bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5746: Circulating cytokine levels, Epstein-Barr viremia and risk of AIDS-related non-Hodgkin lymphoma
Authors: Rabkin Charles S. , Engels Eric A. , Landgren Ola , Schuurman Rob , Goedert James J. 
Published: February 2011

Abstract
BACKGROUND: Human immunodeficiency virus (HIV) infection may lead to cytokine dysregulation and decontrol of Epstein-Barr virus (EBV) latency as potential mechanisms for acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). We therefore examined pre-diagnosis blood levels in AIDS-related NHL cases from three prospective cohort studies of HIV infection. METHODS: Plasma or serum were obtained from cases (n=66) 0.1 - 2.0 (median 1.0) years pre-NHL and from up to three HIV-positive lymphoma-free controls (n=186) sampled at comparable times, matched for cohort, age, race, sex and CD4 count at time of diagnosis. Cytokine measurements used Millipore 30-plex Luminex assays with values normalized by log-transformation; coefficients of variation for blinded replicate samples ranged from 10% - 46%. EBV free viremia was detected by real-time polymerase chain reaction (PCR) assays for the BNRF p143 gene; plasma samples originally collected with heparin anticoagulation (n=110) could not be assessed because of PCR inhibition. Statistical analyses were performed by conditional logistic regression for matched sets. RESULTS: Fifty-seven cases had at least one matched control, with mean (median) CD4 counts of 172 (86)/mm3 for cases and 174 (85)/mm3 for controls. Cases had significantly higher cytokine levels for nine of the 30 measured cytokines, with p&lt;.01 for granulocyte-monocyte colony-stimulating factor (GM-CSF) and interleukin (IL)-15, and p&lt;.05 for IL-1a, IL-4, IL-6, IL-8, IL-12 p40, IL-12 p70 and IL-13. Stepwise selection of a multivariable conditional model identified GM-CSF, IL-12p70 and IL-15 as the most predictive markers, with matched odds ratios (95% confidence intervals) of 1.5 (0.9 - 2.4), 1.5 (0.9 - 2.5) and 1.3 (0.9 - 1.9), respectively. EBV PCR-positivity had a matched odds ratio of 1.6 (0.5-5.0), based on serum and acid-citrate-dextrose plasma samples only. CONCLUSIONS: We found elevations of T-helper type-(Th)1, Th2 and pro-inflammatory cytokines and growth factors up to two years before AIDS-NHL; EBV viremia was not significantly predictive but statistical power was limited. Cytokine hyperstimulation of B-cell proliferation may be an important etiologic pathway to AIDS-related NHL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5746.
Abstract 5747: Anti-inflammatory nutrients and prostate cancer survival in the Örebro Prostate Cancer Survivors Cohort
Authors: Meyer Mara S. , Kasperzyk Julie L. , Andrén Ove , Wolk Alicja , Håkansson Niclas , Andersson Swen-Olof , Johansson Jan-Erik , Fall Katja , Mucci Lorelei A. 
Published: February 2011

