bluuebunny/crossref_metadata_2025_split huggingface dataset:
Removal of Cu2+ and Pb2+ Ions Using CMC Based Thermoresponsive Nanocomposite Hydrogel
Authors: Özkahraman Bengi , Acar Işıl , Emik Serkan 
Published: June 2011

AbstractIn this study, carboxymethylcellulose (CMC) based thermoresponsive nanocomposite hydrogel was synthesized for the removal of Cu2+ and Pb2+ ions from aqueous solutions. To prepare nanocomposite hydrogel, graft copolymerization of N‐isopropyl acrylamide (NIPAm) and acrylic acid (AA) onto CMC was carried out in Na‐montmorillonite (MMT)/water suspension media and ammonium persulfate (APS) used as initiator. The chemical structures of hydrogels were characterized by Fourier transform infrared (FT‐IR) and X‐ray diffraction spectroscopy (XRD). Lower critical solution temperature (LCST), pH responsivity, swelling, and deswelling properties of the hydrogels were also examined. In addition competitive and non‐competitive removal of Cu2+ and Pb2+ studies were carried out. According to heavy metal sorption studies results, removal capacities of nanocomposite hydrogel for both metal ions were found to be higher than those of pure hydrogel. The analyzed adsorption data showed that the adsorption process of Cu2+ and Pb2+ could be explained by pseudo‐second order kinetic model. Moreover, according to competitive sorption studies, it is found to be that both hydrogels are more selective to Cu2+ ion rather than Pb2+.
Design, Synthesis, and Biological Activity of Urea Derivatives as Anaplastic Lymphoma Kinase Inhibitors
Authors: Boije af Gennäs Gustav , Mologni Luca , Ahmed Shaheen , Rajaratnam Mohanathas , Marin Oriano , Lindholm Niko , Viltadi Michela , Gambacorti‐Passerini Carlo , Scapozza Leonardo , Yli‐Kauhaluoma Jari 
Published: June 2011

AbstractIn anaplastic large‐cell lymphomas, chromosomal translocations involving the kinase domain of anaplastic lymphoma kinase (ALK), generally fused to the 5’ part of the nucleophosmin gene, produce highly oncogenic ALK fusion proteins that deregulate cell cycle, apoptosis, and differentiation in these cells. Other fusion oncoproteins involving ALK, such as echinoderm microtubule‐associated protein‐like 4‐ALK, were recently found in patients with non‐small‐cell lung, breast, and colorectal cancers. Recent research has focused on the development of inhibitors for targeted therapy of these ALK‐positive tumors. Because kinase inhibitors that target the inactive conformation are thought to be more specific than ATP‐targeted inhibitors, we investigated the possibility of using two known inhibitors, doramapimod and sorafenib, which target inactive kinases, to design new urea derivatives as ALK inhibitors. We generated a homology model of ALK in its inactive conformation complexed with doramapimod or sorafenib in its active site. The results elucidated why doramapimod is a weak inhibitor and why sorafenib does not inhibit ALK. Virtual screening of commercially available compounds using the homology model of ALK yielded candidate inhibitors, which were tested using biochemical assays. Herein we present the design, synthesis, biological activity, and structure–activity relationships of a novel series of urea compounds as potent ALK inhibitors. Some compounds showed inhibition of purified ALK in the high nanomolar range and selective antiproliferative activity on ALK‐positive cells.
Adamantyl Ethanone Pyridyl Derivatives: Potent and Selective Inhibitors of Human 11β‐Hydroxysteroid Dehydrogenase Type 1
Authors: Su Xiangdong , Pradaux‐Caggiano Fabienne , Vicker Nigel , Thomas Mark P. , Halem Heather , Culler Michael D. , Potter Barry V. L. 
Published: June 2011

