Histomorphological changes in murine fibrosarcoma after hypericin-based photodynamic therapy.

Histomorphological changes in murine fibrosarcoma after photodynamic therapy (PDT) based on the natural photosensitizer hypericin were evaluated. C3H/DiSn mice were inoculated with fibrosarcoma G5:1:13 cells. When the tumour reached a volume of 40-80 mm(3) the mice were intraperitoneally injected with hypericin, either in a single dose (5 mg/kg; 1 or 6 h before laser irradiation) or two fractionated doses (2.5 mg/kg; 6 and 1 h before irradiation with laser light; 532 nm, 70 mW/cm(2), 168 J/cm(2)). All groups of PDT-treated animals with single and fractionated hypericin dosing presented primary vascular reactions including vascular dilatation, congestion, thrombosis and oedema. Two hours after PDT there were necrotic changes with small, rather focal appearance. One day after therapy the necrotic areas were enhanced, often affecting a complete superficial layer of tumour tissue. Necrotic areas were accompanied with inflammation and haemorrhages.

Nutritional depletion in relation to mortality in patients with chronic respiratory insufficiency treated with long-term oxygen therapy.

OBJECTIVE: An association between malnutrition, weight loss and mortality has been demonstrated in patients with chronic obstructive pulmonary disease (COPD), but the prognostic influence of low body-mass index (BMI) and plasma concentrations of albumin and cholesterol is less clear in patients with chronic respiratory insufficiency treated with domiciliary long-term oxygen therapy (LTOT). We therefore analysed the prognostic value of BMI, plasma albumin and cholesterol concentrations in patients receiving LTOT. PATIENTS AND METHODS: From 1996 to 2001, LTOT was initiated in 255 patients. Analysis of the impact of nutritional status on survival was confined to a study group of 108 patients in whom the main outcomes, i.e. BMI, plasma cholesterol and albumin, were measured. Standard laboratory methods were used in the biochemical analyses. Pulmonary function was assessed with bodyplethysmography. RESULTS: 63 patients (58.3%) survived for two years post-initiation of LTOT and 45 patients (41.7%) did not. There were no differences between these two groups in pulmonary function tests and arterial blood gases at the start of LTOT. Overall, 10.2% of the study population were underweight, defined as BMI <20 kg/m2. Compared with patients who survived two years of LTOT, those who did not survive were older (69.3+/-0.9 versus 64.7+/-1.2 years, p<0.01), had significantly lower BMI (24.5+/-0.7 versus 26.5+/-0.7 kg/m2, p < 0.05), lower plasma cholesterol (4.61+/-0.19 versus 5.22+/-0.13 mmol/l, p<0.01) and lower plasma albumin concentrations (41.4+/-0.4 versus 42.8+/-0.4 g/l, p <0.05). Logistic regression analysis revealed that, in addition to age (p < 0.01), both BMI (p < 0.05) and cholesterol (p < 0.05) significantly affected the 2-year survival. CONCLUSION: This study suggests that nutritional status is closely linked with prognosis in patients with chronic respiratory insufficiency treated with domiciliary LTOT: low BMI, low plasma cholesterol and low albumin are related to worse 2-year survival in such patients.

Glutathione S-transferase M1 gene polymorphism is related to COPD in patients with non-small-cell lung cancer.

OBJECTIVE: Oxidative stress contributes to the development of both lung cancer and chronic obstructive pulmonary disease (COPD). Antioxidative enzymes may protect against such damage. We hypothesized that genetic variations in glutathione S-transferase M1 and/or T1 genes (GSTM1 and GSTT1, respectively) may influence susceptibility to COPD in patients with non-small-cell lung cancer. PATIENTS AND METHODS: The polymorphisms in GSTM1 and GSTT1 genes were examined in 110 patients (age: 63+/-1 years) with newly diagnosed non-small-cell lung cancer using the polymerase chain reaction. Respiratory function was assessed by bodyplethysmography. RESULTS: In the GSTM1 null (-/-) genotype, both FEV1 and FEV1/FVC were significantly lower than in the GSTM1 plus genotype (GSTM1 -/+ or +/+) (75.8+/-2.5 versus 86.6+/-3.6%, p<0.02; 69.1+/-1.6 versus 77.0+/-2.4, p<0.01, respectively). Among the patients with GSTM1 null genotype, 49% suffered from COPD as opposed to 21% of patients with GSTM1 plus genotype. In contrast, no differences were seen in FEV1 or FEV1/FVC when comparing patients with GSTT1 null genotype and GSTT1 plus genotype (81.4+/-4.9 versus 79.3+/-2.3, p=NS; 71.1+/-2.9 versus 72.2+/-1.6, p=NS). Multiple stepwise regression analysis identified the GSTM1 genotype (p<0.02) as a significant independent predictor of FEV1 in this group of patients. CONCLUSION: The present study suggests that in patients with non-small-cell lung cancer the presence of at least one active allele in GSTM1 has a protective effect against the development of COPD.

A link between the p53 germ line polymorphisms and white blood cells apoptosis in lung cancer patients.

The p53 protein acts as a checkpoint in the cell cycle, either preventing or initiating apoptosis. Since cancer is the unchecked proliferation of cells, p53s role is critical. Thus, we have sought a link between the p53 polymorphisms and apoptosis. Wild-type p53 tumor suppressor gene exhibits several common single nucleotide polymorphisms (SNP) both in coding and non-coding regions. We focused on two of them, the p53 BstUI SNP on the fourth exon, and the p53 MspI SNP on the sixth intron. We investigated a presence of these two polymorphisms in relation to apoptosis of white blood cells in lung cancer patients and healthy controls. We found that both the p53 BstUI and the p53 MspI homozygous genotypes A2/A2 were associated with significantly higher content of apoptotic white blood cells in comparison to relevant A2/A1 heterozygous genotypes (P<0.001,0.05) in lung cancer patients. These observations suggest that the p53 BstUI and the p53 MspI SNPs may play a certain role in p53 dependent apoptotic pathway.