bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1791: Effects of calcium and vitamin D supplementation on circulating markers of inflammation
Authors: Fedirko Veronika , Latash Julia , Bostick Roberd M. , Barry Elizabeth L. ,   John A. Baron on behalf of Investigators in the PPS4 Study
Published: July 2016

Abstract
Chronic inflammation plays a major role in colon carcinogenesis. Recent evidence from experimental models suggests that vitamin D and calcium may reduce systemic inflammation and local inflammation in the colorectum, thus contributing to reducing risk for colorectal neoplasia. However, human experimental evidence to support these purported anti-inflammatory effects remains inconclusive, coming from very few, small, mainly short-term clinical studies with a variety of doses and administration regimens, with and without calcium supplementation in very different patient populations, and with a limited number of inflammatory biomarkers measured. To address this, we tested the effects of calcium (1.2 g/d) and/or vitamin D3 (1,000 IU/d) supplementation for 3 or 5 years on circulating pro- (IFNγ, TNFα, IL-6, IL-8, IL-12p40) and anti-inflammatory (IL-10) cytokines in 471 participants with previous colorectal adenoma in a recently completed, multi-center, randomized, double-blind, placebo-controlled, modified 2 × 2 factorial chemoprevention clinical trial (NCT00153816). The cytokines were measured in plasma using multiplex electrochemiluminescence detection-based immunoassays. Over a 3- or 5-year treatment period, we found no appreciable effects of calcium and/or vitamin D supplementation on pro-inflammatory cytokines (all P-values &gt; 0.3). However, there was a suggestion that vitamin D may favorably modulate concentrations of IL-10, an anti-inflammatory cytokine. In the calcium, vitamin D, and calcium plus vitamin D groups, the relative increase vs. placebo in IL-10 from baseline to end of follow-up was 3% (P = 0.78), 15% (P = 0.15), 13% (P = 0.35). Our preliminary results indicate no considerable effects of calcium and vitamin D treatment on circulating pro-inflammatory cytokines, and might suggest that vitamin D may increase circulating levels of anti-inflammatory cytokine IL-10, which plays an important role in the Th2-type immune response.
Citation Format: Veronika Fedirko, Julia Latash, Roberd M. Bostick, Elizabeth L. Barry, John A. Baron on behalf of Investigators in the PPS4 Study. Effects of calcium and vitamin D supplementation on circulating markers of inflammation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1791.
Abstract 1795: The feasibility study of a randomized cancer screening trial in China
Authors: Hu Ping , Dai Min , Shi Jufang , Ren Jiansong , Li Jiang , Liao Xianzhen , Du Lingbin , Liu Yuqing , Chen Zhaoli , Wu Ning , Liu Qian , Pinsky Paul , Prorok Philip , Fagerstrom Richard , Taylor Martina , Kramer Barnett , He Jie 
Published: July 2016

