bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cooperative action of tamoxifen and c-Src inhibition in preventing the growth of estrogen receptor–positive human breast cancer cells
Authors: Herynk Matthew H. , Beyer Amanda R. , Cui Yukun , Weiss Heidi , Anderson Elizabeth , Green Tim P. , Fuqua Suzanne A.W. 
Published: December 2006

Abstract
It has long been appreciated that estrogenic signaling contributes to breast cancer progression. c-Src is also required for a number of processes involved in tumor progression and metastasis. We have previously identified the K303R mutant estrogen receptor α (ERα) that confers hypersensitivity to low levels of estrogen. Because ERα and c-Src have been shown to interact in a number of different systems, we wanted to evaluate the role of c-Src kinase in estrogen-stimulated growth and survival of ERα-positive breast cancer cells. MCF-7 cells stably expressing the mutant receptor showed increased c-Src kinase activity and c-Src tyrosine phosphorylation when compared with wild-type ERα-expressing cells. A c-Src inhibitor, AZD0530, was used to analyze the biological effects of pharmacologically inhibiting c-Src kinase activity. MCF-7 cells showed an anchorage-dependent growth IC50 of 0.47 μmol/L, which was increased 4-fold in the presence of estrogen. In contrast, cells stably expressing the mutant ERα had an elevated IC50 that was only increased 1.4-fold by estrogen stimulation. The c-Src inhibitor effectively inhibited the anchorage-independent growth of both of these cells, and estrogen was able to reverse these effects. When cells were treated with suboptimal concentrations of c-Src inhibitor and tamoxifen, synergistic inhibition was observed, suggesting a cooperative interaction between c-Src and ERα. These data clearly show an important role for ERα and estrogen signaling in c-Src–mediated breast cancer cell growth and survival. Here, we show that c-Src inhibition is blocked by estrogen signaling; thus, the therapeutic use of c-Src inhibitors may require inhibition of ERα in estrogen-dependent breast cancer. [Mol Cancer Ther 2006;5(12):3023–31]
The endothelial cytoskeleton as a target of electroporation-based therapies
Authors: Kanthou Chryso , Kranjc Simona , Sersa Gregor , Tozer Gill , Zupanic Anze , Cemazar Maja 
Published: December 2006

Abstract
Electroporation-based therapies, such as electrochemotherapy and electrogene therapy, result in the disruption of blood vessel networks in vivo and cause changes in blood flow and vascular permeability. The effects of electroporation on the cytoskeleton of cultured primary endothelial cells and on endothelial monolayer permeability were investigated to elucidate possible mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were electroporated in situ and then immunofluorescence staining for filamentous actin, β-tubulin, vimentin, and VE-cadherin as well as Western blotting analysis of levels of phosphorylated myosin light chain and cytoskeletal proteins were performed. Endothelial permeability was determined by monitoring the passage of FITC-coupled dextran through endothelial monolayers. Exposure of endothelial cells to electric pulses resulted in a profound disruption of microfilament and microtubule cytoskeletal networks, loss of contractility, and loss of vascular endothelial cadherin from cell-to-cell junctions immediately after electroporation. These effects were voltage dependent and reversible because cytoskeletal structures recovered within 60 min of electroporation with up to 40 V, without any significant loss of cell viability. The cytoskeletal effects of electroporation were paralleled by a rapid increase in endothelial monolayer permeability. These results suggest that the remodeling of the endothelial cytoskeleton and changes in endothelial barrier function could contribute to the vascular disrupting actions of electroporation-based therapies and provide an insight into putative mechanisms responsible for the observed increase in permeability and cessation of blood flow in vivo. [Mol Cancer Ther 2006;5(12):3145–52]
Histone deacetylase inhibitors deplete enhancer of zeste 2 and associated polycomb repressive complex 2 proteins in human acute leukemia cells
Authors: Fiskus Warren , Pranpat Michael , Balasis Maria , Herger Bryan , Rao Rekha , Chinnaiyan Arul , Atadja Peter , Bhalla Kapil 
Published: December 2006

