bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of bile acids on the growth of human cholangiocarcinoma via FXR
Authors: Dai Jiaqi , Wang Hongxia , Shi Yihui , Dong Ying , Zhang Yinxin , Wang Jian 
Published: October 2011

Abstract

Background
The objective of the study was to investigate the effect of different types of bile acids on proliferation of cholangiocarcinoma and the potential molecular mechanisms.

Methods
PCR assay and Western blot were performed to detect the expression of farnesoid × receptor (FXR) in mRNA and protein level. Immunohistochemical analysis was carried out to monitor the expression of FXR in cholangiocarcinoma tissues from 26 patients and 10 normal controls. The effects on in vivo tumor growth were also studied in nude mouse model.

Results
Free bile acids induced an increased expression of FXR; on the contrary, the conjugated bile acids decreased the expression of FXR. The FXR effect has been illustrated with the use of the FXR agonist GW4064 and the FXR antagonist GS. More specifically, when the use of free bile acids combined with FXR agonist GW4064, the tumor cell inhibitory effect was even more pronounced. But adding FXR antagonist GS into the treatment attenuated the tumor inhibitory effect caused by free bile acids. Combined treatment of GS and CDCA could reverse the regulating effect of CDCA on the expression of FXR. Administration of CDCA and GW 4064 resulted in a significant inhibition of tumor growth. The inhibitory effect in combination group (CDCA plus GW 4064) was even more pronounced. Again, the conjugated bile acid-GDCA promoted the growth of tumor. We also found that FXR agonist GW4064 effectively blocked the stimulatory effect of GDCA on tumor growth. And the characteristic and difference of FXR expressions were in agreement with previous experimental results in mouse cholangiocarcinoma tissues. There was also significant difference in FXR expression between normal and tumor tissues from patients with cholangiocarcinoma.

Conclusions
The imbalance of ratio of free and conjugated bile acids may play an important role in tumorigenesis of cholangiocarcinoma. FXR, a member of the nuclear receptor superfamily, may mediate the effects induced by the bile acids.
Long-Term Follow-Up Analysis of HD9601 Trial Comparing ABVD Versus Stanford V Versus MOPP/EBV/CAD in Patients With Newly Diagnosed Advanced-Stage Hodgkin's Lymphoma: A Study From the Intergruppo Italiano Linfomi
Authors: Chisesi Teodoro , Bellei Monica , Luminari Stefano , Montanini Antonella , Marcheselli Luigi , Levis Alessandro , Gobbi Paolo , Vitolo Umberto , Stelitano Caterina , Pavone Vincenzo , Merli Francesco , Liberati Marina , Baldini Luca , Bordonaro Roberto , Pesce Emanuela Anna , Federico Massimo 
Published: October 2011

Purpose The Intergruppo Italiano Linfomi HD9601 trial compared doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus doxorubicin, vinblastine, mechloretamine, vincristine, bleomycin, etoposide, and prednisone (Stanford V [StV]) versus the combination of mechlorethamine, vincristine, procarbazine, prednisone (MOPP) with epidoxorubicin, bleomycin, vinblastine (EBV), lomustine, doxorubicin, and vindesine (CAD) (MOPP/EBV/CAD [MEC]) for the initial treatment of advanced-stage Hodgkin's lymphoma to select which regimen would best support a reduced radiotherapy program (limited to two or fewer sites of either previous bulky or partially remitting disease). Superiority of ABVD and MEC to StV was demonstrated. We report analysis of long-term outcome and toxicity. Patients and Methods Patients with stage IIB, III, or IV were randomly assigned among six cycles of ABVD, three cycles of StV, and six cycles of MEC; radiotherapy was administered in 76, 71, and 50 patients in the three arms, respectively. Results Currently, the median follow-up is 86 months; in the prolonged observation period, eight additional failures, including two relapses, both in the StV arm, and six additional deaths in complete response were recorded. The 10-year overall survival rates were 87%, 80%, and 78% for ABVD, MEC, and StV, respectively (P = .4). The 10-year failure-free survival was 75%, 74%, and 49% in the ABVD, MEC, and StV arms, respectively (P < .001). The 10-year disease-free survival of patients treated or not with radiotherapy (RT) showed no difference for ABVD or MEC (85% v 80% and 93% v 68%), and a statistically significant difference for StV (76% v 33%; P = .004). No significant long-term toxicity was recorded. Conclusion The long-term analysis confirmed ABVD and MEC superiority to StV. The use of RT after StV was established as mandatory. ABVD is still to be considered as the standard treatment with a good balance between efficacy and toxicity.
Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer
Authors: Cuzick Jack , Dowsett Mitch , Pineda Silvia , Wale Christopher , Salter Janine , Quinn Emma , Zabaglo Lila , Mallon Elizabeth , Green Andrew R. , Ellis Ian O. , Howell Anthony , Buzdar Aman U. , Forbes John F. 
Published: October 2011

