bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and prognostic significance of survivin splice variants in diffusely infiltrating astrocytoma
Authors: Huang Ying , Chen Xueqin , Chen Ni , Nie Ling , Xu Miao , Zhou Qiao 
Published: July 2011

BackgroundAlternative splicing of survivin (BIRC5) pre-mRNA generates the common isoform survivin and five additional splice variants: survivin2B, survivinΔEx3, survivin2α, survivin3B and survivin3α. Although the common isoform survivin has been shown to be involved in tumourigenesis and progression of various tumours, including diffusely infiltrating astrocytoma, the expression of other survivin splice variants in astrocytoma has not been fully investigated.AimsTo evaluate the expression status and particularly prognostic significance of survivin splice variants in diffusely infiltrating astrocytoma.MethodsmRNA expression of the six survivin variants in 73 diffusely infiltrating astrocytoma and 18 normal brain tissue samples was investigated by using reverse transcription-PCR (RT-PCR), and the total survivin protein expression by western analysis and immunohistochemistry. Association of survivin and its splice variants with tumour grade and prognosis was examined by statistical and survival analysis.ResultsThe survivin, survivinΔEx3, survivin2B and survivin2α splice variants were significantly elevated in diffusely infiltrating astrocytoma, and were barely detectable or not detectable at all in normal brain tissue. Survivin3B and survivin3α were not detected in these samples. The positive rates of the expressed four variants increased with astrocytoma grade. Significantly, expression of these splice variants was associated with much poorer disease-specific and progression-free survival (Kaplan–Meier analysis, p≤0.002). Cox regression model further indicated survivin2α mRNA expression and nuclear survivin immunostaining to be significant independent negative prognostic factors.ConclusionsThe survivin, survivinΔEx3, survivin2B and survivin2α splice variants were significantly elevated in astrocytoma, and were associated with tumour grade and poorer prognosis.
The frequency of detection of unexpected diabetes mellitus during haemoglobinopathy investigations
Authors: Conroy Mary , Beer Philip , Hughes Carol , Phelan Lorraine , Bain Barbara J 
Published: July 2011

AimsTo establish the frequency of detection of previously undiagnosed diabetes mellitus as a result of detection of an increased glycated fraction of haemoglobin during high performance liquid chromatography (HPLC) for haemoglobinopathy diagnosis.MethodsA prospective study was carried out over a 3-month period. During that period a total of 2094 patient samples were received for haemoglobinopathy investigation and were included in the study.ResultsFifty samples were found to have an apparent increase in the glycated haemoglobin fraction and of these 38 were found to be from patients with known diabetes. Previously undiagnosed diabetes was discovered in 11 patients and it is likely that the twelfth patient also had diabetes.ConclusionsThe detection of evidence of undiagnosed diabetes during HPLC haemoglobinopathy investigations is not rare, there being four cases per month in this study. This incidental observation should be reported to clinical staff.
A tobacco-related carcinogen: assessing the impact of smoking behaviours of cohabitants on benzene exposure in children
Authors: Protano Carmela , Andreoli Roberta , Manini Paola , Guidotti Maurizio , Vitali Matteo 
Published: July 2011

BackgroundSecondhand smoke (SHS) represents a major preventable cause of morbidity for communities, especially for children, who are more susceptible than adults to the adverse effects of passive smoking. SHS contains several carcinogens, including benzene.ObjectiveTo investigate the role of household characteristics and the smoking behaviours of cohabitants in predicting SHS-derived benzene exposure levels.MethodsIn this cross-sectional study, 122 children (aged 5–11 years old) were selected from a school in rural Italy. Characteristics of their home environment and the smoking habits of the children's cohabitants were obtained via questionnaire, and urinary unmodified benzene (u-UB) and cotinine (a specific nicotine metabolite) levels were determined from spot urine samples.ResultsSignificant differences between SHS-exposed and SHS-unexposed children were found with respect to u-UB levels (median values 359.50 and 92.50 ng/litre, respectively; p<0.001). The excretion of u-UB increased significantly in parallel to increased SHS exposure as follows: unexposed to SHS (median value 92.50 ng/litre)<cohabitant(s) smoker(s) not smoking inside the home (282.00 ng/litre)<cohabitant(s) smoking inside the home only when children are out (314.50 ng/litre)<cohabitant(s) smoking inside the home even when children are in (596.00 ng/litre). The difference between groups was significant (p=0.019).ConclusionsAlthough smoke-free legislation has transformed the smoking behaviours of some, domestic environments remain an important source of SHS exposure for children. This fact holds true even in the case of parents and other cohabitants who believe they are fully protecting children by smoking only outdoors or at home only when the children are not present. These findings should be included in Italian community-level health promotion interventions for discouraging tobacco use.
Synthesis, Rietveld refinement of crystal structure, electron diffraction, and electrical transport properties of Ba2(Ca1–x–yFexNby)(Nb1–zFez)O6–δdouble perovskites
Authors: Kan Wang Hay , Trinh Trang T. , Fürstenhaupt Tobias , Thangadurai Venkataraman 
Published: July 2011

