TP53 mutation and survival in aggressive B cell lymphoma

TP53 is mutated in 20–25% of aggressive B‐cell lymphoma (B‐NHL). To date, no studies have addressed the impact of TP53 mutations in prospective clinical trial cohorts. To evaluate the impact of TP53 mutation to current risk models in aggressive B‐NHL, we investigated TP53 gene mutations within the RICOVER‐60 trial. Of 1,222 elderly patients (aged 61–80 years) enrolled in the study and randomized to six or eight cycles of CHOP‐14 with or without Rituximab (NCT00052936), 265 patients were analyzed for TP53 mutations. TP53 mutations were demonstrated in 63 of 265 patients (23.8%). TP53 mutation was associated with higher LDH (65% vs. 37%; p < 0.001), higher international prognostic index‐Scores (IPI 4/5 27% vs. 12%; p = 0.025) and B‐symptoms (41% vs. 24%; p = 0.011). Patients with TP53 mutation were less likely to obtain a complete remission CR/CRu (CR unconfirmed) 61.9% (mut) vs. 79.7% (wt) (p = 0.007). TP53 mutations were associated with decreased event‐free (EFS), progression‐free (PFS) and overall survival (OS) (median observation time of 40.2 months): the 3 year EFS, PFS and OS were 42% (vs. 60%; p = 0.012), 42% (vs. 67.5%; p < 0.001) and 50% (vs. 76%; p < 0.001) for the TP53 mutation group. In a Cox proportional hazard analysis adjusting for IPI‐factors and treatment arms, TP53 mutation was shown to be an independent predictor of EFS (HR 1.5), PFS (HR 2.0) and OS (HR 2.3; p < 0.001). TP53 mutations are independent predictors of survival in untreated patients with aggressive CD20+ lymphoma. TP53 mutations should be considered for risk models in DLBCL and strategies to improve outcome for patients with mutant TP53 must be developed.     

The Effect of Tin on Microstructure and Properties of the Al-10 wt.% Si Alloy

In this paper, the results from studies regarding near-eutectic Al-Si alloys with Sn as an alloying addition are presented. In most Al-Si alloys, tin is regarded as a contaminant; thus, its amount is limited to up to 0.3 wt.%. The few studies that can be found in the literature regarding the behaviour of tin in aluminium alloys suggest the beneficial effect of this element on selected properties. However, these results were obtained for hypereutectic Al-Si alloys or wrought aluminium alloys. In our studies, the influence of tin contents of up to 1.7 wt.% was determined on the AlSi10 alloy. Thermal analysis, measurements of the mechanical properties of the cast and heat-treated alloy, metallographic observations (light microscopy, scanning electron microscopy), and EDS (X-ray energy dispersive spectrometry) measurement allowed us to fully describe the effect of tin on the aluminium alloy. The results of the thermal analysis showed changes in the range of the α-Al solution crystallisation and the α+β eutectic through a decrease in the alloy’s solidification start point and eutectic solidification point. As a result, the elongation of the alloy was more than double in the AlSi10Sn1.7 alloy, with an A5 value of 8.1% and a tensile strength that was above 200 MPa.     

Thermal Diffusivity Characteristics of the IN718 Alloy Tested with the Modified Pulse Method

The article presents the use of the modified pulse method (MPM) to determine the temperature characteristics of the thermal diffusivity of alloy 718. The experiment was carried out in the temperature range of 20–900 °C during the double heating of the sample with an interval of two weeks. The results of our own research showed a good correlation in the temperature range of 300–500 °C, during the first heating of the sample, with the recommended changes in thermal diffusivity by NPL & ASM and data from the MPDB database. On the other hand, clear deviations in the results occurred in the range of temperature changes up to about 300 °C, most likely responsible for the electron component of the conductivity of this alloy, and in the range above 700 °C, where there is a clear minimum that may be caused by the δ phase precipitation phenomenon.     

Correlation between KRAS,NRAS and BRAF mutations and tumor localizations in patients with primary and metastatic colorectal cancer

IntroductionDetection of abnormalities in the KRAS, NRAS and BRAF genes is extremely important for proper qualification of colorectal cancer (CRC) patients for therapy with anti-EGFR (epidermal growth factor receptor) monoclonal antibodies. However, data about prevalence of mutations in these genes, in different localizations of CRC tumors, are limited.Material and methodsWe examined the frequency of mutations in the KRAS, NRAS and BRAF genes in 500 Caucasian CRC patients (200 women and 300 men, median age 66 years). DNA was isolated from formalin-fixed, paraffin-embedded (FFPE) tissues using a Qiagen QIAamp DNA FFPE-kit. Analysis of mutations was carried out using the KRAS/BRAF, NRAS and BRAF Mutation Analysis Kit for Real-Time PCR (EntroGen) with the Cobas 480 real-time PCR apparatus (Roche Diagnostics).ResultsKRAS mutations were detected in 190 (38%) patients, NRAS mutations in 20 (4%) patients, and BRAF mutations in 24 (4.8%) patients. There were no associations between age of CRC patients and frequency of KRAS, NRAS and BRAF gene mutations. These mutations were significantly more often diagnosed in women (55.5%) than in men (41%, p < 0.005). Tumors of the rectum and sigmoideum were the most often observed in both groups of CRC patients – with and without KRAS, NRAS and BRAF gene mutations. However, transverse colon, ascending colon and cecum cancers were the most often affected by mutations.ConclusionsOur study showed that the occurrence of mutations in the KRAS, NRAS and BRAF genes is not accidental and depends on the location of CRC tumors.     

