Article
Oncology
Daniel L. L. Hertz
Summary: This article calls for clinicians and clinical guidelines committees in the United States to re-evaluate the clinical utility of pretreatment DPYD testing. There is no direct evidence of efficacy reduction, and the available indirect evidence suggests that DPYD-guided FP dosing is well calibrated and minimizes the risk of reducing treatment efficacy.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Review
Health Care Sciences & Services
Woorim Kim, Young-Ah Cho, Dong-Chul Kim, Kyung-Eun Lee
Summary: This study aimed to evaluate the risk of fluoropyrimidine-associated toxicity in patients with DPYD rs1801160 polymorphism. The systematic literature review and meta-analysis revealed an association between rs1801160 polymorphism and fluoropyrimidine-associated toxicity.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Daniel L. Hertz, D. Max Smith, Stuart A. Scott, Jai N. Patel, J. Kevin Hicks
Summary: FP chemotherapy has severe toxicities for patients with DPYD gene variants. DPYD testing is standard in Europe but not recommended in the US. The FDA updated the capecitabine package insert to inform patients about the toxicity risk and test availability, but without specific recommendations for testing or dose adjustment. It is important for the FDA to follow European recommendations and promote DPYD testing and genotype-based dose adjustment.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
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)
Review
Oncology
K. Hodroj, D. Barthelemy, J-C Lega, G. Grenet, M-C Gagnieu, T. Walter, J. Guitton, L. Payen-Gay
Summary: Fluoropyrimidine-based chemotherapies are widely used to treat various cancers, but may cause toxicities, hence EMA recommends DPD testing before treatment. Different assays, including direct phenotyping, indirect phenotyping, and genotyping, are used to predict DPD deficiency.
Article
Oncology
Kyoin Koo, Amy L. Pasternak, N. Lynn Henry, Vaibhav Sahai, Daniel L. Hertz
Summary: This study describes the current practice of pretreatment DPYD testing in the United States and identifies factors deterring oncologists from ordering testing. The results show that the clinical adoption of pretreatment DPYD testing is extremely limited in the United States, with low prevalence of DPD deficiency and lack of clinical practice guideline recommendations being the main barriers.
JCO ONCOLOGY PRACTICE
(2022)
Review
Oncology
Marie-Christine Etienne-Grimaldi, Nicolas Pallet, Valerie Boige, Joseph Ciccolini, Laurent Chouchana, Chantal Barin-Le Guellec, Aziz Zaanan, Celine Narjoz, Julien Taieb, Fabienne Thomas, Marie-Anne Loriot
Summary: Fluoropyrimidine drugs are commonly used in chemotherapy for solid tumors, and deficiency in the enzyme DPD can lead to severe toxicity. This review explores the pharmacogenetics and therapeutic recommendations for genotyping and phenotyping DPD to prevent toxicity and optimize dosing adaptation. The mandatory screening for DPD deficiency in France is also discussed.
EUROPEAN JOURNAL OF CANCER
(2023)
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)
Review
Oncology
Sarah Glewis, Marliese Alexander, Muhammad N. H. Khabib, Annabelle Brennan, Smaro Lazarakis, Jennifer Martin, Jeanne Tie, Senthil Lingaratnam, Michael Michael
Summary: Pharmacogenetics Guided Dosing (PGD) improves treatment outcomes by reducing the incidence of toxicities, particularly overall toxicity and diarrhea, without impacting treatment response in patients receiving 5-fluorouracil/capecitabine therapy.
BRITISH JOURNAL OF CANCER
(2022)
Review
Pharmacology & Pharmacy
Lucija Lesnjakovic, Lana Ganoci, Ivan Bilic, Livija Simicevic, Iva Mucalo, Stjepko Plestina, Nada Bozina
Summary: FPs are widely used antineoplastic drugs for solid tumors treatment, but they can cause severe toxicity, especially in patients with reduced DPD activity. European agencies recommend pre-treatment DPD deficiency screening, but American ones do not. Current guidelines recommend testing four DPD gene risk variants, but new evidence on additional common DPYD polymorphisms and rare DPYD variants may help address the missing heritability of DPD deficiency and FP-related toxicity.