We report the synthesis, crystal structure, and electrochemical properties of new Fe-doped Ba2(Ca1–x–yFexNby)(Nb1–zFez)O6–δ(Fe–BCN). The Fe–BCN was synthesized by a solid-state method in air using corresponding metal oxides and salts at elevated temperature. All of the observed powder X-ray diffraction (PXRD) peaks of the investigated Fe–BCN were indexed as cubic Fm-3m (space group No. 225) double perovskite-type structure with cell constants a ∼ 8.4 Å and is consistent with selected area electron diffraction (SAED). Rietveld analysis suggested the distribution of Fe was at both 4a and 4b sites, supported the proposed chemical formula Ba2(Ca1–x–yFexNby)(Nb1–zFez)O6–δ. This was further verified by bond valence sum (BVS) analysis of the cations. The Fe–BCN showed superior chemical stability in pure CO2and boiling H2O confirmed by PXRD and FTIR. The electrical conductivity was determined by AC impedance spectroscopy. Among the samples investigated, Ba2(Ca0.79Fe0.21)(Nb0.71Fe0.29)O6–δshowed the highest total (bulk + grain-boundary) conductivity of 1.1 × 10−2S cm–1in humidified (3%) N2at 600 °C with activation energy of 0.43 eV in the temperature range 200–800 °C.
YB-1 Bridges Neural Stem Cells and Brain Tumor–Initiating Cells via Its Roles in Differentiation and Cell Growth
Authors: Fotovati Abbas , Abu-Ali Samah , Wang Pei-Shan , Deleyrolle Loic P. , Lee Cathy , Triscott Joanna , Chen James Y. , Franciosi Sonia , Nakamura Yasuhiro , Sugita Yasuo , Uchiumi Takeshi , Kuwano Michihiko , Leavitt Blair R. , Singh Sheila K. , Jury Alexa , Jones Chris , Wakimoto Hiroaki , Reynolds Brent A. , Pallen Catherine J. , Dunn Sandra E. 
Published: July 2011

Abstract
The Y-box binding protein 1 (YB-1) is upregulated in many human malignancies including glioblastoma (GBM). It is also essential for normal brain development, suggesting that YB-1 is part of a neural stem cell (NSC) network. Here, we show that YB-1 was highly expressed in the subventricular zone (SVZ) of mouse fetal brain tissues but not in terminally differentiated primary astrocytes. Conversely, YB-1 knockout mice had reduced Sox-2, nestin, and musashi-1 expression in the SVZ. Although primary murine neurospheres were rich in YB-1, its expression was lost during glial differentiation. Glial tumors often express NSC markers and tend to loose the cellular control that governs differentiation; therefore, we addressed whether YB-1 served a similar role in cancer cells. YB-1, Sox-2, musashi-1, Bmi-1, and nestin are coordinately expressed in SF188 cells and 9/9 GBM patient-derived primary brain tumor–initiating cells (BTIC). Silencing YB-1 with siRNA attenuated the expression of these NSC markers, reduced neurosphere growth, and triggered differentiation via coordinate loss of GSK3-β. Furthermore, differentiation of BTIC with 1% serum or bone morphogenetic protein-4 suppressed YB-1 protein expression. Likewise, YB-1 expression was lost during differentiation of normal human NSCs. Consistent with these observations, YB-1 expression increased with tumor grade (n = 49 cases). YB-1 was also coexpressed with Bmi-1 (Spearmans 0.80, P &gt; 0.001) and Sox-2 (Spearmans 0.66, P &gt; 0.001) based on the analysis of 282 cases of high-grade gliomas. These proteins were highly expressed in 10/15 (67%) of GBM patients that subsequently relapsed. In conclusion, YB-1 correlatively expresses with NSC markers where it functions to promote cell growth and inhibit differentiation. Cancer Res; 71(16); 5569–78. ©2011 AACR.
TLR4 Engagement during TLR3-Induced Proinflammatory Signaling in Dendritic Cells Promotes IL-10–Mediated Suppression of Antitumor Immunity
Authors: Bogunovic Dusan , Manches Olivier , Godefroy Emmanuelle , Yewdall Alice , Gallois Anne , Salazar Andres M. , Marie Isabelle , Levy David E. , Bhardwaj Nina 
Published: July 2011

