Comparative study of the effect of PTH (1-84) and strontium ranelate in an experimental model of atrophic nonunion.

UNLABELLED: This study aimed to set up an experimental model of long bone atrophic nonunion and to explore the potential role of PTH-1-84 (PTH 1-84) and strontium ranelate (SrR). A model of atrophic nonunion was created in Sprague-Dawley rats at the femoral midshaft level. The animals were randomised into four groups. Group A1: control rodents, fracture without bone gap; Group A2: rodents with subtraction osteotomy (non-union model control) treated with saline; Group B: rodents with subtraction osteotomy treated with human-PTH (PTH 1-84); and Group C: rodents with subtraction osteotomy treated with strontium ranelate (SrR). The groups were followed for 12 weeks. X-rays were be obtained at weeks 1, 6 and 12. After sacrificing the animals, we proceeded to the biomechanical study and four point bending tests to evaluate the resistance of the callus and histological study. In second phase, the expression of genes related to osteoblast function was analysed by reverse transcription-quantitative PCR in rats subjected to substraction osteotomy and treated for 2 weeks. The animals were randomised into three groups: Group A2: rodents treated with saline; Group B: rodents treated with PTH 1-84 and Group C: rodents treated with SrR. RESULTS: No significant histological differences were found between animals subjected to subtraction osteotomy and treated with either saline or PTH (p=0.628), but significant difference existed between animals receiving saline or SrR (p=0.005). There were no significant differences in X-ray score between the saline and PTH groups at either 6 or 12 weeks (p=0.33 and 0.36, respectively). On the other hand, better X-ray scores were found in the SrR group (p=0.047 and 0.006 in comparison with saline, at 6 and 12 weeks, respectively). In line with this, biomechanical tests revealed improved results in the SrR group. Gene expression analysis revealed a slightly decreased levels of DKK1, a Wnt pathway inhibitor, in rats treated with SrR. CONCLUSIONS: SrR increases has a beneficial effect in this atrophic non-union model in rats. This suggests that it might have a role may have important implications for the potential clinical role in the treatment of fracture nonunion.

Gastrointestinal stromal tumours at present: an approach to burning questions

Because of their well known origin in gene mutations and a revolutionary therapy by means of molecular targets, gastrointestinal stromal tumours (GIST) constitute a plentiful and paradigmatic model of translational investigation, resulting in an avalanche of exponential growth data. In this article, we focus on what we consider to be hot spots in GIST at present. A wide spectrum of events is approached, extending from subtle pathogenic mechanisms at a molecular level (gene mutations and their implications for cell receptors with subsequent activation of signalling pathways) to more practical problems facing diagnosis (molecular markers, role of biopsy), prognosis (risk stratification systems) and different therapeutic aspects (laparoscopic surgery, role of surgery in advanced disease, response criteria, adjuvant and neoadjuvant therapy, treatment for progressing and recurrent disease, therapy directed on mutation analysis and new developments, among others). The review has been endorsed by level of evidence evaluation through a recognised pattern to assist in teaching, and a final summary of recommendations and a management algorithm are included (AU)

[Overexpression of p53 protein in epidermoid carcinoma of the pyriform sinus]. / Sobreexpresión de la proteína p53 en el carcinoma epidermoide de seno piriforme.

Mutation of the p53 protein may be the commonest genetic event in the development of malignant neoplasms in humans. We analyzed the immunohistological expression of p53 in tissue sections from 51 patients with squamous cell carcinoma of the pyriform sinus who were treated with surgery and postoperative radiotherapy. Overexpression of p53 was found in 37 (72.5%) tumors. No correlation was found between p53 overexpression and clinical and histopathological parameters. Recurrence and overall survival did not differ between p53-positive and p53-negative cases.

Sarcomatoid chromophobe cell renal carcinoma: immunohistochemical and lectin study in one case.

We present one case of sarcomatoid chromophobe cell renal carcinoma with an indolent clinical course and assume that the carcinomatous component may affect the biologic behavior. The patient was a 61-year-old man who underwent right radical nephrectomy for a 11.2 cm tumor in the lower pole. The immunohistochemical findings demonstrate that EMA and cytokeratins 8 and 18 are useful markers for the sarcomatoid fraction, and the lectin study shows a loss of surface blood antigen. Chromophobe cell carcinoma may convert into sarcomatoid carcinoma. The existence of sarcomatoid renal cell carcinoma as a distinct entity should be re-considered.