bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4153: Commissioning and radiobiological verification of the small animal radiotherapy research platform (SARRP)
Authors: Kane Jonathan L. 
Published: August 2018

Abstract
Preclinical radiation biology has become increasingly sophisticated due to the implementation of advanced small animal image guided radiation platforms into laboratory investigation. Small animal radiotherapy devices enable state-of-the-art image guided therapy (IGRT) research to be performed in small animal cancer models by combining high-resolution cone beam computed tomography (CBCT) imaging with an isocentric irradiation system. The technological evolution from simple, broad field irradiation configurations, to more sophisticated dose deliveries for preclinical radiobiology experiments has introduced new dosimetry challenges for preclinical small animal cancer research. Because of this, robust QA and dosimetry techniques are a key part of using novel treatment platforms using very small irradiation fields. In this study, we present a dosimetric study of the small animal radiotherapy research platform (SARRP, Xstrahl Inc.) focusing on the small field dosimetry. Physical dosimetry was assessed using ion chambers and radiochromic film, investigating the impact the beam focus size has on the dose rate output as well as beam characteristics (beam shape and penumbra variations). Two film reading modalities have been used to assess the dose output using the 0.5 mm diameter aperture. This study establishes that FilmQA Pro is a suitable tool for small field dosimetry, with a sufficiently small sampling area (0.1 mm) to ensure an accurate measurement. Furthermore, all small field dosimetry data generated in this study are equally comparable with our Monte Carlo simulations for both focal spot sizes. Overall, it was observed that the small focal spot, while having a lower dose-rate output was shown to produce a more stable and homogenous beam with minimum penumbra over time when compared to the larger focal spot. These findings suggest that when preclinical stereotactic irradiation fields are used, a practical compromise (time to deliver a desired dose and field homogeneity) needs to be considered when deciding the optimum treatment plan and beam configuration used.
Citation Format: Jonathan L. Kane. Commissioning and radiobiological verification of the small animal radiotherapy research platform (SARRP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4153.
Abstract 4172: Radiation-induced blood-tumor barrier permeability in a preclinical model of lung cancer brain metastasis
Authors: Sprowls Samuel A. , Shah Neal , Mohammad Afroz S. , Pinti Marc , Tallman Rachel M. , John Devin U. , Lockman Paul R. 
Published: August 2018

Abstract
BACKGROUND: Lung cancer has the highest mortality rate among all cancers and accounts for over half of newly diagnosed brain metastases each year. Standard therapeutic advancements are prolonging lives of lung cancer patients with each new approved formulation, however patients with brain metastases have limited options and no curative measures currently exist. Current treatment modalities for brain metastases from primary lung cancer include differing methodologies of radiotherapy (whole brain radiotherapy and/or stereotactic radiosurgery), systemic chemotherapies, and neurosurgery. Radiation in many cases is not ablative, but palliative. Herein we demonstrate the ability of radiotherapy to influence blood-tumor barrier permeability in a novel preclinical model of lung cancer brain metastasis.
METHODS: Athymic female nude mice were intracardially injected with our novel PC-9-BR brain specific lung cancer cell line. Tumors were allowed to develop and monitored using bioluminescent imaging. Using the Xstrahl XenX small animal irradiator, we were able to deliver 26 Gy to the right hemisphere of the immobilized mouse. 4 hours post radiotherapy, mice were perfused with the passive permeability marker Oregon Green, followed by an indocyanine green (bound to albumin) washout to infer vascular space. Brains were then extracted, snap frozen in isopentane (-50°C), and sliced to 20μm. Florescence was quantified using a MVX microscope and cellsense software.
RESULTS: Analysis of irradiated brain regions demonstrated statistically significant more accumulation of the passive permeability marker, Oregon Green, compared to the contralateral hemisphere.
CONCLUSIONS: Radiation induced permeability was witness in mice after a single dose of 26 Gy when compared to non-irradiated tumor tissue 4 hours post treatment.
FURTURE DIRECTIVES: Experiments utilizing ionizing radiation to simulate treatment of CNS metastases could reveal better adjunctive chemotherapeutic regimens and or provide insight to the mechanism underlying this enhanced permeability.
Citation Format: Samuel A. Sprowls, Neal Shah, Afroz S. Mohammad, Marc Pinti, Rachel M. Tallman, Devin U. John, Paul R. Lockman. Radiation-induced blood-tumor barrier permeability in a preclinical model of lung cancer brain metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4172.
Abstract 4177: An IL13Rα2 peptide inhibits colorectal cancer metastatic progression
Authors: Casal Ignacio , Jaén Marta , Bartolomé Rubén A. 
Published: August 2018

