scholarly journals Platelet–Tumor Cell Hybrid Membrane-Camouflaged Nanoparticles for Enhancing Therapy Efficacy in Glioma

2021 ◽  
Author(s):  
Lingling Wu ◽  
Qin Li ◽  
Junjie Deng ◽  
Weide Xu ◽  
Bingyu Chen ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Tumor Cell ◽  
Tumor Targeting ◽  
Plasma Membranes ◽  
Immune Escape ◽  
Chemotherapeutic Agents ◽  
Tumor Cell Membrane ◽  
Induced Apoptosis

Abstract Cell membrane-camouflaged nanoparticles are drawing increasing attention because their surfaces retain the natural functionalities of the cell plasma membranes, making them a unique class of biomimetic materials combining natural and synthetic components. Modifying the cell membranes or combining the functions of different types of membranes enhances their functionality. Herein, we prepared platelet and tumor cell membrane camouflaged antitumor nanoparticles. The effects of β-mangostin-loaded nanoparticles on the target and its anticancer action in glioma were measured in vitro and in vivo. Multifunctional nanoparticles were manufactured with platelet–C6 hybrid biomimetic coating (PCM), lactic-co-glycolic acid (PLGA), and β-mangostin. PCM increased the proportion of active drug targeting in C6 and immune escape characteristics in THP-1 cells, thus enhancing the cytotoxicity of β-PCNPs. The β-PCNPs were comprehensively characterized to study the inherent properties of both source cells. Compared with bare β-NPs, β-PCNPs exhibited high tumor-targeting ability and induced apoptosis of C6 cells in vitro. Mice experiments with intravenous administration of the drug revealed that the β-PCNP platform enhanced the tumor targeting capability and exhibited excellent chemotherapy with high inhibition rate of glioma tumor growth in vivo. The mice in the β-PCNP group had a markedly prolonged circulation lifetime and exhibited better outcome than those in the β-NP group. These results provide a new strategy of utilizing PCNPs as carriers for drug delivery, which improves the targeting efficiency and therapeutic efficacy of chemotherapeutic agents for glioma therapy.

scholarly journals Homologous tumor cell membrane vesicles active preferential self-recognition of tumor cells in vitro

2022 ◽  
Vol 65 (1) ◽  
Author(s):  
Chenghu Wu ◽  
Ailin Yu ◽  
Yue Chen ◽  
Mingbo Fan
Keyword(s):  
Cell Membrane ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Therapy ◽  
Membrane Vesicles ◽  
Membrane System ◽  
Tumor Cell Membrane ◽  
Self Recognition

AbstractCell membrane vesicles, as delivery carriers of drugs or biological agents in vivo, are an important therapeutic mode in the study of disease treatment. Tumor membrane-derived vesicles have been widely used in tumor therapy because of their good tumor enrichment effect. The most common method is the surface of nanoparticles coated with tumor cell membrane, which can effectively prolong the circulation time of particles in the blood and the enrichment of tumors. In this study, we prepared vesicles of different tumor cell membrane derivate and studied their targeting to tumors detailly. The results showed that homologous vesicles have high targeting to homologous tumor cells. The fluorescence of vesicles in homologous tumor cells was significantly higher than that in other tumor cells. This study will provide a new strategy and guidance for the clinical treatment of cancer based on the tumor cell membrane system. Graphical Abstract

scholarly journals GARP promotes the proliferation and therapeutic resistance of bone sarcoma cancer cells through the activation of TGF-β

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Ana Belén Carrillo-Gálvez ◽  
Juan Esteban Quintero ◽  
René Rodríguez ◽  
Sofía T. Menéndez ◽  
M. Victoria González ◽  
...  
Keyword(s):  
Immune Escape ◽  
Treatment Resistance ◽  
Bone Sarcoma ◽  
Clinical Prognosis ◽  
Solid Malignancies ◽  
Bone Sarcomas ◽  
Induced Apoptosis ◽  
Prognostic And Predictive Markers

