Letter
Surgery
Bing Deng, Chunguang Liu
Summary: This article presents a case of VHL disease with negative VHL variant detected through peripheral blood DNA analysis, suggesting the possibility of somatic mosaicism.
ASIAN JOURNAL OF SURGERY
(2023)
Article
Oncology
Dali Tong, Yao Zhang, Jun Jiang, Gang Bi
Summary: This study diagnosed a rare atypical VHL syndrome using CT scan, pathological and genetic examination methods. The patient had a confirmed VHL mutation associated with bilateral pheochromocytoma, lung carcinoid, and pancreatic neuroendocrine tumor. Based on literature reviews, octreotide-based radionuclide therapy was recommended for the patient, highlighting the relationship between VHL genotype and phenotype.
CANCER CELL INTERNATIONAL
(2021)
Article
Oncology
Wendy P. G. Wolters, Koen M. A. Dreijerink, Rachel H. Giles, Anouk N. A. van der Horst-Schrivers, Bernadette van Nesselrooij, Wouter T. Zandee, Henri J. L. M. Timmers, Tatjana Seute, Wouter W. de Herder, Annemarie A. Verrijn Stuart, Emine Kilic, Willem M. Brinkman, Patricia J. Zondervan, W. Peter Vandertop, Anthony B. Daniels, Tijmen Wolbers, Thera P. Links, Rachel S. van Leeuwaarde
Summary: This article aims to establish a multidisciplinary integrated care pathway for individuals with von Hippel-Lindau (VHL) disease. Through a modified Delphi consensus-making process, a panel of experts developed a comprehensive care pathway for VHL patients, which can be implemented in specialized clinics or nonacademic treatment clinics.
Article
Ophthalmology
Michael Reich, Sabine Jaegle, Elke Neumann-Haefelin, Jan-Helge Klingler, Charlotte Evers, Moritz Daniel, Felicitas Bucher, Franziska Ludwig, Simone Nuessle, Julia Kopp, Daniel Boehringer, Thomas Reinhard, Wolf A. Lagreze, Clemens Lange, Hansjuergen Agostini, Stefan J. Lang
Summary: This study found that the onset age and incidence of HR, CNSH, ccRCC, and PNEN in VHL patients are closely related to the type of genetic mutation, with patients with TV mutations showing higher incidence rates and earlier onset ages compared to those with AASD mutations, indicating a need for closer ophthalmological monitoring.
ACTA OPHTHALMOLOGICA
(2021)
Article
Biochemistry & Molecular Biology
Adam Serghini, Stephanie Portelli, Guillaume Troadec, Catherine Song, Qisheng Pan, Douglas E. Pires, David B. Ascher
Summary: This study manually curated VHL gene mutations and used biophysical tools to characterize their effects, constructing a machine learning model to predict the risk of ccRCC development caused by VHL missense mutations. The results showed that the model accurately identified ccRCC-causing missense mutations and had a significant improvement compared to previous approaches.