Abstract
Lung cancer has been the leading cause of cancer death in China since the 1990s and the disease burden likely will increase. The US National Lung Screening Trial (NLST) showed a 16-20% mortality reduction in a high-risk population that had undergone Low-Dose Computed Tomography (LDCT). China would like to confirm the main result from the US NLST in the Chinese population. The aim of this study is to obtain necessary information on performance of the organizations involved in designing, conducting, monitoring and managing the study. Another goal is to test colorectal cancer screening strategies in China. This is a first randomized trial on lung and colorectal cancer screening in China. The feasibility study will aid in the development of a practical design for the Randomized Cancer Screening Trial in China.
This study has been carried out in three cites (Changsha city, Hunan province; Lanzhou city, Gansu province; and Haining city, Zhejiang province) since August, 2014. Individuals at elevated risk of lung cancer were randomized into three arms: annual low-dose helical CT exams for three years (T0, T1, T2) and baseline colonoscopy (T0); two low-dose helical CT exams (T0, T2) plus annual faecal immunochemical test (OC-faecal immunochemical tests at T0, T1, T2); and annual InSure-faecal immunochemical tests combined with Septin 9 test (T0, T1, T2). All participants will be followed for at least three years from randomization to yield data relevant to answering the study objectives.
As of March 31, 2015, a total of 2696 eligible participants were enrolled at 3 cancer hospitals and randomly assigned to three study arms (894 in arm 1, 902 in arm 2, and 900 in arm 3). The gender distribution is 53% male and 47% female. Baseline characteristics of the study population by age, gender and total pack-year exposure were balanced. The rate of adherence to LDCT screening at the first round (T0) was 89.0%. 1598 participants received LDCT in the first round. The rate of abnormality was 77.4% with LDCT and 6.5% and 6.1% with suspicious for lung cancer for arm 1 and arm 2 respectively at T0. 2150 participants received colorectal cancer screening. The positivity was 34.1% with colonoscopy screening, 8.0% with OC-FIT test, 4.5% with InsureFIT test, and 5.8% with Septin9 test.
Citation Format: Ping Hu, Min Dai, Jufang Shi, Jiansong Ren, Jiang Li, Xianzhen Liao, Lingbin Du, Yuqing Liu, Zhaoli Chen, Ning Wu, Qian Liu, Paul Pinsky, Philip Prorok, Richard Fagerstrom, Martina Taylor, Barnett Kramer, Jie He. The feasibility study of a randomized cancer screening trial in China. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1795.
Abstract 1801: FOXA1, a novel regulator of neuroendocrine differentiation
Authors: Kim Jung , Jin Hongjian , Zhao Jonathan , Parimi Vamsi , Yang Ximing , Yu Jindan 
Published: July 2016

Abstract
Neuroendocrine prostate cancer (NEPC) is a subtype of prostate cancer that is highly aggressive and exhibits a neuroendocrine phenotype, being distinct from prostate adenocarcinoma. Cases of NEPC are predicted to increase rapidly following broader use of new-generation hormonal therapies including abiraterone and enzalutamide. Although androgen deprivation and cytokine induction have been previously suggested to induce neuroendocrine differentiation of prostate cancer, little is known regarding the underlying molecular mechanisms. FOXA1 is a forkhead box family transcription factor that has been shown to act as a pioneer factor for androgen receptor (AR), thereby defining the prostatic transcriptional program. We have recently shown that FOXA1 plays an important role in suppressing epithelial-to-mesenchymal transdifferentiation, but is often downregulated in castration-resistant prostate cancer (CRPC). Along this line, in the present study, we showed that FOXA1 loss, achieved by shRNA-mediated knockdown, led to cell morphology changes typical of neuroendocrine differentiation, accompanied by a strong increase of NEPC marker enolase2 (ENO2), while ectopic FOXA1 overexpression reverses these alterations. This was further linked to ERK phosphorylation, which has been previously reported to be up-regulated following neuroendocrine differentiation. Moreover, to understand the mechanism underlying FOXA1 regulation of neuroendocrine differentiation, we performed bioinformatics analysis and nominated interleukin 8 (IL8) as a direct target of FOXA1 and its up-regulation is critical in mediating neuroendocrine differentiation of FOXA1-depleted cells. Finally, we validated a negative correlation between FOXA1 and neuroendocrine differentiation in primary prostate cancer specimens through analysis of publically available RNA-seq data as well as direct IHC staining of various NEPC markers. In summary, we report a new role of FOXA1 as a critical inhibitor of neuroendocrine differentiation and the importance of balanced FOXA1 expressing in the maintenance of the epithelial phenotype of prostate cancer.
Citation Format: Jung Kim, Hongjian Jin, Jonathan Zhao, Vamsi Parimi, Ximing Yang, Jindan Yu. FOXA1, a novel regulator of neuroendocrine differentiation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1801.
Abstract 1802: ER-positive breast cancer prevention with the use of hormone replacement therapy
Authors: Dembo Anna G. , Greene Geoffrey L. 
Published: July 2016

