bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of utilizing a flexible work schedule on the perceived career advancement potential of women
Authors: Rogier Sara A. , Padgett Margaret Y. 
Published: March 2004

AbstractThis study examined whether a woman working a flexible schedule would be perceived as having less career
advancement potential than a woman on a regular schedule. Participants reviewed a packet of materials
simulating the personnel file of a female employee in an accounting firm who was seeking promotion from manager
to senior manager. Results indicated that participants perceived the female employee on the flexible schedule
as having less job‐career dedication and less advancement motivation; there was no difference in
perceived capability. Implications of these results for implementation of alternative work arrangements are
discussed.
Immunohistochemical analysis of NAD(P)H:quinone oxidoreductase and NADPH cytochrome P450 reductase in human superficial bladder tumours: Relationship between tumour enzymology and clinical outcome following intravesical mitomycin C therapy
Authors: Basu Saurajyoti , Brown John E. , Flannigan G. Michael , Gill Jason H. , Loadman Paul M. , Martin Sandie W. , Naylor Brian , Scally Andrew J. , Seargent Jill M. , Shah Tariq , Puri Rajiv , Phillips Roger M. 
Published: March 2004

AbstractA central theme within the concept of enzyme‐directed bioreductive drug development is the potential to predict tumour response based on the profiling of enzymes involved in the bioreductive activation process. Mitomycin C (MMC) is the prototypical bioreductive drug that is reduced to active intermediates by several reductases including NAD(P)H:quinone oxidoreductase (NQO1) and NADPH cytochrome P450 reductase (P450R). The purpose of our study was to determine whether NQO1 and P450R protein expression in a panel of low‐grade, human superficial bladder tumours correlates with clinical response to MMC. A retrospective clinical study was conducted in which the response to MMC of 92 bladder cancer patients was compared to the immunohistochemical expression of NQO1 and P450R protein in archived paraffin‐embedded bladder tumour specimens. A broad spectrum of NQO1 protein levels exists in bladder tumours between individual patients, ranging from intense to no immunohistochemical staining. In contrast, levels of P450R were similar with most tumours having moderate to high levels. All patients were chemotherapy naïve prior to receiving MMC and clinical response was defined as the time to first recurrence. A poor correlation exists between clinical response and NQO1, P450R or the expression patterns of various combinations of the 2 proteins. The results of our study demonstrate that the clinical response of superficial bladder cancers to MMC cannot be predicted on the basis of NQO1 and/or P450R protein expression and suggest that other factors (other reductases or post DNA damage events) have a significant bearing on tumour response. © 2004 Wiley‐Liss, Inc.
Proteolytic imbalance is reversed after therapeutic surgery in breast cancer patients
Authors: Giannelli Gianluigi , Erriquez Roberta , Fransvea Emilia , Daniele Antonella , Trerotoli Paolo , Schittulli Francesco , Grano Maria , Quaranta Michele , Antonaci Salvatore 
Published: March 2004

AbstractThe occurrence of metastasis severely affects prognosis and survival of breast cancer patients. In order to metastasize, breast cancer cells need to cross the basement membrane (BM) tissue boundaries. Matrix metalloproteases (MMPs) are enzymes with proteolytic activity towards extracellular matrix components (ECM) of the BM, that are blocked by physiological tissue inhibitors (TIMPs). Cancer metastasis occurs as a result of an imbalance between MMPs, in particular MMP‐2 and MMP‐9, and TIMPs, in particular TIMP‐2 and TIMP‐1. This is the first study to report that pro‐MMP‐9 and TIMP‐1 serum concentrations are inversely correlated in breast cancer patients. In the same patients, we determined the pro‐MMP‐9, the TIMP‐1, the pro‐MMP‐2 and TIMP‐2 before and after surgical eradication of the breast cancer. Our results show that after surgery, when the breast cancer tissue was removed, pro‐MMP‐9 concentrations dramatically decreased and TIMP‐1 concentrations strongly increased, with statistically significant differences, so that a new balance was established. No statistically significant differences were observed regarding pro‐MMP‐2 and TIMP‐2. Also, no correlation was found between pro‐MMP‐2, pro‐MMP‐9, TIMP‐1 and TIMP‐2 and a number of clinical and pathological parameters. In conclusion, our study suggests that pro‐MMP‐9 and TIMP‐1 could be used as markers of disease during the follow‐up of breast cancer patients and possibly as prognostic markers, although more studies are needed to address this issue. © 2004 Wiley‐Liss, Inc.
Dietary acrylamide and risk of renal cell cancer
Authors: Mucci Lorelei A. , Lindblad Per , Steineck Gunnar , Adami Hans‐Olov 
Published: March 2004

