bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shift work increases the frequency of duodenal ulcer inH pyloriinfected workers
Authors: Pietroiusti A , Forlini A , Magrini A , Galante A , Coppeta L , Gemma G , Romeo E , Bergamaschi A 
Published: October 2006

Aim:To evaluate whether shift work is associated with an increased rate of peptic ulcer inH pyloriinfected workers.Methods:During a two year period, consecutive dyspeptic workers underwent non-invasive evaluation ofH pyloristatus by means of urea13C breath test or stool testing. Those testing positive were included in the study and divided into two main categories: day-time workers and shift workers. An upper gastrointestinal endoscopy was performed in all workers, and biopsy specimens were taken from the stomach to confirm the presence ofH pyloriinfection (culture and histology).Results:A total of 247 day-time workers and 101 shift workers were included. The prevalence of duodenal ulcer was significantly higher in shift workers than in day-time workers (29 of 101v23 of 247; OR = 3.92, 95% CI 2.13 to 7.21), and persisted after multivariate analysis, taking into account possible confounding factors (OR = 3.96, 95% CI 2.10 to 7.47).Conclusion:Shift work increases the ulcerogenic potential ofH pyloriinfection and should be considered a risk factor for duodenal ulcer in infected shift workers. Treatment of infection in this high risk group may improve the health of workers and may reduce the economic impact of peptic ulcer.
E-Cadherin Regulates Human Nanos1, which Interacts with p120ctn and Induces Tumor Cell Migration and Invasion
Authors: Strumane Kristin , Bonnomet Arnaud , Stove Christophe , Vandenbroucke Roosmarijn , Nawrocki-Raby Beatrice , Bruyneel Erik , Mareel Marc , Birembaut Philippe , Berx Geert , van Roy Frans 
Published: October 2006

Abstract
Down-regulation of the epithelial cell-cell adhesion molecule E-cadherin is frequently associated with tumor formation and progression. Besides its role in physical cell-cell adhesion, E-cadherin is also thought to be involved in intracellular signaling in normal epithelial cells. In these cells, the Armadillo catenin p120ctn binds to the cytoplasmic domain of E-cadherin and stabilizes the adhesion complexes. On loss of E-cadherin, cytoplasmic p120ctn might accumulate and contribute to tumor malignancy. We used suppression subtractive hybridization to search for genes regulated by E-cadherin expression. We isolated human Nanos1 as a transcript of which levels decrease on E-cadherin reexpression in a human breast cancer cell line. The hNanos1 protein bears a COOH-terminal (CCHC)2 zinc finger domain and belongs to an evolutionarily conserved protein family sharing functions in germ cell development in both vertebrates and invertebrates. We found an inverse correlation between E-cadherin and hNanos1 expression in various cell lines and under diverse conditions. Conditional expression of hNanos1 in human colorectal DLD1 cancer cells functionally abolished cell-cell adhesion. It induced cytoplasmic translocation of p120ctn, as well as strong migratory and invasive properties. We also found that the NH2-terminal domain of hNanos1, which is conserved only among mammals, interacts with p120ctn. hNanos1 counteracted the stimulatory effect of p120ctn on cell protrusion formation. Together, these findings describe a new function for hNanos1 as a downstream effector of E-cadherin loss contributing to tumor progression. Targeting hNanos1 might be a promising strategy in the treatment of E-cadherin–negative tumors in particular. (Cancer Res 2006; 12(20): 10007-15)
Connexins Act as Tumor Suppressors in Three-dimensional Mammary Cell Organoids by Regulating Differentiation and Angiogenesis
Authors: McLachlan Elizabeth , Shao Qing , Wang Hong-ling , Langlois Stephanie , Laird Dale W. 
Published: October 2006

