Centenario de la RTU de próstata. (Valoración crítica de su evolución) / Centenary of TURP. Critical appraisal of its evolution

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Estudio comparativo de tres modelos de melanomas murinos Harding-Passey, B16 y B 16F 10 / Comparative study of three murine melanoma models: Harding-Passey, B16 and B16F10

Planteamiento: Estudiamos las características clinicopatológicas, ultraestructurales y el comportamiento biológico de tres líneas de melanomas murinos: Harding-Passey. B16 y B16F10. Material y métodos: Se han utilizado 80 ratones C57B1/6J, a los que se inyectó una suspensión de 10° células tumorales por vía subcutánea a nivel inguinal. Se procesaron muestras de los tumores para el estudio microscópico óptico y electrónico. Se realizó el estudio estadístico. Resultados: Las tres líneas originaban tumores fácilmente trasplantables. De los tres modelos, el Harding-Passey supone el tumor de crecimiento más lento, presentando los menores pesos medios, el menor índice mitótico y una supervivencia mayor de los animales huéspedes. El B16 muestra un crecimiento intermedio con pesos tumorales de casi el doble que el anterior, un índice mitótico ligeramente superior y una supervivencia de los ratones ligeramente inferior. El B16F10 muestra la mayor capacidad de crecimiento, siendo los pesos medios de los tumores seis y cuatro veces mayores, respectivamente, que los de Harding-Passey y B16, con un índice mitótico más alto y una supervivencia de los animales inferior a la mitad de los anteriores. Conclusiones: Las tres líneas estudiadas constituyen modelos experimentales idóneos para el estudio del melanoma. Los tumores muestran un comportamiento biológico distinto, con una capacidad proliferativa variable, siendo el B16F10 el de mayor crecimiento. La baja supervivencia de los animales hace que sea un modelo ideal para estudios cortos. Todos mostraban alteraciones en la ultraestructura de los melanosomas (AU)

Granuloma faciale: an ultrastructural study.

Granuloma faciale is an uncommon process that can easily be confused with other skin diseases. To avoid incorrect treatment, correct diagnosis is of primary importance. A diagnosis of granuloma faciale can be made by a microscopic study of the dense granulomatous infiltrate in the reticular dermis with abundant polynuclear eosinophils and by an ultrastructural study of the eosinophils, which show characteristic alterations in their cytoplasmatic granules. The absence of Langerhans granules differentiates granuloma faciale from histiocytosis X.

The effects of different antineoplastic agents and of pretreatment by modulators on three melanoma lines.

BACKGROUND: The chemotherapy of melanoma patients must be improved because of the naturally poor response and acquired resistance of this disease. METHODS: The authors used mouse (B16F10) and human (SK-MEL-28 and SK-MEL-1) melanoma lines for in vitro treatment with melphalan, lomustine, fotemustine, and 4-hydroxyanisole (4-HA) alone, combined and after pretreatment with buthionine sulfoximine (BSO), ethacrynic acid (EA), and azelaic acid (AZA). RESULTS: Melphalan was the most effective individual drug, followed by lomustine, fotemustine, and 4-HA. The simultaneous administration of two agents was disappointing, although some combinations slightly improved the response compared with the individual treatments. Pretreatment with BSO enhanced the cytotoxicity of melphalan and lomustine 10-fold in B16F10 and 7.5-fold in SK-MEL-28, increasing the toxicity of fotemustine in all 3 lines. EA potentiated lomustine and fotemustine 9-fold and melphalan 5-fold in B16F10 and SK-MEL-28. AZA increased the effectiveness of lomustine and fotemustine in B16F10 and to a lower degree in the two human lines. 4-HA was the poorest drug for sensitization; only B16F10 BSO followed by 4-HA treatment demonstrated increased toxicity, and all other combinations with 4-HA were negative or antagonistic. There was a strong relationship between dopa oxidase activity and the toxicity of 4-HA. CONCLUSIONS: B16F10 was the most sensitive to all treatments and SK-MEL-1 the most resistant. Melphalan was the most active individual drug and 4-HA the least. Combinations of two drugs did not result in improved activity compared with drugs administered alone. Pretreatment with modulator seems to be a potential method for enhancing some treatments.

Relationship between 4-hydroxyanisole toxicity and dopa oxidase activity for three melanoma cell lines.

We studied the response of mouse B16F10 and SK-MEL-28 and SK-MEL-1 human melanoma cell lines to treatment with 4-hydroxyanisole (4-HA), and attempted to relate the response to the dopa oxidase levels and the morphological characteristics of each cell line. Clear dose-response curves were observed after 24 h of treatment in each cell line, the 4-HA being more toxic to the B16F10 cells, with an ID50 value of 215 microM. This was much lower than that observed for the SK-MEL-28 and SK-MEL-1 cell lines (ID50 of 5.98 mM and 7.17 mM, respectively). There was a direct relationship between toxicity levels and dopa oxidase activity, since the highest specific activity was obtained for B16F10 (15.9 mU), while lower activity was registered for SK-MEL-28 (4.59 mU) and SK-MEL-1 (1.24 mU), which also showed lower 4-HA toxicity. Morphologically, we observed the typical characteristics of cellular injury, with swelling and dilation of the internal membranes and organelles, an increased number of vacuoles, and an increased number of abnormal multilamellar melanosomes or thick clumps of irregularly distributed melanin. On the other hand, we observed that the two cell lines with the lowest dopa oxidase activity contained more mature fully melanized melanosomes than B16F10, pointing to possible alterations in the melanosome transference mechanism and lower enzymatic activity in the mature melanosomes of these two human cell lines.

