Results of the JRS-I LRA0401 and LRB0402 Japan Rhabdomyosarcoma Study Group trials for low-risk embryonal rhabdomyosarcoma.

Background: Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4 g/m. However, this dose may increase the risk of adverse events, including infertility, in some patients.

Formation Processes of a Solid Electrolyte Interphase at a Silicon/Sulfide Electrolyte Interface in a Model All-Solid-State Li-Ion Battery.

Understanding the electrochemical reactions at the interface between a Si anode and a solid sulfide electrolyte is essential in improving the cycle stabilities of Si anodes in all-solid-state batteries (ASSBs). Highly dense Si films with very low roughnesses of <1 nm were fabricated at room temperature via cathodic arc plasma deposition, which led to the formation of a Si/sulfide electrolyte model interface. Li (de)alloying through the model interface hardly occurred during the first cycle, whereas it proceeded stably in subsequent cycles.

Multimodal analyses of a non-human primate model harboring mutant amyloid precursor protein transgenes driven by the human EF1α promoter.

Alzheimer's disease (AD) is the leading cause of dementia which afflicts tens of millions of people worldwide. Despite many scientific progresses to dissect the AD's molecular basis from studies on various mouse models, it has been suffered from evolutionary species differences. Here, we report generation of a non-human primate (NHP), common marmoset model ubiquitously expressing Amyloid-beta precursor protein (APP) transgenes with the Swedish (KM670/671NL) and Indiana (V717F) mutations.

Spontaneous pulmonary adenocarcinoma in a common marmoset (Callithrix jacchus).

A seven-year-old female common marmoset (Callithrix jacchus) presented with weight loss. Imaging revealed a left thoracic mass, confirmed at necropsy. Histology and immunohistochemistry suggested a well-differentiated pulmonary adenocarcinoma.

Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing.

Recent advances in genome editing have facilitated the generation of nonhuman primate (NHP) models, with potential to unmask the complex biology of human disease not revealed by rodent models. However, their broader use is hindered by the challenges associated with generation of adult NHP models as well as the cost of their production. Here, we describe the generation of a marmoset model of severe combined immunodeficiency (SCID).

Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney.

Clear cell sarcoma of the kidney (CCSK) is one of the major pediatric renal neoplasms, but its associated genetic abnormalities are largely unknown. We identified internal tandem duplications in the BCOR gene (BCL6 corepressor) affecting the C terminus in 100% (20/20) of CCSK tumors but in none (0/193) of the other pediatric renal tumors. CCSK tumors expressed only an aberrant BCOR allele, indicating a close correlation between BCOR aberration and CCSK tumorigenesis.

DNA methylation profile distinguishes clear cell sarcoma of the kidney from other pediatric renal tumors.

A number of specific, distinct neoplastic entities occur in the pediatric kidney, including Wilms' tumor, clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma (CMN), rhabdoid tumor of the kidney (RTK), and the Ewing's sarcoma family of tumors (ESFT). By employing DNA methylation profiling using Illumina Infinium HumanMethylation27, we analyzed the epigenetic characteristics of the sarcomas including CCSK, RTK, and ESFT in comparison with those of the non-neoplastic kidney (NK), and these tumors exhibited distinct DNA methylation profiles in a tumor-type-specific manner. CCSK is the most frequently hypermethylated, but least frequently hypomethylated, at CpG sites among these sarcomas, and exhibited 490 hypermethylated and 46 hypomethylated CpG sites in compared with NK.

Different incidences of epigenetic but not genetic abnormalities between Wilms tumors in Japanese and Caucasian children.

Epidemiological studies show that the incidence of Wilms tumor (WT) in East-Asian children is half of that in Caucasian children. Abnormalities of WT1, CTNNB1, WTX, and IGF2 were reported to be involved in Wilms tumorigenesis in Caucasians, although none of the studies simultaneously evaluated the four genes. WTX forms the β-catenin degradation complex; however, the relationship between WTX abnormality and CTNNB1 mutation was uncertain in WTs.

A microfabricated scaffold induces the spheroid formation of human bone marrow-derived mesenchymal progenitor cells and promotes efficient adipogenic differentiation.

Here, we report the highly efficient in vitro differentiation of human bone marrow-derived mesenchymal stem/progenitor cells (MPCs) using a novel nanotechnology-based culture plate, nanoculture plate(®) (NCP). The NCP contains uneven microfabrications with diameters of ∼2-3 μm arranged in a honeycomb pattern on its culture surface, which is devoid of animal-derived protein sources. When human MPCs were subjected to three-dimensional (3D) culture using an NCP, they rapidly formed adhesive spheroids.

Two candidate tumor suppressor genes, MEOX2 and SOSTDC1, identified in a 7p21 homozygous deletion region in a Wilms tumor.

A SNP-based array analysis of 100 Wilms tumors (WT) from 97 patients identified 7p alterations (hemizygous and homozygous deletions and uniparental disomy) in nine tumors. The homozygous deletion (HD) region of 7p21 found in one tumor partially overlapped with another HD region reported previously, and was narrowed down to a 2.1-Mb region.

Outcome of pediatric renal tumor treated using the Japan Wilms Tumor Study-1 (JWiTS-1) protocol: a report from the JWiTS group.

Purpose: In 1996, the Japan Wilms Tumor Study (JWiTS) group was founded to elucidate the efficacy and safety of the regimen established by the National Wilms Tumor Study (NWTS) group in the USA, and a multicenter cooperative study (JWiTS-1) was started in Japan. This report reviews the results of JWiTS-1.

Methods: A total of 307 patients with malignant renal tumor were enrolled in the JWiTS-1 study between 1996 and 2005.

EWS/ETS regulates the expression of the Dickkopf family in Ewing family tumor cells.

