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Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098–5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74–35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87–16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915–16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83–15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747–11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831–22.02, p = 0.004, HR = 9.571, 95% CI 2.856–32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669–16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411–13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for ~2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates.

To evaluate the reliability, construct, and criterion validity of the screening tool for childhood cancer (SCAN), stratified by age in oncology patients admitted to a tertiary referral hospital. Hospitalized children from birth to 18 years old, with an oncological diagnosis and expected length of stay (LOS) of >24 hours were included. Interrater and intrarrater agreements were used to evaluate the reliability of SCAN. Construct validity and criterion validity were explored in SCAN. Also, predictive validity was explored by comparing SCAN risk categories against LOS. Three hundred ninety-four children were included in the study. The scores obtained after dietitians and physicians used SCAN showed good agreement (ICC = 0.80, 95%CI 0.71–0.86, P < 0.001). The intrarrater agreement within the evaluation of the same dietitian to the same group of patients was also good (ICC = 0.83, 95%CI 0.75–0.88, P < 0.001). After applying SCAN, 66.2% of participants scored >3 points, classified as at risk of malnutrition. The agreement observed when comparing the risk classification given by the tool with the malnutrition assessment using anthropometry variables as the criterion reference was fair (κ = 0.22, 95%CI 0.15–0.29, P < 0.001). Predictive validity indicated a slight agreement (κ = 0.16, 95%CI 0.08–0.25, P < 0.001) between malnutrition risk by SCAN and LOS. When assessing construct validity, comparing the scores given by SCAN with those provided by STRONGkids, a fair agreement was found (κ = 0.21, 95%CI 0.15–0.26, P < 0.001). Our results show that SCAN is a reliable and valid tool for detecting malnutrition in oncology pediatric patients upon hospital admission. •SCAN tool effectively detects malnutrition risk in pediatric oncology patients.•SCAN showed good interrater (ICC=0.80) and intrarater (ICC=0.83) reliability.•SCAN identified 66.2% of hospitalized children at risk for malnutrition.

Objetivo Describir el proceso de adaptación cultural del programa CASCAdE en línea para padres de supervivientes de cáncer infantil mexicanos. Método Se utilizó el Modelo Ecológico de Validación (MEV), en dos fases la primera consistió en la traducción (inglés-español) y adaptación cultural de los contenidos del programa; la segunda fue la evaluación del contenido e integridad del tratamiento. Resultados Se realizaron cambios en la redacción del texto, se modificó el uso de la segunda persona del singular por la tercera persona del singular “usted”. Del MEV se eligieron para adaptación de materiales Lenguaje, Personas, Metáforas o dichos, Narrativa y Conceptos. Entre los cambios más relevantes se encuentran el uso de la tercera persona del singular (aceptabilidad) y la adaptación de metáforas que fueran entendibles en este contexto (relevancia). Para la intervención se adaptaron Métodos, contexto y objetivos, dando como resultado la aplicación individual, cambios en el diseño gráfico e inclusión de iconografías llamativas y amigables para los padres (aceptabilidad). En la evaluación del contenido por jueces expertos se obtuvieron porcentajes del 50% de acuerdo en redacción de las sesiones de introducción del manual para el facilitador y 75% en redacción de la sesión cuatro del manual para padres. Conclusión Este estudio muestra el proceso de adaptación cultural desde el MEV a fin de contar con los materiales necesarios para que la aplicación del programa CASCAdE en un contexto mexicano.

Antecedentes El miedo a la recurrencia del cáncer (MRC) es el malestar emocional más frecuente en los supervivientes de cáncer. Ha sido poco descrito en supervivientes de cáncer infantil (SCI), a pesar de que uno de los principales predictores de este es ser un superviviente joven. Objetivo Resumir y analizar la evidencia actual sobre la evaluación y manejo del MRC en SCI. MétodoSe realizó una revisión narrativa de los estudios incluidos en cuatro bases de datos (PsycInfo, Medline, CINALH y Web of Science) sin restricciones de idioma en los últimos cinco años. Resultados Se identificó que las escalas más utilizadas en SCI son Scale y el Fear of cancer recurrence inventory short version (FCRI-S) y se ha obtenido la versión para niños FCRI-C; el resto de la evidencia utiliza Cancer Worry Scale, la versión completa o uno a cuatro reactivos adaptados. Respecto a programas de intervención en esta revisión no se identificó algun programa específico para SCI elementos cognitivos que, de incluirse en intervenciones cognitivo-conductuales, para el MRC en SCI.Conclusiones Es necesario el desarrollo de instrumentos válidos, confiables, culturalmente relevantes y adaptados a cada etapa de desarrollo para SCI debido a un índice alto de supervivencia, al mismo tiempo que el desarrollo de programas de intervención que consideren técnicas basadas en evidencia científica como las etapas del desarrollo cognitivo.

Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs.

