Article
Cell Biology
Rosario Yerbes, Rocio Mora-Molina, F. Javier Fernandez-Farran, Laura Hiraldo, Abelardo Lopez-Rivas, Carmen Palacios
Summary: This study reveals a previously unknown cell death mechanism triggered in glutamine-addicted tumor cells in response to glutamine metabolism limitation. The mechanism is regulated by GCN2 activation induced by glutamine starvation and involves the activation of the extrinsic apoptotic pathway mediated by TRAIL-R2.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Valeria Coppola, Ilaria Marino, Uwe Warnken, Mario Falchi, Luca Pasquini, Mauro Biffoni, Ruggero De Maria, Tobias Longin Haas
Summary: We have identified FYCO1 as a protein that promotes the transport of autophagic and endosomal vesicles. It interacts with activated CASP8 and its loss leads to increased sensitivity of cells to apoptosis and impaired transport of TNFRSF10B/TRAIL-R2/DR5.
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
Biochemistry & Molecular Biology
So Rae Song, Seung Un Seo, Seon Min Woo, Ji Yun Yoon, Simmyung Yook, Taeg Kyu Kwon
Summary: In this study, the research focused on the effect of traditional Chinese medicinal herb, Tubeimoside-1 (TBMS-1), on the sensitization of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The results showed that combination therapy using TBMS-1 and TRAIL increased apoptotic cell death. Mechanistically, TBMS-1 destabilized c-FLIP expression by downregulating STAMBPL1, a deubiquitinase (DUB). Moreover, knockdown of STAMBPL1 enhanced TRAIL-mediated apoptosis via c-FLIP downregulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Deepika Raman, Patricia Tay, Jayshree L. Hirpara, Dan Liu, Shazib Pervaiz
Summary: The study shows that TRAIL can induce apoptosis in nasopharyngeal cancer cell lines by activating caspase-3, with the membrane protein TMTC2 playing a crucial role in this process. Patients with high TMTC2 expression have significantly improved disease-free survival, suggesting TMTC2 may serve as a biomarker for TRAIL sensitivity.
Article
Multidisciplinary Sciences
Diego A. Rodriguez, Giovanni Quarato, Swantje Liedmann, Bart Tummers, Ting Zhang, Cliff Guy, Jeremy Chase Crawford, Gustavo Palacios, Stephane Pelletier, Halime Kalkavan, Jeremy J. P. Shaw, Patrick Fitzgerald, Mark J. Chen, Siddharth Balachandran, Douglas R. Green
Summary: This study identifies a molecular mechanism whereby Caspase-8 and FADD suppress spontaneous necroptotic cell death. The absence of Caspase-8 or FADD leads to the activation of RIPK3 and MLKL, resulting in necroptosis. This process relies on the nucleic acid sensor ZBP1 and its associated signaling pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Shuang Liu, Erik Polsdofer, Lukun Zhou, Sanbao Ruan, Hui Lyu, Defu Hou, Hao Liu, Ann D. Thor, Zhimin He, Bolin Liu
Summary: Metformin increases TRAIL expression and induces apoptosis in TNBC and NSCLC cells, showcasing potent antitumor activity by activating the death receptor signaling pathway.
MOLECULAR THERAPY-ONCOLYTICS
(2021)
Article
Oncology
Simon Garinet, Pascal Wang, Audrey Mansuet-Lupo, Ludovic Fournel, Marie Wislez, Helene Blons
Summary: This review discusses the need for improved risk assessment and patient selection for adjuvant and neoadjuvant chemotherapy following resected lung cancer. The current evaluation of recurrence risk is primarily based on TNM classification, but more than 25% of early-stage patients still experience relapse. Validated prognostic and theranostic markers are needed to better stratify patients and guide adjuvant therapies in resected lung cancer.
