bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Application of Proton Pump Inhibitor for the Prevention of Colitis-Induced Colorectal Carcinogenesis beyond Acid Suppression
Authors: Kim Yoon Jae , Lee Jeong Sang , Hong Kyung Sook , Chung Jun Won , Kim Ju Hyun , Hahm Ki Baik 
Published: July 2010

Abstract
Colitis-associated cancers arise in the setting of chronic inflammation wherein an “inflammation-dysplasia-carcinoma” sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid–reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of β-catenin–accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitis-induced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression. Cancer Prev Res; 3(8); 963–74. ©2010 AACR.
Comparison of two infusion rates of antithrombin concentrate in cardiopulmonary bypass surgery
Authors: Lund Philip E. , Wassbäck Göran , Thomas Owain , Carlsson Tony , Schött Ulf 
Published: July 2010

Background: Antithrombin concentrate (AT) is used to treat heparin resistance (HR) in cardiac surgery. It is usually given slowly due to the fear of anaphylaxis. This may delay cardiac catheterisation and the start of cardiopulmonary bypass (CPB). HR is often defined as the failure to reach or maintain a target activated clotting time (ACT) despite a standard dose of heparin. It is not generally possible to predict which patients will display HR, although there are known risk factors. Routine early administration of AT before heparinisation is probably not cost-effective. Infusing AT relatively quickly after demonstrating HR may be more cost-effective, while not delaying surgery. The aim of this study is to investigate the safety and side effects of a faster infusion of AT. Methods: Forty patients undergoing elective heart surgery were included and randomised to two groups in a double-blind fashion. Each group received 1000 IU of AT intravenously (IV). One group received a slow infusion (100 IU/min) before full-dose heparinisation. The other group received a fast infusion (250 IU/min). Haemodynamic and respiratory data were recorded. Any adverse effects were noted. Thrombin-antithrombin, anti-Xa and antithrombin levels in plasma were measured. Results: No anaphylaxis occurred in either group. No differences were found regarding haemodynamics, respiration or laboratory results. Two patients experienced major haemorrhage and recovered; there were two deaths, thought to be unrelated to the study drugs. Conclusion: AT can be infused at a rate of 250 IU/min. This is faster than the current recommendation of 100 IU/min. This rate of infusion allows restricting AT infusion to those patients who display HR, without delaying surgery. Optimal anticoagulant therapy for CPB probably includes point-of-care measurement of ACT and plasma AT and small, but rapid, infusions of AT in heparin-resistant patients.
Low-dose radiation augments vasculogenesis signaling through HIF-1–dependent and –independent SDF-1 induction
Authors: Lerman Oren Z. , Greives Matthew R. , Singh Sunil P. , Thanik Vishal D. , Chang Christopher C. , Seiser Natalie , Brown Daniel J. , Knobel Denis , Schneider Robert J. , Formenti Silvia C. , Saadeh Pierre B. , Levine Jamie P. 
Published: July 2010

Abstract
The inflammatory response to ionizing radiation (IR) includes a proangiogenic effect that could be counterproductive in cancer but can be exploited for treating impaired wound healing. We demonstrate for the first time that IR stimulates hypoxia-inducible factor-1α (HIF-1α) up-regulation in endothelial cells (ECs), a HIF-1α–independent up-regulation of stromal cell–derived factor-1 (SDF-1), as well as endothelial migration, all of which are essential for angiogenesis. 5 Gray IR-induced EC HIF-1α and SDF-1 expression was greater when combined with hypoxia suggesting an additive effect. While small interfering RNA silencing of HIF-1α mRNA and abolition of HIF-1α protein induction down-regulated SDF-1 induction by hypoxia alone, it had little effect on SDF-1 induction by IR, demonstrating an independent pathway. SDF-1–mediated EC migra-tion in hypoxic and/or radiation-treated media showed IR induced strong SDF-1–dependent migration of ECs, augmented by hypoxia. IR activates a novel pathway stimulating EC migration directly through the expression of SDF-1 independent of HIF-1α induction. These observations might be exploited for stimulation of wound healing or controlling tumor angiogenesis.
Nomenclature of monocytes and dendritic cells in blood
Authors: Ziegler-Heitbrock Loems , Ancuta Petronela , Crowe Suzanne , Dalod Marc , Grau Veronika , Hart Derek N. , Leenen Pieter J. M. , Liu Yong-Jun , MacPherson Gordon , Randolph Gwendalyn J. , Scherberich Juergen , Schmitz Juergen , Shortman Ken , Sozzani Silvano , Strobl Herbert , Zembala Marek , Austyn Jonathan M. , Lutz Manfred B. 
Published: July 2010

