bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term survival of T1 and T2 lymph node‐negative breast cancer patients according to mitotic activity index: A population‐based study
Authors: Louwman W.J. , van Beek M.W.P.M. , Schapers R.F.M. , Nolthenius‐Puylaert M.B.C.J.E. Tutein , van Diest P.J. , Roumen R.M. , Coebergh J.W.W. 
Published: December 2005

AbstractNode‐negative breast cancer patients have a relatively good prognosis, but eventually one‐third will die of the disease. Thus, prognostic factors to identify the high‐risk group among these patients are needed. We retrospectively determined the Mitotic Activity Index (MAI) for a large series of node‐negative breast cancer patients (n = 468) with tumours smaller than 5 cm, who only received locoregional treatment. Patients were followed for up to 29 years; crude and relative survival were calculated, both univariate and multivariate. Relative survival differed significantly according to MAI (p = 0.05), the difference occurred in the first 5 years after diagnosis and remained constant thereafter. After adjustment, MAI still significantly affected relative survival (RER, 1.9; 95% CI, 1.1–3.5). Tumour size also increased the risk, but this was not statistically significant (RER, 1.5; 95% CI, 0.8–2.7). Survival of patients with a T1 tumour and MAI < 10 was similar to that for the general population in the first 5 years after diagnosis. In conclusion, MAI significantly predicted long‐term survival for T1/T2N0 breast cancer. Adjuvant systemic therapy appears to have little benefit for node‐negative breast cancer patients with a T1 tumour, regardless of the MAI. For those with a T2 tumour and a MAI ≥ 10 systemic therapy might have reduced mortality. The need for close surveillance of node‐negative breast cancer patients with a T1 tumour and MAI <10 seems limited. © 2005 Wiley‐Liss, Inc.
Insulin‐like growth factor‐I, insulin‐like growth factor binding protein‐3 and the risk of fibrocystic breast conditions among Chinese women
Authors: Chen Chu , Doherty Jennifer A. , Lewis S. Kay , Ray Roberta M. , Gao Dao Li , Stalsberg Helge , Feng Ziding , Thomas David B. 
Published: December 2005

AbstractWe investigated whether circulating insulin‐like growth factor‐I (IGF‐I) and insulin‐like growth factor binding protein‐3 (IGFBP‐3) levels are associated with the risk of fibrocystic breast conditions (FBC), in a case‐control study nested within a randomized trial of breast self‐examination conducted in Shanghai, China. Participants were enrolled during 1989–1991 and were followed over 10 years for the development of breast diseases. Controls (n = 897) were frequency‐matched by age to cases (n = 451), who were diagnosed with FBC between 1995 and 2000. Circulating IGF‐I and IGFBP‐3 levels and their molar ratio were positively associated with risk of FBC. The odds ratios (ORs) and 95% confidence intervals (CI) for the upper fourth of the distribution compared to the lowest fourth for IGF‐I, IGFBP3 and their molar ratio were 3.02 (2.02–4.52), 1.92 (1.37–2.71) and 2.26 (1.52–3.36), respectively. The strength of the association between IGF‐I levels and FBC was attenuated after adjustment for IGFBP‐3 and that for IGFBP‐3 was largely eliminated after adjustment for IGF‐I. Increasing levels of IGF‐I were particularly associated with increasing risk of FBC with proliferative elements (ORs and 95% CIs for the 2nd, 3rd and upper fourth of the distribution of IGF‐I: 3.13 (1.50–6.53), 4.57 (2.22–9.39) and 6.30 (3.08–12.89), compared with the lowest fourth. Our results suggest that elevated levels of IGF‐I may contribute to the development of FBC. © 2005 Wiley‐Liss, Inc.
Genome variation of human papillomavirus types: Phylogenetic and medical implications
Authors: Bernard Hans‐Ulrich , Calleja‐Macias Itzel E. , Dunn S. Terence 
Published: December 2005

