Review
Oncology
Andrea Katharina Lindner, Gennadi Tulchiner, Andreas Seeber, Peter J. Siska, Martin Thurnher, Renate Pichler
Summary: This review summarizes the pathogenesis of a rare renal cell carcinoma caused by FH deficiency, focusing on the activation of HIF and promotion of tumor development due to fumarate accumulation. Therapeutic options for this type of cancer and potential targets within FH-deficient cells are also discussed.
FRONTIERS IN ONCOLOGY
(2022)
Article
Pathology
Valarie McMurtry, Jonathan Mahlow, Joshua F. Coleman, Georgios Deftereos, Rakhi Jattani, Roy R. L. Bastien, Jacob Durtschi, Elke Jarboe, Lesley Lomo, Deepika Sirohi
Summary: The study aims to refine morphologic criteria and identify mutations in FH-deficient smooth muscle tumors (SMTs). The results show that FH-deficient kidney tumors and SMTs have distinctive morphologic features, and only 50% of FH-deficient SMTs have FH gene mutations.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Cell Biology
Ya Fan, Jia Wang, Yuemei Xu, Yipin Wang, Tao Song, Xiubin Liang, Feng Jin, Dongming Su
Summary: Our study showed that HRD1 overexpression decreased aerobic glycolysis, inhibited breast cancer cell proliferation and invasion. HRD1 interacted with PFKP in the cytoplasm, leading to ubiquitination and degradation of PFKP and ultimately reducing its expression and activity in breast cancer cells. HRD1 suppressed breast cancer growth and metastasis in vivo through a PFKP-dependent mechanism.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Medicine, General & Internal
Samar Alkhrait, Munira Ali, Elizabeth Kertowidjojo, Iris L. Romero, Feighanne Hathaway, Obianuju Sandra Madueke-Laveaux
Summary: Uterine leiomyomas or uterine fibroids are common benign tumors in reproductive-aged women. Fumarate hydratase deficient (FH-d) uterine fibroids are a rare subtype and may indicate hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome. Early diagnosis of FH-d uterine fibroids is critical for early diagnosis of HLRCC.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pathology
Talia L. Fuchs, Catherine Luxford, Adele Clarkson, Amy Sheen, Loretta Sioson, Marianne Elston, Michael S. Croxson, Trisha Dwight, Diana E. Benn, Lyndal Tacon, Michael Field, Mahsa S. Ahadi, Angela Chou, Roderick J. Clifton-Bligh, Anthony J. Gill
Summary: Up to 40% of pheochromocytomas (PCCs) and paragangliomas (PGLs) are hereditary, with fumarate hydratase (FH) mutations causing hereditary leiomyomatosis and renal cell carcinoma syndrome. FH-deficient PCC/PGL are underrecognized but can be identified by immunohistochemical (IHC) screening. These tumors are strongly associated with germline missense mutations in FH, have a low incidence of leiomyoma or RCC, and may have a higher risk of metastasis.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2023)
Review
Pharmacology & Pharmacy
Lu Zhan, Fangting Su, Qiang Li, Yueqiang Wen, Feng Wei, Zhelin He, Xiaoyan Chen, Xiang Yin, Jian Wang, Yilin Cai, Yuxia Gong, Yu Chen, Xiao Ma, Jinhao Zeng
Summary: Colorectal cancer (CRC) is a common malignant tumor with high recurrence and metastasis rates. Glycolysis plays a crucial role in CRC cell metabolism and growth. The regulation of CRC glycolysis involves several signal transduction pathways and transcription factors, and targeting this pathway has become a promising approach for CRC therapy. Phytochemicals have demonstrated anti-CRC activity by targeting the glycolytic pathway, offering a new avenue for drug development.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pathology
Xiaobo Zhang, Chen Wang, Danhua Shen
Summary: This study investigated the Clinicopathological features and FH mutation in FH-dUL. FH-dUL is rare and the combination of predictive Clinicopathological evaluation, FH and 2SC IHC test, and molecular test were helpful for the screening of FH-dUL or even HLRCC.
PATHOLOGY RESEARCH AND PRACTICE
(2024)
Review
Agriculture, Multidisciplinary
Asifa Khan, Shumaila Siddiqui, Syed Akhtar Husain, Sybille Mazurek, Mohammad Askandar Iqbal
Summary: The article discusses the differences in metabolism between cancer cells and normal cells, as well as the role of plant-based compounds in modulating cancer metabolism. It proposes a therapeutic strategy of targeting metabolic vulnerabilities of cancer using plant-based compounds.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2021)
Article
Oncology
Eric Lu, Kathryn E. Hatchell, Sarah M. Nielsen, Edward D. Esplin, Karen Ouyang, Keith Nykamp, Shirin Zavoshi, Shantao Li, Liying Zhang, Blake R. Wilde, Heather R. Christofk, Paul C. Boutros, Brian Shuch
Summary: This study found that the prevalence of incidentally discovered HLRCC in germline testing is similar to recent population carrier estimates, suggesting it is a relatively common cancer syndrome. Individuals with VUSs had an elevated risk of RCC compared to those with negative genetic testing, while individuals with AR FMRD variants did not.
