bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5712: Identification and characterization of high affinity thioaptamer ligands against E-selectin
Authors: Mann Aman , Somasunderam Anoma , Nieves Rene , Gorenstein David , Ferrari Mauro , Tanaka Takemi 
Published: February 2011

Abstract
E-selectin (CD62E, ELAM-1 or LECAM-2) is a calcium dependent cell surface glycoprotein that mediates an adhesion of leukocytes on inflamed endothelium through recognition of specific carbohydrate ligands, sialyl Lewis X (sLeX) and sialyl Lewis A (sLeA). E-selectin expression is transcriptionally induced by NF-κB and AP-1 in response to inflammatory cytokines such as IL-1 and TNF-alpha. Accordingly, elevated E-selectin expression was reported in many types of acute and chronic inflammatory diseases including cancer. Aberrant homing of leukocytes to tumor results in tumor progression and local invasion. In addition, E-selectin and its counter ligands have also been reported to trigger the initial adhesive step of circulating cancer cells to endothelial cells. Therefore, blockade of E-selectin is a promising therapeutic strategy to control pathological infiltration of leukocytes and/or metastatic cancer cells. Thioaptamers (TA) are single stranded DNA molecules with thio substitution in the phosphate backbone, which provide stability against nucleases. Thioaptamer can fold into tertiary structures and bind with high affinity and specificity to a target molecule, and thus suitable for in vivo applications. In this study, we aimed to identify thioaptamer ligands that bind to E-selectin with high affinity and specificity. To achieve this goal, we used two-step selection strategies, recombinant protein based thioaptamer selection from a combinatorial thioaptamer library that contains 10E14 random sequences, followed by a cell based binding to tetracycline inducible E-selectin endothelial cells.
We selected 14 different groups of thioaptamer candidates following 10 iterative cycles of binding to recombinant E-selectin protein. Using Tet-on inducible E-selectin endothelial cells, we identified the lead three TA candidates that bind to E-selectin on the surface of endothelial cells at high affinity (nM range) and specificity. In addition, the TA bound to tumor associated vasculature that express E-selectin. Moreover, the TA selected demonstrated significant inhibition of leukocyte adhesion to E-selectin positive endothelial cells at low nanomolar concentrations. In summary, we identified antagonistic TA against E-selectin that binds to endothelial cells and interferes with leukocyte bindings at nM range. Potential applications of this TA could be for 1) inflamed tumor vasculature selective targeted delivery of therapeutic molecules or drug delivery carriers 2) the prevention of pathological diapedesis of leukocytes and/or metastatic cancer cells. We are currently investigating potential clinical applications of the TA.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5712.
Abstract 5716: A study on the mechanism of the chemopreventive effect of different ratios of fish oil and corn oil in experimental colon carcinogenesis
Authors: Agnihotri Navneet , Sarotra Pooja , Sharma Gayatri , Kansal Shevali 
Published: February 2011

Abstract
AIM: The present study was designed to study the effect of different ratios of n-3 rich fish oil and n-6 rich corn oil in the prevention of colon cancer mediated through cell signaling and apoptosis.
Methods: Male Wistar rats were divided into the following groups -
Group-I and Group-II were fed synthetic diets and Group-III and Group-IV modified synthetic diets with 1:1 and 2.5:1 ratio of fish oil and corn oil for 4 weeks. All the groups except group-I (vehicle treated) received 4 injections of dimethyl hydrazine (DMH). The DMH injections were given after initiation on the synthetic diet for a week and subsequently received one injection per week. The animals were sacrificed 48 hrs after last injection. The last 10cm of the distal colon was used for histopathological study while the rest was used for isolation of colonocytes. The differential effect of the different ratios of oil on oxidative stress by measuring reactive oxygen species’(ROS) generation by FACS analysis using dichlorofluorescin diacetate (DCFH-DA) and p53 levels using monoclonal antibody was assessed. The apoptosis was evaluated by DNA fragmentation and by using M30 cytodeath antibody. To understand the role of mitochondria in apoptosis mitochondrial membrane potential was measured using JC-1. Akt levels were also measured using a monoclonal antibody in orderto understand its effect on p53 and apoptosis.
Results: In the carcinogen administered animals as compared to the vehicle treated animals, there was- 1.mild to moderate inflammation 2. a decrease in ROS levels 3. a decrease in p53 4. an increase in apoptosis 5. an increase in mitochondrial membrane potential 6. an increase in Akt.
Administration of fish oil and corn oil led to the following- 1. Fish oil feeding in the ratio 1:1 showed severe inflammation in the animals while feeding a higher ratio showed mild inflammation with normal mucosa. 2. a decrease in ROS levels with equal ratios as compared to the higher ratio of fish oil. 3. an increase in p53 levels with both the ratios 4. a decrease in apoptosis 5. a decrease in mitochondrial membrane potential 6. a decrease in Akt in equal ratios but a significant increase in the higher ratios.
Conclusion: The results of the present study suggest that administration of fish oil in the higher ratio has a beneficial role in colon cancer as shown by histopathological examination. Fish oil derived n-3 PUFA exerts chemopreventive effect mediated by interplay among oxidative stress, apoptosis and cell survival signals depending on the dosage.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5716.
Abstract 5720: Chromosomal instability predicts the progression of premalignant oral lesions
Authors: Hamers Rinske MPT , Siebers Theke JH , Haesevoets Annick , Zwijnenberg Iris R. , Voogd Adri C. , Ramaekers Frans CS , Kremer Bernd , Merkx Thijs MAW , Slootweg Pieter J. , Speel Ernst-Jan M. 
Published: February 2011

