bluuebunny/crossref_metadata_2025_split huggingface dataset:
Race and Time from Diagnosis to Radical Prostatectomy: Does Equal Access Mean Equal Timely Access to the Operating Room?—Results from the SEARCH Database
Authors: Bañez Lionel L. , Terris Martha K. , Aronson William J. , Presti Joseph C. , Kane Christopher J. , Amling Christopher L. , Freedland Stephen J. 
Published: April 2009

Abstract
Background: African American men with prostate cancer are at higher risk for cancer-specific death than Caucasian men. We determine whether significant delays in management contribute to this disparity. We hypothesize that in an equal-access health care system, time interval from diagnosis to treatment would not differ by race.
Methods: We identified 1,532 African American and Caucasian men who underwent radical prostatectomy (RP) from 1988 to 2007 at one of four Veterans Affairs Medical Centers that comprise the Shared Equal-Access Regional Cancer Hospital (SEARCH) database with known biopsy date. We compared time from biopsy to RP between racial groups using linear regression adjusting for demographic and clinical variables. We analyzed risk of potential clinically relevant delays by determining odds of delays &gt;90 and &gt;180 days.
Results: Median time interval from diagnosis to RP was 76 and 68 days for African Americans and Caucasian men, respectively (P = 0.004). After controlling for demographic and clinical variables, race was not associated with the time interval between diagnosis and RP (P = 0.09). Furthermore, race was not associated with increased risk of delays &gt;90 (P = 0.45) or &gt;180 days (P = 0.31).
Conclusions: In a cohort of men undergoing RP in an equal-access setting, there was no significant difference between racial groups with regard to time interval from diagnosis to RP. Thus, equal-access includes equal timely access to the operating room. Given our previous finding of poorer outcomes among African Americans, treatment delays do not seem to explain these observations. Our findings need to be confirmed in patients electing other treatment modalities and in other practice settings. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1208–12)
Secondhand Smoking, 4-Aminobiphenyl, and Bladder Cancer: Two Meta-analyses
Authors: Van Hemelrijck Mieke J.J. , Michaud Dominique S. , Connolly Gregory N. , Kabir Zubair 
Published: April 2009

Abstract
Objective: To quantify the relation between secondhand smoking (SHS) and levels of 4-aminobiphenyl (4-ABP; in urine or blood) and SHS and bladder cancer risk in nonsmokers.
Methods: PubMed and Embase were searched (search terms to represent SHS, bladder cancer, and 4-ABP) to conduct two meta-analyses. Information about gender and age of participants, mean 4-ABP level for each SHS category, number of subjects, relative risk or odds ratio and 95% confidence intervals (95% CI) in each SHS category, and covariates for which adjustment was made was extracted based on predefined inclusion and exclusion criteria. Random-effects analyses were done using STATA (version 9).
Results: A 118 studies were reviewed for information on SHS and 4-ABP (31 studies) and SHS and bladder cancer risk (87 studies). Of those, seven case-control studies were included for analysis of SHS and 4-ABP and eight articles (three cohort and five case-control studies) for SHS and bladder cancer risk. A random-effects model found a pooled standardized mean difference of 1.47 (95% CI, 0.23-2.71), indicating higher levels of 4-ABP among nonsmokers exposed to SHS. A random-effects model showed no evidence for an association between SHS and bladder cancer risk (relative risk, 0.99; 95% CI, 0.86-1.14), comparing nonsmokers with and without SHS exposure.
Conclusion: Higher levels of 4-ABP were significantly associated with SHS exposure, which is consistent with earlier findings for 4-ABP levels in sidestream smoke. The current evidence indicates that there is no association between SHS and bladder cancer, but future studies that address methodologic limitations are needed to further clarify this important question. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1312–20)
Global DNA Hypomethylation (LINE-1) in the Normal Colon and Lifestyle Characteristics and Dietary and Genetic Factors
Authors: Figueiredo Jane C. , Grau Maria V. , Wallace Kristin , Levine A. Joan , Shen Lanlan , Hamdan Randala , Chen Xinli , Bresalier Robert S. , McKeown-Eyssen Gail , Haile Robert W. , Baron John A. , Issa Jean-Pierre J. 
Published: April 2009

