bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4356: Factors predicting lymph node metastasis in resected lung adenocarcinoma of 2cm or smaller
Authors: Hung Jung-Jyh , Chou Teh-Ying , Wu Yu-Chung , Hsu Wen-Hu 
Published: August 2015

Abstract
Objective: The predictive value of the new International Association for the Study of Lung Cancer, American Thoracic Society and European Respiratory Society (IASLC/ATS/ERS) classification of lung adenocarcinoma predicting lymph node metastasis in lung adenocarcinoma has not been well demonstrated.
Methods: Histological classification of 246 patients undergoing anatomical resection for lung adenocarcinoma of 2cm or smaller was determined according to the IASLC/ATS/ERS classification with recording of the percentage of each histologic component (lepidic, acinar, papillary, micropapillary, and solid). Their predictive value of lymph node metastasis was investigated.
Results: Among the 246 patients, there were 215 (87.4%) patients with N0 status, 13 (5.3%) with N1 status, and 18 (7.3%) with N2 status. Greater tumor size (P &lt; 0.001) and predominant pattern group (micropapillary/solid predominant) (P = 0.001) were significantly associated with higher percentage of N1 or N2 lymph node metastasis. In multivariate analysis, greater tumor size (P &lt; 0.001), and micropapillary/solid predominant pattern (P = 0.029) were significant predictors of N1 or N2 lymph node metastasis in tumors of 2cm or smaller. Micropapillary/solid predominant pattern (P = 0.031) was also a significant predictor of N2 lymph node metastasis in multivariate analysis.
Conclusions: The IASLC/ATS/ERS classification has significantly predictive value on lymph node metastasis in lung adenocarcinoma of 2cm or smaller. Micropapillary/solid predominant pattern is a predictor of lymph node metastasis.
Note: This abstract was not presented at the meeting.
Citation Format: Jung-Jyh Hung, Teh-Ying Chou, Yu-Chung Wu, Wen-Hu Hsu. Factors predicting lymph node metastasis in resected lung adenocarcinoma of 2cm or smaller. [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 4356. doi:10.1158/1538-7445.AM2015-4356
Abstract 4373: Targeting lung cancer stem cells with inhibition of multiple drug resistance by demethoxylcurcumin-carrying chitosan-antibody core-shell nanoparticles
Authors: Chiou Shih-Hwa 
Published: August 2015

Abstract
Lung adenocarcinoma (LAC) has been clinically realized to be one of the most deadly malignant tumors with relatively low in 5-year survival rate. High recurrence rates and drug-resistance potential have been reported in LAC even after completion of combined therapy. Herein we demonstrate that cisplatin treatment selecting for resistance with high self-renewal and invasive capabilities in cisplatin-resistant LAC cell (CisR-LAC). For overcoming the multi-drug resistance (MDR) in CisR-LAC, we designed a multifunctional nanocarrier with enhanced targeting ability and inhibition of MDR inhibition in CisR-LAC. The platform provide a high anti-MDR efficacy via a facile synthesis scheme using an amphiphilic chitosan to encapsulate a demethoxylcurcumin (DMC), as a core phase, following surface modification of an anti-EGFR layer, forming a CHC-DMC/anti-EGFR core-shell nanostructure. Experimental outcomes revealed an enhanced therapeutic efficacy of the DMC, forming DMC nano-precipitates in lysosome and endosome, as a result of efficient cellular endocytosis of the core-shell nanoparticles, by a synergistic action of both MDR inhibition and efficacious cell killing. Animal study showed a significant therapeutic efficacy against CisR-LAC-xenograft lung tumor using the core-shell nanocarriers, by a reduction of as high as 5-folded tumor volume compared with control groups. This result indicated the multi-therapeutic efficacy of the multifunctional CHC-DMC/anti-EGFR core-shell nanoparticle, providing a potential capability in anti-MDR LAC for better clinical translation.
Note: This abstract was not presented at the meeting.
Citation Format: Shih-Hwa Chiou. Targeting lung cancer stem cells with inhibition of multiple drug resistance by demethoxylcurcumin-carrying chitosan-antibody core-shell nanoparticles. [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 4373. doi:10.1158/1538-7445.AM2015-4373
Abstract 4374: DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition, focal adhesion, and stemness in clear cell renal carcinoma
Authors: Weygant Nathaniel , Qu Dongfeng , May Randal , Tierney Ryan M. , Berry William L. , Zhao Lichao , Agarwal Shweta , Chandrakesan Parthasarathy , Sureban Sripathi M. , Schlosser Michael J. , Tomasek James J. , Houchen Courtney W. 
Published: August 2015

