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The participation of patients in precision oncology trials needs to fulfill molecular-based selection criteria. This strongly limits accrual, and as a consequence, screening successes have decreased, costs have increased, and fewer subjects are enrolled. To achieve narrowed targets, studies have been forced to be multicenter and multinational to reach a larger pool of candidates. However, this globalization faces many challenges, as, for example, in the case of precision oncology trials. These trials have a complex structure that is dependent upon a high-tech infrastructure and knowledge in a dynamic environment. Given the movement of precision clinical cancer research to regions other than Europe and the U.S., it is important to evaluate the feasibility of performing such trials in lower-middle- and low-income countries. Here we critically discuss the advantages of conducting precision oncology clinical trials in Latin America and make suggestions on how to overcome the main challenges involved. IMPLICATIONS FOR PRACTICE: Precision clinical trials in oncology are studies that require candidates to have tumors with specific molecular alterations, which are considered the target for the trial experimental therapy. Because many molecular alterations are rare, fewer patients are enrolled. This has led to trials being forced to be multicenter and multinational, including trials in Latin America. This article discusses the challenges and opportunities to conduct precision oncology trials in Latin America, aiming to help sponsors and investigators to solve complex issues that ultimately lead to more of such trials being run in the region, potentially benefiting more Latin American patients with cancer.
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Ensayos Clínicos como Asunto/métodos , Terapia Molecular Dirigida/métodos , Neoplasias/tratamiento farmacológico , Medicina de Precisión/métodos , Ensayos Clínicos como Asunto/normas , Humanos , Internacionalidad , América Latina , Terapia Molecular Dirigida/normas , Estudios Multicéntricos como Asunto , Neoplasias/patología , Medicina de Precisión/normasRESUMEN
Cellular membrane is a key component for maintaining cell shape and integrity. The classical membrane structure and function by Singer and Nicolson groundbreaking model has depicted the membrane as a homogeneous fluid structure. This view has changed by the discovery of discrete domains containing different lipid compositions, called lipid rafts, which play a key role in signal transduction in eukaryotic cells. In the past few years, lipid raft-like structures have been found in bacteria also, constituted by cardiolipin and other modified lipids, perhaps involved in generating a specific site for protein clustering. Here, we report the analysis of a protein termed YqiK from Escherichia coli, a prohibitin homolog that has been implicated in stress sensing by the formation of membrane-associated microdomains. The E. coli yqiK-deficient mutant strain showed an enhanced swimming behavior and was resistant to ampicillin but its response to other stressing conditions was similar to that of the wild-type strain. The abnormal swimming behavior is reversed when the protein is expressed in trans from a plasmid. Also, we demonstrate that YqiK is not redundant with QmcA, another flotillin homolog found in E. coli. Our results, along with the data available in the literature, suggest that YqiK may be involved in the formation of discrete membrane-associated signaling complexes that regulate and agglomerate signaling proteins to generate cell response to chemotaxis.
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Proteínas de Escherichia coli/metabolismo , Escherichia coli/fisiología , Proteínas de la Membrana/metabolismo , Proteínas Represoras/metabolismo , Membrana Celular/metabolismo , Quimiotaxis/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Microdominios de Membrana , Proteínas de la Membrana/genética , Mutación , Plásmidos/genética , Prohibitinas , Proteínas Represoras/genética , Transducción de SeñalRESUMEN
PURPOSE: As the fifth international consensus on advanced breast cancer (ABC5) established guidelines for the management of this disease, the aim of this article was to present the applicability of the consensus recommendations and to generate knowledge to improve access. METHODS: Sixty-one recommendation statements were selected and discussed by 15 breast cancer experts from Latin America (LA). After the discussion, the level of consensus was determined through a vote. In addition to this, the level of access to each of the recommendations presented, according to the country and health system, was exposed. RESULTS: Latin American experts had a high level of agreement with the ABC5 consensus recommendations (range, 83%-100%). Twelve of 61 statements are not available for all patients in LA. Among the limitations to access, the following ones are described: limited access to certain technologies (stereotactic body radiotherapy, positron emission tomography-computed tomography), the high costs of drugs that limits access to treatment with CDK4/6 inhibitors, pertuzumab, or poly(ADP-ribose) polymerase inhibitors, and the lack of molecular tests for access to therapeutic targets, as well as the difficult geography and cultural diversity of our continent. CONCLUSION: Despite the great relevance of the recommendations of the ABC5 consensus guidelines, we highlight that we still need to improve access for all patients, regardless of the country or health system they are in, for which we call to action to policy makers and patient groups to improve clinical outcomes of patients with advanced breast cancer in our region.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , América Latina/epidemiología , ConsensoRESUMEN
Cisplatin is the standard of treatment for squamous cell carcinoma of the head and neck (SCCHN) that has demonstrated efficacy, either in locally advanced disease when combined with radiotherapy at high doses, or in metastatic/recurrent disease when combined with other agents. However, the usual toxicities related to cisplatin, such as neurotoxicity, nephrotoxicity, ototoxicity, and hematologic toxicities, especially when high doses have been administered, have important implications in the patients' quality of life. The decision to administer cisplatin depends on several patient factors, such as age, performance status, weight loss, comorbidities, previous toxicities, chronic viral infection, or even the current SARS-CoV-2 pandemic. In order to establish recommendations for the management of patients with SCCHN, a group of experts in medical and radiation oncology from Spain and Latin-American discussed how to identify patients who are not candidates for cisplatin to offer them the most suitable therapeutic alternative.
