Proliferation capacity and p53 expression of HTB140 cells after proton irradiation

Human HTB140 melanoma cells were used to investigate different responses to single irradiation with protons, regarding cell proliferation, induction of apoptosis and expression of p53. Exponentially growing cells were irradiated close to the Bragg peak maximum of the unmodulated 62 MeV proton beam. Doses applied ranged from 8 to 24 Gy at the dose rate of 15 Gy/min. Cell proliferation, measured 6 and 48 h postirradiation, has shown highly significant dose and time dependent decrease. Protons induced apoptosis, 6 and 48 h after irradiation, decreasing with the increase of postirradiation incubation time. The largest number of apoptotic cells was at 6 h after irradiation with 16 Gy protons. High level of p53 expression was detected in all irradiated samples, as well as in controls and was independent of dose applied and postirradiation incubation time.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Sensitivity of HTB140 cell exposed to protons and alkylating agents

Malignant melanoma is a highly aggressive cancer with a poor prognosis due to resistance to radiotherapy and chemotherapy regimens. The mainstay of treatment remains DNA-alkylatingagent dacarbazine (DTIC). Fotemustine (FM), chloroethylnitrosourea agent, also has demonstrated significant antitumoral effects in malignantmelanoma. However, the resistance of melanoma cells limits their clinical application. In order to enhance the inhibition of melanoma cell growth, in this study, combined treatment of FM and DTIC with proton irradiation, was investigated. We analyzed the effects of combined treatment on HTB140 melanoma cell viability and proliferation. Significant inhibition of cell growth, especially cell proliferation, was obtained after treatment with protons and FM compare to single irradiation or drug treatment. Treatment with protons and DTIC has shown improved growth inhibition compare to appropriate single drug treatment, but not compare to irradiation as a single treatment.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Fetiform teratoma in an Italian-Fresian calf: case report and literature review.

Introduction. Fetiform teratoma is a rare form of teratoma in animals and people that resembles a malformed fetus. This paper describes the first case of highly differentiated extragonadal fetiform teratoma with cranial connection in an Italian-Friesian calf. Case presentation. A 35-day-old male Italian-Friesian calf weighing 55 kg was referred because of a mass localized in the fronto-nasal region. The mass contained two lateral structures of similar size and conformation that were recognized as underdeveloped hind limbs, while at its center there was a small tail. The mass was surgically excised and sent to the pathologist for examination. Gross examination identified two femur-like rudimentary limbs and a sketch of bone located in between, morphologically referable to a rudimentary coxae-like bo ne. Some mucinous cysts, a virtual body cavity showing adipose and muscular tissues, some cartilaginous nuclei and a coelomatic body cavity were also noted. Histological examination showed differentiation into skin with dermal appendages, hair, adipose tissue, cartilage, bone, lymphoid tissue, neurovascular bundles, and a rudimentary tail. No neural tissue including spinal cord, brain matter, or gonadal differentiation was seen. On the basis of these findings, the mass was diagnosed as a highly differentiated extragonadal fetiform teratoma. Conclusion. Fetiform teratoma should be included among differential diagnoses in cases of neonatal malformation in bovine. Analyzing the available literature, the Friesian genetic strain seem to be predisposed to fetal malformation, but a systematic reporting of cases is needed, in order to investigate further the epidemiological, etiological, pathophysiological and therapeutic aspect of this kind of congenital disease

Dosimetric characterization of CVD diamonds in photon, electron and proton beams

The purpose of this work is the characterization, in an on line configuration, of the dosimetric response of a commercial CVD diamond. The study shows the possibility of using CVD diamond for dosimetric purposes with clinical, high-energy electron (4-15 MeV), photon (6-15 MV) and proton (62 MeV) beams

Dosimetric characterization with 62 MeV protons of a silicon-segmented detector for 2D dose verifications in radiotherapy

Abstract Due to the features of the modern radiotherapy techniques, namely intensity modulated radiation therapy and proton therapy, where high spatial dose gradients are often present, detectors to be employed for 2D dose verifications have to satisfy very narrow requirements. In particular they have to show high spatial resolution. In the framework of the European Integrated Project—Methods and Advanced Equipment for Simulation and Treatment in Radio-Oncology (MAESTRO, no. LSHC-CT-2004-503564), a dosimetric detector adequate for 2D pre-treatment dose verifications was developed. It is a modular detector, based on a monolithic silicon-segmented sensor, with an n-type implantation on an epitaxial p-type layer. Each pixel element is 2×2 mm 2 and the distance center-to-center is 3 mm. The sensor is composed of 21×21 pixels. In this paper, we report the dosimetric characterization of the system with a proton beam. The sensor was irradiated with 62 MeV protons for clinical treatments at INFN-Laboratori Nazionali del Sud (LNS) Catania. The studied parameters were repeatability of a same pixel, response linearity versus absorbed dose, and dose rate and dependence on field size. The obtained results are promising since the performances are within the project specifications

The GEANT4 toolkit capability in the hadron therapy field: simulation of a transport beam line

