bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2181: Antibody-conjugated nanoparticles for targeting metastatic triple-negative breast cancer
Authors: Khanna Vidhi , Kalscheuer Stephen , Kirtane Ameya , Panyam Jayanth 
Published: July 2017

Abstract
Early detection and the availability of new treatments have improved the survival rates of patients presenting with local or regional breast cancer to as high as 99% and 85%, respectively. On the contrary, patients with metastatic disease have a dismal 5-year survival rate of 17%. Thus, there is an urgent need for treatment strategies directed towards metastasis. Our lab has developed antibodies (Clone 6 and AM6) capable of recognizing tumor cells that have undergone epithelial-to-mesenchymal transition (EMT), a key step in the generation of circulating tumor cells and metastasis. The goal of the current study was to determine whether we use these antibodies as targeting ligands for directing anticancer drug-loaded polymeric nanoparticles to metastatic triple negative breast cancer cells as a novel therapeutic option. Polymeric PLGA nanoparticles loaded with paclitaxel, a chemotherapeutic agent, were functionalized with the antibodies using thiol-maleimide chemistry. We optimized the conjugation reaction in order to achieve maximal cell uptake of nanoparticles without compromising antibody binding. In vitro studies were carried out in an MDA-MB-231 derivative cell line with enhanced lung metastatic potential as well as a melanoma metastatic cell line M12. Clone 6 nanoparticles and AM6 nanoparticles showed significant improvement in cellular uptake as well as retention. A competition experiment confirmed target-mediated uptake of nanoparticles. Cytotoxicity studies showed improved cell kill using Clone 6 nanoparticles and AM6 nanoparticles. Based on these promising in vitro results, we are currently carrying out in vivo studies in mice. The development of a targeted drug delivery system for the treatment of metastatic triple negative breast cancer can significantly enhance the survival rate for patients who often have a life-expectancy of less than one year.
Citation Format: Vidhi Khanna, Stephen Kalscheuer, Ameya Kirtane, Jayanth Panyam. Antibody-conjugated nanoparticles for targeting metastatic triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2181. doi:10.1158/1538-7445.AM2017-2181
Abstract 2190: Theranostical nanoscale metal-organic frameworks-mediated rapid multiplexed microRNA detection and highly therapeutic efficacy in living oral cancer cells
Authors: Yu Pei , Zhuang Zehang , Qiu Guihua , Chen Haolin , Zhao Yuying , Chen Jinxiang , Liu Xiqiang 
Published: July 2017

Abstract
Oral cancer represents the sixth most frequent cancer in the world, characterized by high poor prognosis and low survival rate due to local relapse and metastasis. MicroRNAs (miRNAs) have been discovered as diagnostic biomarkers and therapeutic targets for oral cancer. However, one of the major challenges of miRNAs-based theranostical approach is to achieve efficient and safe delivery. Thus, a reliable sensing strategy that can detect miRNAs expression levels in living cancer cells is urgently needed. Herein, a novel sensing platform based on nanoscale metal-organic framework (NMOF) conjugated with the fluorophores-labeled single-stranded DNA probe (p-DNA) was fabricated to monitor and inhibit multiplexed miRNAs expression in living oral cancer cells. The flow cytometry and confocal laser scanning microscopy (CLSM) were carried out to evaluate the expression levels of miRNAs in oral cancer cells. The miRNA inhibition efficiency was examined by RT-PCR. The effects of the complexes on tumor cell invasion and migration were assessed by transwell assay and wound healing. The flow cytometry, colony formation assay and CCK8 were used to assess cell apoptosis and proliferation. The results showed that NMOF works as fluorescence quencher of the labeled p-DNA. In presence of the target miRNA (including miR-7, miR-21, and miR-155), p-DNA was able to rapidly hybridize and release from the NMOF leading to the recovery of fluorescence in living cells, which can be detected in real-time. Moreover, RT-PCR results demonstrated that the multiplexed miRNAs could be effectively downregulated after treatment of p-DNA@NMOF, resulting in the simultaneous suppression of oral cancer cell proliferation, anti-apoptosis, migration and invasion in vitro. In summary, our study suggests that p-DNA@NMOF possess great potential for combining early diagnosis and gene therapy of oral cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Pei Yu, Zehang Zhuang, Guihua Qiu, Haolin Chen, Yuying Zhao, Jinxiang Chen, Xiqiang Liu. Theranostical nanoscale metal-organic frameworks-mediated rapid multiplexed microRNA detection and highly therapeutic efficacy in living oral cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2190. doi:10.1158/1538-7445.AM2017-2190
Abstract 2200: Dual carfilzomib and doxorubicin carrying nanoparticles for synergistic efficacy in multiple myeloma
Authors: Bilgicer Basar , Kiziltepe Tanyel , Omstead David 
Published: July 2017

