bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3710: Individual and combined effects of Tamoxifen and fish oil on mammary carcinogenesis in polyoma middle T transgenic mice
Authors: Manni Andrea , Xu Haifang , Washington Sharlene , Aliaga Cesar , Cooper Timothy K. , Richie John P. , Prokopczyk Bogdan , Calcagnotto Ana , Trushin Neil , Hamilton Christopher , Demers Laurence M. , Liao Jason , Verderame Michael F. , El-Bayoumy Karam 
Published: June 2012

Abstract
There are currently no known effective regiments able to prevent the development of estrogen-receptor (ER) negative breast cancer in humans. We hypothesize that ER, frequently upregulated in preneoplastic mammary lesions, may contribute to the development of hormone-independent tumors through crosstalk with multiple cellular oncogenic pathways. Therefore, a multi-targeted approach is likely to be necessary to prevent ER negative tumors. In our previous study, we tested this hypothesis in CD rats and we showed that omega-3 rich fish oil (FO) potentiated the suppressive effect of Tamoxifen (Tam) on mammary carcinogenesis (A. Manni, et al. Cancer Prev Res 3:322, 2010). In the present investigations, we tested this hypothesis in polyoma middle T transgenic mice, since in this experimental system the development of ER negative tumors is preceded by preneoplastic lesions overexpressing functional ER, as evidenced by the concomitant upregulation of progesterone receptors which are products of estrogen action. Administration of increasing concentrations of Tam (1 ppm, 10 ppm, and 100 ppm) admixed with 20% corn oil (CO) modified AIN-76A diet, starting at 3 weeks of age, significantly delayed mammary carcinogenesis, inhibited tumor multiplicity by ∼50%, tumor volume by ∼90%, and tumor weight by ∼70% in a dose dependent fashion. At termination (week 12), however, tumor incidence was nearly 100% in all experimental groups. When Tam treatment was started after tumors had developed, no inhibition of tumor growth was observed, a finding consistent with the absence of ER in invasive adenocarcinomas in this experimental model. Administration of increasing concentrations of FO in the diet (5% FO + 15% CO; 10% FO + 10% CO, 17% FO + 3% CO) started at 3 weeks of age did not affect any of the tumor parameters compared to the control 20% CO diet. Combined administration of suboptimal (1 ppm) and optimal (100 ppm) doses of Tam with 17% FO and 10% FO respectively, delayed carcinogenesis and suppressed tumor multiplicity and volume to the same extent as observed with Tam alone. Therefore, the results indicate that, under these experimental conditions, FO failed to potentiate the chemopreventive action of Tam. Our results, however, provide support for the role of ER expression by the preneoplastic lesions in the development of hormone independent tumors and, consequently, for the importance of including ER targeting in combined chemoprevention strategies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3710. doi:10.1158/1538-7445.AM2011-3710
Abstract 3757: PTGS1 and PTGS2 polymorphisms, fatty acid intake, and risk of colon and rectal cancer
Authors: Habermann Nina , Slattery Martha L. , Poole Elizabeth M. , Xiao Liren , Galbraith Rachel L. , Duggan David , Kulmacz Richard J. , Caan Bette J. , Koepl Lisel , Coghill Anna E. , Makar Karen W. , Lundgreen Abbie , Potter John D. , Ulrich Cornelia M. 
Published: June 2012

