bluuebunny/crossref_metadata_2025 huggingface dataset:
Merkel cell carcinoma of the head and neck: Is adjuvant radiotherapy necessary?
Authors: Clark Jonathan R. , Veness Michael J. , Gilbert Ralph , O'Brien Christopher J. , Gullane Patrick J.
Published: December 2006

Background.

Controversy exists regarding the optimal management of patients with Merkel cell carcinoma. The primary aim of this study was to determine whether combined treatment with surgery and radiotherapy improves outcome in a multi‐institutional cohort of patients with Merkel cell carcinoma of the head and neck. The secondary aims were to determine by stage, which patients derive benefit from combined therapy and to identify predictors for survival on multivariable analysis.

Methods.

A retrospective analysis of 110 patients with Merkel cell carcinoma of the head and neck was performed. Data were collected from 3 tertiary care institutions (Westmead Hospital, Sydney, Australia; Princess Margaret Hospital, Toronto, Canada; Royal Prince Alfred Hospital, Sydney). There were 78 males and 32 females, median age was 70 years, and mean follow‐up of survivors was 2.3 years. Sixty‐six patients underwent combined treatment, and 44 patients had either surgery or radiotherapy alone. Analysis by stage was performed using 2 staging systems.

Results.

Local and regional control at 5 years was 84% and 69%, respectively. Combined treatment improved both local (p = .009) and regional control (p = .006). Overall and disease‐specific survival at 5 years was 49% and 62%, respectively. Combined treatment was associated with significantly better disease‐free survival on univariable analysis (p = .013) When analyzed by stage, patients with stage IIb (primary >1 cm, node negative) disease who underwent combined treatment had improved disease‐free (p = .005) and disease‐specific survival (p = .035). Predictors of survival on multivariable analysis were age >70 years (HR 6.19, p < .001), primary tumor size >1 cm (HR 7.55, p < .001), number of nodal metastases divided into none, ≤ 2 and >2 (HR 3.71 per stratum, p < .001). When analyzed with age and disease stage, treatment modality trended toward significance as a predictor of disease‐specific (p = .081) and overall survival (p = .076). Disease stage was the most powerful independent predictor on Cox regression (HR 5.43 per stratum, p < .001).

Conclusions.

Merkel cell carcinoma is an aggressive cutaneous malignancy. Age and disease stage are the most important predictors of survival. Combined surgery and radiotherapy improves both locoregional control and disease‐free survival. Patients with stage II disease appear to derive the greatest benefit from adjuvant radiotherapy, including improved disease specific survival. © 2006 Wiley Periodicals, Inc. Head Neck, 2007.
Pilot study of intraoperative chemotherapy with cisplatin and 5‐fluorouracil in patients with advanced squamous cell carcinoma of the head and neck
Authors: Tulunay Ozlem E. , Enamorado Ileana I. , Kucuk Omer , Heilbrun Lance K. , Otero Jose E. , Korkmaz Hakan , Blumberg Robert , Jacobs John R.
Published: December 2006

Background.

Intraoperative manipulation of the tumor during cancer surgery has long been recognized as a source of metastasis and contamination of the surgical wound during tumor removal. We explored the use of intraoperative chemotherapy to minimize the risk of tumor cell implantation and metastasis during head and neck cancer surgery and conducted a dose escalating intraoperative chemotherapy clinical trial designed to assess the feasibility of this approach and associated toxicities in patients with advanced squamous cell carcinoma of the head and neck.

Methods.

Fourteen patients were treated with 5‐fluorouracil at a dose of 1000 mg/m2 administered intravenously over an 8‐hour period during the surgery with simultaneous cisplatin. The cisplatin dose was escalated and toxicity observed. Cisplatin at 75 mg/m2 was chosen as the maximum tolerated dose level.

Results.

One patient experienced a grade 3 nephrotoxicity, 1 patient a grade 1 neuropathy, and 5 patients grade 2 nausea (36%). There were no grade 4 toxicities.

Conclusion.

Intraoperative chemotherapy is feasible, and the combination of cisplatin at 75 mg/m2 and 5‐fluorouracil at 1000 mg/m2 can be administered during surgery without significant toxicity. © 2006 Wiley Periodicals, Inc. Head Neck, 2007.
Induction of cell cycle arrest and apoptosis by a combined treatment with 13‐cis‐retinoic acid, interferon‐α2a, and α‐tocopherol in squamous cell carcinoma of the head and neck
Authors: Zhang Xin , Chen Zhuo (Georgia) , Khuri Fadlo R. , Shin Dong M.
Published: December 2006

Background.

We have previously conducted phase II trials with a combination of 13‐cis‐retinoic acid (13‐cRA), interferon‐α2a (IFN‐α2a), and α‐tocopherol (α‐TF) in patients with advanced oral premalignant lesions and locally advanced head and neck cancer in the adjuvant settings and achieved promising outcomes. The present study was conducted in vitro to elucidate the mechanisms of anti‐tumor activity of this 3‐drug combination in squamous cell carcinoma of the head and neck (SCCHN).

Methods.

Five SCCHN cell lines were treated with 13‐cRA, IFN‐α2a, and α‐TF as single agents or 2‐ to 3‐drug combinations for 72 hours. Inhibition of cell growth and cell cycle progression and induction of apoptosis by the treatments were evaluated.

Results.

