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B Falkiewicz

Publications and source records attributed to B Falkiewicz.

At least 37 records · Page 2Linked to original sources

New procedure of the Mitsunobu reaction as the key step in peptide nucleic acid (PNA) monomers synthesis.

PNAs are relatively novel DNA analogues, intensively studied due to their potential as gene-targeted drugs with antigene and antisense properties. In 1996 we elaborated a new method of synthesis of PNA monomer backbones based on the Mitsunobu reaction with N-tosyl-protected (Tos) amino acid esters as acidic components of the reaction. Since the method used for the Tos group removal requires conditions incompatible with various functional groups, here we modified the procedure by replacing the tosyl group with o-nitrobenzenesulfonyl (o-NBS) group. Using the new procedure we obtained protected PNA monomer backbones with various amino acid side chains. The pseudodipeptide secondary amine groups were then deprotected by thiolysis, and after standard work-up acylated with thymin-1-ylacetic acid, to give the protected monomers. Since the deprotection of the secondary amine group occurs under mild conditions, the procedure is of general applicability and allows various modifications of PNA structure by using diverse beta-amino alcohols and alpha-amino acid esters.

Amino Acids↗

Lack of squamous cell lung carcinoma in vitro chemosensitivity to various drug regimens in the adenosine triphosphate cell viability chemosensitivity assay.

A pilot study on squamous cell lung carcinoma (LC) chemosensitivity in adenosine triphosphate cell viability chemosensitivity assay (ATP-CVA) was performed. Besides the histological investigation, a modified ATP-CVA was used for the analysis of cancer cell chemosensitivity to four drug regimens, including topotecan, a promising agent for non-small-cell lung cancer (NSCLC) chemotherapy. Results of in vitro chemosensitivity testing showed chemoresistance or only weak response in the predominant amount of tumors.

Aged↗

Peptide nucleic acids and their structural modifications.

Peptide (polyamide) analogues of nucleic acids (PNAs) make very promising groups of natural nucleic acid (NA) ligands and show many other interesting properties. Two types of these analogues may be highlighted as particularly interesting: the first, containing a polyamide with alternating peptide/pseudopeptide bonds as its backbone, consisting of N-(aminoalkyl)amino-acid units (type I), with nucleobases attached to the backbone nitrogen with the carboxyalkyl linker; and the second, containing a backbone consisting of amino-acid residues carrying the nucleobases in their side chains (type II). So far, these two groups have been studied most intensively. The paper describes main groups of peptide nucleic acids, as well as various other amino acid-derived nucleobase monomers or their oligomers, which were either studied in order to determine their hybridisation to nucleic acids, or only discussed with respect to their potential usefulness in the oligomerisation and nucleic acids binding.

In Vitro Techniques↗

Amplification of erbB-4 oncogene occurs less frequently than that of erbB-2 in primary human breast cancer.

ErbB-4 protein is a recently discovered member of the ErbB family. The role of ErbB-4 protein in mammary-gland tissue has not been definitively established. To date, the expression of erbB-4 in breast tissue has been determined in only a few cases and, to the best of our knowledge, its amplification has not been examined. We therefore used the double differential polymerase chain reaction (ddPCR) for determination of the amplification profile of erbB-4 and erbB-2, another gene from the ErbB family, in human primary breast cancer specimens. We examined the amplification of the genes in 20 normal breasts and 176 invasive breast cancer samples. Amplification of erbB-2 was detected in 19% and erbB-4 in 13% of the samples studied. Co-amplification of the two oncogenes was found in only five out of 176 samples. Human breast cancer-derived cell lines in most cases overexpress both erbB-2 and erbB-4 (Beerli et al., 1995. Mol. Cell Biol. 15, 6496-6505; Han et al., 1995. Proc. Natl. Acad. Sci. USA 92, 9747-9751), but data on separate erbB-2 overexpression, without overexpression of erbB-4, were also reported (Wosikowski et al., 1997. Clin. Cancer Res. 3, 2405-2414). At the gene level, we found that co-amplification of the genes in the case of human breast cancer is rare. Moreover, an inverse association of the erbB-4 amplification with estrogen receptor activity and direct correlation with the tumor size were found. Due to these correlations, erbB-4 oncogene amplification can be assumed to be of prognostic or predictive value in the diagnosis of breast cancer.

