The expression of PHOX2B in bone marrow and peripheral blood predicts adverse clinical outcome in non-high-risk neuroblastoma.

Paired-like homeobox 2B (PHOX2B) is a highly sensitive and specific biomarker for diagnosing neuroblastoma, as well as detecting minimal residual disease in neuroblastoma. The clinical significance of PHOX2B expression in bone marrow (BM) and peripheral blood (PB) samples of newly diagnosed patients with very low-, low- and intermediate-risk neuroblastoma remains unknown, to the best of our knowledge. The expression level of PHOX2B in paired BM and PB samples of patients with newly diagnosed neuroblastoma was validated using reverse transcription-quantitative polymerase chain reaction (RTqPCR). Among the 132 patients, 26 exhibited a positive PHOX2B expression BM (19.7%) and 11 in PB (8.3%) samples. PHOX2B was highly expressed in BM and PB samples from patients aged <18 months, with International Neuroblastoma Risk Group Staging System stages M and MS, 1p loss of heterozygosity, and high levels of lactate dehydrogenase, serum ferritin and neuron-specific enolase (p < 0.05). In all eligible patients, the 2-year event-free survival (EFS) and overall survival (OS) rates were 94.7 ± 2.0% and 97.7 ± 1.3%, respectively. However, the 2-year EFS rates were significantly decreased to 76.9 ± 8.3% and 63.6 ± 14.5% in patients with a positive PHOX2B expression in BM and PB samples, respectively (p < 0.05). Similarly, the 2-year OS rates were also decreased to 88.5 ± 6.3% and 81.8 ± 11.6% in patients with a positive PHOX2B expression in BM and PB samples, respectively (p < 0.05). In conclusion, a positive PHOX2B expression in BM and PB samples at diagnosis had a strong adverse prognostic effect on patients with non-high-risk neuroblastoma.

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma.

BACKGROUND: Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence. METHODS: A total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children's Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence. RESULTS: Of the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥ 29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6 and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL. CONCLUSIONS: High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.

Elevated nitric oxide levels associated with hepatic cell apoptosis during liver injury.

Hepatic injury is a major event in liver surgery such as liver transplantation and it always leads to hepatic cell apoptosis. Nitric oxide (NO) is a key signaling regulation molecule. Many researchers have shown that increased NO level can influence liver cell apoptosis by promoting or inhibiting the relative signaling pathways that are involved in the caspase family, Bax/Bcl-2, mitochondria, oxidative stress, death receptors, and mitogen-activated protein kinases. Elucidating the relationships between NO and hepatic cell apoptosis is necessary for ameliorating prognosis of liver surgery. This article reviews the newest research progress in the relationships between higher NO levels and hepatic cell apoptosis in liver injury.

Acute myeloid leukemia following a primary mediastinal germ cell tumor.

INTRODUCTION: There is a known association between primary mediastinal germ cell tumor (PMGCT) and hematologic malignancy that is not linked to treatment. They are exceptionally rare entities with a low morbidity and a poor prognosis. CASE PRESENTATION: An 11-year-old boy presented with an anterior mediastinal mass diagnosed as a malignant germ cell tumor on the basis of an excisional biopsy. He was found to have acute myeloid leukemia (AML) two years after the chemotherapy for his germ cell tumor. The clinical course was very aggressive with a survival time of only 1 week after diagnosis of AML associated with PMGCT. CONCLUSION: AML associated with PMGCT needs to be diagnosed correctly. Relevant examinations should be carried out in patients with PMGCTs during and after chemotherapy, and long-term follow-up is still necessary to reduce the risk of morbidity and mortality.

Role of Reduced Nitric Oxide in Liver Cell Apoptosis Inhibition During Liver Damage.

