Review
Oncology
Kailong Hou, Yuyang Yu, Duda Li, Yanduo Zhang, Ke Zhang, Jinkai Tong, Kunxian Yang, Shuting Jia
Summary: This article reviews the mechanisms and processes of alternative lengthening of telomeres (ALT), and identifies ALT as a potential valuable drug target for clinical telomerase-negative tumor treatment.
Article
Biochemistry & Molecular Biology
Alina Meeser, Christoph Bartenhagen, Lisa Werr, Anna-Maria Hellmann, Yvonne Kahlert, Nadine Hemstedt, Peter Nuernberg, Janine Altmueller, Sandra Ackermann, Barbara Hero, Thorsten Simon, Martin Peifer, Matthias Fischer, Carolina Rosswog
Summary: This study proposes a workflow for reliably detecting telomere maintenance mechanisms in neuroblastoma, which can be used in clinical routine for risk stratification and treatment allocation.
CELL AND BIOSCIENCE
(2022)
Article
Oncology
Banlanjo Umaru, Satarupa Sengupta, Shiva Senthil Kumar, Rachid Drissi
Summary: Pediatric high-grade gliomas (pHGGs) are aggressive tumors with a poor prognosis. This study reveals the heterogeneity of telomere maintenance mechanisms and their association with genetic alterations in pHGGs, including both ALT and telomerase activation. These findings have significant implications for the development of novel therapeutic strategies targeting ALT and telomerase in pHGGs.
Article
Multidisciplinary Sciences
Bruno Silva, Rajika Arora, Claus M. Azzalin
Summary: This study demonstrates that telomere transcription is a major trigger of alternative lengthening of telomeres (ALT) activity. Inhibiting the transcription of telomeric long noncoding RNA TERRA can suppress ALT features. Additionally, experimentally increasing TERRA transcription leads to rapid loss of telomeric DNA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Lilit Nersisyan, Arman Simonyan, Hans Binder, Arsen Arakelyan
Summary: Telomere maintenance is crucial for the indefinite divisions of cancer and stem cells. Understanding the mechanisms of telomere maintenance is important for studying cancers and developing therapies. This study reconstructed signaling pathways for ALT and TEL TMMs, and computational assessment of pathway activities revealed high ALT and TEL pathway activities in testis. This approach offers a novel option for investigating TMM activation patterns across cancers and healthy tissues.
FRONTIERS IN GENETICS
(2021)
Article
Multidisciplinary Sciences
Sabine A. Hartlieb, Lina Sieverling, Michal Nadler-Holly, Matthias Ziehm, Umut H. Toprak, Carl Herrmann, Naveed Ishaque, Konstantin Okonechnikov, Moritz Gartlgruber, Young-Gyu Park, Elisa Maria Wecht, Larissa Savelyeva, Kai-Oliver Henrich, Carolina Rosswog, Matthias Fischer, Barbara Hero, David T. W. Jones, Elke Pfaff, Olaf Witt, Stefan M. Pfister, Richard Volckmann, Jan Koster, Katharina Kiesel, Karsten Rippe, Sabine Taschner-Mandl, Peter Ambros, Benedikt Brors, Matthias Selbach, Lars Feuerbach, Frank Westermann
Summary: Alternative lengthening of telomeres (ALT) is associated with poor prognosis in neuroblastoma, often linked to mutated ATRX and reduced protein abundance, as well as the presence of frequent telomeric repeat loci and heterochromatic telomeric chromatin.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Tanya Tacheva, Shanbeh Zienolddiny, Dimo Dimov, Denitsa Vlaykova, Tatyana Vlaykova
Summary: The study suggests that COPD patients may have shorter leukocyte telomere length, and the genetic variations near TERC, particularly rs12696304 and rs10936599, may independently affect the risk of developing COPD. Carriers of the common homozygous genotype of the SNPs appeared to have a higher risk of COPD.