Abstract
Human enhancer of zeste 2 (EZH2) protein belongs to the multiprotein polycomb repressive complex 2, which also includes suppressor of zeste 12 (SUZ12) and embryonic ectoderm development (EED). The polycomb repressive complex 2 complex possesses histone methyltransferase activity mediated by the Su(var)3-9, enhancer of zeste, and trithorax domain of EZH2, which methylates histone H3 on lysine (K)-27 (H3K27). In the present studies, we determined that treatment with the hydroxamate histone deacetylase inhibitor LBH589 or LAQ824 depleted the protein levels of EZH2, SUZ12, and EED in the cultured (K562, U937, and HL-60) and primary human acute leukemia cells. This was associated with decreased levels of trimethylated and dimethylated H3K27, with concomitant depletion of the homeobox domain containing HOXA9 and of MEIS1 transcription factors. Knockdown of EZH2 by EZH2 small interfering RNA also depleted SUZ12 and EED, inhibited histone methyltransferase activity, and reduced trimethylated and dimethylated H3K27 levels, with a concomitant loss of clonogenic survival of the cultured acute myelogenous leukemia (AML) cells. EZH2 small interfering RNA sensitized the AML cells to LBH589-mediated depletion of EZH2, SUZ12, and EED; loss of clonogenic survival; and LBH589-induced differentiation of the AML cells. These findings support the rationale to test anti-EZH2 treatment combined with hydroxamate histone deacetylase inhibitors as an antileukemia epigenetic therapy, especially against AML with coexpression of EZH2, HOXA9, and MEIS1 genes. [Mol Cancer Ther 2006;5(12):3096–104]
Terbinafine inhibits endothelial cell migration through suppression of the Rho-mediated pathway
Authors: Ho Pei-Yin , Zhong Wen-Bin , Ho Yuan-Soon , Lee Wen-Sen 
Published: December 2006

Abstract
We showed previously that terbinafine, an allylamine with fungicidal activity, could inhibit angiogenesis by suppressing the endothelial cell proliferation. In the present study, we further showed that terbinafine (0–120 μmol/L) dose dependently inhibited the adhesion and migration of human umbilical vascular endothelial cells (HUVEC). Western blot analysis showed that terbinafine decreased the levels of Ras protein and membrane-bound RhoA protein. Moreover, the terbinafine-induced migration inhibition in HUVEC was prevented by pretreatment with farnesol or geranylgeraniol. Pretreatment of HUVEC with Ras inhibitor peptide or a ROCK (a kinase associated with RhoA for transducing RhoA signaling) inhibitor, Y27632, abolished the farnesol- or geranylgeraniol-induced prevention effect on the terbinafine-induced migration inhibition, respectively. These data suggest that the consuming or depletion of geranylgeranyl pyrophosphate and consequent suppression of protein geranylgeranylation and farnesylation, which is essential for activation of Rho GTPases and Ras, respectively, might account for the terbinafine-induced inhibition of HUVEC migration. The levels of phosphorylated focal adhesion kinase and paxillin protein and the mRNA levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 were also decreased by terbinafine treatment. Taken together, these results indicate that suppression of Rho-mediated pathway might be involved in the signal transduction leading to the inhibition of cell migration caused by terbinafine in HUVEC. [Mol Cancer Ther 2006;5(12):3130–8]
Plumbagin induces G2-M arrest and autophagy by inhibiting the AKT/mammalian target of rapamycin pathway in breast cancer cells
Authors: Kuo Po-Lin , Hsu Ya-Ling , Cho Chien-Yu 
Published: December 2006

Abstract
This study is the first to investigate the anticancer effect of plumbagin in human breast cancer cells. Plumbagin exhibited cell proliferation inhibition by inducing cells to undergo G2-M arrest and autophagic cell death. Blockade of the cell cycle was associated with increased p21/WAF1 expression and Chk2 activation, and reduced amounts of cyclin B1, cyclin A, Cdc2, and Cdc25C. Plumbagin also reduced Cdc2 function by increasing the association of p21/WAF1/Cdc2 complex and the levels of inactivated phospho-Cdc2 and phospho-Cdc25C by Chk2 activation. Plumbagin triggered autophagic cell death but not predominantly apoptosis. Pretreatment of cells with autophagy inhibitor bafilomycin suppressed plumbagin-mediated cell death. We also found that plumbagin inhibited survival signaling through the phosphatidylinositol 3-kinase/AKT signaling pathway by blocking the activation of AKT and downstream targets, including the mammalian target of rapamycin, forkhead transcription factors, and glycogen synthase kinase 3β. Phosphorylation of both of mammalian target of rapamycin downstream targets, p70 ribosomal protein S6 kinase and 4E-BP1, was also diminished. Overexpression of AKT by AKT cDNA transfection decreased plumbagin-mediated autophagic cell death, whereas reduction of AKT expression by small interfering RNA potentiated the effect of plumbagin, supporting the inhibition of AKT being beneficial to autophagy. Furthermore, suppression of AKT by plumbagin enhanced the activation of Chk2, resulting in increased inactive phosphorylation of Cdc25C and Cdc2. Further investigation revealed that plumbagin inhibition of cell growth was also evident in a nude mouse model. Taken together, these results imply a critical role for AKT inhibition in plumbagin-induced G2-M arrest and autophagy of human breast cancer cells. [Mol Cancer Ther 2006;5(12):3209–21]
Assessment of celecoxib pharmacodynamics in pancreatic cancer
Authors: Jimeno Antonio , Amador Maria Luz , Kulesza Peter , Wang Xiaofei , Rubio-Viqueira Belen , Zhang Xiangfeng , Chan Audrey , Wheelhouse Jenna , Kuramochi Hidekazu , Tanaka Koji , Danenberg Kathleen , Messersmith Wells A. , Almuete Virna , Hruban Ralph H. , Maitra Anirban , Yeo Charles J. , Hidalgo Manuel 
Published: December 2006

