bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2196: SDF-1/CXCR4 axis-mediated tumor-tropism of monocyte membrane-coated nanoparticles
Authors: Li Yi-Nan , Chang Chien-Wen , Chiang Chi-Shiun 
Published: July 2017

Abstract
Tumor-associated macrophages are one of the most abundant infiltrating cells in solid tumors. These cells are originated from the bone marrow and circulating in peripheral blood. Through the specific chemoattractant released by the tumor cells or stromal cells, bone marrow-derived monocytes (BMDMs) are able to accumulate at the tumor site by their corresponding receptors. In this study, we utilized the characteristics of tumor-tropism of BMDMs on a nanoparticle-based drug delivery system. We hypothesized that the cellular membrane of BMDMs can provide nanoparticle protection from the mononuclear phagocyte system and the chemokine receptor on the membrane can enhance the tumor-tropism of the nanoparticles. To prove the hypothesis, the cellular membrane was extracted from BMDMs and then coated on the drug-loaded nanoparticles. We also found that the expression of chemokine receptor CXCR4 on the bone BMDMs can be induced following the stimulation of tumor conditioned medium. The tumor targeting effect of the monocyte membrane-coated nanoparticles is diminished against SDF-1 knockdown tumor cells. These results indicate that the SDF-1/CXCR4 axis is contributed to the tumor-tropism of the monocyte membrane-coated nanoparticles toward astrocytoma cell line, ALTS1C1, and this effect can be boosted by the stimulation of tumor conditioned medium. In conclusion, we established a nanoparticle-based drug delivery platform against brain tumor with the cellular membrane coating technology and maximized the effect of tumor-targeting by tumor conditioned medium stimulation.
Citation Format: Yi-Nan Li, Chien-Wen Chang, Chi-Shiun Chiang. SDF-1/CXCR4 axis-mediated tumor-tropism of monocyte membrane-coated nanoparticles [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 2196. doi:10.1158/1538-7445.AM2017-2196
Abstract 2201: Downregulation of NF-kB by nanoconjugates to overcome drug resistance in ovarian tumors
Authors: Zambre Ajit P. , Panchal Sarjukumar , Worland Alyssa , Chapman Sarah , Leevy Matthew , Upendran Anandhi , Kannan Raghuraman 
Published: July 2017

Abstract
Ovarian cancer is the fifth leading cause of cancer deaths in women. Globally, around 140k women die from ovarian cancer per year. Recurrence can lead to development of resistance to first line agents such as platinum analogs, taxanes, and doxorubicin. Several studies have shown that decrease of NF-κB expression will inhibit P-glycoprotein maturation and thereby overcome drug resistance. In this context, it is well known that Disulfiram (DSF), a FDA approved drug for anti-alcoholism, have been identified as moderate inhibitor of NF-κB activity. It is also shown that DSF possess mild anti-cancer effects via increased permeability of the outer membrane of mitochondria resulting in leakage of proteins, such as cytochrome C, generation of ROS that simulates the ROS-MAPK pathway leading to apoptosis, and inhibition of P-glycoprotein. As such DSF is not a strong therapeutic agent; however, in combination with copper it showed excellent therapeutic benefit. This effect is mainly attributed to metabolite diethyldithio-carbamate -a proteasome inhibitor that was produced upon complexation of DSF with copper. However, delivery of DSF-Cu complex was not successful in clinical setting. We hypothesized gold nanoparticles can serve as potential delivery vehicle to selectively transfer Cu-DSF to turmor without toxicity. Indeed, cellular studies in drug sensitive (OVCAR) and Adriamycin resistant p-glycoprotein expressing (NCI-ADR/RES) ovarian cancer cells indicated that the gold nanoconjugate exhibit significant cytotoxicity and the IC-50 values was decreased 2.5 fold times compared to the Cu-DSF complex. NF-κB expression was decreased by two folds compared to native Cu-DSF complex. Detailed cellular and mechanistic studies along with the evaluation of [Au(DSF-Cu)NP] in human multi-drug resistant (NCI-ADR/RES) mouse xenografts will be presented.
Citation Format: Ajit P. Zambre, Sarjukumar Panchal, Alyssa Worland, Sarah Chapman, Matthew Leevy, Anandhi Upendran, Raghuraman Kannan. Downregulation of NF-kB by nanoconjugates to overcome drug resistance in ovarian tumors [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 2201. doi:10.1158/1538-7445.AM2017-2201
Abstract 2202: FABP5 in urinary extracellular vesicles is a potential biomarker of high Gleason score prostate cancer
Authors: Fujita Kazutoshi , Kume Hideaki , Matsuzaki Kyosuke , Kawashima Atsunari , Ujike Takeshi , Nagahara Akira , Uemura Motohide , Miyagawa Yasushi , Tomonaga Takeshi , Nonomura Norio 
Published: July 2017