AbstractBackground: Global loss of methylated cytosines in DNA, thought to predispose to chromosomal instability and aneuploidy, has been associated with an increased risk of colorectal neoplasia. Little is known about the relationships between global hypomethylation and lifestyle, demographics, dietary measures, and genetic factors.Methods: Our data were collected as part of a randomized clinical trial testing the efficacy of aspirin and folic acid for the prevention of colorectal adenomas. At a surveillance colonoscopy ∼3 years after the qualifying exam, we obtained two biopsies of the normal-appearing mucosa from the right colon and two biopsies from the left colon. Specimens were assayed for global hypomethylation using a pyrosequencing assay for LINE-1 (long interspersed nucleotide elements) repeats.Results: The analysis included data from 388 subjects. There was relatively little variability in LINE methylation overall. Mean LINE-1 methylation levels in normal mucosa from the right bowel were significantly lower than those on the left side (P &lt; 0.0001). No significant associations were found between LINE-1 methylation and folate treatment, age, sex, body mass index, smoking status, alcohol use, dietary intake, or circulating levels of B vitamins, homocysteine, or selected genotypes. Race, dietary folic acid, and plasma B6 showed associations with global methylation that differed between the right and the left bowel. The effect of folic acid on risk of adenomas did not differ according to extent of LINE-1 methylation, and we found no association between LINE-1 methylation and risk of adenomas.Conclusions: LINE-1 methylation is not influenced by folic acid supplementation but differs by colon subsite. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1041–9)
Independent Effect of EBV and Cigarette Smoking on Nasopharyngeal Carcinoma: A 20-Year Follow-Up Study on 9,622 Males without Family History in Taiwan
Authors: Hsu Wan-Lun , Chen Jen-Yang , Chien Yin-Chu , Liu Mei-Ying , You San-Lin , Hsu Mow-Ming , Yang Czau-Siung , Chen Chien-Jen 
Published: April 2009

Abstract
This study aimed to assess independent effects of EBV and cigarette smoking on nasopharyngeal carcinoma, which have never been assessed in long-term follow-up studies. A cohort of 9,622 men was enrolled from 1984 to 1986. Blood samples collected at study entry were tested for antibodies against EBV antigens (anti-EBV) viral capsid antigen immunoglobulin A and DNase. The cigarette smoking habit was inquired through questionnaire interview. Newly developed nasopharyngeal carcinoma cases were ascertained through computerized linkage with national cancer registry profile. Cox's proportional hazard regression analysis was used to estimate multivariate-adjusted hazard ratio with its 95% confidence interval (95% CI). During the follow-up of 173,706 person-years, 32 pathologically confirmed nasopharyngeal carcinoma cases were identified &gt;1 year after recruitment. Increasing serum levels of anti–EBV viral capsid antigen immunoglobulin A and DNase were significantly associated with nasopharyngeal carcinoma risk in a dose-response relationship. The multivariate-adjusted hazard ratio (95% CI) of developing nasopharyngeal carcinoma for low and high antibody levels compared with seronegatives was 9.5 (2.2-40.1) and 21.4 (2.8-161.7), respectively, for anti–EBV viral capsid antigen immunoglobulin A (P &lt; 0.001 for trend), and 1.6 (0.5-4.6) and 16.0 (5.4-47.1), respectively, for anti–EBV DNase (P &lt; 0.001 for trend). The shorter the time interval between study entry and nasopharyngeal carcinoma diagnosis, the higher was the proportion of anti–EBV viral capsid antigen immunoglobulin A among nasopharyngeal carcinoma patients. The multivariate-adjusted hazard ratio (95% CI) was 3.0 (1.3-7.2) for ≥30 pack-years of cumulative cigarette smoking compared with &lt;30 pack-years as the reference. The longer and heavier the cigarette smoking habit, the higher was the nasopharyngeal carcinoma risk. Anti–EBV viral capsid antigen immunoglobulin A, anti–EBV DNase, and long-term heavy cigarette smoking are independent nasopharyngeal carcinoma risk predictors. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1218–26)
Cervical Carcinoma and Sexual Behavior: Collaborative Reanalysis of Individual Data on 15,461 Women with Cervical Carcinoma and 29,164 Women without Cervical Carcinoma from 21 Epidemiological Studies
Authors:   International Collaboration of Epidemiological Studies of Cervical Cancer
Published: April 2009

