Article
Genetics & Heredity
Atsushi Watanabe, Kunio Miyake, Koshi Akahane, Kumiko Goi, Keiko Kagami, Hideo Yagita, Takeshi Inukai
Summary: Immunotherapies specific for BCP-ALL, such as anti-CD19 CAR T-cells and blinatumomab, have significantly improved outcomes in refractory cases. The methylation status of DR4 and DR5 genes is associated with gene expression levels, cell-surface expression, and TRAIL-sensitivities, suggesting potential clinical relevance in predicting immunotherapy efficacy. Evaluating methylation status of DR4 and DR5 genes may be informative in certain cases with unfavorable karyotypes.
Article
Oncology
Karolina Piechna, Aleksandra Zolyniak, Ewa Jablonska, Monika Noyszewska-Kania, Maciej Szydlowski, Bartlomiej Zerek, Maria Kulecka, Izabela Rumienczyk, Michal Mikula, Przemyslaw Juszczynski
Summary: AD-O51.4 exhibits low-nanomolar cytotoxic activity in DLBCL cells, inducing death-receptor (DR) mediated, caspase-dependent apoptosis. Resistance to AD-O51.4 in primary resistant cells may be associated with changes in multiple genes and pathways related to apoptosis, endocytosis, and HDAC-dependent epigenetic reprogramming. Sensitization of resistant DLBCL cells to AD-O51.4 can be achieved with HDAC inhibitors, BCL2 inhibitors, and endocytosis/dynamin inhibitors.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, Research & Experimental
Judith Lind, Roland Hellinger, Petra Kudweis, Herwig P. Moll, Jasmin Gattringer, Kathrin Thell, Sophie Edtmayer, Christian W. Gruber, Dagmar Stoiber, Karoline Kollmann
Summary: This study found that cyclotide-based compound T20K and its analogs have an inhibitory effect on the proliferation of anaplastic large cell lymphoma, inducing apoptosis and cell cycle arrest through increased STAT5 and p53 signaling. Mouse experiments showed promising activity of T20K on cancer cells, providing new insights for the treatment of ALCL.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Hyeonwoo Je, Gi-Hoon Nam, Gi Beom Kim, Wonjun Kim, Soo Rin Kim, In-San Kim, Eun Jung Lee
Summary: TRAIL shows promising anti-tumor activity, but faces challenges such as resistance and delivery issues. A nanocage has been developed to efficiently deliver TRAIL and a re-sensitizing drug (DOX) to overcome TRAIL-resistant tumors, demonstrating potential as an effective antitumor agent.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Biochemistry & Molecular Biology
Longfei Deng, Xuan Zhai, Ping Liang, Hongjuan Cui
Summary: TRAIL holds therapeutic potential in cancer treatment, but many cancers, including GBM, exhibit resistance. Recent studies have identified new mechanisms in regulating TRAIL-induced apoptosis in GBM and effective combinatorial strategies. The TRAIL/TRAIL death receptor axis may have future clinical applications for GBM treatment.
Review
Physiology
Laurel A. Grisanti
Summary: Cardiovascular disease is a leading cause of death globally. Cardiomyocyte death, which occurs in heart damage and stress, contributes to cardiac dysfunction and further damages the heart. Apoptosis, a regulated form of cell death, can occur through intrinsic or extrinsic pathways. The poorly characterized TNF-related ligand TRAIL and its receptors have been found to play a role in cardiac pathology. This article aims to provide an overview of the current understanding of TRAIL and its receptors in normal and pathological conditions in the heart.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Cell Biology
Emir Bozkurt, Heiko Dussmann, Manuela Salvucci, Brenton L. Cavanagh, Sandra Van Schaeybroeck, Daniel B. Longley, Seamus J. Martin, Jochen H. M. Prehn
Summary: The study reveals that TRAIL signaling not only activates apoptosis in colon cancer cells but also induces entosis through TRAIL receptors and the structural presence of caspase-8. The association of TRAIL signaling with cell-in-cell structures is significant in colorectal cancer, especially in the context of patient prognosis. Factors controlling entosis in tumors remain to be elucidated despite the evidence of entosis in cancers.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Tayyab Shahzad, Cho-Ming Chao, Stefan Hadzic, Judith Behnke, Luisa Biebach, Eva Boettcher-Friebertshaeuser, Jochen Wilhelm, Anne Hilgendorff, Klaus-Peter Zimmer, Rory E. Morty, Saverio Bellusci, Harald Ehrhardt
Summary: Hyperoxia-induced inflammation and tissue damage are crucial steps leading to BPD. TRAIL plays a protective role in lung development, and its depletion leads to structural damage.
