Among various cancers, pediatric brain tumors represent the most common cancer type in children and the second most common cause of cancer related deaths. Anticancer drugs and therapies, such as doxorubicin (Dox), have severe side effects on patients during chemotherapy, especially for children as their bodies are still under development. These side effects are believed to be due to the lack of a delivery system with high efficacy and targeting selectivity, resulting in serious damages of normal cells. To improve the efficacy and selectivity, the transferrin (Trans) receptor mediated endocytosis can be utilized for drug delivery system design, as transferrin receptors are expressed on the blood brain barrier (BBB) and often over expressed in brain tumor cells. Carbon dots (C-Dots) have recently emerged as benign nanoparticles in biomedical applications owing to their good water solubility, tunable surface functionalities and excellent biocompatibility. The unique characteristics of C-Dots make them promising candidates for drug delivery development. In this study, carbon dots-transferrin-doxorubicin covalent conjugate (C-Dots-Trans-Dox) was synthesized, characterized by different spectroscopic techniques and investigated for the potential application as a drug delivery system for anticancer drug doxorubicin to treat pediatric brain tumors. Our in vitro results demonstrate greater uptake of the C-Dots-Trans-Dox conjugate compared to Dox alone presumably owing to the high levels of transferrin receptors on these tumor cells. Experiment showed that C-Dots-Trans-Dox at 10 nM was significantly more cytotoxic than Dox alone, reducing viability by 14-45%, across multiple pediatric brain tumor cell lines.

BACKGROUND.Leukemia is the leading cause of disease‐related death in children, despite significant improvement in survival and modern risk stratification. The prognostic significance of absolute lymphocyte counts (ALC) was evaluated in young patients with acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL).METHODS.In all, 171 consecutive de novo cases of AML and ALL, age ≤21 years, were analyzed. Age, initial white blood cell count, cytogenetics, and bone marrow response were compared with lymphocyte, neutrophil, and platelet counts at weekly intervals during induction chemotherapy.RESULTS.ALC is a significant independent predictor of relapse and survival. For example, in patients with AML an ALC on Day 28 of induction (ALC‐28) <350 cells/μL predicts very poor survival, with a 5‐year relapse‐free survival (RFS) of only 10% (hazard ratio [HR] 3.7, P = .003). In contrast, an ALC‐15 >350 cells/μL carries an excellent prognosis, with a 5‐year overall survival (OS) of 85% (HR 0.2, P = .012). Similarly in ALL, an ALC‐15 <350 cells/μL predicts poor survival, with a 6‐year RFS of 43% (HR 4.5, P = .002), whereas an ALC‐15 >350 cells/μL predicts excellent outcome, with a 6‐year OS of 87% (HR 0.2, P = .018). Importantly, ALC remains a strong predictor in multivariate analysis with known prognostic factors.CONCLUSIONS.ALC is a simple, statistically powerful measurement for patients with de novo AML and ALL. The results, when combined with previous studies, demonstrate that ALC is a powerful new prognostic factor for a range of malignancies. These findings suggest a need for further exploration of postchemotherapy immune status and immune‐modulating cancer therapies. Cancer 2008. © 2007 American Cancer Society.

The data demonstrate that an ALC > or =500 cells/microL on day 15 of the first course of chemotherapy is an independent prognostic factor associated with superior OS in high-risk Ewing sarcoma.

Cancer cells typically display increased rates of aerobic glycolysis that are correlated with tumor aggressiveness and a poor prognosis. Targeting the glycolytic pathway has emerged as an attractive therapeutic route mainly because it should spare normal cells. Here, we evaluate the effects of combining the inhibition of glycolysis with application of the polyphenolic compound resveratrol (RSV) in neuroblastoma (NB) cancer cell lines. Inhibiting glycolysis with 2-deoxy-D-glucose (2-DG) significantly reduced NB cell viability and was associated with increased endoplasmic reticulum (ER) stress and Akt activity. Administration of 2-DG increased the expression of the ER molecular chaperones GRP78 and GRP94, the prodeath protein C/EBP homology protein (CHOP) and the phosphorylation of Akt at S473, T450 and T308. Combined treatment with both RSV and 2-DG reduced GRP78, GRP94 and Akt phosphorylation but increased CHOP and NB cell death when compared with the administration of 2-DG alone. The selective inhibition of Akt activity also decreased 2-DG-induced GRP78 and GRP94 expression and increased CHOP expression, suggesting that Akt can modulate ER stress. Protein phosphatase 1α (PP1α) was activated by RSV, as indicated by a reduction in PP1α phosphorylation at T320. Pretreatment of cells with tautomycin, a selective PP1α inhibitor, prevented the RSV-mediated decrease in Akt phosphorylation, suggesting that RSV enhances 2-DG-induced cell death by activating PP1 and downregulating Akt. The RSV-mediated inhibition of Akt in the presence of 2-DG was not prevented by the selective inhibition of SIRT1, a known target of RSV, indicating that the effects of RSV on this pathway are independent of SIRT1. We propose that RSV inhibits Akt activity by increasing PP1α activity, thereby potentiating 2-DG-induced ER stress and NB cell death.

