NOV在嗅鞘细胞中的表达及活性检测

目的检测肾母细胞瘤过度表达基因(nephroblastoma overexpressed gene,nov)所编码产物(NOV蛋白)转染嗅鞘细胞(olfactory ensheathing cells,OECs)后在OECs中的表达以及活性.方法本研究用nov转染原代培养大鼠OECs,用G418筛选,经过Western blot检测c-myc-NOV的表达以及通过背根神经节(dorsal root ganglion,DRG)与NOV转染后OECs联合培养来对表达的nov活性进行鉴定.结果①Western-blot结果显示,转染了NOVcDNA的OECs总蛋白c-Myc抗体检测可见约28×103条带,即c-myc-NOV融合蛋白.未转染质粒的OECs总蛋白做对照,结果为阴性,无条带出现.②与nov修饰的OECs联合培养DRG有许多DRG细胞向外迁移,细胞折光性强,突起较长而纤细,并形成复杂的网络.未修饰的OECs组只有少量的细胞迁移和突起生长,细胞迁移和突起生长都很局限.空白对照组DRG仅有细胞迁移.结论nov转染OECs后,并能促进与OECs联合培养的DRG细胞的迁移生长,表明产生了具有促神经细胞生长活性的蛋白.     

儿童Wilms瘤分子分型标志物的研究进展

Wilms瘤是儿童最常见的肾脏恶性肿瘤.随着各项医疗手段的发展,Wilms瘤患儿生存率有了很大提高.研究表明,Wilms瘤因不同的组织学分型具有不同的预后.加深对肿瘤分子层面的认识能够使我们更好地了解肿瘤的生物学特性并对不同肿瘤进行区分,以帮助指导儿童Wilms瘤的治疗和预后判断.本文就儿童Wilms瘤在分子分型标志物研究方面的进展作一综述.     

儿童特殊类型肾母细胞瘤5例临床病理学分析

目的：探讨儿童特殊类型肾母细胞瘤的临床病理学特点、诊断要点及鉴别诊断。方法：收集5例儿童特殊类型肾母细胞瘤病例进行临床资料、病理形态学及免疫组织化学分析,并结合文献探讨其诊断与鉴别诊断。结果：5例患儿中男童3例,女童2例,年龄4月~2岁,中位年龄1岁,主因腹部包块、无痛性肉眼血尿或腹胀、发热就诊,左肾(3例)多于右肾(2例)。其中部分囊状分化型3例,镜下见肿瘤由大小不一的囊腔构成,内衬扁平、立方或鞋钉样上皮细胞,间隔见间叶、胚芽或上皮的肾母细胞瘤成分;肾母细胞瘤伴肾源性残余2例,镜下见由间叶、胚芽和上皮等构成的典型肾母细胞瘤成分,周围见胚芽和上皮细胞与正常肾组织混合存在。结论：部分囊状分化的肾母细胞瘤(cystic partially differentiated nephroblastoma,CPDN)、肾母细胞瘤伴肾源性残余是少见特殊类型的肾母细胞瘤,术前临床诊断及鉴别诊断困难,只有依靠术后病理作出准确诊断,为患儿治疗及预后提供可靠依据。     

Next-generation sequencing reveals germline mutations in an infant with synchronous occurrence of nephro- and neuroblastoma

Although neuro- and nephroblastoma are common solid tumors in children, the simultaneous occurrence is very rare and is often associated with syndromes. Here, we present a unique case of synchronous occurrence of neuro- and nephroblastoma in an infant with no signs of congenital anomalies or a syndrome. We performed genetic testing for possible candidate genes as underlying mutation using the next-generation sequencing (NGS) approach to target 94 genes and 284 single-nucleotide polymorphisms (SNPs) involved in cancer. We uncovered a novel heterozygous germline missense mutation p.F58L (c.172T→C) in the anaplastic lymphoma kinase (ALK) gene and one novel heterozygous rearrangement Q418Hfs^*11 (c.1254_1264delins TTACTTAGTACAAGAACTG) in the Fanconi anemia gene FANCD2 leading to a truncated protein. Besides, several SNPs associated with the occurrence of neuroblastoma and/or nephroblastoma or multiple primary tumors were identified. The next-generation sequencing approach might in the future be useful not only in understanding tumor etiology but also in recognizing new genetic markers and targets for future personalized therapy.     

