Feasibility of Ultra-Thin Fiber-Optic Dosimeters for Radiotherapy Dosimetry.

In this study, prototype ultra-thin fiber-optic dosimeters were fabricated using organic scintillators, wavelength shifting fibers, and plastic optical fibers. The sensor probes of the ultra-thin fiber-optic dosimeters consisted of very thin organic scintillators with thicknesses of 100, 150 and 200 µm. These types of sensors cannot only be used to measure skin or surface doses but also provide depth dose measurements with high spatial resolution. With the ultra-thin fiber-optic dosimeters, surface doses for gamma rays generated from a Co-60 therapy machine were measured. Additionally, percentage depth doses in the build-up regions were obtained by using the ultra-thin fiber-optic dosimeters, and the results were compared with those of external beam therapy films and a conventional fiber-optic dosimeter.

Measurement of Cerenkov radiation induced by the gamma-rays of Co-60 therapy units using wavelength shifting fiber.

In this study, a wavelength shifting fiber that shifts ultra-violet and blue light to green light was employed as a sensor probe of a fiber-optic Cerenkov radiation sensor. In order to characterize Cerenkov radiation generated in the developed wavelength shifting fiber and a plastic optical fiber, spectra and intensities of Cerenkov radiation were measured with a spectrometer. The spectral peaks of light outputs from the wavelength shifting fiber and the plastic optical fiber were measured at wavelengths of 500 and 510 nm, respectively, and the intensity of transmitted light output of the wavelength shifting fiber was 22.2 times higher than that of the plastic optical fiber. Also, electron fluxes and total energy depositions of gamma-ray beams generated from a Co-60 therapy unit were calculated according to water depths using the Monte Carlo N-particle transport code. The relationship between the fluxes of electrons over the Cerenkov threshold energy and the energy depositions of gamma-ray beams from the Co-60 unit is a near-identity function. Finally, percentage depth doses for the gamma-ray beams were obtained using the fiber-optic Cerenkov radiation sensor, and the results were compared with those obtained by an ionization chamber. The average dose difference between the results of the fiber-optic Cerenkov radiation sensor and those of the ionization chamber was about 2.09%.

Cryptosporidium parvum: radiation-induced alteration of the oocyst proteome.

Cryptosporidium parvum is a waterborne protozoan parasite that is found intracellularly in host animals, including humans, and causes severe diarrhea, which can lead to the death of an immunocompromised individual. Previously, we found that this organism is highly radioresistant as it can productively infect mice after exposure to a 10-kGy dose of γ-radiation. To understand how C. parvum avoids radiation damage, we characterized its protein expression patterns 6, 24, and 48 h after a 10-kGy dose of γ-radiation using two-dimensional PAGE. The gels showed 10 silver-stained spots that increased or decreased in size following γ-irradiation. Five proteins contained in these spots were identified using MALDI-TOF MS peptide fingerprinting, and two of these showed an increase in expression after γ-irradiation. These proteins were identified by LC-MS/MS as proteasome subunit alpha type 4 (NTN hydrolase fold) and thioredoxin peroxidase-like protein. The roles of these two upregulated proteins as related to the radioresistance of C. parvum remain to be evaluated.

Trends for the past 10 years and international comparisons of the structure of Korean radiation oncology.

OBJECTIVE: Study aims include determination of nationwide structural characteristics of radiation oncology facilities, types of radiation therapy equipment, availability of human resources and trends and comparisons with previous surveys. METHODS: An annual nationwide survey was conducted to collect the statistics of infrastructure since 1997. All requested questionnaires have been identical for 10 years. The questionnaires included status on basic radiation therapy facilities, human resources and radiation therapy equipment. Journal and statistical data reviews were performed to evaluate the structure of other countries. RESULTS: Radiation oncology facilities have steadily increased for 10 years and reached 60 sites in 2006. Also a steady increase of 1.5 times for linear accelerators, 5.8 times for computed tomography simulators and 3.0 times for radiation treatment planning systems was noted. Meanwhile, cobalt-60 teletherapy units and hyperthermia equipment had steadily deceased for 10 years. The number of human resources has steadily increased for the past 10 years, especially for radiation therapy technologists. However, radiation therapy equipment and human resources per population are relatively low compared with advanced countries. CONCLUSIONS: This study will assist preparation of the administrative planning policy of radiation oncology and should be useful to indicate the direction of future development and educational training programs in Korea and possibly in other countries.

