bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis induced by selenomethionine and methioninase is superoxide mediated and p53 dependent in human prostate cancer cells
Authors: Zhao Rui , Domann Frederick E. , Zhong Weixiong 
Published: December 2006

AbstractSelenomethionine (SeMet) is the chemical form or major component of selenium used for cancer chemoprevention in several clinical trials. However, evidence from experimental studies indicates that SeMet has weaker anticancer effects than most other forms of selenium. Recent studies showed that the anticancer activity of SeMet can be enhanced by methioninase (METase), indicating that SeMet metabolites are responsible for its anticancer activity. In the present study, we showed that wild-type p53-expressing LNCaP human prostate cancer cells were more sensitive to cotreatment with SeMet and METase than p53-null PC3 human prostate cancer cells. SeMet and METase cotreatment significantly increased levels of superoxide and apoptosis in LNCaP cells. Cotreatment with SeMet and METase resulted in increased levels of phosphorylated p53 (Ser15), total p53, Bax, and p21Waf1 proteins. LNCaP cells treated with SeMet and METase also showed p53 translocation to mitochondria, decreased mitochondrial membrane potential, cytochrome c release into the cytosol, and activation of caspase-9. The effects of SeMet and METase were suppressed by pretreatment with a synthetic superoxide dismutase mimic or by knockdown of p53 via RNA interference. Reexpression of wild-type p53 in PC3 cells resulted in increases in superoxide production, apoptosis, and caspase-9 activity and a decrease in mitochondrial membrane potential following cotreatment with SeMet and METase. Our study shows that apoptosis induced by SeMet plus METase is superoxide mediated and p53 dependent via mitochondrial pathway(s). These results suggest that superoxide and p53 may play a role in cancer chemoprevention by selenium. [Mol Cancer Ther 2006;5(12):3275–84]
Association of insulin-like growth factor binding protein-3 expression with melanoma progression
Authors: Xi Yaguang , Nakajima Go , Hamil Tray , Fodstad Oystein , Riker Adam , Ju Jingfang 
Published: December 2006

AbstractPrevious studies from our laboratory have identified several endothelial cell–associated marker genes implicated in human melanoma metastasis via tumor vasculogenic mimicry. In this study, we used dual model systems composed of melanoma cell lines and clinical melanoma samples to validate the importance of insulin-like growth factor binding protein-3 (IGFBP-3) as a marker involved in disease progression. Gene expression analysis was done using a microarray approach for both primary and metastatic melanoma samples. The expression of IGFBP-3 was decreased using a small interfering RNA (siRNA) knockdown approach and quantified with real-time quantitative reverse transcription-PCR analysis. The expression of insulin-like growth factor binding protein 3 (IGFBP-3) was up-regulated by nearly 16-fold in WM266-4 compared with WM35 cells. A subsequent parallel analysis using freshly isolated primary and metastatic melanoma cell samples and melanoma tissue array confirmed the previous findings. The functional significance of IGFBP-3 in melanoma invasion was further investigated using a siRNA gene knockdown approach, with the expression of IGFBP-3 markedly reduced. Additionally, siRNA knockdown resulted in a significant reduction in cell motility, migration, and invasive capacity of WM266-4 cells in vitro. These results strongly suggest that IGFBP-3 expression may be a vital cell motility, migration, and proliferation factor necessary for melanoma metastasis and is an important biomarker in human melanoma. [Mol Cancer Ther 2006;5(12):3078–84]
Preclinical pharmacokinetics, tissue distribution, and antitumor activity of a folate-hapten conjugate–targeted immunotherapy in hapten-immunized mice
Authors: Lu Yingjuan , Xu Le-Cun , Parker Nikki , Westrick Elaine , Reddy Joseph A. , Vetzel Marilynn , Low Philip S. , Leamon Christopher P. 
Published: December 2006

