bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3105A: Titanium(IV) regulation by serum transferrin and citrate sheds new insight into the use of chemical transferrin mimetics for Ti(IV) anticancer drug development
Authors: Tinoco Arthur D. , Loza-Rosas Sergio A. , Vazquez Alexandra , Rivero Kennett I. , Negron Lenny M. , Saxena Manoj , Sharma Shweta , Delgado Yamixa , Sanchez Annelis , Zambrana Nicole , Parks Timothy B. 
Published: July 2016

Abstract
A recently resolved structure of Ti(IV) bound human serum transferrin (sTf) and cell viability studies reveal that the small molecule citrate and the iron(III) transport protein sTf work together to maintain Ti(IV) in a nontoxic speciation in the body. Identification of this biomolecular interaction elucidates important factors that must be considered when developing Ti(IV)-based anticancer agents. Chemical transferrin mimetic (cTfm) ligands are being employed in a Ti(IV) anticancer drug design strategy to take advantage of the structural features of the sTf metal binding site favorable for Ti(IV) coordination to facilitate Ti(IV) cytotoxicity. The very strong Fe(III) binding property of these ligands are exploited to create stable Ti(IV) complexes that are able to deliver Ti(IV) into cells but exhibit lability in the presence of Fe(III). These complexes are intended to operate by the dual function of iron depletion and Ti(IV) attack at intracellular sites. Work with the cTfm ligands N,N’-di(o-hydroxybenzyl)ethylenediamine-N,N’-diacetic acid (HBED) and deferasirox reveal the structural features of the cTfm ligands that maximize the stability of the Ti(IV) complex outside the cell but enable sufficient lability to trigger cytotoxicity within the cell. The features are those that minimize induced dissociation due to the presence of citrate and sTf. Preliminary results suggest that while Fe(III) depletion may play an important role in the activity of the Ti(IV) cTfm complexes, the two lead complexes may operate via different mechanisms of action.
Citation Format: Arthur D. Tinoco, Sergio A. Loza-Rosas, Alexandra Vazquez, Kennett I. Rivero, Lenny M. Negron, Manoj Saxena, Shweta Sharma, Yamixa Delgado, Annelis Sanchez, Nicole Zambrana, Timothy B. Parks. Titanium(IV) regulation by serum transferrin and citrate sheds new insight into the use of chemical transferrin mimetics for Ti(IV) anticancer drug development. [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 3105A.
Abstract 3109: The TERT variant rs2736100_AC is associated with reduced risk of upper track urothelial carcinomas
Authors: Yuan Xiaotian , Li Ping , Björkholm Magnus , Xu Dawei 
Published: July 2016

Abstract
Upper tract urothelial carcinomas (UTUCs) are originated from urothelium, and consist predominantly of renal pelvic carcinomas (RPCs) and ureter carcinomas (UTs). The UTUC incidence has increased over the past two decades, and most UTUCs have become invasive when diagnosed. Therefore, it is urgently needed to identify high-risk populations for the preventive intervention and monitoring. Recent genome-wide association study has provided strong evidence that common single nucleotide polymorphisms (SNPs) are associated with susceptibility of various malignancies. However, little is known about the susceptibility loci to UTUC. Here we genotyped the telomerase reverse transcriptase (TERT) SNPs rs2736100 and rs2736098, two SNPs associated with a risk of other malignancies, in Han Chinese patients with UTUC (n = 217) and evaluated the relationship between the rs2736100 polymorphism and UTUC risk by comparing with that in 289 healthy controls. Genotyping was performed using a TaqMan® SNP Genotyping Assays kit. Neither AA nor CC genotypes differed significantly between cases and control subjects, while the AC carriers were associated with the reduced risk of UTUC (OR = 0.6043; 95% CI: 0.4039 - 0.9042; P = 0.0185). When RPCs (n = 100) and UTs (n = 117) were analyzed separately, such protective effect remained significant in UTs (OR = 0.5728; 95% CI: 0.3540 - 0.9269; P = 0.031). The AC genotype was lower in RPC patients than in controls, but the difference was not statistically significant (OR = 0.6484; 95% CI: 0.3811 - 1.103; P = 0.142). In conclusion, we show for the first time that the rs2736100 AC genotype is protective against UTUC development.
