bluuebunny/crossref_metadata_2025_split huggingface dataset:
An assessment of erythroid response to epoetin α as a single agent versus in combination with granulocyte– or granulocyte‐macrophage–colony‐stimulating factor in myelodysplastic syndromes using a meta‐analysis approach
Authors: Mundle Suneel , Lefebvre Patrick , Vekeman Francis , Duh Mei Scheng , Rastogi Ruchi , Moyo Victor 
Published: January 2009

AbstractBACKGROUND:Epoetin α (EPO) continues to be the initial treatment of choice for most anemic patients with myelodysplastic syndromes (MDS). Over the years, different therapeutic strategies have been adopted to optimize the clinical benefits of EPO in this setting.METHODS:In the current meta‐analysis of published literature, erythroid response (ER) rates with EPO as a single agent versus its combination with granulocyte–colony‐stimulating factor (G‐CSF) or granulocyte‐macrophage–colony‐stimulating factor (GM‐CSF) were compared.RESULTS:The assessment indicated that the ER rates were comparable between the 2 EPO‐based therapeutic strategies. Furthermore, EPO monotherapy at a higher dose of 60,000 to 80,000 U weekly produced significantly higher ER rates (64.5%) compared with the standard oncology dose of 30,000 to 40,000 U weekly either as a single agent (49%; P < .001) or in combination with G‐CSF/GM‐CSF (50.6% P = .007). In addition, when transfusion‐dependent patients were assessed separately, both EPO monotherapy and its combination with G‐CSF/GM‐CSF produced comparable and appreciable levels of transfusion independence (28.8% and 24.8%, respectively).CONCLUSIONS:In the current meta‐analysis, higher doses of EPO demonstrated better ER rates compared with EPO at standard doses alone or in combination with G‐CSF/GM‐CSF. Furthermore, the authors concluded that prospective clinical studies are warranted to evaluate the use of higher doses of EPO in anemic patients with MDS. Cancer 2009. © 2009 American Cancer Society.
Comparison of American Joint Committee on Cancer pathologic stage T3a versus T3b urothelial carcinoma: Analysis of patient outcomes
Authors: Boudreaux Kelly J. , Chang Sam S. , Lowrance William T. , Rumohr Jon A. , Barocas Daniel A. , Cookson Michael S. , Smith Joseph A. , Clark Peter E. 
Published: January 2009

AbstractBACKGROUND:The radical cystectomy experience at Vanderbilt University Medical Center was scrutinized to determine whether there was a difference in survival between patients with lymph node‐negative pathologic T3a versus pathologic T3b urothelial carcinoma of the bladder.METHODS:Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1995 and 2005. We excluded patients with nontransitional cell cancer, lymph node disease, or with unknown lymph node status. Of the 790 reviewed patients, 75 patients (9.4%) were diagnosed with pathologic T3 urothelial cancer of the bladder. The impact of pathologic substaging (pT3a vs pT3b) was examined to determine the effect on overall, disease‐specific, and recurrence‐free survival.RESULTS:The mean age was 68.6 years (36 years to 83 years). Median overall follow‐up was 25.3 months (1.13 months to 130.17 months). Median follow‐up for patients alive at last follow‐up was 55.9 months (25.3 months to 130.2 months). Actuarial overall survival at 5 years was 29.5% for pT3a and 29.3% for pT3b (P = .79). Actuarial disease‐specific survival at 5 years was 54.1% for pT3a and 42.4% for pT3b (P = .21). Actuarial recurrence‐free survival at 5 years was 68.1% for pT3a and 71.9% for pT3b (P = .53).CONCLUSIONS:There were no significant differences in overall, disease‐specific, or recurrence‐free survival when comparing lymph node‐negative pT3a versus pT3b urothelial cancer of the bladder following radical cystectomy. Simplification of pathologic staging for urothelial carcinoma of the bladder should be considered at future revisions of the American Joint Committee on Cancer staging system. Cancer 2009. © 2009 American Cancer Society.
Iron supplementation and erythropoiesis‐stimulatory agents in the treatment of cancer anemia
Authors: Pedrazzoli Paolo , Rosti Giovanni , Secondino Simona , Siena Salvatore 
Published: January 2009

