Immunohistochemical expression of C-myc oncogene,heat shock protein 70 and HLA-DR molecules in malignant cutaneous melanoma

The clinical course of malignant melanomas is frequently unpredictable, although a number of prognostically useful variables can be identified. There is a need for additional markers of prognostic value. In a series of 60 malignant cutaneous melanomas, we analysed the immunohistochemical expression of c-myc proto-oncogene, heat shock protein 70 (HSP70) and HLA-DR molecules in order to investigate their prognostic significance. C-myc, HSP70 and HLA-DR were expressed in 43.3%, 56.6% and 38.3% of all melanoma cases, respectively. Advanced Clark levels (Clark III–V) were significantly associated with c-myc expression rate (P<0.05), HSP70 detection (P<0.01) and HLA-DR positivity (P<0.01). Increased Breslow thickness (>1.5 mm) was related to HLA-DR expression (P<0.05). High mitotic rate was closely associated with c-myc positivity (P<0.05), while HSP70 and HLA-DR expression separately correlated to clinical stage of the disease (P<0.05). The evaluation of these variables may be of immunological and prognostic significance. They were found to be associated with melanocyte subpopulations of the vertical growth phase which are arguably characterized by an increased invasive potential.     

Mixed Hyperbranched/Triblock Copolymer Micelle Assemblies: Physicochemical Properties and Potential for Drug Encapsulation

Mixed micelles have numerous advantages while requiring little to no effort in preparation. This study aims to produce mixed micelle nanostructures from a linear triblock copolymer and a hyperbranched random copolymer, and is able to be loaded with the weakly water-soluble drugs curcumin and indomethacin. Different preparation techniques are employed to produce mixed micelles comprised of Pluronic F127 block copolymer, and hyperbranched poly[(ethylene glycol) methyl ether methacrylate-co-lauryl methacrylate], H-[P(OEGMA-co-LMA)], copolymer. Few studies have dabbled in these types of coassemblies, which provides insight into how structural differences of each copolymer can affect the formation of micelles. To determine the properties of the emerging nanostructures in aqueous environments, including their size, homogeneity, and surface charge, different physicochemical techniques are used, such as light scattering and spectroscopic methods. The results reveal that the copolymers combine, and spontaneously self-assemble into mixed micelle-like nanostructures in aqueous environments, whereas both systems of neat and drug-loaded nanostructures exhibit desirable properties such as small average micelle hydrodynamic radii and low size polydispersity indices. The nanostructures that result from the effective encapsulation of curcumin exhibit outstanding stability over 169 days. The fluorescent qualities of curcumin persist after encapsulation, making the novel nanostructures excellent candidates for bioimaging applications.     

Role of asymmetrical dimethylarginine in the progression of renal disease

Asymmetric dimethylarginine (ADMA) is a naturally occurring amino acid found in tissues and cells that circulates in plasma and is excreted in urine. It inhibits nitric oxide synthases (NOs) and produces considerable cardiovascular biological effects. Several studies have suggested that plasma concentrations of ADMA provide a marker of risk for endothelial dysfunction and cardiovascular disease. In animal and in population studies ADMA has been associated with progression of CKD. Several mechanisms may be involved in this association, such as compromise of the integrity of the glomerular filtration barrier and development of renal fibrosis. This review summarizes the existing literature on the biology and physiology of ADMA focusing on its role in the progression of renal disease.     

Platelet‐rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model

Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet‐rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration . Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral‐like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut‐shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant–explant construct was cultured for 2–4 weeks. PRP‐soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push‐out test, was significantly increased in the PRP‐soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP‐treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP‐soaked group had a 3.5‐fold increase in matrix metalloproteinase‐13 gene expression compared with controls. These results suggest that PRP‐soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration.     

3DTEE imaging of a descending aorta floating thrombus in a patient with calciphylaxis

We present a case of a 68‐year‐old man with calciphylaxis, who was found to have a floating thrombus in the descending aorta on a transesophageal echocardiogram. The use of 3D echocardiography demonstrated nicely the free motion of the thrombus, emerging from an atherosclerotic plaque in the descending aorta. Anticoagulation was started for thromboembolism prevention.     

Association of rs1568885, rs1813443 and rs4411591 polymorphisms with anti-TNF medication response in Greek patients with Crohn’s disease

AIM:To investigate the correlation between rs1568885,rs1813443 and rs4411591 polymorphisms and response to infliximab in a cohort of Greek patients with Crohn’s disease(CD).METHODS:One hundred and twenty-six patients diagnosed with CD based on standard clinical,endoscopic,radiological,and pathological criteria were enrolled in this study at the Gastroenterology Unit of the 2nd Department of Surgery and at the Colorectal Unit of the1st Department of Propaedeutic Surgery.Infliximab at a dose of 5 mg/kg was administered intravenously at weeks 0,2,6 and then every 8 wk.Clinical and serological responses were assessed using the HarveyBradshaw Index and serum C-reactive protein(CRP)levels,respectively,and the endoscopic response was evaluated by ileocolonoscopy performed at baseline and after 12-20 wk of therapy.The changes in endoscopic appearance compared to baseline were classified into four categories,and patients were classified as responders and non-responders.Genomic DNA from whole peripheral blood was extracted and genotyping was performed by allele-specific polymerase chain reactions.χ2test with Yate’s correction based on the S-Plus was used to compare the genotype frequencies.RESULTS:Eighty patients(63.49%)were classified as complete and 32(25.39%)as partial responders to infliximab,while 14(11.11%)were primary non-responders.No correlation was found between response to infliximab and patients’characteristics such as age,gender and disease duration.There was consistency between Harvey-Bradshaw index scores and serum CRP levels.The TT genotype of the rs1568885 polymorphism was significantly related to partial response(P=0.024)and resistance to infliximab(P=0.007)while the AT genotype was more frequent in partial responders(P=0.035)and in primary non-responders(P=0.032).Regarding rs1813443,the CC genotype was found to be associated with partial response(P=0.005)and primary resistance(P=0.002)to infliximab while no association was found between the rs4411591 polymorphism and the clinical response to infliximab.CONCLUSION:Based on our results,the rs1568885and rs1813443 polymorphisms are associated with clinical and biochemical response to infliximab in Greek patients with Crohn’s disease.     

Stem cells in colon cancer. A new era in cancer theory begins

Introduction  

Despite the various therapeutic combinations and the emergence of new targeted therapies, there is still no curative treatment for all stages of colorectal cancer. Through the query for the best possible combination and solution, a new theory approaching colorectal cancer as a stem cell disease appeared, with a continuously growing body of evidence supporting this idea. The inability to directly recognize cancer stem cells has led researchers to an attempt of distinguishing those using indirect markers.