bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1833: KRAS-regulated P4HA1 in pancreatic tumor and its hydroxylated peptide as a serum biomarker for early diagnosis
Authors: Deng Zaian , Mann Karen M. , Koay Eugene J. , Ferrari Mauro , Wu Xifeng , Chiao Paul J. , Hu Tony 
Published: August 2015

Abstract
Protein posttranslational modification (PTM) plays a pivotal role in cancer progression through regulating gene expression, protein activities and stabilization. These chemistry events are regarded as potential biomarkers for cancer diagnosis, prognosis, and therapeutic efficacy evaluation. Hydroxylated proline is the most common PTM amino acid residue in the proteome. However, this modification is often overlooked. Here, we demonstrate the expression level of prolyl-4-hydroxylase alpha-1(P4HA1) in tumor tissues and the ratio of its catalyst (hydroxyprolyl-3-bradykinin, Hyp-BK) to its substrate (bradykinin, BK) in blood can serve as biomarkers for early pancreatic cancer diagnosis. First, we found that the P4HA1 expression level responds to the activation of KRAS which is commonly observed in pancreatic cancer cells. Immunohistochemistry testing for tumor tissue array reveals that pancreatic cancer tumor tissues, even in stage I tumor, present higher P4HA1 expression levels than tissues with chronic pancreatitis and healthy control. Peptidomic studies on clinical blood samples revealed that the Hyp-BK/BK value was 2.3 fold higher in pancreatic cancer patients than chronic pancreatitis patients and control group. The results were further validated in an independent sample cohort with blind information. We combined CA19-9 and the Hyp-BK/BK value as a biomarker panel obtaining an area under the curve (AUC) of 0.742 and 0.813 in the comparison of pancreatic cancer to pancreatitis patients and controls, respectively. Our results demonstrate that the measurement of Hyp-BK/BK value in blood, which reflects the hydroxylation level regulated by tumor-localized P4HA1, can be used as a biomarker for early detection of pancreatic cancer.
Citation Format: Zaian Deng, Karen M. Mann, Eugene J. Koay, Mauro Ferrari, Xifeng Wu, Paul J. Chiao, Tony Hu. KRAS-regulated P4HA1 in pancreatic tumor and its hydroxylated peptide as a serum biomarker for early diagnosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1833. doi:10.1158/1538-7445.AM2015-1833
Abstract 1855: Structural requirements for the association of the ETS domain transcription factor Elk1 and the androgen receptor in enabling the growth of prostate cancer cells
Authors: Rosati Rayna , Chari Venkatesh , Patki Mugdha , Ratnam Manohar 
Published: August 2015

Abstract
The ETS domain transcription factor Elk1 tethers the androgen receptor (AR) to chromatin, enabling sustained activation of a set of genes critical for cell growth in established prostate cancer cell lines. This role of Elk1 is independent of the ability of Elk1 to transiently activate immediate early genes in response to phosphorylation by ERK. We compared the structural requirements for the association of AR and Elk1 with that for activation of Elk1 by phosphorylation using mammalian one- and two-hybrid assays. The critical polypeptide segments were mapped by systematic deletion mutagenesis. The amino-terminal A/B domain of AR, which lacks the ligand-binding domain (LBD), was adequate for association with Elk1 and to activate Elk1-AR target genes in LNCaP prostate cancer cells. The AR A/B domain also supported hormone-independent growth of LNCaP cells reflecting the ability of overexpressed natural splice variants of AR, which also lack LBD, to support prostate tumor growth. The association of AR with Elk1 did not require ERK1/2 or serum response factor (SRF), which are the known binding partners of Elk1. We identified two sites on Elk1 that are critical for its association with the AR A/B domain as well as the whole AR molecule. One of those sites spans amino acid residues 297 to 317, overlapping one of two ERK docking sites. The other site on Elk1 mapped to amino acid residues 387 to 397, adjacent to the downstream ERK docking site. The results suggest that the association of AR with Elk1 in situ is direct rather than through the Elk1 ternary complex and that the association may be disrupted by small molecules to selectively inhibit growth signaling in prostate cancer cells.
Citation Format: Rayna Rosati, Venkatesh Chari, Mugdha Patki, Manohar Ratnam. Structural requirements for the association of the ETS domain transcription factor Elk1 and the androgen receptor in enabling the growth of prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1855. doi:10.1158/1538-7445.AM2015-1855
Abstract 1868: Expression of MAS1 in triple-negative breast cancer
Authors: Luo Yi , Kitadai Yasuhiko , Nishiguchi Yukiko , Fujiwara Rina , Sasaki Takamitsu , Ohmori Hitoshi , Kuniyasu Hiroki 
Published: August 2015

