bluuebunny/crossref_metadata_2025_split huggingface dataset:
360‐degree feedback with systematic coaching: Empirical analysis suggests a winning combination
Authors: Luthans Fred , Peterson Suzanne J. 
Published: January 2004

AbstractWanted: High‐performance work practices to gain a competitive advantage. An increasingly common answer
to this desperate call is 360‐degree programs; unfortunately, they have, at best, mixed reviews when
empirically assessed. This study found that a way to improve the effectiveness of 360s may be to combine them with
coaching focused on enhanced self‐awareness and behavioral management. In a small manufacturer, this
feedback‐coaching resulted in improved manager and employee satisfaction, commitment, intentions to
turnover, and at least indirectly, this firm's performance. This feedback‐coaching may be a winning
combination to help in the competitive battles in today's global economy. © 2004 Wiley Periodicals,
Inc.
HR's role in corporate governance: Present and prospective
Authors: Beatty Richard W. , Ewing Jeffrey R. , Tharp Charles G. 
Published: January 2004

AbstractCorporate wrongdoing is damaging investor confidence and tarnishing the credibility of the U.S. business community, guilty and innocent alike. Some misdeeds are clearly criminal, others simply unethical or damaging to reputations. They range from “massaging” numbers (“managed earnings”), which tests the limits of financial prudence, to outright fraud. Caught in the limelight are U.S. corporate giants representing some of the world's best‐known brands and most famous CEOs, many only yesterday lionized in the business press.We have explored this issue from the perspective of the HR function through a survey of the senior HR professionals who attended the Human Resources Forum. The survey was augmented with focus groups. Our purpose was to understand current practices, attitudes, and behaviors with respect to legal standards and professional and ethical codes. We also explored the roles of the CEO, HR leadership, and the HR function in minimizing ethical breaches that have diminished investor and public trust. We hope to shed light on the responsibilities, actions, and risks of the HR function and its leadership now and in the future. © 2004 Wiley Periodicals, Inc.
Redesigning the human resources function at Lafarge
Authors: Som Ashok 
Published: January 2004

AbstractThis article describes the detailed process of redesigning and implementing the human resources (HR)
function at Lafarge. The article argues that a well‐articulated and integrated approach of (1)
recruitment, selection, and induction, (2) retraining and redeployment, (3) a performance
appraisal system, (4) a compensation and reward mechanism, and (5) rightsizing and (6)
integration is required to be aligned with the overall business strategy of the organization. It also reinforces
that the foundation of a value‐added HR function is a business strategy that relies on people as a source of
competitive advantage. Key challenges for Lafarge in the future include (1) maintaining the change
momentum, (2) fast and effective integration of acquired companies and transfer of “best
practices,” and (3) attracting and retaining a diverse workforce through their internationalization
program. © 2004 Wiley Periodicals, Inc.
Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma
Authors: Gao Shan , Worm Jesper , Guldberg Per , Eiberg Hans , Krogdahl Annelise , Liu Chung‐Ji , Reibel Jesper , Dabelsteen Erik 
Published: January 2004

AbstractLoss of histo‐blood group A and B antigen expression is a frequent event in oral carcinomas and is associated with decreased activity of glycosyltransferases encoded by the ABO gene. We examined 30 oral squamous cell carcinomas for expression of A and B antigens and glycosyltransferases. We also examined DNA from these tumors for loss of heterozygosity (LOH) at markers surrounding the ABO locus at chromosome 9q34, for loss of specific ABO alleles, and for hypermethylation of the ABO promoters. Loss of A or B antigen expression was found in 21 of 25 tumors (84%) and was a consistent feature of tumors lacking expression of A/B glycosyltransferases. LOH at 9q34 was found in 7 of 27 cases (26%), and one case showed microsatellite instability. Among 20 AO/BO cases, 3 showed loss of the A/B allele and 3 showed loss of the O allele. Analysis of the proximal ABO promoter by methylation‐specific PCR and melting curve analysis showed hypermethylation in 10 of 30 tumors (33.3%), which was associated with loss of A/B antigen expression. ABO promoter hypermethylation was also found in hyperplastic or dysplastic tissues adjacent to the tumors, suggesting that it is an early event in tumorigenesis. Collectively, we have identified molecular events that may account for loss of A/B antigen expression in 67% of oral squamous cell carcinomas. © 2003 Wiley‐Liss, Inc.
CD4+ T cell‐mediated HER‐2/neu‐specific tumor rejection in the absence of B cells
Authors: Lindencrona Jan Alvar , Preiss Susanne , Kammertoens Thomas , Schüler Thomas , Piechocki Marie , Wei Wei‐Zen , Seliger Barbara , Blankenstein Thomas , Kiessling Rolf 
Published: January 2004

