bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATM and p21 Cooperate to Suppress Aneuploidy and Subsequent Tumor Development
Authors: Shen Kate C. , Heng Henry , Wang Yaolin , Lu Shu , Liu Guo , Deng Chu-Xia , Brooks S.C. , Wang Y. Alan 
Published: October 2005

Abstract
The DNA damage checkpoint protein kinase mutated in ataxia telangiectasia (ATM) is involved in sensing and transducing DNA damage signals by phosphorylating and activating downstream target proteins that are implicated in the regulation of cell cycle progression and DNA repair. Atm−/− cells are defective in cellular proliferation mediated by the Arf/p53/p21 pathway. In this report, we show that increased expression of p21 (also known as Waf1 or CDKN1a) in Atm−/− cells serves as a cellular defense mechanism to suppress further chromosomal instability (CIN) and tumor development because Atm−/−p21−/− mice are predisposed to carcinomas and sarcomas with intratumoral heterogeneity. It was found that Atm-deficient cells are defective in metaphase-anaphase transition leading to abnormal karyokinesis. Moreover, Atm−/−p21−/− primary embryonic fibroblasts exhibit increased CIN compared with either Atm−/− or p21−/− cells. The increased CIN is manifested at the cellular level by increased chromatid breaks and elevated aneuploid genome in Atm−/−p21−/− cells. Finally, we showed that the role of p21 in a CIN background induced by loss of Atm is to suppress numerical CIN but not structural CIN. Our data suggest that the development of aneuploidy precedes tumor formation and implicates p21 as a major tumor suppressor in a genome instability background.
Oncogenes and Angiogenesis: Down-regulation of Thrombospondin-1 in Normal Fibroblasts Exposed to Factors from Cancer Cells Harboring Mutant Ras
Authors: Kalas Wojciech , Yu Joanne L. , Milsom Chloe , Rosenfeld Jack , Benezra Robert , Bornstein Paul , Rak Janusz 
Published: October 2005

Abstract
The onset of angiogenesis in cancer often involves down-regulation of endogenous angiogenesis inhibitors, of which thrombospondin-1 (TSP-1) is a paradigm. As this effect is thought to occur under the influence of transforming genetic lesions (e.g., expression of the mutant ras oncogene), its nature is regarded as intrinsic to cancer cells themselves. Here, we show that ras-transformed cancer cells can also induce TSP-1 down-regulation in their adjacent nontransformed stromal fibroblasts, but not in endothelial cells, in a paracrine and distance-dependent manner. Indeed, several H-ras-expressing fibrosarcoma (528ras1, B6ras, and NIH3T3Ras) and carcinoma (DLD-1 and IEC18Ras3) cells were found to release soluble factors capable of suppressing TSP-1 protein, mRNA, and promoter activity in nontumorigenic, immortalized dermal fibroblastic cell lines in culture (e.g., in fibroblasts expressing enhanced green fluorescent protein/TSP-1 reporter). This effect was abrogated in Id1−/− fibroblasts. At least two low molecular weight (&lt;3 kDa), heat-labile, and trypsin-resistant mediators of TSP-1 suppression were found to be released from 528ras1 cells. Their effects on normal fibroblasts were inhibited (albeit to different extents) by pertussis toxin and, in one case, by dimethylsphingosine, none of which affected TSP-1 expression by 528ras1 cells. Collectively, our study suggests that the effect of mutant ras on tumor neovascularization is not limited to changes in angiogenic properties of cancer cells themselves. Rather, mutant ras, through a different signaling mechanism, may modulate the properties of the adjacent normal stroma, thus eliciting a proangiogenic field effect.
Reduction of Experimental Human Fibrosarcoma Lung Metastasis in Mice by Adenovirus-Mediated Cystatin C Overexpression in the Host
Authors: Kopitz Charlotte , Anton Martina , Gansbacher Bernd , Krüger Achim 
Published: October 2005

