bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies with the azoxymethane–rat preclinical model for assessing colon tumor development and chemoprevention
Authors: Reddy Bandaru S. 
Published: June 2004

AbstractDuring recent years, multidisciplinary studies in epidemiology and molecular biology have contributed to our understanding of the etiology of colorectal cancer; more importantly they have enabled us to approach its prevention. An impressive body of epidemiological data suggests an inverse relationship between colorectal cancer risk and consumption of diets rich in omega (ω)‐3 fatty acids (n‐3 PUFAs) or the regular use of nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin. The development of strategies for the chemoprevention of colorectal cancer have been facilitated by the use of relevant animal models mimicking the neoplastic processes that occur in humans, including similarities in histopathology and molecular and genetic lesions during both the early and promotion/progression stages of carcinogenesis. Studies with the azoxymethane‐F344 rat model indicate that diets rich in n‐3 PUFAs, NSAIDs, selective cyclooxygenase‐2 (COX‐2), inducible nitric oxide synthase (iNOS) inhibitors, and curcumin can reduce the incidence of colon cancer. Advances in the knowledge of the mechanisms by which chemopreventive agents act offer opportunities to use combinations of specific chemopreventive agents, having clinically beneficial aggregate activity with minimal toxicity. This approach is extremely important when a promising chemopreventive agent demonstrates apparent efficacy but may produce toxic effects at high doses. Our studies show that a combination of very low doses of piroxicam (NSAID) and difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, or very low doses of COX‐2 and HMG‐CoA reductase inhibitors are more effective in inhibiting colon carcinogenesis than administration of these compounds as single agents even at higher levels. The natural history of colorectal cancer, from dysplastic aberrant crypts to adenomas and adenocarcinomas, offers multiple opportunities for assessment and intervention. Of further importance is to identify whether the molecular targets that are critical in the growth and survival of the malignant colorectal cell are modulated by n‐3 PUFAs, NSAIDs, or COX‐2 and iNOS inhibitors. Environ. Mol. Mutagen. 44:26–35, 2004. © 2004 Wiley‐Liss, Inc.
Genotoxicity of field‐collected inter‐tidal sediments from Cork Harbor, Ireland, to juvenile turbot (Scophthalmus maximus L.) as measured by the Comet assay
Authors: Kilemade M.F. , Hartl M.G.J. , Sheehan D. , Mothersill C. , van Pelt F.N.A.M. , O'Halloran J. , O'Brien N.M. 
Published: June 2004

AbstractThe alkaline single cell gel electrophoresis (SCGE) or Comet assay was employed to test the potential of surficial sediment collected from Cork Harbor, Ireland, to induce DNA damage in turbot (Scophthalmus maximus L.) in a laboratory exposure experiment. Turbot were exposed for 21 days to field‐collected sediment from Cork Harbor and from a relatively clean reference site at Ballymacoda and sampled at 0, 7, 14, and 21 days. As a positive control for the sediment exposure experiment, a subsample of the turbot was exposed to cadmium chloride‐spiked seawater. DNA damage analysis was performed on epidermal, gill, spleen, liver, and whole blood cell preparations. Liver, gill, and blood were the most sensitive tissues while a lower level of damage was detected in the epidermis and spleen. The blood was determined to be a suitable predictor of DNA damage in the whole organism. Chemical analysis of the sediment indicated that polycyclic aromatic hydrocarbons formed the bulk of the contaminants, with the harbor sites having almost double the levels of those from the reference site. The data indicated that turbot exposed to sediments from Cork Harbor elicited a significant increase in DNA damage in comparison with those exposed to sediment from the reference site and that exposure to the contaminated sediments caused a multi‐organ genotoxic response. Results from the study indicate a relationship between the presence of genotoxicants in sediment and DNA damage. This finding was encouraging with regard to the potential use of the Comet assay as part of a marine biomonitoring strategy. Environ. Mol. Mutagen. 44:56–64, 2004. © 2004 Wiley‐Liss, Inc.
Epigenetic events and protection from colon cancer in New Zealand
Authors: Ferguson Lynnette R. , Karunasinghe Nishi , Philpott Martin 
Published: June 2004