Our results demonstrated that although each single‐agent and 2‐drug combination showed a certain level of cell growth inhibition, the 3‐drug combination apparently further inhibited cell growth in comparison to any single agents and 2‐drug combinations in the 5 SCCHN cell lines. Cell cycle analysis on Tu212 and 886LN cells by flow cytometry exhibited significant accumulation of the cells at S phase in the 3‐drug combination. On the other hand, Annexin‐V binding assay demonstrated that the 3‐drug combination induced more profound apoptosis than any of the single agents or 2‐drug combinations. In parallel, proteolytic cleavages of pro‐caspase‐8, ‐9, ‐3 and poly (ADP ribose) polymerase as well as caspase‐3 activity induced by the 3‐drug treatment were observed.

Conclusions.

Our data suggests that 3‐drug combination biochemopreventive regimen has cooperative inhibitory effect on the growth of SCCHN cells. Both cell cycle arrest and apoptosis contribute to cell growth inhibition of this 3‐drug combination therapy. © 2006 Wiley Periodicals, Inc. Head Neck, 2007.
Prognostic value of plasminogen activator inhibitor‐1 in head and neck squamous cell carcinoma
Authors: Speleman Luciënne , Kerrebijn Jeroen D. F. , Look Maxime P. , Meeuwis Cees A. , Foekens John A. , Berns Els M. J. J.
Published: December 2006

Background.

Tumor cell biological factors, such as urokinase plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor‐1 (PAI‐1), cathepsin D, and c‐myc play a role in tumor invasion, metastasis, and proliferation. In this study, the prognostic importance of these factors in patients with primary head and neck squamous cell carcinoma (HNSCC) was evaluated and correlated with clinicopathologic variables.

Methods.

In 46 paired primary tumors and normal tissues, levels of uPA, PAI‐1, cathepsin D, and c‐myc amplification were determined. The clinical follow‐up was over 10 years. Relationships between cell biological factors and patient and tumor characteristics were studied by the Mann–Whitney test. The Cox proportional hazard model was used for univariate and multivariate analysis.

Results.

In this study, only a high level of PAI‐1 was associated with a significantly shorter disease‐free survival (p < .01). PAI‐1 levels were higher in tumors with perineural invasion (p < .01). Both PAI‐1 and uPA levels were higher in patients who smoked (p < .01 and p = .02). In univariate analysis, smoking (p= .04), excessive alcohol intake (p = .02), perineural invasion (p = .001), and vaso‐invasion (p = .009) were associated with a shorter disease‐free survival. The only factor related to overall survival was perineural invasion (p = .045). The combination of a high PAI‐1 level and perineural invasion appeared to be a significant predictor of a shorter disease‐free interval (p = .01).

Conclusion.

PAI‐1 may present a novel prognostic factor for patients with HNSCC. Perineural invasion and PAI‐1 level combined seemed to be prognostic for disease‐free survival. © 2006 Wiley Periodicals, Inc. Head Neck, 2007.
Treatment of oropharyngeal squamous cell carcinoma with external beam radiation combined with interstitial brachytherapy
Authors: Chen Jergin , Pappas Lisa , Moeller John H. , Rankin Jim , Sharma Pramod K. , Bentz Brandon G. , Christine Fang L. , Hayes John K. , Shrieve Dennis C. , Hitchcock Ying J.
Published: December 2006

Background.

We reviewed the outcomes of oropharyngeal squamous cell carcinoma treated with external beam radiation and interstitial brachytherapy.

Methods.

Ninety patients with squamous cell carcinoma of the oropharynx were treated with interstitial brachytherapy at the University of Utah between 1984 and 2001. Seventy‐two patients received external beam radiotherapy (EBRT) followed by brachytherapy boost, 11 had surgery followed by EBRT and brachytherapy, 4 had surgery and brachytherapy, and 3 were treated with brachytherapy alone. Median doses for EBRT and brachytherapy were 50 and 24 Gy, respectively.

Results.

Median follow‐up after brachytherapy was 48.3 months for all patients. Five‐year local control, disease‐free survival, and overall survival were 76%, 61%, and 55%. For T1, T2, T3, and T4, 5‐year local control rates were 83%, 79%, 79%, and 64%, respectively. Severe complications occurred in 13 patients, including 2 treatment‐related deaths.

Conclusions.

EBRT combined with interstitial brachytherapy provide good local control rates for locally advanced oropharyngeal squamous cell carcinoma. © 2006 Wiley Periodicals, Inc. Head Neck, 2007.
Malignant peripheral nerve sheath tumors of the head and neck: Management of 10 cases and literature review
Authors: Minovi Amir , Basten Oliver , Hunter Ben , Draf Wolfgang , Bockmühl Ulrike
Published: December 2006

Background.

This study analyzes the management and outcomes of a series of 10 malignant peripheral nerve sheath tumors (MPNST) of the head and neck.

Methods.

From 1984 to 2004, 10 patients underwent surgical treatment of a MPNST. We retrospectively reviewed presenting symptoms, radiological findings, surgical management, and follow‐up status and performed a literature review.

Results.

Eight tumors were located at the lateral skull base; 2 involved the vagus nerve in isolation. Two lesions were growing within the sinonasal tract. The most common presenting symptom was a rapidly enlarging cervical mass. Seventy percent of the tumors could be resected completely. Long‐term follow‐up showed a 2‐year disease‐specific survival rate of 50% and 5‐year survival rate of 20%. Negative prognostic indicators were advanced tumor stage, early recurrence, and presumably also the presence of von Recklinghausen's disease. Postoperative adjuvant radiotherapy was found to make no difference in outcome.

Conclusions.

