Article
Biochemistry & Molecular Biology
William G. J. Kerrison, Alexander T. J. Lee, Khin Thway, Robin L. Jones, Paul H. Huang
Summary: Immunotherapy in soft tissue sarcoma has become a popular and promising therapeutic strategy, with immune checkpoint inhibitors showing effectiveness in certain subtypes. Combination therapies have also shown enhanced response rates.
Review
Pharmacology & Pharmacy
Ramu Manjula, Kumari Anuja, Francisco J. Alcain
Summary: Sirtuins, a group of NAD(+) dependent histone deacetylases, play a crucial role in neuroprotection and cellular senescence. They regulate crucial proteins and can be targeted for therapeutic purposes in metabolic disorders. Their modulation shows promise in treating neurodegenerative diseases associated with aging and protein homeostasis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Luc M. Berclaz, Annelore Altendorf-Hofmann, Hans Roland Duerr, Alexander Klein, Martin K. Angele, Markus Albertsmeier, Nina-Sophie Schmidt-Hegemann, Dorit Di Gioia, Thomas Knoesel, Lars H. Lindner
Summary: TOP2A and SIRT1 expression in high-risk soft tissue sarcoma patients can significantly impact chemotherapy efficacy and overall survival, serving as important predictive indicators.
Article
Cell Biology
Na Li, Ning Bai, Xiong Zhao, Rong Cheng, Xuan Wu, Bo Jiang, Xiaoman Li, Mingli Xue, Hongde Xu, Qiqiang Guo, Wendong Guo, Mengtao Ma, Sunrun Cao, Yanling Feng, Xiaoyu Song, Zhuo Wang, Xiaoyu Zhang, Yu Zou, Difei Wang, Hua Liu, Liu Cao
Summary: Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by amyloid-beta (Aβ) deposition and neurofibrillary tangles. The ratio of SIRT2:SIRT1 is elevated in aging mice and AD mouse models, and SIRT1 overexpression prevents Aβ-induced neurotoxicity. SIRT1 inhibits the binding of SIRT2 to APP, thus reducing amyloidogenic processing of APP and providing a potential avenue for therapeutic intervention of AD.
Review
Biochemistry & Molecular Biology
Yuqing Zhang, Shailendra Anoopkumar-Dukie, Andrew Keith Davey
Summary: Depression is a psychiatric disorder with significant health burden, and current antidepressant medications targeting monoamine neurotransmitters have limited efficacy. Recent evidence suggests that neuroinflammation plays a role in depression, highlighting the importance of exploring anti-inflammatory medications for new treatment options. Sirtuins, particularly SIRT1 and SIRT2, have been implicated in inflammation and are being studied for their potential effects on depressive-like behaviors.
Article
Nutrition & Dietetics
Alberto Romano, Silvia Triarico, Emanuele Rinninella, Luigi Natale, Maria Gabriella Brizi, Marco Cintoni, Pauline Raoul, Palma Maurizi, Giorgio Attina, Stefano Mastrangelo, Antonio Gasbarrini, Maria Cristina Mele, Antonio Ruggiero
Summary: In this study, nutritional and sarcopenia status were assessed in pediatric patients with bone and soft tissue sarcomas. It was found that over half of the patients experienced sarcopenia at diagnosis, and there was a significant decrease in prognostic nutritional index (PNI) and total psoas muscle area (tPMA) after 12 months of treatment. Furthermore, a decrease in PNI was associated with poor overall survival (OS) in these patients.
Article
Oncology
Tom Wei-Wu Chen, Ruru Chun-Ju Chiang, Alex Le Cesne, Yu-Chun Hsieh, Antoine Italiano, Ya-Wen Yang, Nicolas Penel, Wen-Chung Lee, Emmanuelle Bompas, Thibaud Valentin, Philippe Anract, Nelly Firmin, Florence Duffaud, Ann-Lii Cheng, Francoise Ducimetiere, K. Arnold Chan, Jean-Yves Blay
Summary: The study found significant differences in the incidence and clinical characteristics of soft tissue sarcoma (STS) among different geographic and ethnic populations, suggesting that geographic and ethnic factors may play a crucial role in the pathogenesis of STS.