AbstractMonocytes and cells of the dendritic cell lineage circulate in blood and eventually migrate into tissue where they further mature and serve various functions, most notably in immune defense. Over recent years these cells have been characterized in detail with the use of cell surface markers and flow cytometry, and subpopulations have been described. The present document proposes a nomenclature for these cells and defines 3 types of monocytes (classical, intermediate, and nonclassical monocytes) and 3 types of dendritic cells (plasmacytoid and 2 types of myeloid dendritic cells) in human and in mouse blood. This classification has been approved by the Nomenclature Committee of the International Union of Immunological Societies, and we are convinced that it will facilitate communication among experts and in the wider scientific community.
Novel targets for endoplasmic reticulum stress-induced apoptosis in B-CLL
Authors: Rosati Emanuela , Sabatini Rita , Rampino Giuliana , De Falco Filomena , Di Ianni Mauro , Falzetti Franca , Fettucciari Katia , Bartoli Andrea , Screpanti Isabella , Marconi Pierfrancesco 
Published: July 2010

Abstract
A better understanding of apoptotic signaling in B-chronic lymphocytic leukemia (B-CLL) cells may help to define new therapeutic strategies. This study investigated endoplasmic reticulum (ER) stress signaling in spontaneous apoptosis of B-CLL cells and whether manipulating ER stress increases their apoptosis. Results show that a novel ER stress-triggered caspase cascade, initiated by caspase-4 and involving caspase-8 and -3, plays an important role in spontaneous B-CLL cell apoptosis. ER stress-induced apoptosis in B-CLL cells also involves CHOP/GADD153 up-regulation, increased JNK1/2 phosphorylation, and caspase-8–mediated cleavage of Bap31 to Bap20, known to propagate apoptotic signals from ER to mitochondria. In ex vivo B-CLL cells, some apoptotic events associated with mitochondrial pathway also occur, including mitochondrial cytochrome c release and caspase-9 processing. However, pharmacologic inhibition studies show that caspase-9 plays a minor role in B-CLL cell apoptosis. ER stress also triggers survival signals in B-CLL cells by increasing BiP/GRP78 expression. Manipulating ER signaling by siRNA down-regulation of BiP/GRP78 or treating B-CLL cells with 2 well-known ER stress-inducers, tunicamycin and thapsigargin, increases their apoptosis. Overall, our findings show that ER triggers an essential pathway for B-CLL cell apoptosis and suggest that genetic and pharmacologic manipulation of ER signaling could represent an important therapeutic strategy.
Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma
Authors: Green Michael R. , Monti Stefano , Rodig Scott J. , Juszczynski Przemyslaw , Currie Treeve , O'Donnell Evan , Chapuy Bjoern , Takeyama Kunihiko , Neuberg Donna , Golub Todd R. , Kutok Jeffery L. , Shipp Margaret A. 
Published: July 2010