Purpose We recently reported that the mRNA-based, 21-gene Genomic Health recurrence score (GHI-RS) provided additional prognostic information regarding distant recurrence beyond that obtained from classical clinicopathologic factors (age, nodal status, tumor size, grade, endocrine treatment) in women with early breast cancer, confirming earlier reports. The aim of this article is to determine how much of this information is contained in standard immunohistochemical (IHC) markers. Patients and Methods The primary cohort comprised 1,125 estrogen receptor–positive (ER-positive) patients from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial who did not receive adjuvant chemotherapy, had the GHI-RS computed, and had adequate tissue for the four IHC measurements: ER, progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Distant recurrence was the primary end point, and proportional hazards models were used with sample splitting to control for overfitting. A prognostic model that used classical variables and the four IHC markers (IHC4 score) was created and assessed in a separate cohort of 786 patients. Results All four IHC markers provided independent prognostic information in the presence of classical variables. In sample-splitting analyses, the information in the IHC4 score was found to be similar to that in the GHI-RS, and little additional prognostic value was seen in the combined use of both scores. The prognostic value of the IHC4 score was further validated in the second separate cohort. Conclusion This study suggests that the amount of prognostic information contained in four widely performed IHC assays is similar to that in the GHI-RS. Additional studies are needed to determine the general applicability of the IHC4 score.
Frequency, Clinical Associations, and Longitudinal Course of Major Depressive Disorder in Adults With Cerebral Glioma
Authors: Rooney Alasdair G. , McNamara Shanne , Mackinnon Mairi , Fraser Mary , Rampling Roy , Carson Alan , Grant Robin 
Published: October 2011

Purpose There is a need for high-quality evidence regarding the frequency, independent clinical associations, and longitudinal course of depression in patients with cerebral glioma. Patients and Methods This was a twin-center, prospective, observational cohort study with 6-month follow-up. Consenting adults with a new diagnosis of cerebral glioma received the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition to diagnose major depressive disorder (MDD). Interviews occurred shortly after the start of radiotherapy (T1), with follow-up interviews 3 months later (T2) and 6 months later (T3). Independent associations between MDD and clinical variables were analyzed using logistic regression. Results One hundred fifty-five patients participated. The frequency of MDD was 13.5% ± 5.4% at T1 (n = 155); 14.8% ± 6.7% at T2 (n = 108); and 6.8% ± 5.3% at T3 (n = 88). Overall, 32 individuals were diagnosed with MDD during the study period (20.6% ± 6.4%). Inter-rater diagnostic agreement for MDD was good (κ = 0.81; 95% CI, 0.60 to 1.00). Independent predictors of MDD were functional impairment (odds ratio, 3.9; 95% CI, 1.5 to 10.8) and a previous history of depression (odds ratio, 2.7; 95% CI, 0.99 to 7.3). MDD persisted for at least 3 months in half of the patients with adequate follow-up, but many depressed patients also dropped out of the study as a result of clinical deterioration. Conclusion In this longitudinal study, one in five patients with glioma developed clinical depression in the 6 months after starting radiotherapy. Patients with functional impairment or previous depression were at higher risk. MDD often persisted for at least 3 months. Clinicians should seek and treat depression in adults with glioma.
End-of-Life Care and Circumstances of Death in Patients Dying As a Result of Cancer in Belgium and the Netherlands: A Retrospective Comparative Study
Authors: Meeussen Koen , Van den Block Lieve , Echteld Michael A. , Boffin Nicole , Bilsen Johan , Van Casteren Viviane , Abarshi Ebun , Donker Gé , Onwuteaka-Philipsen Bregje , Deliens Luc 
Published: October 2011

