• Title, Summary, Keyword: Radiosensitizer

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A Synthesis of Iron Oxide Based and Gadolinium Oxide Based Radiosensitizer for the Therapeutic Enhancement of Proton Beam Cancer (양성자 빔 암치료효과 개선을 위한 산화철 및 산화가돌리늄 나노입자 기반의 방사선증감제 합성)

  • Kang, Bo Sun
    • Journal of the Korean Society of Radiology
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    • v.8 no.6
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    • pp.325-332
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    • 2014
  • Metallic nanoparticles have attractive properties in biomedical applications such as diagnostics and therapeutics. Cross linked dextran coated iron oxide nanoparticles (SPIONs) and silica coated gadolinium oxide nanoparticles (SPGONs) have been synthesized as a radiosensitizer in the proton beam cancer therapy. The dextran and silicaused for the protective moieties on the SPIONs and SPGONs respectively. Size distributions of synthesized nanoparticles were confirmed 3~5 nm for SPIONs and 30~100 nm for SPGONs by transmission electron microscope (TEM). Cell survival fraction measurement and Western blot assay were performed to evaluate the radiosensitization effects of synthesized radiosensitizer. The calculated radiosensitization of SPIONs and SPGONs at 90 % cell death from the measured cell survival curves were 1.23 and 1.03 respectively. Western blotting results also show the same consistent results that the amount of released cytochrome c from mitochondria was considerably increased for the cancer cells taken up SPIONs.

Synthesis of Synchrotron Radiation-induced Gold Nanoparticles as Radiosensitizer in Radiotherapy

  • Oh, Se An;Park, Jae Won;Kim, Seong Hoon;Kim, Sung Kyu;Yea, Ji Woon;Lee, Su Yong;Kang, Hyon Chol
    • Journal of the Korean Physical Society
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    • v.73 no.11
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    • pp.1744-1749
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    • 2018
  • This study investigated the feasibility of synthesizing GNPs using synchrotron radiation X-ray for use as a radiosensitizer in radiotherapy, and examined the morphology of the GNPs. Different concentration ratios of 4-mM gold precursor aqueous solution and 4-mM $NaHCO_3$ were mixed. This gold precursor aqueous solution was continuously irradiated with synchrotron radiation in the 4B X-ray microdiffraction beamline of Pohang Light Source (PLS)-II in Korea. The SEM, EDS, TEM, and XRD spectra of the GNPs synthesized using the synchrotron radiation were investigated. The GNPs synthesized using the synchrotron radiation were nanocrystals predominantly in the (111) direction of the face-centered cubic structure. We found that the shape of the gold nanoparticles was icosahedron at the molar concentrations of 0.25 mM:0.25 mM and 0.5 mM:0.5 mM mixed with 4 mM $HAuCl_4{\cdot}3H_2O$ and 4 mM $NaHCO_3$ solutions.

Radiosensitizing and Topoisomerase I Inhibitory Effects of Aloe vera, Formitella fraxinea, and Ulmus davidiana Extracts

  • Lee, Keyong-Ho;Lee, Jae-Hyun;Cho, Choa-Hyoung;Noh, Moon-Jong;Kim, Young-Bum
    • Natural Product Sciences
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    • v.7 no.2
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    • pp.60-62
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    • 2001
  • Ulmus davidiana, Formitella fraxinea, and Aloe vera extracts were detected to have inhibitory effects against topoisomerase I at treatment of $5{\mu}g$. Ulmus davidiana and Aloe vera extracts were found to show inhibitory effect similar to camptothecin, Formitella fraxinea extract was found to have weak activity. We also found the potential use of those extracts as a radiation sensitizer. Radiosensitizing effect at combination treatment was increased more than 2 times at single treatment of radiation, Ulmus davidiana or Formitella fraxinea extracts. Ulmus davidiana and Formitella fraxinea extracts were found to have significant radiosensitizing effect on test tumor cell line. But, Aloe vera extract was not detected to have activity as a radiosensitizer. Ulmus davidiana and Formitella fraxinea extracts are potent radiosensitizers on tumor cell lines and should be considered for further study of active compounds.

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Notch Inhibitor: a Promising Carcinoma Radiosensitizer

  • Yu, Shu-Dong;Liu, Fen-Ye;Wang, Qi-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5345-5351
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    • 2012
  • Radiotherapy is an important part of modern cancer management for many malignancies, and enhancing the radiosensitivity of tumor cells is critical for effective cancer therapies. The Notch signaling pathway plays a key role in regulation of numerous fundamental cellular processes. Further, there is accumulating evidence that dysregulated Notch activity is involved in the genesis of many human cancers. As such, Notch inhibitors are attractive therapeutic agents, although as for other anticancer agents, they exhibit significant and potential side effects. Thus, Notch inhibitors may be best used in combination with other agents or therapy. Herein, we describe evidence supporting the use of Notch inhibitors as novel and potent radiosensitizers in cancer therapy.

Ethanolic Extract from Derris scandens Benth Mediates Radiosensitzation via Two Distinct Modes of Cell Death in Human Colon Cancer HT-29 Cells

  • Hematulin, Arunee;Ingkaninan, Kornkanok;Limpeanchob, Nanteetip;Sagan, Daniel
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1871-1877
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    • 2014
  • Enhancing of radioresponsiveness of tumors by using radiosensitizers is a promising approach to increase the efficacy of radiation therapy. Recently, the ethanolic extract of the medicinal plant, Derris scandens Benth has been identified as a potent radiosensitizer of human colon cancer HT29 cells. However, cell death mechanisms underlying radiosensitization activity of D scandens extract have not been identified. Here, we show that treatment of HT-29 cells with D scandens extract in combination with gamma irradiation synergistically sensitizes HT-29 cells to cell lethality by apoptosis and mitotic catastrophe. Furthermore, the extract was found to decrease Erk1/2 activation. These findings suggest that D scandens extract mediates radiosensitization via at least two distinct modes of cell death and silences pro-survival signaling in HT-29 cells.

Brain metastasis in human epidermal growth factor receptor 2-positive breast cancer: from biology to treatment

  • Koo, Taeryool;Kim, In Ah
    • Radiation Oncology Journal
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    • v.34 no.1
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    • pp.1-9
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    • 2016
  • Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.

Psammaplin A-Modified Novel Radiosensitizers for Human Lung Cancer and Glioblastoma Cells

  • Wee, Chan Woo;Kim, Jin Ho;Kim, Hak Jae;Kang, Hyun-Cheol;Suh, Soo Youn;Shin, Beom Soo;Ma, Eunsook;Kim, Il Han
    • Journal of Radiation Protection and Research
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    • v.44 no.1
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    • pp.15-25
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    • 2019
  • Background: Psammaplin A (PsA) is a radiosensitizer whereas its clinical application is hampered by poor bioavailability. This study aimed to synthesize novel radiosensitizers using PsA as the lead compound. Materials and Methods: Eight homodimeric disulfides were synthesized from corresponding acid and cystamine dihydrochloride in N-hydroxysuccinimide and dicyclohexylcarbodiimide coupling conditions. One monomeric thiol analog was obtained by reduction of homodimeric disulfide with dithiothreitol. Clonogenic assay was used to measure cell survival after irradiation and drug treatment in human lung cancer (A549) and glioblastoma (U373MG) cells. Results and Discussion: Using the PsA backbone, nine compounds were synthesized. Eight compounds showed variable cytotoxicity with 50% inhibitory concentrations ranging $16.14{\mu}M$ to $150.10{\mu}M$ (A549), and $13.25{\mu}M$ to $50.15{\mu}M$ (U373MG). Four and six compounds radiosensitized A549 and U373MG cells, respectively. Two compounds that radiosensitized both cell lines were tested for its inhibitory effects on DNMT1. One of them was shown to significantly inhibit DNMT1 activity. Conclusion: Novel compounds with radiosensitizing activity were synthesized. These compounds have a great potential to serve as a basis for the development of future radiosensitizers. Further investigation is warranted for their clinical application.

