Oncolytic activity of a new group of non-classified rotavirus of Reoviridae family on human epidermoid carcinoma A431 growth.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15272-e15272
Author(s):  
Sergey A. Kolpakov ◽  
Elena P. Kolpakova ◽  
Elena Yu. Zlatnik ◽  
Evgeniya M. Nepomnyashchaya ◽  
Oksana G. Shulgina ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Nude Mice ◽  
Epidermoid Carcinoma ◽  
Tumor Growth Rate ◽  
In Vivo Model ◽  
Tumor Growth Inhibition ◽  
Early Date ◽  
Oncolytic Activity ◽  
Human Epidermoid Carcinoma

e15272 Background: Significant increase of malignant tumors` incidence all over the world in spite of vast arsenal of anticancer drugs and their combinations challenges the oncologists to develop new approaches to tumor treatment. Application of oncolytic virus is considered to be rather promising. Here we studied two strains of the new group of non-classified rotavirus of Reoviridae family (RVK): 100 and 228 ( http://jbks.ru/archive/issue-10/article-6 ). RVK are attenuated non-pathogenic virus growing on pig embryo kidney cell culture with concentration 5·109 per 1 ml. The aim of the study was to assess the effect of two RVK strains (100 and 228) on the growth of human epidermoid carcinoma A431 transplanted to nude mice in vivo. Methods: Mice Balb/cNude 22-24 g body weight (n = 13) were injected with 4х106 cells of human epidermoid carcinoma A431 subcutaneously in SPF-area of vivarium. After formation of palpable tumors (1 week after transplantation) administration of alive RVK strains 100 and 228 was performed. The 3rd group was the control one and received 0.85% NaCl. The injections were performed once a week 0.3 ml. Tumor growth rate and its` volume were measured. 1 week after the completion of the course mice were sacrificed, tumors were weighted and their morphology was studied. Results: In mice injected with RVK tumor growth inhibition developed in early date after the injection and was statistically significant within 30 - 40 days of monitoring only after the administration of strain 100. In these animals tumor weight was 2.6 times lower than in control mice (6.3±3.0 и 16.6±2.3 g respectively, р < 0.05), in mice having received strain 228 it was 1.7 times less tan in controls. Layers of high-grade sqamous carcinoma cells without keratinization with inflammatory and necrotic foci were observed in tumors of control mice while in tumors inhibited by RVK dystrophic changes and fragmentation, inflammation in places severe and necrotic foci were seen. Implication of the strain 100 resulted in 2-3 time reduction of tumor size, decrease of tumor cells` layers, mononuclear infiltration. Conclusions: In the in vivo model of human epidermoid carcinoma A431 transplanted to nude mice the inhibition of tumor growth under RVK administration was established. Our results confirm the oncolytic activity in RVK, particularly in strain 100.

Model of artificial metastasis of human epidermoid carcinoma A431 in nude mice for the examination of oncolytic activity of the vaccinia virus

2016 ◽  
Vol 6 (4) ◽  
pp. 469-476 ◽  
Author(s):  
G. V. Kochneva ◽  
A. A. Grazhdantseva ◽  
G. F. Sivolobova ◽  
A. V. Tkacheva ◽  
A. N. Shvalov ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Nude Mice ◽  
Epidermoid Carcinoma ◽  
Oncolytic Activity ◽  
Human Epidermoid Carcinoma

scholarly journals Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Haiyong Zhang ◽  
Jing Wu ◽  
Jinqiu Yuan ◽  
Huafu Li ◽  
Yawei Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Nude Mice ◽  
Combined Treatment ◽  
Thioredoxin Reductase ◽  
Tumor Growth Inhibition ◽  
Gastric Cancer Cells

Abstract Background Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. Methods Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. Results We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. Conclusions This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy.

scholarly journals A model of the artificial metastasis of human epidermoid carcinoma A431 in nude mice for examination of the oncolytic activity of vaccinia virus

