Moderately hypofractionated post-operative radiation therapy for breast cancer: preferences amongst radiation oncologists from countries in Latin America and the Caribbean.

Background: The safety and effectiveness of moderately hypofractionated post-operative radiation therapy for breast cancer were demonstrated by several trials. This study aimed to evaluate the current patterns of practice and prescription preference about moderately hypofractionated post-operative radiation therapy to assess possible aspects that affect the decision-making process regarding the use of fractionation in breast cancer patients in Latin America and the Caribbean (LAC). We also aimed to identify factors that can restrain the utilization of moderately hypofractionated post-operative radiation therapy for breast cancer. Materials an methods: Radiation oncologists from LAC were invited to contribute to this study. A 38-question survey was used to evaluate their opinions. Results: A total of 173 radiation oncologists from 13 countries answered the questionnaire. The majority of respondents (84.9%) preferred moderately hypofractionated post-operative radiation therapy as their first choice in cases of whole breast irradiation. Whole breast plus regional nodal irradiation, post-mastectomy (chest wall and regional nodal irradiation) without reconstruction, and post-mastectomy (chest wall and regional node irradiation) with reconstruction hypofractionated post-operative radiation therapy was preferred by 72.2% 71.1%, and 53.7% of respondents, respectively. Breast cancer stage, and flap-based breast reconstruction were the factors associated with absolute contraindications for the use of hypofractionated schedules. Conclusion: Even though moderately hypofractionated post-operative radiation therapy for breast cancer is considered a new standard to the vast majority of the patients, its unrestricted application in clinical practice across LAC still faces reluctance.

MicroRNAs Present in Malignant Pleural Fluid Increase the Migration of Normal Mesothelial Cells In Vitro and May Help Discriminate between Benign and Malignant Effusions.

The sensitivity of pleural fluid (PF) analyses for the diagnosis of malignant pleural effusions (MPEs) is low to moderate. Knowledge about the pathobiology and molecular characteristics of this condition is limited. In this study, the crosstalk between stromal cells and tumor cells was investigated in vitro in order to reveal factors that are present in PF which can mediate MPE formation and aid in discriminating between benign and malignant etiologies. Eighteen PF samples, in different proportions, were exposed in vitro to mesothelial MeT-5A cells to determine the biological effects on these cells. Treatment of normal mesothelial MeT-5A cells with malignant PF increased cell viability, proliferation, and migration, and activated different survival-related signaling pathways. We identified differentially expressed miRNAs in PF samples that could be responsible for these changes. Consistently, bioinformatics analysis revealed an enrichment of the discovered miRNAs in migration-related processes. Notably, the abundance of three miRNAs (miR-141-3p, miR-203a-3, and miR-200c-3p) correctly classified MPEs with false-negative cytological examination results, indicating the potential of these molecules for improving diagnosis. Malignant PF produces phenotypic and functional changes in normal mesothelial cells. These changes are partly mediated by certain miRNAs, which, in turn, could serve to differentiate malignant from benign effusions.

PLA2G12A as a Novel Biomarker for Colorectal Cancer with Prognostic Relevance.

Metastasis is the leading cause of colorectal cancer (CRC)-related deaths. Therefore, the identification of accurate biomarkers predictive of metastasis is needed to better stratify high-risk patients to provide preferred management and reduce mortality. In this study, we identified 13 new genes that modified circulating tumor cell numbers using a genome-wide genetic screen in a whole animal CRC model. Candidate genes were subsequently evaluated at the gene expression level in both an internal human CRC cohort of 153 patients and an independent cohort from the TCGA including 592 patients. Interestingly, the expression of one candidate, PLA2G12A, significantly correlated with both the time to recurrence and overall survival in our CRC cohort, with its low expression being an indicator of a poor clinical outcome. By examining the TCGA cohort, we also found that low expression of PLA2G12A was significantly enriched in epithelial-mesenchymal transition signatures. Finally, the candidate functionality was validated in vitro using three different colon cancer cell lines, revealing that PLA2G12A deficiency increases cell proliferation, migration, and invasion. Overall, our study identifies PLA2G12A as a prognostic biomarker of early-stage CRC, providing evidence that its deficiency promotes tumor growth and dissemination.

Etiologies of outpatient medically attended acute respiratory infections among young Ecuadorian children prior to the start of the 2020 SARS-CoV-2 pandemic.

