Effects of Ectopic Expression of NGAL on Doxorubicin Sensitivity
Authors: Chappell, William H.; Abrams, Stephen L.; Montalto, Giuseppe; Cervello, Melchiorre; Martelli, Alberto M.; Candido, Saverio; Libra, Massimo; Polesel, Jerry; Talamini, Renato; Arlinghaus, Ralph; Steelman, Linda S.; McCubrey, James A.
Neutrophil gelatinase-associated lipocalin (NGAL, a.k.a Lnc2) is a member of the lipocalin family which has diverse roles including stabilizing matrix metalloproteinase-9 from auto-degradation and as siderocalins which are important in the transport of iron. NGAL also has important biological functions involved in immunity and inflammation as well as responses to kidney damage. NGAL expression has also been associated with certain neoplasia and is important in the metastasis of breast cancer. Many advanced cancer patients have elevated levels of NGAL in their urine and it has been proposed that NGAL may be a prognostic indicator for certain cancers (e.g. breast, brain, and others). NGAL expression is detected in response to various chemotherapeutic drugs including doxorubicin and docetaxel. We were interested in the roles of NGAL expression in cancer and whether it is associated with chemotherapeutic drug resistance. In the present study, we investigated whether increased NGAL expression led to resistance to the chemotherapeutic drug doxorubicin in normal breast epithelial cells (MCF-10A), breast cancer cells (MCF-7), and colorectal cancer cells (HT-29). We infected the various cell lines with a retrovirus encoding NGAL which we constructed. Increased NGAL expression was readily detected in the NGAL-infected cells but not the empty vector-infected cells. However, increased NGAL expression did not alter the sensitivity of the cells to the chemotherapeutic drug doxorubicin. Thus, although NGAL expression is often detected after chemotherapeutic drug treatment, it by itself, does not lead to doxorubicin resistance.
The neural basis of analogical reasoning: An event-related potential study
Authors: Qiu, Jiang; Li, Hong; Chen, Antao; Zhang, Qinglin
The spatiotemporal analysis of brain activation during the execution of easy analogy (EA) and difficult analogy (DA) tasks was investigated using high-density event-related brain potentials (ERPs). Results showed that reasoning tasks (schema induction) elicited a more negative ERP deflection (N500-1000) than did the baseline task (BS) between 500 and 1000 ms. Dipole source analysis of difference waves (EA-BS and DA-BS) indicated that the negative components were both localized near the left thalamus, possibly associated with the retrieval of alphabetical information. Furthermore, DA elicited more positive ERP component (P600-1000) than did EA in the same time window. Two generators of P600-1000 were located in the medial prefrontal cortex (BA10) and the left frontal cortex (BA6)which was possibly involved in integrating information in schema abstraction. In the stage of analogy mapping, a greater negativity (N400-600) in the reasoning tasks as compared to BS was found over fronto-central scalp regions. A generator of this effect was located in the left fusiform gyrus and was possibly related to associative memory and activation of schema. Then, a greater negativity in the reasoning tasks, in comparison to BS task, developed between 900-1200 ms (LNC1) and 2000-2500 ms (LNC2). Dipole source analysis (EA-BS) localized the generator of LNC1 in the left prefrontal cortex (BA 10) which was possibly related to mapping the schema to the target problem, and the generator of LNC2 in the left prefrontal cortex (BA 9) which was possibly related to deciding whether a conclusion Correctly follows from the schema. (C) 2008 Elsevier Ltd. All rights reserved.