Abstract
Introduction: Inflammation plays a major role in colorectal cancer. COX-1 and COX-2 convert n-3 and n-6 fatty acids into prostaglandins which have anti- and pro-inflammatory effects, respectively. We examined potential interactions between polymorphisms in PTGS1 (COX-1) and PTGS2 (COX-2) and fat and fatty acid (FA) intake in relation to colon and rectal cancer risk.
Methods: A linkage-disequilibrium-based tagSNP-selection algorithm (r2=0.90, MAF=4%) identified tagSNPs in PTGS1 and PTGS2. We genotyped 16 SNPs in PTGS1 and 17 SNPs in PTGS2 on the same Illumina platform in two independent study populations (colon cancer: 1502 cases, 1862 controls; rectal cancer 713 cases, 914 controls). We investigated potential interactions with intake of total fat, saturated FA (SFA), monounsaturated FA (MUFA), polyunsaturated FA (PUFA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) on risk of colon or rectal cancer.
Results: We observed several statistically significant interactions between PTGS1 and PTGS2 genotypes and fat and FA intake (Table). However, few interactions were consistent across fat variables and fell into three general categories of associations: a) individuals with the variant allele and low intake of total fat, SFA, or MUFA were at increased risk for rectal cancer (PTGS1 rs10306122-G, p int=0.01-0.01; PTGS2 rs4648268-A; p int=0.01-0.02); b) individuals with the variant allele and high EPA and DHA intake were less likely to develop colon cancer (PTGS1 rs10306110-G, p int=0.003-0.006); and c) individuals with the wildtype genotype and high EPA and DHA intake had stronger protection from colon cancer (PTGS2 rs4648310-A, p int=0.01-0.05). No interactions were observed for AA.
Conclusion: Our study provides some evidence that genetic variability in PTGS1 and PTGS2 and intake of total fat, SFA, or MUFA and EPA or DHA may interact in causing rectal and colon cancer, respectively.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3757. doi:10.1158/1538-7445.AM2011-3757
Abstract 3889: Direct evidence that the MRN complex is required for a pathway that processes Top2 covalent complexes
Authors: Soans Eroica , Mishina Margarita , Nitiss John L. 
Published: June 2012

Abstract
Drugs targeting topoisomerase II (Top2) such as etoposide or doxorubicin generate enzyme mediated DNA damage. During the normal Top2 reaction, the enzyme forms a covalent enzyme DNA intermediate consisting of a 5’ phosphotyrosyl linkage between the enzyme and DNA. Many compounds that generate Top2 mediated damage inhibit the enzyme-catalyzed religation step leading to DNA breaks. Therefore an important aspect of the repair of Top2 mediated damage includes removal of the protein covalently bound to DNA. One way of eliminating that protein is by proteolysis. Liu and colleagues have clearly demonstrated that proteolysis plays a role in repairing Top2 beta damage1 and it is likely that proteolysis is also important for repairing Top2 alpha mediated damage. Proteolysis cannot remove all of the peptide bound to DNA; therefore nucleolytic enzymes are also needed for repairing Top2 damage. Since the MRN complex is required for nucleolytic removal of the meiotic Top2-like protein Spo11, it has been hypothesized that the MRN complex also participates in removal of Top2 protein from DNA following cellular treatment with Top2 poisons. However, there is no direct evidence for processing of Top2 mediated damage by the MRN complex. We have used the ICE assay to directly measure Top2 covalent complexes in mammalian cells treated with Top2 poisons such as etoposide. The ICE assay uses CSCl centrifugation to isolate protein:DNA covalent complexes. We have combined this assay with siRNA knockdowns to assess whether specific protein complexes are required for processing Top2 covalent complexes. Since this assay depends on recognition of Top2 epitopes by monoclonal antibodies directed towards Top2 isoforms, we have examined levels of Top2 complexes in cells treated with the proteasome inhibitor, MG132. In cells treated with siRNA directed against Mre11, we observed an increase in Top2:DNA covalent complexes following treatment with either etoposide or mAMSA. These results provide direct evidence that the MRN complex is required for at least one pathway for removal of Top2 covalent complexes. It is likely that this MRN dependent pathway is capable of removing Top2 bound to DNA without proteolytic processing of the covalent complex. We are currently using this approach to assess other recently described processing pathways including pathways requiring CtiP and pathways requiring Tdp2.
(1) Mao, Y.; Desai, S. D.; Ting, C. Y.; Hwang, J.; Liu, L. F. J Biol Chem 2001, 276, 40652.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3889. doi:10.1158/1538-7445.AM2011-3889
Abstract 3900: Formaldehyde induces DNA damage and BRCA1 nuclear export
Authors: Ponce Esmeralda M. , Louie Maggie C. 
Published: June 2012