AbstractThe detection of acrylamide, classified as a probable human carcinogen, in commonly consumed foods created public health alarm. Thus far, only 2 epidemiologic studies have examined the effect of dietary acrylamide on cancer risk. Presently, we reanalyzed data from a large population‐based Swedish case‐control study of renal cell cancer. Food frequency data were linked with national food databases on acrylamide content, and daily acrylamide intake was estimated for participants. The risk of renal cell cancer was evaluated for intake of food items with elevated acrylamide levels and for total daily acrylamide dose. Adjusting for potential confounders, there was no evidence that food items with elevated acrylamide, including coffee (ORhighest vs. lowest quartile = 0.7; 95% CI = 0.4–1.1), crisp breads (ORhighest vs. lowest quartile = 1.0; 95% CI = 0.6–1.6) and fried potatoes (ORhighest vs. lowest quartile = 1.1; 95% CI = 0.7–1.7), were associated with a higher risk of renal cell cancer risk. Furthermore, there was no association between estimated daily acrylamide intake through diet and cancer risk (ORhighest vs. lowest quartile = 1.1; 95% CI = 0.7–1.8; p for trend = 0.8). The results of this study are in line with the 2 previous studies examining dietary acrylamide and suggest there is no association between dietary acrylamide and risk of renal cell cancer. © 2004 Wiley‐Liss, Inc.
Carrier cell‐mediated delivery of oncolytic parvoviruses for targeting metastases
Authors: Raykov Zahari , Balboni Ginette , Aprahamian Marc , Rommelaere Jean 
Published: March 2004

AbstractOver the last few years, naturally occurring or genetically manipulated oncolytic viruses gained increasing attention as novel therapeutics for cancer treatment. The present work provides proof of principle that an organotropic cell‐based carrier system is suitable to deliver oncolytic parvoviruses to a tissue known to be a target for the formation of metastases. Carrier cells were inactivated by γ‐irradiation after infection, which was found not to affect the production and release of parvoviruses that were capable of lysing cocultured target neoplastic cells. Although systemically administered parvovirus H‐1 showed a pronounced therapeutic effect against the development of established Morris hepatoma (MH3924A) lung metastases, the carrier cell strategy offered a number of advantages. Infected carriers were able to sustain H‐1 virus expression for 6 days in the lungs of rats affected by metastatic disease and to reduce the spreading of the virus to peripheral organs. Compared to direct virus injection, the carrier cell protocol led to an improved therapeutic effect (metastases suppression) and a lesser generation of virus‐neutralizing antibodies. These data support the use of carrier cells to deliver oncolytic viruses and/or viral vectors locally in tumors and, more particularly, metastases. © 2004 Wiley‐Liss, Inc.
Increased risk of breast cancer following different regimens of hormone replacement therapy frequently used in Europe
Authors: Stahlberg Claudia , Pedersen Anette Tønnes , Lynge Elsebeth , Andersen Zorana Jovanovic , Keiding Niels , Hundrup Yrsa Andersen , Obel Erik B. , Ottesen Bent 
Published: March 2004

AbstractEpidemiologic studies have shown an increased risk of breast cancer following hormone replacement therapy (HRT). The aim of this study was to investigate whether different treatment regimens or the androgenecity of progestins influence the risk of breast cancer differently. The Danish Nurse Cohort was established in 1993, where all female nurses aged 45 years and above received a mailed questionnaire (n = 23,178). A total of 19,898 women returned the questionnaire (86%). The questionnaire included information on HRT types and regimens, reproductive history and lifestyle‐related factors. Breast cancer cases were ascertained using nationwide registries. The follow‐up ended on 31 December 1999. Women with former cancer diagnoses, women with missing information on HRT, surgical menopause, premenopausal, as well as hysterectomized women were excluded, leaving 10,874 for analyses. Statistical analyses were performed using Cox proportional hazards model. A total of 244 women developed breast cancer during follow‐up. After adjustment for confounding factors, an increased risk of breast cancer was found for the current use of estrogen only (RR = 1.96; 95% CI = 1.16–3.35), for the combined use of estrogen and progestin (RR = 2.70; 95% CI = 1.96–3.73) and for current users of tibolone (RR = 4.27; 95% CI = 1.74–10.51) compared to the never use of HRT. In current users of combined HRT with testosterone‐like progestins, the continuous combined regimens were associated with a statistically significant higher risk of breast cancer than the cyclical combined regimens (RR = 4.16, 95% CI = 2.56–6.75, and RR = 1.94, 95% CI = 1.26–3.00, respectively). An increased risk of breast cancer was noted with longer durations of use for the continuous combined regimens (p for trend = 0.048). The European traditional HRT regimens were associated with an increased risk of breast cancer. The highest risk was found for the use of continuous combined estrogen and progestin. © 2004 Wiley‐Liss, Inc.
Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer
Authors: Agudo David , Gómez‐Esquer Francisco , Martínez‐Arribas Fernando , Núñez‐Villar Mariá José , Pollán Marina , Schneider José 
Published: March 2004

