Gremlin-1 Induces BMP-Independent Tumor Cell Proliferation, Migration, and Invasion

Gremlin-1, a bone morphogenetic protein (BMP) antagonist, is overexpressed in various cancerous tissues but its role in carcinogenesis has not been established. Here, we report that gremlin-1 binds various cancer cell lines and this interaction is inhibited by our newly developed gremlin-1 antibody, GRE1. Gremlin-1 binding to cancer cells was unaffected by the presence of BMP-2, BMP-4, and BMP-7. In addition, the binding was independent of vascular endothelial growth factor receptor-2 (VEGFR2) expression on the cell surface. Addition of gremlin-1 to A549 cells induced a fibroblast-like morphology and decreased E-cadherin expression. In a scratch wound healing assay, A549 cells incubated with gremlin-1 or transfected with gremlin-1 showed increased migration, which was inhibited in the presence of the GRE1 antibody. Gremlin-1 transfected A549 cells also exhibited increased invasiveness as well as an increased growth rate. These effects were also inhibited by the addition of the GRE1 antibody. In conclusion, this study demonstrates that gremlin-1 directly interacts with cancer cells in a BMP- and VEGFR2-independent manner and can induce cell migration, invasion, and proliferation

Perpendicular Magnetic Anisotropy in FePt Patterned Media Employing a CrV Seed Layer

A thin FePt film was deposited onto a CrV seed layer at 400°C and showed a high coercivity (~3,400 Oe) and high magnetization (900–1,000 emu/cm3) characteristic of L10 phase. However, the magnetic properties of patterned media fabricated from the film stack were degraded due to the Ar-ion bombardment. We employed a deposition-last process, in which FePt film deposited at room temperature underwent lift-off and post-annealing processes, to avoid the exposure of FePt to Ar plasma. A patterned medium with 100-nm nano-columns showed an out-of-plane coercivity fivefold larger than its in-plane counterpart and a remanent magnetization comparable to saturation magnetization in the out-of-plane direction, indicating a high perpendicular anisotropy. These results demonstrate the high perpendicular anisotropy in FePt patterned media using a Cr-based compound seed layer for the first time and suggest that ultra-high-density magnetic recording media can be achieved using this optimized top-down approach

Phase II study of weekly paclitaxel and capecitabine in patients with metastatic or recurrent esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>This phase II study assessed the response rate and toxicity profile of weekly paclitaxel and capecitabine in patients with metastatic or recurrent squamous cell carcinoma of the esophagus (SCCE)</p> <p>Methods</p> <p>Patients with histologically confirmed SCCE were treated with paclitaxel 80 mg/m²intravenously on days 1 and 8 plus capecitabine 900 mg/m²orally twice a day on days 1-14. Treatment cycles were repeated every 3 weeks until disease progression or unacceptable toxicity.</p> <p>Results</p> <p>Between 2006 and 2009, 32 patients were enrolled. Twelve patients were chemotherapy-naïve. Twenty patients had received prior chemotherapy including platinum-based regimens. Patients received a median of 5 cycles of treatment (range, 1-12). The response rate was 75% (95%CI; 50.5~99.5%) in the first-line and 45% (95%CI; 26.9~73.1%) in the second-line. With a median follow-up of 20.7 months, median progression-free survival was 5.2 months (95% CI, 4.0 to 6.4) for all patients and median overall survival (OS) was 11.7 months (95% CI, 5.5 to 18.0) for all patients. The median OS was 14.3 months (95% CI, 10.6 to 18.0) for patients receiving therapy as 1^stline and 8.4 months (95% CI, 6.6 to 10.1) for those receiving as 2^nd-line therapy. Grade 3/4 neutropenia was observed in 53.3% of the patients, which was the most common cause of dose reduction. G3 non-hematologic toxicity included stomatitis (9.4%), asthenia (6.3%), and hand-foot skin reaction (3.1%).</p> <p>Conclusions</p> <p>Weekly paclitaxel and capecitabine is a highly active and well-tolerated regimen in patients with metastatic or recurrent SCCE in the first-line as well as second-line setting.</p

