Cilengitide: an RGD pentapeptide ανβ3 and ανβ5 integrin inhibitor in development for glioblastoma and other malignancies

Cilengitide, a cyclicized arginine-glycine-aspartic acid-containing pentapeptide, potently blocks ανβ3 and ανβ5 integrin activation. Integrins are upregulated in many malignancies and mediate a wide variety of tumor-stroma interactions. Cilengitide and other integrin-targeting therapeutics have preclinical activity against many cancer subtypes including glioblastoma (GBM), the most common and deadliest CNS tumor. Cilengitide is active against orthotopic GBM xenografts and can augment radiotherapy and chemotherapy in these models. In Phase I and II GBM trials, cilengitide and the combination of cilengitide with standard temozolomide and radiation demonstrate consistent antitumor activity and a favorable safety profile. Cilengitide is currently under evaluation in a pivotal, randomized Phase III study (Cilengitide in Combination With Temozolomide and Radiotherapy in Newly Diagnosed Glioblastoma Phase III Randomized Clinical Trial [CENTRIC]) for newly diagnosed GBM. In addition, randomized controlled Phase II studies with cilengitide are ongoing for non-small-cell lung cancer and squamous cell carcinoma of the head and neck. Cilengitide is the first integrin inhibitor in clinical Phase III development for oncology

Qualität des Weidefutters in der ökologischen Milchviehhaltung

Grazing of dairy cows is mandatory in organic farming. However, as in conventional farming there is a tendency to increase milk yield per cows by employing other feeding strategies than grazing. On-farm research was initiated on organic dairy farms in Lower Saxony to investigate the current practice of grassland utilization and dairy husbandry and to explore the potential of grazing for milk production. The results show that with an increased focus on grazing of dairy cows there is considerable room for more milk being produced from grazed grass. An in-depth analysis of the spatio-temporal pattern of the quality of the herbage on offer revealed steadily high net energy and protein concentrations almost irrespective of the sward botanical composition and the season of sampling. Research is needed to improve grazing management strategies in organic farming to make better use of the high potential of grazed grasslands and thereby increase the sustainability of milk production

P33. Expression of alpha v beta 3 integrin in patients with high and low grade glioma

Fuente Fuente, Carlos;Puig-Pey, J.;Buenaño Pastor, Manue

Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy†

Background This prospective multicenter study assessed the prognostic influence of the extent of resection when compared with biopsy only in a contemporary patient population with newly diagnosed glioblastoma. Patients and methods Histology, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and clinical data were centrally analyzed. Survival analyses were carried out with the Kaplan-Meier method. Prognostic factors were assessed with proportional hazard models. Results Of 345 patients, 273 underwent open tumor resection and 72 biopsies; 125 patients had gross total resections (GTRs) and 148, incomplete resections. Surgery-related morbidity was lower after biopsy (1.4% versus 12.1%, P = 0.007). 64.3% of patients received radiotherapy and chemotherapy (RT plus CT), 20.0% RT alone, 4.3% CT alone, and 11.3% best supportive care as an initial treatment. Patients ≤60 years with a Karnofsky performance score (KPS) of ≥90 were more likely to receive RT plus CT (P < 0.01). Median overall survival (OS) (progression free survival; PFS) ranged from 33.2 months (15 months) for patients with MGMT-methylated tumors after GTR and RT plus CT to 3.0 months (2.4 months) for biopsied patients receiving supportive care only. Favorable prognostic factors in multivariate analyses for OS were age ≤60 years [hazard ratio (HR) = 0.52; P < 0.001], preoperative KPS of ≥80 (HR = 0.55; P < 0.001), GTR (HR = 0.60; P = 0.003), MGMT promoter methylation (HR = 0.44; P < 0.001), and RT plus CT (HR = 0.18, P < 0.001); patients undergoing incomplete resection did not better than those receiving biopsy only (HR = 0.85; P = 0.31). Conclusions The value of incomplete resection remains questionable. If GTR cannot be safely achieved, biopsy only might be used as an alternative surgical strateg

Challenging fear: Chemical alarm signals are not causing morphology changes in crucian carp (Carassius carassius)

Crucian carp develops a deep body in the presence of chemical cues from predators, which makes the fish less vulnerable to gape-limited predators. The active components originate in conspecifics eaten by predators, and are found in the filtrate of homogenised conspecific skin. Chemical alarm signals, causing fright reactions, have been the suspected inducers of such morphological changes. We improved the extraction procedure of alarm signals by collecting the supernatant after centrifugation of skin homogenates. This removes the minute particles that normally make a filtered sample get turbid. Supernatants were subsequently diluted and frozen into ice-cubes. Presence of alarm signals was confirmed by presenting thawed ice-cubes to crucian carp in behaviour tests at start of laboratory growth experiments. Frozen extracts were added further on three times a week. Altogether, we tested potential body-depth-promoting properties of alarm signals twice in the laboratory and once in the field. Each experiment lasted for a minimum of 50&nbsp;days. Despite growth of crucian carp in all experiments, no morphology changes were obtained. Accordingly, we conclude that the classical alarm signals that are releasing instant fright reactions are not inducing morphological changes in this species. The chemical signals inducing a body-depth increase are suspected to be present in the particles removed during centrifugation (i.e., in the precipitate). Tissue particles may be metabolized by bacteria in the intestine of predators, resulting in water-soluble cues. Such latent chemical signals have been found in other aquatic organisms, but hitherto not reported in fishe

