bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract C61: The role of prostanoid signaling in lung cancer
Authors: Pamarthi Pavan Kumar 
Published: June 2012

Abstract
Rationale: An increasingly large body of evidence indicates that PGE2 promotes tumor growth by stimulating EP4 receptor signalling with subsequent enhancement of cellular proliferation, metastasis and suppression of immune responses. However, the role of other EP receptors is not known.
Objective: We hypothesized that prostanoid receptors other than the EP4 receptor are involved in progression of Lung cancer.
Methods: We analyzed the expression profile of EP receptors in lung adenocarcinoma cell lines A549 and H1299 by using Real Time PCR, western blotting and immunofluorescence. All four EP receptors are getting expressed in both the cell lines. Both L-161982 (EP4 receptor specific antagonist) and SC-51322 (EP1 receptor specific antagonist) inhibited proliferation of both cell lines as assessed by thymidine incorporation assay. EP2 and EP3 receptors have not shown inhibitory affects in proliferation assays. SC-51322 has not decreased cAMP levels in A549 and decreased intracellular calcium levels. SC-51322 has inhibited pERK levels as shown in the western blots. In addition, SC-51322 inhibited migration of A549 cells in transwell migration assay.
Conclusion: We conclude that EP1 receptor may play a role in lung cancer progression and metastasis. Finding out downstream molecules to EP1 receptor will give us a better understanding of this pathway in lung cancer and can provide therapeutic opportunities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C61.
Abstract C9: Quantitative modeling of androgen receptor-mediated transcriptional complexes in human prostate cancer cells
Authors: Hsiao Jordy J. , Martinez Hairyl D. , Wright Michael E. 
Published: June 2012

Abstract
The androgen receptor (AR) is a member of the nuclear receptor superfamily and the key transcription factor of androgen-mediated signaling pathways. AR translocates to the nucleus in response to ligand binding, where it selectively binds canonical androgen response elements (AREs) in DNA to assemble transcriptional complexes at target genes. Aberrant AR signaling resulting from unbalanced AR transcriptional responses at genes involved in cellular proliferation and differentiation drives the development and progression of human prostate cancers. In addition, the AR coregulator proteins, members of a large family that bind AR and modulate AR transcriptional activity, are known to elicit aberrant AR activity in prostate cancers. Although numerous AR coregulators have been identified, in most cases this was through static, binary protein-protein interaction assays (e.g., GST-fusion, yeast two-hybrid assays). Thus, to what degree androgen-sensitive coregulators mediate pathological AR actions in the context of human prostate cancer remains poorly defined. We have devised a biochemical strategy to identify and quantify androgen-sensitive coregulators (coactivators and corepressors) of AR-mediated transcription, based on their in vitro affinity for a model androgen-regulated gene promoter. Specifically, we have used DNA-affinity purification techniques in combination with label-free quantitative mass spectrometry (qMS) to do so. Our preliminary findings show that androgen-sensitive coregulators represent a functionally diverse group of protein involved in a number of signal transduction pathways. Furthermore, future studies utilizing selected reaction monitoring (SRM), a quantitative proteomics method, will be exploited to study the molecular functions of androgen-sensitive coregulators and facilitate the construction of quantitative models of AR-mediated transcription that will make it possible to predict androgenic responses at disease-associated, androgen-regulated genes. Our findings will broadly benefit the biomedical research community in that they define a novel class of androgen-sensitive coregulators and determine how they influence AR-mediated transcriptional processes underlying the development and progression of human prostate cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C9.
Abstract IA11: New insights into the microenvironment and metastasis
Authors: Werb Zena 
Published: June 2012

Abstract
Both extrinsic and intrinsic mechanisms regulate the development of the aberrant tumor organ and regulate its progression. We have used genetic and in vivo imaging techniques to study the interaction between epithelial cancer cells and the tumor microenvironment during tumor progression. Transcriptional regulation of epithelial differentiation, cell-cell interaction and motility is a key intrinsic event in tumor progression. We have investigated GATA3, a master regulator for luminal differentiation, which is lost upon malignant conversion, and found that it allows the malignant tumor cells to disseminate throughout the body. The progressing tumor cells develop in an extrinsic microenvironment rich in inflammatory cells, growth factors, angiogenesis and activated stroma that promotes neoplastic risk. All of these components communicate with each other to contribute to the aberrant tumor organ. The tumor microenvironment regulates access to therapeutics and may alter expression of drug resistance genes. To explore the relationship between microenvironment and cancer cells in drug response, we treated mouse models of mammary carcinoma with doxorubicin. Primary cancer cells isolated from different tumor sizes had the same sensitivity in 2D and 3D cultures. Live imaging confirmed that individual cancer cells in early carcinoma stages were more sensitive to doxorubicin than in earlier or later stages. Imaging intact tumors during treatment with chemotherapy revealed marked differences in drug penetration and sensitivity of cancer cells in different tumor microenvironments. The inflammatory cells modulate the tumor ecology, altering vascular permeability and responses to chemotherapy. These experiments establish that chemosensitivity is determined by cooperation between cancer cell intrinsic and extrinsic factors.
Supported by grants from the National Cancer Institute
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA11.
Abstract A103: The synthetic triterpenoid CDDO-methyl ester targets tumor-associated macrophages to delay carcinogenesis in the PyMT model of estrogen receptor negative breast cancer
Authors: Tran Kim M. , Risingsong Renee , Royce Darlene , Williams Charlotte R. , Sporn Michael B. , Liby Karen 
Published: June 2012

