bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2412: The modulatory effects of H. pylori infection in the DNA mismatch repair
Authors: Santos Juliana C. , Almeida Victor R. de , Fischer Wolfgang , Haas Rainer , Ribeiro Marcelo L. 
Published: May 2015

Abstract
The bacterial pathogen H. pylori chronically infects the human gastric mucosa and is the leading risk factor for the development of gastric cancer. It is believed that during the infection the organism causes an impairment of DNA repair in the gastric epithelium. Thus, we evaluated the in vitro modulatory effects of H. pylori infection in the DNA mismatch repair (MMR).
To evaluate the effects of H. pylori on MMR, AGS gastric carcinoma cell line and the H. pylori strain P12 were used in co-culture experiments for 4, 8 and 12 h. In addition, to analyze the potential effects of virulence factors on MMR, the ΔcagPAI, ΔvacA, ΔbabA, ΔhopQ, and Δtfs4 mutants were also subjected to co-culture experiments. The expression levels of EXO1, MLH1, MSH2, MSH3, MSH6, POLD3, PMS1, and PMS2 were assessed by real-time PCR. Moreover, expression levels of five previously screened miRNAs (miR-142-5p, miR-150-5p, miR-155-5p, miR-3163, and miR-4775), which are predicted to target MMR genes, were also evaluated by real-time PCR.
Our data show that H. pylori infection significantly down-regulates the expression of all selected genes. Regarding the virulence factors, the results suggest that the modulation on gene expression might be dependent on cagPAI, vacA, and the type IV secretion (TFS4) system. Although the infection up-regulates miR-150-5p, miR-155-5p, miR-3163, and miR-4775, only the expression of miR-155-5p is related with virulence factors.
Briefly, this study shows that H. pylori regulates the expression of several MMR genes, and it may be related with cagPAI, vacA, and the TFS4 system. Taking into account that MLH1, MSH2, and MSH6 are the miR-155-5p predicted targets, these preliminary data suggest that the observed virulence factor-dependent repression of miR expression could be responsible for the down-regulation of these MMR genes.
Citation Format: Juliana C. Santos, Victor R. de Almeida, Wolfgang Fischer, Rainer Haas, Marcelo L. Ribeiro. The modulatory effects of H. pylori infection in the DNA mismatch repair. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2412. doi:10.1158/1538-7445.AM2014-2412
Abstract 2416: Protein expression analysis of premature termination codon containing mutant proteins in colon cancers with high microsatellite instability
Authors: Yoon SeongJu , Kim Won Kyu , Park Jeon Han , Kim Hoguen 
Published: May 2015

Abstract
Frameshift mutations at coding mononucleotide repeats (cMNR) are common in the tumors with high microsatellite instability (MSI-H). These mutations invariably generate mRNAs containing abnormal coding sequences and premature termination codons (PTC). Normally, these mRNAs containing PTC are degraded by nonsense mediated mRNA decay (NMD) system. However, mRNAs containing PTC located in the last exon are not subject to be degraded by NMD system, and thus expected to generate truncated mutant proteins. We identified 29 novel mutations at coding region mononucleotide repeats (cMNR) genes by a PCR based method and sequencing. The frequency was varying (10% to 90%) in the 10 MSI-H colon cancer cell lines. To confirm the mRNA level, we analyzed the mutant mRNAs from identified genes in colon cancer cell lines and found that the mutant mRNAs were not degraded in cells. For mutant protein detection, we adopted both immunobloting and a target mass method to detect endogenous mutant proteins in cells. By immunobloting analysis, we found rare level of endogenous mutant proteins in cells. Using a target mass method, however, we could detect potential mutant protein candidates and confirmed one of the mutant candidates (VPS37B mutant proteins) is stably expressed in cells by in vitro overexpression experiments. When mutated, VPS37B mutant proteins came to acquire very short neopeptides (only two novel amino acids) which mainly disturb the stable expression of mutant proteins and this might explain the intact expression of VPS37B mutant proteins. Taken together, our findings suggest that frameshift mutations at cMNR of genes usually lead to the rare expression of the mutant proteins in tumor cells but, some mutant proteins with short neopeptides could be stably detected by a highly sensitive target mass method.
Citation Format: SeongJu Yoon, Won Kyu Kim, Jeon Han Park, Hoguen Kim. Protein expression analysis of premature termination codon containing mutant proteins in colon cancers with high microsatellite instability. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2416. doi:10.1158/1538-7445.AM2014-2416
Abstract 2419: Protective role of thioredoxin-1 in base excision repair under redox modulation
Authors: Kim Hye Lim , Koedrith Preeyaporn , Lee Sang Min , Kim Yeo Jin , Seo Young Rok 
Published: May 2015

