bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of Self-Reported Reason for Colorectal Cancer Testing
Authors: Eberth Jan M. , Vernon Sally W. , White Arica , Abotchie Peter N. , Coan Sharon P. 
Published: January 2010

AbstractAssessment of accuracy of self-reported reason for colorectal cancer testing has been limited. We examined the accuracy and correlates of self-reported reason (screening or diagnosis) for having a sigmoidoscopy or colonoscopy. Patients who had received at least one sigmoidoscopy or colonoscopy within the past 5 years were recruited from a large multispecialty clinic in Houston, TX, between 2005 and 2007. We calculated concordance, positive predictive value, negative predictive value, sensitivity, and specificity between self-reported reason and the medical record (gold standard). Logistic regression was performed to identify correlates of accurate self-report. Self-reported reason for testing was more accurate when the sigmoidoscopy or colonoscopy was done for screening, rather than diagnosis. In the multivariable analysis for sigmoidoscopy, age was positively associated with accurately reporting reason for testing, whereas having two or more colorectal cancer tests during the study period (compared with only one test) was negatively associated with accuracy. In the multivariable analysis, none of the correlates was statistically associated with colonoscopy although a similar pattern was observed for number of tests. Determining the best way to identify those who have been tested for diagnosis, rather than screening, is an important next step. Cancer Epidemiol Biomarkers Prev; 19(1); 196–200
Effects of Supplemental Vitamin D and Calcium on Oxidative DNA Damage Marker in Normal Colorectal Mucosa: A Randomized Clinical Trial
Authors: Fedirko Veronika , Bostick Roberd M. , Long Qi , Flanders W. Dana , McCullough Marjorie L. , Sidelnikov Eduard , Daniel Carrie R. , Rutherford Robin E. , Shaukat Aasma 
Published: January 2010

Abstract
The exact antineoplastic effects of calcium and vitamin D3 in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial to test the effects of calcium and vitamin D3 on a marker of oxidative DNA damage, 8-hydroxy-2′-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800 IU/d vitamin D3 versus placebo over 6 months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P = 0.15) and 25% (P = 0.10) in the calcium and vitamin D3 groups, respectively, but not in the calcium plus vitamin D3 group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall, these preliminary results indicate that calcium and vitamin D3 may decrease oxidative DNA damage in the normal human colorectal mucosa, support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms, and provide support for further investigation of calcium and vitamin D3 as chemopreventive agents against colorectal neoplasms. Cancer Epidemiol Biomarkers Prev; 19(1); 280–91
Breast Cancer Risk 55+ Years After Irradiation for an Enlarged Thymus and Its Implications for Early Childhood Medical Irradiation Today
Authors: Adams M. Jacob , Dozier Ann , Shore Roy E. , Lipshultz Steven E. , Schwartz Ronald G. , Constine Louis S. , Pearson Thomas A. , Stovall Marilyn , Winters Paul , Fisher Susan G. 
Published: January 2010

Abstract
Background: Radiotherapy during childhood increases long-term cancer risk, but the risk from radiation as a result of relatively higher dose diagnostic procedures remains less well known. This study, which evaluates breast cancer incidence in a cohort treated with “lower dose” chest radiotherapy over 50 years ago, can assist with estimating lifetime breast cancer risk in young children exposed to radiation from procedures such as chest computed tomography (CT) or treatment with recent “lower dose” chest radiotherapy protocols.
Methods: A population-based, longitudinal cohort of subjects exposed to thymic irradiation during infancy from 1926 to 1957 and of their unexposed siblings was re-established. Previously followed until 1987, we resurveyed cohort members from 2004 to 2008. Poisson regression models compared breast cancer incidence rates between women in the cohort by treatment and dose category groups.
Results: Breast cancer occurred in 96 treated (mean breast dose, 0.71 Gy) and 57 untreated women during 159,459 person-years of follow-up. After adjusting for attained age and treatment/birth cohort, the rate ratio was 3.01 (2.18-4.21). The adjusted excess relative risk per Gy was 1.10 (95% confidence interval, 0.61-1.86). Traditional breast cancer risk factors did not contribute significantly to multivariate model fit.
Conclusion: Our results show that at radiation doses between those received by the breast from chest CT and cancer therapy during early childhood, breast cancer incidence rates remain elevated &gt;50 years after exposure. This implies that increased breast cancer risk will remain a lifelong concern in females treated during childhood with currently reduced radiotherapy doses and for infants receiving multiple chest CTs. Cancer Epidemiol Biomarkers Prev; 19(1); 48–58
Association of Mitotic Regulation Pathway Polymorphisms with Pancreatic Cancer Risk and Outcome
Authors: Couch Fergus J. , Wang Xianshu , Bamlet William R. , de Andrade Mariza , Petersen Gloria M. , McWilliams Robert R. 
Published: January 2010

