Histopathological growth patterns as biomarker for adjuvant systemic chemotherapy in patients with resected colorectal liver metastases

Adjuvant systemic chemotherapy (CTx) is widely administered in patients with colorectal liver metastases (CRLM). Histopathological growth patterns (HGPs) are an independent prognostic factor for survival after complete resection. This study evaluates whether HGPs can predict the efectiveness of adjuvant CTx in patients with resected CRLM. Two main types of HGPs can be distinguished; the desmoplastic type and the non-desmoplastic type. Uni- and multivariable analyses for overall survival (OS) and disease-free survival (DFS) were performed, in both patients treated with and without preoperative chemotherapy. A total of 1236 patients from two tertiary centers (Memorial Sloan Kettering Cancer Center, New York, USA; Erasmus MC Cancer Institute, Rotterdam, The Netherlands) were included (period 2000–2016). A total of 656 patients (53.1%) patients received preoperative chemotherapy. Adjuvant CTx was only associated with a superior OS in non-desmoplastic patients that had not been pretreated (adjusted hazard ratio (HR) 0.52, 95% confdence interval (CI) 0.37–0.73, p<0.001), and not in desmoplastic patients (adjusted HR 1.78, 95% CI 0.75–4.21, p=0.19). In pretreated patients no signifcant efect of adjuvant CTx was observed, neither in the desmoplastic group (adjusted HR 0.83, 95% CI 0.49–1.42, p=0.50) nor in the non-desmoplastic group (adjusted HR 0.96, 95% CI 0.71–1.29, p=0.79). Similar results were found for DFS, with a superior DFS in non-desmoplastic patients treated with adjuvant CTx (HR 0.71, 95% CI 0.55–0.93, p<0.001) that were not pretreated. Adjuvant CTx seems to improve OS and DFS after resection of non-desmoplastic CRLM. However, this efect was only observed in patients that were not treated with chemotherap

More resistant tendons obtained from the association of Heteropterys aphrodisiaca and endurance training

<p>Abstract</p> <p>Background</p> <p>Popular Brazilian medicine uses <it>Heteropterys aphrodisiaca </it>infusion as a tonic or stimulant, for the treatment of nervous debility and breakdown and for muscle and bone weakness. This study investigated the effects of <it>Heteropterys aphrodisiaca </it>infusion on the tendon properties and extracellular matrix of rats under endurance training.</p> <p>Methods</p> <p>Wistar rats were grouped as follows: CS- control sedentary, HS- <it>H. aphrodisiaca </it>sedentary, CT-control trained, HT- <it>H. aphrodisiaca </it>trained. The training protocol consisted in running on a motorized treadmill, five times a week, with weekly increase in treadmill speed and duration. Control groups received water while the HS and HT groups received <it>H. aphrodisiaca </it>infusion, daily, by gavage for the 8 weeks of training. Achilles tendons were frozen for biochemical and biomechanical analysis or preserved in Karnovsky's fixative, then processed for histomorphological analysis with light microscopy.</p> <p>Results</p> <p>Biomechanical analysis showed significant increase in maximum load, maximum stress, modulus of elasticity and stiffness of the HT animals' tendons. The metalloproteinase-2 activity was reduced in the HT group. The compression region of HT animals' tendons had a stronger and more intense metachromasy, which suggests an increase in glycosaminoglycan concentration in this region of the tendon. The most intense birefringence was observed in both compression and tension regions of HT animals' tendons, which may indicate a higher organizational level of collagen bundles. The hydroxyproline content increased in the HT group.</p> <p>Conclusions</p> <p>The association of endurance training with <it>H. aphrodisiaca </it>resulted in more organized collagen bundles and more resistant tendons to support higher loads from intense muscle contraction. Despite the clear anabolic effects of <it>Heteropterys aphrodisiaca </it>and the endurance exercise association, no side effects were observed, such as those found for synthetic anabolic androgenic steroids.</p

Metabolic constituents of grapevine and grape-derived products

The numerous uses of the grapevine fruit, especially for wine and beverages, have made it one of the most important plants worldwide. The phytochemistry of grapevine is rich in a wide range of compounds. Many of them are renowned for their numerous medicinal uses. The production of grapevine metabolites is highly conditioned by many factors like environment or pathogen attack. Some grapevine phytoalexins have gained a great deal of attention due to their antimicrobial activities, being also involved in the induction of resistance in grapevine against those pathogens. Meanwhile grapevine biotechnology is still evolving, thanks to the technological advance of modern science, and biotechnologists are making huge efforts to produce grapevine cultivars of desired characteristics. In this paper, important metabolites from grapevine and grape derived products like wine will be reviewed with their health promoting effects and their role against certain stress factors in grapevine physiology

FULLERENE MOLECULAR-WEIGHT DISTRIBUTIONS IN GRAPHITE SOOT EXTRACTIONS MEASURED BY LASER DESORPTION FOURIER-TRANSFORM MASS-SPECTROMETRY

Fullerenes were extracted from graphite soot produced by the Huffman-Kratschmer process by using a number of solvents, including refluxing in xylenes, 1,3,5-trimethylbenzene, 1,2,4-trichlorobenzene, alpha,alpha,alpha-trichlorotoluene, and 1-methylnaphthalene, and by using high-pressure, high-temperature o-xylene and supercritical carbon tetrachloride. The extract was dried and analyzed using laser desorption/Fourier transform mass spectrometry in order to measure fullerene molecular weight distributions. Positive and negative ion mass spectra were taken of all samples in order to compare the types of spectra. It is expected from mechanistic considerations and from past results that negative ion spectra should be less sensitive to growth or fragmentation of the fullerenes. The determination of the most reliable fullerene distributions requires a comparison of both positive and negative ion mass spectra, however. The highest mass distribution, with fullerenes to 2500 amu, was found for 1-methylnaphthalene extract, although there was evidence for dimers, trimers, and tetramers of the solvent in the extract. High-pressure o-xylene yielded fullerene distributions to 2000 amu. It was found that, for some solvents, residual solvent or solvent polymerization affected the reliable measurement of fullerene distributions by laser desorption. Extraction with supercritical carbon tetrachloride degraded the fullerenes or the soot into perchlorinated aromatic molecules

EXTRACTION OF GIANT FULLERENE MOLECULES, AND THEIR SUBSEQUENT SOLVATION IN LOW BOILING-POINT SOLVENTS

Carbon soot produced by the graphite arc-synthesis method was solvated to varying extents in four different solvents, after previous removal of some fullerenes, particularly C60 and C70, by toluene extraction. The solvents and weight percentages of soot solvated (in parentheses) are: xylenes (3.5), 1,3,5-trimethylbenzene (7.4), 1,2,4-trichlorobenzene (31.1), and 1-methylnaphthalene (22.5). If one accounts for the C2n fullerene molecules, primarily C60 and C70 extracted from virgin soot by toluene, roughly 37% of the virgin carbon soot can be solvated by the use of 1,2,4-trichlorobenzene. A rough value for the enthalpy of solvation difference is determined for C70 and C60, by van&apos;t Hoff analysis, to be DELTA-DELTA-H = 5 kcal/mol. This method is suggested as a valuable indicator for the difference of enthalpies of binding of C2n molecules to the soot matrix. After filtration and removal of the solvents used in the extractions, the residues can be redissolved in low-boiling-point solvents such as methylene chloride and toluene, two solvents which dissolved essentially none of the (previously) toluene-extracted starting material. This underscores the importance of the soot matrix in inhibiting solvation of C2n fullerene molecules, and suggests that chromatographic separation of large fullerene molecules can be done with low-boiling-point solvents, and may therefore be feasible