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.
Article
Multidisciplinary Sciences
Velko Minchev, Kalina Kamenova, Nadya Hristova-Avakumova, Slavina Surcheva, Rumen Nikolov
Summary: 5-Fluorouracil (5-FU) is a key chemotherapy drug for treating GIT cancer patients. The level of DPD enzyme in blood plasma is correlated with the toxicity of treatment. Higher DPD levels in blood plasma are associated with less severe adverse effects.
COMPTES RENDUS DE L ACADEMIE BULGARE DES SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Paula Soria-Chacartegui, Gonzalo Villapalos-Garcia, Luis A. Lopez-Fernandez, Marcos Navares-Gomez, Gina Mejia-Abril, Francisco Abad-Santos, Pablo Zubiaur
Summary: DPYD gene polymorphism can help predict toxicity in cancer patients treated with fluoropyrimidines, but its current predictive capacity is limited due to unknown mutations affecting enzyme function. Variant rs367619008, rs200643089, and rs76387818 were found to increase the percentage of explained toxicities, while further studies are needed to confirm the clinical relevance of variant rs944174134.
Review
Pharmacology & Pharmacy
Jonathan E. Knikman, Hans Gelderblom, Jos H. Beijnen, Annemieke Cats, Henk-Jan Guchelaar, Linda M. Henricks
Summary: Fluoropyrimidines are widely used in the treatment of solid tumors, but severe toxicity can occur in a significant percentage of patients. Individualized dosing strategies, including upfront genotyping of the DPYD gene, monitoring of DPD enzyme activity, and pharmacokinetically guided follow-up of 5-FU, have shown promise in reducing toxicity. Baseline characteristics such as sex, age, body composition, and renal function also play a role in predicting severe toxicity and should be considered in dose-individualization strategies.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Medical Laboratory Technology
Anne Winther-Larsen, Anne Tranberg Madsen, Peter H. H. Nissen, Elke Hoffmann-Luecke, Eva Greibe
Summary: Plasma uracil is a suitable biomarker for evaluating dihydropyrimidine dehydrogenase activity, with tight homeostatic regulation and little day-to-day variation. However, there is between-subject variation, and four samples are required to establish the homeostatic set-point in a patient.
CLINICAL CHEMISTRY AND LABORATORY MEDICINE
(2023)
Article
Ophthalmology
Fabrizio Gozzi, Raffaella Aldigeri, Valentina Mastrofilippo, Luca De Simone, Elena Bolletta, Jacopo Marzano, Danilo Iannetta, Marco Coassin, Fiorella Ilariucci, Angela Ferrari, Stefano Luminari, Francesco Merli, Stefania Croci, Alessandro Zerbini, Enrico Farnetti, Davide Nicoli, Riccardo Valli, Ione Tamagnini, Alberto Cavazza, Carlo Salvarani, Luigi Fontana, Luca Cimino
Summary: The study found that combined systemic and local chemotherapy significantly improved the survival rate of patients with VRL, especially for the isolated primary VRL group. However, this treatment did not significantly improve progression-free survival.
OCULAR IMMUNOLOGY AND INFLAMMATION
(2022)
Article
Rheumatology
Francesco Muratore, Chiara Marvisi, Paola Castrignano, Davide Nicoli, Enrico Farnetti, Orsola Bonanno, Rosina Longo, Piera Zaldini, Elena Galli, Nicholas Balanda, David B. Beck, Peter C. Grayson, Nicolo Pipitone, Luigi Boiardi, Carlo Salvarani
Summary: By using a phenotype-first approach, this study identified patients with VEXAS syndrome among Italian patients with vasculitis. The study also found a novel association between VEXAS syndrome and ANCA-associated vasculitis.
