bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3553: Modulation of pro-inflammatory signaling pathways by aging T-lymphocytes contributes to a more malignant phenotype in prostate epithelial cells
Authors: Alejandra De Angulo , Faris Robert , Cavazos David , deGraffenried Linda , Jolly Chris 
Published: August 2012

Abstract
Prostate cancer risk is determined largely by age. While some studies have suggested that the slow growing rate of prostate cancer is responsible for the link between aging and prostate cancer, the role of aging T-cells in prostate cancer development remains largely unknown. The objective of this study is to determine how age-related changes in T-lymphocyte function contribute to prostate tumorigenesis. We hypothesized that age related changes in T-lymphocyte function, to a pro-inflammatory phenotype may promote prostate cancer development. For our studies we used the GPAT-1 KO mice model. The GPAT-1 KO mice have T-lymphocytes that mimic aged T-cells. Preliminary data shows that, in agreement with what has been seen in human aged T-cells, aging-mimic GPAT-1 KO T-lymphocytes generate more pro-inflammatory cytokines than T-lymphocytes from age matched wild-type mice. These cytokines turn on inflammatory pathways that stimulate proliferation, tissue disruption and tumor growth. A cytokine array was used to detect the relative protein levels of 40 different cytokines and chemokines in the sera from either young GPAT-1 knockout (KO), young wild-type (WT) or old mice (22 months). We observed a shift to a more pro-inflammatory cytokine profile in the GPAT-1 KO and old mice. Many of the same cytokines that were elevated in the sera from the old and GPAT-1 KO mice, such as IL-17 and IL-6, are also implicated in promoting prostate tumorigenesis primarily through induction of other inflammatory cytokines and transcription factors such as, NF-kB and STAT3. The objective of this study was to determine if the increased levels of pro-inflammatory cytokines in the sera from the GPAT-1 KO mice correlates to a more malignant phenotype in prostate epithelial cells. Malignancy in epithelial cells was assessed by the following phenotypical changes: Immortalization, anchorage independence, proliferation and invasiveness. Exposure to sera from the GPAT-1 KO mice promoted phenotypical changes in epithelial cells that are indicative of early tumorigenesis. Taken together our data suggests that pro-inflammatory cytokines in the sera from mice with aging T-lymphocytes may turn on pro-inflammatory pathways that contribute to a more malignant phenotype in prostate epithelial cells. This is the first study to use the GPAT-1 KO mice model to explore the relationship between aging T-lymphocytes, inflammation and prostate tumorigenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3553. doi:1538-7445.AM2012-3553
Abstract 3568: Progression from benign breast disease to cancer in women with a family history of breast cancer
Authors: Israel Sarah , Warzecha Hind , Gross Amy L. , Tatsas Armanda , Lee Andrew , May Betty , Axilbund Jennifer , Khouri Nagi , Jacobs Lisa , Armstrong Deborah , Visvanathan Kala 
Published: August 2012

