bluuebunny/crossref_metadata_2025_split huggingface dataset:
The cisplatin, epirubicin, 5‐fluorouracil, gemcitabine (PEFG) regimen in advanced biliary tract adenocarcinoma
Authors: Cereda Stefano , Passoni Paolo , Reni Michele , Viganò Maria G. , Aldrighetti Luca , Nicoletti Roberto , Villa Eugenio 
Published: February 2010

AbstractBACKGROUND:Biliary tract adenocarcinoma (BTA) is an uncommon tumor with a poor prognosis and no standard, systemic chemotherapy. The combined cisplatin, epirubicin, 5‐fluorouracil, and gemcitabine (PEFG) regimen is an effective, upfront treatment for advanced pancreatic cancer. In this study, the authors assessed the activity and safety of this combination regimen in patients with advanced BTA.METHODS:PEFG (cisplatin 40 mg/m2 and epirubicin 40 mg/m2 on Day 1; gemcitabine 600 mg/m2 on Days 1 and 8; and 5‐fluorouracil [FU] 200 mg/m2 daily as a continuous infusion) was administered to chemotherapy‐naive patients who had a cytologic or histologic diagnosis of locally advanced or metastatic BTA, aged ≤75 years, and a performance status (PS) >60 either until they had evidence progressive disease or for a maximum of 6 months. Tumor size was assessed every 2 months during treatment.RESULTS:Between May 1999 and December 2005, 37 patients (62% metastatic) who had a median age of 62 years and a median PS of 90 received the PEFG regimen at the authors' institution. Primary tumor sites were the intrahepatic bile duct in 10 patients (27%), the extrahepatic bile duct in 8 patients (22%), the gallbladder in 12 patients (32%), and the ampulla of Vater in 7 patients (19%). A partial response was observed in 16 patients (43%), and stable disease was observed in 12 patients (32%). The median overall survival (OS) was 12.1 months, and the 1‐year OS rate was 52%. The median progression‐free survival (PFS) was 7.9 months, and the 6‐month PFS rate was 67%. The main grade 3/4 toxicity was neutropenia in 18% of cycles followed by thrombocytopenia in 9% of cycles, nausea/vomiting in 5% of cycles, and febrile neutropenia, fatigue, anemia, and stomatitis in 2% of cycles.CONCLUSIONS:The current results demonstrated that PEFG was an active regimen with a manageable toxicity profile for patients with advanced BTA. Cancer 2010. © 2010 American Cancer Society.
A new era in anticancer peptide vaccines
Authors: Perez Sonia A. , von Hofe Eric , Kallinteris Nikoletta L. , Gritzapis Angelos D. , Peoples George E. , Papamichail Michael , Baxevanis Constantin N. 
Published: February 2010

AbstractThe use of synthetic peptides as vaccines aimed at the induction of therapeutic CD8‐positive T‐cell responses against tumor cells initially experienced great enthusiasm, mostly because of advances in vaccine technology, including design, synthesis, and delivery. However, despite impressive results in animal models, the application of such vaccines in humans has met with only limited success. The therapeutic activity of vaccine‐stimulated, tumor‐specific, CD8‐positive T cells can be hampered through the physical burden of the tumor, tolerance mechanisms, and local factors within the tumor microenvironment. Recently, accumulating evidence has suggested that combining a peptide‐based therapeutic vaccination with conventional chemotherapy can uncover the full potential of the antitumor immune response, increasing the success of immunotherapy. In addition, therapeutic vaccination in the preventive setting has been extremely effective in eliciting antitumor responses in preclinical tumor models and has demonstrated good promise clinically in patients with minimal residual disease. The rationale behind preventive vaccination is that patients with minimal tumor burden still have a fully competent immune system capable of developing robust antitumor responses. Finally, therapeutic CD8‐positive T‐cell peptide vaccines have been improved by coimmunization with T‐helper epitopes expressed on long peptides. Cancer 2010. © 2010 American Cancer Society.
Predictors of weight loss during radiotherapy in patients with stage I or II head and neck cancer
Authors: Nourissat Alice , Bairati Isabelle , Samson Elodie , Fortin André , Gélinas Michel , Nabid Abdenour , Brochet François , Têtu Bernard , Meyer François 
Published: February 2010

