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1.  Postoperative Bowel Perforation due to Heterotopic Ossification (Myositis Ossificans Traumatica): A Case Report and Review of the Literature 
Heterotopic ossification (HO) is the ectopic development of normal bone within soft tissue that can occur after traumatic injury. It is uncommon and may be missed or misdiagnosed, which can lead to complications. We report the case of an 84-year-old male with a previous history of a laparotomy who underwent resection of an intra-abdominal tumor through a midline incision. On postoperative day six, the patient was taken to the operating room, as succus was draining from the incision. Upon re-exploration, sharp bone-like material was found in the wound directly adjacent to an enterotomy. Pathology confirmed mature lamellar bone and the diagnosis of HO. This is the first report of postoperative intestinal perforation secondary to HO in a midline wound. We report this case to encourage accurate reporting of HO and its morbidity and complications for the benefit of appropriate surgical planning and epidemiologic tracking of outcomes.
doi:10.1155/2011/908514
PMCID: PMC3350174  PMID: 22606429
2.  Altered RECQ Helicase Expression in Sporadic Primary Colorectal Cancers12 
Translational Oncology  2013;6(4):458-469.
Deregulation of DNA repair enzymes occurs in cancers and may create a susceptibility to chemotherapy. Expression levels of DNA repair enzymes have been shown to predict the responsiveness of cancers to certain chemotherapeutic agents. The RECQ helicases repair damaged DNA including damage caused by topoisomerase I inhibitors, such as irinotecan. Altered expression levels of these enzymes in colorectal cancer (CRC) may influence the response of the cancers to irinotecan. Thus, we assessed RECQ helicase (WRN, BLM, RECQL, RECQL4, and RECQL5) expression in primary CRCs, matched normal colon, and CRC cell lines. We found that BLM and RECQL4 mRNA levels are significantly increased in CRC (P = .0011 and P < .0001, respectively), whereas RECQL and RECQL5 are significantly decreased (P = .0103 and P = .0029, respectively). RECQ helicase expression patterns varied between specific molecular subtypes of CRCs. The mRNA and protein expression of the majority of the RECQ helicases was closely correlated, suggesting that altered mRNA expression is the predominant mechanism for deregulated RECQ helicase expression. Immunohistochemistry localized the RECQ helicases to the nucleus. RECQ helicase expression is altered in CRC, suggesting that RECQ helicase expression has potential to identify CRCs that are susceptible to specific chemotherapeutic agents.
PMCID: PMC3730021  PMID: 23908689
3.  Epigenetics and Colorectal Cancer 
Colorectal cancer is a leading cause of cancer deaths in the world. It results from an accumulation of genetic and epigenetic changes in colon epithelial cells that transforms them into adenocarcinomas. There have been major advances in our understanding of cancer epigenetics over the last decade, particularly regarding aberrant DNA methylation. Assessment of the colon cancer epigenome has revealed that virtually all colorectal cancers have aberrantly methylated genes and the average colorectal cancer methylome has hundreds to thousands of abnormally methylated genes. As with gene mutations in the cancer genome, a subset of these methylated genes, called driver genes, is presumed to play a functional role in colorectal cancer. The assessment of methylated genes in colorectal cancers has also revealed a unique molecular subgroup of colorectal cancers called CpG Island Methylator Phenotype (CIMP) cancers; these tumors have a particularly high frequency of methylated genes. The advances in our understanding of aberrant methylation in colorectal cancer has led to epigenetic alterations being developed as clinical biomarkers for diagnostic, prognostic, and therapeutic applications. Progress in the assessment of epigenetic alterations in colorectal cancer and their clinical applications has shown that these alterations will be commonly used in the near future as molecular markers to direct the prevention and treatment of colorectal cancer.
doi:10.1038/nrgastro.2011.173
PMCID: PMC3391545  PMID: 22009203
Colon cancer; DNA methylation; epigenetics; biomarkers
4.  Impact of base analogs within a CpG dinucleotide on the binding of DNA by the methyl-binding domain of MeCP2 and methylation by DNMT1† 
Biochemistry  2010;49(47):10228-10236.
The epigenetic control of transcription requires the selective recognition of methylated CpG dinucleotides by methylation-sensitive sequence-specific DNA binding proteins. In order to probe the mechanism of selective interaction of the methyl-binding protein with methylated DNA, we have prepared a series of oligonucleotides containing modified purines and pyrimidines at the recognition site, and we have examined the binding of these oligonucleotides to the methyl-binding domain (MBD) of the methyl-CpG-binding protein 2 (MeCP2). Our results suggest that pyrimidine 5-substituents similar in size to a methyl group facilitate protein binding; however, binding affinity does not correlate with the hydrophobicity of the substituent, and neither the 4-amino group of 5-methylcytosine (mC) nor Watson-Crick base pair geometry is essential for MBD binding. However, 5-substituted uracil analogs in one strand do not direct human DNA methyltransferase 1 (DNMT1) methylation of the opposing strand, as does mC. Important recognition elements do include the guanine O6 and N7 atoms present in the major groove. Unexpectedly, removal of the guanine 2-amino group from the minor groove substantially enhances MBD binding, likely resulting from DNA bending at the substitution site. The enhanced binding of the MBD to oligonucleotides containing several cytosine analogs observed here is better explained by a DNA-protein interface mediated by structured water as opposed to hydrophobic interactions.
doi:10.1021/bi1011942
PMCID: PMC2996885  PMID: 20979427
DNA damage; methyl binding proteins; epigenetic alterations; cancer development; electrophoretic mobility shift assays
5.  Incorporation of 5-chlorocytosine into mammalian DNA results in heritable gene silencing and altered cytosine methylation patterns 
Carcinogenesis  2009;30(5):886-893.
Cytosine methylation patterns are essential for the proper control of gene expression in higher vertebrates. Although alterations in methylation patterns are frequently observed in human tumors, neither the mechanisms for establishing methylation patterns during normal development nor the mechanisms leading to pathological alterations of methylation patterns are currently known. While epidemiological studies have implicated inflammation in cancer etiology, a mechanistic link has yet to be established. Investigations of inflammation-mediated DNA damage may have provided important new insights. Our in vitro studies revealed that the inflammation-mediated DNA damage product, 5-chlorocytosine, could direct fraudulent methylation of previously unmethylated CpG sites. The purpose of this study was to recapitulate our in vitro findings by introducing 5-chlorocytosine residues into the DNA of replicating mammalian cells and to examine its impact on gene expression and cytosine methylation patterns. CHO-K1 cells hemizygous for the hprt gene were electroporated with the triphosphates of cytosine [2′-deoxycytidine-5′-triphosphate (dCTP)], 5-methylcytosine [5-methyl-2′-deoxycytidine-5′-triphosphate (MedCTP)] and 5′-chloro-2′-deoxycytidine-5′-triphosphate (CldCTP), and then selected with 6-thioguanine for silencing the hprt gene. Both modified nucleotides, MedCTP and CldCTP, but not unmodified dCTP, silenced hprt gene expression. Subsequent bisulfite pyrosequencing of CpG sites within the hprt promoter region of the selected cells confirmed hypermethylation, although global methylation levels as measured by gas chromatography–mass spectrometry did not change. Modified nucleotide-induced gene silencing could be reversed with 5-aza-2′-deoxycytidine indicating an epigenetic rather than mutagenic alteration. These results provide further evidence that the inflammation damage product 5-chlorocytosine could be a link between inflammation and cancer development.
doi:10.1093/carcin/bgp060
PMCID: PMC2675655  PMID: 19279184

Results 1-5 (5)