Although rare, MPNST is one of the most aggressive tumors in the head and neck area. Complete tumor removal is the mainstay of treatment and most important prognostic factor of MPNST. Adjuvant radiotherapy should be used to assist surgical excision in local control. The role of adjuvant chemotherapy remains controversial. © 2006 Wiley Periodicals, Inc. Head Neck, 2007.
Capabilities, processes, and performance of knowledge management: A structural approach
Authors: Lee Young‐Chan , Lee Sun‐Kyu
Published: December 2006

The purpose of this study is to examine structural relationships among the capabilities, processes, and performance of knowledge management, and suggest strategic directions for the successful implementation of knowledge management. To serve this purpose, the authors conducted an extensive survey of 68 knowledge management‐adopting Korean firms in diverse industries and collected 215 questionnaires. Analyzing hypothesized structural relationships with the data collected, they found that there exists statistically significant relationships among knowledge management capabilities, processes, and performance. The empirical results of this study also support the well‐known strategic hypothesis of the balanced scorecard (BSC). © 2007 Wiley Periodicals, Inc. Hum Factors Man 17: 21–41, 2007.
Pushing strengths under restricted space
Authors: Lee Tzu‐Hsien
Published: December 2006

This study investigates human maximum horizontal isometric pushing strength and rearward foot position while pushing at four different exertion heights (48 cm, 84 cm, 120 cm, and 156 cm) and two exertion spaces (unrestricted and restricted). The restricted space was reduced to an anterior–posterior direction. The results showed that participants' most efficient exertion height and rearward foot position occurred invariably at an exertion height of 84 cm when pushing in an unrestricted exertion space. Restricted space impaired the pushing strength, with a maximal difference of pushing strength between unrestricted and restricted spaces also occurring at the exertion height of 84 cm. The percentages of female to male pushing strength varied little across the four exertion heights. Participants seemed to be prone to utilize only approximately 71% to 82% of the exertion space available while pushing in a restricted space. © 2007 Wiley Periodicals, Inc. Hum Factors Man 17: 95–102, 2007.
Prediction of vortex penetration depth at thermal stratification by cavity flow in a branch pipe with closed end (effect of heat radiation condition on temperature fluctuations)
Authors: Shiina Kouji , Kawamura Tsutomu , Ohtsuka Masaya , Mizuno Tadashi , Hisatsune Masakazu , Ogura Kenji , Tanimoto Kouichi , Fukuda Toshihiko , Minami Yasuhiko , Moriya Shoichi , Madarame Haruki
Published: December 2006

In a branch pipe with one closed end, the cavity flow penetrates into the branch pipe from the main loop and a thermal boundary layer occurs because the cavity flow is a hot fluid, but heat removal causes a colder fluid in the branch pipe. This thermal stratification may affect the structural integrity. Therefore, a pipe design standard to suppress thermal fatigue should be established. The pipe design standard consists of the maximum penetration depth Lsv and the minimum penetration depth Lsh. In order to establish an evaluation method for Lsh, a visualization test and a temperature fluctuation test were carried out. A theoretical formula for thermal stratification was introduced from the heat balance model. Then the model was used to obtain an empirical equation from the map of fluid temperature fluctuation. This method can predict the vortex penetration depth by cavity flow in horizontal branch pipes. © 2006 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(1):38–55, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20135
Preparation and thermal properties of microencapsulated phase change material for enhancing fluid flow heat transfer
Authors: Rao Yu , Lin Guiping , Luo Yan , Chen Shuilin , Wang Liang
Published: December 2006

Microencapsulated phase change material (MEPCM) is formed by packing PCM into a microcapsule with a solid but flexible shell. MEPCM can be used to enhance liquid cooling performance considerably. In this paper, experiments on the preparation of MEPCM with a double‐layered shell have been conducted. An in‐situ polymerization microencapsulation process was used to prepare the MEPCM with melamine resin as the shell material and n‐Docosane (C22H46) as the core material. Interesting parameters like the size of the prepared MEPCM, the core mass fraction in the MEPCM, and the thermal storage capability of the prepared MEPCM have been measured and analyzed. © 2006 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(1): 28–37, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20138
Characteristics of heat transfer and temperature rise of hydrogen during rapid hydrogen filling at high pressure
Authors: Monde Masanori , Mitsutake Yuichi , Woodfield Peter Lloyd , Maruyama Shinichi
Published: December 2006

An experiment has been done to measure the rise in temperature of a gas during filling a tank at high pressure. The experimental condition is that filling gases are nitrogen and hydrogen at a pressure of 5 to 35 MPa and at a filling mass of G=45 to 324 g/min for hydrogen. The temperatures are measured either horizontally or vertically at five positions in the tank. It is found that heat loss transferred from compressed gas to the tank wall has a significant effect on the rise in the filled gas temperature. The heat transfer coefficient is estimated after the end of filling and is about αh=270 W/(m2K) for the hydrogen at 35 MPa. A theoretical procedure is proposed to calculate the temperature increase of the gas on a basis of assumption that the gas temperature in the tank is uniform at any time, and the heat transfer coefficient is given. The calculation shows that the temperature is in reasonable agreement with the measured temperatures by assuming αh=500 W/(m2K) during the filling of hydrogen at 35 MPa, although the estimated heat loss after the end of filling becomes larger than the actual one. © 2006 Wiley Periodicals, Inc. Heat Trans Asian Res, 36(1): 13–27, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.20140
Temperature in lowland Danish streams: contemporary patterns, empirical models and future scenarios
Authors: Pedersen Niels Lagergaard , Sand‐Jensen Kaj
Published: December 2006

