Abstract：
:Gleevec, a selective tyrosine kinase inhibitor, retarded the growth of anaplastic thyroid cancer cell lines in vitro and in vivo through selective inhibition of ABL tyrosine kinase activity. In the present study, we investigated the ability of Gleevec to modulate the in vitro and in vivo radiation response of anaplastic thyroid cancer cells. Cell growth assays, colony formation assays and xenograft models were used to quantify the radiosensitizing effect of Gleevec in cells of the anaplastic thyroid cancer cell lines ARO and FRO. FACS, Western blotting and histochemical techniques were employed to study the mechanisms of radiation response after exposure to Gleevec. Gleevec (7.0 microM) increased the anti-proliferative effect of radiation on the growth ARO and FRO cells in vitro. Clonogenic analysis demonstrated that Gleevec reduced cell survival after irradiation. Gleevec combined with radiation produced an increase in tumor growth inhibition compared to treatment with either modality alone in mice bearing anaplastic thyroid cancer xenografts. The drug suppressed radiation-induced ABL activation and promoted CDKN1A (p21(cip1)) accumulation in irradiated anaplastic thyroid cancer cells. Gleevec had an additional effect on radiation-induced apoptosis in cells of both cell lines and potentiated the induction of terminal growth arrest accompanied by the expression of senescence-associated beta-galactosidase. The antitumor effect of Gleevec is potentiated in adjunctive therapy with radiation not only due to inhibition of proliferative cell growth with transient cell cycle arrest and apoptosis, but also due to the terminal growth arrest associated with senescence, suggesting that tumor cell senescence is a mechanism for tumor targeting therapy in combination with ionizing radiation.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Podtcheko A,Ohtsuru A,Namba H,Saenko V,Starenki D,Palona I,Sedliarou I,Rogounovitch T,Yamashita Sdoi
10.1667/rr3466.1subject
Has Abstractpub_date
2006-01-01 00:00:00pages
35-42issue
1eissn
0033-7587issn
1938-5404pii
RR3466journal_volume
165pub_type
杂志文章abstract：:The monohydroxylated fatty acid content of peripheral blood mononuclear cells from 23 cleanup workers and 16 unexposed individuals was studied in relation to their immune status after the Chernobyl accident. Men with absorbed doses below 0.32 Gy showed higher levels of free and esterified 12-hydroxyeicosatetraenoic ac...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2001)156[0476:mfacip]2.0.co;2
更新日期：2001-11-01 00:00:00
abstract：:To elucidate the nature and kinetics of DNA strand breaks caused by low-energy Auger electron emitters, we compared the yields of DNA breaks in supercoiled pUC19 DNA in the presence of the (.)OH scavenger dimethyl sulfoxide (DMSO) after the decay of (125)I (1) in proximity to DNA after minor-groove binding ((125)I-iod...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：:The relationship between the intracellular glutathione (GSH) concentration and the aerobic radiation response was studied in Chinese hamster ovary cells. Various degrees of GSH depletion were produced by exposure to buthionine sulfoximine (BSO) and/or diethyl maleate (DEM). Diethyl maleate did not act as a classical r...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:To investigate the effects of ionizing radiation on an isolated neuronal network without complicating systemic factors, slices of hippocampus from the guinea pig were isolated and studied in vitro. Slices were irradiated with a 60Co source and compared to paired, sham-irradiated controls. Electrophysiological activity...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1987-12-01 00:00:00
abstract：:The detection of (41)Ca atoms in tooth enamel using accelerator mass spectrometry is suggested as a method capable of reconstructing thermal neutron exposures from atomic bomb survivors in Hiroshima and Nagasaki. In general, (41)Ca atoms are produced via thermal neutron capture by stable (40)Ca. Thus any (41)Ca atoms ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2043.1
更新日期：2010-08-01 00:00:00
abstract：:In pathogen-free mice, but not standard conventionally housed laboratory rodents, two distinctly different modes of early radiation lethality can be identified by modifying the irradiation technique (total-body versus abdominal irradiation) or by therapeutic intervention such as rescue of total-body-irradiated mice wi...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1989-03-01 00:00:00
abstract：:In this study, we investigated the accuracy of using off-line bioluminescence imaging (BLI) and tomography (BLT) to guide irradiation of small soft tissue targets on a small animal radiation research platform (SARRP) with on-board cone beam CT (CBCT) capability. A small glass bulb containing BL cells was implanted as ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2999.1
