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Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the BCR-ABL oncoprotein, known to drive leukemogenesis by orchestrating multiple signaling pathways ultimately involved in cell survival. Despite successful response rates of CML patients to tyrosine kinase inhibitors (TKIs), resistance eventually arises due to BCR-ABL-dependent and independent mechanisms. Survivin is an inhibitor of apoptosis protein acting in the interface between apoptosis deregulation and cell cycle progression. In CML, high levels of survivin have been associated with late stages of disease and therapy resistance. In this review, we provide an overview of important aspects concerning survivin subcellular localization and expression pattern in CML patients and cell lines. Moreover, we highlight the relevance of molecular networks involving survivin for disease progression and treatment resistance. Finally, we discuss the mechanisms accounting for survivin overexpression, as well as novel therapeutic interventions that have been designed to counteract survivin-associated malignancy in CML.

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BACKGROUND: A skin field cancerization is a cutaneous area with subclinical changes resultant from chronic sun exposure, with a higher predisposition to development of pre-neoplastic and neoplastic lesions. So far, there are no well-defined objective parameters that can indicate their degree of activity. OBJECTIVES: To describe and compare morphometric aspects and expression of factors related to apoptosis and cell proliferation in actinic keratosis (AK), in both photoexposed and photoprotected epidermis. METHODS: A cross-sectional study of patients with actinic keratosis in the forearms, biopsied at two points: the actinic keratosis and the axillary region. The biopsies of the actinic keratosis, perilesional area, and axilla were evaluated through keratinocyte intraepithelial neoplasia (KIN), and immunohistochemistry of p53, survivin, and Ki67. Nuclear morphometry of basal layer cells was performed through digital image analysis: entropy, area, perimeter, Ra, fractal dimension, circularity, color intensity, and largest diameter. RESULTS: There were 13 patients included and 38 actinic keratosis biopsied. In morphometry, 1039 nuclei were analyzed, of which 228 represented axillary skin, 396 demonstrated actinic keratosis, and 415 represented the perilesional area to the actinic keratosis. There was a significant difference (p<0.05) in all variables tested for the topographies evaluated. A significant correlation was identified between nucellar morphometric elements, KIN, proliferation markers, and apoptosis. Joint patterns of p53, Ki67, and KIN discriminated the topographies sampled. STUDY LIMITATIONS: This was a cross-sectional study with a small number of patients. CONCLUSIONS: There are patterns of proliferation, resistance to apoptosis, and different cellular morphometrics between photoprotected skin and photoexposed skin. The joint expression of p53, Ki67, and KIN can characterize skin field cancerization activity.

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Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.

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SUMMARY Breast cancer (BC) is one of the primary health problems worldwide. As the most common cancer in women in the world and in Brasil, behind only non-melanoma skin cancer, this neoplasm corresponds to approximately 28% of new cases per year in the country. BC also affects men, although the incidence corresponds to only 1% of total cases. Currently, most of the chemotherapeutic agents used in BC treatment are extremely toxic and cause long-term side effects. There is also a need to obtain earlier diagnoses, more accurate prognoses and make new therapies available that are more selective and effective in order to improve the current scenario. Therefore, this work sought to evaluate the importance of the biomarker survivin (Sur) in relation to BC, through the detailing of the role of Sur as a biomarker, the correlation between this protein and the prognosis of BC patients, and a summary of therapeutic strategies that target Sur for the development of new anticancer therapies.

RESUMO O câncer de mama (CM) é um dos principais problemas de saúde em todo o mundo. Como o câncer mais comum em mulheres no mundo e no Brasil, precedido apenas pelo câncer de pele não melanoma, essa neoplasia corresponde a aproximadamente 28% dos novos casos por ano no país. O CM também afeta homens, embora a incidência corresponda a apenas 1% do total de casos. Atualmente, a maioria dos agentes quimioterápicos utilizados no tratamento do CM são extremamente tóxicos e causam efeitos colaterais a longo prazo. Há também a necessidade de se obterem diagnósticos mais precoces, prognósticos mais precisos e disponibilizar novas terapias seletivas e efetivas, a fim de melhorar o cenário atual. Portanto, este trabalho buscou avaliar a importância do biomarcador Survivina (Sur) em relação ao CM, por meio do detalhamento do papel do Sur como biomarcador, da correlação entre essa proteína com o prognóstico de pacientes com CM e de um resumo do tratamento terapêutico e das estratégias que visam utilizar a Sur para o desenvolvimento de novas terapias anticâncer.

