bluuebunny/crossref_metadata_2025 huggingface dataset:
Production of polycyclic aromatic hydrocarbon metabolites from a peroxynitrite/iron(III) porphyrin biomimetic model and their mutagenicities
Authors: Luo Yunjing , Dai Jing , Zhong Rugang , She Yuanbin , Liu Rui , Wei Huachen
Published: December 2010

Some polycyclic aromatic hydrocarbons (PAHs) are typical promutagens that require metabolic activation to exhibit their mutagenicities and carcinogenicities. The metabolites of three PAHs, pyrene (PY), fluoranthene (FLU), and benzo[a]pyrene (BaP), produced from the peroxynitrite/T(p-Cl)PPFeCl(peroxynitrite/(chloride)iron(III)tetrakis(p-chlorophenyl)porphyrin) system, have been identified with high-performance liquid chromatography coupled with electron spray ionization tandem mass spectrometry. The results demonstrated that three major metabolites were the quinone group, OH group, and nitro group. In the Ames test, all three PAH metabolites became mutagenic without using the enzymatic activating system, whereas their parents did not show positive results. Cell transformation assay indicated that 1,3-nitro-BaP and BaP metabolites produced from this biomimetic system have more serious effects in inducing cancer than the BaP parent. Environ. Toxicol. Chem. 2011; 30:723–729. © 2010 SETAC
Detecting backoff misbehaviour in IEEE 802.11 EDCA
Authors: Szott S. , Natkaniec M. , Canonico R.
Published: December 2010

In this paper, we suggest the use of the chi‐square test for detecting backoff misbehaviour in IEEE 802.11 EDCA networks. A performance evaluation is performed to compare the chi‐square test with two other methods, known in the literature. To perform a suitable comparison, these two methods are extended to support EDCA and the BEB mechanism. We assume a misbehaviour model, which can be easily executed by a selfish user. We show that the chi‐square test outperforms the other methods in terms of the probability of misbehaviour detection and time required to positively identify a misbehaving node. Copyright © 2010 John Wiley & Sons, Ltd.
Residual compressive strength of fire‐damaged mortar after post‐fire‐air‐curing
Authors: Karahan Okan
Published: December 2010

The effects of cooling regimes and post‐fire‐air‐curing on compressive strength of mortar were investigated. Mortars were made with CEN reference sand, CEM I 42.5 R cement and natural spring water. The sand–cement and water–cement materials' ratios were chosen as 3.0 and 0.50 for all mixtures, respectively. At 28 days, the specimens were heated to maximum temperatures of 400, 600, 800 and 1000°C. Specimens were then allowed to cool in the air, furnace and water. After cooling, the specimens were air‐recured. Compressive strength test was carried out before air‐recuring and after 7 days of air‐recuring. The highest reduction in compressive strength was observed at 1000°C regardless of cooling regime. Gradual cooling regime in air and furnace without post curing showed almost no difference in terms of compressive strength reduction for four elevated temperatures. Shock cooling in water caused significant reduction in compressive strength compared with both gradual cooling regimes without post curing. After air and furnace cooling regimes, 7 days air‐recured specimens showed further reduction in compressive strength for four elevated temperatures. Specimens cooled in water and subjected to 7 days air‐recuring showed significant strength gain approximately 39, 100 and 130% for 400, 600 and 800°C elevated temperature, respectively. Copyright © 2010 John Wiley & Sons, Ltd.
Microglia in the CNS: Immigrants from another world
Authors: Prinz Marco , Mildner Alexander
Published: December 2010

Microglia are immunocompetent cells of the brain that continuously survey their environment with highly motile extensions. Although first described almost a century ago, the developmental origin of microglia is still debated. Besides early myeolomonocytic cell populations that colonize the developing neuroectoderm already during embryogenesis, newly migrated myeloid cells are considered important disease modulators in the adult brain. Thus, understanding the mechanisms of myeloid cell recruitment from the periphery and their development into bone marrow‐derived phagocytes in the adult brain is pivotal for manipulating immune cell entry into the CNS and potentially reducing disease burden. A major question is whether bone marrow‐derived mononuclear phagocytes have similar features and fates as their endogenous counterparts. Significant advances in our understanding of microglia biology under physiological as well as under pathological conditions have been made in the last few years, especially by combining novel gene‐targeting techniques that allow cell manipulation and trafficking analysis. These new aspects will be discussed in the present review. ©2010 Wiley‐Liss, Inc.
Signaling through the primary cilium affects glial cell survival under a stressed environment
Authors: Yoshimura Kentaro , Kawate Toyoko , Takeda Sen
Published: December 2010

Sensing extracellular milieu is a fundamental requirement of cells. To facilitate and specify sensory reception, mammalian cells develop an antenna‐like structure denoted as the primary cilia. Nearly all interphase and nondividing cells in vertebrates have a single, nonmotile seemingly unspecialized cilium (called a primary cilium). In the central nervous system, astrocytes express primary cilia, but their function in astrocytes has not been examined. Recent studies have shown that primary cilia unite receptors and the machinery of signal‐transduction components, such as Wnt and Hedgehog (Hh) signaling cascades. Although, Hh signaling cascades are known to be activated in various cells during development, their physiological functions in the adult nervous system, especially in glial cells, are still unknown. In this study, we reveal that glial primary cilia receive the Hh signal and regulate the survival of astrocytes under stressed conditions such as starvation. Interestingly, increased astrocyte survival was reversed by knockdown of Ift20, which is one of the main components for building primary cilia. These results collectively indicate that the activation of Hh signaling in the primary cilia plays an important role in the survival of astrocytes under stressed conditions. © 2010 Wiley‐Liss, Inc.
Differential aminoacylase expression in neuroblastoma
Authors: Long Patrick M. , Stradecki Holly M. , Minturn Jane E. , Wesley Umadevi V. , Jaworski Diane M.
Published: December 2010

