Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 146

Publication Record

Connections

Translating preclinical MRI methods to clinical oncology.
Hormuth DA, Sorace AG, Virostko J, Abramson RG, Bhujwalla ZM, Enriquez-Navas P, Gillies R, Hazle JD, Mason RP, Quarles CC, Weis JA, Whisenant JG, Xu J, Yankeelov TE
(2019) J Magn Reson Imaging 50: 1377-1392
MeSH Terms: Animals, Brain Neoplasms, Diffusion Magnetic Resonance Imaging, Humans, Hydrogen-Ion Concentration, Hypoxia, Image Processing, Computer-Assisted, Immunotherapy, Macromolecular Substances, Magnetic Resonance Imaging, Medical Oncology, Neoplasm Metastasis, Neoplasm Transplantation, Neoplasms, Oxygen, Reproducibility of Results, Theranostic Nanomedicine, Translational Medical Research
Show Abstract · Added March 30, 2020
The complexity of modern in vivo magnetic resonance imaging (MRI) methods in oncology has dramatically changed in the last 10 years. The field has long since moved passed its (unparalleled) ability to form images with exquisite soft-tissue contrast and morphology, allowing for the enhanced identification of primary tumors and metastatic disease. Currently, it is not uncommon to acquire images related to blood flow, cellularity, and macromolecular content in the clinical setting. The acquisition of images related to metabolism, hypoxia, pH, and tissue stiffness are also becoming common. All of these techniques have had some component of their invention, development, refinement, validation, and initial applications in the preclinical setting using in vivo animal models of cancer. In this review, we discuss the genesis of quantitative MRI methods that have been successfully translated from preclinical research and developed into clinical applications. These include methods that interrogate perfusion, diffusion, pH, hypoxia, macromolecular content, and tissue mechanical properties for improving detection, staging, and response monitoring of cancer. For each of these techniques, we summarize the 1) underlying biological mechanism(s); 2) preclinical applications; 3) available repeatability and reproducibility data; 4) clinical applications; and 5) limitations of the technique. We conclude with a discussion of lessons learned from translating MRI methods from the preclinical to clinical setting, and a presentation of four fundamental problems in cancer imaging that, if solved, would result in a profound improvement in the lives of oncology patients. Level of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:1377-1392.
© 2019 International Society for Magnetic Resonance in Medicine.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Insight into the Etiology of Undifferentiated Soft Tissue Sarcomas from a Novel Mouse Model.
Fleming JT, Brignola E, Chen L, Guo Y, Zhao S, Wang Q, Li B, Correa H, Ermilov AN, Dlugosz AA, Chiang C
(2019) Mol Cancer Res 17: 1024-1035
MeSH Terms: Animals, Gene Expression Regulation, Neoplastic, Hedgehog Proteins, Homeodomain Proteins, Humans, Mice, Neoplasm Transplantation, Nerve Tissue Proteins, Sarcoma, Ewing, Signal Transduction, Zebrafish Proteins, Zinc Finger Protein Gli3
Show Abstract · Added April 10, 2019
Aberrant activation of the Hedgehog signaling pathway has been linked to the formation of numerous cancer types, including the myogenic soft tissue sarcoma, embryonal rhabdomyosarcoma (eRMS). Here, we report , a novel mouse model in which human GLI2A, a constitutive activator of Hedgehog signaling, induced undifferentiated sarcomas that were phenotypically divergent from eRMS. Rather, sarcomas arising in mice featured some characteristics that were reminiscent of Ewing sarcoma. Even though it is widely understood that Ewing sarcoma formation is driven by gene fusions, a genetically defined mouse model is not well-established. While gene fusions were not present in sarcomas, precluding their designation as Ewing sarcoma, we did find that GLI2A induced expression of known gene targets essential to Ewing pathogenesis, most notably, . Moreover, we found that naïve mesenchymal progenitors originate tumors in mice. Altogether, our work provides a novel genetic mouse model, which directly connects oncogenic Hedgehog activity to the etiology of undifferentiated soft tissue sarcomas for the first time. IMPLICATIONS: The finding that activation of Gli2 transcription factor is sufficient to induce Ewing-like sarcomas provides a direct transformative role of the Hedgehog signaling pathway in undifferentiated soft tissue sarcoma.
