bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 Arg72Pro and MDM2 T309G Polymorphisms, Histology, and Esophageal Cancer Prognosis
Authors: Cescon David W. , Bradbury Penelope A. , Asomaning Kofi , Hopkins Jessica , Zhai Rihong , Zhou Wei , Wang Zhaoxi , Kulke Matthew , Su Li , Ma Clement , Xu Wei , Marshall Ariela L. , Heist Rebecca Suk , Wain John C. , Lynch Thomas J. , Christiani David C. , Liu Geoffrey 
Published: April 2009

Abstract
Purpose: This study aimed to evaluate the prognostic significance of two functional single nucleotide polymorphisms (SNP) in the p53 pathway (p53 Arg72Pro and MDM2 T309G) in patients with esophageal cancer, and to determine the importance of histologic subtype in the SNP-outcome relationships.
Experimental Design: A cohort of 371 patients with esophageal carcinoma enrolled in Boston, USA from 1999 to 2004 were genotyped for the p53 and MDM2 SNPs. Associations between genotypes and overall survival (OS; the primary outcome) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Cox proportional hazard models, adjusted for age, stage, performance status, and smoking were developed. Interaction analyses were done for histology (adenocarcinoma versus squamous cell carcinoma).
Results: At the median follow-up of 33 months, median survival (MS) and PFS were 29.1 and 15.7 months, respectively. p53 Pro/Pro was strongly associated with shorter survival in the entire cohort (MS of 11.8 versus 29.1 months, P &lt; 0.0001; adjusted hazard ratio for death, 2.05; 95% confidence interval, 1.30-3.24; P = 0.002 for Pro/Pro versus Arg/Arg). MDM2 G/G was associated with markedly reduced survival in squamous cell carcinoma (MS of 10.3 versus 49.4 months; adjusted hazard ratio for death, 7.9; 95% confidence interval, 2.4-26.0; P = 0.0007 for G/G versus T/T) but not in adenocarcinoma (SNP-histology interaction P = 0.004).
Conclusions: In a large prospective cohort, p53 Arg72Pro Pro/Pro was associated with a 2-fold increased risk of death in all esophageal cancers, whereas MDM2 T309G G/G was associated with a 7-fold increased risk of death in squamous cell carcinoma.
The Breast Cancer Susceptibility Mutation PALB2 1592delT Is Associated with an Aggressive Tumor Phenotype
Authors: Heikkinen Tuomas , Kärkkäinen Hanni , Aaltonen Kirsimari , Milne Roger L. , Heikkilä Päivi , Aittomäki Kristiina , Blomqvist Carl , Nevanlinna Heli 
Published: April 2009

Abstract
Purpose: To determine the effect of the breast cancer susceptibility mutation PALB2 1592delT on tumor phenotype and patient survival.
Experimental Design: We defined the PALB2 mutation status in 947 familial and 1,274 sporadic breast cancer patients and 1,079 population controls, and compared tumor characteristics and survival in mutation carriers relative to other familial and sporadic cases and to 79 BRCA1 and 104 BRCA2 mutation carrier cases.
Results: The PALB2 1592delT mutation was found in 19 familial [2.0%; odds ratio, 11.03; 95% confidence interval (95% CI), 2.65-97.78; P &lt; 0.0001] and eight sporadic patients (0.6%; odds ratio, 3.40; 95% CI, 0.68-32.95; P = 0.1207) compared with two (0.2%) control individuals. Tumors of the PALB2 mutation carriers presented triple negative (estrogen receptor negative/progesterone receptor negative/HER negative) phenotype more often (54.5%; P &lt; 0.0001) than those of other familial (12.2%) or sporadic (9.4%) breast cancer patients. They were also more often of higher grade (P = 0.0027 and P = 0.0017, respectively) and had higher expression of Ki67 (P = 0.0004 and P = 0.0490, respectively). Carrying a PALB2 mutation was also associated with reduced survival, especially in familial cases (hazard ratio, 2.30; 95% CI, 1.01-5.24; P = 0.0466) and among familial patients with HER2-negative tumors (hazard ratio, 4.57; 95% CI, 1.96-10.64; P = 0.0004). Carrying a BRCA2 mutation was also found to be an independent predictor of poor survival at 10-year follow-up (P = 0.04).
Conclusions: The PALB2 1592delT mutation has a strong effect on familial breast cancer risk. The tumors rising in patients carrying this mutation manifest a phenotype associated with aggressive disease. Our results also suggest a significant impact of carrying a BRCA2 mutation on long-term breast cancer survival.
KIF5B-ALK, a Novel Fusion Oncokinase Identified by an Immunohistochemistry-based Diagnostic System for ALK-positive Lung Cancer
Authors: Takeuchi Kengo , Choi Young Lim , Togashi Yuki , Soda Manabu , Hatano Satoko , Inamura Kentaro , Takada Shuji , Ueno Toshihide , Yamashita Yoshihiro , Satoh Yukitoshi , Okumura Sakae , Nakagawa Ken , Ishikawa Yuichi , Mano Hiroyuki 
Published: April 2009