Abstract
Renal clear cell carcinoma (RCC) is the most common type of kidney cancer and the 8th most common cancer overall in the US. RCC survival rates drop precipitously with regional and distant spread and recent studies have demonstrated that RCC presents an epithelial-mesenchymal transition (EMT) phenotype linked to increased recurrence and decreased survival. EMT is a key characteristic of tumor stem cells (TSCs) along with chemo-resistance and radio-resistance, which are also phenotypic of RCC.
Targeting these factors is key to increasing the survival of RCC patients.
Doublecortin-like kinase 1 (DCLK1) marks TSCs in pancreatic and colorectal cancer and regulates EMT and stemness. Analysis of the Cancer Genome Atlas’ RCC dataset revealed that DCLK1 is overexpressed and dysregulated on the mRNA and epigenetic level in more than 93% of RCC tumors relative to adjacent normal tissue. Immunohistochemistry using α-DCLK1 antibody confirmed overexpression and demonstrated a major increase in immunoreactivity in stage II-III tumors compared to normal kidney and stage I tumors. Small-interfering RNA (siRNA) mediated knockdown of DCLK1 resulted in decreased expression of EMT and pluripotency factors and significantly reduced invasion, migration, focal adhesion, drug-resistance, and clonogenic capacity. These findings suggest that DCLK1 is a novel, overexpressed factor in RCC progression that may be targeted to suppress EMT, metastasis, and stemness in early-stage and advanced RCC to increase patient survival. Moreover, the possibility that DCLK1 may mark a population of tumor stem-like cells in RCC should be further investigated in light of these findings.
Citation Format: Nathaniel Weygant, Dongfeng Qu, Randal May, Ryan M. Tierney, William L. Berry, Lichao Zhao, Shweta Agarwal, Parthasarathy Chandrakesan, Sripathi M. Sureban, Michael J. Schlosser, James J. Tomasek, Courtney W. Houchen. DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition, focal adhesion, and stemness in clear cell renal carcinoma. [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 4374. doi:10.1158/1538-7445.AM2015-4374
Abstract 4375: Podoplanin (PDPN): novel biomarker and chemotherapeutic target
Authors: Krishnan Harini , Ochoa-alvarez Jhon , Shen Yongquan , Nevel Evan , Kephart David , Nguyen Angels , Han Min , Acharya Nimish , Nagele Robert , Ramirez Maria , Miller W. Todd , Kalyoussef Evelyne , Baredes Soly , Fatahzadeh Mahnaz , Jensen Lasse , Shienbaum Alan , Goldberg Gary 
Published: August 2015

Abstract
Cancer is a leading cause of death. In fact, cancer killed over 8 million people around the world in 2012. Over 90% of these cancer deaths are due to metastasis, which results from tumor cell migration and invasion. Specific cancer biomarkers need to be identified in order to effectively target these motile cells. The transmembrane glycoprotein receptor podoplanin (PDPN) promotes tumor cell motility and metastasis in many aggressive cancers. Indeed, PDPN has emerged as a prime cancer biomarker and chemotherapeutic target. Here, we describe how PDPN can be targeted to inhibit the growth and motility of melanoma and oral cancer cells. PDPN has a short intracellular domain of 9 amino acids which include two conserved serine residues. PDPN also has a large extracellular domain that is extensively O-glycosylated with α2,3-sialic acid linked to galactose. We are developing novel methods to target the intracellular and extracellular domains of PDPN to combat cancer progression. For example, we have found that some activators of protein kinase A can induce phosphorylation of the intracellular serine residues of PDPN to inhibit tumor cell migration. In addition, we have found that Maackia amurensis seed lectin (MASL) can target the extracellular domain of PDPN to inhibit tumor cell growth, migration, and tumor progression in cell culture and animal models. Furthermore, we utilized live cell imaging to find that PDPN expression can be modulated in cancer associated fibroblasts to inhibit neighboring tumor cell migration and survival. Thus, reagents can be used to target PDPN from inside of the cell and outside of the cell to inhibit tumor cell migration and combat cancer progression. This work illuminates novel strategies designed to exploit PDPN as a functionally relevant biomarker and chemotherapeutic target.
Citation Format: Harini Krishnan, Jhon Ochoa-alvarez, Yongquan Shen, Evan Nevel, David Kephart, Angels Nguyen, Min Han, Nimish Acharya, Robert Nagele, Maria Ramirez, W. Todd Miller, Evelyne Kalyoussef, Soly Baredes, Mahnaz Fatahzadeh, Lasse Jensen, Alan Shienbaum, Gary Goldberg. Podoplanin (PDPN): novel biomarker and chemotherapeutic 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 4375. doi:10.1158/1538-7445.AM2015-4375
Abstract 438: Granulocyte-colony stimulating factor (G-CSF) facilitates metastasis of uterine cervical cancer by recruiting myeloid-derived suppressor cells (MDSCs) via CXCL12-CXCR4 axis
Authors: Sasano Tomoyuki , Mabuchi Seiji , Takahashi Ryoko , Kuroda Hiromasa , Sawada Kenjiro , Kimura Tadashi 
Published: August 2015