AbstractHuman papillomaviruses (HPVs) are described as “types” based on their genome sequences and identified by a number. For example, HPV‐6 is associated with genital warts, and HPV‐16 with anogenital cancers. The genomes of many HPV types have been reisolated, sequenced and compared to reference “prototypes” countless times by laboratories throughout the world. It was found that each HPV type occurs in the form of “variants”, identified by about 2% nucleotide differences in most genes and 5% in less conserved regions. Less than 100 variants of any HPV type have been detected, a scenario that is very different from the quasi‐species formed by many RNA viruses. The variants of each HPV type form phylogenetic trees, and variants from specific branches are often unique to specific ethnic groups. Immigrant populations contain, depending on their respective ethnic origins, mixtures of variants. The absence of HPV genomes intermediate to specific types show that all HPV types existed already when humans became a species. Consequently, humans had always suffered from lesions like anogenital cancer, genital warts and common warts. A growing number of epidemiological, etiological and molecular data suggest that variants of the same HPV type are biologically distinct and may confer differential pathogenic risks. Since the distribution of some variants of HPV‐16 and 18 correlates with the distribution of human populations that have an increased risk to develop anogenital cancer, the study of HPV type variation may point to one of the reasons for the higher incidence rates of these lesions in specific cohorts. © 2005 Wiley‐Liss, Inc.
The clinical significance of MAGEA3 expression in pancreatic cancer
Authors: Kim Joseph , Reber Howard A. , Hines Oscar J. , Kazanjian Kevork K. , Tran Andy , Ye Xing , Amersi Farin F. , Martinez Steve R. , Dry Sarah M. , Bilchik Anton J. , Hoon Dave S.B. 
Published: December 2005

AbstractThe MAGEA gene family that encodes cancer testis antigens is differentially expressed in many cancers. Though MAGEA3 expression has been detected in gastrointestinal malignancies, its role in pancreatic ductal adenocarcinoma (PDAC) has not been well established. We assessed 57 patients who underwent intent‐to‐cure surgery for PDAC. Total RNA from paraffin‐embedded pancreatic tumors was extracted and assessed for MAGEA3 gene expression by an optimized probe‐based quantitative real‐time RT‐PCR (qRT) assay. MAGEA3 gene expression was detected by qRT in 25 (44%) patients. For the entire cohort, detection of MAGEA3 expression was associated with significantly decreased overall survival (median, 16 vs 33 months; log‐rank, p = 0.032). When clinicopathologic factors, including age, gender, stage, tumor extent, lymph node metastasis, tumor grade, perineural invasion and lymphovascular invasion were assessed by univariate analysis, MAGEA3 gene expression and tumor grade were significant prognostic factors for poor survival (HR 2.1, 95% CI: 1.0–4.4, p = 0.041; and HR 3.7, 95% CI: 1.8–7.6, p = 0.0004, respectively). Immunohistochemistry (IHC) was performed and confirmed MAGEA3 protein in PDAC specimens. In conclusion, MAGEA3 is differentially expressed in patients with PDAC; its expression correlates with significantly worse survival. Molecular assessment for MAGEA3 should be considered to improve prognostic evaluation and to identify eligible patients for potential immune‐based therapy. © 2005 Wiley‐Liss, Inc.
Multidrug resistance‐1 gene polymorphisms associated with treatment outcomes in de novo acute myeloid leukemia
Authors: Kim Dong Hwan , Park Jae Yong , Sohn Sang Kyun , Lee Nan Young , Baek Jin Ho , Jeon Seok Bong , Kim Jong Gwang , Suh Jang Soo , Do Young Rok , Lee Kyu Bo 
Published: December 2005

AbstractMultidrug resistance‐1 (MDR‐1) gene single nucleotide polymorphisms (SNPs) have been identified as associated with the treatment outcomes of acute myeloid leukemia (AML) in Caucasians; yet, similar evidence is lacking for Asian populations. A total of 101 AML patients were enrolled in the current study. Two MDR1 SNPs (C3435T and G2677T/A) were analyzed with PCR/RFLP assay. As regards C3435T polymorphism, C/C genotype was significantly correlated with lower functional P‐glycoprotein (P‐gp) activity in leukemic blasts (7.5%) compared with C/T (10.7%) or T/T genotype (19.9%, p = 0.029). In genotypic analyses, C/C at −3435 (p = 0.05) and G/G at −2677 (p = 0.04) were strongly associated with a higher probability of complete remission (CR). In addition, the 3‐year event‐free survival (EFS) was higher in G/G genotype at −2677 (60.6%) than nonG/G (21.9%; p = 0.0241), in C/C at −3435 was higher than nonC/C genotype (p = 0.0139), and was higher in GC haplotype homozygote (58.2%) than nonGC homozygote (22.6%; p = 0.0427). In a multivariate analysis, the group without GC haplotype showed worse EFS (p = 0.030), with unfavorable cytogenetic risk (p = 0.008). However, no differences were noted in overall survival according to the MDR1 SNPs (p = 0.491 for C3435T and p = 0.955 for G2677T/A). © 2005 Wiley‐Liss, Inc.
Interatomic potential models for natural apatite crystals: Incorporating strontium and the lanthanides
Authors: Rabone J. A. L. , De Leeuw N. H. 
Published: December 2005

