Glycopolymer Code: Programming Synthetic Macromolecules for Biological Targeting

Targeting in a cellular level is still one of the major challenges in biomedical treatments. However, new synthetic and analytical techniques now allow the development of precisely prepared macromolecules. Thus, glycopolymer chains are reported to be prepared with controlled length, monomer sequences, as well as chain‐folded structures. A high level of complexity in synthetic macromolecules also allows increased selectivity in targeting, which is a key factor in biomedical applications.     

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

Lipid peroxidation, erythrocyte superoxide-dismutase activity and trace metals in young male footballers

Physical training is known to induce oxidative stress in individuals subjected to intense exercise. In this study, we investigated plasma malondialdehyde (MDA) levels and erythrocyte superoxide dismutase (SOD) activity of 25 young male footballers and a control group of similar age. Red blood cell (RBC) count, haemoglobin (Hb) and haematocrit (Hct) values, and copper (Cu) and zinc (Zn) levels were also examined. The maximal oxygen uptake (VO2max) of all subjects was determined in order to establish their functional capacity. The main finding of the present study was that plasma MDA levels, one of the most commonly used markers of lipid peroxidation, of this group of footballers aged under 21 decreased slightly when compared with those of the control group (p < 0.001). In contrast, erythrocyte SOD activity was higher in the footballer group than in the controls (p < 0.001). Footballers who are under regular training showed an improved antioxidant activity in comparison to sedentary controls. Plasma copper concentration, RBC count and Hb concentration of the footballer group were all significantly lower than those of the control group, (p < 0.001, p < 0.01, p < 0.01, respectively). Investigating the footballers' data with Spearman's correlation analyses, the correlation coefficients (r) between Zn/Cu ratio and SOD was positive (r=0.44; p < 0.05); and between VO2max and SOD (r=0.42; p < 0.05) were both positive. On the basis of statistical analysis, we suggest that regular exercise may be beneficial in cases of oxidative damage by reducing the amount of lipid peroxidation and increasing the activity of the antioxidant enzyme SOD.     

Neuraminidase produces a decrease of adherence of slime-forming <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> to gelatin-impregnated polyester fiber graft fabric: an experimental study

Because slime-forming microorganisms are the major causative agents of graft infections, we aimed to investigate bacterial adherence in slime-forming and nonslime-forming Staphylococcus aureus and to determine the role of neuraminidase (NANase) on adherence to gelatin-impregnated polyester fiber graft fabric. An in vitro model was developed to quantitatively measure bacterial adherence to the surface of the graft. The grafts were divided into two groups – those colonized with slime-forming S. aureus and those colonized with nonslime-forming S. aureus. The grafts were put into sterile tubes and human plasma was instilled and incubated at 37°C to perform fibrin deposition on the grafts. After 48 h of incubation, grafts were drained and inoculated with slime-forming or nonslime-forming S. aureus in triptic soy broth in the presence or absence of NANase. Following 36 h of incubation at 36°C, grafts were vortexed and cultured to perform a colony count. Bacterial counts were expressed as total colony-forming units per square centimeter of graft. Slime-forming S. aureus had greater affinity with the graft compared with nonslime-forming S. aureus (P < 0.05). The adherence of slime-forming S. aureus was impaired by NANase treatment (P < 0.001) but NANase treatment of nonslime-forming S. aureus did not change the adherence to the graft (P > 0.05). These results show that slime plays an important role in the pathogenesis of vascular graft infection. Adherence of slime-forming S. aureus can be decreased by NANase treatment. This may have implications for the development of neuraminidase-embedded vascular grafts to diminish biomaterial-related infections.     

Prognostic importance of COX-2 expression in patients with colorectal cancer

A relationship between cyclooxygenase-2 (COX-2) expression and the pathogenesis of colorectal cancer has been reported in recent studies. Moreover, it has been indicated that COX-2 expression may have a prognostic role in colorectal cancer patients. In this study, we investigated the prognostic significance of COX-2 expression in 83 patients with colorectal cancer. COX-2 expression was assessed using immunohistochemical methods and was evaluated by grading both staining intensity and staining extension. The relationships between COX-2 expression and clinicopathological features of the patients and patient survival were evaluated. There was no relationships between COX-2 expression and tumor size (tm < 3 cm or tm > or = 3 cm), tumor histopathological differentiation (poorly differentiated or moderately + well differentiated), number of metastatic lymph nodes (< 4 or 3 > or = 4), histopathology of the tumor, localization of the tumor (colon or rectum), distant metastasis, and vascular invasion of the tumor. In the multivariate analysis, COX-2 expression was not found as an independent prognostic factor. We demonstrated that COX-2 expression was not correlated with clinicopathological characteristics of colon carcinoma and disease outcome.     

Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11alpha in prostate cancer risk and aggressiveness.

Candidate genes involved with androgen metabolism have been hypothesized to affect the risk of prostate cancer. To further investigate this, we evaluated the relationship between prostate cancer and multiple potentially functional polymorphisms in three genes involved in androgen metabolism: CYP1B1 (two single nucleotide polymorphisms: 355G/T and 4326C/G), prostate-specific antigen (PSA/KLK3 (three single nucleotide polymorphisms: -158A/G, -4643G/A, and -5412C/T), and CYP11alpha [(tttta)(n) repeat], using a moderately large (n = 918) sibling-based case-control population. When looking at all subjects combined, no association was observed between any polymorphism-or their haplotypes-and prostate cancer risk. However, among men with more aggressive prostate cancer, the CYP1B1 355G/T variant was positively associated with disease: carrying one or two T alleles gave odds ratios (OR) of 1.90 [95% confidence interval (95% CI), 1.09-3.31; P = 0.02] and 3.73 (95% CI, 1.39-10.0; P = 0.009), respectively. Similarly, carrying the CYP1B1 355T-4326C haplotype was positively associated with prostate cancer among men with high aggressive disease (P = 0.01). In addition, the PSA -158G/-158G genotype was positively associated with prostate cancer among men with less aggressive disease (OR, 2.71; 95% CI, 1.06-6.94; P = 0.04). Our findings suggest that CYP1B1 and PSA variants may affect the risk of prostate cancer and tumor aggressiveness.     

Isolated Ruptured Inter‐Atrial Septal Cystic Echinococcosis during Pregnancy

Herein, we present a case of asymptomatic isolated cardiac cystic echinococcosis localized entirely to the inter‐atrial septum in a pregnant woman. The patient underwent successful surgery. Cardiac cystic echinococcosis is rarely seen in pregnancy. A high index of suspicion is necessary for the diagnosis of a cardiac cyst hydatid. The treatment of cardiac cyst hydatid is surgical and should not be delayed during pregnancy. Early surgery might prevent septic embolization and cardiac life‐threatening complications and save the lives of both mother and baby as in the present case.     

Infarction of the septomarginal band and tricuspid papillary muscle rupture related to alcohol septal ablation for hypertrophic cardiomyopathy

We presented a 77‐year‐old man with hypertrophic obstructive cardiomyopathy applied with flail tricuspid leaflet and severe tricuspid regurgitation leading to right heart failure 2 months after the failed septal ablation. The ruptured anterior tricuspid papillary muscle resulted from infarction of the base of anterior papillary muscle of the right ventricle (RV) confirmed by magnetic resonance imaging. As the septomarginal band is frequently lit up by intracoronary contrast that particular attention should be paid to the RV papillary muscles. And, if the papillary muscles or the RV free wall is brightened, then the use of that septal artery should be avoided.