bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproductive Factors and Exogenous Hormone Use in Relation to Risk of Glioma and Meningioma in a Large European Cohort Study
Authors: Michaud Dominique S. , Gallo Valentina , Schlehofer Brigitte , Tjønneland Anne , Olsen Anja , Overvad Kim , Dahm Christina C. , Kaaks Rudolf , Lukanova Annekatrin , Boeing Heiner , Schütze Madlen , Trichopoulou Antonia , Bamia Christina , Kyrozis Andreas , Sacerdote Carlotta , Agnoli Claudia , Palli Domenico , Tumino Rosario , Mattiello Amalia , Bueno-de-Mesquita H. Bas , Ros Martine M. , Peeters Petra H. M. , van Gils Carla H. , Lund Eiliv , Bakken Kjersti , Gram Inger T. , Barricarte Aurelio , Navarro Carmen , Dorronsoro Miren , Sánchez Maria José , Rodríguez Laudina , Duell Eric J. , Hallmans Göran , Melin Beatrice S. , Manjer Jonas , Borgquist Signe , Khaw Kay-Tee , Wareham Nick , Allen Naomi E. , Tsilidis Konstantinos K. , Romieu Isabelle , Rinaldi Sabina , Vineis Paolo , Riboli Elio 
Published: October 2010

AbstractBackground: The etiologies of glioma and meningioma tumors are largely unknown. Although reproductive hormones are thought to influence the risk of these tumors, epidemiologic data are not supportive of this hypothesis; however, few cohort studies have published on this topic. We examined the relation between reproductive factors and the risk of glioma and meningioma among women in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: After a mean of 8.4 years of follow-up, 193 glioma and 194 meningioma cases were identified among 276,212 women. Information on reproductive factors and hormone use was collected at baseline. Cox proportional hazard regression was used to determine hazard ratios (HR) and 95% confidence intervals (95% CI).Results: No associations were observed between glioma or meningioma risk and reproductive factors, including age at menarche, parity, age at first birth, menopausal status, and age at menopause. A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users. Similarly, current users of oral contraceptives were at higher risk of meningioma than never users (HR, 3.61; 95% CI, 1.75-7.46).Conclusion: Our results do not support a role for estrogens and glioma risk. Use of exogenous hormones, especially current use, seems to increase meningioma risk. However, these findings could be due to diagnostic bias and require confirmation.Impact: Elucidating the role of hormones in brain tumor development has important implications and needs to be further examined using biological measurements. Cancer Epidemiol Biomarkers Prev; 19(10); 2562–9. ©2010 AACR.
Cruciferous Vegetable Intake and Lung Cancer Risk: A Nested Case-Control Study Matched on Cigarette Smoking
Authors: Lam Tram Kim , Ruczinski Ingo , Helzlsouer Kathy J. , Shugart Yin Yao , Caulfield Laura E. , Alberg Anthony J. 
Published: October 2010

Abstract
Background: Due predominantly to cigarette smoking, lung cancer is the leading cancer-related cause of death worldwide. Cruciferous vegetables may reduce lung cancer risk. The association between intake of cruciferous vegetables and lung cancer risk was investigated in the CLUE II study, a community-based cohort established in 1989.
Methods: We matched 274 incident cases of lung cancer diagnosed from 1990 to 2005 to 1,089 cancer-free controls on age, sex, and cigarette smoking. Dietary information was collected at baseline. Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression.
Results: Intake of cruciferous vegetables was inversely associated with lung cancer risk (highest-versus-lowest fourth: OR Q4vsQ1, 0. 57; 95% CI, 0.38-0.85; P-trend = 0.01). The inverse associations held true for former smokers (ORQ4vsQ1, 0.49; 95% CI, 0.27-0.92; P-trend = 0.05) and current smokers (ORQ4vsQ1, 0.52; 95% CI, 0.29-0.95; P-trend = 0.02).
Conclusions: After carefully controlling for cigarette smoking, higher intake of cruciferous vegetable was associated with lower risk of lung cancer.
Impact: The observed inverse association coupled with accumulating evidence suggests that intake of cruciferous vegetables is inversely associated with lung cancer risk, and this association seems to hold true beyond the confounding effects of cigarette smoking. Cancer Epidemiol Biomarkers Prev; 19(10); 2534–40. ©2010 AACR.
High-Throughput Simultaneous Analysis of Five Urinary Metabolites of Areca Nut and Tobacco Alkaloids by Isotope-Dilution Liquid Chromatography-Tandem Mass Spectrometry with On-Line Solid-Phase Extraction
Authors: Hu Chiung-Wen , Chang Yan-Zin , Wang Hsiao-Wen , Chao Mu-Rong 
Published: October 2010