©2019 American Association for Cancer Research.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Quantitative in vivo whole genome motility screen reveals novel therapeutic targets to block cancer metastasis.
Stoletov K, Willetts L, Paproski RJ, Bond DJ, Raha S, Jovel J, Adam B, Robertson AE, Wong F, Woolner E, Sosnowski DL, Bismar TA, Wong GK, Zijlstra A, Lewis JD
(2018) Nat Commun 9: 2343
MeSH Terms: Animals, Cell Line, Tumor, Cell Movement, Chick Embryo, Collagen, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Nude, Mice, SCID, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Transplantation, Phenotype, Prostatic Neoplasms, RNA Interference, RNA, Small Interfering
Show Abstract · Added April 10, 2019
Metastasis is the most lethal aspect of cancer, yet current therapeutic strategies do not target its key rate-limiting steps. We have previously shown that the entry of cancer cells into the blood stream, or intravasation, is highly dependent upon in vivo cancer cell motility, making it an attractive therapeutic target. To systemically identify genes required for tumor cell motility in an in vivo tumor microenvironment, we established a novel quantitative in vivo screening platform based on intravital imaging of human cancer metastasis in ex ovo avian embryos. Utilizing this platform to screen a genome-wide shRNA library, we identified a panel of novel genes whose function is required for productive cancer cell motility in vivo, and whose expression is closely associated with metastatic risk in human cancers. The RNAi-mediated inhibition of these gene targets resulted in a nearly total (>99.5%) block of spontaneous cancer metastasis in vivo.
0 Communities
1 Members
0 Resources
MeSH Terms
lncRNA Epigenetic Landscape Analysis Identifies EPIC1 as an Oncogenic lncRNA that Interacts with MYC and Promotes Cell-Cycle Progression in Cancer.
Wang Z, Yang B, Zhang M, Guo W, Wu Z, Wang Y, Jia L, Li S, Cancer Genome Atlas Research Network, Xie W, Yang D
(2018) Cancer Cell 33: 706-720.e9
MeSH Terms: Animals, Binding Sites, Breast Neoplasms, Cell Cycle, Cell Line, Tumor, CpG Islands, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Humans, Mice, Neoplasm Transplantation, Prognosis, Promoter Regions, Genetic, Proto-Oncogene Proteins c-myc, RNA, Long Noncoding, Up-Regulation
Show Abstract · Added October 30, 2019
We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1,006 lncRNA genes in cancer, including EPIC1 (epigenetically-induced lncRNA1). Overexpression of EPIC1 is associated with poor prognosis in luminal B breast cancer patients and enhances tumor growth in vitro and in vivo. Mechanistically, EPIC1 promotes cell-cycle progression by interacting with MYC through EPIC1's 129-283 nt region. EPIC1 knockdown reduces the occupancy of MYC to its target genes (e.g., CDKN1A, CCNA2, CDC20, and CDC45). MYC depletion abolishes EPIC1's regulation of MYC target and luminal breast cancer tumorigenesis in vitro and in vivo.
Copyright © 2018 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Spin-lock imaging of 3-o-methyl-D glucose (3oMG) in brain tumors.
Zu Z, Jiang X, Xu J, Gore JC
(2018) Magn Reson Med 80: 1110-1117
MeSH Terms: 3-O-Methylglucose, Animals, Brain, Brain Neoplasms, Cell Line, Tumor, Contrast Media, Diagnosis, Computer-Assisted, Glioblastoma, Glucose, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Neoplasm Transplantation, Neuroimaging, Rats
Added March 14, 2018
0 Communities
2 Members
0 Resources
14 MeSH Terms
Lactate Metabolism in Human Lung Tumors.
