bluuebunny/crossref_metadata_2025 huggingface dataset:
Suberoylanilide hydroxamic acid blocks self‐renewal and homotypic aggregation of inflammatory breast cancer spheroids
Authors: Robertson Fredika M. , Woodward Wendy A. , Pickei Ross , Ye Zaiming , Bornmann William , Pal Ashutosh , Peng Zhenghong , Hall Carolyn S. , Cristofanilli Massimo
Published: May 2010

BACKGROUND:

Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer (LABC). Patients with IBC commonly present with skin metastasis, which are observed microscopically as tumor emboli within dermal lymphatics. These metastatic tumor cells aberrantly overexpress E‐cadherin and exhibit the ability to undergo self‐renewal and are highly invasive. There are no therapeutics yet identified that target the structure and functions of IBC tumor emboli. The present studies evaluated the effects of the pan‐histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) using IBC tumor spheroids derived from established IBC cell lines and tumor spheroids derived from pleural effusion (PE) aspirates of patients with IBC and LABC, designated as PE‐IBC and PE‐LABC.

METHODS:

Methods used are as follows: culture of IBC cells from clonal density single cells in low adherence culture conditions that promote formation of IBC tumor spheroids; clonogenic assays; cell fractionation and Western blotting; confocal microscropy; and modified Boyden chamber invasion assays.

RESULTS:

SAHA inhibited self‐renewal of IBC tumor spheroids from established IBC cell lines and PE‐IBC and PE‐LABC, as assessed by decreased clonogenic growth. SAHA blocked homotypic aggregation of the cells that comprised the IBC tumor spheroids leading to loss of their 3‐dimensional (3D) structure, which was associated with a change in location of E‐cadherin protein from the plasma membrane in untreated IBC tumor spheroids to the cytoplasm of cells within IBC tumor spheroids with SAHA treatment. In addition, SAHA blocked the robust invasion exhibited by IBC tumor spheroids of established cell lines as well as by tumor spheroids derived from PE‐IBC and PE‐LABC.

CONCLUSIONS:

SAHA targets the integrity and biological activities of IBC tumor spheroids and may be a promising agent to evaluate for its effectiveness in treatment of IBC. Cancer 2010;116(11 suppl):2760–7. © 2010 American Cancer Society.
Inflammatory breast cancer—The Royal Marsden Hospital experience
Authors: Sutherland Stephanie , Ashley Sue , Walsh Geraldine , Smith Ian E. , Johnston Stephen R. D.
Published: May 2010

BACKGROUND:

Treatments for inflammatory breast cancer (IBC) have changed over the last 15 to 20 years. The authors of this report undertook a retrospective review of patients who were treated at the Royal Marsden Hospital (RMH) to determine whether recurrence‐free survival (RFS) and overall survival (OS) have improved as treatment regimens have altered.

METHODS:

Detailed clinical‐pathologic data were collected on patients who were treated for primary IBC at RMH between 1990 and 2007. A Cox regression model was used to investigate the factors that influenced OS.

RESULTS:

The median OS was 3 years and 4 months, and the median RFS was 1 year and 10 months. RFS was better in patients who had received taxane‐containing regimens; however, there was no OS benefit. A pathologic complete response (pCR) was observed in 13 of 89 patients (15%), and those who achieved a pCR had significantly better RFS but no improvement in OS. The type of chemotherapy did not affect the pCR rate. One hundred thirty of 155 patients received radiotherapy, and those who did not receive radiotherapy had significantly worse outcomes. A multivariate Cox regression analysis indicated that the date of diagnosis, estrogen receptor (ER) status, and the presence of metastatic disease at diagnosis were significant prognostic factors. Patients who were diagnosed during or after 2000 had a relative risk of mortality of 0.5 compared with patients who were diagnosed before 2000. ER‐positive patients had a median OS of 4.5 years and a median of RFS of 2.6 years versus 2.9 years and 1.4 years, respectively, for ER‐negative patients. Patients who had metastatic disease at presentation had an OS of 1.7 years versus 3.9 years for those without metastatic disease at presentation.

CONCLUSIONS:

Achieving a pCR improved RFS but had no impact on OS. Patients who had metastatic disease at the outset fared much worse, and positive ER status conferred a better outlook. Cancer 2010;116(11 suppl):2815–20. © 2010 American Cancer Society.
Human mammary tumor virus in inflammatory breast cancer
Authors: Pogo Beatriz G.‐T. , Holland James F. , Levine Paul H.
Published: May 2010

The authors have found that retroviral sequences with 85% to 95% homology to the mouse mammary tumor virus were present in 40% of the sporadic breast cancers of American women. These sequences were not found in normal breasts or other tumors. A whole proviral structure was detected in 2 tumors. Breast cancer cells in culture were shown to contain and shed betaretroviral particles. This virus was designated human mammary tumor virus (HMTV). The authors have investigated the presence of HMTV sequences in a variety of breast conditions and geographic locations. Here they report that inflammatory breast cancer from American women shows a higher incidence of viral sequences (71%) than sporadic breast cancers. Similar incidence has been found in inflammatory breast cancers from Tunisia, and in gestational breast cancers. Because these conditions represent highly invasive malignancies, it is concluded that HMTV is sometimes associated with a particularly malignant phenotype. Cancer 2010;116(11 suppl):2741–4. © 2010 American Cancer Society.
Atrioventricular conduction and arrhythmias at the initiation of beating in embryonic mouse hearts
Authors: Chen Fuhua , De Diego Carlos , Chang Marvin G. , McHarg Jennifer L. , John Scott , Klitzner Thomas S. , Weiss James N.
Published: May 2010

