Article
Dentistry, Oral Surgery & Medicine
Isabela Ribeiro Madalena, Guido Artemio Maranon-Vasquez, Marjorie Ayumi Omori, Emerson Tavares de Sousa, Heitor Albergoni da Silveira, Jorge Esquiche Leon, Flares Baratto-Filho, Sandra Yasuyo Fukada Alves, Maria Bernadete Sasso Stuani, Paulo Nelson-Filho, Christian Kirschneck, Erika Calvano Kuechler
Summary: The aim of this study was to assess the effects of estrogen deficiency on tooth eruption rate (TER) and gene expression of estrogen receptor alpha and beta (ER alpha and ER beta) in a rat model. The results showed that estrogen deficiency decreased TER in teeth under impeded condition and increased gene expression of ER beta in the odontogenic region of teeth with continuous formation.
CLINICAL ORAL INVESTIGATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jin Bai, Yao Li, Guofeng Yan, Jing Zhou, Alejandra Garcia Salmeron, Olamide Tolulope Fategbe, Sathish Kumar, Xuejin Chen, Dong-Bao Chen
Summary: This study found that endogenous estrogens selectively stimulate uterine artery CBS expression through specific estrogen receptors in pregnant rats, leading to increased production of hydrogen sulfide and enhanced uterine blood flow during pregnancy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Yujiro Hattori, Hirotaka Ishii, Shimpei Higo, Mai Otsuka, Moeko Kanaya, Keisuke Matsumoto, Mina Ozawa, Hitoshi Ozawa
Summary: This study identified a specific monoclonal antibody (PPZ0506) against human ESR2 proteins and confirmed its cross-reactivity with rodent ESR2 proteins. By optimizing immunohistochemical staining conditions, they found that rat ESR2 proteins are more localized than previously assumed, suggesting previous studies using inadequately validated antibodies may have overestimated ESR2 distribution profiles. Optimized immunohistochemical detection with PPZ0506 antibody could help resolve conflicting issues in ESR2 research.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Multidisciplinary Sciences
Roman Moravcik, Sona Olejarova, Jana Zlacka, Iveta Herichova
Summary: miR-34a strongly influences the expression of components of the circadian oscillator independently of p53 status and exerts its tumour suppressor effects by inhibiting the expression of sirt1 and cyclin D1 mRNA. 17-beta-estradiol (E2) administration also inhibits the migration and proliferation of colorectal cancer cells, but this effect is not dependent on the action of miR-34a. The possible ambiguous oncogenic characteristics of miR-34a should be considered in future clinical studies.
Article
Oncology
Dan Huang, Zhiqiang Huang, Rajitha Indukuri, Chandrashekar Bangalore Revanna, Mattias Berglund, Jiyu Guan, Konstantin Yakimchuk, Anastasios Damdimopoulos, Cecilia Williams, Sam Okret
Summary: The use of estrogen receptor beta (ESR2) agonist to treat mantle cell lymphoma (MCL) can impede tumor progression, possibly explaining the difference in incidence between males and females. Additionally, there is an interplay between MCL cells and the tumor microenvironment in response to ESR2 agonist treatment.
Article
Chemistry, Medicinal
David Sedlak, Tyler A. Wilson, Werner Tjarks, Hanna S. Radomska, Hongyan Wang, Jayaprakash Narayana Kolla, Zbigniew J. Lesnikowski, Alena Spicakova, Tehane Ali, Keisuke Ishita, Liva Harinantenaina Rakotondraibe, Sandip Vibhute, Dasheng Wang, Pavel Anzenbacher, Chad Bennett, Petr Bartunek, Christopher C. Coss
Summary: The research synthesized a series of para-carborane estrogen receptor agonists with low nanomolar potency, over 200-fold selectivity for ER beta over ER alpha, limited off-target activity against other nuclear receptors, and minimal CYP450 inhibition at very high concentrations. These para-carborane ER beta selective agonists show favorable pharmacological properties compared to clinically developed ER beta agonists, supporting further evaluation of carborane-based selective estrogen receptor modulators.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Katsuhiko Mitachi, David Mingle, Wendy Effah, Antonio Sanchez-Ruiz, Kirk E. Hevener, Ramesh Narayanan, William M. Clemons, Francisco Sarabia, Michio Kurosu
Summary: A short and flexible total synthesis of tunicamycin V and its analogues was achieved, and a novel analogue with selective cytostatic activity against breast cancer cells was discovered.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Plant Sciences
Leslie N. Aldrich, Joanna E. Burdette, Esperanza Carcache de Blanco, Christopher C. Coss, Alessandra S. Eustaquio, James R. Fuchs, A. Douglas Kinghorn, Amanda MacFarlane, Brittney K. Mize, Nicholas H. Oberlies, Jimmy Orjala, Cedric J. Pearce, Mitch A. Phelps, Liva Harinantenaina Rakotondraibe, Yulin Ren, Djaja Doel Soejarto, Brent R. Stockwell, Jack C. Yalowich, Xiaoli Zhang
Summary: Research progress in the discovery of potential anticancer agents from various organisms has been summarized. Lead compounds with structural diversity have been obtained, and potential antitumor activities have been demonstrated. Further investigations are warranted for promising lead compounds.
