bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of synchronous adenocarcinoma of the esophago-gastric junction and ampulla of Vater: case report of a surgically challenging condition
Authors: Jayaprakash Namita , O'Kelly Fardod , Lim Kheng Tian , Reynolds John Vincent 
Published: September 2009

Abstract
We report herein a case of a synchronous presentation of an adenocarcinoma of esophagago-gastric junction type II and an ampullary tumor that was treated by combined Whipple's pancreaticoduodenectomy, total gastrectomy and esophagectomy. The magnitude of this operation was safely achieved with meticulous surgical techniques and perioperative care without any major short or long term complications. Patient returned to a good quality of life at six-month follow up with no further gastrointestinal symptoms or evidence of disease recurrence.
Candidate metastasis suppressor genes uncovered by array comparative genomic hybridization in a mouse allograft model of prostate cancer
Authors: Yi Yajun , Nandana Srinivas , Case Thomas , Nelson Colleen , Radmilovic Tatjana , Matusik Robert J , Tsuchiya Karen D 
Published: September 2009

Abstract

Background
The purpose of this study was to identify candidate metastasis suppressor genes from a mouse allograft model of prostate cancer (NE-10). This allograft model originally developed metastases by twelve weeks after implantation in male athymic nude mice, but lost the ability to metastasize after a number of in vivo passages. We performed high resolution array comparative genomic hybridization on the metastasizing and non-metastasizing allografts to identify chromosome imbalances that differed between the two groups of tumors.

Results
This analysis uncovered a deletion on chromosome 2 that differed between the metastasizing and non-metastasizing tumors. Bioinformatics filters were employed to mine this region of the genome for candidate metastasis suppressor genes. Of the 146 known genes that reside within the region of interest on mouse chromosome 2, four candidate metastasis suppressor genes (Slc27a2, Mall, Snrpb, and Rassf2) were identified. Quantitative expression analysis confirmed decreased expression of these genes in the metastasizing compared to non-metastasizing tumors.

Conclusion
This study presents combined genomics and bioinformatics approaches for identifying potential metastasis suppressor genes. The genes identified here are candidates for further studies to determine their functional role in inhibiting metastases in the NE-10 allograft model and human prostate cancer.
Synovial tissues concentrate secreted APRIL
Authors: Gabay Cem , Krenn Veit , Bosshard Carine , Seemayer Christian Alexander , Chizzolini Carlo , Huard Bertrand 
Published: September 2009

Abstract
Introduction
A proliferation-inducing ligand (APRIL) from the TNF family, owing to its role in the generation and survival of plasma cells (PCs), is currently targeted for rheumatoid arthritis (RA) treatment. However, little is known about APRIL expression in RA lesions, hampering our understanding of the way APRIL may modulate this autoimmune disease.

Methods
We performed immunological staining of human normal, non-RA and RA synovial tissues with a pair of antibodies specifically recognizing APRIL-producing cells and secreted APRIL.

Results
We detected significant amounts of secreted APRIL in normal synovium mostly concentrated around blood vessels and at the lining layer, but no cells producing APRIL. Meanwhile, we observed that blood neutrophils constitutively secrete APRIL, indicating that blood APRIL may diffuse into the synovium via its fenestrated vessels. Synovium from non-RA and RA patients retained similarly secreted APRIL, but in this case APRIL-producing cells, including neutrophils and macrophages, were present in the tissue. Notably, PCs - when present in RA synovium - accumulated in areas of APRIL retention, spreading from blood vessels towards the lining layer.

Conclusions
PCs accumulate in synovial zones rich in secreted APRIL, consistent with a pro-survival role of APRIL for PCs in RA. The concentration of APRIL by normal synovium indicates that this tissue may constitute a proper environment for PCs even before RA onset.
High resolution transcriptome maps for wild-type and nonsense-mediated decay-defective Caenorhabditis elegans
Authors: Ramani Arun K , Nelson Andrew C , Kapranov Philipp , Bell Ian , Gingeras Thomas R , Fraser Andrew G 
Published: September 2009

Abstract
Background
While many genome sequences are complete, transcriptomes are less well characterized. We used both genome-scale tiling arrays and massively parallel sequencing to map the Caenorhabditis elegans transcriptome across development. We utilized this framework to identify transcriptome changes in animals lacking the nonsense-mediated decay (NMD) pathway.

