Identification and gene expression profiling of tumor-initiating cells isolated from human osteosarcoma cell lines in an orthotopic mouse model.

In the cancer stem cell model a cell hierarchy has been suggested as an explanation for intratumoral heterogeneity and tumor formation is thought to be driven by this tumor cell subpopulation. The identification of cancer stem cells in osteosarcoma (OS) and the biological processes dysregulated in this cell subpopulation, also known as tumor-initiating cells (TICs), may provide new therapeutic targets. The goal of this study, therefore, was to identify and characterize the gene expression profiles of TICs isolated from human OS cell lines.

Cell-specific gene expression in Langerhans cell histiocytosis lesions reveals a distinct profile compared with epidermal Langerhans cells.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by heterogeneous lesions containing CD207(+) Langerhans cells (LCs) and lymphocytes that can arise in almost any tissue and cause significant morbidity and mortality. After decades of research, the cause of LCH remains speculative. A prevailing model suggests that LCH arises from malignant transformation and metastasis of epidermal LCs.

One year follow-up of children and adolescents with chronic immune thrombocytopenic purpura (ITP) treated with rituximab.

Background: We previously showed in a prospective study that rituximab appears to be effective in some children and adolescents with severe chronic immune thrombocytopenia. Eleven of 36 patients achieved and maintained platelet counts over 50,000/mm(3) within the first 12 weeks. These patients were followed for the next year.

Growth patterns and gastrointestinal symptoms in pediatric patients after hematopoietic stem cell transplantation.

Purpose/objectives: To identify growth patterns and gastrointestinal (GI) symptoms in pediatric patients during the first four months after hematopoietic stem cell transplantation (HSCT) and to assess whether an association exists between acute graft-versus-host disease (GVHD) and growth pattern changes or GI symptoms.

Design: A prospective, longitudinal cohort design.

Setting: A tertiary children's hospital in a metropolitan area in the southern United States.

Pharmacokinetics of irinotecan and its metabolites in pediatric cancer patients: a report from the children's oncology group.

Objective: To develop a population pharmacokinetic model of irinotecan and its major metabolites in children with cancer and to identify covariates that predict variability in disposition.

Methods: A population pharmacokinetic model was developed using plasma concentration data from 82 patients participating in a multicenter Pediatric Oncology Group (POG) single agent phase II clinical trial. Patients between 1 and 21 years of age with solid tumors refractory to standard therapy received irinotecan, 50 mg/m(2), as a 60-min intravenous infusion for 5 consecutive days every 3 weeks.

EBV+ lymphoproliferative disease following prolonged chemotherapy for refractory LCH.

Epstein-Barr virus (EBV) is a herpesvirus for which latent infection in B lymphocytes occurs in most individuals by middle childhood. Clinically significant reactivation of this virus occurs in the context of suppressed cell-mediated immunity, occasionally developing into lymphoproliferative disease (EBV-LPD). EBV reactivation is rarely associated with intensive chemotherapy alone.

Intracranial plasma cell granuloma: case report and treatment of recurrence with methotrexate and 6-mercaptopurine.

Plasma cell granulomas are a rare form of idiopathic inflammatory pseudotumors often characterized by non-neoplastic proliferation of plasma cells, clinically mimicking a neoplastic process. Pseudotumors of the central nervous system, however, are exceptional and rare. The authors describe a 14-year-old girl with a mass lesion extending medially along the cavernous sinus into the right middle cranial fossa and pterygopalatine and infratemporal fossae.

Trends in complete blood count values during acute painful episodes in children with sickle cell disease.

Complete blood count (CBC) values are monitored as crude indicators of the hemolytic and inflammatory processes that accompany an acute painful episode in children with sickle cell disease. As part of a larger study that examined the pain experience and pain management of hospitalized children during painful vaso-occlusive episodes, the authors examined trends in CBC values and determined whether there were relationships between these values and pain intensity scores. Children, 5 to 19 years of age, with sickle cell disease whose primary reason for admission was vasoocclusive pain were recruited for participation in the study.

Chronic refractory ITP in children: beyond splenectomy.

Idiopathic (or immune) thrombocytopenic purpura (ITP) is a relatively common hematologic condition, but one that the hematology community has failed to reach a consensus on with regard to treatment. In patients with chronic refractory ITP, there is even less agreement about treatment approaches, as this population represents a small, but challenging, fraction of the total cases of ITP. The aim of this article is to review the treatment options available for children with chronic refractory ITP, including a review of the benefits versus risks, rate of remission, and areas of ongoing and future research.

Inherited coagulation factor abnormalities: a pediatric review.

Clotting factor abnormalities in children provide an interesting challenge to the medical care team. Understanding the diagnostic process and the medical management of children with factor abnormalities is crucial, as life-threatening complications can occur. This article will familiarize the reader with symptoms, laboratory testing, diagnosis, and treatment of hereditary coagulation factor abnormalities.

Granulocytic sarcoma presenting as pneumonia in a child with t(8;21) acute myelogenous leukemia: diagnosis by fluorescent in situ hybridization.

