The activity of a new 2-amino-1,3,4-thiadiazole derivative 4ClABT in cancer and normal cells

The 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole set are well known compounds with interesting in vitro and in vivo anti-cancer profiles. The aim of this study was an in vitro evaluation of the anti-cancer activity of a new synthesized aminothiadiazole derivative 2-(3-chlorophenyloamino)-5-(2,4-dihydroxyphenyl)- -1,3,4-thiadiazole 4ClABT. The effect on tumor cell proliferation, motility and morphology, DNA synthesis as well as the influence on normal cells was assessed. The antiproliferative activity of 4ClABT in tumor cells derived from peripheral cancers including breast carcinoma (T47D), colon carcinoma (HT-29), thyroid carcinoma (FTC-238), teratoma (P19), and T-cell leukemia (Jurkat E6.1), as well as cancers of the nervous system including rhabdomyosarcoma/medulloblastoma (TE671), brain astrocytoma (MOGGCCM) and glioma (C6) was studied by means of MTT assay. DNA synthesis level was determined in BrdU ELISA test. Wound assay model was applied for tumor cell motility assessment. Morphological changes induced by 4ClABT in cancer and normal cells were analyzed in HE staining specimens. Moreover, the influence of 4ClABT on normal cells including skin fibroblasts (HSF), hepatocytes (Fao), astroglia and neurons was studied by means of LDH assay. The tested compound inhibited the proliferation of tumor cells in dose-dependent fashion. The anti-cancer effect was attributed to decreased DNA synthesis, prominent changes in tumor cell morphology as well as reduced cell motility. In antiproliferative concentrations, 4ClABT was not toxic to normal cells. Our study showed prominent anti-cancer effects of the tested aminothiadiazole derivative in the absence of toxicity in normal cells. The obtained results confirmed the promising anti-cancer profile of previously tested 2-(monohalogenphenylamino)- -5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazole derivatives (ClABT — chlorophenyl derivative, FABT and 3FABT — fluorophenyl derivatives and 4BrABT — bromophenyl derivative). The molecular mechanisms and the in vivo activity of aminothiadiazole derivatives will be the subject of further studies. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 3, pp. 436–444

Mediation as a Chance for the Reconciliation of the Perpetrator and Victim of a Criminal Offence

Mediation is a result of searching for new, rational alternative means of responding to crime and methods to include a wider range of the victims’ interests. The aim of mediation is the settlement and reconciliation between the victim and the offender. It is based on negotiations between the mediator, an impartial observer. Parties involved in the mediation process should be able to openly and honestly express their views and feelings and to proceed a voluntary, negotiated conflict-free way to redress the damage caused by the offender in the presence of a mediator.3916919211Studia Edukacyjn

Biological evaluation, molecular docking, and sar studies of novel 2-(2,4-dihydroxyphenyl)- 1H- benzimidazole analogues

In the present study, new 4-(1H-benzimidazol-2-yl)-benzene-1,3-diols, modified in both rings, have been synthesized and their efficacies as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors have been determined. The modified Ellman’s spectrophotometric method was applied for the biological evaluation. The compounds showed strong $IC_{50}$ 5-0.2 $\mu$ M AChE and moderate ($IC_{50}$ 5-0.2 M) BuChE inhibition in vitro. Some compounds were e ective toward AChE/BuChE, exhibiting high selectivity ratios versus BuChE, while the other compounds were active against both enzymes. The structure–activity relationships were discussed. The compounds inhibited also in vitro self-induced A$\beta$ (1-42) aggregation and exhibited antioxidant properties. The docking simulations showed that the benzimidazoles under consideration interact mainly with the catalytic site of AChE and mimic the binding mode of tacrine

Clinical aspects of diagnostics and systemic treatment of malignancies during pregnancy

Nowotwory złośliwe u kobiet w ciąży są rzadkie. Obecnie ryzyko współwystępowania ciąży i nowotworu złośliwego rośnie z powodu coraz późniejszego wieku kobiet rodzących pierwszy raz. Podejmując decyzję dotyczącą leczenia onkologicznego ciężarnej, należy uwzględnić stadium choroby oraz zaawansowanie ciąży. W każdym przypadku należy dążyć do maksymalnej ochrony płodu. Istotne jest także zapewnienie możliwości zachowania zdolności rozrodczej leczonej kobiety. Ze względu na potencjalne działanie teratogenne nie zaleca się stosowania chemioterapii w I trymestrze ciąży. Ostatnio rośnie liczba doniesień o możliwości stosowania u ciężarnych w wybranych przypadkach leków chemicznych po okresie organogenezy. Nie poznano jednak w pełni odległych skutków takiego postępowania. Z tego powodu potencjalne ryzyko oraz korzyści wynikające z zastosowania chemioterapii podczas ciąży powinno się szczegółowo analizować. Hormonoterapia wiąże się z wysokim ryzykiem poronienia i nie zaleca się jej w okresie ciąży. Dostępne dane nie pozwalają w pełni ocenić bezpieczeństwa stosowania podczas ciąży wielu form leczenia biologicznego.The coincidence of malignant disease during pregnancy is uncommon. Today, the incidence of cancer in pregnancy has increased, due to the tendency to postpone childbirth to an older age. Making cancer therapy decision in pregnant women both disease and pregnancy advancement should be considered. In all cases fetal saving as well as mother’s fertility preservation are of great importance. Because of mutagenic effect the use of chemotherapy during the first trimester is contraindicated. Recently, increasing number of studies evaluated in selected pregnant women the use of chemotherapy after organogenesis, however the long-term consequences for children exposed to intra-uterine chemotherapy is not fully determined. The potential risks and benefits of such therapy still have to be cautiously weighted. Hormone therapy increases the risk of spontaneous abortion and during pregnancy is contraindicated. No sufficient data about the use of many form of targeted therapy for pregnant women with cancer are available so far

Prognostic impact of combined fludarabine, treosulfan and mitoxantrone resistance profile in childhood acute myeloid leukemia

Background: The role of cellular drug resistance in childhood acute myeloid leukemia (AML) has not yet been established. The aim of the study was the analysis of the clinical value of ex vivo drug resistance in pediatric AML. Patients and Methods: A cohort of 90 children with de novo AML were assayed for drug resistance profile by the 3-4,5- dimethylthiazol-2-yl-2,5-difenyl tetrazolium bromide (MTT) assay and prognostic model of in vitro drug sensitivity was analyzed. Results: Children who relapsed during follow-up showed higher in vitro resistance of leukemic blasts to most of the drugs tested, except for cytarabine, cladribine, vincristine, mercaptopurine and thioguanine. A combined in vitro drug resistance profile to fludarabine, treosulfan and mitoxantrone (FTM score) was defined and it had an independent prognostic significance for disease free survival in pediatric AML. Conclusion: The combined fludarabine, treosulfan and mitoxantrone resistance profile to possibly may be used for better stratification of children with AML or indicate the necessity for additional therapy