AbstractHER‐2/neu (HER‐2) is a cell surface proto‐oncogene that is often overexpressed in carcinomas. Passive administration of anti‐HER‐2 antibodies in breast cancer patients has achieved promising results, but less is known about the role of antibodies in active immunization. We asked whether B cells/antibodies are needed for tumor immunity induced by plasmid (HER‐2 and GM‐CSF) immunization. HER‐2 specific tumor immunity relied completely on both CD4+ and CD8+ T cells. IFN‐γ, and to a lesser extent IL‐4, seemed to be crucial cytokines during tumor rejection. Protection was associated with production of anti‐HER‐2 IgG antibodies in B cell competent mice. After immunization, however, B cell‐deficient mice rejected HER‐2‐expressing tumors as efficiently as control littermates. We conclude that T cells are the main effector cells in DNA vaccine induced immunity against HER‐2 and that anti HER‐2 antibodies are not necessary to elicit a protective anti tumor immune response in this model. © 2003 Wiley‐Liss, Inc.
Dynamic and intracellular trafficking of P‐glycoprotein‐EGFP fusion protein: Implications in multidrug resistance in cancer
Authors: Fu Dong , Bebawy Mary , Kable Eleanor P.W. , Roufogalis Basil D. 
Published: January 2004

AbstractIn our present study, a P‐glycoprotein‐EGFP (P‐gp‐EGFP) fusion plasmid was constructed and functionally expressed in HeLa cells to investigate the intracellular localization and trafficking of P‐glycoprotein (P‐gp). Using immunocytochemistry and fluorescent confocal microscopy techniques, colocalization studies showed that after transfection, P‐gp‐EGFP was progressively transported from the endoplasmic reticulum (ER) to the Golgi and finally to the plasma membrane within 12–48 hr. The degree of intracellular accumulation of daunorubicin was related to the particular localization of P‐gp‐EGFP. Significant daunorubicin accumulation occurred in transfected cells when P‐gp‐EGFP was localized predominantly within the ER, and accumulation remained high when P‐gp‐EGFP was mainly localized in the Golgi. However, there was little or no intracellular accumulation of daunorubicin when P‐gp‐EGFP was localized predominantly on the plasma membrane. Blocking the intracellular trafficking of P‐gp‐EGFP with brefeldin A (BFA) and monensin resulted in inhibition of traffic of P‐gp‐EGFP and retention of P‐gp‐EGFP intracellularly. Intracellular accumulation of daunorubicin also increased in the presence of BFA or monensin. Our study shows that P‐gp‐EGFP can be used to define the dynamics of P‐gp traffic in a transient expression system, and demonstrates that localization of P‐gp on the plasma membrane is associated with the highest level of resistance to daunorubicin accumulation in cells. Modulation of intracellular localization of P‐gp with agents designed to selectively modify its traffic may provide a new strategy for overcoming multidrug resistance in cancer cells. © 2004 Wiley‐Liss, Inc.
Retinoblastoma protein in human renal cell carcinoma in relation to alterations in G1/S regulatory proteins
Authors: Hedberg Ylva , Ljungberg Börje , Roos Göran , Landberg Göran 
Published: January 2004

AbstractThe retinoblastoma gene product (pRb) is the main substrate for cyclin‐dependent kinases (CDKs) during the G1/S transition. Aberrations in cell cycle regulatory proteins, which have been observed in many malignancies, can theoretically cause increased phosphorylation of pRb due to unbalanced CDK activities. The expression and phosphorylation of pRb and potential associations to cell cycle aberrations in renal cell carcinomas (RCC) has only partly been clarified. We therefore evaluated the presence of pRb and the level of pRb‐phosphorylation in 216 RCCs arranged in tissue microarrays by using different pRb‐antibodies, including pRb‐phosphospecific antibodies. Most RCCs (95%) expressed pRb, while cases with the low pRb levels, potentially indicative for pRb‐inactivation, were few. In order to detect secondary alterations to a potential pRb‐inactivation, the p16 expression was also monitored. None of the tumors exhibited increased p16 levels, confirming that pRb‐inactivation is rare in RCC. Phosphorylated pRb was detected in approximately 50% of the RCCs, using Western blotting or immunohistochemistry. The immunohistochemical ppRbser807/811 levels were associated with high proliferation, cyclin D1, cyclin E and p27 protein content. Surprisingly, there was no association between pRb‐phosphorylation and clinicopathological data. In summary, pRb seemed to be functional and aberrations in G1/S‐regulatory proteins were associated with increased phosphorylation of pRb and proliferation. The data supports that pRb might be one of the main cell cycle regulators in RCC. © 2003 Wiley‐Liss, Inc.
Single nucleotide polymorphisms result in impaired membrane localization and reduced atpase activity in multidrug transporter ABCG2
Authors: Mizuarai Shinji , Aozasa Naohiko , Kotani Hidehito 
Published: January 2004

