bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental RNA is Significantly Degraded During Arabidopsis Seed Germination
Authors: Li Qing , Feng Jian‐Xun , Han Pei , Zhu Yu‐Xian 
Published: January 2006

AbstractGermination is the first and maybe the foremost growth stage in the life cycle of a plant. Herein, we report that initiation of germination in the Arabidopsis Columbia ecotype was accompanied by a sharp decrease in the amount of extractable total RNA. At the beginning of our germination experiment, we were usually able to obtain 35–40 μg total RNA from 100 mg dry seeds. However, after 3 d of cold stratification, we could only obtain less than 5 μg total RNA from the same amount of starting material. Young seedlings contained approximately 100 μg total RNA per 100 mg fresh tissue. Further studies showed that inhibition of de novo RNA synthesis by actinomycin D prevented the degradation of parental RNA and, in the meantime, significantly delayed the germination process. Several ribonuclease‐like genes that were highly expressed in dry seeds, and especially during the cold stratification period, were discovered. We propose that these enzymes are involved in the regulation of parental RNA degradation. These results indicate that parental RNA metabolism may be an important process for Arabidopsis seed germination.(Managing editor: Ya‐Qin Han)
Supply Chain Coordination and Cooperation Mechanisms: An Attribute‐Based Approach
Authors: Xu Lei , Beamon Benita M. 
Published: January 2006

SUMMARYCoordination within a supply chain is a strategic response to the problems that arise from inter‐organizational dependencies within the chain. A coordination mechanism is a set of methods used to manage interdependence between organizations. Given the increasing importance of high‐performance supply, and the advantages to be gained through supply chain coordination, the challenge to an organization is how to select the appropriate coordination mechanism to manage organizational interdependencies. This paper develops and illustrates an attribute‐based, systematic process for selecting coordination mechanisms in a supply chain.
The Implementation of Target Costing in the United States: Theory Versus Practice
Authors: Ellram Lisa M. 
Published: January 2006

SUMMARYTarget costing has been touted as a process that can significantly improve new product development results in the accounting, engineering, operations management, and purchasing literature. The target costing process considers the voice of the customer, incorporates earlier supplier involvement and concurrent engineering, utilizes cross‐functional teams, and focuses on creating a good or service that is both desirable and affordable to the customer and profitable to the producing organization. Unlike previous studies, which have focused on Japanese firms, or used single case studies, this paper uses the findings from case studies of 11 organizations actively engaged in the target costing process. This paper explores how the target costing process is used in practice in the United States, comparing it with the popular theoretical model of target costing. It helps shed light on to target costing practices of U.S. and other Western firms, and highlights the often overlooked role of the purchasing function in successful target costing efforts.
Total Cost of Ownership in the Services Sector: A Case Study
Authors: Hurkens Krisje , van der Valk Wendy , Wynstra Finn 
Published: January 2006

SUMMARYFew detailed studies exist of the trade‐offs to be made when developing a comprehensive, strategically focused total cost of ownership (TCO) model. Moreover, most studies of TCO have been conducted in manufacturing firms, with little or no TCO research directed toward service organizations. This research presents the results of a study conducted at a leading vehicle glass repair and replacement organization. The results show how TCO information can be used for strategic decision making regarding the allocation of volumes. This information can also be used in the identification of improvement areas for preferred suppliers by introducing a limited number of key performance indicators that have a significant impact on the TCO of supplier offerings. The paper highlights some of the trade‐offs required in designing such a model. It fills an existing literature gap that allows service organizations to better understand the development and implementation of total cost measurement systems.
Nitric Oxide Is a Factor in the Stabilization of Hypoxia-Inducible Factor-1α in Cancer: Role of Free Radical Formation
Authors: Quintero Marisol , Brennan Peter A. , Thomas Gareth J. , Moncada Salvador 
Published: January 2006

AbstractWidespread expression of the α-subunit of hypoxia-inducible factor (HIF-1α) was observed in samples of human oral squamous cell carcinoma. In all the cases, this was accompanied by a widespread distribution of nitric oxide (NO) synthases (NOS). Furthermore, in three human cell lines derived from human oral squamous cell carcinoma, the accumulation of HIF-1α was prevented either by inhibition of NOS activity with the nonspecific NOS inhibitor NG-monomethyl-l-arginine or by the antioxidants N-acetyl-l-cysteine and ascorbic acid. We suggest that, in certain forms of cancer, NO might be responsible for the accumulation of HIF-1α by a mechanism dependent on free radicals. (Cancer Res 2006; 66(2): 770-4)
RNA Interference–Mediated Depletion of Phosphoinositide 3-Kinase Activates Forkhead Box Class O Transcription Factors and Induces Cell Cycle Arrest and Apoptosis in Breast Carcinoma Cells
Authors: Reagan-Shaw Shannon , Ahmad Nihal 
Published: January 2006

