Survivin antiapoptotic gene expression as a prognostic factor in non-small cell lung cancer: in situ hybridization study.

Survivin is an inhibitor of apoptosis that plays a significant role in cell cycle regulation and is important for survival prognosis in many neoplasms. Survivin expression was assessed by in situ hybridization (ISH) in 60 consecutive patients (54 males and 4 females) with NSCLC treated between 1993 and 1997. The examined patients had IIB and IIIA stage according to TNM system. In all cases the chemotherapy with cisplatin and etoposide (2 cycles) was administered prior the surgery; in patients responding to the therapy one more cycle was applied. Survivin gene overexpression was observed in 35 patients (58.3%). There was no correlation between survivin mRNA level and histological type of tumor, stage of cell differentiation, stage of disease according to TNM classification, performance status according to WHO and number of chemotherapy regimens administered (p > 0.05). However, the correlation between survivin gene expression and response to the chemotherapy was statistically significant (p = 0.04). Statistical analysis showed that median survival in patients with survivin gene overexpression was shorter (14.0 months) as compared to patients with no expression (60.0 months; p = 0.00002). In survival assessment by means of Kaplan-Meier test, 14.3% of five-year survival was achieved in the former group versus 60% in the latter (p = 0.00003). Univariate analysis (log-rank test) showed that significant independent prognostic factors in NSCLC included: stage of the disease according to TNM classification (p = 0.006), response to chemotherapy (p = 0.005) and pattern of survivin gene expression (p = 0.00003). Multivariate analysis utilizing Cox's model showed that for survival assessment the stage according to TNM, response to the chemotherapy and survivin expression estimated by means of ISH are of statistical significance (p=0.00001). The calculated predictive values showed that ISH technique was quite accurate in assessment of five-year survival. Our data show that survivin expression may be used as a prognostic factor and a target for therapy

242. Analiza ekspresji EGFR i angiogenezv w utkaniu niedrobnokomórkowego raka płuc oraz związku z czasem przeżycia pacjentów w stadiach zaawansowania klinicznego I-IIIA

Cel pracyWciąż niezadowalające wskaźniki przeżycia pacjentów z rakiem płuca, mimo radykalnego leczenia operacyjnego, skłaniają do poszukiwań nowych czynników prognostycznych. Wiadomym jest, że receptor naskórkowego czynnika wzrostu (EGFR) wpływa na wzrost komórek guza i jego progresję, jak również tworzenie przerzutów – głównie poprzez oddziaływanie na tworzenie nowych naczyń krwionośnych. Jego prognostyczna rola u pacjentów z niedrobnokomórkowym rakiem płuca (NRP) jest niejasna. Natomiast gęstość naczyń krwionośnych (GNK), będąca miernikiem angiogenezy w guzie, jest podawana jako marker prognostyczny w wielu nowotworach. Celem naszego badania była ocena zależności między ekspresją EGFR i GNK w utkaniu guza nowotworowego a przeżyciem pacjentów z NRP.Materiał i metodyBadaniem objęto 75 pacjentów z NRP w stadiach zaawansowania klinicznego I-IIIA. Wycinki z guza pobierano z materiału operacyjnego, utrwalonego w formalinie. Na uzyskanych skrawkach parafinowych wykonywano odczyny immunohistochemiczne z zastosowaniem monoklonalnego przeciwciała przeciw receptorowi naskórkowego czynnika wzrostu oraz monoklonalnego przeciwciała przeciw CD31.WynikiWśród 75 pacjentów było 5 kobiet (6.7%) i 70 mężczyzn (93.3%) w wieku od 42 lat do 74 lat (średnio 59 lat). W badanej grupie chorych stwierdzono raka płaskonabłonkowego u 53 pacjentów (70.7%), gruczolakoraka u 11 chorych (14.7%) i raka wielkokomórkowego także u 11 pacjentów. Analizując uzyskane dane nie stwierdzono istotności statystycznej między ekspresją EGFR i czasem przeżycia pacjentów. Również GNK nie miała istotnego wpływu na przeżycie pacjentów. Jedynie stan węzłów chłonnych (cecha N; p<0.05), typ histologiczny raka (p<0.001) oraz wiek (p<0.05) w badanej grupie chorych miały istotny statystycznie wpływ na czas przeżycia.WnioskiUzyskane w tym badaniu wyniki nie są zgodne z wynikami innych doniesień mówiących o tym, że ekspresja EGFR i GNK w NRP mogą być traktowane jako czynniki prognostyczne. Należy jednak podkreślić, że analizowana grupa pacjentów była mała, a większość chorych (59 pacjentów, 78.7%) znajdowała się w stadium znacznego zaawansowania nowotworu

Brain iron accumulation in Wilson disease: a post-mortem 7 Tesla MRI - histopathological study

