Methylation markers: a potential force driving cancer diagnostics forward

Epigenetics, transcending genetics, genomics, and molecular biology, is now poised to be the avant-garde beacon of biological science. The rise of DNA methylation studies marks a new dawn in the field of epigenetics, which only a few decades ago was largely underestimated, but is now a dynamic area of research challenging and revising traditional paradigms of gene expression and behavior. Cancer research enjoys a major share of this attention to DNA methylation and it has been widely accepted for some time now that cancer is as much an epigenetic phenomenon as it is genetic. Epigenetic lesions and perturbations are acquired during the life of an individual and accumulate with aging and represent the flip side of the same coin that bears genetic mutations. Both events, either individually or in cooperation, result in the development and progression of cancer. Epigenetic research and the hunt for strong methylation markers has been ably mitigated by new and improved high throughput technology that has improved the efficacy and enabled the rapid progress of biomarker evaluation and validation. This review looks into some of the recent strides in biomarker research dealing exclusively with methylation markers and the potential key they may hold to the resilient door shut tight on cancer diagnostics and treatment.     

Azurin-like protein blocks invasion of Toxoplasma gondii through potential interactions with parasite surface antigen SAG1

Some pathogenic bacteria produce factors that have evolved a capacity to neutralize competing microbes. The cupredoxin family protein azurin, produced by Pseudomonas aeruginosa, exhibits a remarkable ability to impede invasion of a number of diverse intracellular pathogens, including the human AIDS virus human immunodeficiency virus type 1 and the protozoan parasite Plasmodium falciparum (which causes malaria). Here we report that azurin and an azurin-like protein (Laz) from gonococci/meningococci have activity against Toxoplasma, an apicomplexan parasite that causes opportunistic infection in immunocompromised individuals. We demonstrate that the mechanism of action for Laz involves interfering with the ability of Toxoplasma to adhere to host cells. Computer structural analysis reveals that azurin shares structural features with the predominant surface antigen SAG1, which is known to play an important role in parasite attachment. Interestingly, azurin also has structural similarities to a monoclonal antibody to SAG1. Surface plasmon resonance binding studies validate that SAG1 interacts strongly with Laz and, to lesser extent, azurin. Moreover, Toxoplasma mutants lacking SAG1 are not as susceptible to the growth-inhibitory effects of Laz. Collectively, our data show that Toxoplasma adhesion can be significantly impaired by Laz, and to some extent by azurin, via interactions with SAG1. These observations indicate that Laz can serve as an important tool in the study of host-pathogen interactions and is worthy of further study for development into potential therapeutic agents.     

Use of Flexible Endoscopic Scissors to Cut Obstructing Suture Material in Gastric Bypass Patients

With the epidemic increase in obesity in the USA and consequent increased demand for bariatric surgery, new complications of the surgery are being described. The most common surgery practiced is the Roux-en-Y gastric bypass (RYGBP). Unraveling of suture material at the gastrojejunal anastomosis may occur, which may be troublesome if nonabsorbable suture is employed. We describe, for the first time, two patients who developed obstructive symptoms as a consequence of food matter/bezoars entrapped within a mesh of unraveled nonabsorbable suture material at their anastomoses. One of these patients also developed ulceration, presumably as a result of pressure necrosis from the entrapped bezoar. We describe a third patient where the placement of nonabsorbable sutures led to obstructive symptoms by limiting distensibility at an otherwise satisfactory anastomosis. We also describe for the first time, the use of a new endoscopic scissors in cutting luminal suture material with subsequent resolution of the clinical problem.     

Negative pressure wound therapy with instillation: a pilot study describing a new method for treating infected wounds

This data review reports the results of 15 patients who were treated with Vacuum-Assisted Closure (VAC) negative pressure therapy system in addition to the timed, intermittent delivery of an instilled topical solution for management of their complex, infected wounds. Prospective data for 15 patients treated with negative pressure wound therapy (NPWT)-instillation was recorded and analysed. Primary endpoints were compared to a retrospective control group of 15 patients treated with our institution's standard moist wound-care therapy. Culture-specific systemic antibiotics were prescribed as per specific patient need in both groups. All data were checked for normality of distribution and equality of variance and appropriate parametric and non parametric analyses were conducted. Compared with the standard moist wound-care therapy control group, patients in the NPWT-instillation group required fewer days of treatment (36.5 +/- 13.1 versus 9.9 +/- 4.3 days, P < 0.001), cleared of clinical infection earlier (25.9 +/- 6.6 versus 6.0 +/- 1.5 days, P < 0.001), had wounds close earlier (29.6 +/- 6.5 versus 13.2 +/- 6.8 days, P < 0.001) and had fewer in-hospital stay days (39.2 +/- 12.1 versus 14.7 +/- 9.2 days, P < 0.001). In this pilot study, NPWT instillation showed a significant decrease in the mean time to bioburden reduction, wound closure and hospital discharge compared with traditional wet-to-moist wound care. Outcomes from this study analysis suggest that the use of NPWT instillation may reduce cost and decrease inpatient care requirements for these complex, infected wounds.     

Medical therapies for non-melanoma skin cancer

The epidemic of nonmelanoma skin cancer (NMSC) continues, in part due to aging of the world's population, the frequency of early childhood sunburns, and episodic intense recreational sun exposure as opposed to sun exposure related to outdoor occupations. A nonsurgical approach to selected skin cancers could potentially decrease the expense and morbidity of surgical treatment for NMSC. The increase of comorbid medical conditions in the elderly makes alternatives to surgical management preferable under certain circumstances. This review will discuss medical alternatives ranging from biologic response modifiers to COX-2 inhibitors to lifestyle modifications, as well as their roles in the management of NMSC. This preliminary information will expand to include more therapeutic options for NMSC in the future. Further clinical trials are needed to better elucidate possible alternative treatment strategies for NMSC.     

The conjugation of an AQP1-directed immunotoxin in the study of site-directed therapy within the CNS

Purpose  

The water channel, aquaporin (AQP)1, is highly specific to the choroid plexus (CP) epithelium within the brain. It is therefore a potential target through which therapeutic agents could be selectively directed to the CP. Here we describe the conjugation of a monoclonal antibody (mAb), raised against an extra-cellular domain of AQP1, to the A chain of ricin (RCA). This reagent should allow study of a highly specific chemical lesion of the CP.