bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclin A Is a Proliferative Marker with Good Prognostic Value in Node-Negative Breast Cancer
Authors: Ahlin Cecilia , Zhou Wenjing , Holmqvist Marit , Holmberg Lars , Nilsson Cecilia , Jirström Karin , Blomqvist Carl , Amini Rose-Marie , Fjällskog Marie-Louise 
Published: September 2009

AbstractBackground: Proliferative markers are not recommended as prognostic factors for clinical use in breast cancer due to lack of standardization in methodology. However, proliferation is driving several gene expression signatures emphasizing the need for a reliable proliferative marker for clinical use. Studies suggest that cyclin A is a prognostic marker with satisfying reproducibility. We investigated cyclin A as a prognostic marker in node-negative breast cancer using previously defined cutoff values.Patients and Methods: In a case-control study, we defined 190 women who died from breast cancer as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size ≤50 mm, no lymph node metastases and no adjuvant chemotherapy. Tumor tissues were immunostained for cyclin A using commercially available antibodies.Results: We found a statistically significant association between expression of cyclin A and breast cancer death in a univariate model: odds ratio for cyclin Aave 2.7 [95% confidence interval (CI), 1.7-4.3] and cyclin Amax 3.4 (CI, 2.1-5.5). Corresponding odds ratio for Ki67 were Ki67ave 1.9 (CI, 1.2-3.1) and Ki67max 1.7 (CI, 1.1-2.7) and for grade 3.1 (CI, 1.8-5.1). Cyclin A was strongly correlated to Ki67 and grade why a model including all was not appropriate.Conclusions: Cyclin A is a prognostic factor for breast cancer death in node-negative patients using standardized methodology regarding scoring and cutoff values. Adding cyclin A as a proliferative marker to established clinicopathologic factors will improve the separation of low and high risk breast cancer.(Cancer Epidemiol Biomarkers Prev 2009;18(9):2501–6)
Cigarette Smoking and Prostate Cancer in a Prospective US Cohort Study
Authors: Watters Joanne L. , Park Yikyung , Hollenbeck Albert , Schatzkin Arthur , Albanes Demetrius 
Published: September 2009

AbstractSmoking is an important risk factor for many cancers, yet the relationship between smoking and prostate cancer remains uncertain. We investigated whether smoking affected the risk of prostate cancers within a large prospective cohort study of dietary and environmental cancer risk factors among men ages 50 to 71 upon enrollment in 1995-1996 (n = 283,312). Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (95% CI) were adjusted for age, race, education, height, body mass index, physical activity, family history of prostate cancer, diabetes, self-reported health status, prostate-specific antigen testing, digital rectal exam, total energy, α-tocopherol, calcium, α-linolenic acid, selenium, red meat, fish, and tomato intake. There were 14,810 nonadvanced and 1,830 advanced incident prostate cancers identified through 2003, and 394 men died of their disease through 2005. Current smokers had a decreased risk of nonadvanced prostate cancer (HR, 0.82; 95% CI, 0.77-0.88), but an increased risk of fatal prostate cancer (HR, 1.69; 95% CI, 1.25-2.27). Former smoking was also associated with decreased risk of nonadvanced prostate cancers (HR, 0.89; 95% CI, 0.86-0.92), but not fatal prostate cancers (HR, 1.03; 95% CI, 0.83-1.27). There was no apparent association between smoking and advanced prostate cancer. A number of biologically plausible mechanisms could explain these results, including the direct effects of carcinogens in tobacco smoke and the resulting changes in sex hormone or growth factor profiles. These findings suggest that current and former smokers may be at decreased risk of being diagnosed with prostate cancer and current smokers are at an increased risk of dying from prostate cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2427–35)
Reduced Serum Selenoprotein P Concentrations in German Prostate Cancer Patients
Authors: Meyer Hellmuth-Alexander , Hollenbach Birgit , Stephan Carsten , Endermann Tobias , Morgenthaler Nils G. , Cammann Henning , Köhrle Josef , Jung Klaus , Schomburg Lutz 
Published: September 2009

