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: 11 to 20 of 25

Publication Record

Connections

Low levels of tumor necrosis factor alpha increase tumor growth by inducing an endothelial phenotype of monocytes recruited to the tumor site.
Li B, Vincent A, Cates J, Brantley-Sieders DM, Polk DB, Young PP
(2009) Cancer Res 69: 338-48
MeSH Terms: Animals, Carcinoma, Lewis Lung, Cell Differentiation, Cell Growth Processes, Cells, Cultured, Endothelial Cells, Humans, Lipopolysaccharide Receptors, Melanoma, Experimental, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Monocytes, Neovascularization, Pathologic, Receptors, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha
Show Abstract · Added March 15, 2013
Microenvironmental cues instruct infiltrating tumor-associated myeloid cells to drive malignant progression. A subpopulation of tumor-associated myeloid cells coexpressing endothelial and myeloid markers, although rare in peripheral blood, are primarily associated with tumors where they enhance tumor growth and angiogenesis. These biphenotypic vascular leukocytes result from the endothelial differentiation of myeloid progenitors, a process regulated by tumor necrosis factor (TNF)alpha in vitro. An in vivo increase in tumor-derived TNFalpha expression promoted tumor growth and vascularity of mouse melanoma, lung cancer, and mammary tumors. Notably, tumor growth was accompanied by a significant increase in myeloid/endothelial biphenotypic populations. TNFalpha-associated tumor growth, vascularity, and generation of tumor vascular leukocytes in mouse melanoma tumors were dependent on intact host TNFalpha receptors. Importantly, TNFalpha-expressing tumors did not exhibit increased inflammation over control tumors, suggesting a unique action related to myeloid to endothelial differentiation. Our studies suggest that TNFalpha constitutes a tumor microenvironment signal that biases recruited monocytes toward a proangiogenic/provasculogenic myeloid/endothelial phenotype.
1 Communities
3 Members
0 Resources
18 MeSH Terms
IkappaB kinase-alpha regulates endothelial cell motility and tumor angiogenesis.
DeBusk LM, Massion PP, Lin PC
(2008) Cancer Res 68: 10223-8
MeSH Terms: Animals, Carcinoma, Lewis Lung, Cell Movement, Cells, Cultured, Endothelial Cells, Female, Humans, I-kappa B Kinase, Mice, Neovascularization, Pathologic, Up-Regulation
Show Abstract · Added March 5, 2014
The transcription factor nuclear factor-kappaB (NF-kappaB) is constitutively activated in many types of cancers and has been implicated in gene expression important for angiogenesis, tumor growth, progression, and metastasis. Here, we show that the NF-kappaB activator, IkappaB kinase-alpha (IKKalpha), but not IKKbeta, promotes endothelial cell motility and tumor angiogenesis. IKKalpha is elevated in tumor vasculature compared with normal endothelium. Overexpression of IKKalpha in endothelial cells promoted cell motility and vascular tubule formation in a three-dimensional culture assay, and conversely, knockdown of IKKalpha in endothelial cells inhibited cell motility, compared with controls. Interestingly, blocking NF-kappaB activation totally abolished IKKalpha-induced angiogenic function. Furthermore, using a tumor and endothelial cell cotransplantation model, we show that overexpression of IKKalpha in endothelial cells significantly increased tumor vascular formation compared with controls, which contributed to increased tumor growth and tumor cell proliferation, and decreased tumor cell apoptosis. Collectively, these findings have identified a new function for IKKalpha through the canonical NF-kappaB pathway in tumor angiogenesis.
0 Communities
1 Members
0 Resources
11 MeSH Terms
Host A(2B) adenosine receptors promote carcinoma growth.