Abstract
Objectives: Granulocyte-colony stimulating factor (G-CSF) is known to induce the myeloid-derived suppressor cells (MDSCs) to stimulate the progression of uterine cervical cancer. The aim of this study was to investigate the role of G-CSF and the MDSCs in the invasion and the metastasis of uterine cervical cancer.
Methods: We first established cervical cancer cell lines stably transfected with G-CSF expression vector (ME180-GCSF) or control vector (ME180-control). Then, using mice subcutaneously inoculated with ME180-control or ME180-GCSF cells, the effect of G-CSF on the induction of MDSCs (CD11b+Gr1+ cells) and the metastatic activity of cervical cancer cells. The association of MDSCs infiltration and the clinical outcome was also assessed immunohistochemically using tumor samples obtained from cervical cancer patients. Finally, using MDSCs isolated from the spleen of the ME180-GCSF-bearing mice, we investigated whether the MDSCs facilitate the invasive or metastatic activities of uterine cervical cancer in vitro and in vivo.
Results: 1) ME180-GCSF-derived tumors contain greater number of MDSC, more frequently develop lymphovascular space invasion, and developed greater number of metastatic tumors than ME180-control-tumors. 2) Immunohistochemical analyses using human samples revealed that increased MDSC counts were significantly associated with deep stromal invasion and lymphovascular space invasion. 3) MDSCs were recruited into cervical cancer via CXCL12-CXCR4 axis. 4) Coincubation of MDSCs with ME180 cells increased the invasive activity of ME180 cells. 5) The depletion of MDSCs significantly decreased the invasive and metastatic activities of ME180 cells.
Conclusions: Granulocyte-colony stimulating factor (G-CSF) facilitates metastasis by recruiting MDSCs. MDSCs and CXCL12-CXCR4 axis might be promising therapeutic targets in patients with uterine cervical cancer.
Citation Format: Tomoyuki Sasano, Seiji Mabuchi, Ryoko Takahashi, Hiromasa Kuroda, Kenjiro Sawada, Tadashi Kimura. Granulocyte-colony stimulating factor (G-CSF) facilitates metastasis of uterine cervical cancer by recruiting myeloid-derived suppressor cells (MDSCs) via CXCL12-CXCR4 axis. [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 438. doi:10.1158/1538-7445.AM2015-438
Abstract 4380: IACS-10759: A novel OXPHOS inhibitor which selectively kill tumors with metabolic vulnerabilities
Authors: Protopopova Marina , Bandi Madhavi , Bardenhagen Jennifer , Bristow Christopher , Carroll Christopher , Chang Edward , Feng Ningping , Gay Jason , Geck Do Mary , Greer Jennifer , Konopleva Marina , Matre Polina , Kang Zhijun , Liu Gang , Muller Florian , Lofton Timothy , McAfoos Timothy , Sun Yuting , Smith Melinda , Theroff Jay , Wu Yuanqiang , Chin Lynda , Draetta Giulio , Jones Philip , Toniatti Carlo , Di Francesco M. Emilia , Marszalek Joseph R. 
Published: August 2015

