bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract IA07: In search of racial disparities in HPV vaccination
Authors: Brewer Noel T. , Moss Jennifer L. , Reiter Paul L. 
Published: October 2015

Abstract
Background: Racial disparities in cervical cancer deaths are longstanding, with African American and Latina women more likely to die from the disease. The advent of HPV vaccine created an opportunity to reduce or end these disparities, but only if uptake was either uniformly high across all females or higher among minority than non-minority females. Thus, interest in racial disparities in HPV vaccine coverage has been understandably high.
Findings: Data from several sources show racial disparities and “reverse disparities” in HPV vaccination coverage. First, the most reliable national data are from the National Immunization Survey Teen, a national survey of parents of adolescents with vaccination doses confirmed by physician records. NIS-Teen data show, depending on the year, higher initiation among Black and Latina teen girls. HPV vaccine completion rates in some years have been lower among these groups. Second, several large studies of insured women have shown lower rates of HPV vaccine initiation among Black women. Finally, many national surveys using self-reported data have shown no reliable pattern with respect to disparities in HPV vaccine initiation.
Another source of data is ecological analyses, comparing HPV vaccine coverage in states with lower and higher proportions of minority women. These analyses by Moss, Reiter and Brewer show that states with more African American residents had lower rates of HPV vaccine initiation among adolescent girls. However, we saw no disparities for completion or for proportion of Latina women.
A last source of data are studies of awareness, knowledge, beliefs and attitudes. These studies show a more regular pattern of lower awareness of and lower knowledge related to HPV vaccine among minority women compared to non-minority women. However, racial disparities are not universal across studies and not routinely present for other outcomes.
Commentary: Despite our best efforts to find racial disparities in HPV vaccination coverage, data from various sources suggest no clear pattern of ethnic or racial disparities for outcomes other than 3-dose series completion. Future studies should emphasize HPV vaccine initiation, which likely has a larger public health impact than series completion.
Citation Format: Noel T. Brewer, Jennifer L. Moss, Paul L. Reiter. In search of racial disparities in HPV vaccination. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA07.
Abstract IA15: FDA Center for Tobacco Products: Overview and research relevant to tobacco-related cancer and health disparities
Authors: Hoffman Allison C. 
Published: October 2015

Abstract
The U.S. Food and Drug Administration (FDA) Center for Tobacco Products (CTP) oversees the implementation of the Family Smoking Prevention and Tobacco Control Act (TCA). The Agency's responsibilities under the law include setting product standards for tobacco products, reviewing premarket applications for new and modified risk tobacco products, requiring new health warnings, and establishing and enforcing product advertising and promotion restrictions. The CTP Office of Science was established to ensure that a sound science exists with which to develop and assess the impact of the FDA's tobacco-related regulatory actions. This presentation will provide an overview of CTP, tobacco regulation, and research priorities, including research and activities that include cancer and health disparities outcomes.
Citation Format: Allison C. Hoffman. FDA Center for Tobacco Products: Overview and research relevant to tobacco-related cancer and health disparities. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA15.
Abstract A06: Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness
Authors: Lee Hyeon Jeong , Yue Shuhua , Li Junjie , Lee Seung-Young , Shao Tian , Song Bing , Cheng Liang , Masterson Timothy A. , Liu Xiaoqi , Ratliff Timothy L. , Cheng Ji-Xin 
Published: October 2015

Abstract
Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single-cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.
Citation Format: Hyeon Jeong Lee, Shuhua Yue, Junjie Li, Seung-Young Lee, Tian Shao, Bing Song, Liang Cheng, Timothy A. Masterson, Xiaoqi Liu, Timothy L. Ratliff, Ji-Xin Cheng. Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A06.
Abstract A15: Dual inhibition of the PI3K-mTOR signaling in combination with HER2 inhibitor is necessary for maximal antitumor activity in HER2+ breast cancer cells
Authors: De Pradip , Sun Yuliang , Carlson Jennifer , Friedman Lori , Dey Nandini , Leyland-Jones Brian 
Published: October 2015

