bluuebunny/crossref_metadata_2025_split huggingface dataset:
The alanine detector in BNCT dosimetry: Dose response in thermal and epithermal neutron fields
Authors: Schmitz T. , Bassler N. , Blaickner M. , Ziegner M. , Hsiao M. C. , Liu Y. H. , Koivunoro H. , Auterinen I. , Serén T. , Kotiluoto P. , Palmans H. , Sharpe P. , Langguth P. , Hampel G. 
Published: December 2014

Purpose:The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed.Methods:Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a 60Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes fluka and mcnp. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen & Olsen alanine response model.Results:The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields.Conclusions:The alanine detector can be used without difficulty in neutron fields. The response has been understood with the model used which includes the relative effectiveness. Results and the corresponding discussion lead to the conclusion that application in neutron fields for medical purpose is limited by its sensitivity but that it is a useful tool as supplement to other detectors and verification of neutron source descriptions.
Interspinous process device versus standard conventional surgical decompression for lumbar spinal stenosis: randomised controlled trial
Authors: Moojen Wouter A , Arts Mark P , Jacobs Wilco C H , van Zwet Erik W , van den Akker-van Marle M Elske , Koes Bart W , Vleggeert-Lankamp Carmen L A M , Peul Wilco C 
Published: December 2014

STUDY QUESTIONIs interspinous process device implantation more effective in the short term (eight weeks) than conventional surgical decompression for patients with intermittent neurogenic claudication due to lumbar spinal stenosis?SUMMARY ANSWERThe use of interspinous implants did not result in a better outcome than conventional decompression, but the reoperation rate was significantly higher.WHAT IS KNOWN AND WHAT THIS PAPER ADDSBony decompression and treatment with interspinous process devices are superior to conservative and non-surgical treatment for intermittent neurogenic claudication due to lumbar spinal stenosis. Interspinous implants surgery is not superior to bony decompression, and the reoperation rate is significantly higher.
Accelerated Tumor Progression in Mice Lacking the ATP Receptor P2X7
Authors: Adinolfi Elena , Capece Marina , Franceschini Alessia , Falzoni Simonetta , Giuliani Anna L. , Rotondo Alessandra , Sarti Alba C. , Bonora Massimo , Syberg Susanne , Corigliano Domenica , Pinton Paolo , Jorgensen Niklas R. , Abelli Luigi , Emionite Laura , Raffaghello Lizzia , Pistoia Vito , Di Virgilio Francesco 
Published: December 2014

AbstractThe ATP receptor P2X7 (P2X7R or P2RX7) has a key role in inflammation and immunity, but its possible roles in cancer are not firmly established. In the present study, we investigated the effect of host genetic deletion of P2X7R in the mouse on the growth of B16 melanoma or CT26 colon carcinoma cells. Tumor size and metastatic dissemination were assessed by in vivo calliper and luciferase luminescence emission measurements along with postmortem examination. In P2X7R-deficient mice, tumor growth and metastatic spreading were accelerated strongly, compared with wild-type (wt) mice. Intratumoral IL-1β and VEGF release were drastically reduced, and inflammatory cell infiltration was abrogated nearly completely. Similarly, tumor growth was also greatly accelerated in wt chimeric mice implanted with P2X7R-deficient bone marrow cells, defining hematopoietic cells as a sufficient site of P2X7R action. Finally, dendritic cells from P2X7R-deficient mice were unresponsive to stimulation with tumor cells, and chemotaxis of P2X7R-less cells was impaired. Overall, our results showed that host P2X7R expression was critical to support an antitumor immune response, and to restrict tumor growth and metastatic diffusion. Cancer Res; 75(4); 635–44. ©2014 AACR.
HOXB7 Promotes Malignant Progression by Activating the TGFβ Signaling Pathway
Authors: Liu Shou , Jin Kideok , Hui Yvonne , Fu Jie , Jie Chunfa , Feng Sheng , Reisman David , Wang Qian , Fan Daping , Sukumar Saraswati , Chen Hexin 
Published: December 2014

