scholarly journals Development of Dual-Scale Fluorescence Endoscopy for In Vivo Bacteria Imaging in an Orthotopic Mouse Colon Tumor Model

2020 ◽  
Vol 10 (3) ◽  
pp. 844 ◽  
Author(s):  
Su Woong Yoo ◽  
Dinh-huy Nguyen ◽  
Suhyeon Park ◽  
Hyeri Lee ◽  
Chang-Moon Lee ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Imaging Techniques ◽  
Tumor Model ◽  
Colon Tumor ◽  
Wide Field ◽  
Fluorescence Endoscopy ◽  
Optimal Monitoring ◽  
Mouse Colon ◽  
Bacterial Therapy

Colorectal cancer is a representative cancer where early diagnosis and proper treatment monitoring are important. Recently, cancer treatment using bacteria has actively progressed and has been successfully monitored using fluorescence imaging techniques. However, because subcutaneous tumor models are limited in reflecting the actual colorectal cancer situation, new imaging approaches are needed to observe cancers growing in the colon. The fluorescence endoscopic approach is an optimal monitoring modality to evaluate the therapeutic response of bacteria in orthotopic colon cancer. In this study, we developed dual-scaled fluorescence endoscopy (DSFE) by combining wide-field fluorescence endoscopy (WFE) and confocal fluorescence endomicroscopy (CFEM) and demonstrated its usefulness for evaluating bacterial therapy. Firstly, the endoscopic probe of DSFE was developed by integrating the CFEM probe into the guide sheath of WFE. Secondly, colorectal cancer tumor growth and tumors infiltrating the fluorescent bacteria were successfully monitored at the multi-scale using DSFE. Finally, the bacterial distribution of the tumor and organs were imaged and quantitatively analyzed using CFEM. DSFE successfully exhibited fluorescent bacterial signals in an orthotopic mouse colon tumor model. Thus, it can be concluded that the DSFE system is a promising modality to monitor bacterial therapy in vivo.

Mo1991 - Pharmacologic Inhibition of Integrin ανβ6 Causes Tumor Shrinkage in the DSS/AOM Mouse Colon Tumor Model

2018 ◽  
Vol 154 (6) ◽  
pp. S-874
Author(s):  
Philipp Busenhart ◽  
Larissa Hering ◽  
Kirstin Atrott ◽  
Eleonora Patsenker ◽  
Felix Stickel ◽  
...  
Keyword(s):  
Tumor Model ◽  
Colon Tumor ◽  
Tumor Shrinkage ◽  
Mouse Colon ◽  
Pharmacologic Inhibition

AVIDIO as a novel oncolytic immunotherapy platform for the treatment of colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15210-e15210
Author(s):  
Bijan Almassian ◽  
Bhaskara R Madina ◽  
Ju Chen ◽  
Xiaoyang Ye ◽  
Marie M Krady ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Tumor Growth ◽  
Semliki Forest Virus ◽  
Tumor Model ◽  
Oncolytic Viruses ◽  
Immunomodulatory Agents ◽  
Oncolytic Activity

