bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1831: PET/CT imaging of interleukin-13 receptor alpha-2-targeted peptide to glioblastoma after locoregional delivery
Authors: Sattiraju Anirudh , Xuan Ang , Almaguel Frankis , Herpai Denise , Debinski Waldemar , Mintz Akiva , Sai Kiran Kumar Solingapuram 
Published: July 2017

Abstract
Glioblastoma (GBM) is the most aggressive and common primary malignant astrocytoma which is characterized by tumor heterogeneity, infiltrating margins. Radiotherapy, chemotherapy and experimental targeted therapies have been ineffective at meaningfully increasing patient survival. One significant shortcoming of systemically delivered therapies is their inability to cross the blood brain barrier (BBB) and access infiltrating tumor cells. Therefore, in this work, we tested the potential of locoregionally targeting GBM via IL13Rα2, which we discovered to be expressed on greater than 75% of GBMs. To accomplish this, we intracranially infused copper-64 (64Cu) radiolabeled IL13Rα2 specific peptide Pep-1L, previously developed by Pandya et al., into mice bearing IL13Rα2 expressing orthotopic GBMs. Small animal micro PET/CT imaging showed ~2-fold greater tumor specific localization and lower volume of distribution of 64Cu-Pep-1L within brains of mice. Post-PET biodistribution study showed greater retention of 64Cu-Pep-1L 4 hours (%ID/g = 20.85± 0.65) and 24 hours (%ID/g = 14.65± 0.30) post infusion when compared to similarly infused 64Cu radiolabeled scrambled control peptide 4 hours (%ID/g = 10.73± 2.02) and 24 hours (%ID/g = 5.97± 1.47) post infusion. These results demonstrate that Pep-1L efficiently targets IL13Rα2 expressing GBMs in vivo upon loco-regional delivery and can effectively deliver potential therapeutic agents to GBM tumors while sparing normal brain.
This work was supported by the American Cancer Society Mentored Research Scholar grant # 124443-MRSG-13-121-01-CDD (Mintz), 1R01CA179072-01A1 (Mintz), P30 CA012197 (Pasche), R01CA07414519 (Debinski) and the Translational Imaging Program (TIP) of the Wake Forest CTSA (UL1TR001420).
Citation Format: Anirudh Sattiraju, Ang Xuan, Frankis Almaguel, Denise Herpai, Waldemar Debinski, Akiva Mintz, Kiran Kumar Solingapuram Sai. PET/CT imaging of interleukin-13 receptor alpha-2-targeted peptide to glioblastoma after locoregional delivery [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 1831. doi:10.1158/1538-7445.AM2017-1831
Abstract 1837: High Ras activity promotes neoplasia in pancreatic ductal cells
Authors: Singh Kanchan , Pruski Melissa A. , Dar Wasim A. , Polireddy Kishore , Bynon John S. , Younes Mamoun , Maitra Anirban , Logsdon Craig D. , Bailey Jennifer M. 
Published: July 2017

Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy and is the third leading cause of cancer-related deaths in the United States. Next generation sequencing efforts have revealed KRAS mutations occur in over 99% of pancreatic ductal adenocarcinomas and are thought to be the initiating mutation for pancreatic cancer. Despite the high prevalence of KRAS mutations in pancreatic cancer patients, murine models expressing endogenous levels of mutant Kras in pancreatic cells do not develop PDAC. A number of publications have revealed that acinar cells are more sensitive to early neoplastic lesion formation in the presence of Kras mutations than ductal cells. In these models, a second genetic hit (loss of tumor suppressor TP53, SMAD4 or CDKN) is required for the development of invasive PDAC, including transforming pancreatic ductal cells. Recent data has revealed a novel role for high levels of Ras activity in acinar cells in the tranformation of this cell type to PDAC (Ji, B., 2009). We hypothesized based on other preliminary data that high levels of Ras activity would transform ductal cells. To test this hypothesis, we studied the role of constitutively active high levels of Kras activity in acinar and ductal cells by expressing an inducible KrasG12V allele in Ptf1a:CreERT2 (acinar cell specific) and Hnf1b:CreERT2 (ductal cell specific) mice. Similar to previously published work, high levels of Ras activity in acinar cells resulted in PDAC and a remarkably low survival time of 10 days after mice were injected with tamoxifen. Mice with elevated Ras activity in ductal cells needed to be euthanized two weeks after tamoxifen injection and manifested a cancer cachexic phenotype. Histological analysis of these mice revealed high grade oncocytic intraductal neoplasia and the phenotype extended throughout the pancreatobiliary ducts. Western blot analysis of human PDAC and Cholangiocarcinoma tissue revealed similar levels of Ras activity to our murine models, confirming human equivalent high Ras expression to both animal models. Oncocytic tumors are characterized by an abundance of mitochondria. Thus, we are currently studying metabolic alterations and mitochondria accumulation in ductal and acinar cells expressing high Ras activity. Our goal is to determine how mitochondrial alterations play a role in progression or inhibition of tumors in ductal vs acinar cells.
Citation Format: Kanchan Singh, Melissa A. Pruski, Wasim A. Dar, Kishore Polireddy, John S. Bynon, Mamoun Younes, Anirban Maitra, Craig D. Logsdon, Jennifer M. Bailey. High Ras activity promotes neoplasia in pancreatic ductal 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 1837. doi:10.1158/1538-7445.AM2017-1837
Abstract 1866: Ultrahigh resolution optical coherence microscopy for label-free imaging of human cervical lesions ex vivo
Authors: Zeng Xianxu , Li Canyu , Wang Xiaofang , Jerwick Jason , Xu Tao , Ning Yuan , Zhang Linlin , Ma Yutao , Zhang Xiaoan , Zhou Chao 
Published: July 2017

Abstract
Cervical cancer remains the fourth most common cause of cancer and the fourth leading cause of cancer death in women worldwide. In contrast to the decreasing prevalence in developed countries, incidence of cervical cancer remains high in developing countries, such as China, India and Chile. Effective screening of cervical cancer is crucial for early diagnosis of the disease. Ultrahigh resolution optical coherence microscopy (UHR OCM) is an emerging label free imaging technique that can be used to obtain three dimensional (3D) “optical biopsy” of biological samples with cellular resolution up to 2 mm beneath the tissue surface. The goal of this study is to assess the diagnostic value of UHR OCM for human cervical precancer and cancer screening and identify characteristic features in UHR OCM images that correlate with the gold standard histopathology. Six hundred and fifty eight (658) fresh cervical tissues from cervical biopsy, conization and panhysterectomy were obtained from 254 consenting volunteers. Multiple 3D UHR OCM images were obtained from each specimen before the sample was processed for standard histopathology evaluation. Of the 658 samples imaged, 474 had normal cervix or benign lesions, 110 had low grade squamous intraepithelial lesion (LSIL), 57 had high grade squamous intraepithelial lesions (HSIL) and 17 had invasive cancer. UHR OCM images were compared to histopathology slides obtained from the same specimens in order to identify diagnostic image features. Distinctive patterns for squamous epithelium, columnar epithelium, basement membrane, cervical inflammation and erosion, koilocytic cells, low grade and high grade squamous intraepithelial lesions and cervical cancer were clearly observed. Our results lay the foundation for future non-invasive optical evaluation of cervical tissue in vivo. This could lead to a less invasive and more effective screening strategy for cervical cancer based on OCM guided biopsies.
Citation Format: Xianxu Zeng, Canyu Li, Xiaofang Wang, Jason Jerwick, Tao Xu, Yuan Ning, Linlin Zhang, Yutao Ma, Xiaoan Zhang, Chao Zhou. Ultrahigh resolution optical coherence microscopy for label-free imaging of human cervical lesions ex vivo [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 1866. doi:10.1158/1538-7445.AM2017-1866
Abstract 1878: PDZ-RhoGEF functions as a critical signaling effector for TROY
Authors: Ding Zonghui , Roos Alison , Kloss Jean , Dhruv Harshil , Symons Marc , Tran Nhan L. , Loftus Joseph C. 
Published: July 2017