Abstract
We describe the synthesis and analysis of dual carfilzomib and doxorubicin loaded nanoparticles in their ability to deliver both drugs to multiple myeloma tumor cells at their optimal synergistic ratio. First, to identify the optimal synergistic ratio, various molar ratios of carfilzomib to doxorubicin were screened against multiple myeloma cell lines using the Chou-Talalay method. Both therapeutic agents were then incorporated into liposomes at the identified optimal synergistic ratio of 1:1 to achieve dual drug loaded nanoparticles with a narrow size distribution of ~100 nm and with high reproducibility. Our results established that the dual drug loaded nanoparticles exhibited synergy in vitro and were more efficacious in inhibiting tumor growth in vivo than a combination of free drugs, while at the same time reducing systemic toxicity. In conclusion, this study achieved the preclinical evaluation of dual drug loaded liposomes containing carfilzomib and doxorubicin for enhanced therapeutic efficacy to improve patient outcome in multiple myeloma.
Citation Format: Basar Bilgicer, Tanyel Kiziltepe, David Omstead. Dual carfilzomib and doxorubicin carrying nanoparticles for synergistic efficacy in multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2200. doi:10.1158/1538-7445.AM2017-2200
Abstract 2205: Identification of potential biomarker related to EGFR mutation by functional proteome profiling in primary non-small cell lung cancer
Authors: Hsu Yuan-Ling , Pan Szu-Hua 
Published: July 2017

Abstract
Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancers which the leading cause of cancer-related death worldwide. Recently, epidermal growth factor receptor (EGFR) activating mutations have been proved relevant to NSCLC and let treatment of EGFR tyrosine kinase inhibitors (EGFR-TKIs) become an alternative therapy for NSCLC patients. Despite excellent clinical response to EGFR-TKIs, the intrinsic and acquired resistance to EGFR-TKI created challenges in clinical practice. Although several mechanisms may contribute to solve EGFR-TKIs resistance, there still have 20% to 30% of these patients that how the resistance developed remain unclear. Studies indicated that the increment of membrane efflux may be associated with drug resistance. In this study, we use differential membrane proteomic analysis to identify potential biomarkers for therapeutics of EGFR-TIKs resistance in NSCLC patients.Several primary NSCLC cell lines with different EGFR status were be isolated by our laboratory. Identification of modulators on membrane of primary cancer cells with different EGFR status was analyzed by membrane proteomic assay using LC-MS/ MS. The expression patterns of EGFR mutation cells would compare with that of wild type groups and the potential candidates would be selected by cross the results of interactome profiles of EGFR mutation cell lines. The expression patterns and functional role of these candidates were be examined in NSCLC cells by several molecular, cellular and biochemical analysis; and demonstrated the clinical relevance of these specific targets with EGFR mutation. The expressions of 100 modulators up-regulated in EGFR mutation cells compared with that of wild type group. After cross reacted with the 474 interaction proteins of mutated EGFR, 8 proteins were selected as potential candidates that related to EGFR-TKI resistance, especially the expression of a protein we called SHX in EGFR mutation cells. We demonstrated the real expression levels of SHX in different lung cancer cells, and performed network analysis of SHX and EGFR in translational level.The analysis of differential membrane proteomic found several novelbiomarkers and potential regulation mechanisms that related to the development of EGFR-TKIs resistance in NSCLC. These identification may provide us new direction for exploiting therapeutic strategy for NSCLC treatment in the future.
Citation Format: Yuan-Ling Hsu, Szu-Hua Pan. Identification of potential biomarker related to EGFR mutation by functional proteome profiling in primary non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2205. doi:10.1158/1538-7445.AM2017-2205
Abstract 2229: Prevention by tolfenamic acid and characterization of the molecular targets in Pirc and FAP colorectal adenomas
Authors: Ertem Furkan U. , Zhang Wenqian , Chang Kyle , Dashwood Wan-Mohaiza , Rajendran Praveen , Sun Deqiang , Abudayyeh Ala , Abdulrahim Maen , Vilar Eduardo , Dashwood Roderick H. 
Published: July 2017