Abstract
Menopause occurs in women between the ages of 45 and 55 and often results in undesirable vasomotor symptoms. Hormone replacement therapy (HRT) alleviates these symptoms, including hot flashes, difficulty sleeping, fatigue, and vaginal atrophy. HRT also prevents osteoporosis. PremPro, a currently available HRT formulation that combines conjugated equine estrogens (CE) with medroxyprogesterone acetate, increases the risk of breast cancer. Due to the perceived risk based largely on the results of the Women's Health Initiative (WHI) trial, the number of women taking HRT has decreased dramatically. Duavee, a new form of HRT that combines CE and bazedoxifene (BZA), a selective estrogen receptor modulator (SERM) and degrader (SERD), has recently been approved by the FDA for treatment of moderate to severe hot flashes and to reduce the risk of osteoporosis. Importantly, this CE/BZA mixture not only relieves symptoms associated with menopause, but it also does not stimulate the breast or uterus. Although several preclinical studies suggest that CE/BZA might be protective in the breast, the mechanism of action of this new combination therapy is not known. Our goal, therefore, is to elucidate the underlying molecular mechanisms by which CE/BZA differentially affects estrogen receptor alpha (ERα) action in the mammary gland, using transcriptome and whole genome occupancy analysis in breast cancer cell lines. We are also studying the effects of CE/BZA on early mammary cancer progression in the polyoma middle T antigen (PyMT) transgenic mouse model, which has been shown to be sensitive to estrogens. In addition, we are studying the effects in an ERα-positive patient-derived xenograft mouse model. We have determined that CE modulates gene expression in MCF7 cells similar to 17β-estradiol (E2), and that BZA is able to inhibit these effects. We have also observed that CE increases ERα occupancy versus E2 at response elements associated with some estrogen target genes, whereas CE/BZA decreases this occupancy. In the PyMT mouse model, we have determined that CE/BZA significantly delays the onset of mammary tumors in ovariectomized mice and prolongs their survival when compared to E2 and CE treatment alone. An improved understanding of the molecular mechanisms of CE/BZA action in hormone sensitive breast cancer cell and animal models should have important implications for women considering HRT.
Citation Format: Anna G. Dembo, Geoffrey L. Greene. ER-positive breast cancer prevention with the use of hormone replacement therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1802.
Abstract 1806: TRIM24 is an oncogenic transcriptional activator in prostate cancer
Authors: Groner Anna C. , Cato Laura , de Tribolet-Hardy Jonas , Bernasocchi Tiziano , Zhong Qing , Fankhauser Christian , Fritz Christine , Poyet Cédric , Wagner Ulrich , Garraway Levi A. , Wild Peter J. , Theurillat Jean-Philippe , Brown Myles 
Published: July 2016

Abstract
Androgen receptor (AR) signaling is a key driver of prostate cancer (PC). While androgen-deprivation therapy is transiently effective in advanced disease, tumors often progress to a lethal castration-resistant state (CRPC). We show that recurrent PC-driver mutations in SPOP stabilize the TRIM24 protein, which promotes proliferation under low androgen conditions. TRIM24 augments AR signaling, and AR and TRIM24 co-activated genes are significantly up-regulated in CRPC. Expression of TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 gene signature predict disease-recurrence. Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR-interacting motif are essential to support proliferation. These data provide a rationale for therapeutic TRIM24 targeting in SPOP-mutant and CRPC patients.
Citation Format: Anna C. Groner, Laura Cato, Jonas de Tribolet-Hardy, Tiziano Bernasocchi, Qing Zhong, Christian Fankhauser, Christine Fritz, Cédric Poyet, Ulrich Wagner, Levi A. Garraway, Peter J. Wild, Jean-Philippe Theurillat, Myles Brown. TRIM24 is an oncogenic transcriptional activator in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1806.
Abstract 1808: Nuclear receptor, ESRRG functions as tumor suppressor by preventing Helicobacter pylori infection in gastric cancer
Authors: Kang Myoung-Hee , Lee Yong-Soo , Jung Jin-Hak , Park Young Soo , Jeong Jin-Yong , Kweon Mi-Na , Paik Chan-Ki , Myung Seung-Jae , Park Yun-Yong 
Published: July 2016

