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Biomedical subjects

E Ferrandis

Publications and source records attributed to E Ferrandis.

12 recordsLinked to original sources

[Delayed deltoid-pectoral flap].

Delayed flaps include surgical techniques performed in order to diminish the blood supply of a flap before placing it at the definitive location. The purpose is to improve the irrigation of the distal region of the flap. Three cases of head and neck reconstructions with delayed deltopectoral flaps are reported. Literature about anatomic and physiologic phenomenon occurred during the delay period is reviewed, as well as the different surgical techniques described to delay a flap. We think that the deltopectoral flap remains an adequate technique, being indicated when the reconstruction is impossible with local flaps. That is the case of defects or irradiated regions. In our opinion, if the deltoid region of the flap is necessary to the reconstruction it is recommended to delay the flap, to increase the probability of complete survival at the distal region. In our cases the delay period has been one week, obtaining a complete survival of the flap in all of them.

Aged↗

[Radial free flap with drainage through the cephalic vein dissected up to the deltoid region: a resource in the absence of receptor veins].

Repeated treatments on the neck in head and neck oncological patients make more and more difficult to elaborate microvascularized flaps because sometimes it is necessary to sacrifice receptor veins. In this paper it is showed one way of solving this problem, by dissection of the cephalic vein towards the deltoid region, keeping the venous pedicle intact. In this fashion venous anastomosis is avoided, getting efficient blood drainage. Simplicity and efficiency of this technique make possible thinking about it even with existing receptors veins. The main inconvenience is the surgical scare on the anterior region of the arm.

Arm↗

[Oncogenic factors of metastatic dissemination in neuroblastoma].

Disseminated neuroblastoma frequently show a very poor prognosis. N-myc gene amplification, 1p deletion and lack of CD44 gene expression, are all genetic factors associated with the disease's dissemination. Human neuroblastoma xenografts in nude mice has permitted to characterize, in disseminated neuroblasts, oncogenes overexpression, inactivation of tumor suppressor genes as well as detoxifying genes activation which contributes to increase cellular resistance to chemotherapy. These genetic abnormalities permit to propose a nosology of this very aggressive pediatric solid tumor. Hopefully, this genetic classification could be of great value for new therapeutic approaches.

Animals↗

[Malignant melanoma of the nasal cavity: a case report].

Mucosal malignant Melanomas have worse prognosis than cutaneous melanoma. Elective treatment is surgery, which eradicates the tumor only in a restricted number of cases. The most frequent cause of treatment's failure is recurrence or local persistence of the disease.

Female↗

Evidence for transcriptional control of human mdr1 gene expression by verapamil in multidrug-resistant leukemic cells.

We investigated the mechanism of verapamil (VRP) effects on mdr1 gene expression in two leukemic multidrug-resistant (MDR) cell lines, K562/ADR and CEM VLB100. Exposure to VRP for 24 hr resulted in a decrease in mdr1 mRNA levels that was dose related at concentrations between 15 and 50 microM. The maximal decrease of mdr1 mRNA levels was found to be 6-fold in the K562/ADR cells and 3-fold in the CEM VLB100 cells. The effect of VRP on mdr1 mRNA levels was, however, biphasic. At 100 microM VRP, which strongly inhibited cell proliferation, a 2-fold increase of mdr1 mRNA levels was observed in the K562/ADR cells. To determine whether the decrease of mRNA levels resulted from post-transcriptional mechanisms, mRNA stability was studied after blocking of transcription with actinomycin D in VRP-treated cells and in control cells. This study revealed that mdr1 mRNA was stable in both cell lines and no increase in mdr1 mRNA degradation was observed in the 30 microM VRP-treated cells versus control cells (half-lives of 23 hr versus 14 hr for the K562/ADR cells and 15.5 hr versus 10.0 hr for the CEM VLB100 cells). The suggestion of a transcriptional mechanism was confirmed by nuclear run-on assays. A 4-fold decrease in the mdr1 gene transcription rate was observed in the 30 microM VRP-treated CEM VLB100 cells. The decreased transcription rate could be due to the decrease in mdr1 proximal promoter activity observed in CEM VLB100 cells transiently transfected with the mdr1 promoter fused to the chloramphenicol acetyltransferase gene. Indeed, after exposure to 30 microM VRP, chloramphenicol acetyltransferase activity was decreased by 2-fold. This study reports for the first time a down-regulation of mdr1 gene transcription by a pharmacological agent. These results provide further identification of the regulatory mechanisms involved in the overexpression of mdr1 in MDR cells and may help in the development of new strategies for MDR reversal.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Coactivation of the MDR1 and MYCN genes in human neuroblastoma cells during the metastatic process in the nude mouse.

