Article
Pharmacology & Pharmacy
Eiji Hishinuma, Yoko Narita, Kai Obuchi, Akiko Ueda, Sakae Saito, Shu Tadaka, Kengo Kinoshita, Masamitsu Maekawa, Nariyasu Mano, Noriyasu Hirasawa, Masahiro Hiratsuka
Summary: In this study, an in vitro analysis was conducted on 41 DPD allelic variants to investigate changes in enzymatic activity, with 7 variants showing significantly decreased activity and 2 variants displaying no enzymatic activity. Our findings suggest that DPD dimerization is essential for enzymatic activity and these variants may contribute to the observed inter-individual variability in the pharmacokinetics and pharmacodynamics of 5-FU. Additionally, rare DPYD variants, although at low frequencies, could serve as important pharmacogenomic markers associated with severe 5-FU toxicity in the Japanese population.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Catherine Jolivet, Rami Nassabein, Denis Soulieres, Xiaoduan Weng, Carl Amireault, Jean-Pierre Ayoub, Patrice Beauregard, Normand Blais, Christian Carrier, Alexis-Simon Cloutier, Alexandra Desnoyers, Anne-Sophie Lemay, Frederic Lemay, Rasmy Loungnarath, Jacques Jolivet, Francois Letendre, Mustapha Tehfe, Charles Vadnais, Daniel Viens, Francine Aubin
Summary: Fluoropyrimidines are commonly used in chemotherapy for various cancers. This study demonstrates the feasibility of upfront genotyping for DPYD before fluoropyrimidine-based treatment in clinical practice, which can help prevent severe toxicities without delaying treatment initiation. This approach of administering chemotherapy at reduced doses appears to be safe for patients with DPYD*2A mutations.
Review
Pharmacology & Pharmacy
Anthi Maslarinou, Vangelis G. Manolopoulos, Georgia Ragia
Summary: Fluoropyrimidines, including 5-fluorouracil (5-FU), capecitabine (CAP), and tegafur, are commonly used chemotherapeutic agents for solid tumors. Genetic factors, particularly dihydropyrimidine dehydrogenase (DPYD), play a crucial role in determining the toxicity of fluoropyrimidines. Additional variations in other genes involved in pharmacokinetics and pharmacodynamics of fluoropyrimidines also contribute to the risk of toxicity. Expanding the genetic panel and considering gene*gene and gender*gene interactions may lead to safer prescription of fluoropyrimidines in the future.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Bhavina B. Sharma, Karan Rai, Heather Blunt, Wenyan Zhao, Tor D. Tosteson, Gabriel A. Brooks
Summary: This study systematically evaluated the risk of treatment-related death associated with DPYD gene variants during fluoropyrimidine chemotherapy, and found that patients with pathogenic DPYD gene variants have a significantly increased risk of treatment-related death.
Review
Pharmacology & Pharmacy
Cassandra White, Rodney J. Scott, Christine Paul, Andrew Ziolkowski, David Mossman, Stephen B. Fox, Michael Michael, Stephen Ackland
Summary: Upfront DPYD genotyping can identify high-risk patients for FP treatment and allow personalized dose adjustment, reducing toxicities and improving cost-effectiveness.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Oncology
David K. Lau, Caroline Fong, Faten Arouri, Lillian Cortez, Hannah Katifi, Reyes Gonzalez-Exposito, Muhammad Bilal Razzaq, Su Li, Aislinn Macklin-Doherty, Monica Arenas Hernandez, Michael Hubank, Charlotte Fribbens, David Watkins, Sheela Rao, Ian Chau, David Cunningham, Naureen Starling
Summary: A retrospective study was conducted in a high volume cancer center in London to evaluate the impact of implementing DPYD variant testing for gastrointestinal cancer patients. The results showed that DPYD genotype testing prior to fluoropyrimidine chemotherapy ensured patient safety and the incidence of adverse events was similar to wild-type carriers.