Abstract
Cyclooxygenase-2 (COX-2) inhibitors are being developed as chemopreventive and anticancer agents. This study aimed to determine the biological effect of the COX-2 inhibitor celecoxib in pancreatic cancer as an early step to the further development of the agent in this disease. Eight patients scheduled for resection of an infiltrating adenocarcinoma of the pancreas were randomized to receive celecoxib at a dose of 400 mg twice daily or placebo for 5 to 15 days before the surgery. In addition, carcinomas from nine additional patients were xenografted in nude mice, expanded, and treated with vehicle or celecoxib for 28 days. Celecoxib markedly decreased the intra-tumor levels of prostaglandin E2 in patient carcinomas and in the heterotransplanted xenografts. However, this effect did not result in inhibition of cell proliferation or microvessel density (as assessed by Ki67 and CD31 staining). In addition, a panel of markers, including bcl-2, COX-1, COX-2, and VEGF, did not change with treatment in a significant manner. Furthermore, there was no evidence of antitumor effects in the xenografted carcinomas. In summary, celecoxib efficiently inhibited the synthesis of prostaglandin E2 both in pancreatic cancer surgical specimens and in xenografted carcinomas but did not exert evident antitumor, antiproliferative, or antiangiogenic effect as a single agent. The direct pancreatic cancer xenograft model proved to be a valuable tool for drug evaluation and biological studies and showed similar results to those observed in resected pancreatic cancer specimens. [Mol Cancer Ther 2006;5(12):3240–7]
The Influence of Treadmill Inclination on the Gait of Ambulatory Hemiparetic Subjects
Authors: Werner C. , Lindquist A. R. , Bardeleben A. , Hesse S. 
Published: December 2006

Introduction. This study evaluated the influence of the degree of treadmill belt inclination for training of ambulatory patients with hemiparetic stroke. Methods. Twelve patients were instructed to walk at 5 different levels of inclination (0%-8%) while harness-secured on the treadmill. The gait velocity was kept constant during all conditions. Dependent variables were heart rate, gait cycle-dependent parameters, and electromyographic activation patterns of the weight-bearing muscles. Results. Heart rate increased across all inclination levels, stride length increased and cadence decreased, whereas swing symmetry improved due to shortening of the relative swing phase of the affected side at the 6% and 8% inclination levels. No change in the activation pattern of the leg muscles was found. Conclusion. An inclination up to at least 8% can be accommodated for treadmill training by ambulatory stroke patients. For a given belt speed, heart rate increased without exceeding critical levels and patients walked with a more symmetric pattern. This protocol appeared to be safe in this selected group of subjects.
Constraint-Induced Movement Therapy During Early Stroke Rehabilitation
Authors: Boake Corwin , Noser Elizabeth A. , Ro Tony , Baraniuk Sarah , Gaber Mary , Johnson Ruth , Salmeron Eva T. , Tran Thao M. , Lai Jenny M. , Taub Edward , Moye Lemuel A. , Grotta James C. , Levin Harvey S. 
Published: December 2006