AbstractElevated levels of active glucocorticoids have been implicated in the development of several phenotypes of metabolic syndrome, such as type 2 diabetes and obesity. 11β‐Hydroxysteroid dehydrogenase type 1 (11β‐HSD1) catalyses the intracellular conversion of inactive cortisone to cortisol. Selective 11β‐HSD1 inhibitors have shown beneficial effects in various conditions, including diabetes, dyslipidemia and obesity. A series of adamantyl ethanone pyridyl derivatives has been identified, providing potent and selective inhibitors of human 11β‐HSD1. Lead compounds display low nanomolar inhibition against human and mouse 11β‐HSD1 and are selective for this isoform, with no activity against 11β‐HSD2 and 17β‐HSD1. Structure–activity relationship studies reveal that an unsubstituted pyridine tethered to an adamantyl ethanone motif through an ether or sulfoxide linker provides a suitable pharmacophore for activity. The most potent inhibitors have IC50 values around 34–48 nM against human 11β‐HSD1, display reasonable metabolic stability in human liver microsomes, and weak inhibition of key human CYP450 enzymes.
21‐Gene recurrence scores
Authors: Lund Mary Jo , Mosunjac Marina , Davis Kelly M. , Gabram‐Mendola Sheryl , Rizzo Monica , Bumpers Harvey L. , Hearn Sherita , Zelnak Amelia , Styblo Toncred , O'Regan Ruth M. 
Published: June 2011

AbstractBACKGROUND:African American (AA) women experience higher breast cancer mortality than white (W) women. These differences persist even among estrogen receptor (ER)‐positive breast cancers. The 21‐gene recurrence score (RS) predicts recurrence in patients with ER‐positive/lymph node‐negative breast cancer according to RS score—low risk (RS, 0‐18), intermediate risk (RS, 19‐31), and high risk (RS, >31). The high‐risk group is most likely to benefit from chemotherapy, to achieve minimal benefit from hormonal therapy, and to exhibit lower ER levels (intrinsically luminal B cancers). In the current study, the authors investigated racial differences in RS testing, scores, treatment, and outcome.METHODS:Tumor registry data from 3 Atlanta hospitals identified women who were diagnosed with breast cancers during 2005 through 2009. Medical record abstraction provided information on RS and other tumor/treatment factors. Statistical analyses used chi‐square/exact tests and logistic regression.RESULTS:Of 2186 patients, including 1192 AA women and 992 W women, 853 women had stage I or II, ER‐positive/lymph node‐negative disease and, thus, were eligible for RS testing (AA = 372 [31.2%]; W = 481 [48.5%]; P < .0001); and 272 women (31.8%) received testing (AA = 76 [20.4%]; W = 196 [40.7%]; P < .0001). Tumors were distributed into the following groups according to risk: low risk (n = 133), medium risk (n = 113), and high risk (n = 26). The mean RS did not differ by race, but risk groups did (low‐risk group: 46.1% vs 50% for AA women and W women, respectively; high‐risk group: 15.8% vs 7.1%, respectively; P = .043). In multivariate analyses, AA race (odds ratio, 3.6) was associated independently with high risk scores.CONCLUSIONS:AA women were half as likely as W women to receive 21‐gene RS testing but were 2‐fold more likely to be categorized as high risk. The current data suggested that testing guidelines are not applied equivalently, testing bias may attenuate racial differences in RS, and disparate outcomes may be explained in part by differences in RS, although compliance and pharmacogenomics also may play a role. Cancer 2012;. © 2011 American Cancer Society.
Zinc finger E‐box binding factor 1 plays a central role in regulating Epstein‐Barr virus (EBV) latent‐lytic switch and acts as a therapeutic target in EBV‐associated gastric cancer
Authors: Zhao Junhong , Jin Hongchuan , Cheung Kin Fai , Tong Joanna H. M. , Zhang Sui , Go Minnie Y. Y. , Tian Linwei , Kang Wei , Leung Patrick P. S. , Zeng Zhirong , Li Xiaoxing , To Ka Fai , Sung Joseph J. Y. , Yu Jun 
Published: June 2011