Abstract
Folic acid (pteroylglutamic acid) represents a useful ligand for targeted cancer therapies because it binds to a common epithelial tumor antigen known as the folate receptor. We previously devised an immunotherapy strategy that uses a bispecific ligand, a folate-hapten (FITC) conjugate, to redirect endogenously induced anti-FITC antibodies to folate receptor–positive tumor cells following parenteral administration. Here, we present results from preclinical pharmacokinetic and tissue biodistribution studies using a radioactive folate-FITC conjugate and results from dose optimization studies done in tumor-bearing animals. Folate-FITC was found to be rapidly eliminated in non-immunized mice; however, in immunized hosts, folate-FITC was shown to form immune complexes with FITC-specific antibodies, the consequence of which was a ∼173-fold increase in drug exposure (i.e., area under the curve). Using a newly developed ELISA assay, the extent of circulating anti-FITC antibodies occupied by parenterally given folate-FITC was determined to be proportional to the given dose. Furthermore, high doses of folate-FITC were found to promote the cosaturation of tumor cell surface folate receptors and circulating FITC-specific antibodies, blocking the immune recognition of tumor cells and thereby reducing antitumor activity. Nonetheless, by extending the duration of treatment and administering subsaturating doses of folate-FITC, enhanced antitumor response was observed in mice bearing established folate receptor–positive M109 tumors. Overall, results from the present study may help to guide clinicians through on-going clinical investigations of folate-targeted immunotherapy. [Mol Cancer Ther 2006;5(12):3258–67]
In silico design, synthesis, and biological evaluation of radioiodinated quinazolinone derivatives for alkaline phosphatase–mediated cancer diagnosis and therapy
Authors: Chen Kai , Wang Ketai , Kirichian Agop M. , Al Aowad Ayman F. , Iyer Lakshmanan K. , Adelstein S. James , Kassis Amin I. 
Published: December 2006

Abstract
As part of the development of enzyme-mediated cancer imaging and therapy, a novel technology to entrap water-insoluble radioactive molecules within solid tumors, we show that a water-soluble, radioactive quinazolinone prodrug, ammonium 2-(2′-phosphoryloxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ2-P), is hydrolyzed by alkaline phosphatase to a water-insoluble, radiolabeled drug, 2-(2′-hydroxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ2-OH). Biodistribution data suggest the existence of two isoforms of the prodrug (IQ2-P(I) and IQ2-P), and this has been confirmed by their synthesis and characterization. Structural differences of the two isoforms have been examined using in silico molecular modeling techniques and docking methods to describe the interaction/binding between the isoforms and human placental alkaline phosphatase (PLAP), a tumor cell, membrane-associated, hydrolytic enzyme whose structure is known by X-ray crystallographic determination. Docking data show that IQ2-P, but not IQ2-P(I), fits the active binding site of PLAP favorably and interacts with the catalytic amino acid Ser92, which plays an important role in the hydrolytic process. The binding free energies (ΔGbinding) of the isoforms to PLAP predict that IQ2-P will be the better substrate for PLAP. The in vitro incubation of the isoforms with PLAP leads to the rapid hydrolysis of IQ2-P only and confirms the in silico expectations. Fluorescence microscopy shows that in vitro incubation of IQ2-P with mouse and human tumor cells causes the extracellular, alkaline phosphatase–mediated hydrolysis of the molecule and precipitation of fluorescent crystals of IQ2-OH. No hydrolysis is seen in the presence of normal mouse and human cells. Furthermore, the intratumoral injection of 125IQ2-P into alkaline phosphatase–expressing solid human tumors grown s.c. in nude rats results in efficient hydrolysis of the compound and retention of ∼70% of the injected radioactivity, whereas similar injection into normal tissues (e.g., muscle) does not produce any measurable hydrolysis (∼1%) or retention of radioactivity at the injected site. These studies support the enzyme-mediated cancer imaging and therapy technology and show the potential of such quinazolinone derivatives in the in vivo radiodetection (123I/124I) and therapy (131I) of solid tumors. [Mol Cancer Ther 2006;5(12):3001–13]
Endothelial E-Selectin Potentiates Neovascularization via Endothelial Progenitor Cell–Dependent and –Independent Mechanisms
Authors: Nishiwaki Yasunobu , Yoshida Masayuki , Iwaguro Hideki , Masuda Haruchika , Nitta Noriko , Asahara Takayuki , Isobe Mitsuaki 
Published: December 2006