Article
Biochemistry & Molecular Biology
Tomas Aramburu, Joseph Kelich, Cory Rice, Emmanuel Skordalakes
Summary: Telomeric POT1-TPP1 binding is crucial for maintaining telomere integrity, and disrupting this complex can lead to cancer. This study demonstrates that the stability of POT1 is dependent on its binding with TPP1. The binding of TPP1 to POT1 stabilizes the POT1C domain and protects it from proteasomal degradation. Disruption of the POT1-TPP1 complex leads to reduced intracellular POT1 levels, telomere uncapping, and DNA damage response, which can ultimately result in cellular senescence, genomic instability, and oncogenesis.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Cell Biology
Sarah W. Cai, Titia de Lange
Summary: In this review, the authors discuss the role of the CST-Polα/Primase complex in telomere length regulation. They highlight that this complex not only functions in strand synthesis but also controls telomerase to maintain telomere length. Additionally, they emphasize the importance of this complex in preventing telomeric disorders by replenishing lost sequences and determining telomere length.
GENES & DEVELOPMENT
(2023)
Review
Biochemistry & Molecular Biology
Eleonora Vertecchi, Angela Rizzo, Erica Salvati
Summary: Telomeres, crucial for maintaining genome stability, gradually shorten over time and can determine the senescence of cells and organisms. Targeting telomere maintenance mechanisms has become an important approach for cancer treatment, as telomere length homeostasis plays a critical role in cancer development. Dysfunction in telomeres can affect intracellular signaling pathways, particularly DNA damage signaling and repair, leading to implications for cancer cell survival and proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Ryan L. Brown, Elissa E. Epel, Jue Lin, Dena B. Dubal, Aric A. Prather
Summary: Aging biomarkers may be interconnected through direct co-regulation or common processes associated with aging or stress. Klotho, an aging regulator, is involved in regulating insulin signaling, phosphate homeostasis, oxidative stress, and age-related inflammation. This study investigated the association between klotho levels and telomere length in immune cells among mothers caregiving for children with or without autism spectrum disorder (ASD), to understand the potential impact of high caregiving stress on these aging biomarkers. Our results showed a positive association between klotho levels and telomere length in certain immune cells among high-stress mothers of children with ASD, but not among low-stress mothers of neurotypical children. There were no significant associations between klotho and telomerase activity in either group.
Review
Oncology
Giulio Bonomo, Alessandro Gans, Elio Mazzapicchi, Emanuele Rubiu, Paolo Alimonti, Marica Eoli, Rosina Paterra, Bianca Pollo, Guglielmo Iess, Francesco Restelli, Jacopo Falco, Francesco Acerbi, Marco Paolo Schiariti, Paolo Ferroli, Morgan Broggi
Summary: In this paper, the clinical and diagnostic features of Sporadic Spinal Psammomatous Malignant Melanotic Nerve Sheath Tumor (SSP-MMNST) are reviewed, and possible pathogenetic mechanisms are investigated to improve therapeutic strategies. A case of a young female with SSP-MMNST arising from C5-6 right spinal roots is also reported. The study found that SSP-MMNST has a high recurrence rate and residual disease is associated with a higher risk of systemic disease spreading, suggesting the importance of adjuvant radiation therapy.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Matheus Fabiao de Lima, Monique Oliveira Freitas, Mohammad K. Hamedani, Aline Rangel-Pozzo, Xu-Dong Zhu, Sabine Mai
Summary: Telomere maintenance is crucial in cancer development. This study investigates the effects of inhibiting both telomerase and alternative lengthening of telomere (ALT) pathways in Hodgkin's Lymphoma (HL) cells. The results show that consecutive inhibition of telomerase followed by ALT inhibition significantly reduces cell viability in HL.
Article
Biochemistry & Molecular Biology
Thomas J. Brown, Lewis G. Spurgin, Hannah L. Dugdale, Jan Komdeur, Terry Burke, David S. Richardson
Summary: The length of telomeres, which are important markers of biological age, can both shorten and lengthen with age and environmental stress. This study found that telomere lengthening in females occurs in less stressful circumstances, while telomere shortening is associated with greater stress. Males, on the other hand, did not show an association between telomere dynamics and key stressors. Individuals with lengthened telomeres, both females and males, had improved subsequent survival compared to those with unchanged or shortened telomeres.
Review
Biochemistry & Molecular Biology
Daniela Muoio, Natalie Laspata, Elise Fouquerel
Summary: The ADP-ribose transferase (ART) family consists of 17 enzymes that play important roles in various biological processes, such as DNA repair, replication, and transcription regulation. Five members of this family are crucial for maintaining genome stability and protecting telomere integrity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Oncology
Maria Danieli, Carol J. Swallow, Alessandro Gronchi
Summary: Almost half of retroperitoneal sarcomas are liposarcomas, and surgery is the only potentially curative treatment. Better understanding of different histology-specific patterns and the development of outcome predictors have improved management of these rare tumors.