In Vivo Fluorescence Imaging of Bacteriogenic Cyanide in the Lungs of Live Mice Infected with Cystic Fibrosis Pathogens

10.1371/journal.pone.0021387PLoS ONE67

Narcissism and prosocial behavior

There are many motivations for prosocial behavior, some more altruistic and some more egoistic. We posit that more narcissistic people may perform prosocial acts strategically, for example, to improve their reputations or to receive something in return

Very Late Antigen-4 (α<inf>4</inf>β<inf>1</inf> Integrin) Targeted PET Imaging of Multiple Myeloma

Biomedical imaging techniques such as skeletal survey and 18F-fluorodeoxyglucose (FDG)/Positron Emission Tomography (PET) are frequently used to diagnose and stage multiple myeloma (MM) patients. However, skeletal survey has limited sensitivity as it can detect osteolytic lesions only after 30-50% cortical bone destruction, and FDG is a marker of cell metabolism that has limited sensitivity for intramedullary lesions in MM. Targeted, and non-invasive novel probes are needed to sensitively and selectively image the unique molecular signatures and cellular processes associated with MM. Very late antigen-4 (VLA-4; also called α4β1 integrin) is over-expressed on MM cells, and is one of the key mediators of myeloma cell adhesion to the bone marrow (BM) that promotes MM cell trafficking and drug resistance. Here we describe a proof-of-principle, novel molecular imaging strategy for MM tumors using a VLA-4 targeted PET radiopharmaceutical, 64Cu-CB-TE1A1P-LLP2A. Cell uptake studies in a VLA-4-positive murine MM cell line, 5TGM1, demonstrated receptor specific uptake (P<0.0001, block vs. non-block). Tissue biodistribution at 2 h of 64Cu-CB-TE1A1P-LLP2A in 5TGM1 tumor bearing syngeneic KaLwRij mice demonstrated high radiotracer uptake in the tumor (12±4.5%ID/g), and in the VLA-4 rich organs, spleen (8.8±1.0%ID/g) and marrow (11.6±2.0%ID/g). Small animal PET/CT imaging with 64Cu-CB-TE1A1P-LLP2A demonstrated high uptake in the 5TGM1 tumors (SUV 6.6±1.1). There was a 3-fold reduction in the in vivo tumor uptake in the presence of blocking agent (2.3±0.4). Additionally, 64Cu-CB-TE1A1P-LLP2A demonstrated high binding to the human MM cell line RPMI-8226 that was significantly reduced in the presence of the cold targeting agent. These results provide pre-clinical evidence that VLA-4-targeted imaging using 64Cu-CB-TE1A1P-LLP2A is a novel approach to imaging MM tumors. © 2013 Soodgupta et al

Project FIT: Rationale, design and baseline characteristics of a school- and community-based intervention to address physical activity and healthy eating among low-income elementary school children

<p>Abstract</p> <p>Background</p> <p>This paper describes Project FIT, a collaboration between the public school system, local health systems, physicians, neighborhood associations, businesses, faith-based leaders, community agencies and university researchers to develop a multi-faceted approach to promote physical activity and healthy eating toward the general goal of preventing and reducing childhood obesity among children in Grand Rapids, MI, USA.</p> <p>Methods/design</p> <p>There are four overall components to Project FIT: school, community, social marketing, and school staff wellness - all that focus on: 1) increasing access to safe and affordable physical activity and nutrition education opportunities in the schools and surrounding neighborhoods; 2) improving the affordability and availability of nutritious food in the neighborhoods surrounding the schools; 3) improving the knowledge, self-efficacy, attitudes and behaviors regarding nutrition and physical activity among school staff, parents and students; 4) impacting the 'culture' of the schools and neighborhoods to incorporate healthful values; and 5) encouraging dialogue among all community partners to leverage existing programs and introduce new ones.</p> <p>Discussion</p> <p>At baseline, there was generally low physical activity (70% do not meet recommendation of 60 minutes per day), excessive screen time (75% do not meet recommendation of < 2 hours per day), and low intake of vegetables and whole grains and high intake of sugar-sweetened beverages, French fries and chips and desserts as well as a high prevalence of overweight and obesity (48.5% including 6% with severe obesity) among low income, primarily Hispanic and African American 3^rd-5^thgrade children (n = 403).</p> <p>Trial registration</p> <p><b>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01385046">NCT01385046</a></b></p