Article
Pharmacology & Pharmacy
Georgia Ragia, Anthi Maslarinou, Natalia Atzemian, Eirini Biziota, Triantafyllia Koukaki, Charalampia Ioannou, Ioanna Balgkouranidou, George Kolios, Stylianos Kakolyris, Nikolaos Xenidis, Kyriakos Amarantidis, Vangelis G. Manolopoulos
Summary: This study aimed to analyze the prevalence of DPYD gene variants and assess their association with FP-induced toxicity in Greek cancer patients. The results showed a significant correlation between DPYD variants and FP-related toxicities.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Oncology
Samantha Medwid, Theodore J. Wigle, Richard B. Kim
Summary: This study assessed the impact of specific DPYD gene variants on fluoropyrimidine-related toxicity and found that patients carrying the DPYD c.496A>G variant had an increased risk of severe toxicity during chemotherapy. Additionally, specific haplotypes carrying the c.85T>C or c.496A>G variants were associated with increased fluoropyrimidine toxicity.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ottavia De Luca, Gerardo Salerno, Donatella De Bernardini, Maria Simona Torre, Maurizio Simmaco, Luana Lionetto, Giovanna Gentile, Marina Borro
Summary: NGS exon sequencing can explain approximately 42.5% of DPD deficiencies, significantly improving the prediction of DPD deficiencies, but more genotype-phenotype association data is needed for clinical use.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Sarah A. Morris, Donald C. Moore, Laura W. Musselwhite, Karine Eboli Lopes, Alicia Hamilton, Nury Steuerwald, Sarah L. Hanson, Chris Larck, Kristen Swift, Mathew Smith, Kunal C. Kadakia, Seungjean Chai, Jimmy J. Hwang, Jai N. Patel
Summary: This study aimed to describe the implementation of an in-house genotyping program to detect genetic variants linked to impaired DPD metabolism at a large multisite cancer center. Through stakeholder engagement and the development of workflows, an in-house DPYD test was successfully implemented across multiple clinic locations. Future directions include integrating the test into electronic medical records, establishing a billing infrastructure, and refining workflows to improve the rate of pretreatment testing.
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
(2023)
Article
Oncology
Marta Miarons, Alba Manzaneque Gordon, Pau Riera, Fernando Gutierrez Nicolas
Summary: This study describes the frequency of DPYD variants in a population of Spanish patients with cancer, aiming to create a national registry. The results demonstrate a relatively high frequency of DPYD genetic variants in the Spanish patient population, highlighting the relevance of genetic testing before initiating fluoropyrimidine-containing regimens.
Article
Oncology
Marta Miarons, Alba Manzaneque Gordon, Pau Riera, Fernando Gutierrez Nicolas
Summary: The aim of this study was to determine the frequency of DPYD variants in Spanish oncological patients. The results showed a relatively high prevalence of DPYD genetic variants in the Spanish cancer patient population, highlighting the importance of determining these variants before initiating fluoropyrimidine-containing regimens.
Article
Health Care Sciences & Services
Nicola Personeni, Laura Giordano, Angelica Michelini, Antonio D'Alessio, Antonella Cammarota, Silvia Bozzarelli, Tiziana Pressiani, Maria Giuseppina Prete, Maria Teresa Sandri, Sabine Stioui, Luca Germagnoli, Armando Santoro, Lorenza Rimassa, Rossana Mineri
Summary: This study investigated the impact of UGT1A1 genotyping and genotype-guided dose reductions on the occurrence of severe neutropenia in patients with advanced gastrointestinal cancers. The results show that upfront dose reductions of irinotecan cannot reduce the burden of grade >= 3 neutropenia in homozygous UGT1A1*28 carriers.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Genetics & Heredity
Jorge E. B. da Rocha, Zane Lombard, Michele Ramsay
Summary: This study identified multiple DPYD gene variants in African populations, some of which are known to be deleterious. These findings highlight the importance of African-data informed guidelines for fluorouracil drug safety in sub-Saharan Africans, emphasizing the need for region-specific data to ensure optimal benefits from a precision medicine approach.
