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The delivery of spatially modulated radiation fields has been shown to impact on in vitro cell survival responses. To study the effect of modulated fields on cell survival, dose response curves were determined for human DU-145 prostate, T98G glioma tumour cells and normal primary AGO-1552 fibroblast cells exposed to modulated and non-modulated field configurations delivered using a 6 MV Linac with multi-leaf collimator. When exposed to uniform fields delivered as a non-modulated or modulated configuration, no significant differences in survival were observed with the exception of DU-145 cells at a dose of 8 Gy (p = 0.024). Survival responses were determined for exposure to non-uniform-modulated beams in DU-145 and T98G and showed no deviation from the survival response observed following uniform non-modulated exposures. The results of these experiments indicate no major deviation in response to modulated fields compared to uniform exposures.

Hypoxia confers resistance to common cancer therapies, however, it has also has been shown to result in genetic alterations which may allow a survival advantage and increase the tumorigenic properties of cancer cells. Additionally, it may exert a selection pressure, allowing expansion of tumor cells with a more aggressive phenotype. To further assess the role of hypoxia in malignant progression in prostate cancer we exposed human androgen dependent prostate cancer cells (LNCaP) to cycles of chronic hypoxia and isolated a subline, LNCaP-H1. This article describes the partial characterization of this cell line. The LNCaP-H1 subline showed altered growth characteristics and exhibited androgen independent growth both in vitro and in vivo. Furthermore, these cells were resistant to mitochondrial-mediated apoptosis, probably since the endogenous levels of Bax was lower and Bcl-2 higher than in the parental LNCaP cells. Microarray analysis revealed that a complex array of pathways had differential gene expression between the 2 cell lines, with LNCaP-H1 cells exhibiting a genetic profile which suggests that they may be more likely metastasize to distant organs, especially bone. This was supported by an in vitro invasion assay, and an in vivo metastasis study. This study shows that hypoxia can select for androgen independent prostate cancer cells which have a survival advantage and are more likely to invade and metastasize.

Using agarose gel electrophoresis, we measured the effectiveness of high-Z metal particles of different sizes on SSB and DSB yields for plasmid DNA irradiated with 160 kVp X rays. For plasmid samples prepared in Tris-EDTA buffer, gold nanoparticles were shown to increase G'(SSB) typically by a factor of greater than 2 while G'(DSB) increased by a factor of less than 2. Similar dose-modifying effects were also observed using gold microspheres. Addition of 10(-1) M DMSO typically decreased damage yields by a factor of less than 0.5. Plasmid samples prepared in PBS showed significantly different damage yields compared to those prepared in Tris-EDTA (P0.001) with G'(SSB) and G'(DSB) increasing by factors of 100 and 48, respectively. Furthermore, addition of gold nanoparticles to samples prepared in PBS decreased G'(SSB) and G'(DSB) by factors of 0.2 and 0.3, respectively. The results show plasmid damage yields to be highly dependent on differences in particle size between the micro- and nanometer scale, atomic number (Z) of the particle, and scavenging capacity of preparation buffers. This study provides further evidence using a plasmid DNA model system for the potential of high-Z metal nanoparticles as local dose-modifying agents.

of the histological types of non-SCLC, accounting for 1-3% of all SCLC. The low incidence has precluded the development of randomized clinical trials. To investigate the clinical features, prognostic factors, as well as the role of radiation therapy, we designed this retrospective analysis. Materials/Methods: Between January 2004 and December 2011, patients with histologically diagnosed CSCLC in CIH-CAMS were retrospectively analyzed. The overall survival (OS), progression free survival (PFS), locoregional recurrence free survival (LRFS), and distant metastasis survival (DMFS) were calculated by Kaplan-Meier method. Results: Forty-four patients were enrolled, with a median age of 59 years old. The most common combined component was squamous cell carcinoma (59.1%). The disease of stage I, II, III and IV was 13.6%, 20.5%, 47.7% and 18.2%, respectively. Thirty-seven patients (84.1%) received multimodality treatment, including 37 (84.1%) with chemotherapy, 34 (77.2%) with surgery, and 23 (52.3%) with radiation therapy. The median follow-up was 24 months. The median time of OS, PFS and LRFS was 26.5-, 13.3-, 18.4-month, respectively. The 1-, 3and 5-year OS was 68.6%, 46.9% and 32.8%, respectively, with corresponding PFS of 51%, 45.4% and 32.3%, and LRFS of 61.7%, 43.3% and 34.6%, respectively. The median DMFS of patients with stage I-III disease was 40.8 months, with 1-, 3and 5-year DMFS of 59.5%, 51.5% and 36.6%, respectively. On univariate analysis, KPS 3 cm (p Z 0.049), and positive margin (p Z 0.001) were associated with lower OS. Radiation therapy significantly improved OS in patients with IIIA/IIIB disease (p Z 0.032), positive lymph nodes (p Z 0.006), trended to increase the OS in patients with T3-4 disease (p Z 0.179), but not in those with different age, sex or tumor site. For patients who had received surgery, radiation therapy significantly improved OS only in patient with >4 metastatic lymph nodes (pZ 0.025). Conclusions: CSCLC is a rare type of SCLC with relative limited stage and good prognosis. KPS 3 cm and positive margin were poor prognostic factors. At present, multimodality therapy is recommended. Radiation therapy can benefit the patients with IIIA/IIIB CSCLC, or positive lymph nodes, or those with >4 metastatic lymph nodes after surgery. Author Disclosure: Y. Men: None. H. Zhouguang: None. L. Jun: None. L. Jima: None. Z. Zongmei: None. F. Qinfu: None. C. Dongfu: None. Z. Hongxing: None. X. Zefen: None. W. Luhua: None.