AbstractBACKGROUND:The purpose of the study was to identify predictors of weight loss during radiotherapy (RT) in patients with stage I or II head and neck (HN) cancer.METHODS:This study was conducted as part of a phase 3 chemoprevention trial. A total of 540 patients were randomized. The patients were weighed before and after RT. Their baseline characteristics, including lifestyle habits, diet, and quality of life, were assessed as potential predictors. Predictors were identified using multiple linear regressions. The reliability of the model was assessed by bootstrap resampling. A receiver operating characteristics curve was generated to estimate the model's accuracy in predicting critical weight loss (≥5%).RESULTS:The mean weight loss was 2.2 kg (standard deviation, 3.4). Five factors were associated with a greater weight loss: all HN cancer sites other than the glottic larynx (P<.001), higher pre‐RT body weight (P<.001), stage II disease (P = .002), dysphagia and/or odynophagia before RT (P = .001), and a lower Karnofsky performance score (P = .028). There was no association with pre‐RT lifestyle habits, diet, or quality of life. The bootstrapping method confirmed the reliability of this predictive model. The area under the curve was 71.3% (95% confidence interval, 65.8‐76.9), which represents an acceptable ability of the model to predict critical weight loss.CONCLUSIONS:These results could be useful to clinicians for screening patients with early stage HN cancer treated by RT who require special nutritional attention. Cancer 2010. © 2010 American Cancer Society.
Preparation of 9α‐Fluorinated Sesquiterpenic Drimanes and Evaluation of Their Antifeedant Activities
Authors: Abad Antonio , Agulló Consuelo , Cuñat Ana C. , González‐Coloma Azucena , Pardo David 
Published: February 2010

AbstractThe preparation of 9α‐fluoro analogues of both natural and unnatural drimane‐type sesquiterpenes is described. Their synthesis began with the initial preparation of methyl 8‐keto‐12‐nordriman‐11‐oate from β‐ionone and entailed the electrophilic fluorination of C‐9 for the stereoselective introduction of the fluorine atom. The drimane skeleton was completed from the intermediate 9α‐fluoro‐8‐keto‐12‐nordrimane system by means of different reactions at the C‐8 ketone carbonyl group, essentially Wittig methylenation, cyanohydrin formation or palladium‐catalysed carbonylation of the corresponding enol triflate. Further manipulation of the functionalization derived from these key reactions allowed the preparation, among others, of 9α‐fluorodrimanes, which are structurally and functionally related to albicanic acid, drimenin and olepupuane. Also described are the reactivities of some of the fluorine‐containing systems prepared and a comparative study of the antifeedant activities of a selection of 9α‐fluorodrimanes and the corresponding hydrogen analogues against several insect species with different feeding ecologies (Spodoptera littoralis,Myzus persicaeandRhopalosiphum padi), which revealed a significant increase in the antifeedant activities of some of the fluorinated drimane analogues.
Environmental occurrence and reproductive effects of the pharmaceutical fluoxetine in native freshwater mussels
Authors: Bringolf Robert B. , Heltsley Rebecca M. , Newton Teresa J. , Eads Chris B. , Fraley Stephen J. , Shea Damian , Cope W. Gregory 
Published: February 2010

Abstract
The present study measured the occurrence, distribution, and bioaccumulation of fluoxetine in samples of water, polar organic chemical integrative sampler (POCIS), sediment, and caged freshwater mussels at stream sites near a municipal wastewater treatment facility effluent discharge. We assessed the relation of the environmental concentrations to reproductive endpoints in mussels in acute laboratory tests. Concentrations of fluoxetine in water and POCIS samples were similar (&lt;20% difference) within each site and were greatest in the effluent channel (104–119 ng/L), and decreased at 50 m and 100 m downstream. Likewise, concentrations of fluoxetine in sediment and mussel (Elliptio complanata) tissue were greatest in the effluent channel (17.4 ng/g wet wt for sediment and 79.1 ng/g wet wt for mussels). In 96-h lab tests, fluoxetine significantly induced parturition of nonviable larvae from female E. complanata exposed to 300 µg/L (p = 0.0118) and 3,000 µg/L (p &lt; 0.0001) compared to controls. Fluoxetine exposure at 300 µg/L (p = 0.0075) and 3,000 µg/L (p = 0.0001) also resulted in stimulation of lure display behavior in female Lampsilis fasciola and Lampsilis cardium, respectively. In male E. complanata, 3,000 µg fluoxetine/L significantly induced release of spermatozeugmata during a 48-h exposure. These results suggest that fluoxetine accumulates in mussel tissue and has the potential to disrupt several aspects of reproduction in freshwater mussels, a faunal group recognized as one of the most imperiled in the world. Despite the disparity between measured environmental concentrations of fluoxetine and effects concentrations in our short-term tests with these long-lived animals, additional tests are warranted to evaluate the effects of long-term exposure to environmentally relevant concentrations and critical lifestages (e.g., juveniles). Environ. Toxicol. Chem. 2010;29:1311–1318. © 2010 SETAC
Excisional biopsy with margin control for oral cancers
Authors: Wang Yu‐Chien , Fang Ku‐Hao , Jung Shih‐Ming , Zheng Jie , Hao Sheng‐Po 
Published: February 2010