Background. Limited data are available about the effectiveness of early rehabilitation after stroke. Objective. This is the 1st randomized controlled trial of constraint-induced movement therapy (CIMT) in subacute stroke to investigate neurophysiologic mechanisms and long-term outcome. Methods. Within 2 weeks after stroke, 23 patients with upper extremity (UE) weakness were randomized to 2 weeks of CIMT or traditional therapy at an equal frequency of up to 3 h/day. Motor function of the affected UE was blindly assessed before treatment, after treatment, and 3 months after stroke. Transcranial magnetic stimulation (TMS) measured the cortical area evoking movement of the affected hand. Results. Long-term improvement in motor function of the affected UE did not differ significantly between patients who received CIMT versus intensive traditional therapy. All outcome comparisons showed trends favoring CIMT over intensive traditional therapy, but none was statistically significant except for improvements in the Fugl-Meyer (FM) UE motor scale immediately following treatment and in reported quality of hand function at 3 months. Improvement in UE motor function on the FM was associated with a greater number of sites on the affected cerebral hemisphere where responses of the affected hand were evoked by TMS. Conclusions. Future trials of CIMT during early stroke rehabilitation need greater statistical power, more inclusive eligibility criteria, and improved experimental control over treatment intensity. The relationship between changes in motor function and in evoked motor responses suggests that motor recovery during the 1st 3 months after stroke is associated with increased motor excitability of the affected cerebral hemisphere.
Altered Brain Activation During Cognitive Control in Patients With Moderate to Severe Traumatic Brain Injury
Authors: Scheibel Randall S. , Newsome Mary R. , Steinberg Joel L. , Pearson Deborah A. , Rauch Ronald A. , Mao Hui , Troyanskaya Maya , Sharma Rajkumar G. , Levin Harvey S. 
Published: December 2006

Background. Persistent deficits in cognitive control have been documented following traumatic brain injury (TBI) but are inconsistently related to the presence and location of focal lesions. Objective. Functional magnetic resonance imaging (fMRI) was used to examine brain activation during a cognitive control task in patients with moderate to severe TBI or orthopedic injury (OI). Methods. Fourteen TBI patients and 10 OI patients underwent fMRI at 3 months postinjury using a stimulus-response compatibility task in which response accuracy and reaction time were measured. Performance between the groups was equated by individually adjusting the amount of training. Groups did not differ in age, gender, or education. Results. Brain activation during stimulus-response incompatibility was greater in TBI patients than in OI patients within the cingulate, medial frontal, middle frontal, and superior frontal gyri. However, the positive regression of activation with response accuracy during stimulus-response incompatibility indicated a stronger relationship for OI patients than the TBI group within the anterior cingulate gyrus, medial frontal, and parietal regions, as well as deep brain structures (eg, brainstem). The number of focal lesions within either the whole brain or within prefrontal areas was not related to brain activation, but there was a relationship between activation and TBI severity. Conclusions. These findings suggest that neural networks mediating cognitive control are altered after moderate to severe TBI, possibly as a result of diffuse axonal injury, and that the typical relationship of brain activation to performance is disrupted.
Two unusual minerals in a nigerian soil: (I) fibrous kaolin; (II) bastnaesite
Authors: Hughes J. C. , Brown G. 
Published: December 2006

AbstractA kaolin mineral in the form of long fibres, similar to the fibrous kaolin from Brazil (de Souza Santoset al., 1965), was found in the <2 μm fraction of an Ekiti series soil formed on biotite gneiss at the International Institute of Tropical Agriculture, Ibadan, Nigeria. The fibres, up to 6 µm long, appear tubular in electron micrographs. Scanning electron micrographs show that the mineral is formed by direct weathering of ort oclase and, perhaps, biotite.Bastnaesite occurs in the < 2 µm fraction of the same weathering gneiss but not in the coarser fractions or the overlying soil. It was identified by indexing the X-ray powder pattern of a concentrate obtained by treating the clay with HF. The unit cell thus found as hexagonal witha= 7·056 andc= 9·730 Å, and was confirmed by electron diffraction from selected grains. Evidence of chemical composition was obtained by XRF and IR spectrometry. Bastnaesite can be mistaken for gibbsite because their strongest reflections have nearly the same spacing,d= 4·85 Å, when unheated oriented specimens are used. The occurrence of bastnaesite indicates that it is formed when the rock weathers, but is unstable in the soil.
Luetheite, Cu2Al2(AsO4)2(OH)4·H2O, a new mineral from Arizona, compared with chenevixite
Authors: Williams S. A. 
Published: December 2006

