Molecular analysis of TP53, Ki-Ras and P16 methylation status in tissue and plasma of subjects affected by gastrointestinal cancer (GIC)

BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same alteration both in the plasma and in the tumor tissue. At univariate analysis, Ki-Ras mutations proved to be significantly related to quicker relapse (P <0.01), whereas only a trend towards statistical significance (P = 0.083) was observed for the TP53 mutations CONCLUSIONS: Detection of Ki-Ras and TP53 mutation in plasma should be significantly related to disease recurrence. These data suggest that patients with a high risk of recurrence can be identified by means of the analysis of tumor-derived plasma DNA with the use of fairly non-invasive techniques

Estudio preliminar de algunas variables de crecimiento y fertilidad en ratones de Bioterio

 In the present work, the results obtained in the comparative study of the growth and fertility of Balb/C and CF-1 mice from the Bioterium of the Faculty of Medicine of the National University of the Northeast are exposed, by modifying the environmental conditions of breeding and reproduction of the animals before and after the moving of the Center to its new facilities. The characteristics studied in both strains were: breeding number, weight according to sex before and after weaning, until to the 15th week of life, and fertility rate. The results obtained show that the moving caused stress in both murine strains, and the effect was manifested in the decrease of growth and fertility rates observed in the animals. These values were not statistically significant, which allows us to conclude that the enrichment of the habitat in the new facilities helped to alleviate in some way the stress of the move. This is the first systematic study carried out for this purpose and lays the foundations for others for monitoring the adaptation and production in the new facilities.En el presente trabajo se exponen los resultados obtenidos en el estudio comparativo del crecimiento y la fertilidad de ratones Balb/C y CF-1 del Bioterio de la Facultad de Medicina de la Universidad Nacional del Nordeste, al modificar las condiciones ambientales de cría y reproducción de los animales previa y posteriormente al traslado del Centro a sus nuevas instalaciones. Las características estudiadas en ambas cepas fueron: número de crías, peso según sexo previo y posterior al destete, hasta la semana 15 de vida y tasa de fertilidad. Los resultados obtenidos muestran que el traslado causó estrés en ambas cepas murinas, cuyo efecto se manifestó en la disminución de las tasas de crecimiento y fertilidad en estos animales experimentales. Estos valores resultaron no significativos estadísticamente, lo que nos permite concluir que el enriquecimiento del hábitat en las nuevas instalaciones ayudó a paliar de alguna manera el estrés de la mudanza. Este es el primer estudio sistemático realizado a este efecto y sienta las bases de otros para el seguimiento de la adaptación y producción en las nuevas instalaciones

MR-based simplified extraprostatic extension evaluation: comparison of performances of different predictive models

Objectives To test reproducibility and predictive value of a simplified score for assessment of extraprostatic tumor extension (sEPE grade). Methods Sixty-five patients (mean age &amp; PLUSMN; SD, 67 years &amp; PLUSMN; 6.3) treated with radical prostatectomy for prostate cancer who underwent 1.5-Tesla multiparametric magnetic resonance imaging (mpMRI) 6 months before surgery were enrolled. sEPE grade was derived from mpMRI metrics: curvilinear contact length &gt; 15 mm (CCL) and capsular bulging/irregularity. The diameter of the index lesion (dIL) was also measured. Evaluations were independently performed by seven radiologists, and inter-reader agreement was tested by weighted Cohen K coefficient. A nested (two levels) Monte Carlo cross-validation was used. The best cut-off value for dIL was selected by means of the Youden J index to classify values into a binary variable termed dIL*. Logistic regression models based on sEPE grade, dIL, and clinical scores were developed to predict pathologic EPE. Results on validation set were assessed by the main metrics of the receiver operating characteristics curve (ROC) and by decision curve analysis (DCA). Based on our findings, we defined and tested an alternative sEPE grade formulation. Results Pathologic EPE was found in 31/65 (48%) patients. Average kappa(w) was 0.65 (95% CI 0.51-0.79), 0.66 (95% CI 0.48-0.84), 0.67 (95% CI 0.50-0.84), and 0.43 (95% CI 0.22-0.63) for sEPE grading, CLL &amp; GE; 15 mm, dIL*, and capsular bulging/irregularity, respectively. The highest diagnostic yield in predicting EPE was obtained by combining both sEPE grade and dIL*(ROC-AUC 0.81). Conclusions sEPE grade is reproducible and when combined with the dIL* accurately predicts extraprostatic tumor extension

Genotype analysis of colorectal carcinomas through laser pressare catapulting (LPC)

Recently, new chemotherapy agents which target the non-structural components of mitosis have been developed. An important protein involved in several mitotic phases is the Aurora-A protein. By means of the phosphorylation of different substrates, Aurora-A regulates the correct development of the various phases of mitosis. The kinase activity of this protein makes Aurora-A an excellent candidate as an oncogene. The first data of Aurora-A involvement in cancer regarded the identification of Aurora-A overexpression in primary breast and colon tumour samples. With regard to the predictive role of Aurora-A, it has been shown that its overexpression disrupts the spindle checkpoint activated by paclitaxel (Taxol) or nocodazole treatment, thus inducing the cells to become resistant to these drugs. The development therefore of small molecules with an Aurora-A inhibition function may make it possible to reduce or block the oncogenic activity of Aurora-A and in addition may improve the survival of oncological patients showing resistance to paclitaxel or nocodazole treatment. Three novel Aurora kinase inhibitors have recently been described - Hesperadin, ZM447439 and VX-680. All these three drugs have been designed to target the ATP-binding site of Aurora kinase, so they inhibit all three Aurora kinase family members showing a similar phenotype when tested in cell-based assays. Among these three different molecules, VX-680 has shown promising results in in vitro and in vivo studies. In conclusion, it is clear that we are entering a new era in anti-mitotic therapy with the identification and now clinical translation of new targets in mitosis beyond tubulin but many questions remain with regard to Aurora function. \ua9 2007 European Society for Medical Oncology