AbstractUnresponsiveness to erythropoiesis‐stimulatory agents (ESA), which occurs in 30% to 50% of patients, is a major limitation to the treatment of chemotherapy‐related anemia (CRA). This may be related in part to the dysregulation of iron metabolism, leading to functional iron deficiency. However, the use of iron supplementation during treatment with ESA has not been pursued as rigorously in anemic patients with cancer as it has in patients with chronic kidney disease. In this article, the authors discuss the role of iron supplementation in the setting of CRA in view of recent reports that have addressed this issue. Cancer 2009. © 2009 American Cancer Society.
The hair follicle barrier to involvement by malignant melanoma
Authors: Pozdnyakova Olga , Grossman Joseph , Barbagallo Belinda , Lyle Stephen 
Published: January 2009

AbstractBACKGROUND:Melanoma characteristically grows within the epidermis along the dermal‐epidermal junction, sometimes extending outward up to several centimeters beyond the foci of invasive tumors. Although follicular involvement by malignant melanoma is widely recognized, to the authors' knowledge no previously published data address this phenomenon.METHODS:To examine the growth characteristics of in situ melanomas in relation to the hair follicle microanatomy, the authors analyzed 100 cases of primary cutaneous melanomas (61 in situ and 39 invasive melanomas with significant in situ components) obtained from pathology clinical archives.RESULTS:Eighty‐two (82%) cases of melanoma in situ demonstrated tumor cells within ≥1 hair follicles. Of those, 57 (69.5%) cases demonstrated the tumor cells only within the infundibulum. Extension of the tumor cells down to the isthmus was observed in 24 cases (29.3%). In only 1 exceptional case (1%) were tumor cells detected beneath the level of the hair follicle bulge.CONCLUSIONS:The authors postulate that a physiologic barrier restricts the intraepithelial spread of melanoma tumor cells at or beyond the level of the stem cell niche in the hair follicle bulge. Although the nature of this barrier remains to be elucidated, the distinct biologic characteristics of the hair follicle bulge may provide clues to understanding this phenomenon. Cancer 2009. © 2009 American Cancer Society.
High prevalence of BRAF mutation in a Brazilian cohort of patients with sporadic papillary thyroid carcinomas
Authors: Oler Gisele , Cerutti Janete M. 
Published: January 2009

AbstractBACKGROUND:Although several studies undoubtedly demonstrated that BRAF mutation is an important genetic event in the pathogenesis of papillary thyroid carcinoma (PTC), its prognostic significance and correlation with less differentiated states remains unclear. It has been suggested that the discrepancy may be at least partially due to the insufficient number of cases analyzed, epidemiologic factors, and a combination of different variants of PTC included in these studies.METHODS:In this context, the prevalence of the BRAF mutation in a Brazilian cohort of PTCs (n = 120) was first assessed and correlated with clinicopathologic features. The BRAF exon 15 mutation was evaluated by direct sequencing. Furthermore, using quantitative polymerase chain reaction, the issue of whether the expression level of the iodide‐metabolizing genes (NIS and TSHR) was correlated with BRAF mutational status was investigated.RESULTS:A high prevalence of the BRAF mutation was found in PTC cases (48%). The BRAF mutation was found to be significantly associated with the classic variant of PTC (66%; P < .0001), although it was found in the follicular variant as well (21%). Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC. Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs harboring the BRAF V600E mutation.CONCLUSIONS:These findings provide further evidence that BRAF might be associated with a more aggressive phenotype and less differentiated state due to decreased expression of iodide‐metabolizing genes. The search for a BRAF mutation in the current study population appears to be valuable for predicting prognosis and guiding management in patients with PTC. Cancer 2009. © 2009 American Cancer Society.
Factors associated with local and distant recurrence and survival in patients with resected nonsmall cell lung cancer
Authors: Varlotto John M. , Recht Abram , Flickinger John C. , Medford‐Davis Laura N. , Dyer Ann M. , DeCamp Malcolm M. 
Published: January 2009

