Estudo retrospectivo dos pacientes portadores de melanoma cutâneo atendidos na Universidade Federal de São Paulo / Retrospective study of patients with cutaneous melanoma treated at the Federal University of São Paulo

RESUMO Objetivo: avaliar as características dos pacientes portadores de melanoma cutâneo atendidos no Hospital São Paulo - UNIFESP. Métodos: estudo retrospectivo de 184 casos de melanoma cutâneo. Foram analisadas as informações sobre sexo, idade, características do tumor, características histológicas e estadiamento. Resultados: a média de idade ao diagnóstico foi de 58,7 anos, com distribuição etária homogênea entre os sexos e predominância em indivíduos brancos (70,6%). Observou-se acometimento predominante de tronco, em homens (36,7%), e de membros inferiores, em mulheres (42%). A exposição solar, com queimaduras, foi mais comum entre homens (31,2%) do que entre mulheres (23,5%). Houve aumento de aproximadamente três vezes no acometimento linfonodal quando o índice mitótico subia de zero (11,9%) para uma ou mais mitoses por campo (36,2%), e aumento progressivo do acometimento linfonodal e de desfechos ruins quanto maior a espessura de Breslow: 10,2% quando menor do que 1mm e 59,2% quando maior do que 4mm. Conclusão: as características dos pacientes portadores de melanoma cutâneo atendidos no Hospital São Paulo são semelhantes às encontradas na literatura.

ABSTRACT Objective: to evaluate the characteristics of the patients with cutaneous melanoma treated at the São Paulo Hospital - UNIFESP. Methods: we conducted a retrospective study of 184 cases of cutaneous melanoma. We analyzed information on gender, age, tumor characteristics, histological characteristics and staging. Results: mean age at diagnosis was 58.7 years, with homogeneous age distribution between genders and predominance in white individuals (70.6%). There was a predominance of trunk involvement in men (36.7%) and lower limbs in women (42%). Sun exposure, with sunburns, was more common among males (31.2%) than among females (23.5%). There was an approximately three-fold increase in lymph node involvement when the mitotic index rose from zero (11.9%) to one or more mitosis per field (36.2%). In addition, the greater the Breslow thickness, the greater the lymph node involvement and poor the outcomes: 10.2% when less than 1mm and 59.2% when greater than 4mm. Conclusion: the characteristics of patients with cutaneous melanoma treated at Hospital São Paulo are similar to those found in the literature.

Histone H3.3 regulates mitotic progression in mouse embryonic fibroblasts.

H3.3 is a histone variant that marks transcription start sites as well as telomeres and heterochromatic sites on the genome. The presence of H3.3 is thought to positively correlate with the transcriptional status of its target genes. Using a conditional genetic strategy against H3.3B, combined with short hairpin RNAs against H3.3A, we essentially depleted all H3.3 gene expression in mouse embryonic fibroblasts. Following nearly complete loss of H3.3 in the cells, our transcriptomic analyses show very little impact on global gene expression or on the localization of histone variant H2A.Z. Instead, fibroblasts displayed slower cell growth and an increase in cell death, coincident with large-scale chromosome misalignment in mitosis and large polylobed or micronuclei in interphase cells. Thus, we conclude that H3.3 may have an important under-explored additional role in chromosome segregation, nuclear structure, and the maintenance of genome integrity.

Composição Química e Atividade Antioxidante de Agaricus blazei e seu Efeito Sobre a Modulação da Mitose / Chemical Composition and Antioxidant Activity of Agaricus blazei and its Effect on Mitosis Modulation

Este estudo teve como objetivo verificar a composição química e atividade antioxidante do Cogumelo do Sol (Agaricus blazei) e seu efeito sobre o ciclo celular de Allium cepa. A análise da composição química revelou uma elevada concentração em compostos fenólicos (65,36 mg/ EAG), ácido ascórbico (1,74mg/g), ß-caroteno (384,28µg/mg) e licopeno (33,61µg/mg). A eficiência no sequestro de radicais livres do DPPH foi considerada primária (68,15%) e a análise do ciclo celular mostrou que o tratamento com Agaricus blazei promove atraso na fase de anáfase da mitose em células meristemáticas de Allium cepa. Os resultados sugerem que a composição química e antioxidante de Agaricus blazei pode influenciar na modulação do ciclo celular de Allium cepa e possivelmente reduz a taxa de mutação espontânea, por diminuir a velocidade de disjunção e migração dos cromossomos durante a mitose. (AU)

