bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of Erlotinib in Patients With Advanced Biliary Cancer
Authors: Philip Philip A. , Mahoney Michelle R. , Allmer Cristine , Thomas James , Pitot Henry C. , Kim George , Donehower Ross C. , Fitch Tom , Picus Joel , Erlichman Charles 
Published: June 2006

Purpose Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months. Methods Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally. Results Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash. Conclusion Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.
The Role of UGT1A1*28 Polymorphism in the Pharmacodynamics and Pharmacokinetics of Irinotecan in Patients With Metastatic Colorectal Cancer
Authors: Toffoli Giuseppe , Cecchin Erika , Corona Giuseppe , Russo Antonio , Buonadonna Angela , D'Andrea Mario , Pasetto Lara Maria , Pessa Sergio , Errante Domenico , De Pangher Vincenzo , Giusto Mauro , Medici Michele , Gaion Fernando , Sandri Paolo , Galligioni Enzo , Bonura Salvatore , Boccalon Massimo , Biason Paola , Frustaci Sergio 
Published: June 2006

PurposeUGT1A1*28 polymorphism has been associated with decreased glucuronidation of SN38, the active metabolite of irinotecan. This could increase toxicity with this agent.Patients and MethodsIn a prospective study, 250 metastatic colorectal cancer patients were treated with irinotecan, fluorouracil, and leucovorin as first-line treatment. UGT1A1*28 polymorphism was investigated with respect to the distribution of hematologic and nonhematologic toxicity, objective response rate, and survival. Pharmacokinetics was investigated in a subgroup of patients (71 of 250) who had been analyzed with respect to toxicity and efficacy.ResultsUGT1A1*28 polymorphism was associated with a higher risk of grade 3 to 4 hematologic toxicity (odds ratio [OR], 8.63; 95% CI, 1.31 to 56.55), which was only relevant for the first cycle, and was not seen throughout the whole treatment period for patients with both variant alleles TA7/TA7compared with wild-type TA6/TA6. The response rate was also higher in TA7/TA7patients (OR, 0.32; 95% CI, 0.12 to 0.86) compared with TA6/TA6. A nonsignificant survival advantage was observed for TA7/TA7when compared with TA6/TA6patients (hazard ratio, 0.81; 95% CI, 0.45 to 1.44). Higher response rates were explained by a different pharmacokinetics with higher biliary index [irinotecan area under the curve (AUC)×(SN38 AUC/SN38G AUC)] and lower glucuronidation ratio (SN38G AUC/SN38 AUC) associated with the TA7/TA7genotype and a higher response rate, indicating that the polymorphism is functionally relevant.ConclusionThe results indicate that UGT1A1*28 polymorphism is of some relevance to toxicity; however, it is less important than discussed in previous smaller trials. In particular, the possibility of a dose reduction for irinotecan in patients with a UGT1A1*28 polymorphism is not supported by the result of this analysis.
Novel Prognostic Immunohistochemical Biomarker Panel for Estrogen Receptor–Positive Breast Cancer
Authors: Ring Brian Z. , Seitz Robert S. , Beck Rod , Shasteen William J. , Tarr Shannon M. , Cheang Maggie C.U. , Yoder Brian J. , Budd G. Thomas , Nielsen Torsten O. , Hicks David G. , Estopinal Noel C. , Ross Douglas T. 
Published: June 2006

