bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding High Saving Rate in China
Authors: He Xinhua , Cao Yongfu 
Published: February 2007

AbstractThis paper presents a detailed analysis of the Chinese saving rate based on the flow of funds data. It finds that the most widely adopted view of precautionary saving, which is regarded as the top reason for maintaining a high saving rate in China, is misleading because this conclusion is drawn from the household survey data. In fact, the household saving rate has declined dramatically since the mid‐1990s, as is observed from the flow of funds framework. The high national saving rate is attributed to the increasing shares of both government and corporation disposable incomes. Insufficient consumption demand is caused by the persistent decrease in percentage share of household to national disposable income. Government‐ directed income redistribution urgently needs to be improved to accelerate consumption, which in turn would make the Chinese economy less investment‐led and help to reduce the current account surplus.(Edited by Zhinan Zhang)
How Mobile Are Resources in Chinese Agriculture?— Implications for China's Agricultural Trade Policy
Authors: Zhong Funing , Zhu Jing , Xie Zhengqin 
Published: February 2007

AbstractAgricultural trade policy in China has been the subject of heated discussion since China's accession to the WTO. Studies have been carried out and propositions put forth regarding comparative advantage, food security, development of the industry, and farmers’ income. In this paper, we attempt to provide an analysis from another important perspective: resource mobility, which is an essential assumption in free trade theory. By examining the mobility of different production resources in Chinese agriculture, namely natural resources, capital inputs, human resources and institutional arrangements, we found that for most production resources in Chinese agriculture, mobility is low. The results have significant policy implications in two respects: first, protective measures in the transitional period for certain crops in certain areas in China are legitimate and necessary to ensure social stability; and second, policy instruments to improve resource mobility in Chinese agricultural should be explored and implemented to realize more trade benefit in the future.(Edited by Xinyu Fan)
Is Asian Currency Unit Attractive to East Asian Economies?
Authors: Zhang Bin , He Fan 
Published: February 2007

AbstractPegging the RMB exchange rate to the Asian currency unit (ACU) has not, at least in the short term, been proved a better solution than pegging to the US dollar or pegging to a G‐3 (US$, Japanese yen and euro) currency basket. Although the Asian currency unit can help Asian economies to keep the relative price of regional currencies stable, the cost of joining a formal regional monetary cooperation is the relinquishment of the autonomy of their domestic policies. Asian monetary cooperation needs to provide more potential benefits if it is to attract Asian economies. We argue that Asian monetary cooperation should be designed to solve the problem of regional trade imbalance, and regional exchange rate policy coordination should be adopted as the first step towards exchange rate cooperation.(Edited by Zhinan Zhang)
China's FDI Net Inflow and Deterioration of Terms of Trade: Paradox and Explanation
Authors: Li Huizhong , Huang Ping , Li Jialun 
Published: February 2007

AbstractStarting from the contradiction between China's sustained growth in foreign direct investment (FDI) net inflow and deterioration of the terms of trade, this paper analyzes the characteristics of FDI sectoral structure since the 1990. Moreover, considering the international market competitive environment, this paper gives a concrete analysis of the influence mechanism and concludes that the flowing of FDI into labor‐intensive export sectors caused the deterioration of China's terms of trade. To improve its terms of trade, China needs to direct FDI inflow into capital‐ and technology‐intensive sectors and service sectors.(Edited by Xiaoming Feng)
Existence of Positive Solutions for a Discrete Three-Point Boundary Value Problem
Authors: Yuan Huting , Zhang Guang , Zhao Hongliang 
Published: February 2007

A discrete three-point boundary value problemΔ2xk−1+λfk(xk)=0,k=1,2,…,n, x0=0,axl=xn+1, is considered, where1≤l≤nis a fixed integer,ais a real constant number, andλis a positive parameter. A characterization of the values ofλis carried out so that the boundary value problem has the positive solutions. Particularly, in this paper the constantacan be negative numbers. The similar results are not valid for the three-point boundary value problem of differential equations.
Spontaneous Development of Liver Tumors in the Absence of the Bile Acid Receptor Farnesoid X Receptor
Authors: Yang Fan , Huang Xiongfei , Yi Tangsheng , Yen Yun , Moore David D. , Huang Wendong 
Published: February 2007

