bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular Endothelial Growth Factor Secreted by Activated Stroma Enhances Angiogenesis and Hormone-Independent Growth of Estrogen Receptor–Positive Breast Cancer
Authors: Pinto Mauricio P. , Badtke Melanie M. , Dudevoir Michelle L. , Harrell J. Chuck , Jacobsen Britta M. , Horwitz Kathryn B. 
Published: March 2010

Abstract
“Reactive” or activated stroma characterizes many malignancies including breast cancers. Recently, we isolated a reactive mouse mammary gland stromal cell line called BJ3Z. These cells express α-smooth muscle actin and stromal cell–derived factor 1 (SDF-1) and are tumorigenic when injected into mice. Here we show that, in vivo, BJ3Z cells influence the angiogenesis and proliferation of xenografted estrogen receptor (ER)–positive MCF-7 human breast cancer cell–derived solid tumors. The growth-promoting effects of BJ3Z cells are equivalent to those of estradiol (E2). BJ3Z cells also increase the proliferation of normal mouse mammary luminal cells adjacent to tumors. In vitro, BJ3Z cells reorganize and increase the proliferation of cocultured malignant MCF-7 and normal human breast MCF10A cells grown as organoids in three-dimensional culture. The effects of BJ3Z cells on MCF-7 cells are equivalent to those of E2. In contrast, BJ3Z cells do not alter the growth of highly aggressive ER-negative MDA-MB-231 human breast cancer cells. We show that BJ3Z cells secrete vascular endothelial growth factor (VEGF). The growth of MCF-7 organoids induced by BJ3Z can be inhibited by antagonists of VEGF and SDF-1. Conversely, recombinant VEGF stimulates the proliferation of MCF-7, but not MDA-MB-231, organoids. We conclude that, in addition to angiogenesis, VEGF released by activated stroma increases the growth of ER-positive malignant epithelial cells and of adjacent normal epithelium. Because activated stroma can substitute for E2 and fosters hormone-independent growth of ER-positive tumors, we suggest that breast cancers exhibiting intrinsic hormone resistance may respond to antiangiogenic therapies. Cancer Res; 70(7); 2655–64
MLL-Rearranged B Lymphoblastic Leukemias Selectively Express the Immunoregulatory Carbohydrate-Binding Protein Galectin-1
Authors: Juszczynski Przemyslaw , Rodig Scott J. , Ouyang Jing , O'Donnell Evan , Takeyama Kunihiko , Mlynarski Wojciech , Mycko Katarzyna , Szczepanski Tomasz , Gaworczyk Anna , Krivtsov Andrei , Faber Joerg , Sinha Amit U. , Rabinovich Gabriel A. , Armstrong Scott A. , Kutok Jeffery L. , Shipp Margaret A. 
Published: March 2010

Abstract
Purpose: Patients with mixed lineage leukemia (MLL)–rearranged B-lymphoblastic leukemias (B-ALL) have an unfavorable prognosis and require intensified treatment. Multiple MLL fusion partners have been identified, complicating the diagnostic evaluation of MLL rearrangements. We analyzed molecular markers of MLL rearrangement for use in rapid diagnostic assays and found the immunomodulatory protein, Galectin-1 (Gal-1), to be selectively expressed in MLL-rearranged B-ALL.
Experimental Design: Transcriptional profiling of ALL subtypes revealed selective overexpression of Gal-1 in MLL-rearranged ALLs. For this reason, we analyzed Gal-1 protein expression in MLL-germline and MLL-rearranged adult and infant pediatric B-ALLs and cell lines by immunoblotting, immunohistochemistry, and intracellular flow cytometry of viable tumor cell suspensions. Because deregulated gene expression in MLL-rearranged leukemias may be related to the altered histone methyltransferase activity of the MLL fusion protein complex, we also analyzed histone H3 lysine 79 (H3K79) dimethylation in the LGALS1 promoter region using chromatin immunoprecipitation.
Results: Gal-1 transcripts were significantly more abundant in MLL-rearranged B-ALLs. All 32 primary MLL-rearranged B-ALLs exhibited abundant Gal-1 immunostaining, regardless of the translocation partner, whereas only 2 of 81 germline-MLL B-ALLs expressed Gal-1. In addition, Gal-1 was selectively detected in newly diagnosed MLL-rearranged B-ALLs by intracellular flow cytometry. The LGALS1 promoter H3K79 was significantly hypermethylated in MLL-rearranged B-ALLs compared with MLL-germline B-ALLs and normal pre-B cells.
Conclusion: In B-ALL, Gal-1 is a highly sensitive and specific biomarker of MLL rearrangement that is likely induced by a MLL-dependent epigenetic modification. Clin Cancer Res; 16(7); 2122–30. ©2010 AACR.
Relaxin Enhances S100A4 and Promotes Growth of Human Thyroid Carcinoma Cell Xenografts
Authors: Radestock Yvonne , Willing Cornelia , Kehlen Astrid , Hoang-Vu Cuong , Hombach-Klonisch Sabine 
Published: March 2010

