bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proliferation Markers Are Associated with MET Expression in Hepatocellular Carcinoma and Predict Tivantinib Sensitivity In Vitro
Authors: Rebouissou Sandra , La Bella Tiziana , Rekik Samia , Imbeaud Sandrine , Calatayud Anna-Line , Rohr-Udilova Nataliya , Martin Yoann , Couchy Gabrielle , Bioulac-Sage Paulette , Grasl-Kraupp Bettina , de Koning Leanne , Ganne-Carrié Nathalie , Nault Jean-Charles , Ziol Marianne , Zucman-Rossi Jessica 
Published: March 2017

Abstract
Purpose: Tivantinib was initially reported as a selective MET inhibitor and is under phase III evaluation in "MET-high" hepatocellular carcinoma (HCC) patients. However, it has been also proposed as an antimitotic agent. We aimed to evaluate the antitumor effect of tivantinib in HCC cells by combining pharmacologic and molecular profiling.
Experimental Design: Sensitivity to tivantinib, JNJ-38877605, PHA-665752, vinblastine, and paclitaxel was tested in a panel of 35 liver cancer cell lines analyzed with exome sequencing, mRNA expression of 188 genes, and protein expression. Drug effect was investigated by Western blot analysis and mitotic index quantification. Expression of candidate biomarkers predicting drug response was analyzed in 310 HCCs.
Results: Tivantinib sensitivity profiles in the 35 cell lines were similar to those obtained with antimitotic drugs. It induced blockage of cell mitosis, and high cell proliferation was associated with sensitivity to tivantinib, vinblastine, and paclitaxel. In contrast, tivantinib did not suppress MET signaling, and selective MET inhibitors demonstrated an antiproliferative effect only in MHCC97H, the unique cell line displaying MET gene amplification. HCC tumors with high expression of cell proliferation genes defined a group of patients with poor survival. Interestingly, highly proliferative tumors also demonstrated high MET expression, likely explaining better therapeutic response of MET-high HCC patients to tivantinib.
Conclusions: Tivantinib acts as an antimitotic compound, and cell proliferation markers are the best predictors of its antitumor efficacy in cell lines. Ki67 expression should be tested in clinical trials to predict tivantinib response. Clin Cancer Res; 23(15); 4364–75. ©2017 AACR.
Abstract A18: Gut microbiota changes in response to treatment with ursodeoxycholic acid (UDCA)
Authors: Pearson Talima , Caporaso J Gregory , Yellowhair Monica , Martinez Jessica A. , Wertheim Betsy , Roe Denise , Thompson-Canino Patricia , Lance Peter 
Published: March 2017

Abstract
Compelling evidence suggests that gut flora influences colorectal cancer risk through direct effects on colonic bile acid composition. Bile acids are widely implicated in the etiology of colorectal cancer with the strongest evidence involving a detrimental role for the secondary BA, deoxycholic acid (DCA) and a protective effect of ursodeoxycholic acid (UDCA). In a study of patients with prior colorectal adenomas who were randomized to UDCA (n=188 males, 64 females), a bile acid based intervention aimed at modulating bile acid composition, or placebo (n=162 males, 89 females), we determined effects of the intervention on the gut microbiome through 16S rRNA sequencing and bile acid composition at baseline using mass spectrometry.
We observe a consistent shift in microbial composition for males (t=5.83, p=3.6e-8) and females (t=3.14, p=0.003) treated with UDCA. No effect was observed in the placebo group for either males (t=-0.08, p=0.93) or females (t=-0.09, p=0.92). There were significant correlations between the gut microbiome and BA composition (r=0.31, p&lt;0.001).
This suggests that UDCA treatment had an effect on the gut microbial communities relative to the placebo group. Interestingly, the magnitude of the change in the microbiome over time is similar in the two groups, but UDCA treatment seems to drive specific microbiome changes. These results are consistent with our previously reported observation that UDCA appears to have a greater effect in men for the prevention of colorectal adenomatous polyps, while increasing risk for women.
Citation Format: Talima Pearson, J Gregory Caporaso, Monica Yellowhair, Jessica A. Martinez, Betsy Wertheim, Denise Roe, Patricia Thompson-Canino, Peter Lance. Gut microbiota changes in response to treatment with ursodeoxycholic acid (UDCA). [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr A18.
Abstract B05: The RNA-binding protein HuR enhances exosome secretion in colorectal cancer
Authors: Preet Ranjan , Hung Wei-Ting , Zhuang Shufei , Christenson Lane K. , Dixon Dan A. 
Published: March 2017

