bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokinesis-Blocked Micronucleus Cytome Assay Biomarkers Identify Lung Cancer Cases Amongst Smokers
Authors: El-Zein Randa A. , Fenech Michael , Lopez Mirtha S. , Spitz Margaret R. , Etzel Carol J. 
Published: May 2008

Abstract
The multi-endpoint cytokinesis-blocked micronucleus assay is used for assessing chromosome aberrations. We have recently reported that this assay is extremely sensitive to genetic damage caused by the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and that the binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds in lymphocytes (chromosome damage endpoints measured by the assay) are strong predictors of lung cancer risk. In the current study, we refined our analysis to include toxicity endpoints (micronuclei in mononucleated cells, apoptosis, necrosis, and nuclear division index) to investigate the benefit of including these variables on improving the predictive value of the assay. Baseline and NNK-induced micronuclei in mononucleated cells were significantly higher in patients (n = 139) than controls (n = 130; P &lt; 0.001). Baseline apoptosis was higher among cases; however, the controls showed a significant higher fold increase in NNK-induced apoptosis compared with baseline (P &lt; 0.001). Principal components analysis was used to derive a summary measure for all endpoints and calculate the positive predictive value (PPV) and negative predictive value (NPV) for disease status. First principal component for NNK-induced chromosome damage endpoints (binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds) had an area under the curve = 97.9 (95% confidence interval, 95.9-99.0), PPV = 94.8, and NPV = 92.6. The discriminatory power improved when micronuclei in mononucleated cells were included: area under the curve = 99.1 (95% confidence interval, 97.9-100.0), PPV = 98.7 and NPV = 95.6. The simplicity, rapidity, and sensitivity of the assay together with potential for automation make it a valuable tool for screening and prioritizing potential cases for intensive screening. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1111–9)
Nonsteroidal Anti-inflammatory Drugs and Change in Mammographic Density: A Cohort Study Using Pharmacy Records on Over 29,000 Postmenopausal Women
Authors: Terry Mary Beth , Buist Diana S.M. , Trentham-Dietz Amy , James-Todd Tamarra M. , Liao Yuyan 
Published: May 2008

AbstractBackground: Use of nonsteroidal anti-inflammatory drugs (NSAID) has been associated with a decrease in breast cancer risk, but it is unknown if they also reduce mammographic density, a strong intermediate marker of breast cancer risk.Methods: We investigated NSAID use and mammographic density in 29,284 postmenopausal women who had two screening mammograms at Group Health in Seattle. We used pharmacy records to classify women as NSAID nonusers, continuers, initiators, or discontinuers based on use between the two mammograms and nine separate prescription and nonprescription NSAID classes. Using unordered polytomous logistic regression methods, we modeled the odds ratio (OR) of staying not dense, decreasing density, or increasing density relative to remaining dense based on Breast Imaging Reporting Data System classification of density.Results: There was no association with density change from initiation or continuation of NSAIDs. However, both initiators and continuers of any NSAIDs were more likely to stay not dense than stay dense [OR, 1.12; 95% confidence interval (95% CI), 1.04-1.20; OR, 1.25; 95% CI, 1.05-1.49, respectively]. This association with staying not dense for initiators and continuers of any NSAID use was observed primarily among women ages &lt;65 years at first mammogram (OR, 1.24; 95% CI, 1.12-1.36; OR, 1.48; 95% CI, 1.14-1.93, respectively).Conclusions: Initiation of NSAID use did not reduce mammographic density over the short term. Continuers of NSAID use were more likely to stay not dense compared with nonusers, suggesting that it is plausible that longer-term use of NSAIDs may be needed to reduce density. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1088–95)
Aspirin, Nonsteroidal Anti-inflammatory Drugs, and the Risks of Cancers of the Esophagus
Authors: Sadeghi Shahram , Bain Christopher J. , Pandeya Nirmala , Webb Penelope M. , Green Adèle C. , Whiteman David C. ,   for the Australian Cancer Study
Published: May 2008

