bluuebunny/crossref_metadata_2025 huggingface dataset:
Peroxisome proliferator‐activated receptor γ ligand troglitazone induces cell cycle arrest and apoptosis of hepatocellular carcinoma cell lines
Authors: Yoshizawa Kaname , Cioca Daniel P. , Kawa Shigeyuki , Tanaka Eiji , Kiyosawa Kendo
Published: November 2002

BACKGROUND

Ligand activation of peroxisome proliferator‐activated receptor γ (PPARγ) results in the inhibition of proliferation of various cancer cells. The aim of this study is to investigate the mechanisms of cell growth inhibition of hepatocellular carcinoma (HCC) cell lines by the PPARγ ligand, troglitazone.

METHODS

Six HCC cell lines were used to study the effects of troglitazone on cell growth by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay, on cell cycle by flow cytometry, and on the cell cycle‐regulating factors of late G1 phase by Western blotting. Apoptosis assays were performed by flow cytometry using membrane, nuclear, cytoplasmic, and mitochondrial markers. Caspase inhibitors were used to analyze the mechanisms of apoptosis induced by troglitazone.

RESULTS

Troglitazone showed a potent dose‐dependent effect on the growth inhibition of all six HCC cell lines, which were suppressed to under 50% of control at the concentration of 10 μmol/L. The growth inhibition was linked to the G1 phase cell cycle arrest through the up‐expression of the cyclin‐dependent kinase inhibitors, p21 and p27 proteins, and the hypophosphorylation of retinoblastoma protein. Troglitazone induced apoptosis by caspase‐dependent (mitchondrial transmembrane potential decrease, cleavage of poly [adenosine diphosphate ribose] polymerase, 7A6 antigen exposure, Bcl‐2 decrease, and activation of caspase 3) and caspase‐independent (phosphatidylserine externalization) mechanisms.

CONCLUSIONS

Our data suggest that ligand activation of PPARγ by troglitazone or modified analogs of the thiazolidinedione class of drugs is a novel target for effective therapy against HCC, because of the significant antiproliferative and programmed cell death induction capabilities demonstrated by troglitazone. Cancer 2002;95:2243–51. © 2002 American Cancer Society.

DOI 10.1002/cncr.10906
Absolute risk of a subsequent abnormal pap among oncogenic human papillomavirus DNA‐positive, cytologically negative women
Authors: Castle Philip E. , Wacholder Sholom , Sherman Mark E. , Lorincz Attila T. , Glass Andrew G. , Scott David R. , Rush Brenda B. , Demuth Franklin , Schiffman Mark
Published: November 2002

BACKGROUND

The addition of human papillomavirus (HPV) DNA testing to cytologic screening for cervical carcinoma is now being considered. The majority of women in screening cohorts who test positive for oncogenic types of HPV DNA have concurrent negative Pap tests. The absolute risk of a subsequent abnormal Pap test for these women is uncertain. Therefore, the proper counseling and clinical management of these women is also uncertain.

METHODS

A subcohort of 2020 women with a negative Pap test who tested positive at enrollment for oncogenic HPV DNA types using the Hybrid Capture 2 Test were followed for 57 months at Kaiser Permanente (Portland, OR). Absolute risks of new abnormal cytologic interpretations were computed using Kaplan–Meier methods. Logistic regression models were used to evaluate determinants of a new abnormal Pap test.

RESULTS

The cumulative incidence for a Pap test interpreted as atypical squamous cells or more severe (≥ ASC) was 16.8% (95% confidence interval [CI] = 15.0–18.6%), 6.4% (95% CI = 5.2–7.6%) for low‐grade squamous intraepithelial lesions or more severe, and 2.2% (95% CI = 1.5–2.9%) for high‐grade squamous intraepithelial lesions or more severe. By comparison, the cumulative incidence of greater than or equal to ASC among HPV‐negative women was 4.2% (95% CI = 3.9–4.6%). The highest viral load (100 relative light units per the positive control or greater) was associated with a greater risk of an abnormal Pap test (odds ratio= 2.7, 95% CI = 1.7–4.1) than lower viral loads.

CONCLUSIONS

These results suggest that about 15% of women in annual screening programs who concurrently have a negative Pap test and a positive oncogenic HPV test will have a subsequent abnormal Pap test within 5 years. This risk estimate will be useful to the many clinicians and patients likely to be diagnosed with an HPV infection and negative cytology if HPV DNA is added to general screening. Cancer 2002;95:2145–51. Published 2002 by the American Cancer Society.

DOI 10.1002/cncr.10927
Phase I study of pegylated liposomal doxorubicin and gemcitabine in patients with advanced malignancies
Authors: Fracasso Paula M. , Blum Kristie A. , Tan Benjamin R. , Fears Carole L. , Bartlett Nancy L. , Arquette Matthew A. , Clark Romnee S.
Published: November 2002

BACKGROUND

Pegylated liposomal doxorubicin (PEG‐LD) and gemcitabine have single‐agent activity in breast and ovarian carcinoma patients. We conducted a Phase I trial to evaluate the maximum tolerated dose (MTD) and toxicities of this combination in patients with advanced malignancies.

METHODS

Twenty‐six patients with refractory or recurrent malignancies were enrolled in this dose escalation trial. Dose escalation proceeded from a starting level of PEG‐LD 20 mg/m2 and gemcitabine 1000 mg/m2 administered on Days 1 and 15 of a 28‐day cycle.