Ryzhov S, Novitskiy SV, Zaynagetdinov R, Goldstein AE, Carbone DP, Biaggioni I, Dikov MM, Feoktistov I
(2008) Neoplasia 10: 987-95
MeSH Terms: Animals, Carcinoma, Lewis Lung, Leukocyte Common Antigens, Mice, Neoplasms, Neovascularization, Pathologic, Receptor, Adenosine A2B, Vascular Endothelial Growth Factor A
Show Abstract · Added December 10, 2013
Recent studies suggest that tumor-infiltrating immune cells can benefit the tumor by producing factors that promote angiogenesis and suppress immunity. Because the tumor microenvironment is characterized by high adenosine levels, we hypothesized that the low-affinity A(2B) adenosine receptor located on host immune cells may participate in these effects. In the current study, we tested this hypothesis in a Lewis lung carcinoma isograft model using A(2B) receptor knockout (A(2B)KO) mice. These mice exhibited significantly attenuated tumor growth and longer survival times after inoculation with Lewis lung carcinoma compared to wild type (WT) controls. Lewis lung carcinoma tumors in A(2B)KO mice contained significantly lower levels of vascular endothelial growth factor (VEGF) compared to tumors growing in WT animals. This difference was due to VEGF production by host cells, which comprised 30 +/- 2% of total tumor cell population. Stimulation of adenosine receptors on WT tumor-infiltrating CD45+ immune cells increased VEGF production fivefold, an effect not seen in tumor-associated CD45+ immune cells lacking A(2B) receptors. In contrast, we found no significant difference in VEGF production between CD45- tumor cells isolated from WT and A(2B)KO mice. Thus, our data suggest that tumor cells promote their growth by exploiting A(2B) adenosine receptor-dependent regulation of VEGF in host immune cells.
0 Communities
3 Members
0 Resources
8 MeSH Terms
Imaging mass spectrometry of intact proteins from alcohol-preserved tissue specimens: bypassing formalin fixation.
Chaurand P, Latham JC, Lane KB, Mobley JA, Polosukhin VV, Wirth PS, Nanney LB, Caprioli RM
(2008) J Proteome Res 7: 3543-55
MeSH Terms: Animals, Brain, Carcinoma, Lewis Lung, Desiccation, Electrophoresis, Ethanol, Fixatives, Formaldehyde, Kidney, Liver, Lung, Mice, Paraffin Embedding, Proteome, Solubility, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tissue Preservation
Show Abstract · Added March 5, 2014
Imaging mass spectrometry is becoming a key technology for the investigation of the molecular content of biological tissue sections in direct correlation with the underlying histology. Much of our work has been done with fresh-frozen tissue sections that has undergone minimal protein degradation between the time a tissue biopsy is sampled and the time it is snap-frozen so that no preserving or fixing agents need to be added to the frozen biopsy. However, in many sampling environments, immediate flash freezing may not be possible and so we have explored the use of ethanol-preserved, paraffin-embedded tissue specimens for proteomic analyses. Solvent-only preserved tissue specimens provide long-term preservation at room temperature, generation of high quality histological sections and little if any chemical alteration of the proteins. Using mouse organs, several key steps involved in the tissue dehydration process have been investigated to assess the potential of such preserved specimens for profiling and imaging mass spectrometry investigations.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Integrin alpha2beta1 is the required receptor for endorepellin angiostatic activity.
