Trabectedin and Plitidepsin: Drugs from the Sea that Strike the Tumor Microenvironment

The prevailing paradigm states that cancer cells acquire multiple genetic mutations in oncogenes or tumor suppressor genes whose respective activation/up-regulation or loss of function serve to impart aberrant properties, such as hyperproliferation or inhibition of cell death. However, a tumor is now considered as an organ-like structure, a complex system composed of multiple cell types (e.g., tumor cells, inflammatory cells, endothelial cells, fibroblasts, etc.) all embedded in an inflammatory stroma. All these components influence each other in a complex and dynamic cross-talk, leading to tumor cell survival and progression. As the microenvironment has such a crucial role in tumor pathophysiology, it represents an attractive target for cancer therapy. In this review, we describe the mechanism of action of trabectedin and plitidepsin as an example of how these specific drugs of marine origin elicit their antitumor activity not only by targeting tumor cells but also the tumor microenvironment.     

Ultrasound and computed tomography of sacculitis and appendicitis in a rabbit

A 9‐month‐old neutered male rabbit was referred for lethargy, anorexia, and gastrointestinal stasis. Routine hematology, serum biochemistry, and diagnostic imaging were performed. Computed tomography revealed a wall thickening of the sacculus rotundus and appendix, which was further confirmed on abdominal ultrasound. Full thickness biopsies were collected with histopathology diagnosing a chronic multifocal heterophilic granulomatous sacculitis and appendicitis. The patient was treated medically and at 6 weeks follow‐up, clinical signs and intestinal changes had completely regressed. Inflammation of the sacculus rotundus and appendix should be considered as a cause of gastrointestinal stasis in rabbits.     

Allelic variation of the ACCase gene and response to ACCase-inhibiting herbicides in pinoxaden-resistant Lolium spp

BACKGROUND: The repeated use of acetyl‐coenzyme A carboxylase (ACCase) inhibiting herbicides to control grass weeds has selected for resistance in Lolium spp. populations in Italy. The efficacy of pinoxaden, a recently marketed phenylpyrazoline herbicide, is of concern where resistance to ACCase inhibitors has already been ascertained. ACCase mutations associated with pinoxaden resistance were investigated, and the cross‐resistance pattern to clodinafop, haloxyfop, sethoxydim, clethodim and pinoxaden was established on homo/heterozygous plants for four mutant ACCase alleles. RESULTS: Seven different mutant ACCase alleles (1781‐Leu, 1999‐Leu, 2041‐Asn, 2041‐Val, 2078‐Gly, 2088‐Arg and 2096‐Ala) and 13 combinations with two types of mutation were detected in the pinoxaden‐resistant plants. The 1781‐Leu allele appears to confer a dominant resistance to pinoxaden, clodinafop, haloxyfop, sethoxydim and clethodim at 60 g AI ha^?1. The 2041‐Asn and 2041‐Val alleles are associated with dominant or partially dominant resistance to FOPs, no substantial resistance to DIMs and a moderate resistance to pinoxaden. The 2088‐Arg allele endows a partially dominant resistance to clodinafop, sethoxydim and most likely to pinoxaden. In addition, non‐target‐site resistance mechanisms seem to be involved in pinoxaden resistance. CONCLUSION: Almost all the ACCase mutations selected in the field by other ACCase inhibitors are likely to confer resistance to pinoxaden. Although pinoxaden is sometimes able to control FOP‐resistant populations, it should not be considered as a sustainable ACCase resistance management tool. The presence of non‐ACCase‐based resistance mechanisms that could confer resistance to herbicides with different modes of action further complicates the resistance management strategies. Copyright © 2011 Society of Chemical Industry     

The use of Lactobacillus pentosus 1MO to shorten the debittering process time of black table olives (Cv. Itrana and Leccino): a pilot-scale application

Fifty lactobacilli isolated from black table olive brines were evaluated for their salt tolerance, resistance to oleuropein and verbascoside, and ability to grow in modified filter-sterilized brines. A strain of Lactobacillus pentosus was selected and used as a starter to ferment, in pilot plant, black olives (Itrana and Leccino cv.) in brines modified for pH, carbohydrate, and growth factor concentrations, at 28 degrees C. The temperature-controlled fermentation of Leccino cv. olives resulted in obtaining ready-to-eat, high-quality table olives in a reduced-time process. HPLC analysis of phenolic compounds from fermented olives showed a decrease of oleuropein, a glucoside secoiridoid responsible for the bitter taste of olive drupes, and an increase of the hydroxytyrosol concentration. The selected strain of L. pentosus (1MO) allowed the reduction of the debittering phase period to 8 days.     

