HMGA2 as a potential molecular target in KMT2A-AFF1-positive infant acute lymphoblastic leukaemia.

Acute lymphoblastic leukaemia (ALL) in infants is an intractable cancer in childhood. Although recent intensive chemotherapy progress has considerably improved ALL treatment outcome, disease cure is often accompanied by undesirable long-term side effects, and efficient, less toxic molecular targeting therapies have been anticipated. In infant ALL cells with KMT2A (MLL) fusion, the microRNA let-7b (MIRLET7B) is significantly downregulated by DNA hypermethylation of its promoter region.

DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects.

Cardiac anomaly is one of the hallmarks of DiGeorge syndrome (DGS), observed in approximately 80% of patients. It often shows a characteristic morphology, termed as conotruncal heart defects. In many cases showing only the conotruncal heart defect, deletion of 22q11.

Lineage-dependent skewing of loss of heterozygosity (LOH) of KRAS gene in a case of juvenile myelomonocytic leukemia.

Juvenile myelomonocytic leukemia (JMML) is a clonal disease arising from abnormal hematopoietic stem cells, although the involvement of lymphoid lineage differs among reported cases. Here, we present a case of JMML with a KRAS G13D mutation. The mutation was detected in various hematopoietic lineages, including T and B lymphocytes and also in lineage(-) CD34(+) CD38(-) hematopoietic stem cells, showing a different percentage of affected cells in each lineage.

Novel dominant-negative mutant of GATA3 in HDR syndrome.

HDR syndrome is an autosomal dominant disorder characterized by hypoparathyroidism, sensorineural deafness, and renal anomaly caused by mutation of the GATA3 gene located at chromosome 10p15. We report the case of a neonate with HDR syndrome and a novel GATA3 mutation. We performed genetic and functional analysis of GATA3 in this patient and identified a novel heterozygous 1516G> C missense mutation in exon 5, resulting in a cysteine-to-serine substitution at codon 321 (Cys321Ser).

Membrane-anchored growth factors, the epidermal growth factor family: beyond receptor ligands.

The epidermal growth factor (EGF) family and the EGF receptor (EGFR, ErbB) tyrosine kinase family have been spearheading the studies of signal transduction events that determine cell fate and behavior in vitro and in vivo. The EGFR family and their signaling pathways are giving us tremendous advantages in developing fascinating molecular target strategies for cancer therapy. Currently, two important types of EGFR inhibitors are in clinical use: neutralizing antibodies of EGFR or ErbB2, and synthetic small compounds of tyrosine kinase inhibitors designed for receptors.

Identification of enzyme responsible for erythritol utilization and reaction product in yeast Lipomyces starkeyi.

We have identified the enzyme responsible for erythritol utilization and its reaction product in the yeast Lipomyces starkeyi CBS 1807. The enzyme, a polyol dehydrogenase requiring NAD+ as a coenzyme, was induced by erythritol in this yeast. We confirmed that the enzyme product was L-erythrulose by MS, NMR, and polarimeter analyses, meaning that we clarified the first step of erythritol utilization in yeasts for the first time.

Detection of protein-protein interactions on SiO2/Si surfaces by spectroscopic ellipsometry.

We have applied spectroscopic ellipsometry to sensitive detection of specific protein-protein interactions on SiO2/Si substrates. First, the change of ellipticity of the reflected polarized light (600-1100 nm) was correlated with the thickness of the protein layer immobilized on SiO2/Si surfaces by measuring monomeric (myoglobin) and homotetrameric (hemoglobin) proteins with a similar monomer size. Protein-protein interactions were then measured with the antigen/antibody and cell-surface receptor/ligand systems; in each system either of the two proteins was bound to SiO2/Si substrates.

Nanoparticles for the delivery of genes and drugs to human hepatocytes.

Hepatitis B virus envelope L particles form hollow nanoparticles displaying a peptide that is indispensable for liver-specific infection by hepatitis B virus in humans. Here we demonstrate the use of L particles for the efficient and specific transfer of a gene or drug into human hepatocytes both in culture and in a mouse xenograft model. In this model, intravenous injection of L particles carrying the gene for green fluorescent protein (GFP) or a fluorescent dye resulted in observable fluorescence only in human hepatocellular carcinomas but not in other human carcinomas or in mouse tissues.

Size distribution measurement of vesicles by atomic force microscopy.

Vesicles have been utilized as nanoscale vehicles for reagents including potential drug delivery systems. When used to deliver drugs, vesicle size and the size distribution are important factors in the determination of the dosage, cell specificity, and rate of clearance from the body. Current size measurement techniques for vesicles are electron microscopy and dynamic light scattering, but their results are not equal.