Abstract
Background: Areca nut and tobacco are commonly used drugs worldwide and have been frequently used in combination. We describe the use of on-line solid-phase extraction and isotope-dilution liquid chromatography-tandem mass spectrometry for the simultaneous measurement of five major urinary metabolites of both areca nut and tobacco alkaloids, namely, arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine.
Methods: Automated purification of urine was accomplished with a column-switching device. After the addition of deuterium-labeled internal standards, urine samples were directly analyzed within 13 minutes. This method was applied to measure urinary metabolites in 90 healthy subjects to assess areca nut/tobacco exposure. Urinary time course of arecoline, arecaidine, and N-methylnipecotic acid was investigated in five healthy nonchewers after oral administration of areca nut water extracts.
Results: The limits of detection were 0.016 to 0.553 ng/mL. Interday and intraday imprecision were &lt;10%. Mean recoveries of five metabolites in urine were 97% to 114%. Mean urinary concentrations of arecoline, arecaidine, N-methylnipecotic acid, nicotine, and cotinine in regular areca nut chewers also smokers were 23.9, 5,816, 1,298, 2,635, and 1,406 ng/mg creatinine, respectively. Time course study revealed that after administration of areca nuts extracts, the major urinary metabolite was arecaidine with a half-life of 4.3 hours, followed by N-methylnipecotic acid with a half-life of 7.9 hours, and very low levels of arecoline with a half-life of 0.97 hour.
Conclusions: This on-line solid-phase extraction liquid chromatography-tandem mass spectrometry method firstly provides high-throughput direct analysis of five urinary metabolites of areca nut/tobacco alkaloids.
Impact: This method may facilitate the research into the oncogenic effects of areca nut/tobacco exposure. Cancer Epidemiol Biomarkers Prev; 19(10); 2570–81. ©2010 AACR.
Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development
Authors: Bianco-Miotto Tina , Chiam Karen , Buchanan Grant , Jindal Shalini , Day Tanya K. , Thomas Mervyn , Pickering Marie A. , O'Loughlin Melissa A. , Ryan Natalie K. , Raymond Wendy A. , Horvath Lisa G. , Kench James G. , Stricker Phillip D. , Marshall Villis R. , Sutherland Robert L. , Henshall Susan M. , Gerald William L. , Scher Howard I. , Risbridger Gail P. , Clements Judith A. , Butler Lisa M. , Tilley Wayne D. , Horsfall David J. , Ricciardelli Carmela 
Published: October 2010