AbstractBACKGROUND:The role of Epstein‐Barr virus (EBV) infection in gastric carcinogenesis remains largely unknown. The authors studied the effects of zinc finger E‐box binding factor 1 (ZEB1) on latent‐lytic switch of EBV infection in gastric cancer and explored the importance of EBV in gastric carcinogenesis.METHODS:Loss or gain of ZEB1 function was obtained by ZEB1 small‐interfering RNA (siRNA) knock‐down or forced ZEB1 re‐expression. Cell growth was evaluated by cell viability and colony formation assays, and the cell cycle was assessed by flow cytometry. EBV was detected using quantitative polymerase chain reaction (PCR) and in situ hybridization analyses.RESULTS:ZEB1 knock‐down in a latent EBV‐infected gastric cancer cell line (YCC10) increased lytic gene BamHI W leftward reading frame 1 (BZLF1) expression and decreased the expression of latent gene EB nuclear antigen 1 (EBNA1) concomitant with the inhibition of cell viability (P < .05) and S‐phase DNA synthesis (P < .01). ZEB1 depletion combined with ganciclovir revealed a further reduction in cell viability (P < .001). ZEB1 knock‐down induced cell apoptosis and the up‐regulation of caspase 3 and poly(adenosine diphosphate‐ribose) polymerase cleavage. Conversely, ectopic overexpression of ZEB1 in a lytic EBV‐infected gastric cancer cell line (AGS‐EBV) inhibited BZLF1 promoter (Zp) activity, BZLF1 expression, and apoptosis and promoted cell growth. EBV infection was detected in 11.3% (80 of 711) of gastric cancers. The presence of EBV was associated with age, men, and intestinal type cancer.CONCLUSIONS:ZEB1 was confirmed as a key mediator of the latent‐lytic switch of EBV‐associated gastric cancer, a distinct subtype with different clinicopathologic features. The current results indicated that inhibition of ZEB1 may be a potential target for EBV‐associated gastric cancer therapy. Cancer 2012;. © 2011 American Cancer Society.
Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder
Authors: Scosyrev Emil , Messing Edward M. , van Wijngaarden Edwin , Peterson Derick R. , Sahasrabudhe Deepak , Golijanin Dragan , Fisher Susan G. 
Published: June 2011

AbstractBACKGROUND:The purpose of this study was to investigate the effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) on pathologic down‐staging of patients with locally advanced urothelial cancer (UC) of the bladder.METHODS:This was a retrospective cohort study of patients treated with radical cystectomy (RC) for clinical stage cT2‐T4, N any, M0 bladder UC at Strong Memorial Hospital from 1999 to 2009. The primary exposure variable was use of neoadjuvant chemotherapy (GC vs none). The primary outcome was stage pT0 at RC. Secondary outcomes included other down‐staging end points in the bladder (<pT1, <pT2, <pT3), nodal status, and surgical margins. Linear probability models were used to estimate the effect of neoadjuvant GC on tumor down‐staging with adjustment for clinical staging variables.RESULTS:A total of 160 eligible patients were identified, of whom 25 were treated with neoadjuvant GC before RC (GC + RC) and 135 without neoadjuvant chemotherapy (RC only). Stage pT0 at cystectomy was found in 20% of patients in the GC + RC group and in 5% of patients in the RC group (adjusted risk difference [aRD] = 16%, P = .03). For other down‐staging end points, the estimated treatment effect was as follows (all point estimates favoring chemotherapy): <pT1 aRD = 30% (P = .005); <pT2 aRD = 30% (P = .004); <pT3 aRD = 31% (P = .008); margins aRD = 8% (P = .41); nodes aRD = 4% (P = .74).CONCLUSIONS:Neoadjuvant GC was found to be capable of down‐staging UC in the bladder; however, no effect on disease in nodes was seen in this study. Cancer 2012;. © 2011 American Cancer Society.
Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
Authors: Moore Lee E. , Pfeiffer Ruth M. , Zhang Zhen , Lu Karen H. , Fung Eric T. , Bast Robert C. 
Published: June 2011