Article
Oncology
Do Weon Lee, Han-Soo Kim, Ilkyu Han
Summary: The study found that actual 5-year survival in stage III soft tissue sarcoma patients is associated with tumor size, histological grade, and ASA score. Nevertheless, the majority of long-term survivors still exhibit factors of poor prognosis.
Review
Pharmacology & Pharmacy
Tomoki Nakamura, Akihiro Sudo
Summary: Trabectedin is a safe and effective therapeutic option for patients with advanced STS. While it may be effective as first-line treatment in selected patients, doxorubicin remains the preferred choice for locally advanced or metastatic STS.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xin-Yu Ke, Ye Chen, Valarie Yu-Yan Tham, Ruby Yu-Tong Lin, Pushkar Dakle, Kassoum Nacro, Mark Edward Puhaindran, Peter Houghton, Angela Pang, Victor Kwanmin Lee, Ling-Wen Ding, Sigal Gery, Jeffrey Hill, Leilei Chen, Liang Xu, H. Phillip Koeffler
Summary: Depletion of MNK1/2 suppresses growth of soft tissue sarcoma cells, and a novel MNK inhibitor ETC-168 shows significant antiproliferative efficacy. Combination of ETC-168 with MCL1 inhibitor exerts synergistic antiproliferative activity against STS cells. This study highlights the potential clinical translation of MNK inhibitors for the treatment of soft tissue sarcoma.
Article
Biochemistry & Molecular Biology
Wenjie Gong, Lei Wang, Maria-Luisa Schubert, Christian Kleist, Brigitte Neuber, Sanmei Wang, Mingya Yang, Angela Huckelhoven-Krauss, Depei Wu, Anita Schmitt, Carsten Muller-Tidow, Hiroshi Shiku, Michael Schmitt, Leopold Sellner
Summary: This study investigated the potential of modulating the expression of the cancer-testis antigen NY-ESO-1 using histone deacetylase inhibitors (HDACis). The results showed that pretreatment with HDACi can enhance the cytotoxic efficacy of NY-ESO-1-specific T cells against NY-ESO-1-positive soft tissue sarcoma (STS) cells. Additionally, HDACis can enhance the immune reactivity of NY-ESO-1-specific T cells.
Article
Oncology
Gianni Bisogno, Veronique Minard-Colin, Ilaria Zanetti, Andrea Ferrari, Soledad Gallego, Raquel Davila Fajardo, Henry Mandeville, Anna Kelsey, Rita Alaggio, Daniel Orbach, Sheila Terwisscha van Scheltinga, Gabriela Guillen Burrieza, Myriam Ben-Arush, Heidi Glosli, Peter Mudry, Sima Ferman, Christine Devalck, Anne Sophie Defachelles, Johannes Hendrikus Maria Merks, Meriel Jenney
Summary: Clinical Trial Updates provide an opportunity to disseminate additional results from studies when the primary end point has already been reported. The RMS2005 study demonstrated that 80% of children with localized rhabdomyosarcoma could be long-term survivors. The study has established the standard of care across the European pediatric Soft tissue sarcoma Study Group countries.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Monika Sparber-Sauer, Andrea Ferrari, Sheri L. Spunt, Christian Vokuhl, Dana Casey, Timothy B. Lautz, William H. Meyer, David O. Walterhouse, Kristian W. Pajtler, Rita Alaggio, Andreas Schmidt, Akmal Safwat, Beate Timmermann, Patrizia Dall'Igna, Sonja Chen, Aaron R. Weiss, Daniel Orbach
Summary: The background discusses the controversial issue of margin status following surgery in pediatric soft tissue sarcomas and the need for international harmonized recommendations. The INSTRuCT NRSTS working group aims to develop common guidelines by pooling and mining clinical trial data from various cooperative groups. This review addresses accepted principles, controversies, and perspectives from different specialties to build a framework for future research.