Abstract
Relaxin increases cell motility and in vitro invasiveness in human thyroid carcinoma cells but the underlying molecular mechanisms of this action are largely unknown. In the present study, we show that relaxin transcriptionally upregulates the calcium-binding protein S100A4 (metastasin) and increases the cytosolic 10-kDa monomer and the 20-kDa dimer form of S100A4 in human thyroid carcinoma cells. The relaxin-induced increase in cell motility was blocked completely when S100A4 expression was diminished using an S100A4 small interfering RNA knockdown approach. We have shown previously the expression of the insulin-like family member relaxin in human thyroid carcinoma tissues but not in benign thyroid tissues. Human thyroid carcinoma tissues expressing relaxin also stained positive for S100A4. In nude mouse experiments, human thyroid carcinoma cell transfectants with constitutive expression of relaxin generated large and fast-growing tumors with significantly increased numbers of proliferating cells. We provide evidence in our cell model that the relaxin target protein S100A4 secreted by the thyroid carcinoma transfectants may not only enhance tumor cell motility but also promote xenograft angiogenesis as determined by the higher density of tumor microvessels and the angiogenic potential of S100A4 in in vitro tube formation assays. In conclusion, we have identified S100A4 as a major mediator of the actions of relaxin in thyroid carcinoma cell motility and in vivo thyroid tumor angiogenesis. Mol Cancer Res; 8(4); 494–506. ©2010 AACR.
Transcription Factor Egr-1 Is Essential for Maximal Matrix Metalloproteinase-9 Transcription by Tumor Necrosis Factor α
Authors: Shin Soon Young , Kim Ji Ho , Baker Andrew , Lim Yoongho , Lee Young Han 
Published: March 2010

AbstractMatrix metalloproteinase-9 (MMP-9) is involved in a wide range of normal and pathologic conditions, including inflammation, tissue repair, tumor invasion, and metastasis. Tumor necrosis factor α (TNFα) is a major proinflammatory cytokine that plays crucial roles in tumor progression, including tumor invasion and metastasis in the tumor microenvironment. Egr-1 is a member of the zinc-finger transcription factor family induced by diverse stimuli, including TNFα. However, the role of Egr-1 in MMP-9 expression was previously unknown. This study shows that Egr-1 directly binds to the MMP-9 promoter and plays an essential role for TNFα induction of MMP-9 transcription. Furthermore, Egr-1 together with NF-κB can synergistically activate both basal and TNFα-induced MMP-9 promoter activities in the presence of p300. We found that Egr-1 mediates extracellular signal–regulated kinase and c-jun NH2-terminal kinase mitogen-activated protein kinase–dependent MMP-9 transcription on TNFα stimulation. The requirement for Egr-1 in MMP-9 expression is further supported by the fact that HeLa cells expressing Egr-1 siRNA and Egr-1–null mouse embryonic fibroblasts were refractory to TNFα-induced MMP-9 expression. This report establishes that Egr-1 is essential for MMP-9 transcription in response to TNFα within the tumor microenvironment. Mol Cancer Res; 8(4); 507–19. ©2010 AACR.
Nano-Bio-Chip Sensor Platform for Examination of Oral Exfoliative Cytology
Authors: Weigum Shannon E. , Floriano Pierre N. , Redding Spencer W. , Yeh Chih-Ko , Westbrook Stephen D. , McGuff H. Stan , Lin Alan , Miller Frank R. , Villarreal Fred , Rowan Stephanie D. , Vigneswaran Nadarajah , Williams Michelle D. , McDevitt John T. 
Published: March 2010

