Inhibition of murine melanoma tumor growth in vitro and in vivo using an argon-based plasma jet

2020 ◽  
Vol 19-20 ◽  
pp. 100102 ◽  
Author(s):  
Alireza Rafiei ◽  
Farshad Sohbatzadeh ◽  
Seyedehniaz Hadavi ◽  
Sander Bekeschus ◽  
Mina Alimohammadi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Plasma Jet ◽  
Melanoma Tumor ◽  
Murine Melanoma

Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3837-3844 ◽  
Author(s):  
Farida Djouad ◽  
Pascale Plence ◽  
Claire Bony ◽  
Philippe Tropel ◽  
Florence Apparailly ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Side Effects ◽  
Tumor Growth ◽  
Tumor Model ◽  
Bone Morphogenetic Protein 2 ◽  
Melanoma Tumor ◽  
Immunocompetent Mice

Abstract Mesenchymal stem cells (MSCs) are largely studied for their potential clinical use. Recently, they have gained further interest after demonstration of an immunosuppressive role. In this study, we investigated whether in vivo injection of MSCs could display side effects related to systemic immunosuppression favoring tumor growth. We first showed in vitro that the murine C3H10T1/2 (C3) MSC line and primary MSCs exhibit immunosuppressive properties in mixed lymphocyte reaction. We demonstrated that this effect is mediated by soluble factors, secreted only on “activation” of MSCs in the presence of splenocytes. Moreover, the immunosuppression is mediated by CD8+ regulatory cells responsible for the inhibition of allogeneic lymphocyte proliferation. We then demonstrated that the C3 MSCs expressing the human bone morphogenetic protein 2 (hBMP-2) differentiation factor were not rejected when implanted in various allogeneic immunocompetent mice and were still able to differentiate into bone. Importantly, using a murine melanoma tumor model, we showed that the subcutaneous injection of B16 melanoma cells led to tumor growth in allogeneic recipients only when MSCs were coinjected. Although the potential side effects of immunosuppression induced by MSCs have to be considered in further clinical studies, the usefulness of MSCs for various therapeutic applications still remains of great interest. (Blood. 2003;102:3837-3844)

The chemoattractant chemerin as a natural tumor suppressive cytokine.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21071-e21071
Author(s):  
Russell Kent Pachynski ◽  
Brian Zabel ◽  
Nicole Tejeda ◽  
Justin Monnier ◽  
Alison K Holzer ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Nk Cell ◽  
Suppressor Cells ◽  
Intratumoral Injection ◽  
Relative Reduction ◽  
Melanoma Tumor ◽  
In Vitro Proliferation ◽  
Immune Effector

e21071 Background: Infiltration of specialized immune cells regulates the growth and survival of neoplasia. In a survey of public whole genome expression datasets we found that the gene for chemerin, a widely expressed endogenous chemoattractant protein, is downregulated in melanoma as well as other human cancers. Moreover, high chemerin mRNA expression predicted improved outcomes in human melanoma. Methods: Forced re-expression of chemerin by tumor cells was achieved by transfection. An alternate strategy involved direct intratumoral injection of recombinant chemerin into tumors. Tumor line expression of chemerin was confirmed by ELISA and functionality of expressed, secreted chemerin confirmed by chemotaxis of CMKLR1 (the main receptor for chemerin) positive cells. Tumors were evaluated by FACS and immunofluorescence for presence of recruited leukocytes. Results: In studies of the B16 transplantable mouse melanoma, tumor-expressed chemerin inhibited in vivo tumor growth without altering in vitro proliferation. Growth inhibition was associated with an altered profile of tumor infiltrating cells with an increase in natural killers (NK cells), and a relative reduction in myeloid derived suppressor cells and putative immune inhibitory plasmacytoid DC. Tumor inhibition required host expression of CMKLR1, the chemoattractant receptor for chemerin, and was abrogated by NK cell depletion. Intratumoral injection of chemerin also inhibited tumors, suggesting the potential for therapeutic application. Conclusions: We therefore conclude that chemerin recruits anti-tumor immune effector cells, and that it may act as an endogenous tumor suppressor, whose downregulation in melanoma and potentially other neoplasia contributes to immune evasion and tumor growth.

scholarly journals New derivatives of the antimalarial drug Pyrimethamine in the control of melanoma tumor growth: an in vitro and in vivo study

2016 ◽  
Vol 35 (1) ◽  
Author(s):  
Chiara Tommasino ◽  
Lucrezia Gambardella ◽  
Maria Buoncervello ◽  
Roger J. Griffin ◽  
Bernard T. Golding ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Antimalarial Drug ◽  
In Vivo Study ◽  
Melanoma Tumor ◽  
Derivatives Of

scholarly journals Endogenous Retrovirus Expression Is Required for Murine Melanoma Tumor Growth In vivo

2005 ◽  
Vol 65 (7) ◽  
pp. 2588-2591 ◽  
Author(s):  
Marianne Mangeney ◽  
Julien Pothlichet ◽  
Martial Renard ◽  
Bertrand Ducos ◽  
Thierry Heidmann
Keyword(s):  
Tumor Growth ◽  
Endogenous Retrovirus ◽  
Melanoma Tumor ◽  
Murine Melanoma

scholarly journals The chemoattractant chemerin suppresses melanoma by recruiting natural killer cell antitumor defenses

