bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Progression of LNCaP Human Prostate Cancer Cells to Androgen Independence Involves Decreased FOXO3a Expression and Reduced p27KIP1 Promoter Transactivation
Authors: Lynch Rebecca L. , Konicek Bruce W. , McNulty Ann M. , Hanna Kimberly R. , Lewis Jason E. , Neubauer Blake Lee , Graff Jeremy R. 
Published: September 2005

Abstract
The progression of human prostate cancer from the initial androgen-dependent phase to androgen independence involves diminished apoptosis and a release from the cell cycle block triggered by androgen ablation therapy. FOXO transcription factors play a central role in promoting expression of proapoptotic and cell cycle regulatory genes (e.g., FasL and p27KIP1). Reduced FOXO function might, therefore, play a role in androgen-independent progression of human prostate cancer. Herein, we show that FOXO function is compromised in androgen-independent prostate cancer cells (LNAI) versus androgen-dependent LNCaP cells. The FOXO3a protein, the most highly expressed FOXO family member in prostate cancer cells, is hyperphosphorylated in LNAI cells. FOXO3a expression is also markedly reduced in these androgen-independent LNAI cells when compared with parental LNCaP cells. Together, reduced FOXO3a expression coupled to FOXO3a hyperphosphorylation would suppress FOXO transcriptional activity. Accordingly, activity of the FOXO-responsive p27KIP1 promoter is reduced 60% in these LNAI cells when compared with LNCaP cells. Moreover, mutation of a conserved FOXO response element suppresses p27KIP1 promoter activity, substantiating a regulatory role for this FOXO response element in p27KIP1 promoter transactivation. Finally, we show that the activity of a distinct FOXO-responsive promoter, the 3X-IRS promoter, is also reduced in LNAI cells. Collectively, these data show that reduced FOXO3a expression coupled to increased FOXO3a phosphorylation coincide with reduced FOXO-responsive promoter activity in androgen-independent LNAI cells when compared with androgen-dependent LNCaP cells. To the extent that this model reflects human disease, these data suggest that FOXO function may be compromised with androgen-independent progression of human prostate cancer.
Molecular Characterization of Ring Finger Protein 11
Authors: Connor Michael K. , Azmi Peter B. , Subramaniam Venkateswaran , Li Hoaxia , Seth Arun 
Published: September 2005

Abstract
Ring finger proteins serve many vital functions within the cell. We have identified RNF11, a novel 154-amino acid ring finger–containing protein, which is elevated in breast cancer. Within its ring finger domain, RNF11 contains an AKT phosphorylation site (T135) that is situated within a 14-3-3 binding domain. In WM239 cells with constitutively active AKT, RNF11 exhibits seven distinct phosphopeptides as measured using two-dimensional phosphopeptide mapping. Upon inhibition of the AKT pathway or mutation of T135, the phosphorylation at one of these sites is virtually eliminated, suggesting that AKT may phosphorylate RNF11 at T135. Moreover, RNF11 is phosphorylated by AKT in vitro and is recognized by phospho-AKT substrate antibodies. RNF11 shows enhanced binding to 14-3-3 in WM239 cells compared with that seen in the parental WM35 cells which have low AKT activity. Furthermore, treatment of WM239 cells with LY294002 reduces RNF11/14-3-3 interactions suggesting that RNF11/14-3-3 binding is regulated by AKT. In addition, RNF11/14-3-3 binding is enhanced by constitutively active AKT and is diminished by dominant-negative AKT. There is also reduced 14-3-3 binding to T135E RNF11. RNF11 localization was altered from the cytoplasm to the nucleus by activated AKT. Thus, phosphorylation of RNF11 by AKT either causes its nuclear localization or induces degradation of cytoplasmic RNF11. In addition, T135E RNF11, which does not bind 14-3-3 and is not phosphorylated by AKT, causes a greater enhancement of transforming growth factor-β signaling than wild-type RNF11. It is clear that RNF11 function, localization, and potentially, degradation are regulated by AKT. Disregulation of proper RNF11 function by AKT may prove to be detrimental to patient outcomes, making RNF11 a potential target for novel cancer therapeutics.
Transforming Growth Factor-α Inhibits the Intrinsic Pathway of c-Myc-Induced Apoptosis through Activation of Nuclear Factor-κB in Murine Hepatocellular Carcinomas
Authors: Cavin Lakita G. , Wang Fang , Factor Valentina M. , Kaur Swayamjot , Venkatraman Manickam , Thorgeirsson Snorri S. , Arsura Marcello 
Published: September 2005

