286. Leczenie raka sutka inhibitorami aromatazy II generacji w materiale WCO

Cel pracyInhibitory aromatazy II generacji (Letrozol, Anastrozol) są stosowane w leczeniu zaawansowanego raka sutka, po niepowodzeniu leczenia tamoksifenem oraz coraz częściej jako leczenie pierwszego rzutu w leczeniu uzupełniającym. W pracy przedstawiono wstępne obserwacje i wyniki leczenia inhibitorami aromatazy chorych z nawrotem raka sutka oraz po niepowodzeniu leczenia tamoksifenem.Materiał i metody31 chorych na nowotwór sutka leczonych było inhibitorami aromatazy II generacji w okresie od 01.01.1995 do 31.12.2000 roku w Wielkopolskim Centrum Onkologii. Wiek chorych sięgał od 43 do 85 lat (średnio 61.7 lat). Leczenie inhibitorami rozpoczęto u 23 chorych z nawrotem raka sutka po niepowodzeniu leczenia tamoksifenem oraz u 8 chorych jako leczenie pierwszego rzutu. Wskazania do leczenia inhibitorami były następujące: rozsiew uogólniony (n=7 chorych), przerzuty do kości (n=7), wznowa miejscowa w bliźnie (n=5), rak sutka zaawansowany, nieoperacyjny (n=3), przerzuty do wątroby (n=3), do węzłów chłonnych okolicy nadobojczykowej (n=2) oraz ze względu na objawy uboczne tamoksifenu (n=4).WynikiŚredni okres leczenia inhibitorami wynosił 13 miesięcy. W 7 przypadkach (22,6%) odstąpiono od dalszego leczenia z powodu: dalszej progresji w kościach (n=4), progresji guza w sutku (n=1), rozsiewu do OUN (n=1) i krwawienia z dróg rodnych (n=1). Średni czas do progresji od momentu rozpoczęcia leczenia wynosił 9 miesięcy (w granicach od 1 do 24 miesięcy).WniosekInhibitory aromatazy II generacji wpływają na zahamowanie rozwoju nawrotowego oraz zaawansowanego raka sutka u części chorych. Tolerancja leczenia jest dobra

Microalgae for biofuels production and environmental applications: A review

Microalgae can provide several different types of renewable biofuels. These include methane produced by anaerobic digestion of the algal biomass; biodiesel derived from microalgal oil and photobiologically produced biohydrogen. This review presents the current classification of biofuels, with special focus on microalgae and their applicability for the production of biodiesel. The paper considered issues related with the processing and culturing of microalgae, for not only those that are involved in biofuel production, but as well as the possibility of their utilization in environmental pollution control, especially with relation to greenhouse gas emissions and the process of sewage purification. The paper gives also a characterization of microalgae used in the production of biofuels and of their advantages relative to other raw materials used in fuel production.Keywords: Biodiesel, biofuels, microalgae, photobioreactors, environmental applications

IR Spectrum of the O-H......O Hydrogen Bond of Phthalic Acid Monomethylester in Gas Phase and in CCl4_4 Solution

The absorption spectrum of the title compound in the spectral range of the Hydrogen-bonded OH-stretching vibration has been investigated using a five-dimensional gas phase model as well as a QM/MM classical molecular dynamics simulation in solution. The gas phase model predicts a Fermi-resonance between the OH-stretching fundamental and the first OH-bending overtone transition with considerable oscillator strength redistribution. The anharmonic coupling to a low-frequency vibration of the Hydrogen bond leading to a vibrational progression is studied within a diabatic potential energy curve model. The condensed phase simulation of the dipole-dipole correlation function results in a broad band in the 3000 \cm region in good agreement with experimental data. Further, weaker absorption features around 2600 \cm have been identified as being due to motion of the Hydrogen within the Hydrogen bond.Comment: Contribution to Horizons in Hydrogen Bond Research Conference, Paris 200

QM/MM Lineshape Simulation of the Hydrogen-bonded Uracil NH Stretching Vibration of the Adenine:Uracil Base Pair in CDCl3_3

