MEDICAL APPLICATIONS OF PARTICLE-INDUCED X-RAY EMISSION

2008 ◽  
Vol 18 (03n04) ◽  
pp. 101-110
Author(s):  
S. HARADA ◽  
S. EHARA ◽  
K. ISHII ◽  
H. YAMAZAKI ◽  
S. MATSUYAMA ◽  
...  

We report two medical applications of particle-induced X-ray emission (PIXE) as described below (1) Observation of biological events: The kinetics of trace elements during the initiation of radiation-induced apoptosis (RIA) was observed using a micro-PIXE and PIXE. RIA is a process in which irradiated cells commit suicide; it results in the removal of severely damaged and harmful cells. During RIA, cytochrome c is released from the mitochondria and reaches the nucleus, where it activates a Ca- or Mg-dependent endonuclease. We examined this phenomenon by using a micro-PIXE and PIXE. A high concentration of Fe was detected in the stroma of cells in the early apoptotic phase. We also observed accumulation of large amounts of Ca and Mg in the nucleus.(2) Development of liquid-core microcapsules for novel cancer chemoradiotherapy: Currently, we are developing liquid-core (containing an anticancer drug) microcapsules that release their core content upon irradiation. These microcapsules will localize the anticancer drug within the irradiated field. The outer shell of these microcapsules is prepared from alginate and hyaluronic acid and polymerized by Fe, while the anticancer drug Paraplatin®(carboplatin) containing Pt is the liquid core. The micro-PIXE revealed that these microcapsules released their core content after irradiation, and the amount of carboplatin released was measured by PIXE. More than 83.1% ± 8.3% of the microcapsules were ruptured, and the amount of carboplatin released was more than 81.2% ± 2.3%. Thus, the combination of radiotherapy and chemotherapy showed improved antitumor effects and a decrease in adverse effects because of drug localization.

RSC Advances ◽  
2018 ◽  
Vol 8 (19) ◽  
pp. 10158-10162 ◽  
Author(s):  
Emiko Sekine-Suzuki ◽  
Ikuo Nakanishi ◽  
Kohei Imai ◽  
Megumi Ueno ◽  
Takashi Shimokawa ◽  
...  

A planar catechin analogue showed a significant higher protective activity against X-ray induced apoptosis in rat thymocytes than (+)-catechin.


2007 ◽  
Vol 17 (01n02) ◽  
pp. 33-40 ◽  
Author(s):  
S. HARADA ◽  
S. EHARA ◽  
K. ISHII ◽  
H. YAMAZAKI ◽  
S. MATSUYAMA ◽  
...  

Microcapsules comprising alginate and hyaluronic acid that can be decomposed by radiation are under development. Previously, we observed that radiation efficiently decomposes microcapsules comprising alginate and hyaluronic acid in the ratio 2:1 by weight. In this study, Yttrium ( Y ) was added to these microcapsules to improve their decomposition by radiation. Hyaluronic acid solutions (0.1% weight/volume) were mixed into 0.2% alginate solution, and carboplatin (0.2 mmol) was added; the resultant was used for capsule preparation. Capsules were prepared by spraying the material into mixtures of 4.34% CaCl 2 solution supplemented with Y at final concentrations from 0 to 1.0 × 10−2%. These capsules were irradiated by a single dose of 0.5, 1.0, 1.5, or 2 Gy with 60Co γ-rays. Immediately after irradiation, we observed the release of the core contents of the microcapsule using a micro Particle Induced X-ray Emission (PIXE) camera. The mean diameter of the microcapsules was 37.3 ± 7.8 μm . Maximum content of radiation-induced release was observed for liquid-core microcapsules prepared by polymerization in a 4.34% CaCl 2 solution supplemented with 5.5 × 10−3% Y .


1994 ◽  
Vol 345 (1313) ◽  
pp. 247-250 ◽  

During Drosophila development, large numbers of cells undergo natural cell death. Even though the onset of these deaths is controlled by many different signals, most of the dying cells undergo common morphological and biochemical changes that are characteristic of apoptosis in vertebrates. We have surveyed a large fraction of the Drosophila genome for genes that are required for programmed cell death by examining the pattern of apoptosis in embryos homozygous for previously identified chromosomal deletions. A single region on the third chromosome (in position 75C1,2) was found to be essential for all cell deaths that normally occur during Drosophila embryogenesis. We have cloned the corresponding genomic DNA and isolated a gene, reaper , which is capable of restoring apoptosis when reintroduced into cell death defective deletions. The reaper gene is specifically expressed in cells that are doomed to die, and its expression precedes the first morphological signs of apoptosis by 1-2 h. This gene is also rapidly induced upon X-ray irradiation, and reaper deletions offer significant protection against radiation-induced apoptosis. Our results suggest that reaper represents a key regulatory switch for the activation of apoptosis in response to a variety of distinct signals.


Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 663
Author(s):  
Timur Saliev ◽  
Dinara Baiskhanova ◽  
Dmitriy Beznosko ◽  
Dinara Begimbetova ◽  
Bauyrzhan Umbayev ◽  
...  

