tumor model
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2022 ◽  
Vol 68 ◽  
pp. 103109
Author(s):  
Elaheh Dalir Abdolahinia ◽  
Ghasem Barati ◽  
Zahra Ranjbar-Navazi ◽  
Jamileh Kadkhoda ◽  
Maryam Islami ◽  
...  

2022 ◽  
Vol 23 (2) ◽  
pp. 826
Author(s):  
Mary-Keara Boss ◽  
Remy Watts ◽  
Lauren G. Harrison ◽  
Sophie Hopkins ◽  
Lyndah Chow ◽  
...  

Stereotactic body radiotherapy (SBRT) is known to induce important immunologic changes within the tumor microenvironment (TME). However, little is known regarding the early immune responses within the TME in the first few weeks following SBRT. Therefore, we used the canine spontaneous tumor model to investigate TME responses to SBRT, and how local injection of immune modulatory antibodies to OX40 and TLR 3/9 agonists might modify those responses. Pet dogs with spontaneous cancers (melanoma, carcinoma, sarcoma, n = 6 per group) were randomized to treatment with either SBRT or SBRT combined with local immunotherapy. Serial tumor biopsies and serum samples were analyzed for immunologic responses. SBRT alone resulted at two weeks after treatment in increased tumor densities of CD3+ T cells, FoxP3+ Tregs, and CD204+ macrophages, and increased expression of genes associated with immunosuppression. The addition of OX40/TLR3/9 immunotherapy to SBRT resulted in local depletion of Tregs and tumor macrophages and reduced Treg-associated gene expression (FoxP3), suppressed macrophage-associated gene expression (IL-8), and suppressed exhausted T cell-associated gene expression (CTLA4). Increased concentrations of IL-7, IL-15, and IL-18 were observed in serum of animals treated with SBRT and immunotherapy, compared to animals treated with SBRT. A paradoxical decrease in the density of effector CD3+ T cells was observed in tumor tissues that received combined SBRT and immunotherapy as compared to animals treated with SBRT only. In summary, these results obtained in a spontaneous large animal cancer model indicate that addition of OX40/TLR immunotherapy to SBRT modifies important immunological effects both locally and systemically.


2022 ◽  
Vol 20 (2) ◽  
pp. 359-364
Author(s):  
Zhen You ◽  
Bei Li ◽  
Jun Gao ◽  
Jiong Lu ◽  
Ruihua Xu

Purpose: To investigate the effect of azaindole on proliferation of liver cancer cells, as well as the underlying mechanism. Methods: Colony forming and 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were used to determine the effect of azaindole on cell proliferation. A tumor model was established through subcutaneous administration of HEPG2 cells to rats. Thereafter, in vivo tumor development was measured using Vernier caliper. Results: The proliferation potential of HEPG2 and SNU-398 cells was markedly and dose-dependently suppressed by treatment with azaindole at doses of 2, 4, 8, 16 and 20 μM (p < 0.05). The expression levels of Ki67 and PCNA levels were significantly down-regulated in HEPG2 and SNU-398 cells on treatment with 20 μM azaindole. Moreover, azaindole significantly suppressed mRNA and protein expressions of KIFC1 in HEPG2 and SNU-398 cells (p < 0.05). Tumor volume in azaindole-treated rats on day 21 was greatly reduced, while KIFC1 expression in azaindole-treated rat tumor tissue was significantly down-regulated, when compared to the model group (p < 0.05). Conclusion: Azaindole targets proliferation of liver cancer cells in vitro and inhibits tumor growth in vivo through a mechanism involving down-regulation of KIFCI expression. Thus, azaindole is a potential therapeutic candidate for liver cancer.


2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Grace L. Edmunds ◽  
Carissa C. W. Wong ◽  
Rachel Ambler ◽  
Emily J. Milodowski ◽  
Hanin Alamir ◽  
...  

AbstractTumors generate an immune-suppressive environment that prevents effective killing of tumor cells by CD8+ cytotoxic T cells (CTL). It remains largely unclear upon which cell type and at which stage of the anti-tumor response mediators of suppression act. We have combined an in vivo tumor model with a matching in vitro reconstruction of the tumor microenvironment based on tumor spheroids to identify suppressors of anti-tumor immunity that directly act on interaction between CTL and tumor cells and to determine mechanisms of action. An adenosine 2A receptor antagonist, as enhanced by blockade of TIM3, slowed tumor growth in vivo. Engagement of the adenosine 2A receptor and TIM3 reduced tumor cell killing in spheroids, impaired CTL cytoskeletal polarization ex vivo and in vitro and inhibited CTL infiltration into tumors and spheroids. With this role in CTL killing, blocking A2AR and TIM3 may complement therapies that enhance T cell priming, e.g. anti-PD-1 and anti-CTLA-4.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Rana Vafaei ◽  
Mitra Samadi ◽  
Aysooda Hosseinzadeh ◽  
Khadijeh Barzaman ◽  
MohammadReza Esmailinejad ◽  
...  