AbstractThe incidence of colon cancer is high in many developed nations, especially New Zealand. Molecular understanding of the nature of colon cancer shows a disease whose well‐characterized morphological progression is paralleled at the cellular level by increased numbers of gene or chromosome mutations, loss of heterozygosity, changed methylation patterns, and genomic instability. In the present study, we consider whether an imbalance of factors that affect DNA methylation patterns might explain at least part of the high colon cancer incidence in New Zealand. Folate is the major micronutrient whose intake impacts methylation, particularly through interaction with choline and methionine. Folate is generally somewhat deficient in the New Zealand diet, with the voluntary addition of folate to white flour not producing desired levels. Selenium affects methylation status in several ways and is recognized as being low in New Zealand soils and, therefore, diet. Zinc is also low in the diets of some New Zealand population groups, which can lead to hypomethylation. Several of the components of fruits and vegetables affect methylation patterns, and the average New Zealand intake, at two to three servings per day, is considerably below recommended amounts. Low dietary fiber, high tobacco use, and increasing rates of obesity are also likely New Zealand risk factors that may impact on methylation status. Dietary supplementation is not as common in New Zealand as in countries such as the United States, but may provide a way to raise the levels of nutrients and phytochemicals affecting methylation status, thereby enhancing colon cancer protection. Environ. Mol. Mutagen. 44:36–43, 2004. © 2004 Wiley‐Liss, Inc.
The oldest ape
Authors: Maclatchy Laura 
Published: June 2004

AbstractThis paper recounts the history and significance of Morotopithecus bishopi, an early Miocene East African ape. Morotopithecus differs in intriguing ways from its contemporary Proconsul. While craniodental differences are slight, the known elements of its postcranium suggest that Morotopithecus was capable of modern ape–like positional behaviors, including vertical postures, deliberate climbing, and arm hanging. In contrast, Proconsul and other early and middle Miocene hominoids have been reconstructed as above–branch quadrupeds. Paleoanthropologists are currently divided over whether and which of the anatomical features associated with upright posture and suspension in the modern apes are due to inheritance or independent evolution. This debate has important implications for interpreting the phylogenetic positions of both Morotopithecus and Proconsul, as well as for reconstructing the pattern and timing of the emergence of modern ape adaptations.
The canopy conductance of a boreal aspen forest, Prince Albert National Park, Canada
Authors: Blanken P. D. , Black T. A. 
Published: June 2004

AbstractAnnual fluxes of canopy‐level heat, water vapour and carbon dioxide were measured using eddy covariance both above the aspen overstory (Populus tremuloides Michx.) and hazelnut understory (Corylus cornuta Marsh.) of a boreal aspen forest (53·629 °N 106·200 °W). Partitioning of the fluxes between overstory and understory components allowed the calculation of canopy conductance to water vapour for both species. On a seasonal basis, the canopy conductance of the aspen accounted for 70% of the surface conductance, with the latter a strong function of the forest's leaf area index. On a half‐hour basis, the canopy conductance of both species decreased non‐linearly as the leaf‐surface saturation deficits increased, and was best parameterized and showed similar sensitivities to a modified form of the Ball–Berry–Woodrow index, where relative humidity was replaced with the reciprocal of the saturation deficit. The negative feedback between the forest evaporation and the saturation deficit in the convective boundary layer varied from weak when the forest was at full leaf to strong when the forest was developing or loosing leaves. The coupling between the air at the leaf surface and the convective boundary layer also varied seasonally, with coupling decreasing with increasing leaf area. Compared with coniferous boreal forests, the seasonal changes in leaf area had a unique impact on vegetation–atmosphere interactions. Copyright © 2004 John Wiley & Sons, Ltd.
Involvement of the FGFR4 Arg388 allele in head and neck squamous cell carcinoma
Authors: Streit Sylvia , Bange Johannes , Fichtner Alexander , Ihrler Stephan , Issing Wolfgang , Ullrich Axel 
Published: June 2004

AbstractFibroblast growth factor receptors (FGFRs) have been implicated in various forms of human hyperproliferative disorders such as cancers of the cervix and bladder. We investigated the expression pattern of FGFR4 and the clinical significance of the recently identified Gly/Arg polymorphism (388) in head and neck squamous cell carcinomas (HNSCCs) of the oral cavity and the oropharynx. Sections from 104 paraffin‐embedded tumors were analyzed by a restriction fragment length polymorphism‐based method to determine the FGFR4 genotypes. Protein expression was investigated immunohistochemically and graded into a low, intermediate, or high degree of staining. FGFR4 expression was scored as high in 17, as intermediate in 59 and as low in 28 cases. The FGFR4 Arg388 allele was found in 59 tumors, 46 of them having heterozygous and 13 homozygous genotypes. High expression of the FGFR4 Arg388 allele was significantly associated with reduced overall survival (p = 0.032) and with an advanced tumor stage (p = 0.023), whereas expression of the FGFR4 Gly388 had no impact on disease progression. Our findings indicate that high expression of FGFR4 in connection with the Arg388 allele is associated with poor clinical outcome and support the significance of FGFR4 as a diagnostic marker and a target for therapeutic intervention in human HNSCC. © 2004 Wiley‐Liss, Inc.
Immunodetection and quantification of vascular endothelial growth factor receptor‐3 in human malignant tumor tissues
Authors: Bando Hiroko , Brokelmann Maren , Toi Masakazu , Alitalo Kari , Sleeman Jonathan P. , Sipos Bence , Gröne Hermann‐Josef , Weich Herbert A. 
Published: June 2004