Abstract
Glioblastoma Multiforme (GBM) is the most common tumor of the CNS with a median survival of approximately 15 months. The highly aggressive invasion of malignant cells into the surrounding normal brain tissue renders complete surgical resection impossible, increases therapeutic resistance, and virtually assures tumor recurrence. We have previously demonstrated that TROY (TNFRSF19) has an important role in GBM invasion and resistance. TROY expression is correlated with glial tumor grade and inversely correlated with patient survival. Increased TROY expression stimulated cell migration/invasion in vitro and in vivo and confers resistance to both ionizing radiation- and temozolomide-induced apoptosis via activation of Akt and NF-κB. These data indicate that TROY stimulated migration/invasion is associated with signaling pathways that also increase survival and therapeutic resistance, however, the mechanistic basis of this signaling remains unclear. To investigate the mechanism by which TROY induces GBM cell invasion, we performed immunoprecipitation of the TROY receptor coupled with MALDI-TOF and MS/MS analysis and identified PDZ-RhoGEF as a binding partner for TROY. We validated the interaction of TROY with PDZ-RhoGEF by immunoprecipitation and western blotting, and demonstrated that PDZ-RhoGEF can exchange for both RhoA and RhoC in glioma cells and is implicated in GBM cell invasion, proliferation, and survival. In order to assess the specific role of PDZ-RhoGEF in TROY signaling, we examined the effects of PDZ-RhoGEF on TROY-mediated activation of NF-κB. While overexpression of TROY alone strongly stimulated NF-κB transcriptional activity in serum-free conditions, increased expression of PDZ-RhoGEF alone had no effect on NF-κB activity. Co-transfection of PDZ-RhoGEF with TROY synergistically promoted NF-κB activation. Mutation of the TRAF binding domain (TBD) in the cytoplasmic domain of TROY abolished its capacity to activate NF-κB, even in the presence of PDZ-RhoGEF, suggesting that the TBD is important for TROY induced NF-κB activation. Furthermore, knockdown of PDZ-RhoGEF by shRNA attenuated NF-κB activation in TROY expressing cells, blocked TROY mediated invasion of primary GBM xenograft cells and increased sensitivity to temozolomide. Collectively, these data indicate that PDZ-RhoGEF plays an important role in TROY signaling and provides insights into a potential node of vulnerability to limit GBM cell invasion and decrease therapeutic resistance.
Citation Format: Zonghui Ding, Alison Roos, Jean Kloss, Harshil Dhruv, Marc Symons, Nhan L. Tran, Joseph C. Loftus. PDZ-RhoGEF functions as a critical signaling effector for TROY [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 1878. doi:10.1158/1538-7445.AM2017-1878
Abstract 1891: Annexin A2-binding S100 proteins promote proliferation and cell cycle progression of EGFR positive cancer cells
Authors: Ogama Naoko , Nagashima Ryuuichi , Tanaka Nobuyuki 
Published: July 2017

Abstract
(a) Aim: The purpose of this study is to clarify an unknown function of Annexin A2-binding S100A proteins in tumor growth, cell cycle progression and invasion. Annexin A2 is a membrane bound protein originally identified as v-Src substrate, and often found to be overexpressed in many types of cancers. As a multicompartmental protein that orchestrates a spectrum of dynamic membrane-related events, it is associated with actin cytoskeleton control, vesicle formation and intercellular interaction.
(b) Methods and Results: During our proteomics analysis using solid tumor cell lines, we identified both Annexin A2 and S100A proteins in cancer stem cell-rich population. We next examined S100A proteins expression in several Head and Neck cancer PDX samples. Immunohistochemical data from in vivo specimens as well as western blots showed that S100A expression abundance was well associated with poor prognosis. Annexin A2 has been indicated to be involved in malignant phenotypes such as invasion and metastasis, and Annexin A2 and S100A form (S100-Annexin A2)x2 dimers, we next examined roles of S100A proteins in cancer, by using shRNA-mediated depletion experiments.
(c) New Findings: Depletion of S100A from PDX-derived cancer cells resulted in loss of both in vivo tumor formation and invasion. Furthermore, cell cycle progression was inhibited by the depletion, suggesting its potential role in proliferation controls. Similar to the mutant Ras-driven tumors, EGFR-overexpression increased S100A gene expresssion.
(d) Conclusion: These results strongly suggest that increases in S100A plays significant roles in cancer cell proliferation and invasion.
Note: This abstract was not presented at the meeting.
Citation Format: Naoko Ogama, Ryuuichi Nagashima, Nobuyuki Tanaka. Annexin A2-binding S100 proteins promote proliferation and cell cycle progression of EGFR positive 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 1891. doi:10.1158/1538-7445.AM2017-1891
Abstract 1892: Small molecule NSC59984 prevents cancer cell migration and invasion
Authors: Zhang Shengliang , Wagner Jessica , Zhou Lanlan , El-Deiry Wafik S. 
Published: July 2017

