Comparison of data on Mutation Frequencies of Mice Caused by Radiation - Low Dose Model -

We propose LD(Low Dose) model, the extension of LDM model which was proposed in the previous paper [Y. Manabe et al.: J. Phys. Soc. Jpn. 81 (2012) 104004] to estimate biological damage caused by irradiation. LD model takes account of all the considerable effects including cell death effect as well as proliferation, apoptosis, repair. As a typical example of estimation, we apply LD model to the experiment of mutation frequency on the responses induced by the exposure to low levels of ionizing radiation. The most famous and extensive experiments are those summarized by Russell and Kelly [Russell, W. L. & Kelly, E. M: Proc. Natl Acad. Sci. USA 79 (1982) 539-541], which are known as 'Mega-mouse project'. This provides us with important information of the frequencies of transmitted specific-locus mutations induced in mouse spermatogonia stem-cells. It is found that the numerical results of the mutation frequency of mice are in reasonable agreement with the experimental data: the LD model reproduces the total dose and dose rate dependence of data reasonably. In order to see such dose-rate dependence more explicitly, we introduce the dose-rate effectiveness factor (DREF). This represents a sort of preventable effects such as repair, apoptosis and death of broken cells, which are to be competitive with proliferation effect of broken cells induced by irradiation.Comment: subimitting to J. Phys. Soc. Jpn, 32 pages, 8 figure

Expression Levels of Thymidylate Synthase, Thymidylate Phosphorylase and Dihydropyrimidine Dehydrogenase in Head and Neck Squamous Cell Carcinoma: Preliminary Study

Introduction Pharyngo-laryngeal tumors classified as T3-4, N0-3, M0, are conventionally treated by mutilating surgery (total (pharyngo)-laryngectomy). Neo-adjuvant chemotherapy with 5-FU/platinum salt can be proposed in an attempt to preserve the larynx. The level of the response to chemotherapy ranges from 36 to 54% of cases. Thus, a large number of patients receive chemotherapy that is ineffective and not free from adverse effects. Three main enzymes are involved in the metabolism of 5-FU: thymidylate synthase (TS), thymidylate phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). Several studies suggest that a high level of expression of these three genes correlates with a poor clinical response to 5-FU. The main purpose of our study was to look for a correlation between the levels of expression of the genes for sensitivity to 5-FU (TS, TP, DPD) within the tumor and the clinical response observed after three courses of chemotherapy combining 5-FU/platinum salt in patients presenting with advanced cancer of the pharyngolarynx. Methods This was a prospective genetic study that had required approval from the Ethics Committee. The main assessment criterion was based on the assessment of the clinical response by an ENT panendoscopy and a cervical CT scan, after three courses of chemotherapy. The expression of the genes was determined by quantitative RT-PCR, using total RNA extracted from tumor biopsies taken during the initial panendoscopy. Results The means calculated, in our study, for the three genes of interest (TS, TP, DPD) were lower in the responder group than those in the non-responder group. Discussion Our preliminary findings reveal trends that confirm the hypothesis that the lower the level of expression of the sensitivity genes, the better the clinical response to chemotherapy. They now form part of a larger study that is currently in progress

51. Biological concepts of breast cancer: implications for therapy

The data from over 3000 breast cancer patients treated without adjuvant chemotherapy and followed-up for over 15 years were studied with two aims:1)to analyze the relationship between tumor diameter and incidence of distant metastases during the 25 years after initial treatment. The threshold volume at which dissemination occurs can be estimated in each subset of patients and varies widely; it is inversely correlated with the histologic grade and the number of involved axillary nodes.2)to investigate the impact of a residual tumor on distant dissemination. In patients with local recurrence, the incidence of distant dissemination is elevated. The analysis of the delay between the initial treatment and clinical emergence of the metastases shows that the excess of metastases corresponds to disseminations which are initiated after initial treatment and therefore originated from the residual tumor.This conclusion was supported by the update of s controlled clinical trial comparing two adjuvant treatments: A) a chemotherapy by CMF or B) post-operative radiotherapy (RT) followed by immunothcrapy with poly A – poly U. At 15 years the cumulative incidence of local recurrence and of distant metastases is significantly lower in the B group (42% metastasis-free survival in the RT group and 29% in the CT group p=0.03). This result seems to be due mostly to lower incidence of local recurrence

The proposed Caroline ESA M3 mission to a Main Belt Comet

We describe Caroline, a mission proposal submitted to the European Space Agency in 2010 in response to the Cosmic Visions M3 call for medium-sized missions. Caroline would have travelled to a Main Belt Comet (MBC), characterizing the object during a flyby, and capturing dust from its tenuous coma for return to Earth. MBCs are suspected to be transition objects straddling the traditional boundary between volatile–poor rocky asteroids and volatile–rich comets. The weak cometary activity exhibited by these objects indicates the presence of water ice, and may represent the primary type of object that delivered water to the early Earth. The Caroline mission would have employed aerogel as a medium for the capture of dust grains, as successfully used by the NASA Stardust mission to Comet 81P/Wild 2. We describe the proposed mission design, primary elements of the spacecraft, and provide an overview of the science instruments and their measurement goals. Caroline was ultimately not selected by the European Space Agency during the M3 call; we briefly reflect on the pros and cons of the mission as proposed, and how current and future mission MBC mission proposals such as Castalia could best be approached

Structure and dynamics of ring polymers: entanglement effects because of solution density and ring topology

The effects of entanglement in solutions and melts of unknotted ring polymers have been addressed by several theoretical and numerical studies. The system properties have been typically profiled as a function of ring contour length at fixed solution density. Here, we use a different approach to investigate numerically the equilibrium and kinetic properties of solutions of model ring polymers. Specifically, the ring contour length is maintained fixed, while the interplay of inter- and intra-chain entanglement is modulated by varying both solution density (from infinite dilution up to \approx 40 % volume occupancy) and ring topology (by considering unknotted and trefoil-knotted chains). The equilibrium metric properties of rings with either topology are found to be only weakly affected by the increase of solution density. Even at the highest density, the average ring size, shape anisotropy and length of the knotted region differ at most by 40% from those of isolated rings. Conversely, kinetics are strongly affected by the degree of inter-chain entanglement: for both unknots and trefoils the characteristic times of ring size relaxation, reorientation and diffusion change by one order of magnitude across the considered range of concentrations. Yet, significant topology-dependent differences in kinetics are observed only for very dilute solutions (much below the ring overlap threshold). For knotted rings, the slowest kinetic process is found to correspond to the diffusion of the knotted region along the ring backbone.Comment: 17 pages, 11 figure