bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B47: Exploring the mechanism of cancer stem cell-specific action by salinomycin in yeast as a model
Authors: Siede Wolfram 
Published: June 2012

Abstract
The antibiotic salinomycin represents a selective potassium ionophore. It has recently attracted considerable attention due to its stem-cell specific mode of action as elucidated in a breast cancer stem cell model [1]. Further studies revealed additional benefits, e.g. the triggering of apoptosis in resistant cancer cell lines and reversal of multidrug resistance [2,3]. In budding yeast, we discovered that this agent is active and, similar to nigericin, prominently causes mitochondrial damage as revealed by the emergence of respiration-defective cells. We also noted the frequent occurrence of salinomycin-resistant clones which may prove to be an obstacle in chemotherapy. We used the collection of systematic gene deletions in haploid yeast to characterize genes whose deletion confers sensitivity or resistance to salinomycin if a carbon source is provided (glycerol) that requires active respiration for growth. With this toxicogenomics approach in a model organism, we attempt to elucidate cancer stem cell-specific therapy targets and suggest strategies to avoid the development of salinomycin resistance.
Among salinomycin-sensitive deletion mutants, significant overlap was found with known mutants sensitive to the ionophore monensin. Within this group, mutants that compromise vacuole/Golgi function and autophagy dominate. Novel genes were also uncovered which confer salinomycin sensitivity if deleted, such as CAJ1, encoding a heat shock protein of the dnaJ family, and certain arginine synthesis genes.
On the other hand, deletions of TOR pathway components as well as deletions of the E2-ubiquitin conjugating enzymes UBC13 and MMS2 were among the most salinomycin-resistant mutants we found.
In almost all cases, a strong correlation between salinomycin and nigericin sensitivity was observed. Since salinomycin appears to be the more efficient anti-cancer stem cell agent [1], the few cases of differential sensitivity will be discussed.
[1] Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, et al. (2009) Cell 138:645–659. [2] Fuchs D, Heinold A, Opelz G, Daniel V, Naujokat C (2009) Biochem Biophys Res Commun 390:743–749. [3]Fuchs D, Daniel V, Sadeghi M, Opelz G, Naujokat C (2010) Biochem Biophys Res Commun 394:1098–1104.
Supported by Cancer Prevention and Research Institute of Texas.
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 B47.
Abstract B63: Identification of small molecules that selectively target glioma stemlike cells
Authors: Lim S. Kyun , Wei Shuguang , Samples Darren , Li Yanjiao , Cho Woosung , McKay Renee , Williams Noelle S. , Posner Bruce A. , Parada Luis F. 
Published: June 2012

Abstract
Gliomas are the most frequently occurring primary malignancies in the central nervous system, with glioblastoma multiforme (GBM) the most common and most aggressive of these tumors. GBM is virtually incurable because, following the standard treatment of care—surgical resection, radiation, and chemotherapy—the tumors eventually recur. Recent studies including our own indicate a crucial role for a specific subset of tumor cells (cancer stem cells) in tumor development and recurrence. We have generated fully penetrant, tumor-suppressor-based somatic mouse models of glioma, with gene mutations frequently found in human glioma (p53, NF1, Pten; termed Mut6 tumors). These tumor models develop GBM that histopathologically and molecularly mimics the human disease. Transcriptional profiling of these tumors revealed that they are most similar to human GBM. Using the pooled Mut6 stem-like cancer cells we performed a high-throughput screen designed to identify small molecules that inhibit the growth of these cells, as measured by a luminescence ATP assay. We performed a 200,000 compound library screen, initially identifying 4,480 compounds that were then retested in increasingly stringent assays such that we now have approximately 70 unique compounds that adversely affect glioma stem cell growth. These compound hits were found to have EC50s in the nanomolar range and to act with considerable specificity, affecting the mutant stem cells at concentrations that do not affect cultured astrocytes or mouse embryonic fibroblasts. Among these, we tested 46 compounds in metabolic stability tests and found 17 compounds with excellent stablilty profiles. We believe these compounds present promising lead compounds for drug development as well as for uncovering critical pathways in glioma tumor development and self renewal.
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 B63.
Abstract C12: Identification of potential protein targets of isothiocyanates by proteomics
Authors: Mi Lixin , Hood Brian L. , Stewart Nicolas A. , Xiao Zhen , Govind Sudha , Wang Xiantao , Conrads Thomas P. , Veenstra Timothy D. , Chung Fung-Lung 
Published: June 2012

