Abstract：
:Triple negative breast cancer (TNBC) is an aggressive disease with a high risk of recurrence and death. Here, we present a novel strategy to enhance the radiotherapy of TNBC by combining gold nanoparticles (AuNPs) with pentamidine, a clinically approved anti-parasitic agent with anti-cancer properties. The radiosensitization effects of PEG-stabilized AuNPs (PEG-AuNPs) in combination with pentamidine were evaluated in two human TNBC cell lines (MDA-MB-231 and MDA-MB-436). Our results showed that PEG-AuNPs alone sensitized both cell lines to radiation, achieving dose enhancement factors of 1.26 and 1.15 in MDA-MB-231 and MDA-MB-436, respectively. In combination with pentamidine, the greatest dose enhancement was achieved in MDA-MB-231 after 24 h of treatment with 500 μM PEG-AuNPs and 20 μM pentamidine (dose enhancement factor of 1.55). Based on the in vitro data, it is projected that this combination would result in a 10 log increase in cell kill compared to radiation alone in a clinical setting, where 50 Gy is administered to breast cancer patients in 25 fractions over 5 weeks. Studies to elucidate the underlying mechanism of radiosensitization revealed that the adsorption of pentamidine onto the PEG-AuNP surface increased the cellular uptake of gold compared to PEG-AuNPs alone. In addition, the combination resulted in a significantly greater number of residual DNA double-strand breaks compared to that of either agent alone after a 2 Gy dose. Taken together, the dual action of pentamidine on the physical and biological pathways of radiosensitization by PEG-AuNPs results in superior radiotherapeutic effects of the combined treatment group in MDA-MB-231.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Her S,Cui L,Bristow RG,Allen Cdoi
10.1667/RR14315.1subject
Has Abstractpub_date
2016-05-01 00:00:00pages
549-62issue
5eissn
0033-7587issn
1938-5404journal_volume
185pub_type
杂志文章abstract：:Four programs have been written to enable radiobiologists to build a computer data base of cellular dose-survival data, calculate cell survival with a correction for cell multiplicity at the time of irradiation, fit various survival models to the data by iteratively weighted least squares, and calculate the ratio of s...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1987-11-01 00:00:00
abstract：:While lifespan studies provide basic information for estimating the risk of ionizing radiation, findings on the effect of low-dose/low-dose-rate irradiation on the lifespan of mammals are controversial. Here we evaluate the effect of continuous exposure to low-dose-rate γ radiation on the lifespan of mice with acceler...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2977.1
更新日期：2013-06-01 00:00:00
abstract：:We have previously published the techniques and preliminary results of an SV40 viral probe assay for gamma-radiation-induced single- and double-strand DNA breaks and their intracellular repair in higher cells (Radiat. Res. 101, 356-372, 1985). Those experiments with SV40 infected CV-1 monkey kidney cells suggested tha...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-12-01 00:00:00
abstract：:Fluorescence in situ hybridization procedures were used to examine the influence of chromosome locus on the frequency and type of chromosome aberrations induced by 60Co gamma rays in the human lymphoblastoid cell line TK6. Aberrations involving the X chromosome were compared to those involving the similarly sized auto...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:Solid thymidylyl-(3'-->5')-thymidine (dTpdT) was irradiated in a vacuum with monochromatic photons from 150 to 300 nm; the photoproducts were analyzed quantitatively by high-performance liquid chromatography. The results of the experiment were as follows: (1) above 210 nm the major photoproducts were three dithymine p...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:To determine the linear energy transfer (LET) dependence of the biological effects of densely ionizing radiation in relation to changes in the ionization density along the track, we measured the yields and spectrum of clustered DNA damages induced by charged particles of different atomic number but similar kinetic ene...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2093.1
更新日期：2010-08-01 00:00:00
abstract：:This work provides a description of a new interaction, cross-section-based model for radiation-induced cellular inactivation, sublethal damage, DNA repair and cell survival, with the ability to more accurately elucidate different radiation-response phenomena. The principal goal of this work is to describe the damage-i...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RADE-20-00052.1
