In vitro inhibition of tumor growth by low-dose iron oxide nanoparticles activating macrophages

Macrophages as immunocyte are attracting more and more attention in cancer therapy. Our previous study observed that dimercaptosuccinic acid (DMSA)-coated Fe3O4 magnetic nanoparticles triggered comprehensive immune responses of mouse macrophages (RAW264.7 cells) and induced production of many kinds of cytokines. This study investigated the effects of Fe3O4 magnetic nanoparticles on RAW264.7 cells proliferation, migration, and inhibition of tumor growth in vitro. Fe3O4 magnetic nanoparticles had an average size of about 11 nm with good dispersibility and uniformity. Fe3O4 magnetic nanoparticles internalized efficiently into RAW264.7 cells. Through Cell Counting Kit-8 (CCK-8) detection, the proliferation of RAW264.7 cells significantly increased by the low-dose Fe3O4 magnetic nanoparticles (50 µg/mL) treatment. The results of wound-healing and Transwell assays both displayed a significant promotion of the RAW264.7 cells migratory capability compared with control group ( P<0.01). It is interesting to find that a large number of proliferated RAW264.7 cells were activated to surround quickly and attack mouse liver cancer cell (Hepa1-6) cells by Fe3O4 magnetic nanoparticles. The growth of Hepa1-6 cells was effectively inhibited according to microscope imaging and flow cytometry analysis. The inhibition may be cooperative effects of RAW264.7 cells proliferation, migration, and immune activation. The results suggest potential clinical value of low-dose iron oxide nanomaterials in cancer therapy.

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Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

International Journal of Molecular Sciences ◽

10.3390/ijms22010176 ◽

2020 ◽

Vol 22 (1) ◽

pp. 176

Author(s):

Toshiaki Iba ◽

Jerrold H. Levy ◽

Koichiro Aihara ◽

Katsuhiko Kadota ◽

Hiroshi Tanaka ◽

...

Keyword(s):

Dose Group ◽

Low Dose ◽

Leukocyte Adhesion ◽

Endothelial Glycocalyx ◽

High Dose Group ◽

Control Group ◽

High Dose ◽

Protective Effects ◽

Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

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Low-dose curcumin leads to the inhibition of tumor growth via enhancing CTL-mediated antitumor immunity

International Immunopharmacology ◽

10.1016/j.intimp.2011.04.002 ◽

2011 ◽

Vol 11 (9) ◽

pp. 1234-1240 ◽

Cited By ~ 32

Author(s):

Feifei Luo ◽

Xiao Song ◽

Yi Zhang ◽

Yiwei Chu

Keyword(s):

Tumor Growth ◽

Antitumor Immunity ◽

Low Dose ◽

Inhibition Of Tumor Growth

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Antitumor efficiency of combination of bortezomib and themosolomide on subcutaneous PDX-model of human glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15011 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15011-e15011

Author(s):

A. V. Volkova ◽

Rostorguev Eduard Evgenievich ◽

Anna S. Goncharova ◽

M. V. Mindar ◽

Ekaterina V. Zaikina ◽

...

Keyword(s):

Tumor Growth ◽

Antitumor Effect ◽

Malignant Tumors ◽

Biological Effects ◽

Clinical Effects ◽

Glial Tumor ◽

Human Glioblastoma ◽

Pdx Model ◽

Inhibition Of Tumor Growth

e15011 Background: Poor clinical effects of standard treatment for glioblastoma determine the need for the development of new therapeutic strategies. Aberrant functioning of the proteasome system, as well as activation of the HIF-1α signaling pathway, are characteristic of glial tumor cells; they can be considered as potential therapeutic targets in the treatment of malignant brain tumors. One of the possible options for improving the results of glioblastoma treatment may involve strategies for inhibiting the HIF-1α pathway. Bortezomib, a proteasome inhibitor, can block the biological effects of HIF-1α. Bortezomib showed a pronounced antitumor effect in in vitro testing on various models of solid malignant tumors, giving grounds for further studies of its effectiveness in vivo. Patient-derived xenograft (PDX) models are characterized by a variety of cell subclones and are therefore considered the most reliable tool for predicting therapeutic responses. Methods: A PDX model of glioblastoma was created in 20 Balb/c Nude mice implanted with a subcutaneously inoculated human glioblastoma. Temozolomide (0.5 mg/kg), bortezomib (0.25 mg/kg), or a combination of temozolomide and bortezomib were administered intraperitoneally daily for 21 days. The tumor histotype was confirmed by histological analysis (staining with hematoxylin and eosin). The antitumor effect was determined by the inhibition of tumor growth (ITG%), the volume of tumor nodes, and the index of tumor growth. Results: The highest value of the inhibition of tumor growth (ITG%) was registered in the group of animals receiving a combination of temozolomide and bortezomib – 85.38%. The values in the groups receiving temozolomide or bortezomib monotherapy were 57.32% and 63.11%, respectively. Conclusions: An analysis of the antitumor efficacy of bortezomib combined with temozolomide in human subcutaneous PDX-glioblastomas demonstrated their synergistic effect.

