Ecteinascidin-743, a new marine natural product with potent antitumor activity on human ovarian carcinoma xenografts

The antitumor activity of ecteinascidin (ET)-743, a novel marine natural product, was evaluated against a panel of human ovarian carcinoma xenografts characterized by different malignant behaviors and drug responsiveness in nude mice. These tumor models included three xenografts transplanted s.c. (HOC18, HOC22-S, and MNB-PTX-1) into nude mice, representing different levels of sensitivity to cisplatinum (DDP), which was used as reference drug for ovarian carcinoma, and two other xenografts (HOC22 and HOC8), which are highly malignant in the peritoneal cavity of nude mice, representing the growth pattern of this neoplasm. At the maximum tolerated dose of 0.2 mg/kg using an intermittent schedule of one i.v. injection every 4 days, ET-743 was highly active against HOC22-S (sensitive to DDP), inducing long-lasting, complete regressions, and against HOC18 (marginally sensitive to DDP), inducing partial tumor regressions. Moreover, significant growth delay was observed in mice bearing late-stage HOC18 tumor (400-mg tumor weight; nonresponsive to DDP). ET-743, however, was not active against MNB-PTX-1, a tumor that is highly resistant to chemotherapy, including DDP. In the i.p. ovarian carcinoma xenograft model, ET-743 at the maximum tolerated dose induced complete tumor remissions in all mice bearing HOC22 tumor, with 25% histopathologically confirmed cures, and produced marginal tumor growth delay against HOC8. These results indicate that ET-743 is a potent drug against ovarian carcinoma xenografts, being equally as active or more efficacious than DDP in the same tumor line. Our findings with human ovarian carcinoma xenografts justify clinical assessment of this drug with this tumor target.     

Metabotropic glutamate receptor agonists stimulate polyphosphoinositide hydrolysis in primary cultures of rat hepatocytes

In phytohemagglutinin (PHA) activated human peripheral blood mononuclear cells. [3H]thymidine uptake and interferon gamma production were increased by the delta-opioid receptor agonist, deltorphin-I (10(-14)-10(-10) M) and by the delta-opioid antagonist naltrindole (10(-13)-10(-9) M). Combination of 10-9 M naltrindole with deltrophin-I (10(-12)-10(-8)M) significantly inhibited the proliferative response but did not affect interferon production.     

Blockage of insulin-like growth factor-I receptor inhibits the growth of Ewing's sarcoma in athymic mice

Innovative, more effective treatment modalities are needed for Ewing's sarcoma (ES), a neoplasm with a disappointingly low survival rate despite the use of aggressive multimodal therapeutic approaches. We have previously shown (K. Scotlandi et al, Cancer Res., 56: 4570-4574, 1996) the existence and the pathogenetic relevance of an autocrine loop that is mediated by the insulin-like growth factor-I receptor (IGF-IR) and is crucial for the survival and proliferation of ES cells in vitro. In this study, we report that the IGF-IR-blocking monoclonal antibody alphaIR3 may also significantly inhibit ES cell growth in vivo. In particular, in almost one-half of the animals tested, after s.c. inoculation with TC-71 ES cells, the blockage of IGF-IR by alphaIR3 induced a complete regression of tumors that developed, which suggests that IGF-IR is valuable as a specific target for novel therapeutic strategies. In addition, suramin, a drug that can interfere with growth factor binding with their receptors, inhibited the tumorigenic and the metastatic ability of TC-71 cells and, therefore, is a promising agent to be combined with conventional cytotoxic drugs for the design of more effective therapeutic regimens.     