Abstract
Classical Hodgkin lymphoma (cHL) and mediastinal large B-cell lymphoma (MLBCL) are lymphoid malignancies with certain shared clinical, histologic, and molecular features. Primary cHLs and MLBCLs include variable numbers of malignant cells within an inflammatory infiltrate, suggesting that these tumors escape immune surveillance. Herein, we integrate high-resolution copy number data with transcriptional profiles and identify the immunoregulatory genes, PD-L1 and PD-L2, as key targets at the 9p24.1 amplification peak in HL and MLBCL cell lines. We extend these findings to laser-capture microdissected primary Hodgkin Reed-Sternberg cells and primary MLBCLs and find that programmed cell death-1 (PD-1) ligand/9p24.1 amplification is restricted to nodular sclerosing HL, the cHL subtype most closely related to MLBCL. Using quantitative immunohistochemical methods, we document the association between 9p24.1 copy number and PD-1 ligand expression in primary tumors. In cHL and MLBCL, the extended 9p24.1 amplification region also included the Janus kinase 2 (JAK2) locus. Of note, JAK2 amplification increased protein expression and activity, specifically induced PD-1 ligand transcription and enhanced sensitivity to JAK2 inhibition. Therefore, 9p24.1 amplification is a disease-specific structural alteration that increases both the gene dosage of PD-1 ligands and their induction by JAK2, defining the PD-1 pathway and JAK2 as complementary rational therapeutic targets.
hTERT promoter activity and CpG methylation in HPV-induced carcinogenesis
Authors: de Wilde Jillian , Kooter Jan M , Overmeer Renée M , Claassen-Kramer Debbie , Meijer Chris JLM , Snijders Peter JF , Steenbergen Renske DM 
Published: July 2010

Abstract

Background
Activation of telomerase resulting from deregulated hTERT expression is a key event during high-risk human papillomavirus (hrHPV)-induced cervical carcinogenesis. In the present study we examined hTERT promoter activity and its relation to DNA methylation as one of the potential mechanisms underlying deregulated hTERT transcription in hrHPV-transformed cells.

Methods
Using luciferase reporter assays we analyzed hTERT promoter activity in primary keratinocytes, HPV16- and HPV18-immortalized keratinocyte cell lines and cervical cancer cell lines. In the same cells as well as cervical specimens we determined hTERT methylation by bisulfite sequencing analysis of the region spanning -442 to +566 (relative to the ATG) and quantitative methylation specific PCR (qMSP) analysis of two regions flanking the hTERT core promoter.

Results
We found that in most telomerase positive cells increased hTERT core promoter activity coincided with increased hTERT mRNA expression. On the other hand basal hTERT promoter activity was also detected in telomerase negative cells with no or strongly reduced hTERT mRNA expression levels. In both telomerase positive and negative cells regulatory sequences flanking both ends of the core promoter markedly repressed exogenous promoter activity.
By extensive bisulfite sequencing a strong increase in CpG methylation was detected in hTERT positive cells compared to cells with no or strongly reduced hTERT expression. Subsequent qMSP analysis of a larger set of cervical tissue specimens revealed methylation of both regions analyzed in 100% of cervical carcinomas and 38% of the high-grade precursor lesions, compared to 9% of low grade precursor lesions and 5% of normal controls.

Conclusions
Methylation of transcriptionally repressive sequences in the hTERT promoter and proximal exonic sequences is correlated to deregulated hTERT transcription in HPV-immortalized cells and cervical cancer cells. The detection of DNA methylation at these repressive regions may provide an attractive biomarker for early detection of cervical cancer.
Associations between body mass index, weight control concerns and behaviors, and eating disorder symptoms among non-clinical Chinese adolescents
Authors: Fan Yiou , Li Yanping , Liu Ailing , Hu Xiaoqi , Ma Guansheng , Xu Guifa 
Published: July 2010

Abstract

Background
Previous research with adolescents has shown associations of body weight, weight control concerns and behaviors with eating disorder symptoms, but it is unclear whether these associations are direct or whether a mediating effect exists. This study was conducted to investigate the prevalence of overweight and obesity, weight control concerns and behaviors, and eating disorder symptoms and to examine the mediating function of weight control concerns and behaviors on the relationship between body mass index (BMI) and eating disorder symptoms among non-clinical adolescents in China.

Methods
A cross-sectional survey among 2019 adolescent girls and 1525 adolescent boys in the 7th, 8th, 10th and 11th grades from seven cities in China was conducted. Information on weight control concerns and behaviors, and eating disorder symptoms (Eating Disorder Inventory-3) were collected from the adolescents using a self-administrated questionnaire.

