bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Acupuncture in Western Medicine
Authors: Thompson John 
Published: April 2009

Acupuncture has three main roles in western medicine (i) therapeutic, (ii) research, (iii) cultural and political. (i) Therapeutic: There has been a steady increase in the use of acupuncture in western medicine, both as complementary to orthodox medicine and also on its own. (ii) Research: Basic research is steadily defining the mechanism of action of acupuncture. Controlled clinical research is slowly substantiating the clinical efficacy of acupuncture. (iii) Cultural/political: There is a steady increase in the availability of information about, and training in acupuncture by way of books, Journals and training courses. Acupuncture has been a potent stimulus to cultural exchanges and has thus encouraged peaceful collaboration between East and West.
Activation of the PI3 Kinase Pathway By Retinoic Acid Mediates Sodium/Iodide Symporter Induction and Iodide Transport in MCF-7 Breast Cancer Cells
Authors: Ohashi Emi , Kogai Takahiko , Kagechika Hiroyuki , Brent Gregory A. 
Published: April 2009

Abstract
Iodide uptake in the thyroid and breast is mediated by the sodium/iodide symporter (NIS). NIS activation is used for radioiodide imaging and therapeutic ablation of thyroid carcinoma. NIS is expressed in &gt;70% of breast cancers but at a level insufficient for radioiodine treatment. All-trans retinoic acid (tRA) induces NIS gene expression and functional iodide uptake in human breast cancer cell lines and mouse breast cancer models. tRA usually regulates gene expression by direct interaction of RA receptor (RAR) with a target gene, but it can also act through nongenomic pathways. We report a direct influence of tRA treatment on the phosphoinositide 3-kinase (PI3K) signal transduction pathway that mediates tRA-induced NIS expression in MCF-7 breast cancer cells. MCF-7 cells express all three RAR isoforms, α, β, and γ, and RXRα. We previously identified RARβ and RXRα as important for NIS induction by tRA. Treatment with LY294002, the PI3K inhibitor, or p85α knockdown with siRNA abolished tRA-induced NIS expression. Immunoprecipitation experiments and glutathione S-transferase pull-down assay showed a direct interaction between RARβ2, RXRα, and p85α. RA also induced rapid activation of Akt in MCF-7 cells. Treatment with an Akt inhibitor or Akt knockdown with siRNA reduced NIS expression. These findings indicate that RA induction of NIS in MCF-7 cells is mediated by rapid activation of the PI3K pathway and involves direct interaction with RAR and retinoid X receptor. Defining these mechanisms should lead to methods to further enhance NIS expression, as well as retinoid targets that influence growth and differentiation of breast cancer. [Cancer Res 2009;69(8):3443–50]
Transcriptional Regulation of Estrogen Receptor-α by p53 in Human Breast Cancer Cells
Authors: Shirley Stephanie Harkey , Rundhaug Joyce E. , Tian Jie , Cullinan-Ammann Noirin , Lambertz Isabel , Conti Claudio J. , Fuchs-Young Robin 
Published: April 2009

Abstract
Estrogen receptor α (ER) and p53 are critical prognostic indicators in breast cancer. Loss of functional p53 is correlated with poor prognosis, ER negativity, and resistance to antiestrogen treatment. Previously, we found that p53 genotype was correlated with ER expression and response to tamoxifen in mammary tumors arising in mouse mammary tumor virus–Wnt-1 transgenic mice. These results lead us to hypothesize that p53 may regulate ER expression. To test this, MCF-7 cells were treated with doxorubicin or ionizing radiation, both of which stimulated a 5-fold increase in p53 expression. ER expression was also increased 4-fold over a 24-h time frame. In cells treated with small interfering RNA (siRNA) targeting p53, expression of both p53 and ER was significantly reduced (&gt;60%) by 24 h. Induction of ER by DNA-damaging agents was p53 dependent as either ionizing radiation or doxorubicin failed to up-regulate ER after treatment with p53-targeting siRNA. To further investigate whether p53 directly regulates transcription of the ER gene promoter, MCF-7 cells were transiently transfected with a wild-type (WT) p53 expression vector along with a luciferase reporter containing the proximal promoter of ER. In cells transfected with WT p53, transcription from the ER promoter was increased 8-fold. Chromatin immunoprecipitation assays showed that p53 was recruited to the ER promoter along with CARM1, CBP, c-Jun, and Sp1 and that this multifactor complex was formed in a p53-dependent manner. These data show that p53 regulates ER expression through transcriptional control of the ER promoter, accounting for their concordant expression in human breast cancer. [Cancer Res 2009;69(8):3405–14]
Functional Role of S100A14 Genetic Variants and Their Association with Esophageal Squamous Cell Carcinoma
Authors: Chen Hongyan , Yu Dianke , Luo Aiping , Tan Wen , Zhang Chunpeng , Zhao Dan , Yang Ming , Liu Junniao , Lin Dongxin , Liu Zhihua 
Published: April 2009