AbstractBACKGROUND:When epithelial ovarian cancer is detected at an early stage (I‐II), the 5‐year survival rate is between 70% and 90%; whereas, when it is detected in late stages (III‐IV), the 5‐year survival rate slips to <30%. In a previous report, the authors observed that proteomic biomarkers and cancer antigen 125 (CA 125) exhibited a sensitivity of 84% at a specificity of 98% for identifying sera from patients who had stage I disease at the time of surgery, significantly improving the sensitivity of CA 125 alone. The challenge, however, is to detect ovarian cancer before clinical diagnosis. The current study was part of a large effort to compare different multimarker biomarker panels for the early detection of ovarian cancer. Several biomarkers were evaluated alone and in combination with CA 125 in prediagnostically collected sera from women in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.METHODS:Proximal prediagnostic sera from 118 women with ovarian cancer (cases) and from 951 age‐matched women (controls) (8 controls per case, including 4 randomly selected from the general population, 2 with CA 125 levels ≥35 U/mL, and 2 with a positive family history of breast/ovarian cancer) were analyzed using the CA 125 immunoassay and surface‐enhanced laser desorption and ionization time‐of‐flight mass spectrometry to measure 7 proteins (apolipoprotein A1, truncated transthyretin, transferrin, hepcidin, β‐2 microglobulin, connective tissue activating protein III), and interalpha‐trypsin inhibitor heavy‐chain 4). Data were analyzed by 2 statistical strategies that combined the 7 markers and CA 125 into 1 predictive score for disease classification.RESULTS:CA 125 levels were elevated (≥35 U/mL) in 61.5% of 65 patients who had CA 125 data available from samples that were collected <12 months before cancer diagnosis; however, levels of the additional 7 biomarkers were not different between cases and the 3 control groups individually or combined. Two panels that combined CA 125 and the 7 biomarkers failed to improve the sensitivity of CA 125 alone.CONCLUSIONS:In contrast to earlier findings from analyzes of postdiagnostically collected sera, the addition of 7 biomarkers to CA 125 did not improve sensitivity for preclinical diagnosis beyond CA 125 alone. Cancer 2012;. © 2011 American Cancer Society.
The Association of Robotic Surgical Technology and Hospital Prostatectomy volumes
Authors: Neuner Joan M. , See William A. , Pezzin Liliana E. , Tarima Sergey , Nattinger Ann B. 
Published: June 2011

AbstractBACKGROUND:Despite limited and conflicting evidence for the efficacy of newly developed robotic technology for laparoscopic prostatectomy, this technology is spreading rapidly. Because the newer technology is more costly, reasons for this rapid adoption are unclear. The authors of this report sought to determine whether hospital acquisition of robotic technology was associated with volume of prostate cancer surgery.METHODS:The inpatient dataset of claims records from 2002 to 2008 and the acquisition dates of robotic technology were used to examine the rates of prostatectomy in Wisconsin hospitals. In analyses that accounted for hospital and referral region characteristics, changes in hospital prostatectomy volume were examined for their association with technology acquisition. Overall trends in the rate of prostatectomy also were examined over the study period.RESULTS:In total, 10,021 prostatectomies were performed in 52 hospitals in Wisconsin's 8 health referral regions during the study period. The mean quarterly prostatectomy volume in hospitals that did not acquire the technology was 4.5 in 2002 and 3.1 in 2007/2008. In contrast, the mean quarterly prostatectomy volume in hospitals that went on to acquire robotic technology was 16.5 in 2002 and 24.8 in 2007/2008. In adjusted models, the acquisition of a robot was associated with a 114% annual increase (95% confidence interval, 62%‐177% annual increase) in hospital prostatectomy volume. The average Wisconsin hospital prostatectomy volume was unchanged during 2002 through 2006 but increased by 25.6% in 2007.CONCLUSIONS:Robotic technology acquisition occurred rapidly in Wisconsin hospitals, and hospitals that acquired a robot had large increases in prostatectomy volume. Cancer 2011;. © 2011 American Cancer Society.
Primary radiotherapy versus radical prostatectomy for high‐risk prostate cancer
Authors: Parikh Ravi , Sher David J. 
Published: June 2011

