Application of IMRT in adjuvant treatment of soft tissue sarcomas of the thigh—Preliminary results

Background

Fracture of the femur is the most frequent late complication in patients with soft tissue sarcomas (STS) who receive external beam radiotherapy after limb-sparing surgery.

Aim

To reduce the risk of bone fracture following radiotherapy of STS of the thigh, we minimized the dose to the femur and to surrounding normal tissues by applying intensity modulated radiation therapy (IMRT). We report preliminary results of post-surgery IMRT of the thigh in patients with STS in this extremity.

Materials and methods

10 adult patients undergoing post-operative radiotherapy of STS of the thigh were treated using IMRT. Clinical IMRT plans with simultaneous integrated boost (SIB) and 3-phase three-dimensional conformal radiotherapy (3D-CRT) were designed to adequately treat the planning target volume and to spare the femur to the largest extent possible. Dose distributions and dose-volume histograms were compared.

Results

For either technique, a comparable target coverage was achieved; however, target volume was better covered and critical structures were better spared in IMRT plans. Mean and maximum doses to OAR structures were also significantly reduced in the IMRT plans. On average, the mean dose to the femur in 3D-CRT plans was about two times higher than that in IMRT plans.

Conclusion

Compared with 3D-CRT, the application of IMRT improves the dose distribution within the concave target volumes and reduces dose to the OAR structures without compromising target coverage.     

Smoking and the pathogenesis of gastroduodenal ulcer – recent mechanistic update

Peptic ulcer is a common disorder of gastrointestinal system and its pathogenesis is multifactorial, where smoking and nicotine have significant adverse effects. Smoking and chronic nicotine treatment stimulate basal acid output which is more pronounced in the smokers having duodenal ulcer. This increased gastric acid secretion is mediated through the stimulation of H₂-receptor by histamine released after mast cell degranulation and due to the increase of the functional parietal cell volume or secretory capacity in smokers. Smoking and nicotine stimulate pepsinogen secretion also by increasing chief cell number or with an enhancement of their secretory capacity. Long-term nicotine treatment in rats also significantly decreases total mucus neck cell population and neck-cell mucus volume. Smoking also increases bile salt reflux rate and gastric bile salt concentration thereby increasing duodenogastric reflux that raises the risk of gastric ulcer in smokers. Smoking and nicotine not only induce ulceration, but they also potentiate ulceration caused by H. pylori, alcohol, nonsteroidal anti-inflammatory drugs or cold restrain stress. Polymorphonuclear neutrophils (PMN) play an important role in ulcerogenesis through oxidative damage of the mucosa by increasing the generation of reactive oxygen intermediates (ROI), which is potentiated by nicotine and smoking. Nicotine by a cAMP-protein kinase A signaling system elevates the endogenous vasopressin level, which plays an aggressive role in the development of gastroduodenal lesions. Smoking increases production of platelet activating factor (PAF) and endothelin, which are potent gastric ulcerogens. Cigarette smoking and nicotine reduce the level of circulating epidermal growth factor (EGF) and decrease the secretion of EGF from the salivary gland, which are necessary for gastric mucosal cell renewal. Nicotine also decreases prostaglandin generation in the gastric mucosa of smokers, thereby making the mucosa susceptible to ulceration. ROI generation and ROI-mediated gastric mucosal cell apoptosis are also considered to be important mechanism for aggravation of ulcer by cigarette smoke or nicotine. Both smoking and nicotine reduce angiogenesis in the gastric mucosa through inhibition of nitric oxide synthesis thereby arresting cell renewal process. Smoking or smoke extract impairs both spontaneous and drug-induced healing of ulcer. Smoke extract also inhibits gastric mucosal cell proliferation by reducing ornithine decarboxylase activity, which synthesises growth-promoting polyamines. It is concluded that gastric mucosal integrity is maintained by an interplay of some aggressive and defensive factors controlling apoptotic cell death and cell proliferation and smoking potentiates ulcer by disturbing this balance.     

Notes on the Potentilleæ

Background: Various rare and endangered temperate ferns are being threatened by their recent population decline, but there is limited understanding of the causes behind it.

Aims: This study attempted to identify the possible drivers of regional population decline and extinction in the globally distributed woodland fern Polystichum braunii.

Methods: A comparison was undertaken of the climatic, edaphic and phytosociological characteristics of sites with increasing, decreasing or recently extinct populations in Germany.

Results: A significantly higher frequency of episodes of low relative air humidity (<60%) was found at sites with decreasing or extinct populations compared to habitats with population increases. Sites with decreasing or extinct populations were also characterised as having less summer precipitation (<500 mm year^?1) and a shorter duration of snow cover (<110 days year^?1) than sites with increasing populations. The latter had significantly higher moss cover (56% of the forest floor), but less cover by a tree litter layer (23%) compared to decreasing (36% and 38%) or recently extinct populations (22% and 52%). All increasing populations were located in intact Tilia – Acer ravine forests, while those suffering population decline were mostly located in Fagus-dominated forests.

Conclusions: It was concluded that the probable causes of the recent decline in German P. braunii populations are reduced air humidity levels, decreasing snow duration or a shift from moss-covered to tree litter-covered forest floors due to climate warming or altered forest management.     

Forecasting the start of the pollen season of Poaceæ: evaluation of some methods based on meteorological factors

The pollen of anemogamous plants is responsible for half the allergic diseases, that is to say a prevalence of 10% in the French population. Poaceæ produce the first allergenic pollen almost everywhere. The work described in this article aimed to validate forecast methods for the use of physicians and allergic people who need accurate and early information on the first appearance of pollen in the air. The methods were based on meteorological parameters, mainly temperature. Four volumetric Hirst traps were used from 1995 to 1998, situated in two departments of Burgundy. Two of the methods tested proved to be of particular interest: the sum of the temperatures and the sum of Q ₁₀ values, an agrometeorological coefficient integrating temperature. A multiple regression, using maximum temperature and rainfall, was also performed but it gave slightly less accurate results. A χ ²-test was then used to compare the accuracy of the three methods. It was found that the date of onset of the pollen season could be predicted early enough to be useful in medical practice. Results were verified in 1999, and the research must be continued to obtain better statistical validity.     

Effects of the association between the α-subunit thigh and the β-Subunit EGF2 domains on integrin activation and signaling

Integrin bidirectional signaling is mediated by conformational change. It has been shown that the separation of the α- and β-subunit transmembrane/cytoplasmic tails and the lower legs is required for transmitting integrin bidirectional signals across the plasma membrane. In this study, we address whether the separation of the αβ knee is critical for integrin activation and outside-in signaling. By introducing three disulfide bonds to restrict dissociation of the α-subunit thigh domain and β-subunit I-EGF2 domain, we found that two of them could completely abolish integrin inside-out activation, whereas the other could not. This disulfide-bonded mutant, in the context of the activation mutation of the cytoplasmic domain, had intermediate affinity for ligands and was able to mediate cell adhesion. Our data suggest that there exists rearrangement at the interface between the thigh domain and the I-EGF2 domain during integrin inside-out activation. None of the disulfide-bonded mutants could mediate cell spreading upon adhering to immobilized ligands, suggesting that dissociation of the integrin two knees is required for integrin outside-in signaling. Disrupting the interface by introducing a glycan chain into either subunit is sufficient for high affinity ligand binding and cell spreading.