Combination effect of cetuximab with radiation in colorectal cancer cells.

AIMS AND BACKGROUND: Colorectal cancer (CRC) is one of the commonest malignant disorders and frequently associated with high expression of epidermal growth factor receptor (EGFR), resulting in advanced disease and a poor prognosis. In this study, we investigated the radiosensitizing effects of the selective EGFR inhibitor cetuximab in human CRC cell lines. METHODS: Four human CRC cell lines, CaCo-2, HCT-8, LoVo, and WiDr, were treated with cetuximab and/or radiation. The effects on cell proliferation and viability were measured by MTT and annexin-V staining, and clonogenic survival assay. The in vivo effect on the growth of CRC xenografts was assessed in athymic nude mice. RESULTS: Cetuximab in combination with radiation significantly inhibited the in vitro proliferation of CRC cells, with a concomitant increase in cell death, except in WiDr cells. Clonogenic survival assay confirmed that cetuximab worked as a radiosensitizer in three cetuximab-sensitivie CRC cells. However, no correlations were found between the radiosensitivity and EGFR expression level or mutation status of EGFR signaling molecules. In nude mice bearing CRC cell xenografts, cetuximab plus radiation significantly inhibited the tumor growth over either agent alone. Interestingly, the WiDr xenograft was also sensitive to cetuximab and/or radiation in vivo, suggesting host-mediated effects of cetuximab. CONCLUSIONS: Cetuximab enhanced the radiosensitivity of CRC cells in vitro and efficiently inhibited xenograft tumor growth. This study provided a rationale for the clinical application of the selective EGFR inhibitor cetuximab in combination with radiation in CRC.

Clinical characteristics of radiation oncology in Korea during past 10 years.

To understand trends in the clinical characteristics of radiation oncology over the last 10 yr in Korea, annual survey questionnaires were sent to all of Korean radiation oncology facilities since 1990. Questionnaires addressed basic radiation therapy facilities and the clinical information. Responses were obtained from all facilities, and data collected from 1997 to 2006 was analyzed. The numbers of new patients that have undergone radiation therapy and the numbers of hospitals with a department of radiation oncology have steadily increased over the past 10 yr, and totaled 37,215 patients and 60 hospitals, respectively, in 2006. However, the proportion of patients irradiated among total cancer patients has remained below 30% over the last 10 yr. The numbers of prostate cancer, breast cancer, and hepatoma have increased by more than 3 fold over the past 10 yr. Moreover, the percentage of irradiated patients treated by brachytherapy was 10.3% in 1997, but this gradually fell to only 4.2% in 2006. The information collected described the role played by radiation oncology in Korea. Continuous surveys are required to enable trends to be detected.

Correction: Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4.

[This corrects the article DOI: 10.18632/oncotarget.3218.].

Low-Dose Ionizing γ-Radiation Promotes Proliferation of Human Mesenchymal Stem Cells and Maintains Their Stem Cell Characteristics.

Mesenchymal stem cells (MSCs), which are multipotent and have self-renewal ability, support the regeneration of damaged normal tissue. A number of external stimuli promote migration of MSCs into peripheral blood and support their participation in wound healing. In an attempt to harness the potential beneficial effects of such external stimuli, we exposed human MSCs (hMSCs) to one such stimulus-low-dose ionizing radiation (LDIR)-and examined their biological properties. To this end, we evaluated differences in proliferation, cell cycle, DNA damage, expression of surface markers (CD29, CD34, CD90, and CD105), and differentiation potential of hMSCs before and after irradiation with γ-rays generated using a 137CS irradiator. At doses less than 50 mGy, LDIR had no significant effect on the viability or apoptosis of hMSCs. Interestingly, 10 mGy of LDIR increased hMSC viability by 8% (p < 0.001) compared with non-irradiated hMSCs. At doses less than 50 mGy, LDIR did not induce DNA damage, including DNA strand breaks, or cause cellular senescence or cell-cycle arrest. Surface marker expression and in vitro differentiation potential of hMSCs were maintained after two exposures to LDIR at 10 mGy per dose. In conclusion, a two-dose exposure to LDIR at 10 mGy per dose not only facilitates proliferation of hMSCs, it also maintains the stem cell characteristics of hMSCs without affecting their viability. These results provide evidence for the potential of LDIR as an external stimulus for in vitro expansion of hMSCs and application in tissue engineering and regenerative medicine.