Woodall BP, Nyström A, Iozzo RA, Eble JA, Niland S, Krieg T, Eckes B, Pozzi A, Iozzo RV
(2008) J Biol Chem 283: 2335-43
MeSH Terms: Angiostatic Proteins, Animals, Carcinoma, Lewis Lung, Cell Line, Tumor, Endothelium, Vascular, Female, Heparan Sulfate Proteoglycans, Humans, Integrin alpha1beta1, Integrin alpha2beta1, Mice, Mice, Knockout, Neoplasm Transplantation, Neovascularization, Pathologic, Peptide Fragments, Transplantation, Heterologous
Show Abstract · Added February 24, 2014
Endorepellin, the C-terminal module of perlecan, has angiostatic activity. Here we provide definitive genetic and biochemical evidence that the functional endorepellin receptor is the alpha2beta1 integrin. Notably, the specific endorepellin binding to the receptor was cation-independent and was mediated by the alpha2 I domain. We show that the anti-angiogenic effects of endorepellin cannot occur in the absence of alpha2beta1. Microvascular endothelial cells from alpha2beta1(-/-) mice, but not those isolated from either wild-type or alpha1beta1(-/-) mice, did not respond to endorepellin. Moreover, syngeneic Lewis lung carcinoma xenografts in alpha2beta1(-/-) mice failed to respond to systemic delivery of endorepellin. In contrast, endorepellin inhibited tumor growth and angiogenesis in the wild-type mice expressing integrin alpha2beta1. We conclude that the angiostatic effects of endorepellin in vivo are mediated by a specific interaction of endorepellin with the alpha2beta1 integrin receptor.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Use of bioluminescent imaging to investigate the role of nuclear factor-kappaBeta in experimental non-small cell lung cancer metastasis.
Stathopoulos GT, Sherrill TP, Han W, Sadikot RT, Polosukhin VV, Fingleton B, Yull FE, Blackwell TS
(2008) Clin Exp Metastasis 25: 43-51
MeSH Terms: Animals, Carcinoma, Lewis Lung, Carcinoma, Non-Small-Cell Lung, Humans, I-kappa B Kinase, Luciferases, Luminescent Agents, Lung Neoplasms, Mice, NF-kappa B, Neoplasm Metastasis, Synaptotagmin I
Show Abstract · Added February 26, 2013
Nuclear factor (NF)-kappaB is frequently over-expressed in non-small cell lung cancer (NSCLC), but the exact role of this observation remains unclear. In this regard, activation of the transcription factor may govern distinct steps of NSCLC progression, such as carcinogenesis, angiogenesis, and metastasis. In these studies we attempted to dissect the effects of two proteins of the NF-kappaB pathway (p65/RelA and IkappaBetaalpha) on experimental metastasis of murine NSCLC, using a novel approach of bioluminescent detection of NF-kappaB activation in tumor cells. Stable integration of a NF-kappaBeta reporter confirmed high basal activation of the transcription factor in mouse NSCLC cells in vitro and during experimental metastasis to the lungs, like human NSCLC. In the mouse model of NSCLC metastasis, NF-kappaBeta-dependent luciferase expression served as a reliable indicator of tumor cell delivery to the lungs, establishment of metastatic tumors, and lung tumor burden. In vitro transient p65/RelA and IkappaBetaalpha gene transfer to mouse NSCLC cells resulted, respectively, in significant NF-kappaB activation and inhibition, without affecting cell growth. However, p65/RelA overexpression in NSCLC cells drastically reduced in vivo metastasis to the lungs, while overexpression of IkappaBetaalpha had no effect. In conclusion, using bioluminescent detection of NF-kappaB activation in mouse lug adenocarcinoma cells, we found a negative impact of p65/RelA on NSCLC metastasis.
3 Communities
3 Members
0 Resources
12 MeSH Terms
Noninvasive assessment of tumor vasculature response to radiation-mediated, vasculature-targeted therapy using quantified power Doppler sonography: implications for improvement of therapy schedules.
Kim DW, Huamani J, Niermann KJ, Lee H, Geng L, Leavitt LL, Baheza RA, Jones CC, Tumkur S, Yankeelov TE, Fleischer AC, Hallahan DE
(2006) J Ultrasound Med 25: 1507-17
MeSH Terms: Animals, Apoptosis, Carcinoma, Lewis Lung, Mice, Mice, Inbred C57BL, Radiosurgery, Skin Window Technique, Ultrasonography
Show Abstract · Added November 13, 2013
OBJECTIVE - Stereotactic radiotherapy (ablative radiation) is a modality that holds considerable promise for effective treatment of intracranial and extracranial malignancies. Although tumor vasculature is relatively resistant to small fractionated doses of ionizing radiation, large ablative doses of ionizing radiation lead to effective demise of the tumor vasculature. The purpose of this study was (1) to noninvasively monitor and compare tumor physiologic parameters in response to ablative radiation treatments and (2) to use these noninvasive parameters to optimize the schedule of administration of radiation therapy.
