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Expression microarrays are powerful technology that allows large-scale analysis of RNA profiles in a tissue; these platforms include underexploited detection scores outputs. We developed an algorithm using the detection score, to generate a detection profile of shared elements in retinoblastoma as well as to determine its transcriptomic size and structure. We analyzed eight briefly cultured primary retinoblastomas with the Human transcriptome array 2.0 (HTA2.0). Transcripts and genes detection scores were determined using the Detection Above Background algorithm (DABG). We used unsupervised and supervised computational tools to analyze detected and undetected elements; WebGestalt was used to explore functions encoded by genes in relevant clusters and performed experimental validation. We found a core cluster with 7,513 genes detected and shared by all samples, 4,321 genes in a cluster that was commonly absent, and 7,681 genes variably detected across the samples accounting for tumor heterogeneity. Relevant pathways identified in the core cluster relate to cell cycle, RNA transport, and DNA replication. We performed a kinome analysis of the core cluster and found 4 potential therapeutic kinase targets. Through analysis of the variably detected genes, we discovered 123 differentially expressed transcripts between bilateral and unilateral cases. This novel analytical approach allowed determining the retinoblastoma transcriptomic size, a shared active transcriptomic core among the samples, potential therapeutic target kinases shared by all samples, transcripts related to inter tumor heterogeneity, and to determine transcriptomic profiles without the need of control tissues. This approach is useful to analyze other cancer or tissue types.

Aim: To investigate the role of the transcription factor YY1 in Wilms tumor (WT). Patients & methods: We measured YY1 expression using tissue microarray from patients with pediatric renal tumors, mainly WT and evaluated correlations with the predicted clinical evolution. YY1 expression was measured using immunohistochemical and protein expression was determined by digital pathology. Results & conclusion: YY1 significantly increased in WT patients. In addition, an increase in YY1 expression had a greater risk of adverse outcomes in WT patients with favorable histology. YY1 expression was higher in the blastemal component of tumors, and high nuclear expression positively correlated with metastasis. YY1 may be considered as a metastasis risk factor in WT.

Background and Aims Recurrent and specific chromosomal translocations have been described in four pediatric sarcomas belonging to the small round blue cell (SRBC) group of tumors. Identification of mRNA chimeras using RT-PCR discriminates among alveolar rhabdomyosarcoma (ARMS), Ewing’s sarcoma (ES/pPNET), synovial sarcoma (SS) and desmoplastic small round cell tumor (DSRCT); however, frequencies of these translocations are variable. We present a retrospective study comparing histological examination and occurrence of major chromosomal translocations to validate the diagnosis and to assess the frequency of these molecular markers in a group of 92 small round blue cell (SRBC) tumor samples from Hospital Infantil de Mexico. Methods We tested a panel of RT-PCR assays to each RNA tumor sample from formalin-fixed, paraffin-embedded tumors to detect specific mRNA chimeras in 47 ES/pPNET, 19 ARMS, four SS, three DSRCT, and 19 other SRBC tumors. Results After excluding poor RNA quality samples, we found translocations in 17/31 ES/pPNET (54.8%), 10/19 ARMS (52.6%), 4/4 SS (100%) and 4/4 DSRCT (100%). We found disagreement in only three samples: one ES/pPNET and one embryonal rhabdomyosarcoma harbor a PAX3-FOXO1 translocation (for ARMS), and one neuroepithelioma harboring a EWS-WT1 (for DSRCT). Unsuitable RNA was found in 20/92 samples (21.7%) and was related to necrosis, small amount of tumor tissue, and use of nitric acid in bone biopsies, but was not related to age of the block. Conclusions We found a significantly lower occurrence of chromosomal translocations in ES/pPNET compared to reports from other groups. Differences may exist in the frequencies of these molecular markers among different populations.