Article
Endocrinology & Metabolism
Ali S. Alzahrani, Meshael Alswailem, Balgees Alghamdi, Hindi Al-Hindi
Summary: This study describes a woman with HLRCC syndrome who presented with aggressive poorly differentiated thyroid cancer. It is the first report to link thyroid cancer with HLRCC syndrome.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Biology
Ludovico Pipito, Thomas Arron Illingworth, Giuseppe Deganutti
Summary: Cancer is a disease characterized by abnormal cell growth and invasion of body tissues. The acidic intracellular microenvironment and metabolic shift towards glycolysis are common features of cancer. Targeting the central enzyme pyruvate kinase (hPKM2) in glycolysis could be an effective approach for drug development. Through molecular docking and molecular dynamics simulations, a new molecular entity has been proposed to disrupt hPKM2 and cellular energy balance.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Venkatasubramanian Hemagowri, Velanganni Selvaraj, R. Jesu Jaya Sudan, Sudandiradoss Chinnappan, Anbalagan Bhuvan, Kirankumar Santhakumar
Summary: This study extensively analyzed the binding efficiency of potential human FH inhibitor citrate to zebrafish fh through molecular docking and simulation experiments, revealing a stronger interaction of citrate with fh protein compared to fumarate. Biochemical analysis confirmed the concentration dependent inhibitory effect of citrate on zebrafish fh, confirming the findings of the computational experiments.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Medicinal
Alexandra Glenister, Catherine K. J. Chen, David J. Paterson, Anna K. Renfrew, Michela Simone, Trevor W. Hambley
Summary: A glucose-based vector conjugated to a tris(methylpyridyl)amine ligand is described for generating targeted chaperone and caging complexes for active anticancer agents. The ligand inhibits hexokinase in cells, showing potential for phosphorylation and targeting cancer cells. The Co(III) complex incorporating this ligand demonstrates glucose-dependent cellular accumulation and potential for targeted delivery of highly toxic anticancer agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pathology
Terhi Ahvenainen, Sara Khamaiseh, Amjad Alkodsi, Miika Mehine, Riikka Nevala, Anna Ayravainen, Ralf Buetzow, Pia Vahteristo
Summary: This article reports a case of a patient with uterine leiomyoma who developed pulmonary tumors years after hysterectomy. Molecular analysis revealed similar mutational profiles in all three tumors, suggesting the potential of metastasis and malignant transformation in uterine leiomyomas.
EXPERIMENTAL AND MOLECULAR PATHOLOGY
(2022)
Article
Genetics & Heredity
Jiayu Liang, Guangxi Sun, Xiuyi Pan, Mengni Zhang, Pengfei Shen, Sha Zhu, Jinge Zhao, Linmao Zheng, Junjie Zhao, Yuntian Chen, Xiaoxue Yin, Junru Chen, Xu Hu, Yuhao Zeng, Jianhui Chen, Yongquan Wang, Zhihong Liu, Jin Yao, Minggang Su, Rui Huang, Banghua Liao, Qiang Wei, Xiang Li, Qiao Zhou, Jiyan Liu, Yali Shen, Zhenhua Liu, Ni Chen, Hao Zeng, Xingming Zhang
Summary: In this study, the genomic, epigenomic, and transcriptomic features of metastatic lesions in FH-RCC were investigated. A founding MRCA clone dominated the early evolutionary trajectories in FH-RCC. Metastatic lesions showed higher enrichment of T effector cells, upregulation of immune-related genes, and differential methylation and immune-related genomic loci compared to primary lesions. These findings provide valuable insights into the progression of FH-RCC.
Review
Biochemistry & Molecular Biology
Nunziata Maio, Anshika Jain, Tracey A. Rouault
CURRENT OPINION IN CHEMICAL BIOLOGY
(2020)
Editorial Material
Biochemistry & Molecular Biology
Tracey A. Rouault, Nunziata Maio
Article
Biochemistry & Molecular Biology
Anshika Jain, Anamika Singh, Nunziata Maio, Tracey A. Rouault
HUMAN MOLECULAR GENETICS
(2020)
Article
Hematology
Manik C. Ghosh, De-Liang Zhang, Wade H. Ollivierre, Audrey Noguchi, Danielle A. Springer, W. Marston Linehan, Tracey A. Rouault
Summary: The study demonstrates that treatment with the HIF-2 alpha inhibitor MK-6482 is effective in reversing polycythemia and mitigating pulmonary hypertension, cardiac fibrosis, and pulmonary fibrosis by reducing the expression of HIF-2 alpha and its target genes.
