Vincristine and irinotecan in children with relapsed hepatoblastoma: a single-institution experience.

PURPOSE: This study was to determine the efficacy of vincristine and irinotecan in children with relapsed hepatoblastoma (HB). METHODS: A total of 10 patients with relapsed HB were enrolled. Three patients were excluded. Patients received irinotecan 50 mg/m(2)/day, day 1-5 and vincristine 1.5 mg/m(2)/day, day 1, repeated every 3 weeks. The maximum cycles were eight. Reevaluation of tumor was performed every two cycles. The primary outcome was the rate of complete resection. Secondary outcomes were event-free survival (EFS) and overall survival (OS). RESULTS: Of the seven patients assessable for response, one patient with normal AFP level showed a progressive disease and withdrew. He finally died 6 months later. Four had PR, all of them underwent a second surgery and achieved complete resection. Two patients had SD, one patient relapsed 6 months after orthotopic liver transplantation and died, the other one undergoing surgery had micro margin positive, he relapsed again but alive. The rate of complete resection was 71.4% (including orthotopic liver transplantation). The 2-year EFS and OS for the whole group were 57.1% (95% CI, 12.7% to 34.2%) and 71.4% (95% CI, 16.39% to 37.4%), respectively. CONCLUSIONS: The combination of irinotecan and vincristine has a significant antitumor activity and acceptable toxicity in children with relapsed HB.

Single-agent cisplatin treatment of children with high-risk hepatoblastoma.

PURPOSE: The use of neoadjuvant chemotherapy has improved the survival of patients with hepatoblastoma (HB). However, an increased number of treatment complications and toxic deaths, particularly from heart failure, have been observed with doxorubicin treatment. We have applied cisplatin as a single agent to treat children with high-risk HB to improve event-free survival (EFS). METHODS: Between 2007 and 2009, 14 patients with untreated high-risk HB were enrolled in this study. All the patients received a single-agent treatment of cisplatin. The initial cisplatin cycle was administered in a continuous intravenous 24-hour infusion of 80 mg/m/24 h. The primary outcome was the rate of complete resection. Secondary outcomes were EFS and overall survival (OS). RESULTS: Eleven patients (78.6%) had an overall partial response. Two patients (14.3%) had stable disease. One patient experienced (7.1%) progression. Of the 4 patients who presented with lung metastases initially, 1 patient achieved complete response, 2 patients achieved partial response, and 1 patient experienced progression during preoperative chemotherapy. The complete resection rate was 78.6% (95% CI, 49%-95%). The Kaplan-Meier estimates of 2-year EFS and OS for the whole group were 64.3% (95% CI, 35%-87%) and 85.7% (95% CI, 57%-98%), respectively. The 2-year EFS and OS rates of patients who achieved complete resection were 81.8% (95% CI, 48%-98%) and 100% (95% CI, 62%-100%), respectively. CONCLUSIONS: The single-agent cisplatin had less toxicity than cisplatin plus doxorubicin and achieved an equal rate of complete resection in high-risk HB compared with conventional multiagent chemotherapy.

Diffuse lung metastases in a child with blastic plasmacytoid dendritic cell neoplasm and review.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, highly aggressive hematopoietic malignancy, characterized by cutaneous and bone marrow involvement and leukemic spread. Cutaneous involvement is the most common presentation in BPDCN. At present, the diagnosis and management of BPDCN are still challenging. Due to its rarity, the pediatric experience with BPDCN is especially limited. Herein, we report a special case of BPDCN with diffuse nodular lung metastases and a cutaneous lesion, which achieved a dramatic response to non-Hodgkin lymphoma regimen and remained with complete remission for 2 years. To date, acute lymphoblastic leukemia (ALL)-type chemotherapy followed by hematopoietic stem cell transplantation (SCT) is commonly thought to be related to a favorable outcome in adults with BPDCN. In contrast to it, ALL or non-Hodgkin lymphoma-type therapy alone seems enough in children with BPDCN with or without cutaneous lesions. SCT should only be performed for children who relapse and achieve a second remission. For pediatric BPDCN, further study of larger numbers of cases is needed to better define prognostic factors and optimal treatment strategy, and understand the underling differences in pathogenesis between children and adults.

