DNA polymerase θ up-regulation is associated with poor survival in breast cancer,perturbs DNA replication,and promotes genetic instability

“Replicative stress” is one of the main factors underlying neoplasia from its early stages. Genes involved in DNA synthesis may therefore represent an underexplored source of potential prognostic markers for cancer. To this aim, we generated gene expression profiles from two independent cohorts (France, n = 206; United Kingdom, n = 117) of patients with previously untreated primary breast cancers. We report here that among the 13 human nuclear DNA polymerase genes, DNA Polymerase θ (POLQ) is the only one significantly up-regulated in breast cancer compared with normal breast tissues. Importantly, POLQ up-regulation significantly correlates with poor clinical outcome (4.3-fold increased risk of death in patients with high POLQ expression), and this correlation is independent of Cyclin E expression or the number of positive nodes, which are currently considered as markers for poor outcome. POLQ expression provides thus an additional indicator for the survival outcome of patients with high Cyclin E tumor expression or high number of positive lymph nodes. Furthermore, to decipher the molecular consequences of POLQ up-regulation in breast cancer, we generated human MRC5-SV cell lines that stably overexpress POLQ. Strong POLQ expression was directly associated with defective DNA replication fork progression and chromosomal damage. Therefore, POLQ overexpression may be a promising genetic instability and prognostic marker for breast cancer.     

Changes of acid-producing function of the stomach before and after operation performed for gastric ulcer type I

The gastric acid-producing function changes were analyzed in 48 patients suffering gastric ulcer (Johnson-I type), using the computer pH-metry. The dependence of the gastric glands acid-production on the ulcer defect localization was established. Hyperchlorhydria was revealed in 84.6% of patients suffering gastric distal third ulcer and in its subcardial localization--in 30.8%. In the late follow-up period after the operation, performed for gastric ulcer disease, the gastric stump capacity to restore its glands production of acid depends mainly on the method of surgical procedure applied. The best indices were revealed after application of organpreserving method--the partial resection of gastric ischemized segment according to L. Ya. Kovahlchuk combined with selective proximal vagotomy, comparing with such after application of resectional methods according to Billroth.     

Arzneimitteltherapie im Alter aus der Sicht des klinischen Pharmakologen

Polypragmasy (polypharmacotherapy) is often due to the frequent incidence of multimorbidity among elderly patients. This may evoke unpredictable drug-interactions, which often become a reason for hospitalization. Additional medications might be the consequence. Geriatric patients are often characterized by variant pharmacokinetic parameters. Individualized drug-therapy should take into consideration not only the patients' age, liver and kidney functions but also the individual variability of hepatic metabolization and drug-resorption in the intestine based on genetic polymorphisms. Summing up, it is very important to verify a consisting or a new drug-therapy concerning its risk-benefit ratio and if it is needed, to omit or change some of the medications.     

Flavonoids from Dalbergia louvelii and their antiplasmodial activity

Four new flavonoids (1-4), along with 13 known compounds, were isolated from the heartwood of Dalbergia louvelii by following their potential to inhibit in vitro the growth of Plasmodium falciparum. Of the isolated compounds, four known compounds showed antiplasmodial activity with IC(50) values ranging from 5.8 to 8.7 microM, namely, (R)-4' '-methoxydalbergione (5), obtusafuran (6), 7,4'-dihydroxy-3'-methoxyisoflavone (7), and isoliquiritigenin (8). The structures of the new compounds were determined using spectroscopic techniques as 1-(3-hydroxyphenyl)-3-(4-hydroxy-2,5-dimethoxyphenyl)propane (1), spirolouveline (2), (3R)-7,2'-dihydroxy-4',5'-dimethoxyisoflavanone (3), and 3-(2,4-dihydroxy-5-methoxy)phenyl-7-hydroxycoumarin (4), respectively.