Abstract
Tumor cell invasion and metastasis are associated with degradation of components of the extracellular matrix by different proteinases. Among those, papain-like cysteine proteases, such as cathepsin B, seem to play an important role, as they are associated with poor clinical outcome in different cancers. In this study, we tested whether cystatin C, a natural extracellular inhibitor of papain-like cysteine proteases, can inhibit metastasis when overexpressed at the tumor-host interface. Local overexpression of cystatin C in liver and lungs of CD1 nu/nu mice was achieved by gene transfer with a novel adenoviral construct, which also led to the presence of 60 ng/mL of cystatin C in the serum. Three days after gene transfer, these mice were challenged by i.v. inoculation of lacZ-tagged human fibrosarcoma cells (HT1080lacZ-K15), leading to the formation of experimental lung and liver metastases. In this model, formation of experimental metastatic foci correlated with expression of cathepsin B in lungs, whereas there was no correlation with metastasis to the liver. In mice overexpressing cystatin C, the number of lung metastases was significantly reduced by 92%, as compared with mice receiving control adenovirus. The efficacy of extravasation of HT1080lacZ-K15 cells into the liver was not affected, indicating the independence of this process from the activity of cysteine-cathepsins. The present report is the first evidence of successful reduction of metastasis by inhibition of cysteine-cathepsins by cystatin C overexpression in the host microenvironment. Furthermore, organ-specific protease expression during tumor-host cell interactions could affect the success of antiproteolytic intervention against metastasis.
Stromal Expression of Connective Tissue Growth Factor Promotes Angiogenesis and Prostate Cancer Tumorigenesis
Authors: Yang Feng , Tuxhorn Jennifer A. , Ressler Steven J. , McAlhany Stephanie J. , Dang Truong D. , Rowley David R. 
Published: October 2005

Abstract
Our previous studies have defined reactive stroma in human prostate cancer and have developed the differential reactive stroma (DRS) xenograft model to evaluate mechanisms of how reactive stroma promotes carcinoma tumorigenesis. Analysis of several normal human prostate stromal cell lines in the DRS model showed that some rapidly promoted LNCaP prostate carcinoma cell tumorigenesis and others had no effect. These differential effects were due, in part, to elevated angiogenesis and were transforming growth factor (TGF)-β1 mediated. The present study was conducted to identify and evaluate candidate genes expressed in prostate stromal cells responsible for this differential tumor-promoting activity. Differential cDNA microarray analyses showed that connective tissue growth factor (CTGF) was expressed at low levels in nontumor-promoting prostate stromal cells and was constitutively expressed in tumor-promoting prostate stromal cells. TGF-β1 stimulated CTGF message expression in nontumor-promoting prostate stromal cells. To evaluate the role of stromal-expressed CTGF in tumor progression, either engineered mouse prostate stromal fibroblasts expressing retroviral-introduced CTGF or 3T3 fibroblasts engineered with mifepristone-regulated CTGF were combined with LNCaP human prostate cancer cells in the DRS xenograft tumor model under different extracellular matrix conditions. Expression of CTGF in tumor-reactive stroma induced significant increases in microvessel density and xenograft tumor growth under several conditions tested. These data suggest that CTGF is a downstream mediator of TGF-β1 action in cancer-associated reactive stroma and is likely to be one of the key regulators of angiogenesis in the tumor-reactive stromal microenvironment.
Genetic Disruption of Cytosine DNA Methyltransferase Enzymes Induces Chromosomal Instability in Human Cancer Cells
Authors: Karpf Adam R. , Matsui Sei-ichi 
Published: October 2005

Abstract
DNA methyltransferase 1 (DNMT1)–deficient mice are tumor-prone, and this has been proposed to result from the induction of genomic instability. To address whether loss of DNMT1, or the related protein DNMT3b, results in genomic instability in human cancer cells, we used a near-diploid human colorectal cancer cell line, HCT116, in which one or both DNMT genes were disrupted by homologous recombination. Array-based comparative genomic hybridization analyses indicated that double, but not single, DNMT knock-out cells display two specific alterations in regional DNA copy number, suggesting that DNMT deficiency and genomic DNA hypomethylation are not associated with widespread genomic amplifications or deletions in human cancer cells. However, spectral karyotype analyses revealed that DNMT-deficient HCT116 cells are highly unstable with respect to large-scale chromosomal alterations; furthermore, this effect is characterized by a high degree of individual cell heterogeneity. The induction of chromosomal alterations in DNMT-deficient cells was evidenced both by aneuploidy and by large increases in the number of novel chromosomal translocations. Studies of double knock-out cells indicated that the generation of chromosomal alterations is spontaneous and persistent in vitro, meeting the formal definition of genomic instability. In summary, we show that DNMT deficiency in human cancer cells results in constitutive genomic instability manifested by chromosomal translocations.
Fhit and CHK1 Have Opposing Effects on Homologous Recombination Repair
Authors: Hu Baocheng , Wang Hongyan , Wang Xiang , Lu Hua-Rui , Huang Cuifen , Powell Simon N. , Huebner Kay , Wang Ya 
Published: October 2005