Abstract
Enhanced secretion of exosomes by cancer cells is recognized as a means of transferring oncogenic information within the tumor microenvironment. Through their ability to carry specific RNA and protein cargo, tumor-derived exosomes are now being recognized for their ability to impact the tumor microenvironment and as promising cancer biomarkers. However, our knowledge of the cellular factors that promote increased exosome production from tumor cells and how they impact the loading of specific tumor-promoting RNA cargo is limited. Our prior work has established that colorectal cancer (CRC) cells and tumors overexpress the key RNA-binding protein HuR (ELAVL1) early in GI tumor development. When overexpressed and present in the cytoplasm, HuR can promote mRNA stabilization of tumor-promoting genes through binding of 3'UTR AU-rich elements (ARE). These same mRNAs are within tumor-derived exosomes, suggesting a role for HuR. To test this, Tet-regulated HuR-inducible HeLa cells were used to demonstrate that cytoplasmic HuR overexpression promoted a 4-fold increase in exosome production. Furthermore, HuR was detected in exosomes produced only from HuR-overexpressing cells. The presence of HuR in exosomes directly impacted mRNA cargo, as selective uptake of ARE-containing mRNAs were observed in exosomes derived from HuR overexpressing cells. To assess if these effects were seen in CRC cells that endogenously overexpress HuR, exosome levels from CRC cells were compared to normal human intestinal epithelial and myofibroblast cells. CRC cells secrete ~3-fold greater exosome levels than normal cells and enhanced exosome production was dependent upon HuR. siRNA knockdown and CRISPER/Cas9 knockout of HuR in CRC cells showed a &gt;2-fold decrease in secreted exosomes, similar to the levels observed in normal cells. Furthermore, HuR knockout CRC cells showed a ~3-fold reduction in xenograft tumor growth compared to parental CRC cells. These findings were reflected in vivo where GI-tumor bearing APCMin/+ mice produced ~3-fold more serum exosomes, with HuR as exosomal cargo in APCMin/+ mice, whereas limited expression of exosomal HuR was detected in wild-type mice. This work has identified a novel connection between HuR-mediated post-transcriptional regulation and tumor-derived exosome production, along with providing the first preclinical evidence indicating the presence of exosomal HuR as a serum-based CRC biomarker.
Citation Format: Ranjan Preet, Wei-Ting Hung, Shufei Zhuang, Lane K. Christenson, Dan A. Dixon. The RNA-binding protein HuR enhances exosome secretion in colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr B05.
Abstract IA10: Precision chemoprevention with aspirin
Authors: Chan Andrew T. 
Published: March 2017

Abstract
Remarkably consistent experimental and epidemiologic evidence demonstrates that aspirin is associated with a lower risk of colorectal cancer. Five placebo-controlled randomized controlled trials (RCTs) among individuals with a history of colorectal neoplasia showed that aspirin reduced the risk of recurrent adenomatous polyps, the precursors of the vast majority of cancers. Additionally, data from long-term follow-up of a RCT of aspirin among individuals with the Lynch hereditary colorectal cancer syndrome and a RCT of aspirin among women for primary prevention of cardiovascular disease and cancer demonstrated a lower risk of colorectal cancer associated with randomized aspirin treatment. As a reflection of the strength of the evidence, the U.S. Preventative Services Task Force (USPSTF) updated its primary prevention guidelines for aspirin in 2016. The USPSTF provided low-dose aspirin (81 mg/day) with a recommendation for chronic disease prophylaxis, including colorectal cancer prevention, among U.S. adults between ages 50-59, and possibly ages 60-69, with a greater than 10% ten-year risk of cardiovascular events. The new USPSTF recommendation represents a significant milestone for the field of preventive medicine. With the exception of tamoxifen for women at high-risk for breast cancer, this is the first medication recommended for cancer prevention by USPSTF guidelines. Despite this advance, broader recommendations for aspirin chemoprevention are limited by concerns about risk-benefit profile in view of the established association of aspirin with gastrointestinal bleeding. Thus, in concert with broader efforts to tailor prevention strategies, our group has led several studies into the mechanistic basis of aspirin's anti-cancer effect that has led to the development of intratumoral, germline, and circulating molecular correlates of outcomes. Such biomarkers can be exploited for risk stratification to more effectively target aspirin chemoprevention for those with more favorable risk-benefit profiles. In this presentation, we will review the evidence supporting a role for aspirin in the prevention and treatment of cancer, with a focus on novel strategies for molecular risk stratification.
Citation Format: Andrew T. Chan. Precision chemoprevention with aspirin. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA10.
Abstract IA28: Molecular pathological epidemiology of risk factors and CRC microbial and immune characteristics
Authors: Ogino Shuji 
Published: March 2017