PurposePatients with breast cancer experience progression and respond to treatment in diverse ways, but prognostic and predictive tools for the oncologist are limited. We have used gene expression data to guide the production of hundreds of novel antibody reagents to discover novel diagnostic tools for stratifying carcinoma patients.Patients and MethodsOne hundred forty novel and 23 commercial antisera, selected on their ability to differentially stain tumor samples, were used to stain paraffin blocks from a retrospective breast cancer cohort. Cox proportional hazards and regression tree analysis identified minimal panels of reagents able to predict risk of recurrence. We tested the prognostic association of these prospectively defined algorithms in two independent cohorts.ResultsIn both validation cohorts, the Kaplan-Meier estimates of recurrence confirmed that both the Cox model using five reagents (p53, NDRG1, CEACAM5, SLC7A5, and HTF9C) and the regression tree model using six reagents (p53, PR, Ki67, NAT1, SLC7A5, and HTF9C) distinguished estrogen receptor (ER) –positive patients with poor outcomes. The Cox model was superior and distinguished patients with poor outcomes from patients with good or moderate outcomes with a hazard ratio of 2.21 (P = .0008) in validation cohort 1 and 1.88 (P = .004) in cohort 2. In multivariable analysis, the calculated risk of recurrence was independent of stage, grade, and lymph node status. A model proposed for ER-negative patients failed validation in the independent cohorts.ConclusionA panel of five antibodies can significantly improve on traditional prognosticators in predicting outcome for ER-positive breast cancer patients.
Phase II Trial of Alfimeprase, a Novel-Acting Fibrin Degradation Agent, for Occluded Central Venous Access Devices
Authors: Moll Stephan , Kenyon Peter , Bertoli Luigi , De Maio James , Homesley Howard , Deitcher Steven R. 
Published: June 2006

Purpose Alfimeprase is a recombinantly produced, genetically modified variant of the metalloproteinase, fibrolase. Alfimeprase proteolytically cleaves fibrin, independent of plasminogen activation to plasmin, and directly dissolves thrombi. Based on the direct fibrin degradation effect of alfimeprase, rapid activity in patients with occluded central venous access devices (CVADs) was hypothesized. Patients and Methods We performed a phase II, randomized, double-blind, active-control, multicenter, dose-ranging study to compare the safety and efficacy of one or two instillations of three intraluminal doses of alfimeprase (0.3, 1.0, and 3.0 mg) and alteplase 2.0 mg in re-establishing patency to occluded CVADs in 55 adult patients. Results All three alfimeprase doses were more successful than alteplase during the first 15 and 30 minutes of treatment. The alfimeprase 3.0-mg dose resulted in 40%, 50%, and 60% patency restoration rates at 5, 15, and 30 minutes, respectively, compared with 0%, 0%, and 23% for alteplase. The difference at 15 minutes was highly significant (P = .0075). Alfimeprase 3.0 mg produced the highest patency rate at 120 minutes after the first (60%) and second (80%) doses. No major hemorrhagic or embolic events were reported. Conclusion A single 1- or 3-mg dose of alfimeprase has the potential to restore function to occluded CVADs rapidly and safely, and to facilitate on-time infusion of vital therapies.
Anatomic Site, Sun Exposure, and Risk of Cutaneous Melanoma
Authors: Whiteman David C. , Stickley Mark , Watt Peter , Hughes Maria Celia , Davis Marcia B. , Green Adèle C. 
Published: June 2006

Purpose Sunlight is the principal environmental risk factor for cutaneous melanoma. A current hypothesis postulates that the role of sunlight in causing melanoma differs according to anatomic site. We tested this hypothesis in a population-based case-case comparative study of melanoma patients. Methods Patients were sampled from the Queensland cancer registry in three groups: superficial spreading or nodular melanomas of the trunk (n = 154), of the head and neck (HN; n = 76), and lentigo maligna (LM) and lentigo maligna melanoma (LMM; for both LM and LMM, n = 76). Data were collected on school-age sun exposure and occupational and recreational sun exposure in adulthood. Odds ratios (OR) and 95% CIs were calculated using polytomous logistic regression. Results HN melanoma patients were substantially more likely than trunk patients to have higher levels of sun exposure in adulthood (OR, 2.43; 95% CI, 0.98 to 5.99) and specifically, higher levels of occupational exposure (OR, 3.25; 95% CI, 1.32 to 8.00), but lower levels of recreational sun exposure (OR, 0.50; 95% CI, 0.21 to 1.19). LM and LMM patients reported higher occupational exposure and lower recreational sun exposure than trunk melanoma patients, although this was not significant. We found no significant differences between the groups for school-age sun exposures. Conclusion Melanomas developing at different body sites are associated with distinct patterns of sun exposure. Melanomas of the head and neck are associated with chronic patterns of sun exposure whereas trunk melanomas are associated with intermittent patterns of sun exposure, supporting the hypothesis that melanomas may arise through divergent causal pathways.
Evidence for a respiratory component, similar to mammalian respiratory sinus arrhythmia, in the heart rate variability signal from the rattlesnake,Crotalus durissus terrificus
Authors: Campbell Hamish A. , Leite Cleo A. C. , Wang Tobias , Skals Marianne , Abe Augusto S. , Egginton Stuart , Rantin F. Tadeu , Bishop Charles M. , Taylor Edwin W. 
Published: June 2006