Abstract
Fragile histidine triad (FHIT) gene deletion or promoter methylation and reduced Fhit protein expression occur in ∼70% of human epithelial tumors and, in some cancers, are clearly associated with tumor progression. Specific Fhit signal pathways have not been identified. We previously reported that compared with Fhit+/+ cells, Fhit−/− cells with an overactivated ATR/CHK1 pathway show increased mutation frequency and resistance to DNA damage–induced killing, indicating that Fhit and the CHK1 pathway have opposing roles in cells responding to DNA damage. In this study, we show that cells, with or without Fhit expression, have similar DNA double-strand break induction levels and similar rejoining rates following ionizing radiation, indicating that the effect of Fhit on cell radiosensitivity is independent of nonhomologous end-joining. By combining I-SceI–induced-DNA double-strand break system and small interfering RNA approach, we also show that knocking down Fhit increases the efficiency of homologous recombination repair of cells, but knocking down Chk1 decreases the efficiency of homologous recombination repair, associated with the sensitivity to ionizing radiation–induced killing. Taken together, the results show that the role of Fhit in affecting the sensitivity of cells to ionizing radiation–induced killing is through the CHK1 pathway linked to homologous recombination repair. These results also illustrate the importance of balanced checkpoint activation in genomic stability and suggest a connection between the radioresistance and mutagenesis, carcinogenesis, as well as tumor progression in Fhit-deficient cells or tissue.
The Control Structure of Team-Based Organizations: A Diagnostic Model for Empowerment
Authors: Kuipers Ben S. , de Witte Marco C. 
Published: October 2005

This article describes a diagnostic model for empowerment in team- based organizations that portrays four dimensions of the organization’s control structure: the level of routine, the nature of expertise, the level of dependence and the line of command. The combined positions of the set of job regulation tasks distinguished for these dimensions express empowerment in terms of a functional balance and a balance of authority. The diagnostic model can be used to measure the control structure in practice and to provide input for a well-founded and managerial debate on empowerment and control. The model is illustrated with quantitative data from a pilot study of 16 semi-autonomous work teams within the manufacturing industry. Considerable differences in the local interpretation of the design of the control structure by team managers were observed. In general, the empowerment of teams is rather limited. The impression given is that there is a temporary ‘double control structure’, meaning simultaneous bottom-up and top-down control of the teams.
Self-management in African American Women With Diabetes
Authors: Montague Mamie C. , Nichols Sheryl A. , Dutta Arjun P. 
Published: October 2005

Purpose This study describes demographic and medical characteristics, self-efficacy, locus of control, self-managementd defined by functional status, hemoglobin HbA1c outcomes, and the relationships among these variables based on age group differences (25-44 years, 45-64 years, and 65-84 years) in African American women with type 2 diabetes. Methods Subjects (n = 75) in community medical practices were interviewed to complete a demographic and medical form, the Diabetes Self-efficacy Outcomes Expectancy Questionnaire (DSEQ), the Diabetes Locus of Control Scale, and the Medical Outcomes–Short Form 36 (SF-36). A venous blood sample was taken following the interview. Data were analyzed for the total sample and separately for age groups. Results Scores on the self efficacy (DSEQ) and the locus of control (LOC) were above average for all 3 groups. Significant correlations were found among subscales of the LOC, SF-36, and HbA1c. HbA1c scores were abnormally high across groups. Significant group differences were found in duration of diabetes and number of medications used. Conclusions Despite high levels of internal locus of control and self-efficacy and scores indicating good mental, physical, emotional, and social health, self-management amongthe women was inadequate, as indicated by abnormally high HbA1c levels.
Patient-Provider Communication and Self-care Behavior Among Type 2 Diabetes Patients
Authors: Aikens James E. , Bingham Raymond , Piette John D. 
Published: October 2005