BACKGROUND: Implementation of respiratory virus prevention measures requires detailed understanding of regional epidemiology; however, data from many tropical countries are sparse. We describe etiologies of ambulatory pediatric acute respiratory tract infections (ARTI) in Ecuador immediately preceding the onset of the SARS-CoV-2 pandemic. METHODS: Children < 5 years presenting to a designated study site with an ARTI were eligible. Informed consent was obtained. Demographic and clinical data were recorded. A nasopharyngeal swab was collected, processed, and analyzed using multiplex polymerase chain reaction (PCR) for common respiratory pathogens. Rhinovirus/enterovirus positive samples were further characterized by genomic sequencing. RESULTS: A total of 820 subjects were enrolled in the study between July 2018 and March 2020. A total of 655 (80%) samples identified at least one pathogen. Rhinoviruses (44%) were most common, followed by enteroviruses (17%), parainfluenza viruses (17%), respiratory syncytial virus (RSV) (15%), and influenza viruses (13%). Enterovirus D68 was the most common enterovirus detected and was among the leading causes of bronchiolitis. Seasonal RSV and influenza virus activity were different along the coast compared with the highlands. CONCLUSIONS: Ongoing regional surveillance studies are necessary to optimize available and emerging pathogen-specific preventative measures.

Are Transcription Factors Plausible Oncotargets for Triple Negative Breast Cancers?

Breast cancer (BC) is the most diagnosed cancer worldwide and one of the main causes of cancer deaths. BC is a heterogeneous disease composed of different BC intrinsic subtypes such as triple-negative BC (TNBC), which is one of the most aggressive subtypes and which lacks a targeted therapy. Recent comprehensive analyses across cell types and cancer types have outlined a vast network of protein-protein associations between transcription factors (TFs). Not surprisingly, protein-protein networks central to oncogenesis and disease progression are highly altered during TNBC pathogenesis and are responsible for the activation of oncogenic programs, such as uncontrollable proliferation, epithelial-to-mesenchymal transition (EMT) and stemness. From the therapeutic viewpoint, inhibiting the interactions between TFs represents a very significant challenge, as the contact surfaces of TFs are relatively large and featureless. However, promising tools have emerged to offer a solution to the targeting problem. At the clinical level, some TF possess diagnostic and prognostic value in TNBC. In this review, we outline the recent advances in TFs relevant to TNBC growth and progression. Moreover, we highlight different targeting approaches to inhibit these TFs. Furthermore, the validity of such TFs as clinical biomarkers has been explored. Finally, we discuss how research is likely to evolve in the field.

Microenvironmental Reactive Oxygen Species in Colorectal Cancer: Involved Processes and Therapeutic Opportunities.

Colorectal cancer (CRC) is the fourth most common cause of cancer deaths worldwide. Although screening programs have reduced mortality rates, there is a need for research focused on finding the main factors that lead primary CRC to progress and metastasize. During tumor progression, malignant cells modify their habitat, corrupting or transforming cells of different origins and creating the tumor microenvironment (TME). Cells forming the TME like macrophages, neutrophils, and fibroblasts generate reactive oxygen species (ROS) that modify the cancer niche. The effects of ROS in cancer are very diverse: they promote cellular proliferation, epithelial-to-mesenchymal transition (EMT), evasion of cell death programs, migration, and angiogenesis. Due to the multifaceted role of ROS in cancer cell survival and function, ROS-modulating agents such as antioxidants or pro-oxidants could have therapeutic potential in cancer prevention and/or as a complement to systemic treatments. In this review, we will examine the main ROS producer cells and their effects on cancer progression and metastasis. Furthermore, we will enumerate the latest clinical trials where pro-oxidants and antioxidants have therapeutic uses in CRC.

Spinal Muscular Atrophy autophagy profile is tissue-dependent: differential regulation between muscle and motoneurons.

