bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long‐term effects on recurrence and mortality: A randomized trial among head and neck cancer patients
Authors: Meyer François , Bairati Isabelle , Fortin André , Gélinas Michel , Nabid Abdenour , Brochet François , Têtu Bernard 
Published: December 2007

AbstractThere has been concern that the efficacy of radiation therapy may be reduced when patients smoke or take antioxidant vitamins during treatment. Cancer prevention trials with beta carotene supplements documented adverse effects only among smokers. We conducted a randomized trial with alpha tocopherol (400 IU/day) and beta carotene (30 mg/day) supplements among 540 head and neck cancer (HNC) patients treated by radiation therapy. We examined whether smoking during radiation therapy modified the effects of the supplementation on HNC recurrence and on mortality. During the follow‐up, 119 patients had a HNC recurrence and 179 died. Cox models were used to test the interaction between smoking and supplementation and to estimate the hazard ratios (HR) for HNC recurrence and death associated with the supplementation. Cigarette smoking either before or after radiation therapy did not modify the effects of the supplementation. In contrast, the interactions between supplementation and cigarette smoking during radiation therapy were statistically significant for HNC recurrence (p = 0.03), all‐cause mortality (p = 0.02) and mortality from the initial HNC (p = 0.04). Among cigarette smokers, the HR were 2.41 (95% CI: 1.25–4.64) for recurrence, 2.26 (95% CI: 1.29–3.97) for all‐cause mortality and 3.38 (95% CI: 1.11–10.34) for HNC mortality. All corresponding HR among nonsmokers were close to 1. These results could best be explained by the hypothesis that the combined exposures reduced the efficacy of radiation therapy. Particular attention should be devoted to prevent patients from both smoking and taking antioxidant supplements during radiation therapy. © 2007 Wiley‐Liss, Inc.
The impact of tobacco smoking and alcohol drinking on survival of patients with non‐Hodgkin lymphoma
Authors: Talamini Renato , Polesel Jerry , Spina Michele , Chimienti Emanuela , Serraino Diego , Zucchetto Antonella , Zanet Ernesto , Franceschi Silvia , Tirelli Umberto 
Published: December 2007

AbstractTobacco smoking and alcohol consumption have not been clearly related to the risk of non‐Hodgkin lymphoma (NHL), and the impact of these two factors on survival of NHL patients has received little attention. Cases were 268 subjects with incident histologically‐confirmed NHL, admitted as inpatients to the Division of Medical Oncology, between 1983 and 2002. These individuals were enrolled as cases in case‐control studies conducted at the same institution over the same period. For all patients clinical (histological subtype, major prognostic factors and treatment) and epidemiological data (smoking and drinking habits) were available. Survival analysis was performed using Kaplan‐Meier methods. Hazard ratio (HR) was estimated by Cox proportional hazard model. Compared to never smokers, patients who smoked ≥20 cigarettes/day had higher risks of death (HR = 1.70, 95% confidence interval (CI): 1.06–2.73) and lower survivals at 5 years (60 and 46%, respectively). Likewise, patients who drunk ≥4 drinks/day showed 1.69‐fold higher probability of death (95% CI: 1.04–2.76) in comparison to drinkers of <2 drinks/day (5‐year survival: 47 and 67%, respectively). When combining exposure to alcohol and tobacco, no excess of death emerged in light drinkers (<4 drinks/day), irrespective of their smoking habits, but higher risks of death emerged among heavy drinkers. In the present study, heavy tobacco smoking, and particularly, heavy alcohol drinking were associated with poor survival in NHL patients. Our findings strongly encourage physicians to advice NHL patients to stop smoking and diminish alcohol consumption to obtain improvements in the course of NHL. © 2007 Wiley‐Liss, Inc.
Evidence that senescent human prostate epithelial cells enhance tumorigenicity: Cell fusion as a potential mechanism and inhibition by p16INK4a and hTERT
Authors: Bhatia Bobby , Multani Asha S. , Patrawala Lubna , Chen Xin , Calhoun‐Davis Tammy , Zhou Jianjun , Schroeder Lisa , Schneider‐Broussard Robin , Shen Jianjun , Pathak Sen , Chang Sandy , Tang Dean G. 
Published: December 2007