Continuous temperature measurements at 11 stream sites in small lowland streams of North Zealand, Denmark over a year showed much higher summer temperatures and lower winter temperatures along the course of the stream with artificial lakes than in the stream without lakes. The influence of lakes was even more prominent in the comparisons of colder lake inlets and warmer outlets and led to the decline of cold‐water and oxygen‐demanding brown trout. Seasonal and daily temperature variations were, as anticipated, dampened by forest cover, groundwater input, input from sewage plants and high downstream discharges. Seasonal variations in daily water temperature could be predicted with high accuracy at all sites by a linear air‐water regression model (r2: 0·903–0·947). The predictions improved in all instances (r2: 0·927–0·964) by a non‐linear logistic regression according to which water temperatures do not fall below freezing and they increase less steeply than air temperatures at high temperatures because of enhanced heat loss from the stream by evaporation and back radiation. The predictions improved slightly (r2: 0·933–0·969) by a multiple regression model which, in addition to air temperature as the main predictor, included solar radiation at un‐shaded sites, relative humidity, precipitation and discharge. Application of the non‐linear logistic model for a warming scenario of 4–5 °C higher air temperatures in Denmark in 2070‐2100 yielded predictions of temperatures rising 1·6–3·0 °C during winter and summer and 4·4–6·0 °C during spring in un‐shaded streams with low groundwater input. Groundwater‐fed springs are expected to follow the increase of mean air temperatures for the region. Great caution should be exercised in these temperature projections because global and regional climate scenarios remain open to discussion. Copyright © 2006 John Wiley & Sons, Ltd.
Water and carbon fluxes of European ecosystems: an evaluation of the ecohydrological model RHESSys
Authors: Zierl Bärbel , Bugmann Harald , Tague Christina L.
Published: December 2006

This study investigated whether the regional hydro‐ecological simulation system RHESSys is a suitable tool for long‐term global change impact studies under selected climatic conditions of Europe, taking advantage of the strongly varying climate along elevational gradients in mountain regions. We performed a validation of RHESSys using daily, monthly and yearly data on (1) streamflow and snow cover in five Alpine catchments and (2) water and carbon fluxes at 15 EUROFLUX sites.

The simulation results generally agreed well with observations. RHESSys reasonably reproduced daily and monthly streamflow, as well as the seasonal cycle and amplitude of typical Alpine discharge regimes. Furthermore, RHESSys was capable of capturing the key features of the carbon cycle of various forested ecosystems, including significant differences between managed and close‐to‐natural forests, and more subtle distinctions between coniferous and deciduous systems.

Our analyses confirmed that RHESSys is a suitable tool for studying global change impacts on mountain hydrology. Regarding the simulation of the carbon cycle, this investigation detected some data and model limitations that are discussed in detail. Finally, suggestions for model improvements are made, mainly concerning the formulations of decomposition and respiration rates in biogeochemical models. Copyright © 2006 John Wiley & Sons, Ltd.
Interrelations between maternal smoking during pregnancy, birth weight and sociodemographic factors in the prediction of early cognitive abilities
Authors: Huijbregts S. C. J. , Séguin J. R. , Zelazo P. D. , Parent S. , Japel C. , Tremblay R. E.
Published: December 2006

Maternal prenatal smoking, birth weight and sociodemographic factors were investigated in relation to cognitive abilities of 1544 children (aged 3.5 years) participating in the Québec Longitudinal Study of Children's Development. The Peabody Picture Vocabulary Test (PPVT) was used to assess verbal ability, the Wechsler Preschool and Primary Scale of Intelligence‐Revised (WPPSI‐R) block design test to assess visuospatial ability, and the Visually Cued Recall (VCR) task to assess short‐term memory. Prenatal smoking was related to performance on the WPPSI‐R, the PPVT, and the VCR, although it did not independently predict any cognitive ability after maternal education was taken into account. Birth weight was a more robust predictor of all outcome measures and independently predicted VCR‐performance. Birth weight interacted significantly with family income and maternal education in predicting visuospatial ability, indicating a greater influence of birth weight under relatively poor socio‐economic conditions. Parenting and family functioning mediated associations between maternal education/family income and cognitive task performance under different birth weight conditions, although there were indications for stronger effects under relatively low birth weight. We conclude that investigations of moderating and mediating effects can provide insights into which children are most at risk of cognitive impairment and might benefit most from interventions. Copyright © 2006 John Wiley & Sons, Ltd.
On growth curves and mixture models
Authors: Hoeksma Jan B. , Kelderman Henk
Published: December 2006

The multilevel model of change and the latent growth model are flexible means to describe all sorts of population heterogeneity with respect to growth and development, including the presence of sub‐populations. The growth mixture model is a natural extension of these models. It comes at hand when information about sub‐populations is missing and researchers nevertheless want to retrieve developmental trajectories from sub‐populations. We argue that researchers have to make rather strong assumptions about the sub‐populations or latent trajectory classes in order to retrieve existing population differences. A simulated example is discussed, showing that a sample of repeated measures drawn from two sub‐populations easily leads to the mistaken inference of three sub‐populations, when assumptions are not met. The merits of methodological advises on this issue are discussed. It is concluded that growth mixture models should be used with understanding, and offer no free way to growth patterns in unknown sub‐populations. Copyright © 2006 John Wiley & Sons, Ltd.
Latent growth mixture models: an important new tool for developmental researchers
Authors: Stanger Catherine
Published: December 2006