AbstractThe nuclear pore complex protein Nup88 is overexpressed in tumor cells. Immunohistochemical studies have shown that this overexpression is linked to higher aggressiveness of colorectal carcinoma and to enhanced metastatic potential of melanoma cells. However, the antibodies so far developed against Nup88 have the drawback of recognizing a number of other, up to now unspecified antigens besides Nup88. For this reason, we devised the present study on Nup88 expression at the mRNA level. RNA was extracted from fresh tumor tissue corresponding to 122 breast cancer patients. Nup88 mRNA expression was measured by means of differential RT‐PCR, standardizing against a constitutive internal control gene (β‐actin). The results were dichotomized into “high” and “low” expression levels, using the median value as cut‐off. High Nup88 mRNA expression levels correlated significantly with ductal and tubular histology (p = 0.012), histologic and nuclear grade 3 of tumors (p < 0.001), absence of hormone receptor expression (p < 0.001), expression of the c‐erb‐B2 oncogene (p < 0.001), expression of mutant p53 protein (p < 0.001), high proliferation (defined by Ki67 labeling index >20%, p < 0.001), DNA aneuploidy (p < 0.001) as well as the most important ominous clinical prognostic factor, axillary node invasion (p < 0.001). We also found an inverse correlation (p < 0.001) with expression of the H‐MAM (mammaglobin) gene, a marker of low biologic and clinical aggressiveness of breast cancer. All of these factors, without exception, define a highly aggressive tumor phenotype. These findings appear to be specific to Nup88 and not to nuclear pore proteins in general. Indeed, analysis of Nup107 (which is a limiting component of the nuclear pore complex) under the same conditions in the same tumors did not yield comparable results. © 2004 Wiley‐Liss, Inc.
Disruption of P‐glycoprotein anticancer drug efflux activity by a small recombinant single‐chain Fv antibody fragment targeted to an extracellular epitope
Authors: Haus‐Cohen Maya , Assaraf Yehuda G. , Binyamin Liat , Benhar Itai , Reiter Yoram 
Published: March 2004

AbstractInherent and acquired MDR is characterized by simultaneous resistance to diverse anticancer drugs and continues to be a major impediment in the curative chemotherapy of cancer. The MDR1 gene product, Pgp, is an ATP‐driven efflux pump, which extrudes a variety of dissimilar hydrophobic cytotoxic compounds from MDR cells. Pgp overexpression results in MDR of tumor cell lines in vitro as well as of a variety of human malignancies. Thus, one major goal is to develop strategies aimed at specifically disrupting Pgp drug‐efflux activity. To this end, we have developed a small recombinant antibody capable of potent reversal of MDR, by disrupting Pgp drug‐efflux activity. Using a phage display approach, we isolated a small scFv recombinant antibody fragment that specifically reacts with the first extracellular loop of human Pgp. This scFv fragment binds specifically to various Pgp‐overexpressing human MDR carcinoma cell lines, consequently disrupts Pgp drug‐efflux function and thereby reverses the MDR phenotype. We have successfully disrupted anticancer drug‐extrusion pump activity in MDR cells using a small recombinant scFv fragment. We propose that these novel small Fv‐based recombinant antibody molecules may lead to the development of a new class of antibody fragment‐based agents that specifically inhibit Pgp drug extrusion. Hence, these small recombinant antibody fragments may be applied in combination chemotherapy to overcome MDR in various human cancers. © 2004 Wiley‐Liss, Inc.
Protection against MUC1 expressing mouse tumours by intra‐muscular injection of MUC1 cDNA requires functional CD8+ and CD4+ T cells but does not require the MUC1 tandem repeat domain
Authors: Plunkett Tim , Graham Rosalind , Correa Isobel , Sewell Robert , Miles David , Burchell Joy , Taylor‐Papadimitriou Joyce 
Published: March 2004