Abstract
MAS1 is a receptor for angiotensin 1-7 (A1-7), which is derived from angiotensin II (A-II) by the action of angiotensin converting enzyme (ACE) 2. We examined the role of MAS1 in 132 cases of invasive ductal carcinoma (IDC) of the breast by using immunohistochemistry. While normal mammary tissues expressed MAS1 at high levels, MAS1 expression was attenuated in all IDCs, especially in scirrhous IDCs. The decrease in MAS1 expression was associated with tumor growth, lymph node metastasis, and grade. MAS1 expression was inversely associated with the proliferation index and epidermal growth factor receptor and human epidermal growth factor receptor-2 expression. Of the 132 cases, 12 (9.1%) were triple-negative breast cancer (TNBC) cases. Using the mouse TNBC cell line 4T1, which expresses MAS1, we found that cell growth, anti-apoptotic survival, and invasion were suppressed by A1-7 treatment and enhanced by MAS1 knockdown. Combination treatment with cisplatin, an ACE2 activator, and an A-II type 1 receptor blocker showed synergic effects on tumor growth inhibition. These findings suggest that MAS1 might be a pivotal molecular target for TNBC.
Note: This abstract was not presented at the meeting.
Citation Format: Yi Luo, Yasuhiko Kitadai, Yukiko Nishiguchi, Rina Fujiwara, Takamitsu Sasaki, Hitoshi Ohmori, Hiroki Kuniyasu. Expression of MAS1 in triple-negative breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1868. doi:10.1158/1538-7445.AM2015-1868
Abstract 1890: Dietary intake of 502 polyphenols and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study
Authors: Zamora-Ros Raul , Romieu Isabelle , Scalbert Augustin ,   EPIC Study group
Published: August 2015

Abstract
Introduction. Epidemiological evidence on the association between polyphenol intake and colorectal cancer (CRC) risk is still inconsistent. Case-control studies suggest inverse associations, but these were not confirmed in cohort studies so far. Moreover, to date, only some polyphenol classes (flavonoids and lignans) have been studied. We aimed to explore the association between polyphenol intake and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
Design. The study included 477,386 subjects (29.8% men) aged 35-70 years from 10 European countries. Both lifestyle and dietary questionnaires were collected at enrollment. Dietary polyphenol intakes were estimated using dietary questionnaires and the Phenol-Explorer database, including data on 502 individual polyphenols in 452 plant-based foods. Retention factors for processed and cooked food from the Phenol-Explorer database were also applied.
Results. After a mean follow-up of 11 years, 4,701 validated incident CRC cases (2,979 colon cancer and 1,722 rectal cancer) were identified and included in the analysis. A wide range of total polyphenol intake and a South-to-North geographical gradient (ranging from 584mg/d in Greek women to 1,786mg/d and Danish men) were observed. Phenolic acids (52.6%) were the main contributors to total polyphenol intake, followed by flavonoids (42.4%), alkylphenols (2.7%), tyrosols (1.0%), lignans, stilbenes and other minor polyphenols (&lt;0.3%). Coffee, tea and fruits were the most important food sources of total polyphenols. Cox proportional hazards model will be used to calculate hazard ratios and 95% confidence intervals of CRC for categories of dietary polyphenols intake (total and by classes and subclasses). All analyses will be done separately for CRC and by anatomical subsite: colon, proximal and distal colon, and rectum. Several risk factors known or suspected to influence CRC risk will be considered as potential confounders.
Conclusions. This will be the first study evaluating the association between all polyphenol classes and CRC risk. EPIC is a convenient study to assess these relationships due to the large number of CRC cases, its longitudinal study design, and the high variability in the polyphenol intake amongst the participants across Europe.
Citation Format: Raul Zamora-Ros, Isabelle Romieu, Augustin Scalbert, EPIC Study group. Dietary intake of 502 polyphenols and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1890. doi:10.1158/1538-7445.AM2015-1890
Abstract 1891: Butyric acid reverts DRP1-mediated cell proliferation and migration in colorectal cancer cells
Authors: Tailor Dhanir M. , Hahm Eun Ryeong , Singh Shivendra V. , Singh Rana P. 
Published: August 2015