Abstract
Oral cancer is a deadly and disfiguring disease that could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a noninvasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the epidermal growth factor receptor (EGFR) biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros, including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (P &lt; 0.0001), the nuclear-to-cytoplasmic ratio (P &lt; 0.0001), and EGFR biomarker expression (P &lt; 0.03). Further examination using logistic regression and receiver operating characteristic curve analyses identified morphologic features as the best predictors of disease (area under the curve ≤0.93) individually, whereas a combination of all features further enhanced discrimination of oral cancer and precancerous conditions (area under the curve, 0.94) with high sensitivity and specificity. Further clinical trials are necessary to validate the regression model and evaluate other potential biomarkers, but this pilot study supports the NBC sensor technique as a promising new diagnostic tool for early detection of oral cancer, which could enhance patient care and survival. Cancer Prev Res; 3(4); 518–28. ©2010 AACR.
The Detection of Chromosomal Aneusomy by Fluorescence In situ Hybridization in Sputum Predicts Lung Cancer Incidence
Authors: Varella-Garcia Marileila , Schulte Aline P. , Wolf Holly J. , Feser William J. , Zeng Chan , Braudrick Sarah , Yin Xiang , Hirsch Fred R. , Kennedy Timothy C. , Keith Robert L. , Barón Anna E. , Belinsky Steven A. , Miller York E. , Byers Tim , Franklin Wilbur A. 
Published: March 2010

Abstract
Lung cancer usually is disseminated (advanced) and has a poor prognosis at diagnosis. Current and former smokers are at a high risk for lung cancer and are candidates for prevention and early detection strategies. Sputum is a potential source of biomarkers that might determine either lung cancer risk or the presence of early lung cancer, but no current sputum test is sufficiently sensitive and specific for effective screening. We used fluorescence in situ hybridization (FISH) to measure chromosomal aneusomy (CA) in sputum samples collected prospectively from 100 incident lung cancer cases and 96 controls (matched on age, gender, and date of collection) nested within an ongoing high-risk cohort. The CA-FISH assay was aimed at four DNA targets: epidermal growth factor receptor, MYC, 5p15, and CEP 6. The sensitivity of a positive CA-FISH assay (abnormal for two or more of the four markers) for lung cancer was substantially higher for samples collected within 18 months (76% sensitivity) than for samples collected more than 18 months (31%) before lung cancer diagnosis. Sensitivity was higher for squamous cell cancers (94%) than for other histologic types (69%). CA-FISH specificity based on samples collected within 18 months before diagnosis was 88%. The adjusted odds ratio (OR) of lung cancer for specimens collected within 18 months before a cancer diagnosis was higher for the CA-FISH assay [OR, 29.9; 95% confidence interval (95% CI), 9.5-94.1] than for previously studied ORs of cytologic atypia (OR, 1.8; 95% CI, 1.3-2.6) and gene promoter methylation (OR, 6.5; 95% CI, 1.2-35.5). Whether CA-FISH is an indicator of extreme risk for incident lung cancer or detects exfoliated cancer cells is unknown. The apparent promise of CA-FISH in sputum for assessing lung cancer risk and/or for lung cancer early detection now needs to be validated in a clinical screening trial. Cancer Prev Res; 3(4); 447–53. ©2010 AACR.
Vaccine against MUC1 Antigen Expressed in Inflammatory Bowel Disease and Cancer Lessens Colonic Inflammation and Prevents Progression to Colitis-Associated Colon Cancer
Authors: Beatty Pamela L. , Narayanan Sowmya , Gariépy Jean , Ranganathan Sarangarajan , Finn Olivera J. 
Published: March 2010

Abstract
Association of chronic inflammation with an increased risk of cancer is well established, but the contributions of innate versus adaptive immunity are not fully delineated. There has furthermore been little consideration of the role played by chronic inflammation–associated antigens, including cancer antigens, and the possibility of using them as vaccines to lower the cancer risk. We studied the human tumor antigen MUC1 which is abnormally expressed in colon cancers and also in inflammatory bowel disease (IBD) that gives rise to colitis-associated colon cancer (CACC). Using our new mouse model of MUC1+ IBD that progresses to CACC, interleukin-10 knockout mice crossed with MUC1 transgenic mice, we show that vaccination against MUC1 delays IBD and prevents progression to CACC. One mechanism is the induction of MUC1-specific adaptive immunity (anti-MUC1 IgG and anti-MUC1 CTL), which seems to eliminate abnormal MUC1+ cells in IBD colons. The other mechanism is the change in the local and the systemic microenvironments. Compared with IBD in vaccinated mice, IBD in control mice is dominated by larger numbers of neutrophils in the colon and myeloid-derived suppressor cells in the spleen, which can compromise adaptive immunity and facilitate tumor growth. This suggests that the tumor-promoting microenvironment of chronic inflammation can be converted to a tumor-inhibiting environment by increasing adaptive immunity against a disease-associated antigen. Cancer Prev Res; 3(4); 438–46. ©2010 AACR.
The Ultimate in Cancer Chemoprevention: Cancer Vaccines
Authors: Disis Mary L. 
Published: March 2010