Purpose To examine and compare end-of-life care in patients with cancer dying in Belgium and the Netherlands. Patients and Methods A mortality follow-back study was undertaken in 2008 via representative nationwide sentinel networks of general practitioners (GPs) in Belgium and the Netherlands. By using similar standardized procedures, GPs reported on aspects of end-of-life care and the circumstances of nonsudden death of patients with cancer in their practice. Results Of the 422 reported patients with cancer, most resided at home during the last year of life (Belgium, 91%; the Netherlands, 95%). Death occurred at home in 34% (Belgium) and 61% (the Netherlands) and in the hospital in 29% (Belgium) and 19% (the Netherlands). In the last month of life, end-of-life issues were more often discussed in the Netherlands (88%) than in Belgium (68%). In both countries, physical problems were discussed most often (Belgium, 49%; the Netherlands, 78%) and spiritual issues least often (Belgium, 20%; the Netherlands, 32%). Certain end-of-life treatment preferences were known for 43% (Belgium) and 67% (the Netherlands) of patients. In the last week of life, treatment was most often focused on palliation (Belgium, 94%; the Netherlands, 91%). Physical distress was reported in 84% (Belgium) and 76% (the Netherlands) of patients and psychological distress in 59% and 36%. Most distressing was lack of energy (Belgium, 73%; the Netherlands, 71%) and lack of appetite (Belgium, 61%; the Netherlands, 53%). Two thirds of patients were bedridden (Belgium, 67%; the Netherlands, 69%). Conclusion Although place of death and communication about end-of-life issues differ substantially, a palliative treatment goal is adopted for the vast majority of patients in both countries. However, GPs reported that the majority of patients experienced symptom distress at the end of life, which suggests important challenges remain for improving end-of-life care.
Occult Metastases in Lymph Nodes Predict Survival in Resectable Non–Small-Cell Lung Cancer: Report of the ACOSOG Z0040 Trial
Authors: Rusch Valerie W. , Hawes Debra , Decker Paul A. , Martin Sue Ellen , Abati Andrea , Landreneau Rodney J. , Patterson G. Alexander , Inculet Richard I. , Jones David R. , Malthaner Richard A. , Cohen Robbin G. , Ballman Karla , Putnam Joe B. , Cote Richard J. 
Published: October 2011

Purpose The survival of patients with non–small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. Patients and Methods Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. Results From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). Conclusion In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.
Front-Line Therapy With Second-Generation Tyrosine Kinase Inhibitors in Patients With Early Chronic Phase Chronic Myeloid Leukemia: What Is the Optimal Response?
Authors: Jabbour Elias , Kantarjian Hagop M. , O'Brien Susan , Shan Jianqin , Quintás-Cardama Alfonso , Garcia-Manero Guillermo , Rios Mary Beth , Cortes Jorge E. 
Published: October 2011