Abstract
Nuclear factor-κB (NF-κB) plays an important role during liver neoplastic development through transcriptional regulation of prosurvival genes, which then counteract the death-inducing signals elicited by the host immune response. The c-Myc proto-oncogene is frequently deregulated in liver tumors. Furthermore, enforced expression of c-Myc in the liver promotes the development of hepatocellular carcinomas, a process that is accelerated by coexpression with transforming growth factor-α (TGF-α). TGF-α/c-Myc–derived hepatocellular carcinomas display reduced apoptotic levels compared with those of single c-Myc transgenic hepatocellular carcinomas, suggesting that TGF-α provides a survival advantage to c-Myc-transformed hepatocytes. Given that TGF-α/c-Myc hepatocellular carcinomas display constitutive NF-κB activity, here, we have tested the hypothesis that enforced expression of TGF-α results in constitutive NF-κB activation and enhanced cell survival using TGF-α/c-Myc–derived hepatocellular carcinoma cell lines. We show that TGF-α induces NF-κB through the phosphatidylinositol 3-kinase/Akt axis in these bitransgenic hepatocellular carcinomas. Furthermore, we found that adenovirus-mediated inhibition of NF-κB activity impairs the ability of TGF-α/c-Myc–derived tumor cells to grow in an anchorage-independent fashion due to sensitization to c-Myc-induced apoptosis. Lastly, we show that NF-κB inhibits c-Myc-induced activation of caspase-9 and caspase-3 through up-regulation of the antiapoptotic target genes Bcl-XL and X-linked inhibitor of apoptosis (XIAP). Overall, these results underscore a crucial role of NF-κB in disabling apoptotic pathways initiated by oncogenic transformation.
Components of DNA Damage Checkpoint Pathway Regulate UV Exposure–Dependent Alterations of Gene Expression of FHIT and WWOX at Chromosome Fragile Sites
Authors: Ishii Hideshi , Mimori Koshi , Inageta Taeko , Murakumo Yoshiki , Vecchione Andrea , Mori Masaki , Furukawa Yusuke 
Published: September 2005

Abstract
Common chromosome fragile sites are highly recombinogenic and susceptible to deletions during the development of environmental carcinogen–induced epithelial tumors. Previous studies showed that not only genetic but also epigenetic alterations in cancerous cells are involved in inactivation of the genes FHIT and WWOX at chromosome fragile sites, reported to be potential tumor suppressor genes. Here we investigated the effect of UV light on the gene expression. After exposure to UV, the mRNA and protein of the two genes in murine embryonic fibroblasts (MEF) were unstable, apparently at the G1-S phase of the cell cycle, which was consistent with nuclear run-on assay. A study of MEFs synchronized via a double thymidine block indicated that, after the exposure, the expression of Fhit and Wwox was reduced in E2f-1–deficient cells and markedly in wild-type cells, whereas the reduction was partially inhibited in Trp53-deficient cells; cells at the S phase seemed to be sensitive to exogenous FHIT, suggesting a role of the checkpoint at the G1-S phase in the stability of gene expression and a possible involvement of FHIT function at the S phase. The transfection experiment showed that the UV-induced decrease in expression was partially inhibited by transfection of kinase-dead Atr (ataxia telangiectasia mutated and Rad3 related), which is a sensor of UV-induced damage. Taken together, the present study showed that UV-induced alterations of the fragile site gene expression are involved at least partially in the checkpoint function, suggesting the role in the process of carcinogenesis after exposure to UV.
Category Deficits and Paradoxical Dissociations in Alzheimer's Disease and Herpes Simplex Encephalitis
Authors: Laws Keith R. , Sartori Giuseppe 
Published: September 2005

Abstract
Most studies examining category specificity are single-case studies of patients with living or nonliving deficits. Nevertheless, no explicit or agreed criteria exist for establishing category-specific deficits in single cases regarding the type of analyses, whether to compare with healthy controls, the number of tasks, or the type of tasks. We examined two groups of patients with neurological pathology frequently accompanied by impaired semantic memory (19 patients with Alzheimer's disease and 15 with Herpes Simplex Encephalitis). Category knowledge was examined using three tasks (picture naming, naming-to-description, and feature verification). Both patient groups were compared with age-and education-matched healthy controls. The profile in each patient was examined for consistency across tasks and across different analyses; however, both proved to be inconsistent. One striking finding was the presence of paradoxical dissociations (i.e., patients who were impaired for living things on one task and nonliving things on another task). The findings have significant implications for how we determine category effects and, more generally, for the methods used to document double dissociations across individual cases in this literature.
Audiovisual Integration in Patients with Visual Deficit
Authors: Frassinetti Francesca , Bolognini Nadia , Bottari Davide , Bonora Annalisa , Làdavas Elisabetta 
Published: September 2005