AbstractBackgroundThis study was undertaken to show how an excisional biopsy procedure can be used to remove the entire specimen for oral lesions with difficult diagnoses.MethodsWe retrospectively reviewed 52 cases with 56 oral lesions either suspected to be malignant or with a preliminary controversial diagnosis. These were treated by excisional biopsy with frozen section intraoperatively between January 2003 and June 2008.ResultsTwenty‐eight of 56 lesions were diagnosed with malignancy. We found a high underdiagnosis rate (7 of 12) in patients who had a preliminary controversial diagnosis. Twenty‐one patients without preoperative biopsy were diagnosed to have malignancies. Of the 28 malignant cases, all surgical margins were negative. Neck ultrasound scans with fine‐needle aspiration cytology was carried out and no patient demonstrated simultaneous neck metastasis. One patient died of locoregional recurrence. Two patients died of a second primary cancer.ConclusionExcisional biopsy with margin control is useful both in diagnosis and treatment of oral cancers. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Chemoradiotherapy for locoregionally advanced squamous cell carcinoma of the base of tongue
Authors: Pederson Aaron W. , Haraf Daniel J. , Witt Mary‐Ellyn , Stenson Kerstin M. , Vokes Everett E. , Blair Elizabeth A. , Salama Joseph K. 
Published: February 2010

AbstractBackgroundOur aim was to report the outcomes of base of tongue cancers treated with chemoradiotherapy.MethodsBetween 1990 and 2004, 127 patients with stage III or IV base of tongue cancer were treated with chemoradiotherapy on protocol. Indications included nodal involvement, T3/T4 tumors, positive margins, those patients refusing surgery, or were medically inoperable. The most common regimen was paclitaxel (100 mg/m2 on day 1), infusional 5‐fluorouracil (600 mg/m2/day × 5 days), hydroxyurea (500 mg prescribed orally [PO] 2 × daily [BID]), and 1.5 Gy twice daily irradiation followed by a 9‐day break without treatment.ResultsMedian follow‐up was 51 months. The median dose to gross tumor was 72.5 Gy (range, 40–75.5 Gy). Five‐year locoregional progression‐free survival, overall survival, and disease‐free survival was 87.0%, 58.2%, and 46.0%, respectively.ConclusionConcurrent chemoradiotherapy results in promising locoregional control for base of tongue cancer. As distant relapse was common, further investigation of systemic therapy with novel agents may be warranted. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
The effects of telomerase inhibition on prostate tumor‐initiating cells
Authors: Marian Calin O. , Wright Woodring E. , Shay Jerry W. 
Published: February 2010

AbstractProstate cancer is the most common malignancy in men, and patients with metastatic disease have poor outcome even with the most advanced therapeutic approaches. Most cancer therapies target the bulk tumor cells, but may leave intact a small population of tumor‐initiating cells (TICs), which are believed to be responsible for the subsequent relapse and metastasis. Using specific surface markers (CD44, integrin α2β1 and CD133), Hoechst 33342 dye exclusion, and holoclone formation, we isolated TICs from a panel of prostate cancer cell lines (DU145, C4‐2 and LNCaP). We have found that prostate TICs have significant telomerase activity which is inhibited by imetelstat sodium (GRN163L), a new telomerase antagonist that is currently in Phase I/II clinical trials for several hematological and solid tumor malignancies. Prostate TICs telomeres were of similar average length to the telomeres of the main population of cells and significant telomere shortening was detected in prostate TICs as a result of imetelstat treatment. These findings suggest that telomerase inhibition therapy may be able to efficiently target the prostate TICs in addition to the bulk tumor cells, providing new opportunities for combination therapies.
Enhancement of chemotherapeutic agent‐induced apoptosis by inhibition of NF‐κB using ursolic acid
Authors: Li Yunlong , Xing Da , Chen Qun , Chen Wei R. 
Published: February 2010