AbstractBACKGROUND:This study assessed the impact of surgical, histopathologic and patient‐related factors on the risks of local and distant recurrence and overall survival for patients with stages I through IIIA nonsmall cell lung carcinoma (NSCLC) undergoing definitive resection with or without adjuvant chemotherapy.METHODS:This study included 373 consecutive patients treated between 2000 and 2005 who did not receive adjuvant or neoadjuvant radiotherapy, had at least 3 months of follow‐up, and did not have a history of other cancers within 5 years of the diagnosis of their NSCLC. Of these, 52% had pathologic stage IA disease, 30% had stage IB, 5% had stage IIA, 8% had stage IIB and 5% had stage III disease. Forty‐four patients received chemotherapy.RESULTS:The median follow‐up was 33 months. Local failure rates at 2 years, 3 years, and 5 years were 16%, 22%, and 32%, respectively; distant recurrence rates were 13%, 15%, and 21%, respectively. Multivariable analysis revealed that local recurrence was significantly associated with the presence of lymphatic or vascular invasion (LVI), the use of chemotherapy, and having diabetes; distant recurrence was significantly higher in patients with nonsquamous cell histology, those undergoing pneumonectomy, and those with more advanced TNM stage. Survival was significantly associated with age, history of myocardial infarction, performance of a pneumonectomy, histology, LVI, and the number of positive N1 lymph nodes.CONCLUSIONS:Local recurrence was the predominant type of failure in this series. Patient with diabetes or LVI may benefit from close surveillance and aggressive therapy of asymptomatic local recurrences, especially when chemotherapy is given in addition to surgery. Cancer 2009. © 2009 American Cancer Society.
Understanding bladder cancer death
Authors: Morris David S. , Weizer Alon Z. , Ye Zaojun , Dunn Rodney L. , Montie James E. , Hollenbeck Brent K. 
Published: January 2009

AbstractBACKGROUND:To the authors' knowledge, the extent to which death from bladder cancer is attributable to tumor biology or physician practice patterns is unknown. For this reason, the relative importance of broadening indications for aggressive therapy has unclear implications.METHODS:Patients whose deaths were caused directly by bladder cancer were identified using institutional (n = 126 patients) and administrative (n = 6326 patients) data sources. By using implicit review (clinical data, 2001‐2005) and explicit algorithms (Surveillance, Epidemiology, and End Results [SEER]‐Medicare, 1992‐2002), the authors estimated the proportion of potentially avoidable deaths from bladder cancer.RESULTS:After an implicit review of clinical data, 40 of 126 deaths (31.7%) were classified as potentially avoidable. Compared with those patients who were deemed unsalvageable, these patients generally presented with nonmuscle‐invasive disease (80% vs 25.6%; P < .001), received multiple courses of intravesical therapy (32.5% vs 1.2%; P < .001), and had a more protracted course from diagnosis to aggressive treatment (median, 23 months vs 2 months; P < .001). An explicit review of claims data indicated that between 31.6% and 46.8% of the 6326 bladder cancer deaths identified in the SEER‐Medicare data potentially were avoidable, depending on the survivorship threshold chosen. Patients whose deaths potentially were avoidable more commonly presented with nonmuscle‐invasive disease (66.7% vs 24.7%; P < .0001) and lower grade disease (35.1% vs 15.1%; P < .0001).CONCLUSIONS:The greatest inroads into reducing death from bladder cancer likely hinge on earlier detection or improvement of systemic therapies. However, changing physician practice may translate into nontrivial reductions in bladder cancer mortality. Cancer 2009. © 2009 American Cancer Society.
A novel algorithm to improve pathologic stage prediction of clinically organ‐confined muscle‐invasive bladder cancer
Authors: Margel David , Harel Amir , Yossepowitch Ofer , Baniel Jack 
Published: January 2009

AbstractBACKGROUND:An algorithm was created to predict pathologic stage in patients with clinically organ‐confined muscle‐invasive bladder cancer.METHODS:The sample consisted of 133 consecutive patients scheduled to undergo cystectomy. To develop a tool to predict nonorgan‐confined disease before surgery, principal component analysis (PCA) was applied. Patients were stratified into a training set (n = 89) and a validation set (n = 44), and 7 parameters were evaluated: levels of carcinoembryonic antigen, cancer antigen (CA) 125, and carbohydrate antigen (CA) 19‐9; clinical stage; presence of hydronephrosis; presence of carcinoma in situ; and initial tumor size >3 cm. PCA was applied to the training set to determine the weight of each parameter. A PCA score was generated for each patient in the set, and a cutoff defining nonorgan‐confined disease was established. The accuracy of the cutoff was quantified by the area under the receiver operator characteristics curve (AUC). The model was then applied to the validation set without recalculation; the AUC and the positive and negative predictive values of the validation set were calculated.RESULTS:On pathologic evaluation, 71 patients (53%) were found to have organ‐confined tumors and 62 patients (47%) had extravesical disease. The AUC was 0.85 in the training group (95% confidence interval [95% CI], 0.71‐0.97) and 0.84 in the validation group (95% CI, 0.75‐0.93). The positive and negative predictive values in the validation group were 88% (95% CI, 71%‐96%) and 94% (95% CI, 71%‐99%), respectively.CONCLUSIONS:The newly devised, internally validated, algorithm was 85% accurate in predicting nonorgan‐confined bladder disease before cystectomy. Further external validation in a large cohort was recommended as still necessary. Cancer 2009. © 2009 American Cancer Society.
Comparison of low‐temperature processes for oil and coenzyme Q10 extraction from mackerel and herring
Authors: Laplante Serge , Souchet Nathalie , Bryl Piotr 
Published: January 2009