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
Oncology
Stephanie Chow, Oliver Dorigo
Summary: Adoptive cell transfer of IFN-activated monocytes administered intraperitoneally showed antitumor effects and acceptable tolerability in patients with platinum-resistant ovarian cancer. Exposure of monocytes to IFN-α and IFN-γ upregulated TRAIL, leading to caspase 8 activation and direct cell-to-cell contact-dependent apoptosis of ovarian cancer cells.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Vera Belousova, Oxana Svitich, Elena Timokhina, Irina Ignatko, Irina Bogomazova, Svetlana Pesegova, Tatiana Silaeva, Tatiana Kuzmina, Oxana Skorobogatova
Summary: This article presents the hypothesis that premature placenta apoptosis could be a potential cause of preterm birth, supported by evaluating gene expression. The study found that during pregnancy, the expression of apoptosis-related genes in the placenta is low, but the expression of the apoptosis inhibitor XIAP is high. However, at the onset of preterm labor, the expression of apoptosis-related genes increases significantly, potentially initiating preterm birth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Raiany A. Santos, Daiane M. Cerqueira, Dario S. Zamboni, Sergio C. Oliveira
Summary: This study reveals the key role of caspase-7 in cell death during Brucella infection and highlights the important function of caspase-8 in inflammasome activation and pyroptosis.
FRONTIERS IN MICROBIOLOGY
(2022)
Editorial Material
Oncology
Jordi Remon, Benjamin Besse
Summary: Efforts are being made to incorporate immune-checkpoint inhibitors into therapy for early stage non-small-cell lung cancer. The IMpower010 trial has demonstrated that this strategy can improve disease-free survival in a subset of patients, opening up a new area of research in the quest for the optimal perioperative strategy to increase overall survival.
NATURE REVIEWS CLINICAL ONCOLOGY
(2022)
Review
Oncology
Mingxia Jiang, Ling Qi, Lisha Li, Yiming Wu, Dongfeng Song, Yanjing Li
Summary: Caspase-8 is a key player in cancer, involved in multiple programmed cell death modes and closely associated with tumor growth, invasion, therapeutic resistance, etc.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Cell Biology
Greta Del Mistro, Shamala Riemann, Sebastian Schindler, Stefan Beissert, Roland E. Kontermann, Aurelien Ginolhac, Rashi Halder, Luana Presta, Lasse Sinkkonen, Thomas Sauter, Dagmar Kulms
Summary: Malignant melanoma (MM) is a life-threatening disease that often develops resistance to targeted kinase inhibition. In this study, the researchers found that inhibiting focal adhesion kinase (FAK) could restore sensitivity to treatment in previously resistant MM cells.
CELL DEATH & DISEASE
(2022)
Editorial Material
Medicine, General & Internal
Fraser J. Brims, Annette McWilliams, Susan V. Harden, Ken O'Byrne
MEDICAL JOURNAL OF AUSTRALIA
(2022)
Article
Immunology
Habib Sadeghirad, James Monkman, Ahmed M. Mehdi, Rahul Ladwa, Ken O'Byrne, Brett G. M. Hughes, Arutha Kulasinghe
Summary: By applying targeted spatial proteomic approaches, this study investigated the protein expression in primary and lymph node metastases and found that lymph node metastases had higher levels of proliferation, DNA repair, and apoptosis markers, while pro-apoptotic markers were enriched in the stroma of primary tumors. This study highlights the utility of spatial proteomics for understanding the tumor and stromal composition in locoregional metastasis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Kar Ven Cavan Chow, Connor O'Leary, Fiona Paxton-Hall, Duncan Lambie, Kenneth O'Byrne
Summary: This case report describes a 63-year-old man with metastatic lung adenocarcinoma who developed toxic epidermal necrolysis (TEN) following treatment with pembrolizumab. The patient was managed with immunosuppressive therapy and achieved excellent recovery. This rare occurrence highlights the importance of recognizing and managing this complication, especially considering the increasing use of immune checkpoint inhibitors.
OXFORD MEDICAL CASE REPORTS
(2022)
Article
Oncology
Malinda Itchins, Hannah Ainsworth, Marliese Alexander, Samantha Dean, Devi Dharmaraj, Nick Pavlakis, Stephen J. Clarke, Chris Brown, Javier Torres, Ayesha Saqib, Rahul Ladwa, Kenneth O'Byrne, Melissa Moore, Po Yee Yip, Ben Ben Solomon, Tom John, Steven Kao, Paul Mitchell, Sagun Parakh
Summary: Limited real world data exist on the IMpower150 regimen, and this study adds to the knowledge base by demonstrating its efficacy in EGFR mutant patients, including those with CNS metastases. The overall response rate for all patients was 51%, and for EGFR mutant patients it was 52%, highlighting the positive outcomes of this treatment approach.