Results
We find that while the majority of detectable transcripts map to known gene structures, >5% of transcribed regions fall outside current gene annotations. We show that >40% of these are novel exons. Using both technologies to assess isoform complexity, we estimate that >17% of genes change isoform across development. Next we examined how the transcriptome is perturbed in animals lacking NMD. NMD prevents expression of truncated proteins by degrading transcripts containing premature termination codons. We find that approximately 20% of genes produce transcripts that appear to be NMD targets. While most of these arise from splicing errors, NMD targets are enriched for transcripts containing open reading frames upstream of the predicted translational start (uORFs). We identify a relationship between the Kozak consensus surrounding the true start codon and the degree to which uORF-containing transcripts are targeted by NMD and speculate that translational efficiency may be coupled to transcript turnover via the NMD pathway for some transcripts.

Conclusions
We generated a high-resolution transcriptome map for C. elegans and used it to identify endogenous targets of NMD. We find that these transcripts arise principally through splicing errors, strengthening the prevailing view that splicing and NMD are highly interlinked processes.
Role of Anthracyclines in the Treatment of Early Breast Cancer
Authors: Gianni Luca , Norton Larry , Wolmark Norman , Suter Thomas M. , Bonadonna Gianni , Hortobagyi Gabriel N. 
Published: September 2009

PurposeTo review data relating to anthracyclines in the adjuvant treatment of early breast cancer.DesignThis is a report from a seminar in which the future of anthracyclines in the adjuvant treatment of breast cancer was considered. In particular, the question of whether anthracyclines should now be discarded and replaced by taxanes was addressed.ResultsAccumulating data from large randomized trials indicate that genetic markers may have a role in predicting sensitivity to cytotoxic drugs. However, no reliable, validated test is available for predicting sensitivity to anthracyclines in particular. Topoisomerase IIα amplification and/or deletion, especially in conjunction with human epidermal growth factor receptor-2 amplification, has been proposed to fulfill this role but more data are needed. Currently, only one published trial has shown that a taxane-based regimen may be superior to an anthracycline-based regimen, but several trials indicate that combinations including both anthracyclines and taxanes may be better still. Further studies aimed at optimizing anthracyclines and taxanes in combination, and integrating biologic agents, seem to be the way forward. There is no validated test that can determine whether anthracyclines can be of greater benefit than other agents for individual patients.ConclusionAnthracyclines have been extensively tested in clinical trials spanning several decades; currently, there are insufficient data to recommend replacing them in the adjuvant treatment of breast cancer.
Targeted High-Resolution Ultrasound Is Not an Effective Substitute for Sentinel Lymph Node Biopsy in Patients With Primary Cutaneous Melanoma
Authors: Sanki Amira , Uren Roger F. , Moncrieff Marc , Tran Kayla L. , Scolyer Richard A. , Lin Hui-Yi , Thompson John F. 
Published: September 2009

Purpose To reassess traditional ultrasound descriptors of sentinel lymph node (SLN) metastases, to determine the minimum cross-sectional area (CSA) of an SLN metastasis detectable by ultrasound (US), and to establish whether targeted, high-resolution US of SLNs identified by lymphoscintigraphy before initial melanoma surgery can be used as a substitute for excisional SLN biopsy. Methods US was performed on SLNs identified in 871 lymph node fields in 716 patients. SLN biopsy was performed within 24 hours of lymphoscintigraphy and US examination. The CSA of each SLN metastatic deposit was determined sonographically and histologically. Results The sensitivity of targeted US in the detection of positive SLNs was 24.3% (95% CI, 19.5% to 28.7%), and the specificity was 96.8% (95% CI, 95.9% to 97.7%). The sensitivity was highest for neck SLNs (45.8%) and improved with greater Breslow thickness. The median histologic CSA of the SLN metastatic deposits was 0.39 mm2 (12.75 mm2 for US true-positive results and 0.22 mm2 for US false-negative results). True-positive, US-detected SLNs had significantly greater CSAs (t test P < .001) than undetected SLN metastases and were more likely to be spherical in cross-section. More than two sonographic descriptors of SLN metastases or rounding of the node alone were factors highly suggestive of a melanoma deposit. Conclusion US is not an appropriate substitute for SLN biopsy, but it is of value in preoperative SLN assessment and postoperative monitoring.
Randomized Phase II/III Trial Assessing Gemcitabine/ Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients With Advanced Urothelial Cancer “Unfit” for Cisplatin-Based Chemotherapy: Phase II—Results of EORTC Study 30986
Authors: De Santis Maria , Bellmunt Joaquim , Mead Graham , Kerst J. Martijn , Leahy Michael , Maroto Pablo , Skoneczna Iwona , Marreaud Sandrine , de Wit Ronald , Sylvester Richard 
Published: September 2009