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Localized cancer treatment by radio-frequency hyperthermia using magnetic nanoparticles immobilized on graphene oxide: from novel synthesis to in vitro studies

Journal of Materials Chemistry B ◽

10.1039/c8tb01365a ◽

2018 ◽

Vol 6 (33) ◽

pp. 5385-5399 ◽

Cited By ~ 16

Author(s):

Ravi Kumar ◽

Anjali Chauhan ◽

Sushil K. Jha ◽

Bijoy Kumar Kuanr

Keyword(s):

Graphene Oxide ◽

Iron Oxide ◽

Magnetic Nanoparticles ◽

Radio Frequency ◽

Cancer Treatment ◽

In Vitro Studies ◽

Hybrid Nanocomposite ◽

Novel Synthesis ◽

Hyperthermia Therapy

Innovative, theranostic hybrid nanocomposite of graphene oxide and iron oxide for radio-frequency hyperthermia therapy.

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The HSP90 inhibitor Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy: an in vitro and in vivo approach

Scientific Reports ◽

10.1038/s41598-020-62293-4 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Diana Spiegelberg ◽

Andris Abramenkovs ◽

Anja Charlotte Lundgren Mortensen ◽

Sara Lundsten ◽

Marika Nestor ◽

...

Keyword(s):

Tumor Growth ◽

External Beam Radiotherapy ◽

Heat Shock Protein 90 ◽

Hsp90 Inhibitor ◽

Control Group ◽

A431 Cells ◽

Anti Cancer ◽

Client Proteins

AbstractOncogenic client-proteins of the chaperone Heat shock protein 90 (HSP90) insure unlimited tumor growth and are involved in resistance to chemo- and radiotherapy. The HSP90 inhibitor Onalespib initiates the degradation of oncoproteins, and might also act as a radiosensitizer. The aim of this study was therefore to evaluate the efficacy of Onalespib in combination with external beam radiotherapy in an in vitro and in vivo approach. Onalespib downregulated client proteins, lead to increased apoptosis and caused DNA-double-strands. Monotherapy and combination with radiotherapy reduced colony formation, proliferation and migration assessed in radiosensitive HCT116 and radioresistant A431 cells. In vivo, a minimal treatment regimen for 3 consecutive days of Onalespib (3 × 10 mg/kg) doubled survival, whereas Onalespib with radiotherapy (3 × 2 Gy) caused a substantial delay in tumor growth and prolonged the survival by a factor of 3 compared to the HCT116 xenografted control group. Our results demonstrate that Onalespib exerts synergistic anti-cancer effects when combined with radiotherapy, most prominent in the radiosensitive cell models. We speculate that the depletion and downregulation of client proteins involved in signalling, migration and DNA repair mechanisms is the cause. Thus, individually, or in combination with radiotherapy Onalespib inhibits tumor growth and has the potential to improve radiotherapy outcomes, prolonging the overall survival of cancer patients.

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Blockade of NF-κB and MAPK pathways by ulinastatin attenuates wear particle-stimulated osteoclast differentiation in vitro and in vivo

Bioscience Reports ◽

10.1042/bsr20160234 ◽

2016 ◽

Vol 36 (5) ◽

Cited By ~ 5

Author(s):

Jiang-Ying Ru ◽

Hai-Dong Xu ◽

Dai Shi ◽

Jun-Bo Pan ◽

Xiao-Jin Pan ◽

...