AbstractSarcomas are mesenchymal cancers with poor prognosis, representing about 20% of all solid malignancies in children, adolescents, and young adults. Radio- and chemoresistance are common features of sarcomas warranting the search for novel prognostic and predictive markers. GARP/LRRC32 is a TGF-β-activating protein that promotes immune escape and dissemination in various cancers. However, if GARP affects the tumorigenicity and treatment resistance of sarcomas is not known. We show that GARP is expressed by human osteo-, chondro-, and undifferentiated pleomorphic sarcomas and is associated with a significantly worse clinical prognosis. Silencing of GARP in bone sarcoma cell lines blocked their proliferation and induced apoptosis. In contrast, overexpression of GARP promoted their growth in vitro and in vivo and increased their resistance to DNA damage and cell death induced by etoposide, doxorubicin, and irradiation. Our data suggest that GARP could serve as a marker with therapeutic, prognostic, and predictive value in sarcoma. We propose that targeting GARP in bone sarcomas could reduce tumour burden while simultaneously improving the efficacy of chemo- and radiotherapy.

scholarly journals Immune Escape of Tumors in Vivo by Expression of Cellular Flice-Inhibitory Protein

1999 ◽  
Vol 190 (7) ◽  
pp. 1033-1038 ◽  
Author(s):  
Jan Paul Medema ◽  
Joan de Jong ◽  
Thorbald van Hall ◽  
Cornelis J.M. Melief ◽  
Rienk Offringa
Keyword(s):  
T Cell ◽  
Immune Escape ◽  
Cytotoxic T Cell ◽  
Tumor Control ◽  
Tumor Escape ◽  
Inhibitory Protein ◽  
Cell Immunity ◽  
Induced Apoptosis

The antiapoptotic protein cellular FLICE (Fas-associated death domain–like IL-1β–converting enzyme) inhibitory protein (cFLIP) protects cells from CD95(APO-1/Fas)-induced apoptosis in vitro and was found to be overexpressed in human melanomas. However, cytotoxic T cell–induced apoptosis, which is critically involved in tumor control in vivo, is not inhibited by cFLIP in vitro, as only CD95- and not perforin-dependent lysis is affected. This calls into question whether cFLIP is sufficient to allow escape from T cell–dependent immunity. Using two murine tumors, we directly demonstrate that cFLIP does result in escape from T cell immunity in vivo. Moreover, tumor cells are selected in vivo for elevated cFLIP expression. Therefore, our data indicate that CD95-dependent apoptosis constitutes a more prominent mechanism for tumor clearance than has so far been anticipated and that blockade of this pathway can result in tumor escape even when the perforin pathway is operational.

The Anticancer Effect of Sanguinarine: A Review

2018 ◽  
Vol 24 (24) ◽  
pp. 2760-2764 ◽  
Author(s):  
Chenxing Fu ◽  
Guiping Guan ◽  
Hongbing Wang
Keyword(s):  
Tumor Cell ◽  
In Vivo Studies ◽  
Inhibitory Effects ◽  
Anticancer Effect ◽  
Growth Inhibitory ◽  
Cell Proliferation Inhibition ◽  
Anti Cancer ◽  
Induced Apoptosis

In vitro and in vivo studies have revealed that Sanguinarine has antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects on tumor cells of a variety of cancers. Previous research showed that sanguinarine induced apoptosis (cell death) and/or antiproliferative while reducing tumor cell antiangiogenic and anti-invasive properties. This paper describes various sanguinarine anti-cancer mechanisms, including inhibition of erroneously-activated signal transduction pathways, apoptosis, and tumor cell proliferation inhibition.

scholarly journals Nitric Oxide–Dependent Activation of P53 Suppresses Bleomycin-Induced Apoptosis in the Lung

2000 ◽  
Vol 192 (6) ◽  
pp. 857-870 ◽  
Author(s):  
Darren W. Davis ◽  
Douglas A. Weidner ◽  
Andrij Holian ◽  
David J. McConkey
Keyword(s):  
Nitric Oxide ◽  
Lung Injury ◽  
Environmental Pollutants ◽  
Chemotherapeutic Agents ◽  
Wild Type ◽  
Intratracheal Administration ◽  
P53 Activation ◽  
Induced Apoptosis