Low-Temperature Curable Negative-Tone Photosensitive Polyimides: Structure and Properties.

Low-temperature curable negative-tone photosensitive polyimide (n-LTPI) viscous solutions were prepared by dissolving photo-crosslinkable poly (amic ester) (pc-PAE) resin, photophotocrosslinker, photoinitiator, and the heteroaromatic base as curing catalysts, and other additives in organic solvents. Among them, the pc-PAE resin was synthesized by polycondensation of aromatic diacid chloride and diester of 2-ethoxymathacrylate, aromatic diamines in aprotic solvents. After being spun-coated on a silicon wafer surface, soft-baked, exposed to UV light, and developed, the n-LTPI with 2% of imidazole (IMZ) as a curing catalyst produced high-quality photo-patterns with line via resolution of 5 µm at 5 µm film thickness. The photo-patterned polymer films thermally cured at 230 °C/2 h in nitrogen showed 100% of the imidization degree (ID) determined by in situ FT-IR spectroscopy. The thermally cured polymer films exhibited great combined mechanical and thermal properties, including mechanical properties with tensile strength of as high as 189.0 MPa, tensile modulus of 3.7 GP, and elongation at breakage of 59.2%, as well as glass transition temperature of 282.0 °C, showing great potential in advanced microelectronic packaging applications.

Characteristics and Outcomes of Chinese Children With Advanced Stage Anaplastic Large Cell Lymphoma: A Single-Center Experience.

PURPOSE: To evaluate the clinical characteristics and treatment outcomes of Chinese children with advanced stage anaplastic large cell lymphoma (ALCL) who were treated with the low-intensity APO regimen. METHODS: Clinical data from children newly diagnosed with advanced stage ALCL and treated with the APO regimen were reviewed. RESULTS: Altogether 22 eligible patients with advanced stage ALCL were recruited in this study. 18 (81%) patients achieved complete response (CR) after the initial induction, and 4 experienced relapse. Among patients with relapsed or refractory ALCL, CR was achieved in 3 (50%) who received the BFM95 R3/R4 regimen. Besides, 2 patients received the targeted therapy with crizotinib and were still alive. The 5-year OS and EFS rates were 82 ± 8.7% and 68.2 ± 9.4%%, respectively. According to our results, the elevated LDH level and bone marrow involvement were identified as the poor prognostic factors for EFS (p=0.035 and 0.048, respectively). During APO treatment, only 23% patients experienced grade 3-4 hematologic toxicity. CONCLUSIONS: In this study, bone marrow involvement and elevated serum LDH levels were identified as the poor prognostic factors for EFS. In resource-limited regions, patients with advanced stage ALCL can also achieve comparable outcomes to those in high-income regions, and the BFM95 R3/R4 regimen can take the role of salvage treatment for patients with relapsed or refractory disease. Nonetheless, new therapeutic strategy is still needed.

Serum metabolomic analysis reveals key metabolites in drug treatment of central precocious puberty in female children.

Precocious puberty (PP) is a common condition among children. According to the pathogenesis and clinical manifestations, PP can be divided into central precocious puberty (CPP, gonadotropin dependent), peripheral precocious puberty (PPP, gonadotropin independent), and incomplete precocious puberty (IPP). Identification of the variations in key metabolites involved in CPP and their underlying biological mechanisms has increased the understanding of the pathological processes of this condition. However, little is known about the role of metabolite variations in the drug treatment of CPP. Moreover, it remains unclear whether the understanding of the crucial metabolites and pathways can help predict disease progression after pharmacological therapy of CPP. In this study, systematic metabolomic analysis was used to examine three groups, namely, healthy control (group N, 30 healthy female children), CPP (group S, 31 female children with CPP), and treatment (group R, 29 female children) groups. A total of 14 pathways (the top two pathways were aminoacyl-tRNA biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis) were significantly enriched in children with CPP. In addition, two short peptides (His-Arg-Lys-Glu and Lys-Met-His) were found to play a significant role in CPP. Various metabolites associated with different pathways including amino acids, PE [19:1(9Z)0:0], tumonoic acid I, palmitic amide, and linoleic acid-biotin were investigated in the serum of children in all groups. A total of 45 metabolites were found to interact with a chemical drug [a gonadotropin-releasing hormone (GnRH) analog] and a traditional Chinese medicinal formula (DBYW). This study helps to understand metabolic variations in CPP after drug therapy, and further investigation may help develop individualized treatment approaches for CPP in clinical practice.

