The incidence and survival of acute de novo leukemias in Estonia and in a well-defined region of western Sweden during 1997–2001: A survey of patients aged ≥65 years

Background: In a recently published retrospective population-based study over three 5-year periods (1982–1996) we investigated the outcome for de novo acute leukemia (AL) patients aged ≥65 years at diagnosis in Estonia (a country that had been occupied by the Soviet Union over 5 decades) and in the so-called Western Swedish Health Care Region. The age-standardized yearly incidence rates regarding the total number of de novo AL was 5.3/100 000 inhabitant for Estonia and 8.0 for Sweden, this difference being statistically significant merely as regards acute myeloid leukemia (AML). The relative survival for the total cohort of de novo AL as well as for de novo AML was significantly longer (p < 0.001) for Swedish as compared to Estonian patients. Methods: In view of the miserable outcome for the Estonian patients we decided to prospectively compare the results for incidence and outcome of de novo AL between the two countries. Results: The present report covers the first 5-year period comprising 1997–2001 and deals only with patients aged ≥65 years at diagnosis. The age-adjusted annual incidence rates for de novo AML were lower in Estonia (6.4/100 000) than in Sweden (9.2/100 000) but not significantly so. The present results also show that the outcome for the Estonian AML patients had improved considerably over the study period; thus, at no time point, i.e., at 1, 3 and 5 years did relative survival between the two countries differ significantly. Conclusion: Yet, as compared to the Swedish cohort relative survival for the Estonian patients did still not reach an acceptable level.     

Anti-Helicobacter pylori activity of the methanolic extract of Geum iranicum and its main compounds

Geum iranicum Khatamsaz, belonging to the Rosaceae family, is an endemic plant of Iran. The methanol extract of the roots of this plant showed significant activity against one of the clinical isolates of Helicobacter pylori which was resistant to metronidazole. The aim of this study was the isolation and evaluation of the major compounds of G. iranicum effective against H. pylori. The compounds were isolated using various chromatographic methods and identified by spectroscopic data (1H and 13C NMR, HMQC, HMBC, EI-MS). An antimicrobial susceptibility test was performed employing the disk diffusion method against clinical isolates of H. pylori and a micro dilution method against several Gram-positive and Gram-negative bacteria; additionally the inhibition zone diameters (IZD) and minimum inhibitory concentrations (MIC) values were recorded. Nine compounds were isolated: two triterpenoids, uvaol and niga-ichigoside F1, three sterols, beta-sitosterol, beta-sitosteryl acetate, and beta-sitosteryl linoleate, one phenyl propanoid, eugenol, one phenolic glycoside, gein, one flavanol, (+)-catechin, and sucrose. The aqueous fraction, obtained by partitioning the MeOH extract with water and chloroform, was the most effective fraction of the extract against all clinical isolates of H. pylori. Further investigation of the isolated compounds showed that eugenol was effective against H. pylori but gein, diglycosidic eugenol, did not exhibit any activity against H. pylori. The subfraction D4 was the effective fraction which contained tannins. It appeared that tannins were probably the active compounds responsible for the anti-H. pylori activity of G. iranicum. The aqueous fraction showed a moderate inhibitory activity against both Gram-positive and Gram-negative bacteria. The MIC values indicated that Gram-positive bacteria including Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus subtilis are more susceptible than Gram-neagative bacteria including Escherichia coli and Pseudomonas aeruginosa.     

Association of cyclin-dependent kinase inhibitor 2A/B with increased risk of developing breast cancer

There is a growing body of data reporting the association of genetic alterations in chromosome 9P21 with the risk of developing cancer. In the current study, we studied the association of a genetic variant in CDKN2A/B, rs1333049, with the risk of developing breast cancer. A total of 339 participants with and without breast cancer entered to the study. Genotyping was done by the TaqMan real-time polymerase chain reaction (RT-PCR) method and gene expression analysis was ran by RT-PCR. Our data showed that the minor allele homozygote in the total population was 10%, whereas for heterozygote was 38%. The dominant genetic model demonstrated that individuals with breast cancer had advanced TNM classification. Moreover, the logistic regression revealed that individuals who had CC/CG genotypes might have an enhanced risk of developing breast cancer when compared to the holders of GG genotype (e.g., OR = 2.8; 95% CI,1.4–5.4; p = .001), after regulated for confounders; age and body mass index. Furthermore, our analysis showed that the CDKN2A/B gene was downregulated in patients (p < .001). We showed a meaningful relationship of CDKN2A/B with the risk of breast cancer, cancer, showing the importance of studies in great sample size and several centers for studying the value of the marker as a risk classification in the management of patients with breast cancer.     

Therapeutic potential of targeting the Wnt/β-catenin pathway in the treatment of pancreatic cancer

The Wnt/β-catenin pathway is an important, dysregulated pathway in several tumor types, including pancreatic ductal adenocarcinoma. Although the activation of this pathway is an important component of normal development, its aberrant activation resulting from activating or inactivating mutations in the CTNNB1 gene locus, or in the negative regulators AXIN and APC involving stabilization of β-catenin, and activation of target genes leads to a more aggressive phenotype, suggesting its potential value as a therapeutic target in the treatment of pancreatic ductal adenocarcinoma. A number of small molecule and biologic agents have now been developed for targeting this pathway. This review summarizes the current knowledge about the therapeutic potential of targeting the Wnt pathway with particular emphasis on preclinical/clinical studies in the treatment of pancreatic ductal adenocarcinoma.