bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P6-17-09: Whole brain radiation therapy (WBRT) with or without concurrent temozolomide for brain metastases in breast cancer patients
Authors: El-Sadda WM , Abdel-Halim II , El-Ibrashi MM , Magdi MM 
Published: May 2016

Abstract
Background:
Breast cancer remains the second leading cause of CNS metastases. HER2 positive and triple negative subtypes are especially and independently at higher risk of developing brain metastases. Although surgical resection and radiosurgery may play a role in the management of selected cases, whole brain radiation therapy remains the standard treatment but with limited efficacy. Temozolomide (TMZ); an oral alkylating agent that cross the blood brain barrier has shown radiosensitizing characteristics as well as synergistic effects of radiation therapy (RT).
The aim of the study was to assess the efficacy and safety of WBRT with concomitant TMZ in treatment of brain metastases in breast cancer patients.
Patients and methods:
A prospective randomized study included 60 patients with newly diagnosed brain metastases (BMs) from breast cancer not candidate for surgical resection or radiosurgery. All patients received WBRT 30 Gy/10 fractions with or without TMZ, administered at a dosage of 75 mg/m2/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment defined as partial response (PR) or complete response (CR) on brain MRI (WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurological symptoms and tolerability.
Results:
Between October 2011 and October 2013, 60 patients were enrolled in the study, 30 patients received WBRT+TMZ (group A) and 30 patients received WBRT (group B). Median age was 54 years (30-65), median follow up was 10.4 months (3-36). ORR was 80% in the WBRT+TMZ arm versus 50% in the WBRT (p = 0.017). The median PFS were 11.8 versus 5.8 respectively (p = 0.005). The median OS was 13.8 for group A and 10.8 for group B (p = 0.59). WBRT+TMZ was well tolerated with mostly grade 2 non-hematologic toxicity; headache, nausea & vomiting were 6%, 15% & 12% in group A versus 12%, 9% & 6% in group B, respectively. While the most evident hematologic toxicity recorded was lymphopenia grade 2 & 3 (15% & 12% in group A) and (12% & 9% in group B). No grade 4 toxicities were noted.
Conclusion:
WBRT plus TMZ improve local control and response rate of BMs from breast cancer, which was reflected by improved PFS.
Citation Format: El-Sadda WM, Abdel-Halim II, El-Ibrashi MM, Magdi MM. Whole brain radiation therapy (WBRT) with or without concurrent temozolomide for brain metastases in breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-09.
Abstract PD2-07: Insulin receptor substrate (IRS) targeting by the tyrophostin NT157 inhibits breast cancer cell growth
Authors: Yee D , Temiz NA , Levitzki A , Yang Y 
Published: May 2016

Abstract
Insulin and insulin-like growth factor (IGF) signaling systems regulate the malignant phenotype. However, targeting of the type I IGF receptor (IGF-IR) has shown little activity in clinical trials. One potential reason for these disappointing results is that activation of the closely related insulin receptor (InR) could compensate for IGF-IR blockade. Since both receptors phosphorylate the insulin receptor substrates (IRS), perhaps a better strategy would involving targeting of this key post-receptor protein. Two IRS proteins are expressed in breast cancer cells. IRS-1 is regulated by estradiol in breast cancer cell lines, while IRS-2 is the predominant IRS species in hormone receptor negative cells. NT157, a small-molecule tyrphostin, binds IGF-1R but does not affect receptor autophosphorylation. Instead, it downregulates IRS proteins in several model systems. In primary breast cancers, IRS-1 was positively correlated to ERα expression in the TCGA database. In ERα+ and basal-like breast cancer cell lines NT157 treatment suppressed IRS protein expression in a dose dependent manner. Short term exposure to NT157 treatment did not affect IGF-I, IGF-II, and insulin induced activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), but longer exposure resulted in inhibition of these signaling pathways. NT157 resulted in serine phosphorylation of IRS proteins and was dependent on MAPK activation. Serine phosphorylation resulted in disassociation between IRS proteins and their receptors resulting in IRS degradation. NT157 decreased S phase fraction, monolayer, and anchorage independent growth after IGF/insulin treatment in ERα+ breast cancer cells. NT157 downregulation of IRS protein expression also sensitized ERα+ breast cancer cells to rapamycin. Moreover, NT157 inhibited the growth of tamoxifen resistant ERα+ breast cancer cells. In the basal-like breast cancer cells (MDA-MB-231), NT157 repressed the proliferation (G2/M abrogation) and migration through downregulation of IRS1/2 protein. Given that both IGF-IR and InR play a role in cancer biology, targeting of IRS adapter proteins could be a more effective inhibitory strategy compared to receptor-targeting approaches.