To investigate cardiac physiology at the onset of heart beating in embryonic mouse hearts, we performed optical imaging of membrane potential (Vm) and/or intracellular calcium (Cai). Action potentials and Cai transients were detected in ∼50% of mouse embryo hearts at E8.5, but in all hearts at E9.0, indicating that beating typically starts between E8–E9. Beating was eliminated by Ca channel blocker nifedipine and the If blocker ZD7288, unaffected by tetrodotoxin and only mildly depressed by disabling sarcoplasmic (SR) and endoplasmic (ER) reticulum Ca cycling. From E8.5 to E10, conduction velocity increased from 0.2–1 mm/s to >5 mm/s in first ventricular and then atrial tissue, while remaining slow in other areas. Arrhythmias included atrioventricular reentry induced by adenosine. In summary, at the onset of beating, If‐dependent pacemaking drives both AP propagation and Cai transient generation through activation of voltage‐dependent Ca channels. Na channels and intracellular Ca cycling have minor roles. Developmental Dynamics 239:1941–1949, 2010. © 2010 Wiley‐Liss, Inc.
A circulatory transcriptional regulation among daf‐9, daf‐12, and daf‐16 mediates larval development upon cholesterol starvation in Caenorhabditis elegans†
Authors: Jeong Myung‐Hwan , Kawasaki Ichiro , Shim Yhong‐Hee
Published: May 2010

C. elegans shows dauer‐like larvae formation upon cholesterol starvation (CS), but the genetic epistasis among abnormal dauer formation (daf) genes during the process remains unclear. To clarify the genetic interactions among daf‐9, daf‐12, and daf‐16 in this process, mRNA levels of these genes upon CS were measured. CS increased the mRNA levels of daf‐9, daf‐12, and daf‐16. CS also induced DAF‐16 nuclear localization, which was positively and negatively regulated by DAF‐12 and DAF‐9 activities, respectively. Activated DAF‐16, a FOXO transcription factor, enhanced daf‐12 but suppressed daf‐9 expression, whereas DAF‐9 inhibited daf‐12 expression. Concomitantly, CS‐induced larval arrest was regulated positively by DAF‐12 and DAF‐16, but negatively by DAF‐9. The larval arrest in daf‐9 mutant was suppressed by daf‐12 RNAi, placing DAF‐12 downstream of DAF‐9. These results altogether suggest that circulatory mutual regulation among daf‐9, daf‐12, and daf‐16 at the expression level mediates cholesterol signal to control larval development upon CS. Developmental Dynamics 239:1931–1940, 2010. © 2010 Wiley‐Liss, Inc.
Ion imaging during axolotl tail regeneration in vivo
Authors: Özkucur Nurdan , Epperlein Hans‐Henning , Funk Richard H.W.
Published: May 2010

Several studies have reported that endogenous ion currents are involved in a wide range of biological processes from single cell and tissue behavior to regeneration. Various methods are used to assess intracellular and local ion dynamics in biological systems, e.g., patch clamping and vibrating probes. Here, we introduce an approach to detect ion kinetics in vivo using a noninvasive method that can electrophysiologically characterize an entire experimental tissue region or organism. Ion‐specific vital dyes have been successfully used for live imaging of intracellular ion dynamics in vitro. Here, we demonstrate that cellular pH, cell membrane potential, calcium, sodium and potassium can be monitored in vivo during tail regeneration in the axolotl (Ambystoma mexicanum) using ion‐specific vital dyes. Thus, we suggest that ion‐specific vital dyes can be a powerful tool to obtain electrophysiological data during crucial biological events in vivo. Developmental Dynamics 239:2048–2057, 2010. © 2010 Wiley‐Liss, Inc.
Visualization of embryonic lymphangiogenesis advances the use of the zebrafish model for research in cancer and lymphatic pathologies
Authors: Flores Maria Vega , Hall Christopher J. , Crosier Kathryn E. , Crosier Philip S.
Published: May 2010

Lymphangiogenesis induced during tumor growth contributes to metastasis. Genetic and chemical screens using the zebrafish model have the potential to enhance our understanding of lymphangiogenesis, and lead to the discovery of pharmacological agents with activity in the lymphatic system. Large‐scale screening of lymphatic development in the whole zebrafish embryo requires a specific lymphatic endothelial cell marker. We isolated the zebrafish ortholog of Lyve1, and analyzed its expression pattern during embryogenesis, and under conditions where key regulators of lymphangiogenesis such as Prox1 and VegfC were depleted. Like humans, zebrafish embryos form lymph sacs, lymphangioblasts arise from venous endothelia, and they form asymmetric left and right collecting ducts. By monitoring the earliest lymphatic sprouting in the head, a pilot drug assay was performed showing rapamycin, an inhibitor of mammalian lymphangiogenesis, can also suppress zebrafish lymphangiogenesis. This work opens up a novel opportunity to further the understanding of, and potentially manipulate, human lymphangiogenesis. Developmental Dynamics 239:2128–2135, 2010. © 2010 Wiley‐Liss, Inc.
Metal Cation Controlled Supramolecular Assembly of 1‐Butyl‐4,4′‐bipyridinium and Cucurbit[8]uril
Authors: Xiao Xin , Liu Jing‐Xin , Chen Kai , Zhu Qian‐Jiang , Xue Sai‐Feng , Tao Zhu
Published: May 2010

Three supramolecular assemblies [(C14H17N2)2⊂C48H48N32O16]Cl2·23H2O (1), {[C14H17N2Cu(H2O)5]2⊂C48H48N32O16}[(C14H17N2)2⊂C48H48N32O16]Cl4(NO3)4·32H2O (2), and {[C14H17N2Ni(H2O)5]2⊂C48H48N32O16}[(C14H17N2)2⊂C48H48N32O16]Cl2(NO3)6·22H2O (3) were synthesized in aqueous solution and characterized by X‐ray diffraction. The crystal structures of these supramolecular assemblies show that Q[8] can selectively encapsulate either the bipyridinium or butyl moiety of the 1‐butyl‐4,4′‐bipyridinium guest in its hydrophobic cavity to form ternary complexes through the influence of metal–ligand coordination. The main driving force of the selective formation of these supramolecular assemblies may be due to ion–dipole interactions.
Luminescent CaWO4:Tb3+‐Loaded Mesoporous Silica Composites for the Immobilization and Release of Lysozyme
Authors: Huang Shanshan , Li Chunxia , Yang Piaoping , Zhang Cuimiao , Cheng Ziyong , Fan Yong , Lin Jun
Published: May 2010