Abstract
A major dilemma in the management of patients with precursor lesions of the oral mucosa lies in deciding which lesions will progress into carcinoma. Because a strong association between histological differentiation and clinical prognosis is lacking, the aim of this study was to evaluate the value of chromosomal instability (CIN) detected by fluorescence in situ hybridization (FISH) for the identification of oral premalignant lesions at risk for progression.
We examined a series of premalignant oral mucosa lesions of 106 patients by means of FISH on paraffin-embedded tissue sections using biotin- and digoxigenin-labeled probes specific for the centromeric regions of chromosomes 1 and 7. CIN was indicated by the presence of chromosome imbalances and/or polyploidization for chromosomes 1 and 7. Results were correlated with histopathological data as well as with clinical follow up data.
The 5-year progression-free survival rate was 83%. Outcome of routine histopathology did only predict malignant progression when comparing severe dysplasia with lower stage precursor lesions (hyperplasia, mild en moderate dysplasia) (p&lt;0.001). CIN was detected in all different subgroups of histopathological differentiation. Moreover, the percentage of precursor lesions harboring CIN increased with progressing histopathological stage. CIN was significantly associated with a lower progression-free survival as compared with lesions without CIN (p&lt;0.001).
In conclusion, tumorigenesis of the oral mucosa is associated with the development of CIN, which can reliably identify lesions at risk for progression.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5720.
Abstract 573: 18alpha- glycyrrhetinic acid (AGA) inhibits advanced prostate cancer cell proliferation and induces apoptosis by downregulating inflammation-related cytokine growth factor genes
Authors: Munirathinam Gnanasekar , Dakshinamoorthy Gajalakshmi , Olesen John Eric , Sivasakthivel Thirugnanam , Zheng Guoxing , Chen Aoshuang , Bosland Maarten , Kajdacsy-Balla André , Kalyanasundaram Ramaswamy 
Published: February 2011

Abstract
Glycyrrhetinic acid is an active triterpenoid metabolite of glycyrrhizin abundantly present in licorice roots. Glycyrrhetinic acid exists as alpha and beta stereo-isomeric forms. Both stereo-isomeric forms are known to have anti-inflammatory and anti-cancer activity. However, the effects and anti-cancer mechanism of alpha glycyrrhetinic acid in prostate cancer cells is not yet evaluated. Therefore in this study, we have investigated the growth inhibition, induction of apoptosis and the anti-cancer mechanisms of 18α-glycyrrhetinic acid (AGA) on androgen independent metastatic prostate cell line DU-145. Our results showed that AGA inhibited proliferation and growth of these cells in a time and dose dependent manner. Induction of apoptosis was confirmed by Annexin V-FITC and propidium iodide staining. Further analysis showed that AGA treatment activated caspase- 8 and −3 death related enzymes in DU-145 cells. Interestingly, AGA treatment also simultaneously down regulated the expression of proinflammatory cytokine/growth factor genes HMGB1, IL-6 and IL-8. This is the first report demonstrating that AGA could play a dual role as an inducer of apoptosis and suppressor of pro-inflammatory gene expression in DU-145 prostate cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 573.
Abstract 5736: Household endotoxin levels and risk of non-Hodgkin lymphoma
Authors: Wang Jun , Colt Joanne S. , Thorne Peter S. , Berhane Kiros T. , Richard Severson K. , Davis Scott , Cerhan James R. , Ward Mary H. , Bernstein Leslie , Morton Lindsay M. , Patricia Hartge , Cozen Wendy 
Published: February 2011

