bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bidentate Lewis Acids for the Activation of 1,2‐Diazines – A New Mode of Catalysis
Authors: Kessler Simon N. , Neuburger Markus , Wegner Hermann A. 
Published: May 2011

AbstractBidentate Lewis acids were applied as catalysts for the inverse‐electron‐demand Diels–Alder (IEDDA) reaction of 1,2‐diazines. The concept of catalysis is based on the coordination of the bidentate Lewis acid to both nitrogen atoms of the 1,2‐diazine moiety, thereby reducing the electron density and lowering the energy of the LUMO. This should, according to frontier molecular orbital (FMO) theory, facilitate the cycloaddition step. This new concept was successfully applied to a variety of dienophiles and substituted phthalazine substrates. Careful investigations of the mechanism led to the isolation and characterization of key intermediates; all of which support the presented catalytic cycle.
The Dinosyl Group: A Powerful Activator for the Regioselective Alcoholysis of Aziridines
Authors: Stanetty Christian , Blaukopf Markus K. , Lachmann Bodo , Noe Christian R. 
Published: May 2011

AbstractThe N‐2,4‐dinitrophenylsulfonyl group (dinosyl, DNs) was found to be an excellent choice for the N‐activation of aziridines towards ring cleavage with primary, secondary, andsterically demanding tertiary alcohols. Alcoholysis does not need any additional catalyst and is regioselective for the less‐hindered position. No racemization in the aziridine formation or cleavage step was observed, and the resulting DNs‐sulfonamides can be deprotected quantitatively under mild conditions.
Fluid–structure interaction analysis in microfluidic devices: A dimensionless finite element approach
Authors: Afrasiab Hamed , Movahhedy Mohammad R. , Assempour Ahmad 
Published: May 2011

SUMMARYIn this paper, the so‐called small time‐step instability in finite element simulation of the fluid part is considered in fluid–structure interaction (FSI) problems in which a high‐frequency vibrating structure interacts with an incompressible fluid. Such a situation is common in many microfluid manipulating devices. A treatment has been proposed that uses the dimensionless set of FSI governing equations in order to scale up the problem time step to a proper level that precludes the potential small time‐step instability. Two‐dimensional and three‐dimensional finite element simulations of a mechanical micropumping device are performed to verify the efficiency of the presented approach. Solid structure vibrations of high frequency and nano‐scale amplitude are used to derive the fluid flow in this kind of micropump. Results of FEM simulations are in good agreement with experimental data. The fluid problem is formulated and solved in arbitrary Lagrangian–Eulerian description. Copyright © 2011 John Wiley & Sons, Ltd.
Astrocytic activation of A1 receptors regulates the surface expression of NMDA receptors through a Src kinase dependent pathway
Authors: Deng Qiudong , Terunuma Miho , Fellin Tommaso , Moss Stephen J. , Haydon Philip G. 
Published: May 2011

AbstractChemical transmitters released from astrocytes, termed gliotransmitters, modulate synaptic transmission and neuronal function. Using astrocyte‐specific inducible transgenic mice (dnSNARE mice), we have demonstrated that inhibiting gliotransmission leads to reduced activation of adenosine A1 receptors (A1R) and impaired sleep homeostasis (Halassa et al. (2009) Neuron 61:213–219); Pascual et al. (2005) Science 310:113–116). Additionally, synaptic N‐methyl‐D‐aspartate receptor (NMDAR) currents are reduced in these astrocyte‐specific transgenic animals (Fellin et al. (2009) Proc Natl Acad Sci USA 106:15037–15042). Because of the importance of adenosine and NMDA receptors to sleep processes we asked whether there is a causal linkage between changes in A1R activation and synaptic NMDA receptors. We show that astrocytic dnSNARE expression leads to reduced tyrosine phosphorylation of Src kinase and NR2 subunits concomitant with the decreased surface expression of the NR2 subunits. To test the role of A1R signaling in mediating these actions, we show that incubation of wildtype (WT) slices with an A1R antagonist reduces tyrosine phosphorylation of Src kinase and NR2B, decreases the surface expression of the NR2B subunits and leads to smaller NMDA component of miniature EPSCs. In dnSNARE mice we could rescue WT phenotype by incubation in an A1R agonist: activation of A1 receptor led to increased tyrosine phosphorylation of Src kinase and NR2B subunits as well as increased the surface expression of the NR2B subunit and increased NMDA component of the synaptic mEPSC. These results provide the first demonstration that astrocytes can affect neuronal excitability on a long time scale by regulating the surface expression of NMDA receptors through the activation of specific intracellular signaling pathways. © 2011 Wiley‐Liss, Inc.
Differentiation of postnatal cerebellar glial progenitors is controlled by Bmi1 through BMP pathway inhibition
Authors: Zhang Xinyu , Santuccione Antonella , Leung Carly , Marino Silvia 
Published: May 2011