更新日期：2020-09-16 00:00:00
abstract：:It is well established that high-LET radiations efficiently induce chromosome aberrations. However, data on the effect of protons on telomere maintenance, as involved in genomic stability, are scarce and contradictory. Here we demonstrate that high-LET protons induce telomere lengthening in human primary fibroblasts a...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2127.1
更新日期：2010-11-01 00:00:00
abstract：:The presence of low levels of oxygen may have profound effects on the cytotoxic activity of radiation, radiosensitizers, and bioreductive alkylating agents. As others have shown, low oxygen tensions may significantly alter rates of cellular and chemical oxygen consumption. When experiments are performed at very low ox...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1986-10-01 00:00:00
abstract：:This continues the series of periodic general reports on cancer mortality in the cohort of A-bomb survivors followed by the Radiation Effects Research Foundation. The follow-up is extended by the 5 years 1986-1990, and analysis includes an additional 10,500 survivors with recently estimated radiation doses. Together t...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:A dose-response relationship was established in normal unanesthetized cats for emetic incidence, latency to onset of vomiting, and duration of emetic activity over a period of 24 h after whole-body exposure to 60Co radiation at selected doses between 7.5 and 90 Gy. Each episode of vomiting, i.e., retching and expulsio...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1987-03-01 00:00:00
abstract：:We report here on a qualitative and quantitative comparison of four kinetic photon cell survival models. The commonly used linear-quadratic model extended by a dose protraction factor, the lethal potentially lethal model, the repair misrepair model and the recently reported Giant LOop Binary LEsion (GLOBLE) model are ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR13862.1
更新日期：2015-11-01 00:00:00
abstract：:Survival of colony-forming units-spleen (CFU-S) was measured after single doses of photons or heavy charged particles from the BEVALAC. The purposes were to define the radiosensitivity to heavy ions used medically and to evaluate relationships between relative biological effectiveness (RBE) and dose-averaged linear en...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-10-01 00:00:00
abstract：:The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is the key functional element in the DNA-PK complex that drives nonhomologous end joining (NHEJ), the predominant DNA double-strand break (DSB) repair mechanism operating to rejoin such breaks in mammalian cells after exposure to ionizing radiation. It h...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR2092.1
更新日期：2011-01-01 00:00:00
abstract：:The electroporation of restriction enzymes into mammalian cells results in DNA double-strand breaks that can lead to chromosome aberrations. Four chemicals known to interfere with cellular responses to DNA damage were investigated for their effects on chromosome aberrations induced by AluI and Sau3AI; in addition, the...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:This commentary considers modulation as a factor of potential biological importance in assessment of risk of radiofrequency (RF) energy emitted by communications systems and other technologies. Modulation introduces a spread of frequencies into a carrier waveform, but in nearly all cases this spread is small compared ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3191
更新日期：2004-08-01 00:00:00
abstract：:To compare the genotoxic effects of high-LET ionizing radiation to those of low-LET radiation, we investigated the responses of human lymphoblastoid cells to DNA damage TK6 after treatment with either low-LET X rays or high-LET iron ions (1000 keV/microm). A highly localized distribution of gammaH2AX/RAD51 foci was ob...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2002)158[0678:dccpih]2.0.co;2
更新日期：2002-12-01 00:00:00
abstract：:To determine whether systemic administration of MnSOD-PL protected mice from the acute hematopoietic syndrome and delayed death after total-body irradiation (TBI), C57BL/ 6J mice were injected intravenously with 100 microl liposomes containing 100 microg of human MnSOD-transgene plasmid 24 h prior to irradiation with ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr1286.1
更新日期：2008-10-01 00:00:00
abstract：:The lactose operon functions under the control of the repressor-operator system. Binding of the repressor to the operator prevents the expression of the structural genes. This interaction can be destroyed by the binding of an inducer to the repressor. If ionizing radiations damage the partners, a dramatic dysfunction ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3336
