Review
Immunology
Thais Teixeira Oliveira, Leonam Gomes Coutinho, Laysa Ohana Alves de Oliveira, Ana Rafaela de Souza Timoteo, Guilherme Cavalcanti Farias, Lucymara Fassarella Agnez-Lima
Summary: APE1 is a multifunctional enzyme that is essential for maintaining cellular homeostasis and regulating immune response. It plays important roles in cell signaling, senescence, and inflammatory pathways, and is involved in the pathogenesis of various diseases, including cancer and neurological disorders. APE1 inhibitors have potential therapeutic uses, particularly in infectious and immune diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Gabriella D. Hartman, Nathan A. Lambert-Cheatham, Mark R. Kelley, Timothy W. Corson
Summary: As global population ages, the prevalence of neovascular eye diseases is increasing, highlighting the importance of developing therapies targeting multiple pathways to alleviate the burden and risks associated with current treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Mahmut Mijit, Megan Boner, Ricardo A. Cordova, Silpa Gampala, Eyram Kpenu, Angela J. Klunk, Chi Zhang, MarK R. Kelley, Kirk A. Staschke, Melissa L. Fishel
Summary: Pancreatic cancer is characterized by a hypoxic tumor microenvironment and high heterogeneity. Inhibition of Ref-1 signaling activates the integrated stress response (ISR) pathway and inhibits the growth of pancreatic cancer. Combination treatment with Ref-1 inhibitors and ISR activators shows a significant therapeutic effect in a 3D co-culture model of pancreatic cancer.
FRONTIERS IN MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Sunga Choi, Yu-Ran Lee, Ki-Mo Kim, Euna Choi, Byeong-Hwa Jeon
Summary: The regulation of inflammatory signaling in the tumor microenvironment using adenoviral-mediated PPTLS-APE1/Ref-1 can inhibit the activity of inflammatory immune cells and cancer cells, providing a potential therapeutic strategy for treating triple-negative breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shereen A. Howpay Manage, Aaron M. Fleming, Hsiao-Nung Chen, Cynthia J. Burrows
Summary: This study provides a quantitative survey of cysteine oxidation to sulfenic acid in APE1 and demonstrates how this modification affects APE1's function towards the NEIL3 gene promoter G4. The research suggests that cysteine oxidation to sulfenic acid enhances APE1's affinity for G4 during oxidative stress, but attenuates its endonuclease activity.
ACS CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eun-Ok Lee, Hee-Kyoung Joo, Yu-Ran Lee, Sungmin Kim, Kwon-Ho Lee, Sang-Do Lee, Byeong-Hwa Jeon
Summary: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is involved in DNA repair and redox regulation. It inhibits adipocyte differentiation by regulating adipogenic transcription factors, suggesting it as a potential therapeutic target for regulating adipocyte differentiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Wujun Chen, Shuai Wang, Dongming Xing
Summary: APE1/Ref-1 and ABCA1 play crucial roles in the progression of atherosclerosis, with APE1/Ref-1 suppressing athero-sclerosis via multiple mechanisms and ABCA1 promoting cholesterol efflux and anti-inflammatory responses. Both proteins could be potential therapeutic targets for atherosclerosis treatment.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Zhouyiyuan Xue, Bruce Demple
Summary: Apurinic/apyrimidinic endonuclease 1/redox effector-1 (Ape1/Ref-1) is an important enzyme in mammalian cells that plays a key role in DNA repair and transcription factor activation. Recent studies have shown that APEX1 knockout cell lines are more sensitive to the inhibitors Compound 3 and APX2009, suggesting off-target effects of these inhibitors.
Review
Biochemistry & Molecular Biology
Lauren Sahakian, Ainsley M. Robinson, Linda Sahakian, Rhian Stavely, Mark R. Kelley, Kulmira Nurgali
Summary: Inflammatory bowel disease (IBD) is a chronic relapsing inflammation of the gastrointestinal tract. The prevalence of IBD is increasing worldwide, calling for the development of new treatments. APE1/Ref-1 has been identified as a potential target for IBD therapy due to its role in regulating crucial pathways in inflammatory diseases. This review discusses the current status of IBD treatments, the role of APE1/Ref-1 in intestinal inflammation, and the potential of small molecule inhibitors to modulate inflammation and oxidative stress in IBD.