AbstractNormal human prostate (NHP) epithelial cells undergo senescence in vitro and in vivo but the potential role of senescent NHP cells in prostate tumorigenesis remain unclear. Here we show that senescent NHP cells enhance the in vivo tumorigenicity of low‐tumorigenic LNCaP prostate cancer and low/non‐tumorigenic subset of cells (called L cells) isolated from multiple bulk‐cultured prostate (and other) cancer cell lines. Subsequent studies suggest cell–cell fusion as a potential mechanism for senescent NHP cell‐enhanced tumor development. Using fluorescently tagged tumor cells and/or NHP cells, we find that NHP cells, like fibroblasts, can undergo fusion with unfractionated tumor cells or the L cells. Using 293T‐L cells as the model cell system, we verify NHP and 293T‐L cell fusion by using differential RT‐PCR, karyotyping, and gene expression analyses. Further experiments demonstrate that senescent NHP cells that have lost progenitor markers, accumulated p16INK4a (p16) protein expression, and acquired the AR mRNA expression, appear to be the preferential fusion targets. Strikingly, the tumorigenicity of the NHP/293T‐L hybrid cells was inhibited by exogenous p16 as well as hTERT. Chromosomal analyses revealed that hTERT probably inhibited the in vivo tumorigenicity by maintaining genomic stability. These results suggest that senescent NHP cells, like senescent fibroblasts, may promote tumor development and that one of the mechanisms underlying the senescent NHP cell‐enhanced tumorigenicity could be through cell fusion. © 2007 Wiley‐Liss, Inc.
Does inhibition of degradation of hypoxia‐inducible factor (HIF) α always lead to activation of HIF? lessons learnt from the effect of proteasomal inhibition on HIF activity
Authors: Kaluz Stefan , Kaluzová Milota , Stanbridge Eric J 
Published: December 2007

AbstractAt the cellular level hypoxia induces transcriptional response that is mediated by the transcription factor hypoxia‐inducible factor (HIF). HIF is regulated at the level of its α subunit by 2‐oxoglutarate (2OG)‐dependent oxygenases that hydroxylate specific prolyl and asparaginyl residues of HIF‐α, affecting its stability and activity, respectively. In the presence of O2, the α subunit is degraded in a complex process with several distinct steps. In the first step, the degradation process is initiated by prolyl hydroxylases (PHDs). In the second step, the von Hippel‐Lindau (VHL)/E3 ligase complex recognizes the hydroxylated HIF‐α and mediates its polyubiquitylation by the ubiquitin‐conjugating enzyme E2. In the third step, the polyubiquitylated HIF‐α is translocated to the proteasome where it is degraded. Degradation of HIF‐α can be inhibited at any of the three levels either by various pharmacological inhibitors or due to inactivation of genes whose products regulate the HIF system. The emerging data about inactivation of HIF under conditions of proteasomal inhibition prompted us to provide an overview contrasting the outcome of inhibition at various stages of the degradative pathway for HIF activity. J. Cell. Biochem. 104: 536–544, 2008. © 2007 Wiley‐Liss, Inc.
Renal and carotid vascular resistance assessed with Doppler sonography
Authors: Ohta Yuko , Fujii Koji , Ibayashi Setsuro , Matsumura Kiyoshi , Tsuchihashi Takuya , Kitazono Takanari , Ooboshi Hiroaki , Kamouchi Masahiro , Hirakata Hideki , Ogata Toshiyasu , Kuroda Junya , Iida Mitsuo 
Published: December 2007

AbstractPurposeResistance index (RI) is widely used for the evaluation of circulatory resistance and atherosclerosis with Doppler sonography, but differences in RI among vascular beds have not been fully elucidated. The present study was designed to evaluate the relationship between renal and carotid artery RI and to compare their relative risk factors for an increase in RI.MethodsOne hundred eighty‐five inpatients who underwent sonographic assessment of the renal and carotid arteries were enrolled in the study.ResultsMultivariate analyses revealed that age, pulse pressure (PP), and serum glucose level were positively correlated, whereas diastolic blood pressure (DBP) and creatinine clearance were negatively correlated with the RI of the interlobar arteries. Sex (male) and PP correlated positively, whereas DBP correlated negatively with the RI of the common carotid artery (CCA). The RI of the interlobar arteries was positively associated with that of the CCA, even after adjustment for major cardiovascular risk factors.ConclusionsThese findings suggest that RI of the renal and carotid arteries increase in parallel to a certain extent. On the other hand, risk factors for the increase of RI of the carotid and renal arteries differed in part, suggesting that specific control of respective risk factors may also be needed to prevent vascular damage in each vascular bed. © 2007 Wiley Periodicals, Inc. J Clin Ultrasound, 2008
MR angiography of the pedal arteries with gadobenate dimeglumine, a contrast agent with increased relaxivity, and comparison with selective intraarterial DSA
Authors: Kreitner Karl‐Friedrich , Kunz R. Peter , Herber Sascha , Martenstein Sonja , Dorweiler Bernhard , Dueber Christoph 
Published: December 2007

