bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2675: 18F-FDG-PET/CT imaging analyses for liver metastases of human colon cancer xenografts in NOG mice.
Authors: Chijiwa Tsuyoshi , Kawai Kenji , Tsukada Hideo , Suemizu Hiroshi , Nakamura Masato 
Published: August 2014

Abstract
Colorectal cancer is one of the most common malignant diseases in the world, and its prognosis is generally poor. Liver metastases of colorectal cancer significantly affect the fates of patients. To further understand the pathological aspects of distant metastases, we have established liver metastasis models of human colon cancer xenografts in immune-deficient NOD/Shi-scid/IL-2Rγnull (NOG) mice. 18F-fluorodeoxyglucose positron emission tomography / x-ray computed tomography (18F-FDG-PET/CT) is useful in the clinical evaluation of various human cancers. While PET analysis was established to evaluate subcutaneous lesions of human cancer xenografts in mice, its application to internal lesions including liver metastases is still being developed. We applied PET approaches for the evaluation of in vivo metastatic lesions in the internal organs of living small experimental animals. In this study, we analyzed in vivo liver metastases of human colon cancer cell lines in NOG mice using PET imaging. Experimental liver metastases were established by intrasplenic injection of human colon cancer cell line HCT116 (1.0 x 105 or 1.0 x 106 cells/mouse). 18F-FDG-PET/CT scans were performed 2 weeks after xeno-transplantation. After PET/CT scans, histopathological examinations were also performed to precisely confirm lesions. 18F-FDG-PET/CT imaging clearly demonstrated multiple hot spots on livers in spite of disadvantages in the contrast between tumor soft tissues and markedly swollen livers. PET/CT analysis also disclosed increased standardized uptake values (SUV) of FDG in metastatic foci of NOG mice (control, SUVmean 0.450 ± 0.033, SUVmax 0.635 ± 0.017; 1.0 x 105 cells, 0.853 ± 0.087, 1.254 ± 0.237; 1.0 x 106 cells, 1.211 ± 0.108, 1.701 ± 0.158). There were significant differences in FDG uptakes between the three groups (ANOVA, p=0.017 in SUVmean, p=0.044 in SUVmax, n=2). We clearly and quantitatively detected liver metastasis images in NOG mice by 18F-FDG-PET/CT in vivo. Immunohistochemical examinations confirmed more metastatic foci and more severe hepatomegaly with 1.0 x 106 than 1.0 x 105 of HTC116 cell inoculations. PET/CT analysis of human cancer xenografts is a new and reliable system to evaluate metastatic lesions in internal organs. In conclusion, this model system is useful for analyzing metastatic mechanisms and developing new therapeutic approaches for the liver metastatic lesions of human cancer.
Citation Format: Tsuyoshi Chijiwa, Kenji Kawai, Hideo Tsukada, Hiroshi Suemizu, Masato Nakamura. 18F-FDG-PET/CT imaging analyses for liver metastases of human colon cancer xenografts in NOG mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2675. doi:10.1158/1538-7445.AM2013-2675
Abstract 2676: Measuring extracellular pH within in vivo tumors using acidoCEST MRI.
Authors: Chen Liu Qi , Howison Christine , Jeffery Justin , Robey Ian , Pagel Mark 
Published: August 2014