AbstractUsing a C57Bl/6 mouse model system, where intramuscular (i.m.) injection of full length (FL) MUC1 cDNA protects against subsequent challenge with MUC1‐expressing syngeneic tumour cells, we have investigated the importance of the tandem repeat (TR) domain in the induction of T cell‐dependent tumour rejection. A MUC1 construct engineered to remove the TR domain (MUC1 0TR) was found to be as effective as the full length MUC1 cDNA in inhibiting the growth of RMA MUC1 cells in C57Bl/6 mice. Protection by i.m. injection of either the FL‐MUC1 cDNA or the MUC1 0TR construct depended on the presence of functional CD4+ and CD8+ T cells. Specific CD8+ T cell responses, however, could not be detected in vitro using mouse spleen cells taken after only cDNA injection, but only after challenge in vivo with MUC1‐expressing tumour cells. To attempt to enhance the responses of CD4+ T cells, a cDNA construct was developed, where the extracellular domain of MUC1 was fused to the transmembrane and cytoplasmic domain of Lamp1 (MUC1/Lamp1). This construct was equally effective in inducing tumour rejection but did not induce MUC1‐specific CTL in mice before challenge with MUC1‐expressing tumour cells. Our results indicate that, in this model, T cell responses necessary for protection against MUC1‐expressing tumours that are induced by IM injection of MUC1 cDNA are independent of the tandem repeat domain as well as the transmembrane and cytoplasmic domains. A low level of protection was seen with all constructs in BALB/c mice, which show a defect in Th1 responses. C57Bl/6×BALB/c hybrids were, however, well protected against both H2d and H2b expressing tumour challenge, emphasizing the importance of the host background. © 2004 Wiley‐Liss, Inc.
Homozygous deletion and expression of PTEN and DMBT1 in human primary neuroblastoma and cell lines
Authors: Muñoz Jorge , Lázcoz Paula , del Mar Inda María , Nistal Manuel , Pestaña Angel , Encío Ignacio J. , Castresana Javier S. 
Published: March 2004

AbstractNeuroblastoma is the most common pediatric solid tumor. Although many allelic imbalances have been described, a bona fide tumor suppressor gene for this disease has not been found yet. In our study, we analyzed 2 genes, PTEN and DMBT1, mapping 10q23.31 and 10q25.3‐26.1, respectively, which have been found frequently altered in other kinds of neoplasms. We screened both genes for homozygous deletions in 45 primary neuroblastic tumors and 12 neuroblastoma cell lines. Expression of these genes in cell lines was assessed by RT‐PCR analysis. We could detect 2 of 41 (5%) primary tumors harboring PTEN homozygous deletions. Three of 41 (7%) primary tumors and 2 of 12 cell lines presented homozygous losses at the g14 STS on the DMBT1 locus. All cell lines analyzed expressed PTEN, but lack of DMBT1 mRNA expression was detected in 2 of them. We tried to see whether epigenetic mechanisms, such as aberrant promoter hypermethylation, had any role in DMBT1 silencing. The 2 cell lines lacking DMBT1 expression were treated with 5‐aza‐2′‐deoxycytidine; DMBT1 expression was restored in only one of them (MC‐IXC). From our work, we can conclude that PTEN and DMBT1 seem to contribute to the development of a small fraction of neuroblastomas, and that promoter hypermethylation might have a role in DMBT1 gene silencing. © 2004 Wiley‐Liss, Inc.
Characterization of statically loaded tissue‐engineered mitral valve chordae tendineae
Authors: Shi Yaling , Vesely Ivan 
Published: March 2004