AbstractPurposeTo compare gadobenate dimeglumine (Gd‐BOPTA)–enhanced MR angiography (i.e., contrast‐enhanced MRA [CE‐MRA]) of the pedal vasculature with selective digital subtraction angiography (DSA) in patients with peripheral arterial occlusive disease (PAOD).Materials and MethodsA total of 22 patients with PAOD were prospectively examined at 1.5T. For contrast enhancement, 0.1 mmol/kg body weight of Gd‐BOPTA were applied. MRA consisted of dynamic imaging with acquisition of six consecutive data sets. Acquisition time for each data set was 24 seconds, voxel size was 1.0 × 1.0 × 1.3 mm3. A total of 20 out of 22 patient underwent selective DSA, two patients fine‐needle DSA. DSA and MRA were performed within seven days. Image analysis was independently done by two observers with assessment of overall image quality, motion artifacts, detection of patent vessel segments of the distal calf and pedal vessels, and the number of patent metatarsal arteries. After four weeks, a consensus reading of DSA images was done. A second consensus reading of CE‐MRA was performed after a further six weeks.ResultsConsensus readings of MRA and DSA revealed higher image quality and fewer motion artifacts for MRA (P = 0.021 and P = 0.008, respectively, sign test); interobserver agreement was good (κ = 0.78) for image quality, and moderate (κ = 0.46) for motion artifacts. There were no differences between CE‐MRA and DSA in detecting patent vessel segments with a high degree of agreement (κ = 0.89), and interobserver agreement for MRA was substantial (κ = 0.89). Significantly more vessels were assessed as partially occluded on DSA than on CE‐MRA (P = 0.004). There was a good agreement between DSA and CE‐MRA for assessment of relevant vessel stenosis (κ = 0.61); interobserver agreement for MRA was good (κ = 0.65). CE‐MRA detected significantly more patent metatarsal arteries than did DSA (P < 0.001).ConclusionGd‐BOPTA–enhanced MRA is comparable to DSA for assessment of the pedal vasculature, and is able to delineate significantly more patent vessels without segmental occlusions and more metatarsal arteries than selective DSA. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Improvement in the reproducibility of region of interest using an auditory feedback loop: A pilot assessment using dynamic contrast‐enhanced (DCE) breast MR images
Authors: Chun Hee , Clymer Bradley , Sammet Steffen , Koch Regina M. , Stevens Robert , Knopp Michael V. 
Published: December 2007

AbstractPurposeTo augment traditional visual data perception of complex multiparametric imaging data sets by adding auditory feedback to improve the delineation of regions of interest (ROIs) in tumor assessment in dynamic contrast‐enhanced (DCE) MRI.Materials and MethodsIn addition to conventional display methodologies, we have created an application window which interfaces with audio output using dynamically loadable sound modules, providing goodness of fit (GF) information through auditory feedback. We have assessed effectiveness of conveying sound information with three independent readers on eight DCE‐MR breast image data sets. The assessment was based on either conventional visual only mode or combined visual plus auditory mode. For statistical comparison between two sensory approaches, interobserver repeatability was measured with three different criteria.ResultsAdding auditory feedback improves repeatability significantly (P< 0.01), and the enhanced sensory approach had higher repeatability than visual only mode in visually complex breast tumor cases. However, in easy and moderate cases, visual only mode was more reproducible than the combined mode with very high significance (P< 0.001).ConclusionAdding auditory information to visual based image analysis for identifying tumor ROIs provides higher interobserver repeatability for analyzing complex multidimensional/multiparametric medical image data sets with visually difficult lesions to delineate. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Measurement of longitudinal (T1) relaxation in the human lung at 3.0 Tesla with tissue‐based and regional gradient analyses
Authors: Nichols Michael B. , Paschal Cynthia B. 
Published: December 2007