Purpose The response definitions proposed by the European LeukemiaNet (ELN) are defined on the basis of imatinib front-line therapy. It is unknown whether these definitions apply to patients treated with second-generation tyrosine kinase inhibitors (TKIs). Patients and Methods One hundred sixty-seven patients with newly diagnosed chronic myelogenous leukemia (CML) in chronic phase were treated with second-generation TKIs in phase II trials (nilotinib, 81; dasatinib, 86). Median follow-up was 33 months. Event-free survival (EFS) was measured from the start of treatment to the date of loss of complete hematologic response, loss of complete or major cytogenetic response, discontinuation of therapy for toxicity or lack of efficacy, progression to accelerated or blastic phases, or death at any time. Results Overall, 155 patients (93%) achieved complete cytogenetic response (CCyR), including 146 (87%) with major molecular response (MMR; complete in 46 patients [28%]). According to the ELN definitions, the rates of suboptimal response were 0%, 2%, 1%, and 12% at 3, 6, 12, and 18 months of therapy, respectively. There was no difference in EFS and CCyR duration between patients who achieved CCyR with and without MMR across all the landmark times of 3, 6, 12, and 18 months. Conclusion The use of second-generation TKIs as initial therapy in CML induces high rates of CCyR at early time points. The ELN definitions of response proposed for imatinib therapy are not applicable in this setting. We propose that achievement of CCyR and partial cytogenetic response at 3 months should be considered optimal and suboptimal responses, respectively. The achievement of MMR offered no advantage over CCyR in defining long-term outcome in patients with newly diagnosed CML treated with second-generation TKIs.
Sound-induced tympanal membrane motion in bushcrickets and its relationship to sensory output
Authors: Hummel Jennifer , Kössl Manfred , Nowotny Manuela 
Published: October 2011

SUMMARYIn the auditory system of bushcrickets, sound can reach the receptors via two different paths: (i) by acting on the outside of the tympana situated on both sides of each foreleg or (ii) through the acoustic trachea that opens at a spiracle on the thorax. While the spiracle is considered to be the main point of sound entry for higher audio and ultrasonic frequencies, the role of the tympana is still unclear. The tympana border the air-filled acoustic trachea as well as the fluid-filled haemolymph channel containing the receptor organs. To understand their role during sound transduction, the sound-induced neuronal response of the hearing organ was recorded in combination with measurement of tympanal membrane motion using laser-Doppler vibrometry. For far-field stimulation, the frequency of the most sensitive hearing (∼16 kHz) matched the frequency of a pronounced maximum of tympanal membrane vibration. A second maximum of tympanum motion at lower frequencies (∼7 kHz) was correlated with an increased nerve activity at higher intensities (&gt;70 dB sound pressure level, SPL). These correlations support the hypothesis of functional coupling between tympanum motion and nerve activity. When sound stimuli were applied locally, through either the tympanum or the spiracle, significant differences between tympanum motion and nerve activity were found. These discrepancies show that tympanum motion and neuronal response are not coupled directly and that there is no linear relationship with the applied SPL. Taken together, these data verify a functional, albeit indirect, coupling of tympanum motion and sensory cell activity for one of the pronounced vibration maxima, which appears to represent a resonance frequency of the tympanum.
Thermal adaptation in the intertidal snailEchinolittorina malaccanacontradicts current theory by revealing the crucial roles of resting metabolism
Authors: Marshall David J. , Dong Yun-wei , McQuaid Christopher D. , Williams Gray A. 
Published: October 2011

SUMMARYContemporary theory for thermal adaptation of ectothermic metazoans focuses on the maximization of energy gain and performance (locomotion and foraging). Little consideration is given to the selection for mechanisms that minimize resting energy loss in organisms whose energy gain is severely constrained. We tested a hypothetical framework for thermal performance of locomotor activity (a proxy for energy gain) and resting metabolism (a proxy for energy loss) in energetically compromised snails in the littoral fringe zone, comparing this with existing theory. In contrast to theory, the thermal ranges and optima for locomotor performance and metabolic performance of Echinolittorina malaccana are mismatched, and energy gain is only possible at relatively cool temperatures. To overcome thermal and temporal constraints on energy gain while experiencing high body temperatures (23–50°C), these snails depress resting metabolism between 35 and 46°C (thermally insensitive zone). The resulting bimodal relationship for metabolism against temperature contrasts with the unimodal or exponential relationships of most ectotherms. Elevation of metabolism above the breakpoint temperature for thermal insensitivity (46°C) coincides with the induction of a heat shock response, and has implications for energy expenditure and natural selection. Time-dependent mortality is initiated at this breakpoint temperature, suggesting a threshold above which the rate of energy demand exceeds the capacity for cellular energy generation (rate of ATP turnover). Mortality in a thermal range that elevates rather than limits aerobic metabolism contrasts with the hypothesis that cellular oxygen deficiency underlies temperature-related mortality. The findings of this study point to the need to incorporate aspects of resting metabolism and energy conservation into theories of thermal adaptation.
Anthropogenic noise affects song structure in red-winged blackbirds (Agelaius phoeniceus)
Authors: Hanna Dalal , Blouin-Demers Gabriel , Wilson David R. , Mennill Daniel J. 
Published: October 2011