RESULTS

The MTD was PEG‐LD 20 mg/m2 and gemcitabine 2000 mg/m2 administered on Days 1 and 15 of a 28‐day cycle. Dose‐limiting toxicity, a Grade 3 rash, was observed in one patient during Cycle 1 and Grade 3 stomatitis and a rash were observed in a second patient during Cycle 2 after administration of PEG‐LD 25 mg/m2 and gemcitabine 2000 mg/m2. Other side effects included palmar–plantar erythrodysesthesia, nausea, and fatigue. One complete and two partial responses were observed.

CONCLUSIONS

The recommended Phase II dose is PEG‐LD 20 mg/m2 with gemcitabine 2000 mg/m2 on Days 1 and 15 of a 28‐day cycle. A trial with this combination is currently ongoing at this institution comprising patients with refractory ovarian carcinoma. Cancer 2002;95:2223–29. © 2002 American Cancer Society.

DOI 10.1002/cncr.10937
Marked regional variation in adenocarcinomas of the esophagus and the gastric cardia in the United States
Authors: Kubo Ai , Corley Douglas A.
Published: November 2002

BACKGROUND

Adenocarcinomas of the esophagus and the gastric cardia recently have experienced rapidly increasing incidence rates. Although these sites frequently are combined, they may have different risk factors.

METHODS

The authors compared regional incidence rates of esophageal adenocarcinoma, gastric cardia adenocarcinoma, and esophageal squamous cell carcinoma within the U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registry for the years 1973–1998.

RESULTS

Regional incidence rates varied considerably. The Seattle‐Puget Sound registry's recent average esophageal adenocarcinoma rates were over twice as high as those of the Utah registry (5.3 vs. 2.4 per 100,000 persons per year; P < 0.01); gastric cardia rates also differed (4.0 vs. 2.8 per 100,000 persons per year; P < 0.01). The incidence rate increase also varied markedly between regions. Since 1974, white male esophageal adenocarcinoma rates increased by 800% in Seattle compared with an increase of only 300% in Utah. In contrast, white male cardia adenocarcinoma rates increased by only 16% in Seattle (from 3.1 per 100,000 persons per year in 1974 to 3.6 per 100,000 persons per year in 1998) compared with 300% in Utah (from 0.7 to 2.2 per 100,000 persons per year). Both types of adenocarcinoma were more common in males and in the white population in all regions, but recent esophageal adenocarcinoma rates for black males in Connecticut were significantly higher than the U.S. black male average (3.1 vs. 0.8 per 100,000 persons per year; P < 0.01) and equaled the rates for the white population in some areas. Esophageal adenocarcinoma rates continued rising for white males through 1998, whereas cardia adenocarcinoma rates stabilized after 1988.

CONCLUSIONS

There are substantial regional, temporal, and ethnic differences between esophageal adenocarcinoma incidence rates and gastric cardia adenocarcinoma incidence rates within a single cancer registry system. Thus, these malignancies may differ in important ways and should not be combined routinely in research studies. Individual‐level studies are needed to explain these substantial regional and ethnic differences. Cancer 2002;95:2096–102. © 2002 American Cancer Society.

DOI 10.1002/cncr.10940
A Phase II trial of pegylated liposomal doxorubicin, vincristine, and reduced‐dose dexamethasone combination therapy in newly diagnosed multiple myeloma patients
Authors: Hussein Mohamad A. , Wood Laura , Hsi Eric , Srkalovic Gordan , Karam MaryAnn , Elson Paul , Bukowski Ronald M.
Published: November 2002

BACKGROUND

Patients with multiple myeloma (MM) have increased bone marrow angiogenesis, a low plasma cell labeling index, and multidrug resistance (the primary cause of chemotherapy failure). MM patients receiving the vincristine, doxorubicin, and dexamethasone (VAD) regimen develop resistance and cardiac and steroid toxicity. Pegylated liposomal doxorubicin (Doxil®/CAELYX™) could potentially extend the duration of malignant plasma cell exposure to therapeutic levels of doxorubicin. This Phase II study evaluates combination pegylated liposomal doxorubicin, vincristine, and reduced‐dose dexamethasone in MM patients.

METHODS

Thirty‐three newly diagnosed patients with MM received intravenous pegylated liposomal doxorubicin (40 mg/m2), vincristine (2.0 mg, Day 1), and oral or intravenous dexamethasone (40 mg per day for 4 days) every 4 weeks for six or more cycles and/or for two cycles after the best response.

RESULTS

The overall response rate was 88%: 4 (12%) patients achieved a complete response, 18 (55%) a major response, and 7 (21%) a minor response. Three patients (9%) had stable and one (3%) had progressive disease. The median time to progression was 23.1 months, with 2‐year and 3‐year progression‐free survival rates of 42% and 23%, respectively. The patient survival rate at 3 years was 67%. No patients discontinued treatment due to adverse events. Myelosuppression was manageable. The most common toxicities were Grade 3 palmar–plantar erythrodysesthesia, mucositis, and neutropenia. Only one patient experienced cardiotoxicity.