Abstract
Overexpression of HOXB7 in breast cancer cells induces an epithelial–mesenchymal transition and promotes tumor progression and lung metastasis. However, the underlying mechanisms for HOXB7-induced aggressive phenotypes in breast cancer remain largely unknown. Here, we report that phosphorylation of SMAD3 was detected in a higher percentage in primary mammary tumor tissues from double-transgenic MMTV-Hoxb7/Her2 mice than tumors from single-transgenic Her2/neu mice, suggesting activation of TGFβ/SMAD3 signaling by HOXB7 in breast tumor tissues. As predicted, TGFβ2 was high in four MMTV-Hoxb7/Her2 transgenic mouse tumor cell lines and two breast cancer cell lines transfected with HOXB7, whereas TGFβ2 was low in HOXB7-depleted cells. HOXB7 directly bound to and activated the TGFβ2 promoter in luciferase and chromatin immunoprecipitation assays. Increased migration and invasion as a result of HOXB7 overexpression in breast cancer cells were reversed by knockdown of TGFβ2 or pharmacologic inhibition of TGFβ signaling. Furthermore, knockdown of TGFβ2 in HOXB7-overexpressing MDA-MB-231 breast cancer cells dramatically inhibited metastasis to the lung. Interestingly, HOXB7 overexpression also induced tumor-associated macrophage (TAM) recruitment and acquisition of an M2 tumor-promoting phenotype. TGFβ2 mediated HOXB7-induced activation of macrophages, suggesting that TAMs may contribute to HOXB7-promoted tumor metastasis. Providing clinical relevance to these findings, by real-time PCR analysis, there was a strong correlation between HOXB7 and TGFβ2 expression in primary breast carcinomas. Taken together, our results suggest that HOXB7 promotes tumor progression in a cell-autonomous and non–cell-autonomous manner through activation of the TGFβ signaling pathway. Cancer Res; 75(4); 709–19. ©2014 AACR.
Enterolignan-Producing Phenotypes Are Associated with Increased Gut Microbial Diversity and Altered Composition in Premenopausal Women in the United States
Authors: Hullar Meredith A.J. , Lancaster Samuel M. , Li Fei , Tseng Elizabeth , Beer Karlyn , Atkinson Charlotte , Wähälä Kristiina , Copeland Wade K. , Randolph Timothy W. , Newton Katherine M. , Lampe Johanna W. 
Published: December 2014

Abstract
Background: Lignans in plant foods are metabolized by gut bacteria to the enterolignans, enterodiol (END) and enterolactone (ENL). Enterolignans have biologic activities important to the prevention of cancer and chronic diseases. We examined the composition of the gut microbial community (GMC) as a contributor to human enterolignan exposure.
Methods: We evaluated the association between the GMC in stool, urinary enterolignan excretion, and diet from a 3-day food record in 115 premenopausal (ages 40–45 years) women in the United States. Urinary enterolignans were measured using gas chromatography–mass spectroscopy. The GMC was evaluated using 454 pyrosequencing of the 16S rRNA gene. Sequences were aligned in SILVA (www.arb-silva.de). Operational taxonomic units were identified at 97% sequence similarity. Taxonomic classification was performed and alpha and beta diversity in relationship to ENL production were assessed. Multivariate analysis and regression were used to model the association between enterolignan excretion and the GMC. Bacteria associated with ENL production were identified using univariate analysis and ridge regression.
Results: After adjusting for dietary fiber intake and adiposity, we found a significant positive association between ENL excretion and either the GMC (P = 0.0007), or the diversity of the GMC (P = 0.01). The GMC associated with high ENL production was distinct (UNIFRAC, P &lt; 0.003, MRPP) and enriched in Moryella spp., Acetanaerobacterium spp., Fastidiosipila spp., and Streptobacillus spp.
Conclusion: Diversity and composition of the GMC are associated with increased human exposure to enterolignans.
Impact: Differences in gut microbial diversity and composition explain variation in gut metabolic processes that affect environmental exposures and influence human health. Cancer Epidemiol Biomarkers Prev; 24(3); 546–54. ©2014 AACR.
Baseline Serum β-carotene Concentration and Mortality among Long-Term Asbestos-Exposed Insulators
Authors: Hashim Dana , Gaughan Denise , Boffetta Paolo , Lucchini Roberto G. 
Published: December 2014