CELL DEATH & DISEASE
(2022)
Editorial Material
Hematology
lymphoma Leticia Quintanilla-Martinez, Falko Fend
Summary: In this study, the authors present a novel mechanism involving GPR34 mutations that connect the lymphoepithelial lesions of Sjogren syndrome with the development of MALT lymphoma.
Article
Cell Biology
Oliver H. Voss, Daniel Arango, Justin C. Tossey, Miguel A. Villalona Calero, Andrea Doseff
Summary: Apigenin sensitizes primary lung cancer cells to TRAIL-induced apoptosis through reprogramming alternative splicing of key TRAIL/DISC components and directly binding heat shock protein 70 to promote cell death. These findings emphasize the synergies between diet and cancer treatments, providing new avenues for improved cancer therapies.
CELL DEATH & DISEASE
(2021)
Article
Chemistry, Medicinal
Fangshan Chen, Xianmei Zhong, Qian Dai, Kuo Li, Wei Zhang, Jie Wang, Yueshui Zhao, Jing Shen, Zhangang Xiao, Hongyun Xing, Jing Li
Summary: Genetically engineered umbilical cord-MSCs can continuously express and secrete soluble TRAIL, exerting significant inhibitory effects on B-cell acute lymphocytic leukemia cells, which may become a potential therapeutic strategy for B-ALL treatment.
Article
Pharmacology & Pharmacy
Yu Ren, Xue Wang, Shuaishuai Huang, Yangkai Xu, Guobin Weng, Rui Yu
Summary: In this study, we found that alternol sensitized renal carcinoma cells to TRAIL-induced apoptosis by inhibiting antiapoptotic proteins, upregulating DR5 levels, ROS generation, and the CHOP pathway, thus enhancing TRAIL-mediated apoptosis.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Anderson Luiz-Ferreira, Teresa Pacifico, Alefe Cardoso Cruz, Federica Laudisi, Giovanni Monteleone, Carmine Stolfi
Summary: TRAIL is a promising anticancer agent that selectively induces apoptosis in transformed cells, while flavonoids, natural compounds found in plants, have shown competence in enhancing TRAIL-induced apoptosis. However, bioavailability issues are the main limitations for the clinical use of flavonoids.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Anna-Christina Rambow, Insa Aschenbach, Sofie Hagelund, Doaa Tawfik, Jan-Paul Gundlach, Sebastian Weisse, Nicolai Maass, Anna Trauzold
Summary: Binding of TRAIL to its death domain-containing receptors TRAIL-R1 and TRAIL-R2 can induce cell death and/or pro-inflammatory signaling. The importance of TRAIL and TRAIL-R1/R2 in tumor immune surveillance and cancer biology has meanwhile been well documented. TRAIL also binds to TRAIL-R3 and TRAIL-R4, which have regulatory functions in apoptotic and non-apoptotic signaling pathways. Knockdown of TRAIL-R4 affects the activation of apoptotic and non-apoptotic pathways in cancer cells, showing opposing effects on cell death and clonogenic survival. TRAIL-R4 also regulates the expression of anti-apoptotic proteins and affects the activity of AKT, ERK, p38 and NF-kappa B. This study provides evidence for the important role of endogenous TRAIL-R4 in cancer cells and improves the understanding of the complex TRAIL/TRAIL-R system in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
K. M. A. Zinnah, Sang-Youel Park
Summary: The study demonstrated the mechanism behind the synergistic anticancer effect of amitriptyline and TRAIL, showing that amitriptyline increases TRAIL-induced apoptosis by upregulating death receptors DR4 and DR5. Inhibition of autophagy by amitriptyline was also shown to enhance DR4 and DR5 expression.