This manuscript by Connell and Frye (Infant Child Dev 2006; 15(6): 609–621) provides a clear example of the application of latent growth mixture models (LGMM) to the development of antisocial behaviour in adolescence. The LGMM approach is discussed in the context of this example, and factors influencing the results achieved with these methods are highlighted. Overall, developmental psychologists have much to gain from the use of these new approaches. Copyright © 2006 John Wiley & Sons, Ltd.
Natural killer cell‐mediated ablation of metastatic liver tumors by hydrodynamic injection of IFNα gene to mice
Authors: Takehara Tetsuo , Uemura Akio , Tatsumi Tomohide , Suzuki Takahiro , Kimura Ritsuko , Shiotani Ai , Ohkawa Kazuyoshi , Kanto Tatsuya , Hiramatsu Naoki , Hayashi Norio
Published: December 2006

Interferon (IFN) α is a pleiotropic cytokine acting as an antiviral substance, cell growth inhibitor and immunomodulator. To evaluate the therapeutic efficacy and mechanisms of IFNα on hepatic metastasis of tumor cells, we hydrodynamically injected naked plasmid DNA encoding IFNα1 (pCMV‐IFNa1) into Balb/cA mice having 2 days hepatic metastasis of CT‐26 cells. Single injection of pCMV‐IFNa1 efficiently enhanced the natural killer (NK) activity of hepatic mononuclear cells, induced production of IFNγ in serum and led to complete rejection of tumors in the liver. Mice protected from hepatic metastasis by IFNα therapy displayed a tumor‐specific cytotoxic T cell response and were resistant to subcutaneous challenge of CT‐26 cells. NK cells were critically required for IFNα‐mediated rejection of hepatic metastasis, because their depletion by injecting anti‐asialo GM1 antibody completely abolished the antimetastatic effect. To find whether NK cells are directly activated by IFNα and are sufficient for the antimetastatic effect, the responses to IFNα were examined in SCID mice lacking T cells, B cells and NKT cells. IFNα completely rejected hepatic metastasis in SCID mice and efficiently activated SCID mononuclear cells, as evidenced by activation of STAT1 and a variety of genes, such as MHC class I, granzyme B, tumor necrosis factor‐related apoptosis‐inducing ligand and IFNγ, and also enhanced Yac1 lytic ability. Study of IFNγ knockout mice revealed that IFNγ was not necessary for IFNα‐mediated NK cell activation and metastasis protection. In conclusion, IFNα efficiently activates both innate and adaptive immune responses, but NK cells are critically required and sufficient for IFNα‐mediated initial rejection of hepatic metastasis of microdisseminated tumors. © 2006 Wiley‐Liss, Inc.
Betel quid not containing tobacco and oral cancer: A report on a case–control study in Papua New Guinea and a meta‐analysis of current evidence
Authors: Thomas Steven J. , Bain Christopher J. , Battistutta Diana , Ness Andrew R. , Paissat Darius , Maclennan Robert
Published: December 2006

Smoking and betel quid chewing are associated with increased risk of oral cancer but few studies have reported on associations in populations where betel quid does not contain tobacco. We conducted a case–control study in Papua New Guinea and a systematic review. Our case–control study recruited 143 cases with oral cancer and 477 controls. We collected information on smoking and betel quid chewing. Current smoking was associated with an increased risk of oral cancer with an adjusted odds ratio (OR) for daily smokers of 2.63 (95% confidence intervals (95% CI) 1.32, 5.22) and amongst heaviest smokers of 4.63 (95% CI 2.07, 10.36) compared to never‐smokers. Betel chewing was associated with increased risk of oral cancer with an adjusted OR for current chewers of 2.03 (95% CI 1.01, 4.09) and in the heaviest chewers of 2.47 (95% CI 1.13, 5.40) compared to nonchewers. The OR in those who both smoked tobacco and chewed betel quid was 4.85 (95% 1.10, 22.25), relative to those who neither smoked nor chewed. The systematic review identified 10 previous studies that examined risk of oral cancer associated with betel quid chewing that controlled for smoking in populations where betel quid did not contain tobacco. In studies that reported results for non‐smokers the combined OR was 2.14 (95% CI 1.06, 4.32) in betel quid chewers and in studies that adjusted for smoking the combined OR was 3.50 (95% CI 2.16, 5.65) in betel quid chewers. Preventive efforts should discourage betel quid chewing as well as smoking. © 2006 Wiley‐Liss, Inc.
Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis
Authors: Schmitz Martine , Grignard Gérard , Margue Christiane , Dippel Walter , Capesius Catherine , Mossong Joël , Nathan Michel , Giacchi Sandro , Scheiden René , Kieffer Nelly
Published: December 2006

The EGF/IGF growth factors are potent mitogens that regulate cell proliferation and cell survival and are involved in prostate cancer development. Using laser microdissection technology and real‐time PCR, together with immunohistochemistry, we have explored the growth factor and integrin dependent PI3‐kinase/PTEN/Akt signalling pathway in prostate cell lines and tumour samples by analysing EGF‐R, IGF1‐R, ILK, β3 integrin, PTEN and p‐Akt protein expression. We provide evidence that loss of PTEN expression rather than upregulated EGF/IGF1 receptor expression was responsible for increased p‐Akt in neoplastic prostate cells. We therefore compared PTEN expression in patient biopsies at first time diagnosis recruited prospectively (Study I, 112 patients) and patients with confirmed metastasis recruited retrospectively from the Luxembourg cancer registry (Study II, 42 patients). In Study I, loss of PTEN expression at first time diagnosis was found in 26 of 112 patients (23%). In Study II, 25 of the 42 patients (59%) with lymph node metastasis had complete loss of PTEN expression in both the neoplastic glands of the prostate and the invasive prostate cancer cells in the lymph node, and of these 13 (52%) exhibited already loss of PTEN expression at first diagnosis. These findings demonstrate that loss of PTEN expression is an important factor in progression towards metastatic disease and could potentially serve as an early prognostic marker for prostate cancer metastasis. © 2006 Wiley‐Liss, Inc.
High level of messenger RNA for BRMS1 in primary breast carcinomas is associated with poor prognosis
Authors: Lombardi Grazia , Di Cristofano Claudio , Capodanno Alessandra , Iorio Maria Carla , Aretini Paolo , Isola Patrizia , Tancredi Mariella , Collecchi Paola , Naccarato Antonio Giuseppe , Porta Romana Prosperi , Bevilacqua Generoso , Caligo Maria Adelaide
Published: December 2006

