Baicalein is the flavonoids with multiple pharmacological activities. The aim of our study was to investigate the effects of baicalein on colorectal cancer (CRC) and to recognize the targets of baicalein treatment. To better understand baicalein's target, proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to elucidate proteins differential display. Results from this study investigate that baicalein treatment of CRC cells results in reduced cell proliferation. As a result, differential protein displays between baicalein-treated and untreated CRC were determined and validated. There were 11 differentially expressed proteins between baicalein-treated and untreated CRC. Furthermore, we demonstrate that baicalein inhibits cancer cell proliferation and reduced reactive oxygen species (ROS) by up-regulating the levels of peroxiredoxin-6 (PRDX6). Knockdown of PRDX6 in baicalein-treated CRC cells by specific small interfering RNA resulted in ROS production and proliferation, opposite of the baicalein treatment scenario as indicated by cell cycle distribution. These results illustrate that baicalein up-regulates the expression of PRDX6, which attenuates the generation of ROS and inhibits the growth of CRC cells, whereas baicalein treatment have no effect on normal epithelial cells.

Wu L.-M., Sheen J.-M., Shu H.-L., Chang S.-C.& Hsiao C.-C.(2012) Predictors of anxiety and resilience in adolescents undergoing cancer treatment. Journal of Advanced Nursing00(0), 000-000. doi: 10.1111/j.1365-2648.2012.06003.x ABSTRACT: Aims.  To report a study examining the relationships among coping, anxiety and resilience and to identify predictors of anxiety and resilience in adolescents undergoing cancer treatment. Background.  Anxiety is the main psychological disturbance in adolescents with cancer, but predictors in the context of anxiety related cancer treatments have not been investigated. Design.  Cross-sectional study. Methods.  Adolescents (n = 131) recruited from three medical centres between 2010-2011. The eligible participants were diagnosed with cancer, without mental disease and receiving chemotherapy. Participants were assessed with the paediatric cancer coping scale, revised children's manifest anxiety scale, second edition, and the Haase adolescent resilience in illness scale. Results.  Over 20% of participants scored high on worry. The most commonly used coping strategy was cognitive coping, followed by problem-oriented coping and finally by defensive coping. There was a statistically significant correlation between defensive coping and level of worry. Resilience was positively correlated with cognitive coping and problem-oriented coping. The cognitive coping and defensive coping were found to predict anxiety and resilience significantly by a step-wise multiple regression analysis and accounted for 40·9% and 46·5% of total variance, respectively. Conclusions.  Cognitive coping and defensive coping are predictors for the level of anxiety and resilience in adolescents undergoing cancer treatment. Health providers should evaluate coping behaviour in patients and work towards a cognitive and problem-oriented coping style that will benefit the patient's mental health during treatment.

Melatonin (N-acetyl-5-methoxytryptamine) is an endogenously produced indoleamine secreted by the pineal gland and the secretion is suppressed by light. Melatonin is a highly effective antioxidant, free radical scavenger, and has anti-inflammatory effect. Plenty of evidence supports the utility of melatonin in adults for cancer, neurodegenerative disorders, and aging. In children and neonates, melatonin has been used widely, including for respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia (PVL), hypoxia-ischemia encephalopathy and sepsis. In addition, melatonin can be used in childhood sleep and seizure disorders, and in neonates and children receiving surgery. This review article discusses the utility of melatonin in neonates and children.

