bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4354: Proteomic analysis of acute radiation response following whole brain irradiation: Is Sirt2 a key player of radiation-induced neurotoxicity
Authors: Shukla Sudhanshu , Shankavaram Uma , Smart DeeDee 
Published: August 2012

Abstract
Radiation therapy (RT) is one of the most effective and widely used treatments of both primary and metastatic intracranial tumors. Recent technical advances in RT and multimodality approach to treatment have increased the life span of patients. However, a major concern remains as to radiation's effect on long term neurotoxicity and cognitive impairment. Acute and sub acute effects of RT following whole brain RT appear to be reversible, but we hypothesize that these acute changes provide a platform for alteration of the central nervous system (CNS) microenvironment that is responsible for delayed irreversible neurotoxicity. To improve the quality of life of patients and to improve efficacy of whole brain RT, we require effective and targeted approaches to minimize cognitive dysfunction. In order to understand the acute molecular events involved after RT and to identify potential markers that lead to long-term neurotoxicity and dementia, we performed quantitative mass spectroscopy using the iTRAQ (isobaric tag of relative and absolute quantitation) technique on C57 Bl/6 mouse brain tissue extract 72 hours following whole brain RT versus sham-irradiated controls. We found significant changes up- and down-regulation of critical proteins in multiple canonical pathways to be affected, but interestingly some of the most significant changes were in proteins vital to Huntington and Parkinson's signaling pathways. Additionally, we explored the role of Sirtuin 2 (Sirt2), a Class III histone deacetylase which is abundant in CNS and has been shown to mediate oxidative stress response in animal models of neurodegeneration which produce dementia, within the context of whole brain RT. Our aim was to investigate if Sirt2 might be a potential target to mitigate neurotoxic effects induced by RT. Our proteomic analysis of the brain tissue extracts of Sirt2 genomic knockout mice shows that the absence of Sirt2 affects several metabolic and signaling pathways including Huntington, Parkinson's, as well as mitochondrial-mediated signaling. Several factors were found to be uniquely and differentially expressed in Sirt2 knockout tissues under radiation condition. This study indicates that Sirt2 might be a key player in radio sensitization of the CNS and a potential clinical target for minimizing radiation-induced neurocognitive dysfunction.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4354. doi:1538-7445.AM2012-4354
Abstract 4358: Notch signaling regulates tumor-induced angiogenesis in SPARC-overexpressed neuroblastoma
Authors: Gorantla Bharathi , Bhoopathi Praveen , Gondi Christopher S. , Rao Jasti S. 
Published: August 2012

Abstract
Despite existing aggressive treatment modalities, survival for advanced stage neuroblastoma remains poor with significant long-term illness in disease survivors. Advance stage disease features are associated with tumor vascularity, and as such, angiogenesis inhibitors may prove useful along with current therapies. SPARC (also known as BM-40 or osteonectin), a matricellular protein, is known to inhibit the proliferation and migration of endothelial cells stimulated by growth factors and induces endothelial cell apoptosis. Here, we sought to determine the effect of SPARC on neuroblastoma tumor cell-induced angiogenesis and to decipher the molecular mechanisms involved in angiogenesis inhibition. SPARC overexpression in neuroblastoma cells inhibited neo-vascularization in vivo as determined by the mouse dorsal air sac model. In addition, conditioned medium from SPARC-overexpressed neuroblastoma cancer cells (pSPARC-CM) inhibited endothelial tube formation in vitro. SPARC-overexpressed tumor cell conditioned medium decreased proliferation (as determined by MTT assay and Ki-67 immunofluorescence) and induced apoptosis in endothelial cells (as determined by TUNEL assay). Furthermore, SPARC-overexpressed tumor cell conditioned medium inhibited expression of the pro-angiogenic molecules VEGF, FGF, PDFG, and MMP-9 as determined by human angiogenesis-PCR array. In addition to the inhibition of growth factors, SPARC-overexpressed tumor cell conditioned medium inhibited Notch signaling molecules in HMEC cells as determined by Western blotting. Conditioned medium from neuroblastoma cells overexpressed with Notch intracellular domain after SPARC overexpression, induced growth factors and led to increased tube formation in vitro. In vivo endothelial cell death was confirmed by co-localization studies with TUNEL assay, and an endothelial marker, CD31, in tumor sections from SPARC-overexpressed mice. Our data collectively suggest that SPARC overexpression induces endothelial cell apoptosis in vivo and inhibits angiogenesis both in vitro and in vivo.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4358. doi:1538-7445.AM2012-4358
Abstract 4427: Role of cytochrome P450 (CYP)1A2 in the sustained induction of CYP1A1 by the carcinogen, 3-methylcholanthrene (MC) in mouse heptoma cells (hepa-1)
Authors: Moorthy Bhagavatula , Kondraganti Sudha R. , Wang Lihua , Jiang Weiwu , Chu Chun 
Published: August 2012