AbstractBmi1 is a polycomb group (Pc‐G) protein involved in heritable gene repression, maintenance of cell identity, and proliferation. During the development of the central nervous system, Bmi1 is crucial for self‐renewal of neural stem cells and for proliferation of neuronal (granule cell) progenitors of the cerebellum. Here, we use loss of function mouse models and in vitro assays—granule cell cultures and glial‐neuronal co‐cultures—to show that Bmi1 plays a crucial role in specification of glial progenitors during postnatal cerebellar development. Moreover, we demonstrate in in vitro assays that Bmi1 exerts this novel function through repression of BMP pathway and that this is independent of its known role in mediating the cellular response to Shh signaling. Thus modulation of Bmi1 expression in glial progenitors may represent a key event in determining the differentiation potential of these cells. © 2011 Wiley‐Liss, Inc.
Novel molecular targeted therapies for refractory thyroid cancer
Authors: Perez Cesar A. , Santos Edgardo S. , Arango Belisario A. , Raez Luis E. , Cohen Ezra E. W. 
Published: May 2011

AbstractThe incidence of thyroid cancer continues to increase and this neoplasia remains the most common endocrine malignancy. No effective systemic treatment currently exists for iodine‐refractory differentiated or medullary thyroid carcinoma, but recent advances in the pathogenesis of these diseases have revealed key targets that are now being evaluated in the clinical setting. RET (rearranged during transfection)/PTC (papillary thyroid carcinoma) gene rearrangements, B‐Raf gene mutations, and vascular endothelial growth factor receptor 2 (VEGFR‐2) angiogenesis pathways are some of the known genetic alterations playing a crucial role in the development of thyroid cancer. Several novel agents have demonstrated promising responses. Of the treatments studied, multi‐kinase inhibitors such as axitinib, sorafenib, motesanib, and XL‐184 have shown to be the most effective by inducing clinical responses and stabilizing the disease process. Randomized clinical trials are currently evaluating these agents, results that may soon change the management of thyroid cancer. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
Chondromyxoid fibroma of the nasal septum: Case report and review of literature
Authors: McClurg Stanley W. , Leon Marino , Teknos Theodoros N. , Iwenofu O. Hans 
Published: May 2011

AbstractBackground.Chondromyxoid fibroma (CMF) is a rare bone tumor, accounting for less than 0.5% of all bone tumors, with a predilection for lower extremity bone metaphyses. Involvement of the head and neck is extremely rare, with only 3 cases reported in the nasal septum in world literature.Methods.This is a case report of a CMF in the nasal septum of a 49‐year‐old woman with a 6‐month history of congestion. MRI showed a bilobed mass originating from the nasal septum. Histologic and immunoperoxidase staining as well as electron microscopic studies were performed. A literature review was performed.Results.The patient underwent a midface‐degloving approach for surgical resection. The final pathology was prototypic of CMF. The patient was disease‐free 16 months postoperatively.Conclusions.CMF is a rare, benign neoplasm occasionally occurring in the head and neck. Surgical resection is often curative. CMF must be differentiated from chondrosarcoma, given the substantial differences in treatment. © 2011 Wiley Periodicals, Inc. Head Neck, 2013
Circulating micro‐RNA expression profiles in early stage nonsmall cell lung cancer
Authors: Heegaard Niels H.H. , Schetter Aaron J. , Welsh Judith A. , Yoneda Mitsuhiro , Bowman Elise D. , Harris Curtis C. 
Published: May 2011