Faubert B, Li KY, Cai L, Hensley CT, Kim J, Zacharias LG, Yang C, Do QN, Doucette S, Burguete D, Li H, Huet G, Yuan Q, Wigal T, Butt Y, Ni M, Torrealba J, Oliver D, Lenkinski RE, Malloy CR, Wachsmann JW, Young JD, Kernstine K, DeBerardinis RJ
(2017) Cell 171: 358-371.e9
MeSH Terms: Animals, Blood Chemical Analysis, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Citric Acid Cycle, Disease Models, Animal, Female, Glyceric Acids, Heterografts, Humans, Lactic Acid, Lung Neoplasms, Male, Mice, Monocarboxylic Acid Transporters, Neoplasm Transplantation, Symporters
Show Abstract · Added March 28, 2019
Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small-cell lung cancers (NSCLCs) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here, we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell-autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
LIM-Only Protein 4 (LMO4) and LIM Domain Binding Protein 1 (LDB1) Promote Growth and Metastasis of Human Head and Neck Cancer (LMO4 and LDB1 in Head and Neck Cancer).
Simonik EA, Cai Y, Kimmelshue KN, Brantley-Sieders DM, Loomans HA, Andl CD, Westlake GM, Youngblood VM, Chen J, Yarbrough WG, Brown BT, Nagarajan L, Brandt SJ
(2016) PLoS One 11: e0164804
MeSH Terms: Adaptor Proteins, Signal Transducing, Animals, Carcinoma, Squamous Cell, Cell Line, Tumor, Cell Movement, Cell Proliferation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Humans, LIM Domain Proteins, Mice, Mouth Neoplasms, Neoplasm Metastasis, Neoplasm Transplantation, Tissue Culture Techniques, Transcription Factors
Show Abstract · Added March 29, 2017
Squamous cell carcinoma of the head and neck (HNSCC) accounts for more than 300,000 deaths worldwide per year as a consequence of tumor cell invasion of adjacent structures or metastasis. LIM-only protein 4 (LMO4) and LIM-domain binding protein 1 (LDB1), two directly interacting transcriptional adaptors that have important roles in normal epithelial cell differentiation, have been associated with increased metastasis, decreased differentiation, and shortened survival in carcinoma of the breast. Here, we implicate two LDB1-binding proteins, single-stranded binding protein 2 (SSBP2) and 3 (SSBP3), in controlling LMO4 and LDB1 protein abundance in HNSCC and in regulating specific tumor cell functions in this disease. First, we found that the relative abundance of LMO4, LDB1, and the two SSBPs correlated very significantly in a panel of human HNSCC cell lines. Second, expression of these proteins in tumor primaries and lymph nodes involved by metastasis were concordant in 3 of 3 sets of tissue. Third, using a Matrigel invasion and organotypic reconstruct assay, CRISPR/Cas9-mediated deletion of LDB1 in the VU-SCC-1729 cell line, which is highly invasive of basement membrane and cellular monolayers, reduced tumor cell invasiveness and migration, as well as proliferation on tissue culture plastic. Finally, inactivation of the LDB1 gene in these cells decreased growth and vascularization of xenografted human tumor cells in vivo. These data show that LMO4, LDB1, and SSBP2 and/or SSBP3 regulate metastasis, proliferation, and angiogenesis in HNSCC and provide the first evidence that SSBPs control LMO4 and LDB1 protein abundance in a cancer context.
1 Communities
1 Members
0 Resources
16 MeSH Terms
Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine.
Manning HC, Buck JR, Cook RS
(2016) J Nucl Med 57 Suppl 1: 60S-8S
MeSH Terms: Animals, Breast Neoplasms, Disease Models, Animal, Female, Humans, Mammary Neoplasms, Experimental, Mice, Molecular Imaging, Neoplasm Transplantation, Precision Medicine, Radionuclide Imaging
Show Abstract · Added February 11, 2016
Representing an enormous health care and socioeconomic challenge, breast cancer is the second most common cancer in the world and the second most common cause of cancer-related death. Although many of the challenges associated with preventing, treating, and ultimately curing breast cancer are addressable in the laboratory, successful translation of groundbreaking research to clinical populations remains an important barrier. Particularly when compared with research on other types of solid tumors, breast cancer research is hampered by a lack of tractable in vivo model systems that accurately recapitulate the relevant clinical features of the disease. A primary objective of this article was to provide a generalizable overview of the types of in vivo model systems, with an emphasis primarily on murine models, that are widely deployed in preclinical breast cancer research. Major opportunities to advance precision cancer medicine facilitated by molecular imaging of preclinical breast cancer models are discussed.
© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
0 Communities
2 Members
0 Resources
11 MeSH Terms
Identification of p62/SQSTM1 as a component of non-canonical Wnt VANGL2-JNK signalling in breast cancer.
Puvirajesinghe TM, Bertucci F, Jain A, Scerbo P, Belotti E, Audebert S, Sebbagh M, Lopez M, Brech A, Finetti P, Charafe-Jauffret E, Chaffanet M, Castellano R, Restouin A, Marchetto S, Collette Y, Gonçalvès A, Macara I, Birnbaum D, Kodjabachian L, Johansen T, Borg JP
(2016) Nat Commun 7: 10318
MeSH Terms: Adaptor Proteins, Signal Transducing, Animals, Blotting, Western, Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Lobular, Cell Line, Tumor, Cell Migration Assays, Cell Movement, Cell Polarity, Cell Proliferation, DNA Copy Number Variations, Embryo, Nonmammalian, Female, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, MAP Kinase Signaling System, Mass Spectrometry, Membrane Proteins, Mice, Microscopy, Electron, Middle Aged, Neoplasm Transplantation, Prognosis, Proportional Hazards Models, RNA, Messenger, Sequestosome-1 Protein, Wnt Signaling Pathway, Xenopus
Show Abstract · Added April 10, 2018
The non-canonical Wnt/planar cell polarity (Wnt/PCP) pathway plays a crucial role in embryonic development. Recent work has linked defects of this pathway to breast cancer aggressiveness and proposed Wnt/PCP signalling as a therapeutic target. Here we show that the archetypal Wnt/PCP protein VANGL2 is overexpressed in basal breast cancers, associated with poor prognosis and implicated in tumour growth. We identify the scaffold p62/SQSTM1 protein as a novel VANGL2-binding partner and show its key role in an evolutionarily conserved VANGL2-p62/SQSTM1-JNK pathway. This proliferative signalling cascade is upregulated in breast cancer patients with shorter survival and can be inactivated in patient-derived xenograft cells by inhibition of the JNK pathway or by disruption of the VANGL2-p62/SQSTM1 interaction. VANGL2-JNK signalling is thus a potential target for breast cancer therapy.
0 Communities
1 Members
0 Resources
MeSH Terms
Drug response in organoids generated from frozen primary tumor tissues.
Walsh AJ, Cook RS, Sanders ME, Arteaga CL, Skala MC
(2016) Sci Rep 6: 18889
MeSH Terms: Antineoplastic Agents, Breast Neoplasms, Cell Line, Tumor, Cell Survival, Cryopreservation, Female, Humans, Neoplasm Transplantation, Organoids, Tissue Culture Techniques
Show Abstract · Added February 4, 2016
Primary tumor organoids grown in three-dimensional culture provide an excellent platform for studying tumor progression, invasion, and drug response. However, organoid generation protocols require fresh tumor tissue, which limits organoid research and clinical use. This study investigates cellular morphology, viability, and drug response of organoids derived from frozen tissues. The results demonstrate that viable organoids can be grown from flash-frozen and thawed tissue and from bulk tissues slowly frozen in DMSO supplemented media. While the freezing process affects the basal metabolic rate of the cells, the optical metabolic imaging index correlates between organoids derived from fresh and frozen tissue and can be used to detect drug response of organoids grown from frozen tissues. The slow, DMSO frozen tissue yielded organoids with more accurate drug response than the flash frozen tissues, and thus bulk tissue should be preserved for subsequent organoid generation by slow freezing in DMSO supplemented media.
0 Communities
2 Members
0 Resources
10 MeSH Terms