HSPB1 Inhibits the Endothelial-to-Mesenchymal Transition to Suppress Pulmonary Fibrosis and Lung Tumorigenesis.

The endothelial-to-mesenchymal transition (EndMT) contributes to cancer, fibrosis, and other pathologic processes. However, the underlying mechanisms are poorly understood. Endothelial HSP1 (HSPB1) protects against cellular stress and has been implicated in cancer progression and pulmonary fibrosis. In this study, we investigated the role of HSPB1 in mediating the EndMT during the development of pulmonary fibrosis and lung cancer. HSPB1 silencing in human pulmonary endothelial cells accelerated emergence of the fibrotic phenotype after treatment with TGFß or other cytokines linked to pulmonary fibrosis, suggesting that HSPB1 maintains endothelial cell identity. In mice, endothelial-specific overexpression of HSPB1 was sufficient to inhibit pulmonary fibrosis by blocking the EndMT. Conversely, HSPB1 depletion in a mouse model of lung tumorigenesis induced the EndMT. In clinical specimens of non-small cell lung cancer, HSPB1 expression was absent from tumor endothelial cells undergoing the EndMT. Our results showed that HSPB1 regulated the EndMT in lung fibrosis and cancer, suggesting that HSPB1-targeted therapeutic strategies may be applicable for treating an array of fibrotic diseases.

In vivo monitoring of CD44+ cancer stem-like cells by γ-irradiation in breast cancer.

There is increasing evidence that cancer contains cancer stem cells (CSCs) that are capable of regenerating a tumor following chemotherapy or radiotherapy. CD44 and CD133 are used to identify CSCs. This study investigated non-invasive in vivo monitoring of CD44-positive cancer stem-like cells in breast cancer by γ-irradiation using molecular image by fusing the firefly luciferase (fLuc) gene with the CD44 promoter. We generated a breast cancer cell line stably expressing fLuc gene by use of recombinant lentiviral vector controlled by CD44 promoter (MCF7-CL). Irradiated MCF7-CL spheres showed upregulated expression of CD44 and CD133, by immunofluorescence and flow cytometry. Also, gene expression levels of CSCs markers in irradiated spheres were clearly increased. CD44+ CSCs increased fLuc expression and tumor growth in vivo and in vitro. When MCF7-CL was treated with siCD44 and irradiated, CD44 expression was inhibited and cell survival ratio was decreased. MCF7-CL subsets were injected into the mice and irradiated by using a cobalt-60 source. Then, in vivo monitoring was performed to observe the bioluminescence imaging (BLI). When breast cancer was irradiated, relative BLI signal was increased, but tumor volume was decreased compared to non-irradiated tumor. These results indicate that increased CD44 expression, caused by general feature of CSCs by irradiation and sphere formation, can be monitored by using bioluminescence imaging. This system could be useful to evaluate CD44- expressed CSCs in breast cancer by BLI in vivo as well as in vitro for radiotherapy.

A cytogenetic study of Korean native goat bred in the nuclear power plant using the micronucleus assay.

Cytogenetic and hematological analysis was performed on the peripheral blood lymphocytes (PBLs) obtained from Korean native goats bred in two nuclear power plants (Wolsong and Uljin) and a control area. The frequencies of gamma-ray-induced micronuclei (MN) in the cytokinesis-blocked (CB) lymphocytes at several doses were measured in three Korean native goats. The measurements performed after irradiation showed dose-related increases in the MN frequency in each of the donors. The results were analyzed using a linear-quadratic model with a line of best fit of y=0.1019D+0.0045D2+0.0093 (y=number of MN/CB cells and D=irradiation dose in Gy). The MN rates in the goats from the Wolsong and Uljin nuclear power plant, and the control area were 9.60+/-2.88, 6.83+/-1.47 and 9.88+/-4.32 per 1,000 CB lymphocytes, respectively. The apparent difference is not statistically significant. The MN frequencies of PBLs from goats bred in three areas means that the values are within the background variation in this experiment. The MN frequencies and hematological values were similar regardless of whether the goats were bred in the nuclear power plant or the control area.

Hypoxia/reoxygenation-experienced cancer cell migration and metastasis are regulated by Rap1- and Rac1-GTPase activation via the expression of thymosin beta-4.

