Single actin filaments were confined between bovine-serum-albumine-coated glass plates, with a separation of about 1 ym, and their flickering Brownian movement was observed by fluorescence microscopy. The rigidity of the filaments was measured by extracting the correlation function given by the mean dot product between unit tangent vectors of an isolated filament. The result is consistent with current rigidity values found in the literature.

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BackgroundLarge anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase.The purposes of the study were to estimate:- the PG overdose and the xerostomia risk increase during a “standard” IMRT (IMRTstd);- the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia.Material and methodsFifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched.ResultsCompared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p < 0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p < 0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p < 0.001).ConclusionDuring the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

The majority of current models utilized for predicting toxicity in prostate cancer radiotherapy are based on dose-volume histograms. One of their main drawbacks is the lack of spatial accuracy, since they consider the organs as a whole volume and thus ignore the heterogeneous intra-organ radio-sensitivity. In this paper, we propose a dose-image-based framework to reveal the relationships between local dose and toxicity. In this approach, the three-dimensional (3D) planned dose distributions across a population are non-rigidly registered into a common coordinate system and compared at a voxel level, therefore enabling the identification of 3D anatomical patterns, which may be responsible for toxicity, at least to some extent. Additionally, different metrics were employed in order to assess the quality of the dose mapping. The value of this approach was demonstrated by prospectively analyzing rectal bleeding (≥Grade 1 at 2 years) according to the CTCAE v3.0 classification in a series of 105 patients receiving 80 Gy to the prostate by intensity modulated radiation therapy (IMRT). Within the patients presenting bleeding, a significant dose excess (6 Gy on average, p < 0.01) was found in a region of the anterior rectal wall. This region, close to the prostate (1 cm), represented less than 10% of the rectum. This promising voxel-wise approach allowed subregions to be defined within the organ that may be involved in toxicity and, as such, must be considered during the inverse IMRT planning step.

Mesenchymal stem cells (MSC), multipotent adult stem cells, feature the potential to regenerate tissue damage and, in parallel, inhibit inflammation and fibrosis. MSC can be safely transplanted in autologous and allogeneic ways as they are non-immunogenic, and consequently represent a therapeutic option for refractory connective tissue diseases, fibrosing diseases like scleroderma and fistulizing colitis like in Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, and 22 are on autoimmune diseases. In irradiation-induced colitis, MSC accelerate functional recovery of the intestine and dampen the systemic inflammatory response. In order to provide rescue therapy for accidentally over-irradiated prostate cancer patients who underwent radiotherapy, allogeneic bone marrow-derived MSC from family donors were intravenously infused to three patients with refractory and fistulizing colitis resembling fistulizing Crohn's disease. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhoea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets towards an increase of T regulatory cells and a decrease of activated effector T cells. The current data indicate that MSC represent a promising alternative strategy in the treatment of various immune-mediated diseases. Encouraging results have already been obtained from clinical trials in Crohn's disease and SLE as well as from case series in systemic sclerosis. MSC represent a safe therapeutic measure for patients who suffer from chronic and fistulizing colitis. These findings are instructional for the management of refractory inflammatory bowel diseases that are characterized by similar clinical and immunopathological features.

The management of proctitis in patients who have undergone very-high-dose conformal radiotherapy is extremely challenging. The fibrosis-necrosis, fistulae, and hemorrhage induced by pelvic overirradiation have an impact on morbidity. Augmenting tissue repair by the use of mesenchymal stem cells (MSCs) may be an important advance in treating radiation-induced toxicity. Using a preclinical pig model, we investigated the effect of autologous bone marrow-derived MSCs on high-dose radiation-induced proctitis. Irradiated pigs received repeated intravenous administrations of autologous bone marrow-derived MSCs. Immunostaining and real-time polymerase chain reaction analysis were used to assess the MSCs' effect on inflammation, extracellular matrix remodeling, and angiogenesis, in radiation-induced anorectal and colon damages. In humans, as in pigs, rectal overexposure induces mucosal damage (crypt depletion, macrophage infiltration, and fibrosis). In a pig model, repeated administrations of MSCs controlled systemic inflammation, reduced in situ both expression of inflammatory cytokines and macrophage recruitment, and augmented interleukin-10 expression in rectal mucosa. MSC injections limited radiation-induced fibrosis by reducing collagen deposition and expression of col1a2/col3a1 and transforming growth factor-β/connective tissue growth factor, and by modifying the matrix metalloproteinase/TIMP balance. In a pig model of proctitis, repeated injections of MSCs effectively reduced inflammation and fibrosis. This treatment represents a promising therapy for radiation-induced severe rectal damage.

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