Article
Biology
David Cerna, Bora Lim, Yusuf Adelabu, Stephen Yoo, Donna Carter, Ahmed Fahim, Yasuhiro Mitsuuchi, Beverly A. Teicher, Eric Bernhard, C. Norman Coleman, Naoko Takebe, Mansoor M. Ahmed
Summary: Research has shown that birinapant can enhance the radiosensitivity of glioblastoma cell lines, with particularly significant effects observed in the U-251 cell line. The combination treatment of birinapant and radiation therapy demonstrated tumor growth delay and a survival benefit in both in vitro and in vivo models, warranting further investigation into this potential treatment approach.
RADIATION RESEARCH
(2021)
Article
Cell Biology
Lidia F. Hernandez, Angie B. Dull, Soumya Korrapati, Christina M. Annunziata
Summary: Ovarian cancer, the most lethal gynecological cancer in the US, is characterized by resistance to chemotherapy. Low Caspase 8 expression levels are associated with resistance to apoptotic chemotherapy in ovarian cancers. Combination treatment with a Smac-mimetic can increase cell death in tumor cells with low Caspase 8, leading to decreased tumor growth and enhanced overall survival in mouse models. Timing of drug administration is crucial for optimizing treatment outcomes.
CELL DEATH DISCOVERY
(2021)
Article
Biology
Sahar Rafat, Prabhakar Singh, Kamlesh Kumar Pandey, Saleh A. Almatroodi, Mohammed A. Alsahli, Ahmad Almatroudi, Arshad Husain Rahmani, Kapil Dev
Summary: This study investigates the role of SMAC mimetic compound BV6 in regulating cell death mechanisms and its potential anti-cancer effect in combination with TRAIL and TNFα in breast cancer cells. The study suggests that BV6 alone and in combination with TRAIL and TNFα show promising results in inhibiting cancer growth. Additionally, IAPs and autophagic proteins may serve as important targets for the development of novel anti-cancer drugs.
Article
Biochemistry & Molecular Biology
Lei Wang, Changhua Hu, Yu Zhao, Xiaoquan Hu
Summary: In this study, a novel Smac mimetic, ASTX660, was shown to induce necroptosis in apoptosis-insensitive bladder cancer (BC) cells. Mechanistically, ASTX660 promoted the formation of the necrosome complex, and its efficacy was dependent on TNF-alpha signaling and IRF1 after caspase inhibition. These findings suggest that ASTX660 can overcome the limitation of apoptosis induction and provide important clues for the design of a novel treatment strategy for BC.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jin Koo Kim, Insoon Chang, Younghun Jung, Zach Kaplan, Elliott E. Hill, Russell S. Taichman, Paul H. Krebsbach
Summary: This study reveals that chronic and persistent M. hyorhinis infection induces TNF-alpha secretion from PCa cells, leading to activation of the NF-kappa B pathway. It also shows that M. hyorhinis-induced TNF-alpha plays a crucial role in promoting the malignant transformation of PCa. Furthermore, the study suggests that SMAC mimetics can enhance caspase activation and cell death in M. hyorhinis-infected PCa cells. These findings contribute to the understanding of mycoplasma-oncogenesis process and provide potential approaches for preventing, diagnosing, and treating prostate cancers.
Article
Multidisciplinary Sciences
Moritz Hunkeler, Cyrus Y. Jin, Eric S. Fischer
Summary: Tightly regulating apoptosis is crucial for the development of multicellular organisms and preventing diseases like cancer and neurodegeneration. Caspase activation is key to apoptosis, and inhibitor of apoptosis proteins (IAPs) are important for restraining caspase activity and can be targeted therapeutically. IAPs, in turn, are regulated by proapoptotic factors derived from mitochondria like SMAC and HTRA2. By studying the structures of human baculoviral IAP repeat-containing protein 6 (BIRC6) bound to SMAC, caspases, and HTRA2 through cryo-electron microscopy, we gain a molecular understanding of how BIRC6 inhibits caspase activity and how it is released by SMAC.
