bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma
Authors: Raje Noopur , Kumar Shaji , Hideshima Teru , Roccaro Aldo , Ishitsuka Kenji , Yasui Hiroshi , Shiraishi Norihiko , Chauhan Dharminder , Munshi Nikhil C. , Green Simon R. , Anderson Kenneth C. 
Published: April 2005

AbstractCyclin-dependent kinase (CDK) inhibitors have the potential to induce cell-cycle arrest and apoptosis in cancer cells. Seliciclib (CYC202 or R-roscovitine) is a potent CDK inhibitor currently undergoing phase-2 clinical testing in lung and B-cell malignancies. Here we studied the in vitro cytotoxic activity of seliciclib against multiple myeloma (MM) cells. Our data demonstrate that seliciclib has potent cytotoxicity against MM cells that are both sensitive and resistant to conventional therapy as well as primary MM cells from patients. Cell-cycle and Western blot analysis confirmed apoptosis. Importantly, seliciclib triggered a rapid down-regulation of Mcl-1 transcription and protein expression independent of caspase cleavage. Adherence of MM cells to bone marrow stromal cells (BMSCs) induced increased Mcl-1 expression associated with signal transducer and activator of transcription 3 (STAT3) phosphorylation, which was inhibited in a time- and dose-dependent manner by seliciclib. Furthermore, seliciclib inhibited interleukin 6 (IL-6) transcription and secretion triggered by tumor cell binding to BMSCs. Up-regulation of Mcl-1 expression in cocultures was only partially blocked by neutralizing antibody to IL-6, suggesting alternative mechanisms of Mcl-1 modulation by seliciclib. Finally, combination studies of seliciclib with doxorubicin and bortezomib show in vitro synergism, providing the rationale for testing these drug combinations to improve patient outcome in MM.
Proliferation dynamics of germinative zone cells in the intact and excitotoxically lesioned postnatal rat brain
Authors: Faiz Maryam , Acarin Laia , Castellano Bernardo , Gonzalez Berta 
Published: April 2005

Abstract
Background
The forebrain subventricular zone (SVZ)-olfactory bulb pathway and hippocampal subgranular zone (SGZ) generate neurons into adulthood in the mammalian brain. Neurogenesis increases after injury to the adult brain, but few studies examine the effect of injury on neural and glial precursors in the postnatal brain. To characterize the spatio-temporal dynamics of cell proliferation in the germinative zones, this study utilized a model of postnatal damage induced by NMDA injection in the right sensorimotor cortex at postnatal day 9.
Dividing cell populations were labeled with 5-Bromodeoxyuridine (BrdU) in the intact and damaged postnatal brain. Identity of proliferating cells was determined by double immunolabeling with nestin, GFAP, NeuN and tomato lectin (TL).

Results
In the control brain, grouped BrdU+ cells were observed in the Rostral Migratory Stream (RMS), SVZ and SGZ. Maximal proliferation was seen at P12, persisted until P23 and diminished by P49. After injury, a striking reduction in the number of BrdU+ cells was observed in the ipsilateral SVZ from 10 hours (58% decrease) until 14 days post-lesion (88% decrease). In contrast, an increase in grouped BrdU+ cells was seen in the striatum adjacent to the depleted SVZ. Significantly reduced numbers of BrdU+ cells were also seen in the RMS until 3 days post-lesion. No changes were noted in the SGZ. Both in controls and lesioned hemispheres, BrdU+ cells located in the germinal zones were mostly nestin positive and negative for GFAP, NeuN, and TL. In the SVZ area lining the ventricle, BrdU+/nestin+ cells were mainly located between TL+ ependyma and parenchymal GFAP+ astrocytes. After excitotoxicity, a decrease in the number and orientation of GFAP/nestin+ prolongations leaving the SVZ to the cortex, corpus callosum and striatum was noted until 5 days post-lesion.

