bluuebunny/crossref_metadata_2025_split huggingface dataset:
FluMum: a prospective cohort study of mother–infant pairs assessing the effectiveness of maternal influenza vaccination in prevention of influenza in early infancy
Authors: O'Grady Kerry-Ann F , McHugh Lisa , Nolan Terry , Richmond Peter , Wood Nicholas , Marshall Helen S , Lambert Stephen B , Chatfield Mark , Andrews Ross M 
Published: June 2014

IntroductionInfluenza vaccination in pregnancy is recommended for all women in Australia, particularly those who will be in their second or third trimester during the influenza season. However, there has been no systematic monitoring of influenza vaccine uptake among pregnant women in Australia. Evidence is emerging of benefit to the infant with respect to preventing influenza infection in the first 6 months of life. The FluMum study aims to systematically monitor influenza vaccine uptake during pregnancy in Australia and determine the effectiveness of maternal vaccination in preventing laboratory-confirmed influenza in their offspring up to 6 months of age.Methods and analysisA prospective cohort study of 10 106 mother–infant pairs recruited between 38 weeks gestation and 55 days postdelivery in six Australian capital cities. Detailed maternal and infant information is collected at enrolment, including influenza illness and vaccination history with a follow-up data collection time point at infant age 6 months. The primary outcome is laboratory-confirmed influenza in the infant. Case ascertainment occurs through searches of Australian notifiable diseases data sets once the infant turns 6 months of age (with parental consent). The primary analysis involves calculating vaccine effectiveness against laboratory-confirmed influenza by comparing the incidence of influenza in infants of vaccinated mothers to the incidence in infants of unvaccinated mothers. Secondary analyses include annual and pooled estimates of the proportion of mothers vaccinated during pregnancy, the effectiveness of maternal vaccination in preventing hospitalisation for acute respiratory illness and modelling to assess the determinants of vaccination.Ethics and disseminationThe study was approved by all institutional Human Research Ethics Committees responsible for participating sites. Study findings will be published in peer review journals and presented at national and international conferences.Trial registration numberThe study is registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR) number: 12612000175875.
Next-generation sequencing reveals frequent consistent genomic alterations in small cell undifferentiated lung cancer
Authors: Ross J S , Wang K , Elkadi O R , Tarasen A , Foulke L , Sheehan C E , Otto G A , Palmer G , Yelensky R , Lipson D , Chmielecki J , Ali S M , Elvin J , Morosini D , Miller V A , Stephens P J 
Published: June 2014

AimsSmall cell lung cancer (SCLC) carries a poor prognosis, and the systemic therapies currently used as treatments are only modestly effective, as demonstrated by a low 5-year survival at only ∼5%. In this retrospective collected from March 2013 to study, we performed comprehensive genomic profiling of 98 small cell undifferentiated lung cancer (SCLC) samples to identify potential targets of therapy not currently searched for in routine clinical practice.MethodsDNA from 98 SCLC was sequenced to high, uniform coverage (Illumina HiSeq 2500) and analysed for all classes of genomic alterations.ResultsA total of 386 alterations were identified for an average of 3.9 alterations per tumour (range 1–10). Fifty-two (53%) of cases harboured at least 1 actionable alteration with the potential to personalise therapy including base substitutions, amplifications or homozygous deletions inRICTOR(10%),KIT(7%),PIK3CA(6%),EGFR(5%),PTEN(5%),KRAS(5%),MCL1(4%),FGFR1(4%),BRCA2,(4%),TSC1(3%), NF1(3%),EPHA3(3%)and CCND1.The most common non-actionable genomic alterations were alterations inTP53(86% of SCLC cases),RB1(54%) andMLL2(17%).ConclusionsGreater than 50% of the SCLC cases harboured at least one actionable alteration. Given the limited treatment options and poor prognosis of patients with SCLC, comprehensive genomic profiling has the potential to identify new treatment paradigms and meet an unmet clinical need for this disease.
Mebeverine for Pediatric Functional Abdominal Pain: A Randomized, Placebo-Controlled Trial
Authors: Pourmoghaddas Zahra , Saneian Hossein , Roohafza Hamidreza , Gholamrezaei Ali 
Published: June 2014

