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.

Paget's disease (PD) is a kind of malignant tumor that is usually localized within the epidermis. PD can be divided into mammary PD (MPD) and extramammary PD (EMPD). EMPD is rare, but the actual incidence is not known. Perianal PD (PPD) refers to EMPD that is located within 6 cm of the anal orifice and below the pectinate line. In this study, we summarize the pathogenesis, clinical characteristics, diagnosis, and treatment of PPD. Pubmed and Web of Science data-bases were used to search for the relevant studies, and the key words were "EMPD" and "PPD". The symptoms of PPD are similar to those of other benign skin diseases, and so the diagnosis of PPD is always delayed. Histopathology is necessary for the diagnosis of PPD. Many treatment methods have been used for PPD, but surgical resection remains the treatment of choice. The rarity of PPD has hampered further research.

Although there is an increasing understanding of the signaling pathways that promote cardiac hypertrophy, negative regulatory factors of this process have received less attention. Increasing evidence indicates that Krüppel-like factor 15 (KLF15) plays an important role in maintaining cardiac function by controlling the transcriptional pathways that regulating cardiac metabolism. Recent studies have also revealed a vital role for KLF15 as an inhibitor of pathological cardiac hypertrophy and fibrosis via its effects on factors such as myocyte enhancer factor 2 (MEF2), GATA-binding protein 4 (GATA4), transforming growth factor-β (TGF-β), and myocardin. KLF15 may therefore be an effective therapeutic target for the treatment of heart failure and other cardiovascular diseases. In this review, we focus on the physiological and pathophysiological roles of KLF15 in the heart and the potential mechanisms through which KLF15 is regulated in various cardiac diseases.

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.

A locally administered combination of chemotherapy and photothermal therapy may be suitable for the treatment of cervical cancer. In this study, doxorubicin (DOX) and indocyanine green (ICG) co-loaded mesoporous silica nanoparticles (DIMSN) were prepared. Then the nanoparticles were incorporated into chitosan/poly(vinyl alcohol) (CS/PVA) to form multifunctional composite nanofibers (DIMSN/F) via the electrospinning process. Under the mimic erosion of vaginal secretion, DIMSN/F presented site-specific drug release while the local delivery of a thermosensitive DIMSN-loaded gel (DIMSN/gel) failed in doing so. The vaginal implantation of DIMSN/F could achieve maximized drug accumulation in the vagina of mice compared to the systematic injection of DIMSN. Finally, the photothermalchemotherapy (PTCT) effects of DIMSN/F were studied in both subcutaneous and orthotopic cervical cancer models in mice but drug penetration in the hard nodular tumor posed a great challenge. For all this, the tumor inhibition rate (TIR) for orthotopic cervical/vaginal cancer was still as high as 72.5%, presenting its great potential for the treatment of cervical cancer.

目的 回顾性分析总结儿童外周原始神经外胚层肿瘤/尤文氏肉瘤(pPNET/Ewing'sS)的临床特点、疗效及转归.方法 收集我科2010年06月-2016年08月诊治的16例pPNET/Ewing's S患儿的临床资料,并对本组患儿的临床特点、治疗反应、总体生存率进行统计学分析.结果 16例患儿中13例(81％)获得完全缓解,2例(13％)获得部分缓解,l例(6％)进展;患儿总体生存期为11.5～ 85个月,无事件生存率为63％,1年、3年生存率分别为94％、69％;本组病例中5例复发,其中3例(60％)手术切缘阳性,4例(80％)原发于胸壁或脊椎旁;在5例复发病例中2例病初有远处转移;7例病初伴远处转移患儿中2例复发.复发病例中4例接受二线化疗方案,其中3例仍有缓解.结论 儿童pPNET/Ewing's S对放、化疗敏感;手术切缘是重要的预后影响因素;肿瘤原发于胸壁或脊椎旁预后差;远处转移不是影响预后重要因素;复发病例对化疗仍有反应.