Luminescence‐functionalized silica composites were synthesized by deposition of CaWO4:Tb3+ nanoparticles onto mesoporous silica (MS) materials by a Pechini‐type sol–gel process. The pristine mesoporous silica materials comprise rod‐like and spherical SBA‐15‐type silica materials in micron size, hollow silica spheres of around 2–4 μm, and silica tubes with lengths of tens of micrometers. The X‐ray diffraction (XRD), transmission electron microscopy (TEM), and N2 adsorption/desorption results confirm that the composites still conserve regular mesopore structure after the incorporation of the CaWO4:Tb3+ nanoparticles. These luminescent composites possessing suitable pore size, high BET surface area, and large pore volume (> 1.0 cm3/g) were studied as supports for immobilization of lysozymes. These composites show various lysozyme adsorption capacities at different solution pH values. CaWO4:Tb3+‐loaded SBA‐15‐type composites and hollow spheres adsorb relatively high amounts (> 500 mg/g composite at a solution pH of 10.0) of lysozyme (LYZ). The different enzyme adsorption and release properties of these luminescent mesoporous silica materials make them good candidates for specific bioimmobilization hosts. The emission intensity of Tb3+ in the CaWO4:Tb3+@rod‐like SBA‐15 varies with the total released amount of LYZ, which enables the lysozyme release to be tracked by the change in the luminescence intensity.
Novel O,O′‐Donor Oxo‐MoIV Hydrotris(3‐isopropylpyrazolyl)borate Complexes Formed by Chelation of Potentially Hydrogen‐Bonding Phenolate Ligands on Reduction of Dioxo‐MoVI Complexes
Authors: Ng Victor W. L. , Taylor Michelle K. , Hill Lyndal M. R. , White Jonathan M. , Young Charles G.
Published: May 2010

The oxo‐MoIV complexes formed in the reactions of cis‐TpiPrMoVIO2(OAr‐R) [TpiPr = hydrotris(3‐isopropylpyrazol‐1‐yl)borate, –OAr‐R = phenolate derivative] complexes with PEt3 or PEt2Ph in acetonitrile depend on the nature of the potential hydrogen‐bonding group (R) incorporated into the phenolate ligand. Green, diamagnetic, oxo(phosphoryl)‐MoIV complexes, TpiPrMoIVO(OAr‐R)(OPR′3), are produced when R is absent or is a non‐coordinating group such as 2‐OMe and 3‐NEt2; six‐coordinate TpiPrMoO(OC6H4OMe‐2)(OPEt3) was structurally characterized and exhibits a distorted octahedral geometry typical of such species. When R is a carbonyl functionality, complete oxygen atom transfer leads to green or purple, diamagnetic, chelate complexes of the type, TpiPrMoIVO(OAr‐R‐κ2O,O′). The R = 2‐COEt, 2‐CO2Me and 2‐CO2Ph derivatives exhibit six‐coordinate, distorted‐octahedral structures possessing fac TpiPr, terminal oxo and bidentate O,O′‐donor –OAr‐R ligands. Where R is an amido functionality, CONHPh, the complexes, TpiPrMoIVO(OC6H4CONHPh‐2‐κ2O,O′)·OPR′3 (R′3 = Et3, Et2Ph), are isolated. Here, the six‐coordinate, distorted‐octahedral complex forms an intermolecular NH···OPR′3 hydrogen bond to the lattice OPR′3 molecule. Thus, facile chelation of potential hydrogen‐bonding phenolate ligands suppresses hydrogen‐bond‐stabilized aquation or hydroxylation cis to the oxo group in these MoIV complexes.
Luminescent Hybrids Combining a Metal Complex and a Crown Ether – Receptors for Peptidic Ammonium Phosphates
Authors: Späth Andreas , Koch Carina , König Burkhard
Published: May 2010

Hybrid compounds combining a luminescent aza crown ether and 1,4,7,10‐tetraazacyclododecane (cyclene) or bis(pyridin‐2‐ylmethylamine) (bpa) metal complexes were prepared. These synthetic receptors signal the presence of peptidic ammonium phosphates in buffered aqueous solution by changes in their emission intensity. Reversible phosphate ion coordination to the metal complex binding sites decreases the emission intensity of the phthalic ester fluorophore. Structurally suitable ammonium phosphates, such as the C‐terminal domain of RNA polymerase II or the protein kinase G target sequence, bind to the synthetic receptors by an additional intramolecular interaction between the ammonium ion and the aza crown ether. The binding of the ammonium ion to the aza crown ether increases the emission intensity of the fluorophore. In aqueous solution, this weak interaction can only occur within aggregates of phosphates and metal complex receptors of matching geometry;therefore, it allows the distinction of structurally related phosphorylated peptides in buffered aqueous solution.
Low‐Temperature Synthesis of Meshy Boron Nitride with a Large Surface Area
Authors: Meng Xiang‐Lin , Lun Ning , Qi Yong‐Qiu , Bi Jian‐Qiang , Qi Yong‐Xin , Zhu Hui‐Ling , Han Fu‐Dong , Bai Yu‐Jun , Yin Long‐Wei , Fan Run‐Hua
Published: May 2010

Meshy boron nitride (BN) was synthesized by the reaction of NaBH4 and CS(NH2)2 at 550 °C for 10 h. X‐ray diffraction indicates the formation of hexagonal boron nitride (h‐BN) with lattice constants a = 2.501 and c = 6.724 Å. Observations by TEM show that the BN obtained has a meshy structure with a quantity of pores distributing on each mesh. The nitrogen adsorption–desorption test gives a high surface area of 220 m2 g–1 for the meshy BN. The cathode‐luminescence spectrum exhibits a strong peak at 354 nm in the ultraviolet range. Thermogravimetric analysis proves that the meshy BN has good thermal stability and oxidation resistance up to 800 °C. The formation of meshy BN is due to the promotion of sulfur‐containing compounds for the cross‐linking of borazine and subsequent pyrolysis.
Synthesis, Structural, Redox and Mössbauer Characterization of Four‐Electron‐Oxidized Tetrakis(cyclohexyl)iron(II)porphodimethene with Different Axial Ligations
Authors: Bhattacharya Dibyendu , Sarkar Sabyasachi
Published: May 2010