Cell survival was determined by clonogenic assay in human prostate cancer (DU145) and transformed fibroblast (AG0-1522) cells following exposure to modulated radiation fields created delivered using a X-Rad 225 kV X-ray generator. Uniform survival responses were compared to inand out-of-field responses in which 50% of the cell population was placed outside of the radiation field. Cell survival responses were determined under oxic and hypoxic conditions (0.1 % N2) and differential mechanisms of DNA damage response investigated use specific inhibitors of the DNA damage response pathway including ataxia telangiectasia mutated kinase (ATM, KU55933, Kudos Pharmaceuticals) and ataxia telangiectasia and Rad3-related protein kinase (ATR, Compound 45, Dr Chris Bakkenist, University of Pittsburgh). Temporal dependency of survival responses was determined by reseeding cells from the inand outof-field regions at different time post after irradiation. Differential mechanisms of cellular radiobiological response following exposure to intensity-modulated radiation fields

The unique properties of nanomaterials, in particular gold nanoparticles (GNPs) have applications for a wide range of biomedical applications. GNPs have been proposed as novel radiosensitizing agents due to their strong photoelectric absorption coefficient. Experimental evidence supporting the application of GNPs as radiosensitizing agents has been provided from extensive in vitro investigation and a relatively limited number of in vivo studies. Whilst these studies provide experimental evidence for the use of GNPs in combination with ionising radiation, there is an apparent disparity between the observed experimental findings and the level of radiosensitization predicted by mass energy absorption and GNP concentration. This review summarises experimental findings and attempts to highlight potential underlying biological mechanisms of response in GNP radiosensitization.

High atomic number (Z) materials such as gold preferentially absorb kilovoltage x-rays compared to soft tissue and may be used to achieve local dose enhancement in tumours during treatment with ionizing radiation. Gold nanoparticles have been demonstrated as radiation dose enhancing agents in vivo and in vitro. In the present study, we used multiple endpoints to characterize the cellular cytotoxic response of a range of cell lines to 1.9 nm gold particles and measured dose modifying effects following transient exposure at low concentrations. Gold nanoparticles caused significant levels of cell type specific cytotoxicity, apoptosis and increased oxidative stress. When used as dose modifying agents, dose enhancement factors varied between the cell lines investigated with the highest enhancement being 1.9 in AGO-1522B cells at a nanoparticle concentration of 100 microg ml(-1). This study shows exposure to 1.9 nm gold particles to induce a range of cell line specific responses including decreased clonogenic survival, increased apoptosis and induction of DNA damage which may be mediated through the production of reactive oxygen species. This is the first study involving 1.9 nm nanometre sized particles to report multiple cellular responses which impact on the radiation dose modifying effect. The findings highlight the need for extensive characterization of responses to gold nanoparticles when assessing dose enhancing potential in cancer therapy.

Purpose: In‐vitro investigations are typically performed using a single beam of radiation normally at kV energies. Emerging data has raised questions over whether this methodology results in outcomes that are representative for advanced radiation oncology delivery techniques such as IMRT and VMAT. It is important that cellular studies are undertaken in clinically relevant configurations. This requires the design of suitable phantoms and careful verification of the dosimetric accuracy of the delivery of different IMRT and VMAT techniques to the cells. Method and Materials: A PMMA phantom with an insert for a media filled T75 flask was designed and constructed. Conformal, IMRT and VMAT plans were created using Oncentra MasterPlan v3.3sp1 (Nucletron, BV) such that a uniform dose encapsulated the cell layer. All plans were subsequently recalculated on a CT scan set of a) a Farmer ionization chamber and b) a 2D ionization chamber array (IBA MatriXX Evolution) positioned between slabs of 30×30cm solid water. A constant dose‐rate was assumed during the planning process and a Varian 600CD with 120 leaf millennium MLC at 6MV used. Calculated and measured plans were compared using gamma criteria of 3%/3mm for the 2D array. Each plan was delivered to the phantom with Gafchromic EBT film placed at the bottom of the flask. Film measurements were compared with those calculated. Results:Ion chamber results were within 1.8% of the expected value for all plans. All plans resulted in more than 98.7% pixels passing the gamma criteria. Gafchromic EBT film measurements were within 1.7% of those planned. Conclusion: A PMMA phantom has been constructed which has minimal air gaps and ensures accurate and uniform delivery of dose to cells within a T75 flask. This phantom can be used for in‐vitro studies of complex delivery modalities to cells.