Signaling by small guanosine triphosphatases (GTPase), Rap1/Rac1, is one of the major pathways controlling cancer cell migration and tumor metastasis. Thymosin beta-4 (Tß4), an actin-sequestering protein, has been shown to increase migration of cancer cells. Episodes of hypoxia and re-oxygenation (H/R) are an important phenomenon in tumor microenvironment (TME). We investigated whether Tß4 could play as an intermediary to crosstalk between Rac1- and Rap1- GTPase activation under hypoxia/reoxygenation (H/R) conditions. Inhibition of Tß4 expression using transcription activator-like effector nucleases (TALEN) significantly decreased lung metastasis of B16F10 cells. Rac1 and Rap1 activity, as well as cancer cell migration, increased following induction of Tß4 expression in normoxia- or H/R-experienced cells, but were barely detectable in Tß4-depleted cells. Rap1-regulated Rac1 activity was decreased by a dominant negative Rap1 (Rap1N17), and increased by 8-(4-chloro-phenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (CPT), a Rap1 activator. In contrast, a Rac1-specific inhibitor, NSC23766, and dominant negative Rac1 (Rac1N17) enhanced Tß4 expression and aberrant Rap1 activity. While NSC23766 and Rac1N17 incompletely inhibited tumor metastasis in vivo, and H/R-experienced cancer cell migration in vitro, more efficient attenuation of cancer cell migration was accomplished by simultaneous inactivation of Rap1 and Rac1 with Rap1N17 and Rac1N17, respectively. These data suggest that a combination therapy targeting both Rap1 and Rac1 activity may be an effective method of inhibiting tumor metastasis.

A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF. EXPERIMENTAL DESIGN/RESULTS: Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became evident throughout the irradiated tissues. Accompanied by the collagen deposition, vascular EndMT (endothelial-to-mesenchymal transition) began to develop in the early phase of RIPF, before the appearance of EMT (epithelial-to-mesenchymal transition) of alveolar epithelial (AE) II cells in the substantive fibrotic phase. Concomitant with the EndMT, we detected vascular endothelial cell (EC)-specific hypoxic damage in the irradiated lung tissues. In human pulmonary artery endothelial cells (HPAEC), the radiation-induced EndMT via activation of TGFß-R1/Smad signaling was dependent on HIF1α expression. A novel HIF1α inhibitor, 2-methoxyestradiol (2-ME), inhibited the irradiation-induced EndMT via downregulation of HIF1α-dependent Smad signaling. In vivo, 2-ME inhibited the vascular EndMT, and decreased the collagen deposition associated with RIPF. Furthermore, HIF1α-related EndMT was observed also in human RIPF tissues. CONCLUSIONS: We provide the first evidence that an EndMT occurs in RIPF development and that the EndMT may be effectively inhibited by modulating vascular EC-specific hypoxic damage.

Trends of the effective dose distribution of occupational exposures in medical and research departments for KIRAMS in Republic of Korea.

This work proposes the basic reference data of occupational dose management and statistical dose distribution with the classification of radiation work groups though analysis of occupational dose distribution. Data on occupational radiation exposure from medical and scientific usage of radiation in Korea Institute of Radiological and Medical Sciences for the years 2002-11 are presented and evaluated with the characteristic tendency of radiation working groups. The results of occupational radiation exposure were measured by personal dosemeters. The monitored occupational exposure dose data were evaluated according to the average effective dose and collective dose. The most annual average effective dose for all occupational radiation workers was under 1 mSv. Considering the dose distribution of each department, most overexposure workers worked in radiopharmaceutical product facilities, nuclear medicine department and radiation oncology department. In addition, no monitored workers were found to have received an occupational exposure over 50 mSv in single year or 100 mSv in this period. Although the trend of occupational exposure was controlled <1 mSv after 2007 and the radiation protection status was sufficient, it was consistently necessary to optimise and reduce the occupational radiation exposure.

Evaluation of premature senescence and senescence biomarkers in carcinoma cells and xenograft mice exposed to single or fractionated irradiation.