Abstract
Toll-like receptor (TLR) agonists are promising adjuvants for immune therapy of cancer, but their potential efficacy as single or combinatorial agents has yet to be fully evaluated. Here, we report that among all TLR agonists tested, dendritic cells (DC) stimulated with the TLR3 agonist polyI:C displayed the strongest activity in stimulating proinflammatory responses and the production of melanoma antigen-specific CD8+ T cells. Simultaneous treatment with TLR7/8 agonists further improved these responses, but the inclusion of bacterial lipopolysaccharide (LPS), a TLR4 agonist, suppressed proinflammatory cytokine production. This inhibition was contingent upon rapid induction of the suppressive cytokine interleukin (IL)-10 by LPS, leading to dysregulated immune responses and it could be reversed by signal transducers and activators of transcription 3 knockdown, p38 blockade or antibodies to IL-10 and its receptor. Our findings show how certain TLR agonist combinations can enhance or limit DC responses associated with antitumor immunity, through their relative ability to induce IL-10 pathways that are immune suppressive. Cancer Res; 71(16); 5467–76. ©2011 AACR.
Dual Function of ERRα in Breast Cancer and Bone Metastasis Formation: Implication of VEGF and Osteoprotegerin
Authors: Fradet Anaïs , Sorel Helène , Bouazza Lamia , Goehrig Delphine , Dépalle Baptiste , Bellahcène Akeila , Castronovo Vincent , Follet Hélène , Descotes Françoise , Aubin Jane E. , Clézardin Philippe , Bonnelye Edith 
Published: July 2011

Abstract
Bone metastasis is a complication occurring in up to 70% of advanced breast cancer patients. The estrogen receptor-related receptor alpha (ERRα) has been implicated in breast cancer and bone development, prompting us to examine whether ERRα may function in promoting the osteolytic growth of breast cancer cells in bone. In a mouse xenograft model of metastatic human breast cancer, overexpression of wild-type ERRα reduced metastasis, whereas overexpression of a dominant negative mutant promoted metastasis. Osteoclasts were directly affected and ERRα upregulated the osteoclastogenesis inhibitor, osteoprotegerin (OPG), providing a direct mechanistic basis for understanding how ERRα reduced breast cancer cell growth in bone. In contrast, ERRα overexpression increased breast cancer cell growth in the mammary gland. ERRα-overexpressing primary tumors were highly vascularized, consistent with an observed upregulation of angiogenic growth factor, the VEGF. In support of these findings, we documented that elevated expression of ERRα mRNA in breast carcinomas was associated with high expression of OPG and VEGF and with disease progression. In conclusion, our results show that ERRα plays a dual role in breast cancer progression in promoting the local growth of tumor cells, but decreasing metastatic growth of osteolytic lesions in bone. Cancer Res; 71(17); 5728–38. ©2011 AACR.
Advanced Glycation End Products, Soluble Receptor for Advanced Glycation End Products, and Risk of Colorectal Cancer
Authors: Jiao Li , Taylor Philip R. , Weinstein Stephanie J. , Graubard Barry I. , Virtamo Jarmo , Albanes Demetrius , Stolzenberg-Solomon Rachael Z. 
Published: July 2011