Abstract
Interleukin 13 receptor α2 (IL13Rα2) is an excellent tumoral marker for metastatic colorectal cancer and glioblastoma. Our goal was to block IL-13 binding to IL13Rα2 by using IL13Rα2 synthetic peptides in order to delay or suppress metastatic spread and progression. Peptides were selected from the D1 binding region.
Synthetic peptides were synthesized using solid phase chemistry. Two metastatic colorectal cancer cell lines (KM12SM and SW620) plus two glioblastoma cell lines were used for testing proliferation, adhesion, migration and invasion. We used Biacore assays to demonstrate direct interaction between the peptides and IL-13. In vivo experiments with nude mice were performed to study mice survival to metastasis after peptide treatment.
Peptides containing the highly preserved WKTIITKN motif of the D1 binding domain of IL13Rα2 demonstrated a strong capacity to inhibit migration, invasion and proliferation in metastatic colorectal cancer and glioblastoma cells. Alanine scanning experiments indicated that, at least, residues 82K, 83T, 85I and 86T were essential for IL-13 binding to IL13Rα2. IL13Rα2 D1 peptide inhibited IL-13-mediated cell signaling through FAK, Src, AKT and ERK1/2 in colorectal cancer and glioblastoma cell lines. Moreover, the D1 peptide abolished ligand-mediated receptor internalization and degradation. To improve bioavailability and resistance to proteolytic digestion for in vivo administration, we prepared the D enantiomer version of the peptide. Mice inoculated with metastatic colorectal cancer cells and treated with the enantiomer version of the D1 peptide showed a remarkable increase in survival.
In conclusion, the D1 enantiomer peptide blocked the IL-13/IL13Rα2 binding, paving the way to develop novel and promising therapeutic strategies to inhibit metastatic progression in colorectal cancer and other solid tumors, including glioblastoma.
Citation Format: Ignacio Casal, Marta Jaén, Rubén A. Bartolomé. An IL13Rα2 peptide inhibits colorectal cancer metastatic progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4177.
Abstract 4180: Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis
Authors: Anselmino Nicolás , Chiarella Paula , Ortiz Emiliano G. , Leonardi Daiana B. , Jaworski Felipe M. , Vikers Sofia Lage , Giudice Jimena , Woloszynska-Read Anna , Meiss Roberto P. , Rugiero Raul , Gueron Geraldine , Vazquez Elba S. 
Published: August 2018