Abstract
Background: Mitosis is a highly regulated process that serves to ensure the fidelity of cell division. The disruption of mitotic regulators leading to aneuploidy and polyploidy is commonly observed in cancer cells. Single nucleotide polymorphisms (SNP) in regulators of mitosis may promote chromosome missegregation and influence pancreatic cancer and/or survival.
Methods: Thirty-four SNPs, previously associated with breast cancer risk, from 33 genes involved in the regulation of mitosis, were investigated for associations with pancreatic cancer risk in 1,143 Caucasian patients with pancreatic adenocarcinoma and 1,097 unaffected controls from the Mayo Clinic. Associations with survival from pancreatic cancer were also assessed using 1,030 pancreatic cancer cases with known outcome.
Results: Two SNPs in the APC (rs2431238) and NIN (rs10145182) loci, of 34 examined, were significantly associated with pancreatic cancer risk (P = 0.035 and P = 0.038, respectively). Further analyses of individuals categorized by smoking and body mass index identified several SNPs displaying significant associations (P &lt; 0.05) with pancreatic cancer risk, including APC rs2431238 in individuals with high body mass index (≥30; P = 0.031) and NIN rs10145182 in ever smokers (P = 0.01). In addition, survival analyses detected significant associations between SNPs in EIF3S10 and overall survival (P = 0.009), SNPs from five genes and survival in resected cancer cases (P &lt; 0.05), and SNPs from two other genes (P &lt; 0.05) and survival of locally advanced cancer cases.
Conclusion: Common variation in genes encoding regulators of mitosis may independently influence pancreatic cancer susceptibility and survival. Cancer Epidemiol Biomarkers Prev; 19(1); 251–7
Variation in the FGFR2 Gene and the Effect of a Low-Fat Dietary Pattern on Invasive Breast Cancer
Authors: Prentice Ross L. , Huang Ying , Hinds David A. , Peters Ulrike , Cox David R. , Beilharz Erica , Chlebowski Rowan T. , Rossouw Jacques E. , Caan Bette , Ballinger Dennis G. 
Published: January 2010