Abstract
High-risk human papillomavirus (HPV) types cause most cervical carcinomas and are sexually transmitted. Sexual behavior therefore affects HPV exposure and its cancer sequelae. The International Collaboration of Epidemiological Studies of Cervical Cancer has combined data on lifetime number of sexual partners and age at first sexual intercourse from 21 studies, or groups of studies, including 10,773 women with invasive cervical carcinoma, 4,688 women with cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ, and 29,164 women without cervical carcinoma. Relative risks for invasive cancer and CIN3 were estimated by conditional logistic regression. Risk of invasive cervical carcinoma increased with lifetime number of sexual partners (P for linear trend &lt;0.001). The relative risk for ≥6 versus 1 partner, conditioned on age, study, and age at first intercourse, was 2.27 [95% confidence interval (95% CI), 1.98-2.61] and increased to 2.78 (95% CI, 2.22-3.47) after additional conditioning on reproductive factors. The risk of invasive cervical carcinoma increased with earlier age at first intercourse (P for linear trend &lt;0.001). The relative risk for age at first intercourse ≤14 versus ≥25 years, conditioned on age, study, and lifetime number of sexual partners was 3.52 (95% CI, 3.04-4.08), which decreased to 2.05 (95% CI, 1.54-2.73) after additional conditioning on reproductive factors. CIN3/carcinoma in situ showed a similar association with lifetime number of sexual partners; however, the association with age at first intercourse was weaker than for invasive carcinoma. Results should be interpreted with caution given the strong correlation between sexual and reproductive factors and the limited information on HPV status. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1060–9)
Absence of Deleterious Palladin Mutations in Patients with Familial Pancreatic Cancer
Authors: Klein Alison P. , Borges Michael , Griffith Margaret , Brune Kieran , Hong Seung-Mo , Omura Noriyuki , Hruban Ralph H. , Goggins Michael 
Published: April 2009

Abstract
It has been reported that germline mutations in the palladin gene (PALLD) cause the familial aggregation of pancreatic cancer, but the evidence is weak and controversial. We sequenced the coding regions of PALLD in 48 individuals with familial pancreatic cancer. We did not find any deleterious mutations and find no evidence to implicate mutations in PALLD as a cause of familial pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1328–30)
Molecular Detection of Lymph Node Metastases in Breast Cancer Patients: Results of a Multicenter Trial Using the One-Step Nucleic Acid Amplification Assay
Authors: Tamaki Yasuhiro , Akiyama Futoshi , Iwase Takuji , Kaneko Tomoyo , Tsuda Hitoshi , Sato Kazuhiko , Ueda Shigeto , Mano Masayuki , Masuda Norikazu , Takeda Masashi , Tsujimoto Masahiko , Yoshidome Katsuhide , Inaji Hideo , Nakajima Hiromu , Komoike Yoshifumi , Kataoka Tatsuki R. , Nakamura Seigo , Suzuki Koyu , Tsugawa Koichiro , Wakasa Kenichi , Okino Tsuyoshi , Kato Yo , Noguchi Shinzaburo , Matsuura Nariaki 
Published: April 2009

Abstract
Purpose: Accurate assessment of metastasis in sentinel lymph nodes (SLN) of breast cancer is important but involves a heavy workload for the pathologist. We conducted a multicenter clinical trial in Japan to evaluate a new automated assay system for cytokeratin 19 mRNA, the one-step nucleic acid amplification (OSNA) assay (Sysmex), to detect lymph node metastasis of breast cancer.
Experimental Design: Surgically obtained axillary lymph nodes were sectioned into four pieces, two of which were examined with the OSNA assay. The other two adjacent pieces were examined with H&E and immunohistochemical staining for cytokeratin 19. Serial sections at 0.2-mm intervals were used in trial 1 to determine the specificity of the OSNA assay, and three pairs of sections cut from the sliced surfaces of the pieces were used in trial 2 to compare the accuracy of the OSNA assay with that of a routine pathologic examination for SLNs in Japan.
Results: In trial 1, the sensitivity and specificity were 95.0% [95% confidence interval (95% CI), 75.1-99.9%] and 97.1% (95% CI, 91.8-99.4%), respectively, for 124 axillary lymph nodes obtained from 34 patients. In trial 2, the agreement between findings of the assay and of the pathologic examination was 92.9% (95% CI, 90.1-95.1%) for 450 axillary lymph nodes obtained from 164 patients.
Conclusion: The OSNA assay can detect lymph node metastasis as accurately as can conventional pathology and thus can be an effective addition to or alternative for rapid intraoperative examination of SLNs.
Phase II Trial of Tipifarnib plus Neoadjuvant Doxorubicin-Cyclophosphamide in Patients with Clinical Stage IIB-IIIC Breast Cancer
Authors: Sparano Joseph A. , Moulder Stacy , Kazi Aslamuzzaman , Coppola Domenico , Negassa Abdissa , Vahdat Linda , Li Tianhong , Pellegrino Christine , Fineberg Susan , Munster Pam , Malafa Mokenge , Lee David , Hoschander Shira , Hopkins Una , Hershman Dawn , Wright John J. , Kleer Celina , Merajver Sofia , Sebti Said M. 
Published: April 2009