目的 总结儿童神经母细胞瘤(NB)副肿瘤综合征的临床特点,提高对其认识.方法 通过整理分析我科近年收治的合并有副肿瘤综合征NB患儿的临床资料,并回顾相关文献,归纳总结NB副肿瘤综合征的特点.结果 近年我科收治的68例NB患儿中有9例(13％)伴有副肿瘤综合征的表现;神经系统受累4例(44％),消化系统2例(22％),心血管系统2例(22％),血液系统1例(骨髓未受累,11％);组织学分类:神经母细胞瘤6例,神经节母细胞瘤3例;人血丙种球蛋白和(或)糖皮质激素治疗可缓解副肿瘤综合症;随诊期2例复发,2年生存率71％.结论 NB副肿瘤综合征可涉及多个系统,但以神经系统最常见;免疫治疗可缓解副肿瘤综合征;合并有副肿瘤综合征的NB患儿预后似较好.

Objective To investigate the effect of the combination of topotecan (TOPO) and temozolomide(TOTEM) in the children with refractory or relapsed neuroblastoma.Methods Six children with refractory/relapsed neuroblastoma were analyzed Retrospectively.They were treated by temozolomide,days 1-5,150mg/(m2 · d),orally;topotecan,days 1-5,0.75 mg/(m2 · d),iv,every 3 weeks for a cycle.The total course of treatment for each child for 8-10 cycles.During each cycle of chemotherapy,the general biochemical tests included peripheral blood cell counts,the renal,hepatic and cardiac founctions,etc.Imaging data on computed tomography or MRI was implemented every 2 cycles,with which the treatment responses were evaluated by minimal residual disease of bone marrow involvement cases.Results Totally,6 children received 53 cycles of TOTEM protocol.Three casesachieved complete remission,2 cases achieved partial remission;one case still presented progressive disease after 3 cycles of chemotherapy and quitted.Mean follow-up period was 15 months,4 cases were alive during the 1 years of follow-up.The major of complications during treatment included mo ～ rⅣo myelosuppression (5 cases),Ⅱ° ～Ⅲ° nausea and vomiting (3 cases),no treatment-related death happened.Conclusions Combination of TOTEM presented favorable treatment response and good compliance on children with primary refractory/relapsed NB,and it can be an efficacious treatment choice,but further study on the long-term efficacy is still needed.

Background & Aims: In this study, we investigated the role of salt-inducible kinase 1 (SIK1) and its possible mechanisms in human hepatocellular carcinoma (HCC). Methods: Immunoprecipitation, immunohistochemistry, luciferase reporter, Chromatin immunoprecipitation, in vitro kinase assays and a mouse model were used to examine the role of SIK1 on the beta-catenin signaling pathway.Results: SIK1 was significantly downregulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppresses epithelial-to-mesenchymal transition (EMT), tumor growth and lung metastasis in xenograft tumor models. The effect of SIK1 on tumor development occurs at least partially through regulation of beta-catenin, as evidenced by the fact that SIK1 overexpression leads to repression of beta-catenin transcriptional activity, while SIK1 depletion has the opposite effect. Mechanistically, SIK1 phosphorylates the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) at threonine (T)1391, which promotes the association of nuclear receptor corepressor (NCoR)/SMRT with transducin-beta-like protein 1 (TBL1)/transducing-beta-like 1 X-linked receptor 1 (TBLR1) and disrupts the binding of beta-catenin to the TBL1/TBLR1 complex, thereby inactivating the Wnt/beta-catenin pathway. However, SMRT-T1391A reverses the phenotype of SIK1 and promotes beta-catenin transactivation. Twist1 is identified as a critical factor downstream of SIK1/beta-catenin axis, and Twist1 knockdown (Twist1(KD)) reverses SIK1(KD)-mediated changes, whereas SIK1(KD)/Twistlic double knockdown cells were less efficient in establishing tumor growth and metastasis than SIK1 MD cells. The promoter activity of SIK1 were negatively regulated by Twist1, indicating that a double-negative feedback loop exists. Importantly, levels of SIK1 inversely correlate with Twist1 expression in human HCC specimens.Conclusions: Our findings highlight the critical roles of SIK1 and its targets in the regulation of HCC development and provides potential new candidates for HCC therapy. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

