ABSTRACT
Clear cell carcinoma of ovary is a rare tumour with a very low incidence in pregnancy. It is attributed to develop from an existing background of endometriosis. There are very few case reports of the above combination tumours in pregnancy. It is a very aggressive tumour with a worse prognosis and low survival rate because of its peculiar chemo resistant nature. Early detection and effective treatment are the best approach. The treatment options for advanced stages are still under research.
ABSTRACT
Este trabajo utilizó un modelo macrófago humano-amastigote como herramienta para recrear in vitro la infección causada por aislados de pacientes con fracaso terapéutico y valorar su utilidad en la identificación de aislados de Leishmania con fenotipo quimio-resistente. Objetivos: (1) Evaluar un modelo in vitro de macrófago humano-amastigote y (2) Determinar su utilidad en la identificación de aislados de Leishmania con fenotipo quimio-resistente. Métodos: Se evaluó un protocolo de purificación basado en la capacidad de los monocitos de adherirse al plástico. Monocitos purificados de sangre humana fueron infectados con promastigotes metacíclicos de especies de referencia y aislados de Leishmania de tres pacientes con falla terapéutica a antimoniales. Se determinó el porcentaje de infección inicial y el efecto leishmanicida de glucantime, anfotericinaB y pentamidina; se correlacionó la capacidad leishmanicida con los niveles de producción de óxido nítrico en cada condición estudiada. Resultados: Los resultados sugieren que el modelo macrófago humano-amastigote empleado recrea in vitro la infección causada por especies de referencia, o con aislados de pacientes con fracaso terapéutico. Adicionalmente sugieren que en monocitos infectados (1) con el aislado VE98MR no puede definirse una IC50 para glucantime ni para pentamidina y (2) con el aislado VE96ZC no puede definirse una IC50 para glucantime mas si para pentamidina. De igual forma, se evidencia una disminución efectiva del porcentaje de infección susceptible a anfotericina-B, para todos los aislados y cepas de referencia. El efecto leishmanicida no se correlaciona con aumentos significativos de la producción de óxido nítrico. Conclusiones: El modelo macrófago humano-amastigote empleado constituye una prueba de concepto que permitió identificar como aislados potencialmente quimio-resistentes a L. (L.) amazonensis (VE98MR) y L. (L.) mexicana (VE96ZC), mas no al aislado L. (L.) amazonensis (VE2000MM)(AU)
This work used a human-amastigote macrophage model as a tool to recreate in vitro infection caused by isolates from patient's with therapeutic failure and assess its usefulness in the identification of chemo-resistant Leishmania isolates. Objectives: (1) Evaluate in vitro a human-amastigote macrophage model and (2) determine its usefulness in the identification of Leishmania isolates with chemo-resistant phenotype. Methods: A purification protocol based on the ability of monocytes to adhere to plastic was evaluated. Monocytes purified from human blood were infected with metacyclic promastigotes of reference species and Leishmania isolates from three patients with antimonial therapeutic failure. The percentage of initial infection and the leishmanicidal effect of glucantime, amphotericin-B and pentamidine were determined; the leishmanicidal capacity was correlated with the levels of nitric oxide production in each condition studied. Results: Results suggest that the human-amastigote macrophage model recreates in vitro the infection caused by reference species, or isolates from patients with therapeutic failure. In addition, they suggest that (1) an effective IC50 for glucantime and pentamidine could not be defined in monocytes infected with the isolate VE98MR and (2) an effective IC50 for pentamidine but nor for glucantime could be defined in monocytes infected with the isolate VE96ZC. On the contrary, an effective decrease in the percentage of infection susceptible to amphotericin-B was observed for all isolates and reference strains. The leishmanicidal effect did not correlate with significant increases in nitric oxide production. Conclusion: The human-amastigote macrophage model used constitutes a proof of concept to identify as potentially chemo-resistant isolates L. (L.) amazonensis (VE98MR) and L. (L.) mexicana (VE96ZC), but not L (L.) amazonensis (VE2000MM)(AU)
Subject(s)
Humans , Male , Female , In Vitro Techniques/methods , Leishmaniasis, Cutaneous/physiopathology , Leishmaniasis, Cutaneous/epidemiology , Leishmaniasis, Cutaneous/virology , Tropical Medicine , Public Health , Drug Therapy , Macrophage ActivationABSTRACT
Objective To observe the proliferation and apoptosis of oxaliplatin-resistant colon cancer cell lines and the expression of estrogen receptor related receptor(ERR)α when tetrasoanin was down-regulated. Methods Western blot and quantitative real-time polymerase chain reaction(qRT-PCR)were used to detect the expression of tetrasoanin and ERRα of colon cancer cells and oxaliplatin resistant cells in mRNA and protein levels. ERRα inhibitor XCT790 was used to down-regulate ERRα expression, The expression of ERRα was down regulated by ERR α inhibitor XCT790,and the level of tetrasoanin,apoptosis and proliferation of L-OHP-SW620 cells were detected by Western blot, flow cytometry and MTT.Tetrasoanin expression was down regulated by siRNA, the expression, apoptosis and proliferation of L-OHP-SW620 cells AKT, p-AKT, tetrasoanin and ERRα were detected by Western blot,qRT-PCR,flow cytometry and MTT assay.Results The expression of tetrasoanin and ERRα protein in L-OHP-SW620 cell lines were higher than those in SW620 cells (t=6.127,P<0.01,t=12.579,P<0.01),The expression of tetrasoanin mRNA in L-OHP-SW620 cell line was higher than that in SW620 cell line(t=9.085,P< 0.01). The early apoptosis rate of L-OHP-SW620 cells in XCT790 group after XCT790 inhibited ERR -αexpression was higher than that in NC group(t=3.297, P< 0.01). The survival rate of XCT790 group after 72 h culture was(45.264±6.249)%,lower than that of NC group((63.364 ± 9.472)%)(t=4.537, P<0.01). Compared with NC group,p-AKT protein was up-regulated(t=8.139,P<0.01),ERRα protein was down-regulated(t=6.452,P<0.01),the apoptosis rate was(17.541±2.317)%,lower than that in the sitetrasoanin group((32.892±3.296)%)(t=4.526,P<0.01), the survival in sitetrasoanin group after 72 h culture was(49.653 ± 5.945)%, lower than that in NC group ((67.376±7.934)%)(t=3.109,P<0.05).Conclusion Tetrasoanin down-regulation and p-AKT protein up-regulation decreases ERRα protein and OHP-resistant colon cell proliferation is decreased, apoptosis is increased and drug resistance is decreased.