New trends in the treatment of undifferentiated carcinomas of the thyroid

INTRODUCTION: Malignant tumours of the thyroid are generally classified as either well-differentiated thyroid carcinoma, which is composed of papillary and follicular carcinoma, or undifferentiated/anaplastic thyroid carcinoma (ATC). ATC is not only the most lethal disease in the field of endocrine surgery but also one of the most aggressive tumours characterized by an almost invariable fatal outcome, which only very rarely exceeds a 1-year course. DISCUSSION: The impact of surgical resection in association with external beam radiation on ATC outcome has been extensively investigated also in studies based on multicentric database, and there is a general agreement on the significance of a complete resection of the tumour. It has been difficult up to now to collect data regarding chemotherapy adjuvant treatment. In spite of the lack of an extensive review about the results of this kind of treatment by itself or as part of a multimodal approach, it seems that among the several chemotherapy agents experienced, none proved to influence significantly ATC prognosis. Neither doxorubicin (the most commonly used) nor other drugs, such as cisplatin, bleomycin, fluorouracil or cyclophosphamide, showed any real efficacy in controlling the disease. CONCLUSION: The most recent development in this field seems to be represented by the possibility offered by PPARg agonists; even more promising might be the use of adenovirus-mediated p53 tumour suppressor gene therapy or BMP-7. All these new therapies need further confirmation coming from ongoing clinical trials such as those involving the use of vascular and growth factor-targeted agents.     

Adherence to recommendations for primary prevention of atopic disease in neonatology clinical practice

Passariello A, Terrin G, Baldassarre ME, Bisceglia M, Ruotolo S, Berni Canani R. Adherence to recommendations for primary prevention of atopic disease in neonatology clinical practice.
Pediatr Allergy Immunol 2010: 21: 889–891.
© 2010 John Wiley & Sons A/S The prevalence and severity of atopic manifestations in children are increasing in western countries in the last decades. Specific nutritional intervention may prevent or delay the onset of atopic diseases in infants at high risk of developing allergy. These nutritional interventions should be applied early in the perinatal period to have a chance of success. Thus, we assessed adherence to the dietary management recommendations of the Committee on Nutrition and Section on Allergy and Immunology of the American Academy of Pediatrics (AAP) for the prevention of atopic diseases in neonatal age through an audit study. Questionnaire was administered to the chiefs of 30 maternity units (MU) with more than 1500 live births/yr to report the policy applied in their MU. Twenty‐two MU returned the questionnaire. Identification of high‐risk newborns was routinely performed only in 7/22 MU (31.8%). High‐risk newborns were identified by the presence of at least two or one first‐degree relative (parent or sibling) with documented allergic disease by 18.2% and 45.5% of MU, respectively. Specific maternal dietary restrictions during lactation were adopted in 7/22 MU (31.8%). Extensively or partially hydrolyzed formula was prescribed for bottle‐fed high‐risk infants in 22.7% of MU. Only 2/22 MU have a policy in complete agreement with the nutritional intervention proposed by the AAP. Our study suggest a poor adherence to dietary recommendations for primary prevention of atopic disease in neonatology clinical practice. Further efforts should be planned to improve the knowledge and the application of these preventive strategies.     

The interaction of personality profile and lactation differs between mothers of late preterm and term neonates

Late preterm birth, a rapidly growing segment of premature deliveries, has the potential to cause deleterious effects on women’s psycho-emotional experience of labor and the establishment of successful lactation. We compared personality traits by the Lüscher Color Test, the mother-to-infant bonding attitudes by the Mother-to-Infant Bonding Scale (MIBS) and lactation outcome, between mothers of late preterm and at term infants. Our results indicated that mothers idealize their condition and wish to enjoy this magic and extraordinary time in spite of feeling stressed. However, late preterm mothers feel too sad and distressed to relax in their own space after the premature birth event. In addition, their total MIBS score (mean?±?SD) was significantly higher (1.364 versus 0.581; p 0.026), as related subscales: Dislike (p 0.005) and Disappointed (p 0.012). Finally, they significantly reduced breastfeeding rates from discharge (p?p?p?=?0.002) and sixth postnatal month (p?=?0.0002). We concluded that there is a relation between unconscious deep stress along with bonding limits of late preterm new mothers and impaired breastfeeding initiation and duration.     

Tissue engineering for total meniscal substitution: animal study in sheep model-results at 12 months

The aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Eighteen skeletally mature sheep were treated. The animals were divided into three groups: cell-free scaffold, scaffold seeded with autologous chondrocytes, and meniscectomy alone. The implant was sutured to the capsule and to the meniscal ligament. At a 12-month gross assessment, histology and histomorphometry were used to assess the meniscus implant, knee joint, and osteoarthritis development. All implants showed excellent capsular ingrowth at the periphery. The implant gross assessment showed significant differences between cell-seeded and cell-free groups (p=0.011). The histological analysis indicated a cellular colonization throughout the implanted constructs. Avascular cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Joint gross assessment showed that sheep treated with scaffold implantation achieved a significant higher score than those underwent meniscectomy (p<0.0005), and the Osteoarthritis Research Society International score showed that osteoarthritic changes were significantly less in the cell-seeded group than in the meniscectomy group (p=0.047), even though results were not significantly superior to those of the cell-free scaffold. Seeding of the scaffold with autologous chondrocytes increases its tissue regeneration capacity, providing a better fibrocartilaginous tissue formation. The study suggests the potential of the novel hyaluronic acid/polycaprolactone scaffold for total meniscal substitution, although this approach has to be further improved before being applied into clinical practice.     

Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

ABSTRACT: BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant familyspecific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27- q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.     

Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation

In autosomal dominant polycystic kidney disease (ADPKD), renal cyst development and enlargement, as well as cell growth, are associated with alterations in several pathways, including cAMP and activator protein 1 (AP1) signalling. However, the precise mechanism by which these molecules stimulate cell proliferation is not yet fully understood. We now show by microarray analysis, luciferase assay, mutagenesis, and chromatin immunoprecipitation that CREB and AP1 contribute to increased expression of the amphiregulin gene, which codifies for an epidermal growth factor-like peptide, in ADPKD cystic cells, thereby promoting their cell growth. Increased amphiregulin (AR) expression was associated with abnormal cell proliferation in both PKD1-depleted and -mutated epithelial cells, as well as primary cystic cell lines isolated from ADPKD kidney tissues. Consistently, normal AR expression and proliferation were re-established in cystic cells by the expression of a mouse full-length PC1. Finally, we show that anti-AR antibodies and inhibitors of AP1 are able to reduce cell proliferation in cystic cells by reducing AR expression and EGFR activity. AR can therefore be considered as one of the key activators of the growth of human ADPKD cystic cells and thus a new potential therapeutic target.