Multiscale seascape habitat of necto-benthic littoral species, application to the study of the dusky grouper habitat shift throughout ontogeny.

Describing the spatial patterns of benthic coastal habitats and investigating how those patterns affect the ecology of inhabiting species is a main objective of seascape ecology. Within this emerging discipline spatial scale is a principal topic. Different spatial scales inform on different characteristics of the habitat and therefore the relation between species and their habitats would be better defined when observed at multiple levels of spatial scale. Here we apply a multiscale seascape approach to investigate the habitat preferences of juvenile and adult individuals of dusky grouper (Epinephelus marginatus) in a Mediterranean marine protected area. Results show that the information obtained at different spatial scales is complementary, improving our capability to identify the preferred habitats and how it changes throughout ontogeny. These results show the relevance of implementing multiscale seascape ecology approaches to investigate the species-habitat relationships and to improve management and conservation of necto-benthic endangered top predators.

Differences in delta13C and delta15N stable isotopes in the pearly razorfish Xyrichtys novacula related to the sex, location and spawning period.

In the present study, Xyrichtys novacula (Labridae) were sampled at five locations around the islands of Ibiza and Formentera (western Mediterranean Sea). Isotopic signatures of delta13C, delta15N and the C:N ratio were analysed in relation to locality, sex and size differences. delta13C and delta15N partitioning was also studied in the reproductive spawning period. There were significant differences in the delta13C signature between localities for both sexes, but not for delta15N. Sex differences were also found with a mean +/-s.e. value of -17.38 +/- 0.06 per thousand delta13C and 8.36 +/- 0.05 per thousand delta(15)N for females and -17.17 +/- 0.07 per thousand delta13C and 8.80 +/- 0.06 per thousand delta15N for males. Increasing total length in both sexes was positively correlated with delta15N enrichment and a significant positive linear regression was established for both variables. During the reproductive spawning period, there were changes in delta13C fractioning with enrichment in postspawning females and males (with respect to prespawning and spawning periods) and delta(15)N impoverishment in postspawning females (with respect to prespawning and spawning periods). Xyrichtys novacula uses local food sources, as confirmed by delta(13)C and delta(15)N, and females and males use different food sources, thus avoiding intraspecific competition. This was confirmed by delta15N enrichment as size increased. Spawning leads to special requirements for gonad maturation, which is reflected in the isotopic signatures for both sexes.

Organic compounds temporal trends at some invertebrate species from the Balearics, Western Mediterranean.

Concentrations of persistent organic pollutants (POPs) such as hexachlorobenzene (HCB), dichlore diphenyl trichloretane (DDT), polychlorinated biphenyls (PCBs), and gamma-hexachlorocyclohexane (gamma-HCH or lindane) were determined in tissue of marine benthic invertebrates such as Mytilus galloprovincialis, Chamelea gallina, Venus verrucosa, Lithophaga lithophaga and Paracentrotus lividus. Species were selected due to their habitat, trophic level, feeding behaviour and their consumption. Invertebrate species were systematically sampled from December 1996 to December 2005 from several sites along the Balearic Islands. The highest concentrations of PCBs (785ng/g lipid) were found in M. galloprovincialis while the lowest concentrations were found in the sea-urchin P. lividus (193ng/g lipid). Among the 7 PCB quantified congeners the higher values are mainly obtained for CB138 and CB153. All bivalves presented higher PCBs contents than the sea-urchin P. lividus are possibly linked with the bioaccumulation process of POPs throughout the food web and to differential detoxifying mechanisms. The concentration of SigmaDDT exceeds that of HCB and gamma-HCH at all species and sampling stations. DDT concentrations ranged from 0.4ng/g ww at the bivalve C. gallina in 2002, to values of 15.8ng/g ww at the bivalve L. lithophaga in 1998. The values obtained for the organic compounds (HCH, HCB, PCBs, DDT) depend upon the place and year of sampling and are compared to values found by other authors for the mussel M. galloprovincialis in other Mediterranean areas. gamma-HCH and HCB were found in lower concentrations than the other POPs.

Prognostic factors in resectable pancreatic cancer: p53 and bcl-2.