“Early Rupture of Membranes” during Induced Labor as a Risk Factor for Cesarean Delivery in Term Nulliparas

OBJECTIVE: To determine if "early rupture of membranes" (early ROM) during induction of labor is associated with an increased risk of cesarean section in term nulliparas. STUDY DESIGN: The rate of cesarean section and the timing of ROM during the course of labor were examined in term singleton nulliparas whose labor was induced. Cases were divided into 2 groups according the timing of ROM: 1)"early ROM", defined as ROM at a cervical dilatation<4 cm during labor; and 2) "late ROM", ROM at a cervical dilatation≥4 cm during labor. Nonparametric techniques were used for statistical analysis. RESULTS: 1) In a total of 500 cases of study population, "early ROM" occurred in 43% and the overall cesarean section rate was 15.8%; 2) patients with "early ROM" had a higher rate of cesarean section and cesarean section due to failure to progress than did those with "late ROM" (overall cesarean section rate: 24%[51/215] vs. 10%[28/285], p<0.01; cesarean section rate due to failure to progress: 18%[38/215] vs. 8%[22/285], p<0.01 for each) and this difference remained significant after adjusting for confounding variables. CONCLUSION: "Early ROM" during the course of induced labor is a risk factor for cesarean section in term singleton nulliparas

Induction of G1 and G2/M cell cycle arrests by the dietary compound 3,3'-diindolylmethane in HT-29 human colon cancer cells

<p>Abstract</p> <p>Background</p> <p>3,3'-Diindolylmethane (DIM), an indole derivative produced in the stomach after the consumption of broccoli and other cruciferous vegetables, has been demonstrated to exert anti-cancer effects in both <it>in vivo </it>and <it>in vitro </it>models. We have previously determined that DIM (0 – 30 μmol/L) inhibited the growth of HT-29 human colon cancer cells in a concentration-dependent fashion. In this study, we evaluated the effects of DIM on cell cycle progression in HT-29 cells.</p> <p>Methods</p> <p>HT-29 cells were cultured with various concentrations of DIM (0 – 30 μmol/L) and the DNA was stained with propidium iodide, followed by flow cytometric analysis. [³H]Thymidine incorporation assays, Western blot analyses, immunoprecipitation and <it>in vitro </it>kinase assays for cyclin-dependent kinase (CDK) and cell division cycle (CDC)2 were conducted.</p> <p>Results</p> <p>The percentages of cells in the G1 and G2/M phases were dose-dependently increased and the percentages of cells in S phase were reduced within 12 h in DIM-treated cells. DIM also reduced DNA synthesis in a dose-dependent fashion. DIM markedly reduced CDK2 activity and the levels of phosphorylated retinoblastoma proteins (Rb) and E2F-1, and also increased the levels of hypophosphorylated Rb. DIM reduced the protein levels of cyclin A, D1, and CDK4. DIM also increased the protein levels of CDK inhibitors, p21^CIP1/WAF1and p27^KIPI. In addition, DIM reduced the activity of CDC2 and the levels of CDC25C phosphatase and cyclin B1.</p> <p>Conclusion</p> <p>Here, we have demonstrated that DIM induces G1 and G2/M phase cell cycle arrest in HT-29 cells, and this effect may be mediated by reduced CDK activity.</p

Bone Marrow Cells in Murine Colitis: Multi-Signal Analysis Confirms Pericryptal Myofibroblast Engraftment without Epithelial Involvement

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