Article
Oncology
Yusuke Shibuya, Kei Kudo, Kristen P. Zeligs, David Anderson, Lidia Hernandez, Franklin Ning, Christopher B. Cole, Maria Fergusson, Noemi Kedei, John Lyons, Jason Taylor, Soumya Korrapati, Christina M. Annunziata
Summary: The combination of SMAC mimetics and HDAC inhibitors is a promising strategy for cancer treatment. HDAC inhibitors stimulate TNF-alpha production, which synergizes with SMAC mimetics. Overexpression of IAP proteins is associated with poor survival in ovarian cancer, and SMAC mimetics restore apoptotic pathways by suppressing IAP functions.
Article
Immunology
Xin Liu, Jimmy J. Yao, Zhongxuan Chen, Wei Lei, Rong Duan, Zhenqiang Yao
Summary: We found that lipopolysaccharide (LPS) enhances the efficacy of inhibitor of apoptosis protein (IAP) antagonists in treating breast cancer. LPS induces rapid apoptosis of cancer cells by promoting the production of TNF alpha through TLR4 and MyD88 pathways.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shaikh Maryam Ghufran, Sachin Sharma, Sampa Ghose, Subhrajit Biswas
Summary: TNF alpha induces cell survival in activated hepatic stellate cells (HSCs) through NF-kappa B signaling, and cIAP2 plays a regulatory role in this process. Inhibition of cIAP2 can attenuate TNF alpha-induced cell viability and activation of the NF-kappa B signaling pathway, and it has anti-proliferative effects on activated HSCs. Targeting cIAP2 in the NF-kappa B signaling pathway may be a promising approach for the treatment of liver fibrosis.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Hematology
Naveen Pemmaraju, Bing Z. Carter, Prithviraj Bose, Nitin Jain, Tapan M. Kadia, Guillermo Garcia-Manero, Carlos E. Bueso-Ramos, Courtney D. DiNardo, Sharon Bledsoe, Naval G. Daver, Uday Popat, Marina Y. Konopleva, Lingsha Zhou, Sherry Pierce, Zeev E. Estrov, Gautam M. Borthakur, Maro Ohanian, Wei Qiao, Lucia Masarova, Xuemei Wang, Po Yee Mak, Jorge Cortes, Elias Jabbour, Srdan Verstovsek
Summary: Treatment with SMAC mimetic LCL161 in high-risk and treatment-resistant MF patients showed a 30% objective response rate, with 6 patients achieving clinical improvement in anemia. The median overall survival was 34 months, and while there were some adverse events, two deaths during the study period were unrelated to the study drug.
Article
Biochemistry & Molecular Biology
Simona Dedoni, Alessandra Olianas, Barbara Manconi, Maria Collu, Barbara Tuveri, Maria Elena Vincis, Maria C. Olianas, Pierluigi Onali
Summary: HDAC inhibitors can induce the expression of p75NTR in neuroblastoma cells, which can be exploited to enhance the cytotoxic effect of a toxin-conjugated anti-p75NTR antibody. This novel therapeutic strategy showed promising anti-tumor effects in neuroblastoma cell cultures and murine xenograft models.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Fei Ding, Xi Luo, Yiting Tu, Xianlan Duan, Jia Liu, Lijing Jia, Peilin Zheng
Summary: The findings suggest that Alpk1 plays a crucial role in cytokine-induced beta cell apoptosis and its activation can exacerbate cytokine-induced apoptosis by potentiating the TNF-α signaling pathway. Additionally, Alpk1 activation may further induce the expression of proteins such as TNF-α and Fas, contributing to beta cell failure and T1D development. Treatment with GLP-1 receptor agonist could decrease TNF-α and Fas expression, improving the survival of beta cells exposed to pro-inflammatory cytokines and ADP heptose.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Mohammed Salah Ayou, Yasmin Wahby, Hamida Abdel-Hamid, Marwa M. Abu-Serie, Mohamed Teleb
Summary: This study explores a new approach to induce apoptosis by selectively activating caspase-3 to eliminate tumors. Compounds prepared by optimized Passerini reaction showed highly efficient anticancer activity against cancer cells in vitro. Further mechanistic studies demonstrated the compounds' action through caspase activation and apoptotic induction.