Granulocytic sarcoma is a soft tissue collection of leukemic cells. The authors describe a 4-year-old boy with M2 acute myelogenous leukemia (AML) who presented with fever, mild nonproductive cough, and hematemesis. Although he was initially diagnosed with nodular pneumonia, rapid resolution of a pulmonary infiltrate following induction chemotherapy was suggestive of a pulmonary granulocytic sarcoma.

Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia.

The von Hippel-Lindau (pVHL) protein plays an important role in hypoxia sensing. It binds to the hydroxylated hypoxia-inducible factor 1 alpha (HIF-1 alpha) and serves as a recognition component of an E3-ubiquitin ligase complex. In hypoxia or secondary to a mutated VHL gene, the nondegraded HIF-1 alpha forms a heterodimer with HIF-beta and leads to increased transcription of hypoxia-inducible genes, including erythropoietin (EPO).

Mutations in the VHL gene in sporadic apparently congenital polycythemia.

The congenital polycythemic disorders with elevated erythropoietin (Epo) have been until recently an enigma, and abnormality in the hypoxia-sensing pathway has been hypothesized as a possible mechanism. The tumor suppressor von Hippel-Lindau (VHL) participates in the hypoxia-sensing pathway, as it binds to the proline-hydroxylated form of the hypoxia-inducible factor 1alpha (HIF-1alpha) and mediates its ubiquitination and proteosomal degradation. The loss of VHL function may result in the accumulation of HIF-1alpha and overproduction of HIF-1 downstream target genes including Epo.

Need for a cooperative study: Pulmonary Langerhans cell histiocytosis and its management in adults.

Background: Pulmonary involvement with Langerhans cell histiocytosis (LCH, formerly known as histiocytosis-X) presents as an interstitial process in children and adults either with or without symptoms. In contrast to other manifestations of LCH, most patients with pulmonary disease are adults.

Procedures: We reviewed the literature on pulmonary LCH to determine what were the clinical presentations, prognostic variables, and treatment options for this disease.

Epstein-Barr virus and HIV-AIDS-associated diseases.

Among the secondary problems of patients with the human immune deficiency virus (HIV) infection are lymphadenopathy, atypical lymphoproliferations, and malignant transformations of lymphoid, muscle, and epithelial cells caused by infection with Epstein-Barr virus (EBV). The lymphoproliferative diseases associated with EBV infection include lymphocytic interstitial pneumonitis, lymphomas of primary and extra-nodal sites, such as the central nervous system (CNS), and mucosa-associated lymphoid tissue (MALT). EBV infection causes these diseases through a combination of mechanisms including use of virus-encoded transforming genes, stimulation of diverse cytokines, and interaction with receptors for the tumor necrosis factor (TNF) family of cytokines.

Neoplastic meningitis: diagnosis and treatment considerations.

Neoplastic meningitis is an increasingly recognized complication of advanced metastatic cancer and, if left undiagnosed or untreated, is characterized by rapid neurologic deterioration and death. Thus, the diagnosis and treatment of neoplastic meningitis present challenges for the clinical oncologist. The diagnosis of neoplastic meningitis is based on clinical signs and symptoms, laboratory analysis of cerebrospinal fluid to determine cell count and cytology, and analysis of neuroimaging studies for evidence of leptomeningeal or cranial nerve enhancement.

DNA polymorphisms and mutations of the tumor necrosis factor-alpha (TNF-alpha) promoter in Langerhans cell histiocytosis (LCH).

Langerhans cell histiocytosis (LCH) is a clonal proliferation of dendritic histiocytes expressing elevated levels of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 (IL-1), and leukemia inhibitory factor (LIF). The cause of the increased cytokine levels is unknown, but DNA sequence changes in promoters could alter expression. The TNF-alpha and IFN-gamma promoter DNA sequences of 12 LCH patients were studied and compared with normal individuals by dideoxy fingerprinting and DNA sequencing.

Epstein-Barr Virus EBNA-2 gene expression enhances lymphotoxin production by B lymphocytes.

Epstein-Barr Virus (EBV) effectively transforms B lymphocytes into long-term cell lines or tumors through the interaction of viral gene products and cellular proteins induced secondary to the virus infection. The latent membrane protein (LMP) gene, the EBV nuclear antigens (EBNAs) 1 and 2, and the origin of replication genes of the virus are the principal viral effectors of transformation. One of the cellular proteins that enhances the growth and proliferation of B cells is lymphotoxin (LT).

Intraabdominal desmoplastic small round cell tumor presenting as a gastric mural mass with hepatic metastases.

Purpose: An atypical case of childhood intraabdominal desmoplastic small round cell tumor (DSRCT) is presented.

Patient And Methods: An 11-year-old boy presented with progressive nausea and vomiting, abdominal pain, hepatomegaly, and an epigastric mass. Computed tomographic scanning as well as findings at gastroscopy and laparotomy revealed a large gastric mural tumor accompanied by multiple large intrahepatic masses.

Pancytopenia with chromosomal fragility: vitamin B12 deficiency.

Purpose: Pancytopenia in children may have many etiologies. Chromosomal abnormalities with pancytopenia is of particular concern because clonal abnormalities indicate a neoplastic process. We describe three children who had vitamin B12 deficiency and who displayed pancytopenia with multiple chromosomal breaks, rearrangements, and deletions consistent with chromosomal fragility.