A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer

Long-term outcome of re-irradiation for recurrent or second primary head and neck cancer: A multi-institutional study of AIRO-Head and Neck working group

Background To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published. Methods We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population. Results Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm(3) were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability. Conclusion Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population

Hyades Member K2-136c:The Smallest Planet in an Open Cluster with a Precisely Measured Mass

International audienceK2-136 is a late-K dwarf (0.742 ± 0.039 M ⊙) in the Hyades open cluster with three known, transiting planets and an age of 650 ± 70 Myr. Analyzing K2 photometry, we found that planets K2-136b, c, and d have periods of 8.0, 17.3, and 25.6 days and radii of 1.014 ± 0.050 R ⊕, 3.00 ± 0.13 R ⊕, and 1.565 ± 0.077 R ⊕, respectively. We collected 93 radial velocity (RV) measurements with the High-Accuracy Radial-velocity Planet Searcher for the Northern hemisphere (HARPS-N) spectrograph (Telescopio Nazionale Galileo) and 22 RVs with the Echelle SPectrograph for Rocky Exoplanets and Stable Spectroscopic Observations (ESPRESSO) spectrograph (Very Large Telescope). Analyzing HARPS-N and ESPRESSO data jointly, we found that K2-136c induced a semi-amplitude of 5.49 ± 0.53 m s-1, corresponding to a mass of 18.1 ± 1.9 M ⊕. We also placed 95% upper mass limits on K2-136b and d of 4.3 and 3.0 M ⊕, respectively. Further, we analyzed Hubble Space Telescope and XMM-Newton observations to establish the planetary high-energy environment and investigate possible atmospheric loss. K2-136c is now the smallest planet to have a measured mass in an open cluster and one of the youngest planets ever with a mass measurement. K2-136c has ~75% the radius of Neptune but is similar in mass, yielding a density of ${3.69}_{-0.56}^{+0.67}$ g cm-3 (~2-3 times denser than Neptune). Mass estimates for K2-136b (and possibly d) may be feasible with more RV observations, and insights into all three planets' atmospheres through transmission spectroscopy would be challenging but potentially fruitful. This research and future mass measurements of young planets are critical for investigating the compositions and characteristics of small exoplanets at very early stages of their lives and providing insights into how exoplanets evolve with time

Structured reporting for fibrosing lung disease: a model shared by radiologist and pulmonologist

Objectives: To apply the Delphi exercise with iterative involvement of radiologists and pulmonologists with the aim of defining a structured reporting template for high-resolution computed tomography (HRCT) of patients with fibrosing lung disease (FLD). Methods: The writing committee selected the HRCT criteria\ue2\u80\u94the Delphi items\ue2\u80\u94for rating from both radiology panelists (RP) and pulmonology panelists (PP). The Delphi items were first rated by RPs as \ue2\u80\u9cessential\ue2\u80\u9d, \ue2\u80\u9coptional\ue2\u80\u9d, or \ue2\u80\u9cnot relevant\ue2\u80\u9d. The items rated \ue2\u80\u9cessential\ue2\u80\u9d by &lt; 80% of the RP were selected for the PP rating. The format of reporting was rated by both RP and PP. Results: A total of 42 RPs and 12 PPs participated to the survey. In both Delphi round 1 and 2, 10/27 (37.7%) items were rated \ue2\u80\u9cessential\ue2\u80\u9d by more than 80% of RP. The remaining 17/27 (63.3%) items were rated by the PP in round 3, with 2/17 items (11.7%) rated \ue2\u80\u9cessential\ue2\u80\u9d by the PP. PP proposed additional items for conclusion domain, which were rated by RPs in the fourth round. Poor consensus was observed for the format of reporting. Conclusions: This study provides a template for structured report of FLD that features essential items as agreed by expert thoracic radiologists and pulmonologists