SCIENTIFIC REPORTS
(2022)
Article
Biology
Weiqiang Xu, Fang Fang, Yuexuan Wang, Lijing Qin, Yu Han, Yuwei Huang, Bin Li, Yang Liu, Zhicheng Wang
Summary: Research suggests that inducing pro-apoptosis in cancer cells through TRAIL and Smac overexpression could benefit radiotherapy in enhancing anti-cancer effects. The study designed a novel adenoviral vector with conditional expression of TRAIL and Smac to specifically target tumors, resulting in enhanced proliferation inhibition and radio-sensitivity through apoptosis in breast cancer cells. The findings indicate that the combined treatment of IR and TRAIL/Smac overexpression can activate more apoptotic pathways in tumor cells, potentially providing insights for new radiotherapy plans in breast tumor treatment.
RADIATION AND ENVIRONMENTAL BIOPHYSICS
(2022)
Article
Toxicology
Lisa Haasler, Arun Kumar Kondadi, Thanos Tsigaras, Claudia von Montfort, Peter Graf, Wilhelm Stahl, Peter Brenneisen
Summary: The study demonstrated that (+/-) gossypol induces cell death in A375 melanoma cells without significant toxicity to normal cells. This cell death is achieved through a ROS-independent but caspase-dependent apoptosis pathway.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Multidisciplinary Sciences
Angelika Beyer, Kilson Moon, Peter Penndorf, Thomas Hirsch, Uta Zahn-Tesch, Wolfgang Hoffmann, Holger N. Lode, Neeltje van den Berg
Summary: In regions with a low density of paediatric care facilities, telemedical triage using a video conferencing system can improve acute paediatric care.
Article
Oncology
Monika Scheer, Erika Hallmen, Christian Vokuhl, Joerg Fuchs, Per-Ulf Tunn, Marc Muenter, Beate Timmermann, Sebastian Bauer, Anton George Henssen, Bernarda Kazanowska, Felix Niggli, Ruth Ladenstein, Gustaf Ljungman, Angelika Eggert, Thomas Klingebiel, Ewa Koscielniak
Summary: This study evaluated the effects of neoadjuvant or adjuvant radiation therapy and surgery only on long-term outcomes in patients with synovial sarcoma. The results showed that the best local control was achieved when tumors were irradiated pre-operatively and underwent R0 or R1 resection thereafter.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Letter
Hematology
Michael Launspach, Dennis Temel, Emily Ohlendorf, Felix Zirngibl, Bianca Materne, Lena Oevermann, Hedwig E. Deubzer, Anton G. Henssen, Annette Kunkele, Patrick Hundsdorfer, Horst von Bernuth, Axel Pruss, Angelika Eggert, Arend von Stackelberg, Peter Lang, Johannes H. Schulte
Article
Medicine, Research & Experimental
Michela Carlet, Karin Schmelz, Jenny Vergalli, Tobias Herold, Daniela Senft, Vindi Jurinovic, Thomas Hoffmann, Jutta Proba, Nina Weichert, Christian Junghanss, Mareike Roth, Georg Eschenburg, Malwine Barz, Guenter Henze, Cornelia Eckert, Angelika Eggert, Johannes Zuber, Patrick Hundsdoerfer, Irmela Jeremias
Summary: In this study, researchers found that Smac mimetics (SM) could enhance the sensitivity of relapsed/refractory acute lymphoblastic leukemia (r/r ALL) cells to chemotherapy drugs. They also identified a crucial role of inhibitor of apoptosis proteins (IAP) in r/r ALL, suggesting that IAP could be a potential therapeutic target for r/r ALL.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Jonas Ecker, Florian Selt, Dominik Sturm, Martin Sill, Andrey Korshunov, Steffen Hirsch, David Capper, Nicola Dikow, Christian Sutter, Carina Mueller, Romain Sigaud, Angelika Eggert, Thorsten Simon, Tim Niehues, Andreas von Deimling, Kristian W. Pajtler, Cornelis M. van Tilburg, David T. W. Jones, Felix Sahm, Stefan M. Pfister, Olaf Witt, Till Milde
Summary: The PTT 2.0 program aims to improve diagnostic accuracy and detect actionable alterations in relapsed pediatric oncology patients, even with limited tumor material. The study utilized molecular analyses such as DNA methylation array, targeted gene panel sequencing, RNA sequencing, and immunohistochemistry to provide relevant and robust information for diagnosis and treatment decisions.
