10 years survival of patient with lung cancer and cerebral metastasis

The authors describe the case of survival for the period of 10 years after brain metastasis surgery and removal of the left lung upper lobe due to adeno-squamous cells carcinoma. Surgery did not generate any complications. Within 8 years after the surgery the radiological examination showed infiltrations resembling changes typical for tuberculosis. Microbiological analysis showed a culture of Mycobacterium kansasi leading to diagnosis of mycobacteriosis. Hence the antituberculous treatment was extended to 12 months to be interrupted due to liver damage. Two years later the patient experienced incident of haemoptysis. Detailed examination and assessment of the respiratory tract condition revealed COPD without features of renewal of the neoplastic process or infection by Mycobacterium tuberculosis or mycobacterium other than tuberculosis. This case demonstrates that aggressive surgical approaches to lung cancer with solitary cerebral metastasis significantly improve patient survival and justifies its widespread use.     

Isolates of the Enterobacter cloacae complex induce apoptosis of human intestinal epithelial cells

Strains of the Enterobacter cloacae complex are becoming increasingly important human pathogen. The aim of the study was to identify, by sequencing the hsp60 gene, the species of clinical isolates phenotypically identified as E. cloacae and to examine them for virulence-associated properties: the ability of adhesion, invasion to HEp-2 cells and the induced apoptosis of infected epithelial cells. The majority of the strains were identified as Enterobacter hormaechei with E. hormaechei subsp. steigerwaltii being the most frequent subspecies. Other strains belonged to E. hormaechei subsp. oharae, E. cloacae cluster III, and E. cloacae cluster IV. The strains were examined for virulence-associated properties: the ability to adhesion and invasion to HEp-2 cells and the apoptosis induction of infected epithelial cells. All strains revealed adherence ability and most of them (71%) were invasive to epithelial cells. Analyses of cellular morphology and DNA fragmentation in the HEp-2 cells exhibited typical features of cells undergoing apoptosis. We observed morphological changes, including condensation of nuclear chromatin, formation of apoptotic bodies and blebbing of cell membrane. The lowest apoptotic index did not exceed 6%, whereas the highest reached 49% at 24 h and 98% at 48 h after infection. Forty strains (73%) induced fragmentation of nuclear DNA and characteristic intranucleosomal pattern with the size of about 180–200 bp in DNA extracted from infected cells at 48 h after infection. The results indicated that the bacteria of the E. cloacae complex may adhere to and penetrate into epithelial cells and induce apoptosis, which could be an important mechanism contributing to the development diseases.     

Microarray-based survey of CpG islands identifies concurrent hyper- and hypomethylation patterns in tissues derived from patients with breast cancer

Maintenance of CpG island methylation in the genome is crucial for cellular homeostasis and this balance is disrupted in cancer. Our rationale was to compare the methylation of CpG islands in tissues (tumor, healthy breast and blood) from patients with breast cancer. We studied 72 genes in 103 samples using microarray hybridization and bisulfite sequencing. We observed tumor specific hyper- or hypomethylation of five genes; COL9A1, MT1A, MT1J, HOXA5 and FLJ45983. A general drop of methylation in COL9A1 was apparent in tumors, when compared with blood and healthy breast tissue. Furthermore, one tumor displayed a complete loss of methylation of all five genes, suggesting overall impairment of methylation. The downstream, evolutionary conserved island of HOXA5 showed hypomethylation in 18 tumors and complete methylation in others. This CpG island also displayed a semimethylated state in the majority of normal breast samples, when compared to complete methylation in blood. Distinct methylation patterns were further seen in MT1J and MT1A, belonging to the metallothionein gene family. The CpG islands of these genes are spaced by 2 kb, which shows selective methylation of two structurally and functionally related genes. The promoters of FLJ45983 and MT1A were methylated above 25% in 18 primary and metastatic tumors. Concurrently, there was also >10% methylation of healthy breast tissue in 11 and 5 samples, respectively. This suggests that the methylation process for the latter two genes takes place already in normal breast cells. Our results also point to a considerable heterogeneity of epigenetic disturbance in breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat.     

