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

儿童肿瘤的准确组织学特征对于NCI儿童肿瘤分支（POB）临床试验的患者入组是必要的。儿科实体肿瘤的诊断通常很困难，需要多种诊断技术的结合。大多数儿童实体瘤的特征在于一致的染色体易位，其导致基因融合和随后形成新的嵌合基因。这些分子标志物可以通过RT-PCR或荧光原位杂交（FISH）检测，不仅可以用于建立疑难病例的诊断，而且可以了解这些肿瘤的发病机制。NCI的儿科肿瘤服务很复杂，工作人员24小时参与服务的各个方面，包括与临床医生进行现场咨询，并在收到病理材料后立即进行评估，冷冻切片咨询，组织采购，肉瘤移位研究中肿瘤组织组织学评价和最终体征-所有儿科肿瘤的手术和分子病理学报告。住院医师和研究员的教学发生在儿科肿瘤病例的签出和结构化讲座（部门会议）。<BR>我们的儿科肿瘤材料由以下POB方案决定，包括儿童小圆细胞肿瘤（尤文肉瘤家族肿瘤、横纹肌肉瘤和神经母细胞瘤）、骨肉瘤和各种软组织肉瘤，包括神经纤维瘤病（NF）患者的神经鞘瘤。<BR>1.NCI-99-C-0125：骨肉瘤：基于组织学反应的治疗结果：POB/NCI，德克萨斯儿童医院和俄克拉荷马州大学的合作成果2.<BR>NCI-00-C-0092：在新诊断的肉瘤患者中比较filgastrim-SD/01与filgastrim（G-CSF）联合化疗的II期随机试验3。<BR>NCI-01-C-0222：法尼基转移酶抑制剂R115777治疗1型神经纤维瘤病和进行性丛状神经纤维瘤4的儿童患者的II期、随机、交叉、双盲、安慰剂对照试验。<BR>NCI-02-C-0259：高风险和复发性小儿肉瘤患者异基因/同基因造血干细胞移植的初步研究5。<BR>NCI-04-C-0001：吉西他滨和多西他赛序贯治疗复发性骨肉瘤或尤因肉瘤或不可切除或局部复发性软骨肉瘤患者的II期研究6.<BR>04-N282：儿童癌症和丛状神经纤维瘤组织微阵列用于分子靶点筛选和临床药物开发7.<BR>06-HG-0134：神经纤维瘤病1型中真皮神经纤维瘤的自然史和生物学。<BR>NCI-01-C-0091：Tariquidar（XR 9576）（一种P-糖蛋白抑制剂）与多柔比星、长春瑞滨或多西他赛联合治疗难治性实体瘤（包括脑肿瘤）儿科患者的I期试验和药代动力学研究9.<BR>NCI-02-C-0141：7天或21天ABT-751治疗儿童难治性实体瘤的I期研究10.<BR>NCI-04-C-0080：吡非尼酮在儿童、青少年和年轻成人1型神经纤维瘤病和进行性丛状神经纤维瘤中的II期试验11。<BR>NCI-05-C-0235：丙戊酸在复发性或难治性实体瘤或CNS肿瘤年轻患者中的I期研究12.<BR>NCI-05-C-0239：Talabostat联合替莫唑胺或卡铂治疗复发性或难治性实体瘤（包括脑肿瘤）儿科患者的I期研究13.<BR>NCI-06-C-0043：散发性和1型神经纤维瘤病相关的高度不可切除的恶性外周神经鞘膜瘤的新辅助化疗的II期试验14.<BR>NCI-06-C-0146：伊沙匹隆（BMS-247550）（一种埃博霉素B类似物）在儿童和年轻成人难治性实体瘤中的II期试验15.<BR>NCI-06-C-0233：Raf激酶和受体酪氨酸激酶抑制剂BAY 43 - 9006（索拉非尼）在难治性实体瘤或难治性白血病儿童中的I期研究与POB正在进行的合作项目包括：1.<BR><BR>儿童癌症和丛状神经纤维瘤组织微阵列的开发，用于分子靶点筛选和儿童药物开发（神经纤维瘤病协会开发现场奖）-我们将与其他病理学家一起使用在线系统进行阵列观察和评分，贡献儿科肿瘤组织并解释免疫组织化学染色。<BR>2.对50例骨肉瘤组织进行P-糖蛋白（Pgp）表达的免疫组化评价，以获得关于骨肉瘤中Pgp阳性相对频率的初步数据。这些数据将有助于启动一项临床研究，探讨Pgp抑制剂tariquidar作为骨肉瘤患者治疗方案的可行性