Purpose There is no standard treatment for patients with advanced urothelial cancer who are ineligible (“unfit”) for cisplatin-based chemotherapy (CHT). To compare the activity and safety of two CHT combinations in this patient group, a randomized phase II/III trial was conducted by the EORTC (European Organisation for Research and Treatment of Cancer). We report here the phase II results of the study. Patients and Methods CHT-naïve patients with measurable disease and impaired renal function (30 mL/min < glomerular filtration rate [GFR] < 60 mL/min) and/or performance status (PS) 2 were randomly assigned to receive either GC (gemcitabine 1,000 mg/m2 on days 1 and 8 and carboplatin area under the serum concentration-time curve [AUC] 4.5) for 21 days or M-CAVI (methotrexate 30 mg/m2 on days 1, 15, and 22; carboplatin AUC 4.5 on day 1; and vinblastine 3 mg/m2 on days 1, 15, and 22) for 28 days. End points of response and severe acute toxicity (SAT) were evaluated with respect to treatment group, renal function, PS, and Bajorin risk groups. Results Three of 178 patients who were ineligible or did not start treatment were excluded. SAT was reported in 13.6% of patients on GC and in 23% on M-CAVI. Overall response rates were 42% (37 of 88) for GC and 30% (26 of 87) for M-CAVI. Patients with PS 2 and GFR less than 60 mL/min and patients in Bajorin risk group 2 showed a response rate of only 26% and 20% and an SAT rate of 26% and 25%, respectively. Conclusion Both combinations are active in this group of unfit patients. However, patients with PS 2 and GFR less than 60 mL/min do not benefit from combination CHT. Alternative treatment modalities should be sought in this subgroup of poor-risk patients.
Immuno–Fluorescence In Situ Hybridization Index Predicts Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP: A GELA Study
Authors: Copie-Bergman Christiane , Gaulard Philippe , Leroy Karen , Briere Josette , Baia Maryse , Jais Jean-Philippe , Salles Gilles A. , Berger Françoise , Haioun Corinne , Tilly Herve , Emile Jean-François , Banham Alison H. , Mounier Nicolas , Gisselbrecht Christian , Feugier Pierre , Coiffier Bertrand , Molina Thierry J. 
Published: September 2009

PurposeTo evaluate the prognostic value of cell of origin immunohistochemical markers and BCL2, BCL6, and c-MYC translocations in a homogeneous cohort of patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).Patients and MethodsPatients with CD20+ DLBCL were enrolled in the randomized LNH98-5 and 01-5B Groupe d'Etude des Lymphomes de l'Adulte trials. Paraffin-embedded tumor samples of 119 patients treated with R-CHOP were analyzed by immunohistochemistry for CD10, BCL6, MUM1/IRF4, LMO2, and forkhead box protein P1 (FOXP1) expression and for BCL2, BCL6, and c-MYC breakpoints by fluorescence in situ hybridization (FISH) on tissue microarray.ResultsLMO2 expression and BCL2 breakpoint were associated with the germinal center (GC) subtype defined by Hans' algorithm, respectively (P < .0001; P = .0002) whereas FOXP1 expression and BCL6 breakpoint were associated with the non-germinal center (non-GC) subtype (P = .008 and P = .0001, respectively). The immunohistochemical markers analyzed independently, GC/non-GC phenotype and BCL2 breakpoint did not predict overall survival (OS). BCL6 breakpoint was significantly associated with an unfavorable impact on OS (P = .04). Interestingly, an immunoFISH index, defined by positivity for at least two of three non-GC markers (FOXP1, MUM1/IRF4, BCL6 breakpoint) was significantly associated with a shorter 5-year OS rate (44%; 95% CI, 28 to 60 v 78%; 95% CI, 59 to 89; P = .01) which was independent (P = .04) of the age-adjusted International Prognostic Index (P = .04) in multivariate analysis.ConclusionOur study demonstrates that combining immunohistochemistry with FISH allows construction of an immunoFISH index that significantly predicts survival in elderly DLBCL patients treated with R-CHOP.
Dynamic Model for Predicting Death Within 12 Months in Patients With Primary or Post–Polycythemia Vera/Essential Thrombocythemia Myelofibrosis
Authors: Tam Constantine S. , Kantarjian Hagop , Cortes Jorge , Lynn Alice , Pierce Sherry , Zhou Lingsha , Keating Michael J. , Thomas Deborah A. , Verstovsek Srdan 
Published: September 2009