Abstract
Subclinical variation in immune response may be a risk factor for non-Hodgkin lymphoma (NHL). Endotoxin is a substance located in the cell wall of gram-negative bacteria that elicits a strong innate and inflammatory immune response. It is present in large amounts in animal and human fecal material, other organic material, and cigarette smoke. We hypothesized that higher endotoxin exposure might be a risk factor for NHL because of its effect on B-cell activation. Using a population based, multi-center (Detroit, Iowa, Los Angeles and Seattle) case-control study, we evaluated the association between endotoxin levels in carpet dust and NHL risk. During an in-person interview, we collected used vacuum cleaner bags from participants who had used their vacuum within the past year and had owned at least half of their carpets or rugs for 5 years or more. Dust samples were analyzed using the kinetic chromogenic Limulus amebocyte lysate assay in the Pulmonary Toxicology Facility, University of Iowa. Endotoxin measurements from 629 cases and 467 controls were log-transformed and evaluated as both continuous and categorical variables. In order to examine a possible threshold effect, endotoxin levels among controls were categorized into tertiles, with the highest tertile further split into two equal groups based on a preliminary model search. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for sex, age, race, education, study center, and last change of vacuum bag. The highest category of household endotoxin level in dust was associated with a 35% significantly decreased risk of NHL relative to the lowest category (95% confidence interval [CI] = 0.44, 0.96). The effect was stronger for the diffuse large B-cell lymphoma (DLBCL) subtype (Odds Ratio [OR]= 0.49; 95% CI= 0.26,0.91). In conclusion, contrary to our initial hypothesis, our results suggest an inverse association between high levels of household endotoxin and NHL risk. Further studies are needed to validate this finding, ideally with endotoxin measurements prior to diagnosis. Possible mechanisms of action will be discussed.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5736.
Abstract 5737: Parity and lactation in relation to ER-/PR- breast cancer in African American women
Authors: Palmer Julie R. , Boggs Deborah A. , Adams-Campbell Lucile L. , Rosenberg Lynn 
Published: February 2011

Abstract
Women of African ancestry are more likely than women of European ancestry to be diagnosed with aggressive tumors characterized by negative staining for estrogen receptors (ER) and progesterone receptors (PR). Reasons for the disparity are unclear, and previous studies have lacked statistical power to investigate risk factors for the more aggressive subtypes. A recent report from the Carolina Breast Cancer Study indicated that basal-like breast cancer, a subtype of breast tumors with ER-, PR-, HER2-, HER1+ and/or CK5/6+ characteristics, was positively associated with increased parity, whereas other subtypes were inversely associated with parity. The increased risk of basal-like cancer was strongest for parous women who had never breastfed. The majority of breast tumors with negative staining for both ER and PR would likely be classified as basal-like. We examined the relation of parity and lactation to risk of ER-/PR- breast cancer among 59,000 African American women from the Black Women's Health Study in 12 years of follow-up data. Reproductive history was obtained by questionnaire at baseline in 1995 and updated every two years. ER and PR status were obtained from pathology reports and state cancer registry records. Included in this analysis were 809 incident breast cancer cases with complete data on ER and PR status, with 285 classified as ER-/PR-, 395 as ER+/PR+, 114 as ER+/PR-, and 15 as ER-/PR+. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were derived from proportional hazard models for the relation of each reproductive factor to risk of specific tumor subtype, with control for all other reproductive factors, age, region, education, body mass index, waist-hip ratio, hormone use, alcohol, smoking, and physical activity. Risk of ER-/PR- breast cancer increased with increasing parity (p trend = 0.02), whereas risk of ER+/PR+ cancer decreased with increasing parity (p trend = 0.0002). For ER-/PR- breast cancer, the IRR for women who had 3+ births and never breastfed relative to nulliparous women was 1.66 (95% CI 1.09-2.54). The increased risk associated with higher parity was ameliorated by breast feeding: the comparable IRR for women who had 3+ births but breastfed at least one of the babies was 1.01 (95% CI 0.63-1.63). These results from a cohort of African American women support findings from the previous study of basal-like breast cancer and are consistent with the hypothesis that pregnancy and breastfeeding may influence risk of ER-/PR- cancer through inflammatory/immune system alterations linked to mammary gland involution.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5737.
Abstract 5742: Hand pattern and prostate cancer risk
Authors: Rahman Aneela A. , Lophatananon Artitaya , Harris Duncan , Anderson John , Easton Douglas , Key Tim , Pocock Richard , Dearnaley David , Guy Michelle , Edwards Steven , O'Brien Lynne , Wilkinson Rosemary A. , Hall Amanda L. , Sawyer Emma , Page Elizabeth , Liu Jo-Fen , Eeles Rosalind , Muir Kenneth 
Published: February 2011