Abstract
Isothiocyanates (ITCs), such as phenethyl isothiocyanate (PEITC) and sulforaphane (SFN), are effective cancer chemopreventive compounds. Induction of cell cycle arrest and apoptosis is believed to be a major mechanism for their cancer preventive activity. Our previous studies indicate that covalent binding to target proteins is an important upstream event. However, the identity of ITC binding targets remains largely unknown. To identify proteins that are covalently modified by ITCs, human non-small cell lung cancer A549 cells were treated with 14C-PEITC and 14C-SFN and the cell lysates were extracted for analysis by 2-D gel electrophoresis and mass spectrometry. After superimposing the colloidal Coomassie blue protein staining pattern with the pattern of radioactivity obtained from X-ray films, it was clear that only a small fraction of cellular proteins contained radioactivity, presumably resulting from selective binding with PEITC or SFN via thiocarbamation. In this study, more than 30 proteins with a variety of biological functions, including cytoskeleton, redox regulation, protein quality control, stress response, mitochondria, and signaling transduction, were identified with high confidence. Here we report the identities of these potential ITC target proteins and discuss their biological relevance. The discovery of the protein targets may facilitate studies of the mechanisms by which ITCs exert their cancer preventive activity and provide molecular basis for designing more efficacious ITC compounds.
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 C12.
Abstract C47: Acetaminophen enhances the chemotherapeutic effect of cisplatin and paclitaxel on human ovarian carcinoma cells in vitro
Authors: Wu Yingjen Jeffrey , Neuwelt Alexander J. , Muldoon Leslie L. , Neuwelt Edward A. 
Published: June 2012

Abstract
Chemoresistance is commonly found in treating cancer patients. Acetaminophen enhances the cytotoxicity of cisplatin in human liver cancer cells by depleting glutathione and increasing production of toxic metabolites in vitro. The objective of this study was to investigate potential molecular mechanisms for chemoenhancement in nonhepatic cells. Human ovarian carcinoma SKOV3 cells were treated with cisplatin or paclitaxel with or without acetaminophen in vitro. Cellular mitochondrial membrane potential and reactive oxygen species concentration was measured by using JC-1 and DHR123 stain, respectively. Cellular platinum level was analyzed using ICP-MS. Apoptosis and signaling pathways were examined by immunoblotting and immunohistochemical analyses. A 2-h incubation with acetaminophen (10 mM) decreased cellular glutathione levels and increased mitochondrial membrane potential without affecting reactive oxygen species. Overnight acetaminophen treatment increased reactive oxygen species and enhanced both cisplatin- and paclitaxel-induced apoptosis. In contrast, the combination of acetaminophen with cisplatin but not paclitaxel blocked nuclear translocation of nrf2, a transcription factor that has been implicated in regulation of the antioxidant response. Pretreatment with acetaminophen for 2 h did not affect cellular platinum uptake when compared to cisplatin alone. Regardless of different oxidative stress pathways involved between cisplatin and paclitaxel, the addition of acetaminophen enhanced the cytotoxic effects of both chemotherapeutic drugs in human ovarian carcinoma cells. Our results suggested that acetaminophen could be used as a chemoenhancing adjuvant for conventional chemotherapy drugs in treating ovarian and other malignancies.
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 C47.
Abstract C62: Cancer cell dependence on unsaturated fatty acids implicates stearoyl-coA desaturase as a target for cancer therapy
Authors: Roongta Urvashi V. , Lawrence R. Michael , Wong Tai W. , Rupnow Brent A. , Pabalan Jonathan G. , Wang Xinyu , Ryseck Rolf-Peter , Fargnoli Joseph , Henley Benjamin J. , Yang Wen-Pin , Zhu Jun , Madireddi Malavi T. 
Published: June 2012