更新日期：2013-02-22 00:00:00
abstract：:The nitroxide Tempol, a stable free radical, has recently been shown to protect mammalian cells against several forms of oxidative stress including radiation-induced cytotoxicity. To extend this observation, six additional water-soluble nitroxides with different structural features were evaluated for potential radiopr...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1992-10-01 00:00:00
abstract：:To evaluate whether DNA alterations in mature spermatozoa could stem from DNA damage induced in immature germ cells, testis cells and spermatozoa were analyzed by the comet assay and by the sperm chromatin structure assay 14, 45 and 100 days after in vivo X irradiation of the testes. These times were selected, accordi...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3053
更新日期：2003-10-01 00:00:00
abstract：:A biophysical model has been developed that is based on the assumptions that an interphase chromosome occupies a spherical territory and that chromosome exchanges are formed by the misrejoining of two DNA double-strand breaks induced within a defined interaction distance. The model is used to explain the relative freq...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2001)156[0603:poriia]2.0.co;2
更新日期：2001-11-01 00:00:00
abstract：:The effect of transgenerational exposure to low dose rate (2.4 and 21 mGy/day) gamma irradiation on the yield of DNA double-strand breaks and oxidized guanine (8-hydroxyguanine) has been studied in the muscle and liver tissue of a model organism, the Japanese medaka fish. We found the level of unrepaired 8-hydroxyguan...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR3190.1
更新日期：2013-09-01 00:00:00
abstract：:Asynchronously growing V79 cells were assayed for mutation induction following exposure to hyperthermia either immediately before or after being irradiated with 60Co gamma rays. Hyperthermia exposures consisted of either 43.5 degrees C for 30 min or 45 degrees C for 10 min. Each of these heat treatments resulted in a ...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1989-08-01 00:00:00
abstract：:In the double-strand break (DSB) model, the initial slope (alpha) of the survival curve is determined by the number of DSBs remaining unrepaired at a certain time after irradiation. There are three types of calculations which confirm the validity of this approach. First, the model quite reasonably predicts the low-LET...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:Although conclusive evidence has been obtained for the presence of radiation-induced bystander effects, the mechanisms that trigger and regulate these processes are still largely unknown. The bystander effect may play a critical role in determining the biological effectiveness of low-dose exposures, but questions on h...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3319
更新日期：2005-03-01 00:00:00
abstract：:Using five transplantable murine tumors (SCC-VII, B16F1, KHT-C, KHT-LP1, RIF-1), measurements of tumor hypoxia have been made with two techniques which have the potential to be used for assessing oxygenation in human tumors (the Eppendorf pO2 Histograph and binding of [3H]misonidazole) and have been compared with an e...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
abstract：:Chinese hamster ovary cells in suspension cultures were heated for various times at 41.5, 43.5, and 45.5 degrees C, and quantitative determinations of microblebbing and macroblebbing of the cell membrane were performed for cells maintained at 4, 25, and 37 degrees C after hyperthermia. The percentage of cells with ble...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:The modification of methylglyoxal bis(guanylhydrazone) (MGBG) by 42 degrees C hyperthermia-and/or radiation-induced cell killing was examined in Chinese hamster V-79 cells. At concentrations of more than 10 microM, cell survival decreased exponentially with increased MGBG exposure times. Cell lethality of MGBG (10 mic...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-12-01 00:00:00
abstract：:The effects of multiple-dose gamma irradiation on the shape of survival curves were studied with mouse C3H 10T1/2 cells maintained in contact-inhibited plateau phase. The dose-fractionation intervals included 3, 6, and 24 h. Following three fractionated doses (5 Gy per dose) of exposures, cells responded to further ir...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:Radiation sensitivity was measured by the micronucleus assay in T lymphocytes of the spleen and in fibroblasts derived from three inbred strains of mice, BALB/c, A/J and C3H/He. A linear correlation between the surviving fraction and the micronucleus frequency was obtained. There were clear differences in the radiosen...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1997-10-01 00:00:00