Abstract
Background: Epigenetic alterations are common in prostate cancer, yet how these modifications contribute to carcinogenesis is poorly understood. We investigated whether specific histone modifications are prognostic for prostate cancer relapse, and whether the expression of epigenetic genes is altered in prostate tumorigenesis.
Methods: Global levels of histone H3 lysine-18 acetylation (H3K18Ac) and histone H3 lysine-4 dimethylation (H3K4diMe) were assessed immunohistochemically in a prostate cancer cohort of 279 cases. Epigenetic gene expression was investigated in silico by analysis of microarray data from 23 primary prostate cancers (8 with biochemical recurrence and 15 without) and 7 metastatic lesions.
Results: H3K18Ac and H3K4diMe are independent predictors of relapse-free survival, with high global levels associated with a 1.71-fold (P &lt; 0.0001) and 1.80-fold (P = 0.006) increased risk of tumor recurrence, respectively. High levels of both histone modifications were associated with a 3-fold increased risk of relapse (P &lt; 0.0001). Epigenetic gene expression profiling identified a candidate gene signature (DNMT3A, MBD4, MLL2, MLL3, NSD1, and SRCAP), which significantly discriminated nonmalignant from prostate tumor tissue (P = 0.0063) in an independent cohort.
Conclusions: This study has established the importance of histone modifications in predicting prostate cancer relapse and has identified an epigenetic gene signature associated with prostate tumorigenesis.
Impact: Our findings suggest that targeting the epigenetic enzymes specifically involved in a particular solid tumor may be a more effective approach. Moreover, testing for aberrant expression of epigenetic genes such as those identified in this study may be beneficial in predicting individual patient response to epigenetic therapies. Cancer Epidemiol Biomarkers Prev; 19(10); 2611–22. ©2010 AACR.
EML4-ALK Fusion Gene Assessment Using Metastatic Lymph Node Samples Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Authors: Sakairi Yuichi , Nakajima Takahiro , Yasufuku Kazuhiro , Ikebe Dai , Kageyama Hajime , Soda Manabu , Takeuchi Kengo , Itami Makiko , Iizasa Toshihiko , Yoshino Ichiro , Mano Hiroyuki , Kimura Hideki 
Published: October 2010

Abstract
Purpose: Anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes for non–small cell lung cancers (NSCLC). Several ALK inhibitors have been developed, and are now being evaluated in ALK-positive NSCLC. The feasibility of detecting ALK fusion genes in samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was determined. The clinicopathologic characteristics of ALK-positive lung cancer were also analyzed.
Experimental Design: From April 2008 to July 2009, NSCLC cases with hilar/mediastinal lymph node metastases detected by EBUS-TBNA were enrolled. Positive expression of ALK fusion protein was determined using immunohistochemistry, and ALK gene rearrangements were further examined to verify the translocation between ALK and partner genes using fluorescent in situ hybridization and reverse transcription-PCR. Direct sequencing of PCR products was performed to identify ALK fusion variants.
Results: One hundred and nine cases were eligible for the analysis using re-sliced samples. Screening of these specimens with immunohistochemistry revealed ALK positivity in seven cases (6.4%), all of which possessed echinoderm microtubule–associated protein-like 4–ALK fusion genes as detected by fluorescent in situ hybridization and reverse transcription-PCR. All ALK-positive cases had an adenocarcinoma histology and possessed no EGFR mutations. Compared with ALK-negative cases, ALK-positive cases were more likely to have smaller primary tumors (P &lt; 0.05), to occur at a younger age (&lt;60 years; P &lt; 0.05), and to occur in never/light smokers (smoking index &lt; 400; P &lt; 0.01). Mucin production was frequently observed in ALK-positive adenocarcinomas (29.4%; P &lt; 0.01).
Conclusions: EBUS-TBNA is a practical and feasible method for obtaining tissue from mediastinal and hilar lymph nodes that can be subjected to multimodal analysis of ALK fusion genes in NSCLC. Clin Cancer Res; 16(20); 4938–45. ©2010 AACR.
Simultaneous Blockade of Multiple Immune System Inhibitory Checkpoints Enhances Antitumor Activity Mediated by Interleukin-15 in a Murine Metastatic Colon Carcinoma Model
Authors: Yu Ping , Steel Jason C. , Zhang Meili , Morris John C. , Waldmann Thomas A. 
Published: October 2010