Abstract
Background: Despite huge success in the treatment of HER2 amplified/overexpressed breast cancers, resistance is challenging problem even to combinations of HER2 targeting inhibitors. Multiple mechanisms of resistance have been studied and the PI3K-mTOR pathway inhibition is critical for the efficacy of HER2 inhibitors. Activating mutations in PIK3CA can overlap with HER2 overexpression and have been shown to confer resistance to HER2 inhibitors including trastuzumab (T) in preclinical studies.
Methods: HER2+/T-sensitive/PIK3CA wild type (BT474) and HER2+/PIK3CA mutated (HCC1954) cells were used for this study. The impact of PIK3CA mutation on the effect of HER2 and dual PI3K/mTOR inhibitors was assayed by immunoblot, proliferation and apoptosis assays. PI3K signaling was examined by immunoblot for phosphoproteins in the HER2-PI3K-mTOR signaling cascade. The combination of dual PI3K/mTOR inhibitor (GDC-0980) with HER2 antibodies (T or T-DM1) was studied in HER2 amplified models with wild type or mutant PIK3CA.
Results: Our data showed that 1) PIK3CA mutation in HER2+ cells was responsible for resistance to the HER2-specific antibody trastuzumab, 2) T-resistance conferred by this activating PIK3CA mutation was overcome by blockade of the PI3K-mTOR pathway with GDC-0980, 3) T-DM1 and GDC-0980 combination treatment greatly induced apoptosis of both BT474 and HCC1954 cells as indicated by Annexin V staining, 4) in mice bearing HER2+/T-sensitive/PIK3CA wild type xenografts (BT474), T or T-DM1 blocked tumor growth. The addition of a dual PI3K/mTOR inhibitor more significantly blocked tumor growth when compared to control group, 5) in a HER2+/PIK3CA mutant xenograft (HCC1954), dual PI3K/mTOR inhibition with GDC-0980 in combination with T or T-DM1 was required for blocked of tumor growth and tumor regression, and 6) immununo-staining of tumors from GDC-0980 treated mice showed growth inhibition (Ki67), and a decreased in associated angiogenesis (CD31).
Conclusion: These results suggest that the combination of GDC-0980 may be a potential strategy for the treatment of trastzumab-resistant breast cancer mediated by activating mutation of PIK3CA and this combination also provides benefit to HER2+/PIK3CA wild type tumors.
Citation Format: Pradip De, Yuliang Sun, Jennifer Carlson, Lori Friedman, Nandini Dey, Brian Leyland-Jones. Dual inhibition of the PI3K-mTOR signaling in combination with HER2 inhibitor is necessary for maximal antitumor activity in HER2+ breast cancer cells. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A15.
Abstract A16: DDR-mediated antitumor actions of PARP inhibitor: Can PI3K-mTOR pathway inhibitor be combined with PARP inhibitor in TNBT?
Authors: Dey Nandini , Carlson Jennifer H. , Sun Yuliang , Friedman Lori S. , De Pradip , Leyland-Jones Brian 
Published: October 2015

Abstract
Background: The PI3K pathway is known to contribute to DNA-damage repair (DDR). Recently we have reported that GDC-0980 a dual PI3K-mTOR inhibitor enhanced DNA-damage in triple negative breast cancer cells (De et al., Neoplasia, 2014). We utilized a mechanism-based approach to demonstrate that inhibition of DDR is another mode of action for GDC-0980. Here we hypothesized that GDC-0980 would potentiate an anti-tumor effect when combined with the PARP inhibitor, ABT888 and carboplatin.
Methods: Athymic mice bearing TNBC xenograft tumors were treated with GDC-0980 alone or in combination with ABT888 and carboplatin. Mechanism-based in vitro studies using a panel of 5-7 BRCA-wt/mutants TNBC cell lines (HCC1937, MDA-MB231, MDA-MB468, BT20, SUM149) were performed.
Results: GDC-0980 in combination with ABT888 plus carboplatin blocked the growth of established xenograft tumors by 80-90% with a concomitant increase in cl-caspse3, and a decrease in tumor Ki67, pVEGFR, CD31, p4EBP1, and pS6RP IHC-levels. Mechanistically, GDC-0980 treatment increased pgH2AX (WB, IF), caused gain in PAR and a subsequent sensitization of TNBC cells to ABT888 plus carboplatin in a time-dependent manner. The treatment (1) decreased proliferation signals (pAKT, pP70S6K, p4EBP1, pS6RP), PAR/PARP, PAR/pgH2AX, live/dead cell ratios, cell cycle progression and clonogenic 3D growth, and (2) increased apoptosis markers (cl-caspase3, 9, BIM, cl-PARP, and annexinV positivity). Three-dimensional projection movies showed that (1) GDC-0980 alone attenuated nuclear pgH2AXS139 foci in MDA-MB468 cells at 24 hours and (2) cytoplasmic cl-caspase3 increased and nuclear Ki67 decreased following GDC-0980+ABT888+carboplatin in MDA-MB468 cells at 72 hours.
Conclusion: Our data revealed that PI3K-mTOR pathway inhibition enhances the antitumor efficacy of PARP inhibitor in the presence of carboplatin by inhibiting the DDR system in conjunction with the inhibition of pro-proliferative and anti-apoptotic signals.
Citation Format: Nandini Dey, Jennifer H. Carlson, Yuliang Sun, Lori S. Friedman, Pradip De, Brian Leyland-Jones. DDR-mediated antitumor actions of PARP inhibitor: Can PI3K-mTOR pathway inhibitor be combined with PARP inhibitor in TNBT? [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A16.
Abstract A31: Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation
Authors: Shah Supriya , Lee Joyce V. , Carrer Alessandro , Snyder Nathaniel W. , Wellen Kathryn E. 
Published: October 2015