Background: The Dickkopf (DKK) family comprises a set of proteins that function as regulators of Wnt/beta-catenin signaling and has a crucial role in development. Recent studies have revealed the involvement of this family in tumorigenesis, however their role in tumorigenesis is still remained unclear.

Methodology/principal Findings: We found increased expression of DKK2 but decreased expression of DKK1 in Ewing family tumor (EFT) cells.

Reconstitution of Schwannian stroma in neuroblastomas using human bone marrow stromal cells.

The Schwannian stroma in neuroblastomas is related to patient prognosis. There is debate surrounding the origin of Schwannian stroma in neuroblastomas: one theory is that the Schwann cells are derived from neoplastic cells, and the other is that they arise from normal cells surrounding the neuroblastoma. We examined whether human bone marrow stromal cells (hBMSCs) or human mesenchymal stem cells (hMSCs) could differentiate into Schwann cells in neuroblastomas.

Duplication of paternal IGF2 or loss of maternal IGF2 imprinting occurs in half of Wilms tumors with various structural WT1 abnormalities.

The WT1 gene essential for the embryonic kidney development is mutated in 15-25% of Wilms tumors (WTs). To clarify whether genetic subtypes of WT1 abnormalities are correlated with IGF2 or CTNNB1 alterations or clinicopathological characteristics, we performed comprehensive WT1, IGF2, and CTNNB1 analyses of 36 WTs with WT1 abnormalities using single nucleotide polymorphism arrays, and methylation analysis of the IGF2-H19 differentially methylated region. The tumors were classified into three subtypes based on WT1 abnormalities: 13 with WT1 deletion, 12 with WT1 mutation, and 11 with both deletion and mutation.

Preferential localization of SSEA-4 in interfaces between blastomeres of mouse preimplantaion embryos.

The monoclonal antibody 6E2 raised against the embryonal carcinoma cell line NCR-G3 had been shown to also react with human germ cells. Thin-layer chromatography (TLC) immunostaining revealed that 6E2 specifically reacts with sialosylglobopenta osylceramide (sialylGb5), which carries an epitope of stage-specific embryonic antigen-4 (SSEA-4), known as an important cell surface marker of embryogenesis. The immunostaining of mouse preimplantation embryos without fixation showed that the binding of 6E2 caused the clustering and consequent accumulation of sialylGb5 at the interface between blastomeres.

Inducible expression of chimeric EWS/ETS proteins confers Ewing's family tumor-like phenotypes to human mesenchymal progenitor cells.

Ewing's family tumor (EFT) is a rare pediatric tumor of unclear origin that occurs in bone and soft tissue. Specific chromosomal translocations found in EFT cause EWS to fuse to a subset of ets transcription factor genes (ETS), generating chimeric EWS/ETS proteins. These proteins are believed to play a crucial role in the onset and progression of EFT.

A case of a ewing sarcoma family tumor in the urinary bladder after treatment for acute lymphoblastic leukemia.

We report the first case of a tumor of the Ewing sarcoma family of tumors arising from the urinary bladder 3 years after chemotherapy for acute lymphoblastic leukemia. A 16-year-old boy complained of macrohematuria and dysuria during the posttreatment follow up of his acute lymphoblastic leukemia. Ultrasonography and computed tomography revealed a 1-cm sized intravesical tumor.

Mutated D4-guanine diphosphate-dissociation inhibitor is found in human leukemic cells and promotes leukemic cell invasion.

Objective: Rho GTPase may be involved in human cancer invasion via the augmentation of cell motility and adhesion. We report on two point mutations of the D4-guanine diphosphate (GDP)-dissociation inhibitor (GDI) gene, one of the Rho-GDIs, which were found in a human leukemic cell line, Reh, and the mutated D4-GDI functions as an accelerator of leukemic cell invasion.

Material And Methods: We investigated the altered activity of GDP dissociation by mutated (mt) D4-GDI and the functions of this mt and wild-type (wt) D4-GDI in invasion.

The effect of transgenic expression of TGF-beta1 on transplanted islet graft survival.

Background/aims: Transgenic mice expressing the active form of porcine TGF-beta1 (NOD- TGF-beta1 Tg) were completely protected from autoimmune diabetes in the NOD genetic background in our previous study. Here, we attempted to determine whether transgenic expression of TGF-beta1 in transplanted islets prevents autoimmune destruction in NOD mice.

Methodology: We transplanted islets to the subcapsular region of the kidney using NOD-TGF-beta1 Tg and NOD mice as donor and recipient or vice versa.

Desmoplastic small cell tumor of soft tissue: molecular variant of EWS-WT1 chimeric fusion.

A 7-year-old girl was hospitalized because of a tumorous mass in her left periorbital region. The tumor was removed by local excision. The soft-part tumor recurred in the parotid gland region 4 months later, and a second recurrence was noted on the left side of the neck 3 years and 3 months thereafter.

Increased mobilization of c-kit+ Sca-1+ Lin- (KSL) cells and colony-forming units in spleen (CFU-S) following de novo formation of a stem cell niche depends on dynamic, but not stable, membranous ossification.

Stem cells are thought to inhabit in a unique microenvironment, known as "niche," in which they undergo asymmetric cell divisions that results in reproducing both stem cells and progenies to maintain various tissues throughout life. The cells of osteoblastic lineage have been identified as a key participant in regulating the number of hematopoietic stem cells (HSCs). HSCs receive their regulatory messages from the microenvironment in the bone marrow.

Ewing sarcoma/primitive neuroectodermal tumor of the kidney in a child.

A 6-year-old female was admitted with abdominal pain and a mass in the right abdomen. Her lactose dehydrogenase level was 1,200 IU/L, and neuron specific enolase was 120 ng/ml. Computed tomography scan confirmed a large right renal mass with necrosis.