Citation Format: Yee D, Temiz NA, Levitzki A, Yang Y. Insulin receptor substrate (IRS) targeting by the tyrophostin NT157 inhibits breast cancer cell growth. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD2-07.
Abstract PD3-05: Inhibition of fatty-acid oxidation as a therapy for triple-negative breast cancer
Authors: Goga A , Camarda R , Zhou AY , Kohnz RA , Balakrishnan S , Anderton B , Mahieu C , Eyob H , Krings G , Nomura DK 
Published: May 2016

Abstract
Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC) compared to estrogen, progesterone and/or human epidermal growth factor 2 receptor-positive (RP) breast tumors. We and others have shown that MYC alters metabolism during tumorigenesis. However, the role of MYC in TNBC metabolism remains largely unexplored. We hypothesized that pharmacologic inhibition of MYC-driven metabolic pathways may serve as a therapeutic strategy for this clinically challenging subtype of breast cancer. Using an unbiased metabolomics approach, we identified fatty acid oxidation intermediates as dramatically up-regulated in MYC-driven models of TNBC. A lipid metabolism gene signature was identified in patients with TNBC in the TCGA and multiple other clinical datasets, implicating fatty acid oxidation as a deregulated pathway critical for TNBC metabolism. We find that MYC-overexpressing TNBC, including transgenic models and patient-derived xenografts (PDX), display increased bioenergetic reliance upon fatty-acid oxidation (FAO). Pharmacologic inhibition of FAO catastrophically decreases energy metabolism of MYC over-expressing breast cancer, blocks growth of a MYC-driven transgenic TNBC model and MYC-overexpressing patient-derived xenografts. In vivo inhibition of FAO induced proliferation arrest and increased cell death in PDX models of TNBC. Our results demonstrate that inhibition of FAO is a novel therapeutic strategy against TNBCs that over-express MYC.
Citation Format: Goga A, Camarda R, Zhou AY, Kohnz RA, Balakrishnan S, Anderton B, Mahieu C, Eyob H, Krings G, Nomura DK. Inhibition of fatty-acid oxidation as a therapy for triple-negative breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD3-05.
Abstract PD6-06: Somatic mutation patterns differentially affect survival in breast cancer molecular subtypes
Authors: Gyorffy B , Pongor L , Szabo A , Bottai G , Pusztai L , Santarpia L 
Published: May 2016

Abstract
Background: The prognostic effects of somatic gene mutations and correlated gene expression in breast cancer is argument of debate. In this study we analyzed the impact of specific mutations on gene expression and their relevance in the prognosis of breast cancer subtypes.
Materials and methods: Exome sequencing and RNA-seq data obtained from TCGA were analyzed. Data was processed using MuTect, MapSplice and RSEM. All together data from 757 patients (ER-/HER2- [n=143], HER2+ including ER positive and negative patients, [n=136], and ER+/HER2- [n=478]) were included. Univariate Receiver Operating Characteristic (ROC) analysis was performed for the top mutated genes (mutated in at least 5% of patients) using the ROC Bioconductor library in R to identify genes whose expression was significantly associated with a mutation. Then, the mean expression of the significant genes was designated as a metagene for each genotype. We assessed the correlation with survival for each metagene by Cox proportional hazards regression and by plotting Kaplan-Meier survival plots. A significance threshold of p&lt;1E-04 was set for each gene to be considered in the survival analysis, and only the top 100 genes were used when there were more than 100 genes significant.
