scholarly journals Chitosan-Based Delivery of Avian Reovirus Fusogenic Protein p10 Gene: In Vitro and In Vivo Studies towards a New Vaccine against Melanoma

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Claudia Robles-Planells ◽  
Carlos Barrera-Avalos ◽  
Leonel E. Rojo ◽  
Eugenio Spencer ◽  
Marcelo Cortez-San Martin ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Fusion ◽  
Cytotoxic Effect ◽  
Chitosan Nanoparticles ◽  
Melanoma Cells ◽  
Current Evidence ◽  
Avian Reovirus ◽  
Immune System Activation

Reovirus is known to have an anticancer effect in both the preclinical and clinical assays. Current evidence suggests that the reovirus-mediated impact on tumor growth depends on the activation of specific antitumor immune responses. A feasible explanation for the oncolytic effects and immune system activation is through the expression of the fusogenic reovirus protein. In this work, we evaluated the in vivo antitumor effects of the expression of fusogenic protein p10 of avian reovirus (ARV-p10). We used chitosan nanoparticles (CH-NPs) as a vehicle for the ARV-p10 DNA in murine B16 melanoma models both in vitro and in vivo. We confirmed that ARV-p10 delivery through a chitosan-based formulation (ARV-p10 CH-NPs) was capable of inducing cell fusion in cultured melanoma cells, showing a mild cytotoxic effect. Interestingly, intratumor injection of ARV-p10 CH-NPs delayed tumor growth, without changing lymphoid populations in the tumor tissue and spleen. The injection of chitosan nanoparticles (CH-NPs) also delayed tumor growth, suggesting the nanoparticle itself would attack tumor cells. In conclusion, we proved that in vitro ARV-p10 protein expression using CH-NPs in murine melanoma cells induces a cytotoxic effect associated with its cell fusion. Further studies are necessary for establishing a protocol for efficient in vivo DNA delivery of fusion proteins to produce an antitumoral effect.

scholarly journals Chitosan-Based Nanoparticles for Intracellular Delivery of ISAV Fusion Protein cDNA into Melanoma Cells: A Path to Develop Oncolytic Anticancer Therapies

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Claudia Robles-Planells ◽  
Giselle Sánchez-Guerrero ◽  
Carlos Barrera-Avalos ◽  
Silvia Matiacevich ◽  
Leonel E. Rojo ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Chitosan Nanoparticles ◽  
Syncytium Formation ◽  
Melanoma Cells ◽  
Current Evidence ◽  
Infectious Salmon Anemia ◽  
Melanoma Model ◽  
Anemia Virus

Oncolytic virus therapy has been tested against cancer in preclinical models and clinical assays. Current evidence shows that viruses induce cytopathic effects associated with fusogenic protein-mediated syncytium formation and immunogenic cell death of eukaryotic cells. We have previously demonstrated that tumor cell bodies generated from cells expressing the fusogenic protein of the infectious salmon anemia virus (ISAV-F) enhance crosspriming and display prophylactic antitumor activity against melanoma tumors. In this work, we evaluated the effects of the expression of ISAV-F on the B16 melanoma model, both in vitro and in vivo, using chitosan nanoparticles as transfection vehicle. We confirmed that the transfection of B16 tumor cells with chitosan nanoparticles (NP-ISAV) allows the expression of a fusogenically active ISAV-F protein and decreases cell viability because of syncytium formation in vitro. However, the in vivo transfection induces a delay in tumor growth, without inducing changes on the lymphoid populations in the tumor and the spleen. Altogether, our observations show that expression of ISAV fusion protein using chitosan nanoparticles induces cell fusion in melanoma cells and slight antitumor response.

Chrysin, a natural and biologically active flavonoid suppresses tumor growth of mouse B16F10 melanoma cells: In vitro and In vivo study

2018 ◽  
Vol 283 ◽  
pp. 10-19 ◽  
Author(s):  
Aïcha Sassi ◽  
Mouna Maatouk ◽  
Dorra El gueder ◽  
Imen Mokdad Bzéouich ◽  
Saïda Abdelkefi-Ben Hatira ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Melanoma Cells ◽  
Biologically Active ◽  
In Vivo Study ◽  
B16f10 Melanoma ◽  
B16f10 Melanoma Cells

scholarly journals Forkhead Box Transcription Factor (FOXO3a) mediates the cytotoxic effect of vernodalin in vitro and inhibits the breast tumor growth in vivo

2015 ◽  
Vol 34 (1) ◽  
Author(s):  
Suresh Kumar Ananda Sadagopan ◽  
Nooshin Mohebali ◽  
Chung Yeng Looi ◽  
Mohadeseh Hasanpourghadi ◽  
Ashok Kumar Pandurangan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tumor Growth ◽  
Breast Tumor ◽  
Cytotoxic Effect ◽  
Forkhead Box

scholarly journals Eradication of established human melanoma tumors in nude mice by antibody-directed effector cells.

