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INTRODUCTION Adjuvant radiation therapy (RT) following primary surgery in women affected by early breast cancer (EBC) plays a central role in reducing local recurrences and overall mortality. The FAST-FORWARD trial recently demonstrated that 1-week hypofractionated adjuvant RT is not inferior to the standard schedule in terms of local relapse, cosmetic outcomes and toxicity. The aim of this in silico study was to evaluate the dosimetric aspects of a 1-week RT course, administered through volumetric modulated arc therapy (VMAT), compared with traditional three-dimensional conformal radiation therapy (3D-CRT) with tangential fields. METHODS Patients affected by left-side EBC undergoing adjuvant RT were selected. ESTRO guidelines for the clinical target volume (CTV) delineation and FAST-FORWARD protocol for CTV to planning target volume (PTV) margin definition were followed. Total prescribed dose was 26 Gy in five fractions. The homogeneity index (HI) and the global conformity index (GCI) were taken into account for planning and dose distribution optimisation purposes. Both 3D-CRT tangential fields and VMAT plans were generated for each patient. RESULTS The analysis included 21 patients. PTV coverage comparison between 3D-CRT and VMAT plans showed significant increases for GCI (P

Determining the most appropriate management strategy for patients with large tumor masses is a very challenging issue. Unconventional radiotherapy modalities, such as spatially fractionated radiation therapy (SFRT), are associated with dramatic responses. Recent studies have suggested that systemic immune activation may be triggered by SFRT delivery to primary tumor lesion. This report describes the case of a patient treated with a novel form of immune-sparing partially ablative irradiation (ISPART) for a bulky peritoneal metastasis from renal cell cancer, refractory to anti-PD-1 therapy (nivolumab) as third-line therapy after sequential therapy with sunitinib and cabozantinib. The observed response suggests that there may be a synergistic effect between ISPART and immunotherapy. This case report supports the inclusion of ISPART in patients presenting with bulky lesions treated with checkpoint inhibitors .Lay abstract Managing large tumor masses is a very challenging issue. In recent years, radiotherapy methods have been linked with good responses, which may be due to the activation of immune mechanisms. We describe the case of a patient with a large tumor mass from renal cell cancer. The patient had already been treated with anti-PD-1 therapy, after treatment with sunitinib and cabozantinib, along with radiotherapy. The results suggest that radiotherapy together with immunotherapy is very effective in enhancing immune response.

The concept of abscopal effect is currently gaining importance in modern oncology, as the link between localized irradiation and triggering of immuno-mediated systemic antitumor effects is getting clearer. An increasing number of reports documented abscopal effect mainly after external beam irradiation. Interventional radiotherapy (IR) may be used with sealed radioactive sources as brachytherapy (BT) or with unsealed radioactive sources as transarterial radioembolization (TARE). The aim of this paper is to review the existing clinical IR data and discuss the mechanisms of the abscopal effect.A systematic research of the main bibliographic databases (PubMed, WOS, Scopus, and Google Scholar) from the earliest possible date through August 2019 was performed. The search strategy was based on the terms "abscopal effect", "interventional radiotherapy", "brachytherapy" and "TARE".Thirteen titles were identified. Three papers met inclusion criteria and were included in the review. All of them were case reports.Even though there are still scarce data in literature regarding the association of locoregional interventional treatments with the abscopal effect, this review demonstrates that the immunomodulatory theories, which have been widely used so far for external beam radiotherapy (EBRT), may be actually considered valid also in the contest of IR.

The term "isthmocele" refers to a niche on the anterior wall of the uterine isthmus or of the cervical canal at the site of a previous cesarean delivery scar. Such anatomic defect can cause many gynecologic sequelae that only recently have being identified and described. Hysteroscopy is commonly considered the gold standard for the diagnosis and also for the treatment, at least in the case of defects of small size. The authors described the case of a 37-year-old woman who underwent a cesarean section (CS) seven years before, with a long lasting history of menstrual irregularities, and pelvic pain increasing during menstruation at the hypogastric level. Magnetic resonance imaging (MRI) showed an exceptionally large isthmocele on the anterior wall of a retroflexed uterus which was otherwise misinterpreted as the uterine cavity filled with menstrual blood during a previous hysteroscopy (HSC). Although exceptional, this case highlights the possibility that a large sized isthmocele in a retroflexed uterus could be misinterpreted as the uterine cavity filled by menstrual blood at HSC. In this case MRI definitely clarified the diagnosis.