Abstract
Tumor metastasis is one of the main mechanisms leading to mortality of cancer patients. Searching for new therapeutic strategies to prevent tumor metastasis is one of the anti-tumor approaches in cancer therapy. Cell migration and invasion are crucial initial steps in the complex process and progression of tumor metastasis. Mutant p53 has been known as an important factor associated to cancer cell migration. Therefore, targeting mutant p53 is a potential strategy to avoid tumor metastatic spread. We previously reported an anti-tumor small molecule, NSC59984 which degrades mutant p53 and restores p53 pathway via activation of p73. Here we demonstrate that NSC59984 inhibits cancer cell migration and invasion. Treatment with NSC59984 partially attenuates cell migration in various cancer cells based on the scratch assay and Boyden chamber assay. The effect of NSC59984 on cell migration is partially blocked by knockdown of p73, a member of the p53 family, suggesting that restoration of p53 pathway signaling via p73 is required for NSC59984-inhibition of cell migration in cancer cells. We found that NSC59984 induces ERK2-dependent p53 restoration and mutant p53 degradation. To examine the role of ERK2 in the cell migration, ERK2 signaling is blocked by U0126 treatment in cancer cells. The effect of NSC59984 on cancer cell migration is partially inhibited by U0126 treatment, suggesting that NSC59984 inhibits cancer cell migration partially dependent on ERK1/2 pathway signaling in cancer cells. In addition, the gelatin degradation assay shows that NSC59984 inhibits cancer cell invasion. Consistent to the in vitro assays, NSC59984 decreases tumor invasion of xenograft tumors as compared to the xenograft tumors treated with DMSO as control. Our results, taken together, suggest that NSC59984 not only suppresses tumor growth, but also inhibits cancer cell migration and invasion. Our findings provide the potential administration of p53-restoring compound NSC59984 in cancer therapy by blocking tumor metastasis.
Citation Format: Shengliang Zhang, Jessica Wagner, Lanlan Zhou, Wafik S. El-Deiry. Small molecule NSC59984 prevents cancer cell migration and invasion [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 1892. doi:10.1158/1538-7445.AM2017-1892
Abstract 1898: MEG3 as a competing endogenous RNA binds with miR-27a to promote PHLPP2 protein translation, and consequently impairs bladder cancer invasion
Authors: Huang Chao , Liao Xin , Li Jingxia , Huang Chuanshu 
Published: July 2017

Abstract
Muscle invasion and metastasis of bladder cancer dramatically decrease survival rate, compared to 77% of 5 year survival rate of all bladder cancer, metastasis bladder cancer is only 5%. This truth implies that one of the therapeutic kernels of bladder cancer is to decrease, even block, its invasiveness. In the current study, we find that MEG3 is significantly downregulate in human muscle-invasive bladder cancer tissues compared with non-muscle invasive tissues. We also demonstrate the MEG3 strongly inhibits human bladder cancer cell invasiveness by acting as a ceRNA. We find that MEG3 competes with PHLPP2 mRNA for miR-27a binding, which leads to a decreased miR-27a activity, and subsequently reducing the translation inhibition of miR-27a to PHLPP2. The upregulated PHLPP2 decreases the c-Jun phosphorylation at Ser63/73, and in turn inhibits the c-Myc transcription and its mediated invasiveness of the bladder cancer cells. This is the first demonstration that MEG3 inhibits the invasiveness of human bladder cancer cells via negative regulation of c-Myc as a ceRNA. These findings not only provides a novel insight into understanding the mechanisms behind the MEG3 inhibiting the cancer cell invasion, but also reveals a potential targets for invasive bladder cancer prevention and therapy.
Citation Format: Chao Huang, Xin Liao, Jingxia Li, Chuanshu Huang. MEG3 as a competing endogenous RNA binds with miR-27a to promote PHLPP2 protein translation, and consequently impairs bladder cancer invasion [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 1898. doi:10.1158/1538-7445.AM2017-1898
Abstract 1913: SOX9 regulates cancer stem-like cells in non-small cell lung cancer
Authors: Voronkova Maria , Luanpitpong Sudjit , Riedel Heimo , Rojanasakul Yon 
Published: July 2017

