Mycovirus-Containing Alters Transcription Factors in Normal and Acute Lymphoblastic Leukemia Cells.

Transcription factors control genes to maintain normal hemopoiesis, and dysregulation of some factors can lead to acute lymphoblastic leukemia (ALL). Mycoviruses are known to alter the genetics of their fungal host. The present study evaluates the effects of the products of a mycovirus-containing (MCAF), isolated from the home of a patient with ALL, on certain transcription factors of normal and ALL cell lines.

Mycoviruses in Fungi: Carcinogenesis of Fungal Agents May Not Always Be Mycotoxin Related.

Certain viruses have been found to induce diverse biological pathways to carcinogenesis, evidenced by the presence of viral gene products in some tumors. Despite the fact that many fungal agents contain mycoviruses, until recently, their possible direct effects on human health, including carcinogenesis and leukemogenesis, had not been explored. In this regard, most studies of fungal agents have rightly concentrated on their mycotoxin formation and effects.

Etiology of Acute Leukemia: A Review.

Acute leukemias constitute some of the most common malignant disorders. Despite significant progress made in the treatment of these disorders, their etiology remains unknown. A large and diverse group of genetic and environmental variables have been proposed.

Effect of Poloxamer 188 vs Placebo on Painful Vaso-Occlusive Episodes in Children and Adults With Sickle Cell Disease: A Randomized Clinical Trial.

Importance: Although effective agents are available to prevent painful vaso-occlusive episodes of sickle cell disease (SCD), there are no disease-modifying therapies for ongoing painful vaso-occlusive episodes; treatment remains supportive. A previous phase 3 trial of poloxamer 188 reported shortened duration of painful vaso-occlusive episodes in SCD, particularly in children and participants treated with hydroxyurea.

Objective: To reassess the efficacy of poloxamer 188 for vaso-occlusive episodes.

Exposure to a mycovirus containing Aspergillus Flavus reproduces acute lymphoblastic leukemia cell surface and genetic markers in cells from patients in remission and not controls.

The etiology of acute lymphoblastic leukemia (ALL) remains unknown. A recent "two-hit" model for the occurrence of precursor B cell acute lymphoblastic leukemia propose that this disease arises through a two-step process, including predisposing genetic mutation and exposure to infections. While several genetic mutations are proposed, no infection category has been suggested.

Plasma of Acute Lymphoblastic Leukemia Patients React to the Culture of a Mycovirus Containing Aspergillus flavus.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is also seen in adults. Currently, no plasma-based test for the detection of ALL is available. We have cultured the home of a patient with ALL and isolated a mycovirus containing Aspergillus flavus.

Response-dependent and reduced treatment in lower risk Hodgkin lymphoma in children and adolescents, results of P9426: a report from the Children's Oncology Group.

Background: Hodgkin lymphoma is highly curable but associated with significant late effects. Reduction of total treatment would be anticipated to reduce late effects. This aim of this study was to demonstrate that a reduction in treatment was possible without compromising survival outcomes.

Sudden death after exercise in an adolescent with hemoglobin SE.

Hemoglobin (Hb) S and Hb E are the most common variant hemoglobins, but because of the geographical separation of the areas where they are prevalent, the combination of the 2 is uncommon. Approximately 46 cases of hemoglobin SE compound heterozygosity have been reported. No deaths from the condition have been reported previously, whereas death after vigorous physical activity in individuals with sickle cell trait (hemoglobin AS) has been described in a few case reports.

Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d.

A phase III, open-label, single-arm study of tenecteplase for restoration of function in dysfunctional central venous catheters.

Purpose: To evaluate, in a phase III, single-arm study, the safety and efficacy of the thrombolytic agent tenecteplase in restoring function to dysfunctional central venous catheters (CVCs).

Materials And Methods: Pediatric and adult patients with dysfunctional CVCs were eligible to receive as much as 2 mL (2 mg) of intraluminal tenecteplase, which was left to dwell in the CVC lumen for a maximum of 120 minutes. If CVC function was not restored at 120 minutes, a second dose was instilled for an additional 120 minutes.

Clinicopathologic conference: multiple fetal demises, lactic acidosis and hepatic iron accumulation.

A case of a premature infant with lactic acidosis and hepatic iron accumulation, born to a mother with multiple fetal demises, is presented and discussed by both clinician and pathologist, in this traditional clinico-pathologic conference. The discussion includes the differential diagnoses of lactic acidosis and hepatic iron accumulation in infants.

Composite adrenal anaplastic neuroblastoma and virilizing adrenocortical tumor with germline TP53 R248W mutation.

Composite tumors are extremely rare. Such tumors in adrenal glands are usually of neuroendocrine-neural type and occur mostly in adults. Their pathogenesis remains elusive.

Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease.

Purpose: Pediatric Oncology Group (POG) studies 9426 and 9425 evaluated dexrazoxane (DRZ) as a cardiopulmonary protectant during treatment for Hodgkin's disease (HD). We evaluated incidence and risk factors of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and second malignant neoplasms (SMNs).