Results: In the overall population only few mutated genes including TP53 (HR=1.66), CDH1 (HR=0.61), AKT1 (HR=0.54), ATM (HR=1.76), NF1 (HR=0.58), KMT2D (HR=2.32), and UBR5 (HR=1.94) were significantly associated with survival. In ER-/HER2- mutant samples the PIK3CA (HR=2.79) and MAP3K1 (HR=2.98), and in HER2+ mutant samples the ARID1A (HR=0.26) and PIK3CA (HR=0.27) metagenes were associated with survival, respectively. Overall, using the combined metagene the majority of the significant mutated genes retained their prognostic power. Mutations of specific genes impacted their own expression and prognosis. The expression of TP53 (AUC=0.609, p=2.60E-06), and MAP3K1 (AUC=0.617, p=6.07E-03) was higher in samples with a mutation while the expression of CDH1 (AUC=0.684, p=2.72E-07), PTEN (AUC=0.687, p=1.47E-04), and BRCA1 (AUC=0.608, p=2.24E-02) was lower.
Conclusions: Our finding support that specific mutated genes may differentially impact prognosis in breast cancer subtypes. Further efforts are required to understand the biological and prognostic role of specific activating and inactivating mutations across molecular breast cancer subtypes.
Citation Format: Gyorffy B, Pongor L, Szabo A, Bottai G, Pusztai L, Santarpia L. Somatic mutation patterns differentially affect survival in breast cancer molecular subtypes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr PD6-06.
Abstract A80: The Affordable Care Act dependent coverage expansion and cancer stage at diagnosis among young adults in the United States
Authors: Xiong Ka Zang , Jemal Ahmedin , Han Xuesong 
Published: May 2016

Abstract
Objective: To examine whether the proportion of cancers diagnosed at early stage has increased after the implementation of the Affordable Care Act-Dependent Coverage Expansion provision (ACA-DCE) in 2010, which allows young adults to be covered under their parents' health insurance plan until age 26.
Methods: A total of 44,669 young adults, including 12,016 aged 19-25 and 32,653 aged 26-34, newly diagnosed with cancer in 2007-2009 and 2011-2012 were identified from the 18 registries of the Surveillance, Epidemiology, and End Results Program (SEER). We conducted a difference-in-differences analysis to examine changes in the proportion of stage I disease in young cancer patients aged 19-25 from 2007-2009 (pre-ACA-DCE) to 2011-2012 (post-ACA-DCE), using the corresponding changes in patients aged 26-34 as a control group. Both unadjusted and adjusted linear probability models were fitted for total cancer cases and specific cancer sites controlling for sex, race/ethnicity, absolute age at diagnosis, urban/rural residence, marital status at diagnosis and county-level education.
Results: The uninsured rate (95% confidence interval [95 CI]) in cancer patents aged 19-25 years decreased from 9.9 (8.4, 9.8) % pre-ACA-DCE to 7.7 (6.9, 8.4) % post-ACA-DCE, while it increased from 6.6 (6.2, 6.9) % to 7.2 (6.8, 7.7) % in patients aged 26-34 years. The proportion of stage I disease (95 CI) increased from 51.6 (50.4, 52.8) % to 54.0 (52.9, 55.4) % in patients aged 19-25 years, whereas it decreased from 55.1 (54.4, 55.8) % to 54.9 (54.0, 55.7) % in patients aged 26-34 years, resulting in a net change of 2.6 (0.5, 4.7) percentage-points (P = 0.0155). The net change in multivariate analysis was 2.7 (0.6, 4.8) percentage-points (P=0.0123). When analysis was stratified by specific cancer site, significant changes were confined to carcinoma of cervix and uterus and cases with Osseous & Chondromatous Neoplasms, with an adjusted net change of 11.23 (0.67, 21.79) percentage-points (P=0.0371) and 14.39 (0.3, 28.5) percentage-points (P=0.0453), respectively.