2015 ◽  
Vol 19 (4) ◽  
pp. 480
Author(s):  
G. V. Kochneva ◽  
A. A. Grazhdantseva ◽  
G. F. Sivolobova ◽  
A. V. Tkacheva ◽  
A. N. Shvalov ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Nude Mice ◽  
Epidermoid Carcinoma ◽  
Oncolytic Activity ◽  
Human Epidermoid Carcinoma

scholarly journals FOXO3a shRNA and simultaneous induction of P27Kip1gene Inhibit the Breast Cancer Growth in Nude Mice

2020 ◽  
Author(s):  
Sabah Mayahi ◽  
Masood Golalipour ◽  
Mohammad Ashari ◽  
Majid Shahbazi
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Tumor Growth ◽  
Nude Mice ◽  
Cell Apoptosis ◽  
Immunohistochemical Analysis ◽  
Tumor Growth Inhibition ◽  
Breast Cancers ◽  
Simultaneous Induction

Abstract Background: FOXO proteins, which are overexpressed in multiple human tumors, belong to the Forkhead family of transcription factors that are involved in cell-cycle regulation, cell apoptosis, differentiation, stress response, and metabolism. The p27Kip1 gene leads to cell cycle arrest, cell apoptosis, tumor suppressor genes, and cell adhesion. The low expression level of the p27Kip1 gene is attributed to poor prognosis in patients with colorectal, gastric, pulmonary, and breast cancers. Accordingly, the present study aimed to investigate the possibility of tumor growth inhibition in a mouse model by targeting FOXO3a shRNA and the simultaneous induction of P27Kip1gene.Methods: The tumor model was generated by intratumoral inoculating with plasmids. When tumor size reached an average volume of 8 mm in diameter, the mice received injections of construct and control plasmids three times a week for two weeks, followed by tumor growth assessment.Results: Based on the obtained results, the delivery of construct plasmid significantly inhibited tumor growth in nude mice, as compared to the control plasmid. Moreover, the immunohistochemical analysis indicated that the delivery of construct plasmid significantly suppressed expression of FOXo3a and induced P27Kip1 in tumor samples.Conclusion: The findings of the present study revealed that FOXO3a shRNA, along with simultaneous induction of P27Kip1gene using a useful in vivo gene delivery strategy, seems a practical therapeutic approach for breast cancer treatment and may provide profound insight into gene therapy of solid cancers.

245 Human TLR8 knock-in mice potentiate immunotherapy responses of MC38 syngeneic tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A264-A264
Author(s):  
Shanshan Qi ◽  
Hongjuan Zhang ◽  
Ruilin Sun ◽  
Annie An ◽  
Henry Li ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Growth ◽  
Cancer Immunotherapy ◽  
Tumor Regression ◽  
Tumor Growth Rate ◽  
Tumor Growth Inhibition ◽  
List Type ◽  
Rna Recognition ◽  
Ethical Guidelines ◽  
Ifn Γ