Purpose Current prognostic tools in myelofibrosis (MF) fail to identify patients at the highest risk of death and are limited by their applicability only to the time of diagnosis. We aimed to define an accelerated phase (AP) in MF by characterizing disease features that can identify patients with median overall survival of ≤ 12 months at any time in the disease course. Patients and Methods Baseline characteristics of 370 consecutive patients with MF from a single center were analyzed to identify features associated with a median overall survival of ≤ 12 months. These putative AP features were then validated by following the course of chronic-phase patients (no AP features at baseline) until the development of one or more AP features and determining their subsequent survival. Results The following three characteristics were associated with poor survival at baseline and were selected as putative AP features: blasts in blood or bone marrow ≥ 10%, platelets less than 50 × 109/L, and chromosome 17 aberrations (median overall survival, 10, 12, and 5 months, respectively). In the validation phase, chronic-phase patients who developed AP features during follow-up were found to have short subsequent survival times (median overall survival, 12, 15, and 6 months, respectively). AP was a necessary step in the progression to blast phase, with leukemic transformation being exceedingly rare (3% risk at 10 years) in patients who remained persistently in chronic phase. Conclusion Blood or bone marrow blasts ≥ 10%, platelets less than 50 × 109/L, and chromosome 17 aberrations defined AP in patients with MF. Patients in AP should be candidates for intensive therapeutic interventions.
Genetic Abnormalities of the EGFR Pathway in African American Patients With Non–Small-Cell Lung Cancer
Authors: Leidner Rom S. , Fu Pingfu , Clifford Bradley , Hamdan Ayad , Jin Cheng , Eisenberg Rosana , Boggon Titus J. , Skokan Margaret , Franklin Wilbur A. , Cappuzzo Federico , Hirsch Fred R. , Varella-Garcia Marileila , Halmos Balazs 
Published: September 2009

Purpose Previous studies in non–small-cell lung cancer (NSCLC) have demonstrated a wide variation in responsiveness to epidermal growth factor receptor (EGFR) –targeting agents and in genetic aberrancies of the EGFR pathway according to ethnic background, most notably a higher frequency of activating EGFR mutations among East-Asian patients. We investigated the frequency of EGFR pathway aberrancies among African American patients with NSCLC, for whom limited information presently exists. Patients and Methods EGFR fluorescent in situ hybridization (FISH) was performed on archived tissues from 53 African American patients. Extracted DNA was sequenced for mutational analysis of EGFR exons 18 to 21 and KRAS exon 2. Results were compared by multivariate analysis to an historical control cohort of 102 white patients with NSCLC. Results African Americans were significantly less likely to harbor activating mutations of EGFR than white patients (2% v 17%; P = .022). Only one EGFR mutation was identified, a novel S768N substitution. EGFR FISH assay was more frequently positive for African Americans than for white patients (51% v 32%; P = .018). KRAS mutational frequency did not differ between the groups (23% v 21%; P = .409). Conclusion African American patients with NSCLC are significantly less likely than white counterparts to harbor activating mutations of EGFR, which suggests that EGFR tyrosine kinase inhibitors (TKIs) are unlikely to yield major remissions in this population. Our findings add to a growing body of evidence that points to genetic heterogeneity of the EGFR pathway in NSCLC among different ethnic groups and that underscores the need for consideration of these differences in the design of future trials of agents that target the EGFR pathway.
Phase I, Pharmacokinetic, and Pharmacodynamic Study of AMG 479, a Fully Human Monoclonal Antibody to Insulin-Like Growth Factor Receptor 1
Authors: Tolcher Anthony W. , Sarantopoulos John , Patnaik Amita , Papadopoulos Kyriakos , Lin Chia-Chi , Rodon Jordi , Murphy Barbara , Roth Bruce , McCaffery Ian , Gorski Kevin S. , Kaiser Brianne , Zhu Min , Deng Hongjie , Friberg Greg , Puzanov Igor 
Published: September 2009