abstract：:The basic 30-nm chromatin fiber in the mammalian cell consists of an unknown (possibly helical) arrangement of nucleosomes, with about 1.2 kb of DNA per 10-nm length of fiber. Track-structure considerations suggest that interactions of single delta rays or high-LET particles with the chromatin fiber might result in th...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1996-02-01 00:00:00
abstract：:We have investigated how radiation quality affects the induction of chromosomal aberrations in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated high charge and energy (HZE) particles including oxygen, neon, silicon, titanium and iron. Chromosome damage was assessed using thr...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR3291.1
更新日期：2013-07-01 00:00:00
abstract：:The major limitation to reaching a curative radiation dose in radioresistant tumors such as malignant gliomas is the high sensitivity to radiation and subsequent damage of the surrounding normal tissues. Novel dose delivery methods such as minibeam radiation therapy (MBRT) may help to overcome this limitation. MBRT ut...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR14018.1
更新日期：2015-09-01 00:00:00
abstract：:As a follow-up to the two previous surveys of radiation therapy among the atomic bomb survivors, a large-scale survey was performed to document (1) the number of radiation therapy treatments received by the atomic bomb survivors and (2) the types of radiation treatments conducted in Hiroshima and Nagasaki. The previou...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1998-06-01 00:00:00
abstract：:Evidence is presented for the formation of products in irradiated dinucleoside monophosphates in which both bases are damaged. The dinucleoside monophosphates d(GpT), d(GpC), d(TpG) and d(CpG) were X-irradiated in oxygenated aqueous solution. Product identification was by NMR spectroscopy. In products containing doubl...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1995-01-01 00:00:00
abstract：:As part of a long-term study of the effects of irradiation during development, prenatal and early neonatal mortality were evaluated for beagles exposed in utero at 8 days postcoitus (dpc), 28 dpc, 55 dpc, or 2 days postpartum. Mean doses used were 0,0.16, or 0.83 Gy. A decrease in whelping rates was observed for femal...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-07-01 00:00:00
abstract：:Trp53 heterozygous mice are radiation-sensitive and cancer-prone. Groups of 7-8-week-old female Trp53 heterozygous mice were exposed to 4 Gy of 60Co gamma radiation at high (0.5 Gy/min) or low (0.5 mGy/min) dose rate. Other groups received 10 or 100 mGy at low dose rate 24 h prior to the 4-Gy dose. Tumor frequency and...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3190
更新日期：2004-07-01 00:00:00
abstract：:We have evaluated the effect of X irradiation on the mesenchymal tissue growth (blood capillaries and stromal cells) in an angiogenesis system in the mouse. This was accomplished by implanting a polyvinyl alcohol sponge disc in the subcutis of the thorax, and quantifying the extent of growth reduction of capillaries a...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1990-10-01 00:00:00
abstract：:The effect of sodium bisulfite, a specific inhibitor of chromatin proteolysis, on radiation damage in rat thymocytes in vitro was examined. Rat thymocytes irradiated with 1 kR X rays in vitro were incubated at 37 degrees C with 10 mM glucose for 4 to 6 hr. During that time development of interphase death as judged by ...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-07-01 00:00:00
abstract：:The structural maintenance of chromosome 1 (Smc1) protein is a member of the highly conserved cohesin complex and is involved in sister chromatid cohesion. In response to ionizing radiation, Smc1 is phosphorylated at two sites, Ser-957 and Ser-966, and these phosphorylation events are dependent on the ATM protein kina...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2402.1
更新日期：2011-03-01 00:00:00
abstract：:To understand the biophysical mechanism(s) underlying the induction of cell death by the decay of the Auger electron emitter iodine-125 in DNA, Chinese hamster V79 lung fibroblasts were labeled with 5-[(125)I]iodo-2'-deoxyuridine ((125)IdU) for two doubling times and frozen and stored at -135 degrees C in the presence...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2000)154[0326:todiiq]2.0.co;2
更新日期：2000-09-01 00:00:00