ARTHRITIS & RHEUMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Andrea Palicelli, Stefania Croci, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Magda Zanelli, Alcides Chaux, Sofia Canete-Portillo, Maria Paola Bonasoni, Stefano Ascani, Antonio De Leo, Guido Giordano, Matteo Landriscina, Giuseppe Carrieri, Luigi Cormio, Jatin Gandhi, Davide Nicoli, Enrico Farnetti, Simonetta Piana, Alessandro Tafuni, Martina Bonacini
Summary: This study reviewed the potential correlations between PD-L1 and MMR/MSI/BRCA/PTEN statuses in prostate cancer and discussed several other relevant genes. The results showed that some patients can be treated with specific antibody drugs. Further research is needed to verify the efficacy of these treatment methods and the relationship with the related factors.
Review
Oncology
Maria Gemelli, Douglas M. Noonan, Valentina Carlini, Giuseppe Pelosi, Massimo Barberis, Riccardo Ricotta, Adriana Albini
Summary: Immune checkpoint inhibitors have been widely used in the treatment of non-small cell lung cancer, but not all patients benefit from them. Other cells in the tumor microenvironment, such as NK cells, also play a role and may affect the response to immune checkpoint inhibitors. Further research is needed to understand the role of pro-inflammatory NK cells in NSCLC and their impact on treatment response to ICIs.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Adriana Albini
CANCER PREVENTION RESEARCH
(2022)
Article
Oncology
Giulia Mazzaschi, Fabiana Perrone, Roberta Minari, Michela Verze, Cinzia Azzoni, Lorena Bottarelli, Monica Pluchino, Maria Pia Armillotta, Annalisa Ubaldi, Annalisa Altimari, Elisa Gruppioni, Francesca Sperandi, Elisa Andrini, Giorgia Guaitoli, Stefania Bettelli, Lucia Longo, Federica Bertolini, Fausto Barbieri, Maria Pagano, Candida Bonelli, Elena Tagliavini, Davide Nicoli, Alessandro Ubiali, Adriano Zangrandi, Serena Trubini, Manuela Proietto, Letizia Gnetti, Marcello Tiseo
Summary: The study retrospectively evaluated the clinical impact of KRAS mutations in 297 KRAS-mutant NSCLC patients, finding no significant differences in survival and treatment outcomes based on different KRAS mutations, with chemotherapy-treated patients showing worse prognosis and immunotherapy-based regimens potentially prolonging survival. This research may provide valuable insights for predicting outcomes in KRAS-mutant NSCLC patients.
CLINICAL LUNG CANCER
(2022)
Article
Medicine, Research & Experimental
Roberto Bei, Monica Benvenuto, Chiara Focaccetti, Sara Fazi, Marta Moretti, Daniela Nardozi, Valentina Angiolini, Sara Ciuffa, Loredana Cifaldi, Raffaele Carrano, Camilla Palumbo, Martino Tony Miele, Riccardo Bei, Giovanni Barillari, Vittorio Manzari, Enrico De Smaele, Andrea Modesti, Laura Masuelli
Summary: This study demonstrated that combined treatment with inhibitors of ErbB and Hh signaling pathways is more effective than single treatment in reducing the growth of malignant mesothelioma, suggesting potential clinical implications for targeted therapy approaches.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Chiara Focaccetti, Monica Benvenuto, Chiara Pighi, Alessandra Vitelli, Federico Napolitano, Nicola Cotugno, Doriana Fruci, Paolo Palma, Paolo Rossi, Roberto Bei, Loredana Cifaldi
Summary: Adoptive transfer of engineered NK cells has become an important clinical approach for cancer treatment. This study aimed to improve the clinical efficacy and safety of NK cell-based immunotherapy through the development of new strategies. Human NK cells expressing DNAM-1 or DNAM-1-based chimeric receptors were generated, and their functionality was evaluated. The results showed that DNAM-1-CD3 zeta-engineered NK cells exhibited the strongest response, and the combination with Nutlin-3a could enhance the therapeutic effect for solid tumors carrying dysfunctional p53.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Clementina Sansone, Luigi Pistelli, Angelo Del Mondo, Luana Calabrone, Angelo Fontana, Douglas M. Noonan, Adriana Albini, Christophe Brunet
Summary: This study demonstrates the anti-inflammatory effects of Diatoxanthin (Dt) on human lung cells, specifically the A549-hACE2 cell line. Dt enhances cell metabolism and ACE2 enzymatic activity, while decreasing the production of interleukin-6 and increasing the release of interleukin-10 in response to the SARS-CoV-2 spike glycoprotein. Dt also upregulates genes and proteins related to the interferon pathway and innate immunity response. These findings suggest that Dt may be a promising therapeutic agent for the treatment and/or prevention of severe inflammatory syndrome associated with SARS-CoV-2 infection.
