bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypermethylation of theBreast Cancer–Associated Gene 1Promoter Does Not Predict Cytologic Atypia or Correlate with Surrogate End Points of Breast Cancer Risk
Authors: Bean Gregory R. , Ibarra Drendall Catherine , Goldenberg Vanessa K. , Baker Joseph C. , Troch Michelle M. , Paisie Carolyn , Wilke Lee G. , Yee Lisa , Marcom Paul K. , Kimler Bruce F. , Fabian Carol J. , Zalles Carola M. , Broadwater Gloria , Scott Victoria , Seewaldt Victoria L. 
Published: January 2007

AbstractMutation of the breast cancer–associated gene 1 (BRCA1) plays an important role in familial breast cancer. Although hypermethylation of the BRCA1 promoter has been observed in sporadic breast cancer, its exact role in breast cancer initiation and association with breast cancer risk is unknown. The frequency of BRCA1 promoter hypermethylation was tested in (a) 14 primary breast cancer biopsies and (b) the initial random periareolar fine-needle aspiration (RPFNA) cytologic samples obtained from 61 asymptomatic women who were at increased risk for breast cancer. BRCA1 promoter hypermethylation was assessed from nucleotide −150 to nucleotide +32 relative to the transcription start site. RPFNA specimens were stratified for cytologic atypia using the Masood cytology index. BRCA1 promoter hypermethylation was observed at similar frequency in nonproliferative (normal; Masood ≤10: 18%, 2 of 11), hyperplastic (Masood 11-13: 15%, 6 of 41), and atypical cytology (Masood 14-17: 22%, 4 of 18; P = 0.79). BRCA1 promoter hypermethylation was not associated with (a) family history of breast or ovarian cancer or (b) calculated Gail or BRCAPRO risk score. BRCA1 promoter hypermethylation was associated with (a) age (P = 0.028) and (b) the combined frequency of promoter hypermethylation of the retinoic acid receptor-β2 (RARB) gene, estrogen receptor-α (ESR1) gene, and p16 (INK4A) gene (P = 0.003). These observations show that BRCA1 promoter hypermethylation (a) is not associated with breast cancer risk as measured by mathematical risk models and (b) does not predict mammary atypia in RPFNA cytologic samples obtained from high-risk women. (Cancer Epidemiol Biomarkers Prev 2007;16(1):50–6)
Early Detection of Head and Neck Cancer: Development of a Novel Screening Tool Using Multiplexed Immunobead-Based Biomarker Profiling
Authors: Linkov Faina , Lisovich Alex , Yurkovetsky Zoya , Marrangoni Adele , Velikokhatnaya Lyudmila , Nolen Brian , Winans Matthew , Bigbee William , Siegfried Jill , Lokshin Anna , Ferris Robert L. 
Published: January 2007

Abstract
Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease that has been linked to altered immune, inflammatory, and angiogenesis responses. A better understanding of these aberrant responses might improve early detection and prognosis of SCCHN and provide novel therapeutic targets. Previous studies examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera. We hypothesized that an expanded panel comprised of multiple cytokines, chemokines, growth factors, and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination. Thus, we evaluated a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple serum biomarkers. Concentrations of 60 cytokines, growth factors, and tumor antigens were measured in the sera of 116 SCCHN patients before treatment (active disease group), 103 patients who were successfully treated (no evidence of disease group), and 117 smoker controls without evidence of cancer. The multimarker panel offering the highest diagnostic power was comprised of 25 biomarkers, including epidermal growth factor, epidermal growth factor receptor, interleukin (IL)-8, tissue plasminogen activator inhibitor-1, α-fetoprotein, matrix metalloproteinase-2, matrix metalloproteinase-3, IFN-α, IFN-γ, IFN-inducible protein-10, regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein-1α, IL-7, IL-17, IL-1 receptor-α, IL-2 receptor, granulocyte colony-stimulating factor, mesothelin, insulin-like growth factor binding protein 1, E-selectin, cytokeratin-19, vascular cell adhesion molecule, and cancer antigen-125. Statistical analysis using an ADE algorithm resulted in a sensitivity of 84.5%, specificity of 98%, and 92% of patients in the active disease group correctly classified from a cross-validation serum set. The data presented show that simultaneous testing using a multiplexed panel of serum biomarkers may present a promising new approach for the early detection of head and neck cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(1):102–7)
Papillary Thyroid Cancer and Polymorphic Variants in TSHR- and RET-Related Genes: a Nested Case-Control Study within a Cohort of U.S. Radiologic Technologists
Authors: Lönn Stefan , Bhatti Parveen , Alexander Bruce H. , Pineda Marbin A. , Doody Michele M. , Struewing Jeffery P. , Sigurdson Alice J. 
Published: January 2007