Gas sensors for air quality monitoring: realisation and characterisation of undoped and noble metal-doped SnO2 thin sensing films deposited by the pulsed laser ablation

Undoped and noble metal-doped very thin SnO₂ sensing layers deposited by the pulsed laser ablation (PLA) technique upon micromachined Si substrate heater elements have been extensively characterised. The main objective behind the effort carried out in this work has been the challenging perspective to define a sensing layer technology and a sensor operating mode (continuous (DC) vs. pulsed temperature (PT) mode) which allows the long term measuring and the easy discrimination of very low concentration of benzene by an interfering species like carbon monoxide, both present in the outdoor air. The experimental results reported in this work have shown that combining the sensor technology with a suitable catalytic element (in the present case, gold) and a proper sensor operating mode, very low concentration of benzene can be revealed with a sufficient selectivity towards CO. One of the major problems encountered during the long term test of the sensors has been the loss of the sensitivity to benzene with the time. An attempt has been made to explain the reason of this experimental result. We firmly believe that many factors contribute to it. Among them, the annealing of point defects associated with the oxygen vacancies as well as the loss of the catalytic efficiency by the added Au layer as effect of a possible coalescence of the metal clusters at the sensor working temperature (T400°C). To partially reduce the cluster mobility and to preserve the benzene sensitivity, the last assumption would suggest to operate the sensors, no matter if in DC or in PT mode, at a temperature lower than that used in this work.     

Influence of temperature and concentration on thermophysical properties of yellow mombin (Spondias mombin, L.)

Thermal conductivity, thermal diffusivity, and density of yellow mombin juice were determined at 8.8–49.4 °Brix and at temperature from 0.4 to 77.1 °C. Apparent viscosity was also measured between 7.8 and 30 °Brix and at temperature from 0 to 60 °C. Yellow mombin juice was produced from fruits of two different batches and the concentration process was performed using a roto evaporator or a rising film evaporator, single effect, with recirculation, under vacuum, to obtain concentrated juice. In order to obtain different concentrations, concentrated juice was diluted with distilled water. Multiple regression analysis was performed to fit thermal conductivity, thermal diffusivity and density experimental data obtaining a good fit. Arrhenius and power law relationships were proposed to fit apparent viscosity as a function of temperature and juice concentration at typical shear rates found during processing. The rheological parameters together with experimental values of pressure loss in tube flow were used to calculate friction factors, which were compared to those resulting from theoretical equation.     

Automatic measurement system for degradation analysis in thin-filmAlCu metallizations

Microelectronic devices are required to have high reliability when subjected to stresses within the maximum ratings. Nevertheless, in multilayered integrated circuits (ICs) several degradation phenomena can generate failures. In this paper, the degradation process in thin-film AlCu metallizations by means of the thermal stress test is taken into account. To this aim, an automatic measurement system with programmable performances is designed and realized in order to induce thermal degradation and compute data. The measurement system can be easily replicated with simple equipment and user-friendly LabView software     

Splitting visual space with attention.

The present study aimed at showing a spatial compatibility effect (and, by implication, a right–left subdivision of space) solely attributable to the orienting of attention. Five groups of 8 normal Ss were required to give right–left discriminative responses to stimuli presented within one of 6 empty boxes arranged in a horizontal row. Reaction times and errors were recorded. A right–left grouping of the boxes occurred regardless of whether Ss' fixation was kept at the intermediate position (Exp 1) or at one extremity (Exp 2) of the row. In Exps 3 and 4, Ss' attention was not aligned with a fixed position but was moved, through peripheral cues, from trial to trial and positioned between different pairs of adjacent boxes. Results showed that the display was again subdivided into 2 regions and that the reference point for the right–left subdivision was the focus of attention. In Exp 5, eye position was instrumentally monitored, and Ss' attention was directed by central cues. The results confirmed that the focusing of attention leads to a right–left partitioning of space. Directing attention to a position in space brings about a right–left perceptual organization that predominates over that provided by the other egocentric reference axes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electron transfer and ligand binding in terminal oxidases. Impact of recent structural information

A consensus structure for the active site of terminal oxidases has been recently proposed by Hosler et al. [(1993) J. Bioenerg. Biomem. 25, 121-135]. We exploit the novel structural information to propose a hypothesis for the large difference in the rate of internal electron transfer found when experiments are started either with the reduced or with the oxidized enzyme. This rationale also allows us to discuss the oxidation state of the prevailing oxygen reacting species with reference to the concentration of the two substrates (oxygen and cytochrome c) and to the structural state of the oxidase.