Hepatic injury is a major event in liver surgery and may lead to liver cell apoptosis. Nitric oxide (NO) is an unstable, carbon-centered radical with a short half-time and a key role in molecular signaling. Increasing evidence demonstrates that NO plays an important role in the liver cell apoptosis caused by hepatic ischemia reperfusion (IR) injury and other liver damage. Our recent article summarized the association between elevated nitric oxide levels and hepatic cell apoptosis during liver injury. This article reviews the newest research progress for the relationship between decreased nitric oxide levels and hepatic cell apoptosis inhibition during liver injury. It is shown that decreased NO level can influence liver apoptosis by promoting or inhibiting the signaling pathway involving the caspase family, BCL-2, mitochondria, oxidative stress, death receptors, and mitogen activated protein kinases, etc. This review outlines the literature basis for clinical application of anti-apoptosis treatment to relieve organ injury following liver surgery. NO-related drugs appear to be helpful in clinical treatment of liver diseases.

Analysis of the short-term curative effect of 356 cases of intraocular retinoblastoma in children.

IMPORTANCE: Retinoblastoma (Rb) is the most common primary malignant intraocular cancer in children. Systemic chemotherapy combined with local therapy is safe and effective for intraocular Rb. OBJECTIVE: To summarize the short-term outcomes of patients with Rb to provide evidence for optimizing treatment protocols and improving therapeutic safety and efficacy. METHODS: The clinical data of 356 patients (486 eyes) with intraocular Rb admitted to our center from December 2009 to April 2017 were retrospectively analyzed. The measures included drug toxicity, eye-preservation rate, and survival rate, with an emphasis on safety and short-term efficacy. The date of last follow-up was 30 November, 2017. RESULTS: The patients comprised 226 unilateral Rb and 130 bilateral Rb. Enucleation before chemotherapy was performed in 72 patients. Among the 174 patients with unilateral Rb, enucleation after chemotherapy was performed in 80 patients (46.0%), and the eye was not enucleated in 89 (51.1%); 68 eyes were preserved (68/114, 59.6%) in Group D and 20 eyes (20/59, 33.8%) in Group E. Among the 220 eyes in patients with bilateral Rb, enucleation after chemotherapy was performed for 35 eyes; the eye-preservation rate was 91.7% in Group C, 79.1% in Group D, and 52.1% in Group E. All patients developed grade II to IV myelosuppression after chemotherapy, among whom 18 patients (5%) requiring transfusion. Fourteen patients (3.9%) died of intracranial metastasis following self-elected discontinuation of treatment (n = 7). Patients were followed up for a median of 47 (range, 1-96) months. The expected 5-year overall survival rate was 95.3% (96.7% for unilateral Rb and 92.9% for bilateral Rb, P = 0.074). INTERPRETATION: The VEC (vincristine, etoposide, and carboplatin) regimen with local treatment was safe for intraocular Rb. Intracranial metastasis remains the most common cause of Rb-related death.

Surfactant-free microwave-assisted hydrothermal synthesis of BaMoO4 hierarchical self-assemblies and enhanced photoluminescence properties.

BaMoO(4) with 3D hierarchical multilayer disk-like and nest-like architectures self-assembled from 2D nanosheets was successfully synthesized via a microwave-assisted hydrothermal route without any surfactant. The as-prepared products were characterized by X-ray powder diffractometer (XRD), scanning electron microscope (SEM), field emission transmission electron microscope (FE-TEM), and photoluminescence (PL) spectrometer. The results show that the reaction parameters, including pH value, reactant concentration, and molar ratio of [Ba(2+)]/[MoO(4)(2-)], played important roles on the morphologies of the final products. And the formation mechanism of 3D hierarchical architectures is a stepwise oriented aggregation-based self-assembly process. The superstructure characteristic of 3D nest-like BaMoO(4) architecture was observed in HRTEM image and the corresponding fast Fourier transform (FFT) for the first time, and the superlattice reflections with non-integer indices occurred around the subcell reflections at ±1/6(2a*+2c*). Room temperature photoluminescence spectra of 3D BaMoO(4) architectures reveal a strong and broad blue emission, and the 3D nest-like architectures own the enhanced intensity than multilayer disks.