The p53 tumor suppressor gene and the Bcl-2 proto-oncogene regulate cell cycle progression and apoptosis. We evaluated the expression of these molecular markers with standard pathologic prognostic variables in patients who received multimodality therapy for resectable adenocarcinoma of the pancreas to study the effect of p53 and Bcl-2 on survival duration. Immunohistochemical staining of archival material was performed to determine levels of expression of p53 and Bcl-2 proteins in 70 patients with adenocarcinoma of pancreatic origin. All patients underwent a potentially curative pancreaticoduodenectomy and standardized pathologic analysis of resected specimens. Potential pathologic and molecular prognostic variables were assessed for their effect on survival duration. Nuclear staining for p53 was observed in 33 (47%) of 70 specimens. Immunostaining for Bcl-2 was observed in 23 specimens (33%). A trend toward improved survival duration was seen in patients whose tumors stained positive for either p53 or Bcl-2. Negative staining for both markers predicted short survival (P = 0.01). By univariate and multivariate analyses, no single pathologic factor was associated with survival duration. Immunohistochemical staging using both p53 and Bcl-2 significantly predicted survival duration by univariate and multivariate analysis; patients whose tumors stained positively for p53 and/or overexpressed Bcl-2 had a significantly longer survival than those whose tumors stained negative for both proteins.

Tumor suppressor gene Smad4/DPC4, its downstream target genes, and regulation of cell cycle.

The tumor suppressor gene deleted in pancreatic cancer locus 4 (Smad4/DPC4) is inactivated in about 50% of pancreatic adenocarcinomas. The role of DPC4 in the transforming growth factor-beta (TGF-beta) receptor-mediated signal transduction cascade in human pancreatic, colon, and breast carcinoma cell lines has been investigated by a number of laboratories. The results demonstrate that Smad4/DPC4 protein functions as a key transcription factor required in regulation of TGF-beta inducible gene expression and subsequent growth inhibition. Many transcription regulators that are involved in cell growth, differentiation, and oncogenesis have been identified and cloned. Yet paradoxically, it is much more difficult to identify the important downstream target genes responsible for the biological effects elicited by these transcription factors. Although numerous attempts have been made and different approaches have been used to identify the target genes, only limited success has been achieved. Our data show that p21waf1 is one of the Smad4/DPC4-regulated downstream target genes and suggest that overexpression of the Smad4/DPC4 gene can bypass TGF-beta receptor activation and reestablish one of the key regulatory controls of cell proliferation. Identification of the Smad-regulated downstream target genes responsible for diverse biological processes that they control will extend our understanding of the mechanism for cell cycle regulation and cell differentiation.

Cell cycle regulation of human pancreatic cancer by tamoxifen.

BACKGROUND: Clinical trials have suggested a survival advantage for selected patients with metastatic pancreatic cancer treated with tamoxifen. We sought to identify the molecular mechanism by which tamoxifen inhibits human pancreatic cancer cell (HPCC) growth. METHODS: HPCCs were grown in tamoxifen and growth inhibition was determined by 3H-thymidine uptake and by the MTT assay; changes in cell viability were determined by cell counts. Cell cycle alterations were evaluated by FACS, and the induction of apoptosis was evaluated using the TUNEL assay. Total cellular RNA was isolated after tamoxifen treatment, and Northern blot analysis was performed for p21waf1. RESULTS: Tamoxifen inhibited HPCC growth as measured by inhibition of 3H-thymidine incorporation and by the MTT assay. However, there was no decrease in the total number of viable cells after 6 days of treatment with 10 microM of tamoxifen and no evident apoptosis, confirming the absence of a cytotoxic effect. Cell cycle analysis revealed cellular arrest in the G0/G1 phase, which correlated with p21waf1 mRNA upregulation in response to tamoxifen treatment. CONCLUSIONS: Tamoxifen inhibits HPCC growth by inducing G0/G1 arrest with an associated increase in p21waf1 mRNA expression. Tamoxifen is an effective inhibitor of HPCC growth in vitro and warrants further in vivo study.

Induction of p21waf1 expression and growth inhibition by transforming growth factor beta involve the tumor suppressor gene DPC4 in human pancreatic adenocarcinoma cells.