Article
Oncology
Silpa Gampala, Fenil Shah, Xiaoyu Lu, Hye-Ran Moon, Olivia Babb, Nikkitha Umesh Ganesh, George Sandusky, Emily Hulsey, Lee Armstrong, Amber L. Mosely, Bumsoo Han, Mircea Ivan, Jing-Ruey Joanna Yeh, Mark R. Kelley, Chi Zhang, Melissa L. Fishel
Summary: Inhibiting Ref-1 redox signaling alters cancer cell metabolism by causing TCA cycle dysfunction and reduces pancreatic tumor growth in vitro and in vivo.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Jesse D. Champion, Kayleigh M. Dodd, Hilaire C. Lam, Mohammad A. M. Alzahrani, Sara Seifan, Ellie Rad, David Oliver Scourfield, Melissa L. Fishel, Brian L. Calver, Ann Ager, Elizabeth P. Henske, David Mark Davies, Mark R. Kelley, Andrew R. Tee
Summary: This study suggests that the mechanistic target of rapamycin complex 1 (mTORC1) inhibitors are not fully effective in treating tuberous sclerosis complex (TSC) patients, and proposes that signaling through redox factor-1 (Ref-1) may play a role in TSC pathogenesis. The researchers demonstrate that Ref-1 inhibitors can block the hyperactivity of certain transcription factors involved in inflammation, proliferation, angiogenesis, and hypoxia, and also affect cell invasion and vasculature mimicry. Furthermore, they find that Ref-1 inhibitors alter metabolites associated with redox homeostasis in TSC2-deficient cells. Targeting Ref-1 and associated redox-regulated transcription factors may have additional benefits compared to using mTORC1 inhibitors alone.
Article
Medicine, General & Internal
Xiuhui Shi, Min Wang, Yuqing Zhang, Xingjun Guo, Mingyang Liu, Zhijun Zhou, Yan Zhao, Ruizhi He, Yang Gao, Yuhui Liu, Shutao Pan, Min Zhou, Chunle Zhao, Taoyuan Yin, Xu Li, Hebin Wang, Jingxuan Yang, Feng Zhu, Min Li, Renyi Qin
Summary: High expression levels of alpha-SMA and hypoxia markers are associated with poor prognosis in pancreatic cancer patients. Mechanistically, hypoxia induces HGF expression and secretion in PSC via HIF-1 alpha, which then activates Met and suppresses pancreatic cancer cell sensitivity to EGFR inhibitors. The combination of EGFR inhibitor and Met inhibitor shows promise for pancreatic cancer treatment based on the demonstrated signaling axis between PSC and cancer cells.
Article
Obstetrics & Gynecology
Xiuwei Wang, Huixuan Yue, Shen Li, Jin Guo, Zhen Guan, Zhiqiang Zhu, Bo Niu, Ting Zhang, Jianhua Wang
Summary: The study found significant associations between three polymorphisms of APE1/Ref-1 and NTD subtypes, suggesting that APE1/Ref-1 may be a potential genetic risk factor for encephalocele in high-risk areas of NTDs in China.
REPRODUCTIVE SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Lauren Sahakian, Rhiannon T. Filippone, Rhian Stavely, Ainsley M. Robinson, Xu Sean Yan, Raquel Abalo, Rajaraman Eri, Joel C. Bornstein, Mark R. Kelley, Kulmira Nurgali
Summary: This study demonstrates that targeting APE1/Ref-1 redox activity with APX3330 can alleviate inflammation-induced oxidative stress in a murine model of chronic colitis, improving disease severity, reducing immune cell infiltration, restoring GI function, and providing neuroprotective effects to the enteric nervous system. Inhibition of APE1/Ref-1 redox signaling via APX3330 also reduces mitochondrial superoxide production, oxidative DNA damage, and HMGB1 translocation, suggesting a novel strategy for the treatment of IBD.
INFLAMMATORY BOWEL DISEASES
(2021)
Article
Oncology
Yuchen Zhang, Michael B. Ware, Mohammad Y. Zaidi, Amanda N. Ruggieri, Brian M. Olson, Hannah Komar, Matthew R. Farren, Ganji Purnachandra Nagaraju, Chao Zhang, Zhengjia Chen, Juan M. Sarmiento, Rafi Ahmed, Shishir K. Maithel, Bassel F. El-Rayes, Gregory B. Lesinski
Summary: Studies show that Hsp90 inhibition can limit inflammatory signals, reprogram the PDAC tumor microenvironment, and enhance sensitivity to PD-1 blockade. Hsp90 inhibitors directly affect PSC/CAF growth and enhance the efficacy of anti-PD-1 blockade in vivo.