Abstract
Breast cancer is one of the most common malignancies affecting women in the Western world and one in seven women is predicted to develop invasive breast cancer in their lifetime. Breast cancer arises following the accumulation of a series of somatic changes often including deregulation of key signal transduction pathways. The phosphoinositide 3-kinase (PI3K) pathway has been shown to be activated in breast cancer and overexpression of PI3K is sufficient to confer a malignant phenotype. Activation of the PI3K pathway serves to repress forkhead box class O (FoxO) transcription factor–mediated growth arrest and apoptosis. In this study, we used small interfering RNA (siRNA) to knockdown PI3K in three breast cancer cell lines representing different stages of cancer development. Transfection of PI3K siRNA in breast cancer cells resulted in a significant decrease in cell viability and induction of apoptosis irrespective of their estrogen receptor α (ERα) or ErbB2 status. PI3K depletion also resulted in a significant G1 phase cell cycle arrest in ERα-positive breast cancer cells. Further, our data showed that PI3K knockdown resulted in a significant activation of FoxO; interestingly, a simultaneous knockdown of FoxO1a rescued the cells from apoptosis. Furthermore, the downstream effects of FoxO activation were found to be inhibition of cyclin-dependent kinase 4, cyclin-dependent kinase 6, and cyclin D1, and accumulation of p27/Kip1. Thus, we suggest that (a) PI3K plays a critical role in breast cancer development and (b) gene therapeutic approaches aimed at PI3K or the pharmacologic inhibitors of PI3K could be developed for the management of breast cancer. (Cancer Res 2006; 66(2): 1062-9)
Elevated Expression of ISG15 in Tumor Cells Interferes with the Ubiquitin/26S Proteasome Pathway
Authors: Desai Shyamal D. , Haas Arthur L. , Wood Laurence M. , Tsai Yu-Chen , Pestka Sidney , Rubin Eric H. , Saleem Ahamed , Nur-E-Kamal Alam , Liu Leroy F. 
Published: January 2006

Abstract
IFN-stimulatory gene factor 15 (ISG15) is a ubiquitin-like protein, which is conjugated to many cellular proteins. However, its role in protein degradation is unclear. Here, we show that ISG15 is highly elevated and extensively conjugated to cellular proteins in many tumors and tumor cell lines. The increased levels of ISG15 in tumor cells were found to be associated with decreased levels of polyubiquitinated proteins. Specific knockdown of ISG15 expression using ISG15-specific small interfering RNA (siRNA) was shown to increase the levels of polyubiquitinated proteins, suggesting an antagonistic role of ISG15 in regulating ubiquitin-mediated protein turnover. Moreover, siRNA-mediated down-regulation of the major E2 for ISG15 (UbcH8), which blocked the formation of ISG15 protein conjugates, also increased the levels of polyubiquitinated proteins. Together, our results suggest that the ISG15 pathway, which is deregulated during tumorigenesis, negatively regulates the ubiquitin/proteasome pathway by interfering with protein polyubiquitination/degradation. (Cancer Res 2006; 66(2): 921-8)
Gr-1+CD115+ Immature Myeloid Suppressor Cells Mediate the Development of Tumor-Induced T Regulatory Cells and T-Cell Anergy in Tumor-Bearing Host
Authors: Huang Bo , Pan Ping-Ying , Li Qingsheng , Sato Alice I. , Levy David E. , Bromberg Jonathan , Divino Celia M. , Chen Shu-Hsia 
Published: January 2006

