Tankyrase, a positive regulator of telomere elongation, is over expressed in human breast cancer

Tankyrase promotes telomere elongation by interaction with the telomeric protein binding factor TRF1, a negative regulator of telomere extension. We measured tankyrase mRNA by real-time RT-PCR in 66 breast cancers and in paired normal tissues. Results were compared with hTERT mRNA expression. The levels of tankyrase in breast cancers were significantly higher in comparison to normal tissues (P<0.0001) and significantly related to the status of progesterone receptors. No relationship was found between tankyrase and hTERT mRNA expression in breast cancers. According to our results, tankyrase expression appeared up regulated in breast cancers.     

Spleen-preserving total pancreatectomy with conservation of the spleen vessels:: operative technique and possible indications

Conventional distal pancreatectomy (cDP) and total pancreatectomy (cTP) also involve removal of the spleen. The spleen, however, is an important organ in the immunologic defense of the host and is worthy of preservation if this can be safely achieved. We performed a spleen-preserving total pancreatectomy (SPTP), with good results, in a Caucasian woman, 66-year-old, affected by pancreatic metastases of renal clear cell carcinoma. This is the first report of a SPTP for pancreatic metastases to our knowledge, and we therefore wish to describe the surgical technique and to suggest the possible indications for this new technique.     

Influence of polymorphisms in the factor VII gene promoter on activated factor VII levels and on the risk of myocardial infarction in advanced coronary atherosclerosis

In this study, we investigate the influence of three factor VII (FVII) gene polymorphisms on activated FVII levels (FVIIa), and also on the risk of myocardial infarction (MI) in patients with advanced coronary atherosclerotic disease (CAD). The -323A2 allele in the promoter is known to be associated with low FVII levels, and has been suggested to protect against MI in some studies. The -402GA promoter polymorphism, that in vitro has been associated with having opposite effect, is less well studied clinically. For this study, plasma FVIIa levels and three FVII gene polymorphisms were assessed in 934 subjects of both sexes, all with an angiographic documentation of coronary vessels. Our results show that two promoter polymorphisms, plasma cholesterol, and gender, were significant predictors of FVIIa levels. The -402A allele was associated to a significant increase of FVIIa levels in males (by 19.2%). In a selected clinical model including the patients with severe CAD, with or without a thrombotic complication (MI), male carriers of the -402A had an increased risk of MI (OR=1.79; 95% CI 1.15-2.80). The -323A2 allele was associated to a significant decrease in FVIIa (by 36.02% in males, and 39.7% in females). Male carriers of the -323A2 were protected from MI (OR=0.6; 95% CI 0.39-0.94), but only after correction for the confounding effect of combined heterozygosity for the promoter polymorphisms. We can conclude that FVII gene polymorphisms with an opposite effect on FVIIa levels may modulate the risk of MI in males with advanced CAD. This study highlights a "within-gene" interaction, and the need to explore polymorphisms in candidate gene(s) in detail.     

Effect of maternal feed restriction on blood pressure in the adult guinea pig

Small size at birth has been associated with increased blood pressure in adult men and women. In rats, isocaloric protein restriction reduces fetal growth and increases systolic blood pressure in adult offspring. Balanced maternal undernutrition in the rat also increases adult blood pressure, but not consistently. The aim of this study was to determine the effect of moderate balanced maternal undernutrition (85% of ad libitum intake from 4 weeks before, and throughout pregnancy) on blood pressure of adult offspring in the guinea pig, a species that is relatively mature at birth. Blood pressure was measured in chronically catheterised offspring of ad libitum fed or feed-restricted mothers, at 3 months of age (young adult). Maternal feed restriction reduced birth weight (-17%) and increased systolic blood pressure (+9%, P < 0.03) in young adult male offspring. In offspring of ad libitum fed and feed-restricted mothers, combined data showed that systolic blood pressure and mean arterial pressure correlated negatively with head width at birth (P = 0.02 and P = 0.04, respectively, n = 28). Systolic blood pressure also correlated negatively with birth weight and the ratio birth weight/birth length, but only in offspring of ad libitum fed mothers (P = 0.04 and P = 0.03, respectively, n = 22). The effect of maternal feed restriction on systolic blood pressure in male offspring was not significant when adjusted for these measures of size at birth. Thus, moderate balanced undernutrition in the guinea pig increases systolic blood pressure in young adult male offspring; however, these effects may be mediated, at least in part, through effects on fetal growth.     