Abstract
Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear hormone receptor superfamily, which plays an essential role in regulating bile acid, lipid, and glucose homeostasis. Both male and female FXR−/− mice spontaneously developed liver tumors; however, no other tumors were developed after 15 months of age. In contrast, no liver tumors were observed in wild-type mice of the same age. Histologic analyses confirm that tumors were hepatocellular adenoma and carcinoma. Although there was no obvious tumor at ages 9 to 12 months, FXR−/− livers displayed prominent liver injury and inflammation. Strong labeling of apoptotic hepatocytes and liver damage–induced compensatory regeneration were observed. Deregulation of genes involved in bile acid homeostasis in FXR−/− mice was consistent with abnormal levels of bile acids presented in serum and liver. Genes involved in inflammation and cell cycle were up-regulated in aging FXR−/− mice but not in wild-type controls. Increasing the bile acid levels by feeding mice with a 0.2% cholic acid diet strongly promoted N-nitrosodiethylamine–initiated liver tumorigenesis, whereas lowering bile acid pool in FXR−/− mice by a 2% cholestyramine feeding significantly reduced the malignant lesions. Our results suggest an intriguing link between metabolic regulation and hepatocarcinogenesis. [Cancer Res 2007;67(3):863–7]
Knockdown of XAB2 Enhances All-Trans Retinoic Acid–Induced Cellular Differentiation in All-Trans Retinoic Acid–Sensitive and –Resistant Cancer Cells
Authors: Ohnuma-Ishikawa Kumiko , Morio Tomohiro , Yamada Takayuki , Sugawara Yuji , Ono Makoto , Nagasawa Masayuki , Yasuda Akio , Morimoto Chikao , Ohnuma Kei , Dang Nam H. , Hosoi Hajime , Verdin Eric , Mizutani Shuki 
Published: February 2007

Abstract
Xeroderma pigmentosum group A (XPA)–binding protein 2 (XAB2) is composed of 855 amino acids, contains 15 tetratricopeptide repeat motifs, and associates with Cockayne syndrome group A and B proteins and RNA polymerase II, as well as XPA. In vitro and in vivo studies showed that XAB2 is involved in pre-mRNA splicing, transcription, and transcription-coupled DNA repair, leading to preimplantation lethality, and is essential for mouse embryogenesis. Retinoids are effective for the treatment of preneoplastic diseases including xeroderma pigmentosum and other dermatologic diseases such as photoaging. We therefore focused on defining the effect of XAB2 on cellular differentiation in the presence of ATRA treatment. In the present study, we showed that overexpression of XAB2 inhibited ATRA-induced cellular differentiation in human rhabdomyosarcoma cell line, and that knockdown of XAB2 by small interfering RNA (siRNA) increased ATRA-sensitive cellular differentiation in the human promyelocytic leukemia cell line HL60 at both physiologic (10−9–10−8 mol/L) and therapeutic (10−7 mol/L) concentrations of ATRA. Moreover, we found that XAB2 was associated with retinoic acid receptor α (RARα) and histone deacetylase 3 in the nuclei. Finally, using siRNA against XAB2, we showed that the ATRA-resistant neuroblastoma cell line IMR-32 underwent cellular differentiation induced by ATRA at a therapeutic concentration (10−6 mol/L). These results strongly suggest that XAB2 is a component of the RAR corepressor complex with an inhibitory effect on ATRA-induced cellular differentiation and that XAB2 plays a role in ATRA-mediated cellular differentiation as an important aspect of cancer therapy. [Cancer Res 2007;67(3):1019–29]
DNA Methylation of Tumor Suppressor Genes in Clinical Remission Predicts the Relapse Risk in Acute Myeloid Leukemia
Authors: Agrawal Shuchi , Unterberg Matthias , Koschmieder Steffen , zur Stadt Udo , Brunnberg Uta , Verbeek Walter , Büchner Thomas , Berdel Wolfgang E. , Serve Hubert , Müller-Tidow Carsten 
Published: February 2007