SUMMARYAutonomic control of heart rate variability and the central location of vagal preganglionic neurones (VPN) were examined in the rattlesnake(Crotalus durissus terrificus), in order to determine whether respiratory sinus arrhythmia (RSA) occurred in a similar manner to that described for mammals. Resting ECG signals were recorded in undisturbed snakes using miniature datalogging devices, and the presence of oscillations in heart rate (fh) was assessed by power spectral analysis (PSA). This mathematical technique provides a graphical output that enables the estimation of cardiac autonomic control by measuring periodic changes in the heart beat interval. At fh above 19 min-1spectra were mainly characterised by low frequency components, reflecting mainly adrenergic tonus on the heart. By contrast, at fhbelow 19 min-1 spectra typically contained high frequency components, demonstrated to be cholinergic in origin. Snakes with a fh &gt;19 min-1 may therefore have insufficient cholinergic tonus and/or too high an adrenergic tonus acting upon the heart for respiratory sinus arrhythmia (RSA) to develop. A parallel study monitored fh simultaneously with the intraperitoneal pressures associated with lung inflation. Snakes with a fh&lt;19 min-1 exhibited a high frequency (HF) peak in the power spectrum,which correlated with ventilation rate (fv). Adrenergic blockade by propranolol infusion increased the variability of the ventilation cycle, and the oscillatory component of the fh spectrum broadened accordingly. Infusion of atropine to effect cholinergic blockade abolished this HF component, confirming a role for vagal control of the heart in matching fh and fv in the rattlesnake. A neuroanatomical study of the brainstem revealed two locations for vagal preganglionic neurones (VPN). This is consistent with the suggestion that generation of ventilatory components in the heart rate variability (HRV)signal are dependent on spatially distinct loci for cardiac VPN. Therefore,this study has demonstrated the presence of RSA in the HRV signal and a dual location for VPN in the rattlesnake. We suggest there to be a causal relationship between these two observations.
Characterization of diurnal urea excretion in the mangrove killifish,Rivulus marmoratus
Authors: Rodela Tammy M. , Wright Patricia A. 
Published: June 2006

SUMMARYAn unusual characteristic of nitrogen excretion in the ammoniotelic mangrove killifish Rivulus marmoratus is that urea is excreted(Jurea) in a distinct diurnal pattern, whereas ammonia is excreted (Jamm) at a steady rate. In this study we tested the hypothesis that the diurnal pattern in R. marmoratus is an endogenously generated pattern that is characterized as a circadian rhythm. This hypothesis was tested by measuring Jurea and Jamm following manipulation of feeding or lighting regimes. The diurnal Jurea pattern in food-deprived R. marmoratus had a 24 h periodicity under normal conditions of 12 h:12 h light:dark (12:12 L:D) with 72% more urea excreted during 12:00 h and 18:00 h. In contrast, there was no significant pattern in Jamm. Fed fish (12:12 L:D) demonstrated a diurnal pattern in both Jurea and Jamm with up to an eightfold increase in excretion rates compared with rates obtained from food-deprived fish. Patterns of Jurea were free running with a 24 h period under conditions of continuous darkness (0:24 L:D). Exposure to an inverse photoperiod (12:12 D:L) resulted in entrainment of the Jurea pattern to the new photoperiod, with the highest rates of excretion occurring during midday of the new photoperiod. In contrast to R. marmoratus, nitrogen excretion rates in the zebrafish Danio rerio remained constant over time. The results of this study show that Jurea in R. marmoratus demonstrates the characteristics of a circadian rhythm: a 24 h periodicity, a free-running rhythm in continuous conditions, and entrainment to new photoperiods.
Metabolic substrate use and the turnover of endogenous energy reserves in broad-tailed hummingbirds (Selasphorus platycercus)
Authors: Carleton Scott A. , Bakken Bradley Hartman , del Rio Carlos Martínez 
Published: June 2006