Article
Oncology
S. Bonvalot, C. Roland, C. Raut, C. Le Pechoux, D. Tzanis, A. M. Frezza, A. Gronchi
Summary: Until recently, the recommended approach for primary retroperitoneal sarcomas (RPS) was complete en-bloc gross excision, with (neo) adjuvant treatments as optional and unvalidated by randomized studies, leading to variations in practice among different centers. However, recent studies on surgery and adjuvant treatments have provided insights to refine these recommendations. This review aims to summarize the recent advancements and future directions in RPS management.
Article
Oncology
Anna Maria Frezza, Silvia Stacchiotti, Frederic Chibon, Jean-Michelle Coindre, Antoine Italiano, Cleofe Romagnosa, Silvia Bague, Angelo Paolo Dei Tos, Luca Braglia, Emanuela Palmerini, Vittorio Quagliuolo, Javier Martin Broto, Antonio Lopez Pousa, Giovanni Grignani, Antonella Brunello, Jean-Yves Blay, Robert Diaz Beveridge, Iwona Lugowska, Tom Lesluyes, Roberta Maestro, Franco Domenico Merlo, Paolo Giovanni Casali, Alessandro Gronchi
Summary: The results of this study suggest that CINSARC has weak prognostic power in high-risk, localized soft tissue sarcoma patients.
Article
Cell Biology
Angelo Paolo Dei Tos, Fleur Webster, Abbas Agaimy, Judith Bovee, Brendan Dickson, Leona Doyle, Sarah Dry, Alessandro Gronchi, Meera Hameed, Chris Hemmings, Bernadette Liegl-Atzwanger, Khin Thway, Andrew J. Wagner, Jian Wang, Akihiko Yoshida, Christopher Fletcher
Summary: International consensus-based datasets for the pathology reporting of soft-tissue sarcomas were produced to promote high-quality, standardized reporting and improve patient management. These datasets were developed by an international expert panel under the auspices of a global alliance of pathology and cancer organizations.
Article
Oncology
Philip Heesen, Gabriela Studer, Beata Bode, Hubi Windegger, Benjamin Staeheli, Paul Aliu, Javier Martin-Broto, Alessandro Gronchi, Jean-Yves Blay, Axel Le Cesne, Bruno Fuchs
Summary: This article presents a comprehensive analysis of quality indicators for sarcoma care and introduces a novel interoperable digital platform that gathers information from physicians and patients consecutively and instantly. The platform provides evidence of care quality by analyzing real-time world information, enabling predictive modeling and value-based health care. The lack of global data harmonization and quality standards, as well as discipline, institution, and network fragmentation, hinder the progress in sarcoma care. To improve quality, a common definition of quality indicators and the assessment of longitudinal real-time data are required. An international advisory board defined six categories of quality indicators, which were programmed into the digital platform for analysis and visualization. Standardized quality indicators and their real-time assessment are critical to improving the quality of sarcoma care.
Editorial Material
Oncology
Luca Improta, Sandro Pasquali, Sergio Valeri, Alessandro Gronchi
ANNALS OF SURGICAL ONCOLOGY
(2023)
Letter
Oncology
Jacob Lambdin, Carrie Ryan, Stephanie Gregory, Kenneth Cardona, Jonathan M. Hernandez, Winan J. van Houdt, Alessandro Gronchi
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Luca Improta, Sandro Pasquali, Sara Iadecola, Marta Barisella, Marco Fiore, Stefano Radaelli, Chiara Colombo, Rossana Alloni, Dario Callegaro, Sergio Valeri, Rosalba Miceli, Alessandro Gronchi
Summary: This study investigated the impact of histological organ involvement (HOI) on the prognosis of primary retroperitoneal liposarcoma. Initial and advanced HOIs were frequently detected in both well-differentiated and de-differentiated liposarcomas, suggesting the need for multivisceral resection. HOI stratifies the risk of patients with primary retroperitoneal liposarcoma.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Oncology
Ugo Pastorino, Giovanni Leuzzi, Federica Sabia, Paolo Girotti, Leonardo Duranti, Stefano Radaelli, Marco Fiore, Silvia Stacchiotti, Giannatempo Patrizia, Roberto Salvioni, Alessandro Gronchi
Summary: This study aimed to report the long-term survival rates of patients with rare thoracic cancers (RTCs) based on the complexity of surgical procedures and cancer type. The results showed that surgical complexity and cancer type were associated with 90-day mortality and 10-year survival rates, which can help with clinical decision making.