MOLECULAR CANCER THERAPEUTICS
(2021)
Meeting Abstract
Oncology
Fenil L. Shah, Nadia Atallah, Michelle Grimard, Chunlu Guo, Chi Zhang, Jill Fehrenbacher, Mark R. Kelley, Melissa Fishel
Meeting Abstract
Oncology
Derek Logsdon, Fenil Shah, Fabrizio Carta, Claudiu Supuran, Melissa Fishel, Mark R. Kelley
Article
Chemistry, Medicinal
Richard Trilles, Dmitri Beglov, Qiujia Chen, Hongzhen He, Randall Wireman, April Reed, Spandan Chennamadhavuni, James S. Panek, Lauren E. Brown, Sandor Vajda, John A. Porco, Mark R. Kelley, Millie M. Georgiadis
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Andrew E. Shouksmith, Fenil Shah, Michelle L. Grimard, Justyna M. Gawel, Yasir S. Raouf, Mulu Geletu, Angelika Berger-Becvar, Elvin D. de Araujo, H. Artee Luchman, William L. Heaton, David Bakhshinyan, Ashley A. Adile, Chitra Venugopal, Thomas O'Hare, Michael W. Deininger, Sheila K. Singh, Stephen F. Konieczny, Samuel Weiss, Melissa L. Fishel, Patrick T. Gunning
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Oncology
Melissa Fishel, Hanyu Xia, Jack McGeown, David W. McIlwain, May Faek Mohamed Elbanna, Ariel A. Craft, Hristos Z. Kaimakliotis, George Sandusky, Chi Zhang, Roberto Pili, Mark R. Kelley, Travis J. Jerde
MOLECULAR CANCER THERAPEUTICS
(2019)
Article
Biochemistry & Molecular Biology
Changlin Wan, Wennan Chang, Yu Zhang, Fenil Shah, Xiaoyu Lu, Yong Zang, Anru Zhang, Sha Cao, Melissa L. Fishel, Qin Ma, Chi Zhang
NUCLEIC ACIDS RESEARCH
(2019)
Article
Genetics & Heredity
Marta Codrich, Marina Comelli, Matilde Clarissa Malfatti, Catia Mio, Dilara Ayyildiz, Chi Zhang, Mark R. Kelley, Giovanni Terrosu, Carlo Em Pucillo, Gianluca Tell
Article
Oncology
Charles L. Loprinzi, Christina Lacchetti, Jonathan Bleeker, Guido Cavaletti, Cynthia Chauhan, Daniel L. Hertz, Mark R. Kelley, Antoinette Lavino, Maryam B. Lustberg, Judith A. Paice, Bryan P. Schneider, Ellen M. Lavoie Smith, Mary Lou Smith, Thomas J. Smith, Nina Wagner-Johnston, Dawn L. Hershman
JOURNAL OF CLINICAL ONCOLOGY
(2020)
Review
Pharmacology & Pharmacy
Rachel A. Caston, Silpa Gampala, Lee Armstrong, Richard A. Messmann, Melissa L. Fishel, Mark R. Kelly
DRUG DISCOVERY TODAY
(2020)
Article
Engineering, Biomedical
Chun-Yi Chang, Hunter C. Johnson, Olivia Babb, Melissa L. Fishel, Chien-Chi Lin
Summary: This study presents a dynamic hydrogel system capable of simultaneously increasing stiffness and hyaluronic acid (HA) accumulation, which is crucial for mimicking the tumor microenvironment. The gelatin macromer used in this system allows for primary network crosslinking followed by bioinert or biomimetic stiffening, providing new insights into cancer cell fate processes guided by dynamically changing physicochemical matrix properties.
ACTA BIOMATERIALIA
(2021)
Article
Oncology
Mircea Ivan, Melissa L. Fishel, Oana M. Tudoran, Karen E. Pollok, Xue Wu, Paul J. Smith
Summary: This review focuses on new pharmacological agents that exploit tumor hypoxia or interfere with hypoxia signaling and discusses strategies to maximize their therapeutic impact.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Kexin Li, Qingji Huo, Kazumasa Minami, Keisuke Tamari, Kazuhiko Ogawa, Sungsoo Na, Melissa L. Fishel, Bai-Yan Li, Hiroki Yokota
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a tough and aggressive cancer with low survival rates. This study explores a unique therapeutic approach by utilizing the tumor-modifying potential of oncogenic markers found in PDAC. Surprisingly, certain proteins that are highly expressed in PDAC and associated with poor survival actually exhibit tumor-suppressing qualities when introduced extracellularly. One such protein, PSCA, known to be harmful to patients, can actually help weaken and inhibit the spread of cancer cells when placed outside of the cells. Additionally, PSCA works synergistically with other chemotherapeutic agents used to treat cancer. This discovery has the potential to revolutionize cancer treatment by utilizing proteins that were previously considered to be part of the problem.
Article
Pharmacology & Pharmacy
Changpeng Cui, Qingji Huo, Xue Xiong, Kexin Li, Melissa L. Fishel, Baiyan Li, Hiroki Yokota
Summary: This research identified an anticancer peptide P04 derived from aldolase A (ALDOA) which showed efficient anti-PDAC activities. P04 interacted with epidermal growth factor receptor (EGFR) and downregulated oncoproteins such as Snail and Src. Furthermore, P04 had no inhibitory effect on mesenchymal stem cells (MSCs). The study also demonstrated the potential of converting peripheral blood mononuclear cells (PBMCs) into induced tumor-suppressing cells (iTSCs) through mechanical vibration.
Meeting Abstract
Oncology
Fenil Shah, Olivia Babb, Chi Zhang, Silpa Gampala, Emily Zhang, Steven D. Rhodes, Andrew R. Tee, Brian Calver, Ellie Rad, Verena Staedtke, Karen E. Pollok, D. Wade Clapp, Mark R. Kelley, Melissa L. Fishel
MOLECULAR CANCER THERAPEUTICS
(2019)