AbstractVascular endothelial growth factor recpetor‐3 (VEGFR‐3) and its ligands, vascular endothelial growth factor‐C (VEGF‐C) and –D (VEGF‐D), are the major molecules involved in developmental and pathological lymphangiogenesis. Here we describe for the first time the development of a specific indirect enzyme‐linked immunosorbent assay (ELISA) for the quantification of VEGFR‐3 in different human cell and tissue lysates. A combination of the goat polyclonal anti‐VEGFR‐3 antibody and the mouse monoclonal anti‐human VEGFR‐3 antibody was used. The assay was highly sensitive and reproducible with a detection range of 0.2–25 ng/ml. The assay was specific for VEGFR‐3, with no cross‐reactivity to VEGFR‐1 or VEGFR‐2. Complex formation with VEGF‐C and VEGF‐D had no effect on the sensitivity of the assay. The VEGFR‐3 concentration in the lysates of cultured human dermal microvascular endothelial cells was 14‐fold higher than in the lysates from human umbilical vein endothelial cells. In human kidney, breast, colon, gastric and lung cancer tissues the protein levels of VEGFR‐3 were in the range of 0.6–16.7 ng/mg protein. Importantly, the level of VEGFR‐3 protein detected in the ELISA correlated significantly with the number of VEGFR‐3 positive vessels observed in histochemical sections, suggesting that the ELISA assay may be a reliable surrogate of measuring VEGFR‐3‐positive vessel density. The protein levels of VEGFR‐3 in 27 renal cell carcinoma samples had a significant correlation with the levels of VEGF‐C (p<0.001), or biological active, free VEGF‐A (p<0.0001), but not with VEGFR‐1 or total VEGF‐A. This assay provides a useful tool for the investigations of the expression levels of VEGFR‐3 in physiological and pathological processes, particular in cancer and in lymphangiogenesis‐related disease. © 2004 Wiley‐Liss, Inc.
Suppression of tumor growth and metastasis by a VEGFR‐1 antagonizing peptide identified from a phage display library
Authors: An Ping , Lei Hetian , Zhang Jianzhi , Song Shumei , He Luowen , Jin Genglin , Liu Xiaoying , Wu Jian , Meng Lin , Liu Meisheng , Shou Chengchao 
Published: June 2004

AbstractAlthough the VEGF‐Flk‐1‐pathway has been known as the major driving force of angiogenesis, new evidence has shown that VEGFR‐1/Flt‐1 plays important roles during the neovascularization under pathological conditions including tumor, atherosclerosis and arthritis. In search of Flt‐1 receptor antagonizing peptides, we screened a phage display 12‐mer‐peptide library with recombinant Flt‐1 protein. Seven candidate peptides were identified that specifically bound to VEGF receptor Flt‐1, of which peptide F56 (WHSDMEWWYLLG) almost abolished VEGF binding to receptor Flt‐1 in vitro. In vivo, F56 fused with DHFR (DHFR‐F56) inhibited angiogenesis in a CAM assay. Moreover, DHFR‐F56 significantly inhibited the growth of nodules of human gastric cancer cell line MGC‐803 in BALB/c nude mice. Histological analyses showed that necrosis of the implanted tumor was markedly enhanced following treatment with DHFR‐F56. In the severe combined immunodeficiency disease (SCID) mouse model for studying metastasis of the human breast cancer cell line BICR‐H1, synthetic peptide F56 significantly inhibited tumor growth and lung metastases. Taken together, our results have demonstrated that peptide F56, as a Flt‐1 receptor antagonist, fulfilled the antiangiogenic and antimetastatic effects by specifically interfering with the interaction between VEGF and receptor Flt‐1. Thus, short peptide F56 may have clinical potential in tumor therapy. © 2004 Wiley‐Liss, Inc.
Expression of the tyrosine kinase c‐kit is an independent prognostic factor in patients with small cell lung cancer
Authors: Rohr Ulrich‐Peter , Rehfeld Nina , Pflugfelder Lucy , Geddert Helene , Müller Wolfram , Steidl Ulrich , Fenk Roland , Gräf Thorsten , Schott Matthias , Thiele Klaus‐Peter , Gabbert Helmut Erich , Germing Ulrich , Kronenwett Ralf , Haas Rainer 
Published: June 2004