CONCLUSIONS

Substituting pegylated liposomal doxorubicin for doxorubicin in the VAD regimen and reducing the dose of dexamethasone in patients with MM improve the safety profile and convenience of the treatment regimen without compromising efficacy. Cancer 2002;95:2160–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10946
Targeted insertion results in a Rhombomere 2‐specific Hoxa2 knockdown and ectopic activation of Hoxa1 expression
Authors: Ren Shu‐Yue , Angrand Pierre‐Olivier , Rijli Filippo M.
Published: November 2002

Recent studies indicated that retention of selectable marker cassettes in targeted Hox loci may cause unexpected phenotypes in mutant mice, due to neighborhood effects. However, the molecular mechanisms have been poorly investigated. Here, we analysed the effects of the targeted insertion of a PGK‐neo cassette in the 3′ untranslated region of Hoxa2. Even at this 3′ position, the insertion resulted in homozygous mutants that unexpectedly did not survive beyond 3 weeks of age. Molecular analysis of the targeted allele revealed a selective “knockdown” of Hoxa2 expression in rhombomere 2 and associated patterning abnormalities. Moreover, Hoxa1 was ectopically expressed in the hindbrain and branchial arches of mutant embryos. Of interest, we demonstrated that the ectopic expression was due to the generation of neo‐Hoxa1 fusion transcripts, resulting from aberrant alternative splicing. These defects could be rescued after removal of the PGK‐neo cassette by Flp‐mediated recombination. These results underscore the complexity of transcriptional regulation at Hox loci and provide insights into the in vivo regulation of Hoxa2 segmental expression. They also provide a molecular basis for the interpretation of unexpected Hox knockout phenotypes in which the targeted selectable marker is retained in the locus. © 2002 Wiley‐Liss, Inc.
A comparison of river load estimation techniques: application to dissolved organic carbon
Authors: Cooper D. M. , Watts C. D.
Published: October 2002

The transport of dissolved organic carbon (DOC) from land to ocean is a significant component of the global carbon cycle, and good estimates of the load transported in rivers are needed. Three load estimation techniques are investigated using field data from an upland catchment in Wales. The methods use approximately weekly concentration measurements with corresponding discharge measurement, supplemented by 15 min measurements of discharge. Annual load estimates are obtained for the years 1985–2000 with the following treatment of supplementary information: (i) exclusion using simple extrapolation; (ii) inclusion using the ratio method; (iii) inclusion using the rating curve method with a straight line fitted to the logarithms of load and discharge data. A variance estimate is given for the three load estimation methods. The influence of additional opportunistic DOC concentration measurements on load estimation is discussed and investigated. The importance of an unbiased sampling procedure for simple extrapolation is demonstrated, but the inclusion of opportunistic data from high discharge samples is shown to improve rating curve estimates of load, reducing their variance. The strong influence of parameter uncertainty in the load variance for the rating curve method is demonstrated, as well as the sensitivity of the method to model assumptions. Copyright © 2002 John Wiley & Sons, Ltd.
Stochastic modelling of global solar radiation measured in the state of Kuwait
Authors: Al‐Awadhi S. A. , El‐Nashar N.
Published: October 2002

Two stochastic models that capture the main features of daily exposure of global radiation in Kuwait are proposed. The development of these models is based on removing the annual periodicity and seasonal variation of solar radiation. Thus the daily radiation is decomposed as the sum of the trend component and a stochastic component. In many situations, there are dramatic changes in the radiation series through the year due to the condition of the weather, as is the case of the data from Kuwait. This would affect the accuracy of the model, and therefore the series is divided into two regimes: one corresponds to clear days where the value of the global radiation would be normal and the other to non‐clear days where the value of global radiation would be very low. Then the trend component is expressed as a Fourier series taking into account such apparent breaks in the series. The stochastic component is first tested for linearity and Gaussianity and it is found that it does not satisfy these assumptions. Therefore, a linear time series model (ARMA modeling) may not be adequate and, to overcome this problem, a bilinear time series is used to model the stochastic component of daily global radiation in Kuwait. The method proposed considers first fitting an AR model to the data and then seeing whether a further reduction in the mean sum of squares can be achieved by introducing extra bilinear terms. The Akaike Information Criterion (AIC) is used to select the best model. Copyright © 2002 John Wiley & Sons, Ltd.
The inclusion of exogenous variables in functional autoregressive ozone forecasting
Authors: Damon Julien , Guillas Serge
Published: October 2002

In this article, we propose a new technique for ozone forecasting. The approach is functional, that is we consider stochastic processes with values in function spaces. We make use of the essential characteristic of this type of phenomenon by taking into account theoretically and practically the continuous time evolution of pollution. One main methodological enhancement of this article is the incorporation of exogenous variables (wind speed and temperature) in those models. The application is carried out on a six‐year data set of hourly ozone concentrations and meteorological measurements from Béthune (France). The study examines the summer periods because of the higher values observed. We explain the non‐parametric estimation procedure for autoregressive Hilbertian models with or without exogenous variables (considering two alternative versions in this case) as well as for the functional kernel model. The comparison of all the latter models is based on up‐to‐24 hour‐ahead predictions of hourly ozone concentrations. We analyzed daily forecast curves upon several criteria of two kinds: functional ones, and aggregated ones where attention is put on the daily maximum. It appears that autoregressive Hilbertian models with exogenous variables show the best predictive power. Copyright © 2002 John Wiley & Sons, Ltd.
Bilinear estimation of pollution source profiles and amounts by using multivariate receptor models
Authors: Sug Park Eun , Spiegelman Clifford H. , Henry Ronald C.
Published: October 2002

