Test for symmetry in 2×22 \times 2 contingency tables with nonignorable nonresponses

The McNemar test evaluates the hypothesis that two correlated proportion is common in $2 \times 2$ contingency tables with the same categories. This study discusses a test for symmetry in $2 \times 2$ contingency tables with nonignorable nonresponses. The proposed method is based on Takai and Kano (2008), which discusses a test for independence because a dependency assumption between the two observed outcomes is required to obtain an identification. Here, we focus on three models and propose a test for symmetry in $2 \times 2$ contingency tables with nonignorable nonresponses.Comment: 20 page

Establishment of a novel mouse xenograft model of human uterine leiomyoma

Uterine leiomyoma is the most common benign tumour in women, and an appropriate animal model for leiomyoma would be useful for exploring new therapeutic strategies. Therefore, we have been challenged to develop a new simple mouse model for human leiomyoma. Leiomyoma tissues were harvested from myomas resected by different surgical procedures with or without gonadotropin-releasing hormone agonist (GnRHa) treatment and were subcutaneously implanted into BALB/c nude mice with an estradiol/progesterone-releasing pellet. The implanted leiomyoma tissues that were obtained from the marginal site of large myomas resected by abdominal myomectomy with GnRHa treatment exhibited sufficient tumour growth in the transplanted mice. The leiomyomas that were treated with GnRHa highly expressed the estrogen/progesterone receptor genes, insulin-like growth factor 2 (IGF2) and embryonic smooth muscle myosin heavy chain (SMemb), which suggests that these factors are critical in the establishment of a mouse model of growing leiomyoma. As a result, this model will be useful for the development of new therapeutic strategies

Hedgehog Promotes Neovascularization in Pancreatic Cancers by Regulating Ang-1 and IGF-1 Expression in Bone-Marrow Derived Pro-Angiogenic Cells

http://creativecommons.org/licenses/by/2.0/ PublisherBackground: The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that the oncogenic function of Hh in PDAC involves signaling in the stromal cells rather than cell autonomous effects on the tumor cells. However, the origin and nature of the stromal cell type(s) that are responsive to Hh signaling remained unknown. Since Hh signaling plays a crucial role during embryonic and postnatal vasculogenesis, we speculated that Hh ligand may act on tumor vasculature specifically focusing on bone marrow (BM)-derived cells. Methodology/Principal Findings: Cyclopamine was utilized to inhibit the Hh pathway in human PDAC cell lines and their xenografts. BM transplants, co-culture systems of tumor cells and BM-derived pro-angiogenic cells (BMPCs) were employed to assess the role of tumor-derived Hh in regulating the BM compartment and the contribution of BM-derived cells to angiogenesis in PDAC. Cyclopamine administration attenuated Hh signaling in the stroma rather than in the cancer cells as reflected by decreased expression of full length Gli2 protein and Gli1 mRNA specifically in the compartment. Cyclopamine inhibited the growth of PDAC xenografts in association with regression of the tumor vasculature and reduced homing of BM-derived cells to the tumor. Host-derived Ang-1 and IGF-1 mRNA levels were downregulated by cyclopamine in the tumor xenografts. In vitro co-culture and matrigel plug assays demonstrated that PDAC cell-derived Shh induced Ang-1 and IGF-1 production in BMPCs, resulting in their enhanced migration and capillary morphogenesis activity. Conclusions/Significance: We identified the BMPCs as alternative stromal targets of Hh-ligand in PDAC suggesting that the tumor vasculature is an attractive therapeutic target of Hh blockade. Our data is consistent with the emerging concept that BM-derived cells make important contributions to epithelial tumorigenesis

Nonmetathesis Heterocycle Formation by Ruthenium-Catalyzed Intramolecular [2 + 2] Cycloaddition of Allenamide-enes to Azabicyclo[3.1.1]heptanes

We have developed a novel nonmetathesis reaction, namely, ruthenium-catalyzed intramolecular [2 + 2] cycloaddition of allenamide-enes, to give heterocycles (i.e., azabicyclo[3.1.1]­heptanes). This is the first example of [2 + 2] cycloaddition using a ruthenium carbene catalyst. The reaction proceeds at room temperature, but not under thermal or radical conditions

Nonmetathesis Heterocycle Formation by Ruthenium-Catalyzed Intramolecular [2 + 2] Cycloaddition of Allenamide-enes to Azabicyclo[3.1.1]heptanes

We have developed a novel nonmetathesis reaction, namely, ruthenium-catalyzed intramolecular [2 + 2] cycloaddition of allenamide-enes, to give heterocycles (i.e., azabicyclo[3.1.1]­heptanes). This is the first example of [2 + 2] cycloaddition using a ruthenium carbene catalyst. The reaction proceeds at room temperature, but not under thermal or radical conditions