AbstractA comprehensive set of interatomic potential parameters for modeling natural apatite crystals is presented. These potentials build on those previously used in research on apatites with new potentials fitted empirically to crystal structures and their properties using the GULP program. We demonstrate that the new potentials produce good models for the different compounds used for fitting, as well as for several natural apatites. Also presented are predicted enthalpies of mixing of strontium and calcium apatites and predicted cation site preferences in strontium calcium fluorapatite. © 2005 Wiley Periodicals, Inc. J Comput Chem 27: 253–266, 2006
Application of standard DFT theory for nonbonded interactions in soft matter: Prototype study of poly‐para‐phenylene
Authors: Alves‐Santos Marcelo , Dávila Liliana Y. A. , Petrilli Helena M. , Capaz Rodrigo B. , Caldas Marília J. 
Published: December 2005

AbstractWe present a detailed analysis of the application of density functional theory (DFT) methods to the study of structural properties of molecular and supramolecular systems, using as a paradigmatic example three para‐phenylene‐based systems: isolated biphenyl, single chain poly‐para‐phenylene, and crystalline biphenyl. We use different functionals for the exchange correlation potential, the local density (LDA), and generalized gradient approximations (GGA), and also different basis sets expansions, localized, plane waves (PW), and mixed (localized plus PW), within the reciprocal space formulation for the hamiltonian. We find that regardless of the choice of basis functions, the GGA calculations yield larger interring distances and torsion angles than LDA. For the same XC approximation, the agreement between calculations with different basis functions lies within 1% (LDA) or 0.5% (GGA) for distances, and while PW and mixed basis calculations agree within 1° for torsion angles, the localized basis results show larger angles by ≃ 8° and a nonmonotonic dependence on basis size, with differences within 6°. The most prominent features, namely the torsion between rings for isolated molecule and infinite chain, and planarity for the molecule in crystalline environment, are well reproduced by all DFT calculations. © 2005 Wiley Periodicals, Inc. J Comput Chem 27: 217–227, 2006
Inhibition of collagen gene expression by interferon‐γ: Novel role of the CCAAT/enhancer binding protein β (C/EBPβ)
Authors: Ghosh Asish K , Bhattacharyya Swati , Mori Yasuji , Varga John 
Published: December 2005

AbstractBy inhibiting collagen synthesis, interferon‐γ (IFN‐γ) plays a key role in maintaining connective tissue homeostasis, but the mechanisms are not well‐understood. In addition to intracellular signaling through the canonical JAK–STAT transduction pathway, IFN‐γ was recently shown to regulate gene expression via the CCAAT/enhancer‐binding protein β (C/EBPβ) as well. Because C/EBPβ is a crucial mediator of immune and inflammatory responses, and has been implicated in regulation of collagen synthesis by tumor necrosis factor‐α, we examined its role in the inhibitory effects of IFN‐γ. The results demonstrated that IFN‐γ caused increased C/EBPβ expression in dermal fibroblasts and enhanced its binding to cognate DNA sequences in the α2(I) procollagen gene (COL1A2) promoter in vitro and in vivo. Disruption of C/EBP binding by deletion or site‐directed mutagenesis abrogated the inhibition of collagen promoter activity in transient transfection assays, as did cotransfection with dominant negative C/EBPβ, indicating a functional role of cellular C/EBPβ in mediating the IFN‐γ response. Rapid phosphorylation of the ERK1/2 MAP kinases induced by IFN‐γ was accompanied by phosphorylation and nuclear translocation of cellular C/EBPβ, and pretreatment of fibroblasts with ERK1/2 kinase inhibitor blocked C/EBPβ phosphorylation, as well as inhibition of COL1A2 promoter activity, elicited by IFN‐γ. These results provide compelling evidence for a novel C/EBPβ‐dependent IFN‐γ signaling pathway responsible for inhibition of collagen gene transcription. Taken together with recent reports, the findings indicate that intracellular pathways mediating negative regulation of collagen synthesis in response to distinct inflammatory signals that converge on C/EBPβ. J. Cell. Physiol. 207: 251–260, 2006. © 2005 Wiley‐Liss, Inc.
Tetraploidy/aneuploidy and stem cells in cancer promotion: The role of chromosome passenger proteins
Authors: Nguyen Hao G. , Ravid Katya 
Published: December 2005