Neuroblastoma, a cancer of the sympathetic nervous system, is the most common extracranial solid tumor in children. MYCN amplification and increased BDNF/TrkB signaling are features of high‐risk tumors; yet, only ˜25% of malignant tumors display these features. Thus, the identification of additional biomarkers and therapeutic targets is essential. As aminoacylase 1 (ACY1), an amino acid deacetylase, is a putative tumor suppressor in small cell lung and renal cell carcinomas, we investigated whether it or the other family members aspartoacylase (ASPA, aminoacylase 2) or aminoacylase 3 (ACY3) could serve a similar function in neuroblastoma. Aminoacylase expression was examined in TrkB‐positive, MYCN‐amplified (SMS‐KCNR and SK‐N‐BE) and TrkB‐negative, non‐MYCN‐amplified (SK‐N‐AS, SK‐N‐SH, SH‐SY5Y and SH‐EP) neuroblastoma cell lines. Each aminoacylase exhibited distinct spatial localization (i.e., cytosolic ACY1, membrane‐associated ASPA and nuclear ACY3). When SK‐N‐SH cells were treated with neural differentiation agents (e.g., retinoic acid and cAMP) in media containing 10% serum, ACY1 was the only aminoacylase whose expression was upregulated. ASPA was primarily expressed in SH‐EP cells of a glial sublineage. ACY3 was more highly expressed in the TrkB‐positive, MYCN‐amplified lines. All three aminoacylases were expressed in normal human adrenal gland, a common site of neuroblastoma origin, but only ACY1 and ACY3 displayed detectable expression in primary neuroblastoma tumor. Bioinformatics data mining of Kaplan–Meier survival revealed that high ACY3 expression is correlated with poor prognosis, whereas low expression of ACY1 or ASPA is correlated with poor prognosis. These data suggest that aminoacylase expression is dysregulated in neuroblastoma.
Melanocortin 1 receptor and risk of cutaneous melanoma: A meta‐analysis and estimates of population burden
Authors: Williams Patricia F. , Olsen Catherine M. , Hayward Nicholas K. , Whiteman David C.
Published: December 2010

Polymorphisms in the melanocortin 1 receptor (MC1R) gene have been associated with increased risks of melanoma, but different approaches to study design, analysis, and reporting have hindered comparisons of findings. We aimed to harmonize the published data by conducting a systematic review and meta‐analysis of MC1R variants and thereby estimate relative risks and population attributable fractions (PAFs). We identified 20 analytic studies reporting on 25 populations, which presented quantitative data on melanoma risks associated with any of nine MC1R variants. We separately pooled estimates of risk per person and risk per chromosome using a random effects model. Red hair color (RHC) variants had the highest risk of melanoma [summary odds ratios (OR) 2.44, 95% confidence interval (CI) 1.72–3.45, PAF 16.8% CI 0.119–0.202], but non‐RHC variants were also associated with increased risk (summary OR 1.29, 95% CI 1.10–1.51, PAF 7.4% CI 0.030–0.112). The summary risk of melanoma associated with individual variants ranged from OR 2.40 for R142H to 1.18 for V60L, although significant heterogeneity was evident for most variants. PAFs ranged from 0.55% for I155T to 6.28% for R151C. Our findings suggest the nine most common MC1R variants make a sizeable contribution to the burden of melanoma. Melanoma research would be greatly assisted by standardized classifications for MC1R variants and consistent reporting conventions. More compatible and comparable research would allow for more powerful data that could be clinically applied to predict melanoma risk.
Human leukocyte antigen‐G expression is associated with a poor prognosis in patients with esophageal squamous cell carcinoma
Authors: Lin Aifen , Zhang Xia , Zhou Wen‐Jun , Ruan Yan‐Yun , Xu Dan‐Ping , Wang Qing , Yan Wei‐Hua
Published: December 2010

Human leukocyte antigen (HLA)‐G inhibits functions of immune component cells and promotes malignant cells evading from antitumor immunity. We investigated the clinical relevance of HLA‐G expression in esophageal squamous cell carcinoma (ESCC). In our study, HLA‐G expression in 79 primary ESCC lesions and corresponding adjacent normal tissues were analyzed with immunohistochemistry. Soluble HLA‐G (sHLA‐G) in plasma was detected with enzyme‐linked immunosorbent assay (ELISA) in 41 ESCC patients (including 19 case‐matched lesions and plasma samples) and in 153 normal healthy controls. HLA‐G expression was observed in 65.8% (52/79) of the ESCC lesions but not in adjacent normal esophageal tissues. HLA‐G expression was more frequently observed in patients with advanced disease stage (III/IV vs. I/II, p = 0.01). Patients with HLA‐G expression had a significantly worse survival, and HLA‐G could be an independent prognostic factor. sHLA‐G levels in plasma were significantly increased in patients compared to normal controls (median: 152.4 U/ml vs. 8.9 U/ml, p < 0.001). The area under receiver‐operating characteristic (ROC) curve for sHLA‐G in plasma was 0.992. However, no significant correlation was found between sHLA‐G in plasma and clinical parameters studied. In conclusion, our findings indicated that HLA‐G expression in ESCC is associated with poor survival and could be a prognostic indicator. Furthermore, increased levels of sHLA‐G in plasma might be a useful preoperative biomarker for diagnosis.
Ag‐bearing liposomes engrafted with peptides that interact with CD11c/CD18 induce potent Ag‐specific and antitumor immunity
Authors: Faham Abdus , Altin Joseph. G.
Published: December 2010