Abstract
A critical need exists in sporadic and high-risk colorectal cancer patients for endoscopic screening combined with safe and effective preventive agents. To prioritize molecular targets for prevention studies in vivo, RNA-seq analyses were conducted on colorectal adenomas from familial adenomatous polyposis (FAP) patients, and from the Apc-mutant polyposis in rat colon (Pirc) model. Using a new murine endoscopic polypectomy methodology (F.U. Ertem et al., Gastrointest Endosc 2016;83:1272-6), we evaluated agents that might substitute for the current standard of care, Sulindac, and identified tolfenamic acid (TA) as a promising candidate for further investigation. At clinically-relevant doses in the Pirc model, TA suppressed tumorigenesis significantly both in the small intestine and in the colon. Inhibition by TA of colonic crypt cell proliferation, and the concomitant activation of apoptosis, coincided with reduced expression in target tissues of β-catenin, cyclin D1, Survivin and matrix metalloproteinase 7. Based on the oncogene candidates defined by RNA-seq analysis, endoscopic tracking revealed the time-course of tumor suppression by TA, and the temporal changes in S100a9, Nppb, Aldh1a3 and Mmp7, highlighting their value as potential early biomarkers for prevention in the clinical setting. As an “old drug” repurposed from migraine, TA appears to offer an exciting new therapeutic avenue in FAP and other high-risk colorectal cancer patient populations. This work was supported in part by NIH grants CA090890, CA122959, ES00210, ES023512, the John S. Dunn Foundation, and a Chancellor’s Research Initiative.
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Citation Format: Furkan U. Ertem, Wenqian Zhang, Kyle Chang, Wan-Mohaiza Dashwood, Praveen Rajendran, Deqiang Sun, Ala Abudayyeh, Maen Abdulrahim, Eduardo Vilar, Roderick H. Dashwood. Prevention by tolfenamic acid and characterization of the molecular targets in Pirc and FAP colorectal adenomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2229. doi:10.1158/1538-7445.AM2017-2229
Abstract 2235: Preventive effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on liver tumorigenesis in obese and diabetic mice
Authors: Shirakami Yohei , Obara Koki , Ohnishi Masaya , Ideta Takayasu , Sakai Hiroyasu , Tanaka Takuji , Shimizu Masahito , Seishima Mitsuru 
Published: July 2017

Abstract
Obesity, diabetes mellitus, and their related metabolic abnormalities are associated with increased risk of hepatocellular carcinoma (HCC). Sodium glucose cotransporter (SGLT)-2 inhibitors, recently approved anti-diabetic agents, are expected to ameliorate the abnormalities associated with metabolic syndrome including non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of the SGLT2 inhibitor tofogliflozin on the development of NAFLD-related liver tumorigenesis in C57BL/KsJ-+Leprdb/+Leprdb (db/db) obese and diabetic mice. The direct effects of tofogliflozin on human HCC cell proliferation were also evaluated. Male db/db mice were administered diethylnitrosamine-containing water for two weeks and were treated with tofogliflozin throughout the experiment. Tofogliflozin was kindly provided by Kowa Co., Ltd. and the chemical structure will be disclosed at the time of presentation at the meeting. In mice treated with tofogliflozin, the development of hepatic pre-neoplastic lesions was markedly suppressed, and hepatic steatosis and inflammation significantly reduced, as evaluated using the NAFLD activity score, in comparison to those in the control mice. Serum levels of glucose and free fatty acid and mRNA expression levels of pro-inflammatory markers in the liver were reduced by tofogliflozin treatment. Conversely, the proliferation of SGLT2 protein-expressing HCC cells was not inhibited by this agent. These findings suggest that tofogliflozin suppressed the early phase of obesity- and NAFLD-related liver carcinogenesis by attenuating chronic inflammation and steatosis in the liver, while the agent had no significant direct effect on the proliferation of HCC cells. Therefore, SGLT2 inhibitors may have a chemopreventive effect on obesity-related HCC.
Citation Format: Yohei Shirakami, Koki Obara, Masaya Ohnishi, Takayasu Ideta, Hiroyasu Sakai, Takuji Tanaka, Masahito Shimizu, Mitsuru Seishima. Preventive effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on liver tumorigenesis in obese and diabetic mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2235. doi:10.1158/1538-7445.AM2017-2235
Abstract 2261: Synergistic effect and VEGF/HSP70-hom haplotype analysis: Relationship to prostate cancer risk and clinical outcome
Authors: Sfar Sana , Saad Hamadi , Mosbah Faouzi , Chouchane Lotfi 
Published: July 2017