EUROPEAN JOURNAL OF CANCER
(2023)
Article
Immunology
Sara Marie Ivasko, Kathleen Anders, Laura Grunewald, Michael Launspach, Anika Klaus, Silke Schwiebert, Peter Ruf, Horst Lindhofer, Holger N. N. Lode, Lena Andersch, Johannes H. H. Schulte, Angelika Eggert, Patrick Hundsdoerfer, Annette Kuenkele, Felix Zirngibl
Summary: Despite advances in treatment, relapse is still a concern for a significant number of high-risk neuroblastoma patients. Bispecific trifunctional antibodies (trAbs) have shown promising potential as a new immunotherapy for neuroblastoma. The SUREK trAb has been demonstrated to effectively kill neuroblastoma cells and enhance adaptive immune responses through binding to antigen-presenting cells. Combining trAb therapy with anti-PD-1 checkpoint blockade may further improve treatment outcomes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Sascha Troschke-Meurer, Maxi Zumpe, Lena Meissner, Nikolai Siebert, Piotr Grabarczyk, Hannes Forkel, Claudia Maletzki, Sander Bekeschus, Holger N. N. Lode
Summary: We investigated the effects of combining chemotherapeutics with ch14.18/CHO (dinutuximab beta, DB) in high-risk neuroblastoma patients. The combined treatment showed a significantly stronger cytotoxic effect compared to chemotherapy alone, supporting further clinical evaluation of DB in frontline therapy.
Article
Public, Environmental & Occupational Health
Daniel Maier, Joerg Janne Vehreschild, Barbara Uhl, Sandra Meyer, Karin Berger-Thuermel, Melanie Boerries, Rickmer Braren, Viktor Gruenwald, Boris Hadaschik, Stefan Palm, Susanne Singer, Martin Stuschke, David Juarez, Pierre Delpy, Mohamed Lambarki, Michael Hummel, Caecilia Engels, Stefanie Andreas, Nicola Goekbuget, Kristina Ihrig, Susen Burock, Dietmar Keune, Angelika Eggert, Ulrich Keilholz, Hagen Schulz, Daniel Buettner, Steffen Loeck, Mechthild Krause, Mirko Esins, Frank Ressing, Martin Schuler, Christian Brandts, Daniel P. Brucker, Gabriele Husmann, Thomas Oellerich, Patrick Metzger, Frederik Voigt, Anna L. Illert, Matthias Theobald, Thomas Kindler, Ursula Sudhof, Achim Reckmann, Felix Schwinghammer, Daniel Nasseh, Wilko Weichert, Michael von Bergwelt-Baildon, Michael Bitzer, Nisar Malek, Oeznur Oener, Klaus Schulze-Osthoff, Stefan Bartels, Joerg Haier, Raimund Ammann, Anja Franziska Schmidt, Bernd Guenther, Melanie Janning, Bernd Kasper, Sonja Loges, Stephan Stilgenbauer, Peter Kuhn, Eugen Tausch, Silvana Runow, Alexander Kerscher, Michael Neumann, Martin Breu, Martin Lablans, Hubert Serve
Summary: The Clinical Communication Platform of the German Cancer Consortium is a potential catalyst for translational cancer research, providing comprehensive patient groups and improving understanding of the clinical course of various malignancies. It serves as a decision-making tool for clinical trial design and contributes to the evaluation of scientific findings in real-world conditions.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Oncology
Tim Flaadt, Ruth L. Ladenstein, Martin Ebinger, Holger N. Lode, Helga Bjoerk Arnardottir, Ulrike Poetschger, Wolfgang Schwinger, Roland Meisel, Friedhelm R. Schuster, Michaela Doering, Peter F. Ambros, Manon Queudeville, Joerg Fuchs, Steven W. Warmann, Juergen Schaefer, Christian Seitz, Patrick Schlegel, Ines B. Brecht, Ursula Holzer, Tobias Feuchtinger, Thorsten Simon, Johannes H. Schulte, Angelika Eggert, Heiko-Manuel Teltschik, Toni Illhardt, Rupert Handgretinger, Peter Lang
