bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of compartmental involvement on the patterns of morbidity in soft tissue sarcoma of the thigh
Authors: Rimner Andreas , Brennan Murray F. , Zhang Zhigang , Singer Samuel , Alektiar Kaled M. 
Published: December 2008

AbstractBACKGROUD:The authors sought to determine whether differences existed in patterns of outcome and morbidity between the 3 thigh compartments after limb‐sparing surgery and postoperative radiation therapy (RT).METHODS:A total of 255 patients with primary soft tissue sarcoma (STS) of the thigh were identified in our sarcoma database (1982–2002). More than 80% of tumors were >5 cm, high grade, and deep; 33% had close or positive microscopic resection margins. Adjuvant RT consisted of brachytherapy alone (BRT; 63%), external beam RT alone (EBRT; 31%), or a combination of brachytherapy and EBRT (6%). There were 125 anterior, 58 medial, and 72 posterior lesions. The 3 compartments were balanced as to tumor grade, size, depth, margin status, and RT type.RESULTS:Overall local control (LC) was 89%, distant metastases‐free survival (DMFS) was 61%, and overall survival (OS) was 66% at 5 years (median follow‐up, 71 months). Overall rates for complications at 5 years were wound reoperation (10%), edema (13%), joint stiffness (12%), nerve damage (8%), and bone fractures (7%). Wound reoperation and edema were significantly higher for medial‐compartment tumors (P= .01 and .005, respectively), whereas nerve damage occurred more frequently in posterior‐compartment tumors (P< .001). There were no differences among bone fracture, joint stiffness, DMFS, or OS rates between compartments.CONCLUSIONS:Although tumor control was similar for all 3 compartments, more wound reoperation and edema were observed in the medial compartment, and more nerve damage was noted in the posterior compartment. These results may help guide decisions concerning current patients and improve the design of future treatments tailored to compartments. Cancer 2009. © 2008 American Cancer Society.
Mammary serine protease inhibitor inhibits epithelial growth factor‐induced epithelial‐mesenchymal transition of esophageal carcinoma cells
Authors: Cai Zhen , Zhou Yuan , Lei Ting , Chiu Jen‐Fu , He Qing‐Yu 
Published: December 2008

AbstractBACKGROUND:By using proteomic technology, the authors previously observed the substantial down‐regulation of mammary serine protease inhibitor (maspin) in esophageal squamous cell carcinoma and metastases. In the current study, they examined the effects of maspin re‐expression in a maspin‐null esophageal cancer cell line EC109 and also investigated the underlying mechanism.METHODS:A cell line with stable maspin expression was established. An epithelial growth factor (EGF)‐induced epithelial‐mesenchymal transition (EMT) model was used to mimic some aspects of the metastatic process in vitro. The effects of maspin reintroduction on EGF‐induced EMT and cell growth characteristics were evaluated. Comparative proteomic analysis of transfected cells versus parental cells was then performed to explore the potential mechanism.RESULTS:The introduction of maspin into EC109 cells was able to inhibit EGF‐induced EMT and altered cell growth characteristics, including the serum dependence, proliferative response to EGF stimulation, and colony formation ability in soft agar, indicating a conversion from a malignant phenotype to a benign phenotype. Proteomic analysis revealed a significant down‐regulation of a group of glycolytic enzymes in maspin‐transfected cells. In addition, maspin‐transfected cells expressed much lower levels of hypoxia‐inducible factor 1α than parental cells or empty vector transfected cells.CONCLUSIONS:Maspin exhibited a metastasis‐suppressive effect, which may be a consequence of the reversal of the malignant phenotype of EC109 cells. The switch of cellular metabolic phenotype to low glycolysis by the gain of maspin function may play a key role in the process. This finding provides additional evidence of the tumor metastasis‐suppressive activity of maspin and may indicate a new direction for future studies of the mechanism of maspin. Cancer 2009. © 2008 American Cancer Society.
Phase 1 and pharmacokinetic study of concurrent carboplatin and irinotecan in subjects aged 1 to 21 years with refractory solid tumors
Authors: Levy Adam S. , Meyers Paul A. , Wexler Leonard H. , Jakacki Regina , Angiolillo Anne , Ringuette Sarah N. , Cohen Marvin B. , Gorlick Richard ,   Other site principal investigators: Wayne Furman, MD (St. Jude Children's Research Hospital, Memphis, Tennessee); Rochelle Bagatell, MD (University of Arizona Health Sciences Center, Tucson, Arizona); Lori Luchtman‐Jones, MD (Washington University School of Medicine, St. Louis, Missouri); Luis Eduardo Garcia, MD (Hospital CIMA, San Jose, Costa Rica); and Eric Sandler, MD (Nemours Children's Clinic, Jacksonville, Florida).
Published: December 2008