Abstract
While many studies examine diet and prostate cancer (PCa) risk, few have assessed whether diet could influence prostate cancer-specific survival. Dietary factors that modulate the inflammatory response may alter clinical outcome, as chronic systemic inflammation may enhance PCa progression. As such, dietary zinc and fatty acids affecting the inflammatory response are promising targets for secondary prevention to impact survival after diagnosis.
We studied intake of dietary zinc and fatty acids in relation to cancer survival within the Örebro Swedish Cohort, including 525 confirmed PCa cases living in Örebro County who were diagnosed from 1989 to 1991. At the time of diagnosis, dietary data was collected by food frequency questionnaire specific to the Swedish diet. Use of dietary supplements was negligible in this population, which was assembled before the introduction of PSA testing. We studied intake of zinc and fatty acids (quartiles) and time to death (all cause and PCa-specific through Februrary 2009) using Cox proportional hazards models adjusted for lifestyle and clinical factors. Analyses were also stratified by clinical stage at diagnosis (early: T0-T2/M0, and advanced: T3-T4/M0/M1).
During follow-up, 218 men died from PCa and 257 from other causes. Zinc was not significantly associated with overall PCa-specific mortality, total mortality or in men diagnosed at an advanced stage. Yet among those diagnosed at an early stage, men with the highest zinc intake were 74% less likely to die of PCa (95% CI:0.10-0.68, ptrend=0.005) compared to lowest. High versus low intake of marine omega-3 docosahexaenoic acid (DHA) was associated with a reduced risk of PCa mortality overall (OR: 0.70, 95% CI: 0.47-1.03, ptrend=0.26), particularly among men diagnosed at an early stage (OR: 0.55, 95% CI: 0.23-1.58). DHA was not associated with death from other causes (OR: 1.07, 95% CI: 0.74-1.55, ptrend=0.68). The highest quartiles of saturated (HR: 1.15, 95% CI: 0.78-1.69), monounsaturated (HR: 1.18, 95% CI: 0.80-1.75) and polyunsaturated (HR: 0.90, 95% CI: 0.62-1.31) fatty acids were not associated with PCa survival.
Our results suggest men diagnosed at early stage prostate cancer may be sensitive to dietary zinc levels, which may prolong disease-specific survival. Omega-3 DHA may also be beneficial against prostate cancer-specific mortality, with inflammation being a potential common mechanism. Further research is needed to confirm these findings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5747.
Abstract 575: A subset of small cell lung cancer (SCLC) cell lines are Mcl-1-dependent and undergo apoptosis in response to Flavopiridol-mediated inhibition of cyclin-dependent kinase (cdk) 9
Authors: Qi Li , Shapiro Geoffrey I. 
Published: February 2011

Abstract
Small cell lung cancer (SCLC) accounts for approximately 13% of lung cancer cases. Although SCLC is initially a chemosensitive disease, the development of resistance is a major obstacle. Recently, multiple SCLC cell lines have been found to be responsive to a Bcl-2/Bcl-xL inhibitor, ABT-737, both in vitro and in vivo (Oltersdorf T et al. Nature. 2005 Jun 2; 435(7042): 677-81). Clinical trials of the related orally-available compound ABT-263 have shown promising activity in SCLC patients. However, a subset of SCLC cell lines that express Mcl-1, another anti-apoptotic protein, are resistant to ABT-737 treatment. Furthermore, SCLC lines have elevated expression of Mcl-1 when they become resistant to ABT-737 (Tahir SK et al. Cancer Res. 2007 Feb 1; 67(3): 1176-83). Therefore drugs targeting Mcl-1 may be particularly useful in this disease. Here, we have investigated dependence of a panel of SCLC cell lines on Mcl-1 for survival, using Mcl-1 knockdown achieved by lentiviral-based shRNA technology. Several SCLC cell lines expressing Mcl-1, including NCI-H82 and SHP77 cells, demonstrate apoptosis by TUNEL assay and reduced viability by MTS assay in response to Mcl-1 depletion. However, other SCLC cell lines, including NCI-H69 and SW1271, are not responsive to Mcl-1 knockdown. We have also investigated the efficacy of Flavopiridol, a potent inhibitor of cdk9, against a panel of SCLC cell lines. Flavopiridol acutely down-regulates Mcl-1 expression in NCI-H82, SHP77, H69 and SW1271 cells. Mcl-1-dependent cell lines, including H82 and SHP77, undergo abrupt apoptosis in response to Flavopiridol. In contrast, H69 and SW1271 cells, which were not found to be Mcl-1-dependent, were not effectively killed by Flavopiridol. These data suggest that Mcl-1-dependent SCLC cells may be particularly sensitive to Flavopiridol treatment to overcome ABT-737 resistance. Finally, we have demonstrated that the combination of Flavopiridol and ABT-737 can synergistically kill both Mcl-1-dependent and -independent SCLC cells, with significantly reduced viability in SHP77 and SW1271 cells compared to treatment with either drug alone. Taken together, our studies suggest Flavopiridol-mediated cdk9 inhibition may effectively target Mcl-1 dependent SCLCs, including those resistant to Bcl-2/Bcl-xL inhibition.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 575.
Abstract 5750: Reproductive factors and risks of biliary tract cancers and stones: population-based study in Shanghai, China
Authors: Andreotti Gabriella , Hsing Ann 
Published: February 2011

