In Vivo Imaging of Lung Tumor Growth Using In-Line X-Ray Phase Contrast Technique

AbstractIntratumoral heterogeneity in lung cancer is essential for evasion of immune surveillance by tumor cells and establishment of immunosuppression. Gathering data reveal that circular RNAs (circRNAs), play a role in the pathogenesis and progression of lung cancer. Particularly Kras-driven circRNA signaling triggers infiltration of myeloid-associated tumor macrophages in lung tumor microenvironment thus establishing immune deregulation, and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras signaling in circRNA-related immunosuppression and its involvement in tumoral chemoresistance. The expression pattern of circRNAs HIPK3 and PTK2 was determined using quantitative polymerase chain reaction (qPCR) in lung cancer patient samples and cell lines. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. M2 macrophage polarization and MDSC subset analysis (Gr1−/CD11b−, Gr1−/CD11b+) were determined by flow cytometry. Tumor growth and metastatic potential were determined in vivo in C57BL/6 mice. Findings reveal intra-epithelial CD163+/CD206+ M2 macrophages to drive Kras immunosuppressive chemoresistance through myeloid differentiation. In particular, monocytic MDSC subsets Gr1−/CD11b−, Gr1−/CD11b+ triggered an M2-dependent immune response, creating an immunosuppressive tumor-promoting network via circHIPK3/PTK2 enrichment. Specifically, upregulation of exosomal cicHIPK3/PTK2 expression prompted Kras-driven intratumoral heterogeneity and guided lymph node metastasis in C57BL/6 mice. Consequent co-inhibition of circPTK2/M2 macrophage signaling suppressed lung tumor growth along with metastatic potential and prolonged survival in vivo. Taken together, these results demonstrate the key role of myeloid-associated macrophages in sustaining lung immunosuppressive neoplasia through circRNA regulation and represent a potential therapeutic target for clinical intervention in metastatic lung cancer.

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In vivo imaging of tumor growth after electrochemotherapy with cisplatin

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2006.07.132 ◽

2006 ◽

Vol 348 (3) ◽

pp. 997-1002 ◽

Cited By ~ 12

Author(s):

Maja Cemazar ◽

Muriel Golzio ◽

Jean-Michel Escoffre ◽

Bettina Couderc ◽

Gregor Sersa ◽

...

Keyword(s):

Tumor Growth ◽

In Vivo Imaging

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The versatile X-ray beamline of the Munich Compact Light Source: design, instrumentation and applications

Journal of Synchrotron Radiation ◽

10.1107/s1600577520008309 ◽

2020 ◽

Vol 27 (5) ◽

pp. 1395-1414 ◽

Cited By ~ 2

Author(s):

Benedikt Günther ◽

Regine Gradl ◽

Christoph Jud ◽

Elena Eggl ◽

Juanjuan Huang ◽

...

Keyword(s):

Light Source ◽

Phase Contrast ◽

Phase Contrast Imaging ◽

Contrast Imaging ◽

X Ray ◽

Inverse Compton Scattering ◽

University Of Munich ◽

Inverse Compton ◽

Compact Light Source

Inverse Compton scattering provides means to generate low-divergence partially coherent quasi-monochromatic, i.e. synchrotron-like, X-ray radiation on a laboratory scale. This enables the transfer of synchrotron techniques into university or industrial environments. Here, the Munich Compact Light Source is presented, which is such a compact synchrotron radiation facility based on an inverse Compton X-ray source (ICS). The recent improvements of the ICS are reported first and then the various experimental techniques which are most suited to the ICS installed at the Technical University of Munich are reviewed. For the latter, a multipurpose X-ray application beamline with two end-stations was designed. The beamline's design and geometry are presented in detail including the different set-ups as well as the available detector options. Application examples of the classes of experiments that can be performed are summarized afterwards. Among them are dynamic in vivo respiratory imaging, propagation-based phase-contrast imaging, grating-based phase-contrast imaging, X-ray microtomography, K-edge subtraction imaging and X-ray spectroscopy. Finally, plans to upgrade the beamline in order to enhance its capabilities are discussed.

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In vivo imaging to initialize a biophysical model of tumor growth: Preliminary results

2013 Biomedical Sciences and Engineering Conference (BSEC) ◽

10.1109/bsec.2013.6618487 ◽

2013 ◽

Author(s):

David A. Hormuth ◽

Thomas E. Yankeelov

Keyword(s):

Tumor Growth ◽

In Vivo Imaging ◽

Biophysical Model ◽

Preliminary Results

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Towards automated in vivo tracheal mucociliary transport measurement: Detecting and tracking particle movement in synchrotron phase-contrast x-ray images

Physics in Medicine and Biology ◽

10.1088/1361-6560/ab7509 ◽

2020 ◽

Vol 65 (14) ◽

pp. 145012

Author(s):

Mark Gardner ◽

David Parsons ◽

Kaye Morgan ◽

Alexandra McCarron ◽

Patricia Cmielewski ◽

...

