12. The evaluation of clinical, histological and molecular predictive and grognostic factors in patients with advanced squamous cell cancer of the larynx, meso- and hypopharynx, floor of mouth irradiated after induction chemotherapy

Between 1988–1997 198 patients with HNSCC received induction chemotherapy. Clinical staging was as follows ll-7(52%), lll-45(20%), IV-146(64%). Patients received 1 to 4 cycles of Cisplatin + 5FU. Response to chemotherapy (CR or PR) was observed only in patients who received 2–4 cycles of chemotherapy. The best responses were observed in patients with laryngeal, mesopharyngeal and hypopharyngeal cancers, 55%. Radiotherapy was subsequently performed in 178(90%). Twenty patients were not irradiated because of poor performance status or progression of disease after chemotherapy. Radical radiotherapy was performed in 124 (5-year LC 38%, DFS 35%, DSS 43%, OS 30%). All 25 patients irradiated palliatively dyied during 26 months. The best results were observed in patients with laryngeal cancer; LC 48%, DFS 25%, DSS 32%, OS 22%. The most frequent failure was local recurrence in 29(23%) patients. In the next step of this study we want; 1) to assess prognostic and predictive value of selected clinical, histological and molecular factors by defining its influence on the chance of response to chemotherapy and chance of cure 2) to examine the correlation between theses factors and to establish if they give new predictive and prognostic information 3) to establish which of examined factors may be useful in selecting patients with advanced HNSCCs to combined modality treatment (chemotherapy + radiotherapy), and particularily in selecting patients with advanced laryngeal cancer to larynx preservation treatment. We will examine the cell cycle parameter Ki67, expression of p53 protein and expresion of (EGFr). There will be also reevaluated histological material (grading)

One-dimensional quasi-relativistic particle in the box

Two-term Weyl-type asymptotic law for the eigenvalues of one-dimensional quasi-relativistic Hamiltonian (-h^2 c^2 d^2/dx^2 + m^2 c^4)^(1/2) + V_well(x) (the Klein-Gordon square-root operator with electrostatic potential) with the infinite square well potential V_well(x) is given: the n-th eigenvalue is equal to (n pi/2 - pi/8) h c/a + O(1/n), where 2a is the width of the potential well. Simplicity of eigenvalues is proved. Some L^2 and L^infinity properties of eigenfunctions are also studied. Eigenvalues represent energies of a `massive particle in the box' quasi-relativistic model.Comment: 40 pages, 4 figures; minor correction

A ruthenium(II) hydride carbonyl complex with 4-phenylpyrimidine as co-ligand

The reaction of [RuHCl(CO)(PPh3)3] with 4-phenylpyrimidine gave a new ruthenium(II) complex, namely [RuHCl(CO)(PPh3)2(pyrim-4-Ph)]. The complex has been studied by IR and UV–vis spectroscopy and by X-ray crystallography. The molecular orbitals of the complex have been calculated by density functional theory. The spin-allowed singlet–singlet electronic transitions of the complex have been calculated by time-dependent DFT, and the UV–vis spectrum of the compound has been discussed on this basis. The emission properties of the complex were also studied

Structural characterization of EnpA D,L-Endopeptidase from Enterococcus faecalis prophage provides insights into substrate specificity of M23 peptidases

The best-characterized members of the M23 family are glycyl-glycine hydrolases, such as lysostaphin (Lss) from Staphylococcus simulans or LytM from Staphylococcus aureus. Recently, enzymes with broad specificities were reported, such as EnpACD from Enterococcus faecalis, that cleaves D,L peptide bond between the stem peptide and a cross-bridge. Previously, the activity of EnpACD was demonstrated only on isolated peptidoglycan fragments. Herein we report conditions in which EnpACD lyses bacterial cells live with very high efficiency demonstrating great bacteriolytic potential, though limited to a low ionic strength environment. We have solved the structure of the EnpACD H109A inactive variant and analyzed it in the context of related peptidoglycan hydrolases structures to reveal the bases for the specificity determination. All M23 structures share a very conserved β-sheet core which constitutes the rigid bottom of the substrate-binding groove and active site, while variable loops create the walls of the deep and narrow binding cleft. A detailed analysis of the binding groove architecture, specificity of M23 enzymes and D,L peptidases demonstrates that the substrate groove, which is particularly deep and narrow, is accessible preferably for peptides composed of amino acids with short side chains or subsequent L and D-isomers. As a result, the bottom of the groove is involved in interactions with the main chain of the substrate while the side chains are protruding in one plane towards the groove opening. We concluded that the selectivity of the substrates is based on their conformations allowed only for polyglycine chains and alternating chirality of the amino acids

How much of the predisposition to Hashimoto's thyroiditis can be explained based on previously reported associations?

Purpose Our insight in the genetics of Hashimoto’s thyroiditis (HT) has become clearer through information provided by genome-wide association studies and candidate gene studies, but remains still not fully understood. Our aim was to assess how many different genetic risk variants contribute to the development of HT. Methods 147 HT cases (10.2% men) and 147 controls (13.6% men) were qualified for the analysis. Intrinsic and environmental factors were controlled for. Polymorphisms (SNP) were chosen based on the literature and included markers of the genes PTPN22, CTLA4, TG, TPO among others, and of genomic regions pointed by GWAS studies. SNP were typed on a microarray. Variants in the HLA-DRB1 gene were identified by Sanger sequencing. Results Multivariate predisposition to HT was modeled. Based on the investigated group, a model of seven variables was obtained. The variability explained by this model was assessed at only 5.4821% (p = 2 × 10-6), which indicates that many dozens of factors are required simultaneously to explain HT predisposition. Conclusions We analyzed genetic regions commonly and most significantly associated with autoimmune thyroid disorders in the literature, on a carefully selected cohort. Our results indicated a lack of possibility to predict the risk of HT development, even with a multivariate model. We therefore conclude that strong associations of single genetic regions with HT should be interpreted with great caution. We believe that a change in the attitude towards genetic association analyses of HT predisposition is necessary. Studies including multiple factors simultaneously are needed to unravel the intricacies of genetic associations with HT

A novel mutation (Cys308Phe) of the LDL receptor gene in families from the South-Eastern part of Poland

The purpose of this investigation was to characterize a new mutation in the LDL-receptor (LDLR) gene in three families with clinically diagnosed familial hypercholesterolemia (FH) from the South-Eastern part of Poland. Mutational screening with exon by exon sequencing analysis was performed in all probands. The novel mutation c986G>T (Cys308Phe) in the exon 7 of LDLR gene was found in three apparently unrelated probands with FH. Analysis of the receptor activity of peripheral blood lymphocytes by binding and uptake of DiL-LDL showed a significant reduction (by 24% versus healthy control) of the fluorescent label in the lymphocytes of patients heterozygous for this mutation. Concentrations of serum LDL-C in probands before treatment were between 9.5 and 10.5 mmol/l. All patients had corneal arcus and tendon xanthoma. Clinically, families were characterized by premature coronary artery disease. This mutation occurred relatively frequently in our group of patients with FH, but this could be explained by a founder effect since we demonstrated their common ancestors