AbstractNF‐κB activation is known to reduce the efficiency of chemotherapy in cancer treatment. Ursolic acid, a minimally toxic compound, has shown the capability to inhibit NF‐κB activation in living cells. Here, for the first time, we investigated the effects and mechanisms of NF‐κB inhibition by ursolic acid on chemotherapy treatment (Taxol or cisplatin) of cancer. ASTC‐a‐1 (human lung adenocarcinoma), Hela (human cervical cancer) cells, primary normal mouse cells of lung and liver and mouse in vivo model were used. Activity of signal factors (NF‐κB, Akt, Fas/FasL, BID, Bcl‐2, cytochrome c and caspase‐8, 3) was used to analyze the mechanisms of ursolic acid‐chemo treatment. Ursolic acid‐mediated suppression of NF‐κB drastically reduced the required dosage of the chemotherapeutic agents to achieve identical biological endpoints and enhanced the chemotherapeutic agent‐induced cancer cells apoptosis. Chemosensitization by ursolic acid in cancer cells was dependent on the amplified activation of intrinsic pathway (caspase‐8‐BID‐mitochondria‐cytochrome c‐caspase‐3) by augmentation of BID cleavage and activation of Fas/FasL‐caspase‐8 pathway. Prolonged treatment with relatively low doses of ursolic acid also sensitized cancer cells to the chemotherapeutic agents through suppression of NF‐κB. Chemosensitization by ursolic acid was observed only in cancer cells, but not in primary normal cells. The inhibitive effect of ursolic acid on NF‐κB was reversible, and the reversal was not accompanied by a loss in cells viability. By supplementing chemotherapy with minimally toxic ursolic acid, it is possible to improve the efficacy of cancer treatment by significantly reducing the necessary drug dose without sacrificing the treatment results.
What do we learn from the price of crude oil futures?
Authors: Alquist Ron , Kilian Lutz 
Published: February 2010

AbstractDespite their widespread use as predictors of the spot price of oil, oil futures prices tend to be less accurate in the mean‐squared prediction error sense than no‐change forecasts. This result is driven by the variability of the futures price about the spot price, as captured by the oil futures spread. This variability can be explained by the marginal convenience yield of oil inventories. Using a two‐country, multi‐period general equilibrium model of the spot and futures markets for crude oil we show that increased uncertainty about future oil supply shortfalls under plausible assumptions causes the spread to decline. Increased uncertainty also causes precautionary demand for oil to increase, resulting in an immediate increase in the real spot price. Thus the negative of the oil futures spread may be viewed as an indicator of fluctuations in the price of crude oil driven by precautionary demand. An empirical analysis of this indicator provides evidence of how shifts in the uncertainty about future oil supply shortfalls affect the real spot price of crude oil. Copyright © 2010 John Wiley & Sons, Ltd.
A control model for tibial cortex neovascularization in the bone chamber
Authors: Winet Howard , Bao Joseph Y. , Moffat Robert 
Published: February 2010

Abstract
Neovascularization across a gap defect in a rabbit tibial cortex was monitored using the optical bone chamber implant (BCI). Cortical bone growing by apposition as trabeculae was observed weekly as it penetrated a slit into a tissue space in vivo and in situ. Each rabbit was viewed weekly with an intravital microscope from 3 to 8 weeks postimplantation. The constant field of view was the slit-gap tissue space, which was 100 μm thick and 2 mm in diameter. Vessels were imaged with epi-illuminated fluorescence microscopy as they carried FITC-dextran 70 that had been injected into an aural vein. Observations were videotaped and photographed. Videotape frames were analyzed with a digital image processing system to obtain measures of vessel length per unit volume (L/V) of fibroblastic granular tissue and trabeculae, caliber C, and flow velocity u, all as functions of time.
Observations supported the conclusions that (1) neovascularization precedes neo-osteogenesis, (2) major vessels tend to align with the tibial axis, (3) bone apposition-generated destruction of fibrous granular tissue vessels stimulates fibrous granular tissue angiogenesis, which keeps its L/V constant, (4) L/V in trabeculae increases with time, and (5) blood supply (Q̄) and nutrient exchange in healing trabeculae are not positively correlated. Thus, O2 supply to the trabeculum cannot be predicted from Q̄ alone because the nutrient exchange area is not constant. It was noted that an increase in the potential nutrient exchange area occurred in both fibrous granular tissue and osseous vessels and the volume fraction of blood decreased in the fibrous granular tissue and remained constant in the trabeculae
Effects of bisphosphonates on isolated Rat osteoclasts as examined by reflected light microscopy
Authors: Sato Masahiko , Grasser William 
Published: February 2010