Abstract
Tumor cells normally depend on both glycolysis and oxidative phosphorylation (OXPHOS) to provide the energy and macromolecule building blocks needed to enable continued tumor cell growth. Genetic or epigenetic inactivation of one of these two redundant pathways represents a metabolic vulnerability that should be susceptible to an inhibitor of the other pathway. Through an extensive medicinal chemistry campaign, IACS-10759 was identified as a potent inhibitor of complex I of oxidative phosphorylation. In isolated mitochondria or permeabilized cells, ATP production or oxygen consumption was inhibited at single digit nM concentrations in the presence of malate/glutamate, but not succinate. More directly, IACS-10759 inhibited the conversion of NADH to NAD+ in an immunoprecipitated complex I assay at low nM concentrations. Using genetic and pharmacological approaches, the specific complex I subunit inhibited by IACS-10759 has been identified and the mechanism of complex I inhibition is being investigated. Importantly, IACS-10759 is orally bioavailable with excellent physicochemical properties in preclinical species and achieved significant in vivo efficacy with daily oral dosing of 10-25 mg/kg. Specifically, there was a &gt;50 day extension of median survival in an orthotopic AML cell line xenograft and robust regression in DLBCL and GBM xenograft models. In light of these results, as well as its drug like profile IACS-10759 has entered IND enabling studies with first-in-human studies targeted for third quarter of 2015.
Citation Format: Marina Protopopova, Madhavi Bandi, Jennifer Bardenhagen, Christopher Bristow, Christopher Carroll, Edward Chang, Ningping Feng, Jason Gay, Mary Geck Do, Jennifer Greer, Marina Konopleva, Polina Matre, Zhijun Kang, Gang Liu, Florian Muller, Timothy Lofton, Timothy McAfoos, Yuting Sun, Melinda Smith, Jay Theroff, Yuanqiang Wu, Lynda Chin, Giulio Draetta, Philip Jones, Carlo Toniatti, M. Emilia Di Francesco, Joseph R. Marszalek. IACS-10759: A novel OXPHOS inhibitor which selectively kill tumors with metabolic vulnerabilities. [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 4380. doi:10.1158/1538-7445.AM2015-4380
Abstract 4383: Vitamin E delta-tocotrienol inhibits metastasis and targets cancer stem cell signaling in human pancreatic cancer
Authors: Husain Kazim , Sebti Said M. , Malafa Mokenge P. 
Published: August 2015

Abstract
Background: Pancreatic cancer, a lethal and aggressive malignancy is the fourth leading cause of cancer-related deaths in the United States. One of the main reasons for this outcome includes the lack of effective prevention strategies for recurrent disease. Pancreatic cancer stem cells (CSCs) have been implicated in the development of pancreatic cancer metastasis, resistance to chemotherapy and its recurrence following surgical extirpation. We have shown that natural vitamin E δ-tocotrienol is the most bioactive tocotrienols against pancreatic cancer in vitro as well as in vivo models. The purpose of this study was to evaluate the effect of δ-tocotrienol on tumor metastatic EMT, migration, invasion, angiogenesis and CSCs signaling in metastatic human pancreatic cancer cells.
Methods: Human metastatic pancreatic cancer cells L3.6pl expressing luciferase were orthotopically implanted into pancreas of Athymic nude mice (n = 10) and after one week they were randomized in two groups: 1) vehicle control (ethanol extracted olive oil) and 2) δ-tocotrienol (200 mg/kg, orally twice a day) for 4 weeks. The tumor volume, tumor weight, liver and lung metastasis were recorded. The tumor tissues were analyzed for metastasis markers, epithelial to mesenchymal transition (EMT), and angiogenesis. In vitro L3.6pl cells were treated with δ-tocotrienol (50 μM) and used for migration and invasion assay, isolation of CSCs and spheroid formation, transcription factors and CSCs signaling markers were determined by Western blotting.
Results: Vitamin E δ-tocotrienol significantly inhibited the pancreatic tumor growth [tumor volume (50%) and weight (60%)] and metastasis in the liver and lung, CSCs spheroid formation, migration and invasion compared to control. δ-tocotrienol induced apoptosis (PARP1 cleavage and Bax expression) compared to control. δ-tocotrienol also inhibited EMT (E-cadherin to vimentin), metastasis (MMP9), angiogenesis (VEGF), CSCs transcription factors (Nanog, Oct4, Sox2 and KLF4) and oncogenic signaling (Notch-1 and pERK) compared to control.
Conclusion: Vitamin E δ-tocotrienol inhibited metastasis of human pancreatic tumor through inhibition of EMT, migration, invasion, angiogenesis, cancer stem cell signaling and induction of apoptosis.
Citation Format: Kazim Husain, Said M. Sebti, Mokenge P. Malafa. Vitamin E delta-tocotrienol inhibits metastasis and targets cancer stem cell signaling in human pancreatic 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 4383. doi:10.1158/1538-7445.AM2015-4383
Abstract 4397: Preclinical development of a novel hypoxia-activated EGFR inhibitor using a cobalt(III)-based prodrug design
Authors: Heffeter Petra , Karnthaler-Benbakka Claudia , Groza Diana , Kryeziu Kushtrim , Berger Walter , Keppler Bernhard K. , Kowol Christian R. 
Published: August 2015