Citation Format: Xiaotian Yuan, Ping Li, Magnus Björkholm, Dawei Xu. The TERT variant rs2736100_AC is associated with reduced risk of upper track urothelial carcinomas. [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 3109.
Abstract 3111: Elevated expression of hyaluronan synthase 2 associates with poor prognosis in diffusely infiltrating astrocytomas
Authors: Poukka Mari J. , Haapasalo Hannu , Rilla Kirsi J. , Tyynelä-Korhonen Kristiina , Soini Ylermi , Pasonen-Seppänen Sanna M. 
Published: July 2016

Abstract
Diffusely infiltrating astrocytomas are central nervous system tumors originating from astrocytic glial cells or their precursor cells. In this retrospective study we investigated the content of hyaluronan and the expression of hyaluronan metabolizing enzymes and its cell surface receptor, CD44, in these aggressive tumors. Hyaluronan is a large extracellular matrix molecule synthesized by three hyaluronan synthases (HAS1-3) on the plasma membrane and degraded by two hyaluronidases (HYAL1-2). In many tumors, aberrant hyaluronan metabolism implicates aggressive disease progression and metastatic potential.
Our material consisted of 165 diffusely infiltrating astrocytomas (WHO grades II-IV). Tumor samples were processed into tissue microarray (TMA) blocks. The TMA sections were stained for hyaluronan, CD44, HAS1, HAS2, HAS3 and HYAL2. The staining intensity of astrocytomas was evaluated with a four-level scoring (0-3; no color, weak, moderate and strong) by two independent observers. The immunostaining results were compared with χ2 -test or with Kruskal-Wallis test for correlation with clinicopathological parameters and survival analyses were done with Kaplan-Meier log rank test and Cox regression.
Hyaluronan and CD44 were strongly expressed in astrocytic gliomas but their expression did not correlate with WHO grade, cell proliferation activity by Ki-67, p53 status, epidermal growth factor receptor (EGFR) amplification or IDH1 mutation. Whereas HAS2 staining intensity showed a significant correlation with IDH1 mutation. Tumors with high HAS2 expression were IDH1 negative (p = 0.003). In addition, in non-parametric tests increased HAS2 staining intensity showed association with increased cell proliferation (p = 0.013) and in log rank test with decreased overall survival of patients (p = 0.001). Variables included in the multivariable Cox regression analysis were HAS2 staining intensity, p53 status, EGFR amplification, IDH1 mutation and WHO tumor grade; in this analysis HAS2 expression turned out to be a significant independent prognostic factor (p = 0.008). This study indicates that elevated expression of HAS2 is associated with glioma progression and suggests that HAS2 has a prognostic significance in diffusely infiltrating astrocytomas.
Citation Format: Mari J. Poukka, Hannu Haapasalo, Kirsi J. Rilla, Kristiina Tyynelä-Korhonen, Ylermi Soini, Sanna M. Pasonen-Seppänen. Elevated expression of hyaluronan synthase 2 associates with poor prognosis in diffusely infiltrating astrocytomas. [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 3111.
Abstract 3120: B-Catenin gene expression and its mutations: promising and key component in the pathogenesis of acute myeloid leukemia (AML)
Authors: Maqbool Mohsin , Iqbal Sobuhi , Sharma Atul , Bakhshi Sameer , Vishnubhatla Sreenivas , Upadhyay Ashish Datt , Kumar Lalit 
Published: July 2016

Abstract
INTRODUCTION AND AIM: Wnt signaling pathway plays a critical role in stem cell self-renewal and proliferation of leukemic stem cells and its association with the pathogenesis of acute myeloid leukemia (AML) has also been described. Beta-Catenin, a key regulator of Wnt signaling is highly expressed in cancers. Its role has been recently documented in AML however its prognostic significance in AML is not clear. The present study was carried to determine the potential prognostic implications of B-catenin expression and mutations in de novo AML patients.