Abstract
The bisphosphonates 4-amino-1-hydroxybutylidene-1, 1-bisphosphonic acid (ABP), 3-amino-1, 1-hydroxypropane-1, 1-diphosphonic acid (APD), and 1-hyroxyethane-1, 1-diphosphonic acid (EHDP) were compared for their ability to inhibit the osteoclastic resorption of bone in culture. This was achieved by measuring the effect of bisphosphonate concentration on the number of resorption pits formed and the total area of resorption. During this analysis, a new application of reflected polarized light microscopy was developed that has advantages over other microscopy techniques, including scanning electron microscopy (SEM), as applied to the analysis of resorbed bone surfaces. Based on area analysis, the bisphosphonates were effective for the range 10−7–10−8 M, with ABP about two to five times more effective than EHDP or APD. Similar data were obtained by counting the number of resorption pits but with EC50 10 times higher. At lower concentrations (10−9 M), bisphosphonates may enhance the formation of resorption pits. APD was found to be more toxic (10 times) than ABP or EHDP to osteoclasts and mononuclear cells, but toxic concentrations were at least 102 times higher than the resorption EC50. These data plus immunofluorescence, SEM, and transient incubation experiments show that it is the bisphosphonate-bone complex that directly inhibits the excavation of resorption pits by mature osteoclasts. The mechanism of action does not appear to require inhibition of osteoclast differentiation or toxic elimination of osteoclasts. Bisphosphonates, however, subtly affect the cytoskeleton of osteoclasts
Conditioned medium from ras oncogene-transformed nih 3T3 cells induces bone resorption in vitro
Authors: Krieger Nancy S. , Sukhatme Vikas P. , Bushinsky David A. , Sukhatme Vikas P. 
Published: February 2010

Abstract
Tumor-associated hypercalcemia is due, in part, to enhanced osteoclastic bone resorption induced by soluble factors elaborated from malignant cells. rastransformation of NIH 3T3 cells results in a 50-fold induction of cathepsin L mRNA and secretion of the corresponding protein. Since cathepsin L is an acid proteinase we asked whether conditioned medium from these cells would directly increase calcium release from bone in vitro. We tested conditioned medium obtained after 72 h culture of NIH 3T3rar-transformed cells (DT) or nontransformed NIH 3T3 cells (3T3) and identical medium not exposed to cells (Ctl). Incubation of either live or dead neonatal mouse calvaria for 48 h in DT-conditioned medium increased calcium release compared to bones incubated with 3T3 medium. In both states the increased calcium release with DT medium was blocked by 0.25 mM E-64, a general cysteine proteinase inhibitor, and 1 μM Z-Phe-Ala-CH2F, a specific inhibitor of cathepsin L activity. Thus, conditioned medium fromras-transformed cells enhances calcium release in both live and dead bone. Since cathepsin L is the major protein secreted by these cells and the effect of DT-conditioned medium is blocked by a specific inhibitor of cathepsin L, these studies suggest that this acid proteinase acts directly on bone mineral to enhance net calcium release
Cancellous bone remodeling in type i (postmenopausal) osteoporosis: Quantitative assessment of rates of formation, resorption, and bone loss at tissue and cellular levels
Authors: Eriksen Erik F. , Hodgson Stephen F. , Eastell Richard , DR. RIGGS B. Lawrence , Cedel Sandra L. , O'Fallon W. Michael 
Published: February 2010

Abstract
ABSTRACT: The cellular mechanisms for bone loss in type I (postmenopausal) osteoporosis are highly controversial. We attempted to resolve this by assessing rates of formation and resorption of iliac cancellous bone by a new histomorphometric method in 89 women with osteoporosis (mean age + SD, 66 + 6 years) and in 32 carefully selected normal postmenopausal women (64 + 6 years). In the osteoporotic women, bone resorption rate was increased by 39% (P &lt;0.05) at the cellular level and by 67% (P &lt;0.05) at the tissue level, whereas bone formation was unchanged at the tissue level but decreased by 14% (P &lt;0.01) at the cellular (osteoblast) level. This pronounced remodeling imbalance (P &lt;0.001) was probably exacerbated by a 45% increase (P &lt; 0.1) in activation frequency of new remodeling foci. These abnormalities were associated with a high rate of cancellous bone loss (median, 5.8%/year versus 0.1%/year in controls). Thus, accelerated loss of cancellous bone in type I osteoporosis results from the combination of increased bone resorption and inadequate compensation by bone formation.