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The recent introduction of new drugs such as capecitabine, irinotecan, and oxaliplatinum has greatly improved the clinical outcome of patients with advanced/metastatic colorectal cancer. Nevertheless, some patients may suffer from the adverse drug reactions which will probably be the main cause of chemotherapy failure. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients; the different responses to a particular drug are due, in fact, not only to the specific clinico-pathological features of the patient or to environmental factors, but also to the ethnic origins and the particular individual's genetic profile. Genes which codify for the metabolism enzymes, receptor proteins, or protein targets of chemotherapy agents often present various genetic polymorphisms. The main aim of this review is to provide an overview of the known polymorphisms present in the genes which codify for factors (thymidylate synthase dihydropyrimidine dehydrogenase, uridine diphosphate (UDP)-glucuronosyl-transferase 1A1, enzymes implicated in DNA repair) involved in the action mechanisms of the drugs now utilized in chemotherapeutic treatment of colorectal carcinoma, such as fluoropyrimidines, irinotecan, and platinum agents.

International audience; Sensory properties are important elements to evaluate the qualities of vegetable products and are also determinant factors in purchasing decision. Here we report the Italian results of a preference mapping study conducted within a larger European project with the aim of describing the preferences of European consumers in regard to the diversity of traditional and modern tomato varieties, available on the market. This study has allowed the assessment of fruit quality at 3 levels: objective description of sensory properties, consumer preference tests, and physicochemical measurements. A set of 16 tomato cultivars, with different fruit sizes and shapes, was described and classified according to 18 sensory attributes including flavor, appearance, and texture characteristics. The same cultivars were evaluated by 179 consumers in a “preference mapping” experiment with the goal of identifying the preferred varieties and the reasons for the choice. The consumer data are referred to hedonic ratings (aspect liking and overall liking), familiarity for the analyzed cultivars, and individual features collected by a questionnaire. A hierarchical analysis of the clusters allowed to distinguish, within the sampled Italian consumers, 4 segments with different preferences which represented 19%, 25%, 41%, and 15% of the population, respectively. A partial least square regression model allowed the identification of the sensory attributes that best described consumer cluster preferences for tomato cultivars. Both texture and flavor descriptors were important drivers of consumer preferences, but the relevance (predictive value) of individual descriptors to model tomato liking was different for each consumer segment. Information on demographic and behavioral characteristics, usage habits, and factors relevant for purchasing were also provided on the 4 groups of consumers.

Triterpene saponins are a group of bioactive compounds abundant in the genus Medicago, and have been studied extensively for their biological and pharmacological properties. In this article, we evaluated the effects of the ectopic expression of AsOXA1 cDNA from Aster sedifolius on the production of triterpene saponins in barrel medic (Medicago truncatula Gaertn.). AsOXA1 cDNA encodes beta-amyrin synthase, a key enzyme involved in triterpene saponin biosynthesis. One of the four transgenic lines expressing AsOXA1 accumulated significantly larger amounts of some triterpenic compounds in leaf and root than did control plants. In particular, the leaf exhibited significantly higher levels of bayogenin, medicagenic acid and zanhic acid. The amounts of medicagenic acid and zanhic acid, which represent the core of the M. truncatula leaf saponins, were 1.7 and 2.1 times higher, respectively, than the amounts extracted from the control line. In root, the production of bayogenin, hederagenin, soyasapogenol E and 2beta-hydroxyoleanolic acid was increased significantly. The increase in the total amounts of triterpenic compounds observed in the leaves of transgenic lines correlated with the AsOXA1 expression level. Interestingly, the plants expressing AsOXA1 showed, under different growth conditions, improved nodulation when compared with the control line. Nodulation enhancement was also accompanied by a significant change in the soyasapogenol B content. Our results indicate that the ectopic expression of AsOXA1 in barrel medic leads to a greater accumulation of triterpene saponins and enhanced root nodulation.

A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 μU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies. Thyroid ultrasonography and scintigraphy showed hemiagenesis of the left lobe and no evidence of ectopic tissue. TSH response to thyrotropin-releasing hormone (TRH) injection (200 μg/mq, i.v.) was exaggerated and prolonged, suggesting subclinical hypothyroidism. The biological activity of circulating TSH was slightly below the normal range [TSH bioactivity (B) to immunoreactivity (I) ratio (TSH B/I) = 0.4, normal: 0.6–2.2]. These abnormalities are similar to those seen in patients with hypothalamic hypothyroidism. Thyroid function is not a recognized manifestation of WS and is not routinely investigated. However, abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis and thyroid dysgenesis have been found in other WS cases. Genes mapping at 7q11.23, contiguous to the chromosomal region deleted in most WS patients, may be involved in the development of the thyroid gland, contributing to the complex phenotype of WS. Am. J. Med. Genet. 85:491–494, 1999. © 1999 Wiley-Liss, Inc.