Spinal muscular atrophy (SMA) is a neuromuscular genetic disease caused by reduced survival motor neuron (SMN) protein. SMN is ubiquitous and deficient levels cause spinal cord motoneurons (MNs) degeneration and muscle atrophy. Nevertheless, the mechanism by which SMN reduction in muscle contributes to SMA disease is not fully understood. Therefore, studies evaluating atrophy mechanisms in SMA muscles will contribute to strengthening current knowledge of the pathology. Here we propose to evaluate autophagy in SMA muscle, a pathway altered in myotube atrophy. We analized autophagy proteins and mTOR in muscle biopsies, fibroblasts, and lymphoblast cell lines from SMA patients and in gastrocnemius muscles from a severe SMA mouse model. Human MNs differentiated from SMA and unaffected control iPSCs were also included in the analysis of the autophagy. Muscle biopsies, fibroblasts, and lymphoblast cell lines from SMA patients showed reduction of the autophagy marker LC3-II. In SMA mouse gastrocnemius, we observed lower levels of LC3-II, Beclin 1, and p62/SQSTM1 proteins at pre-symptomatic stage. mTOR phosphorylation at Ser2448 was decreased in SMA muscle cells. However, in mouse and human cultured SMA MNs mTOR phosphorylation and LC3-II levels were increased. These results suggest a differential regulation in SMA of the autophagy process in muscle cells and MNs. Opposite changes in autophagy proteins and mTOR phosphorylation between muscle cells and neurons were observed. These differences may reflect a specific response to SMN reduction, which could imply diverse tissue-dependent reactions to therapies that should be taken into account when treating SMA patients.

15q Duplication Syndrome: Report on the First Patient from Ecuador with an Unusual Clinical Presentation.

BACKGROUND: The 15q11.1-13.1 duplication, also known as Dup15q syndrome, is a rare congenital disease affecting 1 in 30,000 to 1 in 60,000 children worldwide. This condition is characterized by the presence of at least one extra copy of genetical material within the Prader-Willi/Angelman Critical Region (PWACR) of the referred 15q11.2-q13.1 chromosome. Case Report. Our study presents the clinical and genetical features of the first patient with a denovo 15q11.2 interstitial duplication on the maternal allele (inv Dup15q) that mimics a milder Prader-Willi syndrome probably due to an atypical disruption of the SNHG14 gene. Methylation-specific MLPA analysis has confirmed the presence of a very unlikely duplication that lies between breakpoint 1 (BP1) and the middle of BP2 and BP3 (BP3). This atypical alteration might be linked to the milder patient's clinical phenotype. CONCLUSIONS: This is the first Dup15q patient reported in Ecuador and of the very few in South America. This aberration has never been described in a patient with Dup15q, and the unusual clinical presentation is probably due to the atypical distal breakpoint occurring within the gene SNHG14 which lies between BP2 and BP3 and does not therefore contain the whole PWACR. If the duplication disrupted the gene, then it is possible that it is the cause of, or contributing to, the patient's clinical phenotype.

Medically Attended Outpatient Coronavirus Infections in Ecuadorean Children During the 20 Months Preceding Countrywide Lockdown Related to the SARS-CoV-2 Pandemic of 2020.

BACKGROUND: Human coronaviruses (HCoVs) cause respiratory tract infections during childhood manifesting as common colds, bronchiolitis, croup and pneumonia. In temperate geographies, HCoV activity peaks between December and March. The epidemiology and manifestations of HCoV infections have not been previously reported from Ecuador. METHODS: Children <5 years who presented with ≥2 symptoms consistent with an acute respiratory tract infection were eligible for enrollment. After obtaining informed consent, demographic data and details regarding the acute illness were recorded. Secretions collected with a nasopharyngeal swab underwent diagnostic testing using multiplex polymerase chain reaction. RESULTS: A total of 850 subjects were enrolled. A total of 677 (80%) tested positive for at least 1 pathogen, including 49 (7.2%) who tested positive for ≥1 HCoV type. HCoV-NL63 was the most frequent type detected (39%), followed by HCoV-OC43 (27%), 229E (22%) and HKU1 (12%). Nearly all subjects who tested positive for HCoV had nasal congestion or secretions (47/49; 96%). The most frequent syndromic diagnosis was common cold (41%), followed by bronchiolitis (27%). We found no association between the infecting HCoV type and subject's syndromic diagnosis (P > 0.05) or anatomic location of infection (upper vs. lower respiratory tract; P > 0.05). The 2018-2019 peak HCoV activity occurred from October to November; the 2019-2020 peak occurred from January to February. CONCLUSIONS: HCoVs were detected in ~7% of outpatient Ecuadorean children <5 years of age with symptoms of acute respiratory tract infection. The most frequently detected HCoV types, and the period of peak HCoV activity differed for the 2018-2019 and 2019-2020 seasons.

Calpain system is altered in survival motor neuron-reduced cells from in vitro and in vivo spinal muscular atrophy models.