Abstract
Histone acetylation plays important roles in gene regulation, DNA replication, and the response to DNA damage, and it is frequently deregulated in tumors. We postulated that tumor cell histone acetylation levels are determined in part by changes in acetyl-CoA availability mediated by oncogenic metabolic reprogramming. Here, we demonstrate that acetyl-CoA is dynamically regulated by glucose availability in cancer cells and that the ratio of acetyl-CoA: coenzyme A within the nucleus modulates global histone acetylation levels. In vivo, expression of oncogenic Kras or Akt stimulates histone acetylation changes that precede tumor development. Furthermore, we show that Akt's effects on histone acetylation are mediated through the metabolic enzyme ATP-citrate lyase (ACLY), and that pAkt(Ser473) levels correlate significantly with histone acetylation marks in human gliomas and prostate tumors. The data implicate acetyl-CoA metabolism as a key determinant of histone acetylation levels in cancer cells.
Citation Format: Supriya Shah, Joyce V. Lee, Alessandro Carrer, Nathaniel W. Snyder, Kathryn E. Wellen. Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A31.
Abstract A36: Combined inhibition of PI3K isoforms and mTOR kinase is critical for cancer stem cell inhibition by VS-5584
Authors: Kolev Vihren N. , Wright Quentin G. , Weaver David T. , Padval Mahesh V. , Pachter Jonathan A. , Xu Qunli 
Published: October 2015

Abstract
Cancer stem cells (CSCs) have been implicated in resistance to anticancer therapies, disease recurrence, and metastasis, which represent major challenges in the clinical management of cancer. Therapeutic targeting of CSCs thus holds promise in addressing these challenges. VS-5584 is a selective dual PI3K/mTOR kinase inhibitor that potently inhibits mTORC1, mTORC2 and all four Class I PI3K isoforms. We report here that VS-5584 is up to 30-fold more potent at inhibiting the proliferation and survival of CSCs than non-CSCs in breast cancer cell lines using multiple orthogonal CSC assays. Moreover, VS-5584 preferentially induced apoptosis in Aldefluor-positive CSCs relative to Aldefluor-negative non-CSCs as measured by Annexin V and Caspase 3/7 assays. In contrast, paclitaxel induced more apoptosis in non-CSCs than CSCs cells. VS-5584 also preferentially diminished CSCs in human breast and small cell lung cancer xenograft models in vivo, as evidenced by marked reduction of tumor-initiating capacity in an in vivo limiting dilution re-implantation assay. Likewise, ex vivo VS-5584 treatment of surgically removed breast and ovarian patient tumors preferentially reduced CSC populations. In contrast, cytotoxic chemotherapeutic agents such as paclitaxel and cisplatin preferentially eliminate non-CSCs and thus enrich the CSC population. Interestingly, preferential targeting of CSCs requires inhibition of multiple components of the PI3K/mTOR pathway; simultaneous knockdown of PI3Kα, PI3Kβ, and mTOR by siRNA phenocopied the effect of VS-5584 and exhibited the strongest preferential targeting of CSCs, while knocking down of individual PI3K isoform or mTOR failed to do so. Consistent with its strong suppression of CSCs, VS-5584 effectively delayed tumor regrowth following chemotherapy in small cell lung cancer xenograft models including a patient-derived primary tumor model. The preferential targeting of CSCs thus prompts a new paradigm for testing VS-5584 in the clinic: clinical trials designed with CSC-directed endpoints may facilitate demonstration of the therapeutic benefit of VS-5584 at well-tolerated doses and thus enable an optimal therapeutic window. Furthermore, suppression of CSCs by VS-5584 in combination with other agents that target the bulk tumor may represent an appealing strategy to achieve more durable responses for cancer patients.
Citation Format: Vihren N. Kolev, Quentin G. Wright, David T. Weaver, Mahesh V. Padval, Jonathan A. Pachter, Qunli Xu. Combined inhibition of PI3K isoforms and mTOR kinase is critical for cancer stem cell inhibition by VS-5584. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A36.
Abstract A43: Basal expression of insulin-like growth factor 1 receptor determines intrinsic resistance of cancer cells to a PI3K inhibitor ZSTK474
Authors: Isoyama Sho , Kajiwara Gensei , Tamaki Naomi , Mutsumi Okamura , Yoshimi Hisashi , Nakamura Naoki , Nishimura Yumiko , Yamori Takao , Dan Shingo 
Published: October 2015