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O tumor venéreo transmissível (TVT) é uma neoplasia de células redondas de aspecto plasmocitóide ou linfocitóide. O tumor apresenta várias particularidades. Nos últimos anos, tem-se evidenciado aumento progressivo de tumores com elevados porcentuais de agressividade e variável resposta à quimioterapia, inclusive resistência; desta forma, tentar predizer este comportamento torna-se importante para auxiliar decisões quanto ao prognóstico e manejo do tumor antes e durante a terapia. Sabendo-se que a utilização da survivina, bem como da caspase-3, do Ki-67 e da COX-2 são importantes para auxiliar no prognóstico, no manejo do paciente e na monitoração da doença durante e após a terapia, este trabalho visou observar em TVTs diferenças na expressão dos imunomarcadores acima citados. Para tal, foi utilizada a técnica de imunocitoquímica em preparações citológicas de 30 tumores de cães atendidos no Hospital Veterinário da FMVZ-UNESP, Campus de Botucatu e os dados analisados pelo teste de spearman (p<0,05). A positividade da survivina variou de 96,15 a 100% em 200 células contadas por amostra, sendo sua principal localização citoplasmática. A marcação pelo anticorpo anti-caspase-3 nos 30 casos de TVT foi baixa, variando de 0 a 6,5% de positividade em 200 células contadas. Em 21 casos, foi possível observar marcação pelo Ki-67, e houve uma média de positividade de 15,57%. Finalmente, em todos os casos houve expressão de COX-2 com valores que variaram de 90,66 a 100% de positividade em 200 células contadas, exceto por um caso que apresentou 24,5% de positividade. Em conclusão, é possível que o emprego destes marcadores no TVT possa auxiliar no estabelecimento de um tratamento diferenciado, pelo que recomendamos, avaliar sua expressão comparando com o tipo de resposta à terapia.

Transmissible venereal tumor is a neoplasm of round cell plasmocitoide and linfocitoide aspect. The tumor present several particularities, for example, in the recent years has been evidenced a progressive increase of tumor with high percentages of aggressiveness and different response to chemotherapy, including resistance. Research this comportment to predict this behavior becomes important to aid decision as to the prognosis and management of the tumor before and during therapy. It is know that the use of the survivin, caspase-3, Ki67 and COX-2 are important to aid prognosis, the patient management and monitoring the tumor during and after therapy. This study aimed to identify differences in the expression of the above mentioned immunomarkers in TVT. For this purpose, the technique of immunocytochemistry on cytological preparations of 30 tumors of dogs examined at the Veterinary Hospital FMVZ-UNESP, Botucatu was used and the date analyzed by the spearman test (p<0,05). The survivin positivity ranged from 96.15 to 100% in 200 cells counted per sample, and its main cytoplasmic localization. The labeling by the anti-caspase-3 in 30 cases of TVT was low, ranging from 0 to 6.5% positivity in 200 cells counted. In 21 cases it was observed by Ki 67 labeling and there was an average of 15 57% positivity. Finally, in all cases there was expression of COX-2 with values ranging from 90.66 to 100% positivity in 200 cells counted, except for one case which showed 24.5% positivity. In conclusion, it is possible that the use of these markers in the TVT may assist in establishing a differential treatment, and we recommend, evaluate its expression compared with the type of response to therapy.

El tumor venéreo transmisible (TVT) es una neoplasia de células redondas de aspecto plasmocitóide o linfocitoide. El tumor presenta varias particularidades, por ejemplo, en los últimos años se ha evidenciado aumento progresivo de tumores con elevados porcentajes de agresividad y variable respuesta a la quimioterapia, inclusive resistencia; desta forma, intentar predecir este comportamiento se torna importante para auxiliar decisiones relacionadas con el pronóstico y manejo del tumor antes y durante de la terapia. Se sabe que la utilización de la survivina, así como la caspasa-3, del Ki-67 y de la COX-2, son importantes para auxiliar el pronóstico, manejo del paciente y elmonitoramiento de un tumor durante la terapia, así, este trabajo busco identificaren TVTs la diferencia en la expresión de losinmunomarcadores citados. Para ello, fue utilizada la técnica de inmunocitoquímica en preparaciones citológicas de 30 tumores de caninos atendidos en el Hospital Veterinario de la FMVZ-UNESP, Campus Botucatu y los datos análizados a través del test de spearman (p<0,05). La positividad de la survivina vario de 96,15 %a 100% en 200 células contadas. La marcación anti-caspasa -3 en los 30 casos de TVT fue baja variando de 0% a 6,5%. En 21 casos fue posible observar marcación por el Ki67, y hubo una media de positividad de 15,57%. Finalmente, en todos los casos hubo expresión de COX-2 con valores que variaron de 99,66 % a 100% de positividad en 200 células contadas, excepto por un caso que presento 24,5 % de positividad. En conclusión, es posible que el empleo de estos marcadores en TVT puedan auxiliar el establecimiento de un tratamiento diferenciado, por lo que recomendamos, evaluar su expresión comparada con el tipo de respuesta a la terapia.

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