Dendritic cells (DCs) play key role in eliciting antigen (Ag)‐specific immune responses, and crucial to this is the uptake of Ag via surface receptors including the heterodimeric integrin CD11c/CD18. Here we report that CD11c/CD18‐interacting peptides can be used as targeting moieties to deliver liposomal Ag to antigen presenting cells (APCs) and elicit Ag‐specific and antitumor immunity. Two peptides of sequence related to human ICAM‐4 and previously reported to bind CD11c/CD18, and a 12‐mer cyclic peptide previously identified by phage display to bind CD11c/CD18, were produced synthetically, and tested for their ability to target liposomal Ag. The three peptides were designed to contain a shorter spacer to reduce steric hindrance, and a His‐tag to enable engraftment onto liposomes incorporated with chelator lipid. Our results show that the three peptides, denoted as p17, p18 and p30, promote strong binding of liposomes to CD11c+ and CD11b+ cells in vitro and in vivo. Vaccination of mice with Ag‐bearing liposomes engrafted with the peptides, particularly p18 and p30, induced Ag‐specific T cell priming and antibody production. Importantly, the vaccination of C57BL/6 mice with syngeneic B16‐OVA‐derived plasma membrane vesicles (PMVs) engrafted with p18 and p30 peptide showed dramatic antitumor responses, inhibiting tumor growth/metastasis in both the lung and subcutaneous tumor models, with a high proportion of the mice apparently being “cured” of their tumors. The engraftment of p18 and p30 peptides onto liposomes and PMVs, thus provides an effective means to target Ags to DCs in vivo, for the development of effective cancer vaccines and immunotherapies.
Anti‐stromal therapy with imatinib inhibits growth and metastasis of gastric carcinoma in an orthotopic nude mouse model
Authors: Sumida Tomonori , Kitadai Yasuhiko , Shinagawa Kei , Tanaka Miwako , Kodama Michiyo , Ohnishi Mayu , Ohara Eiji , Tanaka Shinji , Yasui Wataru , Chayama Kazuaki
Published: December 2010

Recent studies have revealed that platelet‐derived growth factor (PDGF) plays a role in promoting progressive tumor growth in several organs; however, whether PDGF plays such a role in gastric carcinoma is undetermined. We examined whether inhibition of PDGF receptor (PDGF‐R) tyrosine kinase signaling by imatinib affects tumor growth and metastasis in an orthotopic nude mouse model of human gastric carcinoma. TMK‐1 human gastric carcinoma cells were injected into the gastric wall of nude mice. Groups of mice (n = 10 each) received sterile water (control), low‐dose imatinib (50 mg/kg/day), high‐dose imatinib (200 mg/kg/day), cancer chemotherapeutic agent irinotecan (5 mg/kg/week), or imatinib (50 mg/kg/day or 200 mg/kg/day) and irinotecan (5 mg/kg/week) in combination for 28 days. Tumor growth and metastasis were assessed. Resected tumors were analyzed immunohistochemically. Carcinoma‐associated fibroblasts, pericytes and lymphatic endothelial cells in stroma expressed high levels of PDGF‐R; carcinoma cells did not. Treatment with imatinib alone did not inhibit tumor growth and metastasis; however, treatment with irinotecan alone or combined with imatinib significantly inhibited tumor growth. Only treatment with high‐dose imatinib and irinotecan in combination inhibited lymph node and peritoneal metastases. Immunohistochemically, only imatinib alone or in combination with irinotecan was shown to significantly decrease the stromal reaction, microvessel area and pericyte coverage of tumor microvessels. These effects were marked with high‐dose imatinib. In conclusion, administration of PDGF‐R tyrosine kinase inhibitor in combination with irinotecan appears to impair the progressive growth of gastric carcinoma by blockade of PDGF‐R signaling pathways in stromal cells.
Bystander effect of vinorelbine alters antitumor immune response
Authors: Thomas‐Schoemann Audrey , Lemare François , Mongaret Céline , Bermudez Elisabeth , Chéreau Christiane , Nicco Carole , Dauphin Alain , Weill Bernard , Goldwasser François , Batteux Frédéric , Alexandre Jérôme
Published: December 2010

The bystander effect (BE) is the ability of malignant cells affected by an anticancer agent to induce damage in neighboring cancer cells. In this study, we showed that it could also affect immune cells surrounding the tumor and interfere with the antitumor immune response. We observed that the exposure of human lung cancer cells A549 to vinorelbine induced a BE on neighboring human peripheral blood mononuclear cells (PBMCs) in vitro and on mice splenocytes in vivo. In vitro, the number of PBMCs killed because of their coculture with vinorelbine‐pretreated A549 cells was 33% higher than those killed by A549 control cells (p = 0.003). In addition, we showed that when vinorelbine‐pretreated A549 cells were injected into immunocompetent mice, splenocyte proliferation ex vivo toward tumor cells decreased by 27% compared with that seen in mice injected with untreated A549 cells (p = 0.03). Finally, in vivo experiment in A549 tumor bearing nude mice showed that adoptive transfer of A549 immune splenocytes was not able to delay tumor growth when vinorelbine‐pretreated A549 cells were used for immunization. Inhibition of the BE by the nitric oxide synthase inhibitor, N(G)‐nitro‐L‐arginine methyl ester, and the superoxide dismutase mimic, mangafodipir, suggested that it was mediated by oxidative and nitrosative stress. In conclusion, exposure of cancer cells to vinorelbine alters the antitumor immune response through a BE mediated by cellular oxidative and nitrosative stress. Our results offer new prospects for using oxidative stress modulators to restore the antitumor immune response in patients treated with anticancer agents.
A microdosing approach for characterizing formation and repair of carboplatin–DNA monoadducts and chemoresistance
Authors: Henderson Paul T. , Li Tao , He Miaoling , Zhang Hongyong , Malfatti Michael , Gandara David , Grimminger Peter P. , Danenberg Kathleen D. , Beckett Laurel , de Vere White Ralph W. , Turteltaub Kenneth W. , Pan Chong‐Xian
Published: December 2010