Abstract
Innate and adaptive immunity plays an important role during carcinogenesis and tumor evolution. Evidence indicates that modifiable factors such as aspirin use, physical activity, obesity, smoking, alcohol, diet, and gut microbiota can influence not only cancer risk and outcome but also the human immune system. In addition, tumor molecular pathology and immunity influence each other. Over the past years, molecular pathology and epidemiology has been united to develop the integrative field of molecular pathological epidemiology (MPE). Recently, we have further integrated cancer immunology and MPE, into a new model of “immuno-MPE”. Immuno-MPE utilizes the MPE research framework to test statistical heterogeneity of the differential associations with tumor subtypes, and can decipher the relations between risk factors and subtypes classified by immune response status. We conducted proof-of-principle studies utilizing two large U.S.-nationwide prospective cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study). We have shown that plasma vitamin D level (Song M et al. Gut 2016), germline genetic variation (IBD risk allele rs11676348) (Khalili H et al. Carcinogenesis 2015), and marine omega-3 polyunsaturated fatty acid intake (Song M et al. JAMA Oncology 2016) are associated with altered risk of specific immune subtypes of colorectal carcinoma. We have also shown that tumor neoantigen loads (Giannakis M et al. Cell Reports 2016), CD274 (PD-L1) expression (Masugi Y et al. Gut 2016), and Fusobacterium nucleatum (Mima K et al. JAMA Oncology 2015) are associated with densities of CD3+, CD8+, CD45RO+, or FOXP3+ T cells or lymphocytic response (eg., Crohn's-like lymphoid reaction, tumor-infiltrating lymphocytes, TILs) in rectal and colon cancer. Recently, we have shown that certain dietary patterns are associated with altered risk of colorectal cancer enriched with F. nucleatum, suggesting interactive carcinogenic roles of food, nutrients, and microflora (microbiome). The immuno-MPE approach can integrate tumor and immune data together with exposure risk factors and outcome. Immuno-MPE can not only give insights on how risk factors can interact with the immune system to modify cancer incidence, recurrence and survival, but also help develop strategies of immunoprevention and immunotherapy for precision medicine.
Citation Format: Shuji Ogino. Molecular pathological epidemiology of risk factors and CRC microbial and immune characteristics. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA28.
Abstract P4-03-08: Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer
Authors: Gruosso T , Gigoux M , Bertos N , Zuo D , Manem V , Monette A , Lapointe R , Haibe-Kains B , Park M 
Published: March 2017

Abstract
Triple negative breast cancer (TNBC), defined as tumors lacking expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), are especially difficult to treat effectively. While ER+ and HER2+ breast cancer subtypes can be treated with Tamoxifen and Herceptin, respectively, there are no targeted therapies for TNBC patients. Furthermore, while only 20-30% of TNBC patients respond to chemotherapy in the neoadjuvant setting, overall outcome remains poor for non-responding patients. However, mounting evidence suggests that immune-checkpoint inhibitor immunotherapies may be especially promising for TNBC patients. We and others have shown that the presence of CD8+ T cells, a crucial component of the cytotoxic arm of the adaptive immune response, is a sign of good clinical outcome in TNBC patients. However, good outcome only correlates with CD8 +T cell invasion of the tumor parenchyma. Some patients had an accumulation of CD8+ T cells in the surrounding tumor-associated stroma, but not the tumor epithelia, and these patients responded as poorly as patients with no CD8 T cells at all. Yet how cancer associated fibroblasts (CAFs), the dominant cell type of the tumor-associated stroma, affects CD8+ T cell invasion into the tumor epithelia is still poorly understood. To identify potential stroma-dependent mechanisms which potentiate or inhibit CD8+ T cells invasion into the tumor epithelia, we performed gene expression profiling of laser-capture microdissected tumor-associated stroma (and matched epithelia) from 38 TNBC cases. Here we identify several stromal and epithelial canonical pathways as well as biomarkers that are associated with and may explain the accumulation of CD8 T cells outside of the tumor epithelia.
Citation Format: Gruosso T, Gigoux M, Bertos N, Zuo D, Manem V, Monette A, Lapointe R, Haibe-Kains B, Park M. Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-08.
Abstract P5-09-08: Molecular evaluation of Peruvian patients with hereditary breast cancer reveals a novel germline mutation in BRCA1
Authors: Ponce J , Vigil C , Araujo JM , Castañeda C , Calderon G , Buleje JL , Acosta O , Danos P , Huaman F , Guevara-Fujita ML , Aguilar A , Pinto JA , Gomez HL , Fujita R 
Published: March 2017