AbstractChordae tendineae are essential to the proper function of the mitral valve. Native chordae contain a dense collagenous core and an outer elastin sheath. We have been using the principle of directed collagen gel shrinkage to fabricate tissue‐engineered mitral valve chordae. Because the microstructure of biologic tissues determines their mechanical behavior, the morphology of collagen and elastin in tissue‐engineered chordae should mimic that of native chordae. The objective of this study, therefore, was to examine the morphology of our tissue‐engineered constructs in comparison to native chordae. A collagen‐cell suspension was cast into silicon rubber wells with microporous anchors at the ends and cultured in an incubator. The anchors allowed shrinkage to occur only transverse to the long axis of the wells, thus creating highly aligned collagen fibril constructs. The collagen constructs were cultured for 8 weeks and characterized mechanically, histologically, and biochemically at different culture time points. Histologic sections showed that in all mature constructs collagen fibers were oriented parallel to the long axis of the constructs. At the edge of the tissue collagen fibers were in general straight, whereas in the middle of the tissue they were wavy. Transmission electron microscopy showed a progressive increase in the density and longitudinal orientation of collagen fibrils with culture time. Light and scanning electron microscopy showed the presence of an elastin sheath around the collagen core. Immunostaining demonstrated that smooth muscle cells differentiate during tissue development and TUNEL assay showed that cells in the interior of the constructs undergo apoptosis. This study has demonstrated that collagen‐cell constructs, with material properties and microstructure similar to native mitral valve chordae, can be developed using static culture. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 26–39, 2004
Biocompatibility of adenoviral vectors in poly(vinyl chloride) tubing catheters with presence or absence of plasticizer di‐2‐ethylhexyl phthalate
Authors: Bilbao Roberto , Reay Daniel P. , Koppanati Bhanu M. , Clemens Paula R. 
Published: March 2004

AbstractAdenoviral (Ad) vectors feature attractive characteristics for gene therapy of a wide variety of diseases. In many cases, the Ad vector must be administered using catheters and other plastic medical devices. Although poly(vinyl chloride) is one of the most frequently used catheter materials, it is relatively rigid and requires the addition of a plasticizer such as di‐2‐ethylhexyl phthalate (DEHP) to increase its flexibility. In this study, we demonstrated that exposure to a DEHP‐containing catheter decreased the infectivity of Ad vectors but not the total particle number of the vector. Loss of Ad vector infectivity was directly related to the time of exposure to the DEHP‐containing catheter, but it was not due to simple leaching of the chemical from the plastic. The loss of Ad vector infectivity could be prevented by preflushing the tube with albumin. Careful consideration of the compatibility between gene therapy vectors and medical delivery devices will be critical to the success of human gene therapy applications. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 91–96, 2004
Effect of enamel matrix proteins on the phenotype expression of periodontal ligament cells cultured on dental materials
Authors: Inoue M. , LeGeros R.Z. , Hoffman C. , Diamond K. , Rosenberg P. A. , Craig R.G. 
Published: March 2004

AbstractCells within the periodontal ligament have the potential to regenerate a periodontal connective tissue attachment on pathologically exposed root surfaces as well as on several material surfaces including titanium. However, rather than a periodontal connective tissue attachment, a fibrous encapsulation or chronic inflammatory response has been reported at the material connective tissue interface for most dental materials. Cementum is the first tissue of the periodontal connective tissue attachment to develop and the secretion of enamel matrix related proteins on the newly mineralized dentin surface precedes and is thought to induce cementum formation. Enamel matrix‐related proteins may also function in the adult because the application of an acid extract of porcine enamel protein matrix (Emdogain®, EMD) on pathologically exposed root surfaces has been shown to result in cementum regeneration. Therefore, the objective of the present study was to determine whether the application of EMD to materials that do not normally support cementogenesis in vivo would alter the in vitro phenotype of periodontal ligament (PDL) cells including the synthesis of cementum‐associated extracellular matrix proteins. Primary PDL cells were established from 21‐day‐old Sprague‐Dawley rats, and were cultured on four materials commonly encountered in dental practice (gutta percha, calcium hydroxide, amalgam, and super EBA cement) with and without the application of EMD. After 7 or 14 days of culture, total‐DNA content, collagen synthesis, alkaline phosphatase activity, and the synthesis of a 42‐kDa cementum‐associated extracellular matrix protein were determined. PDL cells cultured on all materials had decreased total DNA content. The application of EMD further decreased total DNA content. PDL cells cultured on gutta percha and calcium hydroxide with the application of EMD had similar levels of collagen synthesis and alkaline phosphatase activity but also expressed a 42‐kDa cementum extracellular matrix‐associated protein when compared to the other groups. These results suggest that EMD can alter the phenotype of PDL cells when cultured on these dental materials. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 69A: 172–179, 2004