bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salt and Gastric Adenocarcinoma: A Population-Based Cohort Study in Norway
Authors: Sjödahl Krister , Jia Chongqi , Vatten Lars , Nilsen Tom , Hveem Kristian , Lagergren Jesper 
Published: August 2008

Abstract
Background: Gastric adenocarcinoma is the second leading cause of cancer death worldwide. It has been suggested that consumption of salted foods is associated with increased risk of this cancer, but the results of the few available prospective studies are contradictory.
Methods: A population-based, prospective cohort study in Nord-Trondelag County in Norway during 1984 to 2002 addressed dietary salt intake in relation to risk of gastric adenocarcinoma. In 1984 to 1986, all adult county residents were invited to a health survey in which participants answered questionnaires concerning dietary salt intake and other factors. Gastric adenocarcinomas were identified in the Norwegian Cancer Registry. Relative risks were calculated using Cox proportional hazards regression models, adjusted for potentially confounding factors.
Results: Follow-up of 1,122,765 person-years at risk among 73,133 cohort members disclosed 313 incident cases of gastric adenocarcinomas occurring at least 3 years after inclusion into the cohort. There were no statistically significant associations between different levels of salt intake and risk of gastric adenocarcinoma. High consumers of dietary salt were not at increased risk of developing gastric adenocarcinoma compared with low consumers (hazard ratio, 1.0; 95% confidence interval, 0.7-1.4), and no dose-response effect was observed (Ptrend = 0.55).
Conclusion: High intake of dietary salt does not appear to increase the risk of gastric adenocarcinoma in this low-incidence western population. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1997–2001)
Breast Cancer Risk Polymorphisms and Interaction with Ionizing Radiation among U.S. Radiologic Technologists
Authors: Bhatti Parveen , Doody Michele M. , Alexander Bruce H. , Yuenger Jeff , Simon Steven L. , Weinstock Robert M. , Rosenstein Marvin , Stovall Marilyn , Abend Michael , Preston Dale L. , Pharoah Paul , Struewing Jeffery P. , Sigurdson Alice J. 
Published: August 2008

Abstract
Genome-wide association studies are discovering relationships between single-nucleotide polymorphisms and breast cancer, but the functions of these single-nucleotide polymorphisms are unknown and environmental exposures are likely to be important. We assessed whether breast cancer risk single-nucleotide polymorphisms interacted with ionizing radiation, a known breast carcinogen, among 859 cases and 1,083 controls nested in the U.S. Radiologic Technologists cohort. Among 11 Breast Cancer Association Consortium risk single-nucleotide polymorphisms, we found that the genotype-associated breast cancer risk varied significantly by radiation dose for rs2107425 in the H19 gene (Pinteraction = 0.001). H19 is a maternally expressed imprinted mRNA that is closely involved in regulating the IGF2 gene and could exert its influence by this or by some other radiation-related pathway. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2007–11)
Phenotype Comparison of MLH1 and MSH2 Mutation Carriers in a Cohort of 1,914 Individuals Undergoing Clinical Genetic Testing in the United States
Authors: Kastrinos Fay , Stoffel Elena M. , Balmaña Judith , Steyerberg Ewout W. , Mercado Rowena , Syngal Sapna 
Published: August 2008

Abstract
Background and Aims: Lynch syndrome is caused by germ-line mismatch repair gene mutations. We examined the phenotypic differences between MLH1 and MSH2 gene mutation carriers and whether mutation type (point versus large rearrangement) affected phenotypic expression.
Methods: This is a cross-sectional prevalence study of 1,914 unrelated probands undergoing clinical genetic testing for MLH1 and MSH2 mutations at a commercial laboratory.
Results: Fifteen percent (285 of 1,914) of subjects had pathogenic mutations (112 MLH1, 173 MSH2). MLH1 carriers had a higher prevalence of colorectal cancer (79% versus 69%, P = 0.08) and younger mean age at diagnosis (42.2 versus 44.8 years, P = 0.03) than MSH2 carriers. Forty-one percent of female carriers had endometrial cancer and prevalence was similar in both groups. Other cancers were more frequent in MSH2 carriers (24% versus 9%, P = 0.001) and their families (P &lt; 0.001). Multivariable analyses confirmed these associations. Of the 1,016 subjects who underwent Southern blot analysis, 42 had large rearrangements (7 MLH1, 35 MSH2). There were no phenotypic differences between carriers with large rearrangements and point mutations.
Conclusions: In this large study of mismatch repair gene mutation carriers from the United States, MLH1 carriers had more colorectal cancer than MSH2 carriers whereas endometrial cancer prevalence was similar. Large genomic rearrangements were more frequent in the MSH2 gene. MSH2 carriers and their relatives have more extracolonic nonendometrial Lynch syndrome–associated cancers and may benefit from additional screening. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2044–51)
Association between Common Genetic Variation in Cockayne Syndrome A and B Genes and Nucleotide Excision Repair Capacity among Smokers
Authors: Leng Shuguang , Bernauer Amanda , Stidley Christine A. , Picchi Maria A. , Sheng Xin , Frasco Melissa A. , Van Den Berg David , Gilliland Frank D. , Crowell Richard E. , Belinsky Steven A. 
Published: August 2008