Multivariate receptor models aim to identify the pollution sources based on multivariate air pollution data. This article is concerned with estimation of the source profiles (pollution recipes) and their contributions (amounts of pollution). The estimation procedures are based on constrained nonlinear least squares methods with the constraints given by nonnegativity and identifiability conditions of the model parameters. We investigate several identifiability conditions that are appropriate in the context of receptor models, and also present new sets of identifiability conditions, which are often reasonable in practice when the other traditional identifiability conditions fail. The resulting estimators are consistent under appropriate identifiability conditions, and standard errors for the estimators are also provided. Simulation and application to real air pollution data illustrate the results. Copyright © 2002 John Wiley & Sons, Ltd.
Importance of identification of the model: some comments on the article ‘Bilinear estimation of pollution source profiles and amounts by using multivariate receptor models’
Authors: Sato M.
Published: October 2002

The original article deals with estimating pollution source profiles and amounts. It makes an important contribution to the study of air pollution. I make some comments on this stimulating article. Copyright © 2002 John Wiley & Sons, Ltd.
Comments on the article ‘Bilinear estimation of pollution source profiles and amounts by using multivariate receptor models’
Authors: El‐Shaarawi A. H.
Published: October 2002

I welcome this article as it sheds new light on the important but difficult problem of the identification of pollution sources and the estimation of their contributions from field monitoring data. The article raises a number of technical issues, which are pertinent to the use of its methods in applications. In particular, a number of assumptions are used but without indicating how they can be tested from the data. I will confine my comments to: (a) the model specification and how it might be used in practice; (b) the estimation of the model's parameters. Copyright © 2002 John Wiley & Sons, Ltd.
Refining the submesh strategy in the two‐level finite element method: application to the advection–diffusion equation
Authors: Franca Leopoldo P. , Hwang Feng‐Nan
Published: October 2002

We introduce a new submesh strategy for the two‐level finite element method. The numerical results show that the new submesh is able to better capture the boundary layer which is caused by the choice of bubble functions. The effect of an improved approximation of the residual free bubbles is studied for the advective–diffusive equation. Copyright © 2002 John Wiley & Sons, Ltd.
Convergence acceleration by self‐adjusted time stepsize using Bi‐CGSTAB method for turbulent separated flow computation
Authors: Tsai W. B. , Lin W. W. , Chieng C. C.
Published: October 2002

Poor convergence behavior is usually encountered when numerical computations on turbulent separated flow are performed. A design of self‐adjusted stepsize concept both in time span and spatial coordinate systems to achieve faster convergence is demonstrated in this study. The determination of the time stepsize based on the concept of minimization of residuals using the Bi‐CGSTAB algorithm is proposed. The numerical results show that the time stepsize adjusted by the proposed method indeed improves the convergence rate for turbulent separated flow computations using advanced turbulence models in low‐Reynolds number forms. Copyright © 2002 John Wiley & Sons, Ltd.
A multi‐block lattice Boltzmann method for viscous fluid flows
Authors: Yu Dazhi , Mei Renwei , Shyy Wei
Published: October 2002

Compared to the Navier–Stokes equation‐based approach, the method of lattice Boltzmann Equation (LBE) offers an alternative treatment for fluid dynamics. The LBE method often employs uniform lattices to maintain a compact and efficient computational procedure, which makes it less efficient to perform flow simulations when there is a need for high resolution near the body and/or there is a far‐field boundary. To resolve these difficulties, a multi‐block method is developed. An accurate, conservative interface treatment between neighboring blocks is adopted, and demonstrated that it satisfies the continuity of mass, momentum, and stresses across the interface. Several test cases are employed to assess accuracy improvement with respect to grid refinement, the impact of the corner singularity, and the Reynolds number scaling. The present multi‐block method can substantially improve the accuracy and computational efficiency of the LBE method for viscous flow computations. Copyright © 2002 John Wiley & Sons, Ltd.
Multigrid convergence of inviscid fixed‐ and rotary‐wing flows
Authors: Allen C. B.
Published: October 2002

The affect of multigrid acceleration implemented within an upwind‐biased Euler method is presented, and applied to fixed‐wing and rotary‐wing flows. The convergence of fixed‐ and rotary‐wing computations is shown to be vastly different, and multigrid is shown to be less effective for rotary‐wing flows. The flow about a hovering rotor suffers from very slow convergence of the inner blade region, where the flow is effectively incompressible. Furthermore, the vortical wake must develop over several turns before convergence is achieved, whereas for fixed‐wing computations the far‐field grid and solution have little significance. Results are presented for single mesh and two, three, four, and five level multigrid, and using five levels a reduction in required CPU time of over 80 per cent is demonstrated for rotary‐wing computations, but 94 per cent for fixed‐wing computations. It is found that a simple V‐cycle is the most effective, smoothing in the decreasing mesh density direction only, with a relaxed trilinear prolongation operator. Copyright © 2002 John Wiley & Sons, Ltd.
Sedimentary record of a tsunami during Roman times, Bay of Cadiz, Spain
Authors: Luque L. , Lario J. , Civis J. , Silva P. G. , Zazo C. , Goy J. L. , Dabrio C. J.
Published: November 2002

Historical data show that the Gulf of Cadiz has been exposed to destructive tsunamis during at least the past 2000 yr. The last tsunami was generated by the AD 1755 Lisbon earthquake, which affected the Atlantic coasts of Spain, Portugal and Morocco. Today, these littoral areas are intensely populated and the expected damage could be much greater. Tsunami studies are of great importance in helping to determine the recurrence interval of these events.