AbstractBACKGROUND:Preclinical testing suggests the combination of carboplatin and irinotecan has at least additive antitumor activity. The primary objectives of the current study were to determine the maximum tolerated doses (MTDs) and recommended phase 2 doses of carboplatin administered with irinotecan to pediatric patients with refractory solid tumors.METHODS:This was a multicenter, open‐label, single‐arm dose escalation study in which subjects with refractory solid tumors received 21‐day treatment cycles of intravenous carboplatin on Day 1 followed by intravenous irinotecan administered daily for 10 days within 2 consecutive weeks. The plasma pharmacokinetics of ultrafiltrable platinum, irinotecan, and 2 irinotecan metabolites were determined during Cycle 1. The interpatient plan for dose escalation at study initiation was to increase irinotecan first followed by increases in carboplatin.RESULTS:Twenty‐eight patients with a median age of 8.5 years (range, 1‐21 years) were enrolled with a variety of solid tumors. Two of 6 subjects at the first dose level (carboplatin target area under the curve [AUC], 4.0 mg/mL*min; irinotecan, 18 mg/m2/dose) experienced dose‐limiting gastrointestinal toxicities requiring a dose de‐escalation scheme (carboplatin AUC, 4.0 mg/mL*min; irinotecan, 15 mg/m2/dose). Three of 6 subjects at the second dose level experienced dose‐limiting gastrointestinal complications and bone marrow suppression. A further dose de‐escalation to carboplatin AUC of 4.0 mg/mL*min and irinotecan of 12 mg/m2/dose resulted in dose‐limiting bone marrow suppression in 1 of 13 patients treated at that dose, and therefore was determined to be the MTD. One complete response (in a patient with medulloblastoma) and 3 partial responses (in patients with neuroblastoma, medulloblastoma, and lymphoendothelial carcinoma, respectively) were observed.CONCLUSIONS:The recommended phase 2 dose in heavily pretreated pediatric patients is carboplatin (AUC, 4 mg/mL*min on Day 1) and irinotecan (12 mg/m2/ day × 10 days) given every 21 days. Cancer 2009. © 2008 American Cancer Society.
Tumor vasculature‐targeted delivery of tumor necrosis factor‐α*
Authors: Tandle Anita , Hanna Engy , Lorang Dominique , Hajitou Amin , Moya Catherine A. , Pasqualini Renata , Arap Wadih , Adem Asha , Starker Elizabeth , Hewitt Stephen , Libutti Steven K. 
Published: December 2008

AbstractBACKGROUND: Recently, considerable efforts have been directed toward antivascular therapy as a new modality to treat human cancers. However, targeting a therapeutic gene of interest to the tumor vasculature with minimal toxicity to other tissues remains the objective of antivascular gene therapy. Tumor necrosis factor‐α (TNF‐α) is a potent antivascular agent but has limited clinical utility because of significant systemic toxicity. At the maximum tolerated doses of systemic TNF‐α, there is no meaningful antitumor activity. Hence, the objective of this study was to deliver TNF‐α targeted to tumor vasculature by systemic delivery to examine its antitumor activity. METHODS: A hybrid adeno‐associated virus phage vector (AAVP) was used that targets tumor endothelium to express TNF‐α (AAVP‐TNF‐α). The activity of AAVP‐TNF‐α was analyzed in various in vitro and in vivo settings using a human melanoma tumor model. RESULTS: In vitro, AAVP‐TNF‐α infection of human melanoma cells resulted in high levels of TNF‐α expression. Systemic administration of targeted AAVP‐TNF‐α to melanoma xenografts in mice produced the specific delivery of virus to tumor vasculature. In contrast, the nontargeted vector did not target to tumor vasculature. Targeted AAVP delivery resulted in expression of TNF‐α, induction of apoptosis in tumor vessels, and significant inhibition of tumor growth. No systemic toxicity to normal organs was observed. CONCLUSIONS: Targeted AAVP vectors can be used to deliver TNF‐α specifically to tumor vasculature, potentially reducing its systemic toxicity. Because TNF‐α is a promising antivascular agent that currently is limited by its toxicity, the current results suggest the potential for clinical translation of this strategy. Cancer 2009. Published 2008 by the American Cancer Society.
Validation of a new prognostic index for patients with chronic lymphocytic leukemia
Authors: Shanafelt Tait D. , Jenkins Greg , Call Timothy G. , Zent Clive S. , Slager Susan , Bowen Deborah A. , Schwager Susan , Hanson Curtis A. , Jelinek Diane F. , Kay Neil E. 
Published: December 2008