AbstractABCG2/MXR/ABCP1/BCRP is a member of the ATP‐binding cassette membrane transporter, which consists of six transmembrane regions and one ATP‐binding cassette. The transporter is known to be involved in the efflux of various anticancer compounds such as mitoxantrone, doxorubicin and topoisomerase I inhibitor. In this study, we analyzed the effects of polymorphisms in ABCG2, V12M and Q141K on transporter function. When polarized LLC‐PK1 cells were transfected with variant ABCG2, drug‐resistance to topoisomerase I inhibitor of cells expressing V12M or Q141K was less than 1/10 that of wild‐type ABCG2 transfected cells, and was accompanied by increased drug accumulation and decreased drug efflux in the variant ABCG2‐expressing cells. We further elucidated the molecular mechanisms of the transport dysfunction by investigating membrane localization and ATPase activity. Confocal microscopic analysis revealed that apical plasma membrane localization of V12M was disturbed, while the localization of wild‐type transporters occurred specifically in the apical plasma membrane of polarized LLC‐PK1 cells. Also, ATPase activities measured in the membrane of SF9 cells infected with variant ABCG2 showed that Q141K decreased activity by 1.3 below that of wild‐type ABCG2. In addition, kinetic analysis of ATPase activity showed that the Km value in Q141K was 1.4‐fold higher than that of wild‐type ABCG2. These results indicated that naturally occurring SNPs alter transport functions of ABCG2 transporter and analysis of SNPs in ABCG2 may hold great importance in understanding the response/metabolism of chemotherapy compounds that act as substrates for ABCG2. © 2003 Wiley‐Liss, Inc.
Survival of cervix cancer patients in Harare, Zimbabwe, 1995–1997
Authors: Chokunonga Eric , Ramanakumar Agnihotram V. , Nyakabau Anna M. , Borok Margaret Z. , Chirenje Z. Michael , Sankila Risto , Parkin D. Maxwell 
Published: January 2004

AbstractThe survival experience of 284 patients with cancer of the cervix uteri registered by the population‐based Zimbabwe National Cancer Registry in 1995–1997 is described. The vital status of these subjects was established by linkage with death registration and by retrieval of patient files from medical records departments. Untraced patients were contacted at home. Of the 284, 177 (62.3%) were dead and 76 (26.8%) were alive at the closing date of the study (31 December 1999), with only 31 cases (10.9%) lost to follow‐up. Overall observed and relative survival at 3 years were 44.2% and 45.2%, respectively. Half of the cases (139) had been referred and treated in the radiotherapy department. Survival was significantly greater in the first 3 years for patients who received radiotherapy treatment compared to those that had not, but this difference had disappeared by the fourth year of follow‐up. Many cases presented late (distant metastasis), and extent of disease was an important determinant of survival; cases with metastases had a risk of death some 3 times that of patients with localized disease. The results demonstrate the importance of earlier diagnosis and availability of effective treatment in the African context. © 2003 Wiley‐Liss, Inc.
Resistance of pancreatic cancer to gemcitabine treatment is dependent on mitochondria‐mediated apoptosis
Authors: Schniewind Bodo , Christgen Matthias , Kurdow Roland , Haye Sieglinde , Kremer Bernd , Kalthoff Holger , Ungefroren Hendrik 
Published: January 2004

