PTEN as a Prognostic and Predictive Marker in Postoperative Radiotherapy for Squamous Cell Cancer of the Head and Neck

BACKGROUND: Tumor suppressor PTEN is known to control a variety of processes related to cell survival, proliferation, and growth. PTEN expression is considered as a prognostic factor in some human neoplasms like breast, prostate, and thyroid cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study we analyzed the influence of PTEN expression on the outcome of a randomized clinical trial of conventional versus 7-days-a-week postoperative radiotherapy for squamous cell cancer of the head and neck. The patients with cancer of the oral cavity, oropharynx, and larynx were randomized to receive 63 Gy in fractions of 1.8 Gy given 5 days a week (CF) or 7 days a week (p-CAIR). Out of 279 patients enrolled in the study, 147 paraffin blocks were available for an immunohistochemical assessment of PTEN. To evaluate the prognostic value of PTEN expression and the effect of fractionation relative to PTEN, the data on the outcome of a randomized clinical trial were analyzed. Tumors with a high intensity of PTEN staining had significant gain in the loco-regional control (LRC) from p-CAIR (5-year LRC 92.7% vs. 70.8%, for p-CAIR vs. CF, p = 0.016, RR = 0.26). By contrast, tumors with low intensity of PTEN did not gain from p-CAIR (5-year LRC 56.2% vs. 47.2%, p = 0.49, RR = 0.94). The intensity of PTEN highly affected the LRC in a whole group of 147 patients (5-year LRC 80.9% vs. 52.3% for high vs. low PTEN, p = 0.0007, RR = 0.32). In multivariate Cox analysis, including neck node involvement, EGFR, nm23, Ki-67, p53, cyclin D1, tumor site and margins, PTEN remained an independent predictor of LRC (RR = 2.8 p = 0.004). CONCLUSIONS/SIGNIFICANCE: These results suggest that PTEN may serve as a potent prognostic and predictive marker in postoperative radiotherapy for high-risk squamous cell cancer of the head and neck

<i>De novo</i> design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy

Despite efforts for over 25 years, de novo protein design has not succeeded in achieving the TIM-barrel fold. Here we describe the computational design of 4-fold symmetrical (β/α)(8)-barrels guided by geometrical and chemical principles. Experimental characterization of 33 designs revealed the importance of sidechain-backbone hydrogen bonding for defining the strand register between repeat units. The X-ray crystal structure of a designed thermostable 184-residue protein is nearly identical with the designed TIM-barrel model. PSI-BLAST searches do not identify sequence similarities to known TIM-barrel proteins, and sensitive profile-profile searches indicate that the design sequence is distant from other naturally occurring TIM-barrel superfamilies, suggesting that Nature has only sampled a subset of the sequence space available to the TIM-barrel fold. The ability to de novo design TIM-barrels opens new possibilities for custom-made enzymes

Update on diffusion MRI in Parkinson's disease and atypical parkinsonism

Item does not contain fulltextDifferentiating Parkinson's disease (PD) from other types of neurodegenerative atypical parkinsonism (AP) can be challenging, especially in early disease stages. Routine brain magnetic resonance imaging (MRI) can show atrophy or signal changes in several parts of the brain with fairly high specificity for particular forms of AP, but the overall diagnostic value of routine brain MRI is limited. In recent years, various advanced MRI sequences have become available, including diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI). Here, we review available literature on the value of diffusion MRI for identifying and quantifying different patterns of neurodegeneration in PD and AP, in relation to what is known of underlying histopathologic changes and clinical presentation of these diseases. Next, we evaluate the value of diffusion MRI to differentiate between PD and AP and the potential value of serial diffusion MRI to monitor disease progression. We conclude that diffusion MRI may quantify patterns of neurodegeneration which could be of additional value in clinical use. Future prospective clinical cohort studies are warranted to assess the added diagnostic value of diffusion MRI

Influence of plant composition on methane emision from Moszne peatland

Methane is the second most important man-made greenhouse gas after carbon dioxide. For more than the last 20 years the increase of the rate of CH4 emission has been varying dramatically each year. This trend is common worldwide, though in different parts of the world unevenly intense, conditioned by the amount of emissions from natural and anthropogenic sources. Peatland ecosystems are one of the natural methane emitters, responsible for about 24% of the total CH4 emissions. Methane emission from wetlands is the balance between the processes of methanogenesis and methanotrophy with an active role of wetlands plants composition. Participation of vegetation in the reduction the emissions by 30-35% was confirmed. Association of methanotrophic bacteria with plants has been already recognized by Raghoebarsing and colleagues, who showed that methanotrophic bacteria, as endosymbionts and epibionts, live both inside and outside the cells of Sphagnum sp. The main aim of this study was to estimate methane emissions from Moszne peatland, dominated by: Sphagnum sp., Eriophorum vaginatum, Carex nigra and Vaccinium uliginosum

Zróżnicowany wpływ inhibitorów polarnego transportu auksyny na ukorzenianie niektórych gatunków z rodziny Crassulaceae

Effects of auxin polar transport inhibitors, 2,3,5-triiodobenzoic acid (TIBA), 1-N-naphthylphthalamic acid (NPA) and methyl 2-chloro-9-hydroxyfluorene-9-carboxylate (morphactin IT 3456), as a lanolin paste, on root formation in cuttings of some species of Crassulaceae, such as Bryophyllum daigremontianum, B. calycinum, Kalanchoe blossfeldiana and K. tubiflora, were studied. Cuttings of these plants were easily rooted in water without any treatment. TIBA and morphactin IT 3456 completely inhibited root formation in the cuttings of these plants but NPA did not when these inhibitors were applied around the stem below the leaves. When TIBA and morphactin were applied around the stem near the top, but leaves were present below the treatment, the root formation was observed in B. calycinum and K. blossfeldiana but in a smaller degree than in control cuttings. These results strongly suggest that endogenous auxin is required for root formation in cuttings of Crassulaceae plants. The differential mode of action of NPA is discussed together with its effect on auxin polar transport.Badano wpływ inhibitorów polarnego transportu auksyny, kwasu 2,3,5-trójjodobenzoesowego (TIBA), kwasu 1-N-naftyloftalamowego (NPA) i morfaktyny, kwasu metylo 2-chloro-9-hydroksy-fluoreno-karboksylowego (IT 3456), na tworzenie korzeni w sadzonkach niektórych gatunków Crassulaceae, Brophyllum daigremontianum, B. calycinum, Kalanchoe blossfeldiana i K. tubiflora. Sadzonki tych gatunków łatwo się ukorzeniają w wodzie bez dodatkowego traktowania. Stwierdzono, że TIBA i morfaktyna całkowicie hamują tworzenie się korzeni, kiedy inhibitory były zastosowane w paście lanolinowej na łodydze poniżej liści. Kiedy TIBA i morfaktynę u B. calycinum i K. blossfeldiana podano wokół łodygi przy wierzchołku, a liście na łodydze były poniżej traktowania, korzenie tworzyły się ale w mniejszym stopniu niż w roślinach nietraktowanych. Otrzymane wyniki sugerują, że endogenna auksyna jest niezbędna dla tworzenia się korzeni w sadzonkach roślin z rodziny Crassulaceae. Zróżnicowane działanie NPA w porównaniu z TIBA i morfaktyną na ukorzenianie jest dyskutowane z różnym wpływem oddziaływania NPA na polarny transport auksyny