The presence of washover fan deposits on the inland margin of the Valdelagrana Spit bar (Cadiz, Spain) indicates the occurrence of a high energy marine event ca. 2300 cal. yr BP. Historical, geomorphological, sedimentological, palaeontological and geochronological data suggest that a tsunami could have affected the area during Roman times. Copyright © 2002 John Wiley & Sons, Ltd.
Defining the centre of glacio‐isostatic uplift of the last Scottish ice‐sheet: the Parallel Roads of Glen Roy, Scottish Highlands
Authors: Dawson Alastair G. , Hampton Shaun , Fretwell Peter , Harrison Stephan , Greengrass Peter
Published: November 2002

The Parallel Roads of Glen Roy, Scottish Highlands, represent a series of ice‐dammed lake shorelines produced during the cold climate of the Younger Dryas. It is shown here that each lake shoreline exhibits evidence of glacio‐isostatic tilting associated with the decay of the last (Late Devensian) ice sheet. The directions of tilting of the three shorelines (in the quadrant between north and east), are at variance with published glacio‐isostatic uplift isobases based on marine shoreline data that suggest a pattern of decreased uplift towards the northwest. The gradient of shoreline tilting (between 0.11 and 0.14 m km−1) is similar to measured regional tilts of a well‐developed marine shoreline (the Main Rock Platform) considered to have been produced in Scotland during the same period of extreme cold climate. Consideration of the ice‐dammed lake shoreline data also points to the former occurrence of two separate episodes of tectonic activity during the Younger Dryas. Copyright © 2002 John Wiley & Sons, Ltd.
Does systematic lymphadenectomy have a benefit on survival of suboptimally debulked patients with stage III ovarian carcinoma? A DEGOG* Study
Authors: Saygili Ugur , Guclu Serkan , Uslu Turhan , Erten Oktay , Ture Sevgi , Demir Namik
Published: October 2002

Background and Objectives

The aim of this study was to investigate whether systematic lymphadenectomy is necessary in suboptimally cytoreduced patients with stage III ovarian carcinoma.

Methods

Prognostic significance and the effect on survival of systematic pelvic and para‐aortic lymphadenectomy were investigated retrospectively in 61 suboptimally debulked patients with stage III ovarian carcinoma. All patients received platinum‐based chemotherapy after surgery; 51 patients had been followed for ≥1 year, or until death. Survival curves were calculated according to the Kaplan‐Meier method and were evaluated by log‐rank test.

Results

Most patients had stage IIIC disease (60.7%), poorly differentiated tumor (45.9%), and serous histological type (59%). Systematic pelvic and para‐aortic lymphadenectomy was performed in 29 patients (47.5%). Lymph node metastases were found in 17 (58.6%) patients; the median number of metastatic nodes was 7 (5–10). Lymph node metastasis was significantly higher in patients with residual disease of >2 cm (P < 0.05). Both univariate and multivariate analyses showed that systematic pelvic and para‐aortic lymphadenectomy was not a significant prognostic factor (P > 0.05). In lymph node‐dissected patients, survival was significantly longer in patients with minimal residual tumor than in those with residual tumor size >2 cm (P = 0.005).

Conclusions

Lymphadenectomy seems not to have an evident prognostic value and a benefit on survival in suboptimally debulked patients with stage III ovarian carcinoma. J. Surg. Oncol. 2002;81:132–137. © 2002 Wiley‐Liss, Inc.
Adenocarcinoma of the stomach in patients age 35 years and younger: No impact of early diagnosis on survival outcome
Authors: Windham T. Christopher , Termuhlen Paula M. , Ajani Jaffer A. , Mansfield Paul F.
Published: October 2002

Background and Objectives

Patients aged 35 years and younger with gastric adenocarcinoma constitute a group of patients who have been observed to have low survival rates as compared with older gastric adenocarcinoma patients. A low index of suspicion for gastric cancer in this age group has been suspected to result in a delay in diagnosis. The use of computed tomography (CT) scanning and endoscopy has become much more common during the past 15 years. We hypothesized that early diagnosis would result in improved survival for these patients.

Methods

We performed a retrospective study of 127 patients aged 35 years and younger with gastric (median follow‐up, 9 months).

Results

High proportions of female patients and Hispanic patients were observed. Overall survival of this group of patients was poor, with a median survival of only 8 months. Comparison of patients diagnosed within 2 months of the onset of symptoms with those diagnosed later revealed no survival advantage to early diagnosis. Similarly, diagnosis within 2 months of presentation to a physician conferred no survival advantage.

Conclusions

Long‐term survival is rare, with a short overall median survival. Early diagnosis conferred no survival advantage. This group of patients should be considered for protocol based multi‐modality therapy, even with potentially resectable disease. J. Surg. Oncol. 2002;81:118–125. © 2002 Wiley‐Liss, Inc.
Phase II study of gemcitabine combined with radiation therapy in patients with localized, unresectable pancreatic cancer
Authors: Epelbaum Ron , Rosenblatt Edward , Nasrallah Suheil , Faraggi David , Gaitini Dianna , Mizrahi Solly , Kuten Abraham
Published: October 2002

Background and Objectives

Gemcitabine is an active agent in pancreatic cancer, with known radiosensitizing properties. Therefore, a phase II study was conducted to evaluate the efficacy of gemcitabine combined with radiation therapy in patients with localized unresectable adenocarcinoma of the pancreas.