Leaching as a pretreatment process to complement torrefaction in improving co-firing characteristics of Jatropha curcas seed cake

The presence of certain inorganic elements in biomass causes issues such as slagging, fouling and corrosion when co-firing with coal for power generation. In this work, the efficacy of leaching to remove these elements from Jatropha curcas seed cake was investigated. Leaching of both untorrefied and torrefied seed cakes was carried out in Milli-Q water at temperatures of 20, 35 and 50 °C. At 20 °C, the two critical elements, potassium and chlorine, decreased by as much as 85 and 97 %, respectively. Leaching at higher temperatures was only beneficial for the more intensely torrefied biomass, since they were more resistant to leaching. The electrical conductivity and ion content of the leachates were measured, as were the inorganic elemental content, dry ash content, volatile matter content and higher heating value (HHV) of the solid seed cake. A secondary benefit of the leaching was an increase in the HHV by up to 10 %

Public-policy responsibilities in a restructured electricity industry

In this report, we identify and define the key public-policy values, objectives, and actions that the US electricity industry currently meets. We also discuss the opportunities for meeting these objectives in a restructured industry that relies primarily on market forces rather than on government mandates. And we discuss those functions that governments might undertake, presumably because they will not be fully met by a restructured industry on its own. These discussions are based on a variety of inputs. The most important inputs came from participants in an April 1995 workshop on Public-Policy Responsibilities and Electric Industry Restructuring: Shaping the Research Agenda. Other sources of information and insights include the reviews of a draft of this report by workshop participants and others and the rapidly growing literature on electric-industry restructuring and its implications. One of the major concerns about the future of the electricity industry is the fate of numerous social and environmental programs supported by today`s electric utilities. Many people worry that a market-driven industry may not meet the public-policy objectives that electric utilities have met in the past. Examples of potentially at-risk programs include demand-side management (DSM), renewable energy, low-income weatherization, and fuel diversity. Workshop participants represented electric utilities, public utility commissions (PUCs), state energy offices, public-interest groups, other energy providers, and the research community

Cervicothoracic Intradural Arachnoid Cyst Misdiagnosed as Motor Neuron Disease

Recognizing syndromes which mimic ALS is crucial both to avoid giving this diagnosis erroneously and since there may be appropriate treatments. We report a 63-year-old woman diagnosed with possible ALS five years ago based on upper and lower motor neuron signs with typical electrophysiology and normal cranial MRI. At reassessment, spinal MRI revealed a cervicothoracic cyst with cord compression that was successfully treated neurosurgically. Histopathology confirmed an arachnoid origin as suspected from MRI. Spinal cysts may mimic ALS and need to be thoroughly excluded by appropriate imaging

A Life Cycle Analysis System to Support D and D, Pollution Prevention, and Asset Recovery

This paper describes a life cycle analysis system (LCAS) developed to support US Department of Energy (DOE) decision-making regarding deactivation and decommissioning (D and D), pollution prevention (P2), and asset recovery, and its deployment to analyze the disposition of facilities and capital assets. Originally developed for use at the Oak Ridge East Tennessee Technology Park, this approach has been refined through application at Ohio Operations Office sites and is now being deployed at a number of DOE sites. Programs such as National Metals Recycle, the D and D Focus Area, P2, and Asset Utilization are successfully using the system to make better decisions resulting in lower cost to the taxpayer and improved environmental quality. The LCAS consists of a user-friendly, cost-effective, and analytically-sound decision-aiding process and a complementary suite of automated tools to handle data administration and multiple criteria life cycle analysis (LCA). LCA is a systematic and comprehensive process for identifying, assessing, and comparing alternatives for D and D, P2, and asset recovery at government sites, and for selecting and documenting a preferred alternative. An LCA includes all of the impacts (benefits and costs) that result from a course of action over the entire period of time affected by the action. The system also includes visualizations that aid communication and help make decision-making transparent. The LCAS has three major components related to data collection, decision alternative assessment, and making the decisions. Each component is discussed in-depth using the example of deployment of the LCAS to support asset recovery

Persistence of the impact of the Hood River Conservation Project on typical and peak loads three years after weatherization

The Hood River Conservation Project (HRCP) was a major residential retrofit demonstration project, operated by Pacific Power & Light Company (Pacific Power) between 1984 and 1988, and funded by the Bonneville Power Administration (Bonneville). The project was designed to install as many cost-effective retrofit measures in as many electrically heated homes as possible in the community of Hood River, Oregon. The Pacific Power HRCP planners statistically selected a special group of 320 Hood River homes that represented a cross-section of the community. The end-use loads (electric space heating, electric water heating, and woodfuel space heating) and the interior temperatures of these homes were monitored for one year before weatherization and three years after weatherization. After more than four years of submetered data collection, 220 single-family, detached homes were available for analysis in the second load study. Weather was normalized for the four heating seasons by matching one day from the pre-program year with one day from each postretrofit year