Abstract
This perspective on Beatty et al. (beginning on page 438 in this issue of the journal) discusses the role of the immune system as nature's ultimate chemoprevention agent. A successful immune response to vaccination results in immunologic memory. In the case of a successful cancer-related response, antigen-specific T cells will be poised to destroy an aberrantly expressed protein even if the host is not exposed until years after the end of immunizations. After the abnormal cell is eradicated, T cells will lie in wait for the next exposure. The ability to develop effective cancer vaccines for prevention is fast becoming a reality as immunogenic aberrant proteins that drive malignant transformation are identified. Cancer Prev Res; 3(4); 406–9. ©2010 AACR.
Reversible Record Breaking and Variability: Temperature Distributions across the Globe
Authors: Anderson Amalia , Kostinski Alexander 
Published: March 2010

AbstractBased on counts of record highs and lows, and employing reversibility in time, an approach to examining natural variability is proposed. The focus is on intrinsic variability; that is, variance separated from the trend in the mean. A variability index α is suggested and studied for an ensemble of monthly temperature time series around the globe. Deviation of 〈α〉 (mean α) from zero, for an ensemble of time series, signifies a variance trend in a distribution-independent manner. For 15 635 monthly temperature time series from different geographical locations (Global Historical Climatology Network), each time series about a century-long, 〈α〉 = −1.0, indicating decreasing variability. This value is an order of magnitude greater than the 3σ value of stationary simulations. Using the conventional best-fit Gaussian temperature distribution, the trend is associated with a change of about −0.2°C (106 yr)−1 in the standard deviation of interannual monthly mean temperature distributions (about 10%).
Composite Structure of Monsoon Low Pressure Systems and Its Relation to Indian Rainfall
Authors: Krishnamurthy V. , Ajayamohan R. S. 
Published: March 2010

AbstractThe tropical disturbances formed in the Bay of Bengal and the Arabian Sea and over land points in central India, known as low pressure systems (LPSs), are shown to contribute significantly to the seasonal monsoon rainfall over India. Analyses of daily rainfall over India and statistics of the LPSs for the period of 1901–2003 show that the rainfall pattern when the LPSs are present captures the most dominant daily rainfall pattern that represents the active monsoon phase. The rainfall pattern when the LPSs are absent is similar to the pattern representing the break monsoon phase. The location, number, and duration of the LPSs are found to be closely related to the phases and propagation of the dominant intraseasonal modes of the Indian rainfall. The LPSs are also associated with the strengthening of the monsoon trough and low-level monsoon winds. The number of LPSs and their total duration and the corresponding rainfall during July and August exceed those in June and September. The LPS tracks reach up to northwest India during flood years, whereas they are confined to central India during drought years. However, the contribution of rainfall during the LPSs to the total seasonal rainfall is same during flood or drought years. Although the LPSs seem to play an important role in the monsoon rainfall, they alone may not determine the interannual variability of the seasonal mean monsoon rainfall.
Perceived Access to Contraception Among Adolescents With Diabetes
Authors: Schwarz Eleanor B. , Sobota Mindy , Charron-Prochownik Denise 
Published: March 2010