METHODS: We performed the gene expression of B-Catenin and its mutations analysis in exon 3. We investigated the expression of B-Catenin gene in bone marrow and/or blood samples by quantitative PCR using SYBR-Green chemistry and analysis was done by ΔΔCT Method. 18S RNA and B2M genes were used as reference genes. B-Catenin mutations analysis was by done direct DNA Sanger sequencing.
RESULTS: Total 117 de novo non M3 AML patients and 40 healthy controls were included for the gene expression and analyzed for their clinicopathologic and prognostic significance. Median age for entire cohort (n = 117) was 17.0 years (Range 1-60 years) with male:female ratio of (1.8:1). FLT3-ITD mutation was positive in 11 (9.5%) patients. Only 4% of AML patients showed genetic alterations in exon 3 of B-catenin and no significant correlation with base line characteristics. B-catenin showed a significantly increased mRNA expression with a 5 fold rise as compared to healthy controls (p&lt;0.05). B-catenin over expression was significantly associated with poor survival at median followup of 17 months and having less CR rates (p = 0.03). There was no significant correlation of B-catenin over expression vs baseline clinical characteristics like Hb, TLC, Platelets, Cyto group (p = 0.11), blast percentage (p = 0.28), Flt3-itd mutations (p = 0.42).
CONCLUSION: These results provide the evidence for WNT signaling activation existence in AML patients and suggest that B-Catenin could be the key component in the pathogenesis and can be prognostically important marker in AML. However B-catenin expression in larger cohort of samples and with longer follow-up is required to confirm our findings.
Citation Format: Mohsin Maqbool, Sobuhi Iqbal, Atul Sharma, Sameer Bakhshi, Sreenivas Vishnubhatla, Ashish Datt Upadhyay, Lalit Kumar. B-Catenin gene expression and its mutations: promising and key component in the pathogenesis of acute myeloid leukemia (AML). [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 3120.
Abstract 313: Type II interleukin 1 receptor-modulated SETBP-1/SET/PP2A/p-ERK signaling reduces the therapeutic activity of regorafenib against human colorectal cancer cells
Authors: Mar Ai-Chung , Chu Chun-Ho , Yang Shung-Haur , Jiang Jeng-Kai , Shiau Chung-Wai , Lee Te-Chang 
Published: July 2016

Abstract
Regorafenib, a newly approved multi-kinase inhibitor by US FDA, has recently demonstrated overall survival benefits in late-stage colorectal cancer (CRC) patients. We have preliminarily observed that the expression type II interleukin 1 receptor (IL1R2), an IL-1 decoy receptor, was closely associated with regorafenib resistance in human CRC cells. We also found that IL1R2 expression was associated with poor prognosis and 5-year survival of CRC patients. In this study, we conducted experiments to elucidate the mechanisms underlying which IL1R2 is involved in regorafenib resistance. We first demonstrated that silencing of IL1R2 in HT29 cells overcame its resistance to regorafenib, whereas ectopic expression of IL1R2 in HCT116 cells reduced its sensitivity to regorafenib in either in vitro or in vivo assay systems. In addition, we established regorafenib-resistant DLD-1 cells (DLD-1-R) by long-term culturing DLD-1 cells in the presence of regorafenib, and we observed that protein expression of IL1R2 was increased in DLD-1-R cells compared to the parental DLD-1 cells. Furthermore, our results showed that IL1R2 expression was positively associated with p-ERK levels, which are crucial for survival of cancer cells. Pretreatment of HT29, IL1R2-overexpressing HCT116, and DLD-1-R cells with MEK/ERK inhibitor U0126 significantly reversed their regorafenib resistance in in vitro and in vivo systems. Mechanistically, we revealed that increased p-ERK levels in IL1R2-overexpressing cells were due to the decrease of PP2A activity instead of its expression levels. Since PP2A is a phosphatase of ERK, we further demonstrated that IL1R2 mediated through transcriptionally enhancing the expression of SETBP-1. The formation of SETBP-1/SET/PP2A complex decreased the activity of PP2A. Taken together, our present study identified IL1R2 was a potential prognostic and staging biomarker of CRC patients. Significantly, we also demonstrated a new molecular mechanism involved in regorafenib resistance and the combination of regorafenib and MEK/ERK inhibitor is a rationale regime to overcome regorafenib resistance in CRC patients.