Abstract
Selenium (Se) is essentially needed for the biosynthesis of selenoproteins. Low Se intake causes reduced selenoprotein biosynthesis and constitutes a risk factor for tumorigenesis. Accordingly, some Se supplementation trials have proven effective to reduce prostate cancer risk, especially in poorly supplied individuals. Because Se metabolism is controlled by selenoprotein P (SEPP), we have tested whether circulating SEPP concentrations correlate to prostate cancer stage and grade. A total of 190 men with prostate cancer (n = 90) and “no evidence of malignancy” (NEM; n = 100) histologically confirmed by prostate biopsy were retrospectively analyzed for established tumor markers and for their Se and SEPP status. Prostate specific antigen (PSA), free PSA, total Se, and SEPP concentrations were determined from serum samples and compared with clinicopathologic parameters. The diagnostic performance was analyzed with receiver operating characteristic curves. Median Se and SEPP concentrations differed significantly (P &lt; 0.001) between the groups. Median serum Se concentrations in the 25th to 75th percentile were 95.9 μg/L (82-117.9) in NEM patients and 81.4 μg/L (67.9-98.4) in prostate cancer patients. Corresponding serum SEPP concentrations were 3.4 mg/L (1.9-5.6) in NEM and 2.9 mg/L (1.1-5.5) in prostate cancer patients. The area under the curve (AUC) of a marker combination with age, PSA, and percent free PSA (%fPSA) in combination with the SEPP concentration, yielded the highest diagnostic value (AUC 0.80) compared with the marker combination without SEPP (AUC 0.77) or %fPSA (AUC 0.76). We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics.(Cancer Epidemiol Biomarkers Prev 2009;18(9):2386–90)
Chronic Periodontitis and the Incidence of Head and Neck Squamous Cell Carcinoma
Authors: Tezal Mine , Sullivan Maureen A. , Hyland Andrew , Marshall James R. , Stoler Daniel , Reid Mary E. , Loree Thom R. , Rigual Nestor R. , Merzianu Mihai , Hauck Linda , Lillis Cheryl , Wactawski-Wende Jean , Scannapieco Frank A. 
Published: September 2009

Abstract
Substantial evidence supports an association between chronic infections/inflammation, and cancer. The aim of this study was to assess the effect of chronic periodontitis on head and neck squamous cell carcinoma (HNSCC). The study population consisted of new patients at the Department of Dentistry and Maxillofacial Prosthetics, Roswell Park Cancer Institute between 1999 and 2005. Cases were patients diagnosed with primary HNSCC. Controls were all patients seen during the same time period but negative for malignancy. Patients age &lt;21 years, edentulous, immunocompromised, and those with history of cancer were excluded. Periodontitis was measured by alveolar bone loss (ABL) from panoramic radiographs by one examiner blind to cancer status. A total of 473 patients (266 cases and 207 controls) were included in the study. Each millimeter of ABL was associated with &gt;4-fold increased risk of HNSCC (odds ratio, 4.36; 95% confidence interval, 3.16-6.01) after adjustment for age, gender, race/ethnicity, marital status, smoking status, alcohol use, and missing teeth. The strength of the association was greatest in the oral cavity, followed by oropharynx and larynx. The association persisted in subjects who never used tobacco and alcohol. There was a significant interaction between smoking and ABL (P = 0.03). Patients with periodontitis were more likely to have poorly differentiated oral cavity SCC than those without periodontitis (32.8% versus 11.5%; P = 0.038). This study suggests that chronic periodontitis is an independent risk factor for HNSCC and smoking modifies this association. These results have implications for practical and safe strategies for prevention, diagnosis, and treatment of HNSCC. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2406–12)
Screening for Colorectal Cancer in a Safety-Net Health Care System: Access to Care Is Critical and Has Implications for Screening Policy
Authors: Gupta Samir , Tong Liyue , Allison James E. , Carter Elizabeth , Koch Mark , Rockey Don C. , Anderson Paula , Ahn Chul , Argenbright Keith , Skinner Celette Sugg 
Published: September 2009