Abstract
Urine collected after prostate massage is a promising source of new biomarkers of prostate cancer, and was reported to contain extracellular vesicles (EVs) that are secreted from prostate cancer cells. EVs are microvesicles secreted from various cell types. EVs contain microRNAs, proteins, and mRNAs and play a role in intercellular communications via the mechanisms of exocytosis and endocytosis. We aimed to discover a new biomarker for high Gleason score (GS) prostate cancer (PCa) in urinary EVs via quantitative proteomics.
Material and methods: Urine samples after massage were collected from 18 patients before prostate needle biopsy. Six patients had negative biopsy outcomes, 6 had Gleason score 6 prostate cancer (GS6), and 6 had Gleason score 8 to 9 prostate cancer (GS8-9). Urinary EVs were isolated from urine with ultracentrifuge. Protein extracted from EVs were labeled with 4-plex iTRAQ and liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for proteome analysis. The candidate proteins were quantitated in the independent set by selected reaction monitoring/multiple reaction monitoring analysis (SRM/MRM).
Results: Seven proteins increased in patients with PCa compared to those with negative biopsy (ratio &gt; 2.0, p-value &lt; 0.05). Thirteen proteins were chosen for further analysis and verified in 29 independent urine samples (negative [n = 11], PCa [n = 18]) using selected reaction monitoring/multiple reaction monitoring. Among these candidate markers, fatty acid binding protein 5 (FABP5) was higher in the cancer group than in the negative group (p-value = 0.009) and was significantly associated with GS (p-value for trend = 0.011).
Conclusions: We applied the proteomic analysis to discover biomarkers in EVs in urine collected after prostate massage. FABP5 in urinary EVs could be a potential biomarker of high GS prostate cancer. Additional large-scale studies are warranted to confirm this finding.
Citation Format: Kazutoshi Fujita, Hideaki Kume, Kyosuke Matsuzaki, Atsunari Kawashima, Takeshi Ujike, Akira Nagahara, Motohide Uemura, Yasushi Miyagawa, Takeshi Tomonaga, Norio Nonomura. FABP5 in urinary extracellular vesicles is a potential biomarker of high Gleason score prostate 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 2202. doi:10.1158/1538-7445.AM2017-2202
Abstract 2218: Quantitative multiplex analysis of immune checkpoint protein expression in circulation and in the tumor microenvironment
Authors: Lie Wen-Rong , Mistry Jehangir 
Published: July 2017

