Biological bases for sexual differences in the brain exist in a wide range of vertebrate species, including chickens. Recently, the dogma of hormonal dependence for the sexual differentiation of the brain has been challenged. We examined whether sexually dimorphic gene expression in the brain precedes gonadal differentiation. Using the Affymetrix GeneChip Chicken Genome Array, we identified 42 female- and 167 male-enhanced genes that were differentially expressed in sex-specific brains from stage 29 chicken embryos. To confirm the efficacy of the microarray, and to investigate the stage-specific expression patterns of the identified genes, we used quantitative real-time PCR analysis. Our real-time PCR results for the differentially expressed genes agreed well with our microarray results. Thus, we postulate that these genes have potential roles in the sexual differentiation of neural function and development in chickens.
Results: Of 91 registered patients, 45 patients were treated with ILF and 45 with PILF. For both arms, 687 chemotherapy cycles were delivered (median = 7 for ILF and 8 for PILF). Both ILF and PILF were generally well tolerated and there was no relevant difference in the occurrence of overall grade 3/4 toxic effects between the two arms. Four patients died during treatment: one in the ILF and three in the PILF arm. The objective response rate was 42% for both arms. There was no significant difference in therapeutic efficacy between ILF and PILF with respect to progression-free survival (4.8 versus 6.2 months; P = 0.523) and overall survival (10.7 versus 10.5 months; P = 0.850).Conclusion: Both ILF and PILF are active as first-line chemotherapy for AGC. The addition of cisplatin, however, has no clear advantage over ILF.
Background: Brown fat is a metabolically active tissue which can take up the 18 FDG tracer used in PET/CT scans, potentially leading to diagnostic uncertainty. Metabolically active brown fat is more prevalent in children than adults with recent studies demonstrating an incidence of brown fat uptake in 34%-40% of children with cancer.The resultant diagnostic uncertainty can impact clinicians' ability to interpret scans in pediatric oncology patients and has the potential to result in unnecessary invasive procedures, upstaged risk stratification, or additional therapy. A lack of clinical consensus remains regarding the safest and most effective method for suppressing brown fat uptake of 18 FDG. Objective:We report the first multi-institutional analysis of the use of fentanyl to mitigate brown fat uptake of 18 FDG in patients receiving PET/CT scans with a focus on safety in pediatric oncology patients.Methods: This is a multi-institutional, retrospective review of pediatric (aged >1 year to <25 years) oncology patients undergoing 18 FDG-PET/ CT scans following pretreatment with fentanyl from April 2021 to January of 2023. Scans were conducted per institutional treatment regimens. Patients received a weight based dose of fentanyl 10 min prior to tracer injection. Vital signs, clinical outcomes, and presence of brown fat was recorded. Similar data was recorded on patients who underwent PET/CT scans without fentanyl premedication during this same time period to serve as the control group.Results: Seventy scans were completed with fentanyl pre-treatment.Patients were evenly split by sex (n = 34, 49% male) with median age of 15 (range 3 y-23 y). Eleven patients (16%) had brown fat uptake and was most common in cervical (n = 9, 82%) supraclavicular (n = 9, 82%), intercostal (n = 2, 18%) and pararenal (n = 4, 36%) areas. There were no adverse events including zero incidents of bradycardia, hypoxia, or hypotension in the pretreated fentanyl cohort. Conclusion:Fentanyl, used for brown fat mitigation in pediatric oncology patients, was well tolerated without any adverse safety events. The observed incidence of brown fat tracer uptake in patients receiving fentanyl pre-medication was higher than previously reported in the literature (16% vs. 6.7%) but lower than reported baseline incidence in the literature (16% vs. 34%-40%). Larger, prospective, multi-institutional clinical trials are warranted to further explore the efficacy of fentanyl for brown fat mitigation pediatric oncology patients.
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