Background—Although potential participation of bone marrow-derived circulating endothelial progenitor cells (EPCs) to neoangiogenesis has been proposed, the precise molecular mechanisms of EPC recruitment to vascular endothelium has not been fully elucidated.Methods and Results—Peripheral blood mononuclear cells were isolated from healthy volunteers and cultured for 7 days to obtain EPCs. Tumor necrosis factor-α–activated human umbilical vein endothelial cells (HUVECs) supported significantly more rolling and adhesion of EPCs compared with inactivated HUVEC monolayer. Pretreatment of activated HUVEC with an adhesion-blocking mAb to E-selectin significantly reduced EPCs adhesion to HUVECs. When HUVECs were transduced with a recombinant adenovirus of E-selectin (AdRSVE-sel) or that of β-galactosidase (AdRSVLacZ), E-selectin-transduced but not LacZ-transduced HUVECs exhibited significantly more EPC rolling as well as adhesion. Further, effect of AdRSVE-sel or AdRSVLacZ was examined in mouse hind limb ischemic model. AdRSVE-sel–transduced mice showed significantly less limb necrosis and higher laser Doppler ratio when compared with AdRSVLacZ-transduced mice. Interestingly, blood flow recovery of ischemic limb observed in AdRSVE-sel–transduced mice was more prominent when combined with EPC administration compared with that of AdRSVLacZ-transduced mice.Conclusions—Endothelial E-selectin plays a crucial role in EPC–endothelial interaction in vitro. The importance of E-selectin was also confirmed in vivo even in the absence of exogenous EPC. These data provide molecular background for novel cell-based therapy for ischemic atherosclerosis.
A Mechanistic Model for Paradoxical Platelet Activation by Ligand-Mimetic αIIbβ3(GPIIb/IIIa) Antagonists
Authors: Bassler Nicole , Loeffler Christoph , Mangin Pierre , Yuan Yuping , Schwarz Meike , Hagemeyer Christoph E. , Eisenhardt Steffen U. , Ahrens Ingo , Bode Christoph , Jackson Shaun P. , Peter Karlheinz 
Published: December 2006

Objective—Integrins are attractive therapeutic targets. Inhibition of integrin αIIbβ3effectively blocks platelet aggregation. However, limitations with intravenous αIIbβ3antagonists and failure of oral αIIbβ3antagonists prompted doubts on the current concept of ligand-mimetic integrin blockade.Methods and Results—Evaluating P-selectin expression on platelets by flow cytometry, we report a mechanism of paradoxical platelet activation by ligand-mimetic αIIbβ3antagonists and define three requirements: (1) Induction of ligand-bound conformation of αIIbβ3, (2) receptor clustering, (3) prestimulation of platelets. Conformational change is inducible by clinically used ligand-mimetic αIIbβ3antagonists, RGD-peptides, and anti-LIBS antibodies. In a mechanistic experimental model, clustering is achieved by crosslinking integrins via antibodies, and preactivation is induced by low-dose ADP. Finally, we demonstrate that platelet adhesion on collagen represents an in vivo correlate of platelet prestimulation and receptor clustering, in which the presence of ligand-mimetic αIIbβ3antagonists results in platelet activation as detected by P-selectin, CD63, and CD40L expression as well as by measuring Ca2+-signaling. Blockade of the ADP receptor P2Y12by AR-C69931MX and clopidogrel inhibits αIIbβ3antagonist-induced platelet activation.Conclusion—These findings can explain limitations of ligand-mimetic anti-αIIbβ3therapy. They describe potential benefits of concomitant ADP receptor blockade and support a shift in drug development from ligand-mimetic toward allosteric or activation-specific integrin antagonists.
Arthroscopically Assisted Percutaneous Repair of Fresh Closed Achilles Tendon Rupture by Kessler's Suture
Authors: Tang Kang-lai , Thermann Hajo , Dai Gang , Chen Guang-xing , Guo Lin , Yang Liu 
Published: December 2006

Background Achilles tendon ruptures are difficult to repair, and the healing rate is low due to this structure's anatomic and physiological characteristics. It is essential to develop new techniques to increase the healing rate and decrease the rate of complications. Objective To propose and evaluate a new percutaneous method of repairing fresh closed Achilles tendon ruptures by Kessler's suture under arthroscopy. Study Design Case series; Level of evidence, 4. Methods Twenty patients were followed at least 12 months in this study. First, the torn ends of the Achilles tendon were debrided during arthroscopy. Then percutaneous repair of the Achilles tendon was performed using Kessler's suture by an inside-out technique. All cases were followed up for an average range of 21 months (range, 12-36 months). All patients were evaluated by clinical examination, magnetic resonance imaging, and the Lindholm scale. Results The torn ends were well aligned and sutured after the debridement under arthroscopy. According to the Lindholm scale, excellent results were seen in 15 cases and good in 5 cases. No patients had complications such as nerve injury, infection, or re-rupture at follow-up. Magnetic resonance imaging results showed that the ruptured Achilles tendons were repaired and remodeled very well in all patients. Conclusion The present method is an effective surgical technique for repair of a closed rupture of the Achilles tendon. The short-term follow-up results were good, and recovery time was short. Few complications were found in our study cases.
Measurement Error in Functional Balance and Mobility Tests for People With Stroke: What Are the Sources of Error and What Is the Best Way to Minimize Error?
Authors: Tyson Sarah F. 
Published: December 2006