Abstract
Purpose: Interleukin 15 (IL-15) is a promising cytokine for immunotherapy of cancer due to its ability to stimulate the immunity of natural killer, B, and T cells. Its effectiveness, however, may be limited by inhibitory checkpoints and pathways that can attenuate immune responses. Finding strategies to abrogate these negative regulators and enhance the efficacy of IL-15 is a critical challenge.
Experimental Design: In a preclinical study, we evaluated IL-15 combined with antibodies to block the negative immune regulators cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death ligand 1 (PD-L1) in a metastatic murine CT26 colon carcinoma model.
Results: IL-15 treatment resulted in a significant prolongation of survival in mice with metastatic tumor. Administration of IL-15, however, also increased expression of PD-1 on the surface of CD8+ T cells including CD8+CD44high memory phenotype T cells. Moreover, IL-15 also increased the secretion of the immunosuppressive cytokine, IL-10. Combining IL-15 with anti-PD-L1 and anti-CTLA-4 (multiple immune checkpoint blockade) exhibited greater CTL killing and IFNγ secretion. Moreover, this combination resulted in a significant reduction in surface expression of PD-1 on CD8+ T cells, a decrease in IL-10 secretion, and led to significantly longer survival of tumor-bearing animals compared with mice treated with IL-15 alone or combined singularly with anti-PD-L1 or anti-CTLA-4.
Conclusions: Combining the immune stimulatory properties of IL-15 with the simultaneous removal of 2 critical immune system inhibitory checkpoints, we showed enhancement of immune responses leading to increased antitumor activity. Clin Cancer Res; 16(24); 6019–28. ©2010 AACR.
The Tissue Is the Issue: Personalized Medicine for Non-Small Cell Lung Cancer
Authors: Hirsch Fred R. , Wynes Murry W. , Gandara David R. , Bunn Paul A. 
Published: October 2010

Abstract
The development of molecular markers is crucial for improving therapy in advanced non-small cell lung cancer (NSCLC). Here, we review perspectives of biomarker-driven personalized therapy in NSCLC, with particular reference to the detection of EML4-ALK gene rearrangements. Different molecular assays, validation, and clinical application to different types of tissue specimens are discussed. Clin Cancer Res; 16(20); 4909–11. ©2010 AACR.
CADPE Inhibits PMA-Stimulated Gastric Carcinoma Cell Invasion and Matrix Metalloproteinase-9 Expression by FAK/MEK/ERK–Mediated AP-1 Activation
Authors: Han Honghui , Du Bing , Pan Xinhua , Liu Junchen , Zhao Qufei , Lian Xiaoyuan , Qian Min , Liu Mingyao 
Published: October 2010

AbstractMetastasis is one of the main causes of death for patients with malignant tumors. Aberrant expression of matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion and metastasis of various cancer cells. Here, we found that caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) could inhibit the migration and invasion of human gastric carcinoma cells in Transwell migration assays. To understand the underlying mechanism, we showed that CADPE significantly inhibited phorbol 12-myristate 13-acetate (PMA)–induced increases in MMP-9 expression and activity in a dose-dependent manner. The inhibitory effect of CADPE on MMP-9 expression correlated well with the suppression of MMP-9 promoter activity and the reduction of MMP-9 mRNA. Reporter gene assay and electrophoretic mobility shift assay showed that CADPE inhibited MMP-9 expression by suppressing the activation of the nuclear transcription factor activator protein-1 (AP-1) and c-Fos, but not NF-κB. Moreover, CADPE inhibited PMA-induced phosphorylation of protein kinases involved in AP-1 activation, such as focal adhesion kinase (FAK), mitogen-activated protein kinase/extracellular signal–regulated kinase (ERK) kinase (MEK), and ERK1/2, whereas CADPE had little effect on the phosphorylation of p38 and c-jun NH2-terminal kinase. Taken together, our findings indicate that CADPE could be a unique antitumor agent that specifically inhibits MMP-9 activity by targeting the activation of FAK/MEK/ERK protein kinases and AP-1 transcription factor. Mol Cancer Res; 8(11); 1477–88. ©2010 AACR.
A Mouse Model for Human Anal Cancer
Authors: Stelzer Marie K. , Pitot Henry C. , Liem Amy , Schweizer Johannes , Mahoney Charles , Lambert Paul F. 
Published: October 2010

