Article
Medicine, General & Internal
Danielle Brazel, Priyanka Kumar, Hung Doan, Tianyu Pan, Weining Shen, Ling Gao, Justin T. Moyers
Summary: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with increasing incidence. This study aimed to identify actionable alterations associated with tumor mutation burden (TMB) using the OncoKB database. The findings suggest that targeted therapies may be a viable treatment option for selected MCC patients.
Review
Biochemistry & Molecular Biology
Elena Dellambra, Maria Luigia Carbone, Francesca Ricci, Francesco Ricci, Francesca Romana Di Pietro, Gaia Moretta, Sofia Verkoskaia, Elisa Feudi, Cristina M. Failla, Damiano Abeni, Luca Fania
Summary: Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin, with increasing incidence worldwide. Treatment of advanced MCC tumors with immune checkpoint inhibitors has shown effective results, highlighting the importance of immunotherapy in managing this disease.
Review
Oncology
Steffi Silling, Alexander Kreuter, Thilo Gambichler, Thomas Meyer, Eggert Stockfleth, Ulrike Wieland
Summary: Merkel cell polyomavirus (MCPyV) is a common virus on human skin, leading to the development of a rare but aggressive Merkel cell carcinoma (MCC) in older individuals, especially those with fair skin, male sex, and immunosuppression. The incidence of MCC, caused by MCPyV or UV damage, is increasing globally, with risk factors including male sex, older age, fair skin, intense UV exposure, and immunosuppression. Early diagnosis and prompt treatment are crucial for reducing MCC morbidity and mortality.
Review
Oncology
Roland Houben, Bueke Celikdemir, Thibault Kervarrec, David Schrama
Summary: By studying the cancer-inducing ability of polyomaviruses, researchers have made significant progress in understanding tumor suppressor proteins and have identified Merkel cell polyomavirus (MCPyV) as a human polyomavirus-induced cancer. Intensive research has since uncovered many details about the virus-host interaction and the molecular mechanisms by which MCPyV causes cancer. This review summarizes the current knowledge on MCPyV and MCC and discusses remaining questions.
Article
Medicine, Research & Experimental
Monique E. Verhaegen, Paul W. Harms, Julia J. Van Goor, Jacob Arche, Matthew T. Patrick, Dawn Wilbert, Haley Zabawa, Marina Grachtchouk, Chia-Jen Liu, Kevin Hu, Michael C. Kelly, Ping Chen, Thomas L. Saunders, Stephan Weidinger, Li-Jyun Syu, John S. Runge, Johann E. Gudjonsson, Sunny Y. Wong, Isaac Brownell, Marcin Cieslik, Aaron M. Udager, Arul M. Chinnaiyan, Lam C. Tsoi, Andrzej A. Dlugosz
Summary: Merkel cell carcinoma (MCC) is an aggressive skin cancer that expresses specific genes similar to skin-resident Merkel cells. Researchers have used ATOH1 to induce MCC development in mice by cellular reprogramming. By conditionally expressing MCPyV TAgs and ATOH1 in mouse epidermal cells, they were able to generate MCC-like tumor cells from hair follicles. The study confirmed the similarity between mouse and human MCCs and revealed that loss of p53 is necessary for the progression of MCC in this mouse model.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Steven D. Forsythe, Richard A. Erali, Preston Laney, Hemamylammal Sivakumar, Wencheng Li, Aleksander Skardal, Shay Soker, Konstantinos Votanopoulos
Summary: This study explores the application of patient tumor organoids (PTOs) in modeling personalized research in Merkel cell carcinoma (MCC). PTOs and immune enhanced organoids (iPTOs) were established from surgical specimens and treated with chemotherapy or immunotherapy agents. Results showed chemotherapy efficacy in some specimens while immunotherapy was not effective. Resistance to pembrolizumab correlated with the corresponding patient's treatment response. The study demonstrates the feasibility of establishing and immune enhancing MCC PTOs for personalized research and exploration of treatment regimens in the preclinical setting.
