Cobalt-alkyne complexes are drugs with remarkable cytotoxicity. From the complexes tested up to now we selected the aspirin derivative [2-acetoxy-(2-propynyl)benzoate]hexacarbonyldicobalt (Co-ASS) as the lead compound. To get more insight into the mode of action, we systematically modified the alkyne ligand and determined the cytotoxic properties of the resulting cobalt complexes. Further investigations were performed on the drug lipophilicity, the cellular uptake into MCF-7 and MDA-MB 231 breast cancer cells, the DNA-binding efficacy, and the nuclear drug content. The ability to inhibit glutathione reductase and cyclooxygenase (COX) enzymes, the binding to the estrogen receptor, and the induction of apoptotic processes were examined for selected compounds. Interestingly, the most antitumor active compounds were potent COX inhibitors (COX-1 and COX-2). The presented results indicate that cobalt-alkyne complexes of the Co-ASS type, represent a new class of organometallic cytostatics with a mode of drug action in which COX inhibition probably plays a major role.

No abstract

The role of literal meaning during the construction of meaning that goes beyond pure literal composition was investigated by combining cross-modal masked priming and ERPs. This experimental design was chosen to compare two conflicting theoretical positions on this topic. The indirect access account claims that literal aspects are processed first, and additional meaning components are computed only if no satisfactory interpretation is reached. In contrast, the direct access approach argues that figurative aspects can be accessed immediately. We presented metaphors (These lawyers are hyenas, Experiment 1a and 1b) and producer-for-product metonymies (The boy read Böll, Experiment 2a and 2b) with and without a prime word that was semantically relevant to the literal meaning of the target word (furry and talented, respectively). In the presentation without priming, metaphors revealed a biphasic N400-Late Positivity pattern, while metonymies showed an N400 only. We interpret the findings within a two-phase language architecture where contextual expectations guide initial access (N400) and precede pragmatic adjustment resulting in reconceptualization (Late Positivity). With masked priming, the N400-difference was reduced for metaphors and vanished for metonymies. This speaks against the direct access view that predicts a facilitating effect for the literal condition only and hence would predict the N400-difference to increase. The results are more consistent with indirect access accounts that argue for facilitation effects for both conditions and consequently for consistent or even smaller N400-amplitude differences. This combined masked priming ERP paradigm therefore yields new insights into the role of literal meaning in the online composition of figurative language.

We report two experiments on the referential resolution of the German subject pronoun er and the demonstrative der ('he'). Using the visual world eye-tracking paradigm, we examined the effects of grammatical role, thematic role and the information status of potential referents in the antecedent clause operationalized by word-order (canonical/non-canonical), in the context of active-accusative verbs (Exp. 1) and dative-experiencer verbs (Exp. 2). In information-structurally neutral contexts, er prefers the proto-agent and der the protopatient. This suggests that agentivity is a better predictor for pronoun resolution than subjecthood or sentence topic as previously proposed. It further supports the claim that agentivity is a core property of language processing and it more generally substantiates the proposal from cognitive sciences that agentivity represents core knowledge of the human attentional system. With non-canonical antecedent clauses, because they lack alignment of prominence features, interpretive preferences become less stable, indicating that multiple cues are involved in pronoun resolution. The data further suggest that the demonstrative pronoun elicits more reliable interpretive biases than the personal pronoun.

Serum levels of vascular endothelial growth factor (VEGF-S) have been reported to correlate with tumor stage and prognosis in various human malignancies. The source of soluble VEGF in peripheral blood remains obscure. We therefore measured the concentration of immunoreactive VEGF in 241 serum samples and 61 plasma samples (VEGF-P) from 20 subjects undergoing myeloablative chemotherapy and from 3 normal platelet donors. A significant correlation between the peripheral blood platelet count (PC) and VEGF-S (r = 0.86) but not VEGF-P was found. VEGF-S levels were 58.43 ± 42.50 pg/ml (mean ± SD) in patients with a PC < 50 × 10⁹/l, 203.29 ± 176.56 pg/ml for a PC of 50–150 × 10⁹/l, and 457.42 ± 475.41 pg/ml for a PC > 150 × 10⁹/l. Interestingly, VEGF-P levels were substantially lower than the corresponding VEGF-S values, namely below the detection limit in most cases. Supernatants from platelet-rich plasma contained no VEGF, but after in vitro lysis of the platelets very high VEGF levels were found. The VEGF content per 10⁹ platelets was calculated at 2.51 ± 2.39 pg and was dependent on the mean platelet volume. In summary, VEGF release from platelets during blood clotting was found to be the main source of VEGF in serum samples. Cancer patients in clinical remission have negligible amounts of soluble VEGF in peripheral blood, and myeloablative chemotherapy causes a significant drop in VEGF-S levels corresponding to the decrease in PC. Thus, studies addressing the diagnostic and prognostic value of VEGF-S in cancer patients must be interpreted with caution. Our data provide the basis for predicting VEGF-S in relation to PC in vivo, and for reevaluating former studies of VEGF-S in patients with malignant or nonmalignant disease.

No abstract

In patients with carcinomatous meningitis, significant amounts of VEGF are released into CSF. This study yields preliminary evidence that VEGF in CSF may be a useful biologic marker for both the diagnosis and evaluation of treatment response in carcinomatous meningitis.

Personal pronouns and demonstratives contribute differently to the encoding of information in the mental model and they serve distinct backward- and forward-looking functions. While (unstressed) personal pronouns are the default means to indicate coreference with the most prominent discourse entity (backward-looking function) and typically mark the maintenance of the current topic, demonstratives are used to refer to a less prominent entity and serve the additional forward-looking function of signaling a possible topic shift. In Experiment 1, we present an ERP study that examines the time course of processing personal and d-pronouns in German (er vs. der) and assesses the impact of two prominence features of the antecedent, thematic role and sentential position, as well as neurophysiological correlates of backward- and forward-looking functions of referential expressions. We tested the comprehension of personal and d-pronouns following context sentences containing two potential antecedents. In addition to the factor pronoun type (er vs. der), we varied the verb type (active accusative verbs vs. dative experiencer verbs) and the thematic role order (canonical vs. non-canonical) in the context sentences to vary the antecedent's prominence. Time-locked to pronoun-onset, the ERPs revealed a general biphasic N400-Late Positivity for d-pronouns over personal pronouns with further subtle interactions of the prominence-lending cues in the early time window. The findings indicate that the calculation of the referential candidates' prominence (backward-looking function) is guided by thematic role and positional information. Thematic role information, in combination with initial position, thus represents a central predictor during referential processing. Coreference with a less prominent entity (assumed for d-pronouns) results in processing costs (N400). The additional topic shift signaled by d-pronouns (forward-looking function) results in attentional reorienting (Late Positivity). This is further supported by Experiment 2, a story continuation study, which showed that personal pronouns trigger topic maintenance, while d-pronouns yield topic shifts.