Expression of proteins associated with therapy resistance in rhabdomyosarcoma and neuroblastoma tumour cells

The activity of multidrug resistance (MDR) proteins in tumour cells is associated with an increased resistance to therapy and in consequence with a decreased effectiveness of chemotherapy. The majority of MDR molecules belong to a family of ABC (ATP binding cassette) transporters. Neuroblastoma (NBL) and rhabdomyosarcoma (RMS) are common solid tumours of childhood. The response to therapy is better in NBL, worse in RMS, but still unsatisfactory despite surgery and aggressive chemotherapy. The immunohistochemical staining for p-gp (p-glycoprotein), MRP1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) expression was performed in primary tumour sections of NBL (10 cases) and RMS (10 cases). A different pattern of MDR expression in NBL and RMS were noted. In NBL, MRP1 was expressed in all studied tumours, p-gp, BCRP only in 3 out of 10 tumours, LRP, in 4 cases. The combination of more than one protein was noted in the majority of NBL tumours. In RMS, the expression of 3 or 4 MDR proteins was noted in 9 cases. The high expression of an MDR protein profile in RMS suggests various mechanisms acting simultaneously, which might explain chemotherapy resistance and a low percentage of long-time survival in this tumour

Formation of Highly Ordered Self-Assembled Monolayers of Alkynes on Au(111) Substrate

Self-assembled monolayers (SAMs), prepared by reaction of terminal n-alkynes (HC≡C(CH2)nCH3, n = 5, 7, 9, and 11) with Au(111) at 60 °C were characterized using scanning tunneling microscopy (STM), infrared reflection absorption spectroscopy (IRRAS), X-ray photoelectron spectroscopy (XPS), and contact angles of water. In contrast to previous spectroscopic studies of this type of SAMs, these combined microscopic and spectroscopic experiments confirm formation of highly ordered SAMs having packing densities and molecular chain orientations very similar to those of alkanethiolates on Au(111). Physical properties, hydrophobicity, high surface order, and packing density, also suggest that SAMs of alkynes are similar to SAMs of alkanethiols. The formation of high-quality SAMs from alkynes requires careful preparation and manipulation of reactants in an oxygen-free environment; trace quantities of O2 lead to oxidized contaminants and disordered surface films. The oxidation process occurs during formation of the SAM by oxidation of the −C≡C– group (most likely catalyzed by the gold substrate in the presence of O2).Chemistry and Chemical Biolog

Microscopic and spetroscopic research on organic self-assembled monolayers

Przedmiotem badań są molekuły alkanotioli z grupami azobenzenowymi osadzone na podłożu Au(111). Zastosowanie techniki mikroskopowej STM oraz spektroskopowej IRRAS pozwoliło wykazać, że badane molekuły na podłożu Au(111) są zdolne do tworzenia monowarstw o wysokim stopniu uporządkowania i dużej gęstości upakowania. Zaobserwowano także systematyczne różnice w strukturze badanych SAMów w zależności od liczby grup metylenowych w łańcuchu alkilowym molekuł bazowych. Zbadane SAMy mogą znaleźć zastosowanie w elektronice molekularnej do funkcjonalizacji powierzchni.The subject of my research were alkanethiol molecules modified with azobenzene group assembled on the Au(111) substrate. In order to show that those molecules are capable to form highly organized monolayers with high packing density, IRRAS and STM measurements were porformed. Moreover, STM and IRRAS measurements enabled to revealed systematic differences in the structure of those molecules depending on the alkanethiol chain length. Self-assembled monolayers based on azobenzene group find their potential application in molecular electronics

Structure analysis and relative stability of self-assembled monolayers of naphtalenethiols and naphtaleneselenols on Au(111) substrate