Abstract
Background
Breast cancer is the leading cancer in women worldwide, while in Peru is the second most frequent cancer with a high incidence of triple negative breast cancers (21%). There is no previous information about BRCA1/BRCA2 mutations in Peruvian high-risk breast cancer patients. Prior studies from International diagnostic laboratories only presented results of our population as a pooled Hispanic data. Our aim was to characterize mutations in BRCA1/BRCA2 genes in Peruvian patients with breast cancer with hereditary patterns.
Methods
We evaluated mutations in BRCA1/BRCA2 genes by Sanger sequencing and large genomic rearrangements by multiplex ligation-dependent probe amplification (MLPA) in 18 families with hereditary breast cancer criteria identified at the Breast Unit of Oncosalud-AUNA (Lima-Peru). Molecular analysis was done in the facilities of Genetics and Molecular Biology Center at the San Martin de Porres University (Lima-Peru).
Results
Sequencing identified 4 pathogenic mutations in 4/18 families, three previously detected (BRCA1: c.302-1G&gt;C y c.815_824dup10; BRCA2: c.5946delT) and a novel germline mutation in exon 15 of BRCA1 (c.4647_4648dupAA, ClinVar SCV000256598.1) producing a frameshift variant. MLPA revealed 2 amplifications in exon 7 (duplication and triplication) in BRCA1 in unrelated patients with potential pathogenic effects, one of this co-existed with the BRCA2: c.5946delT mutation. In addition, three variants of uncertain significance were found (c.140G&gt;T, in exon 5 of BRCA1 and c.464G&gt;A and c.938C&gt;T in exon 5 and 10 of BRCA2, respectively).
Conclusions
After a comprehensive evaluation we found an alteration rate of 27.8% (5/18) in BRCA1/BRCA2 in families with criteria for hereditary breast cancer. We reported BRCA1 c.4647_4648dupAA as a novel mutation. Further studies including a larger sample size of Peruvian patients should evaluate the prevalence or founder effect of this mutation in our population.
Citation Format: Ponce J, Vigil C, Araujo JM, Castañeda C, Calderon G, Buleje JL, Acosta O, Danos P, Huaman F, Guevara-Fujita ML, Aguilar A, Pinto JA, Gomez HL, Fujita R. Molecular evaluation of Peruvian patients with hereditary breast cancer reveals a novel germline mutation in BRCA1 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-09-08.
Abstract P5-14-04: Effects of dose-dense chemotherapy on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomised trials
Authors: Gray R , Bradley R , Braybrooke J , Davies C , Pan H , Peto R , Bliss J , Bruzzi P , Cameron D , Del Mastro L , Norton L ,   For the EBCTCG
Published: March 2017

Abstract
This abstract was withdrawn by the authors.
Abstract A21: Representations of cancer as a national security threat: An examination of public health and public policy discourse
Authors: Ray Amanda , Dwyer Wesley 
Published: March 2017

Abstract
Background: Over the past several decades, practices of western medicine, especially in the context of public health, have become increasingly tied with state security apparatuses. These methodological and epistemological shifts in framing public health in terms of national security have shaped the ways that health care has been performed and articulated, as well as the ways in which both state and private actors have been granted participatory access within fields traditionally reserved for security experts or medical professionals. Since the attacks of September 11th, 2001 against the World Trade Center and the Pentagon, there has been significant medicalization of foreign political actors on the United States' list of Foreign Terrorist Organizations (FTOs) in particular, with both oncologists and national security planners continually using the metaphor of cancer to describe the organizations themselves, as well as the behavior, intentions, and motivations of these groups.
Methods: This project utilized a mixed method approach employing discourse analysis, with an emphasis on metaphor analysis, to examine the way that cancer is deployed as an ideological technology within United States policy planning documents, Department of Defense publications, popular media articles covering the War on Terror, and speeches by senior political figures. This research uses these same methods to examine the ways in which the field of cancer biology/cancer medicine utilizes or participates in constructing the threat of political groups designated as FTOs through academic publications, popular media, and professional research in service of, or funded by, national security interests.
Results: The equation of cancer and war generally, and terrorism specifically, by both medical professionals and national security experts is broad and serves a number of ideological purposes. Often this is done with the explicit purpose of justifying violence against marginalized political groups designated as Foreign Terrorist Organizations by the United States, though public awareness and funding were often found as motivations as well. Several of the cancer metaphors we encountered from security experts were imprecise and medically inaccurate in their descriptions, though still rhetorically powerful in how they were deployed. Given the importance in how the work of medical practitioners is depicted and its influence on how many types of health care are received, especially by marginalized communities, more work is needed in this area.
Citation Format: Amanda Ray, Wesley Dwyer. Representations of cancer as a national security threat: An examination of public health and public policy discourse. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A21.
Abstract A41: [Advocate Abstract:] Thriving
Authors: Watson Yasmeem 
Published: March 2017

Abstract
Quality of life is important. My mission is to simply help people pick up the pieces after cancer. People need to know that they can thrive after a cancer diagnosis. Advocacy is very rewarding because there is change on the horizon. Through research and providing information about life post cancer diagnosis, survivors can obtain a better quality of life.
Citation Format: Yasmeem Watson. [Advocate Abstract:] Thriving. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A41.