Keyword(s):

Cathepsin K ◽

Treated Group ◽

Receptor Activation ◽

Raw264.7 Cells ◽

Control Group ◽

Nuclear Factor ◽

Trabecular Thickness ◽

Tnf Α

Ulinastatin, a urinary trypsin inhibitor (UTI), is widely used to clinically treat lipopolysaccharide (LPS)-related inflammatory disorders recently. Adherent pathogen-associated molecular patterns (PAMPs), of which LPS is the best-studied and classical endotoxin produced by Gram-negative bacteria, act to increase the biological activity of osteopedic wear particles such as polymethyl-methacrylate (PMMA) and titanium particles in cell culture and animal models of implant loosening. The present study was designed to explore the inhibitory effect of UTI on osteoclastogenesis and inflammatory osteolysis in LPS/PMMA-mediated Raw264.7 cells and murine osteolysis models, and investigate the potential mechanism. The in vitro study was divided into the control group, LPS-induced group, PMMA-stimulated group and UTI-pretreated group. UTI (500 or 5000 units/ml) pretreatment was followed by PMMA (0.5 mg/ml) with adherent LPS. The levels of inflammatory mediators including tumour necrosis factor-α (TNF-α), matrixmetallo-proteinases-9 (MMP-9) and interleukin-6 (IL-6), receptor activation of nuclear factor NF-κB (RANK), and cathepsin K were examined and the amounts of phosphorylated I-κB, MEK, JNK and p38 were measured. In vivo study, murine osteolysis models were divided into the control group, PMMA-induced group and UTI-treated group. UTI (500 or 5000 units/kg per day) was injected intraperitoneally followed by PMMA suspension with adherent LPS (2×108 particles/25 μl) in the UTI-treated group. The thickness of interfacial membrane and the number of infiltrated inflammatory cells around the implants were assessed, and bone mineral density (BMD), trabecular number (Tb.N.), trabecular thickness (Tb.Th.), trabecular separation (Tb.Sp.), relative bone volume over total volume (BV/TV) of distal femur around the implants were calculated. Our results showed that UTI pretreatment suppressed the secretion of proinflammatory cytokines including MMP-9, IL-6, TNF-α, RANK and cathepsin K through down-regulating the activity of nuclear factor kappa B (NF-κB) and MAPKs partly in LPS/PMMA-mediated Raw264.7 cells. Finally, UTI treatment decreased the inflammatory osteolysis reaction in PMMA-induced murine osteolysis models. In conclusion, these results confirm the anti-inflammatory potential of UTI in the prevention of particle disease.

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Inhibition of tumor growth induced by histamine: In vivo and in vitro studies

Agents and Actions ◽

10.1007/bf01996451 ◽

1993 ◽

Vol 38 (3-4) ◽

pp. C175-C177 ◽

Cited By ~ 16

Author(s):

G. P. Cricco ◽

C. A. Davio ◽

R. M. Bergoc ◽

E. S. Rivera

Keyword(s):

Tumor Growth ◽

In Vitro Studies ◽

Inhibition Of Tumor Growth

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The mechanism of low molecular weight heparin (LMWH) inhibition of tumor growth

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.13093 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 13093-13093 ◽

Cited By ~ 4

Author(s):

S. L. Smiley ◽

D. O. Henry ◽

M. K. Wong

Keyword(s):

Endothelial Cells ◽

Tumor Growth ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Receptor System ◽

Fgf Receptor ◽

Tumor Inhibition ◽

Inhibition Of Tumor Growth

13093 Background: Clinical studies show that LMWHs improve survival in cancer patients. There is compelling and mounting evidence that non-anticoagulation factors are at play, and that these may be contributing in a major way to improved patient outcome. Methods and Results: Dalteparin, enoxaparin, and tinzaparin were tested for their in vivo ability to inhibit tumor lines engineered for aggressive angiogenesis-driven growth. Therapeutic daily doses of drug administered the day following tumor inoculation resulted in significant angiogenesis and tumor inhibition. We previously showed that LMWHs inhibit fibroblast growth factor (FGF) -induced mitogenesis of Tumor Derived Endothelial Cells (TDECs) in a time and concentration dependent manner in vitro. We now show that this endothelial inhibition occurs through LMWHs-mediated reduction of phosphorylation and down stream signaling through ERK. The potency of LMWH was significantly reduced when TDECs were pretreated with heparinase- suggesting that the molecular target for LMWH may be the cell surface, low affinity FGF receptor system. Both our in vivo and in vitro studies demonstrate that angiogenesis and tumor inhibition are greatest for dalteparin > tinzaparin > enoxaparin. Clues to the heparin-TDECs interaction comes from tracking the real-time movement of FGF using a highly fluorescent nanocrystal bead decorated on its surface with FGF. High resolution video-microscopy shows FGF binding onto TDEC surfaces, but once heparin enters the environment, FGF detaches from the TDECs and migrates to the heparin. This ultimately results in significant TDEC growth inhibition as compared to controls. Conclusion: LMWH treatment at pharmacologic doses significantly blunts tumor growth and angiogenesis. This inhibition resides in part via heparin’s ability to sequester FGF from the low affinity receptor system on tumor endothelial cells. No significant financial relationships to disclose.

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