1985 ◽  
Vol 161 (6) ◽  
pp. 1315-1325 ◽  
Author(s):  
G Schulz ◽  
L K Staffileno ◽  
R A Reisfeld ◽  
G Dennert
Keyword(s):  
Tumor Growth ◽  
Nk Cells ◽  
Nude Mice ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Tumor Rejection ◽  
Nk Activity ◽  
Asialo Gm1

The simultaneous injection of monoclonal antibody 9.2.27, directed against a chondroitin sulfate proteoglycan preferentially expressed on human melanoma cells, and 2 X 10(7) mononuclear splenocytes, eradicated established, progressively growing human melanoma tumors in nude mice. Neither splenocytes nor antibody alone achieved significant tumor regression. The cells responsible for tumor elimination are most likely natural killer (NK) cells: they are present in splenocytes of T cell-deficient nude mice, and cloned cells with NK activity are able to suppress tumor growth. Moreover, splenocytes treated with anti-asialo GM1 and complement or harvested from NK-deficient C57BL/6 beige mice did not cause tumor rejection. Furthermore, treatment of BALB/c nude mice just before injection with anti-asialo GM1 antiserum, which is known to eliminate NK activity in vivo, resulted in better tumor growth. In addition, evidence is presented that cells with NK activity are probably the effectors responsible for melanoma target cell lysis in vitro: Antibody-dependent and -independent cell-mediated lysis of M21 melanoma cells was suppressed when splenocytes were preincubated with complement and antibodies specific for cell surface antigens of NK cells, i.e., anti-asialo GM1, anti-Qa5, and anti-NK1.1. Moreover, splenocytes of C57BL/6 beige mice were not able to lyse M21 cells in vitro. These results strongly support the conclusion that cells with NK activity are indeed responsible for the antibody-dependent destruction of M21 melanoma cells in vivo and in vitro.

scholarly journals Cytotoxic effect of Montivipera bornmuelleri’s venom on cancer cell lines: in vitro and in vivo studies

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9909
Author(s):  
Carol Haddoub ◽  
Mohamad Rima ◽  
Sandrine Heurtebise ◽  
Myriam Lawand ◽  
Dania Jundi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Lines ◽  
Cytotoxic Effect ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
In Vivo Testing ◽  
Murine Fibrosarcoma ◽  
Dose Dependent

Background Montivipera bornmuelleri’s venom has shown immunomodulation of cytokines release in mice and selective cytotoxicity on cancer cells in a dose-dependent manner, highlighting an anticancer potential. Here, we extend these findings by elucidating the sensitivity of murine B16 skin melanoma and 3-MCA-induced murine fibrosarcoma cell lines to M. bornmuelleri’s venom and its effect on tumor growth in vivo. Methods The toxicity of the venom on B16 and MCA cells was assessed using flow cytometry and xCELLigence assays. For in vivo testing, tumor growth was followed in mice after intratumoral venom injection. Results The venom toxicity showed a dose-dependent cell death on both B16 and MCA cells. Interestingly, overexpression of ovalbumin increased the sensitivity of the cells to the venom. However, the venom was not able to eradicate induced-tumor growth when injected at 100 µg/kg. Our study demonstrates a cytotoxic effect of M. bornmuelleri’s venom in vitro which, however, does not translate to an anticancer action in vivo.

In vitro and in vivo tumor growth inhibition by a p16-mimicking peptide in p16INK4A-defective, pRb-positive human melanoma cells

2004 ◽  
Vol 202 (3) ◽  
pp. 922-928 ◽  
Author(s):  
Douglas M. Noonan ◽  
Anna Severino ◽  
Monica Morini ◽  
Alessandra Tritarelli ◽  
Lucrezia Manente ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Growth Inhibition ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Tumor Growth Inhibition ◽  
Human Melanoma Cells

scholarly journals Genetic Manipulation of Sirtuin 3 Causes Alterations of Key Metabolic Regulators in Melanoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Chandra K. Singh ◽  
Jasmine George ◽  
Gagan Chhabra ◽  
Minakshi Nihal ◽  
Hao Chang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Metabolic Regulation ◽  
Genetic Manipulation ◽  
Cellular Metabolism ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Canonical Pathways ◽  
Gene Network Analysis