Abstract
Background: The Women's Health Initiative dietary modification (DM) trial provided suggestive evidence of a benefit of a low-fat dietary pattern on breast cancer risk, with stronger evidence among women whose baseline diet was high in fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to breast cancer risk and could influence intervention effects.
Methods: All 48,835 trial participants were postmenopausal and ages 50 to 79 years at enrollment (1993-1998). We interrogated eight SNPs in intron 2 of the FGFR2 gene for 1,676 women who developed breast cancer during trial follow-up (1993-2005). Case-only analyses were used to estimate odds ratios for the DM intervention in relation to SNP genotype.
Results: Odds ratios for the DM intervention did not vary significantly with the genotype for any of the eight FGFR2 SNPs (P ≥ 0.18). However, odds ratios varied (P &lt; 0.05) with the genotype of six of these SNPs, among women having baseline percent of energy from fat in the upper quartile (≥36.8%). This variation is most evident for SNP rs3750817, with odds ratios for the DM intervention at 0, 1, and 2 minor SNP alleles of 1.06 [95% confidence intervals (95% CI), 0.80-1.41], 0.53 (95% CI, 0.38-0.74), and 0.62 (95% CI, 0.33-1.15). The nominal significance level for this interaction is P = 0.005, and P = 0.03 following multiple testing adjustment, with most evidence deriving from hormone receptor–positive tumors.
Conclusion: Invasive breast cancer odds ratios for a low-fat dietary pattern, among women whose usual diets are high in fat, seem to vary with SNP rs3750817 in the FGFR2 gene. Cancer Epidemiol Biomarkers Prev; 19(1); 74–9
Feasibility Study for Collection of HER2 Data by National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program Central Cancer Registries
Authors: Reichman Marsha E. , Altekruse Sean , Li Christopher I. , Chen Vivien W. , Deapen Dennis , Potts Mary , Wu Xiao-Cheng , Morrell Donna , Hafterson Jennifer , Phipps Amanda I. , Harlan Linda C. , Ries Lynn G. , Edwards Brenda K. 
Published: January 2010

Abstract
The clinical importance of human epidermal growth factor receptor-2 (HER2) in breast cancer is now clearly established, given that expression of this tumor marker is used to guide therapy and as a prognostic indicator. Despite its now routine evaluation in breast cancer patients, population-based data are lacking because information on HER2 status is not routinely collected in the majority of population-based cancer registries. We assessed the feasibility of collecting HER2 data and its completeness in three registries in the Surveillance Epidemiology and End Results (SEER) Program. Among a sample of invasive first primary breast cancer patients diagnosed between June and December 2007, HER2 tests had been done on 96.5% (n = 522), and test results were available for 95.2% (n = 515) of patients. The majority of HER2 tests were performed by immunohistochemistry alone (50.9%), 35.3% by both immunohistochemistry and fluorescence in situ hybridization (FISH), and 11.8% of tests by FISH alone. As a result of these findings, SEER registries will collect HER2 data on all invasive breast cancer patients as an optional data element for those diagnosed in 2009 and HER2 will likely be a required data element for these patients in 2010. Cancer Epidemiol Biomarkers Prev; 19(1); 144–7
Genetic Variation of Genes Involved in Dihydrotestosterone Metabolism and the Risk of Prostate Cancer
Authors: Setlur Sunita R. , Chen Chen X. , Hossain Ruhella R. , Ha Jung Sook , Van Doren Vanessa E. , Stenzel Birgit , Steiner Eberhard , Oldridge Derek , Kitabayashi Naoki , Banerjee Samprit , Chen Jin Yun , Schäfer Georg , Horninger Wolfgang , Lee Charles , Rubin Mark A. , Klocker Helmut , Demichelis Francesca 
Published: January 2010

