Changes in intra-nuclear mechanics in response to DNA damaging agents revealed by time-domain Brillouin micro-spectroscopy.

How DNA damage and repair processes affect the biomechanical properties of the nucleus interior remains unknown. Here, an opto-acoustic microscope based on time-domain Brillouin spectroscopy (TDBS) was used to investigate the induced regulation of intra-nuclear mechanics. With this ultrafast pump-probe technique, coherent acoustic phonons were tracked along their propagation in the intra-nucleus nanostructure and the complex stiffness moduli and thicknesses were measured with an optical resolution. Osteosarcoma cells were exposed to methyl methanesulfonate (MMS) and the presence of DNA damage was tested using immunodetection targeted against damage signaling proteins. TDBS revealed that the intra-nuclear storage modulus decreased significantly upon exposure to MMS, as a result of the chromatin decondensation and reorganization that favors molecular diffusion within the organelle. When the damaging agent was removed and cells incubated for 2 h in the buffer solution before fixation the intra-nuclear reorganization led to an inverse evolution of the storage modulus, the nucleus stiffened. The same tendency was measured when DNA double-strand breaks were caused by cell exposure to ionizing radiation. TDBS microscopy also revealed changes in acoustic dissipation, another mechanical probe of the intra-nucleus organization at the nano-scale, and changes in nucleus thickness during exposure to MMS and after recovery.

Use of metrics to quantify IMRT and VMAT treatment plan complexity: A systematic review and perspectives.

PURPOSE: Fixed-field intensity modulated radiation therapy (FF-IMRT) or volumetric modulated arc therapy (VMAT) beams complexity is due to fluence fluctuation. Pre-treatment Quality Assurance (PTQA) failure could be linked to it. Several plan complexity metrics (PCM) have been published to quantify this complexity but in a heterogeneous formalism. This review proposes to gather different PCM and to discuss their eventual PTQA failure identifier abilities. METHODS AND MATERIALS: A systematic literature search and outcome extraction from MEDLINE/PubMed (National Center for Biotechnology Information, NCBI) was performed. First, a list and a synthesis of available PCM is made in a homogeneous formalism. Second, main results relying on the link between PCM and PTQA results but also on other uses are listed. RESULTS: A total of 163 studies were identified and n = 19 were selected after inclusion and exclusion criteria application. Difference is made between fluence and degree of freedom (DOF)-based PCM. Results about the PCM potential as PTQA failure identifier are described and synthesized. Others uses are also found in quality, big data, machine learning and audit procedure. CONCLUSIONS: A state of the art is made thanks to this homogeneous PCM classification. For now, PCM should be seen as a planning procedure quality indicator although PTQA failure identifier results are mitigated. However limited clinical use seems possible for some cases. Yet, addressing the general PTQA failure prediction case could be possible with the big data or machine learning help.

Dose calculation accuracy of different image value to density tables for cone-beam CT planning in head & neck and pelvic localizations.

PURPOSE: We aimed to identify the most accurate combination of phantom and protocol for image value to density table (IVDT) on volume-modulated arc therapy (VMAT) dose calculation based on kV-Cone-beam CT imaging, for head and neck (H&N) and pelvic localizations. METHODS: Three phantoms (Catphan(®)600, CIRS(®)062M (inner phantom for head and outer phantom for body), and TomoTherapy(®) "Cheese" phantom) were used to create IVDT curves of CBCT systems with two different CBCT protocols (Standard-dose Head and Standard Pelvis). Hounsfield Unit (HU) time stability and repeatability for a single On-Board-Imager (OBI) and compatibility of two distinct devices were assessed with Catphan(®)600. Images from the anthropomorphic phantom CIRS ATOM(®) for both CT and CBCT modalities were used for VMAT dose calculation from different IVDT curves. Dosimetric indices from CT and CBCT imaging were compared. RESULTS: IVDT curves from CBCT images were highly different depending on phantom used (up to 1000 HU for high densities) and protocol applied (up to 200 HU for high densities). HU time stability was verified over seven weeks. A maximum difference of 3% on the dose calculation indices studied was found between CT and CBCT VMAT dose calculation across the two localizations using appropriate IVDT curves. One IVDT curve per localization can be established with a bi-monthly verification of IVDT-CBCT. CONCLUSIONS: The IVDT-CBCTCIRS-Head phantom with the Standard-dose Head protocol was the most accurate combination for dose calculation on H&N CBCT images. For pelvic localizations, the IVDT-CBCTCheese established with the Standard Pelvis protocol provided the best accuracy.

Use of FDG-PET to guide dose prescription heterogeneity in stereotactic body radiation therapy for lung cancers with volumetric modulated arc therapy: a feasibility study.

BACKGROUND: The aim of this study was to assess if FDG-PET could guide dose prescription heterogeneity and decrease arbitrary location of hotspots in SBRT. METHODS: For three patients with stage I lung cancer, a CT-simulation and a FDG-PET were registered to define respectively the PTVCT and the biological target volume (BTV). Two plans involving volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) were calculated. The first plan delivered 4 × 12 Gy within the PTV(CT) and the second plan, with SIB, 4 × 12 Gy and 13.8 Gy (115% of the prescribed dose) within the PTV(CT) and the BTV respectively. The Dmax-PTV(CT) had to be inferior to 60 Gy (125% of the prescribed dose). Plans were evaluated through the D95%, D99% and Dmax-PTV(CT), the D2 cm, the R50% and R100% and the dice similarity coefficient (DSC) between the isodose 115% and BTV. DSC allows verifying the location of the 115% isodose (ideal value = 1). RESULTS: The mean PTV(CT) and BTV were 36.7 (±12.5) and 6.5 (±2.2) cm3 respectively. Both plans led to similar target coverage, same doses to the OARs and equivalent fall-off of the dose outside the PTV(CT). On the other hand, the location of hotspots, evaluated through the DSC, was improved for the SIB plans with a mean DSC of 0.31 and 0.45 for the first and the second plans respectively. CONCLUSIONS: Use of PET to decrease arbitrary location of hotspots is feasible with VMAT and SIB for lung cancer.

Cytotoxic activity of essential oils from labiatae and lauraceae families against in vitro human tumor models.

BACKGROUND: The aim of this work was to study the cytotoxicity of essential oils and their identified constituents from Sideritis perfoliata, Satureia thymbra, Salvia officinalis, Laurus nobilis and Pistacia palestina. MATERIALS AND METHODS: Essential oils were obtained by hydrodistillation and were analysed by gas chromatography (GC) and GC/mass spectrometry (MS). The cytotoxic activity was evaluated in amelanotic melanoma C32, renal cell adenocarcinoma ACHN, hormone-dependent prostate carcinoma LNCaP, and MCF-7 breast cancer cell lines by the sulforhodamine B (SRB) assay. RESULTS: L. nobilis fruit oil exerted the highest activity with IC50 values on C32 and ACHN of 75.45 and 78.24 microg/ml, respectively. The activity of S. perfoliata oil on both cell lines (IC50 of 100.90 mg/ml for C32 and 98.58 microg/ml for ACHN, respectively) was also interesting. Among the tested constituents the highest activity was found when a-humulene was applied to LNCaP cells (IC50 of 11.24 microg/ml). CONCLUSION: This study suggests for the first time the ability of S. perfoliata, S. thymbra, S. officinalis, L. nobilis and P. palestina essential oils and some identified terpenes to inhibit human tumor cell growth.