Abstract
In the present study, we investigated the possibility that bimodal audiovisual stimulation of the affected hemifield can improve perception of the visual events in the blind hemifield of hemianopic patients, as it was previously demonstrated in neglect patients. Moreover, it has been shown that “hetero-modal” and “sensory-specific” cortices are involved in cross-modal integration. Thus, the second aim of the present study was to examine whether audiovisual integration influences visual detection in patients with different cortical lesions responsible of different kinds of visual disorders. More specifically, we investigated cross-modal, audiovisual integration in patients with visual impairment due to a visual field deficit (e.g., hemianopia) or visuospatial attentional deficit (e.g., neglect) and patients with both hemianopia and neglect. Patients were asked to detect visual stimuli presented alone or in combination with auditory stimuli that could be spatially aligned or not with the visual ones. The results showed an enhancement of visual detection in cross-modal condition (spatially aligned condition) comparing to unimodal visual condition only in patients with hemianopia or neglect; by contrast, the multi-sensory integration did not occur when patients presented both deficits. These data suggest that patients with visual disorders can enormously benefit the multisensory integration. Moreover, they showed a different influence of cortical lesion on multi-sensory integration. Thus, the present results show the important adaptive meaning of multisensory integration and are very promising with respect to the possibility of recovery from visual and spatial impairments.
Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein
Authors: Moorman Jonathan P , Fitzgerald S Matthew , Prayther Deborah C , Lee Steven A , Chi David S , Krishnaswamy Guha 
Published: September 2005

AbstractBackgroundRecent studies suggest that HCV infection is associated with progressive declines in pulmonary function in patients with underlying pulmonary diseases such as asthma and chronic obstructive pulmonary disease. Few molecular studies have addressed the inflammatory aspects of HCV-associated pulmonary disease. Because IL-8 plays a fundamental role in reactive airway diseases, we examined IL-8 signaling in normal human lung fibroblasts (NHLF) in response to the HCV nucleocapsid core protein, a viral antigen shown to modulate intracellular signaling pathways involved in cell proliferation, apoptosis and inflammation.MethodsNHLF were treated with HCV core protein and assayed for IL-8 expression, phosphorylation of the p38 MAPK pathway, and for the effect of p38 inhibition.ResultsOur studies demonstrate that soluble HCV core protein induces significant increases in both IL-8 mRNA and protein expression in a dose- and time-dependent manner. Treatment with HCV core led to phosphorylation of p38 MAPK, and expression of IL-8 was dependent upon p38 activation. Using TNFα as a co-stimulant, we observed additive increases in IL-8 expression. HCV core-mediated expression of IL-8 was inhibited by blocking gC1qR, a known receptor for soluble HCV core linked to MAPK signaling.ConclusionThese studies suggest that HCV core protein can lead to enhanced p38- and gC1qR-dependent IL-8 expression. Such a pro-inflammatory role may contribute to the progressive deterioration in pulmonary function recently recognized in individuals chronically infected with HCV.
Metallothionein mediates leukocyte chemotaxis
Authors: Yin Xiuyun , Knecht David A , Lynes Michael A 
Published: September 2005

AbstractBackgroundMetallothionein (MT) is a cysteine-rich, metal-binding protein that can be induced by a variety of agents. Modulation of MT levels has also been shown to alter specific immune functions. We have noticed that the MT genes map close to the chemokines Ccl17 and Cx3cl1. Cysteine motifs that characterize these chemokines are also found in the MT sequence suggesting that MT might also act as a chemotactic factor.ResultsIn the experiments reported here, we show that immune cells migrate chemotactically in the presence of a gradient of MT. This response can be specifically blocked by two different monoclonal anti-MT antibodies. Exposure of cells to MT also leads to a rapid increase in F-actin content. Incubation of Jurkat T cells with cholera toxin or pertussis toxin completely abrogates the chemotactic response to MT. Thus MT may act via G-protein coupled receptors and through the cyclic AMP signaling pathway to initiate chemotaxis.ConclusionThese results suggest that, under inflammatory conditions, metallothionein in the extracellular environment may support the beneficial movement of leukocytes to the site of inflammation. MT may therefore represent a "danger signal"; modifying the character of the immune response when cells sense cellular stress. Elevated metallothionein produced in the context of exposure to environmental toxicants, or as a result of chronic inflammatory disease, may alter the normal chemotactic responses that regulate leukocyte trafficking. Thus, MT synthesis may represent an important factor in immunomodulation that is associated with autoimmune disease and toxicant exposure.
A common variant of endothelial nitric oxide synthase (Glu298Asp) is associated with collateral development in patients with chronic coronary occlusions
Authors: Lamblin Nicolas , Cuilleret François J , Helbecque Nicole , Dallongeville Jean , Lablanche Jean-Marc , Amouyel Philippe , Bauters Christophe , Van Belle Eric 
Published: September 2005

