Lung Cancer in Pulmonary Fibrosis: Tales of Epithelial Cell Plasticity

Lung epithelial cells exhibit a high degree of plasticity. Alterations to lung epithelial cell function are critically involved in several chronic lung diseases such as pulmonary fibrosis. Pulmonary fibrosis is characterized by repetitive injury and subsequent impaired repair of epithelial cells, which leads to aberrant growth factor activation and fibroblast accumulation. Increased proliferation and hyper- and metaplasia of epithelial cells upon injury have also been observed in pulmonary fibrosis; this epithelial cell activation might represent the basis for lung cancer development. Indeed, several studies have provided histopathological evidence of an increased incidence of lung cancer in pulmonary fibrosis. The mechanisms involved in the development of cancer in pulmonary fibrosis, however, remain poorly understood. This review highlights recently uncovered molecular mechanisms shared between lung cancer and fibrosis, which extend the current evidence of a common trait of cancer and fibrosis, as provided by histopathological observations. Copyright (C) 2011 S. Karger AG, Base

Clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer

<p>Abstract</p> <p>Background</p> <p>Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1α (HIF-1α), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1α, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.</p> <p>We immunohistochemically assessed the HIF-1α, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF).</p> <p>Results</p> <p>The positive rates of p53 and HIF-1α (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1α were correlated positively with the depth of invasion (<it>P </it>= 0.015, <it>P </it>= 0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (<it>P </it>= 0.010, <it>P </it>= 0.040, respectively). VEGF overexpression was more frequently observed in the old age group (≥ 60 years old) and the intestinal type (<it>P </it>= 0.013, <it>P </it>= 0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF-1α, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1α was observed to be a poor prognostic factor of disease recurrence or progression (<it>P </it>= 0.002).</p> <p>Conclusion</p> <p>p53, HIF-1α and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1α expression was a poor prognostic factor of disease recurrence or progression in patients with gastric cancers.</p

Network-Based Approach for Modeling and Analyzing Coronary Angiography

Significant intra-observer and inter-observer variability in the interpretation of coronary angiograms are reported. This variability is in part due to the common practices that rely on performing visual inspections by specialists (e.g., the thickness of coronaries). Quantitative Coronary Angiography (QCA) approaches are emerging to minimize observer's error and furthermore perform predictions and analysis on angiography images. However, QCA approaches suffer from the same problem as they mainly rely on performing visual inspections by utilizing image processing techniques. In this work, we propose an approach to model and analyze the entire cardiovascular tree as a complex network derived from coronary angiography images. This approach enables to analyze the graph structure of coronary arteries. We conduct the assessments of network integration, degree distribution, and controllability on a healthy and a diseased coronary angiogram. Through our discussion and assessments, we propose modeling the cardiovascular system as a complex network is an essential phase to fully automate the interpretation of coronary angiographic images. We show how network science can provide a new perspective to look at coronary angiograms

Osteogenesis evaluation of duck’s feet derived collagen/hydroxyapatite sponges immersed in dexamethasone

Background: The aim of this study was to investigate the osteogenesis effects of DC and DC/HAp sponge immersed in without and with dexamethasone. Methods: The experimental groups in this study were DC and DC/HAp sponge immersed in without dexamethasone (Dex(â )DC and Dex(â )-DC/HAp group) and with dexamethasone (Dex(+)-DC and Dex(+)-DC/HAp group). We characterized DC and DC/HAp sponge using compressive strength, scanning electron microscopy (SEM). Also, osteogenic differentiation of BMSCs on sponge (Dex(â )DC, Dex(â )-DC/HAp, Dex(+)-DC and Dex(+)-DC/HAp group) was assessed by SEM, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide (MTT) assay, alkaline phosphatase (ALP) activity assay and reverse transcription-PCR (RT-PCR). Results: In this study, we assessed osteogenic differentiation of BMSCs on Duckâ s feet-derived collagen (DC)/ HAp sponge immersed with dexamethasone Dex(+)-DC/HAp. These results showed that Dex(+)-DC/HAp group increased cell proliferation and osteogenic differentiation of BMSCs during 28 days. Conclusion: From these results, Dex(+)-DC/HAp can be envisioned as a potential biomaterial for bone regeneration applications.This work was supported by Technology Commercialization Support Program [grant number 814005-03-3-HD020], Ministry for Food, Agriculture, Forestry and Fisheries (MIFAFF).info:eu-repo/semantics/publishedVersio

Nuclear-Targeted Deleted in Liver Cancer 1 (DLC1) Is Less Efficient in Exerting Its Tumor Suppressive Activity Both In Vitro and In Vivo