AbstractCirculating micro‐RNA (miR) profiles have been proposed as promising diagnostic and prognostic biomarkers for cancer, including lung cancer. We have developed methods to accurately and reproducibly measure micro‐RNA levels in serum and plasma. Here, we study paired serum and plasma samples from 220 patients with early stage nonsmall cell lung cancer (NSCLC) and 220 matched controls. We use qRT‐PCR to measure the circulating levels of 30 different miRs that have previously been reported to be differently expressed in lung cancer tissue. Duplicate RNA extractions were performed for 10% of all samples, and micro‐RNA measurements were highly correlated among those duplicates. This demonstrates high reproducibility of our assay. The expressions of miR‐146b, miR‐221, let‐7a, miR‐155, miR‐17‐5p, miR‐27a and miR‐106a were significantly reduced in the serum of NSCLC cases, while miR‐29c was significantly increased. No significant differences were observed in plasma of patients compared with controls. Overall, expression levels in serum did not correlate well with levels in plasma. In secondary analyses, reduced plasma expression of let‐7b was modestly associated with worse cancer‐specific mortality in all patients, and reduced serum expression of miR‐223 was modestly associated with cancer‐specific mortality in stage IA/B patients. MiR profiles also showed considerable differences comparing African American and European Americans. In summary, we found significant differences in miR expression when comparing cases and controls and find evidence that expression of let‐7b is associated with prognosis in NSCLC.
Anti‐tumour/metastasis effects of the potassium‐sparing diuretic amiloride: An orally active anti‐cancer drug waiting for its call‐of‐duty?
Authors: Matthews Hayden , Ranson Marie , Kelso Michael J. 
Published: May 2011

AbstractAmiloride.HCl is clinically used as an oral potassium‐sparing diuretic, but multiple studies in biochemical, cellular and animal models have shown that the drug also possesses anti‐tumour and anti‐metastasis activities. The additional effects appear to arise through inhibition of two discrete targets: (i) the sodium–hydrogen exchanger 1 (NHE1), a membrane protein responsible for the characteristically low extracellular pH of tumours and (ii) the urokinase‐type plasminogen activator (uPA), a serine protease mediator of cell migration, invasion and metastasis and well‐known marker of poor prognosis in cancer. This mini‐review summarises for the first time the reported anti‐tumour/metastasis effects of amiloride in experimental models, discusses the putative molecular mechanisms responsible for these effects and concludes by commenting on the pros and cons of trialling amiloride or one of its structural analogues as potential new anti‐tumour/metastasis drugs.
Quinacrine has anticancer activity in breast cancer cells through inhibition of topoisomerase activity
Authors: Preet Ranjan , Mohapatra Purusottam , Mohanty Suchitra , Sahu Sushil Kumar , Choudhuri Tathagata , Wyatt Michael D. , Kundu Chanakya Nath 
Published: May 2011

AbstractThe small molecule Quinacrine (QC, a derivative of 9‐aminoacridine), an anti‐malaria drug, displays activity against cancer cell lines and can simultaneously suppress nuclear factor‐κB (NF‐κB) and activate p53 signaling. In this study, we investigated the anticancer mechanism underlying these drug activities in breast cancer cell lines. QC caused a dose‐dependent decrease of both anchorage dependent and independent growth of breast cancer cells (MCF‐7 and MDA‐MB‐231) without affecting normal breast epithelial cells (MCF‐10A), as evident from clonogenic cell survival, [3‐(4,5‐dimethylthiazol‐2yl‐)‐2,5‐diphenyl tetrazolium bromide] viability, wound healing and soft agar growth. QC activated the proapoptotic marker Bax, PARP cleavage, p53 and its downstream target, p21 (Cip1/Waf1) and downregulated the antiapoptotic marker Bcl‐xL and relative luciferase activity of NF‐κB in MCF‐7 cells. Results of DAPI nuclear staining and FACS analysis show that QC increased apoptosis in a dose‐dependent manner. QC caused apoptosis by increasing the cell population in S‐phase and simultaneously decreasing the G1 and G2/M populations. A dose‐dependent increase of DNA damage as measured by the comet assay was seen in MCF‐7 cells after exposure to QC. With regards to the mechanism of DNA damage, we found that QC inhibited topoisomerase activity in MCF‐7 cells by increasing the unwinding of supercoiled DNA. Collectively, the results demonstrate that QC has efficient anticancer potential against breast cancer cells via not only an induction of p53 and p21 but also an induction of S phase arrest, DNA damage and inhibition of topoisomerase activity.
Aberrations of a cell adhesion molecule CADM4 in renal clear cell carcinoma
Authors: Nagata Masayoshi , Sakurai‐Yageta Mika , Yamada Daisuke , Goto Akiteru , Ito Akihiko , Fukuhara Hiroshi , Kume Haruki , Morikawa Teppei , Fukayama Masashi , Homma Yukio , Murakami Yoshinori 
Published: May 2011