AbstractBackground: Although interventional trials demonstrated that moderate-dose β-carotene supplementation increases lung cancer mortality in smokers and asbestos-exposed workers, differences in serum concentrations in absence of supplementation have not been studied in asbestos-exposed workers.Methods: A mortality analysis was performed to assess the relationship of nonsupplemented serum β-carotene to all-cause and cancer mortalities using 1981 to 1983 serum β-carotene concentration measurements from 2,646 U.S. white male insulators (mean age, 57.7 years). Multivariable-adjusted Cox proportional hazard models that included terms for age, duration of asbestos exposure, smoking, season, and region were fitted to estimate mortality HRs and 95% confidence intervals (CI) according to serum β-carotene concentrations.Results: Median follow-up was 12.8 years and 984 (33.8%) subjects died during the follow-up period, including 415 deaths from overall cancer and 219 deaths from lung cancer. The overall mortality HR for a serum β-carotene increase of 10 μg/dL was 0.97 (95% CI, 0.96–0.99). Compared with the lowest quartile, HRs were 0.90 (95% CI, 0.76–1.07) for the second (38–65 μg/dL), 0.80 (95% CI, 0.67–0.96) for the third (66–104 μg/dL), and 0.63 (95% CI, 0.51–0.77) for the highest serum β-carotene quartile (≥105 μg/dL). There was no association between serum β-carotene and overall cancer mortality (HR, 1.00; 95% CI, 0.97–1.02) or lung cancer mortality (HR, 0.99; 95% CI, 0.96–1.02).Conclusions: Higher nonsupplemented serum β-carotene concentrations were negatively associated with all-cause mortality among asbestos-exposed individuals.Impact: Serum β-carotene can be a marker of one or more determinants of reduced mortality in asbestos-exposed workers. Cancer Epidemiol Biomarkers Prev; 24(3); 555–60. ©2014 AACR.
Variation in Levels of the Lung Carcinogen NNAL and Its Glucuronides in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer
Authors: Park Sungshim L. , Carmella Steven G. , Ming Xun , Vielguth Elizabeth , Stram Daniel O. , Le Marchand Loic , Hecht Stephen S. 
Published: December 2014

AbstractBackground: Results of the Multiethnic Cohort (MEC) study demonstrated that, for the same quantity of cigarettes smoked, African Americans and Native Hawaiians have a higher risk of lung cancer compared with whites, whereas Latinos and Japanese Americans have a lower risk. We hypothesize that the uptake and/or metabolism of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could explain the differences in lung cancer risk.Methods: We measured urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides and their sum (total NNAL), biomarkers of NNK uptake, in 2,252 smokers from the MEC. Ethnic-specific geometric means were compared adjusting for age at urine collection, sex, creatinine and total nicotine equivalents, a marker of total nicotine uptake.Results: African Americans had the highest median total NNAL levels (1.80 pmol/mL urine) and Japanese Americans had the lowest (0.914 pmol/mL urine), with intermediate values in the other three groups. Geometric mean of total NNAL in African Americans was also highest, and in Japanese Americans it was lowest; Japanese American geometric mean was statistically different from whites (P = 0.004).Conclusions: African Americans had higher levels of total NNAL per mL urine than whites, while Japanese Americans had lower levels, consistent with lung cancer risk among smokers in these groups. However, our data were not consistent with the high and low lung cancer risks of Native Hawaiian and Latino smokers, respectively.Impact: The higher lung cancer susceptibility of African-American smokers and the lower susceptibility of Japanese-American smokers compared with whites can be explained in part by exposure to the potent lung carcinogen NNK. Cancer Epidemiol Biomarkers Prev; 24(3); 561–9. ©2014 AACR.
Plasma Isoflavones and Risk of Primary Liver Cancer in Japanese Women and Men with Hepatitis Virus Infection: A Nested Case–Control Study
Authors: Michikawa Takehiro , Inoue Manami , Sawada Norie , Tanaka Yasuhito , Yamaji Taiki , Iwasaki Motoki , Shimazu Taichi , Sasazuki Shizuka , Mizokami Masashi , Tsugane Shoichiro 
Published: December 2014