Abstract
Drug resistance often critically limits the efficacy of molecular targeted drugs. Although pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) is an attractive therapeutic strategy for cancer therapy, molecular determinants for efficacy of PI3K inhibitors remain unclear. We previously identified that overexpression of insulin-like growth factor 1 receptor (IGF1R) contributed to the development of drug resistance after long-term exposure to PI3K inhibitors. In this study, we examined the involvement of basal IGF1R expression in intrinsic resistance of drug-naïve cancer cells to PI3K inhibitors and whether inhibition of IGF1R overcomes the resistance. We found that cancer cells highly expressing IGF1R exhibited resistance to dephosphorylation of Akt and subsequent antitumor effect by ZSTK474 treatment. Knockdown of IGF1R by siRNAs facilitated the dephosphorylation and enhanced the drug efficacy. These cells expressed tyrosine-phosphorylated IRS-1 in high levels, which was dependent on basal IGF1R expression. In these cells, combination with the IGF1R-TKI, OSI-906, improved the efficacy of ZSTK474 in vitro and in vivo. Finally, we found a significant correlation between the basal expression level of IGF1R and the inefficacy of ZSTK474 in in vivo human cancer panel, as well as in vitro. These results suggest that basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474, and IGF1R is a promising target to improve the therapeutic efficacy. The current results provide evidence of combination therapy of PI3K inhibitors with IGF1R inhibitors for treating IGF1R-positive human cancers.
Citation Format: Sho Isoyama, Gensei Kajiwara, Naomi Tamaki, Okamura Mutsumi, Hisashi Yoshimi, Naoki Nakamura, Yumiko Nishimura, Takao Yamori, Shingo Dan. Basal expression of insulin-like growth factor 1 receptor determines intrinsic resistance of cancer cells to a PI3K inhibitor ZSTK474. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A43.
Abstract A47: DNA-PKcs is amplified in high-grade serous ovarian cancer (HGSC), correlates with poor outcome and drives resistance to platinum therapy via the AKT signaling pathway
Authors: Curry Edward , Cheraghchi-Bashi-Astaneh Azadeh , Chen Michelle , Cunnea Paula , Camila De Sousa , Maginn Elaina , Dai Yan , Liu Edison , Wasan Harpreet , Mills Gordon B. , Bowtell David , Gabra Hani , Stronach Euan A. 
Published: October 2015

Abstract
High grade serous ovarian cancer is typified by p53 mutation, high degrees of genomic instability and the development of chemo-resistance. Genomic translocations result from incorrectly repaired DNA double strand breaks (DSBs). DNA-PKcs is a central catalytic component of the error prone non-homologous end joining (NHEJ) DSB repair mechanism. We report here that DNA-PKcs is frequently amplified in copy number in HGSC and that amplification correlates with higher DNA-PKcs gene expression and poorer patient outcome using both in-house and publicly available datasets. Targeting DNA-PKcs, pharmacologically or by RNAi, enhances apoptosis in response to platinum treatment in platinum resistant cell lines and primary models and inhibition of DNA-PK restores response to cisplatin in chemoresistant ovarian cancer cells in vivo. SKOV-3 tumor xenografts were implanted subcutaneously into Balb/c Nu/Nu mice and treated with DNA-PKcs inhibitor NU7441 for 2 weeks alone or in combination with cisplatin. DNA-PK inhibition or cisplatin treatment alone were ineffective however in combination they decreased tumor growth at 14 days by 90%, relative to platinum only treatment. On investigating the mechanism of DNA-PKcs mediated chemoresistance we revealed that, in response to DNA damage, DNA-PKcs phosphorylates AKT on serine residue 473 in platinum resistant ovarian tumor cells, but not sensitive cells from the same patient. Phosphorylation at AKT threonine 308 is unaffected and DNA-PK inhibition does not interfere with insulin-mediated phosphorylation of AKT S473. DNA-PK mediated AKT activation in chemoresistant cells results in inhibitory phosphorylation of the pro-apoptotic protein BAD and stabilization of the anti-apoptotic Bcl-2 protein resulting in the observed attenuation of apoptotic response to platinum treatment. DNA-PK inhibition is an attractive therapeutic strategy for resensitizing resistant tumors to platinum based therapy, directly linking the DNA damage caused by platinum to pro-survival AKT pathway signaling.
Citation Format: Edward Curry, Azadeh Cheraghchi-Bashi-Astaneh, Michelle Chen, Paula Cunnea, De Sousa Camila, Elaina Maginn, Yan Dai, Edison Liu, Harpreet Wasan, Gordon B. Mills, David Bowtell, Hani Gabra, Euan A. Stronach. DNA-PKcs is amplified in high-grade serous ovarian cancer (HGSC), correlates with poor outcome and drives resistance to platinum therapy via the AKT signaling pathway. [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A47.