bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased expression of c‐Ski as a co‐repressor in transforming growth factor‐β signaling correlates with progression of esophageal squamous cell carcinoma
Authors: Fukuchi Minoru , Nakajima Masanobu , Fukai Yasuyuki , Miyazaki Tatsuya , Masuda Norihiro , Sohda Makoto , Manda Ryokuhei , Tsukada Katsuhiko , Kato Hiroyuki , Kuwano Hiroyuki 
Published: January 2004

AbstractTransforming growth factor‐β (TGF‐β) regulates cell growth inhibition, and inactivation of the TGF‐β signaling pathway contributes to tumor development. In our previous study, altered expression of TGF‐β, TGF‐β‐specific receptors and Smad4 was shown to correlate with tumor progression in esophageal squamous cell carcinoma (SCC). These components, however, were maintained normally in some patients with esophageal SCC. In our study, the mechanism by which aggressive esophageal SCC maintains these components was investigated, with particular emphasis on the participation of c‐Ski and SnoN as transcriptional co‐repressors in TGF‐β signaling. Immunohistochemistry for c‐Ski and SnoN was carried out on surgical specimens obtained from 80 patients with esophageal SCC. The expression of c‐Ski and SnoN was also studied in 6 established cell lines derived from esophageal SCC and compared to an immortalized human esophageal cell line by Western blotting. High levels of expression of c‐Ski, detected immunohistologically, were found to correlate with depth of invasion (p = 0.0080) and pathologic stage (p = 0.0447). There was, however, no significant correlation between expression of SnoN and clinicopathologic characteristics. A significant correlation between c‐Ski and TGF‐β expression was observed. Moreover, in patients with TGF‐β negative expression, the survival rates of patients with c‐Ski positive expression were significantly lower than those of patients with c‐Ski negative expression (p = 0.0486). c‐Ski was expressed at a high level in 5 of 6 cell lines derived from esophageal SCC compared to immortalized esophageal keratinocytes. Furthermore, the cyclin‐dependent kinase (CDK) inhibitor, p21 that was up‐regulated by TGF‐β signaling was expressed at a low level in the 5 cell lines. The expression of c‐Ski protein as a transcriptional co‐repressor in TGF‐β signaling seems to be correlated with tumor progression of esophageal SCC. © 2003 Wiley‐Liss, Inc.
Frequent hypermethylation of 5′ flanking region of TIMP‐2 gene in cervical cancer
Authors: Ivanova Tatyana , Vinokurova Svetlana , Petrenko Anatolii , Eshilev Ernest , Solovyova Nina , Kisseljov Fjodor , Kisseljova Natalia 
Published: January 2004

AbstractTissue inhibitor of metalloproteinase‐2 (TIMP‐2) is an endogenous inhibitor of matrix metalloproteinases (MMPs). This multifunctional protein regulates activities of MMPs and possesses growth promoting effect in cell culture, anti‐tumoral, anti‐apoptotic and anti‐angiogenic effects in animal model systems in vivo. It has been shown that this gene is downregulated in cervical carcinomas. The mechanism of inhibition of TIMP‐2 expression remains obscure. We have examined whether aberrant DNA methylation of the 5′CpG island of the TIMP‐2 gene is involved in its inhibition during cervical carcinogenesis. Bisulfite‐modified DNA sequencing and MSP assay showed aberrant methylation of TIMP‐2 5′‐CpG island in 17 of 36 (47%) invasive cervical carcinomas and in 2 of 3 cervical cancer cell lines. TIMP‐2 gene was mostly unmethylated in the morphologically normal tissues adjacent to the tumors, whereas methylated alleles of this gene were found in 4 samples. Each tumor and each cell line DNA was characterized by unique methylation pattern, however a discrete region of TIMP‐2 CpG island upstream to the transcription start site was densely methylated in all hypermethylated DNA samples examined. The expression of TIMP‐2 mRNA can be restored in the cell lines, in which this discrete region of TIMP‐2 CpG island is methylated, by treatment with demethylating agents, 5‐azacytidine and 5‐aza‐2′‐deoxycytidine. Our data suggest that the aberrant methylation of TIMP‐2 favors the development of primary cervical tumors. We describe for the first time the aberrant hypermethylation of TIMP‐2 gene in human cancer. © 2003 Wiley‐Liss, Inc.
Inducible Hsp70 as target of anticancer immunotherapy: Identification of HLA‐A*0201‐restricted epitopes
Authors: Faure Olivier , Graff‐Dubois Stéphanie , Bretaudeau Laurent , Derré Laurent , Gross David‐Alexandre , Alves Pedro M. S. , Cornet Sébastien , Duffour Marie‐Thérèse , Chouaib Salem , Miconnet Isabelle , Grégoire Marc , Jotereau Francine , Lemonnier François A. , Abastado Jean‐Pierre , Kosmatopoulos Kostas 
Published: January 2004