Aims: In Wilson disease (WD), T2/T2*-weighted (T2*w) MRI frequently shows hypointensity in the basal ganglia that is suggestive of paramagnetic deposits. It is currently unknown whether this hypointensity is related to copper or iron deposition. We examined the neuropathological correlate of this MRI pattern, particularly in relation to iron and copper concentrations. Methods: Brain slices from nine WD and six control cases were investigated using a 7T-MRI system. High resolution T2*w images were acquired and R2* parametric maps were reconstructed using a multi-gradient recalled echo sequence. R2* was measured in the globus pallidus (GP) and the putamen. Corresponding histopathological sections containing the lentiform nucleus were examined using Turnbull iron staining, and double staining combining Turnbull with immunohistochemistry for macrophages or astrocytes. Quantitative densitometry of the iron staining as well as copper and iron concentrations were measured in the GP and putamen and correlated to R2* values. Results: T2*w hypointensity in the GP and/or putamen was apparent in WD cases and R2* values correlated with quantitative densitometry of iron staining. In WD, iron and copper concentrations were increased in the putamen compared to controls. R2* was correlated with the iron concentration in the GP and putamen whereas no correlation was observed for the copper concentration. Patients with more pronounced pathological severity in the putamen displayed increased iron concentration, which correlated with an elevated number of iron-containing macrophages. Conclusions: T2/T2*w hypointensity observed in vivo in the basal ganglia of WD patients is related to iron rather than copper deposits

Damping and dynamic sensitivity

W pracy przedstawiono próbę oszacowania wpływu tłumienia na stopień dynamicznej wrażliwości konstrukcji. Rozpatrywane układy konstrukcyjne dyskretyzowano w ramach modelu przemieszczeniowego metody elementów skończonych. Otrzymany układ równań różniczkowych zwyczajnych scałkowano numerycznie metodą superpozycji modalnej. Przeprowadzono i przedyskutowano wyniki analizy wrażliwości dynamicznej dla dużej skali konstrukcji złożonej, wzbudzonej przez uderzenie typu Heaviside'a, w dwóch wariantach, z tłumieniem i bez. Wnioski końcowe wskazują na możliwość zmniejszenia wrażliwości niektórych typów konstrukcji poprzez zastosowanie tłumików.The paper presents an attempt to investigate the influence of damping effects on the sensitivity response of structures from the point of view of dynamics. This means that one should answer not only the well-known question how dampers reduce vibration amplitudes, but also, and first of all, the question how the damping effects affect the structural sensitivity. Namely, whether a damped system is less sensitive to variations of design variables, such as cross sections, thickness or Young module of structural members. After the introduction, in the second section a variational formulation for structure dynamics is presented in the context of the finite element method. In the next section the time instant dynamic sensitivity is described. The system of ordinary differential equations obtained is numerically integrated by the mode superposition algorithm. In the fourth section a large scale complex truss-beam-shell system of 12822 degrees of freedom, Fig. 1, excited by a Heaviside impact is implemented and discussed in two options, damped and undamped. A number of graphs related to dynamic displacements, internal forces and sensitivity for elements is shown, Figs. 2 - 6. The concluding remarks are given with some suggestion to reduce sensitivity of some of types structures by using dampers

Survivin antiapoptotic gene expression as a prognostic factor in non-small cell lung cancer: in situ hybridization study.

Survivin is an inhibitor of apoptosis that plays a significant role in cell cycle regulation and is important for survival prognosis in many neoplasms. Survivin expression was assessed by in situ hybridization (ISH) in 60 consecutive patients (54 males and 4 females) with NSCLC treated between 1993 and 1997. The examined patients had IIB and IIIA stage according to TNM system. In all cases the chemotherapy with cisplatin and etoposide (2 cycles) was administered prior the surgery; in patients responding to the therapy one more cycle was applied. Survivin gene overexpression was observed in 35 patients (58.3%). There was no correlation between survivin mRNA level and histological type of tumor, stage of cell differentiation, stage of disease according to TNM classification, performance status according to WHO and number of chemotherapy regimens administered (p &gt; 0.05). However, the correlation between survivin gene expression and response to the chemotherapy was statistically significant (p = 0.04). Statistical analysis showed that median survival in patients with survivin gene overexpression was shorter (14.0 months) as compared to patients with no expression (60.0 months; p = 0.00002). In survival assessment by means of Kaplan-Meier test, 14.3% of five-year survival was achieved in the former group versus 60% in the latter (p = 0.00003). Univariate analysis (log-rank test) showed that significant independent prognostic factors in NSCLC included: stage of the disease according to TNM classification (p = 0.006), response to chemotherapy (p = 0.005) and pattern of survivin gene expression (p = 0.00003). Multivariate analysis utilizing Cox's model showed that for survival assessment the stage according to TNM, response to the chemotherapy and survivin expression estimated by means of ISH are of statistical significance (p=0.00001). The calculated predictive values showed that ISH technique was quite accurate in assessment of five-year survival. Our data show that survivin expression may be used as a prognostic factor and a target for therapy