Article
Oncology
Daniel Orbach, Max M. Van Noesel, Bernadette Brennan, Nadege Corradini, Rita Alaggio, Myriam Ben Arush, Reineke A. Schoot, Pablo Berlanga, Ilaria Zanetti, Lisa Lyngsie Hjalgrim, Federica Di Corti, Gema Ramirez, Michela Casanova, Andrea Ferrari
Summary: The European pediatric Soft tissue sarcoma Study Group analyzed children with epithelioid hemangioendothelioma and found that most of them survived after treatment, with high five-year progression-free survival and overall survival rates.
PEDIATRIC BLOOD & CANCER
(2022)
Review
Biochemistry & Molecular Biology
Clara Savary, Cecile Picard, Nadege Corradini, Marie Castets
Summary: This article discusses how cellular reprogramming mediated by driver genes in soft tissue sarcoma can reshape the characteristics of transformed cells and emphasizes the importance of the epigenetic context of genetic alterations in the initiation and progression of tumors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Ellin-Kristina Hillert, Slavica Brnjic, Xiaonan Zhang, Magdalena Mazurkiewicz, Amir Ata Saei, Arjan Mofers, Karthik Selvaraj, Roman Zubarev, Stig Linder, Padraig D'Arcy
Article
Biochemistry & Molecular Biology
Margit Kaldmae, Axel Leppert, Gefei Chen, Medoune Sarr, Cagla Sahin, Kerstin Nordling, Nina Kronqvist, Marta Gonzalvo-Ulla, Nicolas Fritz, Axel Abelein, Sonia Lain, Henrik Biverstal, Hans Jornvall, David P. Lane, Anna Rising, Jan Johansson, Michael Landreh
Review
Biochemistry & Molecular Biology
Valentino Clemente, Padraig D'Arcy, Martina Bazzaro
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Chemistry, Medicinal
Gergana Popova, Marcus J. G. W. Ladds, Lars Johansson, Aljona Saleh, Johanna Larsson, Lars Sandberg, Sara Haggblad Sahlberg, Weixing Qian, Hjalmar Gullberg, Neeraj Garg, Anna-Lena Gustavsson, Martin Haraldsson, David Lane, Ulrika Yngve, Sonia Lain
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Oncology
Tanzina Mollick, Sonia Lain
CANCER & METABOLISM
(2020)
Article
Biochemistry & Molecular Biology
Marcus J. G. W. Ladds, Gergana Popova, Andres Pastor-Fernandez, Srinivasaraghavan Kannan, Ingeborg M. M. van Leeuwen, Maria Hakansson, Bjorn Walse, Fredrik Tholander, Ravi Bhatia, Chandra S. Verma, David P. Lane, Sonia Lain
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Pharmacology & Pharmacy
Arjan Mofers, Karthik Selvaraju, Johannes Gubat, Padraig D 'Arcy, Stig Linder
EUROPEAN JOURNAL OF PHARMACOLOGY
(2020)
Article
Multidisciplinary Sciences
Juan Zhang, Graciela Teran, Mihaela Popa, Harsha Madapura, Marcus James Graeme Watson Ladds, Danai Lianoudaki, Jacob Grunler, Marie Arsenian-Henriksson, Emmet McCormack, Martin Enrique Rottenberg, Sergiu-Bogdan Catrina, Sonia Lain, Suhas Darekar
Summary: Pharmacological inhibition of DHODH reduces mitochondrial respiration, promotes glycolysis, enhances GLUT4 translocation, increases expression of GDF15 through p53 activation, and leads to reduced appetite and prolonged lifespan. DHODH inhibitors also elevate levels of circulating GDF15 and improve metabolic balance in obesity-induced diabetes models.