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BACKGROUND: Thymomas are a group of rare neoplasms of the anterior mediastinum. The objective of this study was to describe the demographics, clinical characteristics and treatment approaches in Latin America. METHODS: This was a retrospective multicenter cohort study including patients with histologically proven thymomas diagnosed between 1997 and 2018. Demographics, clinicopathological characteristics and therapeutic outcomes were collected locally and analyzed in a centralized manner. RESULTS: A total of 135 patients were included. Median age at diagnosis was 53 years old (19-84), 53.3% (n = 72) of patients were female and 87.4% had an ECOG performance score ranging from 0-1. A total of 47 patients (34.8%) had metastatic disease at diagnosis. Concurrent myasthenia gravis occurred in 21.5% of patients. Surgery was performed in 74 patients (54.8%), comprising 27 (20%) tumorectomies and 47 (34.8%) thymectomies. According to the Masaoka-Koga system, overall survival (OS) at five-years was 73.4%, 63.8% and 51%, at stages I-II, III-IVA and IVB, respectively (p = 0.005). Furthermore, patients with low lactate dehydrogenase (LDH) (≤373 IU/L) at baseline and myasthenia gravis concurrence showed significantly better OS (p = 0.001 and p = 0.008, respectively). In multivariate analysis, high LDH levels (HR 2.8 [95% confidence interval [CI]: 1.1-7.8]; p = 0.036) at baseline and not performing a surgical resection (HR 4.1 [95% CI: 1.3-12.7]; p = 0.016) were significantly associated with increased risk of death. CONCLUSIONS: Our data provides the largest insight into the clinical characteristics and outcomes of patients with thymomas in Latin America. Survival in patients with thymomas continues to be very favorable, especially when subjected to adequate local control.
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Timoma/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , América Latina , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
RESUMEN Introducción: el cáncer renal es una patología que, al igual que otras neoplasias, si se diagnostica tempranamente puede tener un mejor pronóstico. La variabilidad clínica es un factor que puede afectar su diagnóstico. Objetivo: evaluar el nivel de conocimientos y las percepciones de los médicos oncólogos clínicos ecuatorianos sobre el cáncer renal metastásico. Metodología: se realizó un estudio de corte transversal. La información fue recolectada a través de una encuesta diseñada para esta investigación. Resultados: la variabilidad de conocimientos de los profesionales fue baja, la experiencia en su práctica asistencial con medicamentos complejos es amplia, principalmente con sunitinib, la decisión de manejo sistémico del cáncer metastásico se consigue a partir de grupos de pares o multidisciplinarios, pero siempre se priorizan criterios clínicos antes que administrativos. Conclusiones: los oncólogos tienen baja variabilidad en los conocimientos y amplia experiencia en el uso de medicamentos complejos, sin embargo, la situación de acceso a medicamentos de alto costo es un factor presente en la mayoría.
ABSTRACT Introduction: Renal cancer is a pathology that, like other neoplasms, if it is early diagnosed, it can have a better prognosis. The clinical variability is a factor that could affect its diagnosis. Objective: To evaluate the knowledge level and the perceptions about metastatic renal cancer of the Ecuadorian clinical oncologists. Methodology: This was cross-sectional study. The information was collected using a survey designed for this research study. Results: The variability in the knowledge of the professionals was low. Their experience in their care practice with complex medicines was wide, specially with sunitinib. The decision of systemic handling of the metastatic cancer was achieved from peers or multidisciplinary groups but always clinical criterion were prioritized over the administrative ones. Conclusions: The oncologists had low variability in their knowledge and wide experience in the use of complex medicines, however, the situation of access to high cost medicines was a factor present in the majority.
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Water hyacinth is a beautiful monocotyledon plant that has been dispersed all over the world by humans. The plant has been present in Mexico since 1907, and many water bodies have become infested with it since then. In 2001, we initiated a survey in Yuriria lagoon in southern Guanajuato state to isolate fungi able to biocontrol the plant. We isolated 25 morphologically distinct fungal cultures, of which two were identified as members of the genus Cercospora. Cercospora species are among the most prevalent and destructive of plant pathogens and can be found on leaves, pedicels, stems, fruits, and bracts. Only two species of Cercospora, Cercospora piaropi, and Cercospora rodmanii, have been described on water hyacinth; however, the classification of these species has been controversial. Several molecular approaches have been used for Cercospora identification, and some candidate genes have been identified for use in Cercospora species determination. Although the nrRNA genes alone do not show sufficient resolution for species determination, histone H3, translation elongation factor1-α, ß-tubulin, actin, and calmodulin have been shown in previous studies to have an adequate number of nucleotide changes to allow species identification. In the present study, we used partial sequences of the histone H3, actin, and calmodulin genes to identify our two isolates as C. rodmanii. Our two strains are not specific to water hyacinth, as they are also pathogenic to beet and sugar beet. Similar host ranges were found for C. rodmanii strains isolated from Tabasco in México, Zambia, and Brazil, however, the specificity for water hyacinth persists in Cercospora piaropi Tharp and C. rodmanii Conway, the latter being the most pathogenic.