Fernando Chico-Ponce de León

Glioblastoma multiforme in children: experience at Hospital Infantil de Mexico Federico Gomez

ObjectiveTo evaluate clinical evolution of pediatric patients diagnosed with glioblastoma multiforme (GBM) at Hospital Infantil de México Federico Gómez.MethodsCases of patients treated from January to May, 2007, were included in this study. Variables analyzed were: age, diagnosis, size of tumor, histopathological description, degree of resection, time of stay in hospital, complications and outcome using Pearson’s chi-squared test and logistic regression.ConclusionSixteen patients were identified. Mean age of presentation was 8.8. An increased frequency of complications was observed in younger patients and longer survival rates in patients with greater resections; main mode of presentation was directly related to intracranial hypertension; size of tumor was not related to evolution or outcome. Modern histological classifications especially designed for children are deemed necessary to accurately diagnose GBM.

A new synthesis of monosubstituted succinaldehydes and 3-substituted pyrroles from acetonitriles. Formal synthesis of 2,3-dihydro-7-methyl-2H-pyrrolizidin-1-one (Danaidone), a semiochemical of danaid butterflies

A convenient and versatile synthesis of monosubstituted succinaldehydes and 3-substituted pyrroles from acetonitriles was devised. The methodology was applied to the preparation of 9, the penultimate intermediate in the Meinwald and Meinwald synthesis of Danaidone.12

Genomics and epigenetics: A study of ependymomas in pediatric patients.

OBJECTIVE We identify chromosomal alterations, the methylation pattern and gene expression changes in pediatric ependymomas. METHODS CGH microarray, methylation and gene expression were performed through the Agilent platform. The results were analyzed with the software MatLab, MapViewer, DAVID, GeneCards and Hippie. RESULTS Amplification was found in 14q32.33, 2p22.3 and 8p22, and deletion was found in 8p11.23-p11.22 and 1q21.3. We observed 42.387 CpG islands with changes in their methylation pattern, in which we found 272 genes involved in signaling pathways related to carcinogenesis. We found 481 genes with altered expression. The genes IMMT, JHDMD1D, ASAH1, ZWINT, IPO7, GNAO1 and CISD3 were found to be altered among the three levels. CONCLUSION The 2p22.3, 8p11.23-p11.22 and 14q32.33 regions were identified as the most important; the changes in the methylation pattern related to cell cycle and cancer genes occurred in MIB2, FGF18 and ITIH5. The IPO7, GNAO1 and ASAH1 genes may play a major role in ependymoma development.

Reductions in the expression of miR-124-3p, miR-128-1, and miR-221-3p in pediatric astrocytomas are related to high-grade supratentorial, and recurrent tumors in Mexican children

PurposeAstrocytomas are the most frequent type of tumor of the central nervous system in children. Hence, it is important to describe markers that may improve our understanding of their behavior. Mature microRNAs (miRNAs) may be such biological markers. They are small molecules of RNA that regulate gene expression post-transcriptionally. Due to their importance in cancer, the objective of the present study was to determine the profile of expression of precursor and mature forms of miR-124-3p, miR-128-1, and miR-221-3p using RT-qPCR in pediatric samples.MethodsA total of 57 astrocytomas embedded in paraffin were selected. As controls, the study included 13 samples of normal brain tissue.ResultsThree of eight miRNAs were selected after a preliminary screening. All the miRNAs showed higher levels of expression in normal brain tissue. The expression of miR-124-3p and miR-128-1 decreased in astrocytomas than in normal brain tissue in all grades (p < 0.05 in both cases), and this reduction was most evident in GIV (407- and 1,469-fold, respectively); however, the expression of the precursor forms pre-miR-128-1 and pre-miR-221 was higher in GIV (3.5-fold) than in GI. The levels of miR-128-1 were higher in infratentorial tumors than in supratentorial cases (p = 0.006). Finally, the expression of miR-221-3p was higher in non-recurrent tumors and live patients (p = 0.0185 and p = 0.0004, respectively).ConclusionsThe low expression of these miRNAs may constitute a potential marker of astrocytomas that correlates with localization, possibly due to alterations in the maturation processes of these miRNAs that produced low mature forms in patients with recurrent pediatric astrocytomas.

Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study.

PurposeA 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City.Methods and resultsPresumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome’s Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus.DiscussionFurther analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.

The first neuroanatomical text published on the American continent: Mexico City, 1579

Details of publicationThe first neuroanatomy text published on the American continent was included in the Tractado de Anothomia y Chirugia by Fr. Agustín Farfán, O.S.A., who received his M.D. in 1569 from the Royal and Pontifical University of Mexico. It was printed in 1579 by Antonio Ricardo, a Piedmontese who had settled in Mexico City, capital of New Spain.ContentThis text encompasses a very correct and complete neuroanatomy of an eminently Galenic type.