Abstract
An abrupt increase in metastatic growth as a consequence of the removal of primary tumors suggests that the concomitant resistance (CR) phenomenon might occur in human cancer. CR occurs in murine tumors and ROS-damaged phenylalanine, meta-tyrosine (m-Tyr), was proposed as the serum anti-tumor factor primarily responsible for CR. Herein, we demonstrate for the first time that CR happens in different experimental human solid tumors (prostate, lung anaplastic, and nasopharyngeal carcinoma). Moreover, m-Tyr was detected in the serum of mice bearing prostate cancer (PCa) xenografts. Primary tumor growth was inhibited in animals injected with m-Tyr. Further, the CR phenomenon was reversed when secondary implants were injected into mice with phenylalanine (Phe), a protective amino acid highly present in primary tumors. PCa cells exposed to m-Tyr in vitro showed reduced cell viability, downregulated NFκB/STAT3/Notch axis, and induced autophagy; effects reversed by Phe. Strikingly, m-Tyr administration also impaired both, spontaneous metastasis derived from murine mammary carcinomas (4T1, C7HI, and LMM3) and PCa experimental metastases. Altogether, our findings propose m-Tyr delivery as a novel approach to boost the therapeutic efficacy of the current treatment for metastasis preventing the escape from tumor dormancy.
Citation Format: Nicolás Anselmino, Paula Chiarella, Emiliano G. Ortiz, Daiana B. Leonardi, Felipe M. Jaworski, Sofia Lage Vikers, Jimena Giudice, Anna Woloszynska-Read, Roberto P. Meiss, Raul Rugiero, Geraldine Gueron, Elba S. Vazquez. Game-changing restraint of Ros-damaged phenylalanine, upon tumor metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4180.
Abstract 4188: Preoperative supplementation of branched-chain amino acids suppresses Osteopontin expression in patients with hepatocellular carcinoma
Authors: Hiroshima Yukihiko , Yabushita Yasuhiro , Kikuchi Yutaro , Kawagushi Daisuke , Murakami Takashi , Ichikawa Yasushi , Endo Itaru , Tanaka Kuniya 
Published: August 2018

Abstract
Background: Recently, the new effect of branched-chain amino acid (BCAA) on Osteopontin (OPN), which correlates with cancer progression, has been reported. The aim of this study was that preoperative administration of BCAA could improve prognosis via degradation of OPN expression in hepatocellular carcinoma (HCC).
Methods: Human hepatocellular carcinoma cell lines were treated with BCAA (2nM), and investigated OPN expression, cell proliferation and invasion in vitro. Next, patients undergoing elective liver resections for HCC (n=72) were randomized to receive or not receive preoperative oral supplementation with BCAA. OPN protein levels in HCC patients were examined using immunohistochemistry and compared with the clinicopathologic features of the tumors.
Results: Experimentally, the expression levels of OPN were significantly decreased in HCC cells treated with BCAA. BCAA treatment significantly decreased cell invasion. In the clinical setting, OPN expression correlated with HBV or HCV infection (p = 0.03), venous invasion (p = 0.02) and liver fibrosis (p = 0.07). There was no difference in both DFS and OS between OPN-positive and OPN-negative group, and preoperative BCAA administration did not improve prognosis, either. For the patients without late recurrence, OPN-positive group showed significantly poor outcome in DFS (p = 0.047), and preoperative BCAA administration improved DFS (p = 0.062).
Conclusions: OPN expression was associated with cancer cell invasion and intrahepatic metastasis. BCAA treatment suppressed HCC cell invasion and preoperative BCAA administration prevented early intrahepatic recurrence by decreasing the expression level of OPN in HCC.
Citation Format: Yukihiko Hiroshima, Yasuhiro Yabushita, Yutaro Kikuchi, Daisuke Kawagushi, Takashi Murakami, Yasushi Ichikawa, Itaru Endo, Kuniya Tanaka. Preoperative supplementation of branched-chain amino acids suppresses Osteopontin expression in patients with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4188.
Abstract 4192: C-terminal HSP90 inhibitor, L80, targets cancer stem cell (CSC)-like property and suppresses metastasis via JAK/STAT3 inactivation in triple-negative breast cancer
Authors: Cho Tae-Min , Oh Eunhye , Sung Daeil , Kim Yoon-Jae , Jang Seojin , Lee Jeewoo , Kim Ji Young , Seo Jae Hong 
Published: August 2018