Abstract
Purpose: Dihydrotestosterone (DHT) is an important factor in prostate cancer (PCA) genesis and disease progression. Given PCA's strong genetic component, we evaluated the possibility that variation in genes involved in DHT metabolism influence PCA risk.
Experimental Design: We investigated copy number variants (CNV) and single nucleotide polymorphisms (SNP). We explored associations between CNV of uridine diphospho-glucuronosyltransferase (UGT) genes from the 2B subclass, given their prostate specificity and/or involvement in steroid metabolism and PCA risk. We also investigated associations between SNPs in genes (HSD3B1, SRD5A1/2, and AKR1C2) involved in the conversion of testosterone to DHT, and in DHT metabolism and PCA risk. The population consisted of 426 men (205 controls and 221 cases) who underwent prostate-specific antigen screening as part of a PCA early detection program in Tyrol, Austria.
Results: No association between CNV in UGT2B17 and UGT2B28 and PCA risk was identified. Men carrying the AA genotype at SNP rs6428830 (HSD3B1) had an odds ratio (OR) of 2.0 [95% confidence intervals (95% CI), 1.1-4.1] compared with men with GG, and men with AG or GG versus AA in rs1691053 (SRD5A1) had an OR of 1.8 (95% CI, 1.04-3.13). Individuals carrying both risk alleles had an OR of 3.1 (95% CI, 1.4-6.7) when compared with men carrying neither (P = 0.005). Controls with the AA genotype on rs7594951 (SRD5A2) tended toward higher serum DHT levels (P = 0.03).
Conclusions: This is the first study to implicate the 5α-reductase isoform 1 (SRD5A1) and PCA risk, supporting the rationale of blocking enzymatic activity of both isoforms of 5α-reductase for PCA chemoprevention. Cancer Epidemiol Biomarkers Prev; 19(1); 229–39
The Antitumor Activity of Homoharringtonine against Human Mast Cells Harboring the KIT D816V Mutation
Authors: Jin Yanli , Lu Zhongzheng , Cao Kaiyuan , Zhu Yunhui , Chen Qi , Zhu Feng , Qian Chenchen , Pan Jingxuan 
Published: January 2010

Abstract
Gain-of-function mutations of the receptor tyrosine kinase KIT play a critical role in the pathogenesis of systemic mastocytosis (SM) and gastrointestinal stromal tumors. The various juxtamembrane type of KIT mutations, including V560G, are found in 60% to 70% of patients with gastrointestinal stromal tumors; loop mutant D816V, which exists in ∼80% of SM patients, is completely resistant to imatinib. In the present study, we hypothesized that homoharringtonine (HHT), a protein synthesis inhibitor, would decrease the level of KIT protein by inhibiting translation, resulting in a decreased level of phospho-KIT and abrogating its constitutive downstream signaling. Imatinib-sensitive HMC-1.1 cells harboring the mutation V560G in the juxtamembrane domain of KIT, imatinib-resistant HMC-1.2 cells harboring both V560G and D816V mutations, and murine P815 cells were treated with HHT and analyzed in terms of growth, apoptosis, and signal transduction. The in vivo antitumor activity was evaluated by using the murine mast cell leukemia model. Our results indicated that HHT effectively inhibited the growth and induced apoptosis in cells bearing both V560G and D816V or D814Y KIT. Additionally, HHT inhibited the KIT-dependent phosphorylation of downstream signaling molecules Akt, signal transducer and activator of transcription 3 and 5, and extracellular signal-regulated kinase 1/2. Furthermore, HHT significantly prolonged the survival duration of mice with aggressive SM or mast cell leukemia by inhibiting the expansion and infiltration of imatinib-resistant mast tumor cells harboring imatinib-resistant D814Y KIT. Collectively, we show that HHT circumvents D816V KIT-elicited imatinib resistance. Our findings warrant a clinical trial of HHT in patients with SM harboring D816V or D814Y KIT. Mol Cancer Ther; 9(1); 211–23
Human Sodium/Iodide Symporter–Mediated Radioiodine Gene Therapy Enhances the Killing Activities of CTLs in a Mouse Tumor Model
Authors: Jeon Yong Hyun , Choi Yun , Kim Chul Woo , Kim Young-Hwa , Youn Hyewon , Lee Jaetae , Chung June-Key 
Published: January 2010