Purpose The purpose of this study was to determine whether diabetes self-care behaviors mediate the association between patient-provider communication (PPC) and diabetes outcomes. Methods An ethnically diverse sample of 752 patients with type 2 diabetes was recruited from 3 different health systems. Subjects were interviewed by telephone about their general and diabetes-specific PPC, diabetes self-care behaviors (medication use, glucose testing, eating, and physical activity), and functional status (physical and mental). Glycemic control was assessed with the HbA1c assay. Statistical tests of the hypothetical path model were adjusted for age, gender, marital status, income, ethnicity, medication regimen, and number of comorbid conditions. Results General PPC was associated with mental functioning and physical functioning, and diabetes-specific PPC was associated with glycemic control. However, these associations were not mediated by self-care behaviors, which were independently associated with diabetes outcomes. Conclusions Although self-care and PPC are both important determinants of diabetes patients' health status, these effects are independent. Thus, attempts to improve diabetes outcomes must focus on both good communication and the direct enhancement of illness self-management behaviors.
Feasibility and Effectiveness of System Redesign for Diabetes Care Management in Rural Areas
Authors: Bray Paul , Roupe Melissa , Young Sandra , Harrell Jolynn , Cummings Doyle M. , Whetstone Lauren M. 
Published: October 2005

Purpose Redesigning the system of care for the management of patients with type 2 diabetes mellitus has not been well studied in rural communities with a significant minority population and limited health care resources. This study assesses the feasibility and potential for cost-effectiveness of restructuring care in rural fee-for-service practices for predominantly minority patients with diabetes mellitus. Methods This was a feasibility study of implementing case management, group visits, and electronic registry in 5 solo or small group primary care practices in rural North Carolina. The subjects were 314 patients with type 2 diabetes mellitus (mean age = 61 years; 72% African American; 54% female). An advanced practice nurse visited each practice weekly for 12 months, provided intensive diabetes case management, and facilitated a 4-session group visit educational program. An electronic diabetes registry and visit reminder systems were implemented. Results There was an improvement in the percentage of patients achieving diabetes management goals and an improvement in productivity and billable encounters. The percentage of patients with a documented self-management goal increased from 0% to 42%, a currently documented lipid panel from 55% to 76%, currently documented aspirin use from 25% to 37%, and currently documented foot examination from 12% to 54%. The average daily encounter rate improved from 20.17 to 31.55 on intervention days. Conclusions A redesigned care delivery system that uses case management with structured group visits and an electronic registry can be successfully incorporated into rural primary care practices and appears to significantly improve both care processes and practice productivity.
Fe3+-K-10 Montmorillonite Clay Catalyzed Friedel–Crafts Reaction of Unactivated Baylis–Hillman Adducts: An Efficient Stereoselective Synthesis of Trisubstituted Alkenes Containing a Benzyl Substituent
Authors: Das Biswanath , Majhi Anjoy , Banerjee Joydeep , Chowdhury Nikhil , Venkateswarlu Katta 
Published: October 2005

Abstract
The stereoselective synthesis of trisubstituted alkenes containing a benzyl substituent has been achieved by employing Friedel–Craft reaction of aromatic compounds with unactivated Baylis–Hillman adducts in the presence of Fe3+-K-10 montmorillonite clay as a heterogeneous catalyst. The catalyst can be recovered and reused.
Montmorillonite K10 Clay-catalyzed Synthesis of Substituted 1-Aryl Indenes from Baylis–Hillman Adducts
Authors: Shanmugam Ponnusamy , Rajasingh Paramasivan 
Published: October 2005

Abstract
An eco-friend method for the synthesis of 1-aryl indenes from Baylis–Hillman adducts using Mont. K10 and microwave combination as catalyst system and a procedure for the synthesis of β-phenyl-substituted-protected Baylis–Hillman adducts with highly Z-selectivity have been reported.
Stereoselective syntheses of functionalized cyclic ethers via (Schiff-base)vanadium(V)-catalyzed oxidations
Authors: Hartung Jens 
Published: October 2005

