Disminución de mortalidad en hemopatías malignas con un nuevo método de acondicionamiento para trasplante alogénico mieloablativo

ResumenIntroducciónEl trasplante alogénico de células progenitoras hematopoyéticas (TACPH) es el tratamiento de elección para diversas hemopatías malignas. Sin embargo, la morbimortalidad asociada al procedimiento limita su uso.ObjetivosDescribir la supervivencia de pacientes adultos mexicanos sometidos a un TACPH utilizando BUCY 2 reducido.MétodosEstudio de cohorte retrospectivo de octubre de 1999 a diciembre del 2014. Se evaluaron las características clínicas, la mortalidad asociada a trasplante, la supervivencia libre de enfermedad y la supervivencia global (SG) de 35 pacientes sometidos a TACPH con este nuevo método de acondicionamiento.ResultadosSe incluyó a 35 pacientes sometidos a TACPH, de donador relacionado HLA idéntico, acondicionados con BUCY 2 reducido, con una mediana de edad de 33 años (rango 16-49). El 60% de los pacientes fueron hombres. El diagnóstico más frecuente fue: síndrome mielodisplásico 14 pacientes (40%), leucemia mieloide crónica 9 pacientes (25.7%), leucemias agudas 10 pacientes (23.5%) y hemoglobinuria paroxística 2 pacientes (5.7%). La mediana de células CD34+transfundidas fue de 2.04×106/kg. La mediana de recuperación de neutrófilos y plaquetas fue de 21 y 18 días, respectivamente. La toxicidad más frecuente fue mucositis (91.4%). La mortalidad relacionada al trasplante fue del 5.7% y la SG a 5 años fue del 72.5%.ConclusionesEl método de acondicionamiento BUCY2 reducido conserva un efecto citotóxico que permite erradicar la clona maligna y lograr el injerto con mínima morbimortalidad, representando una mejor alternativa para el TACPH.AbstractIntroductionAllogeneic stem cell transplantation (ASCT) is the ideal treatment for haematological malignancies. However, the morbidity and mortality associated with the procedure limit its use.ObjectivesTo describe clinical characteristics, toxicity, and survival of adult Mexican patients undergoing ASCT using busulfan with a reduced dose of cyclophosphamide (BUCY 2) as a conditioning method.MethodsA prospective cohort study was conducted from October 1999 to December 2014, by performing an analysis of clinical characteristics, complications, and survival of 35 patients using this conditioning regimen.ResultsThe study included 35 patients undergoing ASCT with reduced BUCY 2. All of them had an HLA-matched related donor, with a median age of 33 years (range 16-49), and 60% were male. The patients had the following underlying diseases: myelodysplastic syndrome in 14 patients (40%), chronic myeloid leukaemia in 9 (25.7%), acute leukaemia in 10 (23.5%), and paroxysmal nocturnal haemoglobinuria in 2 (5.7%). The median of transfused CD34+cells was 2.04×106/kg. The median time to neutrophil and platelet recovery was 21 and 18 days, respectively. The most common toxicity was mucositis (91.4%). Transplant related mortality was 