Mucinous cystadenocarcinoma (MCA) of the breast is extremely rare and was only recently described as a distinct variant of invasive ductal carcinoma of the breast. A case of MCA is reported in a 41-year-old woman. Mammographic and ultrasonographic examinations showed an irregularly shaped 10.0 × 8.0 × 5.5 cm lesion with patching calcification in the upper outer quadrant of the left breast. The gross examination revealed that the tumor has a well-circumscribed edge with a gelatinous cut surface and hemorrhage and necrosis were also noticed in the mass. Microscopically, the mass resembled mucinous cystic neoplasm of the ovary and pancreas closely, with cystic areas lined by columnar mucinous cells and associated with abundant extracellular and intracellular mucin, which is distinctively different from mucinous carcinoma with typically nests of low grade neoplastic cells floating in the mucin pool. The tumor cells were positive for CK7, CK20 and CDX2 were negative and displayed a typical immunophenotype of basal-like breast cancer (ER, PR, HER2 were negative, CK5/6 and EGFR were positive). Metastatic carcinoma was identified in three of 14 axillary lymph nodes. We describe here a very unusual case of breast MCA with basal-like immunophenotype.

Calcineurin-nuclear factor of activated T cells signaling controls the differentiation and function of osteoclasts and osteoblasts, and regulator of calcineurin-2 (Rcan2) is a physiological inhibitor of this pathway. Rcan2 expression is regulated by T(3), which also has a central role in skeletal development and bone turnover. To investigate the role of Rcan2 in bone development and maintenance, we characterized Rcan2(-/-) mice and determined its skeletal expression in T(3) receptor (TR) knockout and thyroid-manipulated mice. Rcan2(-)(/)(-) mice had normal linear growth but displayed delayed intramembranous ossification, impaired cortical bone formation, and reduced bone mineral accrual during development as well as increased mineralization of adult bone. These abnormalities resulted from an isolated defect in osteoblast function and are similar to skeletal phenotypes of mice lacking the type 2 deiodinase thyroid hormone activating enzyme or with dominant-negative mutations of TRα, the predominant TR isoform in bone. Rcan2 mRNA was expressed in primary osteoclasts and osteoblasts, and its expression in bone was differentially regulated in TRα and TRβ knockout and thyroid-manipulated mice. However, in primary osteoblast cultures, T(3) treatment did not affect Rcan2 mRNA expression or nuclear factor of activated T cells c1 expression and phosphorylation. Overall, these studies establish that Rcan2 regulates osteoblast function and its expression in bone is regulated by thyroid status in vivo.

In the title compound, C(14)H(11)N(3)O(2), the dihedral angle between the phenyl ring and the benzotriazole ring system is 76.80 (19)° and the mol-ecule has an L-shaped conformation. In the crystal, weak aromatic π-π stacking is observed, the closest centroid-centroid distance being 3.754 (2) Å.

In the title compound,[CuCl(2)(C(12)H(15)N(3)O(2))(2)], the Cu(II) ion is located on an inversion center and is four-coordinated in a distorted square-planar geometry by two chloride anions and two N atoms from two (1H-1,2,3-benzotriazol-1-yl)methyl 2,2-dimethyl-propano-ate ligands. The Cl-Cu-N angles of 90.55 (9) and 89.45 (9)° are close to ideal values. In the crystal, weak π-π stacking inter-actions are observed between inversion-related benzene rings [centroid-centroid distance = 4.0028 (6) Å].

In the title compound, C(12)H(15)N(3)O(2), the dihedral angle between the mean planes of the benzene and triazole rings is 0.331 (53) °. The side chain of the pivalate unit forms a dihedral angle of 69.04 (12)° with the benzotriazole unit. The ester group and two methyl groups of the pivalate unit are disordered with an occupancy ratio of 0.731 (3):0.269 (3). In the crystal, weak π-π stacking inter-actions are observed between inversion-related benzene rings [centroid-centroid distance = 3.9040 (1) Å].

In the crystal structure of the title coordination compound,[Ag(NO(3))(C(14)H(11)N(3)O(2))(2)], the Ag(I) atom is four-coordinated in a distorted tetra-hedral geometry by two O atoms from one nitrate group and two N atoms from two different 1-[(benzo-yloxy)meth-yl]-1H-1,2,3-triazole ligands. In the complex, the two coordinated benzotriazole rings rings are nearly perpendicular, the dihedral angle between their planes being 87.08 (6)°.