Abstract
Gastric cancer (GC) is the most common cancer type in Asia. Surgical resection and chemotherapy is standard treatment of GC. Molecular therapeutic targets and mechanism contributing to develop the gastric cancer is poorly understood. To discover the molecular target in gastric cancer, we analyzed gene expression data from gastric cancer patients. Data analysis reveals that nuclear receptor ESRRG is top candidate gene conferring the tumor suppressive property in gastric cancer. ESRRG expression is down-modulated by Helicobacter pylori (H. pylori) infection, which is one of causing factor triggering gastric cancer. In addition, ectopically over-expressed ESRRG protects the cell from H. pylori infection and suppressed cancer cell growth in vitro and in vivo mouse model. Gene expression profile reveals that TFF1, which is well known as tumor suppressor in gastric cancer is down-stream target of ESRRG and ESRRG well reflects clinical outcome in gastric cancer. Our study provides new molecular insights how ESRRG regulates gastric cancer cell growth induced by H. pylori and suggests possibility that ESSRRG can be therapeutic target for the treatment of gastric cancer patients.
Citation Format: Myoung-Hee Kang, Yong-Soo Lee, Jin-Hak Jung, Young Soo Park, Jin-Yong Jeong, Mi-Na Kweon, Chan-Ki Paik, Seung-Jae Myung, Yun-Yong Park. Nuclear receptor, ESRRG functions as tumor suppressor by preventing Helicobacter pylori infection in gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1808.
Abstract 1809: Endothelin causes transactivation of the EGFR and Her-2/Neu in non-small cell lung cancer cells
Authors: Moody Terry W. , Ramos Alvarez Irene , Mantey Samuel , Jensen Robert T. 
Published: July 2016

Abstract
Endothelin-1 (ET-1) is a 23 amino acid peptide which is present in many lung cancer cell lines (Ahmed et al., Am. J. Respir. Cell Mol. Biol. 2000; 22: 422). Expression of ET-1 or the ETA receptor is associated with poor prognosis of non-small cell lung cancer (NSCLC) patients (Boldrini et al., Eur. J. Cancer 2005; 41: 2828). ET-1 stimulates whereas the ETA antagonist ZD4054 inhibits the proliferation of cancer cells (Bagnato et al., Br. J. Pharmacol. 2011: 163; 220). Here the effects of ET-1 on the transactivation of the EGFR and Her-2/Neu were investigated in NSCLC cells. Twelve of 13 NSCLC cell lines tested had both ETA and ETB mRNA. Addition of ET-1 to adenocarcinoma cell line NCI-H838, which had both ETA and ETB mRNA, elevated cytosolic Ca2+, increased tyrosine phosphorylation of the ERK, EGFR and Her-2/Neu and increased colony number. The ability of ET-1 to increase cytosolic Ca2+, tyrosine phosphorylation of ERK, EGFR and Her-2/Neu and colony number was inhibited by ZD4054 or BQ123 (ETA antagonists). The transactivation of EGFR and Her-2/Neu by ET-1 was inhibited by lapatinib (EGFR and Her-2/Neu TKI), GM6001 (matrix metalloprotease inhibitor), PP2 (Src inhibitor) or N-acetylcysteine (anti-oxidant). ET-1 stimulated whereas lapatinib and ZD4054 inhibited the clonal growth of NSCLC cells. The results indicate that ET-1 may regulate the proliferation of NSCLC cells in an EGFR and Her-2/Neu-dependent manner.
Citation Format: Terry W. Moody, Irene Ramos Alvarez, Samuel Mantey, Robert T. Jensen. Endothelin causes transactivation of the EGFR and Her-2/Neu in non-small cell lung cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1809.
Abstract 1828: Analysis of putative serum biomarker candidates for cardiotoxicity prediction in a cohort of early stage breast cancer patients treated with docetaxel, cyclophosphamide, and bevacizumab
Authors: Murray David W. , O’Farrell Alice C. , Gullo Giuseppe , Maratha Ashwini , Dicker Patrick , Rafferty Mairin , Murphy Verena , Ky Bonnie , Gallagher William M. , O’Donovan Norma , Crown John , Byrne Annette T. 
Published: July 2016