Abstract
Breast cancer is the most common cancer among women in the United States. The incidence rates of breast cancer are no longer significantly declining, and approximately 40,000 women die from the disease each year. Hence, novel drugs are needed for the prevention and treatment of the disease. Synthetic triterpenoids are a promising new class of compounds with chemopreventive activity in a variety of preclinical cancer models. We tested the methyl ester derivative of the synthetic triterpenoid, 2-cyano-3, 12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO-Me), in a relevant model of ER-negative breast cancer. In this mouse model, the polyoma-middle T (PyMT) oncoprotein drives carcinogenesis in the mammary gland. The developing tumors recapitulate key features of the human disease including significant infiltration of tumor-associated macrophages (TAM). Depletion of TAMs has been previously shown to delay tumor progression. PyMT mice were fed CDDO-Me (50 mg/kg diet), starting at 4 weeks of age. CDDO-Me significantly increased the age of mice at onset of first tumor by an average of 4.3 weeks (P &lt; 0.001) and overall survival by 5.2 weeks (P &lt; 0.001). CDDO-Me significantly (P &lt; 0.05) inhibited the infiltration of TAMs into mammary glands of PyMT mice along with levels of the chemokines CXCL12 and CCL2 in primary PyMT mammary tumor cells. Treatment with CDDO-Me also inhibited secretion of MMP-9 in primary tumor cells from PyMT mice and decreased proliferation of these cells by inhibiting cyclin D1 and decreasing phosphorylation of EGFR and STAT3, key breast cancer biomarkers. Thus, CDDO-Me delayed breast carcinogenesis via inhibition of TAM infiltration and by inhibition of key pathways in breast carcinogenesis. Taken together, these findings implicate CDDO-Me as a promising chemopreventive agent for ER-negative breast cancer via inhibition of TAM infiltration and diverse oncogenic pathways.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A103.
Abstract A106: Induction of synthetic lethality in mutant KRAS cells for lung cancer prevention and therapy
Authors: Huang Shaoyi , Ren Xiaoyang , Wang Haizhen , Wu Xiangwei 
Published: June 2012

Abstract
Lung cancer is the leading cause of cancer death in both men and women in the United States, with a low five-year survival rate despite improved treatment strategies. Mutations and activation of KRAS occur frequently in non-small cell lung cancers (NSCLCs) and are associated with higher risk of drug-resistance, tumor recurrence, and poor prognosis. Currently, there are no effective therapies for targeting mutant KRAS and there is a great need to develop such a strategy. We have previously discovered a synthetic lethal interaction among TNF-related apoptosis-inducing ligand (TRAIL), the second mitochondria-derived activator of caspase Smac/DIABLO (Smac), and mutant KRAS in premalignant lung epithelial cells, which allows for chemoprevention of KRAS-driven lung cancer by the combination of TRAIL and Smac mimic [Cancer Prev Res (Phila). 2011 May;4(5):666–73.]. Here we demonstrated that this synthetic lethal interaction also exists in malignant lung cancer cells. We showed that 3 out of 4 lung cancer cell lines harboring mutant KRAS displayed high sensitivity to the combination of TRAIL and Smac mimic and KRAS wild type lung cancer cell lines were resistant to the treatment. Expression of mutant KRAS in KRAS wild type lung cancer cells sensitized these cells to TRAIL and Smac mimic and knocking down of mutant KRAS in mutant KRAS expressing cells resulted in resistance to the treatment. Furthermore, we showed that TRAIL and Smac mimic treatment inhibited xenograft tumor growth in mutant KRAS dependent manner. Mechanistically, we found that mutant KRAS repressed cellular FADD-like interleukin 1β–converting enzyme (FLICE)-like inhibitory protein (c-FLIP) expression through the activation of Erk/mitogen-activated protein kinase (MAPK)-mediated activation of c-Myc. Mutant KRAS also enhanced the secretion of Prostate Apoptosis Response-4 (Par4) to promote TRAIL-induced apoptosis. Our study provided a potential new approach for lung cancer chemoprevention and therapy based on synthetic lethality that targets mutant KRAS for apoptosis using the combination of and Smac mimic.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A106.
Abstract A108: Reproductive and hormonal factors in relation to risk of fatal versus non-fatal invasive epithelial ovarian cancer
Authors: Merritt Melissa A. , Poole Elizabeth M. , Tworoger Shelley S. , De Pari Mary , Cramer Daniel W. , Terry Kathryn L. 
Published: June 2012

