Factores clínicos asociados a complicaciones pulmonares y extrapulmonares en pacientes con fibrosis quística. Un estudio observacional de centro único / Clinical factors associated with pulmonary and extrapulmonary complications in patients with cystic fibrosis. A single-center observational study

Introducción: La fibrosis quística (FQ), afecta el epitelio exocrino, formando una mucosidad espesa que obstruye los conductos de los diferentes órganos, siendo el pulmón y páncreas los más afectados. El objetivo del presente estudio fue determinar la asociación entre los factores clínicos y las complicaciones, así como la supervivencia de pacientes con FQ atendidos en un centro de referencia pediátrica en México. Métodos: El presente estudio observacional, longitudinal, fue realizado en el Instituto Nacional de Pediatría en México, de abril del 2012, a abril del 2022. Con una muestra no probabilística ingresaron al estudio niños con fibrosis quística. Las variables fueron: demográficas, complicaciones pulmonares, extrapulmonares y mortalidad. Se realiza la asociación con chi-cuadrado y la supervivencia con Kaplan-Meir. Resultados: Se analizan 71 pacientes, lactantes menores 41 casos (62%), pre-escolares 12 casos (16.9%). Fueron 40 hom-bres (56.3%). 57 casos (80.3%) tuvieron exacerbación infecciosa, 11 casos (15.5%) aspergi-losis broncopulmonar, 9 casos (12.7%) con hipertensión pulmonar, 5 casos (7%) con neumotórax, 12 casos (16.9%) con ventilación mecánica, 70 casos (98.5) con insuficiencia pancreática, 10 casos (14%) con enfermedad hepatobiliar. Hubo asociación de complica-ciones extrapulmonares con el fenotipo F508. La supervivencia global fue de 150 meses. En pacientes con ventilación mecánica invasiva la supervivencia fue de 55 meses (P<0.001), en pacientes con ventilación mecánica no invasiva fue de 106 meses (P<0.001), en pacientes con neumotórax fue de 25 meses P<0.001, en pacientes con aspergilosis bronco-pulmonar alérgica fue de 125 meses P<0.01. Conclusión: la mayor compli-cación extrapulmonar de pa-cientes con FQ es la insuficien-cia pancreática. La presencia de neumotórax disminuye la supervivencia.

Introduction: Cystic fibrosis (CF) affects the exocrine epithelium, forming a thick mucus that obstructs the ducts of the different organs, with the lungs and pancreas being the most affected. This study aimed to determine the association between clinical factors and complications, as well as the survival of CF patients treated at a pediatric reference center in Mexico. Methods: This observational, longitudinal study was conducted at the National Institute of Pediatrics in Mexico from April 2012 to April 2022. Children with cystic fibrosis were entered into the study with a nonprobabilistic sample. The variables were demographic, pulmonary and extrapulmonary complications and mortality. The association was made with chi-square and survival with Kaplan- Meir. Results: Seventy-one patients were analyzed, including 41 infants (62%) and 12 preschoolers (16.9%). There were 40 men (56.3%). Fifty-seven cases (80.3%) had an infectious exacerbation, 11 cases (15.5%) had allergic bronchopulmonary aspergillosis, 9 cases (12.7%) had pulmonary hypertension, 5 cases (7%) had pneumothorax, 12 cases (16.9%) had mechanical ventilation, 70 cases (98.5%) had pancreatic insufficiency, and 10 cases (14%) had hepatobiliary disease. There was an association of extrapulmonary complications with the F508 phenotype. Overall survival was 150 months. In patients with invasive mechanical ventilation, survival was 55 months (P<0.001); in patients with noninvasive mechanical ventilation, it was 106 months (P<0.001); in patients with pneumothorax, it was 25 months (P<0.001); and in patients with allergic bronchopulmonary aspergillosis, it was 125 months (P<0.01). Conclusion: The most significant extrapulmonary complication in CF patients is pancreatic insufficiency. The presence of pneumothorax markedly decreases survival.

N-(2-hydroxyphenyl)-2-propylpentanamide, a valproic acid aryl derivative designed in silico with improved anti-proliferative activity in HeLa, rhabdomyosarcoma and breast cancer cells.

Epigenetic alterations are associated with cancer and their targeting is a promising approach for treatment of this disease. Among current epigenetic drugs, histone deacetylase (HDAC) inhibitors induce changes in gene expression that can lead to cell death in tumors. Valproic acid (VPA) is a HDAC inhibitor that has antitumor activity at mM range. However, it is known that VPA is a hepatotoxic drug. Therefore, the aim of this study was to design a set of VPA derivatives adding the arylamine core of the suberoylanilide hydroxamic acid (SAHA) with different substituents at its carboxyl group. These derivatives were submitted to docking simulations to select the most promising compound. The compound 2 (N-(2-hydroxyphenyl)-2-propylpentanamide) was the best candidate to be synthesized and evaluated in vitro as an anti-cancer agent against HeLa, rhabdomyosarcoma and breast cancer cell lines. Compound 2 showed a better IC50 (µM range) than VPA (mM range) on these cancer cells. And also, 2 was particularly effective on triple negative breast cancer cells. In conclusion, 2 is an example of drugs designed in silico that show biological properties against human cancer difficult to treat as triple negative breast cancer.