Abstract
Purpose: Tipifarnib is a farnesyl transferase (FTase) inhibitor that has activity in metastatic breast cancer and enhances the efficacy of cytotoxic agents in preclinical models. We evaluated the biological effects of tipifarnib in primary breast cancers in vivo, whether adding tipifarnib to preoperative chemotherapy increased the pathologic complete response rate (pCR) at surgery, and determined whether biomarkers predictive of pCR could be identified.
Experimental Design: Forty-four patients with stage IIB-IIIC breast cancer received up to four cycles of neoadjuvant doxorubicin-cyclophosphamide (AC) every 2 weeks plus tipifarnib and filgrastim followed by surgery. Enzymatic assays measuring FTase activity and Western blotting for phospho (p)-signal transducer and activator of transcription 3 (STAT3), phospho-extracellular signal-regulated kinase, p-AKT, and p27 were done in 11 patients who agreed to optional tissue biopsies before therapy and 2 hours after the final dose of tipifarnib during the first cycle, and predictive biomarkers were evaluated by immunohistochemistry in 33 patients. The trial was powered to detect an improvement in breast pCR rate of 10% or less expected for AC alone to 25% for AC-tipifarnib (α = 0.05, β = 0.10).
Results: Eleven patients had a breast pCR (25%; 95% confidence interval, 13-40%). FTase enzyme activity decreased in all patients (median, 91%; range, 24-100%) and p-STAT3 expression decreased in 7 of 9 (77%) patients. Low tumor Ki-67 expression (below the median of 60%) at baseline was significantly associated with resistance to therapy (P = 0.01).
Conclusion: Tipifarnib inhibits FTase activity in human breast tumors in vivo, is associated with down-regulation of p-STAT3, and enhances the breast pCR rate, thus meriting further evaluation.
Antivascular Actions of Microtubule-Binding Drugs
Authors: Schwartz Edward L. 
Published: April 2009

AbstractMicrotubule-binding drugs (MBD) are widely used in cancer chemotherapy and also have clinically relevant antiangiogenic and vascular-disrupting properties. These antivascular actions are due in part to direct effects on endothelial cells, and all MBDs (both microtubule-stabilizing and microtubule-destabilizing) inhibit endothelial cell proliferation, migration, and tube formation in vitro, actions that are thought to correspond to therapeutic antiangiogenic actions. In addition, the microtubule-destabilizing agents cause prominent changes in endothelial cell morphology, an action associated with rapid vascular collapse in vivo. The effects on endothelial cells occur in vitro at low drug concentrations, which do not affect microtubule gross morphology, do not cause microtubule bundling or microtubule loss and do not induce cell cycle arrest, apoptosis, or cell death. Rather, it has been hypothesized that, at low concentrations, MBDs produce more subtle effects on microtubule dynamics, block critical cell signaling pathways, and prevent the microtubules from properly interacting with transient subcellular assemblies (focal adhesions and adherens junctions) whose subsequent stabilization and/or maturation are required for cell motility and cell-cell interactions. This review will focus on recent studies to define the molecular mechanisms for the antivascular actions of the MBDs, information that could be useful in the identification or design of agents whose actions more selectively target the tumor vasculature.
Protumorigenic Role of HAPLN1 and Its IgV Domain in Malignant Pleural Mesothelioma
Authors: Ivanova Alla V. , Goparaju Chandra M.V. , Ivanov Sergey V. , Nonaka Daisuke , Cruz Christina , Beck Amanda , Lonardo Fulvio , Wali Anil , Pass Harvey I. 
Published: April 2009