Abstract
Prostate cancer (PCa) is a complex disorder resulting from the combined effects of multiple environmental and genetic factors. Our previous single-locus analysis showed that VEGF and HSP70-hom polymorphisms were significantly associated with PCa susceptibility and prognosis. Both genes encoding these proteins were located on chromosome 6p21, and combining the neighboring single nucleotide polymorphisms (SNPs) into haplotypes may increase the association with the disease. Three tagging polymorphisms, the HSP70-hom 2437 T/C, the VEGF-1154 G/A, and the VEGF-634 G/C SNPs were genotyped in 101 cases and 80 controls. For the combined analysis of VEGF and HSP70-hom, we found a positive gradient in the odds ratios (ORs) related to the number of high-risk genotypes with a 3.53-fold increase of prostate carcinoma risk (OR= 3.53; p= 0.015). Furthermore, the TAG and CAG haplotypes at positions HSP70-hom, VEGF-1154 and VEGF -634 exhibited a two-fold (OR= 0.46; p= 0.014) and a seven-fold (OR= 0.14; p= 0.00005) reduction in PCa risk, respectively. Regarding PCa prognosis, the TAG haplotype had a negative association with the aggressive phenotype as defined by the histopathological grade (OR= 0.28; p= 0.006). Our findings confirm the role of at-risk haplotype across the HSP70-hom/VEGF gene cluster in determining susceptibility to PCa.
Note: This abstract was not presented at the meeting.
Citation Format: Sana Sfar, Hamadi Saad, Faouzi Mosbah, Lotfi Chouchane. Synergistic effect and VEGF/HSP70-hom haplotype analysis: Relationship to prostate cancer risk and clinical outcome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2261. doi:10.1158/1538-7445.AM2017-2261
Abstract 2272: A prospective study of urinary prostaglandin E2 metabolite, Helicobacter pylori antibodies, and gastric cancer risk
Authors: Wang Tianyi , Cai Hui , Zheng Wei , Michel Angelika , Pawlita Michael , Milne Ginger , Xiang Yong-Bing , Gao Yu-Tang , Li Hong-Lan , Rothman Nathaniel , Lan Qing , Shu Xiao-Ou , Epplein Meira 
Published: July 2017