At Laboratori Nazionali del Sud of the Instituto Nazionale di Fisica Nucleare of Catania (Sicily, Italy), the first Italian hadron therapy facility named CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) has been realized. Inside CATANA 62 MeV proton beams, accelerated by a superconducting cyclotron, are used for the radiotherapeutic treatments of some types of ocular tumours. Therapy with hadron beams still represents a pioneer technique, and only a few centers worldwide can provide this advanced specialized cancer treatment. On the basis of the experience so far gained, and considering the future hadron-therapy facilities to be developed (Rinecker, Munich Germany, Heidelberg/GSI, Darmstadt, Germany, PSI Villigen, Switzerland, CNAO, Pavia, Italy, Centro di Adroterapia, Catania, Italy) we decided to develop a Monte Carlo application based on the GEANT4 toolkit, for the design, the realization and the optimization of a proton-therapy beam line. Another feature of our project is to provide a general tool able to study the interactions of hadrons with the human tissue and to test the analytical-based treatment planning systems actually used in the routine practice. All the typical elements of a hadron-therapy line, such as diffusers, range shifters, collimators and detectors were modelled. In particular, we simulated the Markus type ionization chamber and a Gaf Chromic film as dosimeters to reconstruct the depth (Bragg peak and Spread Out Bragg Peak) and lateral dose distributions, respectively. We validated our simulated detectors comparing the results with the experimental data available in our facility

Radiobiological studies on the 62 MeV therapeutic proton beam at lns catania: I. survival of HTB140 melanoma cells

The aim of this study was to determine the initial inactivation of cells induced by high-energy proton beam designed for the treatment of eye melanoma. Exponentially growing HTB140 cells were exposed to an unmodulated 62 MeV proton beam delivered over the single dose range from 8 Gy to 24 Gy. Position of samples was in the zone of the Bragg peak, having high LET values. Surviving fractions were evaluated at 6, 24 and 48 h post-irradiation. The survival curves exhibited a well-known shoulder, decreasing for doses higher than 8 Gy. Therefore, a significant dose dependent early cell inactivation after single delivery of 16 Gy to 24 Gy to the cell monolayer was observed. With the increase of the post-irradiation incubation time, a better killing effect, as the consequence of clonogenic survival, was detected.Physical chemistry 2004 : 7th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 21-23 September 200

Radiobiological studies on the 62 MeV therapeutic proton beam at lns catania: II. facs analyses of HTB140 melanoma cells

The objective of this study was to determine whether apoptosis and cell cycle redistribution were influenced by high-LET irradiation. Exponentially growing HTB140 cells were exposed to an unmodulated 62 MeV proton beam, within the Bragg peak, delivered over the single dose range from 8 Gy to 24 Gy. At 6 h post-irradiation, there was a low level of early apoptosis. At 48 h irradiated cells were more damaged, showing the increase in number of apoptotic nuclei. The dose dependent cell cycle phase distribution was detected at 48 h post-irradiation. The cell population exhibited phase redistribution toward G2/M phase.Physical chemistry 2004 : 7th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 21-23 September 200

Designing a range modulator wheel to spread-out the Bragg peak for a passive proton therapy facility

In proton beam therapy, a Spread-Out Bragg peak (SOBP) is used to establish a uniform dose distribution in the target volume. In order to create a SOBP, several Bragg peaks of different ranges, corresponding to different entrance energies, with certain intensities (weights) should be combined each other. In a passive beam scattering system, the beam is usually extracted from a cyclotron at a constant energy throughout a treatment. Therefore, a SOBP is produced by a range modulator wheel, which is basically a rotating wheel with steps of variable thicknesses, or by using the ridge filters. In this study, we used the Geant4 toolkit to simulate a typical passive scattering beam line. In particular, the CATANA transport beam line of INFN Laboratori Nazionali del Sud (LNS) in Catania has been reproduced in this work. Some initial properties of the entrance beam have been checked by benchmarking simulations with experimental data. A class dedicated to the simulation of the wheel modulators has been implemented. It has been designed in order to be easily modified for simulating any desired modulator wheel and, hence, any suitable beam modulation. By using some auxiliary range-shifters, a set of pristine Bragg peaks was obtained from the simulations. A mathematical algorithm was developed, using the simulated pristine dose profiles as its input, to calculate the weight of each pristine peak, reproduce the SOBP, and finally generate a flat dose distribution. Therefore, once the designed modulator has been realized, it has been tested at CATANA facility, comparing the experimental data with the simulation results

Response of Human HTB140 Melanoma Cells to Conventional Radiation and Hadrons

Conventional radiotherapy with X-and gamma-rays is one of the common and effective treatments of cancer. High energy hadrons, i.e., charged particles like protons and (12)C ions, due to their specific physics and radiobiological advantages are increasingly used. In this study, effectiveness of different radiation types is evaluated on the radio-resistant human HTB140 melanoma cells. The cells were irradiated with gamma-rays, the 62 MeV protons at the Bragg peak and in the middle of the spread-out Bragg peak (SOBP), as well as with the 62 MeV/u (12)C ions. The doses ranged from 2 to 24 Gy. Cell survival and proliferation were assessed 7 days after irradiation, whereas apoptosis was evaluated after 48 h. The acquired results confirmed the high radio-resistance of cells, showing better effectiveness of protons than gamma-rays. The best efficiency was obtained with (12)C ions due to higher linear energy transfer. All analyzed radiation qualities reduced cell proliferation. The highest proliferation was detected for (12)C ions because of their large killing capacity followed by small induction of reparable lesions. This enabled unharmed cells to preserve proliferative activity. Irradiations with protons and (12)C ions revealed similar moderate pro-apoptotic ability that is in agreement with the level of cellular radio-resistance