AbstractConnexins are tumor suppressors, and human breast connexin 26 (Cx26) and connexin 43 (Cx43) gap junctions are often down-regulated in breast cancer. We previously showed that Cx26 and Cx43 overexpressed in MDA-MB-231 breast cancer cells inhibited tumor growth in vivo but not in two-dimensional cultures. In the current study, we show that overexpression of Cx26 or Cx43 has tumor-suppressive properties in a three-dimensional environment such that they reduced anchorage-independent cell growth and induced partial redifferentiation of three-dimensional organoids of MDA-MB-231 cells. Importantly, the majority of exogenous connexins did not localize to the cell-cell interface or rescue gap junctional intercellular communication (GJIC) as assessed by dye transfer, providing evidence of a GJIC-independent mechanism of mammary tumor suppression. To further elucidate the mechanisms involved in connexin-induced three-dimensional redifferentiation of tumor cells, we examined whether connexin expression has a role in epithelial to mesenchymal transition (EMT). Cx26 and Cx43 reduced cell migration, increased cytokeratin 18 expression, and decreased vimentin levels, indicating a shift from a mesenchymal towards an epithelial phenotype. In addition, we examined the role of connexins in angiogenesis by probing an angiogenesis antibody array with conditioned media from three-dimensional MDA-MB-231 cultures. This revealed that connexin overexpression regulated various angiogenesis-linked proteins. Furthermore, secreted factors from connexin overexpressing cells inhibited endothelial cell tubulogenesis and migration, and xenografts of Cx43 overexpressing MDA-MB-231 cells showed reduced tumor angiogenesis. In summary, Cx26 and Cx43 inhibit the malignant properties of MDA-MB-231 cells via GJIC-independent mechanisms, including regulation of EMT and angiogenesis. (Cancer Res 2006; 66(20): 9886-94)
Cleavage of Misfolded Nuclear Receptor Corepressor Confers Resistance to Unfolded Protein Response–Induced Apoptosis
Authors: Ng Angela Ping Ping , Howe Fong Jek , Sijin Nin Dawn , Hirpara Jayshree L. , Asou Norio , Chen Chien-Shing , Pervaiz Shazib , Khan Matiullah 
Published: October 2006

Abstract
We have recently reported that accumulation of misfolded nuclear hormone receptor corepressor (N-CoR) as insoluble protein aggregates in acute promyelocytic leukemia (APL) cells induces endoplasmic reticulum (ER) stress and activates unfolded protein response (UPR). Although accumulation of misfolded proteins is known to trigger UPR-induced cytotoxic cell death in several neurodegenerative disorders, APL cells are notably resistant to UPR-induced apoptosis. The molecular basis for the paradoxical response of APL cells to UPR is not known. Here, we report that a glycoprotease, selectively expressed in APL cells, regulates the response of APL cells to UPR-induced apoptosis through processing of misfolded N-CoR protein. Results show that misfolded N-CoR is cleaved selectively in APL cells, and cellular extracts of APL cells and human primary APL cells contain activity that cleaves N-CoR protein. Purification and spectrometric analysis of N-CoR cleaving activity from an APL cell line reveals that it is a glycoprotein endopeptidase known as OSGEP. Furthermore, the cleavage of N-CoR in APL cells could be blocked by the broad-spectrum protease inhibitor AEBSF and by RNA interference–mediated down-regulation of OSGEP expression. AEBSF selectively inhibits growth and promotes apoptosis of APL cells possibly through a mechanism involving AEBSF-induced accumulation of insoluble N-CoR protein and by triggering ER stress. Taken together, these findings suggest that selective induction of protease activity in APL cells may represent a novel cytoprotective component of UPR, which could be exploited by tumor cells to survive the toxic insult of misfolded protein(s). (Cancer Res 2006; 66(20): 9903-12)
ADAM28 Is Overexpressed in Human Breast Carcinomas: Implications for Carcinoma Cell Proliferation through Cleavage of Insulin-like Growth Factor Binding Protein-3
Authors: Mitsui Yoko , Mochizuki Satsuki , Kodama Takahide , Shimoda Masayuki , Ohtsuka Takashi , Shiomi Takayuki , Chijiiwa Miyuki , Ikeda Tadashi , Kitajima Masaki , Okada Yasunori 
Published: October 2006