Citation Format: Ai-Chung Mar, Chun-Ho Chu, Shung-Haur Yang, Jeng-Kai Jiang, Chung-Wai Shiau, Te-Chang Lee. Type II interleukin 1 receptor-modulated SETBP-1/SET/PP2A/p-ERK signaling reduces the therapeutic activity of regorafenib against human colorectal 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 313.
Abstract 3147: Identification of developmental endothelial locus-1 on circulating extracellular vesicles as a novel biomarker for early breast cancer detection
Authors: Moon Pyong-Gon P. , Lee Jeong-Eun , Cho Young-Eun , Lee Soo Jung , Jung Jin Hyang , Chae Yee Soo , Bae Han-Ik , Kim Young-Bum , Kim In-San , Park Hoyong , Baek Moon-Chang 
Published: July 2016

Abstract
Purpose: Currently, there are no molecular biomarkers for the early detection of breast cancer (BC). This study focused on identifying surface proteins found on circulating extracellular vesicles (EVs) for detecting early-stage BC.
Experimental Design: Circulating EVs, isolated from the plasma of 10 patients with BC (stages I and II), and 5 healthy controls, were analyzed using LC-MS/MS. Developmental endothelial locus-1 protein (Del-1) was selected as a candidate biomarker. Two different enzyme-linked immunosorbent assays (ELISAs) were used to measure Del-1 in plasma samples from healthy controls (n = 81), patients with BC (n = 269), BC patients after surgical resection (n = 50), patients with benign breast tumors (n = 64), and patients with non-cancerous diseases (n = 98), in two cohorts.
Results: Plasma Del-1 levels were significantly higher (P &lt; 0.0001) in patients with BC than in all controls and returned to almost normal after tumor removal. The diagnostic accuracy of Del-1 was area under the curve (AUC), 0.961 [95% CI, 0.924-0.983], sensitivity of 94.70% and specificity of 86.36% in test cohort, and 0.968 [0.933-0.988], 92.31% and 86.62% in validation cohort for early-stage BC by one type of ELISA. Furthermore, Del-1 maintained diagnostic accuracy for patients with early-stage BC using the other type of ELISA (0.946 [0.905-0.972], 90.90%, and 77.14% in the test cohort; 0.943 [0.900-0.971], 89.23%, and 80.99% in the validation cohort).
Conclusions: Del-1 on circulating EVs is a promising marker to improve identification of patients with early-stage BC and distinguish BC from benign breast tumors and non-cancerous diseases.
Citation Format: Pyong-Gon P. Moon, Jeong-Eun Lee, Young-Eun Cho, Soo Jung Lee, Jin Hyang Jung, Yee Soo Chae, Han-Ik Bae, Young-Bum Kim, In-San Kim, Hoyong Park, Moon-Chang Baek. Identification of developmental endothelial locus-1 on circulating extracellular vesicles as a novel biomarker for early breast cancer detection. [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 3147.
Abstract 3148: Clinical validation of a next-generation sequencing assay specifically for blood-drop liquid biopsy
Authors: Yeh Chen-Hsiung , Spurgin Jonathan , Ford Andrew , Athanasuleas John , Manne Upender 
Published: July 2016

Abstract
Next-generation sequencing (NGS) technology enables rapid analysis and turnaround of multiple genes for clinically actionable somatic variants. Genetic sequencing on tumor biopsy tissue to inform treatment decisions is the hallmark of precision medicine. However, a one-time, single-site tissue sample may not be a true representation of tumor dynamic profile. A liquid biopsy, based on circulating cell-free DNA (cfDNA), can capture the entire heterogeneity of the disease, and offer what tissue biopsies can’t, the opportunity to take serial samples in order to monitor tumor genomic evolution in real time. We have recently developed a proprietary cfDNA enrichment process that requires only droplet volumes of blood. Here, we presented clinical validation of the blood-drop liquid biopsy NGS assay interrogating 2855 mutation hotspots in 50 cancer-associated genes using the AmpliSeq cancer panel and Ion Torrent Proton sequencer.