Overexpression of heme oxygenase-1 in murine melanoma: increased proliferation and viability of tumor cells, decreased survival of mice

Heme oxygenase-1 (HO-1), a cytoprotective enzyme, can be induced in tumors in response to anti-cancer therapies. We investigated the role of HO-1 in B16(F10), S91, and Sk-mel188 melanoma cells. Overexpression of HO-1 after transduction with adenoviral vectors increased cell proliferation, resistance to oxidative stress generated by H2O2, and angiogenic potential as determined by induction of endothelial cell divisions. Likewise, cells stably transfected with HO-1 cDNA (B16-HO-1) showed higher proliferation, stress resistance, and angiogenic activity than the wild-type line (B16-WT). HO-1 overexpression in tumors significantly shortened survival of mice after subcutaneous injection of cancer cells (38 and 22 days for B16-WT and B16-HO-1, respectively; P=0.017). This also resulted in development of more packed tumors, with more melanoma cells, and reduced inflammatory edemas. Mice injected with B16-HO-1 had lower levels of tumor necrosis factor and higher serum concentrations of its soluble receptor tumor necrosis factor-RI, whereas tumors overexpressing HO-1 displayed augmented vascularization and stronger production of vascular endothelial growth factor. Finally, B16-HO-1 cells injected intravenously formed more metastases in lungs. Thus, HO-1 overexpression increased viability, proliferation, and angiogenic potential of melanoma cells, augmented metastasis, and decreased survival of tumor-bearing mice, suggesting that induction of HO-1 may be detrimental in anti-cancer therapy of melanoma.     

Prognostic value of 5-microRNA based signature in T2-T3N0 colon cancer

The role of adjuvant chemotherapy in stage T2-T3N0 colon cancer (CC) is controversial and there are currently no reliable factors allowing for individual selection of patients with high risk of relapse for such therapy. We searched for microRNA-based signature with prognostic significance in this group. We assessed by qRT-PCR expression of 754 microRNAs (miRNAs) in tumour samples from 85 stage pT2-3N0 CC patients treated with surgery alone. MiRNA expression was compared between two groups of patients: 40 and 45 patients who did and did not develop distant metastases after resection, respectively. Additionally, miRNA expression was compared between CC and normal colon mucosa samples and between the mismatch repair (MMR) competent and deficient tumours. Low expression of miR-1300 and miR-939 was significantly correlated with shorter distant metastasis-free survival (DMFS) in Cox univariate analysis (p.adjusted = 0.049). The expression signature of five miRNAs (miR-1296, miR-135b, miR-539, miR-572 and miR-185) was found to be prognostic [p = 1.28E?07, HR 8.4 (95 % CI: 3.81–18.52)] for DMFS and cross-validated in a leave-one-out analysis, with the sensitivity and specificity of 74 and 78 %, respectively. The expression of miR-592 was significantly associated with the MMR status (p.adjusted <0.01). The expression of several novel miRNAs were found to be tumour specific, e.g. miR-888, miR-523, miR-18b, miR-302a, miR-423-5p, miR-582-3p (p < 0.05). We developed a miRNA expression signature that may be predictive for the risk of distant relapse in early stage CC and confirmed previously reported association between miR-592 expression and MMR status.     

Nitric oxide as a prognostic marker for neurological diseases

The potential value of the nitric oxide (NO) level as a prognostic marker in human brain diseases is investigated. Cerebrospinal fluid (CSF) collected from neurological patients was examined for NO content using electron paramagnetic resonance (EPR) spectroscopy. In adult patients with meningitis, the level of NO was higher than that in other groups of brain disorders, such as brain traumas and brain tumors. Very high levels of NO in the CSF appeared to be correlated with a high incidence of fatal outcomes. In children with meningitis, it was possible to differentiate between viral and bacterial origin of the disease as evidenced by the EPR analysis of the CSF. The results indicated that NO levels in the CSF can be a useful prognostic marker in neurological diseases.     