Abstract
Chemotherapy and therapy with small targeted molecules are two major strategies for therapy of human cancer at the disseminated stage. During the last decades, thousands of compounds have been developed and, consequently, have improved therapy effectiveness. Especially the development of receptor tyrosine kinase inhibitors such as erlotinib or imatinib were major step forwards in cancer treatment. However, despite its success EGFR inhibitor therapy is still limited by strong side effects, resistance development and insufficient tumor accumulation. Aim of the here presented study was the development of novel EGFR inhibitors, which are specifically activated in the malignant tissue. To this end a cobalt(III)-based prodrug strategy was used, which allows targeted release of the active EGFR inhibitor triggered by hypoxic conditions of the solid tumor. As a first step, new inhibitors with bis-chelating moieties were prepared and tested for their efficacy against several cell models with differing EGFR status. The most promising lead candidate was selected based on potent kinase inhibition (confirmed by in vitro kinase assays as well as Western blotting) resulting in activity against EGFR-driven cells in the nM range (MTT assay). Subsequently, the respective cobalt complex was prepared and its activity tested in hypoxia vs. normoxia revealing that the new complex was distinctly more active under hypoxic conditions. Finally, the anticancer activity of the new complex was tested in two xenografts indicationg potent and hypoxia-dependent anticancer activity also in vivo. Summarizing, cobalt(III)-based tumor-targeting represents a promising strategy to reduce the side effects of tyrosine kinase inhibitors such as erlotinib.
Acknowledgements. This work was performed in course of the research platform “Translational Cancer Therapy Research” Vienna, Austria and the COST action CM1105 and supported by “Fonds der Stadt Wien für innovative interdisziplinäre Krebsforschung”.
Citation Format: Petra Heffeter, Claudia Karnthaler-Benbakka, Diana Groza, Kushtrim Kryeziu, Walter Berger, Bernhard K. Keppler, Christian R. Kowol. Preclinical development of a novel hypoxia-activated EGFR inhibitor using a cobalt(III)-based prodrug design. [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 4397. doi:10.1158/1538-7445.AM2015-4397
Abstract 4399: Utilizing cobalt coordination chemistry as a traceless prodrug strategy in targeted drug delivery
Authors: Petros Robby A. , Nguyen Duong T. , Cavazos Ronaldo J. , Morrison Clifford S. , Lampe Jana B. , Harris Alesha N. , McFarlin Brian K. 
Published: August 2015

Abstract
We recently reported the synthesis of albumin nanoparticles using cobalt as a traceless, reductively labile crosslinker. Here, we report in vitro characterization of particle uptake for fluorescently labeled cobalt crosslinked albumin nanoparticles (Co-Alb-FITC NPs) via image-based flow cytometry as well as preliminary toxicity data. Uptake of Co-Alb-FITC NPs by gastric carcinoma cells (SNU-5) was rapid, but could be dramatically reduced through the addition of an inhibitor of macropinocytosis. High levels of non-specific uptake of other particle types were also observed suggesting SNU-5 cells possess high macropinocytic activity. Cancers harboring mutated Ras (&gt;20% of all cancers) are known to take up protein via macropinocytosis to satisfy metabolic demands. Because SNU-5 cells are not known harbor mutated Ras, our findings may indicate that other cancers rely on this mechanism as well, which would have important implications for observing selectivity in active nanoparticle targeting strategies. The Co-Alb NPs themselves were found to exhibit no inherent toxicity. Based on these initial findings, Co-Alb NPs were loaded with the active metabolite of camptothecin, SN-38, to explore their potential as a delivery vector for hydrophobic drugs. An albumin-topotecan prodrug conjugate was also synthesized by crosslinking the amine group in topotecan with lysine residues in the protein, which should be applicable to other amine-containing therapeutics. Characterization of drug loading and release will be discussed along with preliminary in vitro characterization.
Citation Format: Robby A. Petros, Duong T. Nguyen, Ronaldo J. Cavazos, Clifford S. Morrison, Jana B. Lampe, Alesha N. Harris, Brian K. McFarlin. Utilizing cobalt coordination chemistry as a traceless prodrug strategy in targeted drug delivery. [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 4399. doi:10.1158/1538-7445.AM2015-4399