AbstractAmong the fat fish species available from Eastern Quebec (Canada), whole Atlantic mackerel (Scomber scombrus) and herring (Clupea harengus) represent abundant fishery resources which are currently under‐utilized. They have relatively high contents of oil and coenzyme Q10 (CoQ10) in their tissues, which could be valuable for nutraceutical applications. Therefore, two low‐temperature extraction processes were compared for the recovery of oil and CoQ10 from these resources, such as enzymatic hydrolysis using Protamex™ and supercritical CO2 (SCO2) using fish lyophilizates. The results revealed that highest yields of oil and CoQ10 were obtained using the enzymatic hydrolysis process with mackerel. Whatever the process used, CoQ10 concentrations were higher in herring oil, due mainly to a more selective extraction of CoQ10 over that of the oil. The highest CoQ10 recovery rates (extraction efficiencies) were obtained using the enzymatic hydrolysis process with both types of fish, but also the SCO2 process with herring under some conditions. For mackerel, the lower CoQ10 recovery rates obtained from the SCO2 process were explained by its more important matrix effect. An economic assessment of both processes revealed that the enzymatic hydrolysis extraction process would be the most promising for up‐scaling the recovery of oil and CoQ10 from these resources.
CEC with new monolithic stationary phase based on a fluorinated monomer, trifluoroethyl methacrylate
Authors: Yurtsever Arda , Saraçogˇlu Berna , Tuncel Ali 
Published: January 2009

AbstractA new, fluorinated monolithic stationary phase for CEC was first synthesized by a single‐stage, thermally initiated copolymerization of a fluorinated monomer, 2,2,2‐trifluoroethyl methacrylate (TFEM) and ethylene dimethacrylate (EDMA) in the presence of a porogen mixture. In this preparation, 2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid was used as the charge‐bearing monomer. The porogen mixture was prepared by mixing isoamylalcohol and 1,4‐butanediol. A clear increase in the electroosmotic mobility was observed with increasing pH. The electroosmotic mobility decreased with increasing ACN concentration. Poly(TFEM‐co‐EDMA) monolith prepared under optimized polymerization conditions was successfully used in the separation of alkylbenzenes and phenols by CEC. The best chromatographic separation for alkylbenzenes was performed with lower ACN concentrations (i.e. 60% v/v) with respect to the common acrylic‐based CEC monoliths. The theoretical plate numbers up to 220 000 plates/m were achieved in the reversed phase separation of phenols. Poly(TFEM‐co‐EDMA) monolith also allowed the simultaneous separation of aniline and benzoic acid derivatives by a single run and by using a lower ACN concentration in the mobile phase with respect to the similar electrochromatographic separations. A stable retention behaviour in reversed phase separation of alkylbenzenes was obtained with the poly(TFEM‐co‐EDMA) monolith.
Influence of different proteomic protocols on degree of high‐coverage identification of nonspecific lipid transfer protein 1 modified during malting
Authors: Chmelik Josef , Zidkova Jitka , Rehulka Pavel , Petry‐Podgorska Inga , Bobalova Janette 
Published: January 2009

AbstractBoth top‐down (combining protein separation with MS analysis of intact proteins) and bottom‐up (MS analysis of digested proteins) proteomic approaches were used for detailed characterization of nonspecific lipid transfer protein from barley malt. The aim was obtaining high‐coverage of the primary structure of the proteins and the determination of PTMs such as lipid adduction and glycation. Here we present an influence of 15 proteomic protocols (differing in applied separation technique, enzyme and digestion procedure) on the extent of the coverage of the protein primary structure. The most successful protocols were in‐gel digestion with trypsin of alkylated protein and in‐solution digestions with trypsin or trypsin/chymotrypsin mixture of the nonalkylated protein. Totally, full sequence coverage based on the PMF and 85% sequence coverage based on the peptide fragmentation including PTMs was obtained.
Chlorophyllin significantly reduces benzo[a]pyrene‐DNA adduct formation and alters cytochrome P4501A1and1B1expression and EROD activity in normal human mammary epithelial cells
Authors: Keshava Channa , Divi Rao L. , Einem Tracey L. , Richardson Diana L. , Leonard Sarah L. , Keshava Nagalakshmi , Poirier Miriam C. , Weston Ainsley 
Published: January 2009