Abstract

Background
Experimental studies support an important role for endothelial nitric oxide synthase (eNOS) in the regulation of angiogenesis. In humans, a common polymorphism exists in the eNOS gene that results in the conversion of glutamate to aspartate for codon 298. In vitro and in vivo studies have suggested a decreased NOS activity in patients with the Asp298 variant. We hypothesized that a genetic-mediated decreased eNOS activity may limit collateral development in patients with chronic coronary occlusions.

Methods
We selected 291 consecutive patients who underwent coronary angiography and who had at least one chronic (>15 days) total coronary occlusion. Collateral development was graded angiographically using two different methods: the collateral flow grade and the recipient filling grade. Genomic DNA was extracted from white blood cells and genotyping was performed using previously published techniques.

Results
Collateral development was lower in patients carrying the Asp298 variant than in Glu-Glu homozygotes (collateral flow grade: 2.64 ± 0.08 and 2.89 ± 0.08, respectively, p = 0.04; recipient filling grade: 3.00 ± 0.08 and 3.24 ± 0.07, respectively, p = 0.04). By multivariable analysis, three variables were independently associated with the collateral flow grade: female gender, smoking, and the Asp298 variant (p = 0.03) while the Asp298 variant was the sole variable independently associated with the recipient filling grade (p = 0.03).

Conclusion
Collateral development is lower in patients with the Asp298 variant. This may be explained by the decreased NOS activity in patients with the Asp298 variant. Further studies will have to determine whether increasing eNOS activity in humans is associated with coronary collateral development.
Cluster detection methods applied to the Upper Cape Cod cancer data
Authors: Ozonoff Al , Webster Thomas , Vieira Veronica , Weinberg Janice , Ozonoff David , Aschengrau Ann 
Published: September 2005

Abstract

Background
A variety of statistical methods have been suggested to assess the degree and/or the location of spatial clustering of disease cases. However, there is relatively little in the literature devoted to comparison and critique of different methods. Most of the available comparative studies rely on simulated data rather than real data sets.

Methods
We have chosen three methods currently used for examining spatial disease patterns: the M-statistic of Bonetti and Pagano; the Generalized Additive Model (GAM) method as applied by Webster; and Kulldorff's spatial scan statistic. We apply these statistics to analyze breast cancer data from the Upper Cape Cancer Incidence Study using three different latency assumptions.

Results
The three different latency assumptions produced three different spatial patterns of cases and controls. For 20 year latency, all three methods generally concur. However, for 15 year latency and no latency assumptions, the methods produce different results when testing for global clustering.

Conclusion
The comparative analyses of real data sets by different statistical methods provides insight into directions for further research. We suggest a research program designed around examining real data sets to guide focused investigation of relevant features using simulated data, for the purpose of understanding how to interpret statistical methods applied to epidemiological data with a spatial component.
Tumour necrosis factor-α stimulates dehydroepiandrosterone metabolism in human fibroblast-like synoviocytes: a role for nuclear factor-κB and activator protein-1 in the regulation of expression of cytochrome p450 enzyme 7b
Authors: Dulos John , Kaptein Allard , Kavelaars Annemieke , Heijnen Cobi , Boots Annemieke 
Published: September 2005