Abstract
Purpose: EML4-ALK is a transforming fusion tyrosine kinase, several isoforms of which have been identified in lung cancer. Immunohistochemical detection of EML4-ALK has proved difficult, however, likely as a result of low transcriptional activity conferred by the promoter-enhancer region of EML4. The sensitivity of EML4-ALK detection by immunohistochemistry should be increased adequately.
Experimental Design: We developed an intercalated antibody-enhanced polymer (iAEP) method that incorporates an intercalating antibody between the primary antibody to ALK and the dextran polymer-based detection reagents.
Results: Our iAEP method discriminated between tumors positive or negative for EML4-ALK in a test set of specimens. Four tumors were also found to be positive for ALK in an archive of lung adenocarcinoma (n = 130) and another 4 among fresh cases analyzed in a diagnostic laboratory. These 8 tumors were found to include 1 with EML4-ALK variant 1, 1 with variant 2, 3 with variant 3, and 2 with previously unidentified variants (designated variants 6 and 7). Inverse reverse transcription-PCR analysis revealed that the remaining tumor harbored a novel fusion in which intron 24 of KIF5B was ligated to intron 19 of ALK. Multiplex reverse transcription-PCR analysis of additional archival tumor specimens identified another case of lung adenocarcinoma positive for KIF5B-ALK.
Conclusions: The iAEP method should prove suitable for immunohistochemical screening of tumors positive for ALK or ALK fusion proteins among pathologic archives. Coupling of PCR-based detection to the iAEP method should further facilitate the rapid identification of novel ALK fusion genes such as KIF5B-ALK.
Regulation of Breast Cancer Metastasis by Atypical Chemokine Receptors
Authors: Cheng Xiaoyun , Hung Mien-Chie 
Published: April 2009

Abstract
The interaction between chemokines and their G-protein-coupled receptors plays an important role in promoting metastasis of different kinds of human cancers. However, the expression of an atypical chemokine receptor, CCX-CKR, which serves as a decoy receptor to attract chemokines, inhibits the growth and metastasis of breast cancer by sequestration of chemokines.
Thymidylate synthasegene variations: predictive and prognostic markers
Authors: Lurje Georg , Manegold Philipp C. , Ning Yan , Pohl Alexandra , Zhang Wu , Lenz Heinz-Josef 
Published: April 2009

AbstractSince its introduction more than 50 years ago by Heidelberger et al., the fluoropyrimidine 5-fluorouracil (5-FU) has remained the mainstay of therapeutic regimens used in the treatment of colorectal cancer and other human malignancies, with single-agent response rates of 20% to 25% in advanced disease stage. Pharmacogenomics has emerged as a useful tool to address interindividual gene variations by analyzing the interplay of host and tumor genotype and drug efficacy and toxicity. Having a reliable panel of prognostic and predictive markers will be critical in selecting an individualized and tailored chemotherapy regimen based on the particular tumor and host genotype. Although conflicting results have been reported, higher thymidylate synthase (TS) protein and mRNA expression levels in tumors have generally been associated with poor clinical outcome in patients treated with 5-FU–based chemotherapy regimens. However, the cause of the variability in TS expression still remains not fully understood, although several germ-line polymorphisms seem to affect the expression of TS, some of which have been found to have an effect on prognosis and the probability of response to 5-FU–based chemotherapy. This review will provide an update on pharmacogenomic studies of TS that were aimed at elucidating their role as prognostic and predictive markers. [Mol Cancer Ther 2009;8(5):1000–7]
The indenoisoquinoline noncamptothecin topoisomerase I inhibitors: update and perspectives
Authors: Pommier Yves , Cushman Mark 
Published: April 2009

