Melanoma sobre nevus azul en placa o sobre melanocitosis dérmicas: utilidad diagnóstica y pronóstica del BAP1 / Melanoma arising in plaque-type blue nevus and dermal melanocytosis: Diagnostic and prognostic value of BAP1

El melanoma sobre nevus azul o melanoma ex-blue nevus es una variedad de melanoma peculiar que tiene un perfil genético diferente al del resto de los melanomas cutáneos y sorprendentemente superponible al perfil del melanoma uveal. Aunque puede aparecer de novo, el melanoma ex-blue nevus se suele desarrollar sobre un nevus azul previo o sobre una melanocitosis dérmica. No todas las lesiones nodulares desarrolladas sobre un nevus azul o una melanocitosis dérmica son melanomas, y los hallazgos clínicos e histológicos pueden ser insuficientes para llegar a un diagnóstico de certeza. Así, cobran relevancia estudios adicionales, como la hibridación genómica comparada, pues la presencia de aberraciones cromosómicas favorece el diagnóstico de malignidad. Es de especial utilidad el estudio del gen BAP1, cuya pérdida de expresión orienta a melanoma en este espectro de lesiones. Presentamos 3casos del espectro nevus azul a melanoma ex-blue nevus con estudios de biología molecular (AU)

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques (AU)

[Translated article] Melanoma Arising in Plaque-Type Blue Nevus and Dermal Melanocytosis: Diagnostic and Prognostic Value of BAP1 / Melanoma sobre nevus azul en placa o sobre melanocitosis dérmicas: utilidad diagnóstica y pronóstica del BAP1

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques (AU)

El melanoma sobre nevus azul o melanoma ex-blue nevus es una variedad de melanoma peculiar que tiene un perfil genético diferente al del resto de los melanomas cutáneos y sorprendentemente superponible al perfil del melanoma uveal. Aunque puede aparecer de novo, el melanoma ex-blue nevus se suele desarrollar sobre un nevus azul previo o sobre una melanocitosis dérmica. No todas las lesiones nodulares desarrolladas sobre un nevus azul o una melanocitosis dérmica son melanomas, y los hallazgos clínicos e histológicos pueden ser insuficientes para llegar a un diagnóstico de certeza. Así, cobran relevancia estudios adicionales, como la hibridación genómica comparada, pues la presencia de aberraciones cromosómicas favorece el diagnóstico de malignidad. Es de especial utilidad el estudio del gen BAP1, cuya pérdida de expresión orienta a melanoma en este espectro de lesiones. Presentamos 3casos del espectro nevus azul a melanoma ex-blue nevus con estudios de biología molecular (AU)

Melanoma arising in plaque-type blue nevus and dermal melanocytosis: Diagnostic and prognostic value of BAP1. / Melanoma sobre nevus azul en placa o sobre melanocitosis dérmicas: utilidad diagnóstica y pronóstica del BAP1.

Melanoma arising in blue nevus, also known as melanoma ex blue nevus, is a specific form of melanoma whose genetic profile is different to that of other cutaneous melanomas and surprisingly similar to that of uveal melanoma. Although melanoma ex blue nevus can appear de novo, it usually arises in a preexisting blue nevus or dermal melanocytosis. Not all nodular lesions arising in association with blue nevus or dermal melanocytosis are melanomas, however, and because clinical and histologic findings may be insufficient for a definitive diagnosis, additional studies such as comparative genomic hybridization are important. Detection of chromosomal aberrations supports a diagnosis of malignancy. Studies of the BAP1 gene are particularly useful in this setting because loss of expression is indicative of melanoma. We present 3 cases on the spectrum of blue nevus to melanoma ex blue nevus that were studied using molecular biology techniques.

Spatial and temporal variation in artisanal catches of dolphinfish Coryphaena hippurus off north-eastern Brazil.

The sampling of fish from the artisanal fleet operating with surface lines off north-eastern Brazil was carried out between 1998 and 2000. Generalized linear models (GLMs) were used to standardize mean abundance indices using catch and fishing effort data on dolphinfish Coryphaena hippurus and to identify abundance trends in time and space, using 1215 surface line deployments. A standard relative abundance index (catch per unit effort, CPUE) was estimated for the most frequent vessels used in the sets, employing factors and coefficients generated in the GLMs. According to the models, C. hippurus catches are affected by the operating characteristics and power of different fishing vessels. These differences highlight the need for standardization of catch and effort data for artisanal fisheries. The highest mean abundance values for C. hippurus were off the state of Rio Grande do Norte, with an increasing tendency in areas with greater depths and more distant from the coast, reaching maximal values in areas whose depths range from 200 to 500 m. The highest mean abundance values occurred between April and June. The higher estimated abundance of C. hippurus in this period off the state of Rio Grande do Norte and within the 200-500 m depth range may be related to a migration pattern of food sources, as its main prey, the flying fish Hirundichthys affinis, uses floating algae as refuge and to deposit its pelagic eggs.