Abstract
Background: Data on the number of individuals eligible for screening, and rates of screening, are necessary to assess national colorectal cancer screening efforts. Such data are sparse for safety-net health systems.
Methods: A retrospective cohort study of individuals ages 50 to 75 served by a safety-net health system in Tarrant County, TX was conducted to determine (a) the size of the potential screen-eligible population ages 50 to 75, (b) the rate of screening over 5 years among individuals ages 54 to 75, and (c) the potential predictors of screening, including sex, race/ethnicity, insurance status, frequency of outpatient visits, and socioeconomic status.
Results: Of 28,708 potential screen-eligible individuals, 20,416 were ages 54 to 75 and analyzed for screening; 22.0% were screened within the preceding 5 years. Female gender, Hispanic ethnicity, ages 65 to 75, insurance status, and two or more outpatient visits were independently associated with screening. Access to care was an important factor: adjusted odds ratio, 2.57 (95% confidence interval, 2.23-2.98) for any insurance; adjusted odds ratio, 3.53 (95% confidence interval, 3.15-3.97) for two or more outpatient visits.
Conclusions: The screen-eligible population served by our safety-net health system was large, and the projected deficit in screen rates was substantial. Access to care was the dominant predictor of screening participation. If our results are replicable in similar health systems, the data suggest that screening guidelines and policy efforts must take into account the feasibility of proposed interventions. Strong advocacy for more resources for colorectal cancer screening interventions (including research into the best manner to provide screening for large populations) is needed. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2373–9)
Functional and Clinical Significance of Variants Localized to 8q24 in Colon Cancer
Authors: Cicek Mine S. , Slager Susan L. , Achenbach Sara J. , French Amy J. , Blair Hilary E. , Fink Stephanie R. , Foster Nathan R. , Kabat Brian F. , Halling Kevin C. , Cunningham Julie M. , Cerhan James R. , Jenkins Robert B. , Boardman Lisa A. , Petersen Gloria M. , Sargent Daniel J. , Alberts Steven R. , Limburg Paul J. , Thibodeau Stephen N. 
Published: September 2009

Abstract
Multiple genome-wide association studies have identified several susceptibility variants for colon cancer at 8q24. However, the functional roles of these variants have yet to be elucidated. Here, we evaluated the potential role of these markers in tumor progression and examined association with commonly observed structural abnormalities in this region, c-MYC amplification and chromosome fragility at FRA8C and FRA8D. We first replicated the previously reported association by testing 1,178 cases and 1,009 clinic-based controls with eight markers localized to three specific regions at 8q24. We observed significant associations with colon cancer risk with markers rs13254738 (ordinal odds ratio, 0.82; 95% confidence interval, 0.072-0.94; Ptrend = 0.0037) and rs6983267 (ordinal odds ratio, 1.17; 95% confidence interval, 1.03-1.32, Ptrend = 0.013). Survival analysis was done using a separate set of 460 cases to evaluate the clinical significance of these markers. Overall, univariate analysis did not detect survival differences for any of the markers. We also tested a subset of the 460 cases (n = 380) for structural abnormalities at or near the c-MYC locus using fluorescence in situ hybridization analysis. Furthermore, we evaluated a small number of cases homozygous for the rs6983267 alleles to test for differences in fragile site induction. None of the 8q markers correlated with amplification at the c-MYC locus as detected by fluorescence in situ hybridization, and no clear pattern of breakage was observed at the FRA8C and FRA8D sites. In this study, we confirm the association for several single nucleotide polymorphisms at 8q24 in colon cancer but have not detected any structural role relating to c-MYC amplification or chromosomal fragility. Finally, these risk alleles do not seem to be associated with survival. (Cancer Epidemiol Biomarkers Prev 2009;18(9):2492–500)
Ablation of Angiotensin IV Receptor Attenuates Hypofibrinolysis via PAI-1 Downregulation and Reduces Occlusive Arterial Thrombosis
Authors: Numaguchi Yasushi , Ishii Masakazu , Kubota Ryuji , Morita Yasuhiro , Yamamoto Koji , Matsushita Tadashi , Okumura Kenji , Murohara Toyoaki 
Published: September 2009