Abstract
Colorectal cancer (CRC) is fourth most commonly diagnosed cancer in the world and more than 1 million new cases diagnosed annually. Human gastro-intestinal (GI) tract carries more than 100 billion microbial cells of over 1000 different species. These gut microbiota have direct correlation with dietary habits and health. Butyric acid (BA) is the byproduct of anaerobic microbial fermentation inside the GI tract that could reach up to 20 mM, and has been shown to inhibit the growth of various cancers. Recently, we observed that BA induced G2/M phase arrest and apoptosis, and down regulated the expression of DRP1. Further, we evaluated the effect of DRP1 expression on cell proliferation and migration and its response to BA treatment. DRP1 overexpression increased cell proliferation rate by 20% when compared to control vector transfected HCT116 cells. BA treatment (1 mM) for 12 h to DRP1 overexpressed cells reverted cell proliferation by 11% and induced cell cycle arrest in S and G2/M phase, BA caused significant G2/M arrest in control cells. DRP1 overexpression led to pro-survival signaling including activation of ERK1/2 and Akt, and concomitantly decreased the levels of cell cycle inhibitory and pro-apoptotic molecules including p53, p21 and Bax. BA treatment reverted the pro-survival signaling and induced the expression of p53 and p21 as well as enhanced the interaction between DRP1 and p53. DRP1 also led to an increase in cell migration and invasion by 28% and 40%, respectively which was associated with decreased expression of E- cadherin. In presence of BA, DRP1 overexpressing cells loss their ability to migrate up to 70% and increased the expression of E-cadherin. These results suggest that regulation of DRP1-dependent mitochondrial fission mediated the cell proliferation and migration and thus could be a novel target to regulate colon cancer growth, progression and metastasis. BA is product of anaerobic fermentation of dietary fibers which is directly related to the nutritional practices of individuals; thus healthy dietary practices may help to reduce the incidence of colorectal cancer.
Citation Format: Dhanir M. Tailor, Eun Ryeong Hahm, Shivendra V. Singh, Rana P. Singh. Butyric acid reverts DRP1-mediated cell proliferation and migration in colorectal cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1891. doi:10.1158/1538-7445.AM2015-1891
Abstract 1892: Curcumin induces apoptosis in H-Ras transformed human mammary epithelial cells: Cysteine 259 of STAT3 as a putative target
Authors: Hahn Young-Il , Kim Su-Jung , Choi Bu-Young , Na Hye-Kyung , Surh Young-Joon 
Published: August 2015