Abstract
Several variants in the TSHR and RET signaling pathways genes have been reported to be related to cancer risk. We hypothesized that polymorphic variants in these genes are associated with the risk of papillary thyroid cancer. A nested case-control study was conducted within the U.S. Radiologic Technologists cohort. Eligible validated papillary thyroid cancer cases (n = 167) and frequency-matched (by sex and birth year) controls (n = 491) donated blood for analysis. There were no statistically significant associations between papillary thyroid cancer and 10 selected polymorphic variants in analyses of men and women combined. A borderline significant increasing risk was found for RET G691S (Ptrend = 0.05) and was especially pronounced among young women. For women under 38 years (the median age at diagnosis), the odds ratios were 2.1 (95% confidence interval, 1.2-3.7) for those heterozygous for the RET G691S polymorphism and 3.7 (95% confidence interval, 1.1-11.8) for those who were homozygous (Ptrend = 0.001). Our data provide limited evidence that TSHR- and RET-related genes are related to papillary thyroid cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(1):174–7)
Incessant Ovulation, Mucin 1 Immunity, and Risk for Ovarian Cancer
Authors: Terry Kathryn L. , Titus-Ernstoff Linda , McKolanis John R. , Welch William R. , Finn Olivera J. , Cramer Daniel W. 
Published: January 2007

Abstract
Background: Risk for ovarian cancer correlates directly with “ovulatory years or cycles” estimated from time not pregnant, breast-feeding, or using oral contraceptives. Recently, we reported that several factors known to reduce ovarian cancer risk may operate by inducing antibodies against mucin 1 (MUC1), a glycoprotein overexpressed in ovarian cancer. Conversely, other events might increase risk by interfering with the development of protective immunity. In this study, we examined whether the total number of ovulatory cycles decreases the likelihood of anti-MUC1 antibodies and provides an immune basis for the association between “incessant ovulation” and ovarian cancer risk.
Methods: From 1998 to 2003, we enrolled 668 epithelial ovarian cancer cases and 721 controls residing in eastern Massachusetts or New Hampshire, collected information on menstrual and reproductive events, and obtained blood samples from controls to measure anti-MUC1 antibodies. Using logistic regression, we calculated odds ratios to evaluate the influence of reproductive factors, including the estimated lifetime number of ovulatory cycles on ovarian cancer risk and on the presence of MUC1 antibodies in controls.
Results: Overall, we observed that early age at first birth, cycle lengths ≥30 days, and oral contraceptive use increased the likelihood of having anti-MUC1 antibodies. Estimated ovulatory cycles were correlated positively with ovarian cancer risk and inversely with the presence of anti-MUC1 antibodies among controls ages 46 to 60 years.
Conclusions: These data suggest that suppression of MUC1-specific immunity should be considered as an additional explanation for the observation that ovarian cancer risk increases with the lifetime number of ovulatory cycles. (Cancer Epidemiol Biomarkers Prev 2007;16(1):30–5)
Circulating Insulin and C-Peptide Levels and Risk of Breast Cancer among Predominately Premenopausal Women
Authors: Eliassen A. Heather , Tworoger Shelley S. , Mantzoros Christos S. , Pollak Michael N. , Hankinson Susan E. 
Published: January 2007

Abstract
Insulin and insulin resistance have been hypothesized to increase the risk of breast cancer as insulin increases breast cell proliferation and inhibits sex hormone binding globulin. Although insulin is directly related to body weight, adiposity is inversely associated with breast cancer risk in premenopausal women but directly related to risk in postmenopausal women. To explore the association between insulin and c-peptide levels and breast cancer risk, we conducted a nested case-control study of predominantly premenopausal women within the Nurses' Health Study II cohort. From 1996 to 1999, blood samples were collected from 29,611 participants. A total of 317 cases were diagnosed after blood collection and before June 2003 and matched to 634 controls; 75% of these women were premenopausal at blood collection. Logistic regression models, controlling for breast cancer risk factors, were used to calculate relative risks (RR) and 95% confidence intervals (95% CI). Among women with fasting blood samples (n = 211 cases), insulin was suggestively inversely associated with breast cancer risk (highest versus lowest quartile: RR, 0.5; 95% CI, 0.3-1.0; Ptrend = 0.06). Among all women, c-peptide was not associated with breast cancer risk (highest versus lowest quartile: RR, 1.1; 95% CI, 0.7-1.7; Ptrend = 0.79); results were similar among fasting samples. These associations did not differ by age, body mass index, or waist-to-hip ratio. Overall, higher levels of insulin and c-peptide were not associated with a higher risk of breast cancer among predominantly premenopausal women. (Cancer Epidemiol Biomarkers Prev 2007;16(1):161–4)
Viral Determinants of Human Papillomavirus Persistence following Loop Electrical Excision Procedure Treatment for Cervical Intraepithelial Neoplasia Grade 2 or 3
Authors: Kreimer Aimée R. , Katki Hormuzd A. , Schiffman Mark , Wheeler Cosette M. , Castle Philip E. ,   for the ASCUS-LSIL Triage Study Group
Published: January 2007