The mitochondrial sirtuin SIRT3 plays key roles in cellular metabolism and energy production, which makes it an obvious target for the management of cancer, including melanoma. Previously, we have demonstrated that SIRT3 was constitutively upregulated in human melanoma and its inhibition resulted in anti-proliferative effects in vitro in human melanoma cells and in vivo in human melanoma xenografts. In this study, we expanded our data employing knockdown and overexpression strategies in cell culture and mouse xenografts to further validate and establish the pro-proliferative function of SIRT3 in melanocytic cells, and its associated potential mechanisms, especially focusing on the metabolic regulation. We found that short-hairpin RNA (shRNA) mediated SIRT3 knockdown in G361 melanoma cells showed diminished tumorigenesis in immunodeficient Nu/Nu mice. Conversely, SIRT3 overexpressing Hs294T melanoma cells showed increased tumor growth. These effects were consistent with changes in markers of proliferation (PCNA), survival (Survivin) and angiogenesis (VEGF) in xenografted tissues. Further, in in vitro culture system, we determined the effect of SIRT3 knockdown on glucose metabolism in SK-MEL-2 cells, using a PCR array. SIRT3 knockdown caused alterations in a total of 37 genes involved in the regulation and enzymatic pathways of glucose (32 genes) and glycogen (5 genes) metabolism. Functions annotation of these identified genes, using the ingenuity pathway analysis (IPA), predicted cumulative actions of decreased cell viability/proliferation, tumor growth and reactive oxygen species (ROS), and increased apoptosis in response to SIRT3 knockdown. Further, IPA gene network analysis of SIRT3 modulated genes revealed the interactions among these genes in addition to several melanoma-associated genes. Sirtuin pathway was identified as one of the top canonical pathways showing the interaction of SIRT3 with metabolic regulatory genes along with other sirtuins. IPA analysis also predicted the inhibition of HIF1α, PKM, KDM8, PPARGC1A, mTOR, and activation of P53 and CLPP; the genes involved in major cancer/melanoma-associated signaling events. Collectively, these results suggest that SIRT3 inhibition affects cellular metabolism, to impart an anti-proliferative response against melanoma.

scholarly journals Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors

2016 ◽  
Vol 113 (16) ◽  
pp. 4464-4469 ◽  
Author(s):  
Geoffrey Wayne Krampitz ◽  
Benson M. George ◽  
Stephen B. Willingham ◽  
Jens-Peter Volkmer ◽  
Kipp Weiskopf ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Growth ◽  
Neuroendocrine Tumors ◽  
Surface Protein ◽  
Current Evidence ◽  
Cell Surface Protein ◽  
Pancreatic Neuroendocrine Tumors ◽  
Tumor Initiating Cells

Pancreatic neuroendocrine tumors (PanNETs) are a type of pancreatic cancer with limited therapeutic options. Consequently, most patients with advanced disease die from tumor progression. Current evidence indicates that a subset of cancer cells is responsible for tumor development, metastasis, and recurrence, and targeting these tumor-initiating cells is necessary to eradicate tumors. However, tumor-initiating cells and the biological processes that promote pathogenesis remain largely uncharacterized in PanNETs. Here we profile primary and metastatic tumors from an index patient and demonstrate that MET proto-oncogene activation is important for tumor growth in PanNET xenograft models. We identify a highly tumorigenic cell population within several independent surgically acquired PanNETs characterized by increased cell-surface protein CD90 expression and aldehyde dehydrogenase A1 (ALDHA1) activity, and provide in vitro and in vivo evidence for their stem-like properties. We performed proteomic profiling of 332 antigens in two cell lines and four primary tumors, and showed that CD47, a cell-surface protein that acts as a “don’t eat me” signal co-opted by cancers to evade innate immune surveillance, is ubiquitously expressed. Moreover, CD47 coexpresses with MET and is enriched in CD90hi cells. Furthermore, blocking CD47 signaling promotes engulfment of tumor cells by macrophages in vitro and inhibits xenograft tumor growth, prevents metastases, and prolongs survival in vivo.

Ancylostoma caninum Anticoagulant Peptide Blocks Metastasis In Vivo and Inhibits Factor Xa Binding to Melanoma Cells In Vitro

1998 ◽  
Vol 79 (05) ◽  
pp. 1041-1047 ◽  
Author(s):  
Kathleen M. Donnelly ◽  
Michael E. Bromberg ◽  
Aaron Milstone ◽  
Jennifer Madison McNiff ◽  
Gordon Terwilliger ◽  
...  
Keyword(s):  
Active Site ◽  
Thrombin Generation ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Melanoma Cells ◽  
Factor V ◽  
Ancylostoma Caninum ◽  
Metastatic Activity

SummaryWe evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP’s anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme’s active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP’s antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.

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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