Background and objectives: The aim of the study was to scrutinize the ability of epsilon-aminocaproic acid (EACA) to prevent radiation-induced damage to human cells. Materials and Methods: Human peripheral blood mononuclear cells (PBMCs) were exposed to ionizing radiation at three low doses (22.62 mGy, 45.27 mGy, and 67.88 mGy) in the presence of EACA at the concentration of 50 ng/mL. Results: EACA was able to prevent cell death induced by low-dose X-ray radiation and suppress the formation of reactive oxygen species (ROS). EACA also demonstrated a capacity to protect DNA from radiation-induced damage. The data indicated that EACA is capable of suppression of radiation-induced apoptosis. Comparative tests of antioxidative activity of EACA and a range of free radical scavengers showed an ability of EACA to effectively inhibit the generation of ROS. Conclusions: This study showed that the pretreatment of PBMCs with EACA is able to protect the cells from radiation-elicited damage, including free radicals’ formation, DNA damage, and apoptosis.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13558-e13558
Author(s):  
Feng-qin Yan ◽  
Jian-qiu Wang ◽  
Shi-bo Fu ◽  
Fang-zheng Wang ◽  
Zhen-fu Fu ◽  
...  

e13558 Background: To elucidate the effect of p21 on ionizing radiation-induced apoptosis in EL-4 cells. Methods: In EL-4 cells, RT-PCR, immunocytochemistry and flow cytometry (FCM) were used to analyze the changes in the expression of p21 with time and doses caused by ionizing radiation; RNAi was used to silence the expression of p21 in EL-4 cells; FCM was applied to analyze the distribution of cell cycle,the number of the chromosome and the apoptosis in wild or p21-silencing EL-4 cells exposed to X-rays. Results: In EL-4 cells, p21 protein level was markedly increased at 8 ~ 72 h after exposure in 4.0 Gy of X-ray in vitro (p<0.01), as well as exposed in 1.0 ~ 4.0 Gy of X-ray at 24 h in vitro (p<0.05). Results of time-course experiments showed that, in EL-4 cells exposed to 4.0 Gy X-rays, the percentage in G0/G1 phase increased while that in S phase decreased, significantly different with the sham-irradiated groups (p<0.05), during 8-48h after exposure; the percentage of diploid cells increased significantly during 8-48 h (p<0.01), and the percentage of tetraploid and octoploid cells decreased significantly at 2 h and 8 h (p<0.05); the percentage of apoptosis during 2-72 h increased significantly (p<0.05-p<0.01). Compared with wild EL-4 cells, in p21-silencing EL-4 cells, the distribution of cell cycle had no apparent difference; the percentage of diploid cells decreased significantly and the percentage of octoploid cells increased significantly (p<0.01); the percentage of apoptosis increased significantly (p<0.05). Conclusions: p21 inhibited the apoptosis induced by ionizing radiation in EL-4 cells.


2008 ◽  
Vol 99 (9) ◽  
pp. 1442-1452 ◽  
Author(s):  
H Yasui ◽  
A Ogura ◽  
T Asanuma ◽  
A Matsuda ◽  
I Kashiwakura ◽  
...  

1999 ◽  
Vol 09 (03n04) ◽  
pp. 279-289
Author(s):  
Satoshi Harada ◽  
Koichiro Sera ◽  
Shyoji Futatsugawa ◽  
Hirobumi Oikawa ◽  
Yoshiharu Tamakawa

The interactions between mitochondrial and nuclear Mg concentration for the development of radiation-induced apoptosis were tested IN VIVO in Sarcoma-180 in BALB/c mice. The frequency of apoptosis was expressed as a percentage of TUNEL reactivity in the 5 microscopic views under 400 times magnification, and Mg concentration in either mitochondria or nucleus was measured by Particle Induced X-ray Emission (PIXE), on 3, 6, 9, 12 and 24 hours after the 10 or 20 Gy of 60 Co gamma ray radiation, to the mice with or without the 0.01 mMOL MgCl 2 oral administration. There were proximal increases of apoptosis, which peaked on 9 hours after radiation. The Mg concentration of mitochondria strongly correlated with frequency of apoptosis from 3 to 9 hrs after radiation, and that of the nucleus strongly correlated with frequency of apoptosis from 6 to 24 hours after radiation. The oral administration of MgCl 2 did not change those correlations. The two steps are considered: 1st) signaling from mitochondria to nucleus involving Mg on induction of apoptosis; and 2nd) removal of apoptosis involving nuclear Mg .


2010 ◽  
Vol 20 (01n02) ◽  
pp. 29-36 ◽  
Author(s):  
SATOSHI HARADA ◽  
SHIGERU EHARA ◽  
K. ISHII ◽  
H. YAMAZAKI ◽  
S. MATSUYAMA ◽  
...  

The radiation-induced releasing of the liquid-core of the microcapsules was improved using H 2 O 2, which produced O 2 generation of H 2 O 2 after irradiation. Further, we tested whether these microcapsules enhanced the antitumor effects and decreased the adverse effects in vivo in C3He / J mice. The capsules were produced by spraying a mixture of 3.0% hyaluronic acid, 2.0% alginate, 3.0% H 2 O 2, and 0.3 mmol of carboplatin on a mixture of 0.3 mol FeCl 2 and 0.15 mol CaCl 2. The microcapsules were subcutaneously injected into MM46 tumors that had been inoculated in the left hind legs of C3He / J mice. The radiotherapy comprised tumor irradiation with 10 Gy or 20 Gy 60 Co . The antitumor effect of the microcapsules was tested by measuring tumor size and monitoring tumor growth. Three types of adverse effects were considered: fuzzy hair, loss of body weight, and death. The size of the capsule size was 23 ± 2.4 µ m ɸ and that of the liquid core, 20.2 ± 2.2 µ m ɸ. The injected microcapsules localized drugs around the tumor. The production of O 2 by radiation increased the release of carboplatin from the microcapsules. The antitumor effects of radiation, carboplatin, and released oxygen were synergistic. Localization of the carboplatin decreased its adverse effects. However, the H 2 O 2 caused ulceration of the skin in the treated area. The use of our microcapsules enhanced the antitumor effects and decreased the adverse effects of carboplatin. However, the skin-ulceration caused by H 2 O 2 must be considered before these microcapsules can be used clinically.


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