Abstract
Emerging literature suggests that metabolic pathways play an important role in the maintenance and progression of human cancers. In particular, recent studies have implicated lipid biosynthesis and desaturation as a requirement for tumor cell survival. In the studies reported here, we aimed to understand whether tumor cells require the activity of either human isoform of stearoyl-CoA-desaturase (SCD1 or SCD5) for survival. Inhibition of SCD1 by siRNA or a small molecule antagonist results in strong induction of apoptosis and growth inhibition when tumor cells are cultured in reduced (2%) serum conditions but has little impact on cells cultured in 10% serum. Depletion of SCD5 had minimal effects on cell growth or apoptosis. Consistent with the observed dependence on SCD1 but not SCD5, levels of SCD1 protein increased in response to decreasing serum levels. Both induction of SCD1 protein and sensitivity to growth inhibition by SCD1 inhibition could be reversed by supplementing growth media with oleic acid, a product of the enzymatic reaction catalyzed by SCD1. Transcription profiling of cells treated with an SCD inhibitor revealed strong induction of markers of endoplasmic reticulum stress. Underscoring its importance in cancer, SCD1 protein was found to be highly expressed in a large percentage of human cancer specimens. SCD inhibition resulted in tumor growth delay in a human gastric cancer xenograft model. Altogether, these results suggest that desaturated fatty acids are required for tumor cell survival and that SCD may represent a viable target for the development of novel agents for cancer therapy.
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 C62.
Abstract C65: Chemopreventive effects of Brazilian traditional medicine Tabebuia avellanedae on in vitro and in vivo carcinogetic systems.
Authors: Tokuda Harukuni , lida Akira , Suzuki Nobutaka 
Published: June 2012

Abstract
As part of an ongoing project to investigate the antitumor and antitumor promoting properties of Tabebuia avellanedae, its dry powder essence and its active compound, 5-hydroxy-2- {(1-hydroxymethyl)-naphtho 2,3-b} furan-4,9-dione (NQ-801) were carried out. Tabebuia avellanedae (Bignoniaceae) (TA), which is native in South America from Brazil to northern Argentina, is well known in traditional folk medicine used for the treatment of various disease during five hundred years. The inner bark of this plant produced in Brazil is distributed in Asia as a herb tea and healthy purpose. The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and phorbol esters in enabled rapid and easy detection of naturally occurring substances(anti-tumor promoters, chemopreventive agents) with inhibition of Epstein-Barr virus(EBV) activation, using human lymphoblastoid cells. The percentage of the inhibition of TPA-induced EBV-EA activation for these compounds were from 90% to 40%, at experimental concentrations. In addtion, we have now extended these investigations to a new tumorigenesis model in which we initiated the tumors with DMBA initiation and promoted with 1.7 nmol of TPA in two-stage mouse skin test and other models. The control animals exhibited a 100 % papilloma incidence at 20 weeks after promotion. However, treatment with the tested compounds(85 nmol) along with initiator and promoter, reduced the percentage of tumor bearing mice by between 13.3-33.3 at 20 weeks. Employing Western blot analysis studies, we found that H-Ras, MEK and p38 levels observed the effects against carcinogenesis. Base on our data, we suggest that one target of these natural source effect in mouse skin is the modulation of the MAPK signal pathway. These results provide a basis for further development of these botanical supplements for human cancer chemoprevention
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 C65.
Abstract IA23: Harnessing genetic dependencies in cancer therapy
Authors: Ashworth Alan 
Published: June 2012