SUMMARY
Anthropogenic noise can mask animal signals that are crucial for communicating information about food, predators and mating opportunities. In response to noise masking, signallers can potentially improve acoustic signal transmission by adjusting the timing, frequency or amplitude of their signals. These changes can be a short-term modification in response to transient noise or a long-term modification in response to chronic noise. An animal's ability to adapt to anthropogenic noise can be crucial to its success. In this study, we evaluated the effects of anthropogenic noise on the structure of red-winged blackbird song. First, we manipulated the presence of anthropogenic noise by experimentally broadcasting either silence or low-frequency white noise to subjects inhabiting quiet marshes located away from roadsides. Subjects exhibited increased signal tonality when temporarily exposed to low-frequency white noise, suggesting that red-winged blackbirds can alter their signals rapidly in response to sudden noise. Second, we compared songs produced in quiet marshes located away from roadsides with songs produced during quiet periods at roadside marshes that are normally noisy. This allowed us to test whether birds that are exposed to chronic anthropogenic noise exhibit altered song structure during temporarily quiet periods. Subjects residing in roadside marshes that are normally polluted with anthropogenic noise sang songs with increased tonality during quiet periods. Overall, our results show that anthropogenic noise influences the structure of birdsong. These effects should be considered in conservation and wildlife management.
Sound production in red-bellied piranhas (Pygocentrus nattereri, Kner): an acoustical, behavioural and morphofunctional study
Authors: Millot Sandie , Vandewalle Pierre , Parmentier Eric 
Published: October 2011

SUMMARY
Piranhas are known to be sound-producing animals. Nevertheless, the biological significance of piranha calls remains unclear because sounds have been recorded only when specimens were held by hand or trapped in a gill net. These sounds are generated by rapid contractions of sonic muscles that insert on a broad tendon surrounding ventrally the cranial sac of the swimbladder. The piranha swimbladder is thought to play an important role in sound production as an impedance-matching device and as a resonator. However, the vibratory capacities of the cranial and caudal sacs and the exact role of both sacs in sound production remain poorly understood. In this study, three sounds were each associated to a specific behaviour. The first sound (type 1) was produced during frontal display; it had numerous pulses and lasted 140!±17 ms, with a fundamental frequency of 120±4 Hz. It corresponded to the sound made by hand-held fishes. The second sound (type 2) was produced during circling and fighting behaviour; it was a single pulse lasting 36±8 ms, with a fundamental frequency of 43±10 Hz. The third sound (type 3) corresponded to chasing behaviour and comprised three to four pulses, each lasting 3±1 ms, with a fundamental frequency of 1739±18 Hz. Using a laser vibrometer to study the swimbladder displacement when stimulated at different frequencies, it was demonstrated that the first two sounds corresponded to the swimbladder mechanism. By contrast, the third sound was associated with the jaw mechanism. The vibrometer indicated that the swimbladder is a highly damping structure, simply copying the sonic muscle contraction rate. This study provides two interesting insights. First, it shows the relationships between three kinds of piranha sound and three specific behaviours. Second, using muscle stimulation at different rates, it shows which simultaneous conditions are required for production of sound in this species. Swimbladder calls were produced by a muscle contraction rate of approximately 100 Hz because this periodicity allowed the swimbladder to vibrate. At this frequency range, the contraction–relaxation cycles of the swimbladder muscles engendered wall displacements that had short amplitudes and with only a small variability between them.