Abstract
Because camptothecins are effective against previously resistant tumors and are the only class of topoisomerase I (Top1) inhibitors approved for cancer treatment, we developed the indenoisoquinolines. Like camptothecins, the indenoisoquinolines selectively trap Top1-DNA cleavage complexes and have been cocrystallized with the Top1-DNA cleavage complexes. Indenoisoquinolines show antitumor activity in animal models. They have several advantages over the camptothecins: (a) They are synthetic and chemically stable. (b) The Top1 cleavage sites trapped by the indenoisoquinolines have different genomic locations, implying differential targeting of cancer cell genomes. (c) The Top1 cleavage complexes trapped by indenoisoquinolines are more stable, indicative of prolonged drug action. (d) They are seldom or not used as substrates for the multidrug resistance efflux pumps (ABCG2 and MDR-1). Among the &gt;400 indenoisoquinolines synthesized and evaluated, three have been retained as leads for clinical development by the National Cancer Institute: NSC 706744, NSC 725776 (Indimitecan), and NSC 724998 (Indotecan). The trapping of Top1 cleavage complexes by indenoisoquinolines in cells results in the rapid and sustained phosphorylation of histone H2AX (γ-H2AX). We discuss the use of γ-H2AX as a pharmacodynamic biomarker for the clinical development of the indenoisoquinolines. [Mol Cancer Ther 2009;8(5):1008–14]
Decreased levels of UMP kinase as a mechanism of fluoropyrimidine resistance
Authors: Humeniuk Rita , Menon Lata G. , Mishra Prasun J. , Gorlick Richard , Sowers Rebecca , Rode Wojciech , Pizzorno Giuseppe , Cheng Yung-Chi , Kemeny Nancy , Bertino Joseph R. , Banerjee Debabrata 
Published: April 2009

Abstract
5-Fluorouracil (5-FU) continues to be widely used for treatment of gastrointestinal cancers. Because many tumors show primary or acquired resistance, it is important to understand the molecular basis underlying the mechanism of resistance to 5-FU. In addition to its effect on thymidylate synthase inhibition and DNA synthesis, 5-FU may also influence RNA metabolism. Our previous studies revealed that colorectal cancer cells resistant to bolus 5-FU (HCT-8/4hFU) showed significantly decreased incorporation of the drug into RNA. Resistance to bolus 5-FU was associated with lower expression of UMP kinase (UMPK), an enzyme that plays an important role in the activation of 5-FU to 5-FUTP and its incorporation into RNA. Activities of other 5-FU–metabolizing enzymes (e.g., thymidine kinase, uridine phosphorylase, thymidine phosphorylase, and orotate phosphoribosyltransferase) remained unchanged between sensitive and resistant cell lines. Herein, we show that UMPK down-regulation in 5-FU–sensitive cells (HCT-8/P) induces resistance to bolus 5-FU treatment. Moreover, HCT-8/4hFU cells are even more cross-resistant to treatment with 5-fluorouridine, consistent with the current understanding of 5-fluorouridine as a RNA-directed drug. Importantly, colorectal cancer hepatic metastases isolated from patients clinically resistant to weekly bolus 5-FU/leucovorin treatment exhibited decreased mRNA expression of UMPK but not thymidylate synthase or dihydropyrimidine dehydrogenase compared with tumor samples of patients not previously exposed to 5-FU. Our findings provide new insights into the mechanisms of acquired resistance to 5-FU in colorectal cancer and implicate UMPK as an important mechanism of clinical resistance to pulse 5-FU treatment in some patients.[Mol Cancer Ther 2009;8(4):OF1–8]
Dehydrocostuslactone disrupts signal transducers and activators of transcription 3 through up-regulation of suppressor of cytokine signaling in breast cancer cells
Authors: Kuo Po-Lin , Ni Wen-Chiu , Tsai Eing-Mei , Hsu Ya-Ling 
Published: April 2009