Purpose The purpose of this study was to assess beliefs, perceived access to, and practices regarding contraception among adolescent women with type 1 diabetes. Methods Eighty-nine females with type 1 diabetes between the ages of 13 and 19 years, who were recruited from 2 endocrinology practices as part of a larger study, completed a battery of questionnaires designed to assess variables relevant to discussions of sexuality, preconception counseling, contraception, and pregnancy. In addition, items were designed to explore adolescents’ relationship with their health care provider and comfort requesting birth control. Baseline data were analyzed using descriptive statistics. Results Half of the sexually active adolescents in this sample reported having had sex without birth control at a time they were trying to avoid pregnancy. A third (36%) of subjects felt that women with diabetes have very limited choices of birth control, and 43% incorrectly believe that all birth control methods are less effective when used by women with diabetes. Less than half (47%) reported that they had discussed birth control with a health care professional, and 29% of subjects reported they had not received formal instruction on birth control in any setting. Perhaps of greatest concern, only 69% stated they would feel comfortable asking a professional for birth control. Conclusion Many adolescent women with diabetes are at risk of unintended pregnancy and do not feel comfortable asking a health professional for birth control. Diabetes educators who initiate preconception counseling at puberty and discuss contraceptive options with adolescent women with diabetes may improve pregnancy outcomes.
Positive Effect of an Autologous Platelet Concentrate in Lateral Epicondylitis in a Double-Blind Randomized Controlled Trial
Authors: Peerbooms Joost C. , Sluimer Jordi , Bruijn Daniël J. , Gosens Taco 
Published: March 2010

Background Platelet-rich plasma (PRP) has shown to be a general stimulation for repair. Purpose To determine the effectiveness of PRP compared with corticosteroid injections in patients with chronic lateral epicondylitis. Study Design Randomized controlled trial; Level of evidence, 1. Patients The trial was conducted in 2 teaching hospitals in the Netherlands. One hundred patients with chronic lateral epicondylitis were randomly assigned in the PRP group (n = 51) or the corticosteroid group (n = 49). A central computer system carried out randomization and allocation to the trial group. Patients were randomized to receive either a corticosteroid injection or an autologous platelet concentrate injection through a peppering technique. The primary analysis included visual analog scores and DASH Outcome Measure scores (DASH: Disabilities of the Arm, Shoulder, and Hand). Results Successful treatment was defined as more than a 25% reduction in visual analog score or DASH score without a reintervention after 1 year. The results showed that, according to the visual analog scores, 24 of the 49 patients (49%) in the corticosteroid group and 37 of the 51 patients (73%) in the PRP group were successful, which was significantly different (P < .001). Furthermore, according to the DASH scores, 25 of the 49 patients (51%) in the corticosteroid group and 37 of the 51 patients (73%) in the PRP group were successful, which was also significantly different (P = .005). The corticosteroid group was better initially and then declined, whereas the PRP group progressively improved. Conclusion Treatment of patients with chronic lateral epicondylitis with PRP reduces pain and significantly increases function, exceeding the effect of corticosteroid injection. Future decisions for application of the PRP for lateral epicondylitis should be confirmed by further follow-up from this trial and should take into account possible costs and harms as well as benefits.
Cost savings from dose rounding of biologic anticancer agents in adults
Authors: Winger Brenda J , Clements Elizabeth A , DeYoung Jaculin L , O'Rourke Timothy J , Claypool Deborah L , Vachon Steve , VanDyke Thomas H , Zimmer-Young Jennifer , Kintzel Polly E 
Published: March 2010

Purpose: The purpose of this project was to determine the cost savings related to a dose-rounding process for adult biologic anticancer agents. Methods: Biologic anticancer agents prepared by the inpatient pharmacy were identified retrospectively through completed chemotherapy preparation checklists and medication orders on file in the pharmacy or by the clinical pharmacist for adult oncology from the medical records of patients in her practice. The specific products screened for evaluation were aldesleukin, bevacizumab, cetuximab, denileukin diftitox, gemtuzumab, rituximab, and trastuzumab. Data collected included drug name, ordered dose, rounded dose, and product vials not wasted. Specific drug costs were provided by the department’s purchasing office. The project was reviewed and approved by the institutional review board to allow retrospective data collection from patient records. Cost savings were evaluated retrospectively for the time period of January 1, 2005 through March 31, 2005. Results: One hundred and twenty-six orders for biologic anticancer agents were processed by the pharmacy department during the 3-month time period of data collection. Dose rounding could reduce drug wastage for 42% of these orders. Potential cost savings from dose rounding was $24,434 for the 3-month interval evaluated. However, nonadherence to dose rounding for 29 rituximab orders decreased the actual cost savings to $15,922. Individual staff education was reinforced to address nonadherence. Conclusion: Routine dose rounding of biologic anticancer agents to an amount within 10% of the ordered dose achieved cost savings through reduction of drug wastage at our institution.