Abstract
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is latent but constitutively activated in many types of cancers. It is well known that STAT3 plays a key role in inflammation-associated tumorigenesis. Curcumin, a natural compound isolated from the traditional Indian spice turmeric (Curcuma longa.,Zingiberaceae), has anti-tumor, anti-proliferative and anti-inflammatory properties. This compound has been extensively used in traditional herbal medicine over the centuries mainly due to its pronounced anti-inflammatory effects. Many studies suggest that curcumin regulates various cancer-related intracellular signaling pathways without damaging normal cells and tissues. Here, we report that curcumin effectively inhibits activation of STAT3 in dose- and time-dependent manners and causes apoptosis of H-Ras transformed breast epithelial cells (H-Ras MCF10A). Specific cysteine residues present in STAT3 appear to be critical for the activity as well as conformation of this transcription factor. We identified the cysteine residue 259 as a putative target of curcumin. We found that the α,β-unsaturated carbonyl moiety of curcumin appears to be essential in its direct binding to STAT3. Tetrahydrocurcumin that lacks the electrophilic α,β-unsaturated carbonyl moiety failed to inhibit STAT3 activation and to induce apoptosis in the same cell line. Taken together, our findings suggest that curcumin can abrogate persistently activated STAT3 signaling through direct interaction, thereby inhibiting STAT3-mediated mammary carcinogenesis.
Citation Format: Young-Il Hahn, Su-Jung Kim, Bu-Young Choi, Hye-Kyung Na, Young-Joon Surh. Curcumin induces apoptosis in H-Ras transformed human mammary epithelial cells: Cysteine 259 of STAT3 as a putative target. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1892. doi:10.1158/1538-7445.AM2015-1892
Abstract 1923: Distinct evolutionary and mutational patterns in oncogenes and tumor suppressor genes
Authors: Liu Li , Chang Yung , Ye Jieping , Kumar Sudhir 
Published: August 2015

Abstract
Oncogenes and tumor suppressor genes play different roles in carcinogenesis and tumor progression. However, very little attention has been paid to compare their mutational and evolutionary patterns. As such, these two groups of genes are often mingled together in computational modeling and analysis. To bridge this gap, we examined the evolutionary profiles of 150 oncogenes and 102 tumor suppressor genes and their somatic mutations recorded in the COSMIC database. We found that these two groups of genes display distinct evolutionary and mutational patterns. In general, oncogenes are more conserved than tumor suppressor genes, as revealed by multiple-species comparisons. The stronger purifying selection on oncogenes is also reflected at positions harboring somatic missense mutations. Thus, somatic mutations disrupting oncogenes tend to have higher functional impact than those disrupting tumor suppressor genes. However, the mutational landscape of oncogenes is often dominated by one or very few hotspots, while multiple hotspots and frequent sporadic mutations are found in tumor suppressor genes. Furthermore, CpG hypermutations contribute to 58% of highly recurrent mutations in tumor suppressor genes, but only 4% to those in oncogenes. These patterns indicate that most random somatic mutations in oncogenes are also under stronger purifying selection as compared to those in tumor suppressor genes. However, once an advantageous mutation in an oncogene arises, it tends to increase the fitness significantly such that a hard sweep pursues, which eventually reduces the mutational diversity of the tumor. On the contrary, the relatively mild selection on tumor suppressor genes allows more neutral mutations to accumulate. When eventually the deactivation of both copies of a tumor suppressor gene triggers positive selection, the mutational diversity of the tumor has increased significantly. These distinct evolutionary and mutational patterns warrant independent modeling of oncogenes and tumor suppressor genes in studies that incorporate these features in the analysis, such as prediction of driver mutations or inference of evolutionary paths for cancers.
Citation Format: Li Liu, Yung Chang, Jieping Ye, Sudhir Kumar. Distinct evolutionary and mutational patterns in oncogenes and tumor suppressor genes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1923. doi:10.1158/1538-7445.AM2015-1923
Abstract 1931: Mathematical modeling predicts exponential growth kinetics for metastases in the lymphatic vessels in the absence of vascularization
Authors: Griswold Ruth E. , Podgrabinska Simona , Das Suvendu , Griffith Boyce , Peskin Charles S. , Skobe Mihaela 
Published: August 2015

