3D Radiation Therapy Boost Improves the Outcome of Whole Brain Radiation Therapy Treated RPA II Patients with One or Two Brain Metastases

Purpose

to evaluate the role of whole brain radiotherapy (WBRT) and radiation boost (RB) for 208 patients recursive partitioning analysis (RPA) II with 1 or 2 brain metastases (BM) at a single institution.

Methods and Materials

the dose of WBRT was 30 Gy (10 fractions of 3 Gy). One hundred thirty-two patients (63.5%) benefited from RB of 9 Gy in 3 fractions of 3 Gy at the metastatic site. Patients had 1 or 2 BM in 122 (58.7%) and 86 cases (41.3%), respectively.

Results

patients with one or two metastases had similar survival (4.6 and 5.1 months, respectively) (p = 0.4). Median overall survival (OS) for patients treated with WBRT and RB, and with WBRT alone was 5.9 and 3.7 months, respectively (p = 0.03). The 6-, 12- and 24-month OS rates after WBRT and RB were 48.5%, 25% and 10.6%, respectively, while WBRT alone resulted in OS rates of 34%, 22.4% and 3.2%, respectively (p = 0.03). After WBRT and RB, the 6-, 12- and 24-month local control rates were 92%, 82% and 67%, respectively, while they were 81.2%, 75% and 37.5%, respectively, after WBRT alone (p = 0.03). The 6-, 12- and 24-month brain control rates after WBRT and RB were 88.7%, 75.8% and 62%, respectively, and after WBRT alone they were 78.5%, 59% and 37.7%, respectively (p = 0.03).

Conclusion

additional boost delivered with 3D conformal radiotherapy improves local and brain control rates significantly as well as overall survival for RPA II patients with 1 or 2 unresectable BM.     

A New SiF–Dipropargyl Glycerol Scaffold as a Versatile Prosthetic Group to Design Dimeric Radioligands: Synthesis of the [18F]BMPPSiF Tracer to Image Serotonin Receptors

A novel SiX–dipropargyl glycerol scaffold (X: H, F, or ¹⁸F) was developed as a versatile prosthetic group that provides technical advantages for the preparation of dimeric radioligands based on silicon fluoride acceptor pre‐ or post‐labeling with fluorine‐18. Rapid conjugation with the prosthetic group takes place in microwave‐assisted click conjugation under mild conditions. Thus, a bivalent homodimeric SiX–dipropargyl glycerol derivatized radioligand, [¹⁸F]BMPPSiF, with enhanced affinity was developed by using click conjugation. High uptake of the radioligand was demonstrated in 5‐HT_1A receptor‐rich regions in the brain with positron emission tomography. Molecular docking studies (rigid protein–flexible ligand) of BMPPSiF and known antagonists (WAY‐100635, MPPF, and MefWAY) with monomeric, dimeric, and multimeric 5‐HT_1A receptor models were performed, with the highest G score obtained for docked BMPPSiF: ?6.766 as compared with all three antagonists on the monomeric model. Multimeric induced‐fit docking was also performed to visualize the comparable mode of binding under in vivo conditions, and a notably improved G score of ?8.455 was observed for BMPPSiF. These data directly correlate the high binding potential of BMPPSiF with the bivalent binding mode obtained in the biological studies. The present study warrants wide application of the SiX–dipropargyl glycerol prosthetic group in the development of ligands for imaging with enhanced affinity markers for specific targeting based on peptides, nucleosides, and lipids.     

In‐depth characterization of granular starch‐graft‐polyester compositions as obtained by in situ polymerization of lactones from the starch surface