Abstract
Biliary tract cancers, encompassing tumors arising from the gallbladder, extrahepatic bile ducts, and ampulla of Vater, are relatively uncommon but highly fatal. Higher parity has been linked to increased risks of gallbladder cancer and gallstones, but the effects of other reproductive factors are less clear. Thus, we examined the association between reproductive factors and the risks of biliary tract cancers and biliary stones among women in a population-based case-control study in Shanghai, China. A total of 361 incident biliary tract cancer cases (269 gallbladder and 92 extrahepatic bile duct), 647 biliary stone cases, and 586 healthy women randomly selected from the population were included. High parity, early age at first birth, and late age at menarche contributed to a higher risk of gallbladder cancer risk, particularly among women with associated biliary stones. Among women with stones, those who had 4 or more children and had their first child before the age of 23 had a 3.3-fold (95% CI 1.06-10.03) risk of gallbladder cancer, while those with menarche at 16 years or later had a 4.0-fold (95% CI 1.19-13.58) risk. Among parous women, breastfeeding was associated with a reduced risk of bile duct cancer (OR=0.40, 95% CI 0.20-0.81). In contrast, menopausal status, age at menopause, duration of menstruation, and oral contraceptive use were not associated with biliary tract cancer risk. No association was found between biliary stones and any of the reproductive factors examined. Our results provide further support for a role of reproductive factors, especially high parity and late age at menarche, in the development of gallbladder cancer among women with biliary stones.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5750.
Abstract 5752: Molecular mechanisms driving oncogenesis in KRAS mutant non-small cell lung cancer
Authors: Holderfield Matthew , McCormick Frank , Nagel Tobi 
Published: February 2011

Abstract
The poor prognosis associated with Non Small Cell Lung Cancers (NSCLC) harboring KRAS mutations (∼20-30% frequency) has highlighted the need for RAS targeted therapeutics in oncology for decades. However, attempts to target RAS directly using small molecule inhibitors have historically proven unsuccessful. Additionally, pre-clinical data repeatedly demonstrates that KRAS mutated cancer cells show variable responses to inhibition of downstream effectors, RAF, MEK and PI3K, suggesting that proliferation and survival may be driven through additional pathways and that the molecular mechanisms through which KRAS drives oncogenesis have yet to be fully elucidated. Moreover, parallel pathways activated in human lung cancer that might cooperate with RAS to maintain a transformed state, likewise remain poorly defined. By screening a panel of KRAS mutant NSCLCs for functional dependence on KRAS by shRNA knockdown, we have identified cell lines that require KRAS for proliferation and suppression of apoptosis. In an effort to identify the signaling pathways that promote cellular proliferation and survival in KRAS-mutant lung cancers we have conducted an unbiased cellular screen to identify shRNAs that mitigate dependence on the KRAS oncoprotein. Using this method we have identified molecular pathways that appear to cooperate with the KRAS oncogene to promote tumorogenesis and contribute to the distinct proliferative and apoptotic phenotypes of KRAS dependent NSCLC cell lines.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5752.
Abstract 5754: Identification of pharmacologically tractable genes that are associated with oncogenic K-Ras dependency in colorectal cancers
Authors: Singh Anurag , Sweeney Michael F. , Greninger Patricia , Settleman Jeffrey E. 
Published: February 2011

