Successful treatment of hepatosplenic T-cell lymphoma with fludarabine, high-dose cytarabine and subsequent unrelated umbilical cord blood transplantation.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma that occurs most often in adolescents and young adults and is rare in children. Because of the aggressive clinical course, resistance to conventional chemotherapy and poor prognosis of HSTCL, an effective treatment has not been established. We report the case of a 3-year-old girl with HSTCL presenting with trilineage myelodysplasia.

Somatic mosaic mutations of IDH1 and NPM1 associated with cup-like acute myeloid leukemia in a patient with Maffucci syndrome.

Maffucci syndrome is a nonhereditary congenital disorder characterized by multiple enchondromas and with soft-tissue hemangiomas. Somatic mutations of the isocitrate dehydrogenase (IDH) gene have been detected in enchondroma and hemangioma tissue from patients with Maffucci syndrome. The rate of malignant transformation in Maffucci syndrome is high, with enchondromas transforming into chondrosarcomas and the development of secondary neoplasms, including pancreatic and hepatic adenocarcinoma, mesenchymal ovarian tumors, and brain tumors such as glioma.

Paraneoplastic Syndrome of Angiomatoid Fibrous Histiocytoma May Be Caused by EWSR1-CREB1 Fusion-induced Excessive Interleukin-6 Production.

We describe a 7-year-old girl with angiomatoid fibrous histiocytoma (AFH) presenting severe inflammatory symptoms. The cytokine/chemokine profile of serum samples before and after surgery demonstrated that interleukin (IL)-6 had decreased by the greatest percentage. The AFH cells were immunopathologically positive for IL-6 and Tyr705-phosphorylation of signal transducer and activator of transcription 3.

Erythropoietin activates telomerase through transcriptional and posttranscriptional regulation in human erythroleukemic JAS-REN-A cells.

We evaluated the molecular mechanism of telomerase activation by erythropoietin (EPO) in human erythroleukemic JAS-REN-A cells. Telomerase activity increased 3-4 fold after 3-24h of culture with EPO and was associated with increases in c-myc mRNA after 1-3h, of c-Myc protein after 3-6h, and of human telomerase reverse transcriptase (hTERT) mRNA and hTERT protein after 6-24h. Simultaneously EPO induced phosphorylation of signal transducer activator of transcription 5 (STAT5), AKT, and extracellular signal-regulated kinase (ERK).

Histone deacetylase inhibitors valproic acid and depsipeptide sensitize retinoblastoma cells to radiotherapy by increasing H2AX phosphorylation and p53 acetylation-phosphorylation.

Although p53 is intact in most cases of retinoblastoma, it is largely inactivated by the ubiqutin-proteasome system through interaction with murine double minute 2 (MDM2) and murine double minute X (MDMX). The present study showed that the histone deacetylase (HDAC) inhibitors valproic acid (VPA) and depsipeptide (FK228) synergistically enhanced ionizing radiation (IR)-induced apoptosis, associated with activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in Y79 and WER1-Rb1 human retinoblastoma cells. Both VPA and FK228 enhanced IR-induced phosphorylation of histone H2AX on Ser139 preceding apoptosis.

Antitumor activity of TMPyP4 interacting G-quadruplex in retinoblastoma cell lines.

To investigate the molecular mechanism of the antitumor activity of the cationic porphyrin 5, 10, 15, 20-tetra-(N-methyl-4-pyridyl)porphyrin (TMPyP4) in retinoblastoma cell lines, Y79 and WERI-Rb1 cells were treated with TMPyP4 for 0-72 h, after which growth inhibition, modulation of the cell cycle and the induction of apoptosis were examined. In addition, the effect of TMPyP4 on the susceptibility to irradiation was evaluated in Y79 and WERI-Rb1 cells. In vitro telomeric repeat amplification protocol assay showed TMPyP4 (10-100 microM) directly blocked telomerase elongation, suggesting that TMPyP4 can form stable guanine (G)-quadruplexes in extending telomere repeats in substrate oligonucleotides.

Antitumor activity of G-quadruplex-interactive agent TMPyP4 in K562 leukemic cells.

The cationic porphyrin TMPyP4 can bind to and stabilize DNA guanine-quadruplexes. We investigated the molecular mechanism of the antitumor activity of TMPyP4 in K562 cells and human telomere reverse transcriptase subunit (hTERT)-transfected K562 cells in which telomerase activity, followed by telomere elongation, was enhanced. Treatment with 100 microM TMPyP4 significantly inhibited the growth of both types of cell, with decreases of cells in the G(1) phase and increases of those in the S and G(2)/M phases after 48 h, preceding cell death after 72 h.

Sequential analysis of cadherin expression in a 4-year-old girl with intracranial ependymoma.

Introduction: Cadherins are Ca(2+)-dependent cell-to-cell adhesion molecules that play an important role in tissue construction and morphogenesis in multicellular organisms. Cadherin involvement in tumor metastasis has recently been reported.

Case Report: We investigated the expression of E-cadherin and N-cadherin in paraffin-embedded sequential surgical specimens and autopsy specimens from a 4-year-old girl with recurrent ependymoma, subsequent to cerebrospinal fluid (CSF) dissemination.

Lymphocytic hypophysitis with central diabetes insipidus and subsequent hypopituitarism masking a suprasellar germinoma in a 13-year-old girl.

Case Report: We report a case of central diabetes insipidus, hypothyroidism, and subsequent hypopituitarism due to lymphocytic hypophysitis masking a germinoma in a 13-year-old pubertal girl. Magnetic resonance revealed an enlarged pituitary gland and a mass lesion in the pituitary stalk and inferior hypothalamus. Open cranial surgery of the anterior pituitary showed active hypophysitis with lymphocytic infiltrates but without necrosis.