SCIENTIFIC REPORTS
(2022)
Article
Microbiology
Linbo Zhao, Michael J. Imperiale
Summary: BK polyomavirus (BKPyV) is a widespread virus infecting a large portion of the global population, with the potential to cause severe disease in immunosuppressed individuals. Researchers have successfully established an in vitro model of BKPyV persistence, showing that the virus can persist for varying periods before undergoing random genome recombination which enhances its replication ability.
Article
Dermatology
J. H. Wu, A. L. Limmer, D. Narayanan, H. Q. Doan, R. A. Simonette, P. L. Rady, S. K. Tyring
Summary: The study demonstrates that AKT has important regulatory functions in Merkel cell carcinoma cells, and inhibition of AKT has significant inhibitory effects on MCC cell proliferation by affecting proliferative pathways.
CLINICAL AND EXPERIMENTAL DERMATOLOGY
(2021)
Review
Microbiology
Nathan A. Krump, Jianxin You
Summary: MCPyV infection is common in the skin and can lead to MCC, with potential for prophylactic and targeted intervention. Understanding host responses to control MCPyV infection could inform preventive measures, while vulnerabilities in MCC associated with MCPyV could provide insights for potential solutions. The study proposes a model where inadequate restriction of MCPyV infection in aging and chronically UV-damaged skin may contribute to MCC tumorigenesis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell Biology
Thibault Kervarrec, Silke Appenzeller, Anne Tallet, Marie-Laure Jullie, Pierre Sohier, Francois Guillonneau, Arno Rutten, Patricia Berthon, Yannick Le Corre, Ewa Hainaut-Wierzbicka, Astrid Blom, Nathalie Beneton, Guido Bens, Charline Nardin, Francois Aubin, Monica Dinulescu, Sebastien Visee, Michael Herfs, Antoine Touze, Serge Guyetant, Mahtab Samimi, Roland Houben, David Schrama
Summary: This study found that wildtype MCPyV genomes and VP1 transcription exist in a subset of MCC.
Review
Biochemistry & Molecular Biology
John Charles Rotondo, Chiara Mazziotta, Carmen Lanzillotti, Mauro Tognon, Fernanda Martini
Summary: This review discusses the impact of epigenetic mechanisms on Merkel cell polyomavirus (MCPyV)-driven Merkel Cell Carcinoma (MCC), highlighting the importance of histone posttranslational modifications, DNA methylation, and microRNA regulation. The dysregulation of these epigenetic processes may have clinical significance for MCC diagnosis, prognosis, and therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Bizunesh Abere, Hongzhao Zhou, Masahiro Shuda, Donna B. Stolz, Kyle Rapchak, Patrick S. Moore, Yuan Chang
Summary: We report a new recombinase-mediated MCV minicircle (MCVmc) system that allows for easy genetic manipulation and characterization of viral gene expression kinetics during MCV replication. Our findings reveal that MCV has multiple self-encoded viral restriction mechanisms to promote viral latency over lytic replication.
Article
Medicine, General & Internal
Attila Mokanszki, Gabor Mehes, Szilvia Lilla Csoma, Sandor Kollar, Yi-Che Chang Chien
Summary: Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine malignancy often associated with sun exposure, with Merkel cell polyomavirus (MCPyV) implicated in its pathogenesis. Genetic differences were identified between MCPyV-positive and -negative MCC cases, with more pathogenic variants found in virus-associated cases. Further research is needed to understand the clinical implications of these findings.