Chronic inflammation leading to pulmonary fibrosis develops in response to environmental pollutants, radiotherapy, or certain cancer chemotherapeutic agents. We speculated that lung injury might be mediated by p53, a proapoptotic transcription factor widely implicated in the response of cells to DNA damage. Intratracheal administration of bleomycin led to caspase-mediated DNA fragmentation characteristic of apoptosis. The effects of bleomycin were associated with translocation of p53 from the cytosol to the nucleus only in alveolar macrophages that had been exposed to the drug in vivo, suggesting that the lung microenvironment regulated p53 activation. Experiments with a thiol antioxidant (N-acetylcysteine) in vivo and nitric oxide (NO) donors in vitro confirmed that reactive oxygen species were required for p53 activation. A specific role for NO was demonstrated in experiments with inducible nitric oxide synthase (iNOS)−/− macrophages, which failed to demonstrate nuclear p53 localization after in vivo bleomycin exposure. Strikingly, rates of bleomycin-induced apoptosis were at least twofold higher in p53−/− C57BL/6 mice compared with heterozygous or wild-type littermates. Similarly, levels of apoptosis were also twofold higher in the lungs of iNOS−/− mice than were observed in wild-type controls. Consistent with a role for apoptosis in chronic lung injury, levels of bleomycin-induced inflammation were substantially higher in iNOS−/− and p53−/− mice compared with wild-type controls. Together, our results demonstrate that iNOS and p53 mediate a novel apoptosis-suppressing pathway in the lung.

scholarly journals Transferrin-Conjugated Erianin-Loaded Liposomes Suppress the Growth of Liver Cancer by Modulating Oxidative Stress

2021 ◽  
Vol 11 ◽  
Author(s):  
Anhui Yang ◽  
Zhen Sun ◽  
Rui Liu ◽  
Xin Liu ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Tumor Targeting ◽  
Tumor Model ◽  
Aqueous Solubility ◽  
Ethanol Injection ◽  
Expression Levels ◽  
Tumor Tissues ◽  
Induced Apoptosis

BackgroundLiver cancer is one of the most malignant human cancers, with few treatments and a poor prognosis. Erianin (ERN) is a natural compound with multiple pharmacological activities that has been reported to have numerous excellent effects against liver cancer in experimental systems. However, its application in vivo has been limited due to its poor aqueous solubility and numerous off-target effects. This study aimed to improve the therapeutic efficacy of ERN by developing novel ERN-loaded tumor-targeting nanoparticles.ResultsIn this study, ERN was loaded into liposomes by ethanol injection (LP-ERN), and the resulting LP-ERN nanoparticles were treated with transferrin to form Tf-LP-ERN to improve the solubility and enhance the tumor-targeting of ERN. LP-ERN and Tf-LP-ERN nanoparticles had smooth surfaces and a uniform particle size, with particle diameters of 62.60 nm and 88.63 nm, respectively. In HepG2 and SMMC-7721 cells, Tf-LP-ERN induced apoptosis, decreased mitochondrial membrane potentials and increased ERN uptake more effectively than free ERN and LP-ERN. In xenotransplanted mice, Tf-LP-ERN inhibited tumor growth, but had a minimal effect on body weight and organ morphology. In addition, Tf-LP-ERN nanoparticles targeted tumors more effectively than free ERN and LP-ERN nanoparticles, and in tumor tissues Tf-LP-ERN nanoparticles promoted the cleavage PARP-1, caspase-3 and caspase-9, increased the expression levels of Bax, Bad, PUMA, and reduced the expression level of Bcl-2. Moreover, in the spleen of heterotopic tumor model BALB/c mice, ERN, LP-ERN and Tf-LP-ERN nanoparticles increased the expression levels of Nrf2, HO-1, SOD-1 and SOD-2, but reduced the expression levels of P-IKKα+β and P-NF-κB, with Tf-LP-ERN nanoparticles being most effective in this regard. Tf-LP-ERN nanoparticles also regulated the expression levels of TNF-α, IL-10 and CCL11 in serum.ConclusionTf-LP-ERN nanoparticles exhibited excellent anti-liver cancer activity in vivo and in vitro by inducing cellular apoptosis, exhibiting immunoregulatory actions, and targeting tumor tissues, and did so more effectively than free ERN and LP-ERN nanoparticles. These results suggest that the clinical utility of a Tf-conjugated LP ERN-delivery system for the treatment of liver cancer warrants exploration.