Review
Biotechnology & Applied Microbiology
Germana Castelli, Elvira Pelosi, Ugo Testa
ONCOTARGETS AND THERAPY
(2018)
Article
Oncology
Emiliano Fabiani, Giulia Falconi, Nelida Ines Noguera, Ernestina Saulle, Laura Cicconi, Mariadomenica Divona, Cristina Banella, Alessandra Picardi, Anna Maria Cerio, Letizia Boe, Massimo Sanchez, Elvira Pelosi, Ugo Testa, Francesco Lo-Coco, Maria Teresa Voso
Review
Hematology
Domenico Mastrangelo, Elvira Pelosi, Germana Castelli, Francesco Lo-Coco, Ugo Testa
BLOOD CELLS MOLECULES AND DISEASES
(2018)
Review
Respiratory System
Alice Huertas, Christophe Guignabert, Joan A. Barbera, Peter Baertsch, Jahar Bhattacharya, Sunita Bhattacharya, Maria R. Bonsignore, Laurence Dewachter, Anh Tuan Dinh-Xuan, Peter Dorfmuller, Mark T. Gladwin, Marc Humbert, Tom Kotsimbos, Theodoros Vassilakopoulos, Olivier Sanchez, Laurent Savale, Ugo Testa, Martin R. Wilkins
EUROPEAN RESPIRATORY JOURNAL
(2018)
Review
Oncology
Ugo Testa, Germana Castelli, Elvira Pelosi
Review
Oncology
Germana Castelli, Elvira Pelosi, Ugo Testa
Review
Oncology
Ugo Testa, Germana Castelli, Elvira Pelosi
Review
Biochemistry & Molecular Biology
Ugo Testa, Germana Castelli, Elvira Pelosi
Article
Oncology
Cristina Banella, Gianfranco Catalano, Serena Travaglini, Elvira Pelosi, Tiziana Ottone, Alessandra Zaza, Gisella Guerrera, Daniela Francesca Angelini, Pasquale Niscola, Mariadomenica Divona, Luca Battistini, Maria Screnci, Emanuele Ammatuna, Ugo Testa, Clara Nervi, Maria Teresa Voso, Nelida Ines Noguera
Summary: Acute Myeloid Leukemias (AMLs) are rapidly progressing and clonal neoplastic diseases. In this study, the metabolic background of AML cells was characterized, and the combination of ascorbate and buformin was shown to be a potential innovative therapeutic option for elderly AML patients resistant to traditional therapy.
Review
Biochemistry & Molecular Biology
Elvira Pelosi, Germana Castelli, Ugo Testa
Summary: Despite progress in basic research and clinical treatment, acute myeloid leukemia (AML) remains a clinical need for patients of all ages. CD123 is a protein found in certain leukemia cells and is a potential target for therapy due to its higher expression in leukemic cells compared to normal cells. Various drugs targeting CD123, such as antibody-drug conjugates and CAR T cells, have shown promise in clinical trials for AML and other hematologic malignancies. However, more effective therapeutic strategies and combination treatments are needed to improve the outcomes of patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Ugo Testa, Germana Castelli, Elvira Pelosi
Summary: ALK is a potent oncogenic driver of lung adenocarcinoma and can be targeted with drugs to improve patient outcomes. However, resistance mechanisms limit the durability of the therapeutic effects. New therapeutic strategies are being investigated to overcome this resistance.
Review
Biochemistry & Molecular Biology
Ugo Testa, Elvira Pelosi, Germana Castelli
Summary: The current classification of acute myeloid leukemia (AML) relies on genomic alterations. AML with mutated nucleophosmin 1 (NPM1-mut) is the largest genetically defined group, accounting for about 30% of adult AMLs and is recognized as a distinct entity in the current AML classifications. NPM1-mut AML is usually associated with a normal karyotype and relatively favorable prognosis, but it is genetically, transcriptionally, and phenotypically heterogeneous. Recent studies highlight the need for additional stratification to improve therapeutic response for different subgroups of NPM1-mut AML patients.
Review
Oncology
Ugo Testa, Elvira Pelosi, Germana Castelli
Summary: Cholangiocarcinomas (CCAs) are heterogeneous epithelial malignancies that can be found at any location of the biliary tree. Recent studies have identified risk factors, molecular abnormalities, and potential cells of origin that contribute to the heterogeneity of CCAs. While therapeutic progress is limited, understanding the molecular mechanisms underlying CCA may lead to more effective treatment strategies.
TECHNOLOGY IN CANCER RESEARCH & TREATMENT
(2023)
Review
Oncology
Ugo Testa, Germana Castelli, Elvira Pelosi
Summary: Esophageal cancer is a common tumor with poor outcomes, with two main histological subtypes: ESCC and EAC. Molecular analysis has revealed complex genetic alterations that differ between ESCC and EAC. Recent identification of molecular subtypes in ESCC may lead to new therapeutic strategies. Additionally, immunotherapy with ICIs has shown promise in improving overall survival of advanced ESCC patients.
Review
Biochemistry & Molecular Biology
Elvira Pelosi, Germana Castelli, Ugo Testa