In vivo and in vitro properties of STX2484: a novel non-steroidal anti-cancer compound active in taxane-resistant breast cancer.

BACKGROUND: STX2484 is a novel non-steroidal compound with potent anti-proliferative activity. These studies aimed to identify STX2484's mechanism of action, in vivo efficacy and activity in taxane-resistant breast cancer models. METHODS: Effects of STX2484 and paclitaxel on proliferation, cell cycle and apoptosis were assessed in vitro in drug-resistant (MCF-7(DOX)) and non-resistant cells (MCF-7(WT)). STX2484 efficacy in ßIII tubulin overexpression in MCF-7 cells was also determined. Anti-angiogenic activity was quantified in vitro by a co-culture model and in vivo using a Matrigel plug assay. An MDA-MB-231 xenograft model was used to determine STX2484 efficacy in vivo. RESULTS: STX2484 is a tubulin disruptor, which induces p53 expression, Bcl2 phosphorylation, caspase-3 cleavage, cell cycle arrest and apoptosis. In addition, STX2484 is a potent anti-angiogenic agent in vitro and in vivo. In breast cancer xenografts, STX2484 (20 mg kg(-1) p.o.) suppressed tumour growth by 84% after 35 days of daily dosing, with limited toxicity. In contrast to paclitaxel, STX2484 efficacy was unchanged in two clinically relevant drug-resistant models. CONCLUSIONS: STX2484 is an orally bioavailable microtubule-disrupting agent with in vivo anti-angiogenic activity and excellent in vivo efficacy with no apparent toxicity. Crucially, STX2484 has superior efficacy to paclitaxel in models of clinical drug resistance.

[Delayed deltoid-pectoral flap]. / El colgajo deltopectoral diferido.

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.

[Radial free flap with drainage through the cephalic vein dissected up to the deltoid region: a resource in the absence of receptor veins]. / Colgajo libre radial con drenaje por vena cefálica disecada hasta región deltoidea: un recurso ante la ausencia de venas receptoras.

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.

Colgajo libre radial con drenaje por vena cefálica disecada hasta región deltoidea: un recurso ante la ausencia de venas receptoras / Free radial flap with drainage through cephalic vein dissected up to the deltoid region: a resource in the absence of receptor veins

Los sucesivos tratamientos sobre el cuello en el caso de los pacientes oncológicos cérvico-faciales dificultan la práctica de colgajos microvascularizados porque en ocasiones conllevan el sacrificio de los potenciales vasos receptores. Presentamos un caso en el que este problema fue resuelto mediante la disección retrógrada de la vena cefálica hasta la región deltoidea, manteniendo intacto el pedículo venoso. Con ello se evitó la anastomosis venosa, consiguiéndose un drenaje sanguíneo eficaz. La sencillez de la técnica y su eficacia permite planteársela incluso ante la existencia de venas receptoras. El principal inconveniente es la cicatriz en la región anterior del brazo (AU)

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 (AU)

Experiencia en el tratamiento de 98 carcinomas de nasofaringe. Seguimiento a largo plazo y análisis de factores pronósticos / Experience in the treatment of 98 nasopharyngeal carcinomas: Long-term follow-up and analysis of prognostic factors

Se ha efectuado un estudio retrospectivo de 98 pacientes (pts.) con confirmación histológica de carcinomas de nasofaringe. Las características demográficas fueron: edad mediana de 53 años (11-83); 74 varones y 24 mujeres (ratio 3:1); histología OMS 2-3 en 89 pts. (90,8 por ciento); déficits neurológicos en 11 pts. (11,2 por ciento); 50pts. (51 por ciento)fueron T3-4, 68 pts. (69,4 por ciento) N2-3 y 77 pts. (78,6 por ciento) estadio IV. Los tratamientos fueron: radioterapia radical (RT) en 42 casos, quimioterapia (CT) e n 4, RT+ CT complementaria en 10 y CT neoadyuvante+RT en 4-2. La RTfue liberada con altas energías en campos amplios, dosis entre 50-75 Gy y fraccionamiento convencional. La CT consistió en esquemas basados en cisplatino (PF en 34, BEC en 9 y otros en 13 casos). Analizados por tratamientos, se incluyeron más varones, estadios N2N3 y IV en el grupo de CT+RT (p 50 años, histología OMS 1, déficits de pares craneales y estadios T3-4 N2-3 fueron factores pronósticos desfavorables (p 50 años y estadios T3-4 N2-3 fueron significativos (p < 0,05). En definitiva, logramos supervivencias considerables a largo plazo sin diferencias entre los tratamientos aplicados, aunque se precisan nuevas aproximaciones terapéuticas para mejorar la evolución de estos pacientes (AU)

