scholarly journals Image-Guided Neutron Capture Therapy Using the Gd-DO3A-BTA Complex as a New Combinatorial Treatment Approach

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ki-Hye Jung ◽  
Ji-Ae Park ◽  
Jung Young Kim ◽  
Mi Hyun Kim ◽  
Seyoung Oh ◽  
...  
Keyword(s):  
Tumor Size ◽  
Neutron Capture ◽  
Inhibitory Effect ◽  
Accurate Information ◽  
Therapeutic Effects ◽  
Neutron Capture Therapy ◽  
Accumulation Time ◽  
Related Proteins ◽  
Treat Breast Cancer

Gadolinium-neutron capture therapy (Gd-NCT) is based on the nuclear capture reaction that occurs when 157Gd is irradiated with low energy thermal neutrons to primarily produce gamma photons. Herein, we investigated the effect of neutron capture therapy (NCT) using a small molecular gadolinium complex, Gd-DO3A-benzothiazole (Gd-DO3A-BTA), which could be a good candidate for use as an NCT drug due to its ability to enter the intracellular nuclei of tumor cells. Furthermore, MRI images of Gd-DO3A-BTA showed a clear signal enhancement in the tumor, and the images also played a key role in planning NCT by providing accurate information on the in vivo uptake time and duration of Gd-DO3A-BTA. We injected Gd-DO3A-BTA into MDA-MB-231 breast tumor-bearing mice and irradiated the tumors with cyclotron neutrons at the maximum accumulation time (postinjection 6 h); then, we observed the size of the growing tumor for 60 days. Gd-DO3A-BTA showed good therapeutic effects of chemo-Gd-NCT for the in vivo tumor models. Simultaneously, the Gd-DO3A-BTA groups ([Gd-DO3A-BTA(+), NCT(+)]) showed a significant reduction in tumor size (p<0.05), and the inhibitory effect on tumor growth was exhibited in the following order: [Gd-DO3A-BTA(+), NCT(+)] > [Gd-DO3A-BTA(+), NCT(−)] > [Gd-DO3A-BTA(−), NCT(+)] > [Gd-DO3A-BTA(−), NCT(−)]. On day 60, the [Gd-DO3A-BTA(+), NCT(+)] and [Gd-DO3A-BTA(−), NCT(−)] groups exhibited an approximately 4.5-fold difference in tumor size. Immunohistochemistry studies demonstrated that new combinational therapy with chemo-Gd-NCT could treat breast cancer by both the inhibition of tumor cell proliferation and induction of apoptosis-related proteins, with in vivo tumor monitoring by MRI.

scholarly journals Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action

2021 ◽  
Vol 22 (15) ◽  
pp. 8106
Author(s):  
Tianming Song ◽  
Yawei Qu ◽  
Zhe Ren ◽  
Shuang Yu ◽  
Mingjian Sun ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Photodynamic Therapy ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Potential Applications ◽  
Zno Quantum Dots ◽  
Zno Qds

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

scholarly journals Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In vivo Evaluation

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3609 ◽  
Author(s):  
Pulagam ◽  
Gona ◽  
Gómez-Vallejo ◽  
Meijer ◽  
Zilberfain ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Mouse Model ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
The Core ◽  
Boron Neutron Capture ◽  
Biodistribution Studies ◽  
Imaging Results

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]−) with hydrodynamic diameter of 37.8 ± 0.5 nm, core diameter of 19.2 ± 1.4 nm and ξ-potential of −18.0 ± 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4]− could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]−. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.

scholarly journals Therapeutic effects of the novel Leucyl-tRNA synthetase inhibitor BC-LI-0186 in non-small cell lung cancer

2019 ◽  
Vol 11 ◽  
pp. 175883591984679 ◽  
Author(s):  
Eun Young Kim ◽  
Jin Gu Lee ◽  
Jung Mo Lee ◽  
Arum Kim ◽  
Hee Chan Yoo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Antitumor Effect ◽  
Inhibitory Effect ◽  
Trna Synthetase ◽  
Small Cell ◽  
Therapeutic Effects ◽  
Small Cell Lung

Objective: Leucyl-tRNA synthetase (LRS) is an aminoacyl-tRNA synthetase catalyzing ligation of leucine to its cognate tRNA and is involved in the activation of mTORC1 by sensing cytoplasmic leucine. In this study, the usefulness of LRS as a therapeutic target of non-small cell lung cancer (NSCLC) and the anticancer effect of the LRS inhibitor, BC-LI-0186, was evaluated. Methods: LRS expression and the antitumor effect of BC-LI-0186 were evaluated by immunohistochemical staining, immunoblotting, and live cell imaging. The in vivo antitumor effect of BC-LI-0186 was evaluated using Lox-Stop-Lox (LSL) K-ras G12D mice. Results: LRS was frequently overexpressed in NSCLC tissues, and its expression was positively correlated with mTORC1 activity. The guanosine-5’-triphosphate (GTP) binding status of RagB was related to the expression of LRS and the S6K phosphorylation. siRNA against LRS inhibited leucine-mediated mTORC1 activation and cell growth. BC-LI-0186 selectively inhibited phosphorylation of S6K without affecting phosphorylation of AKT and leucine-mediated co-localization of Raptor and LAMP2 in the lysosome. BC-LI-0186 induced cleaved poly (ADP-ribose) polymerase (PARP) and caspase-3 and increase of p62 expression, showing that it has the autophagy-inducing property. BC-LI-0186 has the cytotoxic effect at nanomolar concentration and its GI50 value was negatively correlated with the degree of LRS expression. BC-LI-0186 showed the antitumor effect, which was comparable with that of cisplatin, and mTORC1 inhibitory effect in a lung cancer model. Conclusions: BC-LI-0186 inhibits the noncanonical mTORC1-activating function of LRS. These results provide a new therapeutic strategy for NSCLC and warrant future clinical development by targeting LRS.