Abstract
Epigenetic changes play an important role in leukemia pathogenesis. DNA methylation is among the most common alterations in leukemia. The potential role of DNA methylation as a biomarker in leukemia is unknown. In addition, the lack of molecular markers precludes minimal residual disease (MRD) estimation for most patients with hematologic malignancies. We analyzed the potential of aberrant DNA promoter methylation as a biomarker for MRD in acute leukemias. Quantitative real-time PCR methods with bisulfite-modified DNA were established to quantify MRD based on estrogen receptor α (ERα) and/or p15INK4B methylation. Methylation analyses were done in &gt;370 DNA specimens from 180 acute leukemia patients and controls. Methylation of ERα and/or p15INK4B occurred frequently and specifically in acute leukemia but not in healthy controls or in nonmalignant hematologic diseases. Aberrant DNA methylation was detectable in &gt;20% of leukemia patients during clinical remission. In pediatric acute lymphoblastic leukemia, methylation levels during clinical remission correlated closely with T-cell receptor/immunoglobulin MRD levels (r = +0.7, P &lt; 0.01) and were associated with subsequent relapse. In acute myelogenous leukemia patients in clinical remission, increased methylation levels were associated with a high relapse risk and significantly reduced relapse-free survival (P = 0.003). Many patients with acute leukemia in clinical remission harbor increased levels of aberrant DNA methylation. Analysis of methylation MRD might be used as a novel biomarker for leukemia patients' relapse risk. [Cancer Res 2007;67(3):1370–7]
Growth Factor Stimulation Reduces Residual Quiescent Chronic Myelogenous Leukemia Progenitors Remaining after Imatinib Treatment
Authors: Holtz Melissa , Forman Stephen J. , Bhatia Ravi 
Published: February 2007

Abstract
The BCR/ABL tyrosine kinase inhibitor imatinib mesylate is highly effective in the treatment of chronic myelogenous leukemia (CML) but fails to eliminate all leukemia cells. Residual leukemia stem and progenitor cells persist in imatinib-responsive patients and may be a potential source of relapse. Previous studies indicate that imatinib preferentially targets dividing cells, and nondividing progenitor cells are resistant to imatinib-mediated apoptosis. We investigated whether growth factor stimulation of progenitor proliferation could reduce the number of residual nondividing cells remaining after imatinib treatment. CML and normal CD34+ cells were labeled with 5-(and 6-)-carboxyfluorescein diacetate succinimidyl ester (CFSE) to track cell division and cultured in low or high concentrations of growth factor to determine effects of growth factor stimulation on nondividing cells. High growth factor concentrations significantly enhanced CML proliferation with or without imatinib treatment and significantly reduced the number of viable, nondividing CFSE bright cells remaining after imatinib exposure. Stimulation with high growth factor before imatinib treatment further reduced the number of residual nondividing CML CD34+ cells. Importantly, clinically achievable concentrations of granulocyte macrophage colony-stimulating factor alone or in combination with granulocyte colony-stimulating factor also significantly reduced nondividing CML CD34+ cells. These results support the potential efficacy of growth factor stimulation in reducing the residual leukemia progenitor population in imatinib-treated patients. [Cancer Res 2007;67(3):1113–20]
DNAX Accessory Molecule-1 Mediated Recognition of Freshly Isolated Ovarian Carcinoma by Resting Natural Killer Cells
Authors: Carlsten Mattias , Björkström Niklas K. , Norell Håkan , Bryceson Yenan , van Hall Thorbald , Baumann Bettina C. , Hanson Mikael , Schedvins Kjell , Kiessling Rolf , Ljunggren Hans-Gustaf , Malmberg Karl-Johan 
Published: February 2007

AbstractAlthough natural killer (NK) cells are well known for their ability to kill tumors, few studies have addressed the interactions between resting (nonactivated) NK cells and freshly isolated human tumors. Here, we show that human leukocyte antigen class Ilow tumor cells isolated directly from patients with advanced ovarian carcinoma trigger degranulation by resting allogeneic NK cells. This was paralleled by induction of granzyme B and caspase-6 activities in the tumor cells and significant tumor cell lysis. Ovarian carcinoma cells displayed ubiquitous expression of the DNAX accessory molecule-1 (DNAM-1) ligand PVR and sparse/heterogeneous expression of the NKG2D ligands MICA/MICB and ULBP1, ULBP2, and ULBP3. In line with the NK receptor ligand expression profiles, antibody-mediated blockade of activating receptor pathways revealed a dominant role for DNAM-1 and a complementary contribution of NKG2D signaling in tumor cell recognition. These results show that resting NK cells are capable of directly recognizing freshly isolated human tumor cells and identify ovarian carcinoma as a potential target for adoptive NK cell–based immunotherapy. [Cancer Res 2007;67(3):1317–25]
Bcl-2 Protects Endothelial Cells against γ-Radiation via a Raf-MEK-ERK-Survivin Signaling Pathway That Is Independent of Cytochrome c Release
Authors: Kumar Pawan , Coltas Ila K. , Kumar Bhavna , Chepeha Douglas B. , Bradford Carol R. , Polverini Peter J. 
Published: February 2007