Abstract
Thioredoxin-1 (Trx1) is an antioxidant enzyme with a protective role in the removal of reactive oxygen species (ROS). We investigated the mechanism by which the redox modulator Trx1 affects base excision repair (BER) activity to understand the protective role of Trx1. We constructed a Trx1 knockdown system to demonstrate the specific mechanism of Trx1. DNA damage in terms of relative intensity of the DNA tail and γ-H2AX foci was markedly higher in the Trx1 shRNA cells compared with that in the wild type cells, leading to increased cellular susceptibility to a sublethal dose of BER-inducible toxicant, nitrosomethylurea (NMU). In addition, we observed a modulatory role of Trx1 in the BER pathway via the p53 downstream gene, growth arrest, and DNA-damage-inducible protein 45 α (Gadd45a). The protein level and function of p53, a Trx1 downstream gene, coincidently decreased in the Trx1 shRNA cells. Furthermore, Trx1 shRNA cells showed decreased Gadd45a expression and interaction of Gadd45a with apurynic/apyrimidinic endonuclease 1 (APE1) as well as APE1 activity. In conclusion, Trx1 might cooperate in the control of APE1 function by modulating the p53-mediated BER via the protein-protein interaction between Gadd45a and APE1, providing insight into the novel role of redox factor Trx1 in modulation of BER.
Note: This abstract was not presented at the meeting.
Citation Format: Hye Lim Kim, Preeyaporn Koedrith, Sang Min Lee, Yeo Jin Kim, Young Rok Seo. Protective role of thioredoxin-1 in base excision repair under redox modulation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2419. doi:10.1158/1538-7445.AM2014-2419
Abstract 242: Dietary PUFA's alter the visceral adipose secretome, which modulates mammary stem cell self-renewal
Authors: Esper Ray , Dame Michael , Zora Djuric , Smith William , Max Wicha , Brenner Dean 
Published: May 2015

Abstract
Rationale: Dietary PUFA's alter the expression and secretion of a variety of adipokines. Diets rich in omega-6 fatty acids shift the leptin:adiponectin ratio in favor of leptin, whereas diets rich in omega-3 fatty acids have the opposite effect. We tested the hypothesis that different ratios of adipose-derived factors differentially drive or inhibit normal mammary stem cell self-renewal.
Methods: F344 rats were fed an obesogenic diet supplemented with arachidonic acid (AA) and eicosapentanoic acid (EPA) in either a 1:0 or 1:0.4 ratio. At 20 weeks, the animals were sacrificed and the visceral adipose explants were maintained in culture for up to 10 days. Conditioned media was collected at 48 hours. Adipokine concentrations were measured with the Proteome Profiler Adipokine Array and normalized to a leptin ELISA. Primary human mammary epithelial cells and the MCF10A breast cell line were expanded in a non-adherent sphere-forming assay as a measure of stem cell self-renewal. Cell suspensions were exposed to adipose conditioned media (1 mg/ml total protein concentration). After 10 days, spheres were counted and sphere size was measured using ImageJ.
Results: Adipose explants were maintained in culture for up to 10 days with &gt;99% viability. The secretome from the rats fed omega-6 PUFA's was enriched for leptin, resistin, serpin E1, and lipocalin-2. The omega-3 rich diet led to enrichment for adiponectin, pentraxin, and RBP4 in the adipose secretome. The adipose conditioned media from the omega-6 fed rats increased mammary stem cell self-renewal by 190%, whereas that from the rats fed omega-3 PUFA's attenuated this effect.
Conclusion: The n3:n6 dietary ratio promotes a shift in the ratios of multiple secreted adipokines. These ratios have a differential effect on mammary stem cell self-renewal. A diet rich in omega-6 PUFA's leads to increased stem cell self-renewal, whereas a diet supplemented with EPA attenuated this effect. Further studies will clarify the role of specific adipokines on mammary stem cell self-renewal.
Selected adipokine levels in adipose conditioned mediaOmega-3 rich dietOmega-6 rich dietn6:n3 dietary ratio1:0.41:0.0Adiponectin1864.7778.3Leptin181.2208.7Lipocalin-244.1323.1Pentraxin-277.00.8Pentraxin-319.29.3Pref-122.98.8Resistin737.01372.3Serpin E125.877.4RBP41136.0318.1
Citation Format: Ray Esper, Michael Dame, Djuric Zora, William Smith, Wicha Max, Dean Brenner. Dietary PUFA's alter the visceral adipose secretome, which modulates mammary stem cell self-renewal. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 242. doi:10.1158/1538-7445.AM2014-242
Abstract 2420: Ribonucleotide reductase promotes genomic instability and tumor heterogeneity via increasing dUTP misincorporation into DNA
Authors: Chang Zee-Fen 
Published: May 2015

