Nulliparity enhances the risk of second primary malignancy of the breast in a cohort of women treated for thyroid cancer

<p>Abstract</p> <p>Background</p> <p>Many studies have reported an increased risk of developing a second primary malignancy (SPM) of the breast in women treated for thyroid cancer. In this study, we investigated several potential risk factors for this association. The aim of this retrospective cohort study was to identify a subgroup of women surgically treated for papillary thyroid cancer that may benefit from more careful breast cancer screening.</p> <p>Methods</p> <p>A total of 101 women surgically treated for papillary thyroid cancer from 1996 to 2009 with subsequent follow-up were interviewed by phone regarding personal risk factors and lifestyle habits. Only 75 questionnaires could be evaluated due to a 25.7% rate of patients not retrieved or refusing the interview. Data analysis was performed using a multivariate logistic model.</p> <p>Results</p> <p>The standardised incidence ratio (SIR) for breast cancer was 3.58 (95% IC 1.14 - 8.37). Our data suggest a protective effect of multiparity on the development of a SPM of the breast (O.R. 0.15; 95% IC 0.25 - 0.86). Significant associations were not found with other known risk factors including Body Mass Index (BMI), age at first tumour, concurrent metabolic diseases, smoking, physical activity and familiarity.</p> <p>Conclusions</p> <p>This study confirms that a higher incidence of SPM of the breast is observed in women treated for papillary thyroid cancer. Additionally, this risk is increased by nulliparity, thus a strict breast screening program for nulliparous women treated for thyroid cancer may be advisable.</p

Comparative study of single and multislice computed tomography for assessment of the mandibular canal

OBJECTIVE: The purpose of this study was to evaluate the accuracy of relative measurements from the roof of the mandibular canal to the alveolar crest in multislice (multidetector) computed tomography (MDCT) and single-slice computed tomography (SSCT). MATERIAL AND METHODS: The sample consisted of 26 printed CT films (7 SSCT and 19 MDCT) from the files of the LABI-3D (3D Imaging Laboratory) of the School of Dentistry of the University of São Paulo (FOUSP), which had been acquired using different protocols. Two observers analyzed in a randomized and independent order a series of 22 oblique CT reconstructions of each patient. Each observer analyzed the CT scans twice. The length of the mandibular canal and the distance between the mandibular canal roof and the crest of the alveolar ridge were obtained. Dahlberg test was used for statistical analysis. RESULTS: The mean error found for the mandibular canal length measurements obtained from SSCT was 0.53 mm in the interobserver analysis, and 0.38 mm for both observers. On MDCT images, the mean error was 0.0 mm in the interobserver analysis, and 0.0 and 0.23 mm in the intraobserver analysis. Regarding the distance between the mandibular canal roof and the alveolar bone crest, the SSCT images showed a mean error of 1.16 mm in the interobserver analysis and 0.66 and 0.59 mm in the intraobserver analysis. In the MDCT images, the mean error was 0.72 mm in the interobserver analysis and 0.50 and 0.54 mm in the intraobserver analysis. CONCLUSION: Multislice CT was demonstrated a more accurate method and demonstrated high reproducibility in the analysis of important anatomical landmarks for planning of mandibular dental implants, namely the mandibular canal pathway and alveolar crest height

Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples

<p>Abstract</p> <p>Background</p> <p>Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland.</p> <p>Methods</p> <p>We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP), follicular (XTC-1) or anaplastic origin (8505C, C643 and HTH74). To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125) and DNA copy number information (n = 270) available in the literature on clinical samples of thyroid carcinoma.</p> <p>Results</p> <p>The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines) and losses at 8p, 13q, 18q, and Xp (4/7 cell lines) were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data.</p> <p>Conclusion</p> <p>We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here.</p

Actions of a Proline Analogue, L-Thiazolidine-4-Carboxylic Acid (T4C), on Trypanosoma cruzi