Purpose To determine the maximum-tolerated dose (MTD) and to assess the safety, pharmacokinetics, and evidence of antitumor activity of AMG 479, a fully human monoclonal antibody to insulin-like growth factor receptor 1 (IGF-1R). Patients and Methods Patients with advanced solid malignancies or non-Hodgkin's lymphoma received escalating doses of AMG 479 intravenously (IV) every 2 weeks (Q2W). Blood samples were assayed to determine pharmacokinetic parameters and IGF-1R occupancy on neutrophils; fluorodeoxyglucose–positron emission tomography scans were used to assess tumor metabolic effects. Results Fifty-three patients received 312 infusions of AMG 479 Q2W. Overall, the most common grades 1 to 2 toxicities were fatigue, thrombocytopenia, fever, rash, chills, and anorexia. One dose-limiting toxicity (ie, grade 3 thrombocytopenia) occurred in a patient at 20 mg/kg during course 1; grade 3 thrombocytopenia (n = 8) and grade 3 transaminitis elevations (n = 1) also were reported but not in the escalation phase. The maximum-planned dose of 20 mg/kg was safely administered; thus, an MTD was not reached. High levels of neutrophil IGF-1R binding and increases from baseline in serum IGF-1 levels were observed in the 12- and 20-mg/kg cohorts. Tumor responses included one durable complete response (CR) and one unconfirmed partial response (PR) in two patients with Ewing/primitive neuroectodermal tumors and included one PR and one minor response in two patients with neuroendocrine tumors. The patients with Ewing/PNET who had a CR have remained disease free on therapy after 28 months. Conclusion AMG 479 can be administered safely at 20 mg/kg IV Q2W. The absence of severe toxicities, attainment of serum concentrations associated with high levels of IGF-1R binding on neutrophils, and provocative antitumor activity warrant additional studies of this agent.
How Do Financial Firms Manage Risk? Unraveling the Interaction of Financial and Operational Hedging
Authors: Hankins Kristine Watson 
Published: September 2009

This paper investigates how firms manage risk by examining the relationship between financial and operational hedging using a sample of bank holding companies. Risk management theory holds that capital market imperfections make cash flow volatility costly. I investigate whether financial firms consider this cost or focus exclusively on managing tradable exposures. After documenting that acquisitions provide operational hedging by reducing potentially costly volatility, I find that postacquisition financial hedging declines even after controlling for the specific underlying risks. In addition, the decrease in financial hedging is related to the acquisition's level of operational hedging. Larger increases in operational hedging are followed by larger declines in financial hedging. These results indicate that firms in this sample manage aggregate risk, not just tradable exposures, and that operational hedging can substitute for financial hedging. This paper was accepted by John Birge, focused issue editor.
Relation between response inhibition and symptoms of inattention and hyperactivity–impulsivity in children
Authors: Gambin Małgorzata , Święcicka Małgorzata 
Published: September 2009

Objective. This study assessed the relation of response inhibition with inattention and hyperactivity–impulsivity.Method. The stop signal task was employed to investigate inhibitory control in 76 children with symptoms of inattention and/or hyperactivity–impulsivity and 48 normal control subjects. The Rating Scale for teachers, which measures the intensity of hyperactivity–impulsivity and inattention, was completed for each child.Results. Response inhibition deficit was found in children with symptoms of inattention alone or both inattention and hyperactivity–impulsivity, but not in children with hyperactive–impulsive symptoms alone. Stepwise regression indicated that distractibility–fatigability is the best predictor of the stop signal reaction time.Conclusions. Symptoms of inattention, rather than symptoms of hyperactivity–impulsivity, are associated with the response inhibition impairment.