Abstract
INTRODUCTION. Extracelluar pH (pHe) is a hallmark for tumor microenvironment. We have developed a non-invasive MRI method that can accurately measure pHe to assess tumor acidosis, termed “acidoCEST MRI”. This method measures a ratio of the Chemical Exchange Saturation Transfer (CEST) effects of Iopromide, a FDA approved contrast agent for CT. Iopromide has two amides that generate different CEST effects, and a ratio of these CEST effects is correlated with pH over a range of 6.0-7.2 pH units, with a precision of 0.06 pH units, and in a manner that is independent of the agent's concentration and the sample's T1 relaxation time. We have applied acidoCEST MRI to monitor the effects of bicarbonate treatment on tumors.
METHOD. A CEST-FISP pulse sequence (2.8 μT, 5 sec, 90 Hz), with 54 saturation frequencies (+10 to -10 ppm) was used to acquire an acidoCEST image in 4.7 min on 7T MRI scanner. Each CEST spectrum was fitted to a sum of three Lorentzian line shapes (Matlab R2012B).
A mouse model of MDA-MB-231 mammary carcinoma subcutaneous flank tumor was treated with 200 mM of bicarbonate ad libitum. acidoCEST MRI was performed 1 day before and 1 day after introducing bicarbonate treatment. A bolus of 200 μL of 976 mM iopromide was injected i.v., followed by an infusion of 150 μL/hour of iopromide. Six series of acidoCEST spectroscopic images were acquired for 28 min.
RESULTS: We were able to measure an increased in pH in tumor before and after bicarbonate therapy. As shown in the table, only half of the mice studied showed a significant increase in pH after bicarbonate treatment. This is because the limit of quantification of acidoCEST using Iopromide as contrast agent was pH 7.20.
Discussion: acidoCEST MRI using Iopromide as contrast agent can measure pH of the tumor with good precision and can be applied to monitor pH-modulating therapy such as bicarbonate treatment. Our method has strong clinical translation potential because it uses low saturation powers, incomplete saturation, and a clinically approved contrast agent.
Summary of acidoCEST measurements on mammary carcinoma tumors before and after bicarbonate treatment Mouse before bicarbonate treatment after bicarbonate treatment #1 pH 6.50 ± 0.09 pH 7.15 ± 0.14 (p &lt; 0.01) #2 pH 6.49 ± 0.09 pH 7.20 ± 0.00 (p &lt; 0.01) #3 pH 6.53 ± 0.10 pH 7.14 ± 0.14 (p &lt; 0.01) #4 pH 6.91 ± 0.11 pH 7.10 ± 0.13 (p &lt; 0.02) #5 pH 7.13 ± 0.12 pH 7.16 ± 0.12 #6 pH 7.02 ± 0.13 pH 7.13 ± 0.10 #7 (necrotic tumor) pH 7.20 ± 0.00 pH 7.19 ± 0.06 #8 (necrotic tumor) pH 7.17 ± 0.09 pH 7.17 ± 0.10
Citation Format: Liu Qi Chen, Christine Howison, Justin Jeffery, Ian Robey, Mark Pagel. Measuring extracellular pH within in vivo tumors using acidoCEST MRI. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2676. doi:10.1158/1538-7445.AM2013-2676
Abstract 2680: Improved imaging of orthotopic BxPC3 pancreatic adenocarcinoma xenograft using animal PET/CT.
Authors: Tuomela Johanna M. , Seppänen Jani , Haavisto Laura , Fosrback Sarita , Vahlberg Tero , Solin Olof , Haaparanta Merja 
Published: August 2014

Abstract
Treatment of pancreatic adenocarcinoma is difficult because the location of the lesion is often unknown. 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]FDOPA) is used for imaging of neuroendocrine tumours, which take up and decarboxylate amine precursors. [18F]FDOPA use in diagnostic pancreatic imaging has increased, since the exocrine pancreas synthesises dopamine. We studied the uptake of [18F]FDOPA in healthy and diseased pancreas. Mice bearing orthotopic BxPC3 pancreatic adenocarcinoma and sham-operated controls were pre-treated with enzyme inhibitors of aromatic amino acid decarboxylase (AADC), catechol-O-methyl transferase (COMT), monoamine oxidase A (MAO-A) or combinations of these inhibitors. Mice were injected with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) or [18F]FDOPA and scanned via positron emission tomography/computed tomography. The absolute [18F]FDOPA uptake was determined from selected tissues using a well counter. The intratumoural biodistribution pattern of [18F]FDOPA was recorded autoradiographically. The main FDOPA metabolites present in pancreatic samples were determined with high-performance liquid chromatography. [18F]FDG uptake was high in pancreatic tumours, while [18F]FDOPA uptake was highest in healthy pancreas and significantly lower in tumour-bearing pancreas, independent of pre-treatment. [18F]FDOPA uptake in pancreas was lowest with vehicle pre-treatment and highest with pre-treatment with the inhibitor of AADC. When mice received COMT+MAO-A inhibitors, uptake was high in healthy pancreas but low in tumour-bearing pancreas. Unequal uptake may be due to blockade of metabolism and increased availability of [18F]fluorodopamine due to the employed enzyme inhibitors. Combined use of [18F]FDG and [18F]FDOPA is suitable for imaging pancreatic tumours. Pre-treatment with COMT+MAO-A inhibitors improved the differentiation of pancreas from surrounding tissue and healthy pancreas from tumour.
Citation Format: Johanna M. Tuomela, Jani Seppänen, Laura Haavisto, Sarita Fosrback, Tero Vahlberg, Olof Solin, Merja Haaparanta. Improved imaging of orthotopic BxPC3 pancreatic adenocarcinoma xenograft using animal PET/CT. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2680. doi:10.1158/1538-7445.AM2013-2680
Abstract 2682: Imaging prostate cancer in an orthotopic prostate model using a 68Ga-Bombesin (BB2r) radiopharmaceutical.
Authors: Richmond Kelsey , Rold Tammy , Szczodroski Ashley , Ma Lixin , Cai Quanyu , Hoffman Timothy 
Published: August 2014

