Mitose como fator prognóstico para biópsia de linfonodo sentinela em melanoma fino

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

Allelic imbalance studies of chromosome 9 suggest major differences in chromosomal instability among nonmelanoma skin carcinomas

CONTEXTO: Vários estudos de perda de heterozigozidade na região 9p21-p22, que abriga os genes supressores tumorais CDKN2a/p16INK4a, p19ARF e p15INK4b, têm sido realizados em uma ampla série de tumores humanos, incluindo os melanomas familiares. Perdas e ganhos em outras regiões do cromossomo 9 também têm sido observados com freqüência e podem indicar mecanismos adicionais no processo de tumorigênese dos carcinomas basocelulares da pele. OBJETIVO: Investigar o equilíbrio alélico existente na região 9p21-p22 em carcinomas basocelulares. TIPO DE ESTUDO: Análise molecular de marcadores de microssatélites em tumores e controles. LOCAL: Dois serviços de dermatologia de atendimento terciário em universidades públicas de São Paulo e o Laboratório de Genética Molecular do Câncer da Universidade Estadual de Campinas (UNICAMP), Brasil. PARTICIPANTES: Examinamos 13 casos benignos, incluindo 4 queratoses solares, 3 queratoacantomas, 3 nevos melanocíticos, 2 doenças de Bowen e 1 neurofibroma cutâneo, além de 58 tumores malignos da pele: 14 de células escamosas, 40 carcinomas basocelulares e 4 melanomas; em pacientes consecutivamente encaminhados à clínica de Dermatologia da Unicamp e que concordaram em participar do estudo. VARIÁVEIS ESTUDADAS: O tumor principal e uma porção normal de pele não-adjacente foram removidos cirurgicamente de pacientes que consecutivamente procuraram os ambulatórios de dermatologia da Universidade Estadual de Campinas (UNICAMP) e da Universidade Estadual de São Paulo (Unesp), São Paulo, por causa de lesões cutâneas. Extraímos DNA tanto de tecido tumoral como do correspondente tecido normal de cada paciente. Para amplificar regiões de repetição polimórfica de microssatélites do cromossomo 9, foram utilizados quatro pares de primers, sendo dois deles destinados à região 9p21-p22. RESULTADOS: Identificamos oito casos (20%) de desequilíbrio alélico entre os carcinomas basocelulares, sendo dois casos de perda de heterozigozidade e seis casos de instabilidade de microssatélite na região 9p21-p22. Outros marcadores também mostravam anormalidades em três destes tumores, enquanto nenhuma alteração foi detectada entre os casos benignos e nos outros tumores malignos. CONCLUSÃO: Esta dependência fenotípica sugere que existem diferenças importantes no comportamento das formas mais comuns de tumores cutâneos não-melanocíticos em relação à sua tendência para instabilidade de microssatélite no cromossomo 9. Considerando-se que os genes CDKN2a/p16INK4a, p19ARF e p15INK4b não parecem responsáveis pelas anormalidades observadas, outros genes em 9p21-p22 podem estar envolvidos na etiopatogenia e na progressão dos carcinomas basocelulares.

Histological and immunological reaction of cattle skin to first-instar larvae of Dermatobia hominis

Six cattle that had earlier exposure to Dermatobia hominis were infested experimentally with first-instar larvae of the parasite. Skin biopsies taken at intervals were studied in wax and in plastic sections. The avidin-biotin-peroxidase method was used to detect the presence and localization of host immunoglobulins (Igs) G and M and antigens of first and second instar larvae of Dermatobia hominis. The larvae penetrated actively through the skin and migrated towards the subcutaneous tissues. The great numbers of eosinophils suggest that they are the most important cell in mediating damage to D.hominis larvae. The immunoglobulins bound only to dead or moulting larvae in which access to binding sites may have been altered. This could represent a morphological manifestation of a mechanism that protects larvae from the host immune response. Large amounts of soluble antigens detected along the fistulous tract may be important in the maintenance of this tract by disturbing the normal cicatrization process.

FTY720 in combination with cyclosporine - an analysis of skin allograft survival and renal function

Acute and chronic nephrotoxicity caused by CsA Continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation.FTY720 is a new Compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens.In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney.Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose Could prevent graft rejection and avoid nephrotoxicity. (c) 2006 Elsevier B.V. All rights reserved.

Antitumor effects in vitro and in vivo and mechanisms of protection against melanoma B16F10-Nex2 cells by fastuosain, a cysteine proteinase from Bromelia fastuosa

In the present work, the antitumor effect of fastuosain, a cysteine proteinase from Bromelia fastuosa, was investigated. In the intravenous model of lung colonization in C57Bl/6 mice, fastuosain and bromelain injected intraperitoneally were protective, and very few nodules of B16F10-Nex2 melanoma cells were detected. Tumor cells treated with fastuosain showed reduced expression of CD44 and decreased invasion through Matrigel, lost their cytoplasmic extensions and substrate adherence, and became round and detached, forming strongly bound cell clusters in suspension. Peritoneal cells recruited and activated by fastuosain treatment ( mainly monocytic cells and lymphocytes) migrated to the lung, where pulmonary melanoma metastases grew. Adoptive transference of peritoneal cells recruited by fastuosain had no protective effect against lung metastases in recipient mice. Treatment of green fluorescent protein - chimeric animals with fastuosain did not change the number of cells that migrated to the lung, compared to PBS-injected control mice, but the number of positive major histocompatibility complex class II cells increased with fastuosain treatment. Murine antibodies against fastuosain, bromelain, and cathepsins B and L cross-reacted in ELISA and recognized surface and cytoplasmic components expressed on B16F10-Nex2 cells. Anti-fastuosain antibodies were cytotoxic/lytic to B16F10-Nex2 cells. Antitumor effects of fastuosain involve mainly the direct effect of the enzyme and elicitation of protective antibodies.

Angiogenesis and skin carcinomas with skull base invasion: A case-control study

Background. Some skin carcinomas may be very aggressive. Intensity of angiogenesis, measured by intratumoral vessel density using expression of CD34, has been associated with tumor aggressiveness. In this study, the expression of CD34 in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) with skull base invasion was compared with that in tumors with good outcome.Methods. Expression of CD34 was graded as mild, moderate, and intense, in 24 BCCs and 11 SCCs with skull base invasion. The control group included 23 BCCs and 10 SCCs.Results. Intense expression of CD34 was noted in 25.00% of BCCs with skull base invasion, compared with 4.35% in the control group (p =.058). Regarding SCCs, intense expression of CD34 was found in 54.55% of aggressive tumors, compared with 10.00% in the control group (p = 133).Conclusions. A trend toward denser microvascular angiogenesis was observed in both BCCs and SCCs with skull base invasion compared with less aggressive controls. (C) 2004 Wiley Periodicals, Inc.

Water sorption enthalpy-entropy compensation based on isotherms of plum skin and pulp

The net isosteric heat and entropy of water sorption were calculated for plum, based on sorption isotherms obtained by the static gravimetric method at different temperatures (20 to 70 degrees C). The Guggenheim-Anderson-deBoer model was applied to the experimental data giving a good agreement between experimental and calculated values. The net isosteric heat of water sorption, estimated by applying Claussius-Clapeyron equation to sorption isotherms, was found to be different for plum skin and pulp, mainly at low moisture contents, and could be well adjusted by an empirical exponential relationship. Plots of enthalpy in contrast to entropy provided the isokinetic temperatures for skin and pulp, indicating an enthalpy-controlled sorption process. Thermodynamic data on water sorption for plums are not found in literature, as opposed to prunes for which the data are abundant.