AbstractBACKGROUND:The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. A prognostic index based on widely available clinical and laboratory features was recently developed to predict survival among patients with previously untreated CLL. This index requires validation in an independent series of patients before widespread use can be recommended.METHODS:The Mayo Clinic CLL database was used to evaluate the validity and reproducibility of the new prognostic index.RESULTS:A total of 440 patients with newly diagnosed CLL who were seen at the Mayo Clinic within 12 months of diagnosis and for whom data were available with which to calculate index score were identified. Patients were classified as low, intermediate, or high risk using the prognostic index. The estimated median survival times were: not reached for low risk, 10.1 years for intermediate risk, and 7.2 years for high risk. The estimated median and 5‐year survival by prognostic index risk category were similar to those originally reported. The prognostic index risk category added predictive value beyond that of Rai risk alone (P = .004). The prognostic index risk category remained a predictor of survival when analysis was limited to Rai stage 0 (P = .03) and nonreferred patients (P < .0001) and also predicted time to treatment (P < .0001).CONCLUSIONS:The results of the current study confirm the ability of a newly developed prognostic index to predict survival among patients with previously untreated CLL. The study also extended the utility of the index by demonstrating that it is useful at diagnosis, retains prognostic value when applied exclusively to Rai stage 0 patients, is effective in nonreferred patients, and predicts time to treatment. Cancer 2009. © 2009 American Cancer Society.
Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy
Authors: Vickrey Eric , Allen Sharon , Mehta Jayesh , Singhal Seema 
Published: December 2008

AbstractBACKGROUND:Humoral‐mediated as well as cell‐mediated immunity is compromised in myeloma patients receiving treatment. Immunocompromised patients are at risk of developing herpes zoster. There is evidence from clinical trials that bortezomib therapy is associated with a significant risk of herpes zoster. It is the authors' clinical policy to administer long‐term acyclovir prophylactically to all symptomatic myeloma patients.METHODS:A retrospective review of the records of 125 myeloma patients who were treated with bortezomib and who also received routine acyclovir prophylaxis at the dose of 400 mg daily in >80% of patients was undertaken. Alternatives, used in <20% of patients, were 200 mg of acyclovir, 250/500 mg of valacyclovir, or 500 mg of famciclovir administered daily. This was accompanied by patient education regarding the importance of compliance with these prophylactic medications.RESULTS:The duration of bortezomib therapy was 1 to 164 weeks (median, 16 weeks). The total duration of exposure to bortezomib was 4150 weeks (80 patient‐years). Except for the occasional missed dose, the self‐reported compliance with antiviral prophylaxis was 100%. Not a single episode of herpes zoster was reported during this period. No adverse effects were noted that could be definitely attributed to acyclovir, valacyclovir, or famciclovir.CONCLUSIONS:Daily acyclovir (or a suitable alternative) appears to be effective at preventing herpes zoster virus in patients with myeloma who are receiving bortezomib, with or without corticosteroids. Cancer 2009. © 2008 American Cancer Society.
A QM/MM Investigation of Thymine Dimer Radical Anion Splitting Catalyzed by DNA Photolyase
Authors: Masson Fanny , Laino Teodoro , Rothlisberger Ursula , Hutter Jürg 
Published: December 2008

AbstractOn the mend: The repair reaction of the thymine dimer by DNA photolyase (see picture) is studied by hybrid quantum mechanical/molecular mechanical dynamics simulations based on the X‐ray structure of the enzyme–DNA complex. The dynamics of splitting of the thymine dimer radical anion within the DNA photolyase active site is characterized. The model includes the protein environment.magnified imageDNA photolyase is a highly efficient light‐driven enzyme that repairs the UV‐induced cyclobutane pyrimidine dimer in damaged DNA. Herein, we investigate the repair reaction of the thymine dimer by means of hybrid quantum mechanical/molecular mechanical (QM/MM) dynamics simulations based on the X‐ray structure of an enzyme–DNA complex. In analogy to the self‐repair reaction, we find that the splitting mechanism of the cyclobutane ring is asynchronously concerted and is complete within a few picoseconds upon electron uptake. A few distinct processes characterize the dynamics of splitting of the thymine dimer radical anion within the DNA photolyase active site: continuous solvation reordering of the catalytic region, proton transfer from Glu283 to the dimer, as well as tight interactions of the cationic side chains of Arg232 and Arg350 with the thymine dimer. This points to the important role of the active‐site hydrogen bond and salt‐bridge patterns in stabilizing the thymine dimer anion and slowing down the electron back‐transfer process. Comparison of the repair efficiency with respect to the self‐repair reaction is also discussed.
Laser Microbeams and Optical Tweezers in Ageing Research
Authors: Grigaravičius Paulius , Greulich Karl Otto , Monajembashi Shamci 
Published: December 2008