A comparative analysis of estimation of age at menarche by various methods in women participating in the Krakow Longitudinal Growth Study, Poland.

The purpose of this study was to see whether menarcheal age assessment by means of the most frequently used methods that were conducted every time on the same group of girls would yield the same results. One hundred and one Polish girls, whose ages at menarche were recorded in a longitudinal study between 1976 and 1990, were asked to recall the age of menarche in 2004. The mean menarcheal ages of those women were calculated by means of the probit (PA), prospective (AA), retrospective method without age correction (RA), and retrospective method with the recall age corrected by 0.5 year (RcA). The PA, AA, and retrospective methods: RA and RcA revealed results: 13.14 +/- 1.1; 13.10 +/- 1.1; 13.12 +/- 1.36, and 14.39 +/- 1.34 years, respectively. The menarcheal AA was insignificantly different from the PA (95% CI) and RA. The RcA was significantly higher than the AA and RA (P = 0.05). The correlation coefficient (r) between AA and RA was 0.70. Only 16% of the interviewed women accurately remembered the date of their menarche, 63% of them missed their menarche time by about 1 year, whereas 22% were wrong by 2 and more years. (1) The PA and the AA method yield comparable results when estimating menarcheal age. (2) The menarcheal age determined by the retrospective methods is not very reliable and the application of age correction overestimates the results.     

Experimental studies of deleterious mutation in Saccharomyces cerevisiae

Yeast has proven to be a very useful model organism for studying eukaryotic cell functions. Its applicability for population and quantitative genetics is less well known. Among its advantages is the ease of screening for mutants. The present paper reviews experiments aimed at estimating the parameters of spontaneous mutations deleterious to fitness. The rate of deleterious mutation was found to be moderately high. A large fraction of detectable mutants were lethal; among the non-lethal mutants, the least harmful ones dominated. Deleterious mutations, and especially the lethal ones, were generally very well masked by wild-type alleles when in heterozygous loci. The negative effects of mutations were much stronger under stressful than under benign conditions. Interactions between loci with deleterious mutations did alter their fitness, but no strong overall effect of synergism or antagonisms was observed.     

Plasma asymmetric dimethylarginine predicts restenosis after coronary angioplasty

Introduction

Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase. Asymmetric dimethylarginine may influence the process of restenosis after coronary angioplasty. The aim of the study was to determine if initial plasma ADMA level could predict restenosis after coronary angioplasty and stenting.

Material and methods

The study group consisted of 60 consecutive patients (10 women and 50 men, average age 58.9 ±10.4 years old), who underwent percutaneous coronary angioplasty with bare metal stenting for stable coronary artery disease. All patients underwent follow-up coronary angiography after a 6-month period. Patients were divided into two groups, one with restenosis (n = 22), and the other one without restenosis (n = 38). In addition to measuring acknowledged restenosis risk factors, plasma ADMA level was measured before initial angiography.

Results

Asymmetric dimethylarginine plasma level was significantly higher in the group with restenosis than in the group without restenosis (1.94 ±0.94 µmol/l vs. 0.96 ±0.67 µmol/l; p < 0.05). L-arginine/ADMA ratio was also decreased in the group with restenosis, when compared with the group without restenosis (p < 0.05). Multivariate logistic regression revealed that independent restenosis risk factors were characterised by an initially high ADMA level (p < 0.01), advanced age (p < 0.05) and low level of HDL cholesterol (p < 0.05).

Conclusions

Pre-procedural elevated plasma ADMA level increases the risk of restenosis in patients who underwent coronary angioplasty and stenting with bare metal stents.     

Infective endocarditis complicated with left atrioventricular fistula in a 20-year-old patient. A case study

Intracardiac fistulas are rare complications of infective endocarditis. We report an unusual case of successful surgical repair of intracardiac fistula between the left ventricle and the left atrium in the course of infective endocarditis in a 20-year-old patient. According to this we conclude that timely diagnosis, proper antibiotic treatment, and early surgical intervention should improve the outcomes of infective endocarditis complications.