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by loss of the survival motor neuron 1 (SMN1) gene. SMA is characterized by the degeneration of spinal cord motoneurons (MNs), progressive skeletal muscle atrophy, and weakness. The cellular and molecular mechanisms causing MN loss of function are only partially known. Recent advances in SMA research postulate the role of calpain protease regulating survival motor neuron (SMN) protein and the positive effect on SMA phenotype of treatment with calpain inhibitors. We analyzed the level of calpain pathway members in mice and human cellular SMA models. Results indicate an increase of calpain activity in SMN-reduced MNs. Spinal cord analysis of SMA mice treated with calpeptin, a calpain inhibitor, showed an increase of SMN, calpain, and its endogenous inhibitor calpastatin in MNs. Finally, in vitro calpeptin treatment prevented microtubule-associated protein 1A/1B-light chain 3 (LC3) increase in MNs neurites, indicating that calpain inhibition may reduce autophagosome accumulation in neuron prolongations, but not in soma. Thus, our results show that calpain activity is increased in SMA MNs and its inhibition may have a beneficial effect on SMA phenotype through the increase of SMN in spinal cord MNs.

Radiation Oncology Workforce in Colombia.

Colombia is experiencing an epidemiologic transition, with an increasing incidence of cancerous neoplasms prevalent in high-income countries, while infection-associated tumors remain highly prevalent. According to international standards, Colombia has a deficit of radiotherapy machines (a shortage of about 47 machines) and radiation oncology specialists (a shortage of about 19 to 149 specialists based on number of centers and incident cases, respectively) to meet the national demand, which may induce an inappropriate dynamic in radiation oncology services. Estimates based on cancer incidence trends and the rate of new specialists in radiation oncology expected to graduate per year suggest that the current deficit will remain unchanged or may even increase during the next decades. The situation is critical because of the existence of a single training program in the country for a population of 45 million inhabitants and the low availability of educational programs offered in the Latin American region to cover the national demand. A comprehensive analysis of radiotherapy services should include data on medical physicists, radiotherapists, and the oncology nursing workforce; however, we found no reliable information available. A better balance between the educational programs offered and the demand for radiotherapy is highly valuable.

Actividad antibacteriana in vitro de Croton lechleri sobre Streptococcus mutans / In vitroantibacterial activity of Croton lechleri on Streptococcus mutans

Objetivo: El propósito del presente estudio fue determinar la actividad antibacteriana de Croton lechleri (C. lechleri) sobre cepas de S. mutans ATCC 35668. Métodos: Se utilizó concentraciones al 50, 75 y 100% de C. lechleri, como control positivo a la clorhexidina 0,12% y al agua destilada como control negativo. Se midieron los halos de inhibición producidos alrededor de discos embebidos con cada una de las concentraciones de C. lechleri sobre colonias de S. mutans sembradas en Agar Muller Hinton. Resultados: Las concentraciones al 75% y 100% de C. lechleri mostraron actividad antibacteriana in vitrosobre S. mutans, la concentración al 50% no manifestó ninguna actividad. La clorhexidina al 0,12% mostró mayor actividad antibacteriana in vitro que las concentraciones de C. lechleri en los grupos de estudio evaluados. Conclusiones: Croton lechleri puede ser una alternativa natural, accesible y de bajo costo para métodos de prevención en caries dental al utilizarse al 75 y 100%. Palabras clave: Antibacterianos; Croton; Streptococcus mutans.

Objective: The purpose of this study was to determine the antibacterial activity of Croton lechleri (C. lechleri) on strains of S. mutans ATCC 35668. Methods: It was used 50%, 75% and 100% concentrations of C. lechleri, and chlorhexidine (0.12%) as a positive control and distilled water as a negative control. It was measured the inhibition halos produced around imbibed discs with each of the concentrations of C. lechleri on colonies of S. mutans which were seeded in Muller Hinton Agar. Results: 75% and 100% of C. lechleri concentration showed antibacterial activity in vitro over S. mutans, 50% concentration showed no activity. 0.12% chlorhexidine concentration showed a higher antibacterial activity in vitro than all the concentrations of C. lechleri groups evaluated. Conclusions: Croton lechleri can be a natural, accessible and low-cost alternative for prevention methods in dental caries when used at 75% and 100%. Keywords: Anti-Bacterial agents; Croton; Streptococcus mutans.