Abstract
The objective of this study was to examine how the biophysical characteristics of different metastatic niches influence survival and growth of metastatic cells using mathematical modeling. In the lung, metastases can form in the lung parenchyma or in the lymphatic vessels. The presence of cancer metastases in the lung lymphatics is associated with rapid disease progression and extremely poor prognosis for patients. Remarkably, metastases in pulmonary lymphatics are avascular, yet grow larger than metastases in the lung parenchyma. To explain rapid growth of metastases in the lymphatics in the absence of angiogenesis, we have developed a 3D mathematical model of intralymphatic tumor growth. This is a deterministic continuum model based on partial differential equations used to describe avascular tumor growth and adapted to reflect the unique architecture of the lymphatic vasculature. Our model predicts that the cylindrical shape of the lymphatic vessel, which constrains growth of the tumor in two dimensions yet allows indefinite growth along the vessel, enables oxygen levels to remain high throughout the tumor. The greater diffusion coefficient of oxygen in lymph further improves oxygenation of intralymphatic metastases, which rarely become hypoxic. Improved tumor oxygenation leads to decreased tumor cell death and a rapid increase of metastatic burden in the lymphatics. Importantly, our model predicts that the kinetics of growth of intralymphatic metastases is exponential. This contrasts the established view that all tumors follow Gompertzian growth kinetics, i.e., that tumor growth rate decreases as tumor size increases. Furthermore, these findings indicate that the lymphatic niche is a favorable environment for metastatic growth, and that angiogenesis is not always required for the progressive growth of metastases. Finally, our predictions of different growth kinetics of primary tumors and their metastases suggest that the treatment schedules for metastatic disease could be further optimized to achieve better efficacy.
Citation Format: Ruth E. Griswold, Simona Podgrabinska, Suvendu Das, Boyce Griffith, Charles S. Peskin, Mihaela Skobe. Mathematical modeling predicts exponential growth kinetics for metastases in the lymphatic vessels in the absence of vascularization. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1931. doi:10.1158/1538-7445.AM2015-1931
Abstract 1939: Discovery and proteogenomic investigation of genetic variants in human cancers
Authors: Huang Kuan-lin , Wang Jaiyin , Cao Song , Xie Mingchao , Jayasinghe Reyka , Ning Jie , McLellan Michael , Wendl Michael , Scott Adam , Johnson Kimberly , Davies Sherri , Fenyö David , Townsend Reid , Chen Feng , Parvin Jeffrey , Ellis Matthew , Ding Li 
Published: August 2015

Abstract
A significant fraction of cancers have a heritable component, and require an interplay between somatic and germline variants. Common and rare germline variants have been investigated by previous GWAS and family based studies. However, a comprehensive analysis of both somatic and germline variants in cancer using high throughput sequencing data to discover genetic variants of functional relevance is lacking. Herein, we investigated the potential role of somatic and germline variants from over 20 major cancer types from large-scale studies such as TCGA and ICGC and discovered thousands of somatic and germline variants in cancer genomes. To link these genetic variants to cancer phenotypes, we analyzed the proteomics data in breast, ovarian and colorectal cancers generated by the Clinical Proteomic Tumour Analysis Consortium (CPTAC) using a PepScan pipeline that can detect whether a genomic variant is observed at the peptide level. The pipeline incorporated QUILTS to construct patient-specific protein database and MS-GF+ to identify peptide sequences in the database from MS spectra. Our analysis validated roughly 2% of non-synonymous genetic variants in peptides with matched spectra. We correlated the effect of genetic mutations on proteomic subtypes based on global protein expression levels. Additionally, we assessed the role of genetic variations in kinase genes using phosphoproteome profiles, and identified downstream markers that may be candidate targets for diagnosis or treatment. This analysis also helped us prioritize kinase variants that are likely functional candidates for experimental validation. In conclusion, the comprehensive study of genetic variants utilizing an integrated proteogenomic approach revealed genetic variants with potential functional impacts in cancer.
Citation Format: Kuan-lin Huang, Jaiyin Wang, Song Cao, Mingchao Xie, Reyka Jayasinghe, Jie Ning, Michael McLellan, Michael Wendl, Adam Scott, Kimberly Johnson, Sherri Davies, David Fenyö, Reid Townsend, Feng Chen, Jeffrey Parvin, Matthew Ellis, Li Ding. Discovery and proteogenomic investigation of genetic variants in human cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1939. doi:10.1158/1538-7445.AM2015-1939