scholarly journals Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer

2011 ◽  
Vol 9 (1) ◽  
Author(s):  
Natasja K van den Engel ◽  
Dominik Rüttinger ◽  
Margareta Rusan ◽  
Robert Kammerer ◽  
Wolfgang Zimmermann ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mouse Model ◽  
Tumor Cell ◽  
Combination Immunotherapy ◽  
Cancer Immunity ◽  
Specific Tumor ◽  
Anti Cancer

Effect of green tea polyphenol on changes in cancer-related factors in a mouse model of bladder cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 329-329
Author(s):  
Tomohiro Matsuo ◽  
Yasuyoshi Miyata ◽  
Yuichiro Nakamura ◽  
Yasuda Takuji ◽  
Akihiro Asai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Mouse Model ◽  
Tumor Cell ◽  
Green Tea ◽  
Tumor Cell Proliferation ◽  
Tea Polyphenol ◽  
Green Tea Polyphenol ◽  
Anti Cancer ◽  
Cox 2

329 Background: Many studies have demonstrated the anti-cancer effects of green tea polyphenol (GTP) in a variety of malignancies including bladder cancer, and epidemiologic studies have shown that green tea consumption reduces cancer risk. New cancer treatment strategies in combination with GTP intake have been recommended for several types of cancer. Thus, GTP is thought to be useful not only for cancer prevention but also for treatment. However, the mechanistic basis of these effects is not well understood. Hence, The aims of this study is to clarify the molecular mechanisms of GTP-induced anti-cancer effects, we used a mouse model of chemically induced bladder cancer. Methods: C3H/He mice (8 weeks old; n = 46) were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) solution for 14–24 weeks. Mice in the BBN + GTP group (n = 47) were also treated with 0.5% GTP solution over the same period. Tumor cell proliferation, and microvessel density were evaluated along with immunohistochemical analysis of human antigen R (HuR), vascular endothelial growth factor (VEGF)-A, cyclooxygenase (COX)-2, and hemeoxygenase (HO)-1 expression. Results: Cytoplasmic HuR expression in cancer cells was higher at 14 and 24 weeks in the BBN than in the control group and was associated with increased invasion of tumor cells in muscle. However, these effects were not observed in the BBN + GTP group. A multivariate analysis of GTP intake and cytoplasmic HuR expression revealed that GTP was independently associated with COX-2 and HO-1 expression, while cytoplasmic HuR expression was associated with COX-2 and VEGF-A levels. Expression of COX-2 and HO-1 was associated with cell proliferation and that of VEGF-A and HO-1 was associated with angiogenesis. In regard to nuclear HuR, its expression was not associated with any parameters, such as carcinogenesis, muscle invasion, and GTP intake. Conclusions: Our results supported the opinion that GTP intake can suppress tumor progression and malignant behavior in animal model of bladder cancer. In addition, we speculate that GTP directly and indirectly suppresses tumor cell proliferation and angiogenesis via HuR-related pathways in bladder cancer tissue.

scholarly journals Evidence for Non-Cancer-Specific T Cell Exhaustion in the Tcl1 Mouse Model for Chronic Lymphocytic Leukemia

2021 ◽  
Vol 22 (13) ◽  
pp. 6648
Author(s):  
Thomas Parigger ◽  
Franz Josef Gassner ◽  
Christian Scherhäufl ◽  
Aryunni Abu Bakar ◽  
Jan Philip Höpner ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Mouse Model ◽  
Immune Checkpoint ◽  
Bystander Effect ◽  
Tumor Development ◽  
Lymphocytic Leukemia ◽  
Cancer Immunity ◽  
Anti Cancer ◽  
Efficacy Assessment