Abstract
S100 proteins have been implicated in various human diseases, including certain types of cancer. Among them, S100A14 is down-regulated in esophageal squamous cell carcinoma (ESCC). In this study, we sought to identify functional genetic variants in the S100A14 locus and assessed their associations with susceptibility to ESCC. Thirty individual DNA samples were sequenced to search for genetic variations in S100A14, and the function of the variants was investigated by a set of biochemical assays. A case-control analysis was performed in 1,021 patients with ESCC and 1,253 control subjects. Odds ratios and 95% confidence intervals (95% CI) were computed by logistic regression model. Four single nucleotide polymorphisms, −43A&gt;G, 461G&gt;A, 1493A&gt;G, and 1545A&gt;T, were identified in the S100A14 locus and they are in absolute linkage disequilibrium. Among them, the 461G&gt;A change was shown to diminish a P53-binding site and is therefore associated with decreased expression of S100A14 in vitro and in vivo in the target tissues. Case-control analysis showed that the 461A allele was associated with susceptibility to ESCC among smokers, with the ORs being 2.01 (95% CI, 1.50–2.69) or 2.10 (95% CI, 1.37–3.22) for the 461GA or 461AA genotype, respectively, compared with the 461GG genotype. These data constitute strong evidence in support of the notion that S100A14 might function as a cancer suppressor working in the P53 pathway and play a role in esophageal carcinogenesis. [Cancer Res 2009;69(8):3451–7]
RelB Enhances Prostate Cancer Growth: Implications for the Role of the Nuclear Factor-κB Alternative Pathway in Tumorigenicity
Authors: Xu Yong , Josson Sajni , Fang Fang , Oberley Terry D. , St. Clair Daret K. , Wan X. Steven , Sun Yulan , Bakthavatchalu Vasudevan , Muthuswamy Anantharaman , St. Clair William H. 
Published: April 2009

Abstract
The nuclear factor-κB (NF-κB) classic pathway is thought to be critical for tumorigenesis, but little is known about the role of the NF-κB alternative pathway in cancer development. Recently, high constitutive nuclear levels of RelB have been observed in human prostate cancer specimens with high Gleason scores. Here, we used four complementary approaches to test whether RelB contributes to tumorigenicity of prostate cancer. Inhibiting RelB in aggressive androgen-independent PC-3 cells by stable or conditional expression of a dominant-negative p100 mutant significantly reduced the incidence and growth rate of tumors. The decrease in tumorigenicity coincided with a reduction in the NF-κB target interleukin-8 (IL-8). Consistently, down-regulation of RelB by small interfering RNA targeting also reduced tumor growth and decreased levels of IL-8. Conversely, stable expression of RelB in androgen-responsive LNCaP tumors increased the circulating IL-8 levels. Taken together, these results reveal a tumor-supportive role of RelB, implicate the NF-κB alternative pathway as a potential target for preventing prostate cancer, and suggest the use of IL-8 as a marker for prostate cancer prognosis. [Cancer Res 2009;69(8):3267–71]
The L6 Protein TM4SF1 Is Critical for Endothelial Cell Function and Tumor Angiogenesis
Authors: Shih Shou-Ching , Zukauskas Andrew , Li Dan , Liu Guanmei , Ang Lay-Hong , Nagy Janice A. , Brown Lawrence F. , Dvorak Harold F. 
Published: April 2009