AbstractThe design of a broad application tumor vaccine requires the identification of tumor antigens expressed in a majority of tumors of various origins. We questioned whether the major stress‐inducible heat shock protein Hsp70 (also known as Hsp72), a protein frequently overexpressed in human tumors of various histological origins, but not in most physiological normal tissues, constitutes a tumor antigen. We selected the p391 and p393 peptides from the sequence of the human inducible Hsp70 that had a high affinity for HLA‐A*0201. These peptides were able to trigger a CTL response in vivo in HLA‐A*0201‐transgenic HHD mice and in vitro in HLA‐A*0201+ healthy donors. p391‐ and p393‐specific human and murine CTL recognized human tumor cells overexpressing Hsp70 in a HLA‐A*0201‐restricted manner. Tetramer analysis of TILs showed that these Hsp70 epitopes are targets of an immune response in many HLA‐A*0201+ breast cancer patients. Hsp70 is a tumor antigen and the Hsp70‐derived peptides p391 and p393 could be used to raise a cytotoxic response against tumors of various origins. © 2003 Wiley‐Liss, Inc.
Exposure to cement dust, related occupational groups and laryngeal cancer risk: Results of a population based case‐control study
Authors: Dietz Andreas , Ramroth Heribert , Urban Tobias , Ahrens Wolfgang , Becher Heiko 
Published: January 2004

AbstractA population‐based case‐control study was performed in the Rhein‐Neckar region, Germany, to evaluate occupational risk factors for the development of laryngeal cancer (“Rhein‐Neckar‐Larynx Study”). Between May 1998 and December 2000, 257 patients (236 males, 21 females), aged 37–80, with histologically confirmed laryngeal cancer, as well as 769 population control persons (702 males, 67 females), were included (1:3 frequency matched by age and sex). History of occupational exposures, as well as other risk factors (tobacco, alcohol), was obtained with face‐to‐face interviews using a detailed standardized questionnaire. The complete individual work history was assessed. A detailed assessment of work conditions was obtained by job‐specific questionnaires (JSQs) for selected jobs known to be associated with exposure to potential laryngeal carcinogens. Estimates for total exposure hours by substance were calculated based on JSQs. Published occupational hygiene data were used to infer semiquantitative scores of exposure intensity for specific job tasks. After adjustment for tobacco and alcohol intake, a significant elevated odds ratios (OR) could be demonstrated for persons that were exposed to cement during their work as building and construction workers. An OR of 2.42 was calculated for workers of the high exposed subgroup (95% confidence interval: 1.14‐5.15; p < 0.001). Smoking was the main confounding factor because the unadjusted cement OR of 3.20 dropped down to 2.42 after adjustment for tobacco intake. We conclude that there is good evidence for cement dust exposure acting as a tobacco, alcohol and asbestos independent risk factor for laryngeal carcinoma. Our study gives a base for further toxicologic investigations on this topic. © 2003 Wiley‐Liss, Inc.
The increase of female breast cancer incidence in Japan: Emergence of birth cohort effect
Authors: Minami Yuko , Tsubono Yoshitaka , Nishino Yoshikazu , Ohuchi Noriaki , Shibuya Daisuke , Hisamichi Shigeru 
Published: January 2004

AbstractDuring recent decades, breast cancer incidence has been increasing in Japan. According to the latest reports from several cancer registries in Japan, the breast has become the leading cancer site in female cancer incidence. To analyze the trend of breast cancer incidence in detail, we summarized female breast cancer incidence in Miyagi Prefecture, Japan during 1959–1997, and evaluated the period and cohort effect on breast cancer incidence using the age‐period‐cohort model. Age‐specific and age‐standardized rates have increased over successive calendar periods. Around 1980, an accelerated increase in these incidence rates took place. A full model including age, period and cohort was best fitted to the trend of incidence. In the model, the effects of period and cohort were statistically significant. The nonlinear effect for cohort indicates an increasing trend, beginning with the cohort in 1888–1897, and the nonlinear effect for period showed a clear increase in risk with calendar period. Furthermore, the full model including a linear component showed a steadily upward trend in the cohort effect. Based on our own epidemiologic studies previously conducted in Miyagi Prefecture, and other published reports, the cohort effect is likely to be related to the change in prevalence of women with risk factors such as low parity and insufficient breastfeeding. We believe that the emergence of the cohort effect is an important finding, although the period effect may also persist. The significant cohort effect may give a caution for continuous increase of breast cancer incidence in Japan. © 2003 Wiley‐Liss, Inc.
Differential regulation of VEGF, HIF1α and angiopoietin‐1, ‐2 and ‐4 by hypoxia and ionizing radiation in human glioblastoma
Authors: Lund Eva L. , Høg Anja , Olsen Minna W.B. , Hansen Lasse T. , Engelholm Svend A. , Kristjansen Paul E.G. 
Published: January 2004