Results
Weight control concerns and behaviors, and eating disorder symptoms were prevalent among the study population. A high proportion of adolescents scored at or above the threshold on the eating disorder inventory (EDI) subscale such as bulimia, interoceptive deficits, perfectionism, and maturity fears, which indicated eating disorder symptoms. High BMI was significantly associated with high score of drive for thinness, body dissatisfaction, bulimia, low self-esteem, interceptive deficits and maturity fears, so do perceived body weight status. Almost all weight control concerns and behaviors we investigated were significantly associated with high EDI subscale scores. When weight control concerns were added to the model, as shown in the model, the association between BMI and tendency of drive to thinness and bulimia was attenuated but still kept significant. The association between BMI and body dissatisfaction were no further significant. The association of BMI and drive for thinness, body dissatisfaction and bulimia was considerably weaker than when weight control behaviors were not included.

Conclusions
Weight control concerns and behaviors may be mediators of the association between BMI and eating disorder symptoms. Interpretation of these weight control problems is crucial to develop culturally appropriate educational and intervention programs for adolescents.
Strengthening preventive care programs: a permanent challenge for healthcare systems; lessons from PREVENIMSS México
Authors: Gutiérrez Gonzalo , Pérez-Cuevas Ricardo , Levy Santiago , Reyes Hortensia , Acosta Benjamín , Cantón Sonia Fernández , Muñoz Onofre 
Published: July 2010

Abstract

Background
In 2001, the Instituto Mexicano del Seguro Social (IMSS) carried out a major reorganization to provide comprehensive preventive care to reinforce primary care services through the PREVENIMSS program. This program divides the population into programmatic age groups that receive specific preventive services: children (0-9 years), adolescents (10-19 years), men (20-59 years), women (20-59 years) and older adults (> = 60 years). The objective of this paper is to describe the improvement of the PREVENIMSS program in terms of the increase of coverage of preventive actions and the identification of unmet needs of unsolved and emergent health problems.

Methods
From 2003 to 2006, four nation-wide cross-sectional probabilistic population based surveys were conducted using a four stage sampling design. Thirty thousand households were visited in each survey. The number of IMSS members interviewed ranged from 79,797 respondents in 2003 to 117,036 respondents in 2006.

Results
The four surveys showed a substantial increase in coverage indicators for each age group: children, completed schemes of vaccination (> 90%), iron supplementation (17.8% to 65.5%), newborn screening for metabolic disorders (60.3% to 81.6%). Adolescents, measles - rubella vaccine (52.4% to 71.4%), hepatitis vaccine (9.3% to 46.2%), use of condoms (17.9% to 59.9%). Women, measles-rubella vaccine (28.5% to 59-2%), cervical cancer screening (66.7% to 75%), breast cancer screening (> 2.1%). Men, type 2 diabetes screening (38.6% to 57.8%) hypertension screening (48-4% to 64.0%). Older adults, pneumococcal vaccine (13.2% to 24.9%), influenza vaccine (12.6% to 52.9) Regarding the unmet needs, the prevalence of anemia in children was 30% and a growing prevalence of overweight and obesity, type 2 diabetes, and hypertension was found in men, women and older adults.

Conclusion
PREVENIMSS showed an important increase in the coverage of preventive services and stressed the magnitude of the old and new challenges that this healthcare system faces. The unsolved problems such as anemia, and the emerging ones such as overweight, obesity, among others, point out the need to strength preventive care through designing and implementing innovative programs aimed to attain effective coverage for those conditions in which prevention obtains substandard results.
Analysis of the 5'UTR of HCV genotype 3 grown in vitro in human B cells, T cells, and macrophages
Authors: Revie Dennis , Alberti Michael O , Prichard John G , Kelley Ann S , Salahuddin S Zaki 
Published: July 2010

Abstract

Background
Previously, we have reported the isolation and molecular characterization of human Hepatitis C virus genotype 1 (HCV-1) from infected patients. We are now reporting an analysis of HCV obtained from patients infected with HCV genotype 3 (HCV-3) as diagnosed by clinical laboratories.

Results
HCV was cultured in vitro using our system. HCV RNA was isolated from patients' blood and from HCV cultured in various cell types for up to three months. The 5'UTR of these isolates were used for comparisons. Results revealed a number of sequence changes as compared to the serum RNA. The HCV RNA produced efficiently by infected macrophages, B-cells, and T-cells had sequences similar to HCV-1, which suggests that selection of the variants was performed at the level of macrophages. Virus with sequences similar to HCV-1 replicated better in macrophages than HCV having a 5'UTR similar to HCV-3.