CLINICAL LUNG CANCER
(2022)
Article
Oncology
Joanna Kapeleris, Juliana Muller Bark, Shanon Ranjit, Derek Richard, Ian Vela, Kenneth O'Byrne, Chamindie Punyadeera
Summary: This study found that hypoxic conditions enhance the proliferation and clonogenicity of non-small cell lung cancer cell lines. Additionally, cells exposed to hypoxia and reoxygenation showed altered expression of epithelial-mesenchymal transition-related genes at both mRNA and protein levels. Therefore, considering the epithelial-mesenchymal transition status is essential for a comprehensive understanding of circulating tumor cells in NSCLC.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2022)
Article
Immunology
Arutha Kulasinghe, Ning Liu, Chin Wee Tan, James Monkman, Jane E. Sinclair, Dharmesh D. Bhuva, David Godbolt, Liuliu Pan, Andy Nam, Habib Sadeghirad, Kei Sato, Gianluigi Li Bassi, Ken O'Byrne, Camila Hartmann, Anna Flavia Ribeiro Dos Santos Miggiolaro, Gustavo Lenci Marques, Lidia Zytynski Moura, Derek Richard, Mark Adams, Lucia de Noronha, Cristina Pellegrino Baena, Jacky Y. Suen, Rakesh Arora, Gabrielle T. Belz, Kirsty R. Short, Melissa J. Davis, Fernando Souza-Fonseca Guimaraes, John F. Fraser
Summary: The study reveals distinct transcriptomic profiles in cardiac tissues of SARS-CoV-2 and pH1N1 influenza infection, with upregulation of genes associated with DNA damage and repair, heat shock, and macrophage infiltration in COVID-19 patients' cardiac tissues. In comparison, pH1N1 infection showed upregulation of interferon and complement pathways. This highlights the need for further understanding of the effects on extra-pulmonary organs, including the cardiovascular system, in COVID-19 patients.
Article
Biochemistry & Molecular Biology
Tabassum Khair Barbhuiya, Mark Fisher, Eric D. Boittier, Emma Bolderson, Kenneth J. O'Byrne, Derek J. Richard, Mark Nathaniel Adams, Neha S. Gandhi
Summary: The study investigates the mechanism of CDCA3 binding to APC/C-Cdh1 through the non-canonical ABBA-like motif. The research finds that H-bonds, hydrophobic and ionic interactions within the ABBA-like motif are crucial for the binding. Alanine mutations disrupt the structure of the linker region, leading to altered affinities and binding to alternate sites on Cdh1.
Article
Oncology
Lecia V. Sequist, James Chih-Hsin Yang, Nobuyuki Yamamoto, Kenneth O'Byrne, Vera Hirsh, Tony Mok, Sarayut Lucien Geater, Sergey Orlov, Chun-Ming Tsai, Michael Boyer, Wu-Chou Su, Jaafar Bennouna, Terufumi Kato, Vera Gorbunova, Ki Hyeong Lee, Riyaz Shah, Dan Massey, Victoria Zazulina, Mehdi Shahidi, Martin Schuler
Summary: The study compared the efficacy of chemotherapy with afatinib in the treatment of EGFR-mutated lung adenocarcinoma. Results showed that afatinib prolonged progression-free survival and improved the quality of life for patients, when compared with chemotherapy.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Endocrinology & Metabolism
Mark N. Adams, Laura V. Croft, Aaron Urquhart, Mohamed Ashick Mohamed Saleem, Anja Rockstroh, Pascal H. G. Duijf, Patrick B. Thomas, Genevieve P. Ferguson, Idris Mohd Najib, Esha T. T. Shah, Emma Bolderson, Shivashankar Nagaraj, Elizabeth D. Williams, Colleen C. Nelson, Kenneth J. O'Byrne, Derek J. Richard
Summary: This study evaluated the role of hSSB1/NABP2 in modulating the cellular response to androgens and ionizing radiation in prostate cancer. The expression of hSSB1 in prostate cancer is correlated with genomic instability and it regulates pathways involved in cell cycle progression and transcription. Additionally, hSSB1 is involved in modulating androgen response through transcriptional regulation. Exploiting hSSB1 in prostate cancer treatment might improve patient outcomes in ADT and/or radiotherapy.