One nanogram of cfDNA prepared from 20 uL of plasma/serum was used as template to amplify 207 mutation hotspot amplicons. Deep sequencing of total 95 clinical specimens (≥ 1000× average coverage across the capture regions) achieved high sensitivity for detecting somatic variants at low allele fraction (AF). The variants at AF of ≥ 10% in most samples (90/95), except 5 cases, were confirmed by another laboratory. Repeated sequencing of 15 samples, and progressively diluted samples from two reference standard DNAs with known mutations and AF demonstrated reliable detection sensitivity at 1% for most single nucleotide variants (SNV) with high within-run and between-run reproducibility. Validation also revealed sensitivity and specificity for detecting variants at 5% AF was 100% (95% CI = 95.7-100.0) using Tru-Q 4 NGS reference standard DNA, and NA19240 or NA12878 HapMap individual, respectively.
Overall, our new-generation liquid biopsy NGS assay, with the capability to multiplex and simultaneously sequence multiple patient samples using finger-stick blood, is a robust and sensitive method for mutation analysis of clinical significance, further expedite treatment decision-making and identify targeted therapies for eligible patients in a time- and cost-efficient manner.
Citation Format: Chen-Hsiung Yeh, Jonathan Spurgin, Andrew Ford, John Athanasuleas, Upender Manne. Clinical validation of a next-generation sequencing assay specifically for blood-drop liquid biopsy. [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 3148.
Abstract 3150: Analysis of the extracellular vesicles content present in the plasma of patients with head and neck squamous cell carcinoma for identification of molecular markers for treatment response
Authors: Rodrigues-Junior Dorival Mendes , Tan Soon Sim , Lim Sai Kiang , Iyer N Gopalakrishna , Luiz Vettore Andre 
Published: July 2016

Abstract
Previous data showed that induction chemotherapy (IC) with cisplatin and paclitaxel followed by chemoradiotherapy (CRT) based on cisplatin is safe, well tolerated and improves overall survival for patients with locally advanced head and neck squamous cell carcinoma (HNSCC) (stage III -IV). However, approximately 30% of these patients have incomplete response to IC and CRT and there is no clinical marker able to segregate these patients from those that respond to the treatment. The recent discovery of extracellular vesicles (EVs) in different body fluids carrying proteins and nucleic acids may indicate an alternative route for new specific markers present in the plasma of patients with HNSCC. In this study, Cholera toxin B chain (CTB) and Annexin V (AV) which respectively binds GM1 ganglioside and phosphatidylserine, were used to isolate EVs from plasma of HNSCC patients that respond and not respond to IC and CRT. The proteins in the vesicles were identified using antibody array through a pool of 6 responders’ patients (R) in comparison to 6 patients with incomplete response (IR). A total of 327 proteins were identified into CTB-EVs, from which 54 and 20 proteins were exclusive to R and IR patients, respectively. Beside this, 271 proteins were identified into AV-EVs, from which 20 proteins were present in R patients and other 20 proteins were present only in IR ones. A preliminary analysis of this data revealed that HNSCC resistant patients have elevated levels of TGFβ3 in CTB-EVs while patients with incomplete response have elevated levels of HSP90AB1 in AV-EVs. This study demonstrated the successful use of CTB and AV to isolate circulating plasma EVs for biomarker discovery in HNSCC and represents a novel technology that can be applied to segregate patients that may respond or not to IC or CRT.
Citation Format: Dorival Mendes Rodrigues-Junior, Soon Sim Tan, Sai Kiang Lim, N Gopalakrishna Iyer, Andre Luiz Vettore. Analysis of the extracellular vesicles content present in the plasma of patients with head and neck squamous cell carcinoma for identification of molecular markers for treatment response. [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 3150.