Methods

Weekly gemcitabine at a dose of 1,000 mg/m2 for 7 weeks was given as an induction phase. Patients who showed both clinical benefit response (CBR) and reduced or stable tumor size on computed tomography (CT) scan entered the chemoradiotherapy phase of the treatment. This consisted of gemcitabine 400 mg/m2 weekly ×3 every 28 days for 2 cycles, given concurrently with radiotherapy, for a total dose of 50.4 Gy in 28 fractions. After completion of radiotherapy, gemcitabine was continued as maintenance.

Results

Twenty patients entered this study. Ten patients (50%) achieved CBR to gemcitabine in the induction phase; these patients had no objective tumor progression and were therefore enrolled in the chemoradiotherapy phase. Four patients (20%) had a partial response, and three patients (15%) underwent pancreatectomy. Two patients had negative surgical margins, and in one patient histologic examination of the residual mass showed only fibrosis. The median survival for the entire group was 8 months, and the median survival has not yet been reached for the chemoradiotherapy group.

Conclusions

Treatment with gemcitabine concomitant with radiation therapy according to the present schedule is well tolerated and can provide prolonged CBR and disease stabilization in patients with localized, unresectable pancreatic cancer. J. Surg. Oncol. 2002;81:138–143. © 2002 Wiley‐Liss, Inc.
5‐ and 10‐year survival in cancer patients aged 90 and older: A study of 37,318 patients from SEER
Authors: Saltzstein Sidney L , Behling Cynthia A.
Published: October 2002

Background and Objectives

Uncertainty exists about the value of cancer therapy in patients aged 90 years and older. Because of the relative paucity of these patients, as well as the possibility of selection bias in any one institution, the use of a large, total population‐based cancer registry was employed.

Methods

The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI) offers a large, total population‐based cancer registry. It includes more than 2,000,000 cases in the nine registry data from 1973 to 1998; 37,318 of these are 90 or older and are eligible for follow‐up studies. A cross‐sectional study of relative survival of all these cases, along with younger age groups for comparison, was carried out.

Results

After the first year after diagnosis, the annual relative survival is not affected by a patient's age for up to 10 years.

Conclusions

Age alone is not a contraindication to cancer treatment in the most elderly and, other than in the first year, one can expect the same relative survival in these oldest patients as one does for younger patients. J. Surg. Oncol. 2002;81:113–116. © 2002 Wiley‐Liss, Inc.
Aggressive resection of retroperitoneal sarcoma is superior to simple excision: An animal study using a novel model for retroperitoneal sarcoma
Authors: Tsivian Alexander , Lev‐Chelouche Dina , Shtabsky Alexander , Issakov Josephine , Sidi Ami A. , Gutman Mordechai , Szold Amir
Published: October 2002

Background and Objectives

Retroperitoneal sarcomas constitute a difficult management problem. The need for, and extent of, aggressive surgery continues to be debated. The aim of our study was to compare the impact of radical en bloc resection of retroperitoneal sarcoma with complete resection of the tumor alone in a rat model.

Methods

Under laparoscopic guidance, a fibrosarcoma cell line suspension was injected into the left paranephric space of a rat, resulting in the development of a macroscopic retroperitoneal tumor. Ten days after inoculation, 50 rats were randomized into three groups: (1) local resection, (2) radical resection, and (3) follow‐up only. Groups 1 and 2 were further randomized for sacrifice 1 month after surgery or were followed up for 2 months.

Results

Local recurrence: 46% of group 1, while none in group 2 developed local recurrence during the same follow‐up period (P = 0.02). Survival: 33% of group 1 were alive after 2 months, as compared with 54.5% of group 2. (P = 0.04). All rats in the control group died within <25 days.

Conclusions

Our results suggest that aggressive en bloc resection of retroperitoneal sarcomas with adjacent viscera, even when macroscopically uninvolved with disease, has an advantage over complete local resection alone. J. Surg. Oncol. 2002;81:144–147. © 2002 Wiley‐Liss, Inc.
Quantitative analysis of heparanase messenger RNA expression in hepatocellular carcinoma
Authors: Ikeguchi Masahide , Ueta Tsuyoshi , Yamane Yoshiaki , Hirooka Yasuaki , Kaibara Nobuaki
Published: October 2002

Background and Objectives

In the process of tumor invasion, cancer cells secrete enzymes including heparanase that degrade extracellular matrices and basement membranes of blood vessels. In the present study, the clinical importance of enhanced expression of heparanase messenger RNA (mRNA) in hepatocellular carcinoma (HCC) was evaluated.

Methods

Fresh tumor and noncancerous liver tissue adjacent to a tumor were obtained from 50 patients with HCC immediately after hepatic resection. The expression levels of heparanase mRNA were analyzed quantitatively, using the real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) method, and were compared with clinicopathological findings.

Results

Relative heparanase mRNA expression level in HCC was significantly lower than that of noncancerous liver tissue (P < 0.001). Tumor heparanase expression did not correlate with tumor differentiation, tumor stage, or patient prognosis.

Conclusions

Enhanced heparanase mRNA expression may not be a good biological marker in HCC. J. Surg. Oncol. 2002;81:148–154. © 2002 Wiley‐Liss, Inc.
Lymphatic spread among women with primary peritoneal carcinoma
Authors: Eltabbakh Gamal H. , Mount Sharon L.
Published: October 2002

Background and Objectives

Our knowledge regarding the pathologic lymphatic spread pattern of primary peritoneal carcinoma (PPC) is limited. The aim of this study was to compare the incidence and the pathologic patterns of pelvic and para‐aortic lymph node metastases among women with PPC and those with papillary serous ovarian carcinoma (PSOC).

