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
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)
Article
Oncology
Silpa Gampala, Fenil Shah, Chi Zhang, Steven D. Rhodes, Olivia Babb, Michelle Grimard, Randall S. Wireman, Ellie Rad, Brian Calver, Ren-Yuan Bai, Verena Staedtke, Emily L. Hulsey, M. Reza Saadatzadeh, Karen E. Pollok, Yan Tong, Abbi E. Smith, D. Wade Clapp, Andrew R. Tee, Mark R. Kelley, Melissa L. Fishel
Summary: This study identified a novel therapeutic approach to target key signaling nodes in MPNST using first-in-class small molecules, inhibiting Ref-1 or STAT3 to impair tumor growth and induce apoptosis in both in vitro and in vivo models. Additionally, genes highly expressed in MPNST patients were downregulated following inhibition of Ref-1 or STAT3, highlighting the potential translational impact of this research in the clinic.
BRITISH JOURNAL OF CANCER
(2021)
Article
Cell Biology
Yuqi Guo, Fangxi Xu, Scott C. Thomas, Yanli Zhang, Bidisha Paul, Satish Sakilam, Sungpil Chae, Patty Li, Caleb Almeter, Angela R. Kamer, Paramjit Arora, Dana T. Graves, Deepak Saxena, Xin Li
Summary: Periodontal disease is a common inflammatory disease caused by oral microbial dysbiosis, leading to inflammation and bone loss. This study shows that succinate, which is elevated in the subgingival plaque of patients with severe periodontal disease, activates SUCNR1 and contributes to the development of periodontitis. Therapeutic studies demonstrate that a SUCNR1 antagonist can inhibit inflammation and reduce periodontal bone loss.
Article
Biochemistry & Molecular Biology
Lisa N. Heppler, Sanaz Attarha, Rosanne Persaud, Jennifer Brown, Peng Wang, Boryana Petrova, Isidora Tosic, Foster B. Burton, Yael Flamand, Sarah R. Walker, Jennifer E. Yeh, Roman A. Zubarev, Massimiliano Gaetani, Naama Kanarek, Brent D. G. Page, David A. Frank
Summary: The key transcriptional regulator STAT3 is persistently activated in many types of human cancer. A study has identified the antimicrobial drug pyrimethamine as a specific inhibitor of STAT3 transcriptional activity. It was found that pyrimethamine acts by inhibiting the dihydrofolate reductase enzyme, leading to a deficiency in reduced folate and ultimately affecting the regulation of STAT3 transcriptional activity. This discovery provides new insights into the STAT3 pathway and may contribute to the development of novel strategies for cancer treatment.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
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)
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
Cell Biology
Gayathri Chalikonda, Hoomin Lee, Aliya Sheik, Yun Suk Huh
Summary: Colorectal cancer is a common cancer in developed countries, with early diagnosis being crucial for a better prognosis. Overexpression and activation of STAT3 protein in CRC cells contribute to chemoresistance development. Research has focused on exploring therapeutic STAT3 inhibitors and analogs for controlling and treating CRC.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Cell Biology
Tsung-Yen Huang, Masato Hirota, Daiki Sasaki, Rajkumar Singh Kalra, Hsiao-Chiao Chien, Miho Tamai, Shukla Sarkar, Yang Mi, Mio Miyagi, Yu Seto, Hiroki Ishikawa
Summary: Aerobic glycolysis, essential for effector T cell survival and proliferation, regulates Th17 differentiation through the negative regulation of phosphoenolpyruvate (PEP). PEP supplementation or inhibition of downstream glycolytic enzymes increases PEP levels and inhibits IL-17A expression. Mechanistically, PEP binds to JunB and inhibits DNA binding of the JunB/BATF/IRF4 complex, thereby modulating the Th17 transcriptional program. PEP administration inhibits Th17 generation and improves Th17-dependent autoimmune encephalomyelitis.
Article
Biochemistry & Molecular Biology
Huang Chen, Aiwu Bian, Lian-fang Yang, Xuan Yin, Jie Wang, Chaowen Ti, Ying Miao, Shihong Peng, Shifen Xu, Mingyao Liu, Wen-Wei Qiu, Zhengfang Yi
Summary: A new small-molecule inhibitor N4 shows potent anti-tumor bioactivity in pancreatic cancer by targeting STAT3, effectively suppressing tumor growth and metastasis, and potentially offering clinical benefits for treatment.
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
Yu-Shi Wang, Chen Chen, Shi-Yin Zhang, Yang Li, Ying-Hua Jin
Summary: STAT3 is a crucial player in tumor development, and (20S)G-Rh2 may serve as a potential option for targeted therapy by inhibiting STAT3 activity through interfering with Annexin A2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Suravi Pramanik, Yingling Chen, Heyu Song, Irine Khutsishvili, Luis A. Marky, Sutapa Ray, Amarnath Natarajan, Pankaj K. Singh, Kishor K. Bhakat
Summary: This study identifies a novel role for the protein APE1 in regulating stable G4 formation and KRAS expression in PDAC, suggesting that G4 structures could be potential prognostic markers and therapeutic targets for PDAC.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Yanqiong Chen, Wenting Zhang, Xiufeng Bai, Yi Liu
Summary: This study developed a new method to specifically inhibit the activity of the transcription factor STAT3, which successfully blocked its transcription activity in cancer cells and provided a novel approach for the treatment of cancer and autoimmune diseases.
Article
Medicine, Research & Experimental
Kexiang Yan, Fuxin Zhang, Jie Ren, Qiong Huang, Nikhil Yawalkar, Ling Han
Summary: This study found that miR-125a-5p levels were decreased in peripheral blood CD4+ T cells of psoriatic patients, positively correlated with the proportion of Tregs, and negatively correlated with the PASI score. MiR-125a-5p mimics promoted the differentiation of Tregs and downregulated the mRNA levels of ETS-1, IFN-γ, and STAT3 in murine CD4+ T cells. Additionally, agomir-125a-5p alleviated psoriasis-like inflammation by downregulating the proportion of Th17 cells.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Meeting Abstract
Oncology
Derek Logsdon, Fenil Shah, Fabrizio Carta, Claudiu Supuran, Melissa Fishel, Mark R. Kelley
Article
Pharmacology & Pharmacy
Sheik Pran Babu Sardar Pasha, Kamakshi Sishtla, Rania S. Sulaiman, Bomina Park, Trupti Shetty, Fenil Shah, Melissa L. Fishel, James H. Wikel, Mark R. Kelley, Timothy W. Corson
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2018)
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)