FRONTIERS IN GENETICS
(2021)
Article
Oncology
Mirjam de With, Gemma Brufau, Laila A. van den Berg, Femke M. de Man, Marija Trajkovic, Martine F. Thijs, Rob Castel, Henricus J. Vermeer, Samira el Bouazzaoui, Amber van Hemel, Maja Matic, Ron H. J. Mathijssen, Sander Bins, Ron H. N. van Schaik
Summary: The study confirms that 46% of patients carrying the DPYD*7 variant allele develop severe treatment-related adverse events, even with initial dose reductions. This highlights the need for prospective studies to investigate the required fluoropyrimidine dose for DPYD*7 carriers.
JCO PRECISION ONCOLOGY
(2022)
Article
Allergy
Daniel Brigger, Michael P. Horn, Luke F. Pennington, Abigail E. Powell, Denise Siegrist, Benjamin Weber, Olivier Engler, Vanja Piezzi, Lauro Damonti, Patricia Iseli, Christoph Hauser, Tanja K. Froehlich, Peter M. Villiger, Martin F. Bachmann, Stephen L. Leib, Pascal Bittel, Martin Fiedler, Carlo R. Largiader, Jonas Marschall, Hanspeter Stalder, Peter S. Kim, Theodore S. Jardetzky, Alexander Eggel, Michael Nagler
Summary: This study compared the diagnostic accuracy of serological immunoassays targeting different proteins of SARS-CoV-2 and found that ELISAs targeting RBD and S1 protein have high sensitivity and specificity. Additionally, most SARS-CoV-2 positive individuals showed neutralizing activity against the live virus. Further evaluation in studies verifying diagnostic accuracy and protective immunity against SARS-CoV-2 is warranted.
Article
Allergy
Michael P. Horn, Hulda R. Jonsdottir, Daniel Brigger, Lauro Damonti, Franziska Suter-Riniker, Olga Endrich, Tanja K. Froehlich, Martin Fiedler, Carlo R. Largiader, Jonas Marschall, Benjamin Weber, Alexander Eggel, Michael Nagler
Summary: This study evaluated the diagnostic accuracy of various serological testing strategies for COVID-19 in real-life clinical settings. The results showed that different testing methods and antibody subtypes had varying levels of sensitivity and specificity. These findings are important for estimating the infection burden in specific populations and predicting the likelihood of immune protection.
Article
Oncology
Ekaterina Gurevich, Michael Hayoz, Yolanda Aebi, Carlo R. Largiader, Behrouz Mansouri Taleghani, Ulrike Bacher, Thomas Pabst
Summary: This study compared the use of busulfan/melphalan regimen with treosulfan/melphalan regimen in AML patients. The treosulfan/melphalan regimen was found to be safer and more effective, with no neurotoxicity and irreversible alopecia. There was considerable interindividual biovariability in treosulfan serum levels.