Methods

We conducted a prospective study over the last 4 years among women with FIGO stage III and IV PPC and PSOC who had optimal primary cytoreductive surgery (<1 cm residual). The same surgeon performed pelvic and para‐aortic lymphadenectomy on all the patients using a similar technique. The same pathologist reviewed all lymph nodes and recorded nodal involvement with cancer, diameter of the largest nodal tumor, capsular integrity, and pattern of immune response (lymphocyte predominant, germinal cell predominant, unstimulated, or lymphocyte depletion). Both groups were compared in their characteristics, FIGO stage, tumor grade, number of lymph nodes, proportion of lymph nodes with metastases, and the pathologic characteristics of the positive lymph nodes.

Results

Eleven women had PPC and 27 had PSOC. Patients with PPC were older than those with PSOC (mean age: 63.2 years ± 11.0 vs. 57.4 ± 13.4, P = 0.181). There was no difference in FIGO stage or tumor grade between both groups. There was no difference among the mean numbers of pelvic and para‐aortic lymph nodes between women with PPC and those with PSOC (10.8 ± 7.3 vs. 11.0 ± 6.7 and 3.0 ± 3.3 vs. 3.4 ± 2.1, P = 0.768 and 0.706, respectively). The incidences of pelvic, para‐aortic, and pelvic and/or para‐aortic lymph node metastases were similar among women with PPC and those with PSOC (72.7% vs. 66.6%, P = 0.701, 72.7% vs. 48.1%, P = 0.172, and 72.7% vs. 77.8%, P = 0.736, respectively). Similarly, pelvic and para‐aortic nodal tumor size, capsular integrity, and immune response were similar in both groups. The incidence of significant complications related to lymphadenectomy was low among women with PPC and those with PSOC (9.1% vs. 7.4%, respectively).

Conclusions

PPC and PSOC exhibit similar pathologic lymphatic spread patterns. Pelvic and para‐aortic lymphadenectomy should be considered among women with PPC in whom the tumor could be optimally cytoreduced. J. Surg. Oncol. 2002;81:126–131. © 2002 Wiley‐Liss, Inc.
Hospitality research: a pause for reflection
Authors: Morrison Alison
Published: October 2002

Over recent decades hospitality research has made considerable advancements and contributions to knowledge creation. However, a review of associated literature reveals that there exists a significant degree of debate concerning the definitional, philosophical and conceptual dimensions of hospitality. This paper aims to capture current thinking and key challenges confronting the research community. Conclusions are drawn calling for: definitional precision of hospitality; a clearly articulated research philosophy locating hospitality as a specialist field of study within the social science landscape; an enhanced degree of research philosophy awareness by researchers; and the benefits of formulating and agreeing an internally valid conceptual framework. Copyright © 2002 John Wiley & Sons, Ltd.
Power, social exchanges and tourism in Langkawi: rethinking resident perceptions
Authors: Kayat K.
Published: October 2002

A study was undertaken among the residents on Langkawi Island, Malaysia to explore the utility of a combination of social exchange and power theories to explain residents' attitudes toward tourism and to examine how residents' evaluation of the impact of tourism influences their attitudes. In‐depth, semi‐structured interviews were conducted with 46 residents. The study concludes that the combination of social exchange and power theories is more useful than social exchange theory alone in understanding residents' attitudes concerning the impact of tourism. However, residents' general values, dependence on tourism, and ability and willingness to adapt moderate the influence of power on residents' evaluation of the impact of tourism. Copyright © 2002 John Wiley & Sons, Ltd.
Modelling inbound international tourism demand to Portugal
Authors: Daniel Ana Cristina M. , Ramos Francisco F. R.
Published: October 2002

In this paper the Johansen cointegration analysis of time series is used to model the Portuguese inbound international tourism demand from five countries of origin—France, Germany, The Netherlands, Spain and UK. This approach examines the long‐run relationships between the demand for holiday visits and the variables that affect holiday travel such as income, destination prices and travel costs (airfares and road costs). Demand functions, for each country of origin, are estimated using annual data on tourism flows from 1975 to 1997. Copyright © 2002 John Wiley & Sons, Ltd.
Rural tourism and the development of less favoured areas—between rhetoric and practice
Authors: Ribeiro Manuela , Marques Carlos
Published: October 2002

Tourism has, in recent times, been advocated as a particularly efficient way to promote the development of the so‐called less favoured regions, mostly inland and mountain, owing to its potential for employment and income creation and the synergies it is able to generate in other sectors of activity. Based on the results of empirical research carried out in two distinct inland zones of Portugal, this article tries to demonstrate that a wide gap and considerable contradictions are emerging between the rhetoric and the real benefits that tourism has been producing in the local societies and economies of these regions. Copyright © 2002 John Wiley & Sons, Ltd.
The challenges of economic diversification through tourism: the case of Abu Dhabi
Authors: Sharpley Richard
Published: October 2002

In recent years, tourism has become a ubiquitous vehicle for economic development and diversification and, for many regions and countries both in the developed and less developed worlds, tourism has become an integral element of economic development policy. Even those countries that, in the past, have had neither the desire nor the need to seek alternative economic sectors increasingly have been turning to tourism as a potentially effective means of achieving economic growth and diversification. As this paper argues, however, the justification for using tourism as an agent of economic development must be treated with some caution. Focusing upon the case of Abu Dhabi, the oil‐rich emirate that in recent years, and in common with other countries in the region, has been seeking economic diversification through tourism to counter instability in global oil prices, a number of challenges to tourism development are identified. These may be overcome collectively through significant investment in product and promotion but, as the example of Abu Dhabi demonstrates, tourism may not always be an easy or cost‐effective means of achieving economic growth and diversification. Copyright © 2002 John Wiley & Sons, Ltd.
Booking and flying with low‐cost airlines
Authors: Piga Claudio A. , Filippi Nicola
Published: October 2002

