Purpose: We performed a phase I trial to investigate the safety, clinical responses, and Wilms' tumor 1 (WT1)-specific immune responses following treatment with dendritic cells (DC) pulsed with a mixture of three types of WT1 peptides, including both MHC class I and II-restricted epitopes, in combination with chemotherapy.

Dlgh1 (discs large homolog 1) is a mammalian homolog of the Drosophila tumor suppressor Discs large 1, and is a member of the membrane-associated guanylate kinase (MAGUK) scaffolding proteins that contain three PSD-95/Dlg/ZO-1 (PDZ) domains. Discs large 1 is involved in epithelial polarization and cell-cell adhesion complex formation during Drosophila development. However, the functions of Dlgh1 during mammalian development remain to be elucidated. We generated Dlgh1-knockout mice and found that homozygous Dlgh1-knockout mice developed various abnormalities in their renal and urogenital organs. The kidneys and ureters were hypoplastic and the lower ends of the ureters were ectopic. In addition, the vagina and seminal vesicle, which are derived from the lower part of the Müllerian and Wolffian duct, respectively, were absent. Unexpectedly, loss of Dlgh1 function in the developing ureters did not disrupt cell-cell junctional complexes, but did impair cellular proliferation in the epithelium. These results suggest a novel role for Dlgh1 in regulating epithelial duct formation and morphogenesis during mammalian development. Although congenital absence of the vagina associated with other variable Müllerian duct abnormalities has been reported in humans, its mechanism has not yet been clarified. Our findings might contribute to a better understanding of such abnormalities.

B-Myb is one member of the vertebrate Myb family of transcription factors and is ubiquitously expressed. B-Myb activates transcription of a group of genes required for the G2/M cell cycle transition by forming the dREAM/Myb-MuvB-like complex, which was originally identified in Drosophila. Mutants of zebrafish B-myb and Drosophila myb exhibit defects in cell cycle progression and genome instability. Although the genome instability caused by a loss of B-Myb has been speculated to be due to abnormal cell cycle progression, the precise mechanism remains unknown. Here, we have purified a B-Myb complex containing clathrin and filamin (Myb-Clafi complex). This complex is required for normal localization of clathrin at the mitotic spindle, which was previously reported to stabilize kinetochore fibres. The Myb-Clafi complex is not tightly associated with the mitotic spindles, suggesting that this complex ferries clathrin to the mitotic spindles. Thus, identification of the Myb-Clafi complex reveals a previously unrecognized function of B-Myb that may contribute to its role in chromosome stability, possibly, tumour suppression.

Inhibitor of ␤-catenin and T cell factor (ICAT) inhibits Wnt signaling by interfering with the interaction between ␤-catenin and T cell factor. Here we show that ICAT ؊/؊ embryos exhibit malformation of the forebrain and craniofacial bones and lack the kidney. Analysis of the neuronal differentiation of embryonic stem cells revealed that Wnt3a redirects the fate of neural progenitors to a posterior character, whereas ICAT induces forebrain cells by inhibiting Wnt signaling. Furthermore, ICAT ؊/؊ embryonic stem cells were found to differentiate into neuronal cells possessing a posterior character. These results suggest that ICAT plays an important role in the anteriorization of neural cells by inhibiting the posteriorizing activity of Wnt signaling.W nt signaling plays a crucial role in a number of developmental processes, including body axis formation, development of the central nervous system, and axial specification in limb development (1-8). Wnt signaling stabilizes ␤-catenin, which in turn associates with T cell factor (TCF)͞lymphoid-enhancing factor family transcription factors, ultimately altering the expression of Wnt target genes. In the absence of Wnt signaling, ␤-catenin is recruited into the multiprotein complex containing adenomatous polyposis coli (APC), glycogen synthase kinase-3␤, casein kinase 1␣, and Axin or the closely related factor conductin͞Axil and subjected to proteasome-mediated degradation. Wnt signaling is further inhibited by the association of ␤-catenin with the inhibitor of ␤-catenin and TCF (ICAT) (9-12). ICAT is an 81-aa protein that interferes with the interaction between ␤-catenin and TCF. ICAT contains an amino-terminal helical domain that binds to armadillo repeats 10-12 of ␤-catenin, and a carboxy-terminal tail that competes with TCF for binding to armadillo repeats 5-10 (9, 11, 12). Overexpression of ICAT induces G 2 arrest and cell death of colorectal tumor cells mutated in APC or ␤-catenin and hepatocellular carcinoma cells mutated in Axin (10).It has been shown that Wnt signaling specifies posterior-toanterior fates within the neural plate (13-16). Inhibition of Wnt signaling is required for anterior specification; negative regulators of Wnt signaling play a crucial role in establishing a gradient of Wnt activity patterning the anterior-posterior axis. Mouse embryos lacking Dickkopf1, a secreted protein that acts as an inhibitor of the Wnt coreceptor low density lipoprotein receptor-related protein 6, lack head structures anterior to the midbrain (17). Also, mouse embryos lacking Six3 (sine oculis homeobox homolog 3), a direct negative regulator of Wnt1 expression, lack forebrain structures and exhibit posteriorization of the remaining mutant heads (18). In addition, zebrafish mutants for the negative intracellular regulators of Wnt signaling tcf3͞headless and axin͞masterblind display anterior defects (19 -21). In the present study, we show that mouse embryos lacking ICAT exhibit multiple defects including malformation of the forebrain. Furthermore, by analyzing the neuron...