AbstractA disintegrin and metalloproteinases (ADAMs) are involved in various biological events including cell adhesion, cell fusion, membrane protein shedding, and proteolysis. In the present study, our reverse transcription-PCR analysis showed that among the 12 different ADAM species with a putative metalloproteinase motif, prototype membrane-anchored ADAM28m and secreted-type ADAM28s are selectively expressed in human breast carcinoma tissues. By real-time quantitative PCR, their expression levels were significantly higher in carcinomas than in nonneoplastic breast tissues. In situ hybridization, immunohistochemistry, and immunoblotting analyses indicated that ADAM28 is predominantly expressed in an active form by carcinoma cells within carcinoma tissues. A direct correlation was observed between mRNA expression levels and proliferative activity of the carcinoma cells. Treatment of ADAM28-expressing breast carcinoma cells (MDA-MB231) with insulin-like growth factor-I (IGF-I) increased cell proliferation, cleavage of IGF binding protein (IGFBP)-3, as well as IGF-I cell signaling; these processes were all significantly inhibited by treatment with ADAM inhibitor or anti-ADAM28 antibody. Down-regulation of ADAM28 expression in MDA-MB231 cells with small interfering RNA significantly reduced cell proliferation, IGFBP-3 cleavage, and growth of xenografts in mice. In addition, cleavage of IGFBP-3 in breast carcinoma tissues was correlated with ADAM28 expression levels and inhibited by treatment with ADAM inhibitor or anti-ADAM28 antibody. These results show that ADAM28 is overexpressed in an activated form in human breast carcinoma cells and suggest that ADAM28 is involved in cell proliferation through enhanced bioavailability of IGF-I released from the IGF-I/IGFBP-3 complex by selective IGFBP-3 cleavage in human breast carcinomas. (Cancer Res 2006; 66(20): 9913-20)
Low-Dose Etoposide Enhances Telomerase-Dependent Adenovirus-Mediated Cytosine Deaminase Gene Therapy through Augmentation of Adenoviral Infection and Transgene Expression in a Syngeneic Bladder Tumor Model
Authors: Shieh Gia-Shing , Shiau Ai-Li , Yo Yi-Te , Lin Pey-Ru , Chang Chao-Ching , Tzai Tzong-Shin , Wu Chao-Liang 
Published: October 2006

Abstract
The human telomerase reverse transcriptase (hTERT) promoter can selectively drive transgene expression in many telomerase-positive human cancer cells. Here we evaluated combination therapy of adenoviral vector Ad-hTERT-CD encoding E. coli cytosine deaminase (CD) driven by the hTERT promoter and low-dose etoposide (0.1 μg/mL) for treating bladder cancer. Ad-hTERT-CD conferred sensitivity to 5-fluorocytosine (5-FC) in bladder cancer cells, which could be enhanced by etoposide treatment, but not in normal cells. Such effect was correlated with up-regulation of hypoxia-inducible factor (HIF)-1α expression. By contrast, etoposide activated p53 and down-regulated hTERT promoter activity in normal cells. Etoposide also increased adenoviral infection via enhancement of coxsackie-adenovirus receptor expression on bladder cancer and normal cells. Combination index analysis revealed that combined therapy of Ad-hTERT-CD (109 plaque-forming units)/5-FC (200 mg/kg) with etoposide (2 mg/kg) synergistically suppressed tumor growth and prolonged survival in mice bearing syngeneic MBT-2 bladder tumors. This combination therapy regimen induced complete tumor regression and generated antitumor immunity in 75% of tumor-bearing mice. Furthermore, increased infiltrating CD4+ and CD8+ T cells and necrosis within tumors were found in mice receiving combination therapy of Ad-hTERT-CD and etoposide compared with those treated with either treatment alone. Thus, the potential high therapeutic index of the combination therapy may be an appealing therapeutic intervention for bladder cancer. Furthermore, because a majority of human tumors exhibit high telomerase activity, adenovirus-mediated CD gene therapy driven by the hTERT promoter in combination with low-dose etoposide may be applicable to a broad spectrum of cancers. (Cancer Res 2006; 66(20): 9957-66)
Localization of a Prostate Cancer Predisposition Gene to an 880-kb Region on Chromosome 22q12.3 in Utah High-Risk Pedigrees
Authors: Camp Nicola J. , Farnham James M. , Cannon-Albright Lisa A. 
Published: October 2006