Abstract
Mutagen sensitivity in in vitro cultured lymphocytes challenged by benzo[a]pyrene diolepoxide (BPDE) has been validated as an intrinsic susceptibility factor for several cancers. Bulky BPDE-DNA adducts are repaired via either transcription-coupled repair or global genome nucleotide excision repair depending on the location of lesions. Cockayne syndrome A (CSA) and B (CSB) play essential roles in integrating the recognition of damage, chromatin remodeling, and the core nucleotide excision repair proteins. This study evaluated the hypothesis that common genetic variation in CSA and CSB is associated with mutagen sensitivity induced by BPDE in 276 cancer-free smokers. Tag single nucleotide polymorphisms (SNP; n = 37) selected across the entire coding and putative regulatory regions of CSA and CSB based on a high-density SNP database were genotyped by the Illumina Golden Gate assay. Major principal components of CSA and CSB that captured the linkage disequilibrium from multiple SNPs were globally associated with the number of breaks per cell at the threshold of 80% (P ≤ 0.02 for both genes). Haplotype H125 in CSA and H97 in CSB as well as SNPs in high linkage disequilibrium with these two haplotypes were significantly associated with a 13% to 15% reduction in the mean number of chromatid breaks per cell (P &lt; 0.05). A resampling-based omnibus test supported the significant association between SNPs and haplotypes in CSA and mutagen sensitivity induced by BPDE (P = 0.035). This study implicates transcription-coupled repair in protecting the cell from BPDE-induced DNA damage. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2062–9)
Multiple Novel Prostate Cancer Predisposition Loci Confirmed by an International Study: The PRACTICAL Consortium
Authors: Kote-Jarai Zsofia , Easton Douglas F. , Stanford Janet L. , Ostrander Elaine A. , Schleutker Johanna , Ingles Sue A. , Schaid Daniel , Thibodeau Stephen , Dörk Thilo , Neal David , Cox Angela , Maier Christiane , Vogel Walter , Guy Michelle , Muir Kenneth , Lophatananon Artitaya , Kedda Mary-Anne , Spurdle Amanda , Steginga Suzanne , John Esther M. , Giles Graham , Hopper John , Chappuis Pierre O. , Hutter Pierre , Foulkes William D. , Hamel Nancy , Salinas Claudia A. , Koopmeiners Joseph S. , Karyadi Danielle M. , Johanneson Bo , Wahlfors Tiina , Tammela Teuvo L. , Stern Mariana C. , Corral Roman , McDonnell Shannon K. , Schürmann Peter , Meyer Andreas , Kuefer Rainer , Leongamornlert Daniel A. , Tymrakiewicz Malgorzata , Liu Jo-fen , O'Mara Tracy , Gardiner R.A. (Frank) , Aitken Joanne , Joshi Amit D. , Severi Gianluca , English Dallas R. , Southey Melissa , Edwards Stephen M. , Al Olama Ali Amin ,   The PRACTICAL Consortium, Eeles Rosalind A. 
Published: August 2008

Abstract
A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10−17). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2052–61)
The Multifunctional Protein Glyceraldehyde-3-Phosphate Dehydrogenase Is Both Regulated and Controls Colony-Stimulating Factor-1 Messenger RNA Stability in Ovarian Cancer
Authors: Zhou Yi , Yi Xiaofang , Stoffer Jha'Nae B. , Bonafe Nathalie , Gilmore-Hebert Maureen , McAlpine Jessica , Chambers Setsuko K. 
Published: August 2008