Effectiveness of acupuncture in the management of restless leg syndrome: a systematic review and meta-analysis.

BACKGROUND: Acupuncture is an important component of traditional Chinese medicine which is used to treat an array of health conditions. This study evaluates the effectiveness of acupuncture in the management of restless leg syndrome (RLS). METHODS: A comprehensive literature survey was conducted in electronic databases to identify studies evaluating the effectiveness of acupuncture in the treatment of RLS. Cure, marked effect, effective, ineffective, and total effective rates of individual studies were pooled to achieve their respective overall estimates and a meta-analysis of mean change from baseline in International Restless Legs Syndrome Rating Scale (IRLSRS) was performed. RESULTS: A total of 18 studies were included in this meta-analysis, among which 640 RLS patients were treated with acupuncture alone or combined with other therapies (acupuncture group) and 447 RLS patients were treated with non-acupuncture therapies (control group). Cure, marked effect, and effective rates were 47.8% [95% confidence interval (CI): 38.3% to 57.3%], 27.4% (95% CI: 20.3% to 34.8%), and 24.2% (95% CI: 16.9% to 31.5%) in patients treated with acupuncture either alone or combination with other treatments, and 21.7% (95% CI: 20.7% to 22.7%), 28.0% (95% CI: 20.0% to 32.9%), and 22.3% (95% CI: 17.0% to 27.6%) in patients treated with non-acupuncture therapies, respectively. The ineffective rate was 4.7% (95% CI: 4.3% to 5.0%) in the acupuncture group and 32.9% (95% CI: 22.2% to 43.7%) in non-acupuncture groups. IRLSRS scores improved significantly after acupuncture treatment [mean change from baseline -9.45 (95% CI: -18.42 to -0.49); P=0.04]. DISCUSSION: Although the overall quality of the included studies was low, the results of this meta-analysis suggested that acupuncture is an effective treatment option for RLS. Well-designed randomized controlled trials especially those involving a sham-acupuncture arm are needed to confirm these outcomes.

The inhibitory effects of cisplatin-radiation combination treatment on malignant osteosarcoma MG-63 cells and BRCA1-p53 pathways are more efficient than single treatments.

The poor prognosis of patients with osteosarcoma remains a persistent problem, in particular for patients with unresectable tumors or metastasis. Therefore, combination of radiotherapy and chemotherapy has been considered for patients with metastasis or recurrence, patients unsuitable for surgery and patients refusing surgery. The present study aimed to investigate the effect of the combined treatment with cisplatin and radiation therapy on the biological characteristics of the osteosarcoma cell line MG-63 and the breast cancer 1 (BRCA1)-associated signaling pathways. Cell proliferation was determined using Cell Counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. Cell migration was examined by Transwell assay. The mRNA and protein expression levels of candidate genes, including BRCA1 and p53, were determined by reverse transcription-quantitative PCR and western blotting, respectively. The results demonstrated that combined treatment with radiation and cisplatin significantly inhibited MG-63 cell proliferation compared with radiation or cisplatin treatment alone. Furthermore, radiation, cisplatin or the combined treatment with radiation and cisplatin increased the apoptosis rate of MG-63 cells, which resulted in G2 phase arrest, and significantly decreased the migratory capacity of MG-63 cells. In addition, the apoptosis rate of MG-63 cells following combined radiation and cisplatin treatment was higher compared with the cisplatin group, but lower compared with the radiation group. Furthermore, combined treatment with radiation and cisplatin decreased the mRNA and protein expression levels of BRCA1 and p53. Additionally, combined treatment with radiation and cisplatin had a more potent inhibitory effect on p53 expression than on BRCA1 expression. In addition, combination of radiation and cisplatin had a higher inhibitory effect on Bax protein level and a higher inductive effect on Bcl-2 protein level compared with treatments with radiation and cisplatin alone. The results demonstrated that combined treatment of radiation and cisplatin exhibited superior therapeutic effects on osteosarcoma MG-63 cells compared with radiation or cisplatin treatment alone, which may be mediated by the BRCA1-p53 signaling pathway.