AbstractBACKGROUND:Two evidence‐based therapies exist for the treatment of high‐risk prostate cancer (PCA): external‐beam radiotherapy (RT) with hormone therapy (H) (RT + H) and radical prostatectomy (S) with adjuvant radiotherapy (S + RT). Each of these strategies is associated with different rates of local control, distant metastasis (DM), and toxicity. By using decision analysis, the authors of this report compared the quality‐adjusted life expectancy (QALE) between men with high‐risk PCA who received RT + H versus S + RT versus a hypothetical trimodality therapy (S + RT + H).METHODS:The authors developed a Markov model to describe lifetime health states after treatment for high‐risk PCA. Probabilities and utilities were extrapolated from the literature. Toxicities after radiotherapy were based on intensity‐modulated radiotherapy series, and patients were exposed to risks of diabetes, cardiovascular disease, and fracture for 5 years after completing H. Deterministic and probabilistic sensitivity analyses were performed to model uncertainty in outcome rates, toxicities, and utilities.RESULTS:RT + H resulted in a higher QALE compared with S + RT over a wide range of assumptions, nearly always resulting in an increase of >1 quality‐adjusted life year with outcomes highly sensitive to the risk of increased all‐cause mortality from H. S + RT + H typically was superior to RT + H, albeit by small margins (<0.5 quality‐adjusted life year), with results sensitive to assumptions about toxicity and radiotherapy efficacy.CONCLUSIONS:For men with high‐risk PCA, RT + H was superior to S + RT, and the result was sensitive to the risk of all‐cause mortality from H. Moreover, trimodality therapy may offer local and distant control benefits that lead to optimal outcomes in a meaningful population of men. Cancer 2012;. © 2011 American Cancer Society.
Preclinical xenograft models of human sarcoma show nonrandom loss of aberrations
Authors: Kresse Stine H. , Meza‐Zepeda Leonardo A. , Machado Isidro , Llombart‐Bosch Antonio , Myklebost Ola 
Published: June 2011

AbstractBACKGROUND:Human tumors transplanted into immunodeficient mice (xenografts) are good preclinical models, and it is important to identify possible systematic changes during establishment and passaging in mice.METHODS:High‐resolution microarray‐based comparative genomic hybridization (array CGH) was used to investigate how well a series of sarcoma xenografts, including 9 patient/xenograft pairs and 8 early versus late xenograft passage pairs, represented the patient tumor from which they originated.RESULTS:In all analyses, the xenografts were more similar to their tumor of origin than other xenografts of the same type. Most changes in aberration patterns were toward a more normal genome complement, and the increased aberrations observed were mostly toward more loss. In general, the changes were scattered over the genome, but some changes were significant in osteosarcomas. These were rather focused and consistent with amplifications frequent in patient samples, involving the genes platelet‐derived growth factor receptor A (PDGFRA), cysteine‐rich hydrophobic domain 2 (CHIC2), FIP‐like 1 (FIP1L1), ligand of numb‐protein X1 (LNX1), RAS‐like family 11 member B (RASL11B), and sec1 family domain containing 2 (SCFD2), probably a sign of continued tumor progression. Some changes that disappeared may have been involved in host‐stroma interactions or chemotherapy resistance, possibly because of the absence of selection in the mouse.CONCLUSIONS:Direct xenografts reflected well the genomic patterns of their tumors of origin. The few significant aberrations that were lost during passaging in immune‐defective mice may have been caused by the lack of selection in the new host, whereas aberrations that were gained appeared to be the result of general tumor progression rather than model‐specific artifacts. Cancer 2011;. © 2011 American Cancer Society.
A prospective phase 2 study of surgery followed by chemotherapy and radiation for superior sulcus tumors
Authors: Gomez Daniel R. , Cox James D. , Roth Jack A. , Allen Pamela K. , Wei Xiong , Mehran Reza J. , Kim Jae Y. , Swisher Stephen G. , Rice David C. , Komaki Ritsuko 
Published: June 2011