Abstract
Chromosome 22q has become recently a region of interest for prostate cancer. We identified previously a logarithm of odds (LOD) of 2.42 at chromosome 22q12.3. Additionally, this region has been noted by eight other studies, with linkage evidence ranging from LOD of 1.50 to 3.57. Here, we do fine mapping and localization of the region using a pedigree-specific recombinant mapping approach in 14 informative, high-risk Utah pedigrees. These 14 pedigrees were chosen because they were either “linked” or “haplotype-sharing” pedigrees or both. “Linked” pedigrees were those with significant pedigree-specific linkage evidence (LOD, &gt;0.588; P &lt; 0.05) to the 22q12.3 region, regardless of the number of prostate cancer cases sharing the segregating haplotype. “Haplotype-sharing” pedigrees were those with at least five prostate cancer cases sharing a segregating haplotype in the 22q12.3 region, regardless of the linkage evidence. In each pedigree, the most likely haplotype configuration (in addition to the multipoint LOD graph for linked pedigrees) was used to infer the position of recombinant events and delimit the segregating chromosomal segment in each pedigree. These pedigree-specific chromosomal segments were then overlaid to form a consensus recombinant map across all 14 pedigrees. Using this method, we identified a 881,538-bp interval at 22q12.3, between D22S1265 and D22S277, which is the most likely region that contains the 22q prostate cancer predisposition gene. The unique Utah extended high-risk pedigree resource allows this powerful localization approach in pedigrees with evidence for segregating predisposition to prostate cancer. We are mutation screening candidate genes in this region to identify specific genetic variants segregating in these pedigrees. (Cancer Res 2006; 66(20): 10205-12)
Cyclin D1 Induction of Cellular Migration Requires p27KIP1
Authors: Li Zhiping , Jiao Xuanmao , Wang Chenguang , Ju Xiaoming , Lu Yinan , Yuan Liangping , Lisanti Michael P. , Katiyar Sanjay , Pestell Richard G. 
Published: October 2006

Abstract
The cyclin D1 gene is amplified and overexpressed in human breast cancer, functioning as a collaborative oncogene. As the regulatory subunit of a holoenzyme phosphorylating Rb, cyclin D1 promotes cell cycle progression and a noncatalytic function has been described to sequester the cyclin-dependent kinase inhibitor protein p27. Cyclin D1 overexpression correlates with tumor metastasis and cyclin D1–deficient fibroblasts are defective in migration. The genetic mechanism by which cyclin D1 promotes migration and movement is poorly understood. Herein, cyclin D1 promoted cellular migration and cytokinesis of mammary epithelial cells. Cyclin D1 enhanced cellular migratory velocity. The induction of migration by cyclin D1 was abolished by mutation of K112 or deletion of NH2-terminal residues 46 to 90. These mutations of cyclin D1 abrogated physical interaction with p27KIP1. Cyclin D1−/− cells were p27KIP1 deficient and the defect in migration was rescued by p27KIP1 reintroduction. Conversely, the cyclin D1 rescue of cyclin D1−/− cellular migration was reversed by p27KIP1 small interfering RNA. Cyclin D1 regulated p27KIP1 abundance at the posttranslational level, inhibiting the Skp2 promoter, Skp2 abundance, and induced p27KIP1 phosphorylation at Ser10. Together, these studies show cyclin D1 promotes mammary epithelial cell migration. p27KIP1 is required for cyclin D1–mediated cellular migration. (Cancer Res 2006; 66(20): 9986-94)
Selenium Regulates Cyclooxygenase-2 and Extracellular Signal-Regulated Kinase Signaling Pathways by Activating AMP-Activated Protein Kinase in Colon Cancer Cells
Authors: Hwang Jin-Taek , Kim Young Min , Surh Young-Joon , Baik Haing Woon , Lee Seong-Kyu , Ha Joohun , Park Ock Jin 
Published: October 2006