BACKGROUND: The absence of biallelic TCRγ deletion (ABD) is a characteristic of early thymocyte precursors before V(D)J recombination. The ABD was reported to predict early treatment failure in T-cell acute lymphoblastic leukemia (ALL). This study aimed to investigate its prognostic value in Taiwanese patients with T-cell ALL. PROCEDURE: Forty-five children with T-cell ALL were enrolled from six medical centers in Taiwan. Quantitative DNA polymerase chain reaction (Q-PCR) was performed to check the status of TCRγ deletion. The threshold for homozygous deletions by Q-PCR was defined as a fold-change <0.35. RESULTS: ABD was found in 20 patients [20:45] who had higher incidences of induction failure than those without ABD (P = 0.03; hazard ratio [HR] = 8.13; 95% confidence interval [95% CI] = 1.23-53.77) after multivariate regression analysis. Patents with ABD also had inferior EFS and OS (P = 0.071 and 0.0196, respectively). Multivariate Cox analysis indicated that the association between ABD and overall survival was independent of age and leukocyte count on presentation (P = 0.036; HR = 4.25; 95% CI = 1.10-16.42). CONCLUSIONS: The absence of TCRγ deletion is a predictor of a poor response to induction chemotherapy for pediatric patients with T-cell ALL in Taiwan. Providing patients with T-cell ALL and ABD with alternative regimens may be worthwhile to test in future clinical trials. Pediatr Blood Cancer © 2011 Wiley Periodicals, Inc.

Human newborns are known to be susceptible to microbial infection. This susceptibility is generally attributed to immaturity of the newborn immune system. However, the mechanisms for impaired immunity in newborns are still incompletely defined. In this study, we sought to elucidate the protein differential display between adult and neonatal mononuclear cells (MNC) using a proteomic approach. MNC samples from cord blood and adult peripheral blood were subjected to 2-D PAGE analysis. Differential protein displays between cord blood and adult MNC were determined and validated. There were 34 differentially expressed proteins between cord blood and adult MNC identified by 2-D PAGE. The differentially displayed proteins were clustered into two major signal pathways, cellular processing and purine metabolism. After validation by Western blot, we found more abundant arginase-1 (ARG1) and Rho GDP-dissociation inhibitor 2 (RhoGDI2), while less adenosine deaminase (ADA) and β-actin in cord blood MNC. In functional validation, we found that lower ADA was proven to enhance the TNF-α production by cord blood monocytes. The results from this study discovered the proteomic displays for altered immunity between adult and neonatal MNC that support a understanding of the correction of impaired immune response in newborns.

Despite current risk-directed therapy, approximately 15-20% of pediatric patients with acute lymphoblastic leukemia (ALL) have relapses. Recent genome-wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B-cell progenitor ALL. In this study, we determined the prognostic significance of IKZF1 deletions in patients with childhood ALL. This study analyzed 242 pediatric B-cell progenitor ALL patients in Taiwan. We developed a simple yet sensitive multiplex quantitative PCR coupled with capillary electrophoresis to accurately determine the allele dose of IKZF1, and high resolution melting was used for mutation screening for all coding exons of IKZF1. Twenty-six (10.7%) pediatric B-cell progenitor ALL patients were found to harbor these deletions. Most of the deletions were broader deletions that encompassed exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1 was carried out in all cases and no point mutations were identified. Patients with IKZF1 deletions had inferior event-free survival (P < 0.001), and overall survival (P = 0.0016). The association between IKZF1 deletions and event-free survival was independent of age, leukocyte count at presentation, and cytogenetic subtype by multivariate Cox analysis (P = 0.003, hazard ratio = 2.45). This study indicates that detection of IKZF1 deletions upon diagnosis of B-cell progenitor ALL may help to identify patients at risk of treatment failure. IKZF1 deletions could be incorporated as a new high-risk prognostic factor in future treatment protocols. To the best of our knowledge, this is the first study to examine the poor prognosis of IKZF1 deletions in an Asian population.