Keyword(s):

Phase Contrast ◽

Mucociliary Transport ◽

Particle Movement ◽

Transport Measurement ◽

X Ray

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Rare-Earth-Doped Calcium Carbonate Exposed to X-ray Irradiation to Induce Reactive Oxygen Species for Tumor Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms20051148 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1148 ◽

Cited By ~ 1

Author(s):

Chun-Chen Yang ◽

Wei-Yun Wang ◽

Feng-Huei Lin ◽

Chun-Han Hou

Keyword(s):

Reactive Oxygen Species ◽

Photodynamic Therapy ◽

Tumor Growth ◽

Light Source ◽

Reactive Oxygen ◽

Blood Analysis ◽

Oxygen Species ◽

Tumor Treatment ◽

X Ray

Conventional photodynamic therapy (PDT) is limited by its penetration depth due to the photosensitizer and light source. In this study, we developed X-ray induced photodynamic therapy that applied X-ray as the light source to activate Ce-doped CaCO3 (CaCO3:Ce) to generate an intracellular reactive oxygen species (ROS) for killing cancer cells. The A549 cell line was used as the in vitro and in vivo model to evaluate the efficacy of X-ray-induced CaCO3:Ce. The cell viability significantly decreased and cell cytotoxicity obviously increased with CaCO3:Ce exposure under X-ray irradiation, which is less harmful than radiotherapy in tumor treatment. CaCO3:Ce produced significant ROS under X-ray irradiation and promoted A549 cancer cell death. CaCO3:Ce can enhance the efficacy of X-ray induced PDT, and tumor growth was inhibited in vivo. The blood analysis and hematoxylin and eosin stain (H&E) stain fully supported the safety of the treatment. The mechanisms underlying ROS and CO2 generation by CaCO3:Ce activated by X-ray irradiation to induce cell toxicity, thereby inhibiting tumor growth, is discussed. These findings and advances are of great importance in providing a novel therapeutic approach as an alternative tumor treatment.

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Real-time in vivo imaging of regional lung function in a mouse model of cystic fibrosis on a laboratory X-ray source

Scientific Reports ◽

10.1038/s41598-019-57376-w ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 4

Author(s):

Rhiannon P. Murrie ◽

Freda Werdiger ◽

Martin Donnelley ◽

Yu-wei Lin ◽

Richard P. Carnibella ◽

...

Keyword(s):

Cystic Fibrosis ◽

Lung Function ◽

Mouse Model ◽

Real Time ◽

In Vivo Imaging ◽

X Ray ◽

Regional Lung Function ◽

Regional Lung

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Regulation of Parathyroid Hormone-Related Peptide by Estradiol: Effect on Tumor Growth and Metastasis in Vitro and in Vivo

Endocrinology ◽

10.1210/en.2005-0062 ◽

2005 ◽

Vol 146 (7) ◽

pp. 2885-2894 ◽

Cited By ~ 22

Author(s):

S. A. Rabbani ◽

P. Khalili ◽

A. Arakelian ◽

H. Pizzi ◽

G. Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cell Growth ◽

Tumor Growth ◽

Tumor Volume ◽

In Vivo Studies ◽

Promoting Effect ◽

X Ray ◽

Tumor Bearing ◽

Tumor Growth And Metastasis

Abstract We evaluated the capacity of estradiol (E2) to regulate PTHrP production, cell growth, tumor growth, and metastasis to the skeleton in breast cancer. In estrogen receptor (ER)-negative human breast cancer cells, MDA-MB-231, and cells transfected with full-length cDNA encoding ER (S-30), E2 caused a marked decrease in cell growth and PTHrP production, effects that were abrogated by anti-E2 tamoxifen. E2 also inhibited PTHrP promoter activity in S-30 cells. For in vivo studies, MDA-MB-231 and S-30 cells were inoculated into the mammary fat pad of female BALB/c nu.nu mice. Animals receiving S-30 cells developed tumors of significantly smaller volume compared with MDA-MB-231 tumor-bearing animals. This change in tumor volume was reversed when S-30 cells were inoculated into ovariectomized (OVX) hosts. Inoculation of MDA-MB-231 cells into the left ventricle resulted in the development of lesions in femora and tibia as determined by x-ray analysis. In contrast, these lesions were significantly smaller in volume and number in animals inoculated with S-30, and this lower incidence was reversed in OVX animals. Bone histological analysis showed that the tumor volume to tissue volume ratio was comparable with that seen by x-ray. Immunohistochemical analysis showed that PTHrP production was inhibited in S-30 group and restored to levels comparable to that seen in MDA-MB-231 tumor-bearing animals when S-30 cells were inoculated in OVX animals. Collectively these studies show that E2 production is inversely correlated with PTHrP production and that the growth-promoting effect of PTHrP has a direct impact on tumor growth at both nonskeletal and skeletal sites.

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