AbstractMucin-1 (MUC-1) is a transmembrane glycoprotein, which bears many similarities between dogs and humans. Since the existence of animal models is essential to understand the significant factors involved in breast cancer mechanisms, canine mammary tumors (CMTs) could be used as a spontaneously occurring tumor model for human studies. Accordingly, this review assessed the comparison of canine and human MUC-1 based on their diagnostic and therapeutic aspects and showed how comparative oncology approaches could provide insights into translating pre-clinical trials from human to veterinary oncology and vice versa which could benefit both humans and dogs.


2022 ◽  
Vol 39 (1) ◽  
pp. 162-172
Author(s):  
Hao Li ◽  
Pengfei Chen ◽  
Manzhou Wang ◽  
Wenhui Wang ◽  
Fangzheng Li ◽  
...  

2022 ◽  
Author(s):  
You Chen ◽  
Langtao Xu ◽  
Weilin Li ◽  
Wanqi Chen ◽  
Qiubei He ◽  
...  

Abstract The traditional evaluation of nanoparticles (NPs) is mainly based on 2D cell culture and animal models. However, these models are difficult to accurately represent human tumor microenvironment (TME) and fail to systematically study the complex transportation of NPs, thus limiting the translation of nano-drug formulations to clinical studies. This study reports a tumor model fabricated via 3D bioprinting with decellularized extracellular matrix (adECM) enhanced hybrid bioink. Compared with 2D cultured cells, the 3D printed tumor models with multicellular spheroids formation are closer to real tumor in protein, gene expression and tumorigenicity both in vitro and in vivo. Two characteristics of TME, ECM remodeling and epithelial-mesenchymal transition (EMT), are tracked simultaneously under 3D conditions. Furthermore, the cellular uptake efficiency of two different NPs is significantly lower in the printed 3D tumor model than the 2D individual cells, and higher drug resistance is observed in 3D group, which suggest the ECM barrier of tumor can significantly affect the permeability of NPs. These results suggest that this 3D printed tumor model is capable of mimicking the multiple TME, potentially providing a more accurate platform for the design and development of NPs before moving into animal and clinical trials.


Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 124
Author(s):  
Alessio Malfanti ◽  
Giuseppina Catania ◽  
Quentin Degros ◽  
Mingchao Wang ◽  
Mathilde Bausart ◽  
...  

Glioblastoma is an unmet clinical need. Local treatment strategies offer advantages, such as the possibility to bypass the blood–brain barrier, achieving high drug concentrations at the glioblastoma site, and consequently reducing systemic toxicity. In this study, we evaluated the feasibility of using hyaluronic acid (HA) for the local treatment of glioblastoma. HA was conjugated to doxorubicin (DOX) with distinct bio-responsive linkers (direct amide conjugation HA-NH-DOX), direct hydrazone conjugation (HA-Hz-DOX), and adipic hydrazone (HA-AdpHz-DOX). All HA-DOX conjugates displayed a small size (less than 30 nm), suitable for brain diffusion. HA-Hz-DOX showed the best performance in killing GBM cells in both 2D and 3D in vitro models and displayed superior activity in a subcutaneous GL261 tumor model in vivo compared to free DOX and other HA-DOX conjugates. Altogether, these results demonstrate the feasibility of HA as a polymeric platform for the local treatment of glioblastoma and the importance of rationally designing conjugates.


2022 ◽  
Author(s):  
Chengfang Shangguan ◽  
Chen Yang ◽  
Zhaopeng Shi ◽  
Ying Miao ◽  
Wangxi Hai ◽  
...  

Abstract Background The 68Ga-labelled FAPI provides new oncology imaging option other than 18F-FDG-PET. However, it's unclear about whether the FAPI-PET distinguishes malignancy from benign lesions. Methods We established an AOM/DSS-induced rat colorectal tumor model. A double PET/CT tracer of 68Ga-FAPI-04 and 18F-FDG was used in the rat colorectal tumor model. Histological examination, immunohistochemistry staining, and radioautography were performed in this study. Results 68Ga-FAPI PET imaging distinguishes neoplasia from inflammatory lesions in an AOM/DSS-induced rat colorectal tumor model, and FAPI accumulation gradually increases along with tumor progression. An inflammatory lesion did not interfere with 68Ga-FAPI PET imaging. Conclusion The 68Ga-FAPI-04 PET distinguishes malignant tumors from inflammatory lesions by detecting FAP in a rat colorectal tumor model, suggesting that 68Ga-FAPI-04 PET is a better diagnostic tool than 18F-FDG PET, at least to colorectal cancer patients.


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