Abstract
Humans are constantly exposed to environmental carcinogenic polycyclic aromatic hydrocarbons (PAHs) through cigarette smoke, diesel exhausts, charcoal-broiled meats, etc. Cytochrome P4501A (CYP1A) enzymes play important roles in the activation of PAHs such as 3-methylcholanthrene (MC) to carcinogenic DNA-binding metabolites. We reported earlier that MC causes persistent induction of hepatic and pulmonary CYP1A1 in mice for several weeks after MC ithdrawal, and that the phenomenon of sustained hepatic CYP1A1 induction is lost in Cyp1a2-null mice. In this study, we tested the hypothesis that MC elicits induction of persistent CYP1A1 nduction in hepa-1 cells, and that CYP1A2 contributes mechanistically to this henomenon. Hepa-1 cells were treated ith the MC (2.5 µM), or dimethylsulfoxide (DMSO) as control, and at selected ime points, CYP1A1 promoter activity, CYP1A1 enzyme activities, contents, and CYP1A1 mRNA levels were studied. We fund that MC markedly and persistently induced CYP1A1 promoter activity, transcription, apoprotein expression, and the CYP1A1 associated ethoxyresorufin O-deethylase (EROD) activities for up to 5 days. Transfection of CYP1A2 siRNA resulted in knockdown of CYP1A2 mRNA by 70%, but a statistically significant increase of basal CYP1A1 mRNA by 35-40%. The induction of CYP1A1 promoter ctivity, CYP1A1 mRNA, CYP1A1 protein, and EROD activity by MC were not affected by CYP1A2 siRNA at the 24 h time point, but was significantly ttenuated by Cyp1a2 siRNA on day 5. These results suggest that CYP1A2, possibly via a metabolite, contributes to the sustained induction of CYP1A1 by MC in hepa-I cells. Further investigations into the mechanisms of persistent induction of CYP1A1 by MC could lead to novel preventative/therapeutic strategies against PAH-mediated carcinogenesis in humans. (Supported in part by 2R01 ES009132.)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4427. doi:1538-7445.AM2012-4427
Abstract 4431: NFATc1 silencing increases sensitivity of pancreatic cancer cells to phosphosulindac
Authors: Murray Onika T. , Vrankova Kvetoslava , Johnson Francis , Rigas Basil 
Published: August 2012