Conclusions
Although HCV-3 replicates in cell types such as B-cells, T-cells, and macrophages, it may require a different primary cell type for the same purpose. Therefore, in our opinion, HCV-3 does not replicate efficiently in macrophages, and patients infected with HCV-3 may contain a population of HCV-1 in their blood.
Bilateral transtibial amputation with concomitant thoracolumbar vertebral collapse in a Sichuan earthquake survivor
Authors: Wong Caroline Ngar-Chi , Yu Joseph Man-Kit , Law Sheung-Wai , Lau Herman Mun-Cheung , Chan Cavor Kai-Ming 
Published: July 2010

Abstract
The devastating earthquake in Sichuan, China on 12 May 2008 left thousands of survivors requiring medical care and intensive rehabilitation. In view of this great demand, the Chinese Speaking Orthopaedic Society established the "Stand Tall" project to provide voluntary services to aid amputee victims in achieving total rehabilitation and social integration. This case report highlights the multidisciplinary rehabilitation of a girl who suffered thoracolumbar vertebral collapse and underwent bilateral transtibial amputation. The rehabilitation team was involved in all stages of the care process from the pre-operative phase, through amputation, into prosthetic training, and during her life thereafter. Despite this catastrophic event, early rehabilitation and specially designed bilateral prostheses allowed her a high level of functional ability. The joint efforts of the multidisciplinary team and the advancement of new technology have revolutionized the care process for amputees.
Gonadotropin-releasing hormone type II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo
Authors: Gründker Carsten , Föst Crispin , Fister Stefanie , Nolte Nadine , Günthert Andreas R , Emons Günter 
Published: July 2010

Abstract
Introduction
Triple-negative breast cancer does not express estrogen and progesterone receptors, and no overexpression/amplification of the HER2-neu gene occurs. Therefore, this subtype of breast cancer lacks the benefits of specific therapies that target these receptors. Today chemotherapy is the only systematic therapy for patients with triple-negative breast cancer. About 50% to 64% of human breast cancers express receptors for gonadotropin-releasing hormone (GnRH), which might be used as a target. New targeted therapies are warranted. Recently, we showed that antagonists of gonadotropin-releasing hormone type II (GnRH-II) induce apoptosis in human endometrial and ovarian cancer cells in vitro and in vivo. This was mediated through activation of stress-induced mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK), followed by activation of proapoptotic protein Bax, loss of mitochondrial membrane potential, and activation of caspase-3. In the present study, we analyzed whether GnRH-II antagonists induce apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells that express GnRH receptors. In addition, we ascertained whether knockdown of GnRH-I receptor expression affects GnRH-II antagonist-induced apoptosis and apoptotic signaling.

Methods
Induction of apoptosis was analyzed by measurement of the loss of mitochondrial membrane potential. Apoptotic signaling was measured with quantification of activated MAPK p38 and caspase-3 by using the Western blot technique. GnRH-I receptor protein expression was inhibited by using the antisense knockdown technique. In vivo experiments were performed by using nude mice bearing xenografted human breast tumors.

Results
We showed that treatment of MCF-7 and triple-negative MDA-MB-231 human breast cancer cells with a GnRH-II antagonist results in apoptotic cell death in vitro via activation of stress-activated MAPK p38 and loss of mitochondrial membrane potential. In addition, we showed GnRH-II antagonist-induced activation of caspase-3 in MDA-MB-231 human breast cancer cells. After knockdown of GnRH-I receptor expression, GnRH-II antagonist-induced apoptosis and apoptotic signaling was only slightly reduced, indicating that an additional pathway mediating the effects of GnRH-II antagonists may exist. The GnRH-I receptor seems not to be the only target of GnRH-II antagonists. The antitumor effects of the GnRH-II antagonist could be confirmed in nude mice. The GnRH-II antagonist inhibited the growth of xenotransplants of human breast cancers in nude mice completely, without any apparent side effects.

Conclusions
GnRH-II antagonists seem to be suitable drugs for an efficacious and less-toxic endocrine therapy for breast cancers, including triple-negative breast cancers.