Abstract
Although glyceraldehyde-3-phosphate dehydrogenase's (GAPDH) predilection for AU-rich elements has long been known, the expected connection between GAPDH and control of mRNA stability has never been made. Recently, we described GAPDH binding the AU-rich terminal 144 nt of the colony-stimulating factor-1 (CSF-1) 3′ untranslated region (UTR), which we showed to be an mRNA decay element in ovarian cancer cells. CSF-1 is strongly correlated with the poor prognosis of patients with ovarian cancer. We investigated the functional significance of GAPDH's association with CSF-1 mRNA and found that GAPDH small interfering RNA reduces both CSF-1 mRNA and protein levels by destabilizing CSF-1 mRNA. CSF-1 mRNA half-lives were decreased by 50% in the presence of GAPDH small interfering RNA. RNA footprinting analysis of the 144 nt CSF-1 sequence revealed that GAPDH associates with a large AU-rich–containing region. The effects of binding of GAPDH protein or ovarian extracts to mutations of the AU-rich regions within the footprint were consistent with this finding. In a tissue array containing 256 ovarian and fallopian tube cancer specimens, we found that GAPDH was regulated in these cancers, with almost 50% of specimens having no GAPDH staining. Furthermore, we found that low GAPDH staining was associated with a low CSF-1 score (P = 0.008). In summary, GAPDH, a multifunctional protein, now adds regulation of mRNA stability to its repertoire. We are the first to evaluate the clinical role of GAPDH protein in cancer. In ovarian cancers, we show that GAPDH expression is regulated, and we now recognize that one of the many functions of GAPDH is to promote mRNA stability of CSF-1, an important cytokine in tumor progression. (Mol Cancer Res 2008;6(8):1375–84)
Wilms' Tumor 1 Suppressor Gene Mediates Antiestrogen Resistance via Down-Regulation of Estrogen Receptor-α Expression in Breast Cancer Cells
Authors: Han Youqi , Yang Lin , Suarez-Saiz Fernando , San-Marina Serban , Cui Jie , Minden Mark D. 
Published: August 2008

Abstract
The antiestrogen tamoxifen has been used in the treatment of hormone-responsive breast cancer for over a decade. The loss of estrogen receptor (ER) expression is the most common mechanism for de novo antiestrogen resistance. Wilms' tumor 1 suppressor gene (WT1) is a clinically useful marker that is associated with poor prognosis in breast cancer patients; its high level expression is frequently observed in cases of breast cancer that are estrogen and progesterone receptor negative. The lack of expression of these receptors is characteristic of tumor cells that are not responsive to hormonal manipulation. To determine whether there is a linkage between WT1 expression and antiestrogen resistance in breast cancer cells, we studied the effect of WT1 on tamoxifen responsiveness in ERα-positive MCF-7 cells. We found that overexpression of WT1 in MCF-7 markedly abrogated tamoxifen-induced cell apoptosis and 17β-estradiol (E2)–mediated cell proliferation. The expressions of ERα and its downstream target genes were significantly repressed following overexpression of WT1, whereas the down-regulation of WT1 by WT1 shRNA could enhance ERα expression and the sensitivity to tamoxifen treatment in ERα-negative MDA468 and HCC1954 cells that express high levels of WT1. Furthermore, we have confirmed that the WT1 protein can bind to endogenous WT1 consensus sites in the proximal promoter of ERα and thus inhibit the transcriptional activity of the ERα promoter in a WT1 site sequence–specific manner. Our study clearly implicates WT1 as a mediator of antiestrogen resistance in breast cancer through down-regulation of ERα expression and supports the development of WT1 inhibitors as a potential means of restoring antiestrogen responsiveness in breast cancer therapy. (Mol Cancer Res 2008;6(8):1347–55)
Protein Sialylation by Sialyltransferase Involves Radiation Resistance
Authors: Lee Minyoung , Lee Hae-June , Bae Sangwoo , Lee Yun-Sil 
Published: August 2008