Abstract
Background: Persistent infection with carcinogenic human papillomavirus (HPV) causes cervical precancer (cervical intraepithelial neoplasia grade 2+) which, in the United States, is commonly treated using the loop electrical excision procedure (LEEP). Data from Atypical Squamous Cells of Undetermined Significance–Low-Grade Squamous Intraepithelial Lesion Triage Study were used to evaluate HPV persistence and reappearance after LEEP.
Methods: Cervical specimens, collected before LEEP and at 6-month study visits, were tested by L1-PCR for detection of ≥27 HPV types. HPV persistence, defined as the same HPV type being present before and 6 months after LEEP, was evaluated by: (a) genotype, (b) carcinogenicity, and (c) phylogenetic species. HPV infections that cleared post-LEEP (the complement of persistence) were followed for reappearance of the same type.
Results: HPV infections (n = 1,130) were detected among 481 women who underwent LEEP. Overall, 20.4% [95% confidence interval (95% CI), 18.2-22.9%] of infections persisted. Assessment of heterogeneity within the three categorizations of HPV showed that phylogenetic species best fit the data. Persistence was significantly greater by HPV types in the α3 species [all are noncarcinogenic; 40.9% (95% CI, 31.8-50.4%)] compared with HPV types in the α9 (HPV16 and related types) and α7 species (HPV18 and related types; 17.6% and 17.9%, respectively; P &lt; 0.001 for both). HPV reappeared in 7.8% (95% CI, 6.1-9.9%) of infections that cleared after LEEP. Infections in the α3 species (22.6%) were the most likely to reappear compared with HPV types in the α9 (7.5%) and α7 (6.8%) species.
Conclusions: Patterns of HPV persistence and reappearance following LEEP were better explained by phylogenetic rather than standard classifications. HPV types likely to persist after LEEP as well as those likely to repopulate the cervical/vaginal epithelium were those in the α3 species, which are in effect not treated, but are not associated with cervical cancer and are unlikely to cause disease. (Cancer Epidemiol Biomarkers Prev 2007;16(1):11–6)
Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation
Authors: Marrocco Deborah L. , Tilley Wayne D. , Bianco-Miotto Tina , Evdokiou Andreas , Scher Howard I. , Rifkind Richard A. , Marks Paul A. , Richon Victoria M. , Butler Lisa M. 
Published: January 2007

Abstract
Growth of prostate cancer cells is initially dependent on androgens, and androgen ablation therapy is used to control tumor growth. Unfortunately, resistance to androgen ablation therapy inevitably occurs, and there is an urgent need for better treatments for advanced prostate cancer. Histone deacetylase inhibitors, such as suberoylanilide hydroxamic acid (SAHA; vorinostat), are promising agents for the treatment of a range of malignancies, including prostate cancer. SAHA inhibited growth of the androgen-responsive LNCaP prostate cancer cell line at low micromolar concentrations and induced caspase-dependent apoptosis associated with chromatin condensation, DNA fragmentation, and mitochondrial membrane depolarization at higher concentrations (≥5 μmol/L). Gene profiling and immunoblot analyses showed a decrease in androgen receptor (AR) mRNA and protein in LNCaP cells cultured with SAHA compared with control cells, with a corresponding decrease in levels of the AR-regulated gene, prostate-specific antigen. Culture of LNCaP cells in steroid-free medium markedly sensitized the cells to SAHA. Moreover, a combination of low, subeffective doses of SAHA and the AR antagonist bicalutamide resulted in a synergistic reduction in cell proliferation and increase in caspase-dependent cell death. Addition of exogenous androgen prevented the induction of cell death, indicating that suppression of androgen signaling was required for synergy. At the subeffective concentrations, these agents had no effect, alone or in combination, on proliferation or death of AR-negative PC-3 prostate cancer cells. Our findings indicate that SAHA is effective in targeting the AR signaling axis and that androgen deprivation sensitizes prostate cancer cells to SAHA. Consequently, combinatorial treatments that target different components of the AR pathway may afford a more effective strategy to control the growth of prostate cancer cells. [Mol Cancer Ther 2007;6(1):51–60]
Characterization of a potent and selective small-molecule inhibitor of the PIM1 kinase
Authors: Holder Sheldon , Zemskova Marina , Zhang Chao , Tabrizizad Maryam , Bremer Ryan , Neidigh Jonathan W. , Lilly Michael B. 
Published: January 2007