Resveratrol and piperine enhance radiosensitivity of tumor cells

  • Tak, Jean-Kyoung;Lee, Jun-Ho;Park, Jeen-Woo
    • BMB Reports
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    • v.45 no.4
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    • pp.242-246
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    • 2012
  • The use of ionizing radiation (IR) is essential for treating many human cancers. However, radioresistance markedly impairs the efficacy of tumor radiotherapy. IR enhances the production of reactive oxygen species (ROS) in a variety of cells which are determinant components in the induction of apoptosis. Much interest has developed to augment the effect of radiation in tumors by combining it with radiosensitizers to improve the therapeutic ratio. In the current study, the radiosensitizing effects of resveratrol and piperine on cancer cells were evaluated. Cancer cell lines treated with these natural products exhibited significantly augmented IR-induced apoptosis and loss of mitochondrial membrane potential, presumably through enhanced ROS generation. Applying natural products as sensitizers for IR-induced apoptotic cell death offers a promising therapeutic approach to treat cancer.

Enhanced Radiosensitivity of Tumor Cells Treated with Vanadate in Vitro (Vanadate 처리가 종양세포의 방사선 감수성에 미치는 영향)

  • Lee, Myung-Za;Lee, Won-Young
    • Radiation Oncology Journal
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    • v.12 no.2
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    • pp.129-141
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    • 1994
  • Intracellular ions which have a major role in cellular function have been reported to affect repair of radiation damage. Recently it has been reported that ouabain sensitizes A549 tumor cellls but not CCL-120 normal cells to radiation. Ouabain inhibits the $Na^+-K^+$-pump rapidly thus it increases intracellular Na concentration, Vanadate which is distributed extensively in almost all living organisms is known to be a $Na^+-K^+$-ATPase inhibitors, This study was performed to see any change in radiosensitivity of tumor cell by vanadate and any role of $Na^+-K^+$ATPase in radiosensitization. Experiments have been carried out by pretreatment with vanadate in human cell line(A549, JMG) and mouse cell line(L1210, spleen). For the cell survival MTT assay was performed for A549 and JMC cells and frypan blue dye exclusion test for L120, and spleen cells. Measurements of $Na^+-K^+$-ATPase activity in control, vanadate treated cell, radiation treated cell (9 Gy for A549 and JMG, 2 Gy for L1201, spleen), and combined $10^{-6}M$ vanadate and radiation treated cells were done. The results were summerized as fellows. 1. L1210 cell was most radiosensitive, and spleen cell and JMG cell were intermediate, and A549 cell was least radiosensitive. 2. Mininum or no cytotoxicity was seen with vanadate below concentration of $10^{-6}M$. 3. In A549 cells there was a little change in radiosensitivity with treatment of vanadate. However radiation sensitization was shown in low dose level of radiation i. e. 2- Gy. In JMG cells no change in radiosensitivity was noted. Both L1210 and spleen cell had radiosensitization but change was greater in tumor cell. 4. $Na^+-K^+$-ATPase activity was inhibited significantly in tumor cell by treatment of vanadate. 5. Radiaiton itself inhibited $Na^+-K^+$-ATPase activity of tumor cell with high $Na^+-K^+$-ATPase concention. Increase in radiosensitivity by vanadate was closely associated with orginal $Na^+-K^+$-ATPase contents. From the above results vanadate had little cytotoxicity and it sensitized tumor cells to radiation. Inhibitory effect of vanadate on $Na^+-K^+$-ATPase activity might be one of the contributing factors for radiosensitization to tumor cells which has greater enzyme activity than that of normal cell. It was suggested vanadate could be used as a potential radiosensitizer for tumor cells.

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Hematological change in mice injected with radiosensitizer and irradiated with high-dose radiation (증감약제를 투여한 마우스에 고에너지 방사선 조사 후 혈액학적 변화에 관한 연구)

  • Jung, Myo-Young;Ji, Yeon-Sang;Dong, Kyung-Rae
    • Proceedings of the Korea Contents Association Conference
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    • pp.1136-1140
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    • 2009
  • The current population of elderly is increasing and the with an extended average lifespan, the frequency of cancerous occurrences have also increased, with these increases and the increase in radiotherapy for cancer patients, recognitions of harm and importance have become known. This article was known tumor treatment of patients with hematopoietic disorder by doing a comparative study on the changes in blood cells caused by the acute effects of trace dose to high dose of radiation exposed to mice. According to the sensitizer injection may give rise to harm to the components of peripheral blood. This material needs to be considered when for treating tumor patients and the risks of hematopoietic harm and believe that radiation therapy will be reasonable.

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