Inhibition of aminophylline-induced convulsions in mice by antiepileptic drugs and other agents

Common antiepileptic drugs and agents affecting different neurotransmitter systems were studied against aminophylline (280 mg/kg i.p.)-induced convulsions in mice. All drugs and agents were administered i.p. Diazepam and phenobarbital antagonized the whole seizure pattern and the respective ED50 values for the clonic phase were 3.5 and 62 mg/kg. Valproate at 500 mg/kg protected fewer than 50% of mice against the clonic phase. The remaining antiepileptics (acetazolamide, up to 1,000 mg/kg; carbamazepine and diphenylhydantoin, up to 50 mg/kg; ethosuximide, 500 mg/kg and trimethadione, 400 mg/kg) were totally ineffective in this respect. Propranolol (up to 20 mg/kg), baclofen (20 mg/kg), gamma-hydroxybutyric acid (300 mg/kg), aminooxyacetic acid (20 mg/kg), clonidine (up to 0.2 mg/kg), ketamine (30 mg/kg), atropine (20 mg/kg), papaverine (50 mg/kg) and L-phenylisopropyladenosine (2 mg/kg) did not affect the clonic phase either. Only antagonists of N-methyl-D-aspartic acid excitation, 2-amino-5-phosphonopentanoic acid and 2-amino-7-phosphonoheptanoic acid afforded protection against aminophylline-induced clonic seizure activity. The results show that aminophylline convulsions are relatively resistant to antiepileptic drugs and suggest that antagonists of excitatory transmission are potential antiaminophylline drugs.     

Comparison of different lymph node staging systems for predicting prognosis in patients with colon cancer who have undergone surgical resection

At present, the most widely used lymph node (LN) staging system in colon cancer is number of metastatic LNs in pathological assessment (pN) from the 8th edition of the TNM American Joint Committee on Cancer/Union for International Cancer Control staging system, which considers the number of metastatic LNs, omitting the total number of dissected LNs. The aim of the present study was to compare the prognostic performance of pN with alternative LN staging systems, including LN ratio (LNR) and log odds of positive LNs (LODDS). The clinical and histopathological data of 298 patients with colon cancer who underwent elective surgical resection in a single surgical centre were analysed. LNR and LODDS cut-off values according to two previous studies were selected to separate patients into different subgroups. Univariate and multivariate analyses were performed to distinguish prognostic factors. The three-step multivariate analysis showed that LNR was a superior prognostic indicator compared with pN and LODDS. Additionally, the Akaike Information Criterion, a measure of the relative quality of statistical models, confirmed that LNR displayed the best prognostic performance. Similarly, in a subpopulation of patients with number of dissected LNs (NDLN) ≥12, LNR was the most accurate LN staging system in relation to prognosis. In a subpopulation with NDLN <12, there was no significant difference in LN classification prognosis of 5-year overall survival; however, LNR and LODDS were more independent of NDLN than pN. Among the three LN classifications, LNR is the most accurate LN staging system for predicting prognosis for patients with colon cancer who have undergone surgical resection, particularly those with metastatic LNs subjected to adequate lymphadenectomy.     

Acknowledging the use of human cadaveric tissues in research papers: Recommendations from anatomical journal editors

Research within the anatomical sciences often relies on human cadaveric tissues. Without the good will of these donors who allow us to use their bodies to push forward our anatomical knowledge, most human anatomical research would come to a standstill. However, many research papers omit an acknowledgement to the donor cadavers or, as no current standardized versions exist, use language that is extremely varied. To remedy this problem, 20 editors‐in‐chiefs from 17 anatomical journals joined together to put together official recommendations that can be used by authors when acknowledging the donor cadavers used in their studies. The goal of these recommendations is to standardize the writing approach by which donors are acknowledged in anatomical studies that use human cadaveric tissues. Such sections in anatomical papers will not only rightfully thank those who made the donation but might also encourage, motivate, and inspire future individuals to make such gifts for the betterment of the anatomical sciences and patient care.     

Die Altersbestimmung menschlicher Früchte und ihre gerichtsmedizinische Anwendung

Zusammenfassung Obwohl man sich bereits seit langer Zeit bemüht hat, Methoden zu finden, um das Alter menschlicher Früchte genau bestimmen zu können, ist dieses Ziel bis jetzt noch nicht erreicht worden, da der Zeitpunkt des Eintritts der Befruchtung nicht festzulegen ist. Wir haben erkannt, daß die Schwankungsbreite des Entwicklungszustandes der Frucht in den einzelnen Stadien bedeutend ist. Diese Schwankungsbreite ist ausgezeichnet inZangemeisters (1912) Tabellen dargestellt.