bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract A19: The Srx-Prx IV axis promotes human lung cancer progression through modulation of specific phosphokinase signaling
Authors: Wei Qiou , Jiang Hong , Xiao Zhen , Baker Alyson , Young Matthew R. , Veenstra Timothy D. , Colburn Nancy H. 
Published: January 2011

Abstract
Oxidative stress is known to cause tumorigenesis through induction of DNA and lipid damage. It also promotes tumor progression through a largely unknown mechanism. Sulfiredoxin (Srx) is an oxidation-induced antioxidant protein that catalyzes the reduction of hyperoxidized peroxiredoxins (Prxs) to the reduced form to restore their peroxidase activity. Our previous study demonstrates that Srx is a novel target of activator protein-1 (AP-1) activation and TAM67 (a dominant negative form of c-Jun) inhibition. However, the role of Srx in cell signaling and cancer development has not been well-studied. In this study, our goal is to investigate the function and molecular mechanism of Srx in human lung cancer.
Our current work demonstrates an important oncogenic role of Srx in cancer maintenance and progression through the Srx-Prx IV axis and the modulation of specific phosphokinase signaling cascades. First, tissue microarray was used to evaluate Srx expression in human primary lung cancer tissues. We found that Srx is highly expressed in lung squamous cell carcinoma and adenocarcinoma, but not in the normal lung. By knockdown of Srx in human lung cancer A549 cells, we discovered that Srx is required for anchorage independent colony formation, cell migration and invasion of A549 cells. Second, using immunoprecipitation and mass spectrometry, we identified proteins that interact with Srx. Surprisingly, we found that Prx IV was the predominant protein that interacts with Srx. Using purified recombinant proteins and surface plasmon resonance techniques, we demonstrated that Srx has a higher binding affinity to Prx IV than to other Prxs. Third, we found that knockdown of Prx IV, but not other Prxs, recapitulated the phenotypic outcomes of depleting Srx in A549 cells. In addition, when injected into SCID mice, disruption or enhancement of the Srx-Prx IV axis leads respectively to reduction or acceleration of mouse tumor growth and lung metastasis formation. Furthermore, proteome profiler phosphokinase assay revealed that activation of specific phosphokinase signaling cascades, including AP-1, CREB and MAPK signaling, was dependent on the integrity of the Srx-Prx IV axis. In summary, our findings demonstrate a novel oncogenic role of the Srx-Prx IV axis in human lung cancer, and suggest that targeting the Srx-Prx IV axis may provide novel effective strategies for cancer prevention and treatment.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A19.
Abstract A24: Resveratrol-induced and MTA1-associated miRNAs in prostate cancer prevention
Authors: Kai Li , Levenson Anait S. 
Published: January 2011

Abstract
Prostate cancer (PCa) remains one of the most frequently diagnosed cancers in men in Western countries. Since noticeable geographic variations have been observed in the incidence of PCa, studies have implicated a “Western” diet in the development of PCa. Because of this and the nature of PCa, which is typically diagnosed in the elderly population wth a relatively slower rate of growth and progression, chemoprevention through dietary compounds promises to be an effective approach for PCa. Resveratrol (Res) (3,5,4’-trihydroxy-trans-stilbene), a natural compound found in grapes, peanuts and berries, is one of the most promising diet-derived chemopreventive agent with potential chemotherapeutic capacities. There is growing evidence that Res may contribute to chromatin remodeling that are important in cancer progression. Metastasis-associated protein 1 (MTA1), which is overexpressed in many cancer, is a part of nucleosome remodeling and deacetylation (NuRD) complex that mediates posttranslational modifications of histones and nonhistone proteins resulting in transcriptional gene silencing. The complex also contains histone deacetylases 1 and 2 (HDAC1 and 2). MTA1/HDAC1 subunit plays an essential role in governing deacetylation of histones and other proteins. We recently demonstrated that Res down-regulated MTA1 protein levels in PCa cells, leading to destabilization of MTA1/HDAC1/NuRD complex thus allowing acetylation and activation of tumor suppressor p53. MTA1 silencing by RNA interference further sensitized PCa cells to Res-dependent p53 acetylation, transcriptional activation of p21 and Bax and apoptosis. To further understand Res-induced MTA1-associated epigenetic alterations, we analyzed MTA1-associated and Res-induced microRNAs expression changes using LNCaP cells expressing and silenced for MTA1. We found that expression of 13 miRNA was increase, and 17 miRNAs was decreased in cells silenced for MTA1 gene. In addition, 28 miRNAs were overexpresed, and 23 miRNAs were degreased under Res treatment. Among these miRNAs were some with well-characterized cancer association, such as let-7g, miR-16-2, miR-26a, miR-20b, miR-27a, miR-22, miR-34a, miR-92 and others. The predicted targets for the overlapping miRNAs are significantly enriched for protein-coding oncogenes and tumor suppressors. Our data indicate that MTA1-associated miRNAs are involved in Res-mediated anticancer and preventive effects in prostate cancer.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A24.
Abstract A27: STAT2 contributes to promotion of colorectal and skin carcinogenesis
Authors: Gamero Ana M. , Young Matthew R. , Mentor-Marcel Roycelynn , Bobe Gerd , Scarzello Anthony J. , Wise Jennifer , Colburn Nancy H. 
Published: January 2011