Article
Virology
Chiara Mazziotta, Christian Felice Cervellera, Giada Badiale, Ilaria Vitali, Antoine Touze, Mauro Tognon, Fernanda Martini, John Charles Rotondo
Summary: MCCP and MCCN cells can be distinguished from each other based on their retinoic gene signature, and MCCP has several upregulated genes related to the nervous system and Merkel cell development. The study suggests a neuroendocrine origin for MCCP, which could potentially lead to the development of retinoid-based therapies for MCC.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Luz E. Ortiz, Alexander M. Pham, Hyun Jin Kwun
Summary: MCPyV's LT antigen interacts with E3 ligases to limit viral replication, and Lys 585 residue in LT is identified as the ubiquitin conjugation site, impacting MCPyV genome replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Monica P. de Andres, Richard J. Jackson, Irene Felipe, Sladjana Zagorac, Christian Pilarsky, Anna Melissa Schlitter, Jaime Martinez de Villareal, Gun Ho Jang, Eithne Costello, Steve Gallinger, Paula Ghaneh, William Greenhalf, Thomas Knoesel, Daniel H. Palmer, Petra Ruemmele, Wilko Weichert, Markus Buechler, Thilo Hackert, John P. Neoptolemos, Faiyaz Notta, Nuria Malats, Paola Martinelli, Francisco X. Real
Summary: GATA4 and GATA6 cooperate to maintain the classical phenotype in pancreatic ductal adenocarcinoma (PDAC), and their expression is associated with patient prognosis and therapeutic response, providing a theoretical basis for using them as biomarkers of prognosis and therapeutic response.
Article
Pediatrics
Julia Sanguesa, Jordi Sunyer, Raquel Garcia-Esteban, Alicia Abellan, Ana Esplugues, Judith Garcia-Aymerich, Monica Guxens, Amaia Irizar, Jordi Julvez, Leire Luque-Garcia, Ana Cristina Rodriguez-Dehli, Adonina Tardon, Maties Torrent, Jesus Vioque, Martine Vrijheid, Maribel Casas
Summary: The study suggests that vitamin D levels in pregnant women and children are associated with allergic and asthma-related symptoms in childhood. Higher vitamin D levels at 4 years old are linked to a lower risk of atopic eczema in later years.
PEDIATRIC RESEARCH
(2023)
Article
Environmental Sciences
Francesca Castiello, Beatriz Suarez, Andrea Beneito, Maria-Jose Lopez-Espinosa, Loreto Santa-Marina, Aitana Lertxundi, Adonina Tardon, Isolina Riano-Galan, Maribel Casas, Martine Vrijheid, Nicolas Olea, Mariana F. Fernandez, Carmen Freire
Summary: This study examined the associations between urinary metabolites of non-persistent pesticides and pubertal development in children from urban and rural areas in Spain. The results showed that higher concentrations of certain pesticide metabolites were associated with increased odds of pubertal development, especially in girls, and BMI may modify these associations.
ENVIRONMENTAL POLLUTION
(2023)
Article
Environmental Sciences
Alice Hinchliffe, Juan Alguacil, Wendy Bijoux, Manolis Kogevinas, Florence Menegaux, Marie-Elise Parent, Beatriz Perez Gomez, Sanni Uuksulainen, Michelle C. Turner
Summary: This study found no clear evidence for an association between occupational heat exposure and prostate cancer risk.
ENVIRONMENTAL RESEARCH
(2023)
Article
Environmental Sciences
Manolis Kogevinas, Marianna Karachaliou, Ana Espinosa, Ruth Aguilar, Gemma Castano-Vinyals, Judith Garcia-Aymerich, Anna Carreras, Beatriz Cortes, Vanessa Pleguezuelos, Kyriaki Papantoniou, Rocio Rubio, Alfons Jimenez, Marta Vidal, Pau Serra, Daniel Parras, Pere Santamaria, Luis Izquierdo, Marta Cirach, Mark Nieuwenhuijsen, Payam Dadvand, Kurt Straif, Gemma Moncunill, Rafael de Cid, Carlota Dobano, Cathryn Tonne
Summary: This study found an association between long-term exposure to air pollution and a lower antibody response to COVID-19 vaccines. Among vaccinated individuals without prior infection, higher levels of exposure to PM2.5, NO2, BC, and O3 were associated with lower vaccine antibody responses. This association persisted over time since vaccination.