Abstract
Formaldehyde is a colorless, potent, flammable gas, commonly used to manufacture building materials and other household and personal care products. Most living organisms are exposed to some levels of formaldehyde in one way or another. Studies have shown formaldehyde to have mutagenic and genotoxic effects on proliferating cells. In order to understand the effects of formaldehyde on cancer progression, we examined the effects of formaldehyde on estrogen receptor positive breast cancer cells, MCF-7. Our data suggest that low concentrations of formaldehyde decrease the proliferation of MCF-7 cells. Further analysis at the molecular level suggests that formaldehyde increases the expressions of p53 and BRCA1, two tumor suppressor genes known to play important roles in DNA repair. Consistent with previous reports that high concentrations of formaldehyde results in irreversible DNA damage, our results suggest that exposure to low concentrations of formaldehyde is sufficient to induce DNA damage. Protein and gene expression analyses suggest that p53 and BRCA1 expression levels are dependent on the concentration of formaldehyde and length of exposure. Additionally, our data show that BRCA1 undergoes nuclear export in response to formaldehyde which is consistent with its role in DNA damage surveillance and repair.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3900. doi:10.1158/1538-7445.AM2011-3900
Abstract 3904: Array CGH analysis of cervical cancer
Authors: Zuna Rosemary E. , Aston Christopher E. 
Published: June 2012

Abstract
Introduction: We hypothesize that there are characteristic chromosomal gains and losses in invasive cervical cancers that correlate with histologic cell type and HPV genotype.
Methods and Materials: Array CGH analysis was performed on DNA extracted from 39 formalin-fixed, paraffin embedded invasive cervical cancer cases using 1.4MB BAC microarray chips (HumArray3.2, UCSF Comprehensive Cancer Center Array Core). Significant gains and losses were determined looking for convergent results from a random permutation approach based on GISTIC (Genomic Identification of Significant Targets in Cancer, Beroukhim R et al: PNAS 104: 20007, 2007), a modification of this approach using weighted sums over neighboring loci, frequency of gains and losses at each locus, and t-tests comparing log2 ratios from the cases to those from four control samples from non-cervical cancer tissue. The log2 ratios derived for each of the 2464 individual loci were aggregated for each locus over the entire set of 39 cases and for defined subsets including histologic subtype (squamous [SC:N=19] cancers, adenocarcinomas [AD:12], adenosquamous carcinomas [AS:6]) and HPV genotype [HPV16:12 and HPV18:14].
Results: Significant gains (108 individual loci) and losses (110 loci) were identified in the overall population. Congregations of significant gains were found on chromosomes 3q (8 loci), 1q (7), 1p (5) and losses on 4q (8 loci), 11q, (6) 4p (5), 3p (5). Overall,17 individual loci were significantly increased and 19 were decreased across the overall population as well as for each of the histologic subsets suggesting associations with cervical cancer per se. Individual loci with the most significant gains (P&lt;0.001) were 3q26.3-3q27 (gained in 95% of cases), 19p13.2 (98%), 1q42-43 (93%) and losses (P&lt;0.001) were 4q22 (100%), 11q22 (100%), 3p14 (90%) and 7p12.1 (100%). Differential changes associated with histologic cell type (P&lt;0.001) included multiple gains in 1p (SC), 20q (AC), and losses in 3p (SC), 4p (AS). Multiple gains in 1p and 3q were related to HPV16 lesions while gains in 5p and 19q were related to HPV18. The HPV associations were somewhat influenced by cell type: 8/9 (89%) of AD (3 untyped) were HPV16, but only 2/18 (11%) of SC (1 untyped) were HPV16.
Conclusions: Characteristic chromosome copy number alterations for regions and individual loci were identified for cervical cancer cases including patterns for different histologic subtypes and HPV genotypes. The regions harboring these loci can potentially be developed for screening, assessment of prognosis and therapeutic intervention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3904. doi:10.1158/1538-7445.AM2011-3904
Abstract 3966: Regulation of Chd5 expression by microRNA-211 and microRNA-130b in colorectal cancer
Authors: Cai Chunxiao , Ashktorab Hassan , Smoot Duane T. , Liu Yulan , Gu Xinbin 
Published: June 2012