AbstractWe show how a technique developed within the framework of physics and physical chemistry—in a true interdisciplinary approach—can answer questions in life sciences that are not solvable by using other techniques. Herein, we focus on blood‐pressure regulation and DNA repair in ageing studies. Laser microbeams and optical tweezers are now established tools in many fields of science, particularly in the life sciences. A short glimpse is given on the wide field of non‐age‐research applications in life sciences. Then, optical tweezers are used to show that exerting a vertical pressure on cells representing the inner lining of blood vessels results in bursts of NO liberation concomitant with large changes in cell morphology. Repeated treatment of such human umbilical vein endothelial cells (HUVEC) results in stiffening, a hallmark of manifest high blood pressure, a disease primarily of the elderly. As a second application in ageing research, a laser microbeam is used to induce, with high spatial and temporal resolution, DNA damages in the nuclei of U2OS human osteosarcoma cells. A pairwise study of the recruitment kinetics of different DNA repair proteins reveals that DNA repair starts with non‐homologous end joining (NHEJ), a repair pathway, and may only after several minutes switch to the error‐free homologous recombination repair (HRR) pathway. Since DNA damages—when incorrectly repaired—accumulate with time, laser microbeams are becoming well‐used tools in ageing research.
Index characterization of differential–algebraic equations in hybrid analysis for circuit simulation
Authors: Takamatsu Mizuyo , Iwata Satoru 
Published: December 2008

AbstractModern modeling approaches in circuit simulation naturally lead to differential–algebraic equations (DAEs). The index of a DAE is a measure of the degree of numerical difficulty. In general, the higher the index, the more difficult it is to solve the DAE. The modified nodal analysis (MNA) is known to yield a DAE with index at most two in a wide class of nonlinear time‐varying electric circuits.In this paper, we consider a broader class of analysis method called the hybrid analysis. For linear time‐invariant RLC circuits, we prove that the index of the DAE arising from the hybrid analysis is at most one, and give a structural characterization for the index of a DAE in the hybrid analysis. This yields an efficient algorithm for finding an optimal hybrid analysis in which the index of the DAE to be solved attains zero. Finally, for linear time‐invariant electric circuits that may contain dependent sources, we prove that the optimal hybrid analysis by no means results in a higher index DAE than MNA. Copyright © 2008 John Wiley & Sons, Ltd.
Oxidovanadium Complexes for the Consumption of Alkylating Toxins (Eur. J. Inorg. Chem. 1/2009)
Authors: Fautch Jessica M. , Fanwick Phillip E. , Wilker Jonathan J. 
Published: December 2008

AbstractThe cover picture shows oxidovanadium complexes transforming alkylating toxins into alcohols. Variation of the electron‐donating ability of the ligand was found to permit a degree of control over the reactivity with alkylating agents. Kinetic studies revealed a small range of kobsd. values for this series of K[VO2(salhyph(R)2)] complexes (R = –NO2, –H, –CH3, –OCH3) examined. These experiments were carried out with an ultimate goal of developing compounds to consume toxins and prevent DNA alkylation damage. Details are discussed in the Short Communication by J. J. Wilker et al on p. 33 ff.
Asymmetric Hydrogenation of α‐Keto Phosphonates with Chiral Palladium Catalysts
Authors: Goulioukina Nataliya S. , Bondarenko Grigorii N. , Bogdanov Alexei V. , Gavrilov Konstantin N. , Beletskaya Irina P. 
Published: December 2008