更新日期：2005-04-01 00:00:00
abstract：:Bcl-X(S) is a pro-apoptosis member of the Bcl2 family that has been shown to induce cell death and enhance chemosensitivity. We have investigated the effect of Bcl-X(S) overexpression on radiation sensitivity. Using a tetracycline-repressible system, we found that removal of tetracycline for 16 h induced Bcl-X(S) and ...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3169
更新日期：2004-05-01 00:00:00
abstract：:The hypothesis of boron neutron capture therapy (BNCT) research has been that the short-range, high-linear energy transfer radiation produced by the capture of thermal neutrons by (10)B will potentially control tumor and spare normal tissue only if the boron compound selectively targets tumor tissue within the treatme...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR3592.1
更新日期：2006-08-01 00:00:00
abstract：:The flow cytometry mutation assay is based on detecting mutations in the CD59 gene on human chromosome 11 in CHO A(L) cells with flow cytometry, but the kinetics of mutant expression and the histogram region for mutant selection have not been studied in detail. CHO A(L) cells were analyzed by flow cytometry for CD59 e...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1276.1
更新日期：2008-11-01 00:00:00
abstract：:Abstract Double-strand breaks (DSBs) can be generated in the DNA of mammalian cells when heat-labile sites induced by ionizing radiation within a clustered DNA damage site are thermally transformed to single-strand breaks (SSBs) and combine with other SSBs or heat-labile sites in the opposite DNA strand. When this the...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1745.1
更新日期：2009-08-01 00:00:00
abstract：:Given the distinct characteristics of low-energy electrons (LEEs), particularly at energies less than 30 eV, they can be applied to a wide range of therapeutic modalities to improve cancer treatment. LEEs have been shown to efficiently produce complex molecular damage resulting in substantial cellular toxicities. Sinc...
journal_title：Radiation research
pub_type： 杂志文章,评审
doi：10.1667/RR14727.1
更新日期：2017-08-01 00:00:00
abstract：:These experiments were designed to study the kinetics and magnitude of cell repair and repopulation in tissues whose damage results in the tumor bed effect. The right hind thighs of mice were irradiated with single doses or two equal gamma-ray fractions. Interfraction intervals ranging from 30 min to 24 h (to measure ...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:The interaction function gamma(chi), which was introduced in the theory of dual radiation action as the probability that two energy transfers separated by distance chi combine with each other to produce a lesion, was estimated with sparsely ionizing radiation (60Co gamma rays and 40 kV X rays). Gamma(chi) was deduced ...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1987-10-01 00:00:00
abstract：:Pentamidine is similar to rhodamine-123 in chemical structure and state of electron charge, and rhodamine-123 was previously shown to be a hyperthermic sensitizer under appropriate cell culture conditions. The present experiments were carried out to determine whether pentamidine would potentiate hyperthermic cell kill...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
abstract：:Ionizing radiation induces chronic metabolic oxidative stress and a mutator phenotype in hamster fibroblasts that is mediated by H(2)O(2), but the intracellular source of H(2)O(2) is not well defined. To determine the role of mitochondria in the radiation-induced mutator phenotype, end points of mitochondrial function...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1617.1
更新日期：2009-12-01 00:00:00
abstract：:Blockers of the renin-angiotensin-aldosterone system (RAAS) ameliorate cognitive deficits and some aspects of brain injury after whole-brain irradiation. We investigated whether treatment with the angiotensin II type 1 receptor antagonist L-158,809 at a dose that protects cognitive function after fractionated whole-br...
journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr2560.1
更新日期：2011-07-01 00:00:00
abstract：:We show here that the arrests of cells in G2 phase of the cell cycle induced by either staurosporine or ionizing radiation are closely related phenomena governed by a common kinase signaling pathway. The protein kinase inhibitor staurosporine induces a complete G2-phase arrest in exponentially growing TK6 human lympho...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
