DNA repair capacity of the colorectal cancer patients and the correlation between the pathological parameters.

BACKGROUND: Colorectal cancers are third most common cancer in both genders. They are associated with genetic and environmental factors. Staging is important in the prognosis. Carcinoembryonic Antigen (CEA) provides preliminary information and there is a correlation between Proliferation Index (PI) and prognostic variables. Our aim is to investigate the relationship between DNA repair capacity and clinico-pathologic factors. PATIENTS AND METHODS: The blood samples taken from cancer patients were irradiated. DNA repair capacity by comet technique was calculated. The CEA values were recorded. Pathology reports were collected and PI values were calculated. s. RESULTS: Total of 30 patients; male (n: 14) and female (n: 16) with a median age of 66.37 ± 10.32 were included. Mean CEA value was 42.85 (1.46 - 422.30 µgr/ml) µgr/ml. Mean % DNA repair capacity was 44.49 ± 5.24. In the pathology; 21 (70%) were T3 tumors; 18 (60%) had lymphatic and 12 (40%) had vascular 2 invasion. Perineural invasion was present in 8 (26.7%). According to the proliferation index (PI); 16 (53.3%) were in high percentile (PI > 66%) group. CONCLUSIONS: There was a significant correlation between; perineural invasion and tumor grade (P = 0.043); lymphatic and perineural invasion (P = 0.006); lymphatic invasion and vascular invasion (P = 0.034) and the DNA repair capacity with the lymphatic invasion (P = 0.026). There was also a statistically significant (P = 0.044) relationship between PI and lymphatic invasion. As a result in colorectal cancer patients DNA repair capacity can be used as a biomarker in the staging and also in the prediction of the tumor behavior.

ERCC1 is not expressed in hepatocellular cancer: A turkish oncology group, gastrointestinal oncology subgroup study.

PURPOSE: hepatocellular cancer (HCC) is a common malignancy with a high mortality rate. Existence of excisional repair cross complementation1 (ERCC1) is implicated in resistance to cisplatin treatment. Expression of ERCC1 in HCC is not known. In this study we aimed to find out whether a subset of HCC patients can be identified to benefit from cisplatin. METHODS: sixty-one patients with HCC who had enough tissue to do immunohistochemistry were identified in 3 institutions. Immunohistochemical staining was performed manually using the standard streptavidin-biotin-peroxidase method. Monoclonal anti-ERCC 1 (D-10) antibody from Santa Cruz Biotechnology (Santa Cruz, CA) was used. RESULTS: only one out of 61 patients (1.6%) had ERCC1 expression. CONCLUSION: although around 10% of HCC patients respond to cisplatin, this is unlikely to be due to ERCC1 negativity. Pathways other than ERCC1 should be searched to find ways to help these patients' treatment strategies.

A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp) inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis in rats.

The intestinal microflora is an important cofactor in the pathogenesis of intestinal inflammation; and the epithelial cell barrier function is critical in providing protection against the stimulation of mucosal immune system by the microflora. In the present study, therapeutic role of the antibacterial drugs rifampicin and ciprofloxacine were investigated in comparison to spironolactone, an enzyme inducer, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis of the rats. Drugs were administered for 14 days following induction of colitis. All drug treatments ameliorated the clinical hallmarks of colitis as determined by body weight loss and assessment of diarrhea, colon length, and histology. Oxidative damage and neutrophil infiltration as well as nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α) expressions that were increased during colitis, were decreased significantly. Rifampicin and ciprofloxacin were probably effective due to their antibacterial and immunomodulating properties. The multidrug resistence gene (MDR1) and its product p-glycoprotein (P-gp) has been implicated in the pathogenesis of inflammatory bowel disease (IBD). In the present study, findings of the P-gp expression were inconclusive but regarding previous studies, it can be suggested that the beneficial effects of rifampicin and spironolactone may be partly due to their action as a P-gp ligand. Spironolactone has been reported to supress the transcription of proinflamatory cytokines that are considered to be of importance in immunoinflammatory diseases. It is also a powerful pregnane X receptor (PXR) inducer; thus, inhibition of the expression of NF-κB and TNF-α, and amelioration of inflammation by spironolactone suggest that this may have been through the activation of PXR. However, our findings regarding PXR expression were inconclusive. Activation of PXR by spironolactone probably also contributed to the induction of P-gp, resulting in extrusion of noxious substances from the tissue.

Effect of inhaled cyclosporin on the rat airway: histologic and bronchoalveolar lavage assessment.