AbstractPurposeThe purpose of this study is to measure the longitudinal (T1) relaxation time of human lung parenchyma at 3.0 Tesla (T), independent of large vessel signal, and to examine T1 as a function of position in gravitational, isogravitational, and radial planes.Materials and MethodsSixteen subjects were imaged. A series of 16–20 turbo field echo images was acquired over a 6‐s period after the application of a single nonselective inversion (180°) pulse. Tissue‐based segmentation was used to separate parenchymal tissue from large pulmonary vascular tissue in the resulting images. Time‐intensity curves for each tissue type were constructed and spin‐lattice relaxation time was determined by line‐fitting the time‐intensity curves. The lung slice was divided into 10 regions of interest in the gravitational, isogravitational, and radial directions and regional T1 versus position gradient analyses were performed.ResultsThe T1 relaxation time of human lung parenchyma at 3.0T was determined to be 1374 ± 226 ms, while the T1 of blood in large pulmonary vessels was 1623 ± 236 ms. Whole lung T1 was found to be 1397 ± 214 ms. T1 of lung parenchyma was found to be significantly shorter than the T1 of blood in large pulmonary vessels and whole lung T1. No regional gradient was seen in the gravitational or isogravitational directions, but a significant gradient was seen in the radial direction. J. Magn. Reson. Imaging 2007. © 2007 Wiley‐Liss, Inc.
Fragmentation of aromatic sulfonamides in electrospray ionization mass spectrometry: elimination of SO2 via rearrangement
Authors: Sun Mingjiang , Dai Wenning , Liu David Q. 
Published: December 2007

AbstractArylsulfonamides are attractive pharmacophores for drug candidates. Fragmentation behaviors of selected aromatic sulfonamides were investigated using electrospray ionization mass spectrometry in the positive ion mode. Some of the sulfonamides afforded unique loss of 64 (loss of SO2) ions upon collision‐induced dissociation followed by intramolecular rearrangements in the gas phase. This SO2 elimination‐rearrangement pathway leading to the generation of [M + H − SO2]+ ions appeared to be susceptible to substitutions on the aromatic (Ar) ring that would affect the Arsulfur bond strength and the stability of the partially positive charge developed at the ipso position upon bond dissociation. Electron withdrawing groups such as chlorine attached to the aromatic ring at ortho position seem to promote the SO2 extrusion. Although this fragmentation pathway in atmospheric pressure ionization MS is less predictable than in electron impact MS, it is a frequently encountered reaction. The absence of this fragmentation pathway in some of the arylsulfonamides indicates that other factors such as nucleophilicity of the nitrogen may also play a role in the process. With respect to the site of attachment of the migrating NR′R″, ipso‐substitution on the aromatic ring is evident since this fragmentation mechanism is operative in the fully ortho‐substituted arylsulfonamides. Copyright © 2007 John Wiley & Sons, Ltd.
Posaconazole (Noxafil, SCH 56592), a new azole antifungal drug, was a discovery based on the isolation and mass spectral characterization of a circulating metabolite of an earlier lead (SCH 51048)
Authors: Nomeir Amin A. , Pramanik Birendra N. , Heimark Larry , Bennett Frank , Veals John , Bartner Peter , Hilbert Maryjane , Saksena Anil , McNamara Paul , Girijavallabhan Viyyoor , Ganguly Ashit K. , Lovey Raymond , Pike Russell , Wang Haiyan , Liu Yi‐Tsung , Kumari Pramila , Korfmacher Walter , Lin Chin‐Chung , Cacciapuoti Anthony , Loebenberg David , Hare Roberta , Miller George , Pickett Cecil 
Published: December 2007