AbstractRenal clear cell carcinoma (RCCC) is the most frequent subpopulation of renal cell carcinoma and is derived from the proximal uriniferous tubules. We have previously reported that an actin‐binding protein, 4.1B/DAL‐1, is expressed in renal proximal tubules, whereas it is inactivated in 45% of RCCC by promoter methylation. In the lung and several epithelial tissues, 4.1B is shown to associate with a tumor suppressor protein, CADM1, belonging to the immunoglobulin‐superfamily cell adhesion molecules. Here, we demonstrate by immunohistochemistry that another member of the CADM‐family protein, CADM4, as well as 4.1B is expressed specifically in human proximal tubules, while CADM1 and 4.1N, another member of the 4.1 proteins, are expressed in the distal tubules. Immunoprecipitation analysis coupled with Western blotting revealed that CADM4 associated with 4.1B, while CADM1 associated with 4.1N in the lysate from normal human kidney, implicating that a cascade of CADM4 and 4.1B plays an important role in normal cell adhesion of the proximal tubules. On the other hand, CADM4 expression was lost or markedly reduced in 7 of 10 (70%) RCC cell lines and 28 of 40 (70%) surgically resected RCCC, including 10 of 16 (63%) tumors with T1a. CADM4 expression was more preferentially lost in RCCC with vascular infiltration (p = 0.04), suggesting that loss of CADM4 is involved in tumor invasion. Finally, introduction of CADM4 into an RCC cell line, 786‐O, dramatically suppressed tumor formation in nude mice. These findings suggest that CADM4 is a novel tumor suppressor candidate in RCCC acting with its binding partner 4.1B.
Body fat distribution, weight change during adulthood, and thyroid cancer risk in the NIH‐AARP Diet and Health Study
Authors: Kitahara Cari M. , Platz Elizabeth A. , Park Yikyung , Hollenbeck Albert R. , Schatzkin Arthur , Berrington de González Amy 
Published: May 2011

AbstractBody mass index (BMI) has been positively associated with thyroid cancer risk in several studies, but the underlying mechanisms remain unclear. We examined the associations for waist and hip circumference and weight change during adulthood with thyroid cancer risk among 125,347 men and 72,363 women in the NIH‐AARP Diet and Health Study who completed a second mailed questionnaire in 1996–1997. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated separately by sex and adjusted for race/ethnicity, education and smoking status. During follow‐up (median = 10.1 years), 106 men and 105 women were diagnosed with a first primary thyroid cancer, as identified through linkage to state cancer registries. Having a large waist circumference (above the clinical cutpoint for normal: >102 cm in men and >88 cm in women) was associated with increased risk in both men (HR = 1.79, 95% CI: 1.21–2.63) and women (HR = 1.54, 95% CI: 1.05–2.26). Having both a large waist and BMI in the obese range (≥30 kg/m2) approximately doubled the risk of thyroid cancer (HR in men = 2.13, 95% CI: 1.18–3.85; HR in women = 1.91, 95% CI: 1.31–3.25) compared to having a normal waist circumference/normal BMI (18.5–24.9 kg/m2). We also observed positive association for weight gain between ages 18–35 in men (gained ≥10.0 kg vs. lost/gained <5 kg, HR = 1.49, 95% CI: 0.93–2.39, p‐trend = 0.03), but the association was less pronounced in women. No clear association for weight gain in later life was observed. These results support a potential role for hormonal and metabolic parameters common to central adiposity in thyroid carcinogenesis.
Genetic variability in the metabolism of the tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) to 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL)
Authors: Ter‐Minassian Monica , Asomaning Kofi , Zhao Yang , Chen Feng , Su Li , Carmella Steven G. , Lin Xihong , Hecht Stephen S. , Christiani David C. 
Published: May 2011

AbstractUrinary metabolites of the tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL) and its glucuronides, termed total NNAL, have recently been shown to be good predictors of lung cancer risk, years before diagnosis. We sought to determine the contribution of several genetic polymorphisms to total NNAL output and inter‐individual variability. The study subjects were derived from the Harvard/Massachusetts General Hospital Lung cancer case‐control study. We analyzed 87 self‐described smokers (35 lung cancer cases and 52 controls), with urine samples collected at time of diagnosis (1992–1996). We tested 82 tagging SNPs in 16 genes related to the metabolism of NNK to total NNAL. Using weighted case status least squares regression, we tested for the association of each SNP with square‐root (sqrt) transformed total NNAL (pmol per mg creatinine), controlling for age, sex, sqrt packyears and sqrt nicotine (ng per mg creatinine). After a sqrt transformation, nicotine significantly predicted a 0.018 (0.014, 0.023) pmol/mg creatinine unit increase in total NNAL for every ng/mg creatinine increase in nicotine at p < 10E‐16. Three HSD11B1 SNPs and AKR1C4 rs7083869 were significantly associated with decreasing total NNAL levels: HSD11B1 rs2235543 (p = 4.84E‐08) and rs3753519 (p = 0.0017) passed multiple testing adjustment at FDR q = 1.13E‐05 and 0.07 respectively, AKR1C4 rs7083869 (p = 0.019) did not, FDR q = 0.51. HSD11B1 and AKR1C4 enzymes are carbonyl reductases directly involved in the single step reduction of NNK to NNAL. The HSD11B1 SNPs may be correlated with the functional variant rs13306401 and the AKR1C4 SNP is correlated with the enzyme activity reducing variant rs17134592, L311V.
Candidate driver genes in microsatellite‐unstable colorectal cancer
Authors: Alhopuro Pia , Sammalkorpi Heli , Niittymäki Iina , Biström Mia , Raitila Anniina , Saharinen Juha , Nousiainen Kari , Lehtonen Heli J. , Heliövaara Elina , Puhakka Jani , Tuupanen Sari , Sousa Sónia , Seruca Raquel , Ferreira Ana M. , Hofstra Robert M. W. , Mecklin Jukka‐Pekka , Järvinen Heikki , Ristimäki Ari , Ørntoft Torben F. , Hautaniemi Sampsa , Arango Diego , Karhu Auli , Aaltonen Lauri A. 
Published: May 2011