Monocationic FeIIporphodimethene complexes, [LΔΔFe–X][Y] {1, X = I–and Y = I3–;2, X = Br–and Y = [FeIIIBr4]–; LΔΔ= tetrakis(cyclohexyl)porphodimethene}, were achieved by induced electron‐transfer reactions between the square‐planar, intermediate‐spin, iron(III)porphyrinogen complex [Et4N][LFeIII] [L = tetrakis(cyclohexyl)porphyrinogen tetraanion] and different oxidants. Single‐crystal X‐ray diffraction analysis reveals that1and2have a square‐pyramidal geometry in which the iodide and bromide ligands occupy the axial position, respectively. Compound1exhibits an extended two‐dimensional solid‐state structure that comprises porphodimethene cation and triiodide anion chain columns in a 1:1 ratio, which are packed alternately. Electrochemical assessment with cyclic voltammetry reveals reversibly accessible FeII/IIIoxidation states; however, the redox potential is nearly one volt more positive than that for a typical heme cofactor, which suggests the highly oxidizing nature of the tetrapyrrole framework in the four–electron‐oxidized LΔΔmoiety. In addition, definitive experimental oxidation state and spin state assignments for the intermediate‐spin [Et4N][LFeIII] and high‐spin FeIIstates of1and2were afforded by Mössbauer characterization.
Advancing the Morita–Baylis–Hillman Chemistry of 1‐Formyl‐β‐carbolines for the Synthesis of Indolizino‐indole Derivatives
Authors: Singh Virender , Hutait Samiran , Batra Sanjay
Published: May 2010

The chemistry of the Morita–Baylis–Hillman adducts of 1‐formyl‐β‐carbolines has been extended for obtaining indolizino‐indole derivatives which mimic the harmicine and homofascaplysin frameworks. Adducts of N‐substituted methyl 1‐formyl‐9H‐β‐carboline‐3‐carboxylate yield indolizino‐indole derivatives upon bromination followed by aqueous workup. On the other hand, N‐substituted 1‐formyl‐9H‐β‐carbolines give rise to similar products in a one‐pot DABCO‐promoted reaction of activated alkenes. Alternatively, the DMAP‐mediated Morita–Baylis–Hillman reaction of N‐substituted methyl 1‐formyl‐9H‐β‐carboline‐3‐carboxylate with cycloalkenones yields adducts that cyclize intramolecularly in the presence of PBr3 to yield compounds with the homofascaplysin framework. In contrast, the DMAP‐mediated reaction of N‐substituted 1‐formyl‐β‐carboline with cyclohexenone directly gives a product with similar framework in a single step.
One‐Pot Synthesis of Azanucleosides from Proline Derivatives – Stereoselectivity in Sequential Processes
Authors: Boto Alicia , Hernández Dácil , Hernández Rosendo
Published: May 2010

Common amino acid derivatives can be transformed in one‐step fashion into N‐azanucleosides. The method is a sequential process initiated by a domino radical decarboxylation/oxidation reaction; an acyliminium ion is formed as an intermediate and can be trapped by nitrogen bases (purines, pyrimidines, and benzotriazole). The mildness of the reaction conditions and the good yields obtained make this procedure an interesting alternative to the conventional processes. Good stereoselectivities were obtained with 4‐(silyloxy)proline derivatives as substrates.
(–)‐Myrtenyl N,N‐Diisopropylcarbamate: Stereochemistry of Lithiation and Electrophilic Substitution Directed by Dynamic Kinetic Diastereoisomer Resolution
Authors: Hémery Thérèse , Becker Jochen , Fröhlich Roland , Hoppe Dieter
Published: May 2010

(–)‐Myrtenyl N,N‐diisopropylcarbamate was lithiated bybutyllithium in the presence of achiral and chiral ligands, followed by quench with several electrophiles. The ratio of diastereomeric products allows conclusions regarding the configurational stability of both diastereomeric lithium intermediates and the influence of kinetic diastereoisomer resolution in the substitution step.
A GOG 210 aCGH study of gain at 1q23 in endometrioid endometrial cancer in the context of racial disparity and outcome
Authors: Morrison Carl , Miecznikowski Jeffrey , Darcy Kathleen M. , Dolce Jean M. , Kandel Eugene , Erwin Deborah O. , Liu Song , Shepherd Lori , Cohn David , McMeekin D. Scott , Block AnneMarie W. , Nowak Norma J. , Maxwell Larry
Published: May 2010

The goal of this study was to identify recurrent regions of genomic gain or loss in endometrial cancer of the endometrioid type in the context of racial disparities in mortality for this disease. Array comparative genomic hybridization (aCGH) analysis was performed on 80 frozen primary tumors from the Gynecologic Oncology Group (GOG)‐210 bank using the RPCI 19K BAC arrays. The 80 patients included 20 African American (AA) Stage I, 20 White (W) Stage I, 20 African American (AA) Stage IIIC/IV, and 20 White (W) Stage IIIC/IV. A separate subset of 220 endometrial cancers with outcome data was used for validation. A 1.6‐Mbp region of gain at 1q23 was identified by aCGH in all AA patients and high grade W patients, but not W low grade patients. In the validation arm of 220 patients copy number gain at this region was validated using FISH and locus specific BACs. The number of AA patients in the validation arm was too small to confirm the aCGH association with racial disparity. Kaplan‐Meier curves for survival showed a significant difference for gain at 1q23 versus no gain (log rank P = 0.0014). When subdivided into various groups of risk by stage and grade the survival curves showed a decreased survival for high grade and/or stage tumors, but not for low grade and/or stage endometrioid tumors. Univariate analyses for gain at 1q23 showed a significant association (P = 0.009) with survival. Multivariate analysis for gain at 1q23 did not show a significant association with survival (P = 0.14). © 2010 Wiley‐Liss, Inc.
Accuracy of whole‐body PET and PET‐CT in initial M staging of head and neck cancer: A meta‐analysis
Authors: Xu Guo‐Zeng , Zhu Xiao‐Dong , Li Ming‐Yao
Published: May 2010

Background

A meta‐analysis was conducted to evaluate the accuracy of whole‐body positron emission tomography (PET) and PET‐CT in initial M staging of head and neck cancer.