ENVIRONMENTAL HEALTH PERSPECTIVES
(2023)
Article
Public, Environmental & Occupational Health
Anna Palomar-Cros, Bernard Srour, Valentina A. Andreeva, Leopold K. Fezeu, Alice Bellicha, Emmanuelle Kesse-Guyot, Serge Hercberg, Dora Romaguera, Manolis Kogevinas, Mathilde Touvier
Summary: This study investigated the longitudinal associations of meal timing, number of eating occasions, and night-time fasting duration with the incidence of type 2 diabetes (T2D). The findings showed that individuals who habitually ate breakfast after 9 AM had a higher risk of developing T2D, while the timing of the last meal was not associated with T2D incidence. Each additional eating occasion was associated with a lower risk of T2D. The duration of night-time fasting was not associated with T2D incidence, except for those who had breakfast before 8 AM and fasted for more than 13 hours overnight. This study suggests that breakfast timing affects the incidence of T2D, and an early breakfast should be considered for T2D prevention.
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Oncology
Miriam Marques, Sonia Corral, Maria Sanchez-Diaz, Natalia del Pozo, Jaime Martinez de Villarreal, Norbert Schweifer, Ivana Zagorac, Frank Hilberg, Francisco X. Real
Summary: Bladder cancer is a prevalent tumor that requires the development of novel therapies. Nintedanib, an angio-kinase inhibitor, has shown efficacy in combination with chemotherapy for locally advanced muscle-invasive bladder cancer. Our study investigated the mechanisms of action of nintedanib and identified potential markers and treatment strategies to overcome resistance.
MOLECULAR CANCER THERAPEUTICS
(2023)
Review
Oncology
Lisa M. C. van Hoogstraten, Alina Vrieling, Antoine G. van der Heijden, Manolis Kogevinas, Anke Richters, Lambertus A. Kiemeney
Summary: Bladder cancer is a significant burden for healthcare systems worldwide due to its high incidence and mortality. The occurrence of bladder cancer is influenced by factors such as population growth, aging, and exposure to risk factors like tobacco smoking. Primary prevention efforts are crucial in reducing the burden of bladder cancer, and less-invasive diagnostic approaches using urinary biomarkers show promise. Increasing awareness of risk factors and symptoms among healthcare professionals and high-risk groups is also important. Further research on the relationship between lifestyle factors and bladder cancer outcomes should be prioritized.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Review
Oncology
Belen Caramelo, Sladjana Zagorac, Sonia Corral, Miriam Marques, Francisco X. Real
Summary: Bladder cancer is a highly prevalent tumor, especially among men. The tumor microenvironment, specifically the cancer-associated fibroblasts, play an important role in tumor development and progression. However, the role of cancer-associated fibroblasts in bladder cancer is not well understood.
EUROPEAN UROLOGY ONCOLOGY
(2023)
Article
Environmental Sciences
L. Notario-Barandiaran, A. Irizar, M. Begona-Zubero, R. Soler-Blasco, G. Riutort-Mayol, A. Fernandez-Somoano, A. Tardon, M. Casas, M. Vrijheid, A. Meharg, M. Carey, C. Meharg, K. Ralphs, C. McCreanor, J. O. Grimalt, J. Vioque, A. J. Signes-Pastor
Summary: In this study, the association between adherence to the Mediterranean diet (MD) and urinary metal concentrations in children was evaluated. It was found that high adherence to MD was associated with increased urinary levels of arsenic and copper, but also an increase in non-toxic arsenobetaine concentrations.