Abstract
We examined whether human sodium/iodide symporter (hNIS) radioiodine gene therapy can modulate the phenotype of cancer cells and enhance the killing activities of CTLs in a mouse tumor model. Various doses of I-131 (75, 300, 600, 1,200, and 2,400 μCi/5 mL) were incubated with hNIS-expressing colon cancer (CT26/hNIS) and parental cells (CT26), and numbers of MHC class I and Fas-expressing cells were determined by fluorescence-activated cell sorting (FACS). In addition, CT26/hNIS or CT26 tumor-bearing mice were treated with 1,200 μCi of I-131, and percentages of MHC class I and Fas-expressing tumor cells were determined by FACS. The levels of tumor-infiltrating CD8+IFNγ+ and CD11c+CD86+ cells and CTL killing activities were measured in CT26/hNIS tumor-bearing mice (treated with PBS or 1,200 μCi of I-131) by FACS and lactate dehydrogenase assay, respectively. MHC class I and Fas gene expressions were markedly upregulated in CT26/hNIS cells, but not in CT26 cells, in an I-131 dose-dependent manner. The level of MHC class I and Fas-expressing cancer cell were 4.5-fold and 2.1-fold higher in CT26/hNIS tumors than in CT26 tumors, respectively (P &lt; 0.01). Interestingly, numbers of tumor-infiltrating CD8+IFNγ+ cells and CD11c+CD86+ cells were 5-fold and 2.5-fold higher in I-131–treated tumors than in PBS tumors, respectively (P &lt; 0.001). Furthermore, CTL assays showed significantly more specific tumor cell lysis in I-131 tumors than in PBS tumors (P &lt; 0.01). Our findings suggest that hNIS radioiodine gene therapy can generate tumor-associated immunity in tumor microenvironments and enhance the killing activities of CTLs. Mol Cancer Ther; 9(1); 126–33
Disablingc-Mycin Childhood Medulloblastoma and Atypical Teratoid/Rhabdoid Tumor Cells by the Potent G-Quadruplex Interactive Agent S2T1-6OTD
Authors: Shalaby Tarek , von Bueren André O. , Hürlimann Marie-Louise , Fiaschetti Giulio , Castelletti Deborah , Masayuki Tera , Nagasawa Kazuo , Arcaro Alexandre , Jelesarov Ilian , Shin-ya Kazuo , Grotzer Michael 
Published: January 2010

AbstractWe investigated here the effects of S2T1-6OTD, a novel telomestatin derivative that is synthesized to target G-quadruplex–forming DNA sequences, on a representative panel of human medulloblastoma (MB) and atypical teratoid/rhabdoid (AT/RT) childhood brain cancer cell lines. S2T1-6OTD proved to be a potent c-Myc inhibitor through its high-affinity physical interaction with the G-quadruplex structure in the c-Myc promoter. Treatment with S2T1-6OTD reduced the mRNA and protein expressions of c-Myc and hTERT, which is transcriptionally regulated by c-Myc, and decreased the activities of both genes. In remarkable contrast to control cells, short-term (72-hour) treatment with S2T1-6OTD resulted in a dose- and time-dependent antiproliferative effect in all MB and AT/RT brain tumor cell lines tested (IC50, 0.25–0.39 μmol/L). Under conditions where inhibition of both proliferation and c-Myc activity was observed, S2T1-6OTD treatment decreased the protein expression of the cell cycle activator cyclin-dependent kinase 2 and induced cell cycle arrest. Long-term treatment (5 weeks) with nontoxic concentrations of S2T1-6OTD resulted in a time-dependent (mainly c-Myc–dependent) telomere shortening. This was accompanied by cell growth arrest starting on day 28 followed by cell senescence and induction of apoptosis on day 35 in all of the five cell lines investigated. On in vivo animal testing, S2T1-6OTD may well represent a novel therapeutic strategy for childhood brain tumors. Mol Cancer Ther; 9(1); 167–79
MK-5108, a Highly Selective Aurora-A Kinase Inhibitor, Shows Antitumor Activity Alone and in Combination with Docetaxel
Authors: Shimomura Toshiyasu , Hasako Shinichi , Nakatsuru Yoko , Mita Takashi , Ichikawa Koji , Kodera Tsutomu , Sakai Takumi , Nambu Tadahiro , Miyamoto Mayu , Takahashi Ikuko , Miki Satomi , Kawanishi Nobuhiko , Ohkubo Mitsuru , Kotani Hidehito , Iwasawa Yoshikazu 
Published: January 2010