Azelaic acid was sensitizing effect in the chemotherapeutic treatment of several melanoma cell lines.

Chemotherapy for melanoma results in low response and must be reinforced with sensitizer compounds. We believed that azelaic acid (AZA) could modulate melanomas' resistance to antineoplastics. Therefore we tried to compare in vitro treatment with antineoplastics alone versus AZA treatment followed by antineoplastics. We carried out MTT assays to evaluate the cytotoxicity of melphalan, lomustine (CCNU), fotemustine, and 4-Hydroxyanisole (4-HA) on three melanoma lines (B16F10, SK-MEL-28, and SK-MEL-1), and the modulating effect of pretreatment with AZA (1 mM). AZA showed a dose-dependent antineoplastic activity on the three lines. Melphalan was the most active drug followed by CCNU, fotemustine, and 4-HA. The most sensitive line was B16F10 and the least sensitive was SK-meL-1. Previous treatment with AZA of B16F10 reinforced the effect of melphalan (2.5 times), CCNU (10 times), and fotemustine (14 times); whereas for SK-MEL-28 and SK-MEL-1, only the cytotoxicity of CCNU and fotemustine increased. An antagonist effect was produced by 4-HA on all three lines. We concluded that AZA enhances in vitro cytotoxicity of CCNU and fotemustine.

Ultrastructural investigation of lead-induced intranuclear inclusion bodies in mice.

By means of optical and electron microscopy and by atomic absorption spectrophotometry in a graphite chamber, this study evaluated the effect of temperature (22-35 degrees C) on lesions in the kidney, liver, and brain, and on concentrations of lead caused by the administration of 2 and 5 mg/kg/IP of lead acetate to Swiss mice. The most pronounced effects were observed in the kidney and in groups of animals receiving the highest doses (5 mg/kg at 22 and 35 degrees C). These effects consisted of significantly higher (p < .05) lead concentrations in the tissues, a significant decrease (p < .05) in kidney weights, and progressive kidney atrophy and fibrosis with, at the ultrastructural level, constant intranuclear inclusions, which were also observed in the cytoplasm of renal and endothelial cells.

Comparative study of experimental ocular melanoma using two implantation techniques of B16-F10 melanocytes.

OBJECTIVE: The aim of this work was to evaluate the behaviour of B16-F10 melanoma cell cultures implanted in the anterior chamber of the eye of New Zealand white rabbits by studying the clinical-pathological and ultrastructural characteristics of the lesions. METHODS: One group (A) (consisting of 30 rabbits) was transclerally inoculated (1 mm from sclero-corneal limbus) with 4 x 10(6) melanocytes and another group (B) (also 30 animals) was inoculated once per week for 3 consecutive weeks with 5 x 10(6) cells (total 15 x 10(6)); 30 animals acted as the control group (C). All the lesions were processed for optic and electronic microscopy. RESULTS: Tumoral growth in group A was 43% (13/30) and in group B 80% (24/30). All lesions were pigmented and none perforated the eyeball. Microscopically, they were a mixture of epithelioid and fusiform cells disposed around the blood vessels. Ultrastructurally, the presence of melanosomes in different stages of maturation and aberrant melanosomes were characteristic. CONCLUSION: We suggest that the transcleral inoculation of 15 X 10(6) B16-F10 melanocytes into the anterior chamber of the eye of New Zealand white rabbits may be a valid and reproducible method for obtaining an experimental ocular melanoma model.

The behavior of two cell lines obtained from murine (B16-F10) and human (G-361) melanomas implanted into the eyes of New Zealand white rabbits, and their microscopic, immunohistochemical and ultrastructural appearances.

A transcleral inoculation of 15x10(6) melanocytes of the B16-F10 and G-361 cell lines was carried out in the anterior chamber of one eye in New Zealand white rabbits. Tumor growth occurred in 24 eyes (77%) of the B16-F10 group and in 22 (73%) of the G-361 group. The tumors of the latter group were mostly amelanic and showed local aggression with ocular perforation and extrascleral growth one month post-implant, while the tumors of the B16-F10 group were intensely pigmented and grew over the iris although they did not perforate the eyeball. Microscopically, the tumors of both groups were of the mixed type, made up of epithelioid and fusiform melanocytes. S-100 protein and Nki C3 monoclonal immunohistochemical techniques showed a positive immunoreaction in all cases of tumor growth. Ultrastructurally, the G-361 melanocytes showed a few melanosomes corresponding to maturity state II and, occasionally, state III, while totally melanized state IV cells predominated in the B16-F10 group. Aberrant melanosomes were common in both groups. The inoculation of 15x10(6) melanocytes of either cell line was useful to produce ocular melanomas.

Ocular melanoma: an experimental model in New Zealand white rabbits.

An experimental model is suggested for reproducing ocular melanoma in New Zealand white rabbits using B16 melanoma cells and protocols differing with respect to either tumour origin (subcutaneous fragments of melanoma B16 or B16-F10 tumour cell cultures) or implant site (the anterior chamber or subchoroidal). In 20 animals, 20 mg of methylprednisolone acetate was injected subconjunctivally as a local immunosuppressant. The only protocol resulting in tumour was inoculation of 4 x 10(6) B16-F10 melanocytes into the anterior chamber of the eye. Trans-scleral injections of cell suspensions produced tumour growth in 43% (13/30) of animals so treated. Thirteen animals developed non-neoplastic pigmented lesions formed of numerous melanophages. Another 19 animals showed non-pigmented lesions caused by reaction to the surgical procedures. Subconjunctivally injected methylprednisolone acetate did not increase the incidence of tumour growth.