RESUMO No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.

ABSTRACT The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.

Lymph node metastases are an independent prognosis factor in gastric carcinoma (GC) patients. Radical lymphadenectomy can improve survival but it can also increase surgical morbidity. As a principle, sentinel node (SN) navigation surgery can avoid unnecessary lymphadenectomy without compromising prognosis. In this pilot study, 24 patients with untreated GC were initially screened for SN navigation surgery, of which 12 were eligible. Five patients had T2 tumors, 5 had T3 tumors and 2 had T1 tumors. In 33% of cases, tumor diameter was greater than 5.0 cm. Three hundred and eighty-seven lymph nodes were excised with a median of 32.3 per patient. The SN navigation surgery was feasible in all patients, with a median of 4.5 SNs per patient. The detection success rate was 100%. All the SNs were located in N1 and N2 nodal level. In 70.9% of cases, the SNs were located at lymphatic chains 6 and 7. The SN sensitivity for nodal staging was 91.6%, with 8.3% of false negative. In 4 patients who were initially staged as N0, the SNs were submitted to multisection analyses and immunohistochemistry, confirming the N0 stage, without micrometastases. In one case initially staged as negative for nodal metastases based on SN analyses, metastases in lymph nodes other than SN were found, resulting in a 20% skip metastases incidence. This surgery is a reproducible procedure with 100% detection rate of SN. Tumor size, GC location and obesity were factors that imposed some limitations regarding SN identification. Results from nodal multisection histology and immunohistochemistry analysis did not change initial nodal staging.

A quina (Strychnos pseudoquina A. St.-Hil) é espécie medicinal do Cerrado Brasileiro. As sementes apresentam dormência e, por isso, foram submetidas aos tratamentos pré-resfriamento a 5ºC durante 7 dias, pré-aquecimento a 40ºC durante 7 dias, pré-embebição em ácido sulfúrico P.A. durante 5 e 15 minutos, pré-embebição em água fervente durante 5 e 15 minutos, pré-embebição em ácido giberélico a 100 e 200 ppm, durante 48 horas, pré-embebição em água destilada durante 24 e 48 horas e escarificação mecânica, visando à superação da dormência. Foram realizadas contagens diárias entre o 2º dia após a implantação do experimento até a estabilização da germinação, que ocorreu no 65º dia. Foram avaliados o índice de velocidade de germinação (IVG) e a porcentagem de germinação. Taxas de germinação acima de 96% foram atingidas em sementes pré-embebidas em água durante 48 horas e substrato umedecido com água ou KNO3.

"Quina" (Strychnos pseudoquina A. St. Hil) is a medicinal plant species from the Brazilian Cerrado. As its seeds show dormancy, they were subjected to the treatments pre-cooling at 5ºC during 7 days, pre-heating at 40ºC during 7 days, pre-soaking in sulfuric acid PA during 5 and 15 min, pre-soaking in boiling water during 5 and 15 min, pre-soaking in 100 and 200 ppm gibberellic acid during 48 h, pre-soaking in distilled water during 24 and 48 h, and mechanical scarification to break dormancy. Counts were daily conducted from the 2nd day after the experiment implementation until the germination stabilization at the 65th day. The germination speed index (GSI) and the germination percentage were evaluated. Germination rates above 96% were reached in seeds pre-soaked in water during 48 h and substrate moistened with water or KNO3.

Calcium (Ca2+) is a versatile second messenger that regulates a wide range of cellular functions. Although it is not established how a single second messenger coordinates diverse effects within a cell, there is increasing evidence that the spatial patterns of Ca2+ signals may determine their specificity. Ca2+ signaling patterns can vary in different regions of the cell and Ca2+ signals in nuclear and cytoplasmic compartments have been reported to occur independently. No general paradigm has been established yet to explain whether, how, or when Ca2+ signals are initiated within the nucleus or their function. Here we highlight that receptor tyrosine kinases rapidly translocate to the nucleus. Ca2+ signals that are induced by growth factors result from phosphatidylinositol 4,5-bisphosphate hydrolysis and inositol 1,4,5-trisphosphate formation within the nucleus rather than within the cytoplasm. This novel signaling mechanism may be responsible for growth factor effects on cell proliferation.

This paper addresses the development of an efficient numerical output feedback robust model predictive controller for open-loop stable systems. Stability of the closed loop is guaranteed by using an infinite horizon predictive controller and a stable state observer. The performance and the computational burden of this approach are compared to a robust predictive controller from the literature. The case used for this study is based on an industrial gasoline debutanizer column.

In this paper, a new model predictive controller (MPC), which is robust for a class of model uncertainties, is developed. Systems with stable dynamics and time-invariant model uncertainty are treated. The development herein proposed is focused on real industrial systems where the controller is part of an on-line optimization scheme and works in the output-tracking mode. In addition, the system has a time-varying number of degrees of freedom since some of the manipulated inputs may become constrained. Moreover, the number of controlled outputs may also vary during system operation. Consequently, the actual system may show operating conditions with a number of controlled outputs larger than the number of available manipulated inputs. The proposed controller uses a state-space model, which is aimed at the representation of the output-predicted trajectory. Based on this model, a cost function is proposed whereby the output error is integrated along an infinite prediction horizon. It is considered the case of multiple operating points, where the controller stabilizes a set of models corresponding to different operating conditions for the system. It is shown that closed-loop stability is guaranteed by the feasibility of a linear matrix optimization problem.

This paper addresses the stability of Model Predictive Control (MPC) with output feedback. The proposed controller uses a new state-space formulation of the system, and the control problem is presented as an LMI optimization problem. The stability condition for the closed loop is included as a Lyapunov inequality. The resulting optimization problem becomes nonlinear with the inclusion of the stabilizing condition. A suboptimal solution is developed and the problem reduces to a pair of coupled LMI problems. An iterative solution that converges to a stable output feedback gain is proposed. A polytopic set of process models can be considered. A simulation example is included in the paper and shows that the proposed strategy eliminates the usual practice of enforcing robustness by detuning the MP controller.