Conclusions: These early observations suggest positive benefits of the ACA-DCE in cancer stage at diagnosis among young adults 19-25 years old. Monitoring cancer outcomes in populations targeted by the ACA will be important for assessing the short- and long-term effects of the policy on population health.
Citation Format: Ka Zang Xiong, Ahmedin Jemal, Xuesong Han. The Affordable Care Act dependent coverage expansion and cancer stage at diagnosis among young adults in the United States. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A80.
Abstract B08: Highlighting the maturation of the MSI/NCI P20 South Carolina Cancer Disparities Research Center Partnership
Authors: Ford Marvella E. , Watson Dennis K. , Stukes James , Ahmed Mahtabuddin , Turner David P. , Knowell Ashley Evans , Findlay Victoria J. , Harrison Anita L. , Knight Kendrea D. , Varner Heidi , Cannady Kimberly , Salley Judith D. 
Published: May 2016

Abstract
The South Carolina Cancer Disparities Research Center (SC CaDRe), funded by the NIH/NCI Center to Reduce Cancer Health Disparities (CRCHD) in 2011, is a formal collaboration between the Medical University of South Carolina (MUSC) and South Carolina State University (SCSU, an historically black university). The SC CaDRe focuses on biological mechanisms of disparity in hormone-related cancers (breast and prostate cancer). The Sea Island population plays a prominent role in the three SC CaDRe research projects. The Sea Islanders are an African American ethnic group indigenous to the coastal southeast, with low rates of European American genetic admixture; as such they are ideal for inclusion in biomedical research. Each SC CaDRe research project includes Multiple PIs from MUSC and SCSU. The first research project is titled Biological Implications of DNA Glycation in Prostate Cancer Disparities; the second is titled MicroRNA Mediated Negative Regulation of Caveolin 1 as a Biological Mechanism Driving Breast Cancer Disparities; and the third is titled Feasibility Study of Breast Cancer Candidate Genes in Three Population Groups in South Carolina. The design and results of each project will be presented. The P20 SC CaDRe has led to two funded NIH R21 grants, an R01 grant, an R25E grant, and a DOD research training grant. Three undergraduate students from SCSU and four graduate students from MUSC have participated in SC CaDRe cancer research training, resulting in peer-reviewed publications and presentations at national scientific meetings. As a next step, the SC CaDRe investigators plan to submit an NIH/NCI CRCHD U54 grant application in 2016.
Citation Format: Marvella E. Ford, Dennis K. Watson, James Stukes, Mahtabuddin Ahmed, David P. Turner, Ashley Evans Knowell, Victoria J. Findlay, Anita L. Harrison, Kendrea D. Knight, Heidi Varner, Kimberly Cannady, Judith D. Salley. Highlighting the maturation of the MSI/NCI P20 South Carolina Cancer Disparities Research Center Partnership. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B08.
Abstract B31: A new approach to targeted therapy for obesity-related pancreatic adenocarcinoma
Authors: Tchio Cynthia Ines Mantho , Harbuzariu Adriana , Harmon Tia L. , Beech Derreck J. , Gonzalez-Perez Ruben R. 
Published: May 2016

Abstract
Background: Obesity is an important risk factor of Pancreatic Adenocarcinoma (PA) and it is characterized by the accumulation of excessive body fat and a Body Mass Index (BMI) value greater than 30. Obesity is also characterized by high levels of leptin, which has been consistently associated with the development of many different cancer including pancreatic cancer. Obesity can also alter the epigenome via epigenetics changes as DNA methylation and histones acetylation. Histone lysine residues can be acetylated by Histone Acetyltransferases or deacetylated by Histone Deacetylases (HDAC). Leptin can induce the proliferation of Pancreatic Cancer Stem Cells (PCSC), which are responsible for chemoresistance, invasiveness and reoccurrence of PA. PCSC express specific cell markers and can form tumorspheres in vitro. Our lab developed a leptin antagonist named LPrA2, which was bound to iron oxide nanoparticle (IONP-LPrA2) in order to increase its effectiveness and bioavailability.