目的 总结分析儿童神经母细胞瘤(NB)复发病例的特点,探讨治疗策略改进的可能性.方法 总结2008年10月-2010年5月我科诊治后随诊观察的23例高危NB患儿复发情况,并归纳其特点.结果 23例NB患儿治疗后2年随诊中7例复发,其中临床分期Ⅳ期5例,Ⅲ期2例;中枢神经系统(CNS)复发3例,其中同时伴骨髓复发2例,原发灶复发1例;CNS复发早期症状包括:晕车、恶心、腹部不适、乏力和下肢无力等;香草基扁桃酸(VMA)和高香草酸(HVA)水平在CNS复发病例中升高不明显.结论 CNS是常见的NB复发部位之一,早期临床症状、体征不典型;VMA和HVA对CNS复发缺乏特异性.

Objective To explore the effect of wortmannin (WM),an inhibitor of PI3K signalingpathway,on the radiation sensitivity of human malignant glioma cells (U251) and the underlyingmechanism.Methods U251 cells were pretreated with 10 μmol/L WM for 2 h and irradiated with 10 GyX-rays,then the activity of PI3K/Akt signaling pathway,the colony-forming ability and apoptosis weredetected to evaluate the effect of WM on radiosensitivity.The protein expressions of cleaved Caspase-3,Bax,Bcl-2 and XIAP were detected with Western blot assay.Results The expression of phospho-Akt wassignificantly inhibited by the pretreatment of cells with 10 μ mol/L WM (t =0.000 1,P ＜0.01).The ratioof apoptotic cells in the WM + IR group was significantly increased from (2.14 ± 1.32)％ of control groupand (11.5 ±2.9)％ of IR group to (22.6 ±3.8)％ (t =0.009 3,0.002 7,P＜0.01).The colony-forming rate of WM + IR group was decreased from (88.54 ± 4.76) ％ of control group and (56.31 ±4.05)％ of IR group to (12.25 ±9.59)％ significantly (t=0.000 03,0.000 2,P＜0.01) accompaniedwith the increases of Caspase-3 and Bax/Bcl-2 but decrease of XIAP.Conclusions WM significantlyincreased the radiation sensitivity of human malignant glioma cells by inhibiting the activity of PI3Ksignaling pathway and the expressions of Bcl-2 and XIAP and activating Caspase-3 and Bax.

肾母细胞瘤(wilms tumor,WT)是儿童时期常见的恶性肿瘤之一。随着化疗、手术及放疗技术的不断改善,总体生存率已>90% [1-3] ,但仍有15%组织分型良好和50%间变型WT复发 [4] 。复发WT的长期生存率按临床危险度不同在10% 8 0% [5] 。目前尚无统一的复发WT治疗方案。为进一步了解儿童复发WT的临床诊治特点,现将我院2008年1月至2010年1月收治的复发WT 6例的临床资料总结如下。

神经母细胞瘤(neuroblastoma,NB)是最常见的儿童颅外实体性肿瘤,尽管强化疗、放疗和造血干细胞移植技术已经取得长足发展,但难治性NB的预后仍然很差[1].通常NB的标准治疗方案包括诱导、强化和巩固/造血干细胞移植3个阶段,而难治性NB的治疗在诱导缓解期即陷入困境.拓扑替康(topotecan,TOPO)是拓扑异构酶Ⅰ抑制剂,对小鼠-人神经母细胞瘤异种移植物有较强的抗肿瘤活性,随着不同剂量的TOPO在Ⅰ期和Ⅱ期临床试验中被证实抗NB作用强,耐受性好[2],TOPO已逐渐成为国外各医疗机构用于治疗难治性和复发NB的一线用药.