Abstract
Background: In the general population, benign breast disease (BBD) is an established risk factor for breast cancer, with increased risks ranging from 20 to 50% for atypical proliferative subtypes. There is limited data on the incidence of atypical hyperplasia (AH) and its association with breast cancer risk specifically among women with a strong family history (FH). Methods: In an ongoing, prospective cohort of women with a FH of breast cancer and/or a BRCA1/2 mutation who attend the Breast and Ovarian Surveillance Service (BOSS) at Johns Hopkins (N=1,132), we identified 259 pathology confirmed incident BBD cases diagnosed between 1959 to 2010. Slides were obtained for re-review and evaluation of specific histologic features. Cox proportional hazards models were used to estimate the risk of breast cancer relative to BBD subtype. Results: Of the incident BBD diagnoses, 61.4% were non-proliferative, 26.3% were proliferative without atypia, and 12.4% were AH. AH cases were diagnosed at an older age (p-value=0.04) and were less likely to have a strong FH (p-value=0.01) as compared to non-atypical subtypes. Sixty-one BBD cases progressed to cancer and the median time to diagnosis was significantly shorter for cases of AH (4.2 years) than for non-proliferative disease (8.8 years) (p&lt;0.01). Women with AH were 2.36 (95% confidence interval (CI): 1.15, 4.87) times more likely to develop in-situ or invasive breast cancer compared to non-proliferative cases, adjusting for age and year of incident BBD. In models additionally adjusting for BRCA1/2 mutation status and degree of FH, women with AH had a 4.5-fold (95% CI: 2.16, 9.53) increased risk of breast cancer. BBD subtype and degree of FH were found to be independent risk factors for breast cancer. Prophylactic mastectomy and tamoxifen use post BBD diagnosis did not differ by BBD subtype or the total number of BBD diagnoses. Conclusion: Given the high incidence of AH in this cohort and the increased risk of breast cancer associated with this subtype, AH may be a viable target for preventative strategies in women with a FH of breast cancer. Further, AH does not seem to track with a stronger FH, suggesting two different breast cancer pathways.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3568. doi:1538-7445.AM2012-3568
Abstract 3586: Epigenetic influence on ethnic disparities in non-small cell lung cancer
Authors: Buckingham Lela E. , Sekosan Marin , Ferrar Karen , Hadziahmetovic Emira , Lad Thomas 
Published: August 2012

Abstract
African Americans are more likely to develop lung cancer and die from it than any other ethnic group. Complex biological, environmental, political and cultural factors contribute to this disparity. The purpose of the current project is to examine the relationship between epigenetic factors, gender, ethnicity and outcome in a retrospective study of patients with surgically-treated early stage lung cancer. Fixed primary tumor tissues from a private (RMC) and a public (JHS-CCH) institution were analyzed in this study. The RMC group consisted of 132 patients with stage Ib, IIa and IIb NSCLC, 22% African-American (AA) and 52% female. The JHS-CCH group consisted of 88 patients, 62% AA and 43% female. Five year survival was achieved by 85% of women vs 67% of men in the RMC group (Chi square p=0.022). 68% of Caucasians vs 53% AA survived five years in the RMC group (p=0.186). To investigate the role of epigenetic influences on survival, promoter methylation of Ras association domain family protein 1, RASSF1A, was investigated. Associations between inactivation of the RASSF1A tumor suppressor and poor outcome in lung and other cancers have been reported in several studies. Promoter methylation was quantified using pyrosequencing. Percent methylation of RASSF1 at cytosine position –36 (A of ATG=+1) was more frequent in AA (41% of cases) than in Caucasians (20% of cases) in the RMC group (p=0.023) compared to 69% of cases in the JHS-CCH group. Methylation levels of RASSF1 at all CpG sites tested were higher in the JHS-CCH group than in the RMC group. Kaplan-Meier analysis was performed on dichotomized hypermethylation status compared to five-year survival (5YS). Promoter hypermethylation of RASSF1 was significantly associated with shortened 5YS in AA (p=0.005), compared to Caucasians (p=0.197) in the RMC group. Although 5YS was marginally shortened with hypermethylation of RASSF1 in men in the RMC group (p=0.123), no significant effects were seen with regard to gender. These results suggest that biomarkers can have differential effects, based on genetic background and support analysis of epigenetic biomarkers to address disparities and develop more personalized treatment strategies for individual patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3586. doi:1538-7445.AM2012-3586
Abstract 3589: Comparative expression profile of transmembrane mucin MUC1 in breast cancer from American Indian and Caucasian women
Authors: Maher Diane M. , Stephenson Phillip , Gupta Brij K. , Bauer Nichole A. , Koch Michael , Eliason Susan , Jaggi Meena , Chauhan Subhash C. 
Published: August 2012