Article
Pharmacology & Pharmacy
Ursina B. M. Begre, Markus Jorger, Stefan Aebi, Ursula Amstutz, Carlo R. Largiader
Summary: Despite policies introduced for pre-treatment testing of DPYD gene risk variants in Switzerland, there was no significant increase in testing requests until the release of recommendations by the European Medicines Agency in April 2020, leading to a 14-fold increase in DPYD testing.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Eduard Schmulenson, Cedric Bovet, Regula Theurillat, Laurent Arthur Decosterd, Carlo R. Largiader, Jean-Christophe Prost, Chantal Csajka, Daniela Baertschi, Matthias Guckenberger, Roger von Moos, Sara Bastian, Markus Joerger, Ulrich Jaehde
Summary: This study investigated the potential drug-drug interactions between regorafenib and capecitabine in patients with locally advanced rectal cancer. The results showed that regorafenib reduced the clearance of capecitabine, highlighting the importance of studying drug interactions in the clinical development of combination treatments.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Meeting Abstract
Oncology
S. Bastian, M. Joerger, D. Baertschi, L. Holer, M. Guckenberger, W. Jochum, D. Koeberle, A. R. Siebenhuner, M. D. Berger, R. C. Winterhalder, C. R. Largiader, M. Loffler-Baumann, K. Mosna-Firlejczyk, A. Wicki, A. Fischer Maranta, R. A. F. Von Moos
ANNALS OF ONCOLOGY
(2022)
Article
Genetics & Heredity
Nicholas Kueng, Severine Arcioni, Fanny Sandberg, Christian Kuhn, Vanessa Banz, Carlo R. Largiader, Daniel Sidler, Ursula Amstutz
Summary: Liquid biopsy using quantification of donor-derived cell-free DNA (dd-cfDNA) in plasma has become a novel approach for allograft monitoring in solid organ transplant recipients. This study compared different dd-cfDNA quantification methods and found that the presented high-throughput sequencing method showed strong correlation with existing methods. Absolute levels of dd-cfDNA in urine may be required for allograft surveillance in stable kidney recipients due to extensive variability of relative amounts.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
Cedric Gillich, Dilara Akhoundova, Michael Hayoz, Yolanda Aebi, Carlo R. Largiader, Katja Seipel, Michael Daskalakis, Ulrike Bacher, Thomas Pabst
Summary: Upfront treatment consolidation with TreoMel HDCT and ASCT has promising efficacy and safety in MM patients, achieving a complete response rate of 84% and an OS rate of 83%. Treosulfan pharmacokinetics showed no significant correlation with MM responses, but higher exposure and peak value in female patients were associated with longer hospitalizations.
Article
Oncology
M. de With, A. Sadlon, E. Cecchin, V. Haufroid, F. Thomas, M. Joerger, R. H. N. van Schaik, R. H. J. Mathijssen, C. R. Largiader
Summary: After the release of the EMA recommendations, there was an increase in both genotype and phenotype testing in Europe. Some countries also implemented new local guidelines. Although challenges such as lack of reimbursement and awareness among medical oncologists still existed, the percentage of specialists citing these hurdles decreased after the EMA recommendations.
Article
Infectious Diseases
Peter J. Neyer, Berenger Kabore, Christos T. Nakas, Britta Hartmann, Annelies Post, Salou Diallo, Halidou Tinto, Angelika Hammerer-Lercher, Carlo R. Largiader, Andre J. van der Ven, Andreas R. Huber
Summary: This study investigated the associations between iron homeostasis, inflammation, nutrition, and haemoglobin mutations with asymptomatic malaria infection. The results showed that malnutrition was strongly associated with asymptomatic parasitaemia, and the presence of haemoglobin S mutation could attenuate the infection.
Article
Medicine, General & Internal
Nicholas Kueng, Daniel Sidler, Vanessa Banz, Carlo R. R. Largiader, Charlotte K. Y. Ng, Ursula Amstutz
Summary: This study evaluated the technical biases of single- and double-stranded library preparation methods when applied on cfDNA from plasma and urine, and assessed the proportions of tissue of origin using two deconvolution methods. The results showed that sequencing cfDNA from urine using the double-stranded method resulted in methylation bias and lower global methylation, which were not observed with the single-stranded approach. The deconvolution methods also yielded different results in terms of determining tissue of origin proportions.