AbstractWe examined how ionizing radiation (IR) delivered under either severe hypoxia (< 0.1% O2) or normoxia affects the expression of hypoxia inducible factor 1α (HIF‐1α) and the angiogenic factors vascular endothelial growth factor (VEGF) and angiopoietins 1, 2 and 4 in U87 human glioblastoma cells. IR was delivered as single doses of 0, 2, 5, 10 and 20 Gy after 6‐hr hypoxic incubation and in normoxic controls. Irradiation at any dose did not affect the cellular protein levels of any of the angiopoietins, whereas hypoxia led to increasing levels of both angiopoietin‐4 and angiopoietin‐2. Levels of angiopoietin‐1 protein were unaltered throughout the observation period. A dose‐dependent increase in levels of secreted VEGF in the medium occurred after IR at doses from 5–20 Gy. In hypoxic cells, 20 Gy IR induced an additional significant increase in VEGF relative to nonirradiated hypoxic control cells with elevated baseline VEGF levels induced by hypoxia. HIF‐1α and glucose transporter‐1 (Glut‐1) were not correspondingly upregulated by IR. Blocking HIF‐1α by antisense treatment induced a reduced baseline VEGF at normoxia, while the relative upregulation of VEGF by IR was unaffected. These data provide evidence that VEGF is upregulated by IR by mechanisms independent of HIF‐1 transactivation. © 2003 Wiley‐Liss, Inc.
Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: Involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors
Authors: Fernandez‐Sauze Samantha , Delfino Christine , Mabrouk Kamel , Dussert Christophe , Chinot Olivier , Martin Pierre‐Marie , Grisoli Francois , Ouafik L'Houcine , Boudouresque Françoise 
Published: January 2004

AbstractRecently, we demonstrated that U87 glioblastoma xenograft tumors treated with anti‐adrenomedullin (AM) antibody were less vascularized than control tumors, suggesting that AM might be involved in neovascularization and/or vessel stabilization. Angiogenesis, the sprouting of new capillaries from preexisting blood vessels, is a multistep process that involves migration and proliferation of endothelial cells, remodeling of the extracellular matrix and functional maturation of the newly assembled vessels. In our study, we analyzed the role of AM on human umbilical vein endothelial cell (HUVEC) phenotype related to different stages of angiogenesis. Here we report evidence that AM promoted HUVEC migration and invasion in a dose‐dependent manner. The action of AM is specific and is mediated by the calcitonin receptor‐like receptor/receptor activity‐modifying protein‐2 and ‐3 (CRLR/RAMP2; CRLR/RAMP3) receptors. Furthermore, AM was able to induce HUVEC differentiation into cord‐like structures on Matrigel. Suboptimal concentrations of vascular endothelial growth factor (VEGF) and AM acted synergistically to induce angiogenic‐related effects on endothelial cells in vitro. Blocking antibodies to VEGF did not significantly inhibit AM‐induced capillary tube formation by human endothelial cells, indicating that AM does not function indirectly through upregulation of VEGF. These findings suggest that the proangiogenic action of AM on cultured endothelial cells via CRLR/RAMP2 and CRLR/RAMP3 receptors may translate in vivo into enhanced neovascularization and therefore identify AM and its receptors acting as potential new targets for antiangiogenic therapies. © 2003 Wiley‐Liss, Inc.
Maternal representations during pregnancy and early motherhood
Authors: Ilicali Ebru Taskin , Fisek Guler Okman 
Published: January 2004