A protocol of nucleophilic addition to β-keto esters is reported, aimed to the synthesis of tertiary alcohols with high diastereomeric purity. The combined use of organocerium compounds and TiCl4 makes the procedure very efficient and stereoselective with phenyl ketone derivatives. The effect of the nature of the ester function as well as the group bound to the ketone moiety was investigated and rationalized.

The cerium(III) chloride heptahydrate/sodium iodide complex (CeCl 3 . 7 H 2 O/NaI) acts as a useful promoter in the carbon-carbon bond forming reaction by addition of allyltributylstannanes to aldehydes. The reaction of 2-butenyltributylstannane shows that the regio- and the stereochemical outcomes depend on the reaction conditions. When the promoter is adsorbed on a solid support (aluminum oxide), a highly prevalent formation of the γ-adduct is observed in solvent-free conditions. Conversely, when the reaction is carried out in acetonitrile as the solvent, the α-adduct largely prevails. In the last case, a complete stereocontrol is observed, the less stable (Z)-isomer being obtained in high geometrical purity.

A high incidence of spinal disorders is observed in professional drivers; in particular, back and neck pain result in high rates of morbidity and low retirement age. A sample of 77 drivers, of rubbish-collection vehicles who sit in a standard posture and of road-washing vehicles, who drive with the neck and trunk flexed, bent and twisted, was studied using RULA, a method for the evaluation of the exposure to risk factors associated with work-related upper-limb disorders. Results showed a significant association between trunk and neck scores and all self-reported pains, aches or discomforts in the trunk or neck regions in all subjects. In particular, the neck score was significant in both postures, reflecting high loading of the neck. Significantly different posture scores were also recorded for drivers using an adjustable vs. a non-adjustable seat. In this first RULA study of the working posture of professional truck drivers, the method proved to be a suitable tool for the rapid evaluation of the loading of neck and trunk.

Conjugate addition of heteroatom nucleophiles to carbon-carbon double bonds conjugated with a strong electron-withdrawing group is one of the most important new bond-forming strategies in synthetic organic chemistry. Among the methods for these Michael additions, Lewis acids have shown the best promoter activity, and in particular, the use of reagents impregnated over inorganic supports is rapidly increased. With the increase of environmental consciousness in chemical research, the solvent-free Michael addition has attracted our attention. In continuation of our ongoing program to develop synthetic protocols utilizing cerium trichloride, we report an extension of the CeCl3â7H2O/NaI combination supported under solvent-free conditions to promote heteroatom Michael addition. Using neutral alumina (Al2O3) as solid support permits us to circumvent some of the problems associated with the procedure where the inorganic support is silica gel. The CeCl3â 7H2O/NaI/Al2O3 system works well for hetero-Michael additions utilizing weakly nucleophiles such as imidazoles and carbamates, and also the reaction proceeds with good yields in the case of Michael acceptors different from R,â-unsaturated carbonyl compounds. An important synthetic application of this our methodology is the intramolecular aza-Michael reaction in producing 4-piperidinone derivatives, which are of interest as synthetic intermediates toward important classes of heterocycles.

After briefly reporting the basic concepts of indirect UV detection in HPLC, methods for the quantitative determination of ethanol, glycerol and isopropanol in pharmaceutical forms for human use, and propylene glycol and N,N-dimethylacetamide in pharmaceutical form for veterinary use are proposed. Nicotinamide, sulfanilamide and isoniazid are used as UV-absorbing components (probes) of mobile phase. The last two are new probes suitably selected and proposed to optimize the determination. Also, the dependence of method sensitivity from the probe concentration is shown. Good accuracies and precisions are obtained. The methods are simple and quick and the assays of the analytes do not go through interferences from the other substances present in the pharmaceutical forms.

7167 Background: Recent data have shown the benefit of adding surgery to neoadjuvant chemoradiotherapy, however no data are available for multimodality treatment including surgery in elderly patien...