A hybrid Car-Parrinello QM/MM molecular dynamics simulation has been carried out for the Watson-Crick base pair of 9-ethyl-8-phenyladenine and 1-cyclohexyluracil in deuterochloroform solution at room temperature. The resulting trajectory is analyzed putting emphasis on the N-H$...$N Hydrogen bond geometry. Using an empirical correlation between the \NN-distance and the fundamental NH-stretching frequency, the time-dependence of this energy gap along the trajectory is obtained. From the gap-correlation function we determine the infrared absorption spectrum using lineshape theory in combination with a multimode oscillator model. The obtained average transition frequency and the width of the spectrum is in reasonable agreement with recent experimental data.Comment: revised version with small changes submitted to Chem. Phys. Let

70. Meningiomas treated in Greatpoland Cancer Center between 1990–1997

IntroductionWe analyzed correlation between age of patient with anaplastic meningiomas, extension of tumor excision, histopatological recognition and time to recurrence and survival.Material and methodsBetween 1990–1997 7 patients with anaplastic meningioma, 3 patients with haemangiopericytoma, 2 patients with sarcoma meningeum (6 women and 6 men) have been irradiated. 7 patients underwent radical excision of the tumor, 5 patients non radical. The patients were irradiated from limited fields to total dose 56–60 Gy/T mostly by energy Co-60 (9 patients) and photons 9 MV (3 patients).ResultsThere are 6 patients with anaplasticum meningioma still alive. 3 patients living 96–108 months, 3 other 30–39 months. Recurrence was confirmed in two male participants who underwent radical surgery in 12 and 29 month from the start of treatment. The first patient died after 16 months with recurrence of the disease. One patient (39 years old) with heamangiopericytoma lives 40 months after radical surgery without evidence of recurrence. Two patients died – one 11 months after radical surgery (41 years old) and the other one (42 years old) 21 months after non radical surgery. Both patients (24 and 59 years old) with sarcoma died (one after 8 months, and the other one after 21 months).ConclusionsPatient with anaplastic meningiomas have long survival. The extension of tumor excision didn’t influence on survival

70 Wyniki leczenia chorych na raka sutka w stadium rozsiewu w materiale Wielkopolskiego Centrum Onkologii

WstępLeczenie chorych na raka sutka w stadium rozsiewu (M1) ma charakter paliatywny. Metody leczenia obejmują radioterapię, chemioterapię, hormonoterapię w monoterapii lub jako leczenie skojarzone. Wyniki leczenia są najczęściej złe. Przedstawiamy wyniki leczenia chorych na raka sutka w stadium rozsiewu leczonych w Wielkopolskim Centrum Onkologii.Materiał i metody95 chorych na raka sutka w stadium M1 leczono w latach 1983–1987 w Wielkopolskim Centrum Onkologii. Wiek chorych wahał się od 29 do 74 lat, średnio 51,5 lat. W grupie 65 chorych pierwszym umiejscowieniem przerzutów był kościec, w dalszej kolejności płuca i wątroba. Większość chorych leczona była cytostatykami lub hormonami, u części zastosowano paliatywną radioterapię. Wyniki leczenia opracowano na podstawie historii chorób i przeprowadzonej katamnezie. Grupę badaną poddano 5-letniej obserwacji.Wyniki8 chorych (8,4%) przeżyło 5 lat od momentu rozpoczęcia leczenia zmian przerzutowych. Średni okres przeżycia w całej grupie wyniósł 13,5 miesiąca.WnioskiPomimo złego rokowania leczeniem systemowym udaje się przedłużyć życie części chorych na raka sutka, u których wystąpiły przerzuty odległe

Dimethylarginine Dimethylaminohydrolase II Overexpression Attenuates LPS-Mediated Lung Leak in Acute Lung Injury