Review
Oncology
Eabha O'Sullivan, Anna Keogh, Brian Henderson, Stephen P. Finn, Steven G. Gray, Kathy Gately
Summary: KRAS plays a crucial role in regulating cell growth and survival, and its activation is commonly observed in various types of tumors. Recent discoveries have identified a specific pocket in the structure of KRAS, leading to the development of inhibitors that target the G12C mutation. These inhibitors, such as sotorasib and adagrasib, have been approved for the treatment of non-small-cell lung cancer, but their efficacy may be limited by resistance mechanisms in cancer cells.
Article
Oncology
Ming Tang, Joshua T. Burgess, Mark Fisher, Didier Boucher, Emma Bolderson, Neha S. Gandhi, Kenneth J. O'Byrne, Derek J. Richard, Amila Suraweera
Summary: This study aimed to explore the binding pose of COMMD4-H2B and develop a H2B peptide that disrupts the COMMD4-H2B interaction, which could serve as a potential therapeutic target for non-small cell lung cancer (NSCLC).
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Sugandha Bhatia, Jennifer H. Gunter, Joshua Burgess, Mark N. Adams, Kenneth O'Byrne, Erik W. Thompson, Pascal H. G. Duijf
Summary: Epithelial-mesenchymal plasticity (EMP) is a characteristic of cancer that promotes invasion, metastasis, and therapy resistance. This study shows that non-cancerous human epithelial lung cells can spontaneously shift towards a mesenchymal-like state without genetic changes. This suggests that acquisition of metastasis-associated features may occur prior to genetic alterations and cancerous transformation.
TRANSLATIONAL ONCOLOGY
(2023)
Article
Biology
Zachariah P. Schuurs, Alexander P. Martyn, Carl P. Soltau, Sam Beard, Esha T. Shah, Mark N. Adams, Laura V. Croft, Kenneth J. O'Byrne, Derek J. Richard, Neha S. Gandhi
Summary: This study explores small molecules that bind to hSSB1, an important protein related to the survival of cancer cells. Through computational and experimental approaches, three small molecules were discovered that prevent hSSB1 from binding to DNA, potentially interfering with the cell's ability to repair DNA. Further research is needed to understand the interaction between these compounds and cells, and to develop them as selective hSSB1 inhibitors.
Article
Chemistry, Physical
Ming Tang, Amila Suraweera, Xuqiang Nie, Zilin Li, Pinglin Lai, James W. Wells, Kenneth J. O'Byrne, Robert J. Woods, Emma Bolderson, Derek J. Richard
Summary: In this study, the atomic-level mechanisms of Banf1-DNA binding and the effects of mono- and di-phosphorylation on Banf1's DNA-binding capability were explored using molecular modelling and dynamics simulations. It was found that mono-phosphorylation induces changes in Banf1's secondary structure, leading to the elimination of its DNA-binding capability. The study also demonstrated that phosphorylated Banf1 binds to DNA with lower affinity and less stable binding poses. These findings have implications for predicting the effects of Banf1 mutations on its DNA-binding capability and potential development of therapeutic drugs targeting cell proliferation.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Multidisciplinary Sciences
Thais Sobanski, Amila Suraweera, Joshua T. Burgess, Iain Richard, Chee Man Cheong, Keyur Dave, Maddison Rose, Mark N. Adams, Kenneth J. O'Byrne, Derek J. Richard, Emma Bolderson
Summary: This study reveals that the glycolytic protein ALDOA plays a direct role in DNA double-strand break (DSB) repair. Upon DNA damage, ALDOA translocates into the nucleus and associates with the DNA DSB marker γ-H2AX. Depletion of ALDOA leads to increased DNA damage before and slower repair after ionising radiation. It is suggested that targeting ALDOA may be a potential strategy for simultaneous disruption of cancer metabolism and DNA repair.
SCIENTIFIC REPORTS
(2023)