Abstract
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the U.S. Current chemotherapeutic agents have limited efficacy and play a minor role in its treatment. We previously determined that the novel agent phosphosulindac (P-S) significantly prevents colon cancer and have now extended our studies into pancreatic cancer. Microarray data demonstrated a 5-fold increase in the gene expression of Nuclear Factor of Activated T-cells (NFAT) in MIA PaCa-2 cells after 2 h of treatment with P-S. NFATc1 and NFATc2 isoforms have been shown to be up-regulated in pancreatic cancer. To determine the role NFATc1 played in response to treatment with our compound, we developed a NFATc1 shRNA model in BxPC-3 and GFP positive MIA PaCa-2 cells, and a NFATc1 overexpression model in GFP labeled MIA PaCa-2 cells. Knockdown of NFATc1 expression by shRNA was confirmed by western blot and qRT-PCR. A 2-fold decrease in IC50 of P-S was observed in NFATc1 shRNA cells. In contrast, overexpression of NFATc1 increased the IC50 of P-S by 1.2-fold. The ability of our compound to reduce cell viability more potently in NFATc1 shRNA cells prompted us to assess the effect of the protein on tumor growth in a MIA PaCa-2 xenograft. 5-6 week old female BALB/c nude mice were subcutaneously injected with NFATc1 wt, knock-down, and overexpression GFP labeled MIA PaCa-2 cells. Animals were treated for 5 weeks, euthanized and tumor volume assessed. We observed a 50% reduction in tumor volume in NFATc1 wt, 63% reduction in NFATC1 knock-down, and a 26% reduction in NFATc1 overexpression xenograft. NFATc1 localization is indicative of its activity, with nuclear localization being the active form. We assessed OCT-embedded sections of our xenograft tissue to determine the localization of NFATc1 in GFP labeled tumor cells. Confocal microscopy data showed that in comparison to control, P-S treated tissue demonstrated decreased nuclear localization of the protein, indicating that P-S may suppress the activation of NFATc1. We observed a similar trend in NFATc1 knock-down and overexpression tissue, though our compound demonstrated a greater effect on tumor reduction in NFATc1 knock-down mice. We conclude that P-S is a potentially important agent for the treatment of pancreatic cancer and that our compound may play a role in NFATc1 localization and activation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4431. doi:1538-7445.AM2012-4431
Abstract 444: MACC1 as biomarker for progression and prognosis of human malignant glioma
Authors: Stein Ulrike S. , Fuchs Steffen , Monoranu Camelia M. , Herrmann Pia , Smith Janice , Ernestus Ralf-Ingo , Vince Giles H. , Hagemann Carsten 
Published: August 2012

Abstract
Metastasis-associated in colon cancer-1 (MACC1) is a prognostic indicator for metastasis formation and metastasis-free survival of colon cancer patients. Patients with low MACC1 expressing primary tumors had a 5-year-survival of 80%, whereas subjects with high MACC1 expressing tumors had a 5-year-survival of only 15%. Correlations of MACC1 expression levels with tumor progression, recurrence and metastasis have meanwhile been reported for e.g. gastric, lung and hepatocellular cancer. However, no data are available concerning MACC1 expression in human astrocytic tumors. Glioblastoma multiforme (GBM) are the most prevalent brain tumors of adults either developing de novo without known precursor-lesion (primary GBM), or progressing from low grade astrocytomas (secondary GBM). Patients suffering from GBM have a very disadvantageous prognosis. Although these tumors rarely metastasize, they are characterized by rapid growth, and their invasive and migratory behavior is similar to those of metastatic cells of tumors with different origin. Therefore we tested our hypothesis on MACC1 involvement in progression of human gliomas. MACC1 mRNA expression increased concomitantly with increasing WHO grading, as demonstrated by semi-quantitative and quantitative RT-PCR of biopsies from human low grade astrocytomas and GBM. MACC1 protein expression allowed discrimination of dormant and recurrent LGA and of primary and secondary GBM, as shown by immunohistochemistry of an independent patients’ cohort. Furthermore, strong MACC1 expression was associated with reduced median patients’ survival. Finally, we performed real-time measurements of migration and proliferation in the MACC1-transfected GBM cell line U138/MACC1 and found promoted proliferation and migration. Therefore, MACC1 may be a new biomarker for progression and for prognosis of human malignant gliomas and might represent a new potential therapeutic target for inhibition of their proliferation and migration.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 444. doi:1538-7445.AM2012-444
Abstract 4445: Defining a pipeline to use next generation sequencing for genetic testing in hereditary cancer
Authors: Lazaro Conxi , López-Doriga Adriana , Castellsagué Ester , del Valle Jesús , Tornero Eva , Moreno Víctor , Pineda Marta , González Sara , Feliubadaló Lídia , Capellá Gabriel 
Published: August 2012