e15210 Background: Colorectal cancer is the third deadliest of all cancers causing more than 50,000 deaths per year in the U.S. Oncolytic viruses have seen limited use for the treatment of cancers, and further improvement of these methods with immune-modulating activities may prove crucial for the effectiveness of these agents in the treatment of human malignancies. To this end, we developed an artificial virus for infectious diseases and immuno-oncology (AVIDIO) platform that employs virus-like vesicles (VLV) for both the delivery of immunomodulatory agents to tumors and oncolytic activity. Methods: The AVIDIO platform is comprised of in vitro evolved RNA-dependent RNA polymerase from an alphavirus, Semliki forest virus, and envelope glycoproteins from vesicular stomatitis virus, which together form VLVs. Both unarmed VLVs and VLVs armed with the p35 subunit of IL-12 (VLV-IL12p35), an immunomodulatory cytokine that can induce Th1-mediated immunity, were tested for oncolytic activity against various cancer cell lines, including MC38 colorectal cancer cells, in vitro. Using the MC38 syngeneic murine tumor model, we evaluated the antitumor activity of VLV-IL-12p35 in vivo. We used tumor growth measurements and analyses of tumor-infiltrating cells after consecutive treatments with VLV-IL-12p35 to monitor its antitumor and immunomodulatory activities, respectively. Results: VLV-IL-12p35 showed robust oncolytic activity against MC38 cells in vitro, killing over 80% of cells within 24 h. Treatment of intradermal MC38 tumors by intra-tumoral delivery of VLV-IL-12p35 resulted in more than 65% suppression of tumor growth within 2 weeks ( p< 0.05). VLV-IL-12p35-treated tumors also harbored significantly more CD8+ T cells, IFN-gamma-producing CD4+ T cells, and reduced numbers of Foxp3+ regulatory T cells. Conclusions: Our results show that VLV-IL-12p35 derived from the AVIDIO platform has oncolytic activity in vitro and antitumor and immunomodulatory activities in vivo. Therefore, AVIDIO is a promising platform for the delivery of immunomodulatory agents to tumors. Further optimization of the platform, including the addition of other immunomodulatory agents, is in progress to advance the AVIDIO platform to clinical applications for colorectal cancer.

scholarly journals Application of in vivo imaging techniques to monitor therapeutic efficiency of PLX4720 in an experimental model of microsatellite instable colorectal cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (41) ◽  
pp. 69756-69767 ◽  
Author(s):  
Sarah Rohde ◽  
Tobias Lindner ◽  
Stefan Polei ◽  
Jan Stenzel ◽  
Luise Borufka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Experimental Model ◽  
In Vivo Imaging ◽  
Imaging Techniques ◽  
Therapeutic Efficiency

Diallyl trisulfide (DATS) inhibits mouse colon tumor in mouse CT-26 cells allograft model in vivo

Phytomedicine ◽  
2011 ◽  
Vol 18 (8-9) ◽  
pp. 672-676 ◽  
Author(s):  
Ping-Ping Wu ◽  
Kuo-Ching Liu ◽  
Wen-Wen Huang ◽  
Fu-Shin Chueh ◽  
Yang-Ching Ko ◽  
...  
Keyword(s):  
Colon Tumor ◽  
Diallyl Trisulfide ◽  
Mouse Colon

scholarly journals Biomolecular imaging of colorectal tumor lesions using a FITC-labeled scFv-Cκ fragment antibody

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hyung Il Kim ◽  
Jinhyeon Kim ◽  
Hyori Kim ◽  
Hyeri Lee ◽  
Yong Sik Yoon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Molecular Imaging ◽  
Real Time ◽  
Ex Vivo ◽  
Imaging Techniques ◽  
Antibody Fragment ◽  
Fluorescence Analysis ◽  
Human Colon Cancer

AbstractFor the sensitive diagnosis of colorectal cancer lesions, advanced molecular imaging techniques using cancer-specific targets have emerged. However, issues regarding the clearance of unbound probes and immunogenicity remain unresolved. To overcome these limitations, we developed a small-sized scFv antibody fragment conjugated with FITC for the real-time detection of colorectal cancer by in vivo molecular endoscopy imaging. A small-sized scFv fragment can target colon cancer secreted protein-2 (CCSP-2), highly expressed in colorectal adenocarcinoma tissues; moreover, its full-length IgG probe has been used for molecular imaging previously. To assess the efficacy of anti-CCSP-2 scFv-FITC, surgical specimens were obtained from 21 patients with colorectal cancer for ex vivo molecular fluorescence analysis, histology, and immunohistochemistry. Orthotopic mice were administered with anti-CCSP-2 scFv-FITC topically and intravenously, and distinct tumor lesions were observed by real-time fluorescence colonoscopy. The fluorescence imaging of human colon cancer specimens allowed the differentiation of malignant tissues from non-malignant tissues (p < 0.05), and the CCSP-2 expression level was found to be correlated with the fluorescence intensity. Here, we demonstrated the feasibility and safety of anti-CCSP-2 scFv-FITC for molecular imaging as well as its potential in real-time fluorescence colonoscopy for the differential diagnosis of tumor lesions.