AbstractWhile polyploidy, a state of having fully duplicated sets of chromosomes per cell, has been described in normally developing bone marrow megakaryocytes or as an adaptive response in other cell types, aneuploidy is never detected in normal cells. Tetraploidy or aneuploidy can be induced by several signals and it is highly prevalent in different forms of cancers, suggesting a role for this cell cycle state in promoting cellular transformation. Investigations suggested that loss of heterozygosity of cancer‐related genes in stem cells might contribute to genetic instability in progeny cells and to subsequent cancer development. Deregulated expression of chromosome passenger proteins, such as Aurora kinases or Survivin, is a hallmark of various cancers, and experimentally induced changes in these regulators can promote tetraploidy or aneuploidy and loss of heterozygosity. Our studies described an induction of tetraploidy/aneuploidy by a stable form of Aurora‐B, leading to acquisition of transformation properties. It is intriguing to speculate that in some cancers, tetraploidy/aneuploidy induced by deregulated expression of a mitotic regulator represents a primary event that leads to unbalanced expression of a cluster of crucial genes and to cellular transformation. J.Cell.Physiol. © 2005 Wiley‐Liss, Inc.
A scoring system based on the expression of six surface molecules allows the identification of three prognostic risk groups in B‐cell chronic lymphocytic leukemia
Authors: Zucchetto Antonella , Bomben Riccardo , Dal Bo Michele , Sonego Paolo , Nanni Paola , Rupolo Maurizio , Bulian Pietro , Dal Maso Luigino , Del Poeta Giovanni , Del Principe Maria Ilaria , Degan Massimo , Gattei Valter 
Published: December 2005

AbstractWe have previously identified 12 surface antigens whose differential expression represented the signature of B‐cell chronic lymphocytic leukemia (B‐CLL) subsets with different prognosis. In the present study, expression data for these antigens, as determined in 137 B‐CLL cases, all with survivals, were utilized to devise a comprehensive immunophenotypic scoring system of prognostic relevance for B‐CLL patients. In particular, univariate z score was employed to identify the markers with greater prognostic impact, while maximally selected log‐rank statistics were chosen to define the optimal cut‐off points capable to split patients into two groups with different survivals. A weighted immunophenotypic scoring system was developed by integrating results from these analyses. Six antigens were selected: three positive prognosticators (CD62L, CD54, CD49c) and three negative prognosticators (CD49d, CD38, CD79b), with cut‐off values ranging from 30% to 50% of positive cells. By weighing the expression of each marker according to its statistical power, a complete scoring system, with point values comprised between 0 (complete absence of phenotypic conditions associated with good prognosis) and 9 (all the phenotypic conditions associated with good prognosis fulfilled), allowed to split the whole set of B‐CLL patients, into three distinctive prognostic groups (P = 4.78 × 10−11) with high‐ (score 0–3), intermediate‐ (score 4–6), and low‐ (score 7–9) risk of death. The three risk groups showed different distribution of cases as for Rai's stages, IgVH mutations, and ZAP‐70 expression. The proposed immunophenotypic scoring system may be an additional useful tool in routine diagnostic/prognostic procedures for B‐CLL. J. Cell. Physiol. 207: 354–363, 2006. © 2005 Wiley‐Liss, Inc.
Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs
Authors: Grayson Warren L. , Zhao Feng , Izadpanah Reza , Bunnell Bruce , Ma Teng 
Published: December 2005

AbstractLow oxygen tension is thought to be an integral component of the human mesenchymal stem cell (hMSC) native bone marrow microenvironment. HMSC were cultured under physiologically relevant oxygen environments (2% O2) in three‐dimensional (3D) constructs for up to 1 month in order to investigate the combined effects of chronic hypoxia and 3D architecture on hMSC tissue‐development patterns. Hypoxic hMSC exhibited an extended lag phase in order to acclimatize to culture conditions. However, they subsequently proliferated continuously throughout the culture period, while maintaining significantly higher colony‐forming unit capabilities and expressing higher levels of stem cell genes than hMSC cultured at 20% O2 (normoxic) conditions. Upon induction, hypoxic hMSC also expressed higher levels of osteoblastic and adipocytic differentiation markers than normoxic controls. Hypoxia induced increased total protein levels in hMSC throughout the culture period, as well as significantly different fibronectin expression patterns suggesting that oxygen levels can significantly affect tissue‐development patterns. Importantly, hMSC maintained the ability to thrive in prolonged hypoxic conditions suggesting that hypoxia may be an essential element of the in vivo hMSC niche. Further studies are required to determine how variations in cellular characteristics and ECM expression impact on the physiological properties of the engineered tissue, yet these results strongly indicate that oxygen tension is a key parameter that influences the in vitro characteristics of hMSC and their development into tissues. J. Cell. Physiol. 207: 331–339, 2006. © 2005 Wiley‐Liss, Inc.
Hyaluronan‐based polymer scaffold modulates the expression of inflammatory and degradative factors in mesenchymal stem cells: Involvement of Cd44 and Cd54
Authors: Lisignoli Gina , Cristino Sandra , Piacentini Anna , Cavallo Carola , Caplan Arnold I. , Facchini Andrea 
Published: December 2005