Conclusion
Postnatal excitotoxic injury differentially affects proliferating cells in the germinative zones: no change is observed in the dentate gyrus whereas excitotoxicity causes a significant decrease in proliferating cells in the SVZ and RMS. Depletion of BrdU+ cells in the postnatal SVZ and RMS differs from previous studies after adult brain injury and may affect the SVZ-RMS migration and is suggestive of progenitor recruitment to injured areas.
Halothane potentiates the alcohol-adduct induced TNF-alpha release in heart endothelial cells
Authors: Thiele Geoffrey M , Hill Gary E , Pavlik Jacqueline A , Freeman Thomas L , Tuma Dean J , Duryee Michael J , Klassen Lynell W 
Published: April 2005

Abstract
Background
The possibility exists for major complications to occur when individuals are intoxicated with alcohol prior to anesthetization. Halothane is an anesthetic that can be metabolized by the liver into a highly reactive product, trifluoroacetyl chloride, which reacts with endogenous proteins to form a trifluoroacetyl-adduct (TFA-adduct). The MAA-adduct which is formed by acetaldehyde (AA) and malondialdehyde reacting with endogenous proteins, has been found in both patients and animals chronically consuming alcohol. These TFA and MAA-adducts have been shown to cause the release of inflammatory products by various cell types. If both adducts share a similar mechanism of cell activation, receiving halothane anesthesia while intoxicated with alcohol could exacerbate the inflammatory response and lead to cardiovascular injury.

Methods
We have recently demonstrated that the MAA-adduct induces tumor necrosis factor-α (TNF-α) release by heart endothelial cells (HECs). In this study, pair and alcohol-fed rats were randomized to receive halothane pretreatments intra peritoneal. Following the pretreatments, the intact heart was removed, HECs were isolated and stimulated with unmodified bovine serum albumin (Alb), MAA-modified Alb (MAA-Alb), Hexyl-MAA, or lipopolysaccharide (LPS), and supernatant concentrations of TNF-α were measured by ELISA.

Results
Halothane pre-treated rat HECs released significantly greater TNF-α concentration following MAA-adduct and LPS stimulation than the non-halothane pre-treated in both pair and alcohol-fed rats, but was significantly greater in the alcohol-fed rats.

Conclusion
These results demonstrate that halothane and MAA-adduct pre-treatment increases the inflammatory response (TNF-α release). Also, these results suggest that halothane exposure may increase the risk of alcohol-induced heart injury, since halothane pre-treatment potentiates the HEC TNF-α release measured following both MAA-Alb and LPS stimulation.
Who wants to join preventive trials? – Experience from the Estonian Postmenopausal Hormone Therapy Trial [ISRCTN35338757]
Authors: Hovi Sirpa-Liisa , Hakama Matti , Veerus Piret , Rahu Mati , Hemminki Elina 
Published: April 2005

Abstract
Background
The interest of patients in participating in randomized clinical trials involving treatments has been widely studied, but there has been much less research on interest in preventive trials. The objective of this study was to find out how many women would be interested in a trial involving postmenopausal hormone therapy (PHT) and how the women's background characteristics and opinions correlated to their interest.

Methods
The data come from recruitment questionnaires (n = 2000) sent to women in Estonia in 1998. A random sample of women aged 45 to 64 was drawn from the Population Registry. The trial is a two-group randomized trial comparing estrogen-progestogen therapy with placebo or no drugs. A brief description of the study was attached to the questionnaires. Women were not told at this stage of the recruitment which group they would be assigned to, however, they were told of the chance to receive either hormone, placebo or no treatment.

Results
After two reminders, 1312 women (66%) responded. Eleven percent of the women approached (17% of the respondents) were interested in joining the trial, and 8% wanted more information before deciding. When the 225 women who stated clearly that they were interested in joining and the 553 women who said they were not interested were compared, it was found that interested women were younger and, adjusting for age, that more had given birth; in other respects, the sociodemographic characteristics and health habits of the interested women were similar to those of the non-interested women. The interested women had made more use of more health services, calcium preparations and PHT, they were more often overweight, and more had chronic diseases and reported symptoms. Interested women's opinions on the menopause were more negative, and they favoured PHT more than the non-interested women.

Conclusion
Unlike the situation described in previous reports on preventive trials, in this case Estonian women interested in participating in a PHT trial were not healthier than other women. This suggests that trials involving PHT are more similar to treatment trials than to preventive trials. In a randomized controlled trial, more information should be obtained from those women who decline to participate.
Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma – CapRI: study protocol [ISRCTN62866759]
Authors: Knaebel HP , Märten A , Schmidt J , Hoffmann K , Seiler C , Lindel K , Schmitz-Winnenthal H , Fritz S , Herrmann T , Goldschmidt H , Krempien R , Mansmann U , Debus J , Diehl V , Büchler MW 
Published: April 2005

Abstract
After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation.

Design

The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment.