METHODS - Lewis lung carcinoma tumors were implanted into C57BL/6 mice and treated with ablative radiation. The kinetics of change in physiologic parameters of a response to single-dose 20-Gy treatments was measured. Parameters studied included tumor blood flow, apoptosis, and proliferation rates. Serial tumor sections were stained to correlate noninvasive Doppler assessment of tumor blood flow with microvasculature histologic findings.
RESULTS - A single administration of 20 Gy led to an incomplete tumor vascular response, with subsequent recovery of tumor blood flow within 4 days after treatment. Sustained reduction of tumor blood flow by administering the successive ablative radiation treatment before tumor blood flow recovery led to a 3-fold tumor growth delay. The difference in tumor volumes at each measurement time point (every 2 days) was statistically significant (P=.016).
CONCLUSIONS - This study suggests a rational design of schedule optimization for radiation-mediated, vasculature-directed treatments guided by noninvasive assessment of tumor blood flow levels to ultimately improve the tumor response.
0 Communities
1 Members
0 Resources
8 MeSH Terms
Correlation between estimates of tumor perfusion from microbubble contrast-enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging.
Yankeelov TE, Niermann KJ, Huamani J, Kim DW, Quarles CC, Fleischer AC, Hallahan DE, Price RR, Gore JC
(2006) J Ultrasound Med 25: 487-97
MeSH Terms: Animals, Carcinoma, Lewis Lung, Contrast Media, Gadolinium DTPA, Image Enhancement, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Microbubbles, Neovascularization, Pathologic, Statistics as Topic, Ultrasonography
Show Abstract · Added December 10, 2013
OBJECTIVE - We compared measurements of tumor perfusion from microbubble contrast-enhanced sonography (MCES) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in an animal tumor model.
METHODS - Seven mice were implanted with Lewis lung carcinoma cells on their hind limbs and imaged 14 days later with a Philips 5- to 7-MHz sonography system (Philips Medical Systems, Andover, MA) and a Varian 7.0-T MRI system (Varian, Inc, Palo Alto, CA). For sonographic imaging 100 microL of a perfluoropropane microbubble contrast agent (Definity; Bristol-Myers Squibb Medical Imaging, Billerica, MA) was injected and allowed to reach a pseudo steady state, after which a high-mechanical index pulse was delivered to destroy the microbubbles within the field of view, and the replenishment of the microbubbles was imaged for 30 to 60 seconds. The MRI included acquisition of a T(10) map and 35 serial T(1)-weighted images (repetition time, 100 milliseconds; echo time, 3.1 milliseconds; alpha, 30 degrees ) after the injection of 100 microL of 0.2-mmol/kg gadopentetate dimeglumine (Magnevist; Berlex, Wayne, NJ). Region-of-interest and voxel-by-voxel analyses of both data sets were performed; microbubble contrast-enhanced sonography returned estimates of microvessel cross-sectional area, microbubble velocity, and mean blood flow, whereas DCE-MRI returned estimates of a perfusion-permeability index and the extravascular extracellular volume fraction.
RESULTS - Comparing similar regions of tumor tissue seen on sonography and MRI, region-of-interest analyses revealed a strong (r(2) = 0.57) and significant relationship (P < .002) between the estimates of perfusion obtained by the two modalities.
CONCLUSIONS - Microbubble contrast-enhanced sonography can effectively depict intratumoral heterogeneity in preclinical xenograft models when voxel-by-voxel analysis is performed, and this analysis correlates with similar DCE-MRI measurements.
0 Communities
3 Members
0 Resources
13 MeSH Terms
Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment.