AbstractBACKGROUND:The optimal treatment for locally advanced superior sulcus tumors is not clear. The authors report long‐term results of a trial examining the safety and efficacy of surgery followed by concurrent chemoradiation therapy for this disease.METHODS:Thirty‐two patients with resectable or marginally resectable superior sulcus tumors at The University of Texas MD Anderson Cancer Center from 1994 to 2010 were enrolled in a prospective trial. Surgery involved segmentectomy or lobectomy with en bloc resection of the involved chest wall and complete nodal staging; radiation therapy (RT) began 14 to 42 days later to a dose of 60 grays (Gy) in 50 1.2‐Gy fractions if surgical margins were negative or 64.8 Gy in 54 1.2‐Gy fractions if margins were positive. Two cycles of etoposide (50 mg/m2) and cisplatin (50 mg/m2) were given during RT, and another 3 cycles were given after RT. Eleven patients underwent prophylactic cranial irradiation (PCI).RESULTS:The protocol completion rate was 78%. Gross total resection was accomplished in all 32 patients; 28% underwent R1 resection. Operative mortality was 0%. The most common surgical complication was postoperative pneumonia (25%). At a median follow‐up time of 53.4 months (range, 2‐154 months), the 2‐year, 5‐year, and 10‐year rates of locoregional control were 84%, 76%, and 76%; distant metastasis‐free survival, 52%, 48%, and 48%; disease‐free survival, 49%, 45%, and 45%; and overall survival, 72%, 50%, and 45%, respectively. The brain was the most common site of distant failure (n = 5), but no patient who received PCI experienced brain metastasis.CONCLUSIONS:Surgery followed by postoperative chemoradiation is safe and effective for the treatment of marginally resectable superior sulcus tumors. Cancer 2011;. © 2011 American Cancer Society.
Better prognosis for patients with del(7q) than for patients with monosomy 7 in myelodysplastic syndrome
Authors: Cordoba Iris , González‐Porras José R. , Nomdedeu Benet , Luño Elisa , de Paz Raquel , Such Esperanza , Tormo Mar , Vallespi Teresa , Collado Rosa , Xicoy Blanca , Andreu Rafael , Muñoz Juan A. , Solé Francesc , Cervera Jose , del Cañizo Consuelo ,   On behalf of the Spanish Myelodysplastic Syndrome Registry
Published: June 2011

AbstractBACKGROUND:Abnormalities involving chromosome 7 are frequent in myelodysplastic syndrome (MDS) and suggest a poor prognosis.METHODS:The authors examined the hypothesis that the clinical features and survival associated with isolated deletion (del) of part of the long arm of chromosome 7 (7q) in MDS are different from those associated with isolated monosomy 7 (complete loss of chromosome 7). In total, 133 patients with a diagnosis of de novo MDS (according to the World Health Organization [WHO] classification) and chromosome 7 abnormalities in the Spanish MDS Registry were evaluated retrospectively. Four karyotypic groups were identified: isolated del(7q) (n = 29), isolated monosomy 7 (n = 27), del(7q) with additional abnormalities (n = 24), and monosomy 7 with additional abnormalities (n = 53).RESULTS:Isolated del(7q) was more frequent in patients with less advanced MDS according to the WHO classification or the International Prognostic Scoring System. In addition, isolated del(7q) was associated with fewer blasts in bone marrow than other cytogenetics groups. Survival was significantly superior in patients with isolated del(7) than in those with isolated monosomy 7, del(7q) with additional abnormalities, or monosomy 7 with additional abnormalities. On multivariate analysis, age, the percentage of blasts in bone marrow, and other chromosome 7 abnormalities apart from isolated del(7q) were identified as independent risk factors for survival.CONCLUSIONS:The current results demonstrated that patients who had MDS with isolated del(7q) had some distinct clinical‐pathologic characteristics as well as better survival than patients who had MDS with isolated monosomy 7. Cancer 2012;. © 2011 American Cancer Society.