Methods

After a systematic review of English language studies, sensitivity, specificity, and other measures of whole‐body PET and PET‐CT were pooled. Summary receiver operating characteristic (SROC) curves were also used to summarize overall test performance.

Results

Eight PET and 7 PET‐CT studies were identified. The pooled sensitivity estimates for PET and PET‐CT were 0.848 (95% confidence interval [CI], 0.776–0.905) and 0.875 (95% CI, 0.787–0.936). The pooled specificity estimates were 0.952 (95% CI, 0.933–0.967) and 0.950 (95% CI, 0.931–0.964). The Q* index estimates for PET‐CT (0.9409) were not significantly higher than for PET (0.9154; p > .05).

Conclusion

Whole‐body PET and PET‐CT have good diagnostic performance in initial M staging of head and neck cancer; although PET‐CT tends to have higher accuracy than PET. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Identifying risk factors for postoperative cardiovascular and respiratory complications after major oral cancer surgery
Authors: Dillon Jasjit K. , Liu Stanley Y. , Patel Chirag M. , Schmidt Brian L.
Published: May 2010

Background

Surgical resection of oral cancer can be associated with significant postoperative cardiovascular and respiratory complications that require more sensitive predictors.

Methods

All patients with oral squamous cell carcinoma treated from July 2005 to April 2008 were retrospectively reviewed. The Goldman Revised Cardiac Risk Index (GRCRI) was used to predict cardiovascular complications. Other evidence‐based a priori predictors were applied in an h‐fold cross‐validation model.

Results

Operating room (OR) time was an independent predictor of cardiovascular complications (odds ratio = 1.54, p = .002, 95% confidence interval [CI] = 1.18–2.02) and respiratory complications (odds ratio = 1.3, p = .06, 95% CI = 0.99–1.64) after multivariate adjustment. OR time and estimated blood loss predicted cardiovascular complications with 73% sensitivity. The GRCRI achieved 37% sensitivity. OR time and tracheostomy predicted respiratory complications with 75% sensitivity.

Conclusions

The GRCRI was not prognostic for cardiovascular complications in patients with oral cancer. The most sensitive predictors for cardiovascular complications were OR time and estimated blood loss; for respiratory complications they were OR time and tracheostomy. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Role of core needle biopsy and ultrasonographic finding in management of indeterminate thyroid nodules
Authors: Park Kyung Tae , Ahn Soon‐Hyun , Mo Ji‐Hun , Park Young Joo , Park Do Joong , Choi Sang Il , Park So‐Yeon
Published: May 2010

Background

Thyroid fine‐needle aspiration (FNA) is used as a screening test of choice for evaluation of thyroid nodules. However, approximately 15% to 25% of the cases are classified as indeterminate, posing dilemmas in decision‐making. This study was designed to compare the diagnostic performances of second FNA and core needle biopsy of indeterminate nodules by initial FNA.

Methods

From February 2005 through June 2009, 258 patients who completed scheduled follow‐ups were enrolled and the follow‐up results were analyzed.

Results

Nondiagnostic results were obtained in 41.8% of the second FNA group and in 1.7% of the core needle biopsy group (p < .001; chi‐square). The nodules that show borderline features in preoperative ultrasonography had a malignancy rate of 18.3% and could be identified successfully with core needle biopsy.

Conclusion

Core needle biopsy is a better method for evaluating indeterminate nodules by initial FNA than second FNA, especially in patients with ultrasonographic findings of a borderline nodule. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Dual inhibition of epidermal growth factor receptor and insulin‐like growth factor receptor I: Reduction of angiogenesis and tumor growth in cutaneous squamous cell carcinoma
Authors: Galer Chad E. , Corey Christina L. , Wang Zhuoying , Younes Maher N. , Gomez‐Rivera Fernando , Jasser Samar A. , Ludwig Dale L. , El‐Naggar Adel K. , Weber Randal S. , Myers Jeffrey N.
Published: May 2010

Background

Cutaneous squamous cell carcinoma (CSCC) is the second most common nonmelanoma skin cancer. Most of the approximately 250,000 cases occurring annually in the United States are small, nonaggressive, and cured by excision alone. However, a subset of these tumors which are defined by poorly differentiated histology, large tumor size, invasion of adjacent structures, and/or regional metastases can prove resistant to treatment despite adjuvant radiotherapy and can have an increased risk of recurrence and nodal metastasis. Novel therapeutic approaches are necessary to improve the outcomes for patients with aggressive CSCC.

Methods

We analyzed the effect of targeted therapy on the growth and survival of CSCC cell lines using an anti‐insulin‐like growth factor‐I receptor (IGF‐IR) antibody, A12, alone or in combination with an anti‐epidermal growth factor receptor (EGFR) antibody, cetuximab, both in vitro and in vivo in an athymic nude mouse model of CSCC.

Results

Treatment with A12 and cetuximab inhibited the signaling pathways of IGF‐IR and EGFR and inhibited proliferation and induced apoptosis of squamous cell carcinoma (SCC) cell lines in vitro. Immunohistochemical staining revealed decreased proliferating cell nuclear antigen (PCNA), microvessel density, and increased apoptosis within the treated tumor xenografts. In addition, the administration of A12, alone or in combination with cetuximab inhibited the growth of tumors by 51% and 92%, respectively, and significantly enhanced survival in the nude mouse model of CSCC (p= .044 andp< .001, respectively).