It is well established that L-proline has several roles in the biology of trypanosomatids. In Trypanosoma cruzi, the etiological agent of Chagas' disease, this amino acid is involved in energy metabolism, differentiation processes and resistance to osmotic stress. In this study, we analyzed the effects of interfering with L-proline metabolism on the viability and on other aspects of the T. cruzi life cycle using the proline analogue L- thiazolidine-4-carboxylic acid (T4C). The growth of epimastigotes was evaluated using different concentrations of T4C in standard culture conditions and at high temperature or acidic pH. We also evaluated possible interactions of this analogue with stress conditions such as those produced by nutrient starvation and oxidative stress. T4C showed a dose-response effect on epimastigote growth (IC50 = 0.89±0.02 mM at 28°C), and the inhibitory effect of this analogue was synergistic (p<0.05) with temperature (0.54±0.01 mM at 37°C). T4C significantly diminished parasite survival (p<0.05) in combination with nutrient starvation and oxidative stress conditions. Pre-incubation of the parasites with L-proline resulted in a protective effect against oxidative stress, but this was not seen in the presence of the drug. Finally, the trypomastigote bursting from infected mammalian cells was evaluated and found to be inhibited by up to 56% when cells were treated with non-toxic concentrations of T4C (between 1 and 10 mM). All these data together suggest that T4C could be an interesting therapeutic drug if combined with others that affect, for example, oxidative stress. The data also support the participation of proline metabolism in the resistance to oxidative stress

Biology of Streptococcus mutans-Derived Glucosyltransferases: Role in Extracellular Matrix Formation of Cariogenic Biofilms

The importance of Streptococcus mutans in the etiology and pathogenesis of dental caries is certainly controversial, in part because excessive attention is paid to the numbers of S. mutans and acid production while the matrix within dental plaque has been neglected. S. mutans does not always dominate within plaque; many organisms are equally acidogenic and aciduric. It is also recognized that glucosyltransferases from S. mutans (Gtfs) play critical roles in the development of virulent dental plaque. Gtfs adsorb to enamel synthesizing glucans in situ, providing sites for avid colonization by microorganisms and an insoluble matrix for plaque. Gtfs also adsorb to surfaces of other oral microorganisms converting them to glucan producers. S. mutans expresses 3 genetically distinct Gtfs; each appears to play a different but overlapping role in the formation of virulent plaque. GtfC is adsorbed to enamel within pellicle whereas GtfB binds avidly to bacteria promoting tight cell clustering, and enhancing cohesion of plaque. GtfD forms a soluble, readily metabolizable polysaccharide and acts as a primer for GtfB. The behavior of soluble Gtfs does not mirror that observed with surface-adsorbed enzymes. Furthermore, the structure of polysaccharide matrix changes over time as a result of the action of mutanases and dextranases within plaque. Gtfs at distinct loci offer chemotherapeutic targets to prevent caries. Nevertheless, agents that inhibit Gtfs in solution frequently have a reduced or no effect on adsorbed enzymes. Clearly, conformational changes and reactions of Gtfs on surfaces are complex and modulate the pathogenesis of dental caries in situ, deserving further investigation

Proteins of Leishmania (Viannia) shawi confer protection associated with Th1 immune response and memory generation

<p>Abstract</p> <p>Background</p> <p><it>Leishmania (Viannia) shawi </it>parasite was first characterized in 1989. Recently the protective effects of soluble leishmanial antigen (SLA) from <it>L. (V.) shawi </it>promastigotes were demonstrated using BALB/c mice, the susceptibility model for this parasite. In order to identify protective fractions, SLA was fractionated by reverse phase HPLC and five antigenic fractions were obtained.</p> <p>Methods</p> <p>F1 fraction was purified from L. (V.) shawi parasite extract by reverse phase HPLC. BALB/c mice were immunized once a week for two consecutive weeks by subcutaneous routes in the rump, using 25 μg of F1. After 1 and 16 weeks of last immunization, groups were challenged in the footpad with L. (V.) shawi promastigotes. After 2 months, those same mice were sacrificed and parasite burden, cellular and humoral immune responses were evaluated.</p> <p>Results</p> <p>The F1 fraction induced a high degree of protection associated with an increase in IFN-γ, a decrease in IL-4, increased cell proliferation and activation of CD8⁺T lymphocytes. Long-term protection was acquired in F1-immunized mice, associated with increased CD4⁺central memory T lymphocytes and activation of both CD4⁺and CD8⁺T cells. In addition, F1-immunized groups showed an increase in IgG2a levels.</p> <p>Conclusions</p> <p>The inductor capability of antigens to generate memory lymphocytes that can proliferate and secrete beneficial cytokines upon infection could be an important factor in the development of vaccine candidates against American Tegumentary Leishmaniasis.</p