Oncology

Hepatocellular carcinoma(HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxiainducible factor alpha(HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α m RNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.

关键词： Hypoxia Hypoxia-inducible factor alpha Hepatocellu

Shenqi Fuzheng injection alleviates chemotherapy-induced cachexia by restoring glucocorticoid signaling in hypothalamus

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Journal of Pharmaceutical Analysis 2024年第3期14卷 431-434页

作者： Entezar Berik Zijia Zhang Wei Li Yawen Liu Sihan Chen Wenyong wu Zhaojun Wang Xinqin Kong Wenqiang Pei Huiqing Dong Huali Long Min Lei jennifer Yiyang Wang Liangfeng Liu Jinjun Hou Jing Feng Zhaoxia Li Wanying wu De-an Guo Beijing Key Lab of TCM Collateral Disease Theory Research School of Traditional Chinese MedicineCapital Medical UniversityBeijing100069China National Engineering Research Center of TCM Standardization Technology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of Sciences Beijing100049China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing210029China Limin Pharmaceutical Factory Livzon Group LimitedShaoguanGuangdong512028China Guangdong Corporate Key Laboratory of High-End Liquid Medicine R&D IndustrilizationShaoguanGuangdong512028China Center for Neurological and Psychiatric Research and Drug Discovery Shanghai Institute of Materia MedicaChinese Academy of ScienceShanghai201203China

Chemotherapy-induced cachexia(CIC)is a debilitating condition characterized by weight loss,muscle atrophy,and anorexia[1].While peripheral mechanisms of cachexia have been extensively studied,the involvement of the central nervous system(CNS)in CIC is often *** drugs cause stress responses and inflammation,which may impact the hypothalamus and disrupt systemic energy and neuroendocrine *** hypothalamic roles in regulating these processes can provide insights into CIC's mechanisms and aid in developing novel therapies.

关键词： injection drugs glucocorticoid chemotherapy

Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma

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World Journal of Clinical Oncology 2019年第3期10卷 149-160页

作者： jennifer wu Merly Contratto Krishna P Shanbhogue Gulam A Manji Bert H O'Neil Anne Noonan Robert Tudor Ray Lee Division of Hematology and Oncology Perlmutter Cancer CenterNew York University School of Medicine Department of Radiology at New York University School of Medicine Division of Hematology and Oncology Columbia University Medical Center Division of Hematology and Oncology Indiana University Division of Hematology and Oncology Ohio State University Medical Center Roche Pharmaceutical Company Roche and Teclison Pharmaceutical Company

BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in *** To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to *** In the preclinical study of RO7070179 in a HCC xenograft model, the mice wereseparated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment,received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of *** Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1 b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies(each biopsy was divided into 2 specimens, the tip and the root).CONCLUSION RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased *** study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes

关键词： Hepatocellular carcinoma Hypoxia-inducible factor 1α RO7070179,Superresponder Dynamic contrast-enhanced-magnetic resonance imaging

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