Abstract
Introduction: There continues to remain a significant need to develop molecular imaging agents for the diagnosis and staging of prostate cancer. The association of the bombesin receptor subtype 2 (BB2r) and prostate cancer is well known and several groups including our own have developed unique radiopharmaceutical targeting strategies for the delivery of BB2r agonists and antagonists. Earlier work from our group utilizing BB2r agonists and antagonists labeled with 99mTc and 111In demonstrated selective targeting of simple flank xenograft models of prostate cancer. We are now presenting a preclinical evaluation of 68Ga-BB2r PET imaging using an orthotopic prostate SCID mouse model.
Methods: The BB2r antagonist, DOTA-4-Amino-Carboxymethyl-Piperidine-DPhe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, (Eur J Nucl Med Mol Imaging 38(1):97, 2011) was synthesized commercially. 68Ga was obtained from a commercially available Ge-68/Ga-68 generator. The peptide (40ug) was radiolabeled with 10-20mCi (270-740MBq) of 68Ga using an automated radiosynthesis system. Reverse phase HPLC (C-18) was employed for quality control analysis using a combination of radiometric and UV analysis. Orthotopic prostate xenografted male SCID mice were administered ∼0.3mCi (11.1 MBq) of 68Ga labeled peptide and combined PET/CT imaging was performed 4 hours following injection. Each mouse received 100uL of Visipaque® before imaging commenced. Concurrent 7 T MRI data was obtained for anatomic verification of prostate tumor involvement. Pathologic confirmation of tumor involvement within the prostate bed was obtained.
Results: The 68Ga BB2r antagonists could be readily prepared in high radiochemical yield and purity as verified by HPLC. Orthotopic prostate tumor xenografts were clearly visualized using PET/CT imaging. The predominant renal clearance of the tracer presented challenges in differentiating active tumor involvement within the prostate bed from bladder contents. These challenges could be partially addressed by employing concurrent CT contrast agent administration as an aid in accurately defining bladder contents and balder wall delineation.
Conclusions: These results demonstrate that 68Ga BB2r antagonist PET/CT imaging holds the potential to accurately differentiate BB2r positive prostate tumor growth within the prostate bed as a potential screening and diagnostic tool.
Citation Format: Kelsey Richmond, Tammy Rold, Ashley Szczodroski, Lixin Ma, Quanyu Cai, Timothy Hoffman. Imaging prostate cancer in an orthotopic prostate model using a 68Ga-Bombesin (BB2r) radiopharmaceutical. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2682. doi:10.1158/1538-7445.AM2013-2682
Abstract 2686: RSK2/CREB/Fascin-1 signaling is important for tumor metastasis.
Authors: Li Dan , Jin Lingtao , Alesi Gina , Kim Young Mee , Wang Dongsheng , Lee Benjamin H , Taunton Jack , Magliocca Kelly R , Chen Zhuo Georgia , Kang Sumin 
Published: August 2014

Abstract
Metastasis is the leading cause of death in patients with breast, lung or head and neck cancers. However, the molecular mechanisms underlying metastases in these cancers remain unclear. We found that the p90 ribosomal S6 kinase 2 (RSK2)-cAMP response element-binding (CREB) pathway is commonly activated in diverse metastatic human cancer cells, leading to upregulation of a CREB transcription target Fascin-1. We also observed that the protein expression patterns of RSK2 and Fascin-1 correlate in primary human tumor tissue samples from HNSCC patients. Moreover, knockdown of RSK2 disrupts filopodia formation and bundling in highly invasive cancer cells, leading to attenuated cancer cell invasion in vitro and tumor metastasis in vivo, while expression of Fascin-1 significantly rescues these phenotypes. Furthermore, targeting RSK2 by a small molecule RSK inhibitor FMK-MEA effectively attenuated the invasive and metastatic potential of cancer cells in vitro and in vivo, respectively. Together, our findings for the first time link the RSK2-CREB signaling to filopodia formation and bundling by upregulating Fascin-1, providing a pro-invasive and pro-metastatic advantage to human cancers; protein effectors of RSK2-CREB-Fascin-1 pathway represents promising biomarkers and therapeutic targets in clinical prognosis and treatment of metastatic human cancers.
Citation Format: Dan Li, Lingtao Jin, Gina Alesi, Young Mee Kim, Dongsheng Wang, Benjamin H Lee, Jack Taunton, Kelly R Magliocca, Zhuo Georgia Chen, Sumin Kang. RSK2/CREB/Fascin-1 signaling is important for tumor metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2686. doi:10.1158/1538-7445.AM2013-2686
Abstract 2689: Drivers of cancer cell invasion and metastasis.
Authors: Sharif Ghada M. , Schmidt Marcel O. , Shuptrine Casey , Weiner Louis M. , Hu Zhang-Zhi , Riegel Anna T. , Wellstein Anton 
Published: August 2014