Una causa inusual de fallo hepático agudo: infiltración tumoral por carcinoma neuroendocrino / An unusual cause of acute liver failure: Tumour infiltration by neuroendocrine carcinoma

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Braquiterapia de alta tasa como refuerzo a la radioterapia externa en pacientes con carcinoma de próstata de pronóstico desfavorable / High Ratio Brachytherapy to Reinforce External Radiotherapy in Patients with Prostate Carcinoma of Unfavorable Prognosis

La relativa alta tasa de recaída local en los pacientes con carcinoma de próstata de pronóstico desfavorable tratados con radioterapia externa convencional se debe en parte a factores relacionados con el tumor y en parte a factores técnicos[1, 2]. El tratamiento óptimo para el carcinoma de próstata de pronóstico desfavorable continúa generando controversia en parte por la gran variedad de definiciones de categorías de riesgo en este grupo de pacientes. En la actualidad se sabe que la graduación histológica con la escala cualitativa de Gleason y los niveles séricos pretratamiento del antígeno prostático específico tienen valor predictivo en cuanto a la posibilidad de enfermedad extra-prostática, compromiso de vesículas seminales y metástasis pélvicas ganglionares, siendo indicadores de mal pronóstico los pacientes con Gleason mayor o igual a 7 y niveles de antígeno prostático específico (PSA) mayor o igual a 10 ng/ml.

Carcinoma de vulva: experiencia en el Hospital Oncológico "Padre Machado" / Carcinoma of the vulva: experience in the Hospital Oncologico \"Padre Machado\"

En el presente estudio retrospectivo se evalúan los resultados del tratamiento de 65 pacientes con diagnóstico de Carcinoma de Vulva, vistas en el Servicio de Ginecología del Hospital Oncológico "Padre Machado", entre 1987 y 1992. El Cáncer de Vulva representa el 2,15 por ciento de la patología ginecológica maligna atendida en nuestro servicio. El promedio de edad para las pacientes con carcinoma in situ fue de 47,44 años y, para las pacientes con carcinoma epidermoide invasor fue de 52,05 años. La distribución por estadios fue: Estadio 0:17 pacientes (26,15 por ciento), Estadio I: 3 pacientes (1,54 por ciento, Estadio II: 14 pacientes (21,54 por ciento), Estadio III: 16 pacientes (24,62 por ciento), Estadio IV 15 pacientes (23,08 por ciento), para el carcinoma in situ el tratamiento fue quirúrgico conservador y laserterapia, no se evidenciaron recurrencias locorregionales. En el carcinoma invasor se realizó tratamiento quirúrgico inicial en 24 pacientes (50,00 por ciento), tratamiento con radioterapia y quimioterapia según el Esquema de Nigro en 8 pacientes (16,67 por ciento), radioterapia externa en 7 pacientes (14,58 por ciento, y no recibieron tratamiento 10 pacientes (20,83 por ciento). El tratamiento quirúrgico inicial de acuerdo a la localización y el tamaño de la lesión primaria. Se realizó vulvectomía radical en 15 pacientes (31,25 por ciento). Las complicaciones postoperatorias ocurrieron en el 31,43 por ciento y en la mayor parte de los casos correspondió a la dehiscencia de la herida. La tasa de recurrencia locorregionales fue del 10,64 por ciento

Riesgo de cáncer en el muñon gástrico posterior a gastrectomía por enfermedad benigna / Cancer risk in the gastric stump after to gastrectomy for benign disease

En el presente estudio se revisaron 740 historias de pacientes intervenidos con diagnóstico histológico de carcinoma gástrico, durante un período de 11 años comprendidos entre 1975-1985, en los Servicios de Cirugía general del Hospital Universitario de Caracas. Se realizaron 465 intervenciones quirúrgicas y se encontró una incidencia de 0,67% (4 casos) de pacientes con gastrectomía previa por enfermedad benigna, que desarrollaron cáncer en el muñon gástrico. Se revisó la bibliografía nacional e internacional, edad promedio y sexo, tiempo transcurrido desde la operación inicial y el inicio de los síntomas del cáncer gástrico, la patología previa, el tipo de intervención realizada, tratamiento definitivo y la mortalidad. En este estudio se demostró que el riesgo de cáncer en el muñon gastrico en pacientes gastrectomizados por enfermedad benigna en los primeros 20 años posteriores a la operación, continúa siendo discretamente mayor que el riesgo de carcinoma gástrico en la población general, recomendándose seguimiento y estudios radiológicos y endoscópicos de control