[A Case of Granulocyte-Colony Stimulating Factor Producing Breast Cancer That Caused Rapid Progression].

We report a case of granulocyte-colony stimulating factor(G-CSF)producing breast cancer in a 54-year-old woman. Eight months after surgery, multiple liver and pulmonary metastases appeared. They progressed rapidly in 2 weeks and she had a high fever of 38 degrees. Serum G-CSF was high, and positive cells were found by immunostaining of the primary tumor. Chemotherapy was initially successful but she died 4 months after relapse.

Regulated Nodal signaling promotes differentiation of the definitive endoderm and mesoderm from ES cells.

Nodal signaling induces the formation of the endoderm and mesoderm during gastrulation. Nodal expression persists until the definitive endoderm progenitor has completely formed, and disappears thereafter. A tightly regulated Nodal expression system is essential for the differentiation of embryonic stem (ES) cells into distinct tissue lineages. On this basis, we established an ES cell differentiation system with the tetracycline-regulated expression of Nodal. The upregulated Nodal signaling pathway and its downstream transcriptional targets induced the specification of ES cells into definitive endoderm and mesoderm derivatives, and the subsequent downregulation of Nodal signaling promoted further maturation of the gut tube both in vitro and in vivo. Sustained expression of the Nodal gene inhibited the maturation of the definitive endoderm owing to persistent Oct3 and/or Oct4 expression and teratoma formation. Furthermore, quantitative single cell analysis by flow cytometry using CXCR4, VEGFR2 and PDGFR-alpha indicated that this protocol for definitive endoderm and mesoderm differentiation is superior to any other available protocol. Our findings also indicated that the Nodal or Nodal-related molecules secreted from Nodal-expressing ES cells could cause genetically unmanipulated ES cells to induce the expression of the Nodal signaling pathway and its downstream targets, which consequently leads to the differentiation of the ES cells into definitive endoderm and mesoderm. Our differentiation system, using tightly regulated Nodal expression, enabled us to investigate the mechanism of ES cell differentiation into definitive endoderm or mesoderm derivatives. Our findings also demonstrate that Nodal-expressing ES cells might be a source of highly active proteins that could be used for developing endoderm or mesoderm tissues in regenerative medicine.

Significant role of middle hepatic vein in remnant liver regeneration of right-lobe living donors.

For adult patients with end-stage liver disease, living-donor liver transplantation (LDLT) of right-lobe grafts with or without the middle hepatic vein (MHV) has been increasingly used in recent years. We investigated the role of the MHV in donor remnant liver regeneration after right-lobe LDLT, which has not been described in previous studies. A total of eight living donors were included in this study of right-lobe LDLT. Four donors underwent right lobectomy (without MHV), and the remaining four underwent extended right lobectomy (with MHV). Regeneration of the donor remnant liver was assessed by volumetric computed tomography studies before and 90 days after LDLT. Comparison between the right-lobe and extended right-lobe donors did not show a clear-cut difference in the net increase of remnant liver volume at 3 months. However, the mean volume increase of the medial segment at the 90th postoperative day was 7% in the extended right-lobe donors and 61% in the right-lobe donors, showing a lower value in the remnant livers without MHV. The MHV plays a specific role in remnant liver regeneration of right-lobe living donors. We expect that this knowledge will contribute to securing a margin of safety in right-lobe LDLT.

Bcl6-dependent transcriptional repression by BAZF.

BAZF, a member of Bcl6 gene family, acts as a sequence-specific transcriptional repressor in various cells including NIH3T3 cells. The DNA-binding sequence for BAZF is the same as that for Bcl6 and the repressor activity of BAZF was also inhibited by Tricostatin A, an inhibitor of histone deacetylase, suggesting the functional homology between them. However, BAZF unlike Bcl6 cannot function as a transcriptional repressor in embryonal fibroblasts of Bcl6-deficient mice and in Bcl6-null cell lines such as K562 and WIL2-NS. The BTB/POZ domain and the middle portion of BAZF bound to the BTB/POZ domain and the middle portion of Bcl6, respectively. There is an identical 17 amino acid sequence in their middle portions and the sequence was important for the binding. Since BAZF did not directly bind to mSin3A and histone deacetylase 1 and the repressor activity of BAZF was detected in K562 cells replenished with the BTB/POZ domain or the middle portion of Bcl6, BAZF may display its transrepressor activity by recruiting an mSin3A/histone deacetylase 1 complex through association with Bcl6.