AbstractBackground: Frequent consumption of aspirin and nonsteroidal anti-inflammatory drugs (NSAID) has been associated with reduced occurrence of cancers of the esophagus, although potential modifying effects of other causal factors remain relatively unexplored.Methods: We compared nationwide samples of Australian patients with adenocarcinomas of the esophagus (EAC; n = 367) or esophagogastric junction (EGJAC; n = 426) or esophageal squamous cell carcinoma (ESCC; n = 309) with control participants sampled from a population register (n = 1,580). Intakes of aspirin, other NSAIDs, and acetaminophen (paracetamol) were assessed from self-reports. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using multivariable logistic regression.Results: Compared with never-users of aspirin, those who used aspirin at least weekly had significantly lower risks of EAC (OR, 0.48; 95% CI, 0.32-0.72), EGJAC (OR, 0.71; 95% CI, 0.49-1.01), and ESCC (OR, 0.63; 95% CI, 0.40-0.98). At least weekly use of other NSAIDs was also associated with reduced risks of EAC (OR, 0.74; 95% CI, 0.51-1.08), EGJAC (OR, 0.53; 95% CI, 0.37-0.77), and ESCC (OR, 0.46; 95% CI, 0.30-0.73). No association was observed between frequent use of acetaminophen and esophageal cancer. Risk reductions for EAC among users of aspirin and NSAIDs were greater among those who experienced at least weekly symptoms of reflux (OR, 0.26; 95% CI, 0.12-0.55 and OR, 0.41; 95% CI, 0.21-0.77, respectively) than those who did not experience reflux (OR, 0.96; 95% CI, 0.46-2.00 and OR, 0.78; 95% CI, 0.35-1.72, respectively). Recent use of NSAIDs in the past 5 years was associated with greater risk reductions.Conclusions: Frequent use of aspirin and NSAIDs is associated with reduced occurrence of esophageal cancers, particularly among those with frequent symptoms of gastroesophageal reflux. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1169–9)
High Levels of Carcinogenic Polycyclic Aromatic Hydrocarbons in Mate Drinks
Authors: Kamangar Farin , Schantz Michele M. , Abnet Christian C. , Fagundes Renato B. , Dawsey Sanford M. 
Published: May 2008

Abstract
Background: Drinking mate has been associated with cancers of the esophagus, oropharynx, larynx, lung, kidney, and bladder. We conducted this study to determine whether drinking mate could lead to substantial exposure to polycyclic aromatic hydrocarbons (PAH), including known carcinogens, such as benzo[a]pyrene.
Methods: The concentrations of 21 individual PAHs were measured in dry leaves of eight commercial brands of yerba mate and in infusions made with hot (80°C) or cold (5°C) water. Measurements were done using gas chromatography/mass spectrometry, with deuterated PAHs as the surrogates. Infusions were made by adding water to the leaves, removing the resulting infusion after 5 min, and then adding more water to the remaining leaves. This process was repeated 12 times for each infusion temperature.
Results: The total concentrations of the 21 PAHs in different brands of yerba mate ranged from 536 to 2,906 ng/g dry leaves. Benzo[a]pyrene concentrations ranged from 8.03 to 53.3 ng/g dry leaves. For the mate infusions prepared using hot water and brand 1, 37% (1,092 of 2,906 ng) of the total measured PAHs and 50% (25.1 of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. Similar results were obtained for other hot and cold infusions.
Conclusion: Very high concentrations of carcinogenic PAHs were found in yerba mate leaves and in hot and cold mate infusions. Our results support the hypothesis that the carcinogenicity of mate may be related to its PAH content. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1262–8)
Helicobacter pylori Infection and Development of Pancreatic Cancer
Authors: de Martel Catherine , Llosa Augusto E. , Friedmana Gary D. , Vogelman Joseph H. , Orentreich Norman , Stolzenberg-Solomon Rachael Z. , Parsonnet Julie 
Published: May 2008

Abstract
Background: Infection with Helicobacter pylori is an established risk factor for gastric cancer. Results from two studies suggest that it may also be a risk factor for pancreatic cancer.
Methods: We conducted a nested case control study among 128,992 adult subscribers to the Kaiser Permanente Medical Care Program who had been enrolled in a multiphasic health checkup from 1964 to 1969. Serum collected during the checkup was maintained frozen, and subjects were followed for cancer. Cases consisted of 104 randomly selected subjects among 507 who developed pancreatic cancer in the cohort. Controls consisted of 262 pancreatic cancer–free subjects from a pool of 730 controls previously tested for studies conducted on this cohort. Controls were individually matched to cases on age, gender, race, site, and date of multiphasic health checkup. Control sera were compared with cases for antibodies to H. pylori and the CagA protein. The effects of smoking, alcohol consumption, obesity, and years of education were also investigated.
Results: Neither H. pylori [odds ratio (OR), 0.85; 95% confidence interval (95% CI), 0.49-1.48] nor its CagA protein (OR, 0.96; 95% CI, 0.48-1.92) was associated with subsequent development of pancreatic cancer. Smoking (OR, 2.09; 95% CI, 1.17-3.74) and greater number of years of education (OR, 2.13; 95% CI, 1.23-3.69) were risk factors for pancreatic cancer, whereas alcohol consumption and obesity were not.
Conclusion: Our results suggest that H. pylori infection is not associated with development of pancreatic cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1188–94)
Prognostic Role of Detection Method and Its Relationship with Tumor Biomarkers in Breast Cancer: The University of Texas M. D. Anderson Cancer Center Experience
Authors: Dong Wenli , Berry Donald A. , Bevers Therese B. , Kau Shu-Wan , Hsu Limin , Theriault Richard L. , Shen Yu 
Published: May 2008