BackgroundToll-like receptors (TLRs) serve critical roles in mediating innate immune responses against many pathogens. However, they may also bind to endogenous ligands and lead to the pathogenesis of autoimmunity. Although TLR8 belongs to the same TLR family as TLR7, its role in inflammation and tumor progression is not yet fully understood due to the lack of suitable animal models. In humans, both TLR7 and TLR8 recognize single-stranded self-RNA, viral RNA, and synthetic small molecule agonists.1, 2 However, mouse Tlr8 is non-functional due to the absence of 5 amino acids necessary for RNA recognition. In order to create a mouse model with functional TLR8, we replaced exon 3 of mouse Tlr8 with human TLR8, therefore developing a hTLR8 knock-in (KI) model. Both heterozygous and homozygous hTLR8 KI mice are viable with inflammatory phenotypes, i.e. enlarged spleens and livers, and significantly higher IL-12 p40 levels under TLR8 agonist treatment. In this study, we evaluated the potential use of hTLR8 mice for cancer immunotherapy studies.MethodshTLR8 mice, together with naïve C57BL/6 mice, were inoculated with MC38 syngeneic tumor cells. Tumor bearing mice were grouped at a mean tumor volume of approximately 100 mm3 for treatment with PBS or 10 mg/kg anti-PD-1 (RMP1-14) antibody. At the efficacy endpoint, spleens and tumors were collected for flow cytometry profiling.ResultsAnti-PD-1 treatment of MC38 tumors in naïve C57BL/6 led to moderate tumor growth inhibition (TGI = 54%). Interestingly, anti-PD-1 treatment showed improved efficacy in hTLR8 mice (TGI = 79%), including 2/10 tumors with complete tumor regression. In comparison, non-treated MC38 tumor growth rate was slower in hTLR8 mice than in naïve mice. Anti-PD-1 treated hTLR8 mice also had significantly increased IFN-γ and TNF-a positive CD4+ T cells in the spleen, along with higher numbers of differentiated effector T cells. In addition, hTLR8 mice have activated dendritic cells and macrophages, acting as critical steps in initiation of the inflammatory process, with higher levels of pro-inflammatory cytokines, such as IL-6, IFN-γ, TNF-a, and IL-1β, which may promote Th1 priming and differentiation of T cells into IFN-γ or TNF-a producing cells.ConclusionshTLR8 mice offer a great tool to model cancer immunotherapy in an inflammatory/autoimmunity prone background. Moreover, hTLR8 mice can be effectively used to shift a ‘cold’ tumor phenotype to ‘hot’ tumors in a syngeneic setting.Ethics ApprovalAnimal experiments were conducted in accordance with animal welfare law, approved by local authorities, and in accordance with the ethical guidelines of CrownBio (Taicang).ReferencesKugelberg E. Making mice more human the TLR8 way. Nat Rev Immunol 2014;14:6.Guiducci C, Gong M, Cepika A-M, et al. RNA recognition by human TLR8 can lead to autoimmune inflammation. J Exp Med 2013;210:2903–2919.

scholarly journals Anti-Cancer Effects of Zotarolimus Combined with 5-Fluorouracil Treatment in HCT-116 Colorectal Cancer-Bearing BALB/c Nude Mice

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4683
Author(s):  
Geng-Ruei Chang ◽  
Chan-Yen Kuo ◽  
Ming-Yang Tsai ◽  
Wei-Li Lin ◽  
Tzu-Chun Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Nude Mice ◽  
Colorectal Adenocarcinoma ◽  
Transforming Growth Factor ◽  
Colon Adenocarcinoma ◽  
Future Research ◽  
Related Factors ◽  
Hct 116

Zotarolimus is a semi-synthetic derivative of rapamycin and an inhibitor of mammalian target of rapamycin (mTOR) signaling. Currently, zotarolimus is used to prolong the survival time of organ grafts, but it is also a novel immunosuppressive agent with potent anti-proliferative activity. Here, we examine the anti-tumor effect of zotarolimus, alone and in combination with 5-fluorouracil, on HCT-116 colorectal adenocarcinoma cells implanted in BALB/c nude mice. Compared with the control mice, mice treated with zotarolimus or zotarolimus combined with 5-FU showed retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; reduced inflammation-related factors such as IL-1β, TNF-α, and cyclooxygenase-2 (COX-2) protein; and inhibited metastasis-related factors such as CD44, epidermal growth factor receptor (EGFR), transforming growth factor β (TGF-β), and vascular endothelial growth factor (VEGF). Notably, mice treated with a combination of zotarolimus and 5-FU showed significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with mice treated with 5-FU or zotarolimus alone, indicating a strong synergistic effect. This in vivo study confirms that zotarolimus or zotarolimus combined with 5-FU can be used to retard colorectal adenocarcinoma growth and inhibit tumorigenesis. Our results suggest that zotarolimus may increase the chemo-sensitization of tumor cells. Therefore, zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents in the treatment of human colon adenocarcinoma. Future research on zotarolimus may lead to the development of new therapeutic strategies.

scholarly journals PARP inhibitor olaparib increases the oncolytic activity of dl922-947 in in vitro and in vivo model of anaplastic thyroid carcinoma

2014 ◽  
Vol 9 (1) ◽  
pp. 78-92 ◽  
Author(s):  
Carmela Passaro ◽  
Massimiliano Volpe ◽  
Ginevra Botta ◽  
Eloise Scamardella ◽  
Giuseppe Perruolo ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Parp Inhibitor ◽  
Anaplastic Thyroid Carcinoma ◽  
In Vivo Model ◽  
Oncolytic Activity

Nude mice with lacZ transduced human tumor xenografts as an in vivo model for invasion and metastasis

Lung Cancer ◽  
1991 ◽  
Vol 7 ◽  
pp. 30 ◽  
Author(s):  
Mogens Spang-Thomsen ◽  
James A. Zwiebel ◽  
Jørgen Rygaard ◽  
Nils Brünner
Keyword(s):  
Nude Mice ◽  
Human Tumor ◽  
In Vivo Model ◽  
Invasion And Metastasis ◽  
Human Tumor Xenografts ◽  
Tumor Xenografts

scholarly journals The Anti-Cancer Effects of a Zotarolimus and 5-Fluorouracil Combination Treatment on A549 Cell-Derived Tumors in BALB/c Nude Mice

2021 ◽  
Vol 22 (9) ◽  
pp. 4562
Author(s):  
Ching-Feng Wu ◽  
Ching-Yang Wu ◽  
Robin Y.-Y. Chiou ◽  
Wei-Cheng Yang ◽  
Chuen-Fu Lin ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Growth ◽  
Lung Adenocarcinoma ◽  
Nude Mice ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Transforming Growth Factor Β ◽  
Related Factors ◽  
Human Lung Adenocarcinoma

Zotarolimus is a semi-synthetic derivative of rapamycin and a novel immunosuppressive agent used to prevent graft rejection. The pharmacological pathway of zotarolimus restricts the kinase activity of the mammalian target of rapamycin (mTOR), which potentially leads to reductions in cell division, cell growth, cell proliferation, and inflammation. These pathways have a critical influence on tumorigenesis. This study aims to examine the anti-tumor effect of zotarolimus or zotarolimus combined with 5-fluorouracil (5-FU) on A549 human lung adenocarcinoma cell line implanted in BALB/c nude mice by estimating tumor growth, apoptosis expression, inflammation, and metastasis. We established A549 xenografts in nude mice, following which we randomly divided the mice into four groups: control, 5-FU (100 mg/kg/week), zotarolimus (2 mg/kg/day), and zotarolimus combined with 5-FU. Compared the results with those for control mice, we found that mice treated with zotarolimus or zotarolimus combined with 5-FU retarded tumor growth; increased tumor apoptosis through the enhanced expression of cleaved caspase 3 and extracellular signal-regulated kinase (ERK) phosphorylation; decreased inflammation cytokines levels (e.g., IL-1β, TNF-α, and IL-6); reduced inflammation-related factors such as cyclooxygenase-2 (COX-2) protein and nuclear factor-κB (NF-κB) mRNA; enhanced anti-inflammation-related factors including IL-10 and inhibitor of NF-κB kinase α (IκBα) mRNA; and inhibited metastasis-related factors such as transforming growth factor β (TGF-β), CD44, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). Notably, mice treated with zotarolimus combined with 5-FU had significantly retarded tumor growth, reduced tumor size, and increased tumor inhibition compared with the groups of mice treated with 5-FU or zotarolimus alone. The in vivo study confirmed that zotarolimus or zotarolimus combined with 5-FU could retard lung adenocarcinoma growth and inhibit tumorigenesis. Zotarolimus and 5-FU were found to have an obvious synergistic tumor-inhibiting effect on lung adenocarcinoma. Therefore, both zotarolimus alone and zotarolimus combined with 5-FU may be potential anti-tumor agents for treatment of human lung adenocarcinoma.

Sign in / Sign up

Export Citation Format

Share Document