Abstract
This study investigates the anticancer effect of dehydrocostuslactone (DHE), a plant-derived sesquiterpene lactone, on human breast cancer cells. DHE inhibits cell proliferation by inducing cells to undergo cell cycle arrest and apoptosis. DHE suppresses the expression of cyclin D, cyclin A, cyclin-dependent kinase 2, and cdc25A and increases the amount of p53 and p21, resulting in G0/G1-S phase arrest in MCF-7 cells. In contrast, DHE caused S-G2/M arrest by increasing p21 expression and chk1 activation and inhibiting cyclin A, cyclin B, cdc25A, and cdc25C expression in MDA-MB-231 cells. DHE induces up-regulation of Bax and Bad, down-regulation of Bcl-2 and Bcl-XL, and nuclear relocation of the mitochondrial factors apoptosis-inducing factor and endonuclease G. We also found that DHE inhibits survival signaling through the Janus tyrosine kinase-signal transducer and activator of transcription-3 signaling by increasing the expression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3. Reduction of SOCS-1 and SOCS-3 expression by small interfering RNA inhibits DHE-mediated signal transducer and activator of transcription-3 inhibition, p21 up-regulation, and cyclin-dependent kinase 2 blockade, supporting the hypothesis that DHE inhibits cell cycle progression and cell death through SOCS-1 and SOCS-3. Significantly, animal studies have revealed a 50% reduction in tumor volume after a 45-day treatment period. Taken together, this study provides new insights into the molecular mechanism of the DHE action that may contribute to the chemoprevention of breast cancer. [Mol Cancer Ther 2009;8(5):1328–39]
Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy
Authors: Su David M. , Zhang Qiuyang , Wang Xuexi , He Ping , Zhu Yuelin Jack , Zhao Jianxiong , Rennert Owen M. , Su Yan A. 
Published: April 2009

AbstractHuman malignant melanoma has poor prognosis because of resistance to apoptosis and therapy. We describe identification of the expression profile of 1,037 mitochondria-focused genes and 84 survival-apoptosis genes in 21 malignant melanoma cell lines and 3 normal melanocyte controls using recently developed hMitChip3 cDNA microarrays. Unsupervised hierarchical clustering analysis of 1,037 informative genes, and 84 survival-apoptosis genes, classified these malignant melanoma cell lines into type A (n = 12) and type B (n = 9). Three hundred fifty-five of 1,037 (34.2%) genes displayed significant (P ≤ 0.030; false discovery rate ≤ 3.68%) differences (±≥2.0-fold) in average expression, with 197 genes higher and 158 genes lower in type A than in type B. Of 84 genes with known survival-apoptosis functions, 38 (45.2%) displayed the significant (P &lt; 0.001; false discovery rate &lt; 0.15%) difference. Antiapoptotic (BCL2, BCL2A1, PPARD, and RAF1), antioxidant (MT3, PRDX5, PRDX3, GPX4, GLRX2, and GSR), and proapoptotic (BAD, BNIP1, APAF1, BNIP3L, CASP7, CYCS, CASP1, and VDAC1) genes expressed at higher levels in type A than in type B, whereas the different set of antiapoptotic (PSEN1, PPP2CA, API5, PPP2R1B, PPP2R1A, and FIS1), antioxidant (HSPD1, GSS, SOD1, ATOX1, and CAT), and proapoptotic (ENDOG, BAK1, CASP2, CASP4, PDCD5, HTRA2, SEPT4, TNFSF10, and PRODH) genes expressed at lower levels in type A than in type B. Microarray data were validated by quantitative reverse transcription-PCR. These results showed the presence of two types of malignant melanoma, each with a specific set of dysregulated survival-apoptosis genes, which may prove useful for development of new molecular targets for therapeutic intervention and novel diagnostic biomarkers for treatment and prognosis of malignant melanoma.[Mol Cancer Ther 2009;8(5):OF1–13]
Apollinaire's “Zone,” Catholicism, and the Paradox of French Modernity
Authors: Mitroi Anca 
Published: April 2009

AbstractSince at least the Enlightenment and the French Revolution, modernity in France has been understood primarily in terms of a rupture with Catholicism. Through a close reading of the poem “Zone,” this article shows how Guillaume Apollinaire's poetics challenges the conventional notion of modernity-as-rupture by exposing Catholicism's persistent residuality into the modern era. Instead of breaking with France's Catholic past, Apollinaire's modernism poetically displaces it, thereby holding in suspension both modernity's desire for rupture and the object with which it seeks to break.
“Who Would Believe What We Have Heard?”: Christian Spirituality and Images from the Passion in Religious Art of New Spain
Authors: Greeley June-Ann 
Published: April 2009

AbstractThe colonial art of New Spain/Mexico provides the viewer with a locus of examination into the robust Christianity that emerged over time out of a native spirituality newly laden with the contours and images from the Old World theology of late medieval/early Catholic Reformation Spain. Franciscan and especially Jesuit missionaries, impelled by a devotional zealotry, championed an apocalyptic vision of hope and suffering that was well suited for artistic expression. Religious art, whether or not patronized by European colonizers, became an instrument for the missionaries to teach and for the native artists to interrogate religious doctrine, and some artists, consciously or not, created their art as a response to that catechesis, a subtle fusion of ancient passion with the dramatic intensity of the new Catholic faith. One array of images in particular, that of the dolorous Passion of the Christ, was especially vibrant in the imaginations of the native artists and in the contemplation of the European missionaries and patrons. The image of the Suffering Servant resonated in the hearts and in the daily lives of the people just as it humbled missionary ardor, and excited a spiritual enthusiasm that forged an art of stunning doctrinal intimacy.
Icons' Spirited Love
Authors: Peers Glenn 
Published: April 2009