Abstract
Background: Breast cancer is the leading cause of cancer in women, with 1.8 million patients diagnosed globally each year. In early stage disease, anthracycline regimens are commonly employed, but the risk of cardiotoxicity is high. Replacing anthracyclines with taxanes in combination with cyclophosphamide may improve response [1] and Bevacizumab (BVZ) may provide addtional benefit. However, as BVZ can cause hypertension and increased risk of cardiac failure, a rationale exists for studying biomarkers of cardiotoxicity in this setting.
Methods: We assessed a panel of biomarkers in n = 57 early stage breast cancer patients whom underwent docetaxel/cyclophosphamide/BVZ therapy on the TC-Avastin Trial (NCT00911716). Serum was collected prior to treatment and at 3 months. Cardiotoxicity was defined as decline in left ventricular ejection fraction ≥ 10% to &lt;55% over 1 year treatment + 2 year follow-up. Cardiac troponin I and T [cTnI, cTnT], Endothelin-1, Galectin-3, Placental Growth Factor [PlGF], Platelet Derived Growth Factor, Vascular Endothelial Growth Factor receptors 1 and 2, total nitrous oxide NO and myeloperoxidase [MPO]) were screened by ELISA in a subgroup (n = 16). Pilot and recently published findings [2] implicated PlGF, cTn1 and MPO, which were subsequently assessed in the larger cohort.
Results: Changes in serum MPO or cTnI were not related to cardiotoxicity when analysed in the larger cohort. However, a “cut-off” PlGF fold change of 0.99 could differentiate patients who developed cardiotoxicity from those that did not. 74% of cardiotoxicity patients, compared to only 35% of non-cardiotoxicity fell below the 0.99 cut-off. Conversely, 65% of non-cardiotoxicity patients, compared to 25% of cardiotoxicity patients fell above the cut-off (p = 0.0042).
Conclusions: Our data suggest that decreased PlGF at 3 months may predict cardiotoxicity. These observations require further validation.
This work was funded by AngioTox, an EC FP7 IAPP Marie Curie Award (Grant Agreement 251528). [1]Jones et al., J. Clin. Oncol.27, 1177-1183 (2009); [2] Putt et al., Clin. Chem 61, 1164-1172 (2015).
Citation Format: David W. Murray, Alice C. O’Farrell, Giuseppe Gullo, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Bonnie Ky, William M. Gallagher, Norma O’Donovan, John Crown, Annette T. Byrne. Analysis of putative serum biomarker candidates for cardiotoxicity prediction in a cohort of early stage breast cancer patients treated with docetaxel, cyclophosphamide, and bevacizumab. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1828.
Abstract 1831: Cancer genomic resources and needs in the Latin American region
Authors: Oliver Javier , Perdomo Sandra , Vaca Felipe 
Published: July 2016

Abstract
In 2012, approximately 1,005,255 new cancer cases and 550,164 deaths from cancer occurred in both sexes in central and South American region, by 2025 and increment of nearly 30% of new cases and 35% of deaths from cancer are predicted. One of the priorities of cancer control within the region is to reduce avoidable deaths from cancer by improving early detection and personalized treatment. The development of cancer genomics and their integration to cancer care has shown a great improvement in cancer control worldwide; however, all these key advances have been mainly concentrated in highly developed nations and little is known about the capacities and needs of cancer genomics in the Latin-American (LA) context.
In order to evaluate the capacity and development of cancer genomic applications in the LA we collected available information for all countries in central, South America and Cuba. Data reviewed included: number of cancer research institutions, number of NGS platforms, research groups working in cancer genetics, publications on cancer genetics for the last 10 years, educational programs on genomics and related health policies.
In average 15 Research groups per country were registered as conducting cancer-genetics related projects. In the las 10 years, 206 publications on cancer genetics including reviews were led by (1st, 2nd or corresponding) authors affiliated to LA institutions and only publications in the last 2 years included cancer genomic analysis. Most publications related to breast, gastric and hematological cancers were underrepresented in general. In the past 5 years physical resources have grown markedly by the acquisition of nearly 150 NGS platforms in 9 countries, the majority installed in medical related services and universities. Participation in large genomic consortia has only included two countries Mexico (as partner) and Brazil (as leading). Educational programs in genomics are scarce, almost exclusive of graduate programs and few are applied to cancer.
Despite the recent advances in introducing cancer genomics knowledge and application in LA, the region lacks development of integrated genomic research projects, improved use of platforms dedicated to cancer, educational programs and health policies that focus on the most frequent cancers and could impact cancer care.
Citation Format: Javier Oliver, Sandra Perdomo, Felipe Vaca. Cancer genomic resources and needs in the Latin American region. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1831.