Abstract
Introduction: Considerable disparity exists in breast cancer incidence and mortality among different racial/ethnic populations and geographic locations. For unknown reasons, American Indian women of the Northern Plains have a greater incidence and higher death rate due to breast cancer than Caucasian women living in the same geographical region. Additionally, American Indian women living in the Northern Plains also have a much higher incidence and death rate due to breast cancer than American Indian women living elsewhere in the United States. To investigate the potential molecular basis for this cancer health disparity, we have compared the expression profile of transmembrane mucin, MUC1 on breast cancer cases from American Indian and Caucasian women living on the Northern Plains. MUC1 is known to be overexpressed in breast cancer and nuclear localization of MUC1 can have downstream effects on cell signaling and increase oncogenic phenotypes. We are also exploring the link between smoking, exposure to HPV infection, and the development of breast cancer in American Indian women. Methods: We have examined the expression profile of MUC1 in breast cancer tissue from American Indian (n=40) and Caucasian (n=60) women. The staining was analyzed by experienced pathologists and scored according to intensity (0-4) and percent of cancer cells stained positive (0-4). A composite score was calculated by multiplying the scores of intensity and percent of cells stained. Tissues were categorized by modified Bloom-Richardson's histological grade and the mean composite scores were compared amongst American Indian and Caucasian groups. Results and Conclusions: We have observed that grade 3 breast cancer samples from American Indian women had a higher percent of nuclear MUC1 staining and a lower amount of p53 expression. This result correlates with previous data showing that MUC1 inhibits the expression of p53. In conclusion, breast cancer tissue from American Indian women has a different expression profile of molecular markers and this finding may help to explain the cancer health disparity. Further investigation of these differences may promote understanding of the etiological differences and may identify effective treatment strategies for breast cancer in American Indian women.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3589. doi:1538-7445.AM2012-3589
Abstract 3596: Globally, minorities are at increased risk for lung cancer
Authors: Cox Solange E. , Hulbert Alicia , Brock Malcolm V. 
Published: August 2012

Abstract
Purpose of Study: To determine whether identifiable minority populations in countries of the six regions of the world experience higher incidence rates of lung cancer than do the members of the majority population of those countries. Experimental procedures: The WHO website has codified the world's continents into six regions including Africa, Americas, South East Asia, Europe, The Eastern Mediterranean and the Western Pacific. This definition of world regions was used for this study. Data were available from five of the six regions. Countries were ordered in each region according to population density. In each region, at a minimum, the 10 most densely populated countries were included. A minority population group was defined as a numerically smaller proportion of a population differing from the majority by a specific identifiable characteristic. Minority and majority populations were defined according to the CIA world fact book and the minority rights group international. Each country was evaluated separately for incidence rates of lung cancer within both minority and majority populations. Codified study data were included for a country only if the data met the following specific criteria: (1) the data had to be presented in its original form using a case-control or cohort methodology; (2) lung cancer incidences had to be reported as an outcome. Data were only included for analysis if it were published as a case-control or cohort study with appropriate references in a peer-reviewed journal. No data from non -peer reviewed articles were considered. Results: Table 1: Lung cancer incidence rates in minority and majority populations from countries included in the top ten of the most densely populated of five world regions. Conclusions: Globally, minority populations experience much higher incidence rates for lung cancer within a country than do the majority population. We hypothesize that this is due to marginalization of these minority groups which may lead to increased smoking in the minority group members as a coping mechanism.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3596. doi:1538-7445.AM2012-3596
Abstract 36: The Importance of sticking together; Cdh1 loss in the gastric zymogenic lineage
Authors: Geahlen Jessica Harrison , Swat Filip A. , Mills Jason C. 
Published: August 2012