Abstract
This abstract is being presented as a short talk in Concurrent Session 4. A full abstract is printed in the Proffered Abstracts section (PR-02) of the Conference Proceedings.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A27.
Abstract A28: Expression of D4-GDI, a key regulator of Rho GTPases, in breast cancers
Authors: Rosado Leslie A. Rivera , Canales Jaime Rodriguez , Zhang Baolin 
Published: January 2011

Abstract
D4-GDI is a key regulator of Rho GTPases that have been implicated in many aspects of tumor progression. Despite its hematopoietic origin, we recently found D4-GDI to be expressed in human breast cancer cell lines. Targeted disruption of D4-GDI in a highly invasive breast cancer cell line inhibited tumor growth and experimental metastasis in a xenograft mouse model. The aim of this study was to investigate D4-GDI expression in primary breast tumors and to assess whether the expression levels of this protein could be associated with disease progression or other established clinical parameters. Following antibody validation, D4-GDI protein expression was assessed by tissue-microarray analysis of two human breast tissue arrays. Clinical parameters such as disease stages and/or hormone receptor status were available. Based on statistical analysis of the data we determined that D4-GDI levels were significantly higher in benign and early stage tumors when compared to normal breast tissues, which was followed by a dramatic decrease in high-grade malignant tumors and metastatic lesions to the lymph nodes. Breast cancer is thought to develop mostly from cells of luminal lineage; interestingly we observed that D4-GDI expression was almost exclusively found in the luminal cells of the ducts but not in the myoepithelial cells at the outer layer. In addition we found that alteration in D4-GDI expression levels resulted in changes in the expression of epithelial-to-mesenchymal transition (EMT) markers, a critical process for cancer progression. D4-GDI expression also appeared to be associated with the status of estrogen receptor (ER) whose deficiency is known to be linked with poor prognosis. These data support an important role for D4-GDI in tumorigenic transformation. Given its reverse relationship with ER status, D4-GDI levels might also provide additional information on the state of cancer progression as well as potential risk of metastasis in ER-negative patients.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A28.
Abstract A31: Bukhari molecular grading for squamous cell carcinoma and its correlation with pathologic prognostic factors.
Authors: Bukhari Mulazim Hussain , Iqbal Asifa , Majeed Muhammad M. , Jawad Amaila , Iqbal Sarah , Niazi Shahida , Khalil Muhammad Eyyaz 
Published: January 2011