BACKGROUND Malignant ovarian tumors in children are relatively rare. We reviewed our 15-year experience to understand their clinical presentations, managements, and prognoses. METHODS There were 15 children who were diagnosed to have malignant ovarian tumors from January 1994 to June 2009 in our hospital. The presenting symptoms, treatments, and outcomes were obtained retrospectively from the medical records. RESULTS The median age at presentation was 13 years. The most common presenting symptom was abdominal pain, occurring in 10 patients (66.7%). The tumors were in the left side in 10 patients (66.7%). The pathologic diagnoses were yolk sac tumors in four patients, immature teratomas in four, dysgerminomas in three, malignant mixed germ cell tumors in three, and carcinosarcoma in one patient. According to the Federation Internationale de Gynecologie Oncologique classification, seven girls had Stage I, one had Stage II, and seven had Stage III disease. Thirteen patients received chemotherapy with platinum-based regimens. Three patients died of their disease: one of yolk sac tumor, one of malignant mixed germ cell tumor, and one of carcinosarcoma. They all had Stage III disease at diagnosis. The 10-year overall survival and disease-free survival rates were 77% and 69%, respectively. CONCLUSIONS Pediatric malignant ovarian tumors were highly curable disease if they were not in the advanced stage at presentation. Earlier consideration of malignant ovarian tumor in the differential diagnosis of young girls with abdominal pain is important.

E-selectin expression by endothelial cells (ECs) is crucial for leukocyte recruitment during the inflammatory response. Macrophage accumulation and serum E-selectin elevation are features of type 2 diabetes mellitus. However, the interactions between macrophages and ECs in regulating vascular endothelial function are not clearly understood. We investigated the mechanisms underlying the modulation of EC E-selectin expression by high glucose (HG)-treated macrophages. Macrophage-conditioned media (MCM) were prepared from HG-treated macrophages. EC stimulation with HG-MCM induced increases the expression and secretion of E-selectin. By using specific inhibitors and small interfering RNAs, we demonstrate that the activation of the JNK and p38 MAPK pathways are critical for HG-MCM-induced E-selectin expression. Transcription factor ELISA and chromatin immunoprecipitation assays further showed that HG-MCM increases the NF-κB- and AP-1 DNA-binding activities in ECs. The inhibition of NF-κB and AP-1 activation by specific siRNAs blocks the HG-MCM-induced E-selectin promoter activity and expression. Protein arrays and blocking assays using neutralizing antibodies demonstrated that macrophage inflammatory protein 1α and 1β in HG-MCM are major mediators for the induction of EC E-selectin expression. These data support the hypothesis that E-selectin up-regulation stimulated by macrophages may play an active role in atherogenesis in the HG condition and suggest a new mechanism by which arterial disease is accelerated in diabetes.

Children with acute lymphoblastic leukemia (ALL) frequently present with hepatomegaly and mild liver functional impairment. Severe jaundice is rarely seen as a presenting feature. Such patients often present diagnostic dilemmas and therapeutic difficulties. Here we report a 15-year-old boy presenting with severe jaundice and hyperferritinemia, whose bone marrow smear showed B-lineage precursor ALL. We treated him with intravenous immunoglobulin, steroid, and etoposide; then his condition improved. ALL should be considered as a possible diagnosis in severely jaundiced children. Steroid and etoposide can be used as first aid when many chemotherapeutic drugs are contraindicated.

Understanding the defense mechanisms of the host of an organism is important for infection control. In previous studies, we demonstrated that interferon-α (IFN-α), but not IL-12, was produced by human peripheral blood mononuclear cells infected with varicella-zoster virus (VZV). Here, we investigated what kind of cell(s) and which signal molecule(s) are involved in IFN-α production. Using cell isolation and ELISA, we found that plasmacytoid dendritic cells (pDCs) were responsible for IFN-α production during VZV infection. We also found that Toll-like receptor 9 (TLR9) was involved in VZV-induced IFN-α production because inhibitory CpG oligodeoxynucleotide inhibited IFN-α production. UV-inactivated VZV-induced IFN-α production was lower than that of active VZV, indicating another TLR9-independent pathway. Further studies demonstrated that double-stranded RNA-dependent protein kinase, but not DNA-dependent protein kinase was involved in VZV-induced IFN-α production. Together, these results suggest that pDCs play an important role in IFN-α production during VZV infection through TLR9-dependent and -independent pathways.