Abstract
One of the emerging Next Generation Sequencing (NGS) applications is amplicon resequencing, which can be applied to screen for mutations in defined genes with diagnostic value. However, in this scenario, methods and protocols are still poorly developed. To address this need, we have established a study workflow that integrates experimental work and bioinformatics analyses. Our Unit of Genetic Testing for Hereditary Cancer is using kits for Multiplex Amplification of Specific Targets for Resequencing (MASTR) from the Multiplicom Company in order to generate highly homogeneous gene specific libraries for point mutation detection. Currently we have completed a proof of concept for the Breast Cancer Susceptibility kit (BRCA1 and BRCA2). We analysed a training set of 267 variants in 28 samples, and a validation set of 137 variants in 14 samples. Results from the GS Junior were combined with those resulting from the analysis of the homopolymer sequences in each gene. Sanger confirmation was performed in all the identified DNA variants. Low coverage (&lt;=38x; 1.2% of the target) regions were also Sanger sequenced. The bioinformatics analysis combined the Variant Identification Pipeline software (VIP, De Shrijver, JM et al. BMC Bioinformatics 2010) together with a set of in-house designed R scripts in order to obtain both a Coverage Report as well as a Variant Calling Report. The first training set of 28 samples showed a sensitivity and specificity of 97.6% and 100%, respectively. After the improvement of the kit and the analysis pipeline, the validation set of 14 samples demonstrated an excellent specificity and sensitivity of the pipeline (100% both). In conclusion, we showed that a combined algorithm both at the experimental as well as at the bioinformatics level allows the interpretation of NGS results with a good specificity and sensitivity for diagnosis purposes. We are now finishing our proof of concept for genes responsible for Hereditary Colorectal Cancer, results will be presented at the meeting. This work has been supported by Spanish Ministry of Science and Innovation, Carlos III Health Institute ISCIII (RD06/0020/1050; RD06/0020/1051; PI10/01422; CA10/01474); The Government of Catalonia (2009SGR290) and The Spanish Association Against Cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4445. doi:1538-7445.AM2012-4445
Abstract 4447: In search of the ideal cancer screening test
Authors: Pivot Xavier , Viguier Jérôme , Morère Jean-François , Blay Jean-Yves , Coscas Yvan , Roussel Claire , Eisinger François 
Published: August 2012

Abstract
Background: The success of a cancer screening program partly depends on the compliance level of the screened population for the proposed screening procedure. Since 2005, EDIFICE surveys on cancer screening behaviours are carried out in France in the general population for breast, colon and prostate cancers. In the third edition of the EDIFICE surveys, subjects were questioned on what could be improved on screening tests. Methods: This third nationwide observational study, EDIFICE 3, was conducted through phone interviews among a representative sample of 1603 subjects aged between 40 and 75 years, using the quota method, from July 8th to July 28th, 2011. The question concerning subjects’ expectations for a screening test was: “If scientific progress were made, what kind of cancer screening test would you wish to be proposed?” Results: For breast cancer screening, among 669 women never treated for cancer, the main expectations were: a more reliable imaging or radiological test for 43% of the subjects, a blood test for 32% and no preference for 17% of the subjects. For colon cancer screening, among 1469 subjects never treated for cancer, the main expectations were: a blood test for 35% of the subjects, no preference for 22% and a more reliable imaging or radiological test for 21% of the subjects. Results show a low level of satisfaction for the fecal occult blood test with 9% of the subjects looking for a more reliable fecal test. For prostate cancer screening, among 711 men never treated for cancer, the main expectations were: a blood test for 43% of the subjects, a more reliable imaging or radiological test for 21% and no preference for 21 % of the subjects. Conclusions: For breast cancer and prostate cancer, screening procedures are well accepted by the population. The vast majority prefers a blood test for cancer screening, even if they seem to accept radiological tests. In contrast, the population seems reluctant with fecal occult blood tests. This suggests the need to think over colon cancer screening tests to improve their results.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4447. doi:1538-7445.AM2012-4447
Abstract 4451: The NCI Early Detection Research Network (EDRN) urinary PCA3 validation trial
Authors: Wei John Thomas , Sanda Martin G. , Thompson Ian M. , Partin Alan , Feng Ziding , Sokoll Lori , Groskopf Jack , Brown Elissa , Lotan Yair , Kibel Adam , Lin Daniel , Taneja Samir , Viterbo Rosalia , Busby Erik , Bidair Mohamed , Kagan Jacob , Srivastava Sudhir 
Published: August 2012