We evaluated the effectiveness of an antispasmodic, mebeverine, in the treatment of childhood functional abdominal pain (FAP). Children with FAP (n = 115, aged 6–18 years) received mebeverine (135 mg, twice daily) or placebo for 4 weeks. Response was defined as ≥2 point reduction in the 6-point pain scale or “no pain.” Physician-rated global severity was also evaluated. Patients were followed up for 12 weeks. Eighty-seven patients completed the trial (44 with mebeverine). Per-protocol and intention-to-treat (ITT) analyses were conducted. Treatment response rate in the mebeverine and placebo groups based on per-protocol [ITT] analysis was 54.5% [40.6%] and 39.5% [30.3%] at week 4 (P = 0.117[0.469]) and 72.7% [54.2%] and 53.4% [41.0] at week 12, respectively (P = 0.0503[0.416]). There was no significant difference between the two groups in change of the physician-rated global severity score after 4 weeks (P = 0.723) or after 12 weeks (P = 0.870) in per-protocol analysis; the same results were obtained in ITT analysis. Mebeverine seems to be effective in the treatment of childhood FAP, but our study was not able to show its statistically significant effect over placebo. Further trials with larger sample of patients are warranted.
TRIB1 Supports Prostate Tumorigenesis and Tumor-Propagating Cell Survival by Regulation of Endoplasmic Reticulum Chaperone Expression
Authors: Mashima Tetsuo , Soma-Nagae Taeko , Migita Toshiro , Kinoshita Ryoko , Iwamoto Atsushi , Yuasa Takeshi , Yonese Junji , Ishikawa Yuichi , Seimiya Hiroyuki 
Published: June 2014

Abstract
Endocrine therapy is the standard treatment for advanced prostate cancer; however, relapse occurs in most patients with few treatment options available after recurrence. To overcome this therapeutic hurdle, the identification of new molecular targets is a critical issue. The capability to proliferate in three-dimensional (3D) conditions is a characteristic property of cancer cells. Therefore, factors that regulate 3D growth are considered rational targets for cancer therapy. Here, we applied a functional genomic approach to the 3D spheroid cell culture model and identified TRIB1, a member of the Trib family of serine/threonine kinase-like proteins, as an essential factor for prostate cancer cell growth and survival. RNAi-mediated silencing of TRIB1 suppressed prostate cancer cell growth selectively under the 3D conditions. This effect was rescued by ectopic expression of an RNAi-resistant TRIB1 exogene. Gene signature–based analysis revealed that TRIB1 was related to endoplasmic reticulum (ER) pathways in prostate cancer and was required for expression of the ER chaperone GRP78, which is critical for prostate tumorigenesis. Of note, GRP78 was expressed preferentially in a subpopulation of prostate cancer cells that possess tumor-propagating potential, and these tumor-propagating cells were highly sensitive to TRIB1 and GRP78 depletion. In a xenograft model of human prostate cancer, TRIB1 depletion strongly inhibited tumor formation. Supporting these observations, we documented frequent overexpression of TRIB1 in clinical specimens of prostate cancer. Overall, our results indicated that the TRIB1–ER chaperone axis drives prostate tumorigenesis and the survival of the tumor-propagating cells. Cancer Res; 74(17); 4888–97. ©2014 AACR.
Characteristics of Adenomas Detected by Fecal Immunochemical Test in Colorectal Cancer Screening
Authors: Cubiella Joaquín , Castro Inés , Hernandez Vicent , González-Mao Carmen , Rivera Concepción , Iglesias Felipe , Cid Lucía , Soto Santiago , de-Castro Luisa , Vega Pablo , Hermo Jose Antonio , Macenlle Ramiro , Martínez Alfonso , Martínez-Ares David , Estevez Pamela , Cid Estela , Herreros-Villanueva Marta , Portillo Isabel , Bujanda Luis , Fernández-Seara Javier 
Published: June 2014