Abstract
Purpose: Tumor extracellular matrix (ECM) plays a crucial role in cancer progression mediating and transforming host-tumor interactions. Targeting the ECM is becoming an increasingly promising therapeutic approach in cancer treatment. We find that one of the ECM proteins, HAPLN1, is overexpressed in the majority of mesotheliomas. This study was designed to characterize the protumorigenic role of HAPLN1 in mesothelioma.
Experimental Design: Overexpression of HAPLN1 was assessed and validated on a large set of normal/mesothelioma specimens on the RNA and protein levels. We also analyzed DNA copy number alterations in the HAPLN1 genomic locus using the array-based comparative genomic hybridization representational oligonucleotide microarray analysis tool. Tumorigenic activities of the HAPLN1 domains were evaluated in vitro on mesothelioma cells transfected with HAPLN1-expressing constructs.
Results: We found that HAPLN1 is 23-fold overexpressed in stage I mesothelioma and confirmed it for 76% samples (n = 53) on RNA and 97% (n = 40) on protein levels. The majority of lung cancers showed no differential expression of HAPLN1. Analysis of DNA copy number alterations identified recurrent gain in the 5q14.3 HAPLN1 locus in ∼27% of tumors. Noteworthy, high expression of HAPLN1 negatively correlated with time to progression (P = 0.05, log-rank test) and overall survival (P = 0.006). Proliferation, motility, invasion, and soft-agar colony formation assays on mesothelioma cells overexpressing full-length HAPLN1 or its functional domains strongly supported the protumorigenic role of HAPLN1 and its SP-IgV domain.
Conclusion: Overexpression of HAPLN1 and its SP-IgV domain increases tumorigenic properties of mesothelioma. Thus, targeting the SP-IgV domain may be one of the therapeutic approaches in cancer treatment.
Factor XI contributes to thrombin generation in the absence of factor XII
Authors: Kravtsov Dmitri V. , Matafonov Anton , Tucker Erik I. , Sun Mao-fu , Walsh Peter N. , Gruber Andras , Gailani David 
Published: April 2009

AbstractDuring surface-initiated blood coagulation in vitro, activated factor XII (fXIIa) converts factor XI (fXI) to fXIa. Whereas fXI deficiency is associated with a hemorrhagic disorder, factor XII deficiency is not, suggesting that fXI can be activated by other mechanisms in vivo. Thrombin activates fXI, and several studies suggest that fXI promotes coagulation independent of fXII. However, a recent study failed to find evidence for fXII-independent activation of fXI in plasma. Using plasma in which fXII is either inhibited or absent, we show that fXI contributes to plasma thrombin generation when coagulation is initiated with low concentrations of tissue factor, factor Xa, or α-thrombin. The results could not be accounted for by fXIa contamination of the plasma systems. Replacing fXI with recombinant fXI that activates factor IX poorly, or fXI that is activated poorly by thrombin, reduced thrombin generation. An antibody that blocks fXIa activation of factor IX reduced thrombin generation; however, an antibody that specifically interferes with fXI activation by fXIIa did not. The results support a model in which fXI is activated by thrombin or another protease generated early in coagulation, with the resulting fXIa contributing to sustained thrombin generation through activation of factor IX.
Evolution of ribosomal DNA-derived satellite repeat in tomato genome
Authors: Jo Sung-Hwan , Koo Dal-Hoe , Kim Jihyun F , Hur Cheol-Goo , Lee Sanghyeob , Yang Tae-jin , Kwon Suk-Yoon , Choi Doil 
Published: April 2009

Abstract

Background
Tandemly repeated DNA, also called as satellite DNA, is a common feature of eukaryotic genomes. Satellite repeats can expand and contract dramatically, which may cause genome size variation among genetically-related species. However, the origin and expansion mechanism are not clear yet and needed to be elucidated.

Results
FISH analysis revealed that the satellite repeat showing homology with intergenic spacer (IGS) of rDNA present in the tomato genome. By comparing the sequences representing distinct stages in the divergence of rDNA repeat with those of canonical rDNA arrays, the molecular mechanism of the evolution of satellite repeat is described. Comprehensive sequence analysis and phylogenetic analysis demonstrated that a long terminal repeat retrotransposon was interrupted into each copy of the 18S rDNA and polymerized by recombination rather than transposition via an RNA intermediate. The repeat was expanded through doubling the number of IGS into the 25S rRNA gene, and also greatly increasing the copy number of type I subrepeat in the IGS of 25-18S rDNA by segmental duplication. Homogenization to a single type of subrepeat in the satellite repeat was achieved as the result of amplifying copy number of the type I subrepeat but eliminating neighboring sequences including the type II subrepeat and rRNA coding sequence from the array. FISH analysis revealed that the satellite repeats are commonly present in closely-related Solanum species, but vary in their distribution and abundance among species.

Conclusion
These results represent that the dynamic satellite repeats were originated from intergenic spacer of rDNA unit in the tomato genome. This result could serve as an example towards understanding the initiation and the expansion of the satellite repeats in complex eukaryotic genome.