The synthesis of poly(ε‐caprolactone) (PCL)‐grafted granular starch was carried out either in bulk (without solvent) or in toluene suspension by a two‐step procedure. First step relied upon the activation of the hydroxyl groups available at the starch surface by alkylaluminum derivatives like AlEt₃ and removal of non‐surface‐grafted organo‐aluminum active species. The latter species were made free in solution by reaction with the remaining water molecules still contaminating the polymerization medium despite intensive drying of the starch granules. In the second step, ε‐caprolactone was polymerized via a coordination‐insertion ring‐opening polymerization as initiated by the surface‐grafted aluminum alkoxide species. The present contribution aims at investigating various parameters such as nature of the alkyl aluminum activator and monomer (δ‐valerolactone was studied as well), temperature, concentration, and addition of a solvent (polymerization in toluene suspension), reaction time, and also the experimental procedure used to recover the polyester chains and measure the grafting efficiency. It turns out that, under the studied conditions, dialkylaluminum alkoxides surface‐grafted onto the starch granules were more likely generated and promote a fast polymerization reaction with the formation of grafted PCL chains with a molecular weight that can be as high as 225 000 (M_n value) for polymerization carried out in toluene suspension. Copyright © 2004 Society of Chemical Industry     

Determination of the representativity between two multidimensional data sets by a comparison of their structure

An approach for the investigation and comparison of the data structure in the multidimensional space is proposed. It is based on three properties, namely, the direction of the data sets, the variance–covariance of the data points, and the location of the data sets' centroids. A number of tests have been studied and are presented. It is shown that the combined use of these parameters allows a satisfactory estimation of the representativity between two data sets. Simulated data, as well as real case studies are presented.     

Effect of wheat bran on the mechanical properties of extruded starchy foams

Incorporation of wheat bran has a significant effect on the texture of extruded starchy products. This can be explained by changes in the mechanical parameters of the products. The stress at rupture and elastic modulus of wheat flour-based solid foams, obtained at different extrusion conditions and bran concentration, were measured using a three-point bending test. Both parameters were positively correlated with the foam relative density according to the Gibson–Ashby model. At same relative densities and bran concentration, finer structures with higher density of small cells led to a higher mechanical strength of the foams. The stress at rupture of the unexpanded material was decreased when increasing the bran concentration. Nevertheless, expanded foams with added bran at an intermediate level showed increased mechanical strength. This was attributed to the finer cellular structures obtained. The effect of increasing the bran to a higher concentration on the mechanical properties was depending on the cell wall thickness and bran particle dimensions. At high relative density, the strength of the foams was further increased due to the even finer structures obtained. At low relative density, even though finer structures were also obtained, the stress at rupture of the foams was decreased. This may be explained by the lower cell wall thicknesses and low adhesion properties between bran and starch favoring rupture of the cell walls.     

A Dynamic Combinatorial Approach for Identifying Side Groups that Stabilize DNA-Templated Supramolecular Self-Assemblies

DNA-templated self-assembly is an emerging strategy for generating functional supramolecular systems, which requires the identification of potent multi-point binding ligands. In this line, we recently showed that bis-functionalized guanidinium compounds can interact with ssDNA and generate a supramolecular complex through the recognition of the phosphodiester backbone of DNA. In order to probe the importance of secondary interactions and to identify side groups that stabilize these DNA-templated self-assemblies, we report herein the implementation of a dynamic combinatorial approach. We used an in situ fragment assembly process based on reductive amination and tested various side groups, including amino acids. The results reveal that aromatic and cationic side groups participate in secondary supramolecular interactions that stabilize the complexes formed with ssDNA.     

Three-dimensional investigation and scoring of extracellular matrix remodeling during lung fibrosis using multiphoton microscopy

The organization of collagen during fibrotic processes is poorly characterized because of the lack of appropriate methodologies. Here we show that multimodal multiphoton microscopy provides novel insights into lung fibrosis. We characterize normal and fibrotic pulmonary tissue in the bleomycin model, and show that second-harmonic generation by fibrillar collagen reveals the micrometer-scale three-dimensional spatial distribution of the fibrosis. We find that combined two-photon excited fluorescence and second-harmonic imaging of unstained lung tissue allows separating the inflammatory and fibrotic steps in this pathology, underlining characteristic features of fibroblastic foci in human Idiopathic Pulmonary Fibrosis samples. Finally, we propose phenomenological scores of lung fibrosis and we show that they unambiguously sort out control and treated mice, with a better sensitivity and reproducibility in the subpleural region. These results should be readily generalized to other organs, as an accurate method to assess extracellular matrix remodeling during fibrosis.