2012 ◽  
Vol 209 (8) ◽  
pp. 1427-1435 ◽  
Author(s):  
Russell K. Pachynski ◽  
Brian A. Zabel ◽  
Holbrook E. Kohrt ◽  
Nicole M. Tejeda ◽  
Justin Monnier ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Natural Killer ◽  
Messenger Rna ◽  
Nk Cell ◽  
Killer Cell ◽  
Relative Reduction ◽  
Melanoma Tumor ◽  
In Vitro Proliferation

Infiltration of specialized immune cells regulates the growth and survival of neoplasia. Here, in a survey of public whole genome expression datasets we found that the gene for chemerin, a widely expressed endogenous chemoattractant protein, is down-regulated in melanoma as well as other human tumors. Moreover, high chemerin messenger RNA expression in tumors correlated with improved outcome in human melanoma. In experiments using the B16 transplantable mouse melanoma, tumor-expressed chemerin inhibited in vivo tumor growth without altering in vitro proliferation. Growth inhibition was associated with an altered profile of tumor-infiltrating cells with an increase in natural killer (NK) cells and a relative reduction in myeloid-derived suppressor cells and putative immune inhibitory plasmacytoid dendritic cells. Tumor inhibition required host expression of CMKLR1 (chemokine-like receptor 1), the chemoattractant receptor for chemerin, and was abrogated by NK cell depletion. Intratumoral injection of chemerin also inhibited tumor growth, suggesting the potential for therapeutic application. These results show that chemerin, whether expressed by tumor cells or within the tumor environment, can recruit host immune defenses that inhibit tumorigenesis and suggest that down-regulation of chemerin may be an important mechanism of tumor immune evasion.

A New Synthetic Spiroketal: Studies on Antitumor Activity on Murine Melanoma Model In Vivo and Mechanism of Action In Vitro

2019 ◽  
Vol 19 (4) ◽  
pp. 567-578
Author(s):  
Maria P. Fuggetta ◽  
Pietro Spanu ◽  
Fausta Ulgheri ◽  
Francesco Deligia ◽  
Paola Carta ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Antitumor Effect ◽  
Antitumor Efficacy ◽  
Murine Melanoma ◽  
Melanoma Model ◽  
High Antitumor Activity ◽  
Dose Dependent

Background:In a previous study, we synthesised a new spiroketal derivative, inspired to natural products, that has shown high antiproliferative activity, potent telomerase inhibition and proapoptotic activity on several human cell lines.Objective:This work focused on the study of in vivo antitumor effect of this synthetic spiroketal on a murine melanoma model. In order to shed additional light on the origin of the antitumor effect, in vitro studies were performed.Methods:Spiroketal was administered to B16F10 melanoma mice at a dose of 5 mg/Kg body weight via intraperitoneum at alternate days for 15 days. Tumor volume measures were made every 2 days starting after 12 days from cells injection. The effects of the spiroketal on tumor growth inhibition, apoptosis induction, and cell cycle modification were investigated in vitro on B16 cells. HIF1α gene expression, the inhibition of cells migration and the changes induced in cytoskeleton conformation were evaluated.Results:Spiroketal displayed proapoptotic activity and high antitumor activity in B16 cells with nanomolar IC50. Moreover it has shown to inhibit cell migration, to strongly reduce the HIF1α expression and to induce strongly deterioration of cytoskeleton structure. A potent dose-dependent antitumor efficacy in syngenic B16/C57BL/6J murine model of melanoma was observed with the suppression of tumor growth by an average of 90% at a dose of 5 mg/kg.Conclusion:The synthesized spiroketal shows high antitumor activity in the B16 cells in vitro at nM concentration and a dose-dependent antitumor efficacy in syngenic B16/C57BL/6J mice. The results suggest that this natural product inspired spiroketal may have a potential application in melanoma therapy.

scholarly journals Fibroblast MMP14-Dependent Collagen Processing Is Necessary for Melanoma Growth

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1984
Author(s):  
Elke Pach ◽  
Jürgen Brinckmann ◽  
Matthias Rübsam ◽  
Maike Kümper ◽  
Cornelia Mauch ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Ex Vivo ◽  
Dermal Fibroblasts ◽  
Negative Regulator ◽  
Type I ◽  
Melanoma Tumor ◽  
Stromal Fibroblasts ◽  
Melanoma Growth

Skin homeostasis results from balanced synthesis and degradation of the extracellular matrix in the dermis. Deletion of the proteolytic enzyme MMP14 in dermal fibroblasts (MMP14Sf−/−) leads to a fibrotic skin phenotype with the accumulation of collagen type I, resulting from impaired proteolysis. Here, we show that melanoma growth in these mouse fibrotic dermal samples was decreased, paralleled by reduced tumor cell proliferation and vessel density. Using atomic force microscopy, we found increased peritumoral matrix stiffness of early but not late melanomas in the absence of fibroblast-derived MMP14. However, total collagen levels were increased at late melanoma stages in MMP14Sf−/− mice compared to controls. In ex vivo invasion assays, melanoma cells formed smaller tumor islands in MMP14Sf−/− skin, indicating that MMP14-dependent matrix accumulation regulates tumor growth. In line with these data, in vitro melanoma cell growth was inhibited in high collagen 3D spheroids or stiff substrates. Most importantly, in vivo induction of fibrosis using bleomycin reduced melanoma tumor growth. In summary, we show that MMP14 expression in stromal fibroblasts regulates melanoma tumor progression by modifying the peritumoral matrix and point to collagen accumulation as a negative regulator of melanoma.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

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