Meeting Abstract
Oncology
Huixing Huang, Dominic Schaerer, Remington Schmidt, Ting Zhang, Tanja K. Froehlich, Kelly Bouchonville, Robert B. Diasio, Ursula Amstutz, Carlo Largiader, Steven M. Offer
Meeting Abstract
Clinical Neurology
E. S. Wenz, J. -C. Prost, G. M. Mader, I. Filchenko, J. D. Warncke, M. H. Schmidt, C. R. Largiader, C. L. A. Bassetti
JOURNAL OF SLEEP RESEARCH
(2022)
Meeting Abstract
Clinical Neurology
E. Wenz, J. Prost, I. Filchenko, J. Warncke, M. Schmidt, C. Largiader, C. Bassetti
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Meeting Abstract
Oncology
Ting Zhang, Alisa Ambrodji, Huixing Huang, Kelly Bouchonville, Amy Etheridge, Remington Schmidt, Jose Cardiel Nunez, Zoey Temesgen, Federico Innocenti, Robert Diasio, Carlo Largiader, Steven M. Offer
Article
Medical Laboratory Technology
Jiansheng Lin, Weihua Lin, Yiming Lin, Weilin Peng, Zhenzhu Zheng
Summary: This study retrospectively analyzed the cases of Chinese infants with NICCD and identified multiple genetic mutations. The study also found comorbidity of NICCD and other inborn errors of metabolism in some patients.
CLINICA CHIMICA ACTA
(2024)
Review
Medical Laboratory Technology
Lihua Guan, Wei Su, Jian Zhong, Ling Qiu
Summary: Multiple myeloma is characterized by excessive production of monoclonal immunoglobulins. Routine screening methods are insufficient for detecting low levels of M proteins, but advances in mass spectrometry enable reliable detection of low abundance serum biomarkers for minimal residual disease assessment in multiple myeloma.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
Liya Zhu, Chao Zhu, Jialie Jin, Jinxin Wang, Xiaojing Zhao, Rongxi Yang
Summary: This study found an association between blood-based ITGB2 methylation and coronary heart disease (CHD), with hypomethylation of ITGB2 being a risk factor for CHD. Additionally, the combination of ITGB2 methylation and conventional CHD risk factors could efficiently discriminate CHD patients from controls.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
H. Al Habobe, E. B. Haverkort, K. Nazmi, A. P. Van Splunter, R. H. H. Pieters, F. J. Bikker
Summary: Saliva diagnostics have become popular due to their non-invasive nature and patient-friendly collection process. However, the choice of saliva collection method can affect the measured levels of various biomarkers.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
Abdurrahman Coskun, Anna Carobene, Ozlem Demirelce, Michele Mussap, Federica Braga, Ebru Sezer, Aasne Karine Aarsand, Sverre Sandberg, Pilar Fernandez Calle, Jorge Diaz-Garzon, Metincan Erkaya, Cihan Coskun, Esila Nur Erol, Hunkar Dag, Bill Bartlett, Mustafa Serteser, Niels Jonker, Ibrahim Unsal
Summary: In this study, BV estimates for 22 AAs were provided based on a large sample size, and it was found that there are differences in CVI estimates between males and females for most AAs, which has implications for the clinical interpretation and use of AAs.
CLINICA CHIMICA ACTA
(2024)
Review
Medical Laboratory Technology
Valentinus Besin, Farizky Martriano Humardani, Trilis Yulianti, Matthew Justyn
Summary: The study of Parkinson's Disease in Asian populations has revealed the impact of genetic variants on multiple biological pathways and highlighted shared genetic susceptibility with other diseases. These findings emphasize the importance of personalized treatment based on individual genetic profiles.
CLINICA CHIMICA ACTA
(2024)
Review
Medical Laboratory Technology
Simona Ferraro, Sara Benedetti, Savina Mannarino, Santica Marcovina, Elia Mario Biganzoli, Gianvincenzo Zuccotti
Summary: Risk stratification for cardio-vascular disease should be implemented in childhood to promote early prevention strategies, as atherosclerotic lesions can be present even in very young individuals. Evaluating pediatric CV risk factors/clinical conditions and conducting lipid profile and genetic testing can help identify children at risk of future CV events and guide appropriate therapeutic options.