SUMMARYWe fed broad-tailed hummingbirds (Selasphorus platycercus) diets of contrasting carbon isotope composition and measured changes in theδ 13C of expired breath through time. By measuring theδ 13C in the breath of fed and fasted birds we were able to quantify the fraction of metabolism fueled by assimilated sugars and endogenous energy reserves. These measurements also allowed us to estimate the fractional turnover of carbon in the hummingbirds' energy reserves. When hummingbirds were feeding, they fueled their metabolism largely (≈90%) with assimilated sugars. The rate of carbon isotope incorporation into the energy reserves of hummingbirds was higher when birds were gaining as opposed to losing body mass. The average residence time of a carbon atom in the hummingbirds' energy reserves ranged from 1 to 2 days.
Tiger moth responses to a simulated bat attack: timing and duty cycle
Authors: Barber J. R. , Conner W. E. 
Published: June 2006

SUMMARYMany night-flying insects perform complex, aerobatic escape maneuvers when echolocating bats initiate attack. Tiger moths couple this kinematic defense with an acoustic reply to a bat's biosonar-guided assault. The jamming hypothesis for the function of these moth sounds assumes that tiger moth clicks presented at high densities, temporally locked to the terminal phase of the bat attack will produce the greatest jamming efficacy. Concomitantly, this hypothesis argues that moths warning bats of bad tasting chemicals sequestered in their tissues should call early to give the bat time to process the meaning of the warning signal and that moths calling at low duty cycles are more likely to employ such an aposematic strategy. We report here the first investigation of a tiger moth assemblage's response to playback of a bat echolocation attack sequence. This assemblage of arctiid moths first answered the echolocation attack sequence 960±547 ms (mean ± s.d.) from the end of the bat attack. The assemblage reached a half-maximum response shortly after the first response, at 763±479 ms from the end of the terminal buzz. Tiger moth response reached a maximum at 475±344 ms from the end of the sequence; during the approach phase, well before the onset of the terminal buzz. In short, much of tiger moth response to bat attack occurs outside of the jamming hypotheses' predictions. Furthermore, no relationship exists between the duty cycle of a tiger moth's call (and thus the call's probability of jamming the bat) and its temporal response to bat attack. These data call into doubt the assumptions behind the jamming hypothesis as currently stated but do not directly test the functionality of arctiid sounds in disrupting echolocation in bat-moth aerial battles.
Performance-enhancing role of dietary fatty acids in a long-distance migrant shorebird: the semipalmated sandpiper
Authors: Maillet Dominique , Weber Jean-Michel 
Published: June 2006

