Transfection and expression of mutant p53 protein does not alter the in vivo or in vitro growth characteristics of the AA/C1 human adenoma derived cell line, including sensitivity to transforming growth factor-beta 1.

Mutation of the p53 gene is thought to be a late event in human colorectal carcinogenesis, involved in the malignant conversion of the adenoma to the carcinoma. One of the questions that we hoped to address was whether, in vivo, a single mutational event in one p53 gene is sufficient to confer a significant growth advantage on a colonic epithelial cell. Such a growth advantage could result either from an increase in growth rate and/or loss of response to inhibitory growth signals naturally present in the colonic crypt. We therefore introduced the pC53-SCX3 143 (Val-Ala) p53 mutation into a non tumorigenic adenoma derived cell line, AA/C1, which contained a truncating APC mutation, activating K-ras mutation but was wild-type for the p53 protein. High levels of mutant p53 protein were detected in the pC53-SCX3 transfected AA/C1 cell lines but was found not to affect either the in vitro (colony forming efficiency, anchorage independence) or in vivo (tumorigenicity in nude mice) growth, when compared to vector control or the parental AA/C1 cell line. In addition, to test whether the cells become less sensitive to inhibitory growth factors, the response of the cell lines to the naturally occurring growth inhibitor TGF beta was also investigated. Even though TGF beta had previously been implicated in the control of growth of intestinal epithelium, expression of the mutant p53 protein did not affect the sensitivity of the parental AA/C1 cell line to TGF beta. Under the experimental conditions tested expression of the 143 (Val-Ala) p53 protein was unable to affect the in vitro or in vivo growth characteristics of the adenoma derived AA/C1 cell line. When compared to other studies, these results suggest that the genetic background of the individual recipient cell may greatly influence the effect of expression of a particular p53 mutation.

The impact of cortical remapping interventions on pain and disability in chronic low back pain: a systematic review.

BACKGROUND: Cortical change, in the manner of cortical remapping is a common feature of and potential driver for chronic low back pain (CLBP). Novel interventions such as graded motor imagery (GMI) and mirror visual feedback (MVF) have been shown to facilitate correction of cortical changes and improve symptoms in other chronic pain states. However, little is known regarding the effectiveness of these treatment approaches in CLBP. OBJECTIVE: To identify and assess the current evidence regarding the effectiveness of interventions which target cortical remapping in the management of CLBP. DATA SOURCES: The electronic databases Medline, Embase, CINAHL, AMED, OVID, PEDro, BNI, PsycINFO, HMIC, and Cochrane library were systematically searched. STUDY SELECTION: Of 11 potential citations identified, 5 articles were identified for inclusion and critiqued. These comprised 3 randomised controlled trials (RCTs), 1 randomised cross-over study, and 1 multiple case study design. RESULTS: Visualisation of lumbar movement may significantly improve movement-related pain severity and duration. A combined sensorimotor retraining approach has been shown to produce short-term improvements in both pain and disability outcomes in CLBP. The relative effectiveness of individual interventions and their long-term efficacy have yet to be established. CONCLUSIONS: There is a paucity of robust literature which has examined the application and efficacy of these novel treatments in the management of CLBP. Results from the few CLBP studies which are available are encouraging. Further, robust research is needed to optimise treatment protocols and establish their long-term effectiveness in CLBP.