AbstractPosaconazole (SCH 56592) is a novel triazole antifungal drug that is marketed in Europe and the United States under the trade name ‘Noxafil’ for prophylaxis against invasive fungal infections. SCH 56592 was discovered as a possible active metabolite of SCH 51048, an earlier lead. Initial studies have shown that serum concentrations determined by a microbiological assay were higher than those determined by HPLC from animals dosed with SCH 51048. Subsequently, several animals species were dosed with 3H‐SCH 51048 and the serum was analyzed for total radioactivity, SCH 51048 concentration and antifungal activity. The antifungal activity was higher than that expected based on SCH 51048 serum concentrations, confirming the presence of active metabolite(s). Metabolite profiling of serum samples at selected time intervals pinpointed the peak that was suspected to be the active metabolite. Consequently, 3H‐SCH 51048 was administered to a large group of mice, the serum was harvested and the metabolite was isolated by extraction and semipreparative HPLC. LC‐MS/MS analysis suggested that the active metabolite is a secondary alcohol with the hydroxyl group in the aliphatic side chain of SCH 51048. All corresponding monohydroxylated diastereomeric mixtures were synthesized and characterized. The HPLC retention time and LC‐MS/MS spectra of the diastereomeric secondary alcohols of SCH 51048 were similar to those of the isolated active metabolite. Finally, all corresponding individual monohydroxylated diasteriomers were synthesized and evaluated for in vitro and in vivo antifungal potencies, as well as pharmacokinetics. SCH 56592 emerged as the candidate with the best overall profile. Copyright © 2007 John Wiley & Sons, Ltd.
Glutathione content as a potential mediator of the vulnerability of cultured fetal cortical neurons to ethanol‐induced apoptosis
Authors: Maffi Shivani Kaushal , Rathinam Mary Latha , Cherian Priscilla P. , Pate William , Hamby‐Mason Rhoda , Schenker Steven , Henderson George I. 
Published: December 2007

AbstractEthanol ingestion during pregnancy elicits damage to the developing brain, some of which appears to result from enhanced apoptotic death of neurons. A consistent characteristic of this phenomenon is a highly differing sensitivity to ethanol within specific neuron populations. One possible explanation for this “selective vulnerability” could be cellular variations in glutathione (GSH) homeostasis. Prior studies have illustrated that ethanol elicits apoptotic death of neurons in the developing brain, that oxidative stress may be an underlying mechanism, and that GSH can be neuroprotective. In the present study, both multiphoton microscopy and flow cytometry demonstrate a striking heterogeneity in GSH content within cortical neuron populations. Ethanol differentially elicits apoptotic death and oxidative stress in these neurons. When neuron GSH content is reduced by treatment with butathione sulfoxamine, the ethanol‐mediated enhancement of reactive oxygen species is exacerbated. Sorting of cells into high‐ and low‐GSH populations further exemplifies ethanol‐mediated oxidative stress whereby apoptotic indices are preferentially elevated in the low‐GSH population. Western blot analysis of the low‐GSH subpopulations shows higher ethanol‐mediated expression of active caspase 3 and 24‐kDa PARP‐1 fragments compared with the high‐GSH subpopulation. In addition, neuronal content of 4‐hydroxynonenal adducts is higher in low‐GSH neurons in response to ethanol. These studies suggest that GSH content is an important predictor of neuronal sensitivity to ethanol‐mediated oxidative stress and subsequent cell death. The data support the proposition that the differences in proapoptotic responses to ethanol within specific neuron populations reflect a heterogeneity of neuron GSH content. © 2007 Wiley‐Liss, Inc.
Postnatal developmental regulation of Bcl‐2 family proteins in brain mitochondria
Authors: Soane Lucian , Siegel Zachary T. , Schuh Rosemary A. , Fiskum Gary 
Published: December 2007

AbstractAlthough it has been long recognized that the relative balance of pro‐ and antiapoptotic Bcl‐2 proteins is critical in determining the susceptibility to apoptotic death, only a few studies have examined the level of these proteins specifically at mitochondria during postnatal brain development. In this study, we examined the age‐dependent regulation of Bcl‐2 family proteins using rat brain mitochondria isolated at various postnatal ages and from the adult. The results indicate that a general down‐regulation of most of the proapoptotic Bcl‐2 proteins present in mitochondria occurs during postnatal brain development. The multidomain proapoptotic Bax, Bak, and Bok are all expressed at high levels in mitochondria early postnatally but decline in the adult. Multiple BH3‐only proteins, including direct activators (Bid, Bim, and Puma) and the derepressor BH3‐only protein Bad, are also present in immature brain mitochondria and are down‐regulated in the adult brain. Antiapoptotic Bcl‐2 family members are differentially regulated, with a shift from high Bcl‐2 expression in immature mitochondria to predominant Bcl‐xL expression in the adult. These results support the concept that developmental differences in upstream regulators of the mitochondrial apoptotic pathway are responsible for the increased susceptibility of cells in the immature brain to apoptosis following injury. © 2007 Wiley‐Liss, Inc.