Abstract
Metastatic spread of cancer cells from their primary site requires invasion into the vasculature, evasion at the distant organ site and colonization of the distant organ. Here we studied mechanisms of attachment and invasion into endothelial monolayers by cancer cells to identify driver molecules and signaling pathways that are crucial for the invasive and metastatic phenotype. Different human and mouse cancer cell lines were transduced with lentiviral-based, genome-wide or kinome-targeted shRNA libraries. Cancer cell populations of different invasive and metastatic phenotype were then selected for their loss- or gain-of-function respectively in endothelial invasion in vitro or by tumor growth and metastasis selection in vivo. After several rounds of selection, the respective shRNA targeted genes were identified from the selected cancer cell populations or from clonal cell lines. Eighteen different genes targeted by two to four distinct shRNAs each were identified in the in vitro selection for endothelial attachment and invasion. The function of the genes as well as the clinical significance appear to explain their phenotypic selection.
Citation Format: Ghada M. Sharif, Marcel O. Schmidt, Casey Shuptrine, Louis M. Weiner, Zhang-Zhi Hu, Anna T. Riegel, Anton Wellstein. Drivers of cancer cell invasion and metastasis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2689. doi:10.1158/1538-7445.AM2013-2689
Abstract 2690: The role of musashi-1 in tumor progression in non-small cell lung cancer.
Authors: Boumber Yanis , Kudinov Alexander , Liu Xin , Ahn Young-Ho , Rodriguez Jaime , Wistuba Ignacio , Gibbons Don , Kurie Jonathan 
Published: August 2014

Abstract
We have previously developed an in vivo mouse model of metastatic lung adenocarcinoma by combining a mutant p53 allele (p53R175HΔG) with a KrasG12D allele (KrasLA1). From the tumors arising in KrasLA1/+; p53R172HΔG/+ mice, we have established lung adenocarcinoma cell lines (KP cells) with high (344SQ) or low (393P) metastatic potential. The metastatic potential of KP cells is governed by Zeb-1 and the microRNA-200 family, which interact through a double-negative feedback loop. Given that metastatic KP cells exhibit the capacity to form polarized epithelial spheres in Matrigel and undergo epithelial-to-mesenchymal transition (EMT) in response to extracellular cues, we hypothesized that stem cell factors serve as drivers of tumor cell invasion and metastasis in this model. We examined the expression of 13 stem cell factors in metastatic and non-metastatic KP cell lines using qPCR and found that Musashi-1 (Msi-1) was more highly expressed in metastatic KP cells, which was confirmed by western analysis. Msi1 is an RNA-binding protein that plays a central role during nervous system development, stem cell maintenance, and tumorigenesis. High levels of Msi1 have been reported in several malignancies including brain tumors, colon and breast cancer, and associate with poor survival in patients with breast and colon cancer. We have used a panel of human lung cancer cell lines and found Msi-1 protein to be expressed in lung adenocarcinoma and squamous carcinoma cell lines. Further analysis revealed that Msi-1 expression is up-regulated by Zeb-1 and down-regulated by miR-200, raising the possibility that Msi-1 functions as a downstream mediator of the Zeb-1/miR-200 axis, which we are currently investigating by carrying out Msi-1 loss-of-function and gain-of-function experiments and by analyzing human tissue microarrays to determine whether Msi-1 has prognostic value in patients. Our data suggests that Msi-1 is a candidate driver of tumor progression in NSCLC.
Citation Format: Yanis Boumber, Alexander Kudinov, Xin Liu, Young-Ho Ahn, Jaime Rodriguez, Ignacio Wistuba, Don Gibbons, Jonathan Kurie. The role of musashi-1 in tumor progression in non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2690. doi:10.1158/1538-7445.AM2013-2690
Abstract 2702: WAVE3 regulates NFκB signaling and sensitizes cancer cells to apoptosis and cell death driven by TNFα.
Authors: Davuluri Gangarao , Sossey-Alaoui Khalid , Plow Edward 
Published: August 2014