The purpose of the present study was to elucidate whether premature senescence contributes to the outcome of radiotherapy (RT) and to validate senescence biomarkers in vitro and in vivo. Cultured human cancer cell lines and xenografted mice were exposed to single (SR; 2, 6 or 12 Gy) or fractionated radiation (FR; 3 x 2 Gy or 6 x 2 Gy), and premature senescence was assessed using senescence-associated ß-galactosidase (SA-ß-Gal) activity, hypophosphorylation of pRb and p21 accumulation. A variety of senescence-associated biomarkers including cathepsin D (CD), the eukaryotic translation elongation factors eEF1A1, eEF1B2, decoy receptor 2 and Dec1 were further validated in vivo or in vitro. We demonstrated the beneficial tumor suppressive role of ionizing radiation (IR)-induced premature senescence in vitro and in vivo. FR inhibited tumor growth via induction of premature senescence as effectively as an equivalent SR dose (≥6 Gy). In addition, CD and eEF1 were valuable biomarkers of cellular senescence in either SR- or RF-exposed carcinoma cells or xenograft mice. Our results suggest that 2 Gy of a conventional RT regime could achieve a better clinical outcome if premature senescence could be increased through an improved understanding of its molecular action mechanism.

The effect of oxidized low-density lipoprotein (ox-LDL) on radiation-induced endothelial-to-mesenchymal transition.

PURPOSE: Radiation-induced cardiovascular disease is a potentially severe side-effect of thoracic radiotherapy treatment. Clinically, this delayed side-effect presents as a form of accelerated atherosclerosis several years after irradiation. As general endothelial dysfunction is known to be an initiating event in radiation-induced vascular damage, we examined the effects of radiation on endothelial cells in radiation-induced atherosclerosis. MATERIALS AND METHODS: The effects of radiation on human aortic endothelial cells (HAoEC) were assessed by immunoblotting and immunofluorescence assays. Radiation-induced phenotypic changes of endothelial cells (ECs) were examined using atherosclerotic tissues of irradiated apoprotein E null (ApoE(-/-)) mice. RESULTS: Radiation induced the HAoEC to undergo phenotypic conversion to form fibroblast-like cells, called the endothelial-to-mesenchymal transition (EndMT), which leads to the upregulation of mesenchymal cell markers such as alpha-smooth muscle actin (α-SMA), fibroblast specific protein-1 (FSP-1), and vimentin, and downregulation of endothelial cell-specific markers such as CD31 and vascular endothelial (VE)-cadherin. Furthermore, compared with low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL) significantly augmented radiation-induced EndMT in HAoEC. These fibrotic phenotypes of ECs were found in atherosclerotic tissues of irradiated ApoE(-/-) mice with increased levels of ox-LDL. CONCLUSIONS: Taken together, these observations suggest that ox-LDL accelerates radiation-induced EndMT and subsequently contributes to radiation-induced atherosclerosis, providing a novel target for the prevention of radiation-induced atherosclerosis.

Dosimetric evaluation of a glass dosimeter for proton beam measurements.

PURPOSE: The GD-301 radiophotoluminescent glass dosimeter system has recently become commercially available. The purpose of this study was to investigate the dosimetric characteristics (reproducibility, linearity, dose rate, fading, angular dependence, and depth-dose distribution) of this system for clinical dosimetry in a high-energy proton beam and to compare it with lithium fluoride TLD-100. MATERIALS AND METHODS: The depth-dose distribution measured with the glass dosimeter was compared to those from GEANT4 Monte-Carlo simulation. All measurements were performed in a proton beam (IBA Proton Therapy System-Proteus 235) at the National Cancer Center in Korea. Dosimeters were irradiated in a water phantom using a stair-shaped holder specially designed for this study. Maximum height was 100mm with 1mm steps in each of ten-tiers. RESULTS: Reproducibility in the 200 MeV proton beam was within 1.5% for the glass dosimeter, and within 1.7% for TLD-chip responses. The glass dosimeter signal was linear as a function of applied dose in the range of 1-10 Gy. The dose rate dependence of both dosimeters was within 1.5%. The fading effect of the glass dosimeter was found to be within 1.6% for 6 months. Angular dependence of the glass dosimeter was measured to be approximately 1.3% for angles that were 80° from the beam axis using a cylindrical phantom. Depth-dose distributions in the non-modulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3.0% lower than those measured with the ionization chamber and simulation model using GEANT4 code. The Bragg peak depths determined from the ionization chamber, the glass dosimeter and GEANT4 simulation were 84.8mm, 84.2mm and 85.0mm, respectively. For the modulated proton beam, the SOBP width between the 90% proximal and the distal dose levels as obtained from the glass dosimeter was 48.1mm. The SOBP width measured with the ionization chamber was 52.2mm. CONCLUSIONS: Measurements comparing the glass dosimeter and TLD-100 dosimetric characteristics demonstrated the suitability of use of the glass dosimeter for dose measurement in high-energy proton beam therapy.

