Gliomas de alto grado en pacientes pediátricos post - radioterapia: reporte de dos casos en el Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú / High-Grade gliomas in pediatric patients after radiotherapy: A report of two cases at the Instituto Nacional de Ciencias Neurológicas - Lima, Peru

RESUMEN Los gliomas de alto grado inducidos por radioterapia (GIR) son una complicación poco frecuente, pero con un pronóstico ominoso. Poco se sabe sobre la biología subyacente de los gliomas de alto grado post-radiación, aunque algunos estudios sugieren que no hay características histológicas y/o citogenéticas únicas para distinguirlos de los glioblastomas de novo. En el presente artículo, se reportan dos casos pediátricos que reunen criterios para ser considerados GIR y se discute piezas de literatura pertinente. Dos pacientes menores de 10 años sin antecedentes genéticos y clínicos de relevancia fueron diagnosticados en el Instituto Nacional de Enfermedades Neoplásicas de Lima, como portadores de glioma cerebral primario y luego de la aplicación de ciclos de radioterapia, desarrollaron tumores gliales secundarios de alto grado, que fueron validados histopatológicamente en ambos casos. Este reporte enfatiza la necesidad de determinar los factores de riesgo, las vías moleculares de tumorogenesis post- radioterapia y objetivos terapéuticos probables.

SUMMARY Radiation therapy-induced high-degree gliomas (RIGs) are a rare complication with an ominous prognosis. Little is known about the underlying biology of RIGs, although some studies have suggested that there are no unique histologic or cytogenetic features to distinguish them from de novo glioblastomas. Two cases that meet the criteria to be considered RIG are reported, and pertinent pieces of literature are discussed. Two patients under 10 years of age, neither of whom had relevant genetic or clinical history, were diagnosed with primary cerebral gliomas at the National Institute of Neoplastic Diseases in Lima and, after radiation therapy cycles, developed high-degree secondary gliomas, confirmed in both patients by a histopathologic analysis. This report emphasizes the need to identify risk factors, molecular mechanisms of tumor development after radiotherapy, and probable therapeutic targets.

Evaluación de la toxicidad de chalconas sintéticas con potencial anti-Leishmania en ratones BALB/c / Toxicity assessment of synthetic chalcones with antileishmanial potential in BALB/c mice

RESUMEN Objetivo: Evaluar la toxicidad de tres chalconas sintéticas administradas por vía intraperitoneal en ratones BALB/c. Materiales y métodos: La dosis letal media (DL50) se estimó por el método Up-and-Down de Dixon. La toxicidad subcrónica de las chalconas se evaluó a 20 y 40 mg/kg por 21 días. Se evaluó el efecto tóxico a nivel de comportamiento, fisiológico, bioquímico e histológico. Resultados: La chalcona 43 generó moco en las heces, daño visceral (hígado) y alteración en el coeficiente de órganos (riñón, p = 0,037 y cerebro, p = 0,008) en comparación con el grupo control. Además, en el análisis histológico se observó que esta chalcona produjo edema, inflamación y necrosis en los órganos evaluados, aunque no hubo diferencia significativa con el control. Todos los parámetros bioquímicos no difirieron significativamente entre los grupos de tratamiento a dosis de 40 mg/kg y el control. Conclusiones: La DL50 para las tres chalconas fue superior a 550 mg/kg de peso corporal. Las chalconas 40 y 42 son relativamente no tóxicas. Ambas pueden considerarse seguras para la aplicación vía intraperitoneal en ratones BALB/c y, en consecuencia, son posibles candidatas para ser usadas en el tratamiento contra las leishmaniosis.

ABSTRACT Objective: To evaluate the toxicity of three synthetic chalcones administered intraperitoneally to BALB/c mice. Materials and methods: The median lethal dose (LD50) was estimated by Dixon's Up-and-Down method. Subchronic toxicity of chalcones was evaluated at 20 and 40 mg/kg for 21 days. Behavioral, physiological, biochemical, and histological toxic effects were evaluated. Results: Chalcone 43 produced mucus in feces, visceral damage (liver) and alterations in organ coefficient (kidney, p = 0.037 and brain, p = 0.008) when compared to the control group. In addition, histological analysis showed that this chalcone produced edema, inflammation and necrosis in the evaluated organs, although there was no significant difference with the control. None of the biochemical parameters differed significantly between the treatment groups at 40 mg/kg dose and the control. Conclusions: The LD50 for all three chalcones was greater than 550 mg/kg of body weight. Chalcones 40 and 42 were found to be relatively non-toxic. Both can be considered safe for intraperitoneal application in BALB/c mice and, consequently, are potential candidates for use in the treatment of leishmaniasis.