AbstractThe aim of the present study was to study the maternal representations of pregnant women and mothers in their early postpartum period, by beginning the process of validating the maternal representations questionnaire L'entretien R1 and by developing a means to assess the content‐free aspects of the representations. Participants were 23 primiparous (first‐time mothers) pregnant women in their fourth to seventh month of pregnancy and 22 primiparous mothers in their early (zero to six months) postpartum period. It was found that the four subscales of L'entretien (self‐as‐mother, self‐as‐person, own‐mother, and partner) produced meaningful results for Turkish subjects. The results were compatible with the idea of integrated representations of self‐as‐person and self‐as‐mother even in the second trimester of their pregnancy and also showed that they could differentiate themselves from their mothers as early as that period. The results revealed no significant differences in the content and content‐free dimensions of the representations of pregnant women and mothers. ©2004 Michigan Association for Infant Mental Health.
Maternal limit setting during toddlerhood, delay of gratification, and behavior problems at age five
Authors: Houck Gail M. , Lecuyer‐Maus Elizabeth A. 
Published: January 2004

AbstractIn this study, self‐regulation was examined in relation to maternal limit setting during toddlerhood. Observational coding of limit‐setting interactions was carried out at 12, 24, and 36 months using the Prohibition Coding Scheme (Houck & LeCuyer, 1995; LeCuyer‐Maus & Houck, 2002). At five years, self‐regulation was assessed by observation of self‐imposed delay‐of‐gratification (Shoda, Mischel, & Peake, 1990), and behavior problems were measured by maternal report on a behavior checklist (CBCL; Achenbach, 1991). Maternal limit‐setting patterns at every age differentiated subsequent duration of delay, but not behavior problems. A power‐based maternal pattern in limit setting adversely affected later self‐imposed delay. Although an indirect limit‐setting pattern optimized the child's delay duration, a teaching‐based pattern yielded more consistently positive outcomes at 36 months and normative delay durations at age five years. ©2004 Michigan Association for Infant Mental Health.
Parent‐completed screening for social emotional problems in young children: The effects of risk/disability status and gender on performance
Authors: Squires Jane , Bricker Diane , Twombly Elizabeth 
Published: January 2004

AbstractResults of psychometric studies on the Ages and Stages Questionnaires: Social Emotional (ASQ:SE), a parent‐completed screening tool for infants, toddlers, and preschoolers, are described. The ability of the ASQ:SE to distinguish risk and disabilities groups, and the relationship of gender and ASQ:SE scores were examined. No/low risk, at risk, developmental disabilities, and social emotional disability groups were significantly different at all eight age intervals (i.e., 6, 12, 18, 24, 30, 36, 48, and 60 months). Significant differences were found between males and females at the 30‐, 36‐, 48‐, and 60‐month age intervals. These data support the ASQ:SE as a valid screening test to assist in early identification of social and emotional problems in young children. ©2004 Michigan Association for Infant Mental Health.
Predicting maternal reactivity/sensitivity: The role of infant emotionality, maternal depressiveness/anxiety, and social support
Authors: Mertesacker Bettina , Bade Ulla , Haverkock Antje , Pauli‐Pott Ursula 
Published: January 2004

AbstractIt was hypothesized that an accumulation of unfavorable conditions, i.e., high negative emotionality and low positive emotionality of the infant, maternal depression and anxiety, and lacking social and emotional support can attenuate mothers' reactivity/sensitivity. Maternal reactivity/sensitivity was observed during home visits and in the laboratory. Infant negative and positive emotionality was assessed by mother reports and behavioral observations. Maternal depressiveness/anxiety as well as social support were assessed via questionnaires. All mothers were primiparous and had healthy infants. Data collection was conducted at the infants' ages of four months (37 dyads) and eight months (33 dyads). The sample consisted of 19 male and 18 female infants (four‐months' measurement). Whereas the presence of a single risk factor was not related to maternal reactivity/sensitivity, the combination was. A decrease in maternal reactivity/sensitivity over the course of time was demonstrated for mothers who had to deal with high negative emotionality of the infant in combination with either high depressiveness/anxiety or low social support at the infants' age of four months. No significant main or interaction effects could be shown for infant positive emotionality. ©2004 Michigan Association for Infant Mental Health.
First‐time mothers in home visitation services utilizing child development specialists
Authors: Culp Anne McDonald , Culp Rex E. , Hechtner‐Galvin Tamara , Howell Christina S. , Saathoff‐Wells Tara , Marr Pam 
Published: January 2004