Abstract
Regulation of enzymes in nucleotide synthesis plays a critical role in DNA replication and repair. Ribonucleotide reductase (RNR), which is composed of RRM1/ RRM2A or RRM2B, is the key enzyme that controls the de novo synthesis of all four dNTPs, and the expression of RRM2A subunit is cell cycle-dependent. It has been well established that the level of RRM2A is often elevated in malignant tumor cells and RRM2A transgenic mice develop lung cancer. The molecular mechanism of RRM2A in cancer promotion is still unknown. In this study, we showed that constitutive elevation of RRM2A promotes replication stress, chromosome instability and cellular transformation, all of which are prevented by co-expression of dUTPase that degrades dUTP. Knockdown of dUTPase in cancer cells containing high levels of RRM2A and dUTPase also increased replication stress. Immunohistochemistry staining of surgical tumors from colorectal cancer (CRC) patients showed that high RRM2A/low dUTPase correlates with poorer overall survival, suggesting the opportunity of using RRM2/dUTPase as a prognostic indicator. We proposed that the cellular context of high RRM2/low dUTPase causes chromatin instability to drive tumor evolution, resulting in poor survival in patients. Our findings also imply that tumor cells with elevation of RRM2A are vulnerable to inhibitors against dTTP synthesis in conjunction with DNA damage agent in therapy.
Citation Format: Zee-Fen Chang. Ribonucleotide reductase promotes genomic instability and tumor heterogeneity via increasing dUTP misincorporation into DNA. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2420. doi:10.1158/1538-7445.AM2014-2420
Abstract 2426: Exacerbation of oxidative DNA damage as a synthetic lethal approach in mismatch repair deficient tumors
Authors: Fontebasso Yari , Hewish Madeleine , Lord Chris J. , Ashworth Alan 
Published: May 2015

Abstract
The post-replicative DNA mismatch repair (MMR) pathway plays a key role in the maintenance of genomic stability. MMR corrects mismatches within the DNA helix that arise due to errors in nucleotide incorporation during either semi-conservative replication or synthesis associated with DNA repair. The importance of this system is testified by the fact that mutations affecting components of this repair pathway cause a “mutator” phenotype and predisposition to a wide variety of malignancies including colorectal, gastric, endometrial, and urothelial cancers. For example, the hereditable disorder Lynch syndrome (hereditary nonpolyposis colon cancer) is associated with germline loss of function mutations in the MMR tumor suppressor genes MLH1, MSH2, PMS2, and MSH6. In addition to this familial syndrome, MMR deficiency is present in 15% to 17% of all colorectal cancer cases.
Synthetic lethal relationships have been identified that involve specific MMR genes, suggesting that synthetic lethal treatments could be applied to MMR deficient tumors. Previously, efforts to functionally identify genetic DNA mismatch repair synthetic lethalities and potential therapeutic targets have focused on the analysis of either candidate genes or relatively small gene subsets such as protein kinases. In order to define additional SL targets in MMR-deficient genetic backgrounds, we describe here the application of an shRNA screen in matched isogenic dMMR/pMMR (MMR-deficient/MMR-proficient) model cell lines. Using this screening approach, we identify new synthetic lethal interactions between MMR deficiency and components of the base excision repair and of the nucleotide sanitization systems, which restrict the extent of oxidative DNA damage. We propose that inhibition of the processes that minimize the oxidized DNA load could constitute a promising therapeutic approach in mismatch repair deficient cancers.
Citation Format: Yari Fontebasso, Madeleine Hewish, Chris J. Lord, Alan Ashworth. Exacerbation of oxidative DNA damage as a synthetic lethal approach in mismatch repair deficient tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2426. doi:10.1158/1538-7445.AM2014-2426
Abstract 2437: PKA/AMPK signaling is a mediator of the anti-proliferative effect of adiponectin on multiple myeloma cells
Authors: Medina Edward Antonio , Polusani Srikanth R. , Oberheu Kelli , Oyajobi Babatunde 
Published: May 2015