Depression in women with a diagnosis of breast cancer. Prevalence of symptoms of depression in Peruvian women with early breast cancer and related sociodemographic factors.

We sought to review literature on the prevalence of symptoms of depression in women with a diagnosis of breast cancer (BC) and in the Peruvian population determine the prevalence of symptoms of depression and to describe the association with sociodemographic characteristics. Descriptive cross-sectional analytical study of 254 patients from the National Cancer Institute of Peru (Instituto Nacional de Enfermedades Neoplásicas) with a diagnosis of clinical stage I or II BC. The patients included women aged between 26 and 67 years old. Symptoms of depression were monitored by the Beck Depression Inventory-II. Moreover, clinical features and patient sociodemographic characteristics were analyzed and their association with depression was assessed by logistic regression. The average age of the patients was 47.8 ± 9.2 years; 5.4% of the patients were postmenopausal at the time of the questionnaire. About 55% of women were from Lima, 58.3% had completed secondary education (11 ± 3.2 years), 45.7% were not working, and 46.5% were single. The prevalence of depression was 25.6% at the time of BC diagnosis. Of those patients with symptoms of depression, 16.9% showed symptoms of mild depression, 6.3% moderate, and 2.4% severe. A multivariable logistic regression model showed that in Peruvian women with a diagnosis of BC being married or employed significantly decreased the odds of presenting depressive symptoms (P = 0.029 and 0.017, respectively). Our main limitation was the lack of evaluation of depressive symptoms before the diagnosis, during or at the end of treatment. Another limitation was that the Beck Depression Inventory-II test could only identify depressive symptoms, but not depression as a disease. We have reviewed relevant literature on depression in women with a diagnosis of BC. The data presented suggests an association between both employment and marital status with depressive symptoms among Peruvian women with a diagnosis of BC. Pre-emptive support for women at risk could influence resilience and/or motivation for compliance with antineoplastic treatments.

Epigenética: la relación del medio ambiente con el genoma y su influencia en la salud mental / Epigenetics: The relationship of the environment and mental health

El estudio del genoma humano, cuando efectuado solo a través de la información secuencial de ADN, no explica del todo el alto nivel de variación inter-individual usualmente observado. Es la epigenética la que permite explicar aquellas variaciones de expresión génica como un proceso reversible y hereditario en el corto plazo, bajo la influencia del medio ambiente durante diversas etapas del desarrollo y la edad adulta, sin modificar la secuencia genética. Las alteraciones epigenéticas están siendo ya incorporadas como elementos valiosos en la posible identificación de biomarcadores. Además, debido a su naturaleza reversible, pueden constituirse en factores de mejoría de síntomas de enfermedad mediante el uso de enfoques terapéuticos. El presente artículo explica los mecanismos de inhibición de la expresión génica, su relación con el medio ambiente, la dieta y su influencia en la evolución, la ocurrencia de enfermedades, la conducta humana y la salud mental.

The study of the human genome, when performed only through the DNA sequence information, does not completely explain the high level of inter-individual variation usually observed. It is the control of gene expression by the epigenetics what allows to explain those variations of gene expression, as a reversible and hereditary process in the short term under the influence of the environment during various stages of development and adulthood, without modifying the genetic sequence. Epigenetic alterations are already being studied as valuable candidates in the eventual identification of biomarkers. Furthermore, their reversible nature makes them promising factors in the amelioration of disease symptoms through the use of therapeutic approaches. This article explains the epigenetic mechanisms and its relationship with the environment, diet, and its influence on evolution, the occurrence of diseases, human behavior and mental health.

