bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1920: PC9 AZD9291-resistant (PC9-OSIR) cell line, a useful cell model for novel drug discovery
Authors: Bai Zhaoshuai , Wang Guoqian , Zhou Xiaolin , Mu Zhongquan , Hao Feng , Ning Jinying 
Published: August 2019

Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and the leading cause of lung cancer-related mortality. Identification of EGFR as a driver gene of NSCLC has led to the development of EGFR inhibitors, such as Gefitinib, Erlotinib, Afatinib and Osimertinib (AZD9291). AZD9291, a third-generation EGFR inhibitor, has been approved as the first-line treatment for patients with EGFR T790M mutation-positive NSCLC. Resistance to AZD9291 was observed clinically and C797S mutation was reported to be a major mechanism for resistance to AZD9291.Our group has generated PC9 AZD9291-resistant (PC9-OSIR) cell line using a dose-escalation method after treatment of the cells with mutagenic agent. Specifically, PC9 cells was treated by AZD99291 with increasing dose for 2 weeks, and remaining live cells was retrieved and designated as PC9-OSIR. Cell survival assay showed that IC50 of PC9-OSIR was over 2μM, 100-fold more resistant than the parental PC9 cells. We explored the resistance mechanisms using whole exome sequencing (WES) and RNA-Seq, but did not find EGFR C797S mutation—the most common resistance mechanism to AZD9291—in PC9-OSIR, suggesting a likely novel resistance mechanism, possibly the activation of a bypass signaling pathway, which will be elucidated by further studies.The PC9-OSIR cell line can be a useful cell line model, in addition to cell lines with C797S mutation, in the development of future EGFR inhibitors. It can also be used to explore new mechanisms of resistance to AZD9291 resistance.
Note: This abstract was not presented at the meeting.
Citation Format: Zhaoshuai Bai, Guoqian Wang, Xiaolin Zhou, Zhongquan Mu, Feng Hao, Jinying Ning. PC9 AZD9291-resistant (PC9-OSIR) cell line, a useful cell model for novel drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1920.
Abstract 1922: MYB mimic peptides targeting human and murine MYB-NFIB positive tumor cells
Authors: Jiang Yue , Forbes Lauren , Li Jianping , Freeberg Shelby , Cao Chunxia , Zajac-Kaye Maria , Licht Jonathan , Kentsis Alex , Kaye Frederic 
Published: August 2019

Abstract
Adenoid Cystic Cancer (ACC) is the most aggressive salivary gland tumor with no effective systemic therapy. MYB/MYBL1 fusion event underlies the etiology of ACC with few recurrent variants focused on NOTCH and chromatin remodeling pathways and low overall mutational tumor burden. No chemotherapy or targeted drugs have been approved for ACC. Therefore, there is an urgent need to develop novel therapeutic strategies. To study MYB biology and test new therapeutic agents we have developed and characterized the phenotype of a new murine conditional MYB-NFIB transgene model and have also generated a mammary tumor cell line expressing the human MYB fusion transgene with ACC-like features. We have also generated new human MYB-NFIB positive ACC tumor cell lines and xenografts from patient samples and have tested these tumor cells with newly developed MYB mimic peptides. We analyzed the phenotype of mice carrying conditional MMTV-CRE MYB-NFIB transgene alone or after crossing to heterozygosity with p16/ARF null alleles. We observed shortened survival in two different mouse transgene strains due to development of B-cell leukemia manifested by elevated WBC, low platelets, and marked splenomegaly. We also noted sporadic solid tumors including the development of a murine mammary tumor which generated a MYB-NFIB positive tumor cell line for testing new therapies. In addition, we have generated patient derived xenografts (PDX) and the successful generation of a human ACC tumor cell line from fresh ACC patient biopsies. Using shRNA reagents we observed reduced tumor cell growth and viability assayed by MTS assay following Notch1 and MYB knockdown. We also tested four candidate MYB inhibitors, celastrol, all-trans retinoic acid, and the peptidomimetic inhibitors, MYBMIM and CRYBMIM, against murine and human ACC tumor samples with immortalized normal cells as controls and will discuss these results.
Citation Format: Yue Jiang, Lauren Forbes, Jianping Li, Shelby Freeberg, Chunxia Cao, Maria Zajac-Kaye, Jonathan Licht, Alex Kentsis, Frederic Kaye. MYB mimic peptides targeting human and murine MYB-NFIB positive tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1922.
Abstract 1926: Ba/F3 NTRK cell panel, a powerful cell model for NTRK inhibitor discovery and development
Authors: Hao Feng , Bai Zhaoshuai , Wang Guoqian , He Feng , Liu Changpeng , Ning Jinying 
Published: August 2019