In the US, the Vaccine Safety Datalink (VSD) project, sponsored by the Centers for Disease Control and Prevention, conducts near-real-time, population-based, active surveillance for vaccine safety. One of the steps in analyzing signals, if there are enough cases, is to apply temporal scan statistics. The purpose is to determine if the cases clustered in time within an overall a priori defined post-vaccination observation interval. We presented a relatively efficient and accurate algorithm for the purely temporal scan statistic as applied to vaccine safety investigations. It only needs SAS/BASE(®) software, and the algorithm is simple enough to be programmed in another software languages. Our present work is focused on incorporating the temporal scan statistic algorithm within our previous approach for finding an optimal risk window for studies of vaccine safety.

Hepatocellular carcinoma (HCC) exhibits cellular heterogeneity and embryonic stem cells related genes were preferentially overexpressed in a fraction of cancer cells of poorly differentiated tumors. However, it is not well known whether or how these cancer cells contribute to tumor initiation and progression. Here, our data showed that increased expression of pluripotency transcription factor Nanog in cancer cells correlates with a worse clinical outcome in HCC. Using Nanog promoter as a reporter system, we could successfully isolate a small subpopulation of Nanog positive cells. We demonstrate that Nanog positive cells exhibited enhanced ability of self-renewal, clonogenicity and initiation of tumors, which are consistent with crucial hallmarks in the definition of cancer stem cells (CSCs). Nanog(Pos) CSCs could differentiate to mature cancer cells in vitro and in vivo conditions. In addition, we found that Nanog(Pos) CSCs exhibited resistant to therapeutic agents, sorafenib and cisplatin and have high capacity for tumor invasion and metastasis. Knockdown expression of Nanog in Nanog(Pos) CSCs could decrease self-renewal accompanied with decreased expression of stem cell related genes and increased expression of mature hepatocyte related genes. Overexpression of Nanog in Nanog(Neg) cells could restore self-renewal. Furthermore, we found that IGF2 and IGF1R were upexpressed in Nanog(Pos) CSCs. Knockdown expression of Nanog in Nanog(Pos) CSCs inhibited expression of IGF1R and overexpression of Nanog in Nanog(Neg) cells increased expression of IGF1R. Specific inhibitor of IGF1R signaling could significantly inhibited self-renewal and Nanog expression, indicating that IGF1R signaling participated in Nanog-mediated self-renewal. Conclusion: These data indicate that Nanog could be represented as a novel biomarker for CSCs in HCC and Nanog could play a crucial role in maintaining self-renewal of CSCs through IGF1R signaling pathway.(HEPATOLOGY 2012.).

Many biological traits are discretely distributed in phenotype but continuously distributed in genetics because they are controlled by multiple genes and environmental variants. Due to the quantitative nature of the genetic background, these multiple genes are called quantitative trait loci (QTL). When the QTL effects are treated as random, they can be estimated in a single generalized linear mixed model (GLMM), even if the number of QTL may be larger than the sample size. The GLMM in its original form cannot be applied to QTL mapping for discrete traits if there are missing genotypes. We examined two alternative missing genotype-handling methods: the expectation method and the overdispersion method. Simulation studies show that the two methods are efficient for multiple QTL mapping (MQM) under the GLMM framework. The overdispersion method showed slight advantages over the expectation method in terms of smaller mean-squared errors of the estimated QTL effects. The two methods of GLMM were applied to MQM for the female fertility trait of wheat. Multiple QTL were detected to control the variation of the number of seeded spikelets.Heredity advance online publication, 14 March 2012; doi:10.1038/hdy.2012.10.

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers. Arachidonic acid (AA) and its metabolites play critical role in the development of breast cancer, but the mechanisms through which AA promotes mammary tumorigenesis and progression are poorly understood. We found that the levels of AA and cytosolic phospholipase A2 (cPLA2) strongly correlated with the signaling activity of mTORC1 and mTORC2 as well as the expression levels of vascular epithelial growth factor (VEGF) in human breast tumor tissues. In cultured breast cancer cells, AA effectively activated both mTOR complex 1 (mTORC1) and mTORC2. Interestingly, AA-stimulated mTORC1 activation was independent of amino acids, phosphatidylinositol 3-kinase (PI3-K) and tuberous sclerosis complex 2 (TSC2), which suggests a novel mechanism for mTORC1 activation. Further studies revealed that AA stimulated mTORC1 activity through destabilization of mTOR-raptor association in ras homolog enriched in brain (Rheb)-dependent mechanism. Moreover, we showed that AA-stimulated cell proliferation and angiogenesis required mTOR activity and that the effect of AA was mediated by lipoxygenase (LOX) but not cyclooxygenase-2 (COX-2). In animal models, AA-enhanced incidences of rat mammary tumorigenesis, tumor weights and angiogenesis were inhibited by rapamycin. Our findings suggest that AA is an effective intracellular stimulus of mTOR and that AA-activated mTOR plays critical roles in angiogenesis and tumorigenesis of breast cancer.Oncogene advance online publication, 20 February 2012; doi:10.1038/onc.2012.47.