PET-CT has a high sensitivity when assessing marrow infiltration in pediatric malignancies. Advances in radiologic modalities may obviate the use of invasive, painful, and costly procedures like BMB. Furthermore, biopsy results are limited by insufficient tissue or the degree of marrow infiltration (diffuse vs. focal disease). PET-CT can improve the precision of biopsy when used as a guiding tool. This study proposes the use of PET-CT as first-line screening for bone marrow infiltration to improve the accuracy of staging in new diagnoses.

Object Solitary eosinophilic granuloma (EG) of the calvaria is most commonly treated with surgical excision. The authors hypothesize that many solitary EGs will resolve without intervention, and observation may be a reasonable option. This study was undertaken to investigate that hypothesis. Methods The authors reviewed their institutional records and identified 14 cases of solitary calvarial EG. In 6 cases the patients underwent resection based on family and/or neurosurgeon preferences. A strategy of nonoperative management (purposeful observation) was chosen for the other 8 cases. The authors report the clinical course and imaging results in these 8 cases. Results One of the 8 patients underwent surgery 2 months after presentation because of slight enlargement of the lesion and increasing pain. After a median follow-up period of 1 year (range 6–19 months), none of the other patients had required surgery. Five of these 7 patients had pain at presentation. Pain resolved completely in all 5. The remaining 2 remained asymptomatic. Complete resolution of pain was reported in the 5 patients who had pain at presentation. There was complete clinical resolution of the palpable soft-tissue lesion in all 7 cases. Complete radiographic resolution of the lesion was observed in 5 cases and near-complete resolution in the remaining 2. Conclusions Observation is a safe and reasonable approach in the management of solitary calvarial EG and may prevent unnecessary surgical interventions.

ImportanceThe prevalence of urinary tract infection (UTI), bacteremia, and bacterial meningitis in febrile infants with SARS-CoV-2 is largely unknown. Knowledge of the prevalence of these bacterial infections among febrile infants with SARS-CoV-2 can inform clinical decision-making.ObjectiveTo describe the prevalence of UTI, bacteremia, and bacterial meningitis among febrile infants aged 8 to 60 days with SARS-CoV-2 vs without SARS-CoV-2.Design, Setting, and ParticipantsThis multicenter cross-sectional study was conducted as part of a quality improvement initiative at 106 hospitals in the US and Canada. Participants included full-term, previously healthy, well-appearing infants aged 8 to 60 days without bronchiolitis and with a temperature of at least 38 °C who underwent SARS-CoV-2 testing in the emergency department or hospital between November 1, 2020, and October 31, 2022. Statistical analysis was performed from September 2022 to March 2023.ExposuresSARS-CoV-2 positivity and, for SARS-CoV-2–positive infants, the presence of normal vs abnormal inflammatory marker (IM) levels.Main Outcomes and MeasuresOutcomes were ascertained by medical record review and included the prevalence of UTI, bacteremia without meningitis, and bacterial meningitis. The proportion of infants who were SARS-CoV-2 positive vs negative was calculated for each infection type, and stratified by age group and normal vs abnormal IMs.ResultsAmong 14 402 febrile infants with SARS-CoV-2 testing, 8413 (58.4%) were aged 29 to 60 days; 8143 (56.5%) were male; and 3753 (26.1%) tested positive. Compared with infants who tested negative, a lower proportion of infants who tested positive for SARS-CoV-2 had UTI (0.8% [95% CI, 0.5%-1.1%]) vs 7.6% [95% CI, 7.1%-8.1%]), bacteremia without meningitis (0.2% [95% CI, 0.1%-0.3%] vs 2.1% [95% CI, 1.8%-2.4%]), and bacterial meningitis (&amp;lt;0.1% [95% CI, 0%-0.2%] vs 0.5% [95% CI, 0.4%-0.6%]). Among infants aged 29 to 60 days who tested positive for SARS-CoV-2, 0.4% (95% CI, 0.2%-0.7%) had UTI, less than 0.1% (95% CI, 0%-0.2%) had bacteremia, and less than 0.1% (95% CI, 0%-0.1%) had meningitis. Among SARS-CoV-2–positive infants, a lower proportion of those with normal IMs had bacteremia and/or bacterial meningitis compared with those with abnormal IMs (&amp;lt;0.1% [0%-0.2%] vs 1.8% [0.6%-3.1%]).Conclusions and RelevanceThe prevalence of UTI, bacteremia, and bacterial meningitis was lower for febrile infants who tested positive for SARS-CoV-2, particularly infants aged 29 to 60 days and those with normal IMs. These findings may help inform management of certain febrile infants who test positive for SARS-CoV-2.

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