Abstract
Purpose: Triple-negative breast cancer (TNBC) harbors high level of cancer stem cell (CSC)-like populations, which is associated with aggressive phenotype leading to tumor cell dissemination and poor clinical outcomes. Therefore, new drugs that effectively target both CSCs and tumor bulk cells are needed to improve clinical outcomes. The 90-kDa molecular chaperone heat-shock protein, HSP90 has been implicated in cancer progression and metastasis by modulating the stabilization and maturation of many oncogenic proteins. Our objective was to investigate the effects of L80 on cancer stem-like characteristics, cell proliferation and metastasis in TNBC in vitro and in vivo.
Experimental Design: The effect of L80 on TNBC cell lines in vitro was evaluated in terms of cell viability, apoptosis and mammosphere-forming ability and expression of JAK/STAT3 signaling-related factors. An orthotopic injection model with 4T1 mammospheres with self-renewability was used to examine the effect of L80 on tumor growth, angiogenesis and metastasis.
Results: L80 treatment caused a significant induction of apoptosis, accompanied by caspase-3/-7 activation and the dysregulation of JAK/STAT3 activation in TNBC cells. The latter phenomenon was associated with impairment of cancer stem-like trait, concomitant with a significant suppression of mammosphere formation. To confirm the physiological relevance of our in vitro findings, we examined the impact of L80 on allografted tumor growth, angiogenesis and metastasis in vivo. L80 administration impedes tumor growth and subsequently suppresses angiogenesis, as evidenced by a marked reduction in number of CD31-positive microvessels in the L80-treated groups compared to their counterparts. L80 administration leads to a significant reduction in lung and liver metastases, coinciding with decreased MMP-2 and MMP-9 levels in circulating blood. These responses were intimately associated with dysregulation of JAK/STAT3 activation.
Conclusion: C-terminal HSP90 inhibitor, L80 suppresses tumor growth and metastasis via suppression of JAK/STAT3 activity and CSC-like property. These findings suggest that HSP90 could be a promising target for treatment of metastatic TNBC.
Citation Format: Tae-Min Cho, Eunhye Oh, Daeil Sung, Yoon-Jae Kim, Seojin Jang, Jeewoo Lee, Ji Young Kim, Jae Hong Seo. C-terminal HSP90 inhibitor, L80, targets cancer stem cell (CSC)-like property and suppresses metastasis via JAK/STAT3 inactivation in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4192.
Abstract 4199: Resveratrol induced REG III and inhibited head and neck cancer progression
Authors: Ota Ichiro , Mikami Shinji , Masui Takashi , Kimura Takahiro , Uemura Hirokazu , Okamoto Hideyuki , Takasawa Shin , Kitahara Takashi , Shobatake Ryogo 
Published: August 2018

Abstract
Head and neck squamous cell carcinoma (HNSCC) is one of the 10 most common malignancies in the world and known for clinical progression and poor prognosis. Despite the recent progress of the treatment for improving locoregional control in HNSCC patients, that for recurrence and metastatic control remains insufficient, indicating that there is a continued need for improved treatment strategies. Therefore, the key molecules that enhance chemo- and radio-sensitivity in HNSCC and identification of reliable biomarkers for predicting the recurrence and metastasis would be desirable to improve the prognosis of HNSCC. The human regenerating gene (REG) expression has been reported to be associated with progression of various cancers. Recently, we have reported that REG III expression is associated with an improved survival rate for HNSCC patients as a reliable biomarker. Herein, we investigated the inducer for REG III expression in HNSCC cells and found that resveratrol significantly increased the REG III promoter activity and REG III mRNA. In addition, we demonstrated that the effects of resveratrol on cancer cell progression in HNSCC in vitro and in vivo. To reveal the effects of resveratrol on HNSCC cell proliferation, cell proliferation was measured by using WST-8 assay. Resveratrol significantly inhibited cell growth in FaDu and HSC-4 HNSCC cells. Secondly, to check the effects of resveratrol on chemo- and radio-sensitivity in HNSCC cells, HNSCC cells were expose to cisplatin and radiation, respectively. Resveratrol significantly increased the sensitivity of cisplatin and radiation in HNSCC cells. We also examined the effects of resveratrol on cancer invasion using 24-well Matrigel-coated Transwells. Resveratrol significantly attenuated the cancer invasion of HNSCC cells. Moreover, to assess resveratrol-induced chemo-sensitivity in vivo, we established a xenograft model of HNSCC in BALB/c nude mice. The tumor volumes in the mice receiving combined administration of resveratrol and cisplatin were significantly lower than those of resveratrol or cisplatin alone. These results strongly suggest that resveratrol can inhibit head and neck cancer progression through the REG III expression pathway and can be a potential sensitizer for anticancer therapy for patients with HNSCC.
Citation Format: Ichiro Ota, Shinji Mikami, Takashi Masui, Takahiro Kimura, Hirokazu Uemura, Hideyuki Okamoto, Shin Takasawa, Takashi Kitahara, Ryogo Shobatake. Resveratrol induced REG III and inhibited head and neck cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4199.
Abstract 4202: Resection of primary osteosarcoma tumors terminates self-seeding, increasing lung metastasis
Authors: Roberts Ryan D. , Saraf Amanda J. , Pommellet Helene Le , Evans Randall , Gross Amy C. 
Published: August 2018