Abstract
Purpose: To assess the effect of tumor detection method (screening versus symptom-based diagnosis) in predicting breast cancer survival and investigate how biological features of breast cancer are related to the tumor detection method.
Patients and Methods: The study population consisted of 5,481 women diagnosed with primary invasive breast cancer between 1997 and 2005 and received their treatment at The University of Texas M. D. Anderson Cancer Center.
Results: Patients with symptom-detected tumors had an increased risk of recurrence or death [relative risk (RR), 1.34; P = 0.006] and breast cancer–specific death (RR, 1.31; P = 0.117) than patients with screen-detected tumors after adjusting for tumor characteristics and treatments received. This relationship was especially evident among estrogen receptor (ER)–negative tumors (RR, 1.60 for breast cancer recurrence for ER-negative tumors; RR, 1.18 for ER-positive tumors). ER status and Ki-67 expression were statistically significantly associated with symptom detection rate after adjusting for patients' age, tumor stage, tumor size, and nuclear grade [odds ratio (OR) of ER negative versus ER positive, 1.35; P &lt; 0.001; OR of Ki-67 10-30% versus &lt;10%, 1.40; P = 0.005; OR of Ki-67 &gt;30% versus &lt;10%, 2.11; P &lt; 0.001].
Conclusion: The method of detection was a statistically significant independent predictor of breast cancer recurrence. Information on the method of tumor detection should be collected to improve the prediction of prognosis of breast cancer patients. (Cancer Epidemiol Biomarkers Prev 2008;17(5):1096–103)
N-[N-[(S)-1,3-Dicarboxypropyl]Carbamoyl]-4-[18F]Fluorobenzyl-l-Cysteine, [18F]DCFBC: A New Imaging Probe for Prostate Cancer
Authors: Mease Ronnie C. , Dusich Crystal L. , Foss Catherine A. , Ravert Hayden T. , Dannals Robert F. , Seidel Jurgen , Prideaux Andrew , Fox James J. , Sgouros George , Kozikowski Alan P. , Pomper Martin G. 
Published: May 2008

Abstract
Purpose: Previously, we showed successful imaging of xenografts that express the prostate-specific membrane antigen (PSMA) using small-animal positron emission tomography (PET) and the radiolabeled PSMA inhibitor N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-S-[11C]methyl-l-cysteine. Herein, we extend that work by preparing and testing a PSMA inhibitor of the same class labeled with fluorine-18.
Experimental Design: N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-l-cysteine ([18F]DCFBC) was prepared by reacting 4-[18F]fluorobenzyl bromide with the precursor (S)-2-[3-[(R)-1-carboxy-2-mercaptoethyl]ureido]-pentanedioic acid in ammonia-saturated methanol at 60°C for 10 min followed by purification using C-18 reverse-phase semipreparative high-performance liquid chromatography. Severe combined immunodeficient mice bearing a s.c. PSMA+ PC-3 PIP tumor behind one shoulder and a PSMA− PC-3 FLU tumor behind the other shoulder were injected via the tail vein with either 1.85 MBq (50 μCi) of [18F]DCFBC for ex vivo biodistribution or 7.4 MBq (200 μCi) for imaging. For biodistribution, mice were sacrificed at 5, 15, 30, 60, and 120 min. Tumor, blood, and major organs were harvested and weighed, and radioactivity was counted. Imaging was done on the GE eXplore Vista small-animal PET scanner by collecting 12 consecutive 10-min frames.
Results: Radiochemical yield for [18F]DCFBC averaged 16 ± 6% (n = 8) from 4-[18F]fluorobenzyl bromide. Specific radioactivities ranged from 13 to 133 GBq/μmol (350-3,600 Ci/mmol) with an average of 52 GBq/μmol (1,392 Ci/mmol; n = 6). Biodistribution and imaging studies showed high uptake of [18F]DCFBC in the PIP tumors with little to no uptake in FLU tumors. High radiopharmaceutical uptake was also seen in kidneys and bladder; however, washout of radioactivity from these organs was faster than from the PIP tumors. The maximum PIP tumor uptake was 8.16 ± 2.55% injected dose per gram, achieved at 60 min after injection, which decreased to 4.69 ± 0.89 at 120 min. The PIP tumor to muscle ratio was 20 at 120 min after injection. Based on the mouse biodistribution, the dose-limiting organ is the kidneys (human estimated absorbed dose: 0.05 mGy/MBq; 0.2 rad/mCi).
Conclusion: [18F]DCFBC localizes to PSMA+-expressing tumors in mice, permitting imaging by small-animal PET. This new radiopharmaceutical is an attractive candidate for further studies of PET imaging of prostate cancer.
Mechanisms of Chemoresistance to Alkylating Agents in Malignant Glioma
Authors: Sarkaria Jann N. , Kitange Gaspar J. , James C. David , Plummer Ruth , Calvert Hilary , Weller Michael , Wick Wolfgang 
Published: May 2008

