Preliminary assessment of the risks associated with solar ultraviolet-A exposure.

An approach is proposed to assess the periods of human skin exposure to solar ultraviolet-A (UV-A, 315-400 nm) irradiance in natural conditions that are able to yield doses found to trigger carcinogenesis in laboratory experiments. Weighting functions, adopted to perform such estimate are constructed, allowing for a comparison between environmental and laboratory doses. Furthermore, the impact of stratum corneum (SC) thickness on the studied environmental doses was investigated. Based on laboratory studies, it was found that exposure periods of less than a month, at mid-latitudes, could provide irradiance doses capable of causing tumor formation. The duration of these exposure periods closely depends on the exposure regime, atmospheric conditions and SC thickness. It is believed that the presented evaluations could provide a useful preliminary estimation of the risk associated with environmental UV-A exposure prior to the formulation of the corresponding action spectra and determination of the threshold doses.

Synthesis and characterization of novel cardanol based benzoxazines.

Benzoxazines are a class of phenolic compounds extensively studied in polymer science because of their properties as fiber reinforcements, fire-retardants and curing agents. In this article is described a solvent-less process, based on a Mannich reaction involving a primary amine and an aldehyde, for the preparation of new benzoxazines deriving from cardanol (a well known phenol obtained as a renewable organic resource and harmful by-product of the cashew industry). Particular attention is given to the synthesis and chemical characterization (both by 1H NMR spectroscopy and HPLC), while the thermal polymerization process has been monitored by differential scanning calorimetry.

Molecular characterisation of breast cancer patients at high and low recurrence risk.

The ability to predict the recurrence risk in breast cancer patients is not available for the individual. It is commonly accepted that the different clinical course of tumours with identical histology and stage are the result of differences at the molecular level. This case study of 80 patients affected by breast cancer looked at the messenger ribonucleic acid expression level of 22 genes, by using quantitative reverse transcriptase-polymerase chain reaction. Our results showed that a panel of seven genes is associated to patients' survival. Moreover, the combination of two couples of genes is able to define short- and long-living cohorts of patients. In particular, our findings strongly demonstrate that retinoblastoma (RB) and cyclin-dependent kinase 2 (CDK2) on one side and cytokeratin 8 (CK8) and epidermal growth factor receptor 2 (HER2) on the other may affect the clinical course of the disease in 56% of patients. Groups characterised by low RB and high CDK2 as with low CK8 and high HER2 have a higher risk of recurrences and death in 5 years. The identification of these sub-groups of patients with higher risk of early relapse could have further involvement in the selection of the cases to submit to therapy against HER2 or CDK2 as a possible therapy target.

Expression of cyclin-dependent kinases and CDC25a phosphatase is related with recurrences and survival in women with peri- and post-menopausal breast cancer.

Progression through the mammalian cell cycle is regulated by cyclin-cyclin-dependent kinase (CDKs) complexes that are activated throughout the cell cycle. Alteration in cell cycle control could lead to proliferation and tumourogenesis. This study was designed to analyse, at messenger RNA (mRNA) level, cyclins and CDKs involved in the retinoblastoma pathway, as well as cell division cycle 25a phosphatase (CDC25a), which activates some of the CDKs that were analysed. The aim of the study was to determine the possible prognostic relevance of these molecules in 73 women with peri- and post-menopausal breast cancer. Cyclins A, D1 and E; CDKs 2, 4 and 6 and phosphatase CDC25a expression status were analysed in primary tumours at mRNA level, by reverse transcriptase polymerase chain reaction analysis in paraffin-embedded primary breast cancers. High expression levels of CDK2, CDK4 and CDC25a were related to tumour recurrence. Over-expression of CDK2 and CDC25a was also associated with reduced overall survival; moreover, the CDK2 expression level was able to define a short-living cohort of patients with tumour-positive lymph nodes. CDK2, CDK4 and CDC25a can be used as reliable biomarkers to predict prognosis in women with peri- and post-menopausal breast cancer.

The simultaneous use of telomerase, cytokeratin 20 and CD4 for bladder cancer detection in urine.

OBJECTIVE: Because of the low sensitivity of urinary cytological diagnosis of urinary bladder carcinoma, new molecular diagnostic methods have been proposed. We decided to verify the expression of telomerase mRNA coding for the catalytic component (hTRT), cytokeratin 20 (CK20) and CD4 antigen mRNAs in urine as possible diagnostic tool. METHODS: Evaluation of hTRT, CK20, CD4 mRNAs was performed in 50 ml of naturally voided urine of 205 patients of which 153 with bladder cancer (Tis, n = 11; TaGx, n = 4; TaG1, n = 25; TaG2, n = 26; TaG3, n = 8; T1G1, n = 16; T1G2, n = 17; T1G3, n = 20; T2G2, n = 6; T2G3, n = 13; T3G3, n = 7) and 52 controls. A quantitative expression of hTRT at mRNA level versus TRAP (telomeric repeat amplification protocol) assay was performed in 20 patients and 14 controls. The expression of RT-PCR for hTRT, CK20, CD4 versus urinary cytology was analysed in 44 patients with bladder cancer. Evaluating the three molecular markers together, the result was considered correct when at least two of the markers were positive, suspected when only one marker was positive and negative for diagnosis of tumour when all markers were negative. The performance of the diagnostic model resulted from the logistic analysis evaluated with receiver operating characteristics (ROC) curve analysis. RESULTS: The sensitivity detected for each tumour marker was as follows: for hTRT 90.8%, for CK20 84.3% and for CD4 was 64.7%, while the specificity was 94.2% for CD4 and 78.8% for both hTRT and CK20. When a simultaneous evaluation of the three tumour markers was considered, 88.2% of the diagnoses were correct, 11.8% were suspected for tumour and none were mistaken. When compared with cytology, the simultaneous use of the three markers allowed reaching a correct diagnosis in 88% of the cases in comparison to 25% by urinary cytology. The sensitivity in the detection of bladder cancer was higher for hTRT at mRNA level in comparison with the enzymatic activity detection with TRAP (90% vs. 35%) while the specificity for both markers resulted very high (100%). CONCLUSIONS: These data show that in the future the diagnostic improvement of urine based molecular markers for the detection of bladder cancer in the urine could improve the sensitivity of urinary cytology reducing the need of a cystoscopy.