AbstractProfessionals in the field of child development were employed to provide home visitation services to 156 mothers and infants prenatally through the infants' first birthdays. Compared to a control group of mothers (n = 107), the intervention mothers utilized more community resources, had safer homes, had more appropriate developmental expectations, had better understanding of noncorporal punishment, and had behaviors that were more accepting and respectful to their infants. The home visitors were well educated, with experience in home visitation, and supervised. Program implementation procedures were documented and supervised. Program fidelity and the efficacy of using child development specialists as home visitors are discussed in regards to the positive findings. ©2004 Michigan Association for Infant Mental Health.
Effect of composition of interpenetrating polymer network hydrogels based on poly(acrylic acid) and gelatin on tissue response: A quantitative in vivo study
Authors: Burugapalli Krishna , Koul Veena , Dinda Amit K. 
Published: December 2003

AbstractThe local tissue response of the biomaterial is the most important criteria for determination of its biocompatibility. In the present study, full and semi‐interpenetrating polymer networks (IPN) based on polyacrylic acid (AAc) and gelatin (Ge) crosslinked with 0.5 mol % N,N′‐methylene bisacrylamide (BAm) and 4% glutaraldehyde (GA), respectively, were evaluated for tissue response in rats. IPNs with varying ratios of AAc and Ge were implanted subcutaneously in rats. Gentamicin sulfate (GS)‐loaded IPN samples were also studied to evaluate the possible therapeutic use of these polymers. The site of implantation was biopsied and processed for light microscopy (LM) with image analysis for assessment of tissue reaction at 2‐, 6‐, and 12‐week intervals. The tissue reaction was evaluated as a function of composition and time. The degree of neutrophil, lymphocyte and macrophage infiltration, fibrosis, granuloma formation, integration with extracellular matrix, vascular proliferation, and damage of adjacent structures were assessed. Polymers with >66% crosslinked Ge (Gx) showed persistence of acute inflammatory reaction till 3 months, with marked tissue injury and fibrosis. On the other hand, high crosslinked AAc (Ax) content showed chronic inflammatory reaction with high macrophage infiltration. Macrophages took active part in phagocytosis, degradation, and removal of polymers without granuloma formation or significant giant cell reaction. The IPNs with acrylic acid and gelatin in the ratio of 1:1 showed least tissue reaction and thus appeared to be most biocompatible. The majority of the polymers showed integration with extracellular matrix and growth of capillaries in and around the polymer. The heamogram, liver and renal function tests, and histology of vital organs were all normal. GS loading showed no additional local or systemic reaction suggesting the potential usefulness of the hydrogels as carrier for drugs such as GS. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 210–218, 2004
Carboxymethylcellulose‐stabilized collagenous rhOP‐1 device—a novel carrier biomaterial for the repair of mandibular continuity defects
Authors: Wang Huiming , Springer Ingo N. G. , Schildberg Hendrik , Acil Yahya , Ludwig Klaus , Rueger David R. , Terheyden Hendrik 
Published: December 2003

AbstractHuman recombinant osteogenic protein‐1 (rhOP‐1) is osteoinductive. Efforts are made to develop carrier biomaterials with improved space‐keeping properties. Bovine collagen type I matrix charged with rhOP‐1 was suggested to be an advantageous device of relative liquid quality. We hypothesized that the addition of carboxymethylcellulose (CMC) may stabilize the device and facilitate the regeneration of mandibular continuity defects without further addition of mineralized carrier materials. To test this hypothesis, the anatomical shape, functional remodeling, and mechanical stability of such bony regenerates were evaluated in the course of an animal experiment. Mandibular continuity defects of 5 cm in size were created in five Göttingen minipigs on one side (contralateral hemimandible: control) and bridged with titanium plates. Four animals were treated with the rhOP‐1 device (3000 μg rhOP‐1, 2 g collagen, 1 g CMC), and one animal was treated with a placebo device omitting rhOP‐1. After 12 weeks of experimental period, bony continuity was reestablished in rhOP‐1‐treated hemimandibles. The bony regenerates were of good anatomical shape, volume, and functional remodeling. Placebo treatment led to insufficient bony regenerates of significant lower bone volume (volume in 3D‐CT scan 29.81 cm3 vs 8.85 cm3). To produce 1 mm of bending, 1972 N were needed for rhOP‐1‐treated hemimandibles, 2617 N for control hemimandibles, and 642 N for the placebo treated hemimandible. CMC stabilization of collagen carrier biomaterials for rhOP‐1 provides good plasticity as well as excellent space‐keeping properties and may not interfere with osteoinduction. The results of this preliminary study suggest that the applied rhOP‐1 device offers a potential option for further studies on the reconstruction of mandibular defects. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 68A: 219–226, 2004