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De Lima V.C.C.,Laboratorio Of Inflamacao E Cancer | De Carvalho A.F.,Laboratorio Of Genomica Funcional | Morato-Marques M.,Laboratorio Of Inflamacao E Cancer | Hashimoto V.L.,Laboratorio Of Inflamacao E Cancer | And 7 more authors.
Cytokine | Year: 2013

Background: Cutaneous melanoma displays high morbidity and mortality rates. Isolated limb perfusion with melphalan (Mel) is used for the treatment of non-resectable, locally advanced extremity melanomas. When combined with tumor necrosis factor alpha (TNF-alpha) treatment, the complete response varies between 70% and 90%. The mechanisms underlying the effects of Mel and TNF-alpha are not completely understood. We evaluated the impact of systemic Mel and TNF-alpha administration on tumor growth, analyzed the morphological changes promoted by each treatment, and identified early expressed genes in response to Mel and TNF-alpha treatment, either alone or in combination, in a murine melanoma model. Methods: Six- to eight-week-old male mice were subcutaneously inoculated with B16F10 melanoma cells and then intravenously injected with TNF-alpha, melphalan or a combination of both drugs when the tumors reached 1.0cm2. Tumor growth was monitored every other day, and histological analysis was performed when the tumors reached 3.0cm2. Total RNA was extracted from the resected tumors and submitted to amplification, labeling and hybridization on an oligonucleotide microarray (Fox Chase Cancer Center). Tumor growth and histological parameters were compared using ANOVA. Survival curves were calculated using the Kaplan-Meier method. Two-way ANOVA was used to identify differentially expressed genes among the various treatments, and Dunn's test was used for pair-wise comparisons. Results: Systemic administration of Mel impaired tumor growth (p<0.001), improved animal survival (p<0.001), and decreased mitotic rate (p= 0.049). Treatment with TNF-alpha alone had no impact, neither on tumor growth, nor on survival, but it increased necrosis (p<0.024) and decreased mitotic rates (p= 0.001) in the tumors. Combined treatment with Mel and TNF-alpha had similar effects in tumor growth, survival, necrosis and mitotic rate as observed with individual treatments. Moreover, 118 genes were found differentially expressed by microarray analysis and 10% of them were validated by RT- real time PCR. In our model we found that the treatments regulate genes that play important roles in tumorigenesis such as cell adhesion (Pard3, Pecam1, Ilk, and Dlg5), proliferation (Tcfe3 and Polr1e), cell motility (Kifap3, Palld, and Arhgef6), apoptosis (Bcl2l11), and angiogenesis (Flt1and Ptprj). Conclusions: Our data reproduces, in mice, some of the features observed in melanoma patients treated with the combination of Mel and TNF-alpha. The identification of genes with altered expression by these drugs both individually and in combination might help in the understanding of their mechanism of action and, as a consequence, improved strategies that could impact their clinical application. © 2013 Elsevier Ltd.

Salas A.,Autonomous University of Baja California | Diaz F.,Research Center Cientifica Educacion Superior Of Ensenada | Re A.D.,Research Center Cientifica Educacion Superior Of Ensenada | Galindosanchez C.E.,Laboratorio Of Genomica Funcional | And 5 more authors.
Journal of Shellfish Research | Year: 2014

The preferred temperature of Tegula regina was determined in a horizontal thermal gradient with organisms acclimated to 16°C, 19°C, and 22°C using to acute method, with a preferred temperature of 19.7 ± 1.8°C for the day cycle and 18.8 ± 1.2°C for the night cycle. The final preferred temperature determined for marine snails was 19.2 ± 1.5°C. The displacement velocity decreased to an interval from 99.1 cm/h to 62.5 cm/h. During the third hour, when organisms detected the preferred temperature, the velocity diminished gradually from 25.8 cm/h to 7.5 cm/h. Critical temperature maxima (CTMax), which refers to the temperature at which at least 50% of the experimental group displays a loss of attachment, was measured at three acclimation temperatures (16°C, 19°C, and 22°C). At the acclimation temperature (16°C), 50% of the experimental group had an attachment loss at a CTMax of 29.3°C. At a warmer acclimation temperature (22°C), the observed CTMax was 31.2°C. Marine snail oxygen consumption rate increased significantly (P < 0.05, 31%) from 16°C to 22°C.

Mangeon A.,Laboratorio Of Genomica Funcional | Junqueira R.M.,Laboratorio Of Genomica Funcional | Sachetto-Martins G.,Laboratorio Of Genomica Funcional
Plant Signaling and Behavior | Year: 2010

The first plant glycine-rich proteins (GRPs) have been isolated more than 20 years ago based on their specific expression pattern and/or modulation by several biotic and abiotic factors. This superfamily is characterized by the presence of a glycinerich domain arranged in (Gly)n-X repeats. The presence of additional motifs, as well as the nature of the glycine repeats, groups them in different classes. The diversity in structure as well as in expression pattern, modulation and sub cellular localization have always indicated that these proteins, although classified as members of the same superfamily, would perform different functions in planta. Only now, two decades later, with the first functional characterizations of plant GRPs their involvement in diverse biological and biochemical processes are being uncovered. Here, we review the so far ascribed functions of plant GRPs. © 2010 Landes Bioscience.

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