Hypoglycemia caused by co-secretion of insulin from lung tumor and cardia cancer: first case report

<div><p>ABSTRACT CONTEXT: Non-islet-cell-tumor-induced hypoglycemia (NICTH) is caused on rare occasions by secretion of insulin from tumor cells that are reported to have a single tissue origin. CASE REPORT: A 67-year-old male patient had cardia adenocarcinoma and concomitant lung adenocarcinoma with extensive metastases and repeated episodes of intractable hypoglycemia. Immunohistochemical staining for insulin showed that lung adenocarcinoma stained positive and gastric cardia adenocarcinoma stained weakly positive. These results indicate that tumor cells of different tissue origins co-secreted insulin. CONCLUSIONS: This is the first report on intractable hypoglycemia due to co-secretion of insulin from two kinds of primary tumor cells in a single patient.</p></div

The capability of growth and invasion was increased in the H1650ER cells.

<p>(A) Growth curves of H1650, H1650ER cells and all other cells were performed in routine culture medium. Values show the mean cell number ± S.D. of triplicate wells at each time-point and represent three individual experiments. Error bars show SD; *, P<0.01; **, P<0.001. (B) Parental cells and H1650ER cells were seeded onto Matrigel-coated polycarbonate filters to analyze their invasive potentials. Scale bars: 25 µm. The results were obtained from three experiments, and the bars represent S.D.s; *, P<0.01. (C) Parental cells and H1650ER cell lines were also cultured in soft agar to test their ability to form colonies after 15 days of incubation. Original magnification,×10. The results were obtained from three experiments.</p

Downmodulation of N-cadherin expression and invasion abilities of H1650ER cell line.

<p>(A) N-cadherin expression in the H1650ER cells transfected with siRNAs targeting N-cadherin after 48 hours. Protein expression measured by flow cytometry, one representative experiment. (B) The ability of invasion evaluated after transfection for 48 hours, using a matrigel-coated chamber and 20% FCS as chemoattractant. Scale bars: 25 µm. (C) Changes in AKT and phospho-AKT kinase activity level upon N-cadherin siRNA silencing by Western blot.</p

Up-modulation of N-cadherin expression and the EMT were found in biopsies of resistant cancers.

<p>(A) The loss of E-cadherin and an increase in both vimentin and N-cadherin expression were observed in these tumors (lower panel), compared with their corresponding primary tumors (upper panel). Scale bars:100 µm. Magnification, ×200.</p

Generation of erlotinib-resistant H1650 cancer cells and variable signaling pathway activation.

<p>(A) Erlotinib-resistant cells (H1650ER) were established by long-term exposure to increasing concentrations of erlotinib. H1650 parental cells and H1650ER were seeded in 96-well plates at a density of 103 cells in 100 µL per well, cultured overnight, and treated with different concentrations of erlotinib for 72 h in a humidified incubator at 37°C with 5% CO2. The surviving fractions were determined by CCK-8 assay. Absorbance was measured at 450 nm. All experiments were performed in triplicate and S.D.s were calculated. *, P<0.01. (B) H1650 parental and H1650ER cells were cultured for 3 days with or without erlotinib treatment (10 µmol/L). Whole-cell lysates were prepared and analyzed by Western blot with the indicated antibodies.</p

Summary of thirteen patients acquired resistance to erlotinib.

<p>Time on erlotinib*, Time to progression after erlotinib therapy; Response#, Response to erlotinib; del,deletion; Adeno, adenocarcinoma. CR: Complete response; PR: Partial response; SD: Stable disease; PD: Progressive disease.</p

Up-regulation of N-cadherin expression in the H1650ER cells is accompanied by the induction of an EMT.

<p>(A) The upregulated expression of N-cadherin was detected by FACS analysis. (B) Cell lysates from H1650 and H1650ER cells were detected by Western blot; the lysates were also assessed for the level of N-cadherin protein. (C) The H1650 parental cells and the resistant H1650ER cells were assessed for morphological changes that are consistent with an EMT. Scale bars: 25 µm. (D) Reduced expression of E-cadherin and increased expression of vimentin were detected using Western blot. (E) Immunofluorescence staining was performed to validate the changes of the marker proteins from either the epithelial or the mesenchymal phenotypes. Scale bars: 25 µm.</p

Chemical structures of etomidate and ET-26 HCl.

<p>Chemical structures of etomidate and ET-26 HCl.</p

Schematic diagrams depicting the <i>in vivo</i> and <i>in vitro</i> cardiac function experimental protocol.

<p>ED₅₀: 50% effective dose; TTE: echocardiography; ECG: electrocardiogram; HR: heart rate; LVSP: left ventricular systolic pressure; ± dP/dt_max: maximal rate for left ventricular pressure rising and declining. SD: Sprague-Dawley.</p

Effectiveness of Teriparatide on Fracture Healing: A Systematic Review and Meta-Analysis

<div><p>Purpose</p><p>Nowadays, the efficacy of teriparatide in treating osteoporosis was widely accepted, but the discussion about using teriparatide to enhance fracture healing hasn’t come to an agreement. This meta-analysis was conducted to evaluate the effectiveness of teriparatide for fracture healing.</p><p>Methods</p><p>We searched PubMed, the Cochrane Library, and Embase in August 2016 for randomized controlled trials (RCTs) which concerned the treatment of teriparatide for fracture healing.</p><p>Results</p><p>Finally, a total of 380 patients were randomly assigned in the 5 trials included in this meta-analysis. There was a significant effectiveness with regards to function improvement in patients following fracture, however, there was no significant effectiveness with regards to time of radiographic fracture healing, fracture healing rate and reduction in pain.</p><p>Conclusions</p><p>This analysis showed that administration of teriparatide following fracture lacked the effectiveness for fracture healing. Moreover, teriparatide administration had no apparent adverse effects. These results should be interpreted with caution because of some clear limitations. If we want to confirm whether teriparatide improves fracture healing, more high-quality randomized controlled trials are needed.</p></div