The gene fusions BCR‐ABL1, TCF3‐PBX1, and ETV6‐RUNX1 are recurrent in B‐cell acute lymphoblastic leukemia (B‐ALL) and are found with low frequency in coexistence with CRLF2 (cytokine receptor‐like factor 2) rearrangements and overexpression. There is limited information regarding the CRLF2 abnormalities and dominant‐negative IKZF1 isoforms associated with surrogate markers of Jak2, ABL, and Ras signaling pathways. To assess this, we evaluated 24 Mexican children with B‐ALL positive for recurrent gene fusions at diagnosis. We found CRLF2 rearrangements and/or overexpression, dominant‐negative IKZF1 isoforms, and surrogate phosphorylated markers of signaling pathways coexisting with recurrent gene fusions. All the BCR‐ABL1 patients expressed CRLF2 and were positive for pCrkl (ABL); most of them were also positive for pStat5 (Jak2/Stat5) and negative for pErk (Ras). TCF3‐PBX1 patients with CRLF2 abnormalities were positive for pStat5, most of them were also positive for pCrkl, and two patients were also positive for pErk. One patient with ETV6‐RUNX1 and intracellular CRLF2 protein expressed pCrkl. In some cases, the activated signaling pathways were reverted in vitro by specific inhibitors. We further analyzed a TCF3‐PBX1 patient at relapse, identifying a clone with the recurrent gene fusion, P2RY8‐CRLF2, rearrangement, and phosphorylation of the three surrogate markers that we studied. These results agree with the previous reports regarding resistance to treatment observed in patients with recurrent gene fusions and coexisting CRLF2 gene abnormalities. A marker phosphorylation signature was identified in BCR‐ABL1 and TCF3‐PBX1 patients. To obtain useful information for the assessment of treatment in B‐ALL patients with recurrent gene fusions, we suggest that they should be evaluated at diagnosis for CRLF2 gene abnormalities and dominant‐negative IKZF1 isoforms, in addition to the analyses of activation and inhibition of signaling pathways.

MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators and influence the development and progression of several cancers, yet their roles in pediatric sarcomas remain poorly defined. RNA extracted from formalin-fixed paraffin-embedded tumor tissue scrolls of 108 pediatric tumors, including 32 osteosarcoma (OS), 26 Ewing's sarcoma (EWS), and 50 rhabdomyosarcoma (RMS) cases, were analyzed for microRNA expression using the NanoString multiplex nCounter platform that yielded information on 827 human miRNAs. The expression of candidate miRNAs was validated with in situ hybridization (miRNA-ISH) and QuPath quantification on tissue microarray slides comprising an independent set of 48 OS, 17 EWS, and 104 RMS adult and pediatric cases collectively. The differential expression analysis of nCounter data identified 23 miRNAs enriched in RMS, 33 in EWS, and 45 in OS (>3 fold change and < 0.01). miR-206 was most strongly associated (>55 fold change, < 1 × 10 ) with RMS and demonstrated the highest sensitivity and specificity in distinguishing RMS from EWS and OS; this finding was also confirmed by miRNA-ISH. A combined signature of differentially expressed miRNAs reliably separated alveolar from embryonal RMS. The expression of miR-9-5p in EWS and miR-140-5p in OS discriminated among the different tumors and correlated with adverse patient outcome. The nCounter assay exhibited greater sensitivity than miRNA-ISH in detecting miR-206 and miR-140-5p expression. Collectively, these findings demonstrate that distinct miRNA profiles can differentiate pediatric sarcoma types and subtypes and offer clinically relevant insights into tumor biology, prognosis, and potential diagnostic application.

A high impact of ARID5B SNPs on acute lymphoblastic leukemia (ALL) susceptibility has been described in Hispanic children; therefore, it is relevant to know if they influence the high incidence of childhood-ALL in Mexicans. Seven SNPs (rs10821936, rs10994982, rs7089424, rs2393732, rs2393782, rs2893881, rs4948488) of ARID5B were analyzed in 384 controls and 298 ALL children using genomic DNA and TaqMan probes. The SNPs were analyzed for deviation of Hardy-Weinberg equilibrium; Fisher’s exact test was used to compare the genotypic and allelic frequencies between controls and patients. The association between SNPs and ALL susceptibility was calculated, and haplotype and ancestry analyses were conducted. All SNPs were associated with ALL, pre-B ALL, and hyperdiploid-ALL susceptibility (p < 0.05). No association with T-ALL and gene fusions was found (p > 0.05). The seven SNPs were associated with risk of pre-B ALL in younger children; however, rs2393732, rs2393782, rs2893881, and rs4948488 were not associated with susceptibility in older children and adolescents. The CAG haplotype (rs10821936, rs10994982, rs7089424) was strongly associated with ALL risk in our population (p < 0.00001). The frequency of all risk alleles in our ALL, pre-B, and hyperdiploid-ALL patients was higher than that in Hispanic children reported. This is the first report showing the association between rs2393732, rs2393782, and rs4948488 with pre-B hyperdiploid-ALL children. The G allele at rs2893881 confers major risk for pre-B hyperdiploid-ALL in Mexican (OR, 2.29) than in Hispanic children (OR, 1.71). The genetic background of our population could influence the susceptibility to ALL and explain its high incidence in Mexico.