The tumor suppressor gene deleted in pancreatic cancer locus 4 (DPC4) is inactivated in about 50% of pancreatic adenocarcinomas. DPC4 was found to be homologous to Smad4 and may function as a transcription factor in the transforming growth factor beta (TGF-beta) receptor-mediated signal transduction pathway. We have investigated the role of DPC4 in the TGF-beta receptor-mediated signal transduction cascade in five human pancreatic cancer cell lines (Panc-1, MDAPanc-28, HS766T, Capan-1, and MiaPaCa-2). Our results demonstrate that the loss of responsiveness to TGF-beta-induced growth inhibition correlates with the loss of expression of DPC4. We have shown that TGF-beta induces p21waf1 expression in Panc-1 cells, whereas no induction of p21waf1 expression by TGF-beta was detected in the other four cell lines lacking either DPC4 expression or the TGF-beta type II receptor. No increase in p21waf1 mRNA stability was observed after treatment with TGF-beta, which suggests that the induction of p21waf1 in Panc-1 cells is transcriptionally regulated by TGF-beta. Our data also demonstrate that the expression of DPC4 is directly involved in TGF-beta-mediated induction of the 3TP-lux reporter gene, which contains a known TGF-beta-inducible plasminogen activator inhibitor promoter. These data suggest that: (a) TGF-beta-mediated induction of p21waf1 and subsequent growth inhibition require the expression of DPC4; (b) p21waf1 is a downstream target gene of DPC4; and (c) transfection of the DPC4 gene restores the TGF-beta-inducible gene expression. Inactivation of the tumor suppressor gene DPC4 and other components of the TGF-beta signal cascades may abolish one of the key negative controls of cell proliferation in pancreatic adenocarcinomas.

Peroxisomal fatty acid oxidation and inhibitors of the mitochondrial carnitine palmitoyltransferase I in isolated rat hepatocytes.

Fatty acid oxidation was studied in the presence of inhibitors of carnitine palmitoyltransferase I (CPT I), in normal and in peroxisome-proliferated rat hepatocytes. The oxidation decreased in mitochondria, as expected, but in peroxisomes it increased. These two effects were seen, in variable proportions, with (+)-decanoylcarnitine, 2-tetradecylglycidic acid (TDGA) and etomoxir. The decrease in mitochondrial oxidation (ketogenesis) affected saturated fatty acids with 12 or more carbon atoms, whereas the increase in peroxisomal oxidation (H2O2 production) affected saturated fatty acids with 8 or more carbon atoms. The peroxisomal increase was sensitive to chlorpromazine, a peroxisomal inhibitor. To study possible mechanisms, palmitoyl-, octanoyl- and acetyl-carnitine acyltransferase activities were measured, in homogenates and in subcellular fractions from control and TDGA-treated cells. The palmitoylcarnitine acyltransferase was inhibited, as expected, but the octanoyltransferase activity also decreased. The CoA derivative of TDGA was synthesized and tentatively identified as being responsible for inhibition of the octanoylcarnitine acyltransferase. These results show that inhibitors of the mitochondrial CPT I may also inhibit the peroxisomal octanoyl transferase; they also support the hypothesis that the octanoyltransferase has the capacity to control or regulate peroxisomal fatty acid oxidation.

[Radiation enteritis: the results of surgical treatment]. / Enteritis actínica: resultados del tratamiento quirúrgico.

We reviewed the results of surgical therapy for radiation enteropathy in 18 consecutive patients. Fifteen (83%) were females and the age ranged from 31 to 81 years old. The indication for radiotherapy was cancer of the cervix in 10 patients (56). The mean radiation dose was 5190 rads (range 4000 to 7000). Of 23 radiation lesions, 12 (52%) were located in the ileon, 10 in the rectum and 1 in the sigmoid. Fibrosis and stenosis was the most frequent lesion (70%) followed by fistulae (22%) and proctitis in 2 patients. Resection or derivation was the surgical treatment employed in 22 of the 23 lesions. For lesions of the ileon, we performed resection and anastomosis in 7 patients and derivation in 5. For rectal lesions we performed resection, endoanal descent and colo-anal anastomosis in 7 patients anterior resection in 2 and colostomy in 1. Complications were observed in 5 patients (28%) and 1 patient died (5%). After a mean follow up of 56 months, 5 patients have died from recurrence of the original neoplastic lesions. We feel that surgical treatment allows improvement in quality of life of patients with radiation enteropathy.