Characterization and Future Distribution Prospects of "Carciofo di Malegno" Landrace for Its In Situ Conservation.

"Carciofo di Malegno" is a little-known landrace of Cynara cardunculus subsp. scolymus cultivated in Camonica Valley (northern Italy). The morphological and phytochemical characteristics of this landrace were investigated; furthermore, a species distribution model (MaxEnt algorithm) was used to explore its ecological niche and the geographical area where it could be grown in the future. Due to its spiky shape, "Carciofo di Malegno" was distinct from any other artichoke sample considered, and it appears to be similar to those belonging to the "Spinosi" group. The concentration of chlorogenic acid (497.2 ± 116.0 mg/100 g DW) and cynarine (7.4 ± 1.2 mg/100 g DW) in "Carciofo di Malegno" was comparable to that of the commercial cultivars. In "Carciofo di Malegno," luteolin was detected in a significant amount (9.4 ± 1.5 mg/100 g DW) only in the stems and in the edible parts of the capitula. A MaxEnt distribution model showed that in the coming decades (2040-2060s), the cultivation of this landrace could expand to the pre-Alps and Alps of Lombardy. Climate change may promote the diffusion of "Carciofo di Malegno", contributing to preservation and the enhancement of this landrace and generating sustainable income opportunities in mountain areas through exploring new food or medicinal applications.

Synthesis of N-oxyamide analogues of protein kinase B (Akt) targeting anionic glycoglycerolipids and their antiproliferative activity on human ovarian carcinoma cells.

N-Oxyamides of bioactive anionic glycoglycerolipids based on 2-O-ß-D-glucosylglycerol were efficiently prepared. However, the oxidation step of the primary hydroxyl group of the glucose moiety in the presence of the N-oxyamide function appeared to be a difficult task that was nevertheless conveniently achieved for the first time by employing a chemoenzymatic laccase/TEMPO procedure. The obtained N-oxyamides exhibited a higher inhibition of proliferation of ovarian carcinoma IGROV-1 cells in serum-free medium than in complete medium, similarly to the corresponding bioactive esters. Stability and serum binding studies indicated that the observed reduced activity of the compounds in complete medium could be mainly due to a binding effect of serum proteins rather than the hydrolytic degradation of glycoglycerolipid acyl chains. Furthermore, the results of the cellular studies under serum-free conditions suggested that the N-oxyamide group could increase the antiproliferative activity of a glycoglycerolipid independently of the presence of the anionic carboxylic group. Cellular studies in other cell lines besides IGROV-1 also support a certain degree of selectivity of this series of compounds for tumor cells with Akt hyperactivation.

Caffeic acid phenethyl ester targets ubiquitin-specific protease 8 and synergizes with cisplatin in endometrioid ovarian carcinoma cells.

Deubiquitinases (DUBs) mediate the removal of ubiquitin from diverse proteins that participate in the regulation of cell survival, DNA damage repair, apoptosis and drug resistance. Previous studies have shown an association between activation of cell survival pathways and platinum-drug resistance in ovarian carcinoma cell lines. Among the strategies available to inhibit DUBs, curcumin derivatives appear promising, thus we hypothesized their use to enhance the efficacy of cisplatin in ovarian carcinoma preclinical models. The caffeic acid phenethyl ester (CAPE), inhibited ubiquitin-specific protease 8 (USP8), but not proteasomal DUBs in cell-free assays. When CAPE was combined with cisplatin in nine cell lines representative of various histotypes a synergistic effect was observed in TOV112D cells and in the cisplatin-resistant IGROV-1/Pt1 variant, both of endometrioid type and carrying mutant TP53. In the latter cells, persistent G1 accumulation upon combined treatment associated with p27kip1 protein levels was observed. The synergy was not dependent on apoptosis induction, and appeared to occur in cells with higher USP8 levels. In vivo antitumor activity studies supported the advantage of the combination of CAPE and cisplatin in the subcutaneous model of cisplatin-resistant IGROV-1/Pt1 ovarian carcinoma as well as CAPE activity on intraperitoneal disease. This study reveals the therapeutic potential of CAPE in cisplatin-resistant ovarian tumors as well as in tumors expressing USP8.

Recent Progresses in Conjugation with Bioactive Ligands to Improve the Anticancer Activity of Platinum Compounds.

Platinum (Pt) drugs, including cisplatin, are widely used for the treatment of solid tumors. Despite the clinical success, side effects and occurrence of resistance represent major limitations to the use of clinically available Pt drugs. To overcome these problems, a variety of derivatives have been designed and synthetized. Here, we summarize the recent progress in the development of Pt(II) and Pt(IV) complexes with bioactive ligands. The development of Pt(II) and Pt(IV) complexes with targeting molecules, clinically available agents, and other bioactive molecules is an active field of research. Even if none of the reported Pt derivatives has been yet approved for clinical use, many of these compounds exhibit promising anticancer activities with an improved pharmacological profile. Thus, planning hybrid compounds can be considered as a promising approach to improve the available Pt-based anticancer agents and to obtain new molecular tools to deepen the knowledge of cancer progression and drug resistance mechanisms.