AbstractIn a retrospective analysis of 203 patients with small cell lung cancer (SCLC), we examined the prognostic value of c‐kit expression on survival. Expression of c‐kit was examined immunohistochemically in formalin‐fixed, paraffin‐embedded tissue sections. c‐kit was observed in 87.7% of SCLC tumors. Using the Kaplan‐Meier model, we found that lack of c‐kit expression was associated with significantly shorter survival time compared to the presence of c‐kit expression (mean survival 151 ± 27 vs. 358 ± 49 days, p = 0.0084). Moreover, the proportion of c‐kit+ cells within the tumor was also related to survival time. Patients with tumors in which >75% of cells stained positive for c‐kit had a mean overall survival time of 424 (±72) compared to 295 (±67) days for patients with 25–75% c‐kit+ tumor cells. Patients with tumors containing <25% c‐kit+ cells had the worst survival, with 164 (±24) days (p = 0.0033). Further parameters associated with short survival times were low performance status, elevated levels of lactate dehydrogenase and higher stage according to the TNM classification. Multivariate analysis using the Cox regression model showed that the proportion of c‐kit+ cells within the tumor specimen was one of 3 independent prognostic parameters (p = 0.004) for overall survival next to TNM classification (p = 0.001) and performance status (p < 0.001). © 2004 Wiley‐Liss, Inc.
Reduced expression of class II histone deacetylase genes is associated with poor prognosis in lung cancer patients
Authors: Osada Hirotaka , Tatematsu Yoshio , Saito Hiroko , Yatabe Yasushi , Mitsudomi Tetsuya , Takahashi Takashi 
Published: June 2004

AbstractHDAC genes are thought to be involved in gene expression through the regulation of chromatin structure, alterations of which may cause abnormal gene silencing in cancers. To clarify the possible role of HDAC genes during tumor development and progression, we studied their expression and influence on clinical features. Expression levels of HDAC class I and class II genes in cancer tissues resected from 72 patients with NSCLC were measured with real‐time RT‐PCR. Their association with clinicopathologic features was statistically investigated. Reduced expression of each class II HDAC gene was significantly associated with poor prognosis and an independent predictor of poor prognosis. Of all the genes, HDAC10 was the strongest predictor of poor prognosis. Hierarchical clustering analysis showed that lung cancer tissues could be divided into 3 groups based on the expression level of class I and class II HDAC genes. The group with reduced expression of class II HDACs showed poor prognosis. These results suggest that class II HDACs may repress critical genes and that low expression of these genes may play a role in lung cancer progression. Results of clustering analyses imply that class II HDAC genes may be regulated by a similar mechanism and deregulated during cancer development. © 2004 Wiley‐Liss, Inc.
Long‐run monetary neutrality and long‐horizon regressions
Authors: Coe Patrick J. , Nason James M. 
Published: June 2004

AbstractA prominent test of long‐run monetary neutrality (LRMN) involves regressing long‐horizon output growth on long‐horizon money growth. We obtain limited support for LRMN with this test in long‐annual Australian, Canadian, UK and US samples. Although empirical confidence intervals yield evidence in favour of LRMN, Monte Carlo experiments reveal the power of this test is near its size. Thus, this test is unlikely to detect important deviations from LRMN. These problems arise because the long‐horizon regression test of LRMN relies on estimates of the covariance of long‐horizon output growth and long‐horizon money growth. Copyright © 2004 John Wiley & Sons, Ltd.
Projection pursuit regression and disaggregate productivity effects: the case of the Indian blast furnaces
Authors: Das Sanghamitra , Sengupta Ramprasad 
Published: June 2004

AbstractProductivity of blast furnaces in India is studied by disaggregating the production process and the utilization process. A dimension‐reducing nonparametric approach—projection pursuit regression—is used. We find that productivity can be increased significantly by improving the quality of coal. There is no evidence that executives have a positive marginal product. The production workers have a negative marginal product for the production process and a positive one for the utilization process. But the training of executives has a positive effect whereas that of the production workers has a negative effect on productivity. Copyright © 2004 John Wiley & Sons, Ltd.
A microeconometric evaluation of rehabilitation of long‐term sickness in Sweden
Authors: Frölich Markus , Heshmati Almas , Lechner Michael 
Published: June 2004