Accuracy of percutaneous core biopsy of isolated breast microcalcifications identified by mammography. Experience with a vacuum-assisted large-core biopsy device

PURPOSE: To evaluate the diagnostic accuracy of 11-G vacuum-assisted stereotactic core biopsy (VAB) of isolated clusters of microcalcifications identified by mammography. MATERIALS AND METHODS: Retrospective analysis of 364 consecutive procedures from February 1999 to June 2002. Final outcome was histological diagnosis at surgery or mammographic follow-up. Linkage with local cancer registry was available. Diagnostic accuracy and upgrading of atypical ductal hyperplasia (ADH) to carcinoma or of ductal carcinoma in situ (DCIS) to invasive carcinoma (INV) was evaluated. The positive predictive value (PPV) of radiological judgement (score 1 to 5) and of the cluster volume (only for unifocal lesions) for ADH or more severe lesions was also considered. RESULTS: A total of 364 consecutive VAB procedures were evaluated (average age 54.9, range 33-81). VAB report was negative, ADH, DCIS or INV in 192, 22, 126 or 24 cases, respectively. Of 188 cases with ADH or more severe reports at VAB or surgical biopsy 16 had an originally negative VAB report, yielding a sensitivity of 91.4%. Upgrading at surgical biopsy for cases with follow-up was 29.4% (5/17) for ADH (DCIS=2, INV=3) and 17.3% (20/115) for DCIS. Of 221 cases with known outcome and mammograms available for review PPV was 37.1%, 65.9%, 90.9%, and 89.4% for radiological suspicion degrees 2,3,4 and 5, respectively (chi squared for trend = 32.44, p<10(-6)) and was 70.0%, 72.4% and 89.4% for cluster volumes of 0-60, 61-500 and >500 mmc, respectively (chi squared for trend= 2.36, p=0.12) among 195 unifocal clusters. No microcalcifications were found at core radiography in 20 cases (VAB negative=18, ADH=1, INV=1) with DCIS or INV occurring in 4 or 1 case, respectively, at further surgery. CONCLUSIONS: Core biopsy avoids unnecessary surgery in many subjects with suspicious microcalcifications, although it implies a non negligible risk of false negative report. Surgical biopsy in VAB negative cases could be indicated according to other variables (e.g. the degree of radiological suspicion). VAB has relevant limits in grading breast lesions, as ADH or DCIS are associated to a considerable risk of upgrading at surgical biopsy. VAB reports other than INV need to be confirmed at surgery before an individual treatment strategy may be defined.     

EPIC-Italy cohorts and multipurpose national surveys. A comparison of some socio-demographic and life-style characteristics

BACKGROUND: EPIC-Italy cohort study recruited subjects who voluntarily accepted to participate in the project. From the self-selected bases of the population sample, some bias could derive in the data interpretation when risk estimation for cancer disease related to life-style factors is the principal concern. Knowledge of the bias related to self-selected sampling is important for better directing the interpretation of the EPIC-Italy study results. METHODS: We investigated the characteristics of volunteer subjects recruited in the EPIC-Italy cohorts and compared them with those of the randomly selected subjects recruited in the Multipurpose ISTAT Surveys realized in the same period (1993-1998) in which the EPIC-cohorts were recruited. RESULTS: We found some differences, and in particular a different attitude towards cigarettes smoking and wine consumption, between the EPIC cohort and the Multipurpose ISTAT Surveys, as well as among geographical areas within the EPIC cohort. CONCLUSIONS: The uneven distribution of some characteristics suggests that the self-selected subjects were characterized by an overall lower consumption of wine and cigarette smoking even when the educational level was considered. This could suggest a generally more healthy life-style among subjects recruited on a volountary bases.     

Effects of 0.2 T static magnetic field on human skin fibroblasts

Human skin fibroblasts were exposed to 0.2 T static magnetic field generated by a magnetic resonance tomograph. After 1h exposure, cell morphology was modified in association with a concomitant decrease in the expression of some sugar residues of glycoconjugates. Study of cell proliferation and mitogenic signal transduction showed a decrease of thymidine incorporation and of second messenger formation. However, cell viability, assessed by colony forming assay, was unaffected. These results demonstrate that the static magnetic field generated by routinely used magnetic resonance tomograph induces alterations on human skin fibroblasts.     

International Union of Pharmacology XXXVII. Nomenclature for leukotriene and lipoxin receptors

The leukotrienes and lipoxins are biologically active metabolites derived from arachidonic acid. Their diverse and potent actions are associated with specific receptors. Recent molecular techniques have established the nucleotide and amino acid sequences and confirmed the evidence that suggested the existence of different G-protein-coupled receptors for these lipid mediators. The nomenclature for these receptors has now been established for the leukotrienes. BLT receptors are activated by leukotriene B(4) and related hydroxyacids and this class of receptors can be subdivided into BLT(1) and BLT(2). The cysteinyl-leukotrienes (LT) activate another group called CysLT receptors, which are referred to as CysLT(1) and CysLT(2). A provisional nomenclature for the lipoxin receptor has also been proposed. LXA(4) and LXB(4) activate the ALX receptor and LXB(4) may also activate another putative receptor. However this latter receptor has not been cloned. The aim of this review is to provide the molecular evidence as well as the properties and significance of the leukotriene and lipoxin receptors, which has lead to the present nomenclature.