BACKGROUND: Deleted in liver cancer 1 (DLC1) serves as an important RhoGTPase activating protein (RhoGAP) protein that terminates active RhoA signaling in human cancers. Increasing evidence has demonstrated that the tumor suppressive activity of DLC1 depends not only on RhoGAP activity, but also relies on proper focal adhesion localization through its interaction with tensin family proteins. Recently, there are reports showing that DLC1 can also be found in the nucleus; however, the existence and the relative tumor suppressive activity of nuclear DLC1 have never been clearly addressed. METHODOLOGY AND PRINCIPAL FINDINGS: We herein provide new evidence that DLC1 protein, which predominantly associated with focal adhesions and localized in cytosol, dynamically shuttled between cytoplasm and nucleus. Treatment of cells with nuclear export blocker, Leptomycin B (LMB), retained DLC1 in the nucleus. To understand the nuclear entry of DLC1, we identified amino acids 600-700 of DLC1 as a novel region that is important for its nuclear localization. The tumor suppressive activity of nuclear DLC1 was directly assessed by employing a nuclear localization signal (NLS) fusion variant of DLC1 (NLS-DLC1) with preferential nuclear localization. In SMMC-7721 HCC cells, expression of NLS-DLC1 failed to suppress colony formation and actin stress fiber formation in vitro. The abrogated tumor suppressive activity of nuclear DLC1 was demonstrated for the first time in vivo by subcutaneously injecting p53(-/-) RasV12 hepatoblasts with stable NLS-DLC1 expression in nude mice. The injected hepatoblasts with NLS-DLC1 expression effectively formed tumors when compared with the non-nuclear targeted DLC1. CONCLUSIONS/SIGNIFICANCE: Our study identified a novel region responsible for the nuclear entry of DLC1 and demonstrated the functional difference of DLC1 in different cellular compartments both in vitro and in vivo

Deleted in Liver Cancer 1 (DLC1) Utilizes a Novel Binding Site for Tensin2 PTB Domain Interaction and Is Required for Tumor-Suppressive Function

Background: Deleted in liver cancer 1 (DLC1) is a Rho GTPase-activating protein (RhoGAP) frequently deleted and underexpressed in hepatocellular carcinoma (HCC) as well as in other cancers. Recent independent studies have shown interaction of DLC1 with members of the tensin focal adhesion protein family in a Src Homology 2 (SH2) domain-dependent mechanism. DLC1 and tensins interact and co-localize to punctate structures at focal adhesions. However, the mechanisms underlying the interaction between DLC1 and various tensins remain controversial. Methodology/Principal Findings: We used a co-immunoprecipitation assay to identify a previously undocumented binding site at 375-385 of DLC1 that predominantly interacted with the phosphotyrosine binding (PTB) domain of tensin2. DLC1-tensin2 interaction is completely abolished in a DLC1 mutant lacking this novel PTB binding site (DLC1ΔPTB). However, as demonstrated by immunofluorescence and co-immunoprecipitation, neither the focal adhesion localization nor the interaction with tensin1 and C-terminal tensin-like (cten) were affected. Interestingly, the functional significance of this novel site was exhibited by the partial reduction of the RhoGAP activity, which, in turn, attenuated the growth-suppressive activity of DLC1 upon its removal from DLC1. Conclusions/Significance: This study has provided new evidence that DLC1 also interacts with tensin2 in a PTB domain-dependent manner. In addition to properly localizing focal adhesions and preserving RhoGAP activity, DLC1 interaction with tensin2 through this novel focal adhesion binding site contributes to the growth-suppressive activity of DLC1. © 2009 Chan et al.published_or_final_versio

Beauty photoproduction measured using decays into muons in dijet events in ep collisions at s\sqrt{s}=318 GeV

The photoproduction of beauty quarks in events with two jets and a muon has been measured with the ZEUS detector at HERA using an integrated luminosity of 110 pb$^{- 1}$. The fraction of jets containing b quarks was extracted from the transverse momentum distribution of the muon relative to the closest jet. Differential cross sections for beauty production as a function of the transverse momentum and pseudorapidity of the muon, of the associated jet and of $x_{\gamma}^{jets}$, the fraction of the photon's momentum participating in the hard process, are compared with MC models and QCD predictions made at next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September 200

A Novel Behavioral Assay for Measuring Cold Sensation in Mice

Behavioral models of cold responses are important tools for exploring the molecular mechanisms of cold sensation. To complement the currently cold behavioral assays and allow further studies of these mechanisms, we have developed a new technique to measure the cold response threshold, the cold plantar assay. In this assay, animals are acclimated on a glass plate and a cold stimulus is applied to the hindpaw through the glass using a pellet of compressed dry ice. The latency to withdrawal from the cooled glass is used as a measure of the cold response threshold of the rodents, and the dry ice pellet provides a ramping cold stimulus on the glass that allows the correlation of withdrawal latency values to rough estimates of the cold response threshold temperature. The assay is highly sensitive to manipulations including morphine-induced analgesia, Complete Freund's Adjuvant-induced inflammatory allodynia, and Spinal Nerve Ligation-induced neuropathic allodynia

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

The dependence of dijet production on photon virtuality in ep collisions at HERA

The dependence of dijet production on the virtuality of the exchanged photon, Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 < 2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of 38.6 pb^-1. Dijet cross sections were measured for jets with transverse energy E_T^jet > 7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon momentum entering the hard process, was used to enhance the sensitivity of the measurement to the photon structure. The Q^2 dependence of the ratio of low- to high-xg^obs events was measured. Next-to-leading-order QCD predictions were found to generally underestimate the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models based on leading-logarithmic parton-showers, using a partonic structure for the photon which falls smoothly with increasing Q^2, provide a qualitative description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.