Abstract
Background: Advanced glycation end products (AGE) accumulate in human tissue proteins during aging, particularly under hyperglycemia conditions. AGEs induce oxidative stress and inflammation via the receptor for AGEs (RAGE) and soluble RAGE (sRAGE) can neutralize the effects mediated by RAGE–ligand engagement.
Methods: We examined the association between Nϵ-(carboxymethyl)lysine (CML), a prominent AGE, and sRAGE and colorectal cancer risk in a prospective case–cohort study nested within a cancer prevention trial among 29,133 Finnish male smokers. Among study subjects who were alive without cancer 5 years after baseline (1985–1988), we identified 483 incident colorectal cancer cases and randomly sampled 485 subcohort participants as the comparison group with the follow-up to April 2006. Baseline serum levels of CML-AGE, sRAGE, glucose and insulin were determined. Weighted Cox proportional hazard regression models were used to calculate relative risks (RR) and 95% CI.
Results: Comparing highest with lowest quintile of sRAGE, the RR for incident colorectal cancer was 0.65 (95% CI, 0.39–1.07; Ptrend = 0.03), adjusting for age, years of smoking, body mass index, and CML-AGE. Further adjustment for serum glucose strengthened the association (RR = 0.52; 95% CI, 0.30–0.89; Ptrend = 0.009). Highest quintile of CML-AGE was not associated with an increased risk of colorectal cancer (multivariate RR = 1.20; 95% CI, 0.64–2.26).
Conclusions: Higher prediagnostic levels of serum sRAGE were associated with lower risk of colorectal cancer in male smokers.
Impact: This is the first epidemiologic study to implicate the receptor for AGEs in colorectal cancer development. Cancer Epidemiol Biomarkers Prev; 20(7); 1430–8. ©2011 AACR.
A Large Cohort Study of Long-term Acetaminophen Use and Prostate Cancer Incidence
Authors: Jacobs Eric J. , Newton Christina C. , Stevens Victoria L. , Gapstur Susan M. 
Published: July 2011

AbstractBackground: Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAID), particularly long-term use, has been associated with modestly reduced risk of prostate cancer in previous epidemiologic studies. Acetaminophen, a commonly used pain reliever, is not traditionally considered an NSAID but can have anti-inflammatory effects. Few studies have examined the association between long-term acetaminophen use and prostate cancer incidence.Methods: We examined the association between acetaminophen use and prostate cancer incidence among 78,485 men in the Cancer Prevention Study II Nutrition Cohort. Information on acetaminophen use was obtained from a questionnaire completed at study enrollment in 1992 and updated by using follow-up questionnaires in 1997 and every two years thereafter. Relative risks (RR) were estimated by using proportional hazards regression models. All models were adjusted for age, race, education, body mass index, diabetes, NSAID use, and history of prostate-specific antigen testing.Results: During follow-up from 1992 through 2007, 8,092 incident prostate cancer cases were identified. Current regular use of acetaminophen (30 or more pills per month) for 5 or more years was associated with lower risk of overall prostate cancer (RR = 0.62, 95% CI: 0.44–0.87) and aggressive prostate cancer (RR = 0.49, 95% CI: 0.27–0.88). Current regular use of less than 5 years duration was not associated with prostate cancer risk.Conclusion: These results suggest that long-term regular acetaminophen use may be associated with lower prostate cancer risk.Impact: If the association between acetaminophen use and lower risk of prostate cancer is confirmed, it could provide clues about biological mechanisms that are important in prostate carcinogenesis. Cancer Epidemiol Biomarkers Prev; 20(7); 1322–8. ©2011 AACR.
Understanding Suboptimal Human Papillomavirus Vaccine Uptake Among Ethnic Minority Girls
Authors: Bastani Roshan , Glenn Beth A. , Tsui Jennifer , Chang L. Cindy , Marchand Erica J. , Taylor Victoria M. , Singhal Rita 
Published: July 2011