Acuff HB, Carter KJ, Fingleton B, Gorden DL, Matrisian LM
(2006) Cancer Res 66: 259-66
MeSH Terms: Animals, Bone Marrow Cells, Bone Marrow Transplantation, Carcinoma, Lewis Lung, Cell Growth Processes, Cell Line, Tumor, Humans, Lung Neoplasms, Matrix Metalloproteinase 9, Mice, Mice, Inbred C57BL
Show Abstract · Added March 5, 2014
The role of specific stromal-derived matrix metalloproteinases (MMPs) was analyzed in experimental metastasis assays in wild-type and either MMP-9, MMP-7, or MMP-2 null mice. MMP-9 null mice showed an 81% reduction in Lewis lung carcinoma tumor number, whereas MMP-7 null mice showed a 42% increase in tumor number, and there was no difference in tumor number in MMP-2 null mice compared with wild-type controls. Similarly, in an orthotopic model of lung cancer, 50% fewer MMP-9 null mice were able to establish tumors in the lung compared with control mice, although the size of the tumors was not different. The effect of MMP-9 on lung tumor colonization was dependent on the expression of MMP-9 from bone marrow-derived cells and is most likely contributed by neutrophils. To examine temporal effects of stromal MMP-9, bioluminescence imaging from luciferase-expressing human lung cancer-derived A549 cells revealed that there were fewer tumor cells in the lungs of MMP-9 null mice as early as 19 hours after injection compared with control mice, with no difference in subsequent growth rates. Six hours after injection of tumor cells, MMP-9 null mice showed a 4-fold increase in the percent of tumor cells undergoing apoptosis compared with control mice. We conclude that MMP-9 from the bone marrow contributes to the early survival and establishment of tumors in the lung and has no effect on subsequent growth. These results provide insights into the failure of MMP inhibitors in clinical trials in patients with late-stage lung cancer.
1 Communities
2 Members
0 Resources
11 MeSH Terms
Nuclear factor-kappaB affects tumor progression in a mouse model of malignant pleural effusion.
Stathopoulos GT, Zhu Z, Everhart MB, Kalomenidis I, Lawson WE, Bilaceroglu S, Peterson TE, Mitchell D, Yull FE, Light RW, Blackwell TS
(2006) Am J Respir Cell Mol Biol 34: 142-50
MeSH Terms: Animals, Body Fluids, Carcinoma, Lewis Lung, Chemokine CCL2, Disease Models, Animal, Female, Green Fluorescent Proteins, I-kappa B Proteins, Injections, Intralesional, L-Lactate Dehydrogenase, Male, Mice, Mice, Inbred C57BL, Monocyte Chemoattractant Proteins, NF-kappa B, Pleural Effusion, Malignant, Pleural Neoplasms, Pregnancy
Show Abstract · Added February 26, 2013
We developed a novel mouse model of malignant pleural effusion (MPE) by injecting Lewis lung cancer (LLC) cells directly into the pleural space of syngeneic C57B/6 mice. The pleural effusions in this model share common cellular and biochemical features with human MPEs. Implantation and growth of pleural tumors triggers a host inflammatory response characterized by a mixed inflammatory cell influx into the pleural fluid. LLC cells exhibited high basal nuclear factor (NF)-kappaB activity in vitro and in vivo, which we used to drive expression of a NF-kappaB-dependent green fluorescent protein-firefly luciferase fusion reporter construct. NF-kappaB-dependent reporter expression allowed intravital tracing of pleural tumors. Inhibition of NF-kappaB in LLC cells did not affect cell viability in culture; however, injection of LLC cells expressing a dominant NF-kappaB inhibitor resulted in decreased tumor burden, decreased pleural effusion volume, and decreased pleural effusion TNF-alpha levels. These studies indicate that tumor NF-kappaB activity regulates pleural tumor progression. This reproducible model of MPE can be used to further study the influence of specific host and tumor factors on the pathogenesis of MPE and evaluate new therapeutic strategies.
2 Communities
4 Members
0 Resources
18 MeSH Terms