Methods: The adjuvant effects of IONP-LPrA2 in combination of chemotherapeutic drugs on PCSC and tumorspheres formation in low attachment plates were determined. Additionally, the effects of IONP-LPrA2 in combination with chemotherapeutic drugs on the differential expression of epigenetic markers HDAC-1, HDAC-2, and HDAC-8 were investigated. The PA cells were cultured in vitro and treated with leptin, IONP-LPrA2, and chemotherapeutics. Then, the expression of epigenetic and PCSC markers, cell proliferation and survival were determined via Nexcelom cellometer or Guava EasyCyte flow cytometer analyses. Results were assessed by western blot analysis.
Results: Leptin affects the level of some HDACs and PCSC markers. That was abrogated by IONP-LPrA2. Chemotherapeutics showed differential effects on the epigenetic and PCSC markers and on tumorspheres formation by PA cells.
Conclusion: These findings suggest that IONP-LPrA2 could be useful to design new PA therapies in combination with chemotherapeutics. Furthermore, IONP-LPrA2 may increase the efficiency of chemotherapeutic drug Gemcitabine. These results could be most relevant for obese patients that show the highest incidence of PA and lowest survival rate.
Citation Format: Cynthia Ines Mantho Tchio, Adriana Harbuzariu, Tia L. Harmon, Derreck J. Beech, Ruben R. Gonzalez-Perez. A new approach to targeted therapy for obesity-related pancreatic adenocarcinoma. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B31.
Abstract B84: Influence of acculturation, ethnic identity, and Latino origin on barriers to colonoscopy in low-income Latinos: A longitudinal study
Authors: Santiago-Rivas Marimer , Jandorf Lina , DuHamel Katherine 
Published: May 2016

Abstract
Objectives: Colorectal cancer (CRC) screening rates continue to be lower than projected, particularly in Latinos. Fear of colonoscopy preparation and procedure, worry about colonoscopy results, CRC fatalism, CRC preventability and curability, and CRC perceived risk have been identified as CRC screening barriers in Latinos. The study purpose was to examine change in level of fear of colonoscopy, worry, CRC fatalism, preventability, and perceived risk using longitudinal data of Latinos who participated of a randomized control trial to test the impact of a culturally targeted and theoretically based psycho-educational print intervention designed to increase CRC screening via colonoscopy. Participants were assessed with study measures before and at 4- and 8-months after randomization.
Methods: Our sample included 250 Latinos between the ages of 50 and 81 years who had no personal or immediate family history of CRC, no colonoscopy in the past 5 years before participating in the study, received a referral for colonoscopy, and completed a colonoscopy by the end of the study. Interviews were performed, and data were analyzed using repeated measures MANCOVA to control for acculturation level and ethnic identity score, and to conduct group comparisons by Latino origin.
Results: A significant repeated measures MANOVA, F (16, 180) = 4.13, p&lt;.001, showed an overtime decrease in fear of colonoscopy (p&lt;.001), and worry (p&lt;.01). An initial repeated measures MANCOVA, F (16, 173) =1.74, p&lt;.05, showed a significant association between time and ethnic identity, but not with acculturation or Latino origin. A follow-up repeated measures MANCOVA (with ethnic identity as covariate), F (16, 176) =1.79, p&lt;.05, also showed a decrease in fear (p&lt;.05) and worry (p&lt;.05).
Discussion: We found an association between change in fear and worry scores, and ethnic identity. Interventions that address negative emotions regarding CRC screening procedures/results should also consider addressing the influence of individual characteristics (e.g., commitment and sense of belonging to their ethnic group) on CRC screening among Latinos referred to colonoscopy.
Citation Format: Marimer Santiago-Rivas, Lina Jandorf, Katherine DuHamel. Influence of acculturation, ethnic identity, and Latino origin on barriers to colonoscopy in low-income Latinos: A longitudinal study. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B84.