Numerous studies support the protective role of bioactive peptides against cardiovascular diseases. Cereals represent the primary source of carbohydrates, but they also contain substantial amounts of proteins, therefore representing a potential dietary source of bioactive peptides with nutraceutical activities. The analysis of wheat extracts purified by chromatographic techniques by means of HPLC-UV/nanoLC-nanoESI-QTOF allowed the identification of a signal of about 7 kDa which, following data base searches, was ascribed to a nonspecific lipid-transfer protein (nsLTP) type 2 from Triticum aestivum (sequence coverage of 92%). For the first time nsLTP2 biological activities have been investigated. In particular, in experiments with human umbilical vein endothelial cells (HUVEC), nsLTP2 displayed antioxidant and cytoprotective activities, being able to significantly decrease reactive oxygen species (ROS) levels and to reduce lactate dehydrogenase (LDH) release, generated following oxidative (hydrogen peroxide) and inflammatory (tumor necrosis factor α, interleukin-1β, and lipopolysaccharide) stimulation. The obtained promising results suggest potential protective role of nsLTP2 in vascular diseases prevention. PRACTICAL APPLICATION: nsLTP 2 peptide is resistant to proteases throughout the gastrointestinal tract and exerts antioxidant and cytoprotective activities. These characteristics could be exploited in vascular diseases prevention.

An efficient and highly chemoselective method fo the protection of free hydroxy compounds with 3,4-dihydro-2H-pyran is reported. Since the deprotection of THP-ethers occurs very readily at room temperature, the successful use of this type of protecting group depends only upon how readily it can be introduced. For this we have examined the tetrahydropyranylation of alcohols and phenols catalysed by the CeCl3·7 H2O/NaI system surface under solvent-free conditions. The reaction presents the advantage of being performable under extremely mild conditions by use of catalytic amounts of an interesting Lewis acidic system consisting of the CeCl3·7 H2O/NaI catalyst combination, which can be easily separated from the reaction mixture. The advantages of this procedure, which utilizes cheap and “friendly” reagents, over the previously reported ones are discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

A new protocol of protection of poorly reactive aryl amines and functionalized amines with Boc 2 O in the presence of Zn(ClO 4 ) 2 .6H 2 O as the catalyst is reported. The catalytic action of Zn(ClO 4 ) 2 .6H 2 O is specific forthe activation of the pyrocarbonates, thus acid sensitive functionalities and stereochemical configurations of the starting materials remain unaltered in the protection process.

Nel ricapitolare i caratteri della pittura a Bologna negli anni della legazione di Bertrando del Poggetto (1327-1334), vengono presentati dipinti inediti dello Pseudo-Jacopino di Francesco e dello Pseudo-Dalmasio, artisti di punta in una situazione che si aggiorna su Giotto e sulla Francia.

A protocol of nucleophilic addition to β-keto esters is reported, aimed to the synthesis of tertiary alcohols with high diastereomeric purity. The combined use of organocerium compounds and TiCl4 makes the procedure very efficient and stereoselective with phenyl ketone derivatives. The effect of the nature of the ester function as well as the group bound to the ketone moiety was investigated and rationalized.

The arylidene malonates with two different geminal carboxylate functions, a suitable class of substrates of several synthetic and pharmacological studies, are easily available through Knoevenagel condensation of ethyl tert -butyl malonate and different aromatic aldehydes. The results have increased the potentialities of CeCl 3 ·7H 2 O–NaI system as a type of water-tolerant green Lewis acid promoter for carbon–carbon bond forming procedures.