HUMAN MOLECULAR GENETICS
(2023)
Review
Oncology
Yikeng Huang, Weiwen Hu, Xionggao Huang
Summary: This article describes a rare case of VHL-associated RH with retinal detachment, highlighting the effectiveness of laser photocoagulation and vitreoretinal surgery in visual recovery and providing a new perspective on diagnosis and treatment for this disease. Early detection of lesions, timely follow-up, and appropriate treatment are crucial for managing RH.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Bo Yang, Zhenyu Li, Yubo Wang, Chaoling Zhang, Zhen Zhang, Xianfeng Zhang
Summary: This study described a rare case of a pediatric patient with VHL disease and optic nerve HGB, exploring the genotype-phenotype correlation, clinical features, treatment, and follow-up of VHL-associated hemangioblastomas in pediatric patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Clinical Neurology
Leonille Schweizer, Felix Thierfelder, Christian Thomas, Patrick Soschinski, Hee-Yeong Kim, Ruben Joedicke, Niklas Woltering, Alexandra Foerster, Daniel Teichmann, Christin Siewert, Katharina Klein, Simone Schmid, Maximilian Nunninger, Ulrich-Wilhelm Thomale, Julia Onken, Helmut Muehleisen, Jens Schittenhelm, Marcos Tatagiba, Andreas von Deimling, David E. Reuss, David A. Solomon, Frank L. Heppner, Arend Koch, Christian Hartmann, Ori Staszewski, David Capper
Summary: The study revealed a high prevalence of VHL mutations in sporadic ELSTs, with differences in age, genetic mechanisms, and survival rates between VHL-disease-related tumors and sporadic ELSTs.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Article
Oncology
Shachar Laks, Rachel van Leeuwaarde, Dhaval Patel, Xavier M. Keutgen, Pascal Hammel, Naris Nilubol, Thera P. Links, Thorvardur R. Halfdanarson, Anthony B. Daniels, Amit Tirosh
Summary: This report summarizes the discussion and recommendations by a group of experts on the pancreatic manifestations of Von Hippel-Lindau disease (VHL). The recommendations were based on a comprehensive systematic review of the literature and panel discussions, providing guidance on clinical surveillance and management of VHL-related pancreatic manifestations.
Article
Clinical Neurology
Jorge Cabrera-Montes, Daniel T. Aguirre, Jesus Vinas-Lopez, Laura Lorente-Herraiz, Lucia Recio-Poveda, Virginia Albinana, Julian Perez-Perez, Luisa M. Botella, Angel M. Cuesta
Summary: This case report illustrates the importance of deeper genetic analyses in inherited rare diseases, by presenting the case of a VHL patient with severe manifestations. The analysis revealed pathogenic mutations in CHEK2 and the loss of a VHL allele, as well as additional mutations in BRAF1 and PTPN11 in the tumor sample. The study concludes that the severity of VHL in this patient is attributed to both VHL and CHEK2 mutations.
ACTA NEUROCHIRURGICA
(2023)
Article
Genetics & Heredity
Tabatha Nakakogue Dallagnol, Eduardo Da Cas, Odery Ramos Junior, Jose Claudio Casali-da-Rocha
Summary: This study established the largest VHL registry in Brazil, collecting clinical and genetic data from VHL families, which will help guide VHL care and oncogenetics policies in Brazil. Despite improvements in diagnosis and clinical screening methods, VHL care in Brazil is still deficient, especially regarding surveillance and regular medical appointments with experts.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Medical Laboratory Technology
Sun Joo Yoon, Won Kyung Kwon, Geehay Hong, Ja-Hyun Jang, Byong Chang Jeong, Jae Hyeon Kim, Jong-Won Kim
Summary: This study evaluated the effectiveness and practicality of using a multidisciplinary team in a VHL clinic for the first time in Korea. The results showed that the clinic strategy was useful for comprehensive surveillance and management of VHL disease, and emphasized the need for widespread implementation of VHL clinics in hospitals to improve patient prognosis.
ANNALS OF LABORATORY MEDICINE
(2022)
Article
Clinical Neurology
Reinier Alvarez, Panagiotis Mastorakos, Elizabeth Hogan, Gretchen Scott, Russell R. Lonser, Henry E. Wiley, Emily Y. Chew, Prashant Chittiboina
Summary: This study examined the natural history of retrobulbar hemangioblastomas in a large cohort of VHL patients, finding that symptomatic patients had larger tumor volumes and surgical treatment could improve symptoms. Patients who did not undergo intervention experienced continued symptom progression, while asymptomatic patients' tumors could remain stable and asymptomatic for extended periods.