Formation and repair of platinum (Pt)‐induced DNA adducts is a critical step in Pt drug‐mediated cytotoxicity. Measurement of Pt–DNA adduct kinetics in tumors may be useful for better understanding chemoresistance and therapeutic response. However, this concept has yet to be rigorously tested because of technical challenges in measuring the adducts at low concentrations and consistent access to sufficient tumor biopsy material. Ultrasensitive accelerator mass spectrometry was used to detect [14C]carboplatin–DNA monoadducts at the attomole level, which are the precursors to Pt–DNA crosslink formation, in six cancer cell lines as a proof‐of‐concept. The most resistant cells had the lowest monoadduct levels at all time points over 24 hr. [14C]Carboplatin “microdoses” (1/100th the pharmacologically effective concentration) had nearly identical adduct formation and repair kinetics compared to therapeutically relevant doses, suggesting that the microdosing approach can potentially be used to determine the pharmacological effects of therapeutic treatment. Some of the possible chemoresistance mechanisms were also studied, such as drug uptake/efflux, intracellular inactivation and DNA repair in selected cell lines. Intracellular inactivation and efficient DNA repair each contributed significantly to the suppression of DNA monoadduct formation in the most resistant cell line compared to the most sensitive cell line studied (p < 0.001). Nucleotide excision repair (NER)‐deficient and ‐proficient cells showed substantial differences in carboplatin monoadduct concentrations over 24 hr that likely contributed to chemoresistance. The data support the utility of carboplatin microdosing as a translatable approach for defining carboplatin–DNA monoadduct formation and repair, possibly by NER, which may be useful for characterizing chemoresistance in vivo.
LRIG1 and the liar paradox in prostate cancer: A study of the expression and clinical significance of LRIG1 in prostate cancer
Authors: Thomasson Marcus , Wang Baofeng , Hammarsten Peter , Dahlman Anna , Persson Jenny Liao , Josefsson Andreas , Stattin Pär , Granfors Torvald , Egevad Lars , Henriksson Roger , Bergh Anders , Hedman Håkan
Published: December 2010

The course of prostate cancer varies greatly, and additional prognostic markers are needed. Leucine‐rich repeats and immunoglobulin‐like domains protein 1 (LRIG1) is an endogenous inhibitor of growth factor signaling and a proposed tumor suppressor. Publicly available gene expression datasets indicate that LRIG1 may be overexpressed in prostate cancer. In our study, the expression of LRIG1 protein in prostate cancer was evaluated for the first time. Immunohistochemistry was performed on tissue microarrays from two different patient series: 355 Swedish patients diagnosed by transurethral resection and 293 American patients who underwent radical prostatectomy. In the Swedish series, high expression of LRIG1 correlated with Gleason score, T‐stage, tumor cell proliferation, vascular density and epidermal growth factor receptor (EGFR) phosphorylation. Among the 256 Swedish patients, followed by watchful waiting, high LRIG1 expression was significantly associated with short overall and prostate cancer‐specific survival. In contrast, in the US series, high LRIG1 expression was significantly associated with long overall survival. In vitro cell experiments showed that LRIG1 was induced by androgen stimulation, and its expression inhibited prostate cancer cell proliferation. Thus, LRIG1 expression was an independent marker for poor survival in the untreated patient series, perhaps as a secondary marker of androgen receptor and/or EGFR activation. On the contrary, LRIG1 was a marker for good prognosis after prostatectomy, which might be due to its growth inhibiting properties. We propose that LRIG1 is an important determinant of prostate cancer growth, and the implications of its expression on patient outcome depend on the clinical and biological circumstances.
Identification of candidate predisposing copy number variants in familial and early‐onset colorectal cancer patients
Authors: Venkatachalam Ramprasath , Verwiel Eugène T.P. , Kamping Eveline J. , Hoenselaar Eveline , Görgens Heike , Schackert Hans K. , van Krieken J. Han J.M. , Ligtenberg Marjolijn J.L. , Hoogerbrugge Nicoline , van Kessel Ad Geurts , Kuiper Roland P.
Published: December 2010

In the majority of colorectal cancers (CRCs) under clinical suspicion for a hereditary cause, the disease‐causing genetic factors are still to be discovered. To identify such genetic factors we stringently selected a discovery cohort of 41 CRC index patients with microsatellite‐stable tumors. All patients were below 40 years of age at diagnosis and/or exhibited an overt family history. We employed genome‐wide copy number profiling using high‐resolution SNP arrays on germline DNA, which resulted in the identification of novel copy number variants (CNVs) in six patients (15%) encompassing, among others, the cadherin gene CDH18, the bone morphogenetic protein antagonist family gene GREM1, and the breakpoint cluster region gene BCR. In addition, two genomic deletions were encountered encompassing two microRNA genes, hsa‐mir‐491/KIAA1797 and hsa‐mir‐646/AK309218. None of these CNVs has previously been reported in relation to CRC predisposition in humans, nor were they encountered in large control cohorts (>1,600 unaffected individuals). Since several of these newly identified candidate genes may be functionally linked to CRC development, our results illustrate the potential of this approach for the identification of novel candidate genes involved in CRC predisposition.
Racial/ethnic differences in colorectal cancer risk: The multiethnic cohort study
Authors: Ollberding Nicholas J. , Nomura Abraham M.Y. , Wilkens Lynne R. , Henderson Brian E. , Kolonel Laurence N.
Published: December 2010