Article
Oncology
Claudia Giani, Stefano Radaelli, Rosalba Miceli, Lorenza Gandola, Claudia Sangalli, Anna Maria Frezza, Salvatore Provenzano, Sandro Pasquali, Rossella Bertulli, Marco Fiore, Dario Callegaro, Michela Casanova, Stefano Chiaravalli, Paola Collini, Gian Paolo Dagrada, Carlo Morosi, Nadia Zaffaroni, Paolo G. Casali, Andrea Ferrari, Alessandro Gronchi, Silvia Stacchiotti
Summary: A retrospective study on primary DSRCT was conducted to characterize long-term survivors (LTS). It was found that 13% of patients achieved cure, who had no liver or extra-abdominal metastasis at diagnosis, received complete surgery, and possibly underwent whole abdomino-pelvic radiotherapy (WAP-RT) and maintenance chemotherapy (MC).
Article
Oncology
Roberta Sanfilippo, Nadia Hindi, Josefina Cruz Jurado, Jean-Yves Blay, Antonio Lopez-Pousa, Antoine Italiano, Rosa Alvarez, Antonio Gutierrez, Inmaculada Rincon-Perez, Claudia Sangalli, Jose Luis Perez Aguiar, Jesus Romero, Carlo Morosi, Marie-Pierre Sunyach, Chiara Fabbroni, Cleofe Romagosa, Dominique Ranchere-Vince, Angelo P. Dei Tos, Paolo G. Casali, Javier Martin-Broto, Alessandro Gronchi
Summary: Preclinical data has shown the synergistic activity of radiotherapy and trabectedin. This study explored the effectiveness and safety of combining trabectedin with radiotherapy in treating myxoid liposarcomas.
Article
Orthopedics
A. Borghi, A. Gronchi
Summary: Desmoid tumors are rare fibroblastic proliferations that arise in deep soft tissues. They have locally aggressive behavior and cannot metastasize. These tumors can occur in any part of the body, but are commonly found in the limbs. Despite being benign, they can cause severe pain and functional limitations. The surgical management of desmoid tumors is complex and challenging due to limited literature and uncertainties surrounding their behavior. A shift towards a more conservative approach has occurred recently, and various medical and regional treatments have shown promising results. However, there are still many areas of controversy and further studies are needed to develop a standardized approach.
BONE & JOINT JOURNAL
(2023)
Article
Oncology
Sarah Corn, Carolyn Nessim, Christina L. Roland, Alessandro Gronchi, Carolyn Freeman, Sinziana Dumitra
Summary: Consensus guidelines recommend complete resection of retroperitoneal sarcoma and neoadjuvant radiation for curative treatment. However, a 15-month delay in the publication of the STRASS trial results created a dilemma in managing patients in the interim. This study aimed to understand perspectives on neoadjuvant radiation for RPS during this period and assess the process of integrating data into practice.
Review
Oncology
Maria Danieli, Alessandro Gronchi
Summary: Reliable tools for prognosis prediction are crucially needed by oncologists to tailor individual treatments for sarcoma patients. Nomograms, which incorporate multiple risk factors and return a numerical probability of clinical events, could better account for the granularity of sarcomas compared to the widely used TNM staging system. New dynamic nomograms and prognostic tools have been developed, allowing doctors to recalculate prognosis based on time since primary surgery, event history, and the potential time-dependent effect of covariates. This review provides an overview of available nomograms for sarcomas to assist clinicians in selecting the most suitable tool for each patient.
Letter
Surgery
Armando G. Licata, Chiara M. Ciniselli, Luca Sorrentino, Arianna Micali, Maria Grazia Daidone, Marcello Guaglio, Manuela Gariboldi, Paolo Verderio, Loris De Cecco, Maurizio Cosimelli
BRITISH JOURNAL OF SURGERY
(2023)