CLINICA CHIMICA ACTA
(2024)
Review
Medical Laboratory Technology
Ahmad Mobed, Bita Abdi, Sajjad Masoumi, Mohammad Mikaeili, Elham Shaterian, Hamed Shaterian, Esmat Sadat Kazemi, Mahdiye Shirafkan
Summary: Reproductive biomarkers play important regulatory roles in women. The discovery and quantification of these biomarkers are clinically significant. Various detection strategies, including nanotechnology-based methods, have been developed. This article provides an in-depth introduction to the latest advances in biosensor and nanosensor research for detecting and quantitatively identifying reproductive biomarkers.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
Chengfang Tang, Fang Tang, Yanna Cai, Minyi Tan, Sichi Liu, Ting Xie, Xiang Jiang, Yonglan Huang
Summary: This study proposes an effective method for screening X-ALD and evaluates the performance of newborn screening for X-ALD in Guangzhou. The LC-MS/MS method can accurately identify X-ALD through analysis of C26:0-LPC.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
Lan Liu, Jiamin Wang, Xijing Liu, Jing Wang, Lin Chen, Hongmei Zhu, Jingqun Mai, Ting Hu, Shanling Liu
Summary: The 16p11.2 deletion is a common genetic cause of neurodevelopmental disorders, with prenatal and postnatal presentations including vertebral malformations and language impairment. The majority of deletions are de novo and may be associated with MAPK3 and histidine-associated metabolism.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
Sneha Venkatesalu, Shanmugapriya Dilliyappan, Avanthika Satish Kumar, Thirunavukkarasu Palaniyandi, Gomathy Baskar, Maddaly Ravi, Asha Sivaji
Summary: Microfluidics is a science and technology that deals with less sample-to-more precision in vitro analysis. It has wide applications in cancer theranostics, enabling precise diagnosis and personalized treatment.
CLINICA CHIMICA ACTA
(2024)
Review
Medical Laboratory Technology
Yuanqin Zhao, Wei Deng, Zhaoyue Wang, Yanxia Wang, Hongyu Zheng, Kun Zhou, Qian Xu, Le Bai, Huiting Liu, Zhong Ren, Zhisheng Jiang
Summary: The cardiovascular system and the central nervous system exhibit a coordinated developmental process during embryonic development. Congenital heart disease (CHD) is the most common congenital disorder, and neurodevelopmental disorders (NDD) are common complications in CHD patients. Both genetic and non-genetic factors contribute to the co-occurrence of CHD and NDD. Further research should focus on identifying common molecular mechanisms underlying this co-occurrence and promoting the research and treatment of developmental disorders related to the cardiovascular and central nervous systems.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
Karol Gostomczyk, Ewelina Lukaszewska, Jedrzej Borowczak, Anita Bator, Marek Zdrenka, Magdalena Bodnar, Lukasz Szylberg
Summary: Flow cytometry improves the detection of epithelial cancer cells in peritoneal and pleural fluids compared to conventional cytology. Due to similar speciflcity and higher sensitivity, flow cytometry offers a promising alternative to cytology for patient screening.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
Heping Tian, Genghuan Wang, Qi Zhong, Haihang Zhou
Summary: This study found that the decline of serum ITIH4 concentrations during the early phase after aneurysmal subarachnoid hemorrhage (aSAH) was closely related to the severity and poor prognosis of the disease. Serum ITIH4 may represent a promising prognostic biomarker of aSAH.
CLINICA CHIMICA ACTA
(2024)
Article
Medical Laboratory Technology
Xueting Zhu, Yang Yu, Jun Zhang, Yuxia Zhan, Guanghua Luo, Lu Zheng
Summary: This study successfully established a 2D-PCR method for identifying HLA-B*15:02 through a two-tube reaction. This method can distinguish HLA-B*15:02 from 16 highly homologous HLA-B*15 alleles. Among 1830 samples from the clinical general population, 3 HLA-B*15:02 homozygotes and 84 HLA-B*15:02 heterozygotes were detected.
CLINICA CHIMICA ACTA
(2024)