Abstract
Like many solid tumors, osteosarcoma (OS) kills patients through metastatic spread. In the case of OS, metastasis occurs almost exclusively to lung. Metastases most often arise after both resection of a primary tumor and completion of chemotherapy. In seeking to understand this long-appreciated pattern of spread, we sought to explore whether the presence of a primary tumor protects mice from developing OS lung metastasis through the process of self-seeding, and whether resection then faciliates metastatic lung colonization. Our data show that resection of a primary orthotopic tumor triggers the spread of OS tumor cells into the lung. Mice bearing a primary tumor have fewer labeled tumor cells recovered in the lung after IV inoculation. Many labeled cells can be recovered in the primary tumor. Supernatants from OS cell cultures drive OS cell chemotaxis with greater potency than serum. Several specific soluble factors produced by OS cells also drive chemotaxis of those same cells. Disruption of these signals may prevent self-seeding. Manipulation of this system may be used to remove OS cells from circulation.
Citation Format: Ryan D. Roberts, Amanda J. Saraf, Helene Le Pommellet, Randall Evans, Amy C. Gross. Resection of primary osteosarcoma tumors terminates self-seeding, increasing lung metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4202.
Abstract 4214: Characteristics of carcinoembryonic antigen-producing colorectal cancers: A population based study
Authors: Groover Sarah , Thirunavukarasu Pragatheeshwar , Payton Mark E. , Karippot Asha , Kaul Rashmi 
Published: August 2018

Abstract
Serum Carcinoembryonic Antigen (CEA) is a tumor marker often found to be elevated in colorectal cancer patients. Elevated CEA has been strongly associated with poor prognosis. However, not all colon cancer tumors produce CEA, and little is known about the patient and tumor characteristics between CEA-producing and non-CEA-producing tumors. We performed a retrospective analysis of all patients (n=120,571) diagnosed with colorectal adenocarcinoma from 2010 to 2014 in the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. All patients were designated as either positive/elevated (C1) or negative/normal (C0) based on the pretreatment serum CEA level. We performed univariate and multivariate analyses to identify variables associated with CEA-producing tumors. Of the 68,856 (57.1%) with available CEA information, 33,426 (48.5%) were C1. Median age was 65 years and 36,479 (53.0%) were male. Compared to C0 cancers, C1 cancers were significantly more likely (P&lt;0.001) to be female (49.3%% vs. 47.9%), black (58.4%), separated or never married (55.0% and 54.8%, respectively), higher grade (39.0%, 46.2%, 51.1% and 52.3% of well, moderately, poorly, and undifferentiated cancers, respectively), and of signet ring cell histology (61.1%). Multivariate analysis showed age, sex, race, marital status, and TNM stage to be independent prognostic factors associated with the diagnosis of CEA-producing tumors. This is the first report to describe differences in patient and tumor characteristics between CEA-producing and non-CEA-producing tumors in a large American population. About half of all colorectal adenocarcinomas are associated with elevated pre-treatment serum CEA levels. CEA-producing tumors are associated with female gender, non-Caucasian race, separated or never married marital status at diagnosis, and more extensive local, regional and metastatic disease.
Citation Format: Sarah Groover, Pragatheeshwar Thirunavukarasu, Mark E. Payton, Asha Karippot, Rashmi Kaul. Characteristics of carcinoembryonic antigen-producing colorectal cancers: A population based study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4214.