Article
Oncology
Zachary E. Stiles, Andrew M. Fleming, Paxton Dickson, Miriam Tsao, Evan S. Glazer, David Shibata, Jeremiah L. Deneve
Summary: This study aims to investigate factors associated with lymph node metastases in gastrointestinal stromal tumors (GISTs) and their impact on survival. The results show that lymph node metastases are associated with patient's gender, tumor size, and mitotic activity, and they are also associated with decreased survival.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Article
Medicine, General & Internal
Valentina Indio, Angela Schipani, Margherita Nannini, Milena Urbini, Alessandro Rizzo, Antonio De Leo, Annalisa Altimari, Valerio Di Scioscio, Daria Messelodi, Giuseppe Tarantino, Annalisa Astolfi, Maria Abbondanza Pantaleo
Summary: This study uncovered the gene expression profile of SDH-deficient GIST and identified characteristics such as increased expression of neural markers and activation of fibroblast growth factor receptor signaling. The study also revealed shared features with SDH-deficient pheochromocytoma/paraganglioma and depletion of tumor microenvironment and inflammation gene signatures. The findings provide new insights into the histology and dysregulated biological processes in SDH-deficient GISTs.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Reham Atallah, Andrea Olschewski, Akos Heinemann
Summary: Angiogenesis is the process of developing new blood vessels from existing ones, and it plays a vital role in tissue repair. However, imbalance in angiogenesis can lead to pathological conditions. Succinate, an intermediate of the mitochondrial Krebs cycle, has been found to contribute to angiogenesis through various mechanisms. Understanding the role of succinate as an angiogenic signal can help in understanding diseases with abnormal or excessive angiogenesis and developing strategies to tackle them.
Article
Biochemistry & Molecular Biology
James Whitworth, Ruth T. Casey, Philip S. Smith, Olivier Giger, Jose Ezequiel Martin, Graeme Clark, Jaqueline Cook, Marlee S. Fernando, Phillipe Taniere, Eamonn R. Maher
Summary: This study reports a rare case of a mother-son diad with wild-type GIST, both found to have germline truncating variants in SDHA and PALB2 through comprehensive genetic testing. The mother also developed breast ductal carcinoma in-situ, with immunohistochemistry and molecular analysis showing loss of SDHB expression in the wtGISTs. The presence of multilocus inherited neoplasia alleles syndrome (MINAS) in this family may have contributed to the highly unusual occurrence of familial wtGIST.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Review
Pharmacology & Pharmacy
Homma M. Khosroyani, Lillian R. Klug, Michael C. Heinrich
Summary: Prior to the early 2000s, patients with advanced GIST had poor prognoses due to lack of effective therapies. Tyrosine kinase inhibitors significantly improved the overall survival for these patients. This review discusses the studies that led to the approval of specific targeted therapies for different molecular subtypes of GIST, as well as their impact on future therapeutic approaches.
Article
Biochemistry & Molecular Biology
Andrew D. Tieniber, Ferdinando Rossi, Andrew N. Hanna, Marion Liu, Mark S. Etherington, Jennifer K. Loo, Nesteene Param, Shan Zeng, Kevin Do, Laura Wang, Ronald P. DeMatteo
Summary: Gastrointestinal stromal tumor (GIST) is commonly driven by a single mutation in the Kit or PDGFRA receptor, and tyrosine kinase inhibitors (TKIs) are not curative. This study investigated the role of Kit ligand (KitL) in GIST oncogenesis and tumor growth. The researchers found that in addition to tumor cells, endothelia and smooth muscle cells produced KitL, and genetic reduction of KitL impaired tumor growth. They also observed heterogeneous KitL expression in human GIST specimens, with PDGFRA-mutant tumors showing higher expression. Elevated serum KitL was associated with imatinib resistance. Overall, KitL supports GIST growth and may serve as a biomarker and therapeutic target.
