TP53 rs1042522 polymorphism and early-onset breast cancer.

BACKGROUND: Breast cancer is the leading cause of cancer deaths among women. Early-onset breast cancer is well recognized as it clinically differs from old-age diagnosed breast neoplasms. TP53 rs1042522 polymorphism relates to the risk of breast neoplasms, but this relationship in Turkish early-onset breast cancer patients has not been investigated yet. We aimed to search the relationship between TP53 rs1042522 polymorphism and young Turkish breast cancer patients. MATERIALS AND METHODS: Ninety-six female breast cancer patients who were ≤ 40 years of age and 96 healthy controls were enrolled in our study. Participants were genotyped by the hybridization probe system. RESULTS: We identified that the genotype frequencies of rs1042522 were significantly different between controls and cases (P = 0.027). Participants carrying CG genotype had also reduced breast cancer risk (odds ratio = 0.4196, 95% confidence interval: 0.1941-0.9067, P = 0.027). Our results revealed that there is an association between GG and CG + CC genotype groups with progesterone receptor (PgR) status (P = 0.0219). CONCLUSION: Our findings indicate that the CG genotype is a protective factor against breast neoplasms. No other clinicopathologic parameters except for PgR status were found to be related to rs1042522 polymorphism in young Turkish breast cancer patients.

Genetic engineering of Theileria parva lactate dehydrogenase gene: a new anti-theilerial target

Theileria parva is the causative agent of East Coast Fever (ECF), a tick borne disease, which results in major economic losses in cattle. Major problems in dealing with this illness are the high cost of drugs, development of resistance, and absence of effective vaccines. Thus, exploiting new targets for cost effective and higher therapeutic value drugs are imperative. Glycolysis is the main pathway for generation of ATP in T. parva, given its development inside erythrocytes. Thus, the enzymes of this pathway may prove potential targets for designing new-generation anti-theilerials. Lactate dehydrogenase of T. parva (TpLDH) has the highest activity of all glycolytic enzymes and thus we selected this enzyme as the potential therapeutic target. Our study is the first to report the isolation, removal of introns through directed mutagenesis, and cloning of TpLDH and showing that amino acid insertions or deletions most notably corresponded to a 5-amino acid sequence (Asn-91A, Glu-91B, Glu-91C, Trp-91D, Asn-91E) between Ser-91 ve Arg-92 of the enzyme. This region is also present in other apicomplexan such as Babesia bovis, a pathogen of cattle and Plasmodium falciparum, a human pathogen. Providing as the attachment site for the enzyme inhibitors and not being present in LDH of respective hosts, we propose this site as an attractive drug target. The work here is expected to lead new studies on detailed structural and kinetic aspects of apicomplexan LDHs and development of new inhibitors.(AU)

Molecular Modeling, Structural Analysis and Evaluation of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase (DXR) as a Putative Drug Target For Theileria Parva

ABSTRACT The apicomplexan parasite Theileria parva, the causative agent of ECF, is an important pathogen affecting both domestic and wild animals, causing major economic losses in the world. Problems such as high cost of drugs, development of resistance, and absence of effective vaccines prevent effective combating of the pathogen. Thus, it is necessary to explore new targets for affordable and higher therapeutic value drugs. 1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) in the non-mevalonate isoprene biosynthesis pathway is vital to the organism and therefore has been selected as a target for developing antitheilerial drugs. In this study, the 3D structure of TpDXR was identified by template-based in silico homology modelling method, the constructed model was validated and structurally analysed, and possible ligand binding pockets were identified for the first time in the literature. A reliable 3D model for TpLDH was modelled by using 3AU9 chain 'A' Plasmodium falciparum as a template. The obtained result showed that the model has a good resolution structure with 86.768 overall quality factor and a -9.15 z-score for TpDXR. The present study promises the possibility of exploiting new and safe inhibitors using the structure-based drug design that is effective against ECF through docking studies.

Effects of acetylsalicylic acid on germination, growth and chlorophyll amounts of cucumber (Cucumis sativus L.) seeds.

Germination activities, various growth parameters (primary root length, hypocotyl length, primary leaf length, plant length and increase in fresh weight) and chlorophyll (a+b) amounts of cucumber seeds exposed to 0, 10(-5), 10(-4), 10(-3) and 0.5x 10(-2) M aqueous solutions of acetylsalicylic acid (ASA) for 48 h were established. While 0.5x 10(-2) M ASA significantly prevented germination activity of the seeds, other concentrations did not produce any effect, either positive or negative. Meanwhile, 0.5x 10(-2) M ASA inhibited radicle growth of the germinated seeds, while 10(-5) M ASA increased radicle growth. Other concentrations of ASA did not affect radicle growth. The following findings were obtained from the one-week seedlings exposed to ASA for 48 h: 0.5x10(-2) M ASA prevented growth (lengthening) of root, hypocotyl, leaf and plant and increased chlorophyll (a+b) amount with an increase in fresh weight. Contrary to 0.5x 10(-2) M ASA application, these features of the seedlings (except for the leaf length) were encouraged by 10(-5) M ASA. 10(-3)) M ASA only prevented root growth and reduced chlorophyll (a+b) amount. Other concentrations of ASA did not bring about any positive or negative effect on the features studied.

Effect of cadmium on germination, coleoptile and root growth of barley seeds in the presence of gibberellic acid and kinetin.

Effect of cadmium on barley seeds treated with kinetin and gibberellic acid was investigated. As usual, cadmium has inhibited seed germination, and showed important inhibitory effects on roots and coleoptile growth after germination. In general, increase in cadmium concentration caused a greater inhibition of germination, root and coleoptile growth. The adverse effect of cadmium on root and coleoptile growth was more pronounced than that on germination. While testa was pierced by radicle (an indication of germination), no root or coleoptile development was observed above at concentration of 3-9.5 mM CdCl2xH2O. Low concentrations of cadmium have inhibited the root growth more than it did on coleoptile growth. Treatment of seeds with gibberellic acid and kinetin did not show any significant difference on the effect of cadmium in germination. However, inhibition of coleoptile elongation by cadmium has decreased a very much after kinetin application. The same result, although with lower rates when compared to kinetin, has been obtained for GA3 as well. In addition, the inhibitory effect of cadmium on root growth increased even more after kinetin application. The results have been found statistically significant through the least significant different (LSD) test at levels ofp < 0.05 and p < 0.01.