Histologic and Molecular Characterization of Solid Pediatric Tumors

小儿实体瘤的组织学和分子特征

• 批准号: 7735394
• 负责人: MARIA TSOKOS
• 金额: $ 31.65万
• 依托单位: DIVISION OF CLINICAL SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7735394
• 关键词: ABT-751; Adolescent; Allogenic; Apoptosis; Arts; Award; BAY 43-9006; BAY 54-9085; Biological Markers; Biology; Blood; Brain Neoplasms; Carboplatin; Central Nervous System Neoplasms; Child; Childhood; Childhood Solid Neoplasm; Chondrosarcoma; Chromosomal translocation; Classification; Clinical Drug Development; Clinical Protocols; Clinical Trials; Complex; Consultations; Development; Diagnosis; Diagnostic Procedure; Docetaxel/Gemcitabine; Doxorubicin/Vinorelbine; Drug Kinetics; Educational process of instructing; Enrollment; Epothilone B Analogue; Evaluation; Ewings sarcoma; Family; Farnesyl Transferase Inhibitor; Fluorescent in Situ Hybridization; Frozen Sections; Genetic Crossing Over; Histologic; Hour; Ixabepilone; Malignant Childhood Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Molecular; Molecular Target; Monoclonal Antibodies; Natural History; Neoadjuvant Therapy; Nerve Sheath Tumors; Neuroblastoma; Neurofibromatoses; Neurofibromatosis 1; Newly Diagnosed; Oklahoma; Online Systems; Operative Surgical Procedures; P-Glycoprotein; P-Glycoproteins; Pathogenesis; Pathologist; Pathology; Pathology Report; Patients; Pediatric Hospitals; Pediatric Neoplasm; Pediatric Oncology; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Pilot Projects; Pirfenidone; Plexiform Neurofibroma; Proteins; Protocols documentation; R115777 (Zarnestra); Randomized; Randomized Controlled Clinical Trials; Recurrence; Refractory; Relapse; Reverse Transcriptase Polymerase Chain Reaction; Rhabdomyosarcoma; Risk; Score; Screening procedure; Services; Site; Solid; Solid Neoplasm; Specimen; Staining method; Stains; Stem cell transplant; Structure; Tariquidar; Texas; Tissue Microarray; Tissue Procurements; Tissues; Tumor Pathology; Tumor Tissue; Tyrosine Kinase Inhibitor; University Hospitals; Unresectable; Valproic Acid; XR 9576; base; chemotherapy; chimeric gene; day; dermal neurofibroma; docetaxel; double-blind placebo controlled trial; drug development; fusion gene; inhibitor/antagonist; lectures; leukemia; molecular pathology; neoplastic cell; novel; osteosarcoma; outcome forecast; raf Kinases; receptor; response; sarcoma; symposium; temozolomide; therapy outcome; tumor; young adult