Abstract
Immune checkpoint inhibitors have been proven to be an effective method in improving antitumor immune response. Many immune checkpoint proteins are expressed as soluble forms in circulation and in the tumor and tumor microenvironment. Here we report the development of bead-based Luminex multiplex assays for the quantitative profiling of co-inhibitory and co-stimulating immune checkpoint proteins CTLA-4, PD-1, TIM-3, LAG-3, HVEM. GITRL, BTLA, CD27, CD28, CD40, GITR, PD-L1, B7-1/CD80, B7-2/CD86, and ICOS. In order to explore the use of soluble immune checkpoint proteins as putative cancer biomarkers, we used these multiplex assays to measure checkpoint protein levels in serum samples from breast cancer patients, colon cancer patients, and a corresponding set of normal serum samples. Analysis of the soluble checkpoint protein signatures generated from this multiplex approach revealed a significantly elevated level of soluble TIM-3 protein in the breast cancer serum samples and in the colon cancer serum samples compared to the healthy serum controls (p&lt;0.001). In addition, we analyzed the immune checkpoint protein expression profiles in lysates of tumor and adjacent normal tissues from 3 patients with metastatic breast cancer and 2 patients with colorectal cancer. Differential expression of multiple checkpoint proteins, including BTLA, CD27, TIM-3, HVEM, CD40, GITR, LAG3, CTLA-4, B7-1, PD-L1, or ICOS, were detected in these matched lysates, indicating the roles and complexity of checkpoint proteins in tumor microenvironment. In summary, our results demonstrate that the multiplex assays we developed are useful research tools for the simultaneously quantitation of immune checkpoint proteins, as well as its potential application in cancer biomarker discovery and translational research in cancer immunotherapy.
Citation Format: Wen-Rong Lie, Jehangir Mistry. Quantitative multiplex analysis of immune checkpoint protein expression in circulation and in the tumor microenvironment [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 2218. doi:10.1158/1538-7445.AM2017-2218
Abstract 2222: Sildenafil suppresses inflammation-driven colorectal cancer in mice
Authors: Islam Bianca N. , Sharman Sarah K. , Hou Yali , Bridges Allison , Kolhe Ravindra , Trillo-Tinoco JImena , Singh Nagendra , Kim Sangmi , Sridhar Subbaramiah , Berger Frankin G. , Browning Darren D. 
Published: July 2017

Abstract
Intestinal cyclic guanosine monophosphate (cGMP) signaling regulates epithelial homeostasis, and has been implicated in the suppression of colitis and colorectal cancer (CRC). In this study, we investigated the cGMP-specific phosphodiesterase-5 (PDE5) inhibitor sildenafil to prevent tumorigenesis in the azoxymethane/dextran sulfate sodium (AOM/DSS) inflammation-driven colorectal cancer model. Treatment of mice with sildenafil activated cGMP signaling in the colon mucosa and protected against DSS-induced barrier dysfunction. In mice treated with AOM/DSS, oral administration of sildenafil throughout the disease course reduced polyp multiplicity by 50% compared to untreated controls. Polyps formed in sildenafil-treated mice showed less proliferation and were more differentiated compared to polyps from untreated mice, but apoptosis was unaffected. Polyps in sildenafil-treated mice were also less inflamed; they exhibited reduced myeloid-cell infiltration, and reduced expression of iNOS, IFNγ and IL-6 compared to untreated controls. Most of the protection was observed when sildenafil was added during the initiation stage of carcinogenesis (40% reduction in multiplicity), whereas administration of sildenafil later during the promotion stages did not affect polyp number. While later treatment with sildenafil did not affect multiplicity, it did have a similar effect on polyp phenotype, including increased mucus production, reduced proliferation and inflammation. In summary, our results demonstrate that oral administration of sildenafil suppresses inflammation and polyp formation in mice treated with AOM/DSS. This suggests that PDE5 inhibitors could have therapeutic value for the prevention of CRC in inflammatory bowel disease patients.
Citation Format: Bianca N. Islam, Sarah K. Sharman, Yali Hou, Allison Bridges, Ravindra Kolhe, JImena Trillo-Tinoco, Nagendra Singh, Sangmi Kim, Subbaramiah Sridhar, Frankin G. Berger, Darren D. Browning. Sildenafil suppresses inflammation-driven colorectal cancer in 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 2222. doi:10.1158/1538-7445.AM2017-2222
Abstract 2226: Sildenafil suppresses tumorigenesis in ApcMin/+ mouse model
Authors: Sharman Sarah K. , Islam Bianca N. , Hou Yali , Bridges Allison , Singh Nagendra , Sridhar Subbaramiah , Berger Frankin G. , Browning Darren D. 
Published: July 2017