Abstract
PURPOSE: Chromodomain helicase DNA-binding protein 5 (CHD5) is identified as a novel tumor suppressor in particular of colorectal tumorigenesis. There is limited information about the regulation of CHD5 expression. In this study, we investigated the role of microRNAs (miRNAs) in regulation of CHD5 protein expression in colorectal cancer. DESIGN METHODS: MiR-211 and miR-130b as predictive target CHD5 candidate miRNAs were selected through Targetscan software. A high level of CHD5 protein colorectal cancer HCT-116 cell line was used to establish miR-211 and miR-130b stable transfected cell lines (HCT-116miR-211 and HCT-116miR-130b) as test models, following by MTT, colony assay, flow cytometry for cell viability examination. Quantitative real-time PCR and Western blot analysis were also used for measure miR-211, miR-130b and CHD5 expression levels in HCT-116miR-211 and HCT-116miR-130b. CHD5-associated proteins expression levels were assessed as well. RESULTS: MiR-211 and miR-130b were cloned into lentiviral GFP expression miRNA vector, separately. Retrovirus was produced by using lentiphos TMHT packaging system and infected into HCT-116 cell line. The expression levels of miR-211 in HCT-116miR-211 and miR-130b in HCT-116miR-130b were significantly increased (miR-211 increased 16 times, and miR-130b increased 8 times) and at the same time CHD5 expression levels was decreased. Compared to the vector control cell lines, the levels of cell proliferation and colony formation were higher in HCT-116miR-211 and HCT-116miR-130b. In addition, the proportion of cell number in the G0-G1 phase of HCT-116miR-211 and HCT-116miR-130b was lower than those in the control cell lines. CONCLUSION: Up-regulation of miR-211 and miR-130b induced the malignant phenotype of HCT-116 cells via block of CHD5 expression. That implicated the miRNAs might be one of the mechanisms that lead CHD5 down-regulated in colorectal cancer. This work was supported in part by grants P20 CA118770 and U54 CA091431 from National Cancer Institute.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3966. doi:10.1158/1538-7445.AM2011-3966
Abstract 3976: The role of a novel oncomiR, miR-135b, in lung cancer metastasis and clinical application
Authors: Lin Ching-Wen , Lin Jau-Chen , Chang Yih-Leong , Chen Hsuan-Yu , Pan Szu-Hua , Hong Tse-Ming , Yang Pan-Chyr 
Published: June 2012

Abstract
microRNA(miR) may function endogenous siRNA and regulate a diversity of cellular function through translational repression. Dysregulations of miR expression are involved in carcinogenesis and progression in various cancers. By combining the miR microarray and genomic DNA-methylation array, we identified an intronic miR, miR-135b, which is up-regulated in high invasive lung cancer cell CL1-5. The promoter region of miR-135b is highly de-methylated in high invasive cells and its expression in the less invasive lung cancer cells can be induced by demethylating agent 5’-aza-CdR treatment. Ectopically expression of miR-135b enhanced cell invasive and migratory ability in vitro as well as the orthotopic tumor growth and lung metastasis activity in vivo, whereas specific inhibition of miR-135b decreased tumor growth and metastatic activities. Using the bioinformatic prediction tools, we identified and confirmed that miR-135b could directly repress the expression of Lzts1 through 3’UTR seed-binding. Ectopically-expressed Lzts1 inhibited cell invasion and migration activity, implicating that miR-135b may promote lung cancer cell metastasis by down-regulating Lzts1. Moreover, high level of miR-135b and low level of Lzts1 expressions were associated with poor overall survival in lung cancer patients. We also showed that the miR-135b expression was regulated by NF-κB signaling-cascade and synergistically induced by co-treatment of 5’-aza-CdR and TNF-α, implying that the abnormal expression of miR-135b in cancers may result from inflammatory stimulation and epigenetic modulation. Our results support that miR-135b is an oncogenic miR that may contribute to lung cancer progression and metastasis. The miR-135b/Lzts1 pathway is a promising therapeutic target of lung cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3976. doi:10.1158/1538-7445.AM2011-3976
Abstract 4000: Trastuzumab targeting of HER2 upregulates miRNA-194 and downregulates profilin 2 and DNMT3A in HER2 positive breast cancer
Authors: Le Xiao-Feng , Wu Yun , Spizzo Riccardo , Yoo Suk-Young , Wang Jing , Calin George A. , Bast Robert C. 
Published: June 2012