Abstract
Intrinsic or acquired chemoresistance to alkylating agents is a major cause of treatment failure in patients with malignant brain tumors. Alkylating agents, the mainstay of treatment for brain tumors, damage the DNA and induce apoptosis, but the cytotoxic activity of these agents is dependent on DNA repair pathways. For example, O6-methylguanine DNA adducts can cause double-strand breaks, but this is dependent on a functional mismatch repair pathway. Thus, tumor cell lines deficient in mismatch repair are resistant to alkylating agents. Perhaps the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase, which can eliminate the cytotoxic O6-methylguanine DNA adduct before it causes harm. Another mechanism of resistance to alkylating agents is the base excision repair (BER) pathway. Consequently, efforts are ongoing to develop effective inhibitors of BER. Poly(ADP-ribose)polymerase plays a pivotal role in BER and is an important therapeutic target. Developing effective strategies to overcome chemoresistance requires the identification of reliable preclinical models that recapitulate human disease and which can be used to facilitate drug development. This article describes the diverse mechanisms of chemoresistance operating in malignant glioma and efforts to develop reliable preclinical models and novel pharmacologic approaches to overcome resistance to alkylating agents.
Vascular Endothelial Growth Factor Expression in Ovarian Cancer: A Model for Targeted Use of Novel Therapies?
Authors: Duncan Timothy J. , Al-Attar Ahmad , Rolland Phil , Scott Ian V. , Deen Suha , Liu David T.Y. , Spendlove Ian , Durrant Lindy G. 
Published: May 2008

Abstract
Purpose: Angiogenesis has a vital role in tumor growth and metastasis, and vascular endothelial growth factor (VEGF) represents a potent cytokine in this process. However, the influence of VEGF in ovarian cancer remains controversial. Interest has focused on the use of antiangiogenic drugs in ovarian cancer. This study aims to establish the pattern of expression and effect on prognosis of VEGF in a large population of ovarian cancer patients and to potentially identify a cohort in whom antiangiogenic therapy is appropriate.
Experimental Design: Using a tissue microarray of 339 primary ovarian cancers, the expression of VEGF was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors and survival was studied.
Results: Tumors expressing high levels of VEGF had significantly poorer survival (P = 0.04). Factors shown to predict prognosis independently of each other were age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. VEGF was independently predictive of prognosis on multivariate analysis (P = 0.02). There was no correlation between VEGF and any clinicopathologic variable. High expression of VEGF was seen in only 7% of the tumors, suggesting that the role of antiangiogenic drugs may be limited to a small subset of patients.
Conclusion: High VEGF expression occurs in a small proportion of ovarian cancers, and this independently predicts poor prognosis. The small percentage of tumors with high levels of VEGF activity suggests that the role of bevacizumab may potentially be limited to a few patients; these patients could be targeted by molecular profiling.
Bcl-B Expression in Human Epithelial and Nonepithelial Malignancies
Authors: Krajewska Maryla , Kitada Shinichi , Winter Jane N. , Variakojis Daina , Lichtenstein Alan , Zhai Dayong , Cuddy Michael , Huang Xianshu , Luciano Frederic , Baker Cheryl H. , Kim Hoguen , Shin Eunah , Kennedy Susan , Olson Allen H. , Badzio Andrzej , Jassem Jacek , Meinhold-Heerlein Ivo , Duffy Michael J. , Schimmer Aaron D. , Tsao Ming , Brown Ewan , Sawyers Anne , Andreeff Michael , Mercola Dan , Krajewski Stan , Reed John C. 
Published: May 2008