Abstract
The cGMP signaling pathway regulates homeostasis in the colon epithelium and has been implicated in the suppression of colorectal cancer. Exisulind is a weak phosphodiesterase-5 (PDE5) inhibitor that was previously shown to reduce polyp formation in familial adenomatous polyposis (FAP) patients. Despite this validation of PDE5 as a therapeutic target, the failure of Exisulind due to toxicity halted further trials of cGMP elevating agents. The present study tested the effect of the PDE5 inhibitor sildenafil, and the receptor guanylyl-cyclase C (GCC) agonist linaclotide on tumorigenesis in the ApcMin/+ mouse model of colon cancer. Administration of either sildenafil or linaclotide to both wild type and ApcMin/+ mice caused dramatic effects on homeostasis that included reduced proliferation and increased goblet cell differentiation. With treatment beginning at 4 weeks, sildenafil and linaclotide caused a 50% and 67% (respectively) reduction in the number of polyps per mouse. Furthermore, the polyps in sildenafil and linaclotide treated animals exhibited a reduced proliferative index and increased mucus density compared to polyps from untreated mice. The mean polyp size was not changed by treatment with either drug. In support of a tumor-suppressive role for cGMP signaling in the intestine, the ApcMin/+ mice showed reduced levels of endogenous GCC agonists in the intestinal mucosa compared to wild type animals. This suggests that part of the tumor preventative effects observed here could be due to compensation for this deficit by augmenting cGMP signaling with PDE5 inhibitors or GCC agonists. While the tumor suppressive mechanism is not fully understood, the results presented here demonstrate in a preclinical model, that increasing intestinal cGMP levels by targeting PDE5 or GCC may be a viable chemoprevention strategy for human FAP patients.
Citation Format: Sarah K. Sharman, Bianca N. Islam, Yali Hou, Allison Bridges, Nagendra Singh, Subbaramiah Sridhar, Frankin G. Berger, Darren D. Browning. Sildenafil suppresses tumorigenesis in ApcMin/+ mouse model [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 2226. doi:10.1158/1538-7445.AM2017-2226
Abstract 2249: Integrated multi-level omics-based biomarker models for ovarian cancer survival
Authors: Fu Alan , Chang Shen-Chih , Baecker Aileen , Chang Helena R. , Zhang Zuo-Feng 
Published: July 2017

Abstract
Background: Although a number of prognostic biomarkers for ovarian cancer have been proposed, the pool of clinically useful biomarkers remains small. While the predictive power of individual biomarkers may be weak, the advent of more affordable high-throughput technologies and readily available “omics” level data point toward the possibility of high performance biomarker panels. In this study, we used tumor-based somatic mutation, mRNA and miRNA expression, and DNA methylation data from The Cancer Genome Atlas (TCGA) to construct integrated biomarker models for overall and progression-free survival.
Methods: The somatic mutations, mRNA expression, and DNA methylation of 451 candidate genes, as well as the expression of the miRNAs targeting them, were individually analyzed for association with overall and progression-free survival in 488 TCGA serous cystadenocarcinoma patients of predominantly Caucasian descent. Following correction for multiple comparisons, molecular variations associated with survival were combined to construct integrated cross-validated prediction models for overall and progression-free survival. The discriminative power of these models was then evaluated for 1-, 3-, and 5-year overall and progression-free survival using ROC analysis.
Results: Our cross-validated integrated molecular models were demonstrated to predict 5-year overall survival in the total patient pool with a ROC AUC of 0.801 and 5-year overall and progression-free survival in Caucasian patients with ROC AUCs of 0.866 and 0.809, respectively.
Conclusions: Our findings suggest the potential utility of our multi-omics-based biomarker models in helping to inform clinical decisions following ovarian cancer diagnosis. Although extensive efforts were made to maximize the predictive potential of our models, further retrospective and prospective validation efforts are necessary before their clinical utility can be accurately assessed.
Citation Format: Alan Fu, Shen-Chih Chang, Aileen Baecker, Helena R. Chang, Zuo-Feng Zhang. Integrated multi-level omics-based biomarker models for ovarian cancer survival [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 2249. doi:10.1158/1538-7445.AM2017-2249
Abstract 2303: Entacapone and prostate cancer in patients with Parkinson’s disease: A large Veterans Health Administration study
Authors: Major Jacqueline M. , Cunningham Francesca , Dong Diane , By Kunthel , Hur Kwan , Shih David C. , Pinheiro Simone P. , Podskalny Gerald D. , Graham David J. 
Published: July 2017