AbstractThe accumulation of myeloid suppressor cells (MSCs) is associated with immune suppression in tumor-bearing mice and in cancer patients. The suppressive activity of MSC correlates with the expression of the myeloid markers Gr-1, CD115 (macrophage colony-stimulating factor receptor), and F4/80. Gr-1+CD115+ MSCs, in addition to being able to suppress T-cell proliferation in vitro, can induce the development of Foxp3+ T regulatory cells (Treg) in vivo, which are anergic and suppressive. Furthermore, the secretion of interleukin (IL)-10 and transforming growth factor-β by Gr-1+CD115+ MSCs was induced and enhanced, respectively, on IFN-γ stimulation. The development of Treg requires antigen-associated activation of tumor-specific T cells, depends on the presence of IFN-γ and IL-10, and is independent of the nitric oxide–mediated suppressive mechanism by MSC. Our data provide evidence that Gr-1+CD115+ MSC can mediate the development of Treg in tumor-bearing mice and show a novel immune suppressive mechanism by which MSCs can suppress antitumor responses. (Cancer Res 2006; 66(2): 1123-31)
Phospholipase D Prevents Etoposide-Induced Apoptosis by Inhibiting the Expression of Early Growth Response-1 and Phosphatase and Tensin Homologue Deleted on Chromosome 10
Authors: Kim Joommo , Lee Young Han , Kwon Taeg Kyu , Chang Jong-Soo , Chung Kwang Chul , Min Do Sik 
Published: January 2006

Abstract
Phospholipase D (PLD) has emerged as a critical regulator of cell proliferation and survival signaling. We show for the first time that elevated expression of PLD isozymes attenuates expression of the tumor suppressors early growth response-1 (Egr-1) and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor and apoptosis during etoposide treatment. When formation of phosphatidic acid was inhibited by overexpression of catalytically inactive PLD during etoposide treatment, expression of Egr-1 and PTEN and the apoptotic effect of etoposide were not inhibited. This suggests that PLD inhibits expression of these tumor suppressors and inhibits apoptosis. Deletion of a specific Egr-1-binding site present in the PTEN promoter blocked etoposide-induced PTEN activity and elevated expression of PLD decreased the sensitivity to apoptosis induced by ectopic expression of Egr-1. Etoposide-induced activation of Akt was potentiated by overexpression of PLD and PLD-stimulated suppression of Egr-1 was blocked by inhibition of phosphatidylinositol 3-kinase/Akt survival pathway at the both transcriptional and posttranscriptional levels. These results show that survival signals generated by PLD attenuate expression of Egr-1 by activation of phosphatidylinositol 3-kinase signaling pathway and induction of PTEN by Egr-1, which confers resistance to apoptosis. (Cancer Res 2006; 66(2): 784-93)
PEG10 Is a c-MYC Target Gene in Cancer Cells
Authors: Li Chi-Ming , Margolin Adam A. , Salas Martha , Memeo Lorenzo , Mansukhani Mahesh , Hibshoosh Hanina , Szabolcs Matthias , Klinakis Apostolos , Tycko Benjamin 
Published: January 2006

Abstract
The product of the imprinted gene paternally expressed gene-10 (PEG10) has been reported to support proliferation in hepatocellular carcinomas, but how this gene is regulated has been an open question. We find that MYC knockdown by RNA interference suppresses PEG10 expression in Panc1 pancreatic carcinoma and HepG2 hepatocellular carcinoma cells and that knockdown of PEG10 inhibits the proliferation of Panc1, HepG2, and Hep3B cells. Conversely, PEG10 was up-regulated by inducing c-MYC expression in a B-lymphocyte cell line. Chromatin immunoprecipitation from Panc1 cells showed c-MYC bound to an E-box-containing region in the PEG10 first intron and site-directed mutagenesis showed that the most proximal E-box is essential for promoter activity. In a mouse mammary tumor virus (MMTV)-MYC transgenic mouse model of breast cancer, most but not all of the mammary carcinomas had strongly increased Peg10 mRNA compared with normal mammary gland. By immunohistochemistry, normal human breast and prostate epithelium was negative for the major isoform [reading frame-1 (RF1)] of PEG10 protein, but this cytoplasmic protein was strongly expressed in a subset of breast carcinomas in situ and invasive ductal carcinomas (∼30%) and in a similar percentage of prostate cancers. As in the mouse model, we found positive, but not absolute, correlations between PEG10 and c-MYC in tissue arrays containing 161 human breast cancers (P &lt; 0.002) and 30 prostate cancers (P = 0.014). Immunostaining of human placenta showed PEG10 and c-MYC proteins coexpressed in proliferating cytotrophoblast and coordinately lost in postmitotic syncytiotrophoblast. These findings link cancer genetics and epigenetics by showing that a classic proto-oncogene, MYC, acts directly upstream of a proliferation-positive imprinted gene, PEG10. (Cancer Res 2006; 66(2): 665-72)
Rapamycin Disrupts Cyclin/Cyclin-Dependent Kinase/p21/Proliferating Cell Nuclear Antigen Complexes and Cyclin D1 Reverses Rapamycin Action by Stabilizing These Complexes
Authors: Law Mary , Forrester Elizabeth , Chytil Anna , Corsino Patrick , Green Gail , Davis Bradley , Rowe Thomas , Law Brian 
Published: January 2006

