Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies.

Clear cell sarcoma (CCS), a rare malignant tumor with a predilection for young adults, is of poor prognosis. Recently however, boron neutron capture therapy (BNCT) with the use of p-borono-L-phenylalanine (BPA) for malignant melanoma has provided good results. CCS also produces melanin; therefore, the uptake of BPA is the key to the application of BNCT to CCS. We describe, for the first time, the high accumulation of boron in CCS and the CCS tumor-bearing animal model generated for BNCT studies.

Analysis of PTEN/MMAC1 alteration in neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in children. Although it has been reported that loss of heterozygosity at various loci, including 10q, frequently occurs in neuroblastoma, a bona fide tumor suppressor gene has not been identified. Recently, a gene mapped to chromosome 10q23, PTEN/MMAC1, was identified as a tumor suppressor gene that inhibits cell survival and cell proliferation by catalyzing the dephosphorylation of phosphatidylinositol 3,4,5-triphosphate. To screen for mutations of this gene in neuroblastoma, we analyzed 11 primary neuroblastoma tumors and 16 neuroblastoma cell lines for PTEN/MMAC1 mutations and deletions. All nine exons of the PTEN/MMAC1 gene were examined using the polymerase chain reaction-single strand conformational polymorphism assay and sequencing. Only one of the cell lines showed a mutation, a 1-bp frameshift deletion in exon 7, and an allelic loss in the opposite allele was revealed by a microsatellite analysis. Our results indicate that the disruption of the PTEN/MMAC1 gene is not a frequent event in neuroblastoma, and suggest that this disruption may be responsible for malignant progression in only a limited proportion of cases of neuroblastoma.

Signal transduction pathways through TRK-A and TRK-B receptors in human neuroblastoma cells.

Little is known about the signal transduction pathways of TRK family receptors in neuroblastoma (NB) cells. In this study, an NB cell line, designated MP-N-TS, was established from an adrenal tumor taken from a 2-year-old boy. This cell line expressed both TRK-A and TRK-B receptors, which is rare in a single NB cell line. Therefore, the MP-N-TS cell line was used to determine whether the signal transduction through these constitutive receptors is functional. Three neurotrophins, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-4 / 5 (NT-4 / 5), induced tyrosine phosphorylation of panTRK, and BDNF and NT-4 / 5 induced tyrosine phosphorylation of TRK-B. Tyrosine phosphorylation of panTRK and / or TRK-B by the neurotrophins was inhibited in the presence of a tyrosine kinase inhibitor K252a. Tyrosine phosphorylation of Src homologous and collagen (Shc), extracellular signal-regulated kinase (ERK)-1 and ERK-2, and phospholipase C-gamma1 (PLC-gamma1) was increased by the three neurotrophins and the increase was inhibited in the presence of K252a. Activation of Ras, detected as the GTP-bound form of Ras, was induced by the three neurotrophins. The neurotrophins did not modulate the expressions of TRK-A or TRK-B mRNA, but they did induce the expression of c-fos mRNA. Exogenous NGF induced weak neurite outgrowth, whereas exogenous BDNF and NT-4 / 5 induced distinct neurite outgrowth. Exogenous BDNF and NT-4 / 5 increased the number of viable cells, while NGF did not. Our results demonstrate that the signal transduction pathways through TRK-A and TRK-B in MP-N-TS cells are functional and similar, and the main downstream signaling pathways from the three neurotrophins are mitogen-activated protein kinase (MAPK) cascades through Shc, activated Ras, ERK-1 and ERK-2, and the transduction pathway through PLC-gamma1. Further, BDNF and NT-4 / 5 increased cell viability. The MP-N-TS cell line should be useful for clarifying the TRK-A and TRK-B signaling pathways responsible for the different prognoses in patients with NB.

Renin-producing hepatoblastoma.

Renin-producing tumors of extrarenal origin are rare in children. An 8-year-old boy with hepatoblastoma and hypertension associated with a high plasma renin level is reported. After chemotherapy, the plasma renin level normalized and the hypertension spontaneously resolved. The patient underwent surgery, and a right trisegmentectomy of the liver and a partial resection of the second and third segments were performed. The tumor was as shown the source of renin by immunohistochemical study and reverse transcriptase-polymerase chain reaction.

Donor leukocyte infusion after allogeneic bone marrow transplantation was not effective for relapsed rhabdomyosarcoma.

A 10-year-old boy with metastatic rhabdomyosarcoma had an HLA-identical sibling and received an allogeneic BMT. Recurrence was detected in the BM as the only site of treatment failure 12 months after BMT. Donor leukocyte infusion (DLI) was chosen as salvage therapy. Although sufficient cells (a total of 29.7 x 10(7)/kg) were infused, no signs of acute GVHD nor BM aplasia occurred and the patient died of disease progression 9 months after DLI.