Feasibility study of glass dosimeter for in vivo measurement: dosimetric characterization and clinical application in proton beams.

PURPOSE: To evaluate the suitability of the GD-301 glass dosimeter for in vivo dose verification in proton therapy. METHODS AND MATERIALS: The glass dosimeter was analyzed for its dosimetrics characteristic in proton beam. Dosimeters were calibrated in a water phantom using a stairlike holder specially designed for this study. To determine the accuracy of the glass dosimeter in proton dose measurements, we compared the glass dosimeter and thermoluminescent dosimeter (TLD) dose measurements using a cylindrical phantom. We investigated the feasibility of the glass dosimeter for the measurement of dose distributions near the superficial region for proton therapy plans with a varying separation between the target volume and the surface of 6 patients. RESULTS AND DISCUSSION: Uniformity was within 1.5%. The dose-response has good linearity. Dose-rate, fading, and energy dependence were found to be within 3%. The beam profile measured using the glass dosimeter was in good agreement with the profile obtained from the ionization chamber. Depth-dose distributions in nonmodulated and modulated proton beams obtained with the glass dosimeter were estimated to be within 3%, which was lower than those with the ionization chamber. In the phantom study, the difference of isocenter dose between the delivery dose calculated by the treatment planning system and that measured by the glass dosimeter was within 5%. With in vivo dosimetry, the calculated surface doses overestimated measurements by 4%-16% using glass dosimeter and TLD. CONCLUSION: It is recommended that bolus be added for these clinical cases. We also believe that the glass dosimeter has considerable potential for use with in vivo patient proton dosimetry.

Anti-tumor effects by a synthetic chalcone compound is mediated by c-Myc-mediated reactive oxygen species production.

Overexpression of c-Myc represents the most frequently deregulated genetic event in cancer, and therefore c-Myc may represent a good molecular target for cancer therapy. The human lung carcinoma cell line, NCI-H1299, shows resistance to conventional cancer treatments, such as ionizing radiation (IR) and cisplatin, while the lung carcinoma cell line, NCI-H460, is sensitive to treatment with these agents. However, when treated with a chalcone compound [toluenesulfonylamido-chalcone, 4'-(p-toluene sulfonyl amino)-3,4-dihydroxy chalcone (TSHDC)], cell death was dramatically induced in NCI-H1299 cells as compared to NCI-H460 cells. TSHDC-mediated cytotoxicity was not dependent on the status of p53 and p21. However, TSHDC exerted increased c-Myc-dependent reactive oxygen species (ROS) production in NCI-H1299 cells in which c-Myc is overexpressed, while increased ROS production did not occur in A549 or NCI-H460 cells with a low c-Myc level. Several colon and brain cancer cells also showed a correlation between c-Myc expression and TSHDC-mediated increased cell death. Tumor regression by TSHDC was more dramatic in NCI-H1299 cells than NCI-H460 cells, when these cells were grafted to nude mice. However, in the case of IR and cisplatin, NCI-H460 cells were more sensitive than NCI-H1299 cells. From these results, c-Myc-mediated ROS production may be a good target for screening of novel cancer drugs and TSHDC might be a good candidate as a cancer drug, specifically in cancer cells that overexpress c-Myc.

Effect of ablated hippocampal neurogenesis on the formation and extinction of contextual fear memory.

Newborn neurons in the subgranular zone (SGZ) of the hippocampus incorporate into the dentate gyrus and mature. Numerous studies have focused on hippocampal neurogenesis because of its importance in learning and memory. However, it is largely unknown whether hippocampal neurogenesis is involved in memory extinction per se. Here, we sought to examine the possibility that hippocampal neurogenesis may play a critical role in the formation and extinction of hippocampus-dependent contextual fear memory. By methylazoxymethanol acetate (MAM) or gamma-ray irradiation, hippocampal neurogenesis was impaired in adult mice. Under our experimental conditions, only a severe impairment of hippocampal neurogenesis inhibited the formation of contextual fear memory. However, the extinction of contextual fear memory was not affected. These results suggest that although adult newborn neurons contribute to contextual fear memory, they may not be involved in the extinction or erasure of hippocampus-dependent contextual fear memory.