AbstractGlucocorticoids have successfully been used in the treatment of rheumatoid arthritis. Data suggest that 7α-hydroxy-dehydroepiandrosterone (7α-OH-DHEA), an immunostimulating metabolite of dehydroepiandrosterone, can block glucocorticoid-induced immune suppression. Formation of 7α-OH-DHEA is catalyzed by activity of cytochrome p450 enzyme 7b (Cyp7b). Recently, we reported that tumour necrosis factor (TNF)-α, IL-1α, IL-1β and IL-17 enhance Cyp7b mRNA expression and induce a concomitant increase in the formation of 7α-OH-DHEA by fibroblast-like synoviocytes (FLS) from rheumatoid arthritis patients. The aim of this study was to elucidate which signal transduction pathway is involved in the TNF-α-mediated induction of Cyp7b activity in FLS. We studied the effects of inhibitors of different signal transduction pathways on Cyp7b activity in FLS by measuring Cyp7b mRNA expression using reverse transcription PCR and by measuring the formation of 7α-OH-DHEA. We applied SN50, an inhibitor of nuclear translocation of transcription factors (i.e. activator protein-1 [AP-1] and nuclear factor-κB [NF-κB]); PSI, a proteasome inhibitor that prevents IκB degradation and thereby NF-κB release; SP600125, a c-Jun N-terminal kinase (JNK) inhibitor; and the mitogen-activated protein kinase inhibitors PD98059 (extracellular signal-regulated kinase) and SB203580 (p38). Cyp7b is constitutively expressed in RA FLS and can be activated in response to TNF-α. SN50 and PSI prevented the TNF-α-induced increase in Cyp7b activity, whereas the mitogen-activated protein kinase inhibitors PD98059 and SB203580 had no effect. In addition, inhibition of Cyp7b mRNA expression and activity was observed with SN50, PSI and SP600125, suggesting that NF-κB and AP-1 induce Cyp7b transcription. These findings suggest that NF-κB and AP-1 are involved in the TNF-α-enhanced formation of the dehydroepiandrosterone metabolite 7α-OH-DHEA. Our results are in accordance with presence of AP-1 and NF-κB binding sites in the Cyp7b promoter.
CYP17 gene polymorphism in relation to breast cancer risk: a case-control study
Authors: Einarsdóttir Kristjana , Rylander-Rudqvist Tove , Humphreys Keith , Ahlberg Susanne , Jonasdottir Gudrun , Weiderpass Elisabete , Chia Kee Seng , Ingelman-Sundberg Magnus , Persson Ingemar , Liu Jianjun , Hall Per , Wedrén Sara 
Published: September 2005

Abstract
Introduction
The c.1-34T>C 5' promoter region polymorphism in cytochrome P450c17 (CYP17), a key enzyme in the biosynthesis of estrogen, has been associated with breast cancer risk, but most previous studies have been relatively small.

Methods
We genotyped 1,544 incident cases of primary breast cancer and 1,502 population controls, all postmenopausal Swedish women, for the CYP17 c.1-34T>C polymorphism and calculated odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models.

Results
No overall association was found between CYP17 c.1-34T>C and breast cancer risk, OR 1.0 (95% CI 0.8–1.3) for the A2/A2 (CC) carriers compared to the A1/A1 (TT) carriers, regardless of histopathology. We detected an interaction between CYP17 c.1-34T>C and age at menarche (P = 0.026) but regarded that as a chance finding as no dose-response pattern was evident. Other breast cancer risk factors, including menopausal hormone use and diabetes mellitus, did not modify the overall results.

Conclusion
It is unlikely that CYP17 c.1-34T>C has a role in breast cancer etiology, overall or in combination with established non-genetic breast cancer risk factors.
Response of Serum C-Reactive Protein to Percutaneous Coronary Intervention Has Prognostic Value
Authors: Saleh Nawsad , Svane Bertil , Hansson Lars-Olof , Jensen Jens , Nilsson Tage , Danielsson Olle , Tornvall Per 
Published: September 2005

Abstract
Background: Data are sparse regarding the association between C-reactive protein (CRP) and percutaneous coronary intervention (PCI) in long-term prognosis. Previous studies have shown that PCI evokes an inflammatory response. We tested the hypothesis that the CRP response to PCI has a prognostic value.
Methods: We investigated 891 consecutive patients presenting with stable or unstable angina pectoris, with serum concentrations of cardiac troponin T ≤0.03 μg/L, who were undergoing a variety of PCIs. Serum concentrations of CRP and cardiac troponin T were determined before and the day after PCI. The mean follow-up time after PCI was 2.6 years, and the endpoint was death or nonfatal myocardial infarction.
Results: Seventy-six patients reached the endpoint (4.6% death, 3.9% nonfatal myocardial infarction), whereas 21% developed myocardial infarction during the procedure. CRP increased more than 2-fold after the procedure. Patients in the third tertile of the CRP response to PCI had an increased risk for death or nonfatal myocardial infarction in multivariate analysis.
Conclusions: Increased serum CRP in response to PCI is an independent predictor of death or nonfatal myocardial infarction independent of myocardial injury during the procedure. CRP determinations might be of value in risk stratification after PCI.