Abstract
Background: Fecal immunochemical test (FIT) diagnostic accuracy for colorectal adenoma detection in colorectal cancer screening is limited.
Methods: We analyzed 474 asymptomatic subjects with adenomas detected on colonoscopy in two blinded diagnostic tests studies designed to assess FIT diagnostic accuracy. We determined the characteristics of adenomas (number, size, histology, morphology, and location) and the risk of metachronous lesions (according to European guidelines). Finally, we performed a logistic regression to identify those variables independently associated with a positive result.
Results: Advanced adenomas were found in 145 patients (75.6% distal and 24.3% only proximal to splenic flexure). Patients were classified as low (59.5%), intermediate (30.2%), and high risk (10.3%) according to European guidelines. At a 100-ng/mL threshold, FIT was positive in 61 patients (12.8%). Patients with advanced adenomas [odds ratio (OR), 8.8; 95% confidence interval (CI), 4.76–16.25], distal advanced adenomas (OR, 6.7; 95% CI, 1.9–8.8), high risk (OR, 20.1; 95% CI, 8.8–45.8), or intermediate risk lesions (OR, 6; 95% CI, 2.9–12.4) had more probabilities to have a positive test. The characteristics of adenomas independently associated were number of adenomas (OR, 1.22; 95% CI, 1.04–1.42), distal flat adenomas (OR, 0.44; 95% CI, 0.21–0.96), pedunculated adenomas (OR, 2.28; 95% CI, 1.48–3.5), and maximum size of distal adenomas (mm; OR, 1.24; 95% CI, 1.16–1.32).
Conclusions: European guidelines classification and adenoma location correlates with the likelihood of a positive FIT result.
Impact: This information allows us to understand the FIT impact in colorectal cancer prevention. Likewise, it should be taken into account in the development of new colorectal adenomas biomarkers. Cancer Epidemiol Biomarkers Prev; 23(9); 1884–92. ©2014 AACR.
A Review of the Application of Inflammatory Biomarkers in Epidemiologic Cancer Research
Authors: Brenner Darren R. , Scherer Dominique , Muir Kenneth , Schildkraut Joellen , Boffetta Paolo , Spitz Margaret R. , Le Marchand Loic , Chan Andrew T. , Goode Ellen L. , Ulrich Cornelia M. , Hung Rayjean J. 
Published: June 2014

Abstract
Inflammation is a facilitating process for multiple cancer types. It is believed to affect cancer development and progression through several etiologic pathways, including increased levels of DNA adduct formation, increased angiogenesis, and altered antiapoptotic signaling. This review highlights the application of inflammatory biomarkers in epidemiologic studies and discusses the various cellular mediators of inflammation characterizing the innate immune system response to infection and chronic insult from environmental factors. Included is a review of six classes of inflammation-related biomarkers: cytokines/chemokines, immune-related effectors, acute-phase proteins, reactive oxygen and nitrogen species, prostaglandins and cyclooxygenase-related factors, and mediators such as transcription factors and growth factors. For each of these biomarkers, we provide a brief overview of the etiologic role in the inflammation response and how they have been related to cancer etiology and progression within the literature. We provide a discussion of the common techniques available for quantification of each marker, including strengths, weaknesses, and potential pitfalls. Subsequently, we highlight a few under-studied measures to characterize the inflammatory response and their potential utility in epidemiologic studies of cancer. Finally, we suggest integrative methods for future studies to apply multifaceted approaches to examine the relationship between inflammatory markers and their roles in cancer development. Cancer Epidemiol Biomarkers Prev; 23(9); 1729–51. ©2014 AACR.
Characterization of Transfusion-Derived Iron Deposition in Childhood Cancer Survivors
Authors: Ruccione Kathleen S. , Wood John C. , Sposto Richard , Malvar Jemily , Chen Cheng , Freyer David R. 
Published: June 2014

Abstract
Background: Childhood cancer survivors (CCS) receiving packed red blood cell (PRBC) transfusions may have increased risk for vital organ iron deposition causing serious late effects.
Methods: This cross-sectional cohort study of a CCS cohort quantified organ iron content by magnetic resonance imaging. Iron status by serum markers and hemochromatosis gene mutation status were assessed.
Results: Seventy-five patients who had received a range (0–392 mL/kg) of cumulative PRBC transfusion volumes were enrolled (median age 14 years, range 8–25.6 years at evaluation). Median follow-up time was 4.4 years, and median time since last transfusion was 4.9 years. Cancer diagnoses included acute lymphoblastic or myelogenous leukemia (ALL/AML; n = 33) and solid tumors (n = 42). Liver and pancreatic iron concentrations were elevated in 36 of 73 (49.3%) and 19 of 72 (26.4%) subjects, respectively. Cardiac iron concentration was not increased in this cohort. In multivariate analysis, cumulative PRBC volume (P &lt; 0.0001) and older age at diagnosis (P &lt; 0.0001) predicted elevated liver iron concentration.
Conclusions: Iron overload (IO) may occur in children and adolescents/young adults treated for cancer and is associated with cumulative PRBC transfusion volume and age at diagnosis.
Impact: These findings have implications for development of monitoring and management guidelines for cancer patients and survivors at risk for IO, exploration of the additive risk of liver/pancreatic damage from chemotherapeutic exposures, and health education to minimize further liver/pancreatic damage from exposures such as excessive alcohol intake and hepatotoxic medications. Cancer Epidemiol Biomarkers Prev; 23(9); 1913–9. ©2014 AACR.
Improved Differentiation of Benign and Malignant Breast Tumors with Multiparametric 18Fluorodeoxyglucose Positron Emission Tomography Magnetic Resonance Imaging: A Feasibility Study
Authors: Pinker Katja , Bogner Wolfgang , Baltzer Pascal , Karanikas Georgios , Magometschnigg Heinrich , Brader Peter , Gruber Stephan , Bickel Hubert , Dubsky Peter , Bago-Horvath Zsuzsanna , Bartsch Rupert , Weber Michael , Trattnig Siegfried , Helbich Thomas H. 
Published: June 2014