Extremely potent antifeedant neo-clerodane derivatives of scutecyprol A

Two known neo-clerodane diterpenoids, scutecyprol A (1) and scutalbin C (2), have been isolated from the acetone extract of the aerial parts of Scutellaria sieberi. The antifeedant activity of scutecyprol A (1), of its 15-oxo derivative (3), and of several halohydrins (4-9), synthesized starting from compounds 1 and 3, against Spodoptera littoralis have been determined and structure-antifeedant relationships are discussed.     

Do Collembola affect the competitive relationships among soil-borne plant pathogenic fungi?

The feeding preference of the collembolan Protaphorura armata in the presence of Fusarium culmorum and Gaeumannomyces graminis var. tritici, two soil-borne fungi pathogenic for winter cereals, was studied in a simplified experimental system including wheat seedlings. Analysis of gut content of all animals from microcosms containing inoculum of both fungi showed that F. culmorum was clearly preferred but that G. graminis var. tritici was also fed. At microscopic examination the majority of F. culmorum conidia present in the gut lacked cytoplasmic content, and only few conidial cells were intact. The feeding preference of P. armata favoured G. graminis var. tritici over F. culmorum in the competition for infection sites on wheat plants; in fact, the former resulted the prevalent cause of plant disease.

The viability of fungal propagules after passage through the gut of P. armata was also studied. No colonies of G. graminis var. tritici and only a few colonies of F. culmorum developed from faecal pellets set on agar medium. Fungal propagules dispersed by springtails were not sufficient to induce disease, as demonstrated by introducing animals, previously fed on fungal cultures separately, into microcosms containing a sterile substrate where wheat kernels were seeded.     

Formation of Damascenone under both commercial and model fermentation conditions

The fermentations, at a commercial winery, of six different grape musts encompassing the varieties Riesling, Chardonnay, Sauvignon blanc, Shiraz, Grenache, and Pinot noir were monitored for damascenone concentration. In every case, the concentration of damascenone increased during fermentation from low or undetectable levels to concentrations of several parts per billion. Further increases in damascenone concentration were observed during barrel aging of three of these wines. Two ketones, megastigma-4,6,7-triene-3,9-dione (4) and 3-hydroxymegastigma-4,6,7-trien-9-one (5), were synthesized and subjected to fermentation conditions using two yeasts, AWRI 796, and AWRI 1537. In the case of the former compound, 4, synthesis confirmed the original, tentative assignment of the structure and confirmed 4 as a natural product, isolated from honey. Both compounds, under the action of both yeasts, produced appreciable amounts of damascenone (1), with ketone 5 and AWRI 796 yeast yielding the highest concentration of 1.     

Photoprotective potential of strawberry (Fragaria × ananassa) extract against UV-A irradiation damage on human fibroblasts

Exposure to UV-A radiation is known to induce discrete lesions in DNA and the generation of free radicals that lead to a wide array of skin diseases. Strawberry (Fragaria × ananassa) contains several polyphenols with strong antioxidant and anti-inflammatory activities. Because the major representative components of strawberry are anthocyanins, these may significantly contribute to its properties. To test this hypothesis, methanolic extracts from the Sveva cultivar were analyzed for anthocyanin content and for their ability to protect human dermal fibroblasts against UV-A radiation, as assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide and Comet assays. Five anthocyanin pigments were identified using high-performance liquid chromatography-diode array detection-electrospray ionization/mass spectrometry. Moreover, the strawberry extract showed a photoprotective activity in fibroblasts exposed to UV-A radiation, increasing cellular viability, and diminishing DNA damage, as compared to control cells. Overall, our data show that strawberry contains compounds that confer photoprotective activity in human cell lines and may protect skin against the adverse effects of UV-A radiation.