Incidence rates in the United States show clear racial/ethnic disparities for colorectal cancer. We examined the extent to which ethnic differences in risk factors could explain the age‐adjusted variation in the risk of colorectal cancer, overall and by stage at diagnosis, among 165,711 African Americans, Japanese Americans, Latinos, Native Hawaiians and whites participating in the Multiethnic Cohort Study. Over a median follow‐up period of 10.7 years, 2,564 incident cases of colorectal cancer were identified through surveillance, epidemiology and end result tumor registry linkages in Hawaii and California. Multivariable‐adjusted Cox proportional hazard models were used to estimate relative risks (RR) and 95% confidence intervals (CI) for each ethnic group compared to whites. After accounting for known/suspected risk factors, Japanese Americans (men, RR = 1.27, 95% CI = 1.09–1.48; women, RR = 1.49, 95% CI = 1.24–1.78) and African American women (RR = 1.48, 95% CI = 1.23–1.79) remained at increased risk of colorectal cancer relative to whites; African American and Japanese American women were also at increased risk of advanced disease compared to whites. In site‐specific analyses, after multivariable adjustment, African Americans (both sexes) and Japanese American women remained at increased risk for colon cancer, and Japanese Americans (both sexes) and Native Hawaiian men for rectal cancer compared to whites. The results of our study suggest that differences in the distribution of known/suspected risk factors account for only a modest proportion of the ethnic variation in colorectal cancer risk and that other factors, possibly including genetic susceptibility, are important contributors to the observed disparities in incidence.
MicroRNA expression profiling in human Barrett's carcinogenesis
Authors: Fassan Matteo , Volinia Stefano , Palatini Jeff , Pizzi Marco , Baffa Raffaele , De Bernard Marina , Battaglia Giorgio , Parente Paola , Croce Carlo M. , Zaninotto Giovanni , Ancona Ermanno , Rugge Massimo
Published: December 2010

Barrett's esophagus (BE) is characterized by the native stratified squamous epithelium (N) lining the esophagus being replaced by a columnar epithelium with intestinal differentiation (Barrett's mucosa; BM). BM is considered as the main risk factor for esophageal adenocarcinoma (Barrett's adenocarcinoma; BAc). MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting messenger RNAs and they are reportedly dysregulated in BM. To test the hypothesis that a specific miRNA expression signature characterizes BM development and progression, we performed miRNA microarray analysis comparing native esophageal mucosa with all the phenotypic lesions seen in the Barrett's carcinogenic process. Specimens were collected from 14 BE patients who had undergone esophagectomy, including: 14 with N, 14 with BM, 7 with low‐grade intraepithelial neoplasia, 5 with high‐grade intra‐epithelial neoplasia and 11 with BAc. Microarray findings were further validated by quantitive real‐time polymerase chain reaction and in situ hybridization analyses using a different series of consecutive cases (162 biopsy samples and 5 esophagectomies) of histologically proven, long‐segment BE. We identified a miRNA signature of Barrett's carcinogenesis consisting of an increased expression of 6 miRNAs and a reduced expression of 7 miRNAs. To further support these results, we investigated target gene expression using the Oncomine database and/or immunohistochemical analysis. We found that target gene expression correlated significantly with miRNA dysregulation. Specific miRNAs are directly involved in BE progression to cancer. miRNA profiling significantly expands current knowledge on the molecular history of Barrett's carcinogenesis, also identifying molecular markers of cancer progression.
The prognostic significance of tumor human papillomavirus status for patients with anal squamous cell carcinoma treated with combined chemoradiotherapy
Authors: Yhim Ho‐Young , Lee Na‐Ri , Song Eun‐Kee , Kwak Jae‐Yong , Lee Soo Teik , Kim Jong Hun , Kim Jung‐Soo , Park Ho Sung , Chung Ik‐Joo , Shim Hyun‐Jeong , Hwang Jun‐Eul , Kim Hyeong Rok , Nam Taek‐Keun , Park Moo‐Rim , Shim Hyeok , Park Hyo Sook , Kim Hee Sun , Yim Chang‐Yeol
Published: December 2010

The prognostic relevance of tumor human papillomavirus (HPV) status in anal squamous cell carcinoma (SCC) had not been previously investigated, although its relevance to cervical, head and neck SCC is known. We retrospectively evaluated outcomes in 47 patients with anal SCC treated with combined chemoradiotherapy (CCRT) and determined tumor HPV status by HPV DNA chip method and p16 expression by immunohistochemistry (IHC) from paraffin‐embedded tumor tissues. The median age was 65 years (range, 44–90 years). Sixteen (34%) patients were diagnosed with T stage 3 to 4, and 18 (38%) patients had regional nodal disease (N‐positive). Thirty‐five (75%) patients were HPV positive, and 31 (66%) patients were genotype 16 (HPV16‐positive). Thirty‐nine (83.0%) patients were positive for p16. After median follow‐up of 51.7 months (range, 5.1–136.0 months), HPV16‐positive group had significantly better 4‐year progression‐free survival (PFS, 63.1% vs. 15.6%, p < 0.001) and overall survival (84.6% vs. 39.8%, p = 0.008) than HPV genotype 16 negative (HPV16‐negative) group. Patients with p16‐positive tumor also had a better 4‐year PFS (52.5% vs. 25.0%, p = 0.014) than those with p16‐negative tumor. In multivariate analysis for PFS, N‐positive and HPV16‐negative were independent prognostic factors for shorter PFS. Comparing patterns of failure, time to loco‐regional failure was statistically superior in HPV16‐positive over HPV16‐negative groups (p = 0.006), but time to systemic failure was not different (p = 0.098). Tumor HPV genotype 16 status is a prognostic and predictive factor in anal SCC treated with CCRT, and p16 expression determined by IHC might be advocated as a surrogate biomarker of HPV integration in anal SCC. Further studies are warranted.
Dermatofibrosarcoma protuberans‐derived fibrosarcoma: Clinical history, biological profile and sensitivity to imatinib
Authors: Stacchiotti Silvia , Pedeutour Florence , Negri Tiziana , Conca Elena , Marrari Andrea , Palassini Elena , Collini Paola , Keslair Frederique , Morosi Carlo , Gronchi Alessandro , Pilotti Silvana , Casali Paolo G.
Published: December 2010