SummaryLuetheite was found at a small prospect in Santa Cruz County, Arizona, as crystals in vugs in rhyolite porphyry. A few specimens were found on the dump, none seen in place. Occurs in silicified porphyry (quartzsericite-alunite) with chenevixite and hematite. Crystals indian blue inclining to greenish, H = 3, Dmeas = 4·28.Crystals monoclinic 2/m and tabular on a {100}, also a plane of distinct cleavage; other forms are {110}, {140}, {011}. Space group perhaps P21/m with a = 14·743Å, b = 5·093, c = 5·598, β = 101° 49′; strongest lines are 3·498Å (10), 310, 111; 7·208 (7), 200; 2·507 (5), 120, 510. Feebly pleochroic in pale blue in thin section, γ = β > α. Indices are α = 1·752, β = 1·773, γ = 1·796; 2Vγ = 88° (calc.); dispersion is moderate ν > ρ. α ∥ [010], γ: [001] 10° in obtuse β. Duplicate chemical analyses averaged CuO 28·9%, Al2O3 18·4%, As2O5 40·5%, H2O 9·3% giving 2[Cu2Al2 (AsO4)2(OH)4·H2O].Named for R. D. Luethe, geologist for Phelps Dodge Corporation. Chenevixite from Las Animas, Sonora, analysed to give Cu2Fe2(AsO4)2(OH)4·H2O. Powder data are close to luetheite, and the cell is monoclinic 2/m, probably P21/m, with a = 15·006A, b = 5·189, c = 5·724, β = 102°15. The measured specific gravity is 4·38, Dcale. = 4·59. Crystals tabular on a {100} with a habit very similar to luetheite. Indices are α = 1·92 , β = 1·96, γ = 2·04, 2Vγcale. = 75°; α ∥ [100], γ nearly ∥ [001].
Willemite from the Ilímaussaq alkaline Intrusion
Authors: Metcalf-Johansen John 
Published: December 2006

SummaryDuring the summer of 1967 willcmite was found for the first time in the Ilímaussaq alkaline intrusion, South Greenland. The willemite occurs in an albitite together with aegirine/acmite, albite, analcime, arfvedsonite, apatite, chkalovite, hemimorphite, microcline, monazite, natrolite, naujakasite, neptunite, sphalerite, and polylithionite. Analytical, optical, and X-ray data were obtained from the willemite. Willemite from a calcite vein at Franklin Furnace, New Jersey, and from a quartz vein at Mussartût, South Greenland, were also examined.One of the willemite crystals from Ilimaussaq was a trilling on <100>. This is the first time willemite has been found as a trilling.
Francolite in a concretion from argillaceous sediments in the Westphalian of Yorkshire
Authors: Pearson Mike J. 
Published: December 2006

SynopsisA phosphate-rich carbonate nodule from carboniferous mudstones has been studied by wet chemistry, X-ray diffraction, and electron microprobe. Partial heavy-liquid separation has enabled characterization of the phosphate phase as francolite (carbonate fluorapatite) with a composition Ca10(PO4)5·59(CO3)1·00((OH)1·49F2·10). Diffractometer data for this mineral is presented and cell dimensions are calculated as a = 9·349 Å, c = 6·887 Å. with c/a = 0·737. The problem of the structural positioning of carbon in francolite is discussed.The francolite is seen in thin section as a structureless groundmass enclosing siderite spheru-lites. Electron microprobe X-ray distribution photographs for P, Al, Si, Mg, and Fe show the relationship of these two phases to quartz, pyrite, and at least two clay minerals. One of the latter is intimately mixed with francolite.Possible origins of phosphatic nodules are discussed. Textural evidence in the present case strongly suggests that the francolite is concretionary and formed during early diagenesis possibly by replacement of earlier calcite. Phosphate was probably derived from protein degradation, which also maintained the alkaline pH necessary for francolite formation.
The pentlandite group (Fe,Ni,Co)9S8: New data and an appraisal of structure-composition relationships
Authors: Riley John F. 
Published: December 2006

SummaryAnalyses are presented for an iron-rich pentlandite associated with native copper and troilite from New Zealand and three cobalt-bearing pentlandites from Australia. Examination of 141 published analyses indicates that pentlandites, regardless of their Co content, can be classified on the basis of cell size, Fe content, Fe:Ni ratio, and the sulphide assemblage in which they occur. The cobaltian varieties show two separate trends.
The crystal structure of killalaite
Authors: Taylor H. F. W. 
Published: December 2006

SummaryThe crystal structure of killalaite has been approximately determined, using a crystal from the original locality. The ionic constitution is Ca3+x (H1–2xSi2O7) (OH), with x ≈ 0·2 for the crystal studied. Crystal data are: monoclinic pseudo cell with a 6·807, b 15·459, c 6·811 Å, β 97·76°, space group P21/m, Z = 4, Dx-ray = 2·94 gcm-3. Additional, very weak reflections indicate a B-centred monoclinic true cell with doubled a and c. The structure was determined using only the pseudo cell reflections, and includes one fractionally occupied Ca site; the larger true cell possibly arises from ordering of Ca atoms in these sites, together with associated small shifts of other atoms. There are weak indications that the degree of occupancy of this site may be variable. The X-ray powder pattern has been indexed and a calculated pattern is also given. A synthetic compound called ‘Phase F’ by Aitken and Taylor (1960) appears identical with or closely similar to killalaite.