Article
Biochemistry & Molecular Biology
Wen-Kuan Huang, Hao Shi, Pinar Akcakaya, Katarina Zeljic, Anastasia Gangaev, Stefano Caramuta, Chun-Nan Yeh, Robert Branstrom, Catharina Larsson, Weng-Onn Lui
Summary: The study identified miR-483-3p as a key molecule downregulated in imatinib-treated GIST, which may regulate OXPHOS by modulating mitochondrial respiratory Complex II expression and rescuing imatinib-induced cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Davide Marchi, Fredericus J. M. van Eeden
Summary: Glucocorticoids are essential for regulating physiological processes, but chronic steroid use may lead to limited therapeutic benefits. Understanding how to modulate glucocorticoid receptor activity is crucial for minimizing side effects and improving treatment outcomes.
Article
Cell Biology
Savalan Babapoor-Farrokhran, Deanna Gill, Jafar Alzubi, Sumeet K. Mainigi
Summary: Atrial fibrillation (AF) is a common arrhythmia associated with hypoxia and the HIF pathway. Certain cytokines may serve as biomarkers for AF, aiding in diagnosis and treatment. Targeting these cytokines shows promise for the management of AF.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Zirong Pan, Guodong Ma, Linglei Kong, Guanhua Du
Summary: Stroke is an acute cerebrovascular disease caused by sudden rupture or blockage of blood vessels in the brain, and HIF-1 plays an important role in regulating various pathways in the pathological process. The roles of HIF-1 in stroke are controversial, involving factors such as ischemic time and degree, and its regulatory mechanisms include inflammation, autophagy, oxidative stress, and apoptosis.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Medicine, Research & Experimental
Neetu Saxena, Eliana Beraldi, Ladan Fazli, Syam Prakash Somasekharan, Hans Adomat, Fan Zhang, Chidi Molokwu, Anna Gleave, Lucia Nappi, Kimberly Nguyen, Pavn Brar, Nicholas Nikesitch, Yuzhuo Wang, Colin Collins, Poul H. Sorensen, Martin Gleave
Summary: This study reveals that after AR pathway inhibition, acute adaptive responses support the reactivation of AR and the development of PCa by regulating SDH activity and Hsp27 protein. Co-targeting AR and Hsp27 can enhance the sensitivity of PCa cells to ARPI treatments.
EMBO MOLECULAR MEDICINE
(2021)
Review
Oncology
Lillian R. Klug, Homma M. Khosroyani, Jason D. Kent, Michael C. Heinrich
Summary: When Gastrointestinal Stromal Tumour (GIST) was identified as a distinct pathological entity, effective medical therapies were lacking, leading to poor prognosis. However, the discovery of KIT mutations and the development of TKIs revolutionized GIST treatment. Although there are approved drugs for treating advanced-stage GIST, challenges still remain and new therapeutic approaches are needed.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Kenneth K. Wu
Summary: When tissues are under physiological stresses, such as exercise and cold exposure, skeletal muscle cells secrete succinate for adaptation and survival. However, environmental toxins and injurious agents induce the secretion of succinate to damage tissues and trigger inflammation. This review summarizes the current understanding of extracellular succinate and its implications in both health and disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Yu Wang, Hongmei Tao, Wenjing Tang, Siqi Wu, Yin Tang, Ling Liu
Summary: This study aimed to investigate the alterations of myocardial succinate and fumarate levels with or without SDH inhibitor dimethyl malonate during LPS challenge. The results showed that myocardial succinate and fumarate levels were increased in the initial 9 h of LPS challenge. Dimethyl malonate increased succinate level, decreased fumarate level, aggravated cardiac dysfunction and reduced oxidative stress. After 12 h of LPS challenge, succinate level increased sharply, while fumarate level gradually decreased. Dimethyl malonate effectively reduced succinate level, increased fumarate level, improved cardiac dysfunction and inhibited interleukin-1 beta production during 12-24 h of LPS challenge.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Oncology
Yihang Shi, Li Ding, Chengqiang Mo, Yanji Luo, Shaoqing Huang, Shirong Cai, Yanzhe Xia, Xinhua Zhang
Summary: Carney-Stratakis syndrome (CSS) is a rare syndrome characterized by the coexistence of PGL/PHEO and GIST. This case report presents a CSS patient with a rare bladder PGL and SDH-deficient GIST caused by a germline mutation in the SDHB gene.
FRONTIERS IN ONCOLOGY
(2022)