Abstract
Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the 7th most fatal worldwide. Reproductive and hormonal exposures are known to influence risk of ovarian cancer. We therefore investigated whether these exposures also influence ovarian cancer survival.
We studied survival in relation to hormonal and reproductive history in invasive epithelial ovarian cancer cases and controls from the New England based Case-Control Studies (NECC, 1,642 cases and 2,100 controls). Cases and controls were identified between 1992 and 2008 in New Hampshire and eastern Massachusetts. At the time of enrollment, participants were interviewed in person on a wide range of known and suspected risk factors, including hormone use, childbearing, lifestyle habits and anthropometric characteristics. Polytomous logistic regression was applied to evaluate whether a risk factor was associated differently with fatal (those that died within 3 years of diagnosis) versus non-fatal cases while controlling for other covariates and P-values for heterogeneity (comparing the Odds Ratios (ORs) for fatal ovarian cancer to the ORs for non-fatal ovarian cancer) were calculated based on the maximum likelihood estimates.
A total of 360 of the 1642 women with ovarian cancer (22%) died within 3 years. We found that fatal ovarian cancer was associated with increasing age (multivariate OR 1.05 per 1 year increase in age, 95% CI 1.04 − 1.07, P-value &lt; 0.0001), post-menopausal status (multivariate OR 1.31 vs pre-/dubious menopause, 95% CI 0.97 − 1.77, P-value &lt; 0.0001) and oral contraceptive pill use was consistently more protective across all duration of use categories (P-value = 0.01) as compared with the non-fatal cases. Associations with tubal ligation, total number of ovulatory years, body mass index and family history of breast/ ovarian cancer did not differ significantly between fatal and non-fatal ovarian cancer cases.
These results suggest that the most aggressive subset of invasive epithelial ovarian cancer exhibits important differences in its reproductive and hormonal risk factor profile as compared with non-fatal cases, and that selected protective factors such as oral contraceptive pill use may be especially important for the prevention of the most aggressive subgroup of disease.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A108.
Abstract A114: Dietary magnesium and calcium intake and risk of prostate cancer in Caucasian and African American men
Authors: Rico Stephanie , Forman Michele , Etzel Carol , Strom Sara S. , Hoque Ashraful 
Published: June 2012

Abstract
Dietary magnesium intake is significantly less in African Americans than Caucasians. Deficiency of magnesium influences immune-inflammatory response and induces oxidative stress that leads to increased cell proliferation and DNA damage. Low magnesium level also increases the physiologic effects of calcium. Therefore, we hypothesize that low dietary intake of magnesium and high calcium intake will increase the risk of developing prostate cancer among African American men. To test this hypothesis, we conducted a pilot case-control study to determine whether deficiency of dietary magnesium and a high calcium intake are associated with an increased risk of prostate cancer. This study included 209 cases with histologically confirmed adenocarcinoma of the prostate (110 African American and 99 Caucasian men). 199 population-based controls were frequency matched by age (±5 years) and race. Risk factor questionnaire and nutrition data were collected via telephone interview. Dietary Assessment was performed using Modified Block-NCI Food Frequency Questionnaire with 129 food items, questions about restaurant intake and vitamin mineral supplementation. Dietary intake was calculated using DIETSYS + Plus version 5.9 dietary analysis program. Nutrition data for 166 cases and 155 controls were available for this analysis. Mean magnesium and calcium intake did not vary significantly between cases and controls. The odds ratios for magnesium was 0.79 (95% CI 0.39–1.61) and for calcium 1.35 (95% CI 0.87–2.09). However, among African Americans, the odds ratio for magnesium was 0.28 (95% CI 0.08–1.05) and for calcium 1.9 (95% CI 1.05–3.40). These preliminary data suggest that high dietary magnesium intake is inversely associated with prostate cancer, while higher calcium intake is associated with increased risk among African American men. These data may have significant public health implications since the identification of African American men deficient of magnesium can be targeted for preventive interventions. Results of this study needs to be confirmed in future studies with larger sample size.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A114.
Abstract A31: Effects of Pin1 inhibition on tumorigenicity of glioblastoma multiforme
Authors: Avsar Timucin , Atabay Kutay Deniz , Mehmet Yıldız Taha , Kilic Turker , Karabay Arzu Korkmaz 
Published: June 2012