Abstract
Previously, we identified β-galactoside α(2,6)-sialyltransferase (ST6Gal I) as a candidate biomarker for ionizing radiation. The expression of ST6Gal I and the level of protein sialylation increased following radiation exposure in a dose-dependent manner. Radiation induced ST6Gal I cleavage and the cleaved form of ST6Gal I was soluble and secreted. Sialylation of integrin β1, a glycosylated cell surface protein, was stimulated by radiation exposure and this increased its stability. Overexpression of ST6Gal I in SW480 colon cancer cells that initially showed a low level of ST6Gal I expression increased the sialylation of integrin β1 and also increased the stability of the protein. Inhibition of sialylation by transfection with neuraminidase 2 or neuraminidase 3 or by treatment with short interfering RNA targeting ST6Gal I reversed the effects of ST6Gal I overexpression. In addition, ST6Gal I overexpression increased clonogenic survival following radiation exposure and reduced radiation-induced cell death and caspase 3 activation. However, removal of sialic acids by neuraminidase 2 or knockdown of expression by short interfering RNA targeting ST6Gal I restored radiation-induced cell death phenotypes. In conclusion, radiation exposure was found to increase the sialylation of glycoproteins such as integrin β1 by inducing the expression of ST6Gal I, and increased protein sialylation contributed to cellular radiation resistance. (Mol Cancer Res 2008;6(8):1316–25)
Stress Chaperone GRP78/BiP Confers Chemoresistance to Tumor-Associated Endothelial Cells
Authors: Virrey Jenilyn J. , Dong Dezheng , Stiles Caryn , Patterson John B. , Pen Ligaya , Ni Min , Schönthal Axel H. , Chen Thomas C. , Hofman Florence M. , Lee Amy S. 
Published: August 2008

Abstract
The tumor vasculature is essential for tumor growth and survival and is a key target for anticancer therapy. Glioblastoma multiforme, the most malignant form of brain tumor, is highly vascular and contains abnormal vessels, unlike blood vessels in normal brain. Previously, we showed that primary cultures of human brain endothelial cells, derived from blood vessels of malignant glioma tissues (TuBEC), are physiologically and functionally different from endothelial cells derived from nonmalignant brain tissues (BEC) and are substantially more resistant to apoptosis. Resistance of TuBEC to a wide range of current anticancer drugs has significant clinical consequences as it represents a major obstacle toward eradication of residual brain tumor. We report here that the endoplasmic reticulum chaperone GRP78/BiP is generally highly elevated in the vasculature derived from human glioma specimens, both in situ in tissue and in vitro in primary cell cultures, compared with minimal GRP78 expression in normal brain tissues and blood vessels. Interestingly, TuBEC constitutively overexpress GRP78 without concomitant induction of other major unfolded protein response targets. Resistance of TuBEC to chemotherapeutic agents such as CPT-11, etoposide, and temozolomide can be overcome by knockdown of GRP78 using small interfering RNA or chemical inhibition of its catalytic site. Conversely, overexpression of GRP78 in BEC rendered these cells resistant to drug treatments. Our findings provide the proof of principle that targeting GRP78 will sensitize the tumor vasculature to chemotherapeutic drugs, thus enhancing the efficacy of these drugs in combination therapy for glioma treatment. (Mol Cancer Res 2008;6(8):1268–75)
Bortezomib-Resistant Nuclear Factor-κB Activity in Multiple Myeloma Cells
Authors: Markovina Stephanie , Callander Natalie S. , O'Connor Shelby L. , Kim Jihoon , Werndli Jae E. , Raschko Martha , Leith Catherine P. , Kahl Brad S. , Kim KyungMann , Miyamoto Shigeki 
Published: August 2008