Abstract
Aurora-A kinase is a one of the key regulators during mitosis progression. Aurora-A kinase is a potential target for anticancer therapies because overexpression of Aurora-A, which is frequently observed in some human cancers, results in aberrant mitosis leading to chromosomal instability and possibly tumorigenesis. MK-5108 is a novel small molecule with potent inhibitory activity against Aurora-A kinase. Although most of the Aurora-kinase inhibitors target both Aurora-A and Aurora-B, MK-5108 specifically inhibited Aurora-A kinase in a panel of protein kinase assays. Inhibition of Aurora-A by MK-5108 in cultured cells induced cell cycle arrest at the G2-M phase in flow cytometry analysis. The effect was confirmed by the accumulation of cells with expression of phosphorylated Histone H3 and inhibition of Aurora-A autophosphorylation by immunostaining assays. MK-5108 also induced phosphorylated Histone H3 in skin and xenograft tumor tissues in a nude rat xenograft model. MK-5108 inhibited growth of human tumor cell lines in culture and in different xenograft models. Furthermore, the combination of MK-5108 and docetaxel showed enhanced antitumor activities compared with control and docetaxel alone–treated animals without exacerbating the adverse effects of docetaxel. MK-5108 is currently tested in clinical trials and offers a new therapeutic approach to combat human cancers as a single agent or in combination with existing taxane therapies. Mol Cancer Ther; 9(1); 157–66
Overexpression of EpCAM in Uterine Serous Papillary Carcinoma: Implications for EpCAM-Specific Immunotherapy With Human Monoclonal Antibody Adecatumumab (MT201)
Authors: El-Sahwi Karim , Bellone Stefania , Cocco Emiliano , Casagrande Francesca , Bellone Marta , Abu-Khalaf Maysa , Buza Natalia , Tavassoli Fattaneh A. , Hui Pei , Rüttinger Dominik , Silasi Dan-Arin , Azodi Masoud , Schwartz Peter E. , Rutherford Thomas J. , Pecorelli Sergio , Santin Alessandro D. 
Published: January 2010

AbstractWe evaluated the expression of epithelial cell adhesion molecule (EpCAM) and the potential of MT201 (adecatumumab), a human monoclonal antibody against EpCAM, in uterine serous papillary carcinoma (USPC). EpCAM expression was evaluated by real-time PCR and immunohistochemistry in a total of 56 USPC fresh-frozen biopsies and paraffin-embedded tissues. EpCAM surface expression was also evaluated by flow cytometry and immunohistochemistry in six USPC cell lines. Sensitivity to MT201 antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity was tested against a panel of primary USPC cell lines expressing different levels of EpCAM in standard 5-h 51Cr release assays. EpCAM transcript was significantly overexpressed in fresh-frozen USPC when compared with normal endometrial cells (NEC). Median (minimum–maximum) copy number was 943.8 (31.5–1568.3) in tumor samples versus 12.9 (1.0–37.0) in NEC (P &lt; 0.001). By immunohistochemistry, EpCAM expression was found in 96% (26 out of 27) of USPC samples with significantly higher expression compared with NECs (P &lt; 0.001). High surface expression of EpCAM was found in 83% (five out of six) of the USPC cell lines tested by flow cytometry. EpCAM-positive cell lines were found highly sensitive to MT201-mediated antibody-dependent cellular cytotoxicity in vitro, whereas primary USPC cell lines were resistant to natural killer cell–dependent cytotoxicity. Human plasma IgG did not significantly inhibit MT201-mediated cytotoxicity against USPC. EpCAM is highly expressed in uterine serous carcinoma at mRNA and protein levels, and primary USPC are highly sensitivity to MT201-mediated cytotoxicity. MT201 might represent a novel therapeutic strategy in patients harboring advanced/recurrent or metastatic USPC refractory to standard treatment modalities. Mol Cancer Ther; 9(1); 57–66