Article
Pharmacology & Pharmacy
Elshad Hasanov, Eric Jonasch
Summary: Von Hippel-Lindau (VHL) disease is a genetic syndrome caused by mutations in the VHL gene, resulting in tumors and cysts in multiple organs. Surgery is the standard treatment for localized tumors, but repeated surgeries lead to significant morbidity. MK-6482, a small-molecule HIF 2 alpha inhibitor, has shown promising efficacy and safety in VHL disease-related tumors.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
Article
Ophthalmology
Ayako Takahashi, Yuki Muraoka, Sho Koyasu, Yoshiki Arakawa, Eijiro Nakamura, Akitaka Tsujikawa
Summary: The purpose of this study was to investigate the clinical characteristics of atypical retinal vascular proliferation in patients with von Hippel-Lindau (VHL) disease using OCT angiography (OCTA). Among 57 patients with VHL disease, 12.1% showed atypical flat retinal hemangioblastomas (RHs). These flat RHs appeared as retinal hemorrhages or faint abnormal retinal vessels and displayed abundant blood flow in the lesions on OCTA. During a mean follow-up period of 20.4 months, no significant changes or complications were observed in flat RHs.
Review
Neurosciences
Lin Gao, Victoria Bonilla-Henao, Paula Garcia-Flores, Ignacio Arias-Mayenco, Patricia Ortega-Saenz, Jose Lopez-Barneo
JOURNAL OF PHYSIOLOGY-LONDON
(2017)
Article
Cell Biology
Jingwei Sim, Andrew S. Cowburn, Asis Palazon, Basetti Madhu, Petros A. Tyrakis, David Macias, David M. Bargiela, Sandra Pietsch, Michael Gralla, Colin E. Evans, Thaksaon Kittipassorn, Yu C. J. Chey, Cristina M. Branco, Helene Rundqvist, Daniel J. Peet, Randall S. Johnson
Article
Cell Biology
Ignacio Arias-Mayenco, Patricia Gonzalez-Rodriguez, Hortensia Torres-Torrelo, Lin Gao, M. Carmen Fernandez-Agueera, Victoria Bonilla-Henao, Patricia Ortega-Saenz, Jose Prime Lopez-Barneo
Article
Biology
David Macias, Andrew S. Cowburn, Hortensia Torres-Torrelo, Patricia Ortega-Saenz, Jose Lopez-Barneo, Randall S. Johnson
Correction
Biology
David Macias, Andrew S. Cowburn, Hortensia Torres-Torrelo, Patricia Ortega-Saenz, Jose Lopez-Barneo, Randall Johnson
Letter
Multidisciplinary Sciences
Hortensia Torres-Torrelo, Patricia Ortega-Saenz, David Macias, Masayo Omura, Ting Zhou, Hiroaki Matsunami, Randall S. Johnson, Peter Mombaerts, Jose Lopez-Barneo
Article
Physiology
Susan F. Fitzpatrick, Milos Gojkovic, David Macias, Tetyana Tegnebratt, Li Lu, Erik Samen, Helene Rundqvist, Randall S. Johnson
FRONTIERS IN PHYSIOLOGY
(2018)
Article
Cell & Tissue Engineering
Ya-Hsuan Ho, Raquel del Toro, Jose Rivera-Torres, Justyna Rak, Claudia Korn, Andres Garcia-Garcia, David Macias, Cristina Gonzalez-Gomez, Alberto del Monte, Monika Wittner, Amie K. Waller, Holly R. Foster, Carlos Lopez-Otin, Randall S. Johnson, Claus Nerlov, Cedric Ghevaert, William Vainchenker, Fawzia Louache, Vicente Andres, Simon Mendez-Ferrer
Article
Physiology
Susan F. Fitzpatrick, Simon Lambden, David Macias, Zudin Puthucheary, Sandra Pietsch, Lee Mendil, Mark J. W. McPhail, Randall S. Johnson
FRONTIERS IN PHYSIOLOGY
(2020)
Article
Cell Biology
Estela Gonzalez-Gualda, Marta Paez-Ribes, Beatriz Lozano-Torres, David Macias, Joseph R. Wilson, Cristina Gonzalez-Lopez, Hui-Ling Ou, Sofia Miron-Barroso, Zhenguang Zhang, Araceli Lerida-Viso, Juan F. Blandez, Andrea Bernardos, Felix Sancenon, Miguel Rovira, Ljiljana Fruk, Carla P. Martins, Manuel Serrano, Gary J. Doherty, Ramon Martinez-Manez, Daniel Munoz-Espin
Article
Respiratory System
David Macias, Stephen Moore, Alexi Crosby, Mark Southwood, Xinlin Du, Huiling Tan, Shanhai Xie, Arlette Vassallo, Alexander J. T. Wood, Eli M. Wallace, Andrew S. Cowburn
Summary: The study demonstrates that targeting HIF2α with the inhibitor PT2567 may offer a new therapeutic approach for PAH, reducing pulmonary vascular hemodynamics and remodeling while improving patient prognosis. This data suggests a potential treatment option for PAH patients.