AbstractHyaluronan (HA), in the bone marrow stroma, is the major non‐protein glycosaminoglycan component of extracellular matrix (ECM) involved in cell positioning, proliferation, differentiation as well as in receptor‐mediated changes in gene expression. Repair of bone and regeneration of bone marrow is dependent on ECM, inflammatory factors, like chemokines and degradative factors, like metalloproteinases. We analyzed the interaction between human mesenchymal stem cells (h‐MSCs) and a three‐dimensional (3‐D) HA‐based scaffold in vitro. The expression of CXC chemokines/receptors, CXCL8 (IL‐8)/CXCR1‐2, CXCL10 (IP‐10)/CXCR3, CXCL12 (SDF‐1)/CXCR4, and CXCL13 (BCA‐1)/CXCR5, and metalloproteinases/inhibitors MMP‐1, MMP‐3, MMP‐13/TIMP‐1 were evaluated in h‐MSCs grown on plastic or on HA‐based scaffold by Real‐time PCR, ELISA, and immunocytochemical techniques. Moreover, the expression of two HA receptors, CD44 and CD54, was analyzed. We found both at mRNA and protein levels that HA‐based scaffold induced the expression of CXCR4, CXCL13, and MMP‐3 and downmodulated the expression of CXCL12, CXCR5, MMP‐13, and TIMP‐1 while HA‐based scaffold induced CD54 expression but not CD44. We found that these two HA receptors were directly involved in the modulation of CXCL12, CXCL13, and CXCR5. This study demonstrates a direct action of a 3‐D HA‐based scaffold, widely used for cartilage and bone repair, in modulating both h‐MSCs inflammatory and degradative factors directly involved in the engraftment of specific cell types in a damaged area. Our data clearly demonstrate that HA in this 3‐D conformation acts as a signaling molecule for h‐MSCs. J. Cell. Physiol. 207: 364–373, 2006. © 2005 Wiley‐Liss, Inc.
Elastic fiber macro‐assembly is a hierarchical, cell motion‐mediated process
Authors: Czirok Andras , Zach Julia , Kozel Beth A. , Mecham Robert P. , Davis Elaine C. , Rongish Brenda J. 
Published: December 2005

AbstractElastic fibers are responsible for the extensibility and resilience of many vertebrate tissues, and improperly assembled elastic fibers are implicated in a number of human diseases. It was recently demonstrated that in vitro, cells first secrete tropoelastin into a punctate pattern of globules. To study the dynamics of macroassembly, that is, the assembly of the secreted tropoelastin globules into elastic fibers, we utilized long‐term time‐lapse immunofluorescence imaging and a tropoelastin p Timer fusion protein, which shifts its fluorescence spectrum over time. Pulse‐chase immunolabeling of the fibroblast‐like RFL‐6 cells demonstrates that tropoelastin globules aggregate in a hierarchical manner, creating progressively larger fibrillar structures. By analyzing the correlation between cell and extracellular matrix movements, we show that both the aggregation process and shaping the aggregates into fibrillar form is coupled to cell motion. We also show that the motion of non‐adjacent cells becomes more coordinated as the physical size of elastin‐containing aggregates increases. Our data imply that the formation of elastic fibers involves the concerted action and motility of multiple cells. J. Cell. Physiol. 207: 97–106, 2006. © 2005 Wiley‐Liss, Inc.
All the three ParaHox genes are present in Nuttallochiton mirandus (Mollusca: polyplacophora): evolutionary considerations
Authors: Barucca Marco , Biscotti Maria A. , Olmo Ettore , Canapa Adriana 
Published: December 2005

AbstractThe ParaHox gene cluster contains three homeobox genes, Gsx, Xlox and Cdx and has been demonstrated to be an evolutionary sister of the Hox gene cluster. Among deuterostomes the three genes are found in the majority of taxa, whereas among protostomes they have so far been isolated only in the phylum Sipuncula.We report the partial sequences of all three ParaHox genes in the polyplacophoran Nuttallochiton mirandus, the first species of the phylum Mollusca where all ParaHox genes have been isolated. This finding has phylogenetic implications for the phylum Mollusca and for its relationships with the other lophotrochozoan taxa. J. Exp. Zool. (Mol. Dev. Evol.) 306B, 2006. © 2005 Wiley‐Liss, Inc.