A high stereochemical induction has often been observed in the reduction of ketones with stereogenic centres close to the carbonyl function. The level of stereoselectivity is particularly high when “hard” donor groups such as nitrogen or oxygen atoms are present in the molecule. These results have been commonly explained in terms of a chelate-controlled process. However, this interpretation has recently been challenged, and in many cases an open-chain mechanism can better account for the observed results. Thus, Lewis-acid-mediated chelation and nonchelation control is one of the most fundamental and practical concepts in transferring a nucleophile moiety to carbonyl compounds. In order to clarify the role of a hard Lewis acid in controlling the stereochemical outcome of a given reaction, the Lewis acid mediated reduction of a series of α-alkyl-β-functionalized carbonyl compounds with metallic hydrides in various solvents was recently investigated. In particular, the results derived from the reductions in the presence of dry CeCl3 were compared to those obtained under the same experimental conditions but in the presence of TiCl4, whose ability to form chelation complexes is well established. These investigations show a stereochemical outcome that is fully consistent with a chelation-controlled pathway in the case of titanium, and an open-chain-controlled pathway in the case of CeCl3. The strongly chelating TiCl4 led to the syn isomer in high diastereomeric excess in noncoordinating solvents at –78 °C with borane–Lewis base complex reducing agents, while nonchelating CeCl3 produced a high excess of the anti isomer in coordinating solvents at the same temperature with metal borohydrides as reducing agent. Therefore, our method based on the choice of CeCl3 or TiCl4 as a Lewis acid under the reported conditions represents a significant contribution to the development of new stereoselective reductions of α-alkyl-β-functionalized ketones. These procedures are one of the best known ways to obtain an alcoholic moiety. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The cerium(III)chloride heptahydrate/so- dium iodide complex (CeCl3 ·7H2 O/NaI)acts as a useful promoter in the carbon-carbon bond forming reaction by addition of allyltributylstannanes to alde- hydes.The reaction of 2-butenyltributylstannane shows that the regio-and the stereochemical out- comes depend on the reaction conditions.When the promoter is adsorbed on a solid support (aluminum oxide),a highly prevalent formation of the g -adduct is observed in solvent-free conditions.Conversely, when the reaction is carried out in acetonitrile as the solvent,the a -adduct largely prevails.In the last case,a complete stereocontrol is observed,the less stable (Z )-isomer being obtained in high geometrical purity.

Applications of CeCl3·7H2O-NaI system towards the formation of heterocyclic structures Enrico Marcantoni,1 Massimo Massaccesi,1 Marino Petrini,1 Giuseppe Bartoli,2 Letizia Sambri2 1 Department of Chemical Sciences, University of Camerino, via S. Agostino 1, I-62032 Camerino (MC), Italy 2 Department of Organic Chemistry “A. Mangini”, University of Bologna, V.le Risorgimento 4, I-40136, Bologna, Italy massimo.massaccesi@unicam.it CeCl3·7H2O-NaI system has emerged in the last years as a “friendly” Lewis acid,(1) able to promote a wide range of organic transformations. Its high and specific affinity for O-containing functionalities prompted us to employ such a promoter in the field of heterocyclic chemistry. We present some our recent applications of CeCl3·7H2O-NaI combination directed towards the formation of heterocyclic systems, within an organic synthetic view. Continuing our work on solvent-free conditions, we found that CeCl3·7H2O-NaI system supported on silica gel promotes the addition of a variety of indoles 1 to nitroalkenes 2, giving 2-indolyl-1-nitroalkanes 3 in good yields.(2) Our methodology was applied to the synthesis of β-carbolines 4, a large group of naturally occurring heterocyclic alkaloids.(3) The tetrahydro-2H-pyran heterocyclic structure (THP) is frequently used for the protection of alcohols in organic synthesis. We have developed a practical procedure for the introduction of THP group by using the CeCl3·7H2O-NaI system. After screening various reaction conditions, we found that 3,4-dihydro-2H-pyran ring reacts with the hydroxy function in the presence of a catalytic amount of CeCl3·7H2O-NaI, for the conversion of alcohols into the corresponding THP ethers 5. The scope of the reaction was investigated through several examples, which revealed both the chemoselective action of our Lewis acid system and its marked capacity to act as a promoter even in solvent-free conditions. (1) Bartoli, G.; Marcantoni, E.; Sambri, L. Synlett. 2003, 14, 2101; (2) Bartoli, G.; Bosco, M.; Giuli, S.; Giuliani, A.; Lucarelli, L.; Marcantoni, E.; Sambri, L.; Torregiani, E. J. Org. Chem. 2005, 70, 1941; (3) Cacchi, S.; Fabrizi, G.; Parisi, L. M. Org. Lett. 2003, 5, 3843; Wang, H.; Usui, T.; Osada, H.; Ganesan, A. J. Med. Chem. 2000, 43, 1577.

Zinc perchlorate hexahydrate,Zn(ClO4 )2 · 6H2 O,efficiently catalyses the esterification be- tween nearly equimolar amounts of carboxylic acids and alcohols.The reaction works under solvent-free conditions at relatively low temperatures.Excellent results were obtained with a wide range of substrates.

The dynamic processes due to restricted intramolecular motions have been observed in a number of variously substituted b-hydroxyesters by variable temperature NMR spectroscopy. The barriers for three such processes (i.e. Ph-C, t-Bu-C and Cα-Cβ bond rotation) have been measured.