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MET Exon 14 Skipping and Novel Actionable Variants: Diagnostic and Therapeutic Implications in Latin American Non-Small-Cell Lung Cancer Patients
(MDPI AG, 2024-12-22)
RIVAS VERA, SOLANGE VERÓNICA
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Romina V. Sepúlveda
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TAPIA DUFEY, JUAN IGNACIO
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Catalina Estay
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Vicente Soto
<jats:p>Targeted therapy indications for actionable variants in non-small-cell lung cancer (NSCLC) have primarily been studied in Caucasian populations, with limited data on Latin American patients. This study utilized a 52-genes next-generation sequencing (NGS) panel to analyze 1560 tumor biopsies from NSCLC patients in Chile, Brazil, and Peru. The RNA sequencing reads and DNA coverage were correlated to improve the detection of the actionable MET exon 14 skipping variant (METex14). The pathogenicity of MET variants of uncertain significance (VUSs) was assessed using bioinformatic methods, based on their predicted driver potential. The effects of the predicted drivers VUS T992I and H1094Y on c-MET signaling activation, proliferation, and migration were evaluated in HEK293T, BEAS-2B, and H1993 cell lines. Subsequently, c-Met inhibitors were tested in 2D and 3D cell cultures, and drug affinity was determined using 3D structure simulations. The prevalence of MET variants in the South American cohort was 8%, and RNA-based diagnosis detected 27% more cases of METex14 than DNA-based methods. Notably, 20% of METex14 cases with RNA reads below the detection threshold were confirmed using DNA analysis. The novel actionable T992I and H1094Y variants induced proliferation and migration through c-Met/Akt signaling. Both variants showed sensitivity to crizotinib and savolitinib, but the H1094Y variant exhibited reduced sensitivity to capmatinib. These findings highlight the importance of RNA-based METex14 diagnosis and reveal the drug sensitivity profiles of novel actionable MET variants from an understudied patient population.</jats:p>
Scopus© Citations 4 8
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Access to Treatment for Chronic Obstructive Pulmonary Disease in the Americas: A Call for Action. A Joint Perspective from the Brazilian Thoracic Society, Canadian Thoracic Society, Latin American Thoracic Society, and the American Thoracic Society
(2024)
Francesca Polverino
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Mohit Bhutani
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Gustavo Zabert
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Frederico Leon Arrabal Fernandes
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CZISCHKE LJUBETIC, KAREN NICOLE
Scopus© Citations 2
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The Future Impact and Role of the Journal<i>Radiology</i>in Latin America
(2023)
SILVA FUENTE ALBA, CLAUDIO SERGIO
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Guillermo Elizondo-Riojas
6Scopus© Citations 1
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Setting up regional diagnostic reference levels for pediatric computed tomography in Latin America: preliminary results, challenges and the work ahead
(2023)
Lina Cadavid
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Lina Karout
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Mannudeep K. Kalra
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Flavio Morgado
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María Antonieta Londoño
Scopus© Citations 4 2
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The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial
(2023)
Lu Ma
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Xin Hu
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Lili Song
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Xiaoying Chen
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Menglu Ouyang
Scopus© Citations 221 1
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Minimally Invasive Surgery for Traumatic Thoracolumbar Fractures: A Cross-Sectional Study of Spine Surgeons
(2023)
Guillermo A. Ricciardi
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Juan Ignacio Cirillo Totera
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Juan P. Cabrera
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Alfredo Guiroy
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Charles A. Carazzo
7Scopus© Citations 3
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Management of radioiodine refractory differentiated thyroid cancer: the Latin American perspective
(2023)
Fabian Pitoia
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Rafael Selbach Scheffel
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Ines Califano
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Alicia Gauna
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TALA JURY, HERNAN PABLO
Scopus© Citations 5 1
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Biosimilars approvals by thirteen regulatory authorities: A cross-national comparison
(2023)
Fernanda Lacerda da Silva Machado
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Martín Cañás
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Svetlana V. Doubova
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Martín A. Urtasun
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Gustavo H. Marín
Scopus© Citations 9 1
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Frontotemporal Dementias in Latin America: History, Epidemiology, Genetics, and Clinical Research
(2021)
Jorge J. Llibre-Guerra
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BEHRENS PELLEGRINO, MARIA ISABEL
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Mirna Lie Hosogi
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Lucia Montero
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Teresa Torralva
<jats:p><jats:bold>Introduction:</jats:bold> The historical development, frequency, and impact of frontotemporal dementia (FTD) are less clear in Latin America than in high-income countries. Although there is a growing number of dementia studies in Latin America, little is known collectively about FTD prevalence studies by country, clinical heterogeneity, risk factors, and genetics in Latin American countries.</jats:p><jats:p><jats:bold>Methods:</jats:bold> A systematic review was completed, aimed at identifying the frequency, clinical heterogeneity, and genetics studies of FTD in Latin American populations. The search strategies used a combination of standardized terms for FTD and related disorders. In addition, at least one author per Latin American country summarized the available literature. Collaborative or regional studies were reviewed during consensus meetings.</jats:p><jats:p><jats:bold>Results:</jats:bold> The first FTD reports published in Latin America were mostly case reports. The last two decades marked a substantial increase in the number of FTD research in Latin American countries. Brazil (165), Argentina (84), Colombia (26), and Chile (23) are the countries with the larger numbers of FTD published studies. Most of the research has focused on clinical and neuropsychological features (<jats:italic>n</jats:italic> = 247), including the local adaptation of neuropsychological and behavioral assessment batteries. However, there are little to no large studies on prevalence (<jats:italic>n</jats:italic> = 4), biomarkers (<jats:italic>n</jats:italic> = 9), or neuropathology (<jats:italic>n</jats:italic> = 3) of FTD.</jats:p><jats:p><jats:bold>Conclusions:</jats:bold> Future FTD studies will be required in Latin America, albeit with a greater emphasis on clinical diagnosis, genetics, biomarkers, and neuropathological studies. Regional and country-level efforts should seek better estimations of the prevalence, incidence, and economic impact of FTD syndromes.</jats:p>
Scopus© Citations 10 1
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Higher Prevalence of Extended-Spectrum Cephalosporin-Resistant Enterobacterales in Dogs Attended for Enteric Viruses in Brazil Before and After Treatment with Cephalosporins
(2021)
Marília Salgado-Caxito
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Andrea I. Moreno-Switt
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Antonio Carlos Paes
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Carlos Shiva
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MUNITA SEPULVEDA, JOSE MANUEL
<jats:p>The extensive use of antibiotics is a leading cause for the emergence and spread of antimicrobial resistance (AMR) among dogs. However, the impact of using antibiotics to treat viral infections on AMR remains unknown. In this study, we compared the prevalence of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E) between dogs with a suspected infection of canine parvovirus (CPV) and canine distemper (CDV) before and after treatment with third-generation cephalosporins. We found a higher prevalence of ESCR-E faecal carriage in dogs suspected of CPV (37%) and CDV (15%) compared to dogs with noninfectious pathologies (9%) even prior to the start of their treatment. A 7-day course of ceftriaxone or ceftiofur administrated to CPV and CDV-suspected dogs substantially increased their ESCR-E faecal carriage during treatment (85% for CPV and 57% for CDV), and 4 weeks after the treatment ended (89% for CPV and 60% for CDV) when dogs were back in their households. Most of the observed resistance was carried by ESCR-E. coli carrying blaCTX-M genes. Our results suggest the need to optimize prophylactic antibiotic therapy in dogs treated for a suspected viral infection to prevent ESCR-E emergence and spread in the community.</jats:p>
5Scopus© Citations 15

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