scholarly journals Osteopontin Blockade Immunotherapy Increases Cytotoxic T Lymphocyte Lytic Activity and Suppresses Colon Tumor Progression

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1006
Author(s):  
John D. Klement ◽  
Dakota B. Poschel ◽  
Chunwan Lu ◽  
Alyssa D. Merting ◽  
Dafeng Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphoid Cells ◽  
Colon Tumor ◽  
Tumor Bearing

Human colorectal cancers are mostly microsatellite-stable with no response to anti-PD-1 blockade immunotherapy, necessitating the development of a new immunotherapy. Osteopontin (OPN) is elevated in human colorectal cancer and may function as an immune checkpoint. We aimed at elucidating the mechanism of action of OPN and determining the efficacy of OPN blockade immunotherapy in suppression of colon cancer. We report here that OPN is primarily expressed in tumor cells, myeloid cells, and innate lymphoid cells in human colorectal carcinoma. Spp1 knock out mice exhibit a high incidence and fast growth rate of carcinogen-induced tumors. Knocking out Spp1 in colon tumor cells increased tumor-specific CTL cytotoxicity in vitro and resulted in decreased tumor growth in vivo. The OPN protein level is elevated in the peripheral blood of tumor-bearing mice. We developed four OPN neutralization monoclonal antibodies based on their efficacy in blocking OPN inhibition of T cell activation. OPN clones 100D3 and 103D6 increased the efficacy of tumor-specific CTLs in killing colon tumor cells in vitro and suppressed colon tumor growth in tumor-bearing mice in vivo. Our data indicate that OPN blockade immunotherapy with 100D3 and 103D6 has great potential to be further developed for colorectal cancer immunotherapy and for rendering a colorectal cancer response to anti-PD-1 immunotherapy.

Integrated Raman spectroscopy and trimodal wide-field imaging techniques for real-time in vivo tissue Raman measurements at endoscopy

2009 ◽  
Vol 34 (6) ◽  
pp. 758 ◽  
Author(s):  
Zhiwei Huang ◽  
Seng Khoon Teh ◽  
Wei Zheng ◽  
Jianhua Mo ◽  
Kan Lin ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Real Time ◽  
Imaging Techniques ◽  
Wide Field ◽  
Field Imaging ◽  
Wide Field Imaging

scholarly journals Maintenance BEZ235 Treatment Prolongs the Therapeutic Effect of the Combination of BEZ235 and Radiotherapy for Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1204 ◽  
Author(s):  
Yu-Hsuan Chen ◽  
Chun-Wei Wang ◽  
Ming-Feng Wei ◽  
Yi-Shin Tzeng ◽  
Keng-Hsueh Lan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Viability ◽  
Cell Lines ◽  
Tumor Model ◽  
Study Groups ◽  
Mtor Signaling ◽  
The Other ◽  
Dsb Repair

