8896689
Secretory Low Molecular Weight Phospholipase A2 Plays Important Roles in Cell Elongation and Shoot Gravitropism in Arabidopsis Article, publication date, and citation information can be found at www.plantcell.org/cgi/doi/10.1105/tpc.014423.
To elucidate the cellular functions of phospholipase A2 in plants, an Arabidopsis cDNA encoding a secretory low molecular weight phospholipase A2 (AtsPLA2β) was isolated. Phenotype analyses of transgenic plants showed that overexpression of AtsPLA2β promotes cell elongation, resulting in prolonged leaf petioles and inflorescence stems, whereas RNA interference–mediated silencing of AtsPLA2β expression retards cell elongation, resulting in shortened leaf petioles and stems. AtsPLA2β is expressed in the cortical, vascular, and endodermal cells of the actively growing tissues of inflorescence stems and hypocotyls. AtsPLA2β then is secreted into the extracellular spaces, where signaling for cell wall acidification is thought to occur. AtsPLA2β-overexpressing or -silenced transgenic plants showed altered gravitropism in inflorescence stems and hypocotyls. AtsPLA2β expression is induced rapidly by auxin treatment and in the curving regions of inflorescence stems undergoing the gravitropic response. These results suggest that AtsPLA2β regulates the process of cell elongation and plays important roles in shoot gravitropism by mediating auxin-induced cell elongation.
31435250
Multiple forms of secretory phospholipase A2 in plants.
Multiple secretory phospholipase A2 (sPLA2) genes have been identified in plants and encode isoforms with distinct regulatory and catalytic properties. Elucidation of this genetic and biochemical heterogeneity has provided important clues to the regulation and function of the individual enzymes. An increasing body of evidence shows that their lipid products, lysophospholipids and free fatty acids, mediate a variety of cellular responses, including plant growth, development, and responses to stress and defense. This review discusses the newly-acquired information on plant sPLA2s including the molecular and biochemical characteristics, and signaling functions of each isoform.
22843758
Insulin-like growth factor binding protein-3 inhibits the growth of non-small cell lung cancer.
Insulin-like growth factors (IGFs) have mitogenic and antiapoptotic properties and have been implicated in the development of lung cancer. The effects of IGFs are modulated by insulin-like growth factor binding proteins (IGFBPs). This study explored the effects of IGFBP-3 on non-small cell lung cancer (NSCLC) cells after infection with an adenovirus constitutively expressing IGFBP-3 under the control of the cytomegalovirus promoter (Ad5CMV-BP3). We found that IGFs, especially IGF-I, stimulated the growth of NSCLC cells, and Ad5CMV-BP3 suppressed this IGF-I-induced NSCLC cell growth. We also found that the clonogenicity of H1299 cells in soft agar was markedly reduced by Ad5CMV-BP3. Furthermore, direct injection of Ad5CMV-BP3 into H1299 NSCLC xenografts s.c. established in athymic nude mice induced massive destruction of the tumors. Ad5CMV-BP3 did not induce detectable cytotoxicity on normal human bronchial epithelial cells, suggesting therapeutic efficacy of this virus. Ad5CMV-BP3 infection was accompanied by apoptotic cell death in vitro as detected by flow cytometry, DNA fragmentation analysis, and Western blot analysis on the expression of Bcl-2 and on the cleavage of poly(ADP-ribose) polymerase, a substrate of caspase 3. Immunofluorescence confocal microscopy was also used to show the apoptotic effect of Ad5CMV-BP3 in H1299 tumors established in nude mice. These findings indicated that IGFBP-3 was a potent inducer of apoptosis in NSCLC cells in vitro and in vivo. To delineate the underlying mechanism, we examined the effect of IGFBP-3 on Akt/protein kinase B and glycogen synthase kinase-3beta, downstream mediators of the phosphatidylinositol 3-kinase pathway, and on mitogen-activated protein kinase (MAPK), all three of which are activated by IGF-mediated signaling pathways and have important roles in cell survival. IGFBP-3 overexpression inhibited the phosphorylation of Akt and glycogen synthase kinase-3beta and the activity of MAPK. Furthermore, IGF-I rescued the NSCLC cells from serum depletion-induced apoptosis, and this rescue was blocked in Ad5CMV-BP-3-infected H1299 NSCLC cells. Transient transfection with activated Akt or constitutively active MAPK kinase-1, an upstream activator of MAPK, partially blocked IGFBP-3-induced apoptosis of NSCLC cells. These findings suggested that the growth-regulatory effect of IGFBP-3 on NSCLC cells was attributable in part to the inhibition of the IGF-induced survival pathway. These data demonstrate the importance of IGFBP-3 in the regulation of NSCLC cell proliferation, clonogenicity, and tumor growth, suggesting that IGFBP-3 is a target for the treatment of lung cancer and that Ad5CMV-BP3 is a potential therapeutic agent.