AbstractThis article examines three instances of Byzantine icons' declaration and demonstration of love: the Mandylion, the miraculous self-portrait of Christ, which arrived in Edessa in part as a veil that transfigured the wearer, the apostle Thaddaeus, and recipient, king Abgar; the icon of St. Paul that St. John Chrysostom kept by him when he wrote, which guaranteed the presence of that holy figure, as witnessed by John's peeping-tom assistant Proclus; and the icon of St. Macarius the Great and his Cherub that shows the fellow-love of that saint projected into the apparition of the Cherub. The writings of Pseudo-Dionysius the Areopagite are the underpinning for the love these objects respond to and generate: love here is the desire to be unified with the divine and the good, and this unity is always brought about through human desire.
Parenting Gifted and Talented Children: Conceptual and Empirical Foundations
Authors: Morawska Alina , Sanders Matthew R. 
Published: April 2009

There is a paucity of research focusing on the needs of gifted children and their families, in particular, there is a lack of empirically supported parenting strategies to help parents in parenting their gifted child. This article provides an overview of the literature on difficulties experienced by parents of gifted and talented children, followed by a description of the development of a parenting program designed specifically for this population. Qualitative data from a survey of parents of gifted and talented children are presented to identify key themes for supporting and assisting parents. Gifted and Talented Triple P is a customized version of Triple P—Positive Parenting Program, consisting of nine sessions, specifically tailored for the needs of parents of gifted and talented children. The program is described and the clinical implications and future research directions in assisting parents in parenting their gifted and talented child are discussed. Putting the Research to Use: The results of this study provide some key insights into the specific aspects of raising a gifted and talented child which parents struggle with, and the sorts of information they would like to receive to assist them in their role. The findings have led to the development and tailoring of a parenting intervention for parents of gifted and talented children, and have the potential to inform further research to support parents.
A Randomized Trial of a Church-Based Diabetes Self-management Program for African Americans With Type 2 Diabetes
Authors: Samuel-Hodge Carmen D. , Keyserling Thomas C. , Park Sola , Johnston Larry F. , Gizlice Ziya , Bangdiwala Shrikant I. 
Published: April 2009

Purpose This study developed and tested a culturally appropriate, church-based intervention to improve diabetes self-management. Research Design and Methods This was a randomized trial conducted at 24 African American churches in central North Carolina. Churches were randomized to receive the special intervention (SI; 13 churches, 117 participants) or the minimal intervention (MI; 11 churches, 84 participants). The SI included an 8-month intensive phase, consisting of 1 individual counseling visit, 12 group sessions, monthly phone contacts, and 3 encouragement postcards, followed by a 4-month reinforcement phase including monthly phone contacts. The MI received standard educational pamphlets by mail. Outcomes were assessed at 8 and 12 months; the primary outcome was comparison of 8-month A1C levels. Results At baseline, the mean age was 59 years, A1C 7.8%, and body mass index 35.0 kg/m2; 64% of participants were female. For the 174 (87%) participants returning for 8-month measures, mean A1C (adjusted for baseline and group randomization) was 7.4% for SI and 7.8% for MI, with a difference of 0.4% (95% confidence interval [CI], 0.1-0.6, P = .009). In a larger model adjusting for additional variables, the difference was 0.5% (95% CI, 0.2-0.7, P < .001). At 12 months, the difference between groups was not significant. Diabetes knowledge and diabetes-related quality of life significantly improved in the SI group compared with the MI group. Among SI participants completing an acceptability questionnaire, intervention components and materials were rated as highly acceptable. Conclusions The church-based intervention was well received by participants and improved short-term metabolic control.
Past environmental sun exposure and risk of multiple sclerosis: a role for the Cdx-2 Vitamin D receptor variant in this interaction
Authors: Dickinson JL , Perera DI , van der Mei AF , Ponsonby A-L , Polanowski AM , Thomson RJ , Taylor BV , McKay JD , Stankovich J , Dwyer T 
Published: April 2009

Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based sample where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A > G), rs10735810 ( Fok1T > C), or rs731236 ( Taq1C > T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.