Abstract
ABSTRACT
WAVE3, a member of actin nucleation proteins promotes cancer invasion and metastasis, in part through regulation of expression and activity of key matrix metalloproteinases (MMPs) MMP9, which is centrally involved in invadopodia-mediated degradation of the extracellular matrix (ECM). MMP9 is also a major NFκB target gene, suggesting a potentially important role of WAVE3 in this pathway. Mechanistically, we found that loss of WAVE3 in cancer cells leads to significant inhibition of TNFα-induced NFκB activation as a result of de-stabilization of the IκBα-NFκB complex. Conversely, overexpression of WAVE3 was sufficient to enhance NFκB activity by stabilizing the IκBα-NFκB complex. We used both pharmacological and genetic manipulations of NFκB effector molecules and identified IKKβ but not IKKα as the primary upstream target for WAVE3-mediated regulation of NFκB activity. We also showed that loss of WAVE3 resulted in a significant inhibition of TNFα-mediated MMP9 expression and activity. Loss of WAVE3 also sensitized cancer cells to TNFα-driven apoptosis and cell death. Finally, we showed that either the basic rich (BR) or the proline rich (PR) domain of WAVE3 is sufficient to modulate NFkB signaling. Our results identify a novel function of WAVE3 in NFκB signaling, where its activity is essential for the stabilization of NFκB complex that promotes the metastatic phenotype of cancer cells. Therefore, therapeutic targeting of WAVE3 may prove beneficial for preventing or reducing the metastatic burden in cancer patients.
Citation Format: Gangarao Davuluri, Khalid Sossey-Alaoui, Edward Plow. WAVE3 regulates NFκB signaling and sensitizes cancer cells to apoptosis and cell death driven by TNFα. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2702. doi:10.1158/1538-7445.AM2013-2702
Abstract 2704: Ectopic expression of CHST11 promotes proliferation and migration of human breast cancer cells.
Authors: Behrens Alice , Jousheghany Fariba , Yao-Borengasser Aiwei , Kieber-Emmons Thomas , Monzavi-Karbassi Behjatolah 
Published: August 2014

Abstract
Introduction. We have previously demonstrated that the expression levels of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with P-selectin binding and aggressiveness (basal-like, triple-negative and mesenchymal phenotype) of human breast cancer. The present study was performed to establish stably transfected cell lines and study the functional role of CHST11 in human breast cancer cells. Methods. MCF7 cells were transfected with a plasmid vector containing the CHST11 coding sequence. Stable transfectants, MCF-7-CHST11, were established. Flow cytometry and real-time PCR were used for expression analysis. Metastatic phenotype of cells was characterized through conduction of proliferation and migration assays. Morphology and growth pattern of MCF-7-CHST11 cells were monitored and compared to parental MCF-7 cells. Results. We observed that MCF-7-CHST11 reacted strongly with anti-chondroitin sulfate A (CS-A) antibody and recombinant P-selectin. CS-A is the immediate product of CHST11 activity. CHST11 expression significantly affected cell proliferation as MCF-7-CHST11 cells grew much faster. Migration assay using transwell chamber showed high migratory potential for MCF-7-CHST11 cells as compared to the parental MCF-7 cells. The significant migratory advantage was not proliferation dependent. The CHST11expression affected the morphology of cells and cell spreading behavior consistent with more efficient anchorage independent growth. Colony formation in soft agar, Invasion and adhesion assays are being performed at the present time. We are planning more experiments to study mechanisms involved. Conclusions. The data confirm that the CHST11 products on the cell surface can serve as P-selectin ligands. The results indicate that the CHST11 expression can affect metastatic phenotype of cancer cells by promoting cellular proliferation and migratory potential.
Citation Format: Alice Behrens, Fariba Jousheghany, Aiwei Yao-Borengasser, Thomas Kieber-Emmons, Behjatolah Monzavi-Karbassi. Ectopic expression of CHST11 promotes proliferation and migration of human breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2704. doi:10.1158/1538-7445.AM2013-2704