Abstract
Rapamycin and its derivatives are promising anticancer agents, but the exact mechanisms by which these drugs induce cell cycle arrest and inhibit tumor growth are unknown. A biochemical analysis of human mammary tumor cell lines indicated that rapamycin-induced antiproliferative effects correlated with down-regulation of cellular p21 levels and the levels of p21 in cyclin-dependent kinase (Cdk) 2 and 4 complexes. Cyclin D1 overexpression reversed rapamycin action and this reversal correlated with increased levels of cellular p21, higher levels of p21 associated with Cdk2, and stabilization of cyclin D1/Cdk2/p21/proliferating cell nuclear antigen (PCNA) complexes. Experiments using a novel cyclin D1-Cdk2 fusion protein or a kinase-dead mutant of the fusion protein indicated that reversal of rapamycin action required not only the formation of complexes with p21 and PCNA but also complex-associated kinase activity. Similar results were observed in vivo. The rapamycin derivative RAD001 (everolimus) inhibited the growth of mouse mammary tumors, which correlated with the disruption of cyclin D1/Cdk2 complexes. The potential implications of these results with respect to the use of rapamycin derivatives in breast cancer therapy are discussed. (Cancer Res 2006; 66(2): 1070-80)
Tagging Single-Nucleotide Polymorphisms in Antioxidant Defense Enzymes and Susceptibility to Breast Cancer
Authors: Cebrian Arancha , Pharoah Paul D. , Ahmed Shahana , Smith Paula L. , Luccarini Craig , Luben Robert , Redman Karen , Munday Hannah , Easton Douglas F. , Dunning Alison M. , Ponder Bruce A.J. 
Published: January 2006

Abstract
It is generally believed that the initiation of breast cancer is a consequence of cumulative genetic damage leading to genetic alterations and provoking uncontrolled cellular proliferation and/or aberrant programmed cell death, or apoptosis. Reactive oxygen species have been related to the etiology of cancer as they are known to be mitogenic and therefore capable of tumor promotion. The aim of this study was to assess the role of common variation in 10 polymorphic genes coding for antioxidant defense enzymes in modulating individual susceptibility to breast cancer using a case-control study (N cases = 4,474 and N controls = 4,580). Both cases and controls were from the East Anglian region of the United Kingdom. We have identified a set of 54 single nucleotide polymorphisms (SNPs) that efficiently tag all the known SNPs in the 10 genes and are also expected to tag any unknown SNPs in each gene. We found no evidence for association of common variants in SOD1, SOD2, GPX1, GPX4, GSR, TXNRD1, and TXN2. There was borderline evidence for association of variants in CAT g27168a {P [2 degrees of freedom (df)] = 0.05}, TXN t2715c [P (2 df) = 0.007], and TXNRD2 A66S and TXNRD2 g23524a (Ptrend = 0.074 and 0.046, respectively). For TXNRD2 A66S [AS versus AA: odds ratio (OR), 1.05; 95% confidence intervals (95% CI), 0.96-1.15; SS versus AA: OR, 1.12; 95% CI, 0.98-1.29], there are bioinformatics data to suggest that it is functional but confirmation in independent data sets is required before they can be regarded as definitive breast cancer susceptibility alleles. Even if confirmed, these four alleles would account for just 0.32% of the excess familial risk of breast cancer. (Cancer Res 2006; 66(2): 1225-33)
De novo CpG Island Methylation in Human Cancer Cells
Authors: Jair Kam-Wing , Bachman Kurtis E. , Suzuki Hiromu , Ting Angela H. , Rhee Ina , Yen Ray-Whay Chiu , Baylin Stephen B. , Schuebel Kornel E. 
Published: January 2006