Abstract
Purpose: To assess whether multiparametric 18fluorodeoxyglucose positron emission tomography magnetic resonance imaging (MRI) (MP 18FDG PET-MRI) using dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), three-dimensional proton MR spectroscopic imaging (3D 1H-MRSI), and 18FDG-PET enables an improved differentiation of benign and malignant breast tumors.
Experimental Design: Seventy-six female patients (mean age, 55.7 years; range, 25–86 years) with an imaging abnormality (BI-RADS 0, 4–5) were included in this Institutional Review Board (IRB)-approved study. Patients underwent fused PET-MRI of the breast with 18FDG-PET/CT and MP MRI at 3T. The likelihood of malignancy was assessed for all single parameters, for MP MRI with two/three parameters, and for MP 18FDG PET-MRI. Histopathology was used as the standard of reference. Appropriate statistical tests were used to assess sensitivity, specificity, and diagnostic accuracy for each assessment combination.
Results: There were 53 malignant and 23 benign breast lesions. MP 18FDG PET-MRI yielded a significantly higher area under the cure (AUC) of 0.935 than DCE-MRI (AUC, 0.86; P = 0.044) and the combination of DCE-MRI and another parameter (AUC, 0.761–0.826; P = 0.013–0.020). MP 18FDG PET-MRI showed slight further improvement to MP MRI with three parameters (AUC, 0.925; P = 0.317). Using MP 18FDG PET-MRI there would have been a reduction of the unnecessary breast biopsies recommended by MP imaging with one or two parameters (P = 0.002–0.011).
Conclusion: This feasibility study shows that MP 18FDG PET-MRI enables an improved differentiation of benign and malignant breast tumors when several MRI and PET parameters are combined. MP 18FDG PET-MRI may lead to a reduction in unnecessary breast biopsies. Clin Cancer Res; 20(13); 3540–9. ©2014 AACR.
Functional p38 MAPK Identified by Biomarker Profiling of Pancreatic Cancer Restrains Growth through JNK Inhibition and Correlates with Improved Survival
Authors: Zhong Yi , Naito Yoshiki , Cope Leslie , Naranjo-Suarez Salvador , Saunders Tyler , Hong Seung-Mo , Goggins Michael G. , Herman Joseph M. , Wolfgang Christopher L. , Iacobuzio-Donahue Christine A. 
Published: June 2014

Abstract
Purpose: Numerous biomarkers for pancreatic cancer have been reported. We determined the extent to which such biomarkers are expressed throughout metastatic progression, including those that effectively predict biologic behavior.
Experimental Design: Biomarker profiling was performed for 35 oncoproteins in matched primary and metastatic pancreatic cancer tissues from 36 rapid autopsy patients. Proteins of significance were validated by immunolabeling in an independent sample set, and functional studies were performed in vitro and in vivo.
Results: Most biomarkers were similarly expressed or lost in expression in most samples analyzed, and the matched primary and metastases from a specific patient were most similar to each other than to other patients. However, a subset of proteins showed extensive interpatient heterogeneity, one of which was p38 MAPK. Strong positive pp38 MAPK immunolabeling was significantly correlated with improved postresection survival by multivariate analysis (median overall survival 27.9 months, P = 0.041). In pancreatic cancer cells, inhibition of functional p38 by SB202190 increased cell proliferation in vitro in both low-serum and low-oxygen conditions. High functional p38 activity in vitro corresponded to lower levels of pJNK protein expression, and p38 inhibition resulted in increased pJNK and pMKK7 by Western blot analysis. Moreover, JNK inhibition by SP600125 or MKK7 siRNA knockdown antagonized the effects of p38 inhibition by SB202190. In vivo, SP600125 significantly decreased growth rates of xenografts with high p38 activity compared with those without p38 expression.
Conclusions: Functional p38 MAPK activity contributes to overall survival through JNK signaling, thus providing a rationale for JNK inhibition in pancreatic cancer management. Clin Cancer Res; 20(23); 6200–11. ©2014 AACR.
miR-409-3p/-5p Promotes Tumorigenesis, Epithelial-to-Mesenchymal Transition, and Bone Metastasis of Human Prostate Cancer
Authors: Josson Sajni , Gururajan Murali , Hu Peizhen , Shao Chen , Chu Gina Chia-Yi , Zhau Haiyen E. , Liu Chunyan , Lao Kaiqin , Lu Chia-Lun , Lu Yi-Tsung , Lichterman Jake , Nandana Srinivas , Li Quanlin , Rogatko Andre , Berel Dror , Posadas Edwin M. , Fazli Ladan , Sareen Dhruv , Chung Leland W.K. 
Published: June 2014