AbstractPalliative chemotherapy with gemcitabine, a common mode of treatment of pancreatic cancer, has little influence on patients' survival. We investigated the impact of anti‐apoptotic Bcl‐xL protein and its antagonist Bax on gemcitabine‐induced apoptosis in human pancreatic carcinoma cells in vitro and in vivo. The level of Bcl‐xL and Bax expression was determined in 3 established pancreatic cancer cell lines that differ in their sensitivity to gemcitabine‐mediated apoptosis. Bcl‐xL and Bax genes were transduced into Colo357 cells by retroviral infection. In addition, cells were transfected with c‐FLIP to assess involvement of CD95 and caspase‐8. The impact of Bax/Bcl‐xL expression on gemcitabine‐sensitivity in vivo was evaluated in orthotopic Colo357 tumors in SCID mice. The apoptotic index revealed a strong inverse correlation between Bcl‐xL expression and gemcitabine‐induced apoptosis in the pancreatic carcinoma cell lines tested. Caspase‐8 and Bid were cleaved in Colo357 cells exposed to gemcitabine, and there was no correlation with either Bcl‐xL or with Bax expression. In contrast, the lack of mitochondrial transmembrane potential transition, release of cytochrome‐c and absence of caspase‐9‐ and PARP‐cleavage showed a strong correlation with Bcl‐xL expression. Expression of c‐FLIP significantly increased the resistance towards gemcitabine. Orthotopically growing Colo357‐bcl‐xl tumors in SCID mice were refractory to gemcitabine treatment, and in contrast to the in vitro data, Colo357‐bax tumors exhibited a 12‐fold greater tumor regression than Colo357‐wild‐type tumors in the control group. Gemcitabine‐induced apoptosis involves the mitochondria‐mediated signaling pathway. A functional restoration of this pathway appears to be essential to overcome the resistance mechanisms of pancreatic tumor cells and to improve the response to therapy as demonstrated by Bax overexpression in a clinically relevant tumor model. © 2003 Wiley‐Liss, Inc.
MHC class I antigen processing pathway defects, ras mutations and disease stage in colorectal carcinoma
Authors: Atkins Derek , Breuckmann Aldona , Schmahl Gerd E. , Binner Priska , Ferrone Soldano , Krummenauer Frank , Störkel Stephan , Seliger Barbara 
Published: January 2004

AbstractColorectal tumorigenesis has been associated with the progressive acquisition of a variety of genetic alterations. These include mutations of the Ki‐ras proto‐oncogene in codons 12 and 13, which account for 85% of genetic changes in colorectal cancer. In murine in vitro models of oncogenic transformation, an association between ras‐mediated transformation and downregulation of different components of the MHC class I antigen processing machinery (APM) has been described. In order to investigate whether this association also exists in human tumors, 10 cases of high‐grade intraepithelial neoplasia (HIN), as well as primary tumors and autologous lymph node metastases from 42 patients with colorectal carcinoma, were monitored by allele‐specific restriction analysis for Ki‐ras mutations. In parallel, APM component expression and tumor cell proliferation were analyzed by immunohistochemistry. In comparison to autologous colorectal mucosa, TAP1, LMP2 and tapasin loss was found in 68%, 67% and 80% of HIN, respectively. In contrast, impaired TAP1, LMP2 and tapasin expression was found in 42%, 42% and 63% of primary adenocarcinomas of stage III disease and in 63%, 47% and 79% of the matched lymph node metastases, respectively. More than 60% of colorectal tumor lesions with TAP1, LMP2 and/or tapasin defects displayed Ki‐ras mutations. The frequency of TAP1, LMP2 and tapasin loss varied between 33% of primary adenocarcinomas, 40% of HIN to approximately 67% of metastases. These data suggest that i) APM component deficiencies occur more frequently in Ki‐ras‐mutated colorectal carcinoma lesions and ii) APM abnormalities in conjunction with Ki‐ras mutations appear to be associated with disease stage. These findings support the hypothesis that Ki‐ras mutations may contribute to immune escape mechanisms of tumors by downregulating the MHC class I APM component expression. © 2003 Wiley‐Liss, Inc.
Esophageal squamous cell cancer in patients with head and neck cancer: Prevalence of human papillomavirus DNA sequences
Authors: de Villiers Ethel‐Michele , Gunst Karin , Stein Harald , Scherübl Hans 
Published: January 2004