Article
Immunology
Saeid Najafi-Fard, Elisa Petruccioli, Chiara Farroni, Linda Petrone, Valentina Vanini, Gilda Cuzzi, Andrea Salmi, Anna Maria Gerarda Altera, Assunta Navarra, Tonino Alonzi, Emanuele Nicastri, Fabrizio Palmieri, Gina Gualano, Valentina Carlini, Douglas McClain Noonan, Adriana Albini, Delia Goletti
Summary: In COVID-19 patients, levels of IL-10 and other immune factors were significantly elevated, with some reaching peak levels in the second week of infection. Exogenous IL-10 addition significantly downregulated IFN-gamma response and other immune factors in both COVID-19 patients and unvaccinated controls in a study population.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Andrea Sonaglioni, Michele Lombardo, Adriana Albini, Douglas M. Noonan, Margherita Re, Roberto Cassandro, Davide Elia, Antonella Caminati, Gian Luigi Nicolosi, Sergio Harari
Summary: This study investigated the clinical predictors of in-hospital mortality in hospitalized patients with COVID-19 infection. It found that high comorbidity burden, high levels of neutrophil-to-lymphocyte ratio (NLR), and undertreatment with ACEI/ARBs were the main prognostic indicators of in-hospital mortality.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Giuseppina Bonizzi, Lorenzo Zattoni, Maria Capra, Cristina Cassi, Giulio Taliento, Mariia Ivanova, Elena Guerini-Rocco, Marzia Fumagalli, Massimo Monturano, Adriana Albini, Giuseppe Viale, Roberto Orecchia, Nicola Fusco
Summary: Biobanks are crucial for precision medicine research, with specific protocols and guidelines necessary to maintain optimal quality. Standard operating procedures should cover protocols, troubleshooting, and quality controls.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Clinical Neurology
P. M. F. Cristaldi, A. Parlangeli, D. Nicoli, M. Incerti
Summary: A posterolateral transpedicular approach is a safe and efficient surgical corridor for resecting intradural extramedullary lesions located anterolaterally at C7-T1 level, providing direct access without extensive manipulation of the spinal cord and spine instability.
ACTA NEUROCHIRURGICA
(2023)
Review
Oncology
Beatrice Melli, Pietro Gentile, Davide Nicoli, Enrico Farnetti, Stefania Croci, Fabrizio Gozzi, Elena Bolletta, Luca De Simone, Francesca Sanguedolce, Andrea Palicelli, Maurizio Zizzo, Stefano Ricci, Fiorella Ilariucci, Cristiana Rossi, Alberto Cavazza, Stefano Ascani, Luca Cimino, Magda Zanelli
Summary: Primary vitreoretinal lymphoma is a rare aggressive malignancy that poses diagnostic challenges for clinicians and pathologists. Delays in diagnosis and treatment can result in visual impairments and life-threatening consequences. The difficulties in diagnosis include the scarcity of neoplastic cells and the fragility of lymphoma cells with degenerative changes.
Article
Cardiac & Cardiovascular Systems
Nadia Benedetto, Luana Calabrone, Karolina Gutmanska, Nicoletta Macri, Maria Grazia Cerrito, Riccardo Ricotta, Giuseppe Pelosi, Antonino Bruno, Douglas M. Noonan, Adriana Albini
Summary: This study investigated the cooperation between polyphenol-rich extract from olive mill wastewater (OMWW) and chemotherapy in breast cancer cells, revealing its cardiovascular protective effects and enhancing the efficacy of breast cancer chemotherapy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)