Abstract
Background: Optimal patient management requires correct pathologic information regarding its prognostic value and definitive discrimination between the biological behavior of tumors. Traditional microscopic information often fails, especially when base on hematoxyllin and eosin methods. New grading system fills this void. The study was undertaken to determine the molecular grades of squamous cell carcinoma based on cumulative scores of histopathology, and proliferative activity and to see their correlation with pathological prognostic factors.
Materials and Methods: Scoring for histology, Ki-67 index, and p63 immunohistochemistry was done for 180 samples of squamous cell carcinoma with different histologic grades. Data regarding pathologic prognostic factors e.g., lymph node metastasis, local invasion, distance metastasis and recurrence was also collected for each case. Spearman correlation and Kendall's Tau-b test was used to assess association of molecular grading with pathologic prognostic factors. P &lt;0.05 was considered statistically significant.
Results: Three grades (low, intermediate, and high) were determined by the sum of point values assigned to each 4 scores of histological differentiation, 5 p63 immunoreactivity scores and 4 scores of Ki-67. p63 scores were found to be related to the Ki-67 in the histological scoring of SCC. A significant correlation was found between the tumor grades and pathologic prognostic factors like stages (The molecular grades and the surgical stages are highly positively correlated, i.e. Spearman correlation = 0.721, p-value = 0.000) local invasion, lymph node involvement, distance metastasis (Kendall's Tau-b = 0.394; p-value = 0.00) and recurrence (Kendall's Tau — b = −0.966, p-value = 0.025).
Conclusion: Molecular features of the malignant cells were related to the pathological prognostic factors. New molecular grading is better in understanding the pathologic and clinical behavior of SCC at the molecular level.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A31.
Abstract A33: Identification of potential immunologic targets in mice and man that are overexpressed in colon adenomas and colorectal cancer
Authors: Broussard Elizabeth K. , Pritchard David K. , Lubet Ronald A. , Disis Mary L. 
Published: January 2011

Abstract
Multiple recent studies have demonstrated that colorectal cancer (CRC) is immunogenic and that host adaptive immunity (especially by CD4+ T cells) may play a role in inhibiting disease relapse or progression. We have shown that overexpressed tumor associated proteins, those abundant in the cancer state but expressed at basal levels in normal cells, can be immunogenic. The purpose of this study was to identify genes overexpressed in colorectal adenoma that maintain upregulation in CRC using publicly available microarray datasets in the NCBI Gene Expression Omnibus (GEO). Such genes may encode proteins that could be suitable as immunologic targets for a CRC vaccine. We identified 7 high quality datasets from 5 experiments (GSE 867, 4183, 1095, 5206, 15960) where human pre-malignant or cancerous tissue (3 adenoma and 4 CRC) was directly compared to normal colon. Inclusion criteria for the datasets included: commercial microarray platforms (Illumina or Affymetrix), primary tissue, normal colon expression included, data generated after 2005, and access to microarray raw data. We identified 100 genes that were at least 2-fold upregulated in both adenomas and CRC, relative to normal colon. We further characterized and ranked these genes by assigning numerical values to the following criteria: 1) strong expression in CRC as compared to normal colon at both the RNA and protein level, 2) evidence that the gene is biologically important in CRC initiation or progression, 3) limited gene expression in normal tissues, and 4) proven immunogenicity of the encoded protein. These analyses identified 83 candidate targets. We hypothesized that genes highly conserved across species would potentially have greater biologic relevance, so we analyzed relevant microarray studies in mouse CRC models (GSE 422, 784). We identified 226 murine genes upregulated in adenoma and CRC. Comparison of the human and rodent data sets revealed an overlap of 10 genes. We conclude that there are a limited number of genes upregulated in adenoma and CRC and conserved across disease in mouse and man. If these proteins are immunogenic, they may serve as novel immunologic targets to prevent the progression from normal colonic epithelium to adenoma or carcinoma.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A33.
Abstract A34: Cholesterol depletion in cell membrane induces apoptosis of oral cavity cancer cells
Authors: Kim So Yeon , Cho Chang Il , Kim Kyung-Su 
Published: January 2011

