Microwave assisted synthesis of novel bis-flavone dimers as new anticancer agents

In this study we describe a microwave based click chemistry method used to prepare a family of novel bis-flavone dimers. The substituted 7-hydroxy and 4’-hydroxy flavonoids were linked through a triazole ring. The compounds were easily synthesized and purified in high yields. The bis-flavonoids were tested on different cell lines including HCT116, HepG2, MCF7 and MOLT-4. Several analogues showed to have anticancer activity with IC50 values in the range of 20-60 µM. Flavonoids are known for their anticancer properties and this method provides the basis for new medicinal structures

Thermal hysteresis measurement of the VO 2 dielectric function for its metal-insulator transition by visible-IR ellipsometry

International audienceThe real and imaginary parts of the dielectric function of VO2 thin films, deposited on r-plane sapphire via pulsed laser deposition, are measured by means of visible-infrared ellipsometry for wavelengths ranging from 0.4 to 15 μm and temperatures within its phase transition. For both the insulator-to-metal (heating) and metal-to-insulator (cooling) transitions, it is shown that the two ellipsometric signals exhibit three temperature-driven behaviors, which are well described by appropriate combinations of the Tauc-Lorentz, Gaussian, and Drude oscillator models. By fitting Bruggeman's effective medium model for the dielectric function to the corresponding measured experimental values, using the volumetric fraction of the VO2 metallic domains as a fitting parameter for different temperatures within the VO2 phase transition, we have found that this model is suitable for describing the dielectric function in visible and near-infrared wavelengths (∼0.4 to ∼3.0 μm), but it generally fails for longer infrared ones. Furthermore, the hysteresis loop of the VO2 emissivity averaged over a relevant interval of wavelengths is determined and shown to vary from ∼0.49, in the insulator phase, to ∼0.16, in the metallic one. These values, based on the VO2 dielectric function, are consistent with previous measurements reported in the literature, and therefore, our measured data are expected to be useful for describing the behavior of VO2 films involved in optical and radiative applications

Phase II study of weekly Kahalalide F in patients with advanced malignant melanoma

This phase II clinical trial evaluated the antitumour response of Kahalalide F (KF) 650 lg/m2 given as a 1-h weekly infusion in advanced malignant melanoma patients, both untreated and those who relapsed or progressed after one line of systemic therapy. Of 24 enrolled patients (median age, 55 years; range, 28–89), 14 patients had been previously treated with chemotherapy or biological therapy. No RECIST responses occurred; five chemotherapynaı¨ve patients with cutaneous melanoma had disease stabilisation for P3 months; median progression-free survival was 1.7 months (95% CI, 1.2–1.9 months); and median overall survival was 10.8 months (95% CI, 5.0-upper limit not reached). The most common laboratory toxicities were non-cumulative increase of transaminases (ALT/AST) and gamma-glutamyltransferase (GGT). No patients experienced leukopenia and thrombocytopenia during the study. KF was a well-tolerated and safe chemotherapy regimen. Despite a favourable safety profile, this trial was closed after the first stage because of the lack of objective response in patients with malignant melanom

Safety of pembrolizumab as adjuvant therapy in a pooled analysis of phase 3 clinical trials of melanoma, non-small cell lung cancer, and renal cell carcinoma.

The safety profile of adjuvant pembrolizumab was evaluated in a pooled analysis of 4 phase 3 clinical trials. Patients had completely resected stage IIIA, IIIB, or IIIC melanoma per American Joint Committee on Cancer, 7th edition, criteria (AJCC-7; KEYNOTE-054); stage IIB or IIC melanoma per AJCC-8 (KEYNOTE-716); stage IB, II, or IIIA non-small cell lung cancer per AJCC-7 (PEARLS/KEYNOTE-091); or postnephrectomy/metastasectomy clear cell renal cell carcinoma at increased risk of recurrence (KEYNOTE-564). Patients received adjuvant pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for approximately 1 year. Adverse events (AEs) were summarized for patients who received ≥ 1 dose of treatment. Data were pooled from 4125 patients treated with pembrolizumab (n = 2060) or placebo (n = 2065). Median (range) duration of treatment was 11.1 months (0.0-18.9) with pembrolizumab and 11.2 months (0.0-18.1) with placebo. Treatment-related AEs occurred in 78.6 % (1620/2060) of patients in the pembrolizumab group (grade 3-5, 16.3 % [336/2060]) and 58.7 % (1212/2065) in the placebo group (grade 3-5, 3.5 % [72/2065]). Immune-mediated AEs (e.g. adrenal insufficiency, hypophysitis, and thyroiditis) occurred in 36.2 % (746/2060) of patients in the pembrolizumab group (grade 3-5, 8.6 % [177/2060]) and 8.4 % (174/2065) in the placebo group (grade 3-5, 1.1 % [23/2065]). Of patients with ≥ 1 immune-mediated AE or infusion reaction, systemic corticosteroids were required for 35.2 % (268/761) and 20.2 % (39/193) of patients in the pembrolizumab and placebo groups, respectively. Adjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease