Expression of glypican 3 in placental site trophoblastic tumor

<p>Abstract</p> <p>Background</p> <p>Glypican-3 (GPC3) is a membrane-bound heparan sulfate proteoglycan that functions in embryonic cell growth and differentiation and is highly expressed in the placenta. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, which is characterized by tissue overgrowth and an increased risk of embryonal malignancies. GPC3 has also been implicated in sporadic cancer, particularly hepatocellular carcinoma, for which it has been shown to be a useful diagnostic marker. Although GPC3 expression has been studied in non-neoplastic placental tissue, its presence in gestational trophoblastic diseases has not been previously explored. The purpose of this study was to investigate the immunohistochemical expression of GPC3 in placental site trophoblastic tumor (PSTT), a very rare gestational trophoblastic neoplasm which may be morphologically confused with non-trophoblastic tumors, and to assess its possible utility as a diagnostic marker.</p> <p>Methods</p> <p>Fifteen cases of PSTT, as well as samples from placental site nodule (PSN) (n = 2), leiomyosarcoma (n = 1), leiomyoma (n = 1), invasive cervical squamous cell carcinoma (n = 7) and endometrial adenocarcinoma (n = 11) were examined. Immunoreactivity was semi-quantitatively evaluated as negative (0, < 5% of cells stained), focally positive (1+, 5-10% of cells stained), positive (2+, 11-50% of cells stained) or diffusely positive (3+, > 50% of cells stained). Staining intensity for each subtype was graded from 0 to 3 and a mean intensity was calculated.</p> <p>Results</p> <p>Eighty percent of PSTT (12/15) were immunoreactive for GPC3 (0, 20; 1+, 20%; 2+, 40%; 3+, 20%) with a mean intensity of 1.3. Stronger, predominately cytoplasmic staining was seen in larger multi- and mononucleated cells with smaller mononucleate cells showing weak muddy cytoplasmic staining. Both PSN cases were positive (1+, 50%; 2+, 50%) and two of nine invasive cervical squamous cell carcinomas showed staining (0, 57%; 1+, 29%; 2+, 14%), predominately in a basal distribution. Other uterine tumors and non-neoplastic tissues were negative.</p> <p>Conclusions</p> <p>Identification of GPC3 in PSTT and PSN is consistent with the derivation of these lesions from intermediate trophoblasts, which have been described to express GPC3. GPC3 may be a useful adjunct immunohistochemical marker in differentiating PSTT from non-trophoblastic tumors.</p

4-(1H-Tetra­zol-5-yl)-1H-indole

There are two mol­ecules with similar configurations in the asymmetric unit of the title compound, C9H7N5, which are linked by inter­molecular N—H⋯N hydrogen bonds into chains with graph-set motif C 2 2(8) along the b axis. The indole core has the expected planar geometry in the two mol­ecules, with a maximum deviation of 0.008 (8) Å from the least-squares plane defined by the nine constituent atoms, and the dihedral angles between the indole and tetra­zole rings are similar [42.4 (2) and 42.7 (2)°]

Developing Routinized Information Processing Capabilities for Operational Agility: Insights from China

Operational agility, which reflects the agile practices at business process level, is increasingly deemed as a significant determinant of business success in a turbulent business environment. Despite its importance, how operational agility can be attained is not answered by existing research. Drawing on the classic organization theory—information processing view of firms, the main contribution of this study is that it provides a process model of developing routinized information processing capabilities for operational agility in a turbulent business environment which fulfills this theoretical gap. It indicates the significant roles played by IT-enabled information processing networks and organizational controls during the process. It also identifies three routinized information processing capabilities including information sensitivity, information fluidity, and information decomposability. This is achieved by conducting a case study of Haier, one of the largest producers of household appliances in China. This paper concludes with a discussion of potential theoretical and practical contributions

Garlic Accelerates Red Blood Cell Turnover and Splenic Erythropoietic Gene Expression in Mice: Evidence for Erythropoietin-Independent Erythropoiesis

Garlic (Allium sativum) has been valued in many cultures both for its health effects and as a culinary flavor enhancer. Garlic's chemical complexity is widely thought to be the source of its many health benefits, which include, but are not limited to, anti-platelet, procirculatory, anti-inflammatory, anti-apoptotic, neuro-protective, and anti-cancer effects. While a growing body of scientific evidence strongly upholds the herb's broad and potent capacity to influence health, the common mechanisms underlying these diverse effects remain disjointed and relatively poorly understood. We adopted a phenotype-driven approach to investigate the effects of garlic in a mouse model. We examined RBC indices and morphologies, spleen histochemistry, RBC half-lives and gene expression profiles, followed up by qPCR and immunoblot validation. The RBCs of garlic-fed mice register shorter half-lives than the control. But they have normal blood chemistry and RBC indices. Their spleens manifest increased heme oxygenase 1, higher levels of iron and bilirubin, and presumably higher CO, a pleiotropic gasotransmitter. Heat shock genes and those critical for erythropoiesis are elevated in spleens but not in bone marrow. The garlic-fed mice have lower plasma erythropoietin than the controls, however. Chronic exposure to CO of mice on garlic-free diet was sufficient to cause increased RBC indices but again with a lower plasma erythropoietin level than air-treated controls. Furthermore, dietary garlic supplementation and CO treatment showed additive effects on reducing plasma erythropoietin levels in mice. Thus, garlic consumption not only causes increased energy demand from the faster RBC turnover but also increases the production of CO, which in turn stimulates splenic erythropoiesis by an erythropoietin-independent mechanism, thus completing the sequence of feedback regulation for RBC metabolism. Being a pleiotropic gasotransmitter, CO may be a second messenger for garlic's other physiological effects

Epstein-Barr Virus BGLF4 Kinase Retards Cellular S-Phase Progression and Induces Chromosomal Abnormality

Epstein-Barr virus (EBV) induces an uncoordinated S-phase-like cellular environment coupled with multiple prophase-like events in cells replicating the virus. The EBV encoded Ser/Thr kinase BGLF4 has been shown to induce premature chromosome condensation through activation of condensin and topoisomerase II and reorganization of the nuclear lamina to facilitate the nuclear egress of nucleocapsids in a pathway mimicking Cdk1. However, the observation that RB is hyperphosphorylated in the presence of BGLF4 raised the possibility that BGLF4 may have a Cdk2-like activity to promote S-phase progression. Here, we investigated the regulatory effects of BGLF4 on cell cycle progression and found that S-phase progression and DNA synthesis were interrupted by BGLF4 in mammalian cells. Expression of BGLF4 did not compensate Cdk1 defects for DNA replication in S. cerevisiae. Using time-lapse microscopy, we found the fate of individual HeLa cells was determined by the expression level of BGLF4. In addition to slight cell growth retardation, BGLF4 elicits abnormal chromosomal structure and micronucleus formation in 293 and NCP-TW01 cells. In Saos-2 cells, BGLF4 induced the hyperphosphorylation of co-transfected RB, while E2F1 was not released from RB-E2F1 complexes. The E2F1 regulated activities of the cyclin D1 and ZBRK1 promoters were suppressed by BGLF4 in a dose dependent manner. Detection with phosphoamino acid specific antibodies revealed that, in addition to Ser780, phosphorylation of the DNA damage-responsive Ser612 on RB was enhanced by BGLF4. Taken together, our study indicates that BGLF4 may directly or indirectly induce a DNA damage signal that eventually interferes with host DNA synthesis and delays S-phase progression