Good clinical practice: International quality standard for clinical trials

A clinical trial is one of the most important examples of experimental studies. Clinical trials represent an indispensable tool for testing, in a rigorous scientific manner, the efficacy of new therapies. Good Clinical Practice is an international ethical and scientific quality standard for clinical trials, concerning the design, conduct, performance, monitoring auditing, recording, analysis and reporting. This is an assurance to the public that the rights, safety and well-being of trial subjects are protected, and that clinical trial data is credible. The above definitions are consistent with the principles that have their origin in the declaration of Helsinki. The objectives of Good Clinical Practice are to protect the rights of trial subjects, to enhance credibility of data and to improve the quality of science

Preclinical pharmacology of bombesin antagonists

Ispitivana je serija analoga bombesina na antikancersku aktivnost prema različitim humanim tumorima u in vitro i in vivo uslovimaPreclinial pharmacology of different bombesin anatgonists has been investigated in vitro and in vivo against various human cancer

Complex formation reactions of gallium(III) and iron(III/II) with L-proline-thiosemicarbazone hybrids: A comparative study

Three new gallium(III) and iron(III) complexes with l-proline-thiosemicarbazone hybrids, namely [GaCl(l-Pro-FTSC–2H)]·0.7H2O·0.5CH3OH (1·0.7H2O·0.5CH3OH), [GaCl(dm-l-Pro-FTSC–2H)]·0.4H2O (2·0.4H2O) and [FeCl(l-Pro-FTDA–H)]Cl (3) were synthesised and comprehensively characterised by spectroscopic methods (1H, 13C NMR, UV–vis), ESI mass spectrometry and X-ray crystallography. The complexes are soluble in biological media to allow for assaying their antiproliferative activity. The complexes were tested in three human cancer cell lines, namely HeLa, A549 (non-small cell lung cancer), LS174 and nontumorigenic MRC5. Complex formation equilibrium processes of l-Pro-FTSC with gallium(III), iron(II) and iron(II) ions were investigated in solution. The formation of mono-ligand iron(II) and gallium(III) complexes with pentadentate ligands and relatively low aqueous solution stability was found. Between iron(III) and the ligands, a redox reaction takes place via the oxidative cyclisation of the thiosemicarbazone.This work was also supported by the Hungarian Research Foundation OTKA project PD103905 and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. Supplementary material CCDC-1452613, -1452614 and -1452615 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (email: [email protected]

Trans-platinum complexes as anticancer drugs: Recent developments and future prospects

Cisplatin represents one of the most potent drugs available in the cancer chemotherapy for several solid tumors, such as germ cell tumors, ovarian, lung, head and neck, and bladder cancers. Structure-activity relationship studies showed that leaving groups (generally chlorine) and two amine ligands in platinum complexes must be in the cis orientation and that the corresponding trans compounds are inactive. During the 1990's, several groups have reported trans-platinum compounds with in vitro growth inhibitory and in vivo antitumor properties. Some of these complexes were active against tumor cells resistant to cisplatin. More interestingly, there is a difference in cellular and biochemical pharmacology between trans-platinum complexes and cisplatin. Thus, monofunctional adducts might be related to the cytotoxicity of the trans-platinum-iminoether compounds against cis-DDP sensitive/resistant cell lines; unusual structure of long-range interstrand cross-links might be relevant for great effectivity of bifunctional polinuclear trans-platinum(II) compounds against cis-DDP resistant variants. Trans-platinum compounds, appear to follow different pattern of cell killing in comparison to cisplatin, thus giving a reason for optimism in their development as a new class of platinum-based antitumor drugs

Breast cancer susceptibility genes: Options for those carrying BRCA1 mutations

The discovery of the association between breast and ovarian cancer and the BRCA genes and the development of methods for genetic testing made it possible to screen women for genetic predisposition to develop hereditary breast cancer (HBC). Parallelly, prevention strategies, including clinical surgical and medical interventions become available in order to reduce cancer risk. In a meantime, we became aware of limitations of genetic testing from the aspect of BRCA gene penetrance, negative result interpretation etc. All of these, together with data that invasive prevention strategies such as prophylactic surgery demonstrate better results in risk reduction than regimens including self and clinical-examination, face BRCA mutation carriers with difficult choice for risk reduction options. Therefore, the patients at high risk of HBC can best make informed decisions when guided by a multidisciplinary genetic counseling team

Antiproliferative activity of some cis-/trans-platinum(II) complexes on HeLa cells

Purpose of this work was to synthesize several cis-/trans- isomer pairs of the platinum(II) complexes, and study the extent and the mode of their antiproliferative activity on HeLa cells. Six platinum(II) isomer pairs have a general formula cis-/trans-[PtA(2) X-2] where A is ligand: ammonia (NH3), pyridine (Py); and X is ligand: chloride ion (Cl-), bromide ion (Br-), iodide ion (I-), thiocyanato, ion (SCN-); four compounds have different structural formulas, and these are cis-/trans-[Pt(NH2OH)(2) (NH3)(2)]Cl-2, and cis-/trans- Pt(Gly)(2), where Gly is bidentate glycinato ligand. Results of the MTT assay, showed that six cis- and one trans-platinum(II) complexes exhibited cytotoxicity (IC50) ranging between 5 and 33 muM. Most of the cis-platinum(II) isomers caused significant alteration of cell cycle phases progression, and induced apoptosis in degree that varied among different compounds, as evaluated using flowcytometry and morphological study. Spectrophotometric analysis (AAS) indicated that there is no correlation between intracellular platinum(II) accumulation and cytotoxicity of tested complexes

Germline mutation analysis of BRCA1 and BRCA2 genes in Yugoslav breast/ovarian cancer families

The frequency of germline BRCA1 and BRCA2 mutations was tested in Yugoslav breast and breast/ovarian cancer families using combined heteroduplex/single-strand conformation polymorphism analysis for the entire coding region of both genes. Three different recurrent BRCA1 mutations (one 185delAG, one 3447del4 and two 5382insC) were identified in 4 of 12 families (33%), whereas no definite disease-causing alterations of BRCA2 was detected. Genotype analysis revealed a possible common founder effect for each 185delAG and 5382insC. The relatively high frequency of germline BRCA1 mutations determined in this panel of families confirms the important role of BRCA1 in disease predisposition in the Yugoslav population, while the lack of population specific founder and/or unique mutations show the need of further analysis of samples from this yet unexamined region of Europe

Synthesis and biological activity of Pd(II) and Cu(II) complexes with acylhydrazones of usnic acid

The complexes of Pd(II) and Cu(II) with the condensation products of usnic acid with hydrazides were prepared and characterized by elemental analyses, IR, H-1 NMR, and C-13 NMR spectroscopy. In all cases, the complexes appear to be monomeric and square-planar, with three binding sites occupied by the dianionic tridentate ligand, and the fourth position occupied by ethanol. The complexes were tested for in vitro growth inhibitory activity against Aspergillus niger, Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis and were found to possess significant activity. The cytotoxic tests were carried out by utilization of the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) microculture colorimetric assay in which human cervix carcinoma HeLa cells were treated by continuous exposure (48 h) to the test agents. All investigated compounds showed cytotoxic activity against HeLa cells with IC50 values between 1.8 and 86.0 muM