Discussion

The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.
Why nutraceuticals do not prevent or treat Alzheimer's disease
Authors: Fisher Anna EO , Naughton Declan P 
Published: April 2005

AbstractA great deal of research has pointed to deleterious roles of metal ions in the development of Alzheimer's disease. These include: i) the precipitation and aggregation of amyloid β (Aβ) peptides to form senile plaques and neurofibrillary tangles, and/or ii) the augmentation of oxidative stress by metal ion mediated production and activation of hydrogen peroxide. The growing trend in nutraceutical intake is in part a result of the belief that they postpone the development of dementias such as Alzheimer's disease. However, pathogenic events centred on metal ions are expected to be aggravated by frequent nutraceutical intake. Novel therapeutic approaches centred on chelators with specificity for copper and iron ions should be fully explored.
Synthesis and Structure of a Germylene Bearing a 1,8-Dimethoxyanthracene Ligand
Authors: Yamashita Makoto , Murakami Hiromi , Unrin-in Toshifumi , Kawachi Atsushi , Akiba Kin-ya , Yamamoto Yohsuke 
Published: April 2005

Abstract
A novel chlorogermylene compound, (1,8-dimethoxy-9-anthracenyl)chlorogermylene, has been synthesized by the reaction of GeCl2·dioxane and 9-lithio-1,8-dimethoxyanthracene. X-ray crystallographic study of the germylene revealed the bis-coordination of the oxygen atoms at the 1,8-positions to the germanium(II) center and the elongation of the Ge–Cl bond caused by the coordination.
Supercritical Water as a Solvent
Authors: Weingärtner Hermann , Franck Ernst Ulrich 
Published: April 2005

AbstractWater is not restricted to moderate temperatures and low pressures, but can exist up to very high temperatures, far above its critical point at 647 K. In this supercritical regime, water can be gradually compressed from gas‐like to liquid‐like densities. The resulting dense supercritical states have extraordinary properties which can be tuned by temperature and pressure, and form the basis for innovative technologies. This Review covers the current knowledge of the major properties of supercritical water and its solutions with nonpolar, polar, and ionic compounds, and of the underlying molecular processes.
Enhance Cyanide Recovery by UsingAir‐Sparged Hydrocyclone
Authors: Parga Torres J.R. , Cocke D.L. 
Published: April 2005

AbstractHuman health and environmental concerns dictate that industrial processes be improved or replaced. Recovery or recycling is an important activity that allows cyanide residue from the industrial processes to be re‐used, reducing its production cost and disposal problems. In this regard, the air‐sparged hydrocyclone (ASH) has been used as a reactor for the treatment of cyanide solutions for cyanide recycling by acidification/volatilization using the Mexican modification of the Mills‐Crowe process. Aqueous cyanide‐ion concentration can be reduced from 250 ppm to below 20 ppm in the ASH with recoveries greater than 80 % in a single stage.
Tuning Photoinduced Energy‐ and Electron‐Transfer Events in Subphthalocyanine–Phthalocyanine Dyads
Authors: González‐Rodríguez David , Claessens Christian G. , Torres Tomas , Liu Shenggao , Echegoyen Luis , Vila Nuria , Nonell Santi 
Published: April 2005

AbstractA series of subphthalocyanine–phthalocyanine dyads has been prepared by means of palladium‐catalyzed cross‐coupling reactions between a monoalkynylphthalocyanine and different monoiodosubphthalocyanines. Electronic coupling between the two photoactive units is ensured by a rigid and π‐conjugated alkynyl spacer. In addition, the electronic characteristics of the subphthalocyanine moiety were modulated by the introduction of different peripheral substituents. Cyclic and Osteryoung square‐wave voltammetry experiments revealed that the reduction potential of this subunit can be decreased by about 400 mV on going from thioether or no substituents to nitro groups. As a consequence, the energy level of the charge‐transfer state could be fine‐tuned so as to gain control over the fate of the photoexcitation energy in each subunit. The diverse steady‐state and time‐resolved photophysical techniques employed demonstrated that, when the charge‐transfer state lies high in energy, a quantitative singlet–singlet energy‐transfer mechanism from the excited subphthalocyanine to the phthalocyanine takes place. On the contrary, stabilization of the radical pair by lowering the redox gap between electron donor and acceptor results in a highly efficient photoinduced electron‐transfer process, even in solvents of low polarity such as toluene (ΦET≈0.9). These features, together with the extraordinary absorptive cross section that these molecular ensembles display across the whole UV/Vis spectrum, make them model candidates for application in situations where broadband light sources are needed.
Assembly of Heteropoly Acid Nanoparticles in SBA‐15 and Its Performance as an Acid Catalyst
Authors: Yu Shu‐Yuan , Wang Li‐Ping , Chen Bo , Gu Ying‐Ying , Li Jing , Ding Han‐Ming , Shan Yong‐Kui 
Published: April 2005