BRMS1 is regarded as a metastasis suppressor gene for its ability to reduce metastatic potential of human and murine breast cancer cells as well as human melanoma cells. However, BRMS1 association to human tumor progression is not clearly understood. In the present study we analyzed BRMS1 mRNA expression in tumor progression and its potential prognostic value for breast carcinoma. BRMS1 mRNA expression level was quantified by real‐time PCR in 47 tumoral, in 14 peritumoral and in 15 metastatic microdissected cellular populations from 47 breast cancer patients with 10‐year follow up. We found BRMS1 expression to be higher in carcinoma cells than in matching normal epithelial cell populations in 10 out of 14 cases (p = 0.0005), while lymph‐nodal carcinoma cells showed lower BRMS1 expression in 9 out of 15 cases (p = 0.001). Using both in vivo (human mammary breast carcinomas) and in vitro systems (breast cancer cell lines) we were able to demonstrate that BRMS1 overexpression was not a bias effect induced by cell proliferation rate. BRMS1 expression levels did not correlate with standard breast cancer prognostic factors but BRMS1 higher expression was associated with patient shorter disease‐free and overall survival. Our findings are apparently inconsistent with the concept of BRMS1 as a metastasis suppressor gene. One possible explanation is that epithelial cells increase their BRMS1 expression as a compensatory response to tumor formation or metastasis progression, which is elevated in proportion to tumor aggressiveness, whereas those cells of the primary tumor that cannot upregulate BRMS1 escape to form metastasis. © 2006 Wiley‐Liss, Inc.
FOXA1: Growth inhibitor and a favorable prognostic factor in human breast cancer
Authors: Wolf Ido , Bose Shikha , Williamson Elizabeth A. , Miller Carl W. , Karlan Beth Y. , Koeffler H. Phillip
Published: December 2006

The transcription factor Forkhead‐box A1 (Foxa1), a member of the FOX class of transcription factors, has been implicated in the pathogenesis of lung, esophageal and prostate cancers. We have recently identified transcriptional activation of p27 by FOXA1. In this study, we analyzed the activities and expression pattern of FOXA1 in breast cancer. Forced expression of FOXA1 inhibited clonal growth of breast cancer cell lines, and FOXA1 levels inversely correlated with growth stimuli. In the estrogen receptor (ER)‐positive MCF‐7 cells, FOXA1 increased p27 promoter activity and inhibited the ER pathway activity. Analysis of FOXA1 expression in breast tissue arrays revealed significantly higher expression in pure ductal carcinomas in situ compared to invasive ductal carcinomas (IDC); and in IDC, high expression of FOXA1 was associated with favorable prognostic factors. Yet, FOXA1 expression was noted in a subset of the ER‐negative tumors. Taken together, our findings suggest a growth inhibitory role for FOXA1, and identify it as a novel, potential prognostic factor in breast cancer. © 2006 Wiley‐Liss, Inc.
Prospective study of vitamins C, E, and A and carotenoids and risk of oral premalignant lesions in men
Authors: Maserejian Nancy Nairi , Giovannucci Edward , Rosner Bernard , Joshipura Kaumudi
Published: December 2006

Case–control studies indicate that vitamins C, E, A and carotenoids decrease risk of oral premalignant lesions (OPLs) and oral cancer, but clinical trials have failed to find protective effects of β‐carotene and suggest that vitamin E may increase risk. The authors prospectively evaluated the association between intake of vitamins C, E, A and carotenoids and incidence of OPL. Participants were 42,340 men in the Health Professionals Follow‐up Study who provided information on supplement use and diet every 2–4 years by food frequency questionnaire. The authors confirmed 207 clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review. Multivariate‐adjusted relative risks (RR) of OPL were calculated with proportional hazards models. Total intake of vitamin C, vitamin A or carotenoids was not significantly associated with OPL risk. Dietary vitamin C was significantly associated with reduced risk (quintile 5 vs. 1, RR = 0.52, 95% CI 0.31–0.85, ptrend = 0.04), but no association with supplemental vitamin C was observed. Inverse associations were apparent for β‐cryptoxanthin and α‐carotene intake. No clear relationship emerged with β‐carotene, lycopene or lutein/zeaxanthin. Vitamin E was associated with increased risk (quintile 5 vs. 1, RR = 1.86, 95% CI 1.06–3.19), particularly among current smokers and with supplemental intake (current‐smokers, supplement dose tertile 3 vs. 1, RR = 3.07, 95% CI 1.28–7.34, ptrend = 0.01). For current smokers, β‐carotene also increased risk. Vitamin C from dietary sources, but not supplements, was associated with a reduced risk of OPL. The observed increased risk for current smokers with high vitamin E or β‐carotene intake should be explored further. © 2006 Wiley‐Liss, Inc.
Lipophilin B: A gene preferentially expressed in breast tissue and upregulated in breast cancer
Authors: Culleton Jane , O'Brien Neil , Ryan Bríd M. , Hill Arnold D.K. , McDermott Enda , O'Higgins Niall , Duffy Michael J.
Published: December 2006