ENVIRONMENTAL RESEARCH
(2023)
Article
Urology & Nephrology
Stella Koutros, Lambertus A. Kiemeney, Parichoy Pal Choudhury, Roger L. Milne, Evangelina Lopez de Maturana, Yuanqing Ye, Vijai Joseph, Oscar Florez-Vargas, Lars Dyrskjot, Jonine Figueroa, Diptavo Dutta, Graham G. Giles, Michelle A. T. Hildebrandt, Kenneth Offit, Manolis Kogevinas, Elisabete Weiderpass, Marjorie L. McCullough, Neal D. Freedman, Demetrius Albanes, Charles Kooperberg, Victoria K. Cortessis, Margaret R. Karagas, Alison Johnson, Molly R. Schwenn, Dalsu Baris, Helena Furberg, Dean F. Bajorin, Olivier Cussenot, Geraldine Cancel-Tassin, Simone Benhamou, Peter Kraft, Stefano Porru, Angela Carta, Timothy Bishop, Melissa C. Southey, Giuseppe Matullo, Tony Fletcher, Rajiv Kumar, Jack A. Taylor, Philippe Lamy, Frederik Prip, Mark Kalisz, Stephanie J. Weinstein, Jan G. Hengstler, Silvia Selinski, Mark Harland, Mark Teo, Anne E. Kiltie, Adonina Tardon, Consol Serra, Alfredo Carrato, Reina Garcia-Closas, Josep Lloreta, Alan Schned, Petra Lenz, Elio Riboli, Paul Brennan, Anne Tjonneland, Thomas Otto, Daniel Ovsiannikov, Frank Volkert, Sita H. Vermeulen, K. K. Aben, Tessel E. Galesloot, Constance Turman, Immaculata De Vivo, Edward Giovannucci, David J. Hunter, Chancellor Hohensee, Rebecca Hunt, Alpa V. Patel, Wen-Yi Huang, Gudmar Thorleifsson, Manuela Gago-Dominguez, Pilar Amiano, Klaus Golka, Mariana C. Stern, Wusheng Yan, Jia Liu, Shengchao Alfred, Shilpa Katta, Amy Hutchinson, Belynda Hicks, William A. Wheeler, Mark P. Purdue, Katherine A. McGlynn, Cari M. Kitahara, Christopher A. Haiman, Mark H. Greene, Thorunn Rafnar, Nilanjan Chatterjee, Stephen J. Chanock, Xifeng Wu, Francisco X. Real, Debra T. Silverman, Montserrat Garcia-Closas, Kari Stefansson, Ludmila Prokunina-Olsson, Nuria Malats, Nathaniel Rothman
Summary: A meta-analysis of 32 studies identified novel genetic variants associated with bladder cancer risk and constructed a polygenic risk score (PRS) to stratify lifetime risk. These findings provide insights into the biological underpinnings of bladder cancer and have the potential to inform future preventive strategies.
Article
Nutrition & Dietetics
Fanny Petermann-Rocha, Desiree Valera-Gran, Daniel Prieto-Botella, Dries S. Martens, Sandra Gonzalez-Palacios, Isolina Riano-Galan, Mario Murcia, Amaia Irizar, Jordi Julvez, Loreto Santa-Marina, Adonina Tardon, Jordi Sunyer, Jesus Vioque, Tim Nawrot, Eva-Maria Navarrete-Munoz
Summary: This study found that the use of high-dose folic acid supplements during pregnancy may be associated with shorter telomere length in children at age four, particularly in boys.
Article
Mathematics
Rocio Fernandez-Iglesias, Pablo Martinez-Camblor, Adonina Tardon, Ana Fernandez-Somoano
Summary: This study presents an analysis of cardiovascular measures in children, discussing the challenges in dealing with missing data and selecting the appropriate regression model. It also explores the impact of different decisions on the results.
Article
Biochemical Research Methods
Jaime Martinez de Villarreal, Mark Kalisz, Gabriel Piedrafita, Osvaldo Grana-Castro, Dafni Chondronasiou, Manuel Serrano, Francisco X. Real
Summary: Transposable elements have played a major role in shaping mammalian genomes, but little is known about their cell-type-specific expression. A cost-efficient single-cell-resolution TE expression analytical approach is needed.
Review
Biochemistry & Molecular Biology
Maria Ramal, Sonia Corral, Mark Kalisz, Eleonora Lapi, Francisco X. Real
Summary: This study systematically analyzed the transcription factors (TFs) in urothelium and bladder cancer using RNA-Seq and ATAC-Seq data. The results identified known TFs associated with luminal and basal phenotypes, as well as novel candidate TFs involved in bladder cancer and differentiation. Additionally, several TF families were suggested to be involved in urothelial cell differentiation and bladder cancer.