AbstractDefects in the mismatch repair system lead to microsatellite instability (MSI), a feature observed in ∼ 15% of all colorectal cancers (CRCs). Microsatellite mutations that drive tumourigenesis, typically inactivation of tumour suppressors, are selected for and are frequently detected in MSI cancers. Here, we evaluated somatic mutations in microsatellite repeats of 790 genes chosen based on reduced expression in MSI CRC and existence of a coding mononucleotide repeat of 6–10 bp in length. All the repeats were initially sequenced in 30 primary MSI CRC samples and whenever frameshift mutations were identified in >20%, additional 70 samples were sequenced. To distinguish driver mutations from passengers, we similarly analyzed the occurrence of frameshift mutations in 121 intronic control repeats and utilized a statistical regression model to determine cut‐off mutation frequencies for repeats of all types (A/T and C/G, 6–10 bp). Along with several know target genes, including TGFBR2, ACVR2, and MSH3, six novel candidate driver genes emerged that harbored significantly more mutations than identical control repeats. The mutation frequencies in 100 MSI CRC samples were 51% in G8 of GLYR1, 47% in T9 of ABCC5, 43% in G8 of WDTC1, 33% in A8 of ROCK1, 30% in T8 of OR51E2, and 28% in A8 of TCEB3. Immunohistochemical staining of GLYR1 revealed defective protein expression in tumors carrying biallelic mutations, supporting a loss of function hypothesis. This is a large scale, unbiased effort to identify genes that when mutated are likely to contribute to MSI CRC development.
Targeting of pancreatic and prostate cancer stem cell characteristics by Crambe crambe marine sponge extract
Authors: Ottinger Sabine , Klöppel Anne , Rausch Vanessa , Liu Li , Kallifatidis Georgios , Gross Wolfgang , Gebhard Martha‐Maria , Brümmer Franz , Herr Ingrid 
Published: May 2011

AbstractCancer stem cells (CSCs) are suggested as reason for resistance of tumors toward conventional tumor therapy including pancreatic and advanced prostate cancer. New therapeutic agents are urgently needed for targeting of CSCs. Marine sponges harbor novel and undefined compounds with antineoplastic activity but their potential to eliminate CSC characteristics is not examined so far. We collected 10 marine sponges and one freshwater sponge by diving at the seaside and prepared crude methanolic extracts. The effect to established pancreatic and prostate CSC lines was evaluated by analysis of apoptosis, cell cycle, side population, colony and spheroid formation, migratory potential in vitro and tumorigenicity in vivo. While each sponge extract at a 1:10 dilution efficiently diminished viability, Crambe crambe marine sponge extract (CR) still strongly reduced viability of tumor cells at a dilution of 1:1,000 but was less toxic to normal fibroblasts and endothelial cells. CR inhibited self‐renewal capacity, apoptosis resistance, and proliferation even in gemcitabine‐selected pancreatic cancer cells with acquired therapy resistance and enhanced CSC characteristics. CR pretreatment of tumor cells diminished tumorigenicity of gemcitabine‐resistant tumor cells in mice and totally abolished tumor take upon combination with gemcitabine. Our data suggest that CR contains substances, which render standard cancer therapy more effective by targeting of CSC characteristics. Isolation of bioactive metabolites from CR and evaluation in mice are required for development of new CSC‐specific chemotherapeutic drugs from a marine sponge.