Abstract
Glioblastoma multiforme (GBM) is the most common and most aggressive type of primary brain tumor, accounting for 20% of all intracranial tumors. Current approaches in pursuit of treatment of GBM are not efficient in terms of increasing patient survivability or preventing recurrence after traditional treatments. Hunt for key molecules that might turn into drug targets have been rigorously continuing for GBM as well as other various types of tumors. Pin1, which was shown to be broadly overexpressed in various types of tumors, bears the potential to be one of the key molecular players in tumorigenesis. Molecular mechanisms underlying development and growth of the GBM, which is not completely curable by the means of chemotherapy, radiotherapy, and surgery, are not yet clearly identified. For the fact that the rate of treatment success of the agents in use against GBM is lower than acceptations, investigations for potential inhibitory target molecules for GBM development are increasing. Pin1 (peptidyl-prolyl cis/trans isomerase) is one of the molecules, recently identified and trying to be clarified during the search for potential target molecules on tumorigenicity. When compared with the health cells level of the Pin1 protein in many tumor cells like prostate, lung, breast and brain tumors is found to be extremely high. Recent studies aiming to identify Pin1's role on tumorigenicity have shown that increase in level of Pin1 in cells also led in increase of VEGF (Vascular Endothelial Growth Factor) as well. Our study aims to reveal the possible role for Pin1 as a therapeutic target and also inhibit the angiogenesis mechanism, which is common for tumors to develop, through inhibition of Pin1
U87 MG Glioblastoma cell line was used and Pin1 inhibition was performed via juglone, a Pin1 specific inhibitor molecule, and Pin1 siRNAs. Effects on Pin1 inhibition on tumorigenicity was assessed by MTT proliferation assay, wound healing assay to observe the migration characteristics, confocal microscopy technique to define morphological changes and apoptosis, and western blotting to define if angiogenesis related proteins are expressed.
It is observed that Pin1 inhibition has affected and diminished the migration ability of U87 MG Glioblastoma cells. Changes on cell morphology and activation of apoptosis were also observed with reduced expression levels of angiogenesis related genes. We believe that, this study has a potential to reveal the effects of Pin1 inhibition as a therapeutic approach and will contribute to literature and clinical care in the future.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A31.
Abstract A33: Modulation of gene expression by a cooked novel resistant starch in the colon of AOM-treated Fisher 344 rats
Authors: Zhao Yinsheng , Hasjim Jovin , Ai Yongfeng , Jane Jay-lin , Birt Diane F. 
Published: June 2012

Abstract
We previously reported that a cooked novel steric acid complexed high amylose starch (SAC) diet fed to Azoxymethane (AOM)-treated Fisher 344 rats significantly reduced the preneoplastic lesions, Aberrant Crypt Foci (ACF) and Mucin Depleted Foci (MDF), in comparison with water-boiled normal cornstarch (CS) diet or high amylose cornstarch (HA) diet. To determine the effect of water-boiled SAC diet on the global gene expression patterns we performed Affymetrix Genechip microarray analysis on rat colon mucosa after the rats were treated with AOM and then fed 3 different diets for 8 weeks. Genes that were significantly differentially regulated by AOM or by diet were identified. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was followed as a subsequent examination confirmed the reliability of this analysis. Microarray and qRT-PCR data showed that AOM affected gene expression for 389 genes when considering q&lt;0.1 for AOM effect, i.e., 307 up-regulated and 82 down-regulated genes when comparing AOM-treated water-boiled CS diet group with the same diet group without AOM treatment. Further, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses indicated that most of these differentially expressed genes were associated with several important biological function such as Wnt signaling pathway, TGF-beta signaling pathway, cell cycle, and Chemokine signaling pathways. A genome-wide microarray analysis was also performed to identify the gene expression modulation by water-boiled SAC diet in AOM-treated rats comparing with AOM-treated water-boiled CS diet rats. In this analysis 408 genes were observed as differentially expressed when q&lt;0.01, i.e., 208 up-regulated and 200 down-regulated genes, included in the signaling pathways such as DNA replication, cell cycle, RNA degradation, Steroid biosynthesis, Graft-versus-host disease, Allograft rejection, and Autoimmune thyroid disease pathways. The reliability of the microarray data was further validated by qRT-PCR. These results showed differential regulation of gene expression profiles in Fisher 344 rats fed water-boiled SAC diet compared with normal starch diet. Gene expression modification was also confirmed in the rats treated with AOM. These results provided promising targets for the suppress colonic preneoplastic lesions by SAC starch.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A33.