Abstract
Summary
We have previously shown that KRAS mutant lung and pancreatic cancer cells can be classified into two broad groups based on their requirement or dependency for sustained K-Ras activity. By supervised gene expression analyses, we derived a gene expression signature associated with K-Ras dependency, components of which represent candidate therapeutic targets. We have applied this strategy to KRAS mutant colorectal cancers (CRCs), which are notoriously refractory to conventional and targeted therapeutics. Moreover, the KRAS gene is now routinely sequenced to identify CRC patients that harbor KRAS mutations. Thus, patients with KRAS mutation-positive CRCs are given little recourse in terms of treatment options. We have found that, like lung and pancreatic cancer cell lines, KRAS mutant can be classified into K-Ras dependent and K-Ras independent groups. However, whereas K-Ras dependency in KRAS mutant lung and pancreatic cancer cells is associated with a well differentiated epithelial-like phenotype, K-Ras dependent CRC cells do not exhibit such an association. As such K-Ras dependent CRC cells exhibit a distinct molecular profile compared to K-Ras dependent lung and pancreatic cancer cells. We have identified a number of distinct kinase genes whose expression is associated with K-Ras dependency specifically in CRCs. Depletion of these genes by RNAi results in selective cytotoxic effects in K-Ras dependent CRC cells, suggesting that these genes may serve as candidate therapeutic targets in a subset of KRAS mutant CRCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5754.
Abstract 5757: A genome-wide screen for microdeletions reveals disruption of polarity complex genes in diverse human cancers
Authors: Rothenberg Stephen M. , Mohapatra Gayatry , Rivera Miguel N. , Winokur Daniel , Greninger Patricia , Cohen Ezra E.W. , Louis David N. , Settleman Jeffrey , Haber Daniel A. 
Published: February 2011

Abstract
In a genome-wide screen of 684 cancer cell lines, we identified homozygous intragenic microdeletions involving genes encoding components of the apical-basal cell polarity complexes. Among these, PARD3 is disrupted in cell lines and primary tumors from squamous carcinomas and glioblastomas. Reconstituting PARD3 expression in both cell types restores tight junctions and retards contactdependent proliferation. Searching specifically for small intragenic microdeletions using high resolution genomic arrays may be complementary to other genomic deletion screens and resequencing efforts in identifying new tumor suppressor genes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5757.
Abstract 5759: The landscape of copy-number changes across multiple human cancer types
Authors: Beroukhim Rameen , Meyerson Matthew , Garraway Levi , Prensner John 
Published: February 2011

Abstract
Genomic regions undergoing frequent alteration in human cancers often point to genes that play causal roles in oncogenesis. We have performed high-resolution analyses of copy-number alterations from 3131 cancer specimens across multiple histological types. We identified 158 regions of that are significantly altered by focal copy-number changes. Among these, 122 regions cannot be explained by the presence of a known cancer gene. Several gene families are enriched among these regions, including the BCL2 family of apoptosis regulators and the NF-κB pathway. Cell lines with amplifications of the anti-apoptotic genes MCL1 and BCL2L1 depend upon these genes for survival. Finally, we find that the majority of copy-number changes identified in individual cancer types are present across multiple cancer types.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5759.
Abstract 576: Hydrogen peroxide and iron released from nitroprusside cooperate to induce melanoma cell death: role of the p53 genotype
Authors: Gomez Luis A. , Strasberg Mary , Rieber Manuel 
Published: February 2011