Abstract
Cell membrane cholesterol is not distributed evenly, but it mainly exists in a specific microdomain of cell membrane called lipid raft. The lipid rafts consist of cholesterol and glycosphingolipid, and are associated with the regulation of transmembrane receptors. Cholesterol depletion has been reported to bring structural disruption of the raft and functional change of associated receptors which leads to the induction of apoptosis in certain types of cells. In this study, the cell membrane cholesterol of oral cavity cancer cells such as SCC-15, SCC-25, and SCC-QLL1 cell line was depleted by treating with methyl β-cyclodextrin (MβCD), and the effect of cholesterol depletion on the induction of apoptosis was evaluated. Treating oral cavity cancer cells for 1 hour with 1% MβCD inhibited cell proliferation. The cholesterol analysis and the filipin fluorescence staining demonstrated that MβCD selectively depleted cholesterol in oral cavity cancer cells. Furthermore, flow cytometry, poly (ADP-ribose) polymerase (PARP) cleavage assay, ELISA cell death assay showed that this inhibition of cell proliferation was caused by apoptosis. To evaluate the relationship between Mitogen-activated protein kinases (MAPK) and this apoptosis, Western blot analysis of the oral cavity cancer cells treated with MβCD was performed using the antibodies of Phospho-Extracellular signal-regulated kinase (p-ERK), phospho-p38 MAPK, and phosho-Jun-N-terminal kinases (p-JNK). The activity of ERK, p38 MAPK, and JNK in each oral cavity cancer cells was changed after treating with MβCD. In conclusion, cholesterol depletion of cell membrane may be considered as one of treatment modalities for oral cavity cancer, but further studies on its mechanism will be needed.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A34.
Abstract A36: Topoisomerase II-dependent apoptosis induced by dietary isothiocyanates
Authors: Lin Ren-Kuo , Zhou Nai , Tsai Yuan-Chin , Lu Chang-Hsieh , Lyu Lisa Y. , Liu Leroy F. 
Published: January 2011

Abstract
Cruciferous vegetables, such as broccoli and watercress, have been studied extensively for their chemopreventive activities in animal models. It has been demonstrated that the thiol-reactive isothiocyanates (ITCs) are primarily responsible for their chemopreventive activity. While ITCs are known to induce Phase II enzymes and hence detoxification of certain carcinogens to prevent initiation of carcinogenesis, they also exhibit antitumor activity at a post-initiation phase, suggesting their additional role(s) in cancer prevention. In vitro studies have demonstrated that ITCs induce apoptosis which could be linked to their chemopreventive activity in the post-initiation phase. A number of studies have suggested that IKK inhibition, NF-κB suppression and/or STAT3 down-regulation may contribute to ITC-induced apoptosis. Here, we provide evidence that topoisomerase II (Top2) is involved in ITC-induced apoptosis in cultured tumor cells: (1) BITC (benzyl isothiocyanate) and PEITC (phenethyl isothiocyanate) induced much reduced apoptosis in HL-60 cells and T-antigen transformed MEFs transfected with Top2α siRNA. (2) Similarly, the induction of the DSB signal, γ-H2AX, was also reduced in HL-60 cells transfected with Top2α siRNA. (3) BITC and PEITC induced Top2-mediated DNA damage in vitro through the formation of topoisomerase II-DNA covalent complexes. Together, these results suggest a possible role of Top2 in ITC-induced cell death, presumably through the formation of topoisomerase II-DNA cleavage complexes.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A36.
Abstract A37: A study on the mechanism of chemoprevention by celecoxib and fish oil in experimental mammary carcinogenesis
Authors: Agnihotri Navneet , Negi Anjana K. , Sarotra Pooja , Kansal Shevali , Sharma Gayatri 
Published: January 2011