AbstractKeggin‐type 12‐tungstophosphoric acid (TPA) nanocrystals have been assembled inside the pores of mesoporous silica through a vacuum impregnation method by using large‐pore SBA‐15 as a nanoreactor. The product was characterized by Brunauer–Emmet–Teller particle size distribution (BET‐PSD), NMR and FT‐IR spectroscopy, X‐ray diffraction (XRD), tranmsission electron microscopy (TEM), differential thermal analysis (DTA) and FT‐IR of adsorbed pyridine. The experimental results illustrate that the TPA nanocrystals are excellent Brønsted acid catalytic materials at room temperature.
Influence of dT20 and [d(AT)10]2 on Cisplatin Hydrolysis Studied by Two‐Dimensional [1H,15N] HMQC NMR Spectroscopy
Authors: Vinje Jo , Sletten Einar , Kozelka Jiří 
Published: April 2005

AbstractThe influence of the presence of DNA on the kinetics of cisplatin (cis‐[PtCl2(NH3)2]) aquation (replacement of Cl− by H2O) and anation (replacement of H2O by Cl−) involved in the hydrolysis of cisplatin have been determined by two‐dimensional [1H,15N] HMQC NMR spectroscopy. Single‐stranded dT20 and double‐stranded [d(AT)10]2 oligonucleotides were used as DNA models, avoiding guanines which are known to react rapidly with aquated cisplatin forms. Reactions starting from cis‐[PtCl2(15NH3)2], or from a stoichiometric mixture of cis‐[Pt(15NH3)2(H2O)2]2+ and Cl− (all 0.5 mM PtII; in ionic strength, adjusted to 0.095 M or 0.011 M with NaClO4, pH between 3.0 and 4.0) were followed in an NMR tube in both the absence and presence of 0.7 mM dT20 or [d(AT)10]2. In the presence of dT20, we observed a slight and ionic‐strength‐independent decrease (15–20 %) of the first aquation rate constant, and a more significant decrease of the second anation rate constant. The latter was more important at low ionic strength, and can be explained by efficient condensation of cis‐[Pt(15NH3)2(H2O)2]2+ on the surface of single‐stranded DNA, in a region depleted of chloride anions. At low ionic strength, we observed an additional set of [1H,15N] HMQC spectral signals indicative of an asymmetric species of PtN2O2 coordination, and we assigned them to phosphate‐bound monoadducts of cis‐[Pt(15NH3)2(H2O)2]2+. Double‐stranded [d(AT)10]2 slowed down the first aquation step also by approximately 15 %; however, we could not determine the influence on the second hydrolysis step because of a significant background reaction with cis‐[Pt(NH3)2(H2O)2]2+.
Preparation of a chiral ferrocenyl derivative containing a biphenyl unit via nickel‐mediated homocoupling
Authors: Patti Angela , Pedotti Sonia 
Published: April 2005

AbstractFerrocenyl derivative 2, which possesses a biphenyl unit, was prepared by nickel(0)‐mediated homocoupling of a chiral ferrocenyloxazoline. Compound 2 exists as an equilibrium mixture of two diastereomers, in a ratio dependent on temperature and solvent, due to the partially hindered rotation around biaryl bond. Upon complexation with Cu(I) or Zn(II), complete fixation of the stereogenic axis was obtained and a single stable atropoisomer was formed, whose absolute configuration was assigned on the basis of its NOESY spectrum. The 2–Cu(I) complex was used as catalyst in the cyclopropanation of styrene. Chirality 17:233–236, 2005. © 2005 Wiley‐Liss, Inc.
Expression and structure of interleukin 4 receptors in primary meningeal tumors
Authors: Puri Sachin , Joshi Bharat H. , Sarkar Chitra , Mahapatra Ashok Kumar , Hussain Ejaz , Sinha Subrata 
Published: April 2005