Abstract
NTRK (Neurotrophic tyrosine kinase receptor)family, also named as TRK (Tropomyosin receptor kinase),is composedof three transmembrane protein receptors, TrkA, TrkB and TrkC,which play important rolesin neuronal differentiation and survival. Over-activation of NTRK1, NTRK2 and NTRK3 due to chromosomal rearrangement and mutations, was found in congenital fibrosarcoma, secretory breast carcinoma cancer and other types ofcancer. The identification of NTRK fusions as diver cancer genes has led to rapid development of anticancer therapeutic agents, including LOXO101, LOXO195 and TPX0005.Ba/F3 line is a popular system for studying both kinases and their inhibitors, because some protein kinases can render the Ba/F3 cells to be depended on the activation of the kinases instead of IL-3 supplement, while their inhibitors can antagonize the kinase-dependent growth effects. Our group used Ba/F3 cells togenerate a celllinepanel with 14 different NTRK fusion genes or mutations for NTRK inhibitor screening and development. Inaddition to use the cell lines for in vitro assays, thetransformed Ba/F3 linescan grow well in immune-deficient miceas in vivo models. LOXO101—a NTRK inhibitor—was used to test tumor growth inhibition, the results showedthat threewild-type fusion cell lineswere sensitive to LOXO101, but not other tumor models containing NTRK gatekeeper mutations. All the tumor models were sensitive to TPX0005, another NTRK inhibitor. Ourdata indicatethatthe celllinepanel of Ba/F3is apowerful cell model for new NTRK inhibitor discovery and development.
Citation Format: Feng Hao, Zhaoshuai Bai, Guoqian Wang, Feng He, Changpeng Liu, Jinying Ning. Ba/F3 NTRK cell panel, a powerful cell model for NTRK inhibitor discovery and development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1926.
Abstract 1934: Development of spectrally distinct silica coated gold nanorods for detection of cancer using MSOT
Authors: Thomas Karl N. , Samykutty Abhilash , McNally Molly , McNally Lacey R. 
Published: August 2019