Abstract
Background: The introduction of human papillomavirus (HPV) vaccines represents a breakthrough in the primary prevention of cervical cancer. However, little is known about vaccination uptake and correlates among low-income, ethnic minority, and immigrant populations in the U.S. who may benefit most from the vaccine.
Methods: Telephone interviews (N = 490) were conducted in six languages between January and November 2009 among mothers of vaccine-eligible girls (ages 9–18) using the Los Angeles County Department of Public Health, Office of Women's Health service referral hotline. HPV and vaccine awareness, knowledge, beliefs, barriers, and daughter's vaccine receipt were assessed.
Results: The sample consisted of low-income, uninsured, ethnic minority, and immigrant women. Only 29% of daughters initiated the vaccine and 11% received all three doses. No ethnic differences were observed in initiation or completion rates. Ethnic differences were observed in HPV awareness, perceived risk, and other vaccine-related beliefs. The strongest predictor of initiation was vaccine awareness (OR = 12.00). Daughter's age and reporting a younger acceptable age for vaccination were positively associated with initiation. Mothers of unvaccinated girls reported lacking information about the vaccine to make a decision (66%) and not knowing where they could obtain the vaccine (74%).
Conclusion: Vaccination rates in this sample were lower than state and national estimates, and were associated with low levels of vaccine awareness. Interventions, including culturally targeted messaging, may be helpful for enhancing HPV–vaccine knowledge, modifying vaccine-related beliefs and increasing uptake.
Impact: Our findings provide valuable guidance for developing interventions to address suboptimal HPV vaccination in high-risk groups. Cancer Epidemiol Biomarkers Prev; 20(7); 1463–72. ©2011 AACR.
Rapamycin Is a Potent Inhibitor of Skin Tumor Promotion by 12-O-Tetradecanoylphorbol-13-Acetate
Authors: Checkley L. Allyson , Rho Okkyung , Moore Tricia , Hursting Steve , DiGiovanni John 
Published: July 2011

AbstractAberrant activation of phosphoinositide-3-kinase (PI3K)/Akt signaling has been implicated in the development and progression of multiple human cancers. During the process of skin tumor promotion induced by treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), activation of epidermal Akt occurs as well as several downstream effectors of Akt, including the activation of mTORC1. Rapamycin, an established mTORC1 inhibitor, was used to further explore the role of mTORC1 signaling in epithelial carcinogenesis, specifically during the tumor promotion stage. Rapamycin blocked TPA-induced activation of mTORC1 as well as several downstream targets. In addition, TPA-induced epidermal hyperproliferation and hyperplasia were inhibited in a dose-dependent manner with topical rapamycin treatments. Immunohistochemical analyses of the skin from mice in this multiple treatment experiment revealed that rapamycin also significantly decreased the number of infiltrating macrophages, T cells, neutrophils, and mast cells seen in the dermis following TPA treatment. Using a two-stage skin carcinogenesis protocol with 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and TPA as the promoter, rapamycin (5–200 nmol per mouse given topically 30 minutes prior to TPA) exerted a powerful antipromoting effect, reducing both tumor incidence and tumor multiplicity. Moreover, topical application of rapamycin to existing papillomas induced regression and/or inhibited further growth. Overall, the data indicate that rapamycin is a potent inhibitor of skin tumor promotion and suggest that signaling through mTORC1 contributes significantly to the process of skin tumor promotion. The data also suggest that blocking this pathway either alone or in combination with other agents targeting additional pathways may be an effective strategy for prevention of epithelial carcinogenesis. Cancer Prev Res; 4(7); 1011–20. ©2011 AACR.
Role of Autophagy in Cancer Prevention
Authors: Chen Hsin-Yi , White Eileen 
Published: July 2011

Abstract
Macroautophagy (autophagy hereafter) is a catabolic process by which cells degrade intracellular components in lysosomes. This cellular garbage disposal and intracellular recycling system maintains cellular homeostasis by eliminating superfluous or damaged proteins and organelles and invading microbes and by providing substrates for energy generation and biosynthesis in stress. Autophagy thus promotes the health of cells and animals and is critical for the development, differentiation, and maintenance of cell function and for the host defense against pathogens. Deregulation of autophagy is linked to susceptibility to various disorders including degenerative diseases, metabolic syndrome, aging, infectious diseases, and cancer. Autophagic activity emerges as a critical factor in the development and progression of diseases that are associated with increased cancer risk as well as in different stages of cancer. Given that cancer is a complex process and autophagy exerts its effects in multiple ways, the role of autophagy in tumorigenesis is context-dependent. As a cytoprotective survival pathway, autophagy prevents chronic tissue damage that can lead to cancer initiation and progression. In this setting, stimulation or restoration of autophagy may prevent cancer. In contrast, once cancer occurs, many cancer cells upregulate basal autophagy and utilize autophagy to enhance fitness and survive in the hostile tumor microenvironment. These findings revealed the concept that aggressive cancers can be addicted to autophagy for survival. In this setting, autophagy inhibition is a therapeutic strategy for established cancers. Cancer Prev Res; 4(7); 973–83. ©2011 AACR.