Dermatofibrosarcoma Protuberans (DFSP) carries a translocation resulting in the COL1A1/PDGFB fusion‐gene, responsible for platelet derived growth factor beta receptor (PDGFRB) activation. Fibrosarcomatous (FS) transformation in DFSP rarely occur. The fusion‐gene and PDGFRB expression/activation pattern and imatinib role in DFSP‐derived FS is less defined. We reviewed all consecutive patients operated for localized DFSP at our institution from 1994 to 2009, selecting cases with FS component. We also reviewed patients treated with imatinib for advanced FS‐DFSP over the same period. When cryopreserved material was available, biochemical/molecular analyses were performed. Of 275 DFSPs, 13 (4.7%) showed a FS component. Fifteen percent of these patients developed metastases, one to the brain. Four patients with DFSP‐derived FS received imatinib, with a Response Evaluation Criteria in Solid Tumor Partial Response. Response was followed by early secondary progression in two. One died for brain metastases. Three patients underwent surgery after imatinib. The fusion‐gene was detected in all cases in both the classical and FS component, before and after imatinib. PDGFRB expression/activation was confirmed in all cases. mTOR was switched‐off, despite the phosphorylation of its effectors. However, a strong phosphorylation of S6 and 4EBP1 was restricted to the FS component. In conclusion, DFSP‐derived FS maintains the fusion‐gene, being sensitive to imatinib. However, responses are short‐lasting. Secondary resistance to imatinib is not related to PDGFRB.
Differential effects of teriparatide on regional bone formation using 18F-fluoride positron emission tomography
Authors: Frost Michelle L , Siddique Musib , Blake Glen M , Moore Amelia EB , Schleyer Paul J , Dunn Joel T , Somer Edward J , Marsden Paul K , Eastell Richard , Fogelman Ignac
Published: December 2010

Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study 18F-fluoride plasma clearance (Ki) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 µg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine Ki values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine Ki values increased by 24% (p = .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k3/[k2 + k3]), which increased by 23% (p = .0006). In contrast to Ki, spine SUVs increased by only 3% (p = .84). The discrepancy between changes in Ki and SUVs was explained by a 20% decrease in 18F− plasma concentration. SUVs increased by 37% at the femoral shaft (p = .0019), 20% at the total hip (p = .032), and 11% at the pelvis (p = .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by 18F− PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. © 2011 American Society for Bone and Mineral Research.
Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of nonfractured bones
Authors: Ominsky Michael S , Li Chaoyang , Li Xiaodong , Tan Hong L , Lee Edward , Barrero Mauricio , Asuncion Franklin J , Dwyer Denise , Han Chun-Ya , Vlasseros Fay , Samadfam Rana , Jolette Jacquelin , Smith Susan Y , Stolina Marina , Lacey David L , Simonet William S , Paszty Chris , Li Gang , Ke Hua Z
Published: December 2010

Therapeutic enhancement of fracture healing would help to prevent the occurrence of orthopedic complications such as nonunion and revision surgery. Sclerostin is a negative regulator of bone formation, and treatment with a sclerostin monoclonal antibody (Scl-Ab) results in increased bone formation and bone mass in animal models. Our objective was to investigate the effects of systemic administration of Scl-Ab in two models of fracture healing. In both a closed femoral fracture model in rats and a fibular osteotomy model in cynomolgus monkeys, Scl-Ab significantly increased bone mass and bone strength at the site of fracture. After 10 weeks of healing in nonhuman primates, the fractures in the Scl-Ab group had less callus cartilage and smaller fracture gaps containing more bone and less fibrovascular tissue. These improvements at the fracture site corresponded with improvements in bone formation, bone mass, and bone strength at nonfractured cortical and trabecular sites in both studies. Thus the potent anabolic activity of Scl-Ab throughout the skeleton also was associated with an anabolic effect at the site of fracture. These results support the potential for systemic Scl-Ab administration to enhance fracture healing in patients. © 2011 American Society for Bone and Mineral Research.
Discrepancies between community violence exposure and perceived neighborhood violence
Authors: Cammack Nicole L. , Lambert Sharon F. , Ialongo Nicholas S.
Published: December 2010

Community violence exposure (CVE) has been identified as a significant public health concern given its association with numerous mental health problems. Perceptions of neighborhood violence (PNV) also may adversely affect youth adjustment. In recognition that PNV may differ from individuals own experience of CVE, the current study utilized latent class analysis to examine the degree and consequences of consistency and discrepancy in adolescents community violence exposure and PNV. Participants included an epidemiologically‐defined community sample of 456 African American adolescents (52% male; mean age=11.77). Results revealed three groups of youth: high CVE/high PNV, low CVE/low PNV, and low CVE/high PNV. Longitudinal analyses suggest that a discrepancy between CVE and PNV is important for understanding depressive and anxious symptoms among urban African American youth. Implications for intervention are discussed. © 2010 Wiley Periodicals, Inc.
Extraction of naringin from pomelo peels as dihydrochalcone's precursor
Authors: Tang Dong‐Mei , Zhu Chun‐Feng , Zhong Shi‐An , Zhou Ming‐Da
Published: December 2010