Abstract
Epidemiologic and experimental evidences indicate that selenium, an essential trace element, can reduce the risk of a variety of cancers. Protection against certain types of cancers, particularly colorectal cancers, is closely associated with pathways involving cyclooxygenase-2 (COX-2). We found that AMP-activated protein kinase (AMPK), which functions as a cellular energy sensor, mediates critical anticancer effects of selenium via a COX-2/prostaglandin E2 signaling pathway. Selenium activated AMPK in tumor xenografts as well as in colon cancer cell lines, and this activation seemed to be essential to the decrease in COX-2 expressions. Transduction with dominant-negative AMPK into colon cancer cells or application of cox-2−/−-negative cells supported the evidence that AMPK is an upstream signal of COX-2 and inhibits cell proliferation. In HT-29 colon cancer cells, carcinogenic agent 12-O-tetradecanoylphorbol-13-acetate (TPA) activated extracellular signal-regulated kinase (ERK) that led to COX-2 expression and selenium blocked the TPA-induced ERK and COX-2 activation via AMPK. We also showed the role of a reactive oxygen species as an AMPK activation signal in selenium-treated cells. We propose that AMPK is a novel and critical regulatory component in selenium-induced cancer cell death, further implying AMPK as a prime target of tumorigenesis. (Cancer Res 2006; 66(20): 10057-63)
Down-regulation of Androgen Receptor by 3,3′-Diindolylmethane Contributes to Inhibition of Cell Proliferation and Induction of Apoptosis in Both Hormone-Sensitive LNCaP and Insensitive C4-2B Prostate Cancer Cells
Authors: Bhuiyan Mohammad M.R. , Li Yiwei , Banerjee Sanjeev , Ahmed Fakhara , Wang Zhiwei , Ali Shadan , Sarkar Fazlul H. 
Published: October 2006

Abstract
Despite the initial efficacy of androgen deprivation therapy, most patients with advanced prostate cancer eventually progress to hormone-refractory prostate cancer, for which there is no curative therapy. Previous studies from our laboratory and others have shown the antiproliferative and proapoptotic effects of 3,3′-diindolylmethane (DIM) in prostate cancer cells. However, the molecular mechanism of action of DIM has not been investigated in androgen receptor (AR)–positive hormone-responsive and -nonresponsive prostate cancer cells. Therefore, we investigated the effects of B-DIM, a formulated DIM with greater bioavailability, on AR, Akt, and nuclear factor κB (NF-κB) signaling in hormone-sensitive LNCaP (AR+) and hormone-insensitive C4-2B (AR+) prostate cancer cells. We found that B-DIM significantly inhibited cell proliferation and induced apoptosis in both cell lines. By Akt gene transfection, reverse transcription-PCR, Western blot analysis, and electrophoretic mobility shift assay, we found a potential crosstalk between Akt, NF-κB, and AR. Importantly, B-DIM significantly inhibited Akt activation, NF-κB DNA binding activity, AR phosphorylation, and the expressions of AR and prostate-specific antigen, suggesting that B-DIM could interrupt the crosstalk. Confocal studies revealed that B-DIM inhibited AR nuclear translocation, leading to the down-regulation of AR target genes. Moreover, B-DIM significantly inhibited C4-2B cell growth in a severe combined immunodeficiency–human model of experimental prostate cancer bone metastasis. These results suggest that B-DIM-induced cell proliferation inhibition and apoptosis induction are partly mediated through the down-regulation of AR, Akt, and NF-κB signaling. These observations provide a rationale for devising novel therapeutic approaches for the treatment of hormone-sensitive, but more importantly, hormone-refractory prostate cancer by using B-DIM alone or in combination with other therapeutics. (Cancer Res 2006; 66(20): 10064-72)
A Novel Mechanism for p53 to Regulate Its Target Gene ECK in Signaling Apoptosis
Authors: Jin Y. Jenny , Wang Jianli , Qiao Changhong , Hei Tom K. , Brandt-Rauf Paul W. , Yin Yuxin 
Published: October 2006