Lipophilin B (LPB), which is also known as BU101, is a secretoglobin which exists in vivo as a complex with the mammary‐specific protein, mammaglobin A (MGA). The aim of our study was to investigate the expression of LPB in a panel of breast and nonbreast tissues and compare its expression with that of MGA. Using RT‐PCR, LPB mRNA was detected in 16/25 (64%) of normal breast specimens, 23/30 (77%) of fibroadenomas, 102/156 (65%) of primary breast cancers and in 8/36 (22%) nonbreast tissues. Levels of expression of LPB mRNA were significantly higher in breast cancers compared to both normal breast tissues (p = 0.02) and nonbreast tissue (p < 0.001). In the primary breast cancers, expression of LPB mRNA was positively correlated with the estrogen receptor (p = 0.045) but inversely related to both tumor grade (p < 0.001) and proliferation rates (p = 0.0345). Compared to MGA, expression of LPB was more sensitive but less specific for breast cancer. Using Western blotting, LPB migrated with an approximate molecular mass of 7–8 kDa, the expected molecular mass of free LPB. Immunohistochemical analysis of breast cancers showed that LPB expression was predominantly confined to the cytoplasm of tumor cells. We conclude that expression of LPB is preferentially but not exclusively restricted to breast tissue. Since LPB was expressed relatively specifically in breast tissue and was significantly upregulated in breast carcinomas, it is a promising candidate biomarker for breast cancer. © 2006 Wiley‐Liss, Inc.
An empirical model of the multi‐unit, sequential, clock auction
Authors: Donald Stephen G. , Paarsch Harry J. , Robert Jacques
Published: December 2006

We construct a model of participation and bidding at multi‐unit, sequential, clock auctions when bidders have multi‐unit demand. We describe conditions sufficient to characterize a symmetric, perfect‐Bayesian equilibrium and then demonstrate that this equilibrium induces an efficient allocation. We propose an algorithm, based on the generalized Vickrey auction, to calculate the expected winning bid for each unit sold. This algorithm allows us to construct a simulation‐based estimator of the parameters for both the participation process and the distribution of latent valuations. We apply our method to data from 37 multi‐lot, sequential, English auctions of export permits for timber held in Russia. Copyright © 2006 John Wiley & Sons, Ltd.
A re‐interpretation of the linear quadratic model when inventories and sales are polynomially cointegrated
Authors: Banerjee Anindya , Mizen Paul
Published: December 2006

Estimation of the linear quadratic model, the workhorse of the inventory literature, traditionally takes inventories and sales to be first‐difference stationary series, and the ratio of the two variables to be stationary. However, these assumptions do not always match the properties of the data for the last two decades in the United States. We propose a model that allows for the non‐stationary characteristics of the data, using polynomial cointegration. We show that the closed‐form solution has other recent models as special cases. The resulting model performs well on aggregate and disaggregated data. Copyright © 2006 John Wiley & Sons, Ltd.
Nonlinear dynamics of interest rate and inflation
Authors: Lanne Markku
Published: December 2006

According to several empirical studies US inflation and nominal interest rates as well as the real interest rate can be described as unit root processes. These results imply that nominal interest rates and expected inflation do not move one‐for‐one in the long run, which is incongruent with theoretical models. In this paper we introduce a new nonlinear bivariate mixture autoregressive model that seems to fit quarterly US data (1953 : II–2004 : IV) reasonably well. It is found that the three‐month Treasury bill rate and inflation share a common nonlinear component that explains a large part of their persistence. The real interest rate is devoid of this component, indicating one‐for‐one movement of the nominal interest rate and inflation in the long run and, hence, stationarity of the real interest rate. Copyright © 2006 John Wiley & Sons, Ltd.
Inter‐state dynamics of invention activities, 1930–2000
Authors: Co Catherine Y. , Landon‐Lane John S. , Yun Myeong‐Su
Published: December 2006

We study the dynamics of the cross‐section distribution of patents per capita for the 48 continental US states from 1930 to 2000 using a discrete‐state Markov chain. We test for and find evidence in favor of the (knowledge) convergence hypothesis. The distribution of patents is converging to a limiting distribution that is significantly more concentrated than its initial distribution. States in the extreme are more mobile than states in the middle of the cross‐sectional distribution and are likely to move to the middle. However, the rate of convergence to the limiting distribution is ‘slow’. Copyright © 2006 John Wiley & Sons, Ltd.
Is there a risk–return trade‐off? Evidence from high‐frequency data
Authors: Bali Turan G. , Peng Lin
Published: December 2006

This paper examines the intertemporal relation between risk and return for the aggregate stock market using high‐frequency data. We use daily realized, GARCH, implied, and range‐based volatility estimators to determine the existence and significance of a risk–return trade‐off for several stock market indices. We find a positive and statistically significant relation between the conditional mean and conditional volatility of market returns at the daily level. This result is robust to alternative specifications of the volatility process, across different measures of market return and sample periods, and after controlling for macro‐economic variables associated with business cycle fluctuations. We also analyze the risk–return relationship over time using rolling regressions, and find that the strong positive relation persists throughout our sample period. The market risk measures adopted in the paper add power to the analysis by incorporating valuable information, either by taking advantage of high‐frequency intraday data (in the case of realized, GARCH, and range volatility) or by utilizing the market's expectation of future volatility (in the case of implied volatility index). Copyright © 2006 John Wiley & Sons, Ltd.
Metabolism of chlorpyrifos and chlorpyrifos oxon by human hepatocytes*
Authors: Choi Kyoungju , Joo Hyun , Rose Randy L. , Hodgso Ernest
Published: December 2006