Abstract
Many tumors harbor defects in their ability to maintain genomic integrity. This contributes to the mutational burden and likely fosters pathogenesis. We have been exploring therapeutic strategies to exploit these defects. We have used a synthetic lethal approach to target the defect in DNA repair by homologous recombination in tumors with a BRCA1 or BRCA2 mutation. This strategy using PARP inhibitors is showing considerable promise in the clinic. Here, I will describe the approach as well recent work defining determinants of sensitivity and resistance to PARP inhibitors. The application of the synthetic lethal approach to other cancer types will also be discussed. In addition, we have been using high- and medium-throughput RNAi screens to uncover new therapeutic targets for cancer as well as biomarkers of patients who might respond to specific treatments. In particular, I will discuss the integration of genomic, gene expression, and RNAi data to generate functional maps of cancer cell lines.
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 IA23.
Abstract IA8: Natural killer cells in host defense against cancer
Authors: Lanier Lewis L. 
Published: June 2012

Abstract
Natural killer (NK) cells provide host defense against cancer and infections with pathogens. NK cells express a sophisticated repertoire of activating and inhibitory receptors that regulate their ability to discriminate between healthy cells and cells that have become transformed as a consequence of genomic aberration or infected by pathogens. NKG2D is an activating receptor on NK cells and T cells that detects host-encoded cell surface glycoproteins preferentially displayed by “stressed” cells. In humans these include the MICA, MICB, and ULBP molecules that are frequently over-expressed by many types of human cancers. Despite expression of these ligands, tumors nonetheless can continue to grow and evade elimination by the immune system. We will present and discuss new mechanisms by which tumors can evade the NKG2D system of immunosurveillance and allow tumor progression.
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 IA8.
Abstract A74: Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) Study, 1990–2006
Authors: Joshu Corinne E. , Elizabeth Selvin , Prizment Anna E. , Dluzniewski Paul J. , Menke Andy , Folsom Aaron R. , Coresh Josef , Yeh Hsin C. , Brancati Frederick L. , Platz Elizabeth A. 
Published: June 2012

Abstract
Background: Diabetes is a risk factor for many cancers; chronic hyperglycemia is hypothesized to be, in part, explanatory. We evaluated the association between glycated hemoglobin, a time-integrated glycemia measure, and cancer incidence and mortality in non-diabetic and diabetic men and women.
Methods: We conducted a prospective study of 12,792 cancer-free participants attending the second visit (1990–1992) of the Atherosclerosis Risk in Communities (ARIC) Study. We measured glycated hemoglobin in whole-blood samples using HPLC. Incident cancers were ascertained from registries and hospital records through 2006. We estimated multivariable-adjusted hazard ratios (HR) of cancer incidence and mortality for non-diabetic participants with values ≥5.7% (elevated), non-diabetic participants with &lt;5.0% (low), and diabetic participants all compared with non-diabetic participants with 5.0–5.6% (normal).
Results: We ascertained 2,349 incident cancer cases and 887 cancer deaths. Compared with non-diabetic women with normal glycated hemoglobin, non-diabetic women with elevated values had an increased risk of cancer incidence (HR:1.24; 95% CI:1.07,1.44) and mortality (HR:1.58; 95% CI:1.23,2.05) as did diabetic women (incidence, HR:1.30; 95% CI:1.06,1.60, mortality, HR:1.96; 95% CI:1.40,2.76). Non-diabetic women with low values also had increased risk. Diabetic women with good glycemic control (&lt;7.0%) had a lower cancer risk than those with higher values. Glycated hemoglobin in non-diabetic and diabetic men, and diabetes were not associated with risk.
Conclusions: Our findings support the hypothesis that chronic hyperglycemia, even in the non-diabetic range, increases cancer risk in women, but not men. Maintaining normal glycated hemoglobin overall, and good glycemic control among diabetic adults, may reduce the burden of cancer.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A74.
Abstract B112: Physical activity, sedentary behavior, and leukocyte telomere length in women
Authors: Du Mengmeng , Prescott Jennifer , Kraft Peter , Han Jiali , Giovannucci Edward , Hankinson Susan E. , De Vivo Immaculata 
Published: June 2012