Abstract
Background: Cyclooxygenase (COX)-2 inhibitor, celecoxib and n-3 poly unsaturated fatty acid (PUFA) rich fish oil has been reported to have a synergistic chemopreventive effect on colon and breast cancer in animal models and this effect may be mediated through alteration in apoptosis and cell cycle. Therefore, the present study was designed to understand the mechanism of action of this combinatorial strategy in 7,12-Dimethylbenz(a) anthracene (DMBA) induced mammary carcinogenesis.
Study Design: Female Wistar rats were distributed into six groups: group-1 (vehicle treated), group-2 (DMBA treated), group-3 (20mg/kg body weight celecoxib + DMBA), group-4 (0.5 ml fish oil + DMBA), group-5 (20 mg/kg body weight celecoxib+0.5 ml fish oil) and group-6 (20 mg/kg body weight celecoxib+0.5 ml fish oil + DMBA). The animals were pretreated with the respective dose regimens orally for one week prior to the DMBA (15mg) dose. The animals were subsequently maintained for 90 days and then sacrificed. The levels of reactive oxygen species (ROS) by 2’,7’-dichlorofluorescein diacetate (DCFH-DA), intracellular Ca2+ by fluo-3-penta-acetoxymethylester (fluo-3-AM) dye, p53 by monoclonal antibody and mitochondrial membrane potential (MMP) by 5,5,6,6-tetrachloro-1,1,3,3-tetraethylbenzamidazolo-carbocyanin iodide (JC-1) dye were estimated in isolated mammary epithelial cells.
Results: A significant increase in ROS, intracellular calcium and p53 levels and a decrease in MMP were observed in DMBA treated rats as compared to control animals.
There was a significant decrease in p53, intracellular calcium and ROS generation on pretreatment with either celecoxib, fish oil or combination dosage of celecoxib and fish oil in DMBA treated animals with respect to only DMBA treated animals (group 2) with a comparatively marked alteration in combination dose regimen. However, an increase in MMP was observed in fish oil and the combination dosage regimen with respect to DMBA treated animals. Fish oil treatment in comparison to celecoxib in DMBA treated animals led to a significant increase in calcium, ROS and MMP levels. To conclude a synergistic effect of celecoxib and fish oil was observed in intracellular calcium, ROS and p53 levels in DMBA treated animals which may be responsible for the better chemopreventive efficacy of the combinatorial regimen.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A37.
Abstract A38: Chemopreventive effect of different ratios of fish oil and corn oil in experimental colon carcinogenesis
Authors: Sarotra Pooja , Kansal Shevali , Sandhir Rajat , Agnihotri Navneet 
Published: January 2011

Abstract
Aim: The present study was designed to study the chemopreventive effect of different ratios of n-3 PUFA rich fish oil and n-6 PUFA rich corn oil on prognostic markers, DNA damage and cell cycle phases in experimentally induced colon carcinoma.
Methods: Male Wistar rats were divided into control, dimethylhydrazine dihydrochloride (DMH) treated, FO+CO(1:1)+DMH and FO+CO(2.5:1)+DMH. All the groups, except control received a weekly injection of DMH for 4 weeks. The animals were sacrificed either 48 hrs later (initiation phase) or kept for 16 weeks (post initiation phase). The chemopreventive efficacy was evaluated by analyzing the regression of preneoplastic lesions, total sialic acid (TSA), lipid associated sialic acid (LASA). To study the underlying mechanisms DNA damage, distribution of cells in various phases of cell cycle, cyclin D1 and p53 levels were assessed in the isolated colonocytes.
Results: The animals treated with DMH in the initiation phase and post initiation phase studies showed increase in Multiple plaque lesions (MPL), total sialic acid (TSA), lipid associated sialic acid (LASA), DNA damage and cell proliferation with increased percentage of cells in G2M and S phase. However, levels of p53 and cyclin D 1 were not significantly altered in the initiation phase while levels were significantly elevated in the post initiation phase study on treatment with DMH.
The FO+CO(1:1)+DMH treatment in the initiation phase and post initiation phase led to a decrease in the MPL, DNA damage, TSA, LASA as compared to the control and DMH treated group. The cells were arrested in the G1 phase with a decrease in G2M and S phase. The levels of p53 and cyclin D1 were not significantly altered while a decrease in the levels was observed in the post initiation phase as compared to the DMH treated animals.
Treatment with FO+CO(2.5:1)+DMH in the initiation phase study and post initiation phase study led to a decrease in the MPL, TSA, LASA and DNA damage as compared to the DMH treated animals. The levels of p53 and cyclin D1 remain unaltered on treatment with FO+CO(2.5:1)+DMH in the initiation phase study. However a decrease was observed in the post initiation phase as compared to the DMH treated animals. The cells were arrested in the G1 phase in the initiation phase and revert to normal in the post initiation phase showing the protective effect. There was more protective effect in the FO+CO(2.5:1)+DMH treated animals as compared to the FO+CO(1:1)+DMH treated animals in the initiation phase and the post initiation phase showing the dose and time dependent effect of n-3 PUFAs.
Conclusion: The results of the present study suggest that fish oil and corn oil in the ration of 2.5;1 is more effective in chemoprevention of experimental colon carcinogenesis.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):A38.