Patients And Methods: Treatment for low- and high-risk HD with doxorubicin, bleomycin, vincristine, and etoposide (ABVE) or dose-intensified ABVE with prednisone and cyclophosphamide (ABVE-PC), respectively, was followed by low-dose radiation.

Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness.

Rosai-Dorfman disease (RDD) is a rare, sporadic histiocytic disorder characterized by painless but protracted lymphadenopathy. Its etiology remains unclear. The observation of congenital disease and reports of familial cases with seven pairs of siblings including three sets of identical twins suggests a genetic predisposition in some patients with this condition.

Treatment of stage I, IIA, IIIA1 pediatric Hodgkin disease with doxorubicin, bleomycin, vincristine and etoposide (DBVE) and radiation: a Pediatric Oncology Group (POG) study.

Purpose: The objectives of this study were to evaluate the feasibility of reducing therapy, while maintaining treatment efficacy, in the context of a cooperative group clinical trial that allowed for clinical staging in early stage Hodgkin disease (HD).

Patients And Methods: Between August 1992 and December 1993, 51 eligible children < or =21 years of age, 31 male and 20 female, were enrolled in this study which was designed for low stage (IA, IIA, IIIA1) HD. Laparotomy and surgical staging was optional.

Lymphocyte predominant Hodgkin disease: clinico-pathologic features and results of treatment--the Pediatric Oncology Group experience.

Purpose: In this report, the Pediatric Oncology Group (POG) experience with lymphocyte predominant Hodgkin Disease (LPHD) in children is reviewed.

Materials And Methods: From 1984-1993, the POG conducted 3 clinical trials for advanced stage HD and 2 for early stage HD. There were 26 cases of LPHD in 613 patients in these trials.

Treatment compliance in childhood and adolescence.

Experience reveals that there is significant noncompliance with self-administered medication, especially in chronic conditions such as cancer. Noncompliance transcends the boundary of disease categories and age group. However, this is most prevalent during the adolescent years when the process of transition from parental dependency to autonomy produces confusion as to who is responsible for administration of medication.

Reversal of C1300 murine neuroblastoma multidrug resistance by cremophorEL, a solvent for cyclosporin A.

We previously developed a homoharringtonine resistant C-1300 neuroblastoma cell line with cross-resistance to adriamycin and increased levels of p-glycoprotein, and showed that drug resistance could be reversed in this cell line by cyclosporin A. The present study shows that cremophor EL, a parenteral vehicle for cyclosporin A, can also completely reverse this multidrug resistance in a clonogenic assay system. Cremophor EL incubated with resistant cells for up to six days did not reduce levels of p-glycoprotein.

1-beta-D-arabinofuranosylcytosine conjugates of ether and thioether phospholipids. A new class of ara-C prodrug with improved antitumor activity.

The 1-beta-D-arabinofuranosylcytosine (ara-C) conjugates 1-O-alkyl (ether) and 1-S-alkyl (thioether) phospholipids, being analogues of ara-CDP-sn-1,2-O-dipalmitoylglycerol (1), showed significant antitumor activity against L1210 and P388 leukemia in vivo. The more active conjugates include the 1-O-alkyl analogues, ara-CDP-rac-1-O-hexadecyl-2-O-palmitoylglycerol (2) and ara-CDP-rac-1-O-octa-decyl-2-O-palmitoylglycerol (3), and the corresponding 1-S-alkyl analogues, ara-CDP-rac-1-S-hexadecyl-2-O-palmitoyl-1-thioglycerol (4) and ara-CDP-rac-1-S-octadecyl-2-O-palmitoyl-1-thioglycerol (5, Cytoros). The conjugates were formulated by sonication, in which the conjugates existed as discs (size 0.

Modulation of drug resistance in homoharringtonine-resistant C-1300 neuroblastoma cells with cyclosporine A and dipyridamole.

The development of resistance accounts for therapy failure in the majority of advanced cases of neuroblastoma in children. A new transplantable murine C-1300 neuroblastoma cell line was developed in vitro, by repeated exposure of a sensitive cell line to increasing, but sublethal, doses of Homoharringtonine (HHT). The ED50 of the highly resistant cells for HHT, using a standard agar colony assay, is 480 ng/ml, compared with 13 ng/ml for the sensitive parental line.

Toxicity of high-dose cytosine arabinoside in the treatment of advanced childhood tumors resistant to conventional therapy. A Pediatric Oncology Group study.

Experience with high-dose cytosine arabinoside (HDAC) in pediatric solid tumors is limited. Sixteen children with solid tumors resistant to conventional therapies were registered in a pilot Pediatric Oncology Group (POG) study that required the administration of HDAC at 3 g/m2 every 12 hours for four doses. There were four cases of rhabdomyosarcoma, two cases of fibrosarcoma, four cases of neuroblastoma, and one case each of germ cell tumor, Wilm's tumor, retinoblastoma, hepatocellular carcinoma, Ewing's sarcoma, and Burkitt's lymphoma.