Abstract
Transmembrane-4-L-six-family-1 (TM4SF1) was originally described as a cancer cell protein. Here, we show that it is highly expressed in the vascular endothelium of human cancers and in a banded pattern in the filopodia of cultured endothelial cells (EC). TM4SF1 knockdown prevented filopodia formation, inhibited cell mobility, blocked cytokinesis, and rendered EC senescent. Integrin-α5 and integrin-β1 subunits gave a similar staining pattern and interacted constitutively with TM4SF1, whereas integrin subunits often associated with angiogenesis (αV, β3, β5) interacted with TM4SF1 only after vascular endothelial growth factor (VEGF)-A or thrombin stimulation. TM4SF1 knockdown substantially inhibited maturation of VEGF-A164–induced angiogenesis. Thus, TM4SF1 is a key regulator of EC function in vitro and of pathologic angiogenesis in vivo and is potentially an attractive target for antiangiogenesis therapy. [Cancer Res 2009;69(8):3272–7]
Nucleotide Excision Repair Pathway Polymorphisms and Pancreatic Cancer Risk: Evidence for role of MMS19L
Authors: McWilliams Robert R. , Bamlet William R. , de Andrade Mariza , Rider David N. , Cunningham Julie M. , Petersen Gloria M. 
Published: April 2009

Abstract
Background: Nucleotide excision repair is a vital response to DNA damage, including damage from tobacco exposure. Single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway may encode alterations that affect DNA repair function and therefore influence the risk of pancreatic cancer development.
Methods: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls. Twenty-seven genes directly and indirectly involved in the nucleotide excision repair pathway were identified and 236 tag-SNPs were selected from 26 of these (one had no SNPs identified). Association studies were done at the gene level by principal components analysis, whereas recursive partitioning analysis was utilized to identify potential gene-gene and gene-environment interactions within the pathway. At the individual SNP level, adjusted additive, dominant, and recessive models were investigated, and gene-environment interactions were also assessed.
Results: Gene level analyses showed an association of the MMS19L genotype (chromosome 10q24.1) with altered pancreatic cancer risk (P = 0.023). Haplotype analysis of MMS19L also showed a significant association (P = 0.0132). Analyses of seven individual SNPs in this gene showed both protective and risk associations for minor alleles, broadly distributed across patient subgroups defined by smoking status, sex, and age.
Conclusion: In a candidate pathway SNP association study analysis, common variation in a nucleotide excision repair gene, MMS19L, was associated with the risk of pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1295–302)
Observational Epidemiologic Studies of Nutrition and Cancer: The Next Generation (with Better Observation)
Authors: Schatzkin Arthur , Subar Amy F. , Moore Steven , Park Yikyung , Potischman Nancy , Thompson Frances E. , Leitzmann Michael , Hollenbeck Albert , Morrissey Kerry Grace , Kipnis Victor 
Published: April 2009

Abstract
It would be of enormous public health importance if diet and physical activity, both modifiable behavioral factors, were causally related to cancer. Nevertheless, the nutritional epidemiology of cancer remains problematic, in part because of persistent concerns that standard questionnaires measure diet and physical activity with too much error. We present a new strategy for addressing this measurement error problem. First, as background, we note that food frequency and physical activity questionnaires require respondents to report “typical” diet or activity over the previous year or longer. Multiple 24-hour recalls (24HR), based on reporting only the previous day's behavior, offer potential cognitive advantages over the questionnaires, and biomarker evidence suggests the 24-hour dietary recall is more accurate than the food frequency questionnaire. The expense involved in administering multiple 24HRs in large epidemiologic studies, however, has up to now been prohibitive. In that context, we suggest that Internet-based 24HRs, for both diet and physical activity, represent a practical and cost-effective approach for incorporating multiple recalls in large epidemiologic studies. We discuss (1) recent efforts to develop such Internet-based instruments and their accompanying software support systems; (2) ongoing studies to evaluate the feasibility of using these new instruments in cohort studies; (3) additional investigations to gauge the accuracy of the Internet-based recalls vis-à-vis standard instruments and biomarkers; and (4) new statistical approaches for combining the new instruments with standard assessment tools and biomarkers The incorporation of Internet-based 24HRs into large epidemiologic studies may help advance our understanding of the nutritional determinants of cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1026–32)
Generalizability of Associations from Prostate Cancer Genome-Wide Association Studies in Multiple Populations
Authors: Waters Kevin M. , Le Marchand Loic , Kolonel Laurence N. , Monroe Kristine R. , Stram Daniel O. , Henderson Brian E. , Haiman Christopher A. 
Published: April 2009