This was a retrospective study of 98 patients (pts.) with histologically confirmed nasopharyngeal carcinoma. The clinico-demographic characteristics were: median age of 53 years (11-83); 74 males and 24 females (ratio 3:1); histology subtype OMS 2-3 in 89 pts. (90.8%); cranial nerve deficits in 11 pts. (11.2%); 50 (51%) were stage T3T4; 68 pts. (69.4%) N2N3 and 77 pts. (78.6%) stage IV. The therapeutic modalities were: radical radiotherapy (RT) alone in 42 pts., chemotherapy (CT) alone in 4 pts., RT + adjuvant CT in 10 pts. and neoadjuvant CT + RT in 42 pts. RT was delivered in wide fields, doses between 50-75 Gy with conventional fractionation. CT consisted in cisplatinum-based schedules (PF in 34 pts., BEC in 9 and others in 13 pts.). Analyzed by treatment, more males and stages N2N3 and IV were accrued in neoCT + RT arm (p < or = 0.05). For the entire population, the overall complete response was achieved in 65 pts. (66.3%); in 27/35 pts. (77.1%) of the RT group and 30/51 pts. (58.8%) of CT + RT group (p 0.07) of pts. with III-IV stages. With a median follow-up of 74.5 months, 32 pts. (32.65%) are alive and free of disease. The projected OS for all pts. was 40 months (m), 51.4% at 3 years (y) and 45.5% at 5 y with a disease free survival of 37 m (0-236). No differences between treatment arms were found (p 0.4). In univariant analysis for OS in stage III-IV pts., age > 50 y, histology OMS1, cranial nerve deficits, stage T3T4 and N2N3, were considered adverse prognostic factors (p < or = 0.05). In multivariant analysis, only age > 50 y and stages T3-T4, N2-N3 were significant (p < or = 0.05). In conclusion, we demonstrated good long term survival without any differences among treatment modalities in pts. with advanced nasopharyngeal carcinomas. New therapeutic approaches are warranted in order to improve the outcome of this patients (AU)

[Experience in the treatment of 98 carcinomas of the nasopharynx. Long-term follow-up and analysis of prognostic factors]. / Experiencia en el tratamiento de 98 carcinomas de nasofaringe. Seguimiento a largo plazo y análisis de factores pronósticos.

This was a retrospective study of 98 patients (pts.) with histologically confirmed nasopharyngeal carcinoma. The clinico-demographic characteristics were: median age of 53 years (11-83); 74 males and 24 females (ratio 3:1); histology subtype OMS 2-3 in 89 pts. (90.8%); cranial nerve deficits in 11 pts. (11.2%); 50 (51%) were stage T3T4; 68 pts. (69.4%) N2N3 and 77 pts. (78.6%) stage IV. The therapeutic modalities were: radical radiotherapy (RT) alone in 42 pts., chemotherapy (CT) alone in 4 pts., RT + adjuvant CT in 10 pts. and neoadjuvant CT + RT in 42 pts. RT was delivered in wide fields, doses between 50-75 Gy with conventional fractionation. CT consisted in cisplatinum-based schedules (PF in 34 pts., BEC in 9 and others in 13 pts.). Analyzed by treatment, more males and stages N2N3 and IV were accrued in neoCT + RT arm (p < or = 0.05). For the entire population, the overall complete response was achieved in 65 pts. (66.3%); in 27/35 pts. (77.1%) of the RT group and 30/51 pts. (58.8%) of CT + RT group (p 0.07) of pts. with III-IV stages. With a median follow-up of 74.5 months, 32 pts. (32.65%) are alive and free of disease. The projected OS for all pts. was 40 months (m), 51.4% at 3 years (y) and 45.5% at 5 y with a disease free survival of 37 m (0-236). No differences between treatment arms were found (p 0.4). In univariant analysis for OS in stage III-IV pts., age > 50 y, histology OMS1, cranial nerve deficits, stage T3T4 and N2N3, were considered adverse prognostic factors (p < or = 0.05). In multivariant analysis, only age > 50 y and stages T3-T4, N2-N3 were significant (p < or = 0.05). In conclusion, we demonstrated good long term survival without any differences among treatment modalities in pts. with advanced nasopharyngeal carcinomas. New therapeutic approaches are warranted in order to improve the outcome of this patients.

[Reconstruction of the floor of the nasal cavity, hemipalate, bucal cheek and lower lip]. / Reconstrucción de suelo de fosa nasal, hemipaladar, región yugal y labio inferior.

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.

[Oncogenic factors of metastatic dissemination in neuroblastoma]. / Facteurs oncogéniques de la dissémination métastatique du neuroblastome.

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.

Tuberculosis parotídea / Parotyde tuberculosis

La tuberculosis de la glandula parotida es una rara entidad con dos formas clinicas de presentación: la forma difusa, tipo agudo inflamatorio y extremadamente rara, y la forma localizada, clinicamente indistinguible de otras tumoraciones benignas parotideas, y que representa la forma más frecuente, de ahí la importancia de esta patologia en llegar a un diagnostico correcto que requerirá casi siempre una parotidectomia. Presentamos un nuevo caso de esta afección a proposito del cual realizamos una revision de la literatura

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.

[Malignant melanoma of the nasal cavity: a case report]. / Melanoma maligno de fosa nasal. A propósito de un caso.

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.

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.

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.

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)