The first part of the paper develops a theoretical framework for the analysis of strategic behaviour of European low‐cost airlines that emphasises the role of product differentiation. The second part uses original survey data to assess the effectiveness of low‐cost airlines' distribution strategies. Finally, an econometric model is developed to assess the joint impact of the factors affecting the level of the fares charged by low‐cost airlines. The evidence suggests that, among other things, the highest prices normally are paid for tickets bought between 30 and 8 days before departure, and thus indicates an original pricing strategy that differentiates low‐cost airlines from traditional carriers. Copyright © 2002 John Wiley & Sons, Ltd.
Structures and properties of the hydrides of light elements
Authors: Smith Garry T. , Smith Vedene H. , Frolov Alexei M.
Published: November 2002

Basic geometric and other properties for a number of neutral holovalent hydrides of light elements (M = Li − F)(MHn) are discussed. Their molecular geometries, energies, and vibrational frequencies have been determined from ab initio calculations of benchmark quality. We calculated harmonic vibrational frequencies, zero point vibrational energies, and atomization energies for the deuterides, tritiides, and combinations of them for these light elements. These isotopomers are of great interest for thermonuclear applications because they are often used as thermonuclear fuels or components of such fuels. In fact, only for these substances thermonuclear energy gain exceeds (at some densities and temperatures) the bremsstrahlung loss and other high‐temperature losses, i.e., thermonuclear burn‐up is possible. The vibrational frequencies are useful in determining the composition of mixed samples by means of spectroscopy. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Protein‐folding simulations in generalized ensembles
Authors: Hansmann Ulrich H. E.
Published: November 2002

We demonstrate that modern simulation techniques such as the generalized‐ensemble approach allow one to study secondary structure formation and folding in peptides and small proteins. Two systems are investigated. For the simple artificial peptide, Ala10‐Gly5‐Ala10, we research the relation between helix formation and folding. The 36‐residue villin headpiece peptide HP‐36 is used to study the structure prediction of proteins with our techniques. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Site preference occupation of Ti, Ni, and Cr in Fe3Al compound
Authors: Fuks David , Dorfman Simon , Liubich Vlad , Kutsenko Larisa
Published: November 2002

Nonempirical study of the site preference occupation for Ni, Ti, and Cr substituting for Fe in Fe0.75‐xMexAl0.25 has been carried out for a number of Me dopant concentrations in the framework of the coherent potential approximation. Obtained values of total energies confirmed experimental observations that Ni atoms occupy the sublattice Fe(1) (see Fig. 1), Ti atoms occupy the sublattice Fe(2), and Cr atoms do not show any preference in substitution of Fe in Fe0.75‐xMexAl0.25. We demonstrated also that Ni addition to Fe0.75‐xMexAl0.25 does not change the type of bonding in Fe0.75‐xNixAl0.25, while Cr and Ti additions lead to sufficient hybridization of d‐electrons. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Environment effects on chemical reactivity of heme proteins
Authors: Scherlis Damián A. , Martí Marcelo A. , Ordejón Pablo , Estrin Darío A.
Published: November 2002

Heme proteins are involved in a variety of physiological processes, such as O2 transport, electron transfer, sensing of O2 or CO, and catalysis of redox reactions. Despite the differences in biologic function, all these proteins have iron protoporphyrin IX (heme b) as the active site. The amino acids surrounding the active site are responsible for the specific reactivity of each protein. We analyzed the environment effects on binding of small ligands such as O2 and NO to several heme proteins using density functional theory (DFT) calculations of model systems including selected amino acid residues, and also DFT calculations of the active site coupled to an electrostatic representation of the rest of the protein. Specifically, we considered the following problems: (1) the mechanisms underlying inactivation by nitric oxide of cytochrome P450; (2) O2 affinity of human and Ascaris hemoglobin and the role of oxygen hydrogen bonding to the distal amino acids; (3) the influence of the amino acid residues surrounding the proximal histidine in the Fehistidine bond cleavage upon binding of NO in FixL, horseradish peroxidase, and human hemoglobin. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Virtues and potentialities of the Fourier transform method for electronic structure calculations of 1‐D periodic systems at the Hartree–Fock level and beyond
Authors: Delhalle Joseph , Fripiat Joseph G. , Harris Frank E.
Published: November 2002

A major challenge in electronic structure calculations of extended systems is to compute to appropriate accuracy the lattice sums arising in the various ab initio formalisms. Unsatisfactory convergence of all or some of these contributions can lead to such imbalance in the matrix elements that total energy, hence the most stable structure, and other more sensitive properties such as force constants cannot be computed. The purpose of this article is to point out the intrinsic virtues of the Fourier transform method for handling accurately the lattice sums arising in Hartree–Fock and many‐body approaches such as MP2. The infinite chain of Be atoms, (‐Be‐)∞, is used to illustrate some of the points addressed in the present contribution. Even in this simple system it is seen that direct‐space methods do not permit the exchange energy sum to be converged sufficiently to permit computations near the equilibrium lattice spacing. However, the Fourier transform method enables identification of the equilibrium configuration in a stable and accurate fashion. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002