Our previous study demonstrated that administration of NVP-BEZ235 (BEZ235), a dual PI3K/mTOR inhibitor, before radiotherapy (RT) enhanced the radiotherapeutic effect in colorectal cancer (CRC) cells both in vitro and in vivo. Here, we evaluated whether maintenance BEZ235 treatment, after combinatorial BEZ235 + RT therapy, prolonged the antitumor effect in CRC. K-RAS mutant CRC cells (HCT116 and SW480), wild-type CRC cells (HT29), and HCT116 xenograft tumors were separated into the following six study groups: (1) untreated (control); (2) RT alone; (3) BEZ235 alone; (4) RT + BEZ235; (5) maintenance BEZ235 following RT + BEZ235 (RT + BEZ235 + mBEZ235); and (6) maintenance BEZ235 following BEZ235 (BEZ235 + mBEZ235). RT + BEZ235 + mBEZ235 treatment significantly inhibited cell viability and increased apoptosis in three CRC cell lines compared to the other five treatments in vitro. In the HCT116 xenograft tumor model, RT + BEZ235 + mBEZ235 treatment significantly reduced the tumor size when compared to the other five treatments. Furthermore, the expression of mTOR signaling molecules (p-rpS6 and p-eIF4E), DNA double-strand break (DSB) repair-related molecules (p-ATM and p-DNA-PKcs), and angiogenesis-related molecules (VEGF-A and HIF-1α) was significantly downregulated after RT + BEZ235 + mBEZ235 treatment both in vitro and in vivo when compared to the RT + BEZ235, RT, BEZ235, BEZ235 + mBEZ235, and control treatments. Cleaved caspase-3, cleaved poly (ADP-ribose) polymerase (PARP), 53BP1, and γ-H2AX expression in the HCT116 xenograft tissue and three CRC cell lines were significantly upregulated after RT + BEZ235 + mBEZ235 treatment. Maintenance BEZ235 treatment in CRC cells prolonged the inhibition of cell viability, enhancement of apoptosis, attenuation of mTOR signaling, impairment of the DNA-DSB repair mechanism, and downregulation of angiogenesis that occurred due to concurrent BEZ235 and RT treatment.

Establishment of an Isogenic Human Colon Tumor Model forNQO1 Gene Expression: Application to Investigate the Role of DT-Diaphorase in Bioreductive Drug Activation In Vitro and In Vivo

2000 ◽  
Vol 58 (5) ◽  
pp. 1146-1155 ◽  
Author(s):  
Swee Y. Sharp ◽  
Lloyd R. Kelland ◽  
Melanie R. Valenti ◽  
Lisa A. Brunton ◽  
Steve Hobbs ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Model ◽  
Human Colon ◽  
Colon Tumor ◽  
Dt Diaphorase ◽  
Drug Activation

scholarly journals Analysis and Model of Cortical Slow Waves Acquired with Optical Techniques

2020 ◽  
Vol 3 (1) ◽  
pp. 14 ◽  
Author(s):  
Marco Celotto ◽  
Chiara De Luca ◽  
Paolo Muratore ◽  
Francesco Resta ◽  
Anna Letizia Allegra Mascaro ◽  
...  
Keyword(s):  
Large Scale ◽  
Temporal Dynamics ◽  
Imaging Techniques ◽  
Simulated Data ◽  
Neuronal Population ◽  
Slow Waves ◽  
Wide Field ◽  
Analysis Pipeline ◽  
Spatio Temporal

Slow waves (SWs) are spatio-temporal patterns of cortical activity that occur both during natural sleep and anesthesia and are preserved across species. Even though electrophysiological recordings have been largely used to characterize brain states, they are limited in the spatial resolution and cannot target specific neuronal population. Recently, large-scale optical imaging techniques coupled with functional indicators overcame these restrictions, and new pipelines of analysis and novel approaches of SWs modelling are needed to extract relevant features of the spatio-temporal dynamics of SWs from these highly spatially resolved data-sets. Here we combined wide-field fluorescence microscopy and a transgenic mouse model expressing a calcium indicator (GCaMP6f) in excitatory neurons to study SW propagation over the meso-scale under ketamine anesthesia. We developed a versatile analysis pipeline to identify and quantify the spatio-temporal propagation of the SWs. Moreover, we designed a computational simulator based on a simple theoretical model, which takes into account the statistics of neuronal activity, the response of fluorescence proteins and the slow waves dynamics. The simulator was capable of synthesizing artificial signals that could reliably reproduce several features of the SWs observed in vivo, thus enabling a calibration tool for the analysis pipeline. Comparison of experimental and simulated data shows the robustness of the analysis tools and its potential to uncover mechanistic insights of the Slow Wave Activity (SWA).

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