In Vivo and In Vitro Uptake Study of Boronated Porphyrins for Neutron Capture Therapy

2001 ◽  
pp. 1015-1020 ◽  
Author(s):  
Akira Matsumura ◽  
Yasushi Shibata ◽  
Tetsuya Yamamoto ◽  
Fumiyo Yoshida ◽  
Kei Nakai ◽  
...  
Keyword(s):  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
Uptake Study ◽  
In Vitro Uptake

Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo

2019 ◽  
Vol 133 (13) ◽  
pp. 1523-1536 ◽  
Author(s):  
Xiao Sun ◽  
Xiuli Feng ◽  
Dandan Zheng ◽  
Ang Li ◽  
Chunyan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
Cordyceps Sinensis ◽  
Chronic Obstructive ◽  
Therapeutic Effects ◽  
Related Proteins ◽  
And Oxidative Stress

Abstract Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in Cordyceps sinensis (C. sinensis), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo. Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both in vitro and in vivo, whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both in vitro and in vivo. Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured C. sinensis on COPD patients.

scholarly journals In vivo neutron capture therapy of cancer using ultrasmall gadolinium oxide nanoparticles with cancer-targeting ability

RSC Advances ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 865-874 ◽  
Author(s):  
Son Long Ho ◽  
Garam Choi ◽  
Huan Yue ◽  
Hee-Kyung Kim ◽  
Ki-Hye Jung ◽  
...  
Keyword(s):  
Neutron Capture ◽  
Gadolinium Oxide ◽  
Growth Suppression ◽  
Cancer Growth ◽  
Oxide Nanoparticles ◽  
Cancer Targeting ◽  
Neutron Capture Therapy ◽  
Targeting Ability ◽  
Gadolinium Oxide Nanoparticles

A cancer growth suppression was observed due to the GdNCT effects of the RGD-PAA-UGNPs.

ChemInform Abstract: Boronated Porphyrins for Neutron Capture Therapy: Synthesis and in vivo Distribution of Boronated Porphyrins

ChemInform ◽  
1988 ◽  
Vol 19 (8) ◽  
Author(s):  
D. GABEL ◽  
R. G. FAIRCHILD ◽  
M. HILLMAN ◽  
G. OENBRINK ◽  
R. MUELLER
Keyword(s):  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
In Vivo Distribution

scholarly journals Dosimetry of In Vivo Experiment for Lung Cancer Based on Boron Neutron Capture Therapy on Radial Piercing Beam Port Kartini Nuclear Reactor by MCNPX Simulation Method

2018 ◽  
Vol 35 (3) ◽  
pp. 213-216
Author(s):  
Atika Maysaroh ◽  
Kusminarto Kusminarto ◽  
Dwi Satya Palupi ◽  
Yohannes Sardjono
Keyword(s):  
Lung Cancer ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Boron Concentration ◽  
Gamma Ray ◽  
Neutron Capture Therapy ◽  
Thermal Neutrons ◽  
Boron Neutron Capture ◽  
Beam Port

Cancer is one of the leading causes of death globally, with lung cancer being among the most prevalent. Boron Neutron Capture Therapy (BNCT) is a cancer therapy method that uses the interaction between thermal neutrons and boron-10 which produces a decaying boron-11 particle and emits alpha, lithium 7 and gamma particles. A study was carried out to model an in vivo experiment of rat organisms that have lung cancer. Dimensions of a rat’s body were used in Konijnenberg research. Modeling lung cancer type, non-small cell lung cancer, was used in Monte Carlo N Particle-X. Lung cancer was modeled with a spherical geometry consisting of 3 dimensions: PTV, GTV, and CTV. In this case, the neutron source was from the radial piercing beam port of Kartini Reactor, Yogyakarta. The variation of boron concentration was 20, 25, 30, 35, 40, and 40 µg/g cancer. The output of the MCNP calculation was neutron scattering dose, gamma-ray dose and neutron flux from the reactor. A neutron flux was used to calculate the alpha proton and gamma-ray dose from the interaction of tissue material and thermal neutrons. The total dose was calculated from a four-dose component in BNCT. The results showed that the dose rate will increase when the boron concentration is higher, whereas irradiating time will decrease.

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