Abstract
BACKGROUND. We recently reported that sodium nitroprusside or nitroferricyanide (III) (SNP), an iron nitrosyl complex clinically used as a powerful vasodilator, promotes melanoma cell apoptosis independently of the status of the p53 tumor suppressor gene. This occurred with intact SNP but was delayed when using its light-exhausted form (lex-SNP) devoid of nitric oxide (NO) (1). OBJECTIVES. Since extracellular NO and hydrogen peroxide (H2O2) are increased after SNP treatment (2), to define antitumor effects of H2O2 plus NO or iron, we used sub-toxic exogenous H2O2 singly or together with either: a) SNP; b) lex-SNP; c) potassium ferricyanide or d) ferric ammonium sulphate, against genetically-matched human C8161 melanoma harboring wild type (wt) or mutant p53, since the latter contributes to drug resistance. METHODS. Cell survival was assayed by crystal violet staining or by determining percentage of calcein AM retention and lack of propidium iodide uptake. DNA damage was assessed by laser scanning cytometry and PARP fragmentation was measured by immune blotting. RESULTS. While each treatment alone showed low efficacy, a synergistic cytotoxicity was demonstrated only between either intact or lex-SNP + H2O2. Shorter treatments of these combinations were preferentially cytotoxic against wt p53 melanoma compared to their mutant p53 matched counterparts, in crystal violet survival assays. However, longer treatments with [SNP + H2O2] induced apoptosis-associated PARP cleavage irrespective of cellular p53 genotype. All these changes were antagonized by anti-oxidant N-acetyl cysteine (NAC) or metal chelator o-phenanthroline, suggesting that metal-dependent redox changes are important in this anti-tumor activity. CONCLUSIONS. When using alternative iron sources like those provided by potassium ferricyanide, ferric ammonium sulphate or sodium nitroferricyanide (III) (SNP), we show for the first time that in vitro anti-tumor combination therapy with sub-toxic H2O2 is achieved only with iron made available by SNP, since H2O2 did not synergize with iron provided by potassium ferricyanide or ferric ammonium sulphate. Lex-SNP devoid of NO (1) also potentiated the effect of H2O2, implying that the cooperative effect of [SNP + H2O2] is independent of its NO-donating ability.
REFERENCES
(1) Gomez-Sarosi LA, Strasberg-Rieber M, Rieber M. ERK activation increases nitroprusside induced apoptosis in human melanoma cells irrespective of p53 status: role of superoxide dismutases. Cancer Biol Ther 2009; 8:1173-82. (2) Rabkin SW and Kong JY. Nitroprusside induces cardiomyocyte death: interaction with hydrogen peroxide. Am J Physiol Heart Circ Physiol 2000; 279:H3089-H3100.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 576.
Abstract 5762: Role of BMP7 in dormancy and recurrence of prostatic tumor stem cell in the bone metastasis
Authors: Kobayashi Aya , Okuda Hiroshi , Furuta Eiji , Pandey Puspa R. , Watabe Misako , Pai Sudha K. , Xing Fei , Liu Wen , Watabe Kounosuke 
Published: February 2011

Abstract
Prostate cancer is becoming a curable disease when it is diagnosed at an early stage. However, even those patients who have localized cancer and have been “successfully” treated with surgery often experience recurrent disease after many years of dormancy. In the case of prostate cancer, bone is the most common metastatic site which affects approximately 70% of patients with advanced disease. The growth of the tumor cells in the bone is generally slow and they often become dormant until an appropriate microenviroment is established for their re-growth. How these metastatic tumor cells become dormant and how they recur at the target organs is virtually unknown. To address this critical question, we have studied an interaction of prostate cancer cell (PC3mm) and bone stromal cell (HS5). Our data indicate that the conditioned medium of HS5 cells was able to induce growth arrest and senescence to prostate cancer cells through activation of p38 MAP kinase. Western blot, qRT-PCR and reporter assay showed that this effect was mediated by induction of the tumor metastasis suppressor gene, N-myc downstream regulated gene 1 (NDRG1). We found that this secretory factor is bone morphogenetic protein 7 (BMP7) and that a specific inhibitor of p38 significantly abrogated up-regulation of NDRG1 by BMP7, suggesting that BMP7 induces NDRG1 through activation of p38. We also found that BMP7 significantly activated p21 and that this effect was inhibited by siRNA to NDRG1. Importantly, our results indicate that BMP7 was able to induce senescence to PC3mm cell; however, this senescence was reversible and the tumor cells re-gained the ability of their growth upon withdrawal of BMP7, suggesting that BMP7-induced senescence is reversible. Notably, our results of the existing database analysis indicate that the expression level of BMPR2, one of the BMP7 receptors, showed inverse correlation with bone metastasis and recurrence of prostate cancer. Furthermore, we isolated tumor stem population from PC3mm, and examined the effect of BMP7 on these cells. BMP7 indeed induced p38, NDRG1 and p21 in the prostate tumor stem cells. BMP7 also significantly suppressed sphere forming ability of the tumor stem cells followed by activation of NDRG1 and this effect was reversed by withdrawal of BMP7. These results suggest that the BMP7-NDRG1axis plays a critical role in the regulation of dormancy and recurrence of prostate tumor cells in bone metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5762.