The chemical composition and antioxidant activity of mushrooms Agaricus blazei and its effect on the Allium cepa cell cycle was investigated. Chemical analysis showed high concentration of phenolic compounds (65.36 mg/GAE), ascorbic acid (1.74 mg/g), ß-carotene (384.28 µg/mg) and lycopene (33.61 µg/mg). The efficiency free radical DPPH scavenging acitvity was primary (68.15%). Analysis of cell cycle demonstrated that treatment with Agaricus blazei delayed the mitosis anaphase phase in meristem cells of Allium cepa. The results suggest that the chemical composition and antioxidant activity of Agaricus blazei may affect the modulation of the Allium cepa cell cycle, and possibly reduce the spontaneous mutation rate, by decreasing the disjunction and migration speed of chromosomes during mitosis. (AU)

[Pseudosarcomatous chorangioma: A macroscopic and microscopic atypical tumor]. / Chorangiome pseudosarcomateux : une tumeur atypique sur le plan macroscopique et microscopique.

We report a case of an unusual chorangioma in a 26-year-old gravida 2, para 1 female. The clinical course was complicated by premature birth at 34 weeks' gestation. The baby presented with congenital cardiac and renal malformations. The tumor was 11 cm in size, separated from the main placental mass and exhibited atypical histologic characteristics such as fibromatous areas, high cellularity, nuclear atypia and high mitotic index. These histologic features must not be interpreted as malignancy.

Ubiquitin in regulation of spindle apparatus and its positioning: implications in development and disease.

Emerging data implicates ubiquitination, a post-translational modification, in regulating essential cellular events, one of them being mitosis. In this review we discuss how various E3 ligases modulate the cortical proteins such as dynein, LGN, NuMa, Gα, along with polymerization, stability, and integrity of spindles. These are responsible for regulating symmetric cell division. Some of the ubiquitin ligases regulating these proteins include PARK2, BRCA1/BARD1, MGRN1, SMURF2, and SIAH1; these play a pivotal role in the correct positioning of the spindle apparatus. A direct connection between developmental or various pathological disorders and the ubiquitination mediated cortical regulation is rather speculative, though deletions or mutations in them lead to developmental disorders and disease conditions.

Seasonal temperature variations influence tapetum mitosis patterns associated with reproductive fitness.

Environmental stress in plants impacts many biological processes, including male gametogenesis, and affects several cytological mechanisms that are strongly interrelated. To understand the likely impact of rising temperature on reproductive fitness in the climate change regime, a study of tapetal mitosis and its accompanying meiosis over seasons was made to elucidate the influence of temperature change on the cytological events occurring during microsporogenesis. For this we used two species of an environmentally sensitive plant system, i.e., genus Cymbopogon Sprengel (Poaceae), namely Cymbopogon nardus (L.) Rendle var. confertiflorus (Steud.) Bor (2n = 20) and Cymbopogon jwaruncusha (Jones) Schult. (2n = 20). Both species flower profusely during extreme summer (48 °C) and mild winter (15 °C) but support low and high seed fertility, respectively, in the two seasons. We have shown that tapetal mitotic patterns over seasons entail differential behavior for tapetal mitosis. During the process of tapetum development there are episodes of endomitosis that form either (i) an endopolyploid genomically imbalanced uninucleate and multinucleate tapetum, and (or) (ii) an acytokinetic multinucleate genomically balanced tapetum, with the progression of meiosis in the accompanying sporogenous tissue. The relative frequency of occurrence of the two types of tapetum mitosis patterns is significantly different in the two seasons, and it is found to be correlated with the temperature conditions. Whereas, the former (genomically imbalanced tapetum) are prevalent during the hot summer, the latter (genomically balanced tapetum) are frequent under optimal conditions. Such a differential behaviour in tapetal mitosis vis-à-vis temperature change is also correspondingly accompanied by substantial disturbances or regularity in meiotic anaphase disjunction. Both species show similar patterns. The study underpins that tapetal mitotic behaviour per se could be a reasonable indicator to elucidate the effect of climate change on reproductive fitness.

Heterochromatin and sibling species of Simulium praelargum s.l. (Diptera: Simuliidae).