2572634
Effects of interscalene brachial plexus block to intra-operative hemodynamics and postoperative pain for arthroscopic shoulder surgery
Background Although arthroscopic shoulder surgery is less invasive and painful than open shoulder surgery, it can often cause intra-operative hemodynamic instability and severe post-operative pain. This study was conducted to investigate the efficacy of the interscalene brachial plexus block (IBPB) on intra-operative hemodynamic changes and post-operative pain during arthroscopic shoulder surgery. Methods After institutional review board approval, 50 consecutive patients that had undergone arthroscopic shoulder surgery under general anesthesia were randomly assigned to one of two groups to evaluate intra-operative hemodynamic changes and post-operative pain control. Group 1 patients received an IBPB with 10 ml of normal saline guided by a nerve stimulator before induction, and Group 2 patients received 10 ml of 0.5% ropivacaine hydrochloride with the same technique. The heart rate and systolic and diastolic blood pressures were recorded before the incision and 1, 3, 5, 10, and 20 minutes after the incision. Pre-operative and post-operative pain was evaluated with a visual analog scale 1, 3, 6, 12, and 24 hours after surgery. The patients were given tramadol as a rescue medication option. The total volume of tramadol that was injected was also evaluated over the same intervals. Results Group 2 showed significantly lower systolic and diastolic blood pressures and heart rates intra-operatively compared to Group 1 (P < 0.05). The visual analog scale pain scores, except at 24 hours after surgery, were significantly lower in Group 2 (P < 0.05). The total tramadol consumption significantly reduced in Group 2 (P < 0.05). Conclusions IBPB effectively controlled the hemodynamic changes that occurred during arthroscopic shoulder surgery as well as post-operative pain.
1467835
Time to follow up after an abnormal finding in organized gastric cancer screening in Korea
BackgroundThe prognosis for an abnormal medical finding is affected by both early detection and adherence to the presecribed schedule for follow-up examinations. In this study, we examined the time to follow up after an abnormal finding and determined the risk factors related to delays in follow up in a population-based screening program.MethodsThe study population consisted of patients who were newly diagnosed with gastric cancer through a gastric cancer screening program sponsored by the National Cancer Screening Program (NCSP) in 2005. Due to the skewed nature of the distribution of time to follow up, medians and interquartile ranges (IQR) are presented, and we analyzed the number of days preceding the follow-up time as a binary variable (≤90 days or >90 days). We used logistic regression analyses to evaluate the risk factors for a long delay.ResultsThe median number of days to follow-up initiation after an abnormal finding was 11 (IQR 7–27); 13.9% of the patients with gastric cancer obtained their follow-up evaluation more than 90 days. Age, type of health insurance, screening method, and screening results were risk factors for delays in follow up.ConclusionsThis study examined delays from the time of the discovery of an abnormal finding to time of the follow-up evaluation. Because inadequate follow up of abnormal exam results undermines the potential benefits of cancer screening, it is important to organize services that minimize delays between cancer screening and treatment.
1084707
Mixed-type paratesticular rhabdomyosarcoma--a case report.
Rhabdomyosarcoma (RMS) is the most common soft tissue tumor of childhood; about 80% of cases occur before the age of 21 with the remaining 20% evenly spread throughout the remaining decades. A primary paratesticular site is considered to have a good prognosis in comparison with other RMS sites. Histologically, any subtype of RMS, including alveolar, pleomorphic, embryonal, and mixed type, may occur in the paratesticular region, but only a relatively small number of cases are mixed and this variant has a poor prognosis. We report a case of paratesticular RMS (mixed embryonal and alveolar type) in a 16-year-old boy.
25306146
Response of Non–Small Cell Lung Cancer Cells to the Inhibitors of Phosphatidylinositol 3-Kinase/Akt- and MAPK Kinase 4/c-Jun NH2-Terminal Kinase Pathways: An Effective Therapeutic Strategy for Lung Cancer
Purpose: We previously showed that phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways cooperate to promote non–small cell lung cancer (NSCLC) cell proliferation in vitro. This study was designed to explore whether inhibition of these pathways effectively inhibits NSCLC tumor growth in vivo. Experimental Design: The effects of PI3K/Akt inhibitors {LY294002, adenoviruses expressing dominant-negative mutant of the p85α adaptor subunit of PI3K (Ad-dnp85α), dominant-negative Akt [Ad-HA-Akt(KM)], or PTEN (Ad-PTEN)}, MKK4/c-jun NH2-terminal kinase (JNK) inhibitor [SP600215, adenovirus expressing dominant-negative MKK4, Ad-MKK4(KR)], and their combinations on proliferation and apoptosis in NSCLC cells were tested in vitro and in vivo using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, a flow cytometry-based terminal deoxynucleotidyl transferase–mediated nick-end labeling assay, Western blot and immunohistochemical analyses, and an NSCLC xenograft tumor model. Results: Ad-dnp85α significantly inhibited proliferation of a subset of NSCLC cell lines used in our study. Intratumoral injection of Ad-dnp85α induced a significant decrease in the growth of H1299 NSCLC xenograft tumors. Concurrent inhibition of the PI3K/Akt and MKK4/JNK pathways showed enhanced antiproliferative effects on H1299 cells in vitro and in vivo by increasing apoptosis. Conclusions: PI3K/Akt and MKK4/JNK pathways cooperate to stimulate NSCLC cell proliferation by maintaining cell survival, suggesting that simultaneously targeting these two pathways might be an effective therapeutic strategy against NSCLC.