Abstract
INTRODUCTION: Widespread use of PSA screening has raised concerns of overdiagnosis of low risk and underdiagnosis of high grade cancer. This is primarily due to the low sensitivity and specificity of PSA. PCA3, a non-coding large chain ribonucleic acid, is significantly over-expressed in cancer tissue and quantitatively measured by a novel urinary assay. The objective of this NCI EDRN trial was to conduct a comprehensive, independent validation of the PROGENSA PCA3 Assay for the detection of prostate cancer. METHODS: A prospective, PROBE-compliant NCI validation trial was undertaken at 11 clinical sites to evaluate PCA3 positive predictive value (PPV, PCA3 score &gt;60) in the initial biopsy setting and negative predictive value (NPV, PCA3 score &lt;20) in the repeat biopsy setting. PCA3 was obtained prior to biopsy but following an attentive DRE. We hypothesized that PPV for an initial prostate biopsy to be at least 55% and that NPV for a repeat biopsy to be at least 75%. The accuracy of PCA3 in detecting any prostate cancer and secondarily, high grade cancer (Gleason &gt; 7), was compared to PCPT risk calculator through ROC curve analysis. RESULTS: 880 eligible men (mean age 62 years) were enrolled; 305 had a prior negative prostate biopsy. 99% had an informative PCA3 test. For the detection of any cancer, PPV was 80% (95% CI: 0.72 - 0.86) in the initial biopsy group while NPV was 88% (95% CI: 0.81 - 0.93) in the repeat biopsy group. PCA3 performance was superior to PCPT risk estimation and improved upon the detection of any cancer (p&lt;0.006) and high grade cancer (p&lt;0.02) when combined with the PCPT risk model. CONCLUSIONS: PCA3 ability to detect prostate cancer was superior to PCPT risk calculator in both the initial (p &lt; 0.0001) and repeat biopsy setting (p=0.001)Independent validation of PCA3 demonstrated a high PPV in the initial biopsy setting and a high NPV in the repeat biopsy setting. Given the significant improvements in risk estimation over PCPT, PCA3 is expected to greatly enhance clinical decision making.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4451. doi:1538-7445.AM2012-4451
Abstract 4452: Mother-daughter communication and breast cancer prevention knowledge, attitudes, and behaviors between Hispanic and non-Hispanic college women
Authors: Kratzke Cynthia , Vilchis-Licon Hugo 
Published: August 2012

Abstract
Background: Although breast cancer prevention programs focus primarily on women ages 40 and older, little is known about breast cancer prevention awareness among young women. Cancer communication is essential for early detection and treatment for Hispanic and non-Hispanic women. Data trends show Hispanic women are more likely to be diagnosed with more advanced stages of breast cancer at an early age. Aim: The purpose of this exploratory study is to examine mother-daughter communication and breast cancer prevention knowledge, attitudes, and breast self-examination (BSE) behaviors between Hispanic and non-Hispanic college women. Method: Using a cross sectional study design, a convenience sample of college women ages 18 and older were surveyed in Fall 2010 at a southwestern university. Survey items were developed using the Health Belief Model framework. An open-ended item was included to elicit descriptions of breast cancer prevention advice received from their mothers. Results: Self-reported data were obtained from 71 college women (44% Hispanic and 56% non-Hispanic) ages 18 to 49 with a mean age of 22.6 (SD = 5.6). Overall, 33% received mother-daughter communication about breast cancer prevention, 80% received a provider's recommendation to conduct BSE, and 62% conducted BSE. Nearly 74% knew someone with breast cancer. Bivariate analysis revealed no significant differences for mother-daughter communication, knowledge, and self-efficacy for breast cancer prevention. In content analysis, only non-Hispanic college women received advice from their mothers about modifiable risk factors for breast cancer prevention. Hispanic college women (84%) were more likely compared to non-Hispanic women (63%) to have friends who supported BSE (p=.023). In addition, Hispanic college women (61%) were more likely compared to non-Hispanic women (38%) to seek online breast cancer information (p=.023). Conclusion: Our preliminary findings support the need for college educational breast cancer prevention programs including risk factors. Future research is suggested with a larger sample size to validate findings as well as to explore Internet use to seek quality online health information with an emphasis on breast cancer prevention information.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4452. doi:1538-7445.AM2012-4452