Abstract
The Bcl-2 oncoprotein is a potent inhibitor of apoptosis and is overexpressed in a wide variety of malignancies. Until recently, it was generally accepted that Bcl-2 primarily mediates its antiapoptotic function by regulating cytochrome c release from mitochondria. However, more recent studies have shown that Bcl-2 is present on several intracellular membranes and mitochondria may not be the only site where Bcl-2 exercises its survival function. In this study, we investigated if Bcl-2 can protect endothelial cells against γ-radiation by a cytochrome c–independent signaling pathway. Human dermal microvascular endothelial cells (HDMEC), when exposed to γ-radiation, exhibited a time-dependent activation of caspase-3 that was associated with increased cytochrome c release from mitochondria. Bcl-2 expression in endothelial cells (HDMEC-Bcl-2) significantly inhibited irradiation-induced caspase-3 activation. However, Bcl-2–mediated inhibition of caspase-3 was significantly reversed by inhibition of the Raf-mitogen-activated protein kinase (MAPK)/extracellular signal–regulated kinase (ERK) kinase (MEK)-ERK pathway. Interestingly, caspase-3 activation in HDMEC-Bcl-2 cells was not associated with cytochrome c release. We also observed that endothelial cell Bcl-2 expression significantly increased the expression of survivin and murine double minute-2 (Mdm2) via the Raf-MEK-ERK pathway. Endothelial cells expressing Bcl-2 also inhibited γ-radiation–induced activation of p38 MAPK and p53 accumulation. Inhibition of p53 accumulation in HDMEC-Bcl-2 could be due to the enhanced expression of Mdm2 in these cells. Taken together, these results show three mechanisms by which Bcl-2 may mediate endothelial cell cytoprotection independently of cytochrome c release: (a) increased survivin expression, (b) inhibition of p53 accumulation, and (c) inhibition of p38 MAPK. [Cancer Res 2007;67(3):1193–202]
Antiadhesive Effects of GRN163L—An Oligonucleotide N3′→P5′ Thio-Phosphoramidate Targeting Telomerase
Authors: Jackson Shalmica R. , Zhu Chun-Hong , Paulson Vera , Watkins Linda , Dikmen Z. Gunnur , Gryaznov Sergei M. , Wright Woodring E. , Shay Jerry W. 
Published: February 2007

Abstract
We determined previously that a novel human telomerase RNA (hTR) antagonist, GRN163L, inhibited the tumorigenic potential of A549-luciferase (A549-luc) lung cancer cells in vitro and in vivo. Further studies revealed that A549-luc cells were also morphologically altered by GRN163L. A549-luc cells treated before cell attachment with a single dose of GRN163L only weakly attached to the substrate and remained rounded, whereas control mismatch-treated cells exhibited typical epitheloid appearance and adhesion properties. These morphologic changes were independent of hTR expression and telomerase inhibition and were unrelated to telomere length. This effect is dependent on the molecular properties of the lipid moiety, the phosphorothioate backbone, and the presence of triplet-G sequences within the GRN163L structure. Altered adhesion was manifested by a 50% reduction in rapid cellular attachment and a 3-fold decrease in total cell spreading surface area. Administration of a single dose of GRN163L (15 mg/kg) at the time of cell inoculation, using an in vivo model of lung cancer metastasis, resulted in significant reductions in tumor burden at days 13, 20, and 27 of tumor progression. Thus, the potent antimetastatic effects of GRN163L may be related, in part, to the antiadhesive effects of this novel cancer therapeutic conferred via specific structural determinants and that these effects are independent of telomerase inhibition or telomere shortening. [Cancer Res 2007;67(3):1121–9]
Tbx3 Is a Downstream Target of the Wnt/β-Catenin Pathway and a Critical Mediator of β-Catenin Survival Functions in Liver Cancer
Authors: Renard Claire-Angélique , Labalette Charlotte , Armengol Carolina , Cougot Delphine , Wei Yu , Cairo Stefano , Pineau Pascal , Neuveut Christine , de Reyniès Aurélien , Dejean Anne , Perret Christine , Buendia Marie-Annick 
Published: February 2007