A new method for the separation of naringin from pomelo peels was investigated by using ultrasonic‐assisted extraction and macroporous resin purification technology. The ultrasonic extraction efficiency was dependent on agent's concentration, ratio of sample and solvent and ultrasonic time. Several parameters of macroporous resin‐purified process, including resin selection, initial concentration, concentration of eluted agent and pH, were optimized. The experimental results showed that the naringin content in the mature pomelo peels was 2.20% and purification rate of naringin was 77.26% under optimum conditions of purification. The structure of synthetic naringin dihydrochalcone was determined by a series of spectroscopic methods, such as UV, NMR and MS.
Influence of the FID and off‐resonance effects in dense MRI
Authors: Haraldsson Henrik , Sigfridsson Andreas , Sakuma Hajime , Engvall Jan , Ebbers Tino
Published: December 2010

Accurate functional measurement in cardiovascular diseases is important as inaccuracy may compromise diagnostic decisions. Cardiac function can be assessed using displacement encoding with stimulated echoes, resulting in three signal components. The free induction decay (FID), arising from spins undergoing T1‐relaxation, is not displacement encoded and impairs the displacement acquired. Techniques for suppressing the FID exist; however, a residual will remain. The effect of the residual is difficult to distinguish and investigate in vitro and in vivo. In this work, the influence of the FID as well as of off‐resonance effects is evaluated by altering the phase of the FID in relation to the stimulated echo. The results show that the FID and off‐resonance effects can impair the accuracy of the displacement measurement acquired. The influence of the FID can be avoided by using an encoded reference. We therefore recommend the assessment of this influence of the FID for each displacement encoding with stimulated echoes protocol. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Longitudinal analysis of MRI T2 knee cartilage laminar organization in a subset of patients from the osteoarthritis initiative: A texture approach
Authors: Carballido‐Gamio Julio , Joseph Gabby B. , Lynch John A. , Link Thomas M. , Majumdar Sharmila
Published: December 2010

Cartilage magnetic resonance imaging T2 relaxation time is sensitive to hydration, collagen content, and tissue anisotropy, and a potential imaging‐based biomarker for knee osteoarthritis. This longitudinal pilot study presents an improved cartilage flattening technique that facilitates texture analysis using gray‐level co‐occurrence matrices parallel and perpendicular to the cartilage layers, and the application of this technique to the knee cartilage of 13 subjects of the osteoarthritis initiative at baseline, 1‐year follow‐up, and 2‐year follow‐up. Cartilage flattening showed minimum distortion (∼ 0.5 ms) of mean T2 values between nonflattened and flattened T2 maps. Gray‐level co‐occurrence matrices texture analysis of flattened T2 maps detected a cartilage laminar organization at baseline, 1‐year follow‐up, and 2‐year follow‐up by yielding significant (P < 0.05) differences between texture parameters perpendicular and parallel to the cartilage layers. Tendencies showed higher contrast, dissimilarity, angular second moment, and energy perpendicular to the cartilage layers; and higher homogeneity, entropy, variance, and correlation parallel to them. Significant (P < 0.05) longitudinal texture changes were also detected reflecting subtle signs of a laminar disruption. Tendencies showed decreasing contrast, dissimilarity, and entropy; and increasing homogeneity, energy, and correlation. Results of this study warrant further investigation to complete the assessment of the usefulness of the presented methodology in the study of knee osteoarthritis. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Iodanalytik: Wie man einen Flüchtigen einfängt
Authors: Monse Grit
Published: December 2010

Moderne ICP‐OE‐Spektrometer messen bis weit in den UV‐Bereich hinein und bestimmen so Elemente wie Iod und Schwefel, die früher nicht spektroskopisch zugänglich waren. Beim Iod bringen diese neuen Möglichkeiten aber auch neue Herausforderungen mit sich.
Lost mit Teekannen in Bomben gefüllt
Authors: Sietz Henning
Published: December 2010

Ein Buch enthüllt Neues zur Geschichte der chemischen Kampfstoffe in Russland.
CO2 als Rohstoff
Authors: Bazzanella Alexis , Krämer Dennis , Peters Martina
Published: December 2010

Chemische Industrie und Energieversorger entwicklen Konzepte, die Kohlendioxid als Edukt in chemischen Prozessen nutzen, sowie Produkte, die es als Synthesebaustein enthalten.
Was bei einer Änderung des Geschäftsmodells zu bedenken ist
Authors: Schmidt Ralf
Published: December 2010

Unternehmen müssen prüfen, auf welche Art sie Geld verdienen und wie sie mit Kunden und Lieferanten umgehen. Mit angepassten Modellen sind größere Gewinne möglich. Gerade in Commodity‐Märkten sind Strategien gefragt, um Wettbewerbsvorteile aufzubauen.
Richtiges analytisches Wägen — was Justus von Liebig dazu sagte
Authors: Opfer Karl‐Armin
Published: December 2010

Beim analytischen Wägen läuft oft vieles falsch, doch die meisten Fehler sind leicht zu vermeiden.
Coaching im Team
Authors: Schmitz Karin
Published: December 2010