Abstract
Purpose: miR-409-3p/-5p is a miRNA expressed by embryonic stem cells, and its role in cancer biology and metastasis is unknown. Our pilot studies demonstrated elevated miR-409-3p/-5p expression in human prostate cancer bone metastatic cell lines; therefore, we defined the biologic impact of manipulation of miR-409-3p/-5p on prostate cancer progression and correlated the levels of its expression with clinical human prostate cancer bone metastatic specimens.
Experimental Design: miRNA profiling of a prostate cancer bone metastatic epithelial-to-mesenchymal transition (EMT) cell line model was performed. A Gleason score human tissue array was probed for validation of specific miRNAs. In addition, genetic manipulation of miR-409-3p/-5p was performed to determine its role in tumor growth, EMT, and bone metastasis in mouse models.
Results: Elevated expression of miR-409-3p/-5p was observed in bone metastatic prostate cancer cell lines and human prostate cancer tissues with higher Gleason scores. Elevated miR-409-3p expression levels correlated with progression-free survival of patients with prostate cancer. Orthotopic delivery of miR-409-3p/-5p in the murine prostate gland induced tumors where the tumors expressed EMT and stemness markers. Intracardiac inoculation (to mimic systemic dissemination) of miR-409-5p inhibitor–treated bone metastatic ARCaPM prostate cancer cells in mice led to decreased bone metastasis and increased survival compared with control vehicle–treated cells.
Conclusion: miR-409-3p/-5p plays an important role in prostate cancer biology by facilitating tumor growth, EMT, and bone metastasis. This finding bears particular translational importance as miR-409-3p/-5p appears to be an attractive biomarker and/or possibly a therapeutic target to treat bone metastatic prostate cancer. Clin Cancer Res; 20(17); 4636–46. ©2014 AACR.
Targeting TBK1 Inhibits Migration and Resistance to MEK Inhibitors in Mutant NRAS Melanoma
Authors: Vu Ha Linh , Aplin Andrew E. 
Published: June 2014

Abstract
Melanoma is a devastating form of skin cancer with limited therapeutic options. Fifteen to 20% of patients with melanoma have an activating mutation in the GTPase, NRAS. The major downstream effectors of RAS are RAFs (ARAF, BRAF, and CRAF), phosphoinositide 3-kinase (PI3K), and the Ral guanine exchange factors (RalGEF). TANK-binding kinase 1 (TBK1) is an atypical IκB kinase family member that acts downstream of RalGEFs. Whereas many studies have analyzed RAF and PI3K signaling in mutant NRAS melanoma, the role of RalGEF/Ral is understudied and TBK1 has not been examined. To address this, TBK1 was modulated with knockdown approaches and targeted therapies to determine the role of TBK1 in motility, apoptosis, and signaling. In melanoma, NRAS overexpression increased TBK1 phosphorylation. TBK1 depletion inhibited migration and invasion, whereas its constitutive overexpression led to an increase in invasion. In three-dimensional systems that mimic the dermal microenvironment, TBK1 depletion or inhibition cooperated with MEK inhibitors to promote apoptosis, particularly in the context of MEK-insensitive mutant NRAS. This effect was absent in melanoma cells that are wild-type for NRAS. These results suggest the utility of TBK1 inhibitors as part of a treatment regimen for patients with mutant NRAS melanoma, for whom there are no current effective therapies.
Implications: TBK1 promotes the malignant properties of NRAS-mutant melanoma and its targeting, in combination with MEK, promotes apoptosis, thus providing a potential novel targeted therapeutic option. Mol Cancer Res; 12(10); 1509–19. ©2014 AACR.