EUROPEAN RESPIRATORY JOURNAL
(2021)
Article
Critical Care Medicine
Simon Lambden, Andrew S. Cowburn, David Macias, Tessa A. C. Garrud, Bernardo J. Krause, Dino A. Giussani, Charlotte Summers, Randall S. Johnson
Summary: The deficiency of HIF-1 alpha in the systemic or pulmonary endothelium is associated with increased systemic blood pressure and metabolic rate, a pattern that persists in both normoxic conditions and in response to acute stress.
INTENSIVE CARE MEDICINE EXPERIMENTAL
(2021)
Article
Multidisciplinary Sciences
Daniel Cabello-Rivera, Patricia Ortega-Saenz, Lin Gao, Ana M. Munoz-Cabello, Victoria Bonilla-Henao, Paul T. Schumacker, Jose Lopez-Barneo
Summary: Acute oxygen sensing is crucial for adapting to hypoxic environments or medical conditions with restricted gas exchange. The carotid body plays a main role in this process, with Glomus cells in the body's response to low oxygen levels. These cells have specialized mitochondrial properties that are essential for sensing hypoxia and regulating breathing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Scott Haston, Estela Gonzalez-Gualda, Samir Morsli, Jianfeng Ge, Virinder Reen, Alexander Calderwood, Ilias Moutsopoulos, Leonidas Panousopoulos, Polina Deletic, Gabriela Carreno, Romain Guiho, Saba Manshaei, Jose Mario Gonzalez-Meljem, Hui Yuan Lim, Daniel J. Simpson, Jodie Birch, Husayn A. Pallikonda, Tamir Chandra, David Macias, Gary J. Doherty, Doris M. Rassl, Robert C. Rintoul, Massimo Signore, Irina Mohorianu, Arne N. Akbar, Jesus Gil, Daniel Munoz-Espin, Juan Pedro Martinez-Barbera
Summary: The accumulation of senescent cells in the tumor microenvironment can promote tumorigenesis through the senescence-associated secretory phenotype (SASP). Macrophages and endothelial cells are the predominant senescent cell types in murine KRAS-driven lung tumors. Through single cell transcriptomics, a population of tumor-associated macrophages with pro-tumorigenic SASP factors and surface proteins is identified. Genetic or senolytic ablation of senescent cells, or macrophage depletion, leads to decreased tumor burden and increased survival in KRAS-driven lung cancer models.
Meeting Abstract
Hematology
Ya-Hsuan Ho, Raquel del Toro, Jose Rivera-Torres, Justyna Rak, Claudia Korn, Andres Garcia-Garcia, Lucia Kubovcakova, David Macias, Lorena Arranz, Cristina Gonzalez-Gomez, Monika Wittner, Ronny Nienhold, Amie K. Waller, Holly R. Foster, Carlos Lopez-Otin, Randall S. Johnson, Claus Nerlov, William Vainchenker, Cedric Ghevaert, Fawzia Louache, Radek C. Skoda, Vicente Andres, Simon Mendez-Ferrer