Acute lung injury (ALI) is a severe hypoxemic respiratory insufficiency associated with lung leak, diffuse alveolar damage, inflammation, and loss of lung function. Decreased dimethylaminohydrolase (DDAH) activity and increases in asymmetric dimethylarginine (ADMA), together with exaggerated oxidative/nitrative stress, contributes to the development of ALI in mice exposed to LPS. Whether restoring DDAH function and suppressing ADMA levels can effectively ameliorate vascular hyperpermeability and lung injury in ALI is unknown, and was the focus of this study. In human lung microvascular endothelial cells, DDAH II overexpression prevented the LPS-dependent increase in ADMA, superoxide, peroxynitrite, and protein nitration. DDAH II also attenuated the endothelial barrier disruption associated with LPS exposure. Similarly, in vivo, we demonstrated that the targeted overexpression of DDAH II in the pulmonary vasculature significantly inhibited the accumulation of ADMA and the subsequent increase in oxidative/nitrative stress in the lungs of mice exposed to LPS. In addition, augmenting pulmonary DDAH II activity before LPS exposure reduced lung vascular leak and lung injury and restored lung function when DDAH activity was increased after injury. Together, these data suggest that enhancing DDAH II activity may prove a useful adjuvant therapy to treat patients with ALI

Interference of H-bonding and substituent effects in nitro- and hydroxy-substituted salicylaldehydes

Two intramolecular interactions, i.e., (1) hydrogen bond and (2) substituent effect, were analyzed and compared. For this purpose, the geometry of 4- and 5-X-substituted salicylaldehyde derivatives (X = NO2, H or OH) was optimized by means of B3LYP/6-311 + G(d,p) and MP2/aug-cc-pVDZ methods. The results obtained allowed us to show that substituents (NO2 or OH) in the para or meta position with respect to either OH or CHO in H-bonded systems interact more strongly than in the case of di-substituted species: 4- and 3-nitrophenol or 4- and 3-hydroxybenzaldehyde by ∼31%. The substituent effect due to the intramolecular charge transfer from the para-counter substituent (NO2) to the proton-donating group (OH) is ∼35% greater than for the interaction of para-OH with the proton-accepting group (CHO). The total energy of H-bonding for salicylaldehyde, and its derivatives, is composed of two contributions: ∼80% from the energy of H-bond formation and ∼20% from the energy associated with reorganization of the electron structure of the systems in question

Flexibility of a biotinylated ligand in artificial metalloenzymes based on streptavidin—an insight from molecular dynamics simulations with classical and ab initio force fields

In the field of enzymatic catalysis, creating activity from a non catalytic scaffold is a daunting task. Introduction of a catalytically active moiety within a protein scaffold offers an attractive means for the creation of artificial metalloenzymes. With this goal in mind, introduction of a biotinylated d6-piano-stool complex within streptavidin (SAV) affords enantioselective artificial transfer-hydrogenases for the reduction of prochiral ketones. Based on an X-ray crystal structure of a highly selective hybrid catalyst, displaying significant disorder around the biotinylated catalyst [η6-(p-cymene)Ru(Biot-p-L)Cl], we report on molecular dynamics simulations to shed light on the protein–cofactor interactions and contacts. The results of these simulations with classical force field indicate that the SAV-biotin and SAV-catalyst complexes are more stable than ligand-free SAV. The point mutations introduced did not affect significantly the overall behavior of SAV and, unexpectedly, the P64G substitution did not provide additional flexibility to the protein scaffold. The metal-cofactor proved to be conformationally flexible, and the S112K or P64G mutants proved to enhance this effect in the most pronounced way. The network of intermolecular hydrogen bonds is efficient at stabilizing the position of biotin, but much less at fixing the conformation of an extended biotinylated ligand. This leads to a relative conformational freedom of the metal-cofactor, and a poorly localized catalytic metal moiety. MD calculations with ab initio potential function suggest that the hydrogen bonds alone are not sufficient factors for full stabilization of the biotin. The hydrophobic biotin-binding pocket (and generally protein scaffold) maintains the hydrogen bonds between biotin and protein