Tehran University Medical Journal

Background: Conservative treatment needs to be tried prior to surgical treatment of knee osteoarthritis. This study was designed to evaluate the short-term effects of dextrose prolotherapy on pain relief and functional improvement in knee osteoarthritis in comparison with intra-articular hyaluronic acid injections.

Methods: In this double blind clinical trial, 100 patients, aged 40-70 years, with complaints of knee pain lasting >3 months were recruited in Akhtar hospital during the years 2010 to 2011. The patients met the criteria proposed by the American College of Rheumatology (ACR) for knee osteoarthritis. 50 patients in hyaluronic acid group received five 2 ml injections of hyaluronic acid (Synocrom Forte® 1%) weekly and 50 patients in dextrose prolotherapy group received three 2 ml bimonthly injections of 25% dextrose. The patients were evaluated before and after treatment in terms of pain and functionality using the Knee injury and Osteoarthritis Outcome Score (KOOS) self-questionnaire. The patients were followed up for 12 weeks and were examined 12 weeks after the injections by an observer unaware of group assignments. The data were recorded for statistical analysis.

Results: The mean age of the patients was 60.68.2 years. No significant differences were found between the two groups with respect to pre- and post-treatment KOOS scores. The scores showed significant improvements in all items following treatment in both groups (P<0.001).

Conclusion: It seems that intra-articular injections of 25% dextrose prolotherapy could be as effective as hyaluronic acid injections for the treatment of knee pain due to OA.

Stable molecular changes during cell division without any change in the sequence of DNA molecules is known as epigenetic. Molecular mechanisms involved in this process, including histone modifications, methylation of DNA, protein complex and RNA antisense. Cancer genome changes happen through a combination of DNA hypermethylation, long-term epigenetic silencing with heterozygosis loss and genomic regions loss. Different combinations of N-terminal’s changes cooperate with histone variants with a specific role in gene regulation. It have led to load a setting histone that determine transcription potential of a particular gene or genomic regions. DNA methylation analysis in genome region using methylation-specific digital karyotyping of normal breast tissue detect gene expression patterns and DNA specific methylation can be found in breast carcinoma too more than 100 genes in breast tumors or cell lines of breast cancer are reported hypermethylated. Important of DNA methylation on cancer has been concentrated CpG islands hypermethylation. Most of the techniques are able to identify hypermethylated areas. Often, methylated genes play important role in cell cycle regulation, apoptosis, metastasis and tissue invasion, angiogenesis and hormonal signaling. Cyclin D2 (CCND2) gene is an important regulator of cell cycle and increased of expression inhibits the transition from G1 to S cell cycle. This gene is frequently methylated in breast cancer and has been proposed as the first event. Other cell cycle regulator is p16ink4A / CDKN2A that methylated in a large number of human cancers, including breast cancer. Another regulator of the proliferation of breast cancer that methylated is tumor suppressor RAR-β cancer that has been found in lobular and ductal carcinoma. Recent studies have showed the role of epigenetic silencing in the pathogenesis of breast cancer in which tumor suppressor genes have been changed by acetylation and DNA deacetylation. Histone deacetylase inhibitors have different roles in cancer cells and could show the ways of new treatment for breast cancer. In this review, various aspects of breast cancer epigenetics and its applications in diagnosis, prediction and treatment are described.