Abstract
A major obstacle toward understanding how patterns of abnormal mammalian cytosine DNA methylation are established is the difficulty in quantitating the de novo methylation activities of DNA methyltransferases (DNMT) thought to catalyze these reactions. Here, we describe a novel method, using native human CpG island substrates from genes that frequently become hypermethylated in cancer, which generates robust activity for measuring de novo CpG methylation. We then survey colon cancer cells with genetically engineered deficiencies in different DNMTs and find that the major activity against these substrates in extracts of these cells is DNMT1, with minor contribution from DNMT 3b and none from DNMT3a, the only known bona fide de novo methyltransferases. The activity of DNMT1 against unmethylated CpG rich DNA was further tested by introducing CpG island substrates and DNMT1 into Drosophila melanogaster cells. The exogenous DNMT1 methylates the integrated mammalian CpG islands but not the Drosophila DNA. Additionally, in human cancer cells lacking DNMT1 and DNMT3b and having nearly absent genomic methylation, gene-specific de novo methylation can be initiated by reintroduction of DNMT1. Our studies provide a new assay for de novo activity of DNMTs and data suggesting a potential role for DNMT1 in the initiation of promoter CpG island hypermethylation in human cancer cells. (Cancer Res 2006; 66(2): 682-92)
Cisplatin Mimics ARF Tumor Suppressor Regulation of RelA (p65) Nuclear Factor-κB Transactivation
Authors: Campbell Kirsteen J. , Witty James M. , Rocha Sonia , Perkins Neil D. 
Published: January 2006

Abstract
The RelA (p65) nuclear factor-κB (NF-κB) subunit can contribute towards tumor cell survival through inducing the expression of a variety of antiapoptotic genes. However, the NF-κB response can show great diversity and is not always antiapoptotic. Here, we find that cisplatin, a DNA cross-linking agent and commonly used anticancer compound, does not affect RelA nuclear translocation but modulates its transcriptional activity. Similar to other genotoxic agents, such as daunorubicin and UV light, cisplatin treatment in the U-2 OS osteosarcoma cell line represses RelA activity and inhibits expression of the NF-κB antiapoptotic target gene Bcl-xL. The mechanism through which cisplatin achieves these effects is different to daunorubicin and UV light but shows great similarity to the RelA regulatory pathway induced by the ARF tumor suppressor: cisplatin regulation of RelA requires ATR/Chk1 activity, represses Bcl-xL but not XIAP expression, and results in phosphorylation of RelA at Thr505. In contrast to these results, another chemotherapeutic drug etoposide activates NF-κB and induces expression of these target genes. Thus, within a single tumor cell line, there is great heterogeneity in the NF-κB response to different, commonly used chemotherapeutic drugs. These observations suggest that it might be possible to minimize the ability of RelA to inhibit cancer therapy by diagnostically predicting the type of chemotherapeutic drug most compatible with NF-κB functionality in a tumor cell type. Moreover, our data indicate that at least with respect to RelA, cisplatin functions as an ARF mimic. Other drugs capable of mimicking this aspect of ARF function might therefore have therapeutic potential. (Cancer Res 2006; 66(2): 929-35)
Intracellular Signaling Pathways Involved in the Cell Growth Inhibition of Glioma Cells by Melatonin
Authors: Martín Vanesa , Herrera Federico , Carrera-Gonzalez Pilar , García-Santos Guillermo , Antolín Isaac , Rodriguez-Blanco Jezabel , Rodriguez Carmen 
Published: January 2006

Abstract
Melatonin is an indolamine mostly produced in the pineal gland, soluble in water, and highly lipophilic, which allows it to readily cross the blood-brain barrier. Melatonin possesses antioxidant properties and its long-term administration in rodents has not been found to cause noteworthy side effects. In the present work, we found that millimolar concentrations of this indolamine reduced cell growth of C6 glioma cells by 70% after 72 hours of treatment, inhibiting cell progression from G1 to S phase of the cell cycle. Intraperitoneal administration of 15 mg/kg body weight of melatonin to rats previously injected in the flank with C6 glioma cells reduces tumor growth by 50% 2 weeks after the implant. Inhibition of cell growth does not depend on melatonin membrane receptor activation whereas it seemingly relates to the reduction of intracellular basal free radical levels by 30%. Increase of basal redox state of the cells and constitutive activation of tyrosine kinase receptor [receptor tyrosine kinase (RTK)] pathways, including the extracellular signal–regulated kinase 1/2 (ERK1/2) and the Akt and protein kinase C (PKC) signaling pathways, contribute to the progression of the gliomas leading to the constitutive activation of the redox-dependent survival transcription factor nuclear factor κB (NF-κB). The antioxidant effect of melatonin in C6 cells is associated to inhibition of NF-κB and Akt, but not of ERK1/2. The antiproliferative effect of the indolamine on these cells is partially abolished when coincubated with the PKC activator 12-O-tetradecanoylphorbol-13-acetate, thus indicating that the ability of melatonin to change cellular redox state may be inactivating the pathway RTK/PKC/Akt/NF-κB. (Cancer Res 2006; 66(2): 1081-8)