Abstract
Stomach Cancer is the second leading cause of cancer related death worldwide. The adult stomach is a renewing system with cells simultaneously differentiating and migrating along invaginations termed gastric units. One such lineage is the zymogenic lineage in which neck cells differentiate to form mature zymogenic cells at the base of the gastric units. The transcription factor Mist1 plays a key role in this differentiation and is lost in the formation of precancerous metaplasia. Another important protein in proper zymogenic cell formation is the cellular adhesion protein Cdh1. Cdh1 has been characterized as a tumor suppressor protein and is often lost in cancer cells allowing for metastasis. In some forms of Hereditary Diffuse Gastric Cancer, loss of Cdh1 is thought to be an initiating event in tumor formation. I have genetically engineered mice in which I can temporally knock out Cdh1 within zymogenic cells both in the presence and absence of Mist1. It is my hypothesis that cells lacking both of these tumor suppressors will be more likely to develop gastric tumors. Preliminary immune-fluorescence analysis of these stomachs indicates that in absence of both MIST1 and CDH1, fully differentiated and normally post mitotic zymogenic cells show greatly reduced size and increased re-entry into the cell cycle. This data suggests that deletion of both MIST1 and CDH1 disrupts the terminal differentiation program of zymogenic cells and promotes metaplastic growth in a manner that could resemble the origins of gastric cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 36. doi:1538-7445.AM2012-36
Abstract 3605: Effects of antibody-mediated EGF-receptor inhibition on ERK 1/2 isoform phosphorylation in organoid cultures
Authors: Unger Florian T. , Rosenbrock Cordula , Krueger Jana , Schaller Janina , Rabe Birgit , Juhl Hartmut , David Kerstin A. 
Published: August 2012

Abstract
Inhibition of the EGF-receptor activity has been widely integrated into clinical practice for different tumor entities, e.g. non small lung cancer and colorectal cancer. Besides the application of tyrosine kinase inhibitors, anti-EGF-receptor treatment is mainly based on the application of therapeutic antibodies. As a standard procedure, patients are tested for KRAS mutation and only those without mutation are selected for anti-EGF-receptor therapy. Although KRAS testing is used to guide colorectal cancer treatment, clear heterogeneity in responses to treatment has been observed. The molecular mechanisms responsible for this heterogenity are still not fully understood, In the present study, we used a preclinical model based on tumor tissue slices for a more detailed evaluation of antibody-mediated EGF-receptor inhibition. In previous experiments, the diffusion of antibodies into organoid cultures and the detection of their functional effects had been successfully shown. Tumor tissue slices from five colorectal cancer patients have been treated with an anti-EGF-receptor antibody for 48 hours. Using immunohistochemical staining, one patient showed a strong expression of the EGF-receptor, one was weak positive and three displayed a moderate staining. As readout of treatment effects, the expression and phosphorylation levels of selected key proteins from two EGF-receptor downstream pathways, the MAPK-pathway and Akt-pathway, were measured using the multiplex technology platform from Meso Scale Discovery. For a more detailed view, we have integrated the NanoPro technology in our pathway analysis approach. This new method enables the identification of distinct isoform phosphorylations and thus is able to display the complex regulation of phosphorylation patterns in detail. By using both methods, we observed a dose-dependent regulation of total- and phospho-ERK in the organoid cultures after anti-EGF-receptor treatment. Deeper analysis using the NanoPro technology showed that the regulation of isoform phosphorylation patterns of ERK1/2 differed among patients, representing the heterogeneity of individual responses among patients. In summary, the combination of the organoid drug testing platform and the NanoPro technology can potentially be useful to identify predictive phosphorylation patterns of tumor cells within their natural tumor microenvironment. This may facilitate the discovery of predictive biomarker for the response to anti-EGF-receptor treatment and further improve personalized medicine.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3605. doi:1538-7445.AM2012-3605
Abstract 3609: Generation and characterization of a novel monoclonal antibody recognizing both the blood and tissue form of human PCBP-1
Authors: Alper Özge , Vortmeyer Alexander O. , Herrmann Marille , Akoa Achille , Alper Özgül M. , Auerbach Aaron , Chen Cui P. 
Published: August 2012