Abstract
Transcription factor p53 regulates its target genes through binding to DNA consensus sequence and activating the promoters of its downstream genes. The conventional p53 consensus binding sequence was defined as two copies of the 10-bp motif 5′-PuPuPuC(A/T)(T/A)GPyPyPy-3′ with a spacer of 0 to 13 bp, which exists in the regulatory regions of some p53 target genes. However, there is no such p53 consensus sequence in the promoters of a number of p53-responsive genes, suggesting that there might be other mechanisms whereby p53 transactivates the promoters of its target genes. We report here that p53 uses a novel binding mechanism to regulate the transcription of epithelial cell kinase (ECK), a receptor protein-tyrosine kinase implicated in signal transduction. We show that p53 binds to a 10-bp perfect palindromic decanucleotide (GTGACGTCAC) in the ECK promoter, activates the ECK promoter, and increases the transcription of ECK. This palindrome is required for p53-mediated transactivation of the ECK promoter. ECK is highly responsive to oxidative damage that leads to cell death. Ectopic expression of ECK causes spontaneous apoptosis in breast cancer cells. We found that ectopic expression of a mutant ECK fails to induce apoptosis in cancer cells. Our findings show that p53 is a transcriptional regulator of ECK in mediating apoptosis. The discovery of the novel p53-binding motif in the promoter may lead to the identification of a new class of p53 target genes. (Mol Cancer Res 2006;4(10):769–78)
Mapping Global Values
Authors: Inglehart Ronald 
Published: October 2006

AbstractModernization goes through two main phases, each of which brings distinctive changes in people's worldviews. The Industrial Revolution was linked with a shift from traditional to secular-rational values, bringing bureaucratization, centralization, standardization and the secularization of authority. In the post-industrial phase of modernization, a shift from survival values to self-expression values, brings increasing emancipation from both religious and secular-rational authority. Rising mass emphasis on self-expression values makes democracy increasingly likely to emerge.Although the desire for freedom is a universal human aspiration, it does not take top priority when people grow up with the feeling that survival is uncertain. But when survival seems secure, increasing emphasis on self-expression values makes the emergence of democracy increasingly likely where it does not yet exist, and makes democracy increasingly effective where it already exists.
Democratization in the Human Development Perspective
Authors: Welzel Christian 
Published: October 2006

AbstractThis article describes a model that considers the emergence and florescence of democracies as something embedded in a more encompassing evolutionary process. Democratization in this light is the institutional component of a broader process of human development that promotes people empowerment on various fronts. In this process increasing individual resources give rise to emancipative values that in turn release democratizing social pressures.
Visit to the Tomb of Al-Husayn B. 'Alī in Shiite Poetry: First to Fifth Centuries AH (8th-11th Centuries CE)
Authors: Sindawi Khalid 
Published: October 2006

AbstractThe present study concerns visiting the tomb of Husayn b. 'Alī (d. 680 CE) in Karbalī', as reflected in Shiite poetry written between the first and fifth centuries AH. The article opens with a description of the visit, the ceremonies it involves, the virtues and purposes attributed to it, as well as the motivation behind the poetry associated with it. The study then describes the characteristics of this "visit poetry," its language and its artistic structure.