In metastatic human neuroblastoma, MYCN amplification and MDR1 overexpression are frequently observed. No in vivo model is yet available for the study of the regulation of these two genes during the metastatic process of this disease. Culture of an involved bone marrow of a patient with stage IV neuroblastoma gave rise to an established in vitro neuroblastoma cell line, IGR-N-91, and a subsequent s.c. xenograft model in nude mice. When cultured in vitro, blood cells, bone marrow, and the myocardium of mice bearing s.c. tumor xenograft reproducibly yielded cells with morphological and molecular features of neuroblastoma cells, including consistent MYCN amplification (60 copies/haploid genome). Compared to the neuroblastoma cells of the primitive s.c. tumor xenograft, metastatic cells showed a significant increase in the MYCN gene transcript levels associated with an overexpression of the MDR1 gene mRNA levels leading to a P-glycoprotein capable of extruding Adriamycin. This study offers compelling evidence that (a) IGR-N-91 is a human neuroblastoma xenograft model able to induce metastasis in nude mice, (b) an increase in MYCN and MDR1 transcripts levels is associated with the metastatic process, and (c) IGR-N-91 provides a biological tool for the study of gene activations during tumor dissemination in neuroblastoma.

Animals↗

Retinoic acid and forskolin activate the human MDR1 gene promoter in differentiated neuroblasts.

To determine whether over-expression of the MDR1 gene may result from activation of its promoter by differentiating agents, the activity of the human MDR1 proximal promoter (MDR1 pp) transfected to 2 neuroblastoma lines treated with retinoic acid and forskolin was first measured using transient expression assays while the MDR1 mRNA levels were measured by Northern blots. The results indicate that retinoic acid and forskolin were able to activate the human MDR1 pp in a dose dependent manner after transfection of the MDR1pp- CAT constructs in the 2 cell models tested, i.e., SK-N-SH and IGR-N-91, a new human neuroblastoma cell line. A significant increase in MDR1 gene transcript levels was observed upon treatment with differentiation inducers in SK-N-SH but not in IGR-N-91 neuroblasts. These results suggest that the induction of the MDR1 gene promoter is necessary but not sufficient to lead to an increase in MDR1 gene transcript levels, according to the neuroblast cell line considered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Prognostic value of MDR1 gene expression in neuroblastoma: results of a multivariate analysis.

The prognostic value of the MDR1 gene expression in neuroblastoma (NB) was assessed in a multivariate analysis performed in a series of 84 patients (pts) taking into account the main known clinical and biological factors of the disease, i.e., age, stage, MYCN genomic content and DNA ploidy index. Twenty seven children were < 1 year (yr), 13 presented with stage I and II, 7 with stage IV-S, 17 with stage III and 47 (56%) with stage IV. Tumor specimens were obtained from involved bone marrow (n = 12) or surgical primary tumor specimens (n = 72). MDR1 gene expression was measured by Northern hybridization technique and expressed in arbitrary units (a. u.) (Goldstein et al., 1989). Analysis of MYCN genomic content and DNA ploidy index were performed by Southern blot hybridization technique and flow cytometry, respectively. Out of 84 tumor specimens 19 (23%) showed MYCN amplification (> 3 copies/haploid genome). In 24 cases (29%) no detectable MDR1 gene transcript was found (0 a.u.) whereas 42 (50%) had a value in the range 1-30 a.u., and 18 (21%) a value beyond 30 a.u.. High transcript levels were found in localized as well as in metastatic NB (NS). No significant correlation between MDR1 gene expression, age, stage, or MYCN genomic content was found In univariate analysis stage IV, age > 1 yr, MYCN amplification, diploid DNA content and high MDR1 gene transcript levels were significantly related to an increased risk of death. In multivariate analysis only stage IV, MYCN amplification and MDR1 overexpression remained significantly associated with an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Activation of the human MDR1 gene promoter in differentiated neuroblasts.

When treated in vitro with retinoic acid, many neuroblastoma cell lines undergo neuronal differentiation and show a significant increase in human multi-drug resistance gene (MDRI) transcript levels. To determine whether over-expression of the gene may result from activation of its promoter by differentiating agents, the activity of the human MDRI proximal promoter (MDRI pp) transfected to 2 neuroblastoma lines treated with retinoic acid and forskolin was first measured using transient expression assays. The MDRI gene transcript levels of these 2 lines were then measured by Northern blots. The results indicate that retinoic acid and forskolin were able to activate the human MDRI pp in a dose-dependent manner after transfection of the MDRI pp-CAT constructs in the 2 cell models tested, i.e., SK-N-SH and IGR-N-91, a new human neuroblastoma cell line. A significant increase in MDRI gene transcript levels was observed upon treatment with differentiation inducers in SK-N-SH but not in IGR-N-91 neuroblasts. These results suggest that the induction of the MDRI gene promoter is necessary but not sufficient to lead to an increase in MDRI gene transcript levels, according to the neuroblast cell line considered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Reconstruction of the floor of the nasal cavity, hemipalate, bucal cheek and lower lip].

We describe the surgical technique used to reconstruct a defect created by resection of a tumor of the palate, malar mucosa, lower lip and adjacent gingival mucosa. We used a microvascular radial forearm flap. A strip across the flap is de-epithelialized and the flap is folded in half at that point. The sides are used for the oral and nasal linings, respectively. The thinness of this flap, its vascularization and the length of its pedicle make this design possible. Four months after the surgery the patient was free of disease and had achieved adequate phonation and swallowing.

Carcinoma, Squamous Cell↗