AbstractAn etiologic role for human papillomavirus (HPV) infections in either head and neck (HNC) or esophageal carcinogenesis remains debatable. Patients with head and neck cancer are at high risk for developing a second esophageal squamous cell cancer (ESCC). The aim of our study was to determine whether HPV infections play a role in this multifocal carcinogenesis. Samples from 2 groups of HNC patients were studied: Random esophageal biopsies were collected from the first group of 60 patients who had been screened for asymptomatic ESCC. The second group consisted of 21 patients with pairs of HNC and ESCC. Both the fresh frozen biopsy samples of the first group and the paraffin‐embedded specimens of the second group were evaluated for the presence of HPV DNA sequences by PCR amplification, cloning and sequencing. HPV DNA sequences were detected in 66.7% of normal/inflammatory (34/51) and dysplastic and malignant (6/9) esophageal tissues from HNC patients being screened endoscopically. Similarly, in the second group of 21 patients with both HNC and ESCC, HPV DNA sequences were demonstrated in 13 (61.9%) of the HNC biopsies and in 14 (66.7%) of the ESCC biopsies. The prevalence of high‐risk‐type HPV 16 was low (5/51, 9.8%) in normal/inflammatory esophageal mucosa but higher (10/24, 47.6%) in ESCC. The low‐risk HPV 11 was present in 37.3% (19/51) of normal/inflammatory, 66.7% (4/6) of dysplastic and 28.9% (13/45) of the carcinoma samples. The same HPV type was present in only 3/21 pairs of HNC and ESCC samples, suggesting that a clonal expansion from the HNC to a subsequent ESCC, or visa versa, is unlikely. The high prevalence of “low‐risk” HPV infections points to the need for studies on possible interactions of these infections with the use of alcohol and tobacco in the pathogenesis of these tumors. © 2003 Wiley‐Liss, Inc.
Effects of trastuzumab on epidermal growth factor receptor‐dependent and ‐independent human colon cancer cells
Authors: Kuwada Scott K. , Scaife Courtney L. , Kuang Jinqiu , Li Xiufen , Wong Robert F. , Florell Scott R. , Coffey Robert J. , Gray Phillip D. 
Published: January 2004

AbstractLittle information is available as to the potential role of HER‐2 as a therapeutic target in colon cancers, which express much fewer HER‐2 receptors than breast cancer cells. Treatment of certain human colon cancer cell lines with the HER‐2 inhibitory antibody mAb 4D5 demonstrated a role for HER‐2 in mediating proliferation, apoptosis and tumorigenicity. However, only the cell lines that were dependent on autocrine EGFR‐mediated cell proliferation were susceptible to the antiproliferative and antitumorigenic effects of HER‐2 inhibition. The relative levels of HER‐2, EGFR, HER‐3 and HER‐4 were not predictive of responsiveness to mAb 4D5. Treatment with HER‐2 antibodies caused a decrease in HER‐2 protein levels in all of the colon cancer cell lines and also significantly decreased EGFR levels but only in the EGFR‐dependent cell lines. Treatment with mAb 4D5 caused the rapid ubiquitination and ligand‐dependent downregulation of the EGFR in an EGFR‐dependent colon cancer cell line. Treatment of athymic mice engrafted with EGFR‐dependent colon cancer cells with mAb 4D5 caused tumor regression and a decrease in EGFR tyrosine phosphorylation in the tumor cells. EGFR‐independent colon cancer cell xenografts were resistant to mAb 4D5 therapy. Combined inhibition of HER‐2 and EGFR caused large areas of necrosis in EGFR‐dependent colon cancer xenografts, suggesting a benefit of combined HER‐2 and EGFR inhibitor therapy. Predicting clinical responsiveness of human colon cancer cells to anti‐HER‐2 and anti‐EGFR therapy may require demonstration of EGFR tyrosine kinase dependency of the cells. © 2003 Wiley‐Liss, Inc.
Fibre intake and prostate cancer risk
Authors: Pelucchi Claudio , Talamini Renato , Galeone Carlotta , Negri Eva , Franceschi Silvia , Dal Maso Luigino , Montella Maurizio , Conti Ettore , La Vecchia Carlo 
Published: January 2004

AbstractDietary fibre has been reported to protect from several neoplasms, but the issue remains controversial. No previous study considered in depth the topic of fibres and prostate cancer. A multicentre case‐control study was conducted in Italy from 1991 to 2002, including 1,294 men with incident, histologically confirmed prostate cancer and 1,451 controls admitted to the same network of hospitals as cases with acute nonmalignant conditions. Multivariate odds ratios (OR) and 95% confidence intervals (CI) were obtained after allowance for major identified confounding factors, including total energy intake. Compared to the lowest quintile, the OR of prostate cancer for the highest quintile of total fibre intake was 0.93 (95% CI 0.71–1.22). The risk was inversely related with soluble fibre (OR = 0.89, 95% CI 0.78–1.02, for a difference between 80th and 20th percentile), cellulose (OR = 0.88, 95% CI 0.78–1.01) and vegetable fibre (OR = 0.82, 95% CI 0.73–0.93). These relationships were consistent across strata of age, family history of prostate cancer, body mass index and education. Vegetable fibres appear, therefore, to have a favourable association with prostate cancer risk. © 2003 Wiley‐Liss, Inc.