Article
Biochemistry & Molecular Biology
Daniel R. Crooks, Nunziata Maio, Martin Lang, Christopher J. Ricketts, Cathy D. Vocke, Sandeep Gurram, Sevilay Turan, Yun-Young Kim, G. Mariah Cawthon, Ferri Sohelian, Natalia De Val, Ruth M. Pfeiffer, Parthav Jailwala, Mayank Tandon, Bao Tran, Teresa W-M Fan, Andrew N. Lane, Thomas Ried, Darawalee Wangsa, Ashkan A. Malayeri, Maria J. Merino, Youfeng Yang, Jordan L. Meier, Mark W. Ball, Tracey A. Rouault, Ramaprasad Srinivasan, W. Marston Linehan
Summary: Understanding the mechanism of Warburg shift to aerobic glycolysis is essential for defining the metabolic basis of cancer. HLRCC, an aggressive cancer, is characterized by impaired mitochondrial respiratory chain, loss of expression of mtDNA-encoded subunits, and accumulation of fumarate, leading to the promotion of aerobic glycolysis and disease progression. Accumulation of fumarate in HLRCC tumors disrupts mtDNA replication and proofreading, causing loss of respiratory chain components.
Article
Multidisciplinary Sciences
Nunziata Maio, Bernard A. P. Lafont, Debangsu Sil, Yan Li, J. Martin Bollinger, Carsten Krebs, Theodore C. Pierson, W. Marston Linehan, Tracey A. Rouault
Summary: Research has shown that the catalytic subunit nsp12 of the SARS-CoV-2 RdRp complex ligates two iron-sulfur metal cofactors which are essential for viral replication and interaction with the viral helicase. Oxidation of these clusters by TEMPOL inhibits RdRp activity and blocks SARS-CoV-2 replication in cell culture, indicating that these iron-sulfur clusters could be targeted for therapy of COVID-19.
Article
Hematology
Nunziata Maio, De-Liang Zhang, Manik C. Ghosh, Anshika Jain, Anna M. SantaMaria, Tracey A. Rouault
Summary: Humans and other vertebrates have evolved effective mechanisms to maintain iron balance through the regulation of iron concentration and utilization at the cellular and systemic levels, involving iron-regulatory hormone hepcidin and iron regulatory proteins.
SEMINARS IN HEMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nunziata Maio, Tracey A. Rouault
Article
Biochemistry & Molecular Biology
Nunziata Maio, Tracey A. Rouault
Article
Multidisciplinary Sciences
Forson Chan, Simon Lai, Marcus Pieterman, Lisa Richardson, Amanda Singh, Jocelynn Peters, Alex Toy, Caroline Piccininni, Taiysa Rouault, Kristie Wong, James K. Quong, Adrienne T. Wakabayashi, Anna Pawelec-Brzychczy
Summary: A new prototype symptom checker was developed and tested for safety and accuracy in real patient scenarios. The study found that the prototype outperformed patients in deciding the most appropriate treatment setting for medical issues. Compliance with the symptom checker recommendations could significantly reduce unnecessary hospital visits while maintaining accuracy and safety outcomes.
Article
Multidisciplinary Sciences
Jin-Seon Yook, Mikyoung You, Jiyoung Kim, Ashley M. Toney, Rong Fan, Bhanwar Lal Puniya, Tomas Helikar, Sophie Vaulont, Jean-Christophe Deschemin, Meshail Okla, Liwei Xie, Manik C. Ghosh, Tracey A. Rouault, Jaekwon Lee, Soonkyu Chung
Summary: This study investigates the iron-regulatory network underlying beige adipogenesis, showing that thermogenic stimulus leads to redistribution of iron into beige fat through interplay between adipocyte iron demands and systemic iron liberation. Disruption of systemic iron homeostasis impairs beige fat development, suggesting coordinated interplay between renal hypoxia and hepcidin down-regulation as a key mechanism for activating adaptive thermogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Christina A. Porras, Tracey A. Rouault
Summary: This review provides an overview of the role of iron homeostasis disruption in various neurological disorders, discussing the consequences of both iron accumulation and deficiency. It also examines the history of animal models and presents a comparison of patients with a newly discovered neurodegenerative disorder caused by mutations in iron regulatory protein 2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Nunziata Maio, Sara Cherry, David C. Schultz, Brett L. Hurst, W. Marston Linehan, Tracey A. Rouault
Summary: TEMPOL has been shown to inhibit the RNA-dependent RNA polymerase of SARS-CoV-2 and effectively block viral replication in the Syrian hamster model. These findings support the potential application of TEMPOL as a highly efficacious antiviral against COVID-19 in humans.
Article
Multidisciplinary Sciences
Wing-Hang Tong, Hayden Ollivierre, Audrey Noguchi, Manik C. Ghosh, Danielle A. Springer, Tracey A. Rouault
Summary: Cardiomyopathy is a primary cause of death in Friedreich ataxia patients with defective iron-sulfur cluster biogenesis. The mTOR and AKT signaling cascades play crucial roles in regulating cardiovascular growth and homeostasis, with mTOR and AKT hyperactivations possibly as part of the metabolic stress response to ISC deficiencies.
Article
Clinical Neurology
Nunziata Maio, Russell P. Saneto, Richard Steet, Marcio A. Sotero de Menezes, Cindy Skinner, Tracey A. Rouault
Summary: Altered brain iron homeostasis can contribute to neurodegeneration. Mutations in the IREB2 gene can cause a newly characterized type of early onset progressive neurodegenerative disease, impacting iron metabolism regulation.
BRAIN COMMUNICATIONS
(2022)