Aged↗

Applications of the Mitsunobu reaction in peptide chemistry.

The Mitsunobu reaction--the nucleophilic substitution of an alcoholic hydroxyl group mediated by the redox system trialkylphosphine/dialkyl azodicarobxylate--is widely used in the chemistry of biologically active compounds. The paper deals with applications of the Mitsunobu reaction in amino acid and peptide chemistry. The process provides easy access to many unnatural amino acids and derivatives. Since the reaction occurs with complete inversion of the configuration at the carbinol chiral centre, it can be used for the synthesis of diastereoisomers of hydroxy- and tioprolines. Cyclization of beta-hydroxy amino acid containing peptides under Mitsunobu reaction conditions leads to a constrained peptide that mimics the stabilizing reverse turn secondary structure.

Amino Acids↗

[Low zinc levels in metabolic X syndrome (mzX) patients measured by hair zinc composition analysis].

The hair zinc content in 16 patients with metabolic X syndrome (mzX) was measured by means of atomic absorption spectrometry method. The mean concentration (125.13 mg/kg) was lower than in the majority of other published studies. The differences among groups of patients with different sex or diseases (e.g. coronary heart disease, hypertension, type II diabetes mellitus) were not significant. It seems to be probably that deficiency of zinc plays a role in pathogenesis of mzX or that it is a consequence of mzX.

Aged↗

[Porphyria cutanea tarda--new views on its pathogenesis and therapy].

Literature data and the results of our studies on the prevalence of the HCV infection markers in patients with porphyria cutanea tarda (PCT) are presented. We also present new views on the PCT pathogenesis in some cases, therapy of the cutaneous changes, and the use of interferon in the patients as a prevention of the hepatocellular carcinoma.

Biomarkers↗

HCV infection in Poland.

BACKGROUND: Hepatitis C virus (HCV) infection is one of the most prevalent infectious diseases in the world. In 1997, hepatitis C became a statutorily noticeable disease in Poland. Nevertheless, to date, only a few notable studies on the prevalence of HCV infection have been carried out in Poland. Therefore, a study to determine the prevalence of HCV infection markers in an unselected population of Polish subjects was performed. METHODS: After several advertisements (in the print media and on television, radio, and other public media) concerning free testing for all volunteers in a hospital laboratory, serum samples of 2,561 subjects (765 men and 1,796 women), with a mean age of 43 years (range 1-88 years), were collected and assessed. In the samples, we first tested for the presence of IgG anti-HCV antibodies using the third generation enzyme immunoassay Anti-HCV EIA Cobas(R) Core Test (Hoffmann La Roche, Basel, Switzerland). The determination of HCV-RNA was then performed on anti-HCV IgG-positive samples by qualitative reverse transcription-polymerase chain reaction (RT-PCR) by automatic Cobas Amplicor (Roche Molecular Systems Hepatitis C Virus Test 2.0, Roche Molecular Systems, Nutley, NJ, USA). RESULTS: The presence of anti-HCV IgG was detected in a total of 48 cases (1.9%). Prevalence was significantly higher in men (2.3%) than in women (1.7%) (p = 0.0057), but was not significantly related to the subject's age (p = 0.51) or domicile (p = 0.35). The presence of HCV-RNA was detected in 31 (65%) anti-HCV-positive cases tested, with no significant relationship to either the age (p = 0.15), domicile (p = 0.24), or gender (p = 0.79) of the subjects. CONCLUSIONS: To the best of our knowledge, this is the largest study on the prevalence of HCV infection in the general population in Poland. The study has several limitations, such as, the use of a nonrandomized population. Nevertheless, the results obtained may be more realistic and applicable to the general population in Poland than those obtained previously (i.e., in voluntary blood donors).

Adolescent↗