Cytological descriptions are given for two sympatric sibling species, Simulium praelargum IIIL-st and Simulium praelargum IIIL-1.2, from Darjeeling, West Bengal, India. Sibling IIIL-1.2 differs from IIIL-st by a two step fixed included inversion (IIIL-1.2) found on the long arm of chromosome III. Both siblings possess heterochromatinized IIIS polytene chromosome ends, while IIIL-1.2 is unique within the Simuliidae in that it exhibits a very large enhanced chromocentre that persists in normal somatic tissue, contrary to other chromocentre-containing taxa. In IIIL-1.2, the chromocentre occurs as a positively allocyclic heteropycnotic body in normal mitotic interphase cells of neuroblast ganglia, oogonia, and spermatogonia. In mitotic metaphase chromosomes, the chromocentre forms large pronounced primary (centromere) constrictions and appears to be associated with nonhomologous pairing. Initial cytological studies on taxa within the feuerborni group have revealed heterochromatic chromosomal polymorphisms. Progressive fixation of these polymorphisms in different taxa within the group opens up the possibility of using comparative molecular or genomic approaches to begin to define the functional and structural aspects of the epigenome and to further characterize mitosis and meiosis in S. praelargum IIIL-1.2.

Atividade fitotóxica de Croton doctoris S. Moore / Phytotoxic activity of Croton doctoris S. Moore

O objetivo deste trabalho foi caracterizar o efeito fitotóxico do extrato etanólico bruto e frações semipurificadas do caule e folhas de C. doctoris na germinação, crescimento inicial e divisão celular das células radiculares de alface (Lactuca sativa) e cebola (Allium cepa), em laboratório. O experimento foi realizado em delineamento inteiramente casualizado, sendo utilizadas quatro concentrações dos tratamentos (0, 250, 500, 1.000mg L-1), com quatro repetições. O extrato bruto e as frações do caule e folhas inibiram a germinação e crescimento de alface e cebola, sendo o maior efeito fitotóxico promovido pela fração acetato de etila (FAE) do caule e folhas que afetou significativamente o crescimento e índice mitótico das células radiculares de alface e cebola. Com os resultados obtidos, verifica-se que a espécie C. doctoris apresenta substâncias capazes de influenciar no crescimento e divisão celular das espécies avaliadas.

The aim of this study was to verify the phytotoxic effect of the crude ethanol extract and semipurified fractions from the stem and leaves of Croton doctoris on the germination, growth and cell division of roots cells of lettuce (Lactuca sativa) and onion (Allium cepa), in the laboratory. The bioassays was conducted in using completely randomized design, with four concentrations (0, 250, 500, 1.000mg L-1) and four replications. The crude extract and the fractions from the stem and leaves inhibited germination and seedling growth of lettuce and onion, with greater phytotoxic effect observed in the ethyl acetate fraction (EAF) from the stems and leaves that significantly affected the growth and mitotic index of root cells of lettuce and onions. With these results it appears that C. doctoris contains substances capable of influencing the germination, growth and cell division of the species studied.

The jejunoileal bypass provokes morphological changes in the large intestine? An experimental study in rats / A derivação jejuno-ileal provoca alterações morfológicas no intestino grosso? Estudo experimental em ratos

PURPOSE: To analyse histopathological alterations characterized by the mitotic index in the mucosa of the large intestine in Wistar rats submitted to jejunoileal bypass operation after continued administration of sodium nitrite and vitamin C to different groups. METHODS: Eighty male Wistar rats were employed and separated into 12 groups. In the control group (20 rats): five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the sham group (20 rats), the animals were anesthetized and underwent midline laparotomy and only intestinal manipulation was performed: five animals ingested only water; five animals received vitamin C; five animals received sodium nitrite and five received sodium nitrite + vitamin C. In the operated group 40 rats underwent a jejunoileal bypass surgery: ten animals ingested only water; ten animals received vitamin C; ten animals received sodium nitrite and ten received sodium nitrite + vitamin C. The mean weight of the animals was measured weekly. The large intestine was subdivided into cecum (S1), ascending colon (S2), transverse colon (S3), descending colon (S4) and rectum (S5) for histopathological analysis and mitotic counts. The statistical analysis was used to compare the mitotic indices. The level of significance was 5%. RESULTS: The mean of all the segments indicates that the sodium nitrite+vitamin C group obtained the lowest mitotic index compared to the other treatments in the control group. The segments S1 and S2 showed a statistical difference with the vitamin C treatment: a higher mitotic index and better preservation of the mucosa in the operated group. In the sham group the main statistical difference occurred only in the sodium nitrite+vitamin C group between the means of the segments. CONCLUSIONS: The comparison of all the colonic segments of the various groups revealed a lower mitotic index in the animals treated with sodium nitrite+vitamin C. In addition, it was found that vitamin C did not present a statistically significant inhibiting effect on the preservation of the mucosa and the mitotic index.