Abstract
Background: Poly(rC)-binding protein-1 (PCBP-1) is a nucleic-acid-binding protein that localizes in nucleus and/or cytoplasm of cells. Shuttling between nucleus and cytoplasm has been related to its function in regulation of RNA transcription, translation and also implicated its involvement in cancer metastasis, progression and chemoresistance. In the present study, we investigated the levels and expression of PCBP-1 in breast carcinoma and its potential use as a biomarker in breast carcinoma differential diagnosis. Methods/Results: We generated a novel monoclonal antibody (mAb), AB-PCBP-1 using hybridoma technology and native protein in cell culture medium as immunogen. This mAb is of IgG1 (kappa) type. It specifically recognized both native and denatured human PCBP-1 protein and displayed high affinity as assessed by ELISA, immunohistochemistry assay, western blot and flow cytometry applications. Using this mAb in competitive ELISA, we showed for the first time that soluble PCBP-1 level is significantly increased in the plasma of metastatic breast cancer patients’ plasma. PCBP-1 is also expressed in metastatic breast carcinoma tissue by immunohistochemistry. Seventy percent of normal breast ducts and lobules expressed strong nuclear staining whereas cytoplasmic staining was less specific and found in most cancer tissues. We examined 90 cases of breast carcinoma tissues classified as either ductal and lobular carcinoma. To evaluate the immunoreactivity of PCBP-1, the staining intensity and intracellular distribution were compared and scored as 0, 1+, 2+ and 3+ based on intensity. Seventy nine % (60 out of 76) of ductal carcinomas showed strong cytoplasmic staining (2+ and 3+) and 45% also exhibited strong nuclear localization for PCBP-1. Lobular carcinomas (n=14), on the other hand, showed an exclusively nuclear staining pattern.Conclusion: AB-PCBP-1 mAb showed high performance in blood and tissue assays. PCBP-1 levels were significantly increased in blood and demonstrated a distinct pattern of expression related to histological tumor types, suggesting that PCBP-1 may be involved in a regulatory mechanism that differs in various subtypes of breast carcinoma. The results suggest the potential clinical use of PCBP-1 as a therapeutic target and/or a biomarker in blood and tissue for the diagnosis and prognosis of breast carcinoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3609. doi:1538-7445.AM2012-3609
Abstract 3629: HOXA10 expression profiles in prostate cancer
Authors: Hatanaka Yuji , De Velasco Marco A. , Kura Yurie , Yamamoto Yuji , Kodama Mitsumasa , Nozawa Masahiro , Shimizu Nobutaka , Yoshimura Kazuhiro , Yoshikawa Kazuhiro , Nishio Kazuto , Uemura Hirotsugu 
Published: August 2012

Abstract
HOXA10 is a member of the homeobox gene family and is a transcription factor primarily involved in embryonic development. Perturbed HOX gene expression has been identified in numerous cancers and thus suggests that these genes may play important roles in diagnosis and treatment of cancer. We initially identified altered HOXA10 expression in prostate tumors form prostate-specific PTEN conditional knockout mice. HOXA10 is highly expressed in the normal prostate glands from wildtype and PTEN-mutant mice and gradually decreases with tumor development and decreased differentiation. However, focal expression of HOXA10 is observed in poorly differentiated tumors and is highly expressed in metastases. To determine clinical significance of HOXA10 in human prostate cancer, we examined HOXA10 expression by immunohistochemistry in matched normal and cancer specimens from prostatectomy cases. HOXA10 nuclear expression was measured according to intensity and distribution. Our analysis shows that HOXA10 is strongly expressed in benign glands and low expression is significantly correlated with Gleason grade (p&lt;0.001), tumor differentiation (p&lt;0.02), pathological stage (p&lt;0.001) and PSA-failure (p&lt;0.001). Expression of HOXA10 was also evaluated in human prostate cell lines and was strong in the benign prostatic hyperplasia BPH-1 human prostate cell line and weak to absent in the malignant human prostate cancer cell lines PC3, DU145 and LNCaP. These data show that HOXA10 is related to tumorigenesis of prostate cancer prostate cancer and warrants further investigation into the functional role of HOXA10 in tumor development.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3629. doi:1538-7445.AM2012-3629