Conclusion

These data suggest that dual treatment with monoclonal antibodies to the EGFR and IGF‐IR may be therapeutically useful in the treatment of CSCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Field research on the performance of a rice husk envelope in a subsurface drainage system (case study Behshahr, Iran)
Authors: Ebrahimian Hamed , Parsinejad Massoud , Liaghat Abdolmajid , Akram Mojtaba
Published: May 2010

This study was conducted to evaluate the performance of subsurface drainage and a rice husk envelope in Behshahr, a coastal region in the northern part of Iran. The subsurface drainage system was monitored in the rainfall seasons of 2006 and 2007 (22 November to 19 March). Various parameters such as daily groundwater table fluctuations and drain discharge rate were measured. To evaluate the drainage envelope, the gradation curve, bulk density and natural durability of rice husk and also the head loss of the groundwater table in the vicinity of the drain were measured. The large difference between the approach‐flow head and entrance‐flow head could be related to clogging of the external part of the rice husk envelope. The overall conclusion of this study was that subsurface drainage system performance was not satisfactory due to poor control of groundwater table depth, which could be related to clogging of the rice husk drain envelope. Hooghoudt's equation is not recommended to be used for evaluation of design parameters in this case. The basic uncertainty in application of a rice husk envelope was its durability, which was found to be very variable and depended on soil environmental conditions. Copyright © 2010 John Wiley & Sons, Ltd.
Ribonucleoprotein immunoprecipitation (RNP‐IP): A direct in vivo analysis of microRNA‐targets
Authors: Hassan Mohammad Q. , Gordon Jonathan A.R. , Lian Jane B. , van Wijnen Andre J. , Stein Janet L. , Stein Gary S.
Published: May 2010

We have developed a novel Ribonucleoprotein Immunoprecipitation (RNP‐IP) method to isolate miR‐RISC complexes, associated microRNAs and target mRNAs. Our method characterizes mRNAs present in immunoprecipitates containing miR‐RISC complexes that were obtained using GW182 and AGO2 antibodies. MicroRNA bound transcripts were reverse transcribed and amplified using seed sequence and 3′UTR derived primers. This flexible IP‐based assay is a straightforward method to identify miRs participating in gene regulation and their cognate mRNAs in real time. J. Cell. Biochem. 110: 817–822, 2010. © 2010 Wiley‐Liss, Inc.
The effects of peptides with estrogen‐like activity on cell proliferation and energy metabolism in human derived vascular smooth muscle cells
Authors: Somjen D. , Knoll E. , Gayer B. , Kasher R. , Kohen F. , Stern N.
Published: May 2010

Hormone replacement therapy (HRT) for post‐menopausal symptoms in diabetes is associated with increased risk of coronary heart disease and stroke. Therefore, there is a need for new HRT with no adverse effects on diabetic post‐menopausal women. We developed peptides as potential estrogen mimetic compounds and now we evaluated the effects of the most efficacious peptide; hexapeptide estrogen‐mimetic peptide 1 (EMP‐1) (VSWFFE) in comparison to estrogen (E2) and peptides with weak activity A44 (KAWFFE) and A45 (KRAFFE) on modulation of cell proliferation of vascular smooth muscle cells (VSMC) growing in normal (ng) or high glucose (hg) concentrations. In ng EMP‐1‐like E2 inhibited cell proliferation at high concentration, and stimulated at low concentration. EMP‐1 did not affect E2 stimulation of DNA, but inhibited E2 inhibition of cell proliferation at high concentration. All effects by the combination of EMP‐1 and E2 were abolished at hg. A44‐stimulated cell proliferation at all concentrations and A45 had no effect. When A44 was co‐incubated with E2 at both concentrations, DNA synthesis was stimulated, but abolished at hg. A45 abolished E2 stimulation and inhibition of cell proliferation at both glucose concentrations. All peptides tested except A45‐stimulated CK‐specific activity at both glucose concentrations. In hg A44 stimulation of DNA was unaffected as well as its inhibition by EMP‐1. EMP‐1 and A44 similar to E2‐stimulated MAPK activity in ng or hg, suggesting similar mechanism of action. The results presented here suggest that EMP‐1 provided it acts similarly in vivo can replace E2 for treatment of post‐menopausal women in hyperglycemia due to diabetes. J. Cell. Biochem. 110: 1142–1146, 2010. Published 2010 Wiley‐Liss, Inc.
QSG‐7701 human hepatocytes form polarized acini in three‐dimensional culture
Authors: Zhang Fang , Xu Ren , Zhao Mu‐jun
Published: May 2010

Hepatocytes are polarized and fulfill a variety of liver‐specific functions in vivo; but the polarized tissue structure and many of these functions are lost when the cells are cultured on plastic. To recapitulate the polarized structure and tissue‐specific function of liver cells in culture, we established a three‐dimensional (3D) culture assay with the human hepatocyte line QSG‐7701. In 3D Matrigel culture, QSG‐7701 cells formed polarized spheroids with a center lumen, which is reminiscent of bile canaliculi in the liver. Immunofluoresence analysis showed that F‐actin bundles and radixin were mainly located at the apical membrane and that α6 and β1 integrins were localized basally in 3D culture. Lumen formation was associated with the selective apoptosis of centrally located cells and was accompanied by proliferative suppression during acinar development. Compared to QSG‐7701 cells in 2D or agarose gel cultures, the cells in 3D Matrigel culture maintained a given direction of biliary excretion and acquired higher levels of cytochrome P450 and albumin expression. Our study shows that the immortal human hepatocytes, QSG‐7701, in 3D Matrigel culture reacquire cardinal features of glandular epithelium in vivo, providing an ex vivo model to study liver‐specific function and tumorigenesis. J. Cell. Biochem. 110: 1175–1186, 2010. Published 2010 Wiley‐Liss, Inc.
Jmjd3 activates Mash1 gene in RA‐induced neuronal differentiation of P19 cells
Authors: Dai Jin‐po , Lu Jian‐yi , Zhang Ye , Shen Yu‐fei
Published: May 2010