OBJETIVO: Analisar as alterações histopatológicas caracterizada pelo índice mitótico na mucosa do intestino grosso em ratos Wistar submetidos a operação de bypass jejunoileal após a administração continuada de nitrito de sódio e vitamina C para diferentes grupos. MÉTODOS: Oitenta ratos Wistar foram utilizados e separados em 12 grupos. No grupo controle (20 ratos): cinco animais ingeriram apenas água; cinco animais receberam vitamina C, cinco animais receberam nitrito de sódio e cinco receberam nitrito de sódio + vitamina C. No grupo sham (20 ratos), os animais foram anestesiados e submetidos a laparotomia mediana e só a manipulação intestinal foi realizada: cinco animais ingeriram apenas água; cinco animais receberam vitamina C, cinco animais receberam nitrito de sódio e cinco receberam nitrito de sódio + vitamina C. No grupo operado 40 ratos foram submetidos a uma cirurgia de bypass jejunoileal: dez animais ingeridos apenas água; dez animais receberam vitamina C, dez animais receberam nitrito de sódio e dez nitrito de sódio + vitamina C. O peso médio dos animais foi medido semanalmente. O intestino grosso foi subdividido em ceco (S1), cólon ascendente (S2), cólon transverso (S3), cólon descendente (S4) e reto (S5) para análise histopatológica e contagem das mitoses. A análise estatística foi utilizado para comparar os índices mitóticos. O nível de significância foi de 5%. RESULTADOS: A média de todos os segmentos indica que o grupo que ingeriu nitrito de sódio + vitamina C obteve o menor índice mitótico em relação aos demais tratamentos no grupo controle. Os segmentos S1 e S2 mostraram uma diferença estatística com a vitamina C de tratamento: um maior índice mitótico e melhor preservação da mucosa no grupo operado. No grupo sham a principal diferença estatística ocorreu apenas no grupo que ingeriu nitrito de sódio + vitamina C entre as médias dos segmentos. CONCLUSÕES: A comparação de todos os segmentos do colon dos vários grupos revelaram um menor índice de mitose nos animais tratados com nitrito de sódio + vitamina C. Além disso, a vitamina C não apresentou efeito inibidor, estatísticamente significativo, na preservação da mucosa e do índice de mitoses.

Mitose como fator prognóstico para biópsia de linfonodo sentinela em melanoma fino / The importance of mitosis as a factor for predicting sentinel lymph node biopsy for thin melanoma

Paciente, sexo feminino, 23 anos, com melanoma extensivo superficial em dorso, Breslow 0,35 mm, Clark II, sem ulcerações e com 2 mitoses / mm². Foi submetida à ampliação de margem e biópsia de dois linfonodos sentinela (axila esquerda). O exame anatomopatológico mostrou micrometástases, no seio subcapsular de ambos. Seguindo a recomendação do "American Joint Commitee on Cancer" 2009, a paciente foi submetida à linfadenectomia axilar total, sem outros linfonodos metastáticos. A aplicação da dermatoscopia vem permitindo maior precisão diagnóstica de melanoma cutâneo, contribuindo para maior proporção de melanoma fino ao diagnóstico. A taxa mitótica foi incluída como um importante fator prognóstico para melanomas finos pelo "American Joint Commitee on Cancer" 2009, sugerindo biópsia para esses pacientes.

23-year-old female patient, with superficial spreading melanoma (SSM) on the back, Breslow 0.35 mm, Clark II, without ulceration and with 2 mitosis/mm². Patient was submitted to margin enlargement and sentinel biopsy of 2 lymph nodes (left armpit). Histopathology revealed micrometastasis in the subcapsular sinus of both. Following the recommendation of the 2009 American Joint Committee on Cancer Melanoma Staging (AJCC), the patient underwent complete axillary lymphadenectomy. No other lymph nodes were metastatic. The clinical application of dermoscopy has enabled more accurate diagnosis of cutaneous melanoma, probably contributing to a greater proportion of thin melanomas at diagnosis. The mitotic rate was included as an important prognostic factor for thin melanomas by the AJCC, suggesting biopsy for these patients.