Abstract
Trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of oncoprotein HER2, is widely used in standard therapy for women with HER2-positive breast cancer. Although the effects of trastuzumab on cancer cell proliferation, angiogenesis, and apoptosis have been intensively investigated, the effect of trastuzumab on microRNA (miRNA) is unknown. Since miRNA provides a novel layer of gene regulation and may play role in trastuzumab action, we have consequently performed miRNA microarray profiling before and after trastuzumab treatment in both SKBr3 and BT474 breast cancer cells that overexpress HER2. Trastuzumab significantly decreased five human miRNAs and increased three others in SKBr3 cells, whereas in BT474 cells it significantly decreased two miRNAs and increased ten. The only miRNA that shared the same change in both cell lines was miRNA-194 (miR194), which was upregulated following trastuzumab treatment. Upregulation of miR194 by trastuzumab was further validated in vitro and in vivo by quantitative reverse transcription PCR (QRT-PCR) or Northern blotting. miR194 expression in 92 cases of breast cancer and 21 normal breast tissues (all were FFPE samples) was examined by QRT-PCR. miR194 levels were significantly higher in breast cancer samples versus normal tissues (p=0.0003), in estrogen-positive breast cancer samples (p=0.002), and in HER2-negative breast cancer samples (p=0.032). Importantly, expression of precursor miR194 specifically downregulated the protein levels of DNA methytransferase DNMT3A and actin cytoskeleton organizer profilin 2. miR-194 specifically inhibited the luciferase activity of wild type DNMT3A 3’-UTR construct, but not that of mutant vector, indicating that DNMT3A is a direct downstream target of miR-194. Both trastuzumab treatment and overexpression of miR-194 inhibited cell motility of breast cancer cells, which may result from the inhibition of DNMT3A and profilin 2. In summary, trastuzumab treatment upregulates miR194 expression and may exert its therapeutic effects through downregulation of miR194-downstream targets DNMT3A and profilin 2 in HER2-positive breast cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4000. doi:10.1158/1538-7445.AM2011-4000
Abstract 4005: The leukemia-associated fusion protein DEK-NUP214 induces proliferation through an mTOR-dependent mechanism
Authors: Sandén Carl , Ageberg Malin , Gullberg Urban 
Published: June 2012

Abstract
Acute myeloid leukemia (AML) is characterized by the dysregulated proliferation and impaired differentiation of myeloid precursor cells. The majority of these leukemias harbor genetic translocations, which determine both the molecular mechanistics and the prognosis of the disease. The t(6;9)(p22;q34) chromosomal translocation is found in 1% of AML, where it is associated with young age and poor prognosis. The translocation occurs between specific introns in the gene DEK on chromosome 6 and the gene NUP214 on chromosome 9, creating the fusion gene DEK-NUP214. The role of DEK-NUP214 in leukemogenesis is still largely uncharacterized. To obtain an experimental model of the disease, we expressed the fusion gene in the myeloid cell line U937 and studied the phenotype of the stable clones. We show that cells expressing DEK-NUP214 proliferate faster and also sustain their proliferative capacity longer in culture than their normal counterparts. Cellular proliferation is regulated by a wide range of signaling pathways, but many converge on the activating phosphorylation of the mechanistic target of rapamycin (mTOR) at Ser2448. Western blot analysis of the clones revealed that cells expressing DEK-NUP214 have higher levels of both phosphorylated and total mTOR protein. To determine the effect on downstream cellular functions, we proceeded to study mTOR-dependent translation and metabolism. We performed a global translation assay where the incorporation of radioactively labeled amino acids into newly synthesized proteins reflects the rate of translation. The results show that cells expressing DEK-NUP214 have a markedly increased translation rate. Cellular metabolism was studied by measuring the consumption of glucose and the production of lactate in cell supernatant. We demonstrate that cells expressing DEK-NUP214 produce less lactate, despite equal glucose consumption and increased proliferation. In concordance with increased mTOR activity, our results suggest that cells expressing DEK-NUP214 shift their metabolism from glycolysis to oxidative phosphorylation. The increased activity of mTOR thus leads to translational and metabolic changes that could play a role in the leukemogenic effect of DEK-NUP214. Interestingly, proliferation induced by DEK-NUP214 is highly dependent on mTOR. Treatment with the mTOR inhibitor everolimus (RAD001) reduces the proliferation of the DEK-NUP214 cells to the level of the control cells, without affecting the control cells. This pivotal role of mTOR suggests that leukemias harboring the t(6;9)(p22;q34) translocation may be susceptible to treatment with either rapamycin or the novel mTOR inhibitors that are approaching the clinic.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4005. doi:10.1158/1538-7445.AM2011-4005