JOURNAL OF NATURAL PRODUCTS
(2022)
Article
Oncology
Xueyun Huo, Wenjing Zhang, Guannan Zhao, Zhenwen Chen, Peixin Dong, Hidemichi Watari, Ramesh Narayanan, Todd D. Tillmanns, Lawrence M. Pfeffer, Junming Yue
Summary: FAK PROTAC effectively inhibits both FAK kinase activity and its scaffold protein activity and shows high effectiveness in inhibiting ovarian tumor growth and metastasis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Justin Thomas, Molly A. Torok, Kriti Agrawal, Timothy Pfau, Trang T. Vu, Justin Lyberger, Hsiaochi Chang, Alyssa Marie M. Castillo, Min Chen, Bryan Remaily, Kyeongmin Kim, Zhiliang Xie, Mary E. Dillhoff, Samuel K. Kulp, Gregory K. Behbehani, Zobeida Cruz-Monserrate, Latha P. Ganesan, Dwight H. Owen, Mitch A. Phelps, Christopher C. Coss, Thomas A. Mace
Summary: The neonatal Fc receptor (FcRn) is responsible for recycling antibodies and albumin in the body. However, little is known about its expression in circulating immune cells. In this study, FcRn expression was found to be elevated in immune cells of pancreatic ductal adenocarcinoma (PDAC) patients and mice with PDAC. These findings may contribute to understanding the mechanisms behind poor efficacy of antibody immunotherapies in PDAC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Mingqi Li, Ling Li, Sarah Asemota, David Kakhniashvili, Ramesh Narayanan, Xusheng Wang, Francesca-Fang Liao
Summary: This study identifies the molecular mechanisms of how the deubiquitinase OTULIN counteracts LUBAC-mediated NF-kappa B activation. The physical interaction between OTULIN and LUBAC is crucial for genotoxic NF-kappa B signaling, and disruption of this interaction leads to NF-kappa B overactivation. These findings have implications for developing therapeutic strategies against cancer chemoresistance and necroptotic processes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Emma J. Montgomery, Enming Xing, Moray J. Campbell, Pui-Kai Li, James S. Blachly, Allan Tsung, Christopher C. Coss
Summary: Hepatocellular carcinoma (HCC) is a common type of liver cancer and a leading cause of cancer-related death worldwide. The androgen receptor (AR) has been found to play an important role in HCC, although current AR-targeted therapies have not shown efficacy in HCC. However, by building upon research in prostate cancer (PCa), potential AR-targeted therapeutic approaches for HCC could be developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Thirumagal Thiyagarajan, Suriyan Ponnusamy, Dong-Jin Hwang, Yali He, Sarah Asemota, Kirsten L. Young, Daniel L. Johnson, Vera Bocharova, Weidong Zhou, Abhinav K. Jain, Emanuel F. Petricoin, Zheng Yin, Lawrence M. Pfeffer, Duane D. Miller, Ramesh Narayanan
Summary: This study investigates the transcriptional regulation function of AR and AR-V7 splice variants in PCa and identifies molecular condensates formed by liquid-liquid phase separation. The study also presents a selective inhibitor for the treatment of PCa.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Dong-Jin Hwang, Yali He, Suriyan Ponnusamy, Thirumagal Thiyagarajan, Michael L. Mohler, Ramesh Narayanan, Duane D. Miller
Summary: A major challenge in new drug discovery of androgen receptor antagonists is predicting the druggable properties necessary for potency and stability. This study synthesized new compounds with improved stability while maintaining potent antagonistic activity. Through a structure-activity relationship study, two compounds were found to be potent AR antagonists with improved in vivo pharmacokinetics and antiandrogen activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Elizabeth N. Kaweesa, Jaqueline M. Bazioli, Herma C. Pierre, Daniel D. Lantvit, Samuel K. Kulp, Kasey L. Hill, Mitch A. Phelps, Christopher C. Coss, James R. Fuchs, Cedric J. Pearce, Nicholas H. Oberlies, Joanna E. Burdette
Summary: Verticillins, isolated from a fungus, show nanomolar anti-tumor activity in high-grade serous ovarian cancer. They significantly reduce tumor burden and induce apoptosis, but liver toxicity is observed in some cases.
MOLECULAR PHARMACEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Farhan Khan, Obianuju Mercy Anelo, Qandeel Sadiq, Wendy Effah, Gary Price, Daniel L. Johnson, Suriyan Ponnusamy, Brandy Grimes, Michelle L. Morrison, Jay H. Fowke, D. Neil Hayes, Ramesh Narayanan
Summary: Expression of androgen receptor splice variants (AR-SVs) is associated with the aggressive growth of castration-resistant prostate cancer (CRPC). Compared to Caucasian American (CA) men, African American (AA) men are more likely to be diagnosed with aggressive PCa. Therefore, AR-SV expression may serve as an indicator of aggressive growth in PCa, especially in AA men.
Article
Chemistry, Medicinal
Dong-Jin Hwang, Yali He, Suriyan Ponnusamy, Thirumagal Thiyagarajan, Michael L. Mohler, Ramesh Narayanan, Duane D. Miller
Summary: A major challenge in new drug discovery is predicting the druggable properties of small molecules for potent and stable activity. In this study, new small molecules with improved stability and potent antagonistic activity against androgen receptor (AR) were synthesized. Structure-activity relationship (SAR) analysis identified two compounds with high efficacy as AR antagonists, exhibiting improved pharmacokinetics in vivo and antiandrogen activity in tumor xenograft models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)