Accurate histologic characterization of pediatric tumors is necessary for the enrolment of patients in the clinical trials of the Pediatric Oncology Branch (POB) at the NCI. The diagnosis of the solid pediatric tumors is often difficult and requires a combination of diagnostic techniques. Most pediatric solid tumors are characterized by consistent chromosomal translocations which result in the fusion of genes and subsequent formation of novel chimeric genes. These molecular markers can be detected by RT-PCR or fluorescence in situ hybridization (FISH) and can be used not only to establish the diagnosis in difficult cases, but also to understand the pathogenesis of these tumors. The pediatric tumor service at the NCI is complex and the staff is involved in 24-hour coverage of all aspects of the service, including on site-consultation with clinicians and prompt evaluation of pathology material upon its receipt, frozen section consultation, tissue procurement, histologic evaluation of tumor tissue for sarcoma translocation studies and final sign-out of surgical and molecular pathology reports on all pediatric tumors submitted through POB. Teaching of residents and fellows occurs during sign-out of pediatric tumor cases and in structured lectures (departmental conferences). Our pediatric tumor material is dictated by the following POB protocols and consists of small round cell tumors of childhood (Ewing sarcoma family tumors, rhabdomyosarcoma and neuroblastoma), osteosarcoma and various soft tissue sarcomas, including nerve sheath tumors in neurofibromatosis (NF) patients. 1.NCI-99-C-0125: Osteosarcoma: Outcome of Therapy Based on Histologic Response: A Collaborative Effort of the POB/NCI, Texas Children's Hospital and University of Oklahoma 2. NCI-00-C-0092: Phase II Randomized Trial of filgastrim-SD/01 vs. filgastrim(G-CSF) with concurrent chemotherapy in patients with newly diagnosed sarcoma 3. NCI-01-C-0222: Phase II Randomized, Cross-Over, Double-Blinded, Placebo-Controlled Trial of the Farnesyltransferase Inhibitor R115777 in Pediatric Patients With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas 4. NCI-02-C-0259: Pilot Study of Allogeneic/Syngeneic Blood Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas 5. NCI-04-C-0001: Phase II Study of Sequential Gemcitabine and Docetaxel in Patients with Recurrent Osteosarcoma or Ewing's Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma 6. 04-N282: Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target screening and Clinical Drug Development 7. 06-HG-0134: Natural history and biology of dermal neurofibromas in neurofibromatosis type 1 8. NCI-01-C-0091: Phase I Trial and Pharmacokinetic Study of Tariquidar (XR9576), a P-Glycoprotein Inhibitor, in Combination With Doxorubicin, Vinorelbine or Docetaxel in Pediatric Patients With Refractory Solid Tumors Including Brain Tumors 9. NCI-02-C-0141: Phase I Study of 7-Day or 21-Day ABT-751 in Children with Refractory Solid Tumors 10. NCI-04-C-0080: Phase II trial of Pirfenidone in Children, Adolescents, and Young Adults With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas 11. NCI-05-C-0235: Phase I Study of Valproic Acid in Young Patients with Recurrent or Refractory Solid Tumors or CNS Tumors 12. NCI-05-C-0239: Phase I study of Talabostat in Combination with Temozolomide or Carboplatin in Pediatric Patients with Relapsed or Refractory Solid Tumors, Including Brain Tumors 13. NCI-06-C-0043: Phase II Trial of Neoadjuvant Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated High Grade Unresectable Malignant Peripheral Nerve Sheath Tumors 14. NCI-06-C-0146: Phase II Trial of Ixabepilone (BMS-247550), an Epothilone B Analog, in Children and Young Adults With Refractory Solid Tumors 15. NCI-06-C-0233: A Phase I Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor BAY 43-9006 (Sorafenib) in Children with Refractory Solid Tumors or Refractory Leukemias NCI-07-C-0040: A Phase I Trial of Monoclonal Antibody HGS-ETR2 (Lexatumumab) in Patients with Refractory Pediatric Solid Tumors On-going collaborative projects with the POB include: 1. the development of childhood cancer and plexiform neurofibroma tissue microarray for molecular target screening and childhood drug development (Neurofibromatosis Consortium Development Site Award)- We will contribute pediatric tumor tissues and interpret immunohistochemical staining along with a group of other pathologists using an on line system for array viewing and scoring. 2. immunohistochemical evaluation of solid pediatric sarcoma tissues from patients enrolled in the HGS-ETR2 clinical protocol for apoptosis-related proteins.

项目成果

Hemihypertrophy and a poorly differentiated embryonal rhabdomyosarcoma of the pelvis.

偏侧肥大和分化不良的骨盆胚胎横纹肌肉瘤。

• DOI: 10.1002/(sici)1096-911x(199901)32:1<38::aid-mpo8>3.0.co;2-h
• 发表时间: 1999
• 期刊: Medical and pediatric oncology
• 作者: Samuel,DP;Tsokos,M;DeBaun,MR
• 通讯作者: DeBaun,MR

Cytological identification of metastatic epithelial nephroblastoma in pleural fluid: report of a case and review of literature.

胸水中转移性上皮性肾母细胞瘤的细胞学鉴定：一例报道并文献复习。

• DOI: 10.1002/dc.20535
• 发表时间: 2006
• 期刊: Diagnostic cytopathology
• 影响因子: 1.3
• 作者: Schinstine,Malcolm;Abati,Andrea;Tsokos,Maria;Fox,Elizabeth;Filie,ArmandoC
• 通讯作者: Filie,ArmandoC

Sensitive detection of rare Ewing's sarcoma cells in peripheral blood by reverse transcriptase polymerase chain reaction.

通过逆转录酶聚合酶链反应灵敏检测外周血中罕见的尤文氏肉瘤细胞。

• DOI: 10.1016/s0046-8177(99)90304-0
• 发表时间: 1999
• 期刊: Human pathology
• 影响因子: 3.3
• 作者: Fidelia-Lambert,MN;Zhuang,Z;Tsokos,M
• 通讯作者: Tsokos,M

Neural differentiation and prognosis in peripheral primitive neuroectodermal tumor.

周围原始神经外胚层肿瘤的神经分化和预后。

• DOI: 10.1200/jco.2000.18.10.2187
• 发表时间: 2000
• 期刊: Journal of clinical oncology : official journal of the American Society of Clinical Oncology
• 作者: Wexler,LH;Meyer,WH;Parham,DM;Tsokos,M
• 通讯作者: Tsokos,M

Absence of EWS/FLI1 fusion in olfactory neuroblastomas indicates these tumors do not belong to the Ewing's sarcoma family.

嗅神经母细胞瘤中缺乏 EWS/FLI1 融合表明这些肿瘤不属于尤文氏肉瘤家族。

• DOI: 10.1016/s0046-8177(99)90068-0
• 发表时间: 1999
• 期刊: Human pathology
• 影响因子: 3.3
• 作者: Kumar,S;Perlman,E;Pack,S;Davis,M;Zhang,H;Meltzer,P;Tsokos,M
• 通讯作者: Tsokos,M