Abstract
Human anal cancers are associated with high-risk human papillomaviruses (HPV) that cause other anogenital cancers and head and neck cancers. As with other cancers, HPV16 is the most common high-risk HPV in anal cancers. We describe the generation and characterization of a mouse model for human anal cancer. This model makes use of K14E6 and K14E7 transgenic mice in which the HPV16 E6 and E7 genes are directed in their expression to stratified squamous epithelia. HPV16 E6 and E7 possess oncogenic properties including, but not limited to, their capacity to inactivate the cellular tumor suppressors p53 and pRb, respectively. Both E6 and E7 were found to be functionally expressed in the anal epithelia of K14E6/K14E7 transgenic mice. To assess the susceptibility of these mice to anal cancer, mice were treated topically with dimethylbenz[a]anthracene (DMBA), a chemical carcinogen that is known to induce squamous cell carcinomas in other sites. Nearly 50% of DMBA-treated HPV16 E6/E7 transgenic mice showed overt signs of tumors, whereas none of the like-treated nontransgenic mice showed tumors. Histopathologic analyses confirmed that the HPV16 transgenic mice were increased in their susceptibility to anal cancers and precancerous lesions. Biomarker analyses demonstrated that these mouse anal cancers exhibit properties that are similar to those observed in HPV-positive precursors to human anal cancer. This is the first mouse model for investigating the contributions of viral and cellular factors in anal carcinogenesis, and should provide a platform for assessing new therapeutic modalities for treating and/or preventing this type of cancer. Cancer Prev Res; 3(12); 1534–41. ©2010 AACR.
Low Hemoglobin A1c and Risk of All-Cause Mortality Among US Adults Without Diabetes
Authors: Carson April P. , Fox Caroline S. , McGuire Darren K. , Levitan Emily B. , Laclaustra Martin , Mann Devin M. , Muntner Paul 
Published: October 2010

Background—
Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c.

Methods and Results—
National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76).

Conclusions—
In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.
Board multimodal vibration control using piezoelectric synchronized switch damping techniques
Authors: Richard Thibaut , Magnet Christophe , Richard Claude , Guyomar Daniel 
Published: October 2010

Several types of vibration control using piezoelectric materials exist. The method used here is Synchronized Switching Damping (SSD). It offers several advantages, for example a multimodal damping is achievable without complex circuits. This paper deals with the application of the SSD techniques to the vibration control of a clamped board. An example of possible application is an embedded electronic Printed Circuit Board. The experimental structure is exposed. A model taking into account the multimodal behaviour of the structure is then developed. After that, two different improvements are presented in order for the SSD techniques to accept a multimodal excitation. Finally, theoretical and experimental results are compared. Both show an attenuation of, respectively, 20 dB, 6 dB and 8 dB on the three first flexion modes of the board simultaneously.
Secondary solid cancers after allogeneic hematopoietic cell transplantation using busulfan-cyclophosphamide conditioning
Authors: Majhail Navneet S. , Brazauskas Ruta , Rizzo J. Douglas , Sobecks Ronald M. , Wang Zhiwei , Horowitz Mary M. , Bolwell Brian , Wingard John R. , Socie Gerard 
Published: October 2010

AbstractRisks of secondary solid cancers among allogeneic hematopoietic cell transplant (HCT) recipients who receive conditioning without total body irradiation are not well known. We evaluated the incidence and risk factors for solid cancers after HCT using high-dose busulfan-cyclophosphamide conditioning in 4318 recipients of first allogeneic HCT for acute myeloid leukemia in first complete remission (N = 1742) and chronic myeloid leukemia in first chronic phase (N = 2576). Our cohort represented 22 041 person-years at risk. Sixty-six solid cancers were reported at a median of 6 years after HCT. The cumulative-incidence of solid cancers at 5 and 10 years after HCT was 0.6% and 1.2% among acute myeloid leukemia and 0.9% and 2.4% among chronic myeloid leukemia patients. In comparison to general population incidence rates, HCT recipients had 1.4× higher than expected rate of invasive solid cancers (95% confidence interval, 1.08-1.79, P = .01). Significantly elevated risks were observed for tumors of the oral cavity, esophagus, lung, soft tissue, and brain. Chronic graft-versus-host disease was an independent risk factor for all solid cancers, and especially cancers of the oral cavity. Recipients of allogeneic HCT using busulfan-cyclophosphamide conditioning are at risk for developing solid cancers. Their incidence continues to increase with time, and lifelong cancer surveillance is warranted in this population.