Tractography of the Spider Monkey (Ateles geoffroyi) Corpus Callosum Using Diffusion Tensor Magnetic Resonance Imaging

The objective of this research was to describe the organization, connectivity and microstructure of the corpus callosum of the spider monkey (Ateles geoffroyi). Non-invasive magnetic resonance imaging and diffusion-tensor imaging were obtained from three subjects using a 3T Philips scanner. We hypothesized that the arrangement of fibers in spider monkeys would be similar to that observed in other non-human primates. A repeated measure (n = 3) of fractional anisotropy values was obtained of each subject and for each callosal subdivision. Measurements of the diffusion properties of corpus callosum fibers exhibited a similar pattern to those reported in the literature for humans and chimpanzees. No statistical difference was reached when comparing this parameter between the different CC regions (p = 0.066). The highest fractional anisotropy values corresponded to regions projecting from the corpus callosum to the posterior cortical association areas, premotor and supplementary motor cortices. The lowest fractional anisotropy corresponded to projections to motor and sensory cortical areas. Analyses indicated that approximately 57% of the fibers projects to the frontal cortex and 43% to the post-central cortex. While this study had a small sample size, the results provided important information concerning the organization of the corpus callosum in spider monkeys.

Expression of histone acetylases p300 and PCAF in pediatric astrocytomas

ObjectsThe protein 300 (p300) and p300/CBP-binding protein-associated factor (PCAF) are enzymes with histone acetyltransferase (HAT) activity, a function that can become deregulated in different tumors and affect biological responses.MethodsDue to the lack of information on the deregulation of these HATs in pediatric tumors, this study evaluated the expression of both the mRNA and proteins of p300 and PCAF in 54 samples of pediatric astrocytomas embedded in paraffin.ResultsPCAF was not expressed in normal brain tissue. In grade I tumors, the expression of p300 (1.1 ± 0.1) and PCAF (1.2 ± 0.11) was greater than those observed in grade III tumors: 0.72 ± 0.15 for p300 and 0.55 ± 0.11 for PCAF, and grade IV tumors: 0.74 ± 0.13 for p300 and 0.55 ± 0.13 for PCAF (p < 0.05). Immunohistochemical staining revealed the same tendency towards a decrease in the expression of the protein as the degree of clinical severity increased. Patients with recurrent grades I, III, and IV tumors had the highest levels of PCAF, compared to those who showed no recurrence (p < 0.05).ConclusionsThis work describes and confirms that these HATs play important roles in regulating genes and in the biological behavior of pediatric astrocytomas.

Lunar and Seasonal Rhythms and Childhood Mortality

The aim of the present study was to assess the effect of the lunar cycle phases, the lunar apogee and perigee, and the geophysical factors (humidity, temperature, and rainfall) on the childhood mortality. We designed a retrospective study by reviewing the clinical charts of the population of patient deceases during the lunar pre-phase (a day before), phase (day of lunar change of phase), and post-phase (a day after), between the years 1991–1996 in a children’s hospital. From the 44,982 discharges from the hospital in the interval between 1991 and 1996, 2003 corresponded to mortal cases, and 522 died within the 3 days we considered as representative for each phase. The number of deaths was approximately the same in between phases. The percentage of male deaths was higher during phase days than interphase ones. Male deceases exhibited a statistically significant predominance during lunar first quarter, full moon, and new moon. A discreet increase of mortality was present in the months of March, June, August, September, October, and November, as well as during summer and fall, but these increments were not significant. Minimum and maximum temperatures exhibited no relation to this behavioral pattern for deceases, nor the humidity index. Early lactating infants presented a significant higher mortality during November, December, and March. We suggest to investigate the causes of the increase of deceases in males in relation to the circalunar rhythms, as well as the lift up of deceases in neonates and early lactating children during November and December.

Pediatric pineal germinomas: Epigenetic and genomic approach

OBJECTIVE We identify and correlate chromosomal alterations, methylation patterns and gene expression in pediatric pineal germinomas. METHODS CGH microarray, methylation and gene expression were performed through the Agilent platform. The results were analyzed with MatLab software, MapViewer, DAVID, GeneCards and Hippie. RESULTS Amplifications were found in 1q24.2, 1q31.3, 2p11.2, 3p22.2, 7p13, 7p15.2, 8p22, 12p13.2, 14q24.3 y 22q12; and deletions were found in 1q21.2, 9p24.1, 10q11.22, 11q11, 15q11.2 and 17q21.31. In the methylation analysis, we observed 10,428 CpG Islands with a modified methylation status that may affect 11,726 genes. We identified 1260 overexpressed genes and 470 underexpressed genes. The genes RUNDC3A, CDC247, CDCA7L, ASAH1, TRA2A, LPL and NPC2 were altered among the three levels. CONCLUSIONS We identified the 1q24.2 and 1q31.3 amplified regions and the 1q21.3 and 11q11 deleted regions as the most important aims. The genes NPC2 and ASAH1 may play an important role in the development, progression and tumor maintenance. The ASAH1 gene is an ideal candidate to identify drug responses. These genomic and epigenetic studies may help to characterize the formation of pineal germ cell tumors to determine prognostic markers and also to identify shared characteristics in gonadal and extragonadal tumors.