AbstractUnder atmospheric hydrogen pressure, a catalytic amount of palladium(II) trifluoroacetate and (R)‐MeO‐BIPHEP in 2,2,2‐trifluoroethanol promoted the asymmetric hydrogenation of diisopropyl α‐keto phosphonates 1 to afford the corresponding α‐hydroxy phosphonates 2 in excellent yields and with a moderate enantioselectivities of up to 55 % ee. Racemic α‐aryl‐α‐hydroxy phosphonates can be prepared by using palladium on carbon as the catalyst. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Arsenic Release from a Natural Rock under Near‐natural Oxidizing Conditions
Authors: Noubactep C. , Chen‐Braucher D. , Schlothauer T. 
Published: December 2008

AbstractThe effects of carbonate concentration and the presence of iron hydroxide phases on the process of arsenic release from an ore material were investigated under experimental oxic conditions and in the pH range from 6.0 to 9.0. These experimental conditions are pertinent to arsenic leaching from tailings and mining wastes. The leaching tests lasted for ≤ 99 days and were performed with materials of five different particle sizes (≤ 2 mm). Carbonate ions were produced in‐situ by dolomite dissolution or were contained in used waters (0 to 30 mM as HCO3–). Iron hydroxide phases were formed in situ by oxidative dissolution of metallic iron (Fe0) or pyrite (FeS2). Non‐disturbed batch experiments and air‐homogenized experiments were conducted with a constant amount (10 g/L) of an arsenic‐bearing rock (ore material) of a given particle size and different types of water (deionized, tap and mineral water). For comparison, experiments were conducted with 0.1 M EDTA, 0.1 M Na2CO3, and 0.1 M H2SO4. Neither the use of dolomite nor the use of water containing various carbonate (HCO3–) concentrations could confirm the recent results on the favorable role of AsIII‐carbonate complexes on the arsenic transport in the environment. On the other hand, iron hydroxide phases (from Fe0 and FeS2) univocally delayed the As release in both experimental procedures. Furthermore, the theoretically expected effects of the particle size of the ore material was observed. If one takes into consideration that the used HCO3– concentrations were up to six times larger then those of natural surface waters (≤ 5.5 mM) but up to five times lower than those currently used in the literature (≥ 100 mM), it is concluded that the reported conflicting results for As leaching from sediments may be a misinterpretation of processes occurring in the sediment and yielding increased As release with increasing HCO3–/CO32– concentration.
Influence of Arsenic from Anthropogenic Loaded Soils on the Mine Water Quality in the Tin District Ehrenfriedersdorf, Erzgebirge (Germany)
Authors: Greif A. , Klemm W. , Klemm K. 
Published: December 2008

AbstractThe central part of the tin ore deposit Ehrenfriedersdorf/Erzgebirge, which was exploited from the 13th century to 1990, was flooded from 1994 to 1996. Since that time mine waters have flown through the gallery “Tiefer Sauberger Stolln” to the creek Wilisch in the Elbe river catchment area. The water at the mine portal shows high concentrations of arsenic and heavy metals. The average arsenic concentration is about 0.5 mg/L. Approximately two thirds of arsenic are transported dissolved. Where the mine water ascends from deeper levels, arsenic concentrations of about 0.4 mg/L were found. Here arsenic occurs predominantly particular. The mining gallery “Tiefer Sauberger Stolln” provides the unique opportunity of subsurface sampling for the identification of the arsenic sources under different hydrological conditions (normal and high water level). The sources of dissolved arsenic in the gallery part between the raise and the portal were determined and analyzed. Between these two monitoring points, many inflows of infiltration water were detected. The concentration of As in the infiltration water reaches up to 1.8 mg/L, which varies depending on the location in the gallery and the hydrological situation. The first part of the gallery was straightened, heightened and partly concreted with modern mining technique. The arsenic concentrations can decrease owing to high precipitation rates and snow melt events. The last part of the gallery was preserved due to low coverage. Here the arsenic concentrations in the infiltration waters increase with the surface water inflow. At a normal water level, 1 kg arsenic per day leaves the raise and 2.1 kg the gallery portal, which means that 50 % of the arsenic load comes from the infiltration water. At a high water level, 2.5 kg arsenic per day are transported through the raise and 8.2 kg per day through the gallery portal, which means that about 70 % of the arsenic load comes from infiltration water. The area of Ehrenfriedersdorf is characterized by a superposition of anthropogenic soil pollution over the geogenic inventory. There is a close connection between ancient soil contaminations by high amounts of water‐soluble arsenic compounds, e.g. arsenic trioxide formed by roasting the ores during ancient tin smelting, and high concentrations of dissolved arsenic in the infiltration water. The contamination of surface water and river sediments by arsenic is originating from an anthropogenic pollution of soils by ancient tailings via infiltration of water rich in arsenic into the mine gallery.