AbstractWe hypothesized that chlorophyllin (CHLN) would reduce benzo[a]pyrene‐DNA (BP‐DNA) adduct levels. Using normal human mammary epithelial cells (NHMECs) exposed to 4 μM BP for 24 hr in the presence or absence of 5 μM CHLN, we measured BP‐DNA adducts by chemiluminescence immunoassay (CIA). The protocol included the following experimental groups: BP alone, BP given simultaneously with CHLN (BP+CHLN) for 24 hr, CHLN given for 24 hr followed by BP for 24 hr (preCHLN, postBP), and CHLN given for 48 hr with BP added for the last 24 hr (preCHLN, postBP+CHLN). Incubation with CHLN decreased BPdG levels in all groups, with 87% inhibition in the preCHLN, postBP+CHLN group. To examine metabolic mechanisms, we monitored expression by Affymetrix microarray (U133A), and found BP‐induced up‐regulation ofCYP1A1andCYP1B1expression, as well as up‐regulation of groups of interferon‐inducible, inflammation and signal transduction genes. Incubation of cells with CHLN and BP in any combination decreased expression of many of these genes. Using reverse transcription real time PCR (RT‐PCR) the maximal inhibition of BP‐induced gene expression, >85% forCYP1A1and >70% forCYP1B1, was observed in the preCHLN, postBP+CHLN group. To explore the relationship between transcription and enzyme activity, the ethoxyresorufin‐O‐deethylase (EROD) assay was used to measure the combined CYP1A1 and CYP1B1 activities. BP exposure caused the EROD levels to double, when compared with the unexposed controls. The CHLN‐exposed groups all showed EROD levels similar to the unexposed controls. Therefore, the addition of CHLN to BP‐exposed cells reduced BPdG formation andCYP1A1andCYP1B1expression, but EROD activity was not significantly reduced. Environ. Mol. Mutagen. 2009. Published 2009 Wiley‐Liss, Inc.
Molecular cytogenetic evaluation of the mechanism of micronuclei formation induced by camptothecin, topotecan, and irinotecan
Authors: Attia Sabry M. , Aleisa Abdulaziz M. , Bakheet Saleh A. , Al‐Yahya Abdulaziz A. , Al‐Rejaie Salim S. , Ashour Abdelkader E. , Al‐Shabanah Othman A. 
Published: January 2009

AbstractWe used the conventional bone marrow micronucleus test complemented with the fluorescent in situ hybridization with the minor satellite DNA probe to investigate the mechanisms of induction of micronuclei in mice treated with camptothecin and its clinical antineoplastic analogues topotecan and irinotecan. All experiments were performed with male Swiss albino mice. Single doses of 1 mg/kg camptothecin or 0.6 mg/kg topotecan were injected intraperitoneally and bone marrow was sampled at 30 hr (camptothecin) or 24 hr (topotecan) after treatment. A dose of 60 mg/kg irinotecan was injected intravenously, once every fourth day for 13 days and bone marrow was sampled 24 hr after the last treatment. In animals treated with camptothecin, a total of 1.07% micronuclei were found and 70% of them were centromere‐negative, indicating their formation by DNA strand breaks and reflecting the predominant clastogenic activity of camptothecin. Exposure to topotecan and irinotecan yielded 1.71 and 0.83% micronuclei, respectively. About 52.7 and 48.8% of the induced micronuclei, respectively, were centromere‐positive, indicating their formation by whole chromosomes and reflecting the aneugenic activity of both compounds. Correspondingly, about 47.3 and 51.2% of the induced micronuclei, respectively were centromere‐negative, demonstrating that topotecan and irinotecan not only induce chromosome loss but also DNA strand breaks. Both the clastogenic and aneugenic potential of these drugs can lead to the development of secondary tumors and abnormal reproductive outcomes. Therefore, the clinical use of these agents must be weighed against the risks of secondary malignancies in cured patients and persistent genetic damage of their potential offspring. Environ. Mol. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.