Abstract
Background. Previous studies suggest that a stable end-product of prostaglandin E2, the urinary metabolite PGE-M, is excreted in the urine and can be used as an index of systemic prostaglandin E2 (PGE2) production. In the present study we investigate the PGE-M, Helicobacter pylori (H. pylori), and gastric cancer association.
Methods. The present analysis included 359 prospectively ascertained gastric cancer cases and 700 individually matched controls from two population-based prospective cohort studies, the Shanghai Women’s Health Study and Shanghai Men’s Health Study. Urinary PGE-M was measured by a liquid chromatography/tandem mass spectrometric method. Sero-positivity to 15 H. pylori recombinantly expressed fusion proteins was detected by H. pylori multiplex serology.
Results. Adjusting for H. pylori, increasing PGE-M was associated with higher risk of gastric cancer (Quartile 4 vs. 1, OR=1.76, 95% CI: 1.17-2.66, Ptrend =0.004). This association remained after excluding those diagnosed within two years from sample collection (OR=1.73, 95% CI: 1.12-2.65, Ptrend =0.007). However it was no longer present among individuals with 10 or more years of follow-up (2-4.9 years, OR=3.15, 95% CI: 1.11-8.91; 5-9.9 years, OR=2.23, 95% CI: 1.22-4.06; ≥10 years, OR=0.73, 95% CI: 0.31-1.70). The association of PGE-M with gastric cancer risk was not modified by H. pylori status, but added predictive ability beyond H. pylori; compared to H. pylori-negative individuals with below-median PGE-M levels, H. pylori-positive individuals with above-median PGE-M levels had a 5-fold increase in the odds ratio of gastric cancer (OR=5.08, 95% CI: 2.47-10.43).
Conclusion. In China, higher PGE-M levels may indicate an increased risk of gastric cancer independent of the risk conferred by H. pylori infection status, particularly for cancers diagnosed within 10 years of sample collection.
Citation Format: Tianyi Wang, Hui Cai, Wei Zheng, Angelika Michel, Michael Pawlita, Ginger Milne, Yong-Bing Xiang, Yu-Tang Gao, Hong-Lan Li, Nathaniel Rothman, Qing Lan, Xiao-Ou Shu, Meira Epplein. A prospective study of urinary prostaglandin E2 metabolite, Helicobacter pylori antibodies, and gastric cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2272. doi:10.1158/1538-7445.AM2017-2272
Abstract 2273: Serum choline, methionine, betaine, dimethylglycine, and trimethylamine-N-oxide in relation to pancreatic cancer risk in two nested case-control studies in Asian populations
Authors: Huang Joyce , Butler Lesley , Midttun Øivind , Wang Renwei , Jin Aizhen , Gao Yu-Tang , Ueland Per , Koh Woon-Puay , Yuan Jian-Min 
Published: July 2017

Abstract
Background: Choline, methionine, and betaine are methyl group donors associated with DNA methylation. Diets deficient in choline and methionine have been shown to promote pancreatic carcinogenesis in experimental animals. We have previously reported an inverse association between dietary intake of choline and pancreatic cancer risk in a prospective cohort of Singapore Chinese. In the present study biomarkers of dietary choline and other methyl donor nutrients were evaluated in relation to pancreatic cancer risk.
Method: Two case-control studies were nested within the Shanghai Cohort Study (129 cases and 258 matched controls) and the Singapore Chinese Health Study (58 cases and 104 matched controls). Concentrations of choline, methionine, betaine, dimethylglycine (DMG), and trimethylamine-N-oxide (TMAO) were
measured by LC-MS/MS in pre-diagnostic serum samples. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression method with adjustment for potential confounders.
Results: Choline, methionine, and betaine were moderately associated with each other (spearman correlation coefficient: 0.28 ~0.43). In the pooled analysis, serum choline, betaine, and methionine were inversely associated with risk of pancreatic cancer, while TMAO, an oxidative metabolite of choline produced by gut microbiota, was positively associated with risk of pancreatic cancer. Compared with the lowest quartile, ORs (95%CIs) of pancreatic cancer for the highest quartiles of choline, methionine, betaine, and TMAO were 0.37 (0.17-0.80), 0.39 (0.22-0.69), 0.49 (0.28-0.85), and 1.60 (0.94-2.74), respectively (all Ps for trend &lt; 0.05). DMG was not associated with pancreatic cancer risk.
Conclusion: The novel inverse associations of serum choline, methionine, and betaine with risk of pancreatic cancer support the notion that methyl groups related to DNA methylation may modulate the risk of pancreatic cancer development. The positive association between TMAO and pancreatic cancer risk suggested gut microbiota may play an important role in pancreatic carcinogenesis.
Citation Format: Joyce Huang, Lesley Butler, Øivind Midttun, Renwei Wang, Aizhen Jin, Yu-Tang Gao, Per Ueland, Woon-Puay Koh, Jian-Min Yuan. Serum choline, methionine, betaine, dimethylglycine, and trimethylamine-N-oxide in relation to pancreatic cancer risk in two nested case-control studies in Asian populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2273. doi:10.1158/1538-7445.AM2017-2273