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: 7594796
• 负责人: MARIA TSOKOS
• 金额: $ 36.89万
• 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/7594796
• 关键词: ABT-751; Address; Adolescent; Allogenic; 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 Research; Clinical Trials; Complex; Consultations; Data; 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; Frequencies; Frozen Sections; Genetic Crossing Over; Histologic; Hour; Ixabepilone; Malignant Childhood Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Molecular; Molecular Target; 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; Protocols documentation; R115777 (Zarnestra); Randomized; Randomized Controlled Clinical Trials; Recurrence; Refractory; Relapse; Relative (related person); Reverse Transcriptase Polymerase Chain Reaction; Rhabdomyosarcoma; Risk; Score; Screening procedure; Services; Site; Solid Neoplasm; Specimen; Staining method; Stains; Stem cell transplant; Structure; Tariquidar; Texas; Therapeutic; Tissue Microarray; Tissue Procurements; Tissues; Treatment Protocols; 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).<BR> 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. <BR>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 <BR>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 <BR> 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 <BR> 4. NCI-02-C-0259: Pilot Study of Allogeneic/Syngeneic Blood Stem Cell Transplantation in Patients With High-Risk and Recurrent Pediatric Sarcomas <BR> 5. NCI-04-C-0001: Phase II Study of Sequential Gemcitabine and Docetaxel in Patients with Recurrent Osteosarcoma or Ewings Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma <BR> 6. 04-N282: Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target screening and Clinical Drug Development <BR> 7. 06-HG-0134: Natural history and biology of dermal neurofibromas in neurofibromatosis type 1 <BR> 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 <BR> 9. NCI-02-C-0141: Phase I Study of 7-Day or 21-Day ABT-751 in Children with Refractory Solid Tumors <BR>10. NCI-04-C-0080: Phase II trial of Pirfenidone in Children, Adolescents, and Young Adults With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas <BR> 11. NCI-05-C-0235: Phase I Study of Valproic Acid in Young Patients with Recurrent or Refractory Solid Tumors or CNS Tumors <BR> 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 <BR> 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 <BR>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 <BR>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 <BR> On-going collaborative projects with the POB include:<BR>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. <BR>2. immunohistochemical evaluation of 50 osteosarcoma tissues for P-glycoprotein (Pgp) expression in order to obtain preliminary data regarding relative frequency of Pgp positivity in osteosarcoma. The data will help initiate a clinical study which will address the feasibility of the Pgp inhibitor tariquidar as a therapeutic regimen in patients with osteosarcoma

小儿肿瘤的准确组织学表征对于在NCI的小儿肿瘤学分支（POB）的临床试验中入学是必需的。固体小儿肿瘤的诊断通常很困难，需要诊断技术的组合。大多数儿科实体瘤的特征是一致的染色体易位，这些染色体易位会导致基因融合并随后形成新型嵌合基因。可以通过RT-PCR或原位杂交（FISH）检测这些分子标记物，不仅可以用来在困难情况下建立诊断，还可以理解这些肿瘤的发病机理。 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).<BR> 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神经纤维瘤病（NF）患者的肿瘤。 <br> 1.NCI-99-C-0125：骨肉瘤：基于组织学反应的治疗结果：POB/NCI，德克萨斯州儿童医院和俄克拉荷马大学的合作努力<br> 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 <BR> 3. NCI-01-C-0222: Phase II Randomized, Cross-Over, Double-Blinded, Placebo-Controlled Trial of the Farnesyltransferase Inhibitor R115777 in Pediatric Patients与1型神经纤维瘤病和进行性丛生神经纤维瘤<br>4。NCI-02-C-0259：高风险和经常性小儿肉瘤的患者同种异体/同性血干细胞移植的试验研究 Osteosarcoma or Ewings Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma <BR> 6. 04-N282: Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target screening and Clinical Drug Development <BR> 7. 06-HG-0134: Natural history and biology of dermal neurofibromas in neurofibromatosis type 1 <BR> 8. NCI-01-C-0091：P型折磨的I阶段试验和药代动力学研究（XR9576），一种P-糖蛋白抑制剂，结合了肉毒抑制性固体肿瘤在内ABT-751患有固体瘤儿童的儿童<br> 10。 NCI-04-C-0080：对1型神经纤维瘤病的儿童，青少年和年轻人的吡非酮的II期试验，以及进行性或逆转抑制性固体或CRACRACTION抗逆性固体或c型co-nci-05-C-0235的11. NCI-05-C-0235：I期研究的年轻人或CRACRACTIROR固体或Cnc-cn 39.12959：第一阶段的研究与复发或难治性实体瘤的儿科患者（包括脑肿瘤在内的儿科患者）结合使用，包括脑肿瘤<br>13。NCI-06-C-0043：Neoadjuvant化学疗法的II期试验在1型孢子虫和神经原纤维症中<14阶段的神经原纤维症中的高级别的nce <blybrablabl shernecter sheriganter sheriment sherigncter sheptip sheptip sheptip sheptip sherignatip sheptip sherignter sherignter sheptip。 NCI-06-C-0146：IXABEPILONE（BMS-247550）的II阶段试验，一种Epothilone b类似物，在患有难治性实体瘤的儿童和年轻人中<br> 15。 NCI-06-C-0233：对Raf激酶和受体酪氨酸激酶抑制剂BAY 43-9006（Sorafenib）的I期研究，对患有难治性实体瘤或难治性白血病的儿童<br>与POB进行的共同协作项目包括：<br> 1。儿童癌症和神经纤维瘤组织的开发用于分子靶标和儿童药物开发（神经纤维瘤病联盟发育场所奖） - 我们将与其他病理学家一起使用阵列观看和评分阵列的线条系统来贡献儿童肿瘤组织，并解释免疫组织化学染色。 <br> 2。 P-糖蛋白（PGP）表达的50个骨肉瘤组织的免疫组织化学评估，以获取有关骨肉瘤中PGP阳性相对频率的初步数据。数据将有助于启动一项临床研究，该研究将解决PGP抑制剂苦苦植物作为骨肉瘤患者的治疗方案的可行性