Abstract
Telomeres are repetitive DNA-protein complexes that protect the ends of linear chromosomes and maintain genomic stability. They undergo erosion with each cycle of cell division, and oxidative stress and inflammation accelerate this shortening. Critically short telomeres may lead to several processes implicated in carcinogenesis, including chromosomal degradation, end-to-end fusion, and atypical recombination. Telomere length in peripheral blood leukocytes (PBLs) is a potential indicator of cellular aging and shortened leukocyte telomere length (LTL) has been linked to an increased risk of various cancer types, such as bladder, lung, and renal-cell. Regular physical activity reduces the risk of developing many cancers, and studies have observed lower levels of oxidative stress and inflammation in regularly active individuals. However, few population-based studies have examined the relation between physical activity and LTL, and none has addressed sedentary behavior. In addition, information is scarce on the role of exercise intensity and type in this relation. The authors therefore examined cross-sectionally the association between physical activity, sedentary behavior, and LTL among 7,813 women ages 43–70 in the Nurses' Health Study. Participants self-reported activity by questionnaire in 1988 and 1992, and sedentary behavior in 1992. Telomere length in PBLs, collected in 1989–1990, was measured by quantitative polymerase chain reaction. Least squares mean telomere length (z-score) was calculated after adjustment for age and other potential confounders. Total activity was positively associated with LTL. Compared with the least active women, those moderately or highly active had a 0.07 standard deviation (SD) increase in LTL (p-trend=0.02), a difference corresponding on average to 4.4 years of aging. Greater moderate-or vigorous-intensity activity was also associated with increased LTL; women who exercised 2–4 hours per week, an amount corresponding to current US guidelines, had the longest telomeres (0.11 SD increase for 2–4 vs. &lt;1 hours/week; 0.04 SD increase for 7+ vs. &lt;1 hours/week; p-trend=0.02). Among the individual activities, greater calisthenics or aerobics was associated with longer telomeres (0.10 SD increase for &gt;2.5 vs. 0 hours/week; p-trend=0.04). Associations remained after additionally adjusting for body mass index. Time spent on other activities and time spent sitting were unassociated with LTL. Although associations were modest, these findings suggest that even moderate amounts of activity may be associated with longer telomeres, providing insight into the understanding of how exercise may influence cancer risk on the cellular level. These findings warrant further investigation in large prospective studies.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B112.
Abstract B95: A dietary pattern that is associated with C-peptide and risk of colorectal cancer in women
Authors: Fung Teresa , Hu Frank , Schulze Matthias , Pollak Michael , Wu Tianying , Fuchs Charles , Giovannucci Edward 
Published: June 2012

Abstract
Higher serum C-peptide concentrations is associated with increased risk of colorectal cancer (CRC). Therefore, we used diet and C-peptide information from a subsample of women from a large cohort and applied stepwise linear regression to identify food groups that correlated with serum levels of C-peptide. These food contributors then formed dietary patterns for predicting the risk of CRC in the main cohort of women. In up to 22 years of follow-up, we ascertained 985 cases of CRC and 758 colon cancer cases. After adjusting for confounders, we observed that the C-peptide pattern, characterized by higher meat, fish, and sweetened beverage intake, but lower coffee, high fat dairy, and whole grains intake, showed direct association with CRC risk (comparing extreme quintiles, RR=1.35, 95% CI=1.07–1.70. p trend=0.009). In stratified analysis, we did not observe an association between the C-peptide pattern and colon cancer among lean and active women (RR comparing extreme quintiles=0.84, 95% CI=0.50–1.41, p trend=0.23). However, among women who were overweight or sedentary, RR for the same comparison was 1.58 (95% CI=1.20–2.07, p trend=0.002) (p for interaction=0.007). In addition, the association between the C peptide pattern and serum C peptide concentrations is also stronger in the sedentary or overweight group (r=0.23, p&lt;0.0001 vs r=0.15, p=0.01 among lean and active women). In conclusion, we derived a dietary pattern that correlated with C peptide concentrations. This pattern was associated with an increase of colon cancer, especially among women who were at risk for insulin resistance.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B95.