To the Editor: Herein, we report an extremely rare case of a localized neuroblastoma (NB) with Kawasaki (KD) in a child. We suggest that KD might represent a new paraneoplastic syndrome associated with neural crest tumors. A 2-y-old boy was admitted to our institution with a fever for 10 d and puffy red eyes. He represented febrile, irritable and acutely ill. Other significant findings included red fissured lips, strawberry tongue, mild swelling and periungual desquamation over the distal parts of his extremities. Echocardiography demonstrated a 3.9 mm dilatation in his left coronary artery and a 2.4 mm dilatation in his right coronary artery. The diagnosis of KD was identified. He received 2 g/kg intravenous immunoglobulin (IVIG) as well as aspirin for two consecutive days. Symptom of fever improved quickly after treatment, however, it recurred 5 d later. The ultrasound study revealed an abdominal mass in her left adrenal gland, measuring 6 cm×5 cm. Diagnosis of poorly undifferentiated NB was made by fine needle biopsy. Chemotherapy with NB 97 protocol was initiated. Within 1 mo, all symptoms and signs of KD had completely resolved, including bilateral coronary artery dilatation. Although there are a few reports of cases with NB identified following a diagnosis of KD, the relationship between them remains unknown. The tumor diagnosis is often achieved incidentally or by autopsy. Recently, Lim et al. have reported two patients of KD with hidden NB [1]. Until now, six NB cases following the diagnosis of KD have been reported. NB is known to produce substances that cause paraneoplastic syndrome [2]. The demonstration of tumorspecific anti-Hu antineuronal antibody in the serum and cerebrospinal fluid of a child with opsomyclonus, tonic pupils, a progressive neurologic disorder with deafness, areflexia, and seizures and subsequent response to intravenous immunoglobulin, strongly support the autoimmune hypothesis [3]. Immune disorder is known as the major etiology for paraneoplastic syndrome and KD [4]. It is questionable whether the metabolics and immune disorder caused by NB play any role in the pathogenesis of KD. Even though paraneoplastic neurologic disorders are the most common ones involved in NB, the potential effects on other systems should be paid attention to.

弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)是起源于成熟B细胞的恶性肿瘤性疾病,约占儿童非霍奇金淋巴瘤的10％[u.基因表达谱分析DLBCL有两种表型,一种为双中心细胞样,一种为活跃B细胞样.现有研究表明儿童DLBCL与成人DLBCL有很大不同,83％的儿童DLBCL为双中心细胞表型,而在成人中双中心细胞表型只占45％[2];另外儿童DLBCL的生物学行为及预后与成人也存在较大的区别.为了进一步探讨儿童DLBCL的临床特点,现将我院2009～2011年收治的12例DLBCL患儿的临床资料总结分析如下.

Objective: To evaluate the feasibility of Pegaspargase instead of L-asparaginase to treat children with advanced-stage lymphoblastic lymphoma (LBL) on the Berlin-Frankfurt-Munster (BFM)-95 protocol. Methods: Fifty-four newly diagnosed patients with stage III or IV LBL and without any treatment were enrolled in this study. Pegaspargase took place of L-asparaginase in BFM-95. The complications and treatment responses of patients treated on the BFM-95 protocol and modified BFM-95 protocol were then evaluated respectively. Findings : For LBL patients treated with BFM-95 protocol or modified BFM-95 protocol, the complete response, event-free survival, overall survival were similar. Stage 4 myelosuppression was the most common complication in both groups. Besides that, among 31 patients receiving modified BFM-95 protocol, coagulation defects were the most common complication. In contrast, anaphylactic reaction was the most common complication in the other 23 patients receiving BFM-95 protocol. Conclusion: Modified BFM-95 protocol is available to children with advanced-stage LBL with an equal outcome and enhances its compliance and decreases the incidence of anaphylactic reaction, compared to BFM-95 protocol. Coagulation defects are the major complication and tolerable in modified one.

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.

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(2)/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.