Ein Trainingsprogramm unterstützt Chemiker mit erster Berufserfahrung bei der persönlichen und beruflichen Entwicklung.
Absurd oder irgendwie nützlich?
Authors: Schneider Christoph
Published: December 2010

Wie viel taugen die Herbstausgaben der weltweiten Hochschulrankings?
Vorstandssitzung
Authors: Koch Wolfram
Published: December 2010

Die zweite Sitzung des Vorstands der Gesellschaft Deutscher Chemiker im Jahr 2010 fand am 30. August in Verbindung mit dem 3rd EuCheMS Chemistry Congress in Nürnberg statt.
Analytical model for the prediction of building deflections induced by ground movements
Authors: Deck Oliver , Singh Amresh
Published: December 2010

The objective of this study is to develop an analytical model that can predict the building‐relevant deflections induced by tunnelling or mining subsidence. The model takes into account soil–structure interactions due to differences in stiffness between the ground and the building.

The ground is modelled by the Winkler model with an initial ground curvature equivalent to the free‐field ground movements. The building is modelled by a horizontal beam with uniform loading. The static and cinematic equilibrium of both the ground and the building are then calculated to assess the final building and ground shape, and the building deflection is derived.

The resulting analytical model is used to investigate the influence of the ground and the building's mechanical properties, the building load and the initial value of the free‐field ground curvature (hogging or sagging). The model appears to be more comprehensive than those reported elsewhere that address the problem with numerical models. In particular, the analytical model makes it possible to distinguish two different final situations—with continuous or discontinuous contact between the ground and the building. The model is compared with numerical results and used to analyse a case study. Copyright © 2010 John Wiley & Sons, Ltd.
Cyclic scheduling in robotic flowshops with bounded work‐in‐process levels
Authors: Che Ada , Kats Vladimir , Levner Eugene
Published: December 2010

This study addresses cyclic scheduling in robotic flowshops with bounded work‐in‐process (WIP) levels. The objective is to minimize the cycle time or, equivalently, to maximize the throughput, under the condition that the WIP level is bounded from above by a given integer number. We present several strongly polynomial algorithms for the 2‐cyclic robotic flowshop scheduling problems for various WIP levels. © 2010 Wiley Periodicals, Inc. Naval Research Logistics 58: 1–16, 2011
Elevation of WNT5A expression in polyp formation in Lkb1+/− mice and Peutz–Jeghers syndrome
Authors: Lai Cecilia , Robinson James , Clark Sue , Stamp Gordon , Poulsom Richard , Silver Andrew
Published: December 2010

Peutz‐Jeghers syndrome (PJS) is a rare, inherited disease caused by germline mutation of the LKB1 gene. Patients with PJS develop characteristic polyps in the digestive tract and carry an elevated risk of cancers in multiple organs, including the intestinal tract. While LKB1 is capable of phosphorylating AMPK and regulates the mTOR pathway, it is also known to be a multitasking protein that can influence other cellular processes, including cell polarity. We hypothesized that there may be other biological pathways directly or indirectly affected by the loss of LKB1 in PJS and aimed to investigate this possibility through transcriptional profiling of polyps harvested from an Lkb1+/− mouse model of PJS and from PJS patients. We identified alterations in the mRNA level of a wide range of genes, including some that are involved in Wnt signalling (Wnt5a, Wif1, Dixdc1, Wnt11, Ccnd1, and Ccnd2), although we did not observe nuclear localization of β‐catenin in over 93 human PJS intestinal polyps or in 24 gastric polyps from Lkb1+/− mice. Among these genes, WNT5A, a non‐canonical and non‐transforming Wnt, is consistently up‐regulated in both Lkb1+/− mice and human PJS polyps at a high level. We performed in situ hybridization to further define the spatial expression pattern of WNT5A and observed a strong signal in the stroma of mouse and human polyps compared to no or very low expression in the mucosa. Our findings indicate that WNT5A plays an important role in PJS polyposis. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mannose‐binding lectin (MBL) and the risk for febrile neutropenia and infection in pediatric oncology patients with chemotherapy
Authors: Frakking F.N.J. , Israëls J. , Kremer L.C.M. , Kuijpers T.W. , Caron H.N. , van de Wetering M.D.
Published: December 2010

Background

We determined whether mannose‐binding lectin (MBL) deficiency is associated with an increased risk of febrile neutropenia (FN) and/or infection in pediatric oncology patients.

Procedure

We systematically searched and reviewed all the literature on MBL and infections in children with cancer, identified from a literature search of Medline, Embase, and Central (1966–April 2010). We extracted information on the type of study, patient characteristics, definition of MBL deficiency, definition of infection and method of detection, follow‐up period and the results of the outcome in different groups. The validity of each study was assessed.

Results

Six cohort studies were retrieved, consisting of 581 children with leukemia (n = 2) or varying types of cancer (n = 4). Many different outcome definitions were used. In only one out of three genotype studies, variant MBL2 genotypes, as well as MBL levels <1,000 µg/L, were associated with an increased duration of FN. In one additional MBL level study the number of FN episodes, bacteremia and severe bacterial infection were increased in patients with MBL levels <100 µg/L as compared to those with MBL levels of 100–999 µg/L. Sepsis, pneumonia, viral infection, and fungal infection were not associated with either MBL levels or genotypes in any of the studies.

Conclusions

MBL deficiency could not be identified as an independent risk factor for FN or infection in pediatric oncology patients. A multicenter study of children with comparable chemotherapy regimens, relevant and equal outcome definitions and measuring both MBL levels and genotypes, will be required to avoid clinical and methodological inconsistencies. Pediatr Blood Cancer 2011;57:89–96. © 2010 Wiley‐Liss, Inc.