Abstract
Background: An increased risk of prostate cancer was observed in Parkinson’s disease (PD) patients treated with entacapone during a pre-approval randomized clinical trial.
Objective: To investigate a potential association between entacapone use and prostate cancer in an ambulatory setting.
Methods: Using data from the Department of Veterans Affairs (VA) healthcare system, new-user cohorts were created of PD patients treated with add-on entacapone or add-on dopamine agonist/monoamine oxidase B inhibitors between January 2000 and December 2014. Patients were followed on-treatment for occurrence of prostate cancer, identified via VA cancer registry linkage. Cox proportional hazards regression with time-dependent exposure was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Confounding was controlled by using inverse probability treatment weighting calculated from propensity scores.
Results: Mean follow-up time was 3.1 and 4.0 years in the entacapone and control cohort, respectively. There were 17,666 subjects meeting study criteria (mean age, 74 (SD 8.6) years); the group treated with entacapone comprised 5,257 subjects. Twenty-three prostate cancers occurred in the entacapone cohort and 97 in the control cohort. The overall incidence of prostate cancer was 1.8 per 1000 person-years of risk. There was no difference in risk of prostate cancer between the cohorts for increased duration of entacapone intake (adjusted HR: 1.08; 95% confidence interval: 0.46-2.51 for cumulative exposure of ≥2 years). Time since starting drug therapy and cumulative dose (mg) were also examined.
Conclusion: In this cohort of PD patients, extended duration of entacapone use was not associated with an increased incidence of prostate cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Jacqueline M. Major, Francesca Cunningham, Diane Dong, Kunthel By, Kwan Hur, David C. Shih, Simone P. Pinheiro, Gerald D. Podskalny, David J. Graham. Entacapone and prostate cancer in patients with Parkinson’s disease: A large Veterans Health Administration study [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 2303. doi:10.1158/1538-7445.AM2017-2303
Abstract 2312: Feasibility study of a fractionation method in the treatment of tumor treating fields
Authors: Jo Yunhui , Sung Jiwon , Song Hyo Sook , Kim Eun Ho , Yoon Myonggeun 
Published: July 2017

Abstract
Tumor treating fields (TTFs) treatment has been reported to have great potential to treat various cancers. Inspired by a similarity between TTFs and radiotherapy in electromagnetic property, TTFs using a fractionated treatment scheme originally designed for radiotherapy were applied to cancer (Human glioblastoma, U373) and normal cells (intestinal epithelial, IEC-6) for three days with durations of 3, 6, 9, or 24 hours/day. As the treatment time of TTFs increases from 3 to 24 hours/day, the relative cancer cell growth rates in both cell lines were reduced. While the difference in cancer cell growth rate compared to control was ~25% (decreased from 100% to ~75%) for the treatment time of 6 hours/day, the growth rates of cells treated for additional 6 hours (i.e., 12 hours/day) and additional 18 hours (i.e., 24 hours/day) differed only ~5% and ~8% from that of cells treated for 6 hours/day, respectively. Our results suggested that the dependence on treatment time in cancer cell inhibition is weakened distinctly at treatment times over 6 hours/day. For normal cells, the relative growth rates corresponding to the treatment time of TTFs was not decreased much for the treatment time of 3, 6, 12 hours/day revealing 93.3%, 90.0%, 89.3% of cell growth rates compared to control, respectively, but it suddenly reduced to ~73% for 24 hours/day of treatment. The experimental results indicated that the effects of TTFs on growth rates of cancer cells are higher than the effects of TTFs on growth rates of normal cells for treatment times of 3-12 hours/day, but the difference became minimal for treatment times of 24 hours/day. Our results suggest that the fractionated scheme in the treatment of tumor treating fields may reduce treatment time while maintaining efficacy, suggesting that this method can increase patients’ quality of life.
Citation Format: Yunhui Jo, Jiwon Sung, Hyo Sook Song, Eun Ho Kim, Myonggeun Yoon. Feasibility study of a fractionation method in the treatment of tumor treating fields [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 2312. doi:10.1158/1538-7445.AM2017-2312