Abstract
Bortezomib (Velcade/PS341), a proteasome inhibitor used in the treatment of multiple myeloma (MM), can inhibit activation of nuclear factor-κB (NF-κB), a family of transcription factors often deregulated and constitutively activated in primary MM cells. NF-κB can be activated via several distinct mechanisms, including the proteasome inhibitor–resistant (PIR) pathway. It remains unknown what fraction of primary MM cells harbor constitutive NF-κB activity maintained by proteasome-dependent mechanisms. Here, we report an unexpected finding that constitutive NF-κB activity in 10 of 14 primary MM samples analyzed is refractory to inhibition by bortezomib. Moreover, when MM cells were cocultured with MM patient-derived bone marrow stromal cells (BMSC), microenvironment components critical for MM growth and survival, further increases in NF-κB activity were observed that were also refractory to bortezomib. Similarly, MM-BMSCs caused PIR NF-κB activation in the RPMI8226 MM cell line, leading to increased NF-κB–dependent transcription and resistance to bortezomib-induced apoptosis. Our findings show that primary MM cells frequently harbor PIR NF-κB activity that is further enhanced by the presence of patient-derived BMSCs. They also suggest that this activity is likely relevant to the drug resistance development in some patients. Further elucidation of the mechanism of PIR NF-κB regulation could lead to the identification of novel diagnostic biomarkers and/or therapeutic targets for MM treatment. (Mol Cancer Res 2008;6(8):1356–64)
Alternative Splicing and Caspase-Mediated Cleavage Generate Antagonistic Variants of the Stress Oncoprotein LEDGF/p75
Authors: Brown-Bryan Terry A. , Leoh Lai S. , Ganapathy Vidya , Pacheco Fabio J. , Mediavilla-Varela Melanie , Filippova Maria , Linkhart Thomas A. , Gijsbers Rik , Debyser Zeger , Casiano Carlos A. 
Published: August 2008

Abstract
There is increasing evidence that an augmented state of cellular oxidative stress modulates the expression of stress genes implicated in diseases associated with health disparities such as certain cancers and diabetes. Lens epithelium–derived growth factor p75 (LEDGF/p75), also known as DFS70 autoantigen, is emerging as a survival oncoprotein that promotes resistance to oxidative stress–induced cell death and chemotherapy. We previously showed that LEDGF/p75 is targeted by autoantibodies in prostate cancer patients and is overexpressed in prostate tumors, and that its stress survival activity is abrogated during apoptosis. LEDGF/p75 has a COOH-terminally truncated splice variant, p52, whose role in stress survival and apoptosis has not been thoroughly investigated. We observed unbalanced expression of these proteins in a panel of tumor cell lines, with LEDGF/p75 generally expressed at higher levels. During apoptosis, caspase-3 cleaved p52 to generate a p38 fragment that lacked the NH2-terminal PWWP domain and failed to transactivate the Hsp27 promoter in reporter assays. However, p38 retained chromatin association properties and repressed the transactivation potential of LEDGF/p75. Overexpression of p52 or its variants with truncated PWWP domains in several tumor cell lines induced apoptosis, an activity that was linked to the presence of an intron-derived COOH-terminal sequence. These results implicate the PWWP domain of p52 in transcription function but not in chromatin association and proapoptotic activities. Consistent with their unbalanced expression in tumor cells, LEDGF/p75 and p52 seem to play antagonistic roles in the cellular stress response and could serve as targets for novel antitumor therapies. (Mol Cancer Res 2008;6(8):1293–307)
Estimating Spatial Variability in Atmospheric Properties over Remotely Sensed Land Surface Conditions
Authors: Bertoldi Giacomo , Kustas William P. , Albertson John D. 
Published: August 2008

Abstract
This paper investigates the spatial relationships between surface fluxes and near-surface atmospheric properties (AP), and the potential errors in flux estimation due to homogeneous atmospheric inputs over heterogeneous landscapes. A large-eddy simulation (LES) model is coupled to a surface energy balance scheme with remotely sensed surface temperature Ts as a key boundary condition. Simulations were performed for different agricultural regions having major contrasts in Ts, canopy cover, and surface roughness z0 between vegetated/irrigated and bare soil areas. If AP from a single weather station in a nonrepresentative location within the landscape are applied uniformly over the domain, significant differences in surface flux estimation with respect to the LES output are observed. The spatial correlations of AP with the fluxes, the land cover properties, and surface states were examined and the spatial scaling of these fields is analyzed using a two-dimensional wavelet technique. The results indicate a significant local correlation of the spatial distributions of the air temperature Ta with the sensible heat flux H, the specific humidity q with the latent heat flux LE, and the wind speed U with z0. These relationships can be described by a general linear form, suggesting that a simple regression relation may be applicable for most agricultural landscapes to estimate spatially variable AP fields. A simple yet practical method is proposed using remotely sensed observations and the land surface scheme, based on general linear expressions derived between Ta and H, q and LE, and U and z0. The method is shown to reproduce the main spatial patterns of AP and to reduce potential errors in local and regionally averaged heat flux estimation. This approach is recommended when only local weather station observations are available.