Abstract
The pim-1 kinase is a true oncogene that has been implicated in the development of leukemias, lymphomas, and prostate cancer, and is the target of drug development programs. We have used experimental approaches to identify a selective, cell-permeable, small-molecule inhibitor of the pim-1 kinase to foster basic and translational studies of the enzyme. We used an ELISA-based kinase assay to screen a diversity library of potential kinase inhibitors. The flavonol quercetagetin (3,3′,4′,5,6,7-hydroxyflavone) was identified as a moderately potent, ATP-competitive inhibitor (IC50, 0.34 μmol/L). Resolution of the crystal structure of PIM1 in complex with quercetagetin or two other flavonoids revealed a spectrum of binding poses and hydrogen-bonding patterns in spite of strong similarity of the ligands. Quercetagetin was a highly selective inhibitor of PIM1 compared with PIM2 and seven other serine-threonine kinases. Quercetagetin was able to inhibit PIM1 activity in intact RWPE2 prostate cancer cells in a dose-dependent manner (ED50, 5.5 μmol/L). RWPE2 cells treated with quercetagetin showed pronounced growth inhibition at inhibitor concentrations that blocked PIM1 kinase activity. Furthermore, the ability of quercetagetin to inhibit the growth of other prostate epithelial cell lines varied in proportion to their levels of PIM1 protein. Quercetagetin can function as a moderately potent and selective, cell-permeable inhibitor of the pim-1 kinase, and may be useful for proof-of-concept studies to support the development of clinically useful PIM1 inhibitors. [Mol Cancer Ther 2007;6(1):163–72]
Baseline Disease Activity, Hyperlipidemia, and Hypertension Are Predictive Factors for Ischemic Stroke and Stroke Severity in Systemic Lupus Erythematosus
Authors: Mikdashi Jamal , Handwerger Barry , Langenberg Patricia , Miller Michael , Kittner Steven 
Published: January 2007

Background and Purpose—To determine factors associated with ischemic stroke and stroke severity in patients with systemic lupus erythematosus.Methods—Between 1992 and January 2005, 238 consecutive systemic lupus erythematosus patients with no history of stroke were followed-up longitudinally at the Maryland Lupus Clinic. Patients were monitored quarterly for a mean of 8 years after their systemic lupus erythematosus diagnosis, and 44 patients (19%) developed first-ever ischemic stroke. At the end of study, Cox proportional regression analyses were used to determine the effect of baseline clinical variables of systemic lupus erythematosus patients in relation to the subsequent occurrence of ischemic stroke and stroke severity after first-ever ischemic strokes. Severe stroke was defined as having a National Institute of Health Stroke Scale ≥6.Results—Severe ischemic strokes occurred in 34 of 44 (77%) patients. Baseline predictors of ischemic strokes and severe ischemic strokes included disease activity, hyperlipidemia, and hypertension.Conclusions—Severe ischemic strokes in systemic lupus erythematosus are not uncommon. Aggressive primary and secondary stroke prevention measures, particularly treatment of hyperlipidemia and hypertension, as well as vigorous treatment of clinical symptoms of active lupus, are needed to prevent serious morbidity and neurological disability.
Effects of Initial Graft Tension on the Tibiofemoral Compressive Forces and Joint Position after Anterior Cruciate Ligament Reconstruction
Authors: Brady Mark F. , Bradley Michael P. , Fleming Braden C. , Fadale Paul D. , Hulstyn Michael J. , Banerjee Rahul 
Published: January 2007