Covalent modifications of histone tails have fundamental roles in chromatin structure and function. Tri‐methyl modification on lysine 27 of histone H3 (H3K27me3) usually correlates with gene repression that plays important roles in cell lineage commitment and development. Mash1 is a basic helix‐loop‐helix regulatory protein that plays a critical role in neurogenesis, where it expresses as an early marker. In this study, we have shown a decreased H3K27me3 accompanying with an increased demethylase of H3K27me3 (Jmjd3) at the promoter of Mash1 can elicit a dramatically efficient expression of Mash1 in RA‐treated P19 cells. Over‐expression of Jmjd3 in P19 cells also significantly enhances the RA‐induced expression and promoter activity of Mash1. By contrast, the mRNA expression and promoter activity of Mash1 are significantly reduced, when Jmjd3 siRNA or dominant negative mutant of Jmjd3 is introduced into the P19 cells. Chromatin immunoprecipitation assays show that Jmjd3 is efficiently recruited to a proximal upstream region of Mash1 promoter that is overlapped with the specific binding site of Hes1 in RA‐induced cells. Moreover, the association between Jmjd3 and Hes1 is shown in a co‐Immunoprecipitation assay. It is thus likely that Jmjd3 is recruited to the Mash1 promoter via Hes1. Our results suggest that the demethylase activity of Jmjd3 and its mediator Hes1 for Mash1 promoter binding are both required for Jmjd3 enhanced efficient expression of Mash1 gene in the early stage of RA‐induced neuronal differentiation of P19 cells. J. Cell. Biochem. 110: 1457–1463, 2010. © 2010 Wiley‐Liss, Inc.
Bone matrix proteins and extracellular acidification: Potential co‐regulators of osteoclast morphology
Authors: Gramoun Azza , Goto Tetsuya , Nordström Tommy , Rotstein Ori D. , Grinstein Sergio , Heersche Johan N.M. , Manolson Morris F.
Published: May 2010

Osteoclasts are signaled by the bone matrix proteins fibronectin (FN), vitronectin (VN), and osteopontin (OPN) via integrins. To perform their resorptive function, osteoclasts cycle between compact (polarized), spread (non‐resorbing) and migratory morphologies. Here we investigate the effects of matrix proteins on osteoclast morphology and how those effects are mediated using RAW 264.7 cells differentiated into osteoclasts on FN, VN, and OPN‐coated culture dishes. After 96 h, 80% of osteoclasts on FN were compact while 25% and 16% on VN were in compact and migratory states respectively. In contrast, OPN induced osteoclast spreading. Furthermore, osteoclasts formed on VN and FN were two‐ to fourfold smaller than those formed on OPN in the 21–30 nuclei/osteoclast group. These effects were not due to defects in cytoskeletal reorganization of osteoclasts on VN and FN, demonstrated by the ability of these cells to spread in response to 35 ng/ml macrophage colony stimulating factor (M‐CSF). Conversely, osteoclasts on OPN failed to spread when induced by M‐CSF. Moreover, the extracellular pH on FN and VN (7.25 and 7.3, respectively) was significantly lower than that on OPN (∼7.4). We further investigated the role of extracellular pH and found that at pH 7.5 the duration of an osteoclast's compact phase was 25.6 min and that of the spread phase was 62.5 min. Reducing the pH to 7.0 increased the frequency of osteoclast cycling by threefold. These results show that matrix proteins play a role in regulating osteoclast morphology, possibly via altering extracellular and intracellular pH. J. Cell. Biochem. 111: 350–361, 2010. © 2010 Wiley‐Liss, Inc.
OCT3/4 regulates transcription of histone deacetylase 4 (Hdac4) in mouse embryonic stem cells
Authors: Addis Russell C. , Prasad Megana K. , Yochem Robert L. , Zhan Xiangcan , Sheets Timothy P. , Axelman Joyce , Patterson Ethan S. , Shamblott Michael J.
Published: May 2010

OCT3/4 is a POU domain transcription factor that is critical for maintenance of pluripotency and self‐renewal by embryonic stem (ES) cells and cells of the early mammalian embryo. It has been demonstrated to bind and regulate a number of genes, often in conjunction with the transcription factors SOX2 and NANOG. In an effort to further understand this regulatory network, chromatin immunoprecipitation was used to prepare a library of DNA segments specifically bound by OCT3/4 in undifferentiated mouse ES (mES) cell chromatin. One segment corresponds to a region within the first intron of the gene encoding histone deacetylase 4 (Hdac4), a Class II histone deacetylase. This region acts as a transcriptional repressor and contains at least two functional sites that are specifically bound by OCT3/4. HDAC4 is not expressed in the nuclei of OCT3/4+ mES cells and is upregulated upon differentiation. These findings demonstrate the participation of OCT3/4 in the repression of Hdac4 in ES cells. J. Cell. Biochem. 111: 391–401, 2010. © 2010 Wiley‐Liss, Inc.
Novel 14S,21‐dihydroxy‐docosahexaenoic acid rescues wound healing and associated angiogenesis impaired by acute ethanol intoxication/exposure
Authors: Tian Haibin , Lu Yan , Shah Shraddha P. , Hong Song
Published: May 2010

Acute ethanol intoxication and exposure (AE) has been known to impair wound healing and associated angiogenesis. Here, we found that AE diminished the formation of novel reparative lipid mediator 14S,21‐dihydroxy‐docosa‐4Z,7Z,10Z,12E,16Z,19Z‐hexaenoic acid (14S,21‐diHDHA) and its biosynthetic intermediate 14S‐hydroxy‐DHA (14S‐HDHA) from docosahexaenoic acid (DHA) in murine wounds. However, AE did not reduce the formation of DHA and the intermediate 21‐HDHA. These results indicate that in the biosynthetic pathways of 14S,21‐diHDHA in wounds, AE suppresses the 14S‐hydroxy‐generating activity of 12‐lipoxygenase‐like (LOX‐like), but does not suppress the 21‐hydroxy‐generating activity of cytochrome P450 and DHA‐generating activities. The AE‐suppression of 12‐LOX‐like activity was further confirmed by the diminished formation of 12‐hydroxy‐eicosatetraenoic acid in wounds under AE. Supplementing 14S,21‐diHDHA to wounds rescued the AE‐impaired healing and vascularization. 14S,21‐diHDHA restored AE‐impaired processes of angiogenesis in vitro: endothelial cell migration, tubulogenesis, and phosphorylation of p38 mitogen‐activated protein kinase (MAPK). Taken together, the suppression of 14S,21‐diHDHA formation is responsible, at least partially, for the AE‐impairment of cutaneous wound healing and angiogenesis. Supplementing 14S,21‐diHDHA to compensate its deficit in AE‐impaired wounds rescues the healing and angiogenesis. These results provide a novel mechanistic insight for AE‐impaired wound healing that involves the necessary roles of 14S,21‐diHDHA. They also offer leads for developing 14S,21‐diHDHA‐related therapeutics to ameliorate AE‐impairment of wound healing. J. Cell. Biochem. 111: 266–273, 2010. © 2010 Wiley‐Liss, Inc.
A new nuclear protease with cathepsin L properties is present in HeLa and Caco‐2 cells
Authors: Puchi Marcia , García‐Huidobro Jenaro , Cordova Candy , Aguilar Rodrigo , Dufey Estefanie , Imschenetzky Maria , Bustos Paula , Morin Violeta
Published: May 2010