scholarly journals Tumor cell-intrinsic PD-1 receptor is a tumor suppressor and mediates resistance to PD-1 blockade therapy

2020 ◽  
Vol 117 (12) ◽  
pp. 6640-6650 ◽  
Author(s):  
Xiaodong Wang ◽  
Xiaohui Yang ◽  
Chang Zhang ◽  
Yang Wang ◽  
Tianyou Cheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Suppressor ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Colony Formation ◽  
Immune Escape ◽  
Potential Biomarker

The programmed cell death 1 (PD-1) receptor on the surface of immune cells is an immune checkpoint molecule that mediates the immune escape of tumor cells. Consequently, antibodies targeting PD-1 have shown efficacy in enhancing the antitumor activity of T cells in some types of cancers. However, the potential effects of PD-1 on tumor cells remain largely unknown. Here, we show that PD-1 is expressed across a broad range of tumor cells. The silencing of PD-1 or its ligand, PD-1 ligand 1 (PD-L1), promotes cell proliferation and colony formation in vitro and tumor growth in vivo. Conversely, overexpression of PD-1 or PD-L1 inhibits tumor cell proliferation and colony formation. Moreover, blocking antibodies targeting PD-1 or PD-L1 promote tumor growth in cell cultures and xenografts. Mechanistically, the coordination of PD-1 and PD-L1 activates its major downstream signaling pathways including the AKT and ERK1/2 pathways, thus enhancing tumor cell growth. This study demonstrates that PD-1/PD-L1 is a potential tumor suppressor and potentially regulates the response to anti-PD-1/PD-L1 treatments, thus representing a potential biomarker for the optimal cancer immunotherapeutic treatment.

scholarly journals EBV+ tumors exploit tumor cell-intrinsic and -extrinsic mechanisms to produce regulatory T cell-recruiting chemokines CCL17 and CCL22

2022 ◽  
Vol 18 (1) ◽  
pp. e1010200
Author(s):  
Aparna Jorapur ◽  
Lisa A. Marshall ◽  
Scott Jacobson ◽  
Mengshu Xu ◽  
Sachie Marubayashi ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Immune Escape ◽  
Wide Spectrum ◽  
Effective Means ◽  
Mouse Tumor ◽  
Tumor Type ◽  
Chemokine Production ◽  
Barr Virus

The Epstein-Barr Virus (EBV) is involved in the etiology of multiple hematologic and epithelial human cancers. EBV+ tumors employ multiple immune escape mechanisms, including the recruitment of immunosuppressive regulatory T cells (Treg). Here, we show some EBV+ tumor cells express high levels of the chemokines CCL17 and CCL22 both in vitro and in vivo and that this expression mirrors the expression levels of expression of the EBV LMP1 gene in vitro. Patient samples from lymphoblastic (Hodgkin lymphoma) and epithelial (nasopharyngeal carcinoma; NPC) EBV+ tumors revealed CCL17 and CCL22 expression of both tumor cell-intrinsic and -extrinsic origin, depending on tumor type. NPCs grown as mouse xenografts likewise showed both mechanisms of chemokine production. Single cell RNA-sequencing revealed in vivo tumor cell-intrinsic CCL17 and CCL22 expression combined with expression from infiltrating classical resident and migratory dendritic cells in a CT26 colon cancer mouse tumor engineered to express LMP1. These data suggest that EBV-driven tumors employ dual mechanisms for CCL17 and CCL22 production. Importantly, both in vitro and in vivo Treg migration was effectively blocked by a novel, small molecule antagonist of CCR4, CCR4-351. Antagonism of the CCR4 receptor may thus be an effective means of activating the immune response against a wide spectrum of EBV+ tumors.