AbstractBACKGROUNDIt was reported previously that malignant human tumors, like glioma and medulloblastoma, express high‐density interleukin (IL‐4) receptor mRNA and protein. Because IL‐4 receptors (R) are sensitive targets for targeted therapeutics, knowledge of the expression of these receptors in other central nervous system tumors is of great interest. In this study, the authors examined the expression and subunit composition of IL‐4R complex in primary human meningiomas.METHODSReverse transcription‐polymerase chain reaction (RT‐PCR) analysis for IL‐13Rα1, IL‐4Rα and IL‐2Rγc was performed on total RNA extracted from 35 meningiomas and a normal human brain tissue sample. Results were confirmed in nine randomly selected tumors by quantitative real‐time PCR and in situ immunofluorescence assay.RESULTSTranscripts for the IL‐4Rα and IL‐13Rα1 chains were overexpressed in meningiomas compared with normal brain tissue. The levels of IL‐4Rα mRNA appeared to be higher compared with the levels of IL‐13Rα1 mRNA. The results also showed that tumors with higher disease grade tended to have increased mRNA expression for the IL‐4Rα chain. This IL‐4Rα mRNA overexpression appeared to be more frequent in younger patients (age < 37 years). The transcripts for IL‐2Rγc chain were not detected in any of the tumor samples or in normal brain tissue. Quantitative real‐time PCR confirmed the results of the RT‐PCR analysis. Meningiomas also demonstrated a bright immunofluorescent staining for the IL‐4Rα and IL‐13Rα1 chains but no staining for IL‐2Rγc.CONCLUSIONSExpression of the IL‐4Rα and IL‐13Rα1 chains and absence of IL‐2γc expression established that meningiomas expressed type II IL‐4Rs. These receptors may serve as a target for cytotoxin/immunotoxin therapy in patients with meningioma who are not amenable to surgical resection or for recurrent tumors. Cancer 2005. © 2005 American Cancer Society.
Modulation of tamoxifen sensitivity by antisense Bcl‐2 and trastuzumab in breast carcinoma cells
Authors: Kim Ryungsa , Tanabe Kazuaki , Emi Manabu , Uchida Yoko , Toge Tetsuya 
Published: April 2005

AbstractBACKGROUNDBecause the overexpression of HER‐2 and Bcl‐2 is associated with resistance to tamoxifen (TAM), the authors examined the effect of antisense (AS) Bcl‐2 on sensitivity to TAM compared with the effect of trastuzumab on sensitivity to TAM in breast carcinoma cell lines.METHODSDrug sensitivity was assessed in vitro using a [3‐4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide assay with the breast carcinoma cell lines ZR‐75‐1, MDA‐MB‐453, and BT‐474. AS Bcl‐2 18‐mer phosphorothioate oligonucleotide was applied. Apoptotic cell death was assessed with the terminal deoxynucleotidyl transferase‐mediated biotinylated UTP nick‐end labeling method, and gene expression was evaluated with Western blot analysis.RESULTSThe expression of Bcl‐2 was identified in ZR‐75‐1 and BT‐474 cells and, to a lesser extent, in MDA‐MB‐453 cells. Overexpression of HER‐2 was identified in BT‐474 cells, and moderate expression was identified in MDA‐MB‐453 and ZR‐75‐1 cells. Combination treatment with trastuzumab or AS Bcl‐2 enhanced TAM sensitivity in ZR‐75‐1 cells, which showed 50% inhibitory concentration (IC50) values of 0.9 μM (7.2‐fold increase) and 0.5 μM (13.0‐fold), respectively. Combination treatment with trastuzumab or AS Bcl‐2 slightly enhanced TAM sensitivity of BT‐474 cells, with IC50 values of 3.0 μM (1.3‐fold) and 1.5 μM (2.6‐fold), respectively. The sensitivity of MDA‐MB‐453 cells to TAM was not enhanced by combination with trastuzumab or AS Bcl‐2. Modulation of TAM sensitivity by AS Bcl‐2 was superior to modulation by trastuzumab in HER‐2‐expressing and Bcl‐2‐expressing breast carcinoma cells. Enhanced sensitivity in combination with AS Bcl‐2 was associated with down‐regulation of Bcl‐2 and pAkt, which was correlated with the induction of Bax and caspase‐3, leading to apoptosis.CONCLUSIONSAS Bcl‐2 appeared to be superior to trastuzumab with respect to regulating the signal‐transduction pathways involved in breast carcinoma cells. Cancer 2005. © 2005 American Cancer Society.