Abstract
Purpose: Apoptosis plays an important role in neoplastic processes. Bcl-B is an antiapoptotic Bcl-2 family member, which is known to change its phenotype upon binding to Nur77/TR3. The expression pattern of this protein in human malignancies has not been reported.
Experimental Design: We investigated Bcl-B expression in normal human tissues and several types of human epithelial and nonepithelial malignancy by immunohistochemistry, correlating results with tumor stage, histologic grade, and patient survival.
Results: Bcl-B protein was strongly expressed in all normal plasma cells but found in only 18% of multiple myelomas (n = 133). Bcl-B immunostaining was also present in normal germinal center centroblasts and centrocytes and in approximately half of diffuse large B-cell lymphoma (n = 48) specimens, whereas follicular lymphomas (n = 57) did not contain Bcl-B. In breast (n = 119), prostate (n = 66), gastric (n = 180), and colorectal (n = 106) adenocarcinomas, as well as in non–small cell lung cancers (n = 82), tumor-specific overexpression of Bcl-B was observed. Bcl-B expression was associated with variables of poor prognosis, such as high tumor grade in breast cancer (P = 0.009), microsatellite stability (P = 0.0002), and left-sided anatomic location (P = 0.02) of colorectal cancers, as well as with greater incidence of death from prostate cancer (P = 0.005) and shorter survival of patients with small cell lung cancer (P = 0.009). Conversely, although overexpressed in many gastric cancers, Bcl-B tended to correlate with better outcome (P = 0.01) and more differentiated tumor histology (P &lt; 0.0001).
Conclusions: Tumor-specific alterations in Bcl-B expression may define subsets of nonepithelial and epithelial neoplasms with distinct clinical behaviors.
Critical Role of Notch Signaling in Osteosarcoma Invasion and Metastasis
Authors: Zhang Pingyu , Yang Yanwen , Zweidler-McKay Patrick A. , Hughes Dennis P.M. 
Published: May 2008

Abstract
Purpose: Notch signaling is an important mediator of growth and survival in several cancer types, with Notch pathway genes functioning as oncogenes or tumor suppressors in different cancers. However, the role of Notch in osteosarcoma is unknown.
Experimental Design: We assessed the expression of Notch pathway genes in human osteosarcoma cell lines and patient samples. We then used pharmacologic and retroviral manipulation of the Notch pathway and studied the effect on osteosarcoma cell proliferation, survival, anchorage-independent growth, invasion, and metastasis in vitro and in vivo.
Results: Notch pathway genes, including Notch ligand DLL1, Notch1 and Notch2, and the Notch target gene HES1, were expressed in osteosarcoma cells, and expression of HES1 was associated with invasive and metastatic potential. Blockade of Notch pathway signaling with a small molecule inhibitor of γ secretase eliminated invasion in Matrigel without affecting cell proliferation, survival, or anchorage-independent growth. Manipulation of Notch and HES1 signaling showed a crucial role for HES1 in osteosarcoma invasiveness and metastasis in vivo.
Conclusion: These studies identify a new invasion and metastasis-regulating pathway in osteosarcoma and define a novel function for the Notch pathway: regulation of metastasis. Because the Notch pathway can be inhibited pharmacologically, these findings point toward possible new treatments to reduce invasion and metastasis in osteosarcoma.
Histone Deacetylase Inhibition and Blockade of the Glycolytic Pathway Synergistically Induce Glioblastoma Cell Death
Authors: Egler Vivian , Korur Serdar , Failly Mike , Boulay Jean-Louis , Imber Roland , Lino Maria M. , Merlo Adrian 
Published: May 2008

AbstractPurpose: High-grade gliomas are difficult to treat due to their location behind the blood-brain barrier and to inherent radioresistance and chemoresistance.Experimental Design: Because tumorigenesis is considered a multistep process of accumulating mutations affecting distinct signaling pathways, combinations of compounds, which inhibit nonoverlapping pathways, are being explored to improve treatment of gliomas. Histone deacetylase inhibitors (HDI) have proven antitumor activity by blocking cell proliferation, promoting differentiation, and inducing tumor cell apoptosis.Results: In this report, we show that the HDIs trichostatin A, sodium butyrate, and low nanomolar doses of LAQ824 combined with the glycolysis inhibitor 2-deoxy-d-glucose induce strong apoptosis in cancer cell lines of brain, breast, and cervix in a p53-independent manner. HDIs up-regulate p21, which is blocked by concomitant administration of 2-deoxy-d-glucose.Conclusions: We propose simultaneous blockade of histone deacetylation and glycolysis as a novel therapeutic strategy for several major cancers.