Objective. To assess the degree and source of measurement error in functional balance and mobility tests for people with stroke, and to identify the most effective method of data collection to minimize error. Design. To assess the degree and source of error, the total, systematic, and random error were calculated for within-session, test-retest, and interrater testing. To identify the most effective method of data collection, the total error was calculated for 4 data collection methods: 1 familiarization trial, then scoring a 2nd trial; 2 familiarization trials, then scoring a 3rd trial; averaging 2 trials, then averaging 3 trials. Setting. Stroke services in National Health Service hospitals. Patients. Thirty-five people with a poststroke hemiplegia. Interventions. None. Main Outcome Measures. Five tests provided interval-level data: arm raise (sitting and standing), weight shift, tap, and step-up. Four tests provided ratio-level data: forward reach (sitting and standing) and 5-m timed walk (with and without an aid). Results. Total measurement error ranged from zero for the step-up test to 55% for within-session error for the 5-m walk without an aid. Ratio data tests showed somewhat greater error than interval data tests (5%-55% vs. 0%-46%). A within-session practice effect for the standing forward reach, 5-m walk (with and without an aid), and weight shift tests was found. For the other tests, random error was greater than the systematic error. Interrater testing had the least error. For most tests, the average of 2 trials produced the least measurement error. For the 5-m walk, the mean obtained from 2 or 3 trials was equally effective. For the step-up test, the mean of 3 trials was slightly more effective. The overall error from all 3 sources was 3 lifts for sitting arm raise, 11 cm for sitting forward reach, 3 lifts for the standing arm raise, 7.5 cm for standing forward reach, 4.5 s for walking with an aid, 3 shifts on the weight shift test, 1.1 s for walking without an aid, 2 taps, and 1 step up. Conclusion. The tests using interval data showed less error than ratio-data tests and may be preferable measurement tools. Taking an average of 2 trials was the most accurate data collection method.
Effects of a Rostral Motor Cortex Lesion on Primary Motor Cortex Hand Representation Topography in Primates
Authors: Friel Kathleen M. , Barbay Scott , Frost Shawn B. , Plautz Erik J. , Stowe Ann M. , Dancause Numa , Zoubina Elena V. , Nudo Randolph J. 
Published: December 2006

Background. Small lesions to rostral versus caudal portions of the hand representation in the primary motor cortex (M1) produce different behavioral deficits. The goal of the present study was to determine if rehabilitative training has similar effects on functional topography of the spared M1 after rostral versus previously reported caudal M1 lesions. Methods. Following a lesion to the rostral M1 hand area, monkeys were trained for 1 h/day for 30 days to retrieve food pellets from small wells using their impaired hand. Electrophysiological maps of the M1 were derived in anesthetized monkeys before infarct and after rehabilitative training using intracortical microstimulation. Results. After a lesion to the rostral M1 and rehabilitative training, the size of the spared hand representation decreased 1.2%. This change is not statistically different from the 9% increase seen after caudal M1 lesion and rehabilitative training ( P > 0.2). Conclusion. Postlesion training spares peri-infarct hand area regardless of whether the lesion is in the rostral or caudal M1.
Selective extraction of the amorphous Al, Fe and Si oxides using an alkaline Tiron solution
Authors: Biermans V. , Baert L. 
Published: December 2006

AbstractA selective chemical dissolution method has been worked out in order to characterize quantitatively amorphous Al, Fe and Si oxides simultaneously in soils. Based on theoretical considerations an alkaline Tiron solution was tried out. Experiments on well-characterized synthetic and natural substrates were carried out in order to find the optimum set of conditions of pH, temperature and reaction time. These are: an alkaline medium consisting of 0·1 m Tiron and buffered at pH 10·5, an extraction temperature of 80°C and an extraction time of 1 h.
Petrographic and isotopic studies of the altered acid volcanics of the Tolfa-Cerite area, Italy: the genesis of the clays
Authors: Lombardi G. , Sheppard S. M. F. 
Published: December 2006