Abstract
Obesity increases the risk of developing multiple myeloma (MM). Adiponectin is a cytokine produced primarily by adipocytes, but paradoxically decreased in obesity, that has been implicated in progression of multiple myeloma. Herein, we evaluated the effects of prolonged exposure to adiponectin on the survival of MM cells as well as putative signaling mechanisms. We found that adiponectin activates PKA, which leads to decreased AKT activity and increased AMPK activation. AMPK, in turn, induces cell cycle arrest and apoptosis. Adiponectin-induced apoptosis may be mediated, at least in part, by the PKA/AMPK-dependent decline in the expression of the enzyme acetyl-CoA-carboxylase (ACC), which is critical to lipogenesis and thus cell survival. Importantly, supplementation with palmitic acid, the preliminary end product of fatty acid synthesis, rescues MM cells from adiponectin-induced apoptosis. Furthermore, 5-(tetradecyloxy)-2-furan carboxylic acid (TOFA), an ACC inhibitor, exhibited potent anti-proliferative effects on MM cells that could also be inhibited by fatty acid supplementation. Thus, the effect of adiponectin to reduce survival of MM cells appear to be mediated via its ability to suppress lipogenesis. Our findings suggest that activators of the PKA/AMPK pathway, or inhibitors of ACC, may be useful adjuvants in the treatment of MM. Moreover, the anti-myeloma effect of adiponectin supports the concept that decreased circulating levels of the adipokine, as occurs in obesity, promotes MM tumor progression.
Citation Format: Edward Antonio Medina, Srikanth R. Polusani, Kelli Oberheu, Babatunde Oyajobi. PKA/AMPK signaling is a mediator of the anti-proliferative effect of adiponectin on multiple myeloma cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2437. doi:10.1158/1538-7445.AM2014-2437
Abstract 245: Consumption of a high-fat diet abrogates inhibitory effects of selenium on spontaneous metastasis of Lewis lung carcinoma in mice
Authors: Yan Lin 
Published: May 2015

Abstract
The present study investigated the effects of dietary supplementation with selenium (Se) on spontaneous metastasis of Lewis lung carcinoma (LLC) in mice fed a high-fat diet using a 2x2 design. Three-week-old male C57BL/6 mice were fed the AIN93G diet or that diet modified with 45% calories from fat supplemented with or without 2.5 mg Se/4029 kcal as methylseleninic acid for 6 weeks, at which time they were injected subcutaneously with 2.5x105 LLC cells. The resulting primary tumor was removed surgically 10 days later, and the experiment was terminated after an additional 10 days. Consumption of the high-fat diet significantly increased the body fat mass, regardless of Se supplementation, compared to the AIN93G diet (p&lt;0.01). The high-fat diet increased lung metastases by 17% compared to the AIN93G diet (p&lt;0.01). Selenium supplementation reduced the metastases by 11% compared to non-supplemented controls (p&lt;0.05); however, the reduction was greater in AIN93G-fed mice (18%) than in mice fed the high-fat diet (5%). Supplemental Se reduced plasma concentrations of proteolytic proteases (uPA, p&lt;0.01; MMP-9, p&lt;0.05) and angiogenic factors (VEGF, p&lt;0.01; TIMP-1, p&lt;0.01) compared to non-supplemented controls. The high-fat diet significantly increased plasma concentrations of adipokines PAI-1, MCP-1, TNF-α and leptin regardless of the level of dietary Se; however, supplemental Se reduced plasma PAI-1 (p≤0.05) and MCP-1 (p≤0.05) in AIN93G-fed mice. These results demonstrate that consumption of a high-fat diet abrogated the anti-metastatic effects of Se, and that such an abrogation may involve adipose-derived inflammatory cytokines.
Citation Format: Lin Yan. Consumption of a high-fat diet abrogates inhibitory effects of selenium on spontaneous metastasis of Lewis lung carcinoma in mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 245. doi:10.1158/1538-7445.AM2014-245
Abstract 2454: Ampk and hdac pathways and regulation rassf1c gene expression
Authors: Amaar Yousef G. , Reeves Mark E. , Firek Matthew 
Published: May 2015

