Neoplasms

Eye Diseases

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Retinoblastoma

Sarcoma

Osteosarcoma

Neuroblastoma

Sarcoma, Ewing

Rhabdomyosarcoma

Adrenal Cortex Neoplasms

Soft Tissue Sarcoma

Ewing Sarcoma

Hematinics

All Drugs and Chemicals

Liver Extracts

Sara M. Federico, MD

This study will prospectively characterize the molecular, cellular and genetic properties of primary and metastatic neuroblastoma, osteosarcoma, retinoblastoma, Ewing sarcoma family of tumors, soft tissue sarcomas, adrenocortical tumors and liver malignancies. These cell isolates will be used for gene expression array analysis, genomic analysis by \[SNP\] single nucleotide polymorphism chip, array \[CGH\] comparative genomic hybridization and next generation sequencing, and \[TEM\] transmission electron microscopy analysis. Additionally cell lines and orthotopic xenografts will be created from the obtained tumor specimens.

The specificity of TCRs will be examined by comparing paired TCR from peripheral blood and tumor infiltrating CD4+ and CD8+ T cells. Epigenetic studies will be performed looking at the methylation profile of these cells and to investigate the anti-tumor T cell response both pre- and post-PD1 inhibition.

Each year approximately 2,200 children in the United States are diagnosed with neuroblastoma, osteosarcoma, Ewing sarcoma family of tumors (ESFT), retinoblastoma, soft tissue sarcomas, adrenocortical tumors and liver malignancies. These aggressive pediatric solid tumors are developmental tumors that initiate during periods of tissue growth and morphogenesis in the neural crest, bone and soft tissues. The overall survival rate of these tumors in the advanced stage is less than 30%. Despite intensive efforts over the past three decades using multiple therapeutic modalities including chemotherapy, surgery, radiation, autologous bone marrow transplant and biological agents there has been modest improvement in the long-term survival of these advanced stage pediatric solid tumors. A better understanding of the molecular, cellular and genetic changes that occur in the developing tissues as tumors form could improve the treatment of these devastating cancers. In particular, chemotherapeutic agents may be more effectively targeted to key regulatory enzymes or proteins if the study had a better understanding of the pathways that are disrupted as cells progress from preneoplastic lesions to metastatic disease. The specific aim of this proposal is to identify the changes in gene expression that occur in neuroblastoma, retinoblastoma, osteosarcoma, Ewing sarcoma family of tumors \[ESFT\] and soft tissue sarcoma cells and to correlate these changes with genetic and cellular changes in the tumor cells. \[RNA\] ribonucleic acid and genomic \[DNA\] deoxyribonucleic acid will be isolated from neuroblastoma, retinoblastoma, osteosarcoma, ESFT \[Ewing sarcoma family of tumors\] and soft tissue sarcomas (both primary and metastatic lesions) following surgery or bone marrow aspiration of previously untreated patients. Additional testing will be conducted on tumor samples at any point during or following therapy in which a surgical specimen is obtained. When there is sufficient tumor sample remaining after pathological analysis and banking, fresh primary tumor cells will be used to prepare orthotopic xenografts and to establish models of each disease that recapitulate the advanced forms of neuroblastoma, osteosarcoma, Ewing sarcoma family of tumors \[ESFT\], retinoblastoma and soft tissue sarcomas. For a small group of these excess samples, this study will perform fixation for electron microscopy and process the samples for \[TEM\] transmission electron microscopy analysis. These studies will complement our active research program characterizing the molecular, cellular and genetic features of genetically engineered mouse models of each of these diseases. Biological samples from the cohort of patients treated at St. Jude Children's Research Hospital will be complemented with samples collected and processed by collaborating institutions around the world. Samples collected from international collaborators will be used for analysis of \[DNA\] deoxyribonucleic acid and \[RNA\] ribonucleic acid to complement the St. Jude Children's Research Hospital cohort. Through this collaboration the study anticipates that they will be able to obtain enough fresh tumor samples to improve their understanding of multistage tumorigenesis in pediatric solid malignancies.

Tumor tissue - Tumor tissue will be obtained from patients with a diagnosis of neuroblastoma, retinoblastoma, osteosarcoma, Ewing sarcoma or soft tissue sarcoma at some or all of the following time points: initial biopsy, primary tumor resection, time of disease recurrence. Whole blood - 5 ml of whole blood will be collected from each patient and be used as a matched control. Bone marrow aspiration - 5ml of bone marrow will be taken at the time a patient is having a bone marrow aspirate performed and processed to remove only tumor cells.

Molecular Analysis Of Solid Tumors

Alex's Lemonade Stand Foundation

St. Jude Children's Research Hospital

Symptoms and General Pathology

Digestive System Diseases

Carcinoma

Neoplasm Metastasis

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplastic Processes

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Patients with tumors in the right posterior section of the liver (segments 6-7)

The technique consists in IOUS-guided finger compression of the right posterior portal pedicle at the level closest to the tumor but oncologically suitable. This method allows us to anatomically mark the area of resection with nor hilar plate nor IOUS-guided puncture of vessels, which are up to date the only two techniques available to perform anatomical right posterior sectionectomy - namely the removal of segment 6 and 7.

Anatomical right posterior sectionectomy of the liver by IOUS-guided finger compression.

Guido Torzilli, MD, PhD

The use of intraoperative ultrasound (IOUS) allows us to perform new conservative hepatectomies. The investigators previously reported the systematic subsegmentectomy by IOUS-guided finger compression for segments 2-3, which is currently applied for patients with hepatocellular carcinoma (HCC)on cirrhosis. The investigators herein describe a novel technique, which consists in the systematic right posterior sectionectomy by IOUS-guided finger compression.

A novel technique for the demarcation of the resection area by means of IOUS-guided finger compression to accomplish a right posterior sectionectomy is described. Dissection or encirclement of the sectional pedicles for resection area demarcation is thus avoided. Ten patients underwent this technique successfully without mortality or major morbidity. IOUS-guided finger compression of sectional portal pedicle feeding the right posterior section is a feasible, safe, and effective method.

Anatomical Right Posterior Sectionectomy of the Liver by IOUS-Guided Finger Compression

A Novel Simple Technique for Performing Anatomical Right Posterior Sectionectomy of the Liver: the Ultrasound-Guided Finger Compression

University of Milan

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Molecular Analysis Of Solid Tumors	NCT01050296	Pediatric Solid...		- 25 Years	St. Jude Children's Research Hospital
Anatomical Right Posterior Sectionectomy of the Liver by IOUS-Guided Finger Compression	NCT00797251	Colorectal Live... Hepatocellular ... Liver Malignanc...	Anatomical righ...	18 Years - 85 Years	University of Milan
Molecular Analysis Of Solid Tumors	NCT01050296	Pediatric Solid...		- 25 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for liver malignancies