Summary: This study investigates the use of haploidentical stem cell transplantation and the anti-GD2 antibody dinutuximab beta (DB) in treating patients with relapsed high-risk neuroblastoma (rHR-NB). The results show that DB therapy is feasible and improves the chances of cure in rHR-NB patients.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Genetics & Heredity
Rocio Chamorro Gonzalez, Thomas Conrad, Maja C. Stoeber, Robin Xu, Madalina Giurgiu, Elias Rodriguez-Fos, Katharina Kasack, Lotte Brueckner, Eric van Leen, Konstantin Helmsauer, Heathcliff Dorado Garcia, Maria E. Stefanova, King L. Hung, Yi Bei, Karin Schmelz, Marco Lodrini, Stefan Mundlos, Howard Y. Chang, Hedwig E. Deubzer, Sascha Sauer, Angelika Eggert, Johannes H. Schulte, Roland F. Schwarz, Kerstin Haase, Richard P. Koche, Anton G. Henssen
Summary: This study presents a method called scEC&T-seq that allows parallel sequencing of circular DNA and full-length mRNA from individual cancer cells. The research reveals intercellular differences in ecDNA content, structural heterogeneity, and transcriptional impact. The findings suggest that oncogene-containing ecDNAs are clonally present in cancer cells and drive intercellular oncogene expression differences, while other small circular DNAs are exclusive to individual cells.
Article
Immunology
Julia Scheiermann, Annette Kuenkele, Arend von Stackelberg, Angelika Eggert, Peter Lang, Felix Zirngibl, Luise Martin, Johannes Hubertus Schulte, Horst von Bernuth
Summary: Chronic granulomatous disease is a congenital immunodeficiency disorder caused by a disruption in the function of the NADPH oxidase complex. It leads to impaired respiratory burst and inadequate killing of bacteria and fungi. Allogeneic HSCT is the only available curative therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Niklas Abele, Soenke Langner, Ute Felbor, Holger Lode, Norbert Hosten
Summary: This study analyzed the quantified diffusion weighed imaging in MRI for neuroblastoma. It found that there is a significant increase in the apparent diffusion coefficient for regressive diseases and a decrease for progressive diseases. This change can be observed within the first 120 days of therapy. Neuroblastoma is a common malignant tumor in children, and MRI with contrast-enhanced and diffusion-weighted imaging is used for staging and therapy monitoring. The study evaluated the early change in the ADC values under therapy and its correlation with the form of therapy and prognosis.
Article
Health Care Sciences & Services
Tabea Troschke, Aleksandra Wieczorek, Konrad Kulinski, Tomasz Ociepa, Karolina Zielezinska, Holger N. Lode, Tomasz Urasinski
Summary: This article presents the development, implementation, and management of a German-Polish telemedicine network in pediatric oncology and hematology in the Euroregion Pomerania. It discusses the achievements and challenges of joint medical case reviews and cross-border education activities. The article also includes a progress report, evaluation results of participants and teachers, and knowledge growth measurement.
Article
Medicine, General & Internal
Tim Flaadt, Martin Ebinger, Malin Schreiber, Ruth L. Ladenstein, Thorsten Simon, Holger N. Lode, Barbara Hero, Martin U. Schuhmann, Jurgen Schaefer, Frank Paulsen, Beate Timmermann, Angelika Eggert, Peter Lang
Summary: Haploidentical stem cell transplantation (haplo-SCT) followed by dinutuximab beta+/- subcutaneous interleukin-2 (scIL-2) is a promising treatment option with good tolerability for patients with high-risk neuroblastoma (HRNB) and central nervous system (CNS) relapse.
JOURNAL OF CLINICAL MEDICINE
(2023)