AbstractIn this study the effects of various types of rehabilitation programmes on labour market outcomes are estimated. A main feature of this study is that it jointly evaluates multiple treatments by nonparametric matching estimators. The study is based on a large sample of persons in western Sweden who are long‐term sick and could participate in rehabilitation programmes. Our results suggest that workplace training is superior to the other rehabilitation programmes with respect to labour market outcomes, but compared to non‐participation no positive effects are found. Copyright © 2004 John Wiley & Sons, Ltd.
Poverty comparisons with dependent samples
Authors: Zheng Buhong 
Published: June 2004

AbstractStandard inference procedures for poverty comparisons require samples to be independent. For many commonly used income samples, however, this requirement is not fulfilled since samples are rotated. This article introduces an easy‐to‐use method of correction for sample dependency. We also apply the method to test changes in US poverty in the 1990s and to evaluate the marginal effects of public assistance on poverty before and after the recent welfare reform. Copyright © 2004 John Wiley & Sons, Ltd.
Mechanical signals and IGF‐I gene splicing in vitro in relation to development of skeletal muscle
Authors: Cheema Umber , Brown Robert , Mudera Vivek , Yang Shi Yu , McGrouther Gus , Goldspink Geoffrey 
Published: June 2004

AbstractIt has been shown that the insulin‐like growth factor (IGF‐I) gene is spliced in response to mechanical signals producing forms of IGF‐I which have different actions. In order to study how mechanical signals influence this gene splicing in developing muscle, C2C12 cells were grown in three‐dimensional (3D) culture and subjected to different regimens of mechanical strain. IGF‐IEa which initiates the fusion of myoblasts to form myotubes was found to be constitutively expressed in myoblasts and myotubes (held under endogenous tension) and its expression upregulated by a single ramp stretch of 1‐h duration but reduced by repeated cyclical stretch. In contrast, mechano growth factor (MGF), which is involved in the proliferation of mononucleated myoblasts that are required for secondary myotube formation and to establish the muscle satellite (stem) cell pool, showed no significant constitutive expression in static cultures, but was upregulated by a single ramp stretch and by cycling loading. The latter types of force simulate those generated in myoblasts by the first contractions of myotubes. These data indicate the importance of seeking to understand the physiological signals that determine the ratios of splice variants of some growth factor/tissue factor genes in the early stages of development of skeletal muscle. © 2005 Wiley‐Liss, Inc.
Increased expression of VEGF in retinal pigmented epithelial cells is not sufficient to cause choroidal neovascularization
Authors: Oshima Yuji , Oshima Sachiko , Nambu Hiroyuki , Kachi Shu , Hackett Sean F. , Melia Michele , Kaleko Michael , Connelly Sheila , Esumi Noriko , Zack Donald J. , Campochiaro Peter A. 
Published: June 2004

AbstractIncreased expression of vascular endothelial cell growth factor (VEGF) in the retina is sufficient to stimulate sprouting of neovascularization from the deep capillary bed of the retina, but not the superficial retinal capillaries or the choriocapillaris. Coexpression of VEGF and angiopoietin 2 (Ang2) results in sprouting of neovascularization from superficial and deep retinal capillaries, but not the choriocapillaris. However, retina‐derived VEGF and Ang2 may not reach the choriocapillaris, because of tight junctions between retinal pigmented epithelial (RPE) cells. To eliminate this possible confounding factor, we used the human vitelliform macular dystrophy 2 (VMD2) promoter, an RPE‐specific promoter, combined with the tetracycline‐inducible promoter system, to generate double transgenic mice with inducible expression of VEGF in RPE cells. Adult mice with increased expression of VEGF in RPE cells had normal retinas and choroids with no choroidal neovascularization (CNV), but when increased expression of VEGF in RPE cells was combined with subretinal injection of a gutless adenoviral vector containing an expression construct for Ang2 (AGVAng2), CNV consistently occurred. In contrast, triple transgenic mice with induced expression of Ang2 and VEGF in RPE cells, did not develop CNV. These data suggest that increased expression of VEGF and/or Ang2 in RPE cells is not sufficient to cause CNV unless it is combined with a subretinal injection of a gutless adenoviral vector, which is likely to perturb RPE cells. These data also suggest that the effects of angiogenic proteins may vary among vascular beds, even those that are closely related, and, therefore, generalizations should be avoided. © 2004 Wiley‐Liss, Inc.