Abstract
Introduction: We have previously shown that RASSF1C promotes cell proliferation, migration and attenuates apoptosis in cancer cells. We have also shown that RASSF1C is significantly up-regulated in breast and lung cancer tissues compared to normal tissues. Together these demonstrate that RASSF1C, is not a tumor suppressor like RASSF1A, but instead appears to function as an oncoprotein.
Currently nothing is known about the upstream signaling cascades involved in regulating RASSF1C gene expression and thus we performed transcriptome PCR array study to identify chemicals inhibitors that modulate(s) RASSF1C expression.
Method: A transcriptome PCR array was obtained from Qiagen. It consisted of cDNA from breast cancer cell line MCF7 cells treated with 90 different chemical inhibitors that regulate various signaling pathways. The array was screened with RASSF1C gene specific primers. Data analysis was performed by importing the Ct values obtained into data analysis software.
Results: The PCR array screen identified several chemical reagents that appear to up-regulate and several that seem to down-regulate RASSF1C expression by ≥ 1.5 fold. The two most notable reagents are Dorsopmorhin (AMPK inhibitor) which up-regulates RASSF1C expression by 2.8 fold and Trichostatin A (HDAC inhibitor) which down regulates RASSF1C expression by 2 fold. We are in process of confirming the effect of these inhibitors in a panel of breast and lung cancer cells.
Conclusion: The findings are novel and suggest that inhibition of AMPK pathway induces RASSF1C expression while inhibition of HDAC pathway suppresses RASSF1C gene expression. We should note that Trichostatin A has been shown to activate AMPK, inhibits HDAC, arrests cell growth, and induces apoptosis in human cancers. Our findings provide a potential mechanism for regulating RASSF1C gene expression through the modulation of AMPK and HDAC pathways.
Citation Format: Yousef G. Amaar, Mark E. Reeves, Matthew Firek. Ampk and hdac pathways and regulation rassf1c gene expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2454. doi:10.1158/1538-7445.AM2014-2454
Abstract 2458: Automated analysis of four color PTEN deletion in prostate cancer using FISHQuant on a whole slide image
Authors: Csizmadia Annamaria , Szipocs Ferenc , Park Janet , Harris Mohammmed , Hartmayer Peter , Moss Thomas J. 
Published: May 2015

Abstract
Mutations within the Phosphatase and tensin homolog (PTEN) gene have been linked to the development of many cancers. PTEN is one of the most commonly lost tumor suppressors in human cancer; in fact, up to 40% of men with prostate cancer are estimated to have lost a copy of the PTEN gene at the time of diagnosis. Slides stained with CymogenDx's PTEN del-TECT FOUR COLOR probe, developed for reliably detecting PTEN deletion, are scanned using 3DHISTECH's Panoramic 250 FLASH II digital slide scanner and the resulting whole slides are subsequently analyzed using 3DHISTECH's FISHQuant software. The ability to capture fluorescent signals from 9 independent channels and up to 29 different Z layers with perfect co-localization enables the creation of multiple labelled fluorescent slides. 3DHISTECH's “Extended Focus” feature creates a single in-focus image where all the in-focus parts of each captured layer is merged into one composite image. This enables the use of automated algorithms to evaluate different FISH probes in tissue and cytology whole slide samples. The FISHQuant software segments nuclei and spots automatically and scores the resulting data. For PTEN deletion, it measures the deletion clusters for the 3 colors involved. It also uses the control to check for numerical deviation of the 10th chromosome's signals. These two measurements are run automatically and displayed on a two-dimensional “HistoPlot”. This proof of concept study, using prostate core needle biopsies, demonstrates that the PTEN deletion FISH signals captured on a digital slide and overlaid in bright field and fluorescence modes can be subsequently analyzed using automated algorithms. The ability to identify tumor heterogeneity in a prostate core biopsy (and other sample preps) thus becomes possible. “Extended focus” and the patent pending PTEN del-TECT FOUR COLOR probe limits truncations artifact and makes a huge difference as sections get thinner due to other tests needing to be performed. Having access to the whole slide for analysis provides enough cells of interest.
Citation Format: Annamaria Csizmadia, Ferenc Szipocs, Janet Park, Mohammmed Harris, Peter Hartmayer, Thomas J. Moss. Automated analysis of four color PTEN deletion in prostate cancer using FISHQuant on a whole slide image. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2458. doi:10.1158/1538-7445.AM2014-2458