Abstract
ABSTRACT
Background
Hand pattern (pattern of index compared to ring finger on the right hand, 2D:4D) has been studied for a number of decades as a potential predictor for disease occurrence. It is known to be associated with certain hormone related diseases developed during adult life but there have been no studies so far of 2D:4D ratio and prostate cancer risk. This study assesses the association between hand and prostate cancer.
Methods
We analysed the right hand pattern and prostate cancer risk in 1524 cases aged ≤ 80 and 3044 population-based controls. Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate logistic regression (to allow for adjustment of confounders) estimating whether there was any association between right hand pattern and the risk of prostate cancer.
Results
The reference group was chosen to be the commonest hand pattern seen in males which is index finger shorter than ring finger. Compared to this group there was no difference in men with index finger equal to ring finger (OR 1.05, 95% CI 0.88-1.25) whereas men with index finger longer than ring finger showed a negative association indicative of a marker of a protective effect with a 33% risk reduction compared to index finger shorter than ring finger (OR 0.67, 95% CI 0.57-0.80).
Conclusion
This study showed that the pattern of finger lengths appears to be a community based surrogate marker of prostate cancer risk with length of 2D greater than 4D indicative of lower risk which has previously been shown to be also associated with lower prenatal testicular activity.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5742.
Abstract 5753: RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
Authors: Hatzivassiliou Georgia , Song Kyung , Yen Ivana , Brandhuber Barbara J. , Anderson Daniel J. , Alvarado Ryan , Ludlam Mary JC , Stokoe David , Gloor Susan L. , Vigers Guy , Morales Tony , Aliagas Ignacio , Liu Bonnie , Sideris Steve , Hoeflich Klaus , Jaiswal Bijay S. , Seshagiri Somasekar , Koeppen Hartmut , Belvin Marcia , Friedman Lori S. , Malek Shiva 
Published: February 2011

Abstract
Activating mutations in KRAS or B-RAF are found in over 30% of all human tumors and targeting this pathway could have broad therapeutic impact. Small molecule ATP-competitive RAF kinase inhibitors have potent anti-tumor effects on B-RAFV600E tumors but, in contrast to MEK inhibitors, are not potent against RAS mutant tumor models, despite RAF functioning as a key effector downstream of RAS and upstream of MEK. In this study we show that ATP-competitive RAF inhibitors have two opposing mechanisms of action depending on cellular context. In B-RAFV600E tumors, RAF inhibitors effectively block the MAPK signaling pathway and decrease tumor growth. Surprisingly, in KRAS mutant and RAS/RAF wildtype tumors, RAF inhibitors activate the RAF/MEK/ERK pathway in a RAS-dependent manner, thus enhancing tumor growth in some xenograft models. Inhibitor binding activates wildtype RAF isoforms by inducing dimerization, membrane localization and interaction with RAS-GTP. These events occur independently of kinase inhibition and are, rather, linked to direct conformational effects of inhibitors on the RAF kinase domain. Based on these findings, we demonstrate that ATP-competitive kinase inhibitors can have opposing functions as inhibitors or activators of signaling pathways, depending upon cellular context. In addition, this work provides new insights into the therapeutic use of ATP-competitive RAF inhibitors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5753.
Abstract 5760: 14-3-3zeta cooperates with ErbB2 to promote ductal carcinoma in situ progression to invasive breast cancer by inducing epithelial-mesenchymal transition
Authors: Lu Jing , Li Ping , Yu Dihua 
Published: February 2011

Abstract
ErbB2, a metastasis-promoting oncoprotein, is overexpressed in approximately 25% of invasive/metastatic breast cancers, but in 50%-60% of noninvasive ductal carcinomas in situ (DCIS). It has been puzzling how a subset of ErbB2-overexpressing DCIS develops into invasive breast cancer (IBC). We found that co-overexpression of 14-3-3zeta in ErbB2-overexpressing DCIS conferred a higher risk of progression to IBC. ErbB2 and 14-3-3zeta overexpression, respectively, increased cell migration and decreased cell adhesion, two prerequisites of tumor cell invasion. 14-3-3zeta overexpression reduced cell adhesion by activating the TGF-beta/Smads pathway that led to ZFHX1B/SIP-1 upregulation, E-cadherin loss, and epithelial-mesenchymal transition. Importantly, patients whose breast tumors overexpressed both ErbB2 and 14-3-3zeta had higher rates of metastatic recurrence and death than those whose tumors overexpressed only one. Therefore, we discovered that 14-3-3zeta overexpression is a “second hit” or “risk factor” facilitating a subset of ErbB2-overexpressing DCIS transition into IBC and identified molecular mechanisms/pathways through which ErbB2 and 14-3-3zeta co-overexpression promotes invasion. This study identified biomarkers that allow selection of high-risk DCIS patients for more aggressive treatments at early stages of cancer development, while saving low-risk patients from ablative clinical procedures. Moreover, it provided promising targets for future intervention strategies to prevent DCIS progression to IBC.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5760.