Objectives—Reduced fibrinolytic activity is associated with adverse cardiovascular events. Although insulin-regulated aminopeptidase (IRAP) was recently identified as the angiotensin (Ang) IV receptor (AT4R), the impact of AngIV-AT4R signaling distal to AngII on the activation of type-1 plasminogen activator inhibitor (PAI-1) in the fibrinolytic process and subsequent formation of thrombosis remains unclarified.Methods and Results—To determine whether AngIV would inhibit fibrinolysis via PAI-1 activation and promote thrombosis, we evaluated the degree of fibrinolysis in thrombosis models and investigated the roles of AT4R after vascular injury using IRAP knockout mice (IRAP−/−). In endothelial cells from control mice (WT; C57Bl6/J), both AngII and AngIV treatments increased PAI-1 mRNA expression in a dose-dependent manner, whereas the response was blunted in endothelial cells fromIRAP−/−mice. FeCl3-induced thrombosis was suppressed in the carotid arteries ofIRAP−/−mice when compared with WT mice. Similarly, in a model of carotid artery ligation and cuff placement,IRAP−/−mice demonstrated accelerated fibrinolysis 7 days after surgery and reduced occlusive thrombosis with negative remodeling at 28 days.Conclusions—AngIV-AT4R signaling has a key role in fibrinolysis and the subsequent formation of arterial thrombosis after vascular injury. AT4R may be a novel therapeutic target against cardiovascular disease.
VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy
Authors: Arons Evgeny , Suntum Tara , Stetler-Stevenson Maryalice , Kreitman Robert J. 
Published: September 2009

AbstractHairy cell leukemia variant (HCLv) presents with high disease burden, lack of typical antigens like CD25, and poor response to standard treatments like cladribine. Occasionally, patients with classic HCL respond poorly. Clinical and molecular features of HCL and HCLv has not been compared. Rearrangements expressing immunoglobulin VH chain were sequenced, including 22 from 20 patients with HCLv and 63 from 62 patients with classic HCL. Most patients were seeking relapsed/refractory trials, representing a poor-prognosis population. VH4-34, a gene commonly used in autoimmune disorders, was observed in 8 (40%) HCLv and 6 (10%) classic (P = .004) HCL patients. Compared with 71 VH4-34− rearrangements, 14 VH4-34+ rearrangements were more frequently (P < .001) unmutated, defined as greater than 98% homologous to germline sequence. VH4-34+ patients had greater white blood cell counts at diagnosis (P = .002), lower response rate (P < .001) and progression-free survival (P = .007) after initial cladribine, and shorter overall survival from diagnosis (P < .001). Response and survival were more closely related to VH4-34 status than to whether or not patients had HCLv. VH4-34+ HCL is an important disorder that only partly overlaps with the previously described HCLv. Response to initial single-agent cladribine therapy is suboptimal; these patients should be considered for alternative approaches, including antibody-related therapy.
Aberrant splicing of the E-cadherin transcript is a novel mechanism of gene silencing in chronic lymphocytic leukemia cells
Authors: Sharma Sanjai , Lichtenstein Alan 
Published: September 2009

AbstractPremature termination codon (PTC) mutations are due to insertion or deletion of nucleotides causing a frameshift and premature termination codon in RNA. These transcripts are degraded by the nonsense-mediated decay pathway and have a very short half-life. We used a microarray technique to screen for genes that up-regulate their RNA signal upon nonsense-mediated decay pathway blockade in chronic lymphocytic leukemia (CLL) specimens and identified an E-cadherin transcript with PTC. Sequencing revealed an aberrant E-cadherin transcript lacking exon 11, resulting in a frameshift and PTC. The aberrant E-cadherin transcript was also identified in normal B cells, but occurred at a much lower level compared with CLL cells. In CLL specimens, E-cadherin expression was depressed more than 50% in 62% cases (relative to normal B cells). By real-time polymerase chain reaction analysis, the relative amounts of wild-type transcript inversely correlated with amounts of aberrant transcript (P = .018). Ectopic expression of E-cadherin in CLL specimens containing high amounts of aberrant transcript resulted in down-regulation of the wnt–β-catenin pathway reporter, a pathway known to be up-regulated in CLL. Our data point to a novel mechanism of E-cadherin gene inactivation, with CLL cells displaying a higher proportion of aberrant nonfunctional transcripts and resulting up-regulation of the wnt–β-catenin pathway.
Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes
Authors: Calin George A. , Croce Carlo M. 
Published: September 2009