scholarly journals Adenovirus-Mediated Transfer of siRNA against Survivin Induced Apoptosis and Attenuated Tumor Cell Growth in Vitro and in Vivo

2004 ◽  
Vol 10 (1) ◽  
pp. 162-171 ◽  
Author(s):  
Hiroaki Uchida ◽  
Toshihiro Tanaka ◽  
Katsunori Sasaki ◽  
Kazunori Kato ◽  
Hironari Dehari ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth ◽  
Induced Apoptosis

scholarly journals 712 Preclinical characterization of GT-00A x IL15: A novel IL-15-based immunocytokine with unique tumor targeting properties

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A741-A741
Author(s):  
Anika Jaekel ◽  
Patrik Kehler ◽  
Timo Lischke ◽  
Christoph Goletz ◽  
Anke Flechner ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Cell ◽  
Tumor Targeting ◽  
Immune Cell ◽  
Mechanisms Of Action ◽  
Immune Cell Infiltration ◽  
Efficacy And Safety ◽  
Control Construct

BackgroundIL-15 is a potent pro-inflammatory cytokine that enhances the differentiation, proliferation and cytolytic activity of NK cells and T cells. Due to the huge potential of IL-15 to activate both innate and adaptive anti-tumor immunity, several IL-15-based immunocytokines are currently in clinical development. However, all of them preferentially act in the periphery and not locally within the tumor. To further increase the efficacy and safety of IL-15-based immunocytokines, we developed GT-00A x IL15, an immunocytokine targeting a tumor-associated, glycosylated epitope of MUC-1 (TA-MUC1). GT-00A x IL15 was designed to induce anti-tumor responses directly within the tumor microenvironment for the treatment of solid tumors.MethodsGT-00A x IL15 was extensively studied in vitro and in vivo to adequately characterize its complex mechanisms of action and to analyze its anti-tumor efficacy. The relevance of TA-MUC1 binding as differentiation criteria against untargeted IL-15 (super)agonists was investigated in detail. In vitro cytotoxicity and 3D tumor spheroid immune cell infiltration mediated by GT-00A x IL15 was compared to the parental antibody GT-00A and an untargeted IL-15 control. In vivo, several pharmacokinetic, pharmacodynamic, biodistribution and efficacy studies were performed in tumor-free or tumor-bearing mice.ResultsWe could show in vitro that GT-00A x IL15 increased the cytotoxic activity of PBMC against TA-MUC1-positive tumor cell lines compared to parental GT-00A and an untargeted IL-15 control construct. Additionally, dose-dependent infiltration of NK and T cells into MCF-7 tumor spheroids is mediated by GT-00A x IL15 but not the untargeted IL15 control construct or parental GT-00A. In vivo single agent efficacy of GT-00A x IL15 was shown in different tumor models by means of tumor growth inhibition and increased survival. Subsequent flow cytometric analysis of tumor samples confirmed activation and expansion of tumor-infiltrating NK and CD8+ T cells. Furthermore, in a biodistribution study using radioactively labelled GT-00A x IL15 we observed significantly increased enrichment in the tumor compared to the untargeted IL-15 control construct.ConclusionsOur results confirm the relevance of TA-MUC1-mediated tumor cell binding for the mechanisms of action of our immunocytokine. GT-00A x IL15 shows increased accumulation in the tumor and mediates enhanced cytotoxicity and immune cell infiltration compared to an untargeted IL-15 control construct highlighting the potential to increase the efficacy and safety of IL-15-based immunocytokines by tumor targeting. GT-00A x IL15 shows great promise for the treatment of TA-MUC1-positive solid tumors either as monotherapeutic agent or as valuable combination partner.

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