AbstractAlunite-kaolinite deposits occur in argillized zones in acid volcanic rocks at Tolfa. Over seventy samples were examined by one or more of the following methods: thin section, DTA, X-ray, IR, TG, SEM, chemical, and hydrogen and oxygen isotope analysis. Kaolinite and dickite, of high structural order, are the dominant clays with micamontmorillonite and halloysite subordinate. In many samples kaolinite and dickite coexist; their relative amounts are variable but the dickite content tends to increase with depth. SEM studies show that dickite crystals—up to 30 µm—are bigger than kaolinite.The D/H and18O/16O ratios of six clays, a whole rock, two biotites from fresh host rock, two chalcedony veins and three local meteoric waters indicate that the clays formed in a meteoric-hydrothermal environment of acid hot spring type at about 80°C. The fresh volcanic host rocks are strongly enriched in18O relative to ‘normal’ igneous rocks due to derivation from or exchange with18O-rich sedimentary rocks at depth prior to hydrothermal and solfataric activity. In the absence of present-day geothermal activity the life of this hot spring system was less than 4 m.y.
Fine structure in the selected area diffraction patterns of beidellite, and its dark-field images
Authors: Güven N. , Pease R. W. , Murr L. E. 
Published: December 2006

AbstractCommonly streaks and rarely extra spots are observed on the selected area diffraction patterns of beidellite. The streaks are non-radial, and are restricted along the direction parallel to [11], [11], and [01]. Extra spots appear instead of streaks between the normal Bragg spots along the direction parallel to [11] and [11]. These extra spots suggest the formation of a superlattice with the a and b cell parameters twice as large as those of the beidellite lattice. Dark-field images on the strong 020 reflection reveal the presence of a network of dislocations in some of the beidellite crystallites. These dislocations suggest that the chemistry is not uniform over the successive layers in these crystallites. The structural difference between the layers seems to be accommodated by the dislocations.
Density and structure of allophane
Authors: Wada Shin-Ichiro , Wada Koji 
Published: December 2006

AbstractThe densities of two allophane samples measured by displacement with water were 2·72–2·78 g/cm3, while those measured by a float-sink test in CH3OH-, CH3 COCH3-, C6H6- and CCl4-C2H2Br4 mixtures were 1·84, 1·94–1·98, 2·35 and 2·35–2·39 g/cm3, respectively. The results of the density determinations for montmorillonite, kaolinite, halloysite, imogolite and volcanic glass are also reported. The data were interpreted in terms of the accessibility of the displacement liquids to void spaces within and between the layers or ‘structure units’ of the minerals and a model of the ‘structure units’ of allophane is proposed.
Archerite, (K,NH4)H2PO4, a new mineral from Madura, Western Australia
Authors: Bridge P. J. 
Published: December 2006

SummaryArcherite, (K, NH4)H2PO4, a new mineral, has been found in Petrogale Cave, 36 km east of Madura Motel (31° 54′S, 127°00′E) Western Australia. Archerite and biphosphammite together with aphthitalite, halite, syngenite, stercorite, oxammite, weddellite, whitlockite, guanine, newberyite, calcite, (NH4)2Ca(HPO4)2·H2O, and an unknown occur as stalactites and wall and floor crusts.Archerite is tetragonal with second order prisms and pyramids in crystals up to 2 mm in length with D 2·23, ω 1·513, ε 1·470, all close to artificial KH2PO4. The mineral is soft, has a white streak, and is soluble in cold H2O. Cell dimensions of natural archerite were not determined and the composition was calculated from measurements of selected powder lines correlated with charts prepared from end-member data and by chemistry which gave 81% KH2PO4 and K2O 10·8, NH2 3·46 respectively, the latter corresponding to (K0·74(NH4)0·26)H2PO4.The name is for Dr. M. Archer, Curator of Mammals, Queensland Museum. Type material is stored in the collections of the Government Chemical Laboratories, Perth, Western Australia.
Westerveldite from Igdlúnguaq, Ilímaussaq alkaline massif, South Greenland
Authors: Oen I. S. , Burke E. A. J. , Kieft C. 
Published: December 2006

SummaryMicroprobe and X-ray investigation of a mineral occurring with breithauptite, nickeline, and other arsenides in the naujaite at Igdlúnguaq, Ilímaussaq alkaline massif, S. Greenland, shows that this mineral, which was formerly misidentified as ‘maucherite’, is a westerveldite (Fe0·85Ni0·15)As, of much iron-richer composition than the nickeloan westerveldites from the only two other known occurrences of this mineral. Westerveldite from Igdlúnguaq was presumably formed by reaction of nickeline with iron-rich solutions under conditions of reheating at temperatures of about 450° C and under partial pressures of arsenic below those necessary to stabilize nickeline. Sulphur-bearing löllingite occurs as exsolution blades in the westerveldite. Iron-rich nickeline, up to a composition (Ni0·82Fe0·18)As0·95Sb0·05, was presumably formed by recrystallization of nickeline in the transition stage just before this mineral became unstable and was replaced by westerveldite.