The metabolism of chlorpyrifos (CPS) and chlorpyrifos oxon (CPO) by human hepatocytes and human liver S9 fractions was investigated using LC‐MS/MS. Cytochrome P450 (CYP)‐dependent and phase II‐related products were determined following incubation with CPS and CPO. CYP‐related products, 3,5,6‐trichloro‐2‐pyridinol (TCP), diethyl thiophosphate, and dealkylated CPS, were found following CPS treatment and dealkylated CPO following CPO treatment. Diethyl phosphate was not identified because of its high polarity and lack of retention with the chromatographic conditions employed. Phase II‐related conjugates, including O‐ and S‐glucuronides as well as 11 GSH‐derived metabolites, were identified in CPS‐treated human hepatocytes, although the O‐sulfate of TCP conjugate was found only when human liver S9 fractions were used as the enzyme source. O‐Glucuronide of TCP was also identified in CPO‐treated hepatocytes. CPS and CPO were identified using HPLC–UV after CPS metabolism by the human liver S9 fraction. However, CPO was not found following treatment of human hepatocytes with either CPS or CPO. These results suggest that human liver plays an important role in detoxification, rather than activation, of CPS. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:279–291, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20145
670 nanometer light treatment attenuates dioxin toxicity in the developing chick embryo
Authors: Yeager Ronnie L. , Lim Jinhwan , Millsap Deborah S. , Jasevicius Ashley V. , Sanders Ruth A. , Whelan Harry T. , Watkins John B. , Eells Janis T. , Henshel Diane S.
Published: December 2006

2,3,7,8‐Tetrachlorodibenzo‐p‐dioxin (TCDD) is an acutely toxic anthropogenic chemical. Treatment with a red to near‐infrared (630–1000 nm) light‐emitting diode (LED) attenuates the toxicant‐induced oxidative stress and energy deficit in neuronal cell culture. For this study, fertile chicken (Gallus gallus) eggs were injected once at the start of incubation with sunflower oil vehicle or 200 pg TCDD/g egg (200 parts per trillion), an environmentally relevant dose. Daily LED treatment after TCDD exposure reduced embryonic mortality by 47%. LED treatment of TCDD‐exposed eggs also decreased the hepatic oxidized‐to‐reduced glutathione ratio by 88%. Activities of other hepatic indicators of oxidative stress, such as glutathione reductase and catalase, were increased after LED treatment of TCDD‐exposed eggs. Our study demonstrates that 670 nm phototherapy can mitigate the oxidative stress and energy deficit resulting from developmental exposure to TCDD while reducing TCDD‐induced embryo mortality. Moreover, LED treatment restores hepatic enzyme activities to control levels in TCDD‐exposed embryos. The effective attenuation of TCDD‐induced embryo toxicity by LED treatment could extend to mitigating the effects of other teratogens that induce oxidative and energy stress. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:271–278, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20146
Hepatic chemoprotective enzyme responses to 2‐substituted selenazolidine‐4(R)‐carboxylic acids
Authors: El‐Sayed Wael M. , Franklin Michael R.
Published: December 2006

In epidemiology and human supplementation studies, as well as many animal models, selenium has shown antitumorigenic activity. The mechanism of action, however, has not been satisfactorily resolved. Selenium supplementation affects many enzymes in addition to those where selenocysteine is an essential component. Such enzymes include cytoprotective detoxifying enzymes, and the regulation of these enzymes by a set of 2‐substituted selenazolidine‐4(R)‐carboxylic acids (SCAs) has been investigated. Following seven consecutive daily doses of these prodrugs of L‐selenocysteine, changes in hepatic enzyme activities and/or mRNA levels of glutathione transferase (GST), microsomal epoxide hydrolase (mEH), NAD(P)H‐quinone oxidoreductase (NQO), UDP‐glucuronosyltransferase (UGT), glutathione peroxidase (GPx), and thioredoxin reductase (TR) have been observed. Among the enzymes examined, UGTs and GPx were found to be the least affected. Among the compounds, 2‐oxoSCA produced the most changes and 2‐phenylSCA produced the least, none. For no two compounds was the pattern of changes identical, and for a single compound, few changes were reproduced in common by the two routes of administration investigated. In general, more changes were elicited following intraperitoneal (i.p.) administration than with the intragastric (i.g.) route. This dominance was typified by 2‐butylSCA and 2‐cyclohexylSCA where enzyme activity elevations (TR and mEH with both, NQO with 2‐butylSCA) were seen only with the i.p. route. With 2‐oxoSCA, however, GST, TR, and NQO activities were found to be elevated independent of route. Only with GST (both routes) and TR (i.p. route), elevations in mRNAs accompanied the 2‐oxoSCA elicited elevations of activities at the time of sacrifice. For some enzymes, most notably mEH with compounds administered i.p., elevations in mRNAs were not manifest as increased enzyme activity. Thus, although constituting a closely related series of compounds, each 2‐substituted SCA produced its own unique pattern of changes, and for most members, changes were predominant following i.p. administration. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:292–301, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20148