Abstract
Traditional cancer imaging devices are limited in their ability to screen for multiple contrast agents simultaneously in real time. Multispectral Optoacoustic Tomography (MSOT) is an emerging imaging modality capable of real-time imaging of numerous contrast agents with enhanced spatial resolution of 75µm at depths of 5 cm. The use of exogenous contrast agents in MSOT remains largely unexplored, so we developed two species of spectrally distinct gold nanorod as contrast agents for use in MSOT. Our goal was to evaluate the potential of MSOT to spectrally differentiate two exogenous contrast agents simultaneously. Two gold nanorod species were created using hydrogen peroxide (GNR-H2O2) or ascorbic (GNR-ASC) acid as reducing agents to modify the length of each species to create nanorods with individual light absorbance spectra in the IR range (680-900 nm). These gold nanorods were highly stabilized via encapsulation with mesoporous silica along with a subsequent chitosan capping. Human epidermal growth factor receptor 2 positive (HER2+) cells were specifically targeted by conjugating these mesoporous silica-coated chitosan capped gold nanorods (CMGs) to Trastuzumab resulting in TRA-CMG particles. Both TRA-CMG-ASC and TRA-CMG-H2O2 resulted in optoacoustic spectrally distinct signals when imaged in tissue phantoms both individually as well as mixed within the same well after multispectral processing using linear regression. Treatment of HER2+ breast cancer cell lines, DY36T2Q and SKBR3, with TRA-CMG-H2O2 resulted in 2.5x and 3.1x enhanced signal, respectively, as compared to HER2- MDA-MD468 cells. Treatment of DY36T2Q and SKBR3 cells with TRA-CMG-ASC demonstrated 3.7x and 6.9x, respectively, compared to MDA-MD468. In all three cell lines treated with a combination of TRA-CMG-H2O2’s and TRA-CMG-ASC’s clear and distinct signals were observed for each particle, demonstrating that each TRA-CMG possessed and maintained a detectibly distinct optoacoustic spectrum, in the IR range, allowing them to be detectable as separate contrast agents in MSOT while proximate to other targeted contrast agents. Both particles have demonstrated that they can be simultaneously administered and targeted at HER2+ cell while also maintaining distinct photoacoustic signals in MSOT upon consolidation. Each particle species, targeted to the same cells, were capable of being monitored individually in the presence of the other gold nanorod contrast agent.
Citation Format: Karl N. Thomas, Abhilash Samykutty, Molly McNally, Lacey R. McNally. Development of spectrally distinct silica coated gold nanorods for detection of cancer using MSOT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1934.
Abstract 1938: Implantable nanosensor for non-invasive ovarian cancer biomarker detection with wearable interface
Authors: Heller Daniel A. , Williams Ryan M. , Levine Douglas A. 
Published: August 2019

Abstract
Patients with high-grade serous ovarian carcinoma (HGSC) exhibit poor 5-year survival rates, which may be significantly improved by early-stage detection. The US FDA-approved biomarkers for HGSC—CA-125 and HE4—do not generally appear at detectable levels in the serum until advanced stages of the disease. An implantable device placed proximal to disease sites, such as in or near the fallopian tube, ovary, uterine cavity, or peritoneal cavity, may constitute a feasible strategy to improve detection of HGSC. Furthermore, a sensor implant under the skin may allow real-time measurements after diagnosis, to monitor treatment for example, via interrogation using a wearable device. We engineered a prototype optical sensor composed of an antibody-functionalized carbon nanotube complex, which responds quantitatively to HE4 via modulation of the nanotube optical bandgap. The complexes measured HE4 with nanomolar sensitivity to differentiate disease from benign patient biofluids. The sensors were implanted into four models of ovarian cancer, within a semipermeable membrane, enabling the optical detection of HE4 within the live animals. We thus present the first in vivo optical nanosensor capable of noninvasive cancer biomarker detection in orthotopic models of disease. This technology may potentially be implanted locally in the uterine cavity, for point-of-care measurement, or under the skin, to then interface with a wearable device.
Citation Format: Daniel A. Heller, Ryan M. Williams, Douglas A. Levine. Implantable nanosensor for non-invasive ovarian cancer biomarker detection with wearable interface [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1938.
Abstract 1940: Comparison of anti-hepatocellular carcinoma efficacy between regorafenib and sorafenib using multimodality molecular imaging: A preclinical study
Authors: Du Yang , Tian Jie 
Published: August 2019