Article
Biochemistry & Molecular Biology
Karthik Selvaraju, Kourosh Lotfi, Johannes Gubat, Maria Miquel, Amanda Nilsson, Julia Hill, Lasse D. Jensen, Stig Linder, Padraig D'Arcy
Summary: The dienone compound VLX1570 exhibits tumor cell selectivity, targeting the ubiquitin-proteasome system (UPS) in acute myeloid leukemia (AML) cells. It induces ER stress, accumulation of ubiquitin complexes, and loss of cell viability in a dose-dependent manner, with Caspase activation but not glutathione depletion correlating to sensitivity.
Article
Pharmacology & Pharmacy
Diego Colombo, Laura Gatti, Linda Sjostrand, Nives Carenini, Matteo Costantino, Elisabetta Corna, Noemi Arrighetti, Marco Zuccolo, Michelandrea De Cesare, Stig Linder, Padraig D'Arcy, Paola Perego
Summary: This study reveals the therapeutic potential of the curcumin derivative CAPE in enhancing the efficacy of cisplatin in ovarian carcinoma, especially in cisplatin-resistant tumors. The synergy between CAPE and cisplatin is dependent on the expression level of the ubiquitin-specific protease 8 (USP8).
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Oncology
Johannes Gubat, Karthik Selvaraju, Linda Sjoestrand, Dhananjay Kumar Singh, Maria V. Turkina, Bernhard Schmierer, Pierre Sabatier, Roman A. Zubarev, Stig Linder, Padraig D'Arcy
Summary: Dienone compounds have tumor-selective anti-cancer activity regardless of TP53 mutation status. Previous studies have shown that these compounds induce cell death by inhibiting the ubiquitin-proteasome system (UPS). In this study, it was found that the dienone compound b-AP15 inhibits proteasomal degradation of long-lived proteins.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Suhas Darekar, Sonia Lain
Summary: Enzymes involved in nucleotide synthesis can form large filament structures called rods and rings, which may be asymmetrically inherited during mammalian cell division and influence cell fate. This asymmetric inheritance, coupled with the dynamic nature of these structures, enables plasticity in a cell population.
Article
Cell Biology
Twana Alkasalias, Juan Zhang, Harsha Madapura, Basile Dalarun, Oscar Bedoya Reina, Rolf Lewensohn, Kristina Viktorsson, Abbas Salihi, Suhas Darekar, Sonia Lain
Summary: This study aims to explore strategies to protect activated T cells from DHODH inhibitors and identify cancer types hypersensitive to these inhibitors. The findings suggest that selecting patients with low-CDA expressing cancers in combination with strategies to increase cytidine or the cytidine/uridine ratio in the extracellular environment can improve the therapeutic index of DHODH inhibitors.
CELL DEATH DISCOVERY
(2022)
Correction
Cell Biology
Twana Alkasalias, Juan Zhang, Harsha Madapura, Basile Dalarun, Oscar Bedoya Reina, Rolf Lewensohn, Kristina Viktorsson, Abbas Salihi, Suhas Darekar, Sonia Lain
CELL DEATH DISCOVERY
(2022)
Article
Nanoscience & Nanotechnology
Geyunjian H. Zhu, Mohammad Azharuddin, Bapan Pramanik, Karin Roberg, Sujoy Kumar Biswas, Padraig D'arcy, Meng Lu, Apanpreet Kaur, Alexander Chen, Ashis Kumar Dhara, Alexandru Chivu, Yunhui Zhuang, Andrew Baker, Xiewen Liu, David Fairen-Jimenez, Bismoy Mazumder, Rongjun Chen, Clemens F. Kaminski, Gabriele S. Kaminski Schierle, Jorma Hinkula, Nigel K. H. Slater, Hirak K. Patra
Summary: Despite advancements in nanomedicine research, there are limited nanoformulations available on the market and few have been translated to clinics. This study introduces an instant drug formulation method using a coacervate-like nanosystem, which enhances intracellular drug delivery. The results demonstrate the feasibility of this technique and its potential application in the nanomedicine field to overcome the challenges of large-scale production and long-term storage of nanomaterials.
ACS APPLIED MATERIALS & INTERFACES
(2023)