Przedmiotem badań są molekuły 2-cyjano-6-naftalenotiolu oraz 2-cyjano-6-naftalenoselenolu osadzone na podłożu Au(111), celem badań jest natomiast ocena struktury oraz względnej stabilności obu układów. Zastosowanie techniki mikroskopowej STM pozwoliło wykazać, że badane molekuły na podłożu Au(111) są zdolne do tworzenia monowarstw o wysokim stopniu uporządkowania i porównywalnej, wysokiej gęstości upakowania. Pomiar kąta zwilżania w eksperymencie wymiany wskazuje na znacznie większą stabilność interfejsu złoto-selen. Badane SAMy aromatyczne potencjalnie mogą znaleźć zastosowanie w funkcjonalizacji powierzchni elementów elektronicznych.The subject of my research are molecules of 2-cyano-6-naphtalenethiol and 2-cyano-6-naphtaleneselenol assembled on the Au(111) substrate. In order to show that the molecules are capable of forming highly organized monolayers, STM measurements had been performed. The two systems exhibit comparable and high packing density. Exchange experiments had been carried out by using contact angle measurements which revealed much higher stability of the gold-selenolate interface in comparison to the gold-thiolate one. Self-assembled monolayers based on aromatic moieties may be potentially applied as functional coverage in electronic elements

Formation of highly ordered self-assembled monolayers of alkynes on Au(111) substrate

Self-assembled monolayers (SAMs), prepared by reaction of terminal n-alkynes (HC≡C(CH2)nCH3, n = 5, 7, 9, and 11) with Au(111) at 60 °C were characterized using scanning tunneling microscopy (STM), infrared reflection absorption spectroscopy (IRRAS), X-ray photoelectron spectroscopy (XPS), and contact angles of water. In contrast to previous spectroscopic studies of this type of SAMs, these combined microscopic and spectroscopic experiments confirm formation of highly ordered SAMs having packing densities and molecular chain orientations very similar to those of alkanethiolates on Au(111). Physical properties, hydrophobicity, high surface order, and packing density, also suggest that SAMs of alkynes are similar to SAMs of alkanethiols. The formation of high-quality SAMs from alkynes requires careful preparation and manipulation of reactants in an oxygen-free environment; trace quantities of O2 lead to oxidized contaminants and disordered surface films. The oxidation process occurs during formation of the SAM by oxidation of the −C≡C– group (most likely catalyzed by the gold substrate in the presence of O2)

Mutation c.256_257delAA in RAG1 Gene in Polish Children with Severe Combined Immunodeficiency : diversity of Clinical Manifestations

Mutations in RAG1 gene may result in different types of severe combined immunodeficiencies. In this study, we compare clinical symptoms and laboratory findings in four children with identical mutation in RAG1 gene. All of analyzed patients presented symptoms of severe combined immunodeficiencies associated or not with Omenn syndrome (OS) features. In our patients two different types of variants in RAG1 gene were detected. The first of the mutation was the deletion of AA dinucleotide at position c.256_257 (p.Lys86ValfsTer33), the second gene variant was substitution c.2867T>C (p.Ile956Thr). In Patient 1 we detected that compound heterozygous mutations involved both of the mentioned variants. Whereas, in Patients 2, 3 and 4, we confirmed the presence of the dinucleotide deletion but in a homozygous state. In all described patients, sequence analysis of RAG2 gene did not reveal any nucleotide changes. Our data show that mutation c.256_257delAA in RAG1 gene seems to occur quite frequently in the polish patients with severe combined immunodeficiency and may result in classical OS as well as in severe combined immunodeficiency without clinical and laboratory features of OS when occurred in homozygous state. The same mutation but in heterozygous state, in combination with other mutation in RAG1 gene, may result in incomplete OS

Thiolate versus selenolate : structure, stability, and charge transfer properties

Selenolate is considered as an alternative to thiolate to serve as a headgroup mediating the formation of self-assembled monolayers (SAMs) on coinage metal substrates. There are, however, ongoing vivid discussions regarding the advantages and disadvantages of these anchor groups, regarding, in particular, the energetics of the headgroup–substrate interface and their efficiency in terms of charge transport/transfer. Here we introduce a well-defined model system of 6-cyanonaphthalene-2-thiolate and -selenolate SAMs on Au(111) to resolve these controversies. The exact structural arrangements in both types of SAMs are somewhat different, suggesting a better SAM-building ability in the case of selenolates. At the same time, both types of SAMs have similar packing densities and molecular orientations. This permitted reliable competitive exchange and ion-beam-induced desorption experiments which provided unequivocal evidence for a stronger bonding of selenolates to the substrate as compared to the thiolates. Regardless of this difference, the dynamic charge transfer properties of the thiolate- and selenolate-based adsorbates were found to be nearly identical, as determined by the core–hole–clock approach, which is explained by a redistribution of electron density along the molecular framework, compensating the difference in the substrate–headgroup bond strength