Diagnóstico molecular de pérdida de heterocigosidad para 1p/19q en tumores oligodendrogliales por PCR multiplex en el Instituto Nacional de Enfermedades Neoplásicas, Lima- Perú / Molecular diagnosis of heterozygosity loss for 1p/19q in oligodendroglial tumors by multiplex PCR at the National Institute of Neoplastic Diseases, Lima-Peru

La pérdida de heterocigosidad 1p/19q tiene valor pronóstico clínico y está fuertemente asociada con características histológicas clásicas de oligodendroglioma. Objetivos: El presente artículo, propone un método molecular para determinar la pérdida de heterocigosidad (LOH por sus siglas en inglés) para 1p/19q y permitir la clasificación de tumores oligodendrogliales. Material y Métodos: Se utilizaron muestras en fresco del Banco de Tejidos Tumorales del Instituto Nacional de Enfermedades Neioplásicas (INEN) y biopsias de tejido embebido en parafina de tumores oligodendrogliales, con diagnóstico patológico de oligodendroglioma y oligoastrocitoma. Los métodos propuestos son PCR Multiplex y amplificación de fragmentos por electroforesis capilar de los productos de PCR, y fueron aplicados a un total de 39 casos que presentaban grado histológico II y III. Resultados: Los resultados obtenidos permiten una adecuada clasificación molecular de los tumores oligodendrogliales.

A heterozygosity loss of 1p/19q has clinical prognostic value and is strongly associated with classical histologic features of oligodendroglioma. Objectives: The present article proposes a molecular method to determine the loss of heterozygosity (LOH) for 1p/19q and to allow the classification of oligodendroglial tumors. Material and Methods: Fresh samples from the National Institute of Neoplastic Diseases’ Tumor BioBank and paraffin-embedded tissue biopsies of oligodendroglial tumors with pathological diagnosis of oligodendroglioma and oligoastrocytoma were used. The proposed methods are Multiplex PCR and amplification of fragments by capillary electrophoresis of PCR products, and were applied to a total of 39 cases which presented histological grade II and III. Results: The results obtained allow an adequate molecular classification of oligodendroglial tumors.

Bancos de cerebro: Un reto para Latinoamérica / Brain Banks: A challenge for Latin America

Muchos de los progresos recientes en la comprensión de la patogénesis de trastornos comunes y raros del sistema nervioso se han producido mediante el uso de tejido cerebral humano post-mortem. Los bancos de cerebros han tenido un papel crucial en este proceso, proporcionando material raro e invaluable. La función de un banco de cerebro moderno es recolectar material post-mortem o de biopsia de casos clínicamente y patológicamente bien caracterizados de manera continua y sistemática, considerando cuestiones de seguridad y éticas que rodean el uso de tejido humano donado para investigación médica. El presente artículo llama la atención sobre la importancia de los bancos de cerebro, en la recolección y almacenamiento de material post-mortem para satisfacer las necesidades de proyectos de investigación específicos, los aspectos tanto técnicos como éticos y legales, relacionados a la donación y manipulación de material biológico, así como proponer el desarrollo de una red en América Latina de bancos de cerebro que permita contar con material de estudio de diversos padecimientos en nuestra población.

Many of the latest findings to understand the pathogenesis of common and rare disorders of the nervous system have been produced by the use of post-mortem human brain tissue. Brain banks have played a crucial role in this process, rare and invaluable material. The function of a modern brain bank is the collection of post-mortem material or biopsy of clinically and pathologically well-characterized cases in a continuous and systematic manner, considering safety and ethical issues surrounding the use of human tissue for medical research. This review give importance of brain banks in the collection and storage of post-mortem material to satisfy the needs of specific research projects, the technical, ethical and legal aspects related to donation and manipulation of biological material, as well as proposing the development of a network in Latin America of brain banks that allows us to have material for the study of various diseases in our population.

Deterioro cognitivo por quimioterapia adyuvante en pacientes con cáncer de mama: Una problemática por definir en el Perú / Cognitive impairment due to adjuvant chemotherapy in breast cancer patients: A problem awaiting definition in Peru

El deterioro cognitivo inducido por quimioterapia es un proceso biológico poco entendido; sin embargo, existe evidencia de que podría afectar a pacientes en tratamiento adyuvante por cáncer de mama cuya incidencia varía ampliamente según la población en estudio, el esquema terapéutico aplicado y la metodología utilizada en su evaluación. La presente revisión busca iniciar discusiones sobre la necesidad de generar información en nuestro medio acerca de este trastorno, a fin de plantear estrategias de prevención y control por parte del personal de salud y mejorar la calidad de vida de las pacientes sometidas a este tipo de tratamiento.

Chemotherapy-induced cognitive impairment is a poorly understood biological process; however, there is evidence that it could affect patients in adjuvant treatment for breast cancer whose incidence varies widely according to the study population, the therapeutic scheme applied and the methodology used in its evaluation. The present review seeks to initiate discussions about the need to generate information in our milieu about this disorder, in order to propose preventive and control strategies by healthcare personnel staff, and improve the quality of life of patients undergoing this type of treatment.