The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer.

BACKGROUND: Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survival percentages in various cancer patients. We also investigated the changes of DNA-PK activity in PBLs after radiotherapy. METHODS: A total of 167 of untreated cancer patients participated in this study. Peripheral blood was collected, separated, and centrifuged. DNA-PK activity was measured by DNA-pull-down assay. Chromosomal aberrations were examined by cytogenetic methods. RESULTS: DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage. The patients with lower DNA-PK activity in PBLs tended to have the lower disease-specific survivals and distant metastasis-free survivals than those with higher DNA-PK activity in advanced stages. There was also a tendency of inverse correlation between DNA-PK activity and excess fragments. The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased. CONCLUSION: Cancer patients in advanced stage, with lower DNA-PK activity of PBLs might have higher distant metastasis and exhibit poorer prognosis. Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis.

Long-term efficacy of catheter ablation for atrial fibrillation: impact of additional targeting of fractionated electrograms.

OBJECTIVES: To investigate long-term efficacy of catheter ablation for atrial fibrillation (AF) and the impact of ablating complex or fractionated electrograms (CFEs) in addition to pulmonary vein isolation and linear lesions in persistent AF (PeAF). METHODS: Consecutive cases from 2002-2007 were analysed. All the patients underwent a wide-area circumferential ablation with confirmation of electrical isolation. For PeAF, linear lesions were added, with additional targeting of CFE from 2005. Data were collected in a prospective database. Attempts were made to contact all patients for follow-up. RESULTS: 285 patients underwent 530 procedures. The mean (SD) age was 57 (11) years, 75% were male, 20% had structural heart disease and 53% had paroxysmal AF (PAF). The mean number of procedures was 1.9 per patient (1.7 for PAF and 2.0 for PeAF). Procedural complications included stroke or transient ischemic attack in 0.6% and pericardial effusion requiring drainage in 1.7%. During 2.7 years (0.2 to 7.4 years) of follow-up from the last procedure, there were seven deaths (unrelated to their ablation or AF) and three strokes or transient ischemic attack (0.3% per year). Freedom from AF/atrial tachyarrhythmia was 86% for PAF and 68% for PeAF. Late recurrence was 3 per 100 years of follow-up after >3 years. The Kaplan-Meier analysis showed that CFE ablation improved the outcome for PeAF after the first cluster of procedures (p=0.049), with a trend towards improved final outcome (p=0.130). CONCLUSIONS: Long-term freedom from AF is achievable in most patients with PAF and PeAF with low rates of late recurrence. Additional targeting of CFE improves outcome for PeAF. Late adverse events including stroke are few.

Elevated prolidase activity in keloids: correlation with type I collagen turnover.

BACKGROUND: Keloid pathogenesis involves an altered balance of extracellular matrix metabolism, mainly accumulation of type I collagen. This could be due to excessive synthesis or decreased degradation of matrix, or a combination of both processes. Prolidase, an imidodipeptide-cleaving cytosolic enzyme, plays an important role in the collagen catabolic process by recycling proline for collagen synthesis. Collagen accumulation in keloids is due to an imbalance in the steady state of collagen turnover. OBJECTIVES: To investigate prolidase activity and its role in the steady state of collagen turnover between normal skin and keloid tissue and their derived fibroblasts. METHODS: Ten sets of keloid and normal skin tissues and their derived fibroblasts were employed. Measurements were made of tissue prolidase activity, free proline level, and concentrations of the collagen synthesis product aminoterminal propeptide of type I procollagen (PINP) and the collagen degradative product carboxyterminal telopeptide of type I collagen (ICTP). Also, synthesis of collagens type I and III and matrix metalloproteinases 1 and 2 was investigated using Western blot analysis. RESULTS: Keloid tissues had a significant increase in prolidase activity, up to fourfold that in normal skin. The elevated prolidase activity was accompanied by an increase in tissue PINP and ICTP concentrations in keloid; in addition, the collagen turnover index (PINP/ICTP) was higher in keloids. CONCLUSIONS: The combination of elevated prolidase activity and associated higher collagen synthesis to degradation ratio in keloids suggests a possible metabolic process for the excessive accumulation of type I collagen in keloids.