Abstract
Purpose: Sorafenib has been used as a targeted therapy for HCC for more than a decade, and regorafenib has recently been approved for HCC treatment and shown to prolong survival for advanced HCC patients after treatment failure with sorafenib. However, there has been no systematic study to directly compare the therapeutic effects of regorafenib and sorafenib against HCC. In this study, we systematically compared the therapeutic effects of sorafenib and regorafenib against HCC in vitro and in vivo using multimodality molecular imaging.
Experimental Design: we systemically investigated and compared the anti-tumorigenic and anti-angiogenic efficacy of regorafenib and sorafenib in vitro and in vivo using multi-modality molecular imaging as bioluminescence imaging (BLI), bioluminescence tomography (BLT), fluorescence molecular imaging (FMI), and computer tomography angiography (CTA) etc. Moreover, the safety and side effects of two drugs were simultaneously systemically evaluated.
Results: The results showed that compared with sorafenib treatment, regorafenib exerted stronger antitumor and antiangiogenic effects and significantly increased the survival rate of HCC model mice. Although both drugs caused side effects, their severity was usually higher with sorafenib, except that regorafenib caused hypertension, which was not observed with sorafenib.
Conclusions: The study suggests that multimodality molecular imaging can help sensitively evaluate the drug treatment efficacy against HCC before tumor anatomical changes occur and also helps understand the underlying antitumor mechanism of a drug at the molecular and cellular levels. Our data may provide an experimental basis for clinical application of HCC targeted treatment with regorafenib and sorafenib.
Citation Format: Yang Du, Jie Tian. Comparison of anti-hepatocellular carcinoma efficacy between regorafenib and sorafenib using multimodality molecular imaging: A preclinical study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1940.
Abstract 1943: Highly specific tumor-targeting near-infrared persistent luminescence nanomaterials (ZGO and LGGO) for lung cancer bioimaging
Authors: Chan Ming-Hsien , Liu Ru-Shi , Hsiao Michael 
Published: August 2019

Abstract
Lung cancer cells grow in-situ usually results in metastasis and is frequently recurrent after therapy. Moreover, treatment of lung cancer using surgery or chemotherapy is difficult to determine that all tumor tissue has been removed. ZnGa2O4/La3GaGe5O16 (ZGO and LGGO) persistent luminescence nanomaterials (PLNs) which are based on the biological characteristics of metastatic or remaining lung cancer cells, to promote the clinical application of these nanomaterials for long-term specific tracking. A silica shell-assisted synthetic route for mono-disperse, near infrared-PLNs, will be developed and applied in the, in vitro cell model and in vivo mouse model. The Cr3+-doped PLNs can hold the emitted light longer than several hours. These NIR-PLNs will absorb the energy of UV or X-ray light first and retain fluorescence emission. Moreover, we will identify the specific aptamer, MAGE-A3, and modify the PLN’s design accordingly, to increase the ability of cancer targeting. These targeted molecules can track the metastatic cell with specific binding. The advancement of nanoscale techniques in lung cancer is an urgent need. Hence, this research will deliver a credible diagnostic strategy and a novel method for therapeutic administration. To evaluate the luminescent effect in vitro and in vivo of NIR-PLNs, repeated in vivo NIR persistent luminescence images of a mouse after intravenous injection (I.V.) and intratracheal injection (I.T.) of NIR-PLNs. After the NIR-PLNs is irradiated with UV light for 120 seconds in vitro, the particles are entering in the mouse by I.V. and I.T. It is seen that NIR persistent luminescence signal could be repeatedly observed over the mouse’s lung tumor tissue for more than 6 hours. Interestingly, no significant NIR luminescence signal can be observed in the other parts of the mice. The major task is, providing a potential strategy for diagnostic in lung cancer. The current diagnostic approach does not easily distinguish the metastatic and remaining tumor cells. Moreover, we anticipate that our designed nanoplatform or accessed procedure
could be applied to other types of materials or cancers, leading NIR-PLNs nanomaterials to the exploration of gene-scale research.
Citation Format: Ming-Hsien Chan, Ru-Shi Liu, Michael Hsiao. Highly specific tumor-targeting near-infrared persistent luminescence nanomaterials (ZGO and LGGO) for lung cancer bioimaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1943.
Abstract 1954: Tracking of orally-administered particles within the gastrointestinal tract of murine models using multispectral optoacoustic tomography
Authors: Bhutiani Neal , Samykutty Abhilash , McMasters Kelly , Egilmez Nejat , McNally Lacey R. 
Published: August 2019