SUMMARYAt the end of summer, semipalmated sandpipers (Calidris pusilla)traveling from the Arctic stop in the Bay of Fundy (east coast of Canada) to build large fat reserves before a non-stop flight to South America. During a 2-week stopover, the body mass of this small shorebird is doubled (∼20 g to 40 g) by feeding on a burrowing amphipod, Corophium volutator,that contains unusually high levels of n-3 polyunsaturated fatty acids (PUFA). In mammals, high n-3 PUFA content of membrane phospholipids (PL) is linked to improved exercise performance due to increased membrane fluidity that accelerates transmembrane lipid transport. We hypothesized that dietary n-3 PUFA could be used as a natural `performance-enhancing substance' by semipalmated sandpipers to prepare their flight muscles for migration. Also,PUFA stored as fuel in neutral lipids (NL) can be mobilized more quickly than saturated fatty acids, but they contain less energy per unit mass. It is therefore unclear whether dietary fatty acids are modified before storage. Birds were collected at various stages of fat loading to examine changes in the composition of tissue PL (membranes) and NL (fuel stores). Results show that dietary n-3 PUFA are incorporated in tissue lipids in less than 2 weeks. During the stopover, the double bond index of muscle PL increases by 25% and the fatty acid profiles of both muscle PL and adipose NL converge with that of the diet. However, &gt;50% of dietary n-3 PUFA are converted to other fatty acids before storage, mainly to oleate (18:1), possibly because monounsaturates offer a compromise between high energy density and ease of mobilization. This study shows that long-distance migrant birds can (1) use natural diets rich in specific lipids to prime flight muscles for endurance exercise, and (2) modify dietary fatty acids before storing them as fuel.
Acoustic radiation from the head of echolocating harbor porpoises(Phocoena phocoena)
Authors: Au Whitlow W. L. , Kastelein Ronald A. , Benoit-Bird Kelly J. , Cranford Ted W. , McKenna Megan F. 
Published: June 2006

SUMMARY
An experiment was conducted to investigate the sound pressure patterns on the melon of odontocetes by using four broadband hydrophones embedded in suction cups to measure echolocation signals on the surface of the forehead of two harbor porpoises (Phocoena phocoena). It has long been hypothesized that the special lipids found in the melon of odontocetes, and not in any other mammals, focus sounds produced in the nasal region that then propagate through the melon, producing a beam that is directional in both the horizontal and vertical planes. The results of our measurements supported the melon-focusing hypothesis, with the maximum click amplitude, representing the axis of the echolocation beam, located approximately 5.6-6.1 cm from the edge of the animal's upper lip along the midline of the melon. The focusing is not sharp but is sufficient to produce a transmission beam of about 16°. Click amplitude dropped off rapidly at locations away from the location of site of maximum amplitude. Based on comparisons of forehead anatomy from similar sized porpoises, the beam axis coincided with a pathway extending from the phonic lips through the axis of the low-density/low sound velocity lipid core of the melon. The significant interaction between click number and hydrophone position suggests that the echolocation signals can take slightly different pathways through the melon, probably as a result of how the signals are launched by the production mechanism and the position of the acoustically reflective air sacs.
Evidence for a role of orcokinin-related peptides in the circadian clock controlling locomotor activity of the cockroachLeucophaea maderae
Authors: Hofer Sabine , Homberg Uwe 
Published: June 2006

SUMMARYThe accessory medulla (AMe), a small neuropil in the optic lobe, houses the master circadian clock in the brain of the cockroach Leucophaea maderae and controls circadian rhythms in locomotor activity. Recently,members of the orcokinin family of crustacean neuropeptides were identified in a cockroach and a locust and were shown by immunocytochemistry to be prominently present in the AMe. In the cockroach L. maderae, about 30 neurons in five of six established cell groups of the AMe showed orcokinin immunostaining. By means of tracer injections into one AMe and immunostaining with anti-orcokinin antiserum, we show here that one orcokinin-immunoreactive ventral neuron and three ventromedian neurons directly connect both AMae. To determine a possible circadian function of orcokinin in the cockroach, we injected 150 fmol Asn13-orcokinin into the vicinity of the AMe at different circadian times. These experiments resulted in stable phase-dependent phase shifts of circadian locomotor activity of the cockroach. The shape of the resulting phase-response curve closely matched the phase-shifting effects of light pulses, and its amplitude was dependent on the amount of the injected peptide. Together with the anatomical data, the results suggest that orcokinin-related peptides play an important role in light entrainment pathways to the circadian clock via the contralateral compound eye. This study, furthermore, provides the first evidence for a physiological role of an orcokinin-related peptide in insects.