Hyperplastic perilobar nephroblastomatosis: long-term survival of 52 patients

BACKGROUND: This study provides insight into the clinical behavior, diagnostic complexities, and long-term management of patients with hyperplastic perilobar nephroblastomatosis (HPLN). PROCEDURE: Fifty-two patients with HPLN with available long-term follow-up were retrospectively analyzed for pathologic, radiologic, and clinical features. RESULTS: The mean age at diagnosis was 16 months; the lesions were bilateral in 49 patients. Of 33 patients who initially underwent diagnostic biopsy and adjuvant chemotherapy, 18 (55%) developed Wilms tumor (WT) at a mean of 35 months from diagnosis. Of 16 patients whose initial therapy included nephrectomy and adjuvant therapy, three (19%) developed WT at a mean of 36 months from diagnosis. All three patients who underwent initial diagnostic biopsy and received no adjuvant therapy during their initial course developed WT 4, 4, and 10 months following diagnosis. 24/52 patients developed either a single (13 patients) or multiple (11 patients) WT throughout their course; 8/24 (33%) of WT were anaplastic. The time from initial diagnosis to the development of the last WT ranged from 13 to 116 months (mean 42 months). Three children with HPLN died of WT at 3, 5, and 6 years of age; 2/3 were anaplastic. CONCLUSIONS: HPLN is a self-limited, pre-neoplastic proliferative process associated with a high risk of developing WT. The accurate diagnosis and the choices of therapy during the often-complex course of HPLN depend on the availability and accurate interpretation of a combination of pathologic, radiologic, and clinical information. When such information is appropriately obtained, the long-term survival of patients with HPLN is excellent.     

Irinotecan for children with relapsed solid tumors

Irinotecan is expected to become a new drug for childhood solid tumors. Sixteen children with relapsed solid tumors received irinotecan 180 mg/m²/day for 3 consecutive days, repeated once after 25 days off. Their original tumors were neuroblastoma in 7, rhabdomyosarcoma in 3, nephroblastoma and undifferentiated sarcoma in 2 each, and primitive neuroectodermal tumor and leiomyosarcoma in 1 each. The average age at trials was 6 years. Partial response was achieved in 5 (31.3%) (neuro-blastoma, rhabdomyosarcoma, nephroblastoma, undifferentiated sarcoma, and leiomyosarcoma), and decrease in tumor marker in the other 2. Irinotecan appears promising, and could become included in the first-line treatment.     

Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry

OBJECTIVE: To characterize the association of pleuropulmonary blastoma (PPB) with cystic nephroma (CN) and other renal tumors. STUDY DESIGN: Complete clinicopathologic review of cases from the International PPB Registry and literature. RESULTS: We identified 18 patients with PPB associated with 20 renal tumors (15 CN), either in themselves or family members. All patients with PPB were <5 years of age. All but one of the renal diagnoses were made before 4 years of age. Eleven children had both PPB and renal tumor, one of whom also had a sibling with CN. Six children with PPB alone had one or more family members with CN. The mother of one child with PPB had Wilms' tumor. Pulmonary disease was bilateral in four patients. Renal disease was bilateral in three patients. Two children with PPB and bilateral renal cystic tumors also had intussusceptions because of small bowel juvenile polyps. In six families, dysplasia/neoplasia affected organs other than lung and kidney. CONCLUSIONS: CN or related tumors were found in 9.2% of 152 Registry-reviewed PPB cases. The occurrence of rare pulmonary and renal tumors together in patients and/or family members, the early age of onset, and the multiplicity of tumors is compatible with a constitutional genetic predisposition.