Abstract
Genome-wide association studies have identified multiple common alleles associated with prostate cancer risk in populations of European ancestry. Testing these variants in other populations is needed to assess the generalizability of the associations and may guide fine-mapping efforts. We examined 13 of these risk variants in a multiethnic sample of 2,768 incident prostate cancer cases and 2,359 controls from the Multiethnic Cohort (African Americans, European Americans, Latinos, Japanese Americans, and Native Hawaiians). We estimated ethnic-specific and pooled odds ratios and tested for ethnic heterogeneity of effects using logistic regression. In ethnic-pooled analyses, 12 of the 13 variants were positively associated with risk, with statistically significant associations (P &lt; 0.05) noted with six variants: JAZF1, rs10486567 [odds ratio (OR), 1.23; 95% confidence interval (95% CI, 1.12-1.35); Xp11.2, rs5945572 (OR, 1.31; 95% CI, 1.13-1.51); HNF1B, rs4430796 (OR, 1.15; 95% CI, 1.06-1.25); MSMB, rs10993994 (OR, 1.13; 95% CI, 1.04-1.23); 11q13.2, rs7931342 (OR, 1.13; 95% CI, 1.03-1.23); 3p12.1, rs2660753 (OR, 1.11; 95% CI, 1.01-1.21); SLC22A3, rs9364554 (OR, 1.10; 95% CI, 1.00-1.21); CTBP2, rs12769019 (OR, 1.11; 95% CI, 0.99-1.25); HNF1B, rs11649743 (OR, 1.10; 95% CI, 0.99-1.22); EHBP1, rs721048 (OR, 1.08; 95% CI, 0.94-1.25); KLK2/3, rs2735839 (OR, 1.06; 95% CI, 0.97-1.16); 17q24.3, rs1859962 (OR, 1.04; 95% CI, 0.96-1.13); and LMTK2, rs6465657 (OR, 0.99; 95% CI, 0.89-1.09). Significant ethnic heterogeneity of effects was noted for four variants (EHBP1, Phet = 3.9 × 10−3; 11q13, Phet = 0.023; HNF1B (rs4430796), Phet = 0.026; and KLK2/3, Phet = 2.0 × 10−3). Although power was limited in some ethnic/racial groups due to variation in sample size and allele frequencies, these findings suggest that a large fraction of prostate cancer variants identified in populations of European ancestry are global markers of risk. For many of these regions, fine-mapping in non-European samples may help localize causal alleles and better determine their contribution to prostate cancer risk in the population. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1285–9)
Menopausal Hormone Therapy and Risk of Clinical Breast Cancer Subtypes
Authors: Slanger Tracy E. , Chang-Claude Jenny C. , Obi Nadia , Kropp Silke , Berger Jürgen , Vettorazzi Eik , Braendle Wilhelm , Bastert Gunter , Hentschel Stefan , Flesch-Janys Dieter 
Published: April 2009

Abstract
Background: Breast cancer is a heterogeneous disease with subtypes that may vary in their etiologies. Menopausal hormone therapy has been associated more strongly with lobular and tubular than ductal histologic types and with tumors that are smaller, hormone receptor–positive, and of lower grade. At the same time, correlations have been observed between histology and clinical characteristics. To identify those tumor subtypes most strongly associated with hormone therapy use, it is necessary to disentangle these interrelationships.
Methods: Based on 3,464 postmenopausal breast cancer cases and 6,657 controls from the population-based Mammary carcinoma Risk factor Investigation study, we used polytomous logistic regression to evaluate associations between hormone therapy use and risk of invasive breast cancer subtypes. We assessed variations in risk for selected tumor characteristics among histologic and hormone receptor subtypes, both overall and for specific hormone therapy regimens.
Results: Lobular and mixed types showed less variation by prognostic factors than did ductal tumors. Current hormone therapy use had the strongest associations with prognostic variables in estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive ductal tumors and in lobular tumors regardless of ER/PR status, with little effect on ER/PR-negative ductal tumors. The observed associations varied minimally by hormone therapy type or regimen.
Conclusion: Current hormone therapy use was associated with more favorable breast cancer characteristics for ductal tumors but had less effect on prognostic characteristics in women with lobular tumors. Both histologic type and estrogen receptor/progesterone receptor status seem to be important in explaining the role of hormone therapy in the etiology of breast cancer subtypes. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1188–96)
HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells
Authors: Urbich Carmen , Rössig Lothar , Kaluza David , Potente Michael , Boeckel Jes-Niels , Knau Andrea , Diehl Florian , Geng Jian-Guo , Hofmann Wolf-Karsten , Zeiher Andreas M. , Dimmeler Stefanie 
Published: April 2009