Abstract
While particle carriers have potential to revolutionize disease treatment, using these carriers requires knowledge of spatial and temporal biodistribution. The goal of this study was to track orally administered particle uptake and trafficking through the murine gastrointestinal (GI) tract using multispectral optoacoustic tomography (MSOT).
Polylactic acid (PLA) particles encapsulating AlexaFluor 680 (AF680) dye conjugated to bovine serum albumin (BSA) were orally gavaged into mice. Particle uptake and trafficking were observed using MSOT imaging with subsequent confirmation of particle uptake via fluorescent microscopy. Mice treated with PLA-AF680-BSA particles exhibited MSOT signal within the small bowel wall at 1 and 6 h, colon wall at 6, 12, and 24 h, and mesenteric lymph node 24 and 48h. Particle localization identified using MSOT correlated with fluorescence microscopy. Despite the potential of GI tract motion artifacts, MSOT allowed for teal-time tracking of particles within the GI tract in a non-invasive and real-time manner.
Future use of MSOT in conjunction with particles containing both protein-conjugated fluorophores as well as therapeutic agents could allow for non-invasive, real time tracking of particle uptake and drug delivery.
Citation Format: Neal Bhutiani, Abhilash Samykutty, Kelly McMasters, Nejat Egilmez, Lacey R. McNally. Tracking of orally-administered particles within the gastrointestinal tract of murine models using multispectral optoacoustic tomography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1954.
Abstract 1967: Nab-paclitaxel chemotherapy of breast tumors upregulates chemokines that increase chemotaxis of myeloid-lymphatic progenitors
Authors: Volk-Draper Lisa D. , Ran Sophia 
Published: August 2019

Abstract
Introduction: Lymph node metastasis is the main prognostic indicator for poor survival of breast cancer patients. Metastasis is promoted by tumor-induced lymphangiogenesis mediated, in part, through recruitment of myeloid-derived lymphatic endothelial cell progenitors (M-LECP). We previously showed that differentiation of M-LECP is induced by activated Toll-like receptor-4 (TLR4). The goal of this study was to identify TLR4-induced chemokines produced by tumors alone or in response to nab-paclitaxel (nab-PXL) chemotherapy that enhance bone marrow (BM) differentiation and tumor recruitment of M-LECP.
Methods: Profile of BM composition for lymphatic-like, myeloid and progenitor cells was assessed by flow cytometry in normal and tumor-bearing mice treated either with saline or nab-PXL. We used two TLR4 overexpressing tumor models: MDA-MB-231 and HCC1806-TLR4+. RT-qPCR was used to determine differences in expression of 130 cytokines in cultured tumor cells and tumors from mice treated either with saline or nab-PXL. Targets with &gt;2-fold upregulation were analyzed for protein expression by ELISA. ELISA-validated cytokines were tested for their ability to induce migration of M-LECP.
Results: Both MDA-MB-231 or HCC1806-TLR4+ tumors significantly increased the levels of differentiated M-LECP in the BM, and that was further enhanced by treatment with taxane chemotherapy. Expression of progenitor markers CD117, CD33, and Sca-1 was increased up to 7-fold in both tested tumor models, and further upregulated by nab-PXL treatment by additional 3 to 9-fold. Out of 23 cytokines measured in tumor lysates by ELISA, 40% were upregulated by nab-PXL. Migration assay showed that several of these cytokines increased chemotaxis of M-LECP with CXCL1 being the strongest. Neutralization of CXCL1 in the conditioned medium of nab-PXL-treated MDA-MB-231 cells inhibited migration of lymphatic progenitors by 75%.
Conclusion: Taxane chemotherapy acting presumably as a ligand for TLR4 significantly expanded M-LECP population in the BM. Our analysis suggests that these lymphatic precursors can mobilize to tumors by chemokines such as CXCL1 that are highly upregulated in TLR4-positive tumor cells, particularly when activated by paclitaxel. These data suggest that CXCL1 plays an important role in recruiting myeloid-lymphatic progenitors to breast tumors, which, in turn, promotes lymphatic vessel formation and metastasis. Blocking this cytokine might have clinical utility for prevention of tumor mobilization of M-LECP, and by extension, breast cancer metastasis to lymph nodes.
Citation Format: Lisa D. Volk-Draper, Sophia Ran. Nab-paclitaxel chemotherapy of breast tumors upregulates chemokines that increase chemotaxis of myeloid-lymphatic progenitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1967.