Splice variants of zinc finger protein 695 mRNA associated to ovarian cancer.

BACKGROUND: Studies of alternative mRNA splicing (AS) in health and disease have yet to yield the complete picture of protein diversity and its role in physiology and pathology. Some forms of cancer appear to be associated to certain alternative mRNA splice variants, but their role in the cancer development and outcome is unclear. METHODS: We examined AS profiles by means of whole genome exon expression microarrays (Affymetrix GeneChip 1.0) in ovarian tumors and ovarian cancer-derived cell lines, compared to healthy ovarian tissue. Alternatively spliced genes expressed predominantly in ovarian tumors and cell lines were confirmed by RT-PCR. RESULTS: Among several significantly overexpressed AS genes in malignant ovarian tumors and ovarian cancer cell lines, the most significant one was that of the zinc finger protein ZNF695, with two previously unknown mRNA splice variants identified in ovarian tumors and cell lines. The identity of ZNF695 AS variants was confirmed by cloning and sequencing of the amplicons obtained from ovarian cancer tissue and cell lines. CONCLUSIONS: Alternative ZNF695 mRNA splicing could be a marker of ovarian cancer with possible implications on its pathogenesis.

Prognostic factors including neoadjuvant chemotherapy in Mexican children with neuroblastoma.

INTRODUCTION: There are several prognostic factors in children with neuroblastoma that have been outlined in the international literature. MATERIAL AND METHODS: A retrospective study was carried out analysing the medical records of patients with the pathological diagnosis of neuroblastoma seen at the Department of Oncology from the Instituto Nacional de Pediatriá (Mexico) between January 1984 to January 1997. A total of 32 clinical prognostic factors were assess in our population. RESULTS: Fifty five patients whose age ranged from 1 to 168 months old, mean of 35 months were included. Out of 32 prognostic factors only 6 including sex (p= 0.0039), metastatic disease to bone (p= 0.003), bone marrow involvement (p= 0.0027), staging system (p= 0.000015), surgical treatment (p 0,0022) and neoadjuvant chemotherapy (p.005) were the most significant. CONCLUSIONS: It was concluded that besides the prognostic factors outlined, neoadjuvant chemotherapy is of utmost importance. It decreases tumor volume and allows surgery to be more successful, therefore believing that this variable represents a specific prognostic factor in cases of advanced neuroblastoma.

Prognostic factors including neoadjuvant chemotherapy in Mexican children with neuroblastoma

Introducción. Existen diferentes factores pronósticos en los niños con neuroblastoma, estos factores tienen diferente peso específico de acuerdo a la literatura internacional. Material y métodos. Se realizó un estudio retrospectivo, analizando los expedientes clínicos de los pacientes con el diagnóstico de neuroblastoma, tratados en el Instituto Nacional de Pediatría (México) de enero de 1984 a enero de 1997. Se analizaron un total de 32 factores pronósticos clínicos dentro de nuestra población. Resultados. Se incluyeron un total de 55 pacientes, con un rango de edad de 1 a 68 meses, con una media de 36 meses de edad. De los 32 factores pronósticos evaluados, únicamente 6 fueron significativos, los cuales incluyeron el sexo (p= 0,0039), enfermedad metastásica a hueso (p= 0,003), infiltración a médula ósea (p= 0,0027), estadificación (p= 0,000015), tratamiento quirúrgico (p= 0,0022) y el uso de quimioterapia neoadyuvante (p= 0,005). Conclusiones. En análisis de los resultados de los diferentes factores pronósticos nos permiten concluir que la quimioterapia neoadyuvante realiza un papel importante al permitir la disminución del volumen tumoral, lo que permite que la resección quirúrgica pueda ser completa. El resto de las variables que fueron significativas están asociadas directamente con la presencia de neuroblastoma en estadio avanzado

Introduction. There are several prognostic factors in children with neuroblastoma that have been outlined in the international literature. Material and methods. A retrospective study was carried out analysing the medical records of patients with the pathological diagnosis of neuroblastoma seen at the Department of Oncology from the Instituto Nacional de Pediatría (Mexico) between January 1984 to January 1997. A total of 32 clinical prognostic factors were assess in our population. Results. Fifty five patients whose age ranged from 1 to 168 months old, mean of 35 months were included. Out of 32 prognostic factors only 6 including sex (p= 0.0039), metastatic disease to bone (p= 0.003), bone marrow involvement (p= 0.0027), staging system (p= 0.000015), surgical treatment (p 0,0022) and neoadjuvant chemotherapy (p.005) were the most significant. Conclusions. It was concluded that besides the prognostic factors outlined, neoadjuvant chemotherapy is of utmost importance. It decreases tumor volume and allows surgery to be more successful, therefore believing that this variable represents a specific prognostic factor in cases of advanced neuroblastoma