Abstract
Tbx3 encodes a transcriptional repressor that is important for diverse patterning events during development, and Tbx3 mutation in humans causes the ulnar-mammary syndrome. Here, we describe the identification of Tbx3 in array-based search for genes downstream Wnt/β-catenin that are implicated in liver tumorigenesis. Overexpression of Tbx3 is closely associated with the mutational status of β-catenin in murine liver tumors induced by Myc as well as in human hepatocellular carcinomas and hepatoblastomas. Moreover, Tbx3 transcription is activated by ectopic expression of β-catenin in mouse liver and in human tumor cell lines. Evidence that Tbx3 transcription is directly regulated by β-catenin is provided by chromatin immunoprecipitation and reporter assays. Although HepG2 cells stably transfected with Tbx3 display moderately enhanced growth rate, the dominant negative mutant Tbx3-Y149S drastically inhibits hepatoma cell growth in vitro and in vivo. Moreover, small interfering RNAs (siRNA) directed against Tbx3 inhibit anchorage-independent growth of liver and colon carcinoma cells. We further show that inhibition of Tbx3 expression by specific siRNAs blocks β-catenin–mediated cell survival and renders cells sensitive to doxorubicin-induced apoptosis. Conversely, ectopic expression of Tbx3 inhibits apoptosis induced by β-catenin depletion. Marked overexpression of Tbx3 in a subset of hepatoblastomas is associated with chemotherapy-resistant phenotype and unfavorable patient outcome. These results reveal an unsuspected role of Tbx3 as a mediator of β-catenin activities on cell proliferation and survival and as an important player in liver tumorigenesis. [Cancer Res 2007;67(3):901–10]
RASSF1C, an Isoform of the Tumor Suppressor RASSF1A, Promotes the Accumulation of β-Catenin by Interacting with βTrCP
Authors: Estrabaud Emilie , Lassot Irina , Blot Guillaume , Le Rouzic Erwann , Tanchou Valérie , Quemeneur Eric , Daviet Laurent , Margottin-Goguet Florence , Benarous Richard 
Published: February 2007

Abstract
The Ras-association domain family 1 (RASSF1) gene has seven different isoforms; isoform A is a tumor-suppressor gene (RASSF1A). The promoter of RASSF1A is inactivated in many cancers, whereas the expression of another major isoform, RASSF1C, is not affected. Here, we show that RASSF1C, but not RASSF1A, interacts with βTrCP. Binding of RASSF1C to βTrCP involves serine 18 and serine 19 of the SS18GYXS19 motif present in RASSF1C but not in RASSF1A. This motif is reminiscent of the canonical phosphorylation motif recognized by βTrCP; however, surprisingly, the association between RASSF1C and βTrCP does not occur via the βTrCP substrate binding domain, the WD40 repeats. Overexpression of RASSF1C, but not of RASSF1A, resulted in accumulation and transcriptional activation of the β-catenin oncogene, due to inhibition of its βTrCP-mediated degradation. Silencing of RASSF1A by small interfering RNA was sufficient for β-catenin to accumulate, whereas silencing of both RASSF1A and RASSF1C had no effect. Thus, RASSF1A and RASSF1C have opposite effects on β-catenin degradation. Our results suggest that RASSF1C expression in the absence of RASSF1A could play a role in tumorigenesis. [Cancer Res 2007;67(3):1054–61]
Ability to Acquire Drug Resistance Arises Early during the Tumorigenesis Process
Authors: Yagüe Ernesto , Arance Ana , Kubitza Loïc , O'Hare Michael , Jat Parmjit , Ogilvie Caroline M. , Hart Ian R. , Higgins Christopher F. , Raguz Selina 
Published: February 2007

Abstract
Resistance to chemotherapy is one of the principal causes of cancer mortality and is generally considered a late event in tumor progression. Although cellular models of drug resistance have been useful in identifying the molecules responsible for conferring drug resistance, most of these cellular models are derived from cell lines isolated from patients at a late stage in cancer progression. To ask at which stage in the tumorigenic progression does the cell gain the ability to acquire drug resistance, we generated a series of pretumorigenic and tumorigenic cells from human embryonic skin fibroblasts by introducing, sequentially, the catalytic subunit of telomerase, SV40 large T and small T oncoproteins, and an oncogenic form of ras. We show that the ability to acquire multidrug resistance (MDR) can arise before the malignant transformation stage. The minimal set of changes necessary to obtain pretumorigenic drug-resistant cells is expression of telomerase and inactivation of p53 and pRb. Thus, the pathways inactivated during tumorigenesis also confer the ability to acquire drug resistance. Microarray and functional studies of drug-resistant pretumorigenic cells indicate that the drug efflux pump P-glycoprotein is responsible for the MDR phenotype in this pretumorigenic cell model. [Cancer Res 2007;67(3):1130–7]