Recently many authors have reported that cathepsin L can be found in the nucleus of mammalian cells with important functions in cell‐cycle progression. In previous research, we have demonstrated that a cysteine protease (SpH‐protease) participates in male chromatin remodeling and in cell‐cycle progression in sea urchins embryos. The gene that encodes this protease was cloned. It presents a high identity sequence with cathepsin L family. The active form associated to chromatin has a molecular weight of 60 kDa, which is higher than the active form of cathepsin L described until now, which range between 25 and 35 kDa. Another difference is that the zymogen present in sea urchin has a molecular weight of 75 and 90 kDa whereas for human procathepsin L has a molecular weight of 38–42 kDa. Based on these results and using a polyclonal antibody available in our laboratory that recognizes the active form of the 60 kDa nuclear cysteine protease of sea urchin, ortholog to human cathepsin L, we investigated the presence of this enzyme in HeLa and Caco‐2 cells. We have identified a new nuclear protease, type cathepsin L, with a molecular size of 60 kDa, whose cathepsin activity increases after a partial purification by FPLC and degrade in vitro histone H1. This protease associates to the mitotic spindle during mitosis, remains in the nuclei in binuclear cells and also translocates to the cytoplasm in non‐proliferative cells. J. Cell. Biochem. 111: 1099–1106, 2010. © 2010 Wiley‐Liss, Inc.
Connectivity and binding‐site recognition: Applications relevant to drug design
Authors: Illingworth Christopher J. R. , Scott Paul D. , Parkes Kevin E. B. , Snell Christopher R. , Campbell Matthew P. , Reynolds Christopher A.
Published: May 2010

Here, we describe a family of methods based on residue–residue connectivity for characterizing binding sites and apply variants of the method to various types of protein–ligand complexes including proteases, allosteric‐binding sites, correctly and incorrectly docked poses, and inhibitors of protein–protein interactions. Residues within ligand‐binding sites have about 25% more contact neighbors than surface residues in general; high‐connectivity residues are found in contact with the ligand in 84% of all complexes studied. In addition, a k‐means algorithm was developed that may be useful for identifying potential binding sites with no obvious geometric or connectivity features. The analysis was primarily carried out on 61 protein–ligand structures from the MEROPS protease database, 250 protein–ligand structures from the PDBSelect (25%), and 30 protein–protein complexes. Analysis of four proteases with crystal structures for multiple bound ligands has shown that residues with high connectivity tend to have less variable side‐chain conformation. The relevance to drug design is discussed in terms of identifying allosteric‐binding sites, distinguishing between alternative docked poses and designing protein interface inhibitors. Taken together, this data indicate that residue–residue connectivity is highly relevant to medicinal chemistry. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Closed loop folding units from structural alignments: Experimental foldons revisited
Authors: Chintapalli Sree V. , Yew Boon K. , Illingworth Christopher J. R. , Upton Graham J. G. , Reeves Philip J. , Parkes Kevin E. B. , Snell Christopher R. , Reynolds Christopher A.
Published: May 2010

Nonoverlapping closed loops of around 25–35 amino acids formed via nonlocal interactions at the loop ends have been proposed as an important unit of protein structure. This hypothesis is significant as such short loops can fold quickly and so would not be bound by the Leventhal paradox, giving insight into the possible nature of the funnel in protein folding. Previously, these closed loops have been identified either by sequence analysis (conservation and autocorrelation) or studies of the geometry of individual proteins. Given the potential significance of the closed loop hypothesis, we have explored a new strategy for determining closed loops from the insertions identified by the structural alignment of proteins sharing the same overall fold. We determined the locations of the closed loops in 37 pairs of proteins and obtained excellent agreement with previously published closed loops. The relevance of NMR structures to closed loop determination is briefly discussed. For cytochrome c, cytochrome b562 and triosephophate isomerase, independent folding units have been determined on the basis of hydrogen exchange experiments and misincorporation proton‐alkyl exchange experiments. The correspondence between these experimentally derived foldons and the theoretically derived closed loops indicates that the closed loop hypothesis may provide a useful framework for analyzing such experimental data. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
The youth coping responses inventory: development and initial validation
Authors: Hernandez Brittany C. , Vigna Julia F. , Kelley Mary L.
Published: May 2010

This study aimed to develop a comprehensive and representative measure of youths' dispositional coping. A sample of 450 youth, aged 10 to 16 years old, were recruited from public and private schools. The majority of the sample consisted of African American and Caucasian youth. After initial item generation, pilot testing, and item elimination, exploratory factor analyses resulted in a 44‐item coping measure with a 3‐factor solution (Diversion, Ameliorative Coping, and Destructive Coping). Internal consistency analyses indicated strong reliabilities (all coefficient alphas above .85) for the three scales and the composite score across races. Preliminary validity data confirmed that Diversion is the most adaptive coping factor and Destructive Coping the most maladaptive. These preliminary results indicate that the Youth Coping Responses Inventory presents a promising new measure of youths' coping. © 2010 Wiley Periodicals, Inc. J Clin Psychol: 66:1–18, 2010.