AbstractClass IIa histone deacetylases (HDACs) are signal-responsive regulators of gene expression involved in vascular homeostasis. To investigate the differential role of class IIa HDACs for the regulation of angiogenesis, we used siRNA to specifically suppress the individual HDAC isoenzymes. Silencing of HDAC5 exhibited a unique pro-angiogenic effect evidenced by increased endothelial cell migration, sprouting, and tube formation. Consistently, overexpression of HDAC5 decreased sprout formation, indicating that HDAC5 is a negative regulator of angiogenesis. The antiangiogenic activity of HDAC5 was independent of myocyte enhancer factor-2 binding and its deacetylase activity but required a nuclear localization indicating that HDAC5 might affect the transcriptional regulation of gene expression. To identify putative HDAC5 targets, we performed microarray expression analysis. Silencing of HDAC5 increased the expression of fibroblast growth factor 2 (FGF2) and angiogenic guidance factors, including Slit2. Antagonization of FGF2 or Slit2 reduced sprout induction in response to HDAC5 siRNA. Chromatin immunoprecipitation assays demonstrate that HDAC5 binds to the promoter of FGF2 and Slit2. In summary, HDAC5 represses angiogenic genes, such as FGF2 and Slit2, which causally contribute to capillary-like sprouting of endothelial cells. The derepression of angiogenic genes by HDAC5 inactivation may provide a useful therapeutic target for induction of angiogenesis.
Lack of association between PRNP 1368 polymorphism and Alzheimer's disease or vascular dementia
Authors: Jeong Byung-Hoon , Lee Kyung-Hee , Lee Yun-Jung , Kim Yun Joong , Choi Eun-Kyoung , Kim Young-Hoon , Cho Young-Sook , Carp Richard I , Kim Yong-Sun 
Published: April 2009

Abstract

Background
Polymorphisms of the prion protein gene (PRNP ) at codons 129 and 219 play an important role in the susceptibility to Creutzfeldt-Jakob disease (CJD), and might be associated with other neurodegenerative disorders. Several recent reports indicate that polymorphisms outside the coding region of PRNP modulate the expression of prion protein and are associated with sporadic CJD, although other studies failed to show an association. These reports involved the polymorphism PRNP 1368 which is located upstream from PRNP exon 1. In a case-controlled protocol, we assessed the possible association between the PRNP 1368 polymorphism and either Alzheimer's disease (AD) or vascular dementia (VaD).

Methods
To investigate whether the PRNP 1368 polymorphism is associated with the occurrence of AD or VaD in the Korean population, we compared the genotype, allele, and haplotype frequencies of the PRNP 1368 polymorphism in 152 AD patients and 192 VaD patients with frequencies in 268 healthy Koreans.

Results and conclusion
Significant differences in genotype, allele and haplotype frequencies of PRNP 1368 polymorphism were not observed between AD and normal controls. There were no significant differences in the genotype and allele frequencies of the PRNP 1368 polymorphism between Korean VaD patients and normal controls. However, in the haplotype analysis, haplotype Ht5 was significantly over-represented in Korean VaD patients. This was the first genetic association study of a polymorphism outside the coding region of PRNP in relation to AD and VaD.
Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology
Authors: Abdurahman Samir , Végvári Ákos , Levi Michael , Höglund Stefan , Högberg Marita , Tong Weimin , Romero Ivan , Balzarini Jan , Vahlne Anders 
Published: April 2009

AbstractBackgroundFormation of an HIV-1 particle with a conical core structure is a prerequisite for the subsequent infectivity of the virus particle. We have previously described that glycineamide (G-NH2) when added to the culture medium of infected cells induces non-infectious HIV-1 particles with aberrant core structures.ResultsHere we demonstrate that it is not G-NH2itself but a metabolite thereof that displays antiviral activity. We show that conversion of G-NH2to its antiviral metabolite is catalyzed by an enzyme present in bovine and porcine but surprisingly not in human serum. Structure determination by NMR suggested that the active G-NH2metabolite was α-hydroxy-glycineamide (α-HGA). Chemically synthesized α-HGA inhibited HIV-1 replication to the same degree as G-NH2, unlike a number of other synthesized analogues of G-NH2which had no effect on HIV-1 replication. Comparisons by capillary electrophoresis and HPLC of the metabolite with the chemically synthesized α-HGA further confirmed that the antiviral G-NH2-metabolite indeed was α-HGA.Conclusionα-HGA has an unusually simple structure and a novel mechanism of antiviral action. Thus, α-HGA could be a lead for new antiviral substances belonging to a new class of anti-HIV drugs, i.e. capsid assembly inhibitors.