Background A significant association of cola beverage consumption and increased risk of bone fractures has been recently reported. The present study was carried out to examine the relationship of cola soft drink intake and bone mineral density in ovariectomized rats. Methods Study 1. Four groups of 10 female Sprague-Dawley rats were studied. Animals from groups II, III, and IV were bilaterally ovariectomized. Animals from groups I and II received tap water for drinking, while animals from groups III and IV each drank a different commercial brand of cola soft drink. After 2 months on these diets, the following were measured: solid diet and liquid consumption; bone mineral density; calcium in bone ashes; femoral cortex width; calcium; phosphate; albumin; creatinine; alkaline phosphatase; 25-OH hydroxyvitamin D, and PTH. Study 2. Two groups of seven ovariectomized rats were compared. Group A animals received the same management as the group III animals from study 1 (cola soft drink and rat chow ad libitum), while rats from group B received tap water for drinking and pair-feeding. After 2 months plasmatic ionized calcium, phosphate, creatinine, albumin, calcium in femoral ashes, and femoral cortex width were measured. Results Study 1. Rats consuming cola beverages (groups III and IV) had a threefold higher liquid intake than rats consuming water (groups I and II). Daily solid food intake of rats consuming cola soft drinks was one-half that of rats consuming water. Rats consuming soft drinks developed hypocalcemia and their femoral mineral density measured by DEXA was significantly lower than control animals as follows: group I, 0.20 ± 0.02; group II, 0.18 ± 0.01; group III, 0.16 ± 0.01, and group IV, 0.16 ± 0.01 g/cm 2 . Study 2. To rule out the possibility that these calcium and bone mineral disorders were caused by decreased solid food intake, a pair-fed group was studied. Despite a lower body weight, pair-fed animals consuming tap water did not develop bone mineral reduction or hypocalcemia. Conclusions These data suggest that heavy intake of cola soft drinks has the potential of reducing femoral mineral density.

Primary central nervous system lymphoma is a very rare condition in pediatric patients. We describe the case of a 10-year old girl who presented with acute bilateral vision impairment. At the time of presentation, the only positive finding was optic disk swelling, and the brain MRI scan was normal. Seventeen months later, she developed a large-cell non-Hodgkin lymphoma in the brain, with no evidence of neoplasia elsewhere. Immunodeficiencies and Epstein–Barr virus infection could not be demonstrated. The patient was successfully treated with a combination of cyclophosphamide, etoposide, vincristine, methotrexate, and cytarabine, plus intrathecal chemotherapy. Craneospinal irradiation was not used. The patient’s condition is still in remission 68 months after completing the treatment. This case is the only non-Hodgkin lymphoma with primary central nervous system location treated in our institution in the last 10 years and represents less than 0.5% of our non-Hodgkin lymphoma series. Due to its rare occurrence, not much is known about the clinical features and treatment outcome of primary central nervous system lymphoma in pediatric patients.

We previously showed by using biochemical parameters that male Sprague-Dawley rats receiving a single intraperitoneal (i.p.) administration of alloxan (120 mg/kg body weight) with no further treatment recovered endocrine pancreatic function after 12 days.Male Sprague-Dawley rats received an i.p. injection of alloxan (120 mg/kg body wt), were killed at 3, 6, 9, or 12 days (n=7), and their capacity to recover endocrine function was evaluated by means of a) biochemical parameters, which included glucose, triglyceride, and total cholesterol measurements and b) nuclear incorporation of 5'-bromodeoxyuridine (BrdU) by beta and acinar cells as well as presence of neogenesis from either ductal or acinar cells using double-staining BrdU-insulin immunohistochemical technique.Three days after receiving a single i.p. administration of alloxan, rats showed increase in serum glucose, triglyceride, and total cholesterol concentrations, reaching levels of 542.4+/-63.1, 907.6+/-154.9, and 106.0+/-2.7 mg/dL (mean+/-standard deviation [SD]), respectively. At this time, increase in beta-cell replication was also observed, although this reached maximum by day 6 (p0.001). Replication was also present in acinar cells, but these cells showed their maximum at day 3 (p0.001) and subsequently decreased, as did beta-cells, almost steadily to normal values by day 12. Neogenesis of beta-cells was observed mainly as transdifferentiation from acinar cells at day 3 and from ductal cells at day 6, after which it tended to be normal.Male Sprague-Dawley rats receiving a single i.p. alloxan dose tended to normalize their endocrine function by day 12 after alloxan administration. This process included both regeneration and neogenesis of pancreatic beta-cells from either ductal or acinar cells.