Airway inflammation plays a pivotal role in asthma. Over the last 10 years, evidence has accumulated for the potential role of lymphocytes in airway inflammation. Since cyclosporin A (Cyc-A) can profoundly influence lymphocyte activation, it is appropriate to consider this drug as a novel antiasthmatic. The effect of inhalation of low doses of Cyc-A on airway inflammation remains unclear. The purpose of this study was to investigate the bronchoalveolar lavage (BAL), peripheral blood cell profiles, and lung biopsy specimens in Cyc-A-pretreated rats. Twenty-nine rats (8 controls, 10 ovalbumin sensitized, and 11 Cyc-A inhaling and ovalbumin sensitized) were included in the study. A commercial intravenous Cyc-A solution was given as a single dose of 20 mg/kg 1 h prior to inhalation of ovalbumin via nebulizer. The total number of BAL cells significantly increased in rats inhaling Cyc-A when compared with ovalbumin-sensitized rats (2.37 +/- 2.34 x 10(6)/ml and 1.01 +/- 0.49 x 10(6)/ml respectively, p < 0.05). There was a significant increase in the percentage of lymphocytes (14.5 +/- 8.5 versus 27.4 +/- 7.4%, p < 0.03), a nonsignificant increase in the percentage of eosinophils (0.8 +/- 1.0 versus 3.0 +/- 4.6%), and a significant decrease in the percentage of polymorphonuclear leukocytes (9.4 +/- 6.9 versus 3.4 +/- 3.8%, p < 0.01) and macrophages (75.4 +/- 5.1 versus 50.2 +/- 11.8%, p < 0.02) in BAL in the ovalbumin-sensitized group as compared with controls. Differential cell counts revealed a higher percentage of neutrophils and macrophages in the BAL of Cyc-A-pretreated rats than in that of the ovalbumin-sensitized group (26.3 +/- 26.8 versus 3.4 +/- 3.8%, p < 0.01 and 66.1 +/- 7.7 versus 50.2 +/- 11.8%, p < 0.02). There was a nonsignificant decrease of lymphocytes and eosinophils in the Cyc-A-pretreated group when compared with the ovalbumin-sensitized group (27.4 +/- 7.4 versus 21.1 +/- 12.4 and 3.0 +/- 4.6% versus 2.4 +/- 2.6%). The peripheral blood total white blood cell count decreased in the ovalbumin-sensitized and Cyc-A-pretreated groups as compared with the control group (2,520 +/- 1,098/mm3, 3,591 +/- 2,251/mm3, and 5,975 +/- 2,787/mm3, respectively, p < 0.01). In addition, peripheral eosinophilia was detected in the Cyc-A-pretreated group when compared with controls and the ovalbumin-sensitized group (6.9 +/- 4.7, 2.4 +/- 1.1, and 2.6 +/- 2.4%, respectively, p < 0.01). Light-microscopic examination of the airways revealed prominent eosinophilia in tracheal, bronchial, and bronchiolar sections in the ovalbumin-sensitized group: counts were 1.8 +/- 2.3/HPF, 10.3 +/- 11.4/HPF, 63.3 +/- 45.0/HPF, respectively. Cyc-A resulted in a decrease of the eosinophil counts/HPF to 0/HPF in trachea (p < 0.05), to 4.3 +/- 9.4/HPF in bronchi (p < 0.02), to 19.4 +/- 38.4 in bronchioles (p < 0.004). In conclusion, the present study supports the theory that locally administered inhaled low-dose Cyc-A is effective on inflammatory cells of sensitized airways and peripheral cells. It may therefore be useful in elucidating the inflammatory mechanisms involved in asthma.

Flow cytometric DNA studies and AgNOR counts in patients with transitional cell carcinoma of the bladder.

Flow cytometry appears to be a promising diagnostic method which may influence the therapeutic approach to transitional cell carcinoma (TCC) of the bladder. The number of silver-stained nuclear organizer regions (AgNORs) seems to correlate with the growth fractions of the cells. In this study, we report the results of combined flow cytometric analysis and AgNOR in 37 patients with TCC of the bladder. A positive correlation was observed in the histological grade, stage and growth pattern in relation to the ploidy of tumors. There were statistically significant differences among the mean AgNOR counts of the different groups as defined by DNA content, histological grade, growth pattern and disease outcome. In different stage groups, the AgNOR counts were related both to recurrence and progression. It was concluded that AgNOR counts performed on routine formalin-fixed paraffin sections furnish significant kinetic information. According to our preliminary results AgNOR counts and the DNA content of the tumors should also be measured to decide on more aggressive treatment in some cases.

Stage IV Hodgkin's disease presenting with spinal epidural involvement and cauda equina compression as the initial manifestation: case report.

Hodgkin's disease very rarely presents clinically, initially with a paraspinal mass, but this should be considered in the differential diagnosis. A patient presenting with back pain was diagnosed to have Stage IV Hodgkin's disease. MRI revealed an extradural and intraspinal soft tissue mass with bone infiltration. The importance of MRI in the early evaluation of a paraspinal mass and in determining the extent of the disease is emphasized.