Abstract
One of the most unexpected and fascinating discoveries in oncology over the past few years is the interplay between abnormalities in protein-coding genes and noncoding RNAs (ncRNAs) that is causally involved in cancer initiation, progression, and dissemination. MicroRNAs (miRNAs), small regulatory ncRNAs, are involved in the pathogenesis of all types of human cancers, including leukemias, mainly via dysregulation of expression of cancer genes. Increasing evidence shows that miRNAs can work as tumor suppressors (inhibiting malignant potential) or oncogenes (activating malignant potential). Researchers first identified this new paradigm of molecular oncology in patients with chronic lymphocytic leukemia (CLL). Understanding the roles of miRNAs and other ncRNAs in leukemic cells is not only uncovering a new layer of gene regulation but also providing new markers for improved diagnosis and prognosis, as well as novel therapeutic options for CLL patients. Herein we focus on the roles of miRNAs and ultraconserved ncRNA genes in CLL, highlighting what is already known about their function, proposing a novel model of CLL predisposition and progression, and describing the challenges for the near future.
Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2
Authors: Bernard Veronica , Minnerop Martina , Bürk Katrin , Kreuz Friedmar , Gillessen-Kaesbach Gabriele , Zühlke Christine 
Published: September 2009

Abstract

Background
The autosomal recessively inherited ataxia with oculomotor apraxia 2 (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum AFP levels. AOA2 is caused by mutations within the senataxin gene (SETX). The majority of known mutations are nonsense, missense, and splice site mutations, as well as small deletions and insertions.

Methods
To detect mutations in patients showing a clinical phenotype consistent with AOA2, the coding region including splice sites of the SETX gene was sequenced and dosage analyses for all exons were performed on genomic DNA. The sequence of cDNA fragments of alternative transcripts isolated after RT-PCR was determined.

Results
Sequence analyses of the SETX gene in four patients revealed a heterozygous nonsense mutation or a 4 bp deletion in three cases. In another patient, PCR amplification of exon 11 to 15 dropped out. Dosage analyses and breakpoint localisation yielded a 1.3 kb LINE1 insertion in exon 12 (patient P1) and a 6.1 kb deletion between intron 11 and intron 14 (patient P2) in addition to the heterozygous nonsense mutation R1606X. Patient P3 was compound heterozygous for a 4 bp deletion in exon 10 and a 20.7 kb deletion between intron 10 and 15. This deletion was present in a homozygous state in patient P4.

Conclusion
Our findings indicate that gross mutations seem to be a frequent cause of AOA2 and reveal the importance of additional copy number analysis for routine diagnostics.
Epigenetic inheritance of an inducibly nucleosome-depleted promoter and its associated transcriptional state in the apparent absence of transcriptional activators
Authors: Ohsawa Ryosuke , Adkins Melissa , Tyler Jessica K 
Published: September 2009

Abstract

Background
Dynamic changes to the chromatin structure play a critical role in transcriptional regulation. This is exemplified by the Spt6-mediated histone deposition on to histone-depleted promoters that results in displacement of the general transcriptional machinery during transcriptional repression.

Results
Using the yeast PHO5 promoter as a model, we have previously shown that blocking Spt6-mediated histone deposition on to the promoter leads to persistent transcription in the apparent absence of transcriptional activators in vivo. We now show that the nucleosome-depleted PHO5 promoter and its associated transcriptionally active state can be inherited through DNA replication even in the absence of transcriptional activators. Transcriptional reinitiation from the nucleosome-depleted PHO5 promoter in the apparent absence of activators in vivo does not require Mediator. Notably, the epigenetic inheritance of the nucleosome-depleted PHO5 promoter through DNA replication does not require ongoing transcription.

Conclusion
Our results suggest that there may be a memory or an epigenetic mark on the nucleosome-depleted PHO5 promoter that is independent of the transcription apparatus and maintains the promoter in a nucleosome-depleted state through DNA replication.