Abstract
(Schiff-base)vanadium(V) complexes catalyze the oxidation of Br- (formation of Br2) and the stereoselective synthesis of functionalized tetrahydrofurans from substituted bishomoallylic alcohols. In both instances, tert-butyl hydroperoxide (TBHP) serves as primary oxidant. The oxidation of Br- was applied as the key step for stereo- and 6-endo-selectively constructing the 2,2,3,5,6,6-substituted tetrahydropyran nucleus of the marine natural product aplysiapyranoid A starting from an adequately substituted bishomoallylic alcohol. In the absence of Br-, 1-alkyl-, 1-vinyl-, and 1-phenyl-5,5-dimethyl-substituted bishomoallylic alcohols are selectively oxygenated to furnish 2,5-cis-configured tetrahydrofurans as major products. 2- Or 3-substituted ω,ω-dimethyl-substituted bishomoallylic alcohols afford trans-disubstituted tetrahydrofurans under these conditions. Oxidation of substituted 4-penten-1-ols, i.e., substrates with a terminal π-bond, proceeds with a preference for formation of trans-disubstituted tetrahydrofurans. According to data from (i) 51V NMR spectroscopy, (ii) mass spectrometry, (iii) a structure-selectivity survey, (iv) competition kinetics, and (v) a stereochemical analysis, the oxygen atom transfer onto a bishomoallylic alcohol occurs in a peroxide- and alkenol-loaded (Schiff-base)vanadium(V) complex.
New developments of insulinomimetic dinuclear vanadyl(IV)-tartrate complexes
Authors: Sakurai Hiromu , Funakoshi Satoko , Adachi Yusuke 
Published: October 2005

Abstract
The number of patients suffering from diabetes mellitus (DM) is increasing year by year throughout the world. In 2003, the world population was 6.3 billion, and the number of patients with DM in the adult population (20-79 years old) was 0.194 billion, which corresponded to 5.1 % of all disease incidence in that age range. In 2005, it is forecasted that the world population will increase to 8.0 billion and the ratio of DM to total disease incidence will increase to 6.3 %, with a disproportionate number of cases in Southeast Asia, the West Pacific, Central Asia, and North, Central, and South America. To treat Type 1 and Type 2 DM clinically, insulin preparations and synthetic drugs, respectively, have been used. However, these treatments are associated with some problems, such as several times of daily insulin injections following blood glucose monitoring and side effects in the case of the synthetic drugs. Consequently, a new class of therapeutic compounds is anticipated. After many trials, vanadium-containing complexes have been proposed to improve and treat both types of DM by in vivo experiments. We present an overview of insulinomimetic and antidiabetic vanadyl (+4 vanadium, V) complexes, and propose new candidates for dinuclear vanadyl complexes with naturally occurring ligands. The current state of research on the dinuclear vanadyl(IV)-tartrate complexes is described in regard to the physicochemical characteristics, in vitro insulinomimetic and in vivo blood-glucose-lowering effects of the prepared complexes.
‘Discovery’ as a site for the collective construction of scientific knowledge
Authors: CANEVA KENNETH L. 
Published: October 2005

ABSTRACT:
Hans Christian Ørsted and Thomas Johann Seebeck are recognized as the discoverers of electromagnetism and thermoelectricity. Yet what each man believed he had discovered differed markedly from what many contemporaries saw in those discoveries and from subsequent canonized representations of them. The central historical concern of this paper is to track the details of how scientists' understanding of what was discovered in these two cases, as embodied in their preferred language, evolved over time in response to different interests, conceptual preferences, and ontological beliefs. The very concept of discovery, in accordance with which scientists bestow recognition only on someone who has discovered something held to be true of the world, plays an important role in the process of consensus formation by the interacting collectivity of scientists. In its historiographical assessment of such episodes, this study builds upon Thomas Kuhn's recognition that “discovering a new sort of phenomena is necessarily a complex process which includes recognizing both that something is and what it is”; upon augustine Brannigan's analysis of the social construction of discovery accounts, whereby “the attribution of discovery is structured…by the perception that the achievement is coherent with existing knowledge in the field”; and upon Ludwik Fleck's analysis of the creative role of an interacting “thought collective” in the “genesis and development of a scientific fact.”