Abstract
Lung cancer is the leading cause of cancer death worldwide in both men and women, every year killing more people than breast, prostate and colon cancers combined. Drug/radiation resistance and tumor relapse contribute to low patient survival, which has largely been attributed to the acquisition of stem-like cells (CSCs), or tumor initiating cells. Moreover, conventional therapies are not effective against CSCs. This signifies the need to identify mechanisms of CSC regulation which could lead to the discovery of CSC-specific drug targets and the development of more effective drug therapies. An embryonic transcription factor SOX9 has been implicated in CSC regulation in a number of cancer types, but little is known about its role in non-small cell lung cancer (NSCLC). We demonstrated that high SOX9 expression correlates with poor survival in lung cancer patients by analyzing The Cancer Genome Atlas (TCGA) data. We hypothesized that SOX9 plays a key role in tumor progression and chemoresistance by upregulating CSCs in NSCLC. To test this hypothesis, SOX9 expression was stably or transiently knocked down in NSCLC cells, and their effects on CSC formation and biomarkers, and on drug resistance were investigated. Our results showed that SOX9 knockdown decreased the number of tumor spheres in NSCLC cell lines. Furthermore, SOX9 knockdown downregulated the expression and activity of stem cell marker ALDH1A1 as determined by Western blot and flow cytometric assays. Consistent with this finding, overexpression of SOX9 in non-cancer lung epithelial Beas-2B cells elevated tumor sphere formation, supporting the role of SOX9 in CSC regulation. Analysis of the soft agar colony formation assay further showed that SOX9 knockdown inhibited anchorage-independent growth in NSCLC cells. More importantly, SOX9 knockdown resulted in an increased sensitivity of the cells to a chemotherapeutic drug cisplatin, whereas SOX9 overexpression decreased it. Together, our results indicate an important role of SOX9 in the regulation of CSCs in NSCLC and suggest its potential utility as a drug target for chemoresistant lung cancer.
Citation Format: Maria Voronkova, Sudjit Luanpitpong, Heimo Riedel, Yon Rojanasakul. SOX9 regulates cancer stem-like cells in 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 1913. doi:10.1158/1538-7445.AM2017-1913
Abstract 1925: Modeling physiologic microenvironments in three-dimensional microtumors facilitates brain tumor initiating cell maintenance
Authors: Gilbert Ashley , Walker Kiera , Tran Anh , Gillespie Yancey , Singh Raj , Hjelmeland Anita B. 
Published: July 2017

Abstract
Development of effective novel anti-tumor treatments will require improved in vitro models that incorporate physiologic microenvironments and maintain intratumoral heterogeneity including tumor initiating cells. Brain tumor initiating cells (BTIC) are a target for cancer therapy because they are highly tumorigenic and contribute to tumor angiogenesis, invasion, and therapeutic resistance. Current leading studies rely on BTIC isolation from patient-derived xenografts followed by propagation as neurospheres. As this process is expensive and time-consuming, we determined whether three-dimensional microtumors were an alternative in vitro method for modeling tumor growth via BITC maintenance and/or enrichment. Brain tumor cells were grown as neurospheres or as microtumors produced using a human-derived biomatrix HuBiogelTM and maintained with physiologically relevant microenvironments. Percentages of BITCs were determined based on cell surface marker expression (CD133), label retention (carboxyfluorescein succinimidyl ester; CFSE), and tumorsphere formation capacity. Our data demonstrate that expansion of brain tumor cells as hypoxic and nutrient restricted microtumors significantly increased the percentage of both CD133+ and CFSE+ cells. We further demonstrate that BTIC-marker positive cells isolated from microtumors maintain neurosphere formation capacity in the in vitro limiting dilution assay and tumorigenic potential in vivo. These data demonstrate that microtumors can be a useful three-dimensional biological model for the study of BTIC maintenance and targeting.
Citation Format: Ashley Gilbert, Kiera Walker, Anh Tran, Yancey Gillespie, Raj Singh, Anita B. Hjelmeland. Modeling physiologic microenvironments in three-dimensional microtumors facilitates brain tumor initiating cell maintenance [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 1925. doi:10.1158/1538-7445.AM2017-1925