Dual-active antifungal agents containing strobilurin and SDHI-based pharmacophores.

Crop disease management often implies repeated application of fungicides. However, the increasing emergence of fungicide-resistant pathogens requires their rotation or combined use. Tank-mix combinations using fungicides with different modes of action are often hard to manage by farmers. An alternative and unexploited strategy are bifunctional fungicides, i.e. compounds resulting from conjugation of the pharmacophores of fungicides with different mechanisms of action. In this paper we describe a new approach to antifungal treatments based on the synthesis of dual agents, obtained by merging the strobilurin and succinate dehydrogenase inhibitor pharmacophores into a new entity. The compounds were tested against important fungal plant pathogens and showed good inhibition of Pyricularia oryzae and Sclerotinia sclerotiorum with activity comparable to commercial fungicides. The inhibition of the cytochrome bc1 and the succinate dehydrogenase enzyme activity confirmed that the new molecules are endowed with a dual mechanism of action. These results were further supported by molecular modelling which showed that selected compounds form stable complexes with both cytochrome b subunit and succinate dehydrogenase enzyme. This work can be considered an important first step towards the development of novel dual-action agents with optimized structure and improved interaction with the targets.

Samarium Iodide-Promoted Asymmetric Reformatsky Reaction of 3-(2-Haloacyl)-2-oxazolidinones with Enals.

3-(2-Haloacyl)-2-oxazolidinones were shown to react with enals in an asymmetric SmI2-promoted Reformatsky reaction to give stereochemically well-defined 3-hydroxy-4-alkenyl- and 3-hydroxy-2-methyl-4-alkenyl imides. Chirality transfer of the Evans (S)-oxazolidinone unit via a Zimmerman-Traxler-like transition state resulted in Reformatsky products with a relative syn-configuration. The absolute configuration of compounds obtained is opposite to the corresponding products obtained via aldol addition of boron enolates to enals using the same Evans oxazolidinones.

Minimally invasive esophagectomy in a previously pneumonectomized patient.

INTRODUCTION: Surgical resection represents the only therapeutic action having a radical intent for the treatment of resectable esophageal neoplasms. Minimally invasive esophagectomy for esophageal cancer is being more and more frequently performed. Few cases of esophagectomy after pneumonectomy have been described in the literature, and, to our knowledge, none of them was performed by the minimally invasive technique. SUBJECT AND METHODS: A 77-year-old woman, who had undergone left thoracotomic pneumonectomy due to squamous cell lung cancer 2 years before, underwent minimally invasive esophagectomy because of esophageal cancer at the authors' institution. The intervention was performed by right thoracoscopic esophageal mobilization with the patient in the prone position, followed by the laparoscopic and cervicotomic stages, with cervical anastomosis. RESULTS: Total operative time was 230 minutes. Intensive care unit stay was 1 day, followed by a hospital stay of 13 days. We did not observe any major postoperative complication. CONCLUSIONS: Minimally invasive esophagectomy with thoracoscopic esophageal mobilization in the prone position is a valid option in the treatment of esophageal cancer and may be feasible in previously left pneumonectomized patients.

Minimally invasive esophagectomy: thoracoscopic esophageal mobilization for esophageal cancer with the patient in prone position.

BACKGROUND: Surgical resection is the mainstay treatment for resectable esophageal cancer. Minimally invasive esophagectomy is performed with increasing frequency and proves to be a safe and effective surgical alternative to the open technique. Minimally invasive esophagectomy using thoracoscopic esophageal mobilization with the patient in prone position seems to offer some advantages with regard to surgeon ergonomics and clinical outcome. METHODS: Between July 2005 and September 2010, 46 patients (35 men and 11 women) underwent minimally invasive esophagectomy in the prone position at the authors' institution. Three patients had previously undergone a thoracic intervention (one patient had previously undergone left pneumonectomy because of lung cancer). The preoperative indication was squamous cell carcinoma for 35 patients and adenocarcinoma for 11 patients. In one case, the histology of the biopsy samples showed a squamous cell carcinoma with neuroendocrine differentiation. Neoadjuvant treatment was administered to 15 patients. RESULTS: All 46 patients underwent esophagectomy using minimally invasive thoracic mobilization of the esophagus with the patient in prone position. The abdominal stage of intervention was performed by laparoscopy for 37 patients and by laparotomy for 9 patients. No thoracotomic conversion was performed. In all cases, a cervical end-to-side anastomosis was performed using a circular stapler. The mean operative time was 263 min. The median intensive care unit stay was 2 days, and the median postoperative hospital stay was 15 days. The mean number of procured lymph nodes was 13. The perioperative morbidity rate was 37%, and the perioperative mortality rate was 4.4%. CONCLUSIONS: Minimally invasive esophagectomy is safe and technically feasible. It entails a lower mortality rate and a shorter hospital stay than those reported in most open series. Thoracoscopy with the patient in prone position offers results comparable with those obtained using other minimally invasive techniques regarding the number of procured lymph nodes. This technique shows considerable advantages such as improved surgeon ergonomics, increased operative field exposure, and satisfactory respiratory results.