The reinvigoration of anti-cancer immunity by immune checkpoint therapies has greatly improved cancer treatment. In chronic lymphocytic leukemia (CLL), patients as well as in the Tcl1 mouse model for CLL, PD1-expressing, exhausted T cells significantly expand alongside CLL development; nevertheless, PD1 inhibition has no clinical benefit. Hence, exhausted T cells are either not activatable by simple PD1 blocking in CLL and/or only an insufficient number of exhausted T cells are CLL-specific. In this study, we examined the latter hypothesis by exploiting the Tcl1 transgenic CLL mouse model in combination with TCR transgene expression specific for a non-cancer antigen. Following CLL tumor development, increased PD1 levels were detected on non-CLL specific T cells that seem dependent on the presence of (tumor-) antigen-specific T cells. Transcriptome analysis confirmed a similar exhaustion phenotype of non-CLL specific and endogenous PD1pos T cells. Our results indicate that in the CLL mouse model, a substantial fraction of non-CLL specific T cells becomes exhausted during disease progression in a bystander effect. These findings have important implications for the general efficacy assessment of immune checkpoint therapies in CLL.

scholarly journals Chemopreventive Effects of Dietary Isothiocyanates in Animal Models of Gastric Cancer and Synergistic Anticancer Effects With Cisplatin in Human Gastric Cancer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Hanne-Line Rabben ◽  
Yosuke Kodama ◽  
Masahiko Nakamura ◽  
Atle Magnar Bones ◽  
Timothy Cragin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Genetically Engineered ◽  
Human Gastric Cancer ◽  
M Cell ◽  
Gastric Cancer Cells ◽  
Combination Strategy ◽  
Genetically Engineered Mouse Model ◽  
Anti Cancer

Naturally occurring isothiocyanates (ITCs) from edible vegetables have shown potential as chemopreventive agents against several types of cancer. The aims of the present study were to study the potential of ITCs in chemoprevention and in potentiating the efficacy of cytotoxic drugs in gastric cancer treatment. The chemoprevention was studied in chemically induced mouse model of gastric cancer, namely N-methyl-N-nitrosourea (MNU) in drinking water, and in a genetically engineered mouse model of gastric cancer (the so-called INS-GAS mice). The pharmacological effects of ITCs with or without cisplatin were studied in human gastric cell lines MKN45, AGS, MKN74 and KATO-III, which were derived from either intestinal or diffused types of gastric carcinoma. The results showed that dietary phenethyl isothiocyanate (PEITC) reduced the tumor size when PEITC was given simultaneously with MNU, but neither when administrated after MNU nor in INS-GAS mice. Treatments of gastric cancer cells with ITCs resulted in a time- and concentration-dependent inhibition on cell proliferation. Pretreatment of gastric cancer cells with ITCs enhanced the inhibitory effects of cisplatin (but not 5-fluorouracil) in time- and concentration-dependent manners. Treatments of gastric cancer cells with PEITC plus cisplatin simultaneously at different concentrations of either PEITC or cisplatin exhibited neither additive nor synergetic inhibitory effect. Furthermore, PEITC depleted glutathione and induced G2/M cell cycle arrest in gastric cancer cells. In conclusion, the results of the present study showed that PEITC displayed anti-cancer effects, particularly when given before the tumor initiation, suggesting a chemopreventive effect in gastric cancer, and that pretreatment of PEITC potentiated the anti-cancer effects of cisplatin, possibly by reducing the intracellular pool of glutathione, suggesting a possible combination strategy of chemotherapy with pretreatment with PEITC.

scholarly journals Human Ferritin Platform and Its Optimized Structures to Enhance Anti‐Cancer Immunity

2020 ◽  
pp. 2000208
Author(s):  
Bo‐Ram Lee ◽  
Hyo‐Jung Lee ◽  
June Huh ◽  
Chul Joo Yoon ◽  
Se Jin Oh ◽  
...  
Keyword(s):  
Cancer Immunity ◽  
Anti Cancer ◽  
Human Ferritin

scholarly journals Differential effects of zoledronic acid and oestrogen on anti-cancer immunity

Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 101024
Author(s):  
Chris George ◽  
Diane Lefley ◽  
Victor Canuas-Landero ◽  
Claudia Tulotta ◽  
Hannah Corness ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Differential Effects ◽  
Cancer Immunity ◽  
Anti Cancer

scholarly journals Single-cell evaluation reveals shifts in the tumor-immune niches that shape and maintain aggressive lesions in the breast

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vidya C. Sinha ◽  
Amanda L. Rinkenbaugh ◽  
Mingchu Xu ◽  
Xinhui Zhou ◽  
Xiaomei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Mouse Model ◽  
Transition State ◽  
Tumor Cell ◽  
Single Cell ◽  
Tumor Cells ◽  
Breast Lesions ◽  
Aggressive Tumor ◽  
Insight Into

AbstractThere is an unmet clinical need for stratification of breast lesions as indolent or aggressive to tailor treatment. Here, single-cell transcriptomics and multiparametric imaging applied to a mouse model of breast cancer reveals that the aggressive tumor niche is characterized by an expanded basal-like population, specialization of tumor subpopulations, and mixed-lineage tumor cells potentially serving as a transition state between luminal and basal phenotypes. Despite vast tumor cell-intrinsic differences, aggressive and indolent tumor cells are functionally indistinguishable once isolated from their local niche, suggesting a role for non-tumor collaborators in determining aggressiveness. Aggressive lesions harbor fewer total but more suppressed-like T cells, and elevated tumor-promoting neutrophils and IL-17 signaling, disruption of which increase tumor latency and reduce the number of aggressive lesions. Our study provides insight into tumor-immune features distinguishing indolent from aggressive lesions, identifies heterogeneous populations comprising these lesions, and supports a role for IL-17 signaling in aggressive progression.

scholarly journals TMOD-24. GENERATION AND CHARACTERIZATION OF A NOVEL TRANSGENIC IDO REPORTER MOUSE FOR IDO POSTTRANSLATIONAL MODIFICATION ANALYSIS IN SITU

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii233-ii233
Author(s):  
April Bell ◽  
Lijie Zhai ◽  
Erik Ladomersky ◽  
Kristen Lauing ◽  
Lakshmi Bollu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Cell ◽  
Central Nervous System Tumor ◽  
Post Translational Modifications ◽  
Reporter Mouse ◽  
C Terminus ◽  
Human Gbm

Abstract Glioblastoma (GBM) is the most common and aggressive primary central nervous system tumor in adults with a median survival of 14.6 months. GBM is a potently immunosuppressive cancer due in-part to the prolific expression of immunosuppressive indoleamine 2,3 dioxygenase 1 (IDO). Tumor cell IDO facilitates the intratumoral accumulation of regulatory T cells (Tregs; CD4+CD25+FoxP3+). Although immunosuppressive IDO activity is canonically characterized by the conversion of tryptophan into kynurenine, we have utilized transgenic and syngeneic mouse models and mutant glioma lines to demonstrate that tumor cell IDO increases Treg accumulation independent of tryptophan metabolism. Here, we address the gap in our understanding of IDO signaling activity in vivo. Subcutaneously-engrafted human GBM expressing human IDO-GFP cDNA was isolated from immunodeficient humanized NSG-SGM3 mice. The tumor was immunoprecipitated for the GFP tag using GFP-TRAP followed by mass spectrometry which revealed a novel methylation site on a lysine residue at amino acid 373 in the IDO C-terminus region. Western blot analysis of IDO protein also revealed the presence of tyrosine phosphorylation. Additionally, we recently created a new transgenic IDO reporter mouse model whereby endogenous IDO is fused to GFP via a T2A linker (IDO→GFP). This model allows for the isolation of IDO+ cells in real-time and without causing cell death, thereby creating the opportunity for downstream molecular analysis of in situ-isolated GFP+ cells. Collectively, our work suggests that IDO non-enzyme activity may involve the post-translational modifications we recently identified. As IDO activity may differ between in vitro and in vivo modeling systems, we will use the new IDO→GFP reporter mouse model for an improved mechanistic understanding of how immunosuppressive IDO facilitates Treg accumulation in vivo.

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