Background The initial tension applied to an anterior cruciate ligament graft at the time of fixation modulates knee motion and the tibiofemoral compressive loads. Purpose To establish the relationships between initial graft tension, tibiofemoral compressive force, and the neutral tibiofemoral position in the cadaveric knee. Study Design Controlled laboratory study. Methods The tibiofemoral compressive forces and joint positions were determined in the anterior cruciate ligament-intact knee at 0°, 20°, and 90° of knee flexion. The anterior cruciate ligament was excised and reconstructed with a patellar tendon graft using graft tensions of 1, 15, 30, 60, and 90 N applied at 0°, 20°, and 90° of knee flexion. The compressive forces and neutral positions were compared between initial tension conditions and the anterior cruciate ligament-intact knee. Results Increasing initial graft tension increased the tibiofemoral compressive forces. The forces in the medial compartment were 1.8 times those in the lateral compartment. The compressive forces were dependent on the knee angle at which the tension was applied. The greatest compressive forces occurred when the graft was tensioned with the knee in extension. An increase in initial graft tension caused the tibia to rotate externally compared with the anterior cruciate ligament-intact knee (1.5° and 7.7° of external rotation when tensioned to 90 N at 0° and 90° of knee flexion, respectively). Increases in initial graft tension also caused a significant posterior translation of the tibia relative to the femur (0.9 and 5.3 mm of posterior translation when tensioned to 90 N at 0° and 90° of knee flexion, respectively). Conclusion Different initial graft tension protocols produced predictable changes in the tibiofemoral compressive forces and joint positions. Clinical Relevance The tibiofemoral compressive force and neutral joint position were best replicated with a low graft tension (1-15 N) when using a patellar tendon graft.
Biomechanical Analysis of Femoral Tunnel Pull-out Angles for Anterior Cruciate Ligament Reconstruction with Bioabsorbable and Metal Interference Screws
Authors: Zhang Alan L. , Lewicky Yuri M. , Oka Richard , Mahar Andrew , Pedowitz Robert 
Published: January 2007

Background Fixation strength of metal and bioabsorbable interference screws has not been evaluated while varying the anterior cruciate ligament graft tension angle. Hypothesis There is no difference in fixation strength between 2 types of interference screws for anterior cruciate ligament graft fixation while the graft tension angle is varied relative to the femoral tunnel. Study Design Controlled laboratory study. Methods Forty-eight anterior cruciate ligament reconstructions were performed using immature porcine femurs stripped of soft tissue and doubled-over porcine flexor digitorum profundus tendon grafts. Specimens were randomized to bioabsorbable or titanium interference screw fixation. Specimens were randomized to one of three pull angles (0°, 30°, 60°) representing loading at different knee flexion angles (n = 8/group). Reconstructed ligaments were tensioned to 10 N followed by 200 loading cycles between 10 and 150 N and a final failure test. Construct elongation (mm) at 100 and 200 cycles and failure load (N) were analyzed using a 2-way analysis of variance (P < .05). Results Screw material interacted significantly with graft tension angle, as the bioabsorbable screw specimens demonstrated significantly greater fixation strength when tensioned at greater angles. Specimens fixed with bioabsorbable screws showed significantly less elongation at both 100 and 200 cycles and significantly greater failure load compared with titanium screws. Conclusion Bioabsorbable interference screws acutely have increased fixation strength compared with titanium interference screws for anterior cruciate ligament grafts loaded at greater tension angles. Clinical Relevance The strength of anterior cruciate ligament reconstruction fixation increases with increasing divergence between the tension angle and femoral tunnel, a condition seen when the knee approaches full extension.
Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation
Authors: Roy Cindy N. , Mak Howard H. , Akpan Imo , Losyev Grigoriy , Zurakowski David , Andrews Nancy C. 
Published: January 2007

Abstract
The anemia of inflammation is an acquired disorder affecting patients with a variety of medical conditions, and it is characterized by changes in iron homeostasis and erythropoiesis. Mounting evidence suggests that hepcidin antimicrobial peptide plays a primary role in the pathogenesis of the anemia of inflammation. To evaluate which features of this anemia can be attributed to hepcidin, we have generated mice carrying a tetracycline-regulated hepcidin transgene. Expression of the hepcidin transgene resulted in down-regulation of endogenous hepcidin mRNA. The transgenic mice developed a mild-to-moderate anemia associated with iron deficiency and iron-restricted erythropoiesis. Similar to the anemia of inflammation, iron accumulated in tissue macrophages, whereas a relative paucity of iron was found in the liver. Circulating erythrocytes in transgenic animals had normal survival rates, but transgenic animals had an impaired response to erythropoietin. Thus, hepcidin transgenic mice recapitulate each of the key features of anemia of inflammation in human patients and serve as a useful model of this prevalent disorder.