Abstract
Background: Evidence suggests that estrogen plays a preventive role in primary liver cancer development, and it might be thought that isoflavones, which are structurally similar to estrogens and bind to estrogen receptors, are associated with the risk of liver cancer. We investigated this suspected association by measuring plasma concentrations of isoflavones in a nested case–control study of a population-based prospective cohort in Japan.
Methods: From 18,628 target participants ages 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or hepatitis C virus infection at baseline (n = 1,544). Among these, 90 (28 women and 62 men) were newly diagnosed with primary liver cancer from 1993 through 2006; they were matched with 175 controls (54 women and 121 men). Plasma concentrations of isoflavones (genistein, daidzein, glycitein, and equol) were measured using triple quadrupole tandem liquid chromatography-mass spectrometry. The ORs of liver cancer development based on plasma concentrations were estimated with a conditional logistic regression model.
Results: Basically, distributions of plasma isoflavone concentrations did not differ between the cases and controls. No statistically significant associations of genistein, daidzein, glycitein, and equol with primary liver cancer risk were found in either women or men.
Conclusions: In middle-aged Japanese women and men with hepatitis virus infection, plasma isoflavones were unassociated with the occurrence of primary liver cancer.
Impact: The role of isoflavones in liver carcinogenesis merits further study using both biomarkers and data on dietary intake of isoflavones. Cancer Epidemiol Biomarkers Prev; 24(3); 532–7. ©2014 AACR.
Vitamin D–Associated Genetic Variation and Risk of Breast Cancer in the Breast and Prostate Cancer Cohort Consortium (BPC3)
Authors: Mondul Alison M. , Shui Irene M. , Yu Kai , Weinstein Stephanie J. , Tsilidis Konstantinos K. , Joshi Amit D. , Agudo Antonio , Berg Christine D. , Black Amanda , Buring Julie E. , Chasman Daniel I. , Gaudet Mia M. , Haiman Christopher , Hankinson Susan E. , Henderson Brian E. , Hoover Robert N. , Hunter David J. , Khaw Kay-Tee , Kühn Tilman , Kvaskoff Marina , Le Marchand Loic , Lindström Sara , McCullough Marjorie L. , Overvad Kim , Peeters Petra H. , Riboli Elio , Ridker Paul M. , Stram Daniel O. , Sund Malin , Trichopoulos Dimitrios , Tumino Rosario , Weiderpass Elisabete , Willett Walter , Kraft Peter , Ziegler Regina G. , Albanes Demetrius 
Published: December 2014

Abstract
Background: Two recent genome-wide association studies (GWAS) identified SNPs in or near four genes related to circulating 25-hydroxyvitamin D [25(OH)D] concentration. To examine the hypothesized inverse relationship between vitamin D status and breast cancer, we studied the associations between SNPs in these genes and breast cancer risk in a large pooled study of 9,456 cases and 10,816 controls from six cohorts.
Methods: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped and examined both individually and as a 4-SNP polygenic score. Logistic regression was used to estimate the associations between the genetic variants and risk of breast cancer.
Results: We found no association between any of the four SNPs or their polygenic score and breast cancer risk.
Conclusions: Our findings do not support an association between vitamin D status, as reflected by 25(OH)D–related genotypes, and breast cancer risk.
Impact: These findings may contribute to future meta-analyses and scientific review articles, and provide new data about the association between vitamin D–related genes and breast cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 627–30. ©2014 AACR.
Expression, Clinical Significance, and Receptor Identification of the Newest B7 Family Member HHLA2 Protein
Authors: Janakiram Murali , Chinai Jordan M. , Fineberg Susan , Fiser Andras , Montagna Cristina , Medavarapu Ramadevi , Castano Ekaterina , Jeon Hyungjun , Ohaegbulam Kim C. , Zhao Ruihua , Zhao Aimin , Almo Steven C. , Sparano Joseph A. , Zang Xingxing 
Published: December 2014

Abstract
Purpose: HHLA2 (B7H7/B7-H5/B7y) is a newly identified B7 family member that regulates human T-cell functions. However, its protein expression in human organs and significance in human diseases are unknown. The objective of this study was to analyze HHLA2 protein expression in normal human tissues and cancers, as well as its prognostic significance, to explore mechanisms regulating HHLA2 expression, and to identify candidate HHLA2 receptors.
Experimental Design: An immunohistochemistry protocol and a flow cytometry assay with newly generated monoclonal antibodies were developed to examine HHLA2 protein. HHLA2 gene copy-number variation was analyzed from cancer genomic data. The combination of bioinformatics analysis and immunologic approaches was established to explore HHLA2 receptors.
Results: HHLA2 protein was detected in trophoblastic cells of the placenta and the epithelium of gut, kidney, gallbladder, and breast, but not in most other organs. In contrast, HHLA2 protein was widely expressed in human cancers from the breast, lung, thyroid, melanoma, pancreas, ovary, liver, bladder, colon, prostate, kidney, and esophagus. In a cohort of 50 patients with stage I–III triple-negative breast cancer, 56% of patients had aberrant expression of HHLA2 on their tumors, and high HHLA2 expression was significantly associated with regional lymph node metastasis and stage. The Cancer Genome Atlas revealed that HHLA2 copy-number gains were present in 29% of basal breast cancers, providing a potential mechanism for increased HHLA2 protein expression in breast cancer. Finally, Transmembrane and Immunoglobulin Domain Containing 2 (TMIGD2) was identified as one of the receptors for HHLA2.
Conclusions: Wide expression of HHLA2 in human malignancies, together with its association with poor prognostic factors and its T-cell coinhibitory capability, suggests that the HHLA2 pathway represents a novel immunosuppressive mechanism within the tumor microenvironment and an attractive target for human cancer therapy. Clin Cancer Res; 21(10); 2359–66. ©2014 AACR.
See related commentary by Xiao and Freeman, p. 2201
Neuregulin 1 Expression Is a Predictive Biomarker for Response to AV-203, an ERBB3 Inhibitory Antibody, in Human Tumor Models
Authors: Meetze Kristan , Vincent Sylvie , Tyler Steven , Mazsa Elizabeth K. , Delpero Andrea R. , Bottega Steve , McIntosh Donna , Nicoletti Richard , Winston William M. , Weiler Solly , Feng Bin , Gyuris Jeno , Weng Zhigang 
Published: December 2014

Abstract
Purpose: ERBB3 is overexpressed in a broad spectrum of human cancers, and its aberrant activation is associated with tumor pathogenesis and therapeutic resistance to various anticancer agents. Neuregulin 1 (NRG1) is the predominant ligand for ERBB3 and can promote the heterodimerization of ERBB3 with other ERBB family members, resulting in activation of multiple intracellular signaling pathways. AV-203 is a humanized IgG1/κ ERBB3 inhibitory antibody that completed a first-in-human phase I clinical trial in patients with advanced solid tumors. The purpose of this preclinical study was to identify potential biomarker(s) that may predict response to AV-203 treatment in the clinic.
Experimental Design: We conducted in vivo efficacy studies using a broad panel of xenograft models representing a wide variety of human cancers. To identify biomarkers that can predict response to AV-203, the relationship between tumor growth inhibition (TGI) by AV-203 and the expression levels of ERBB3 and NRG1 were evaluated in these tumor models.
Results: A significant correlation was observed between the levels of NRG1 expression and TGI by AV-203. In contrast, TGI was not correlated with ERBB3 expression. The correlation between the levels of NRG1 expression in tumors and their response to ERBB3 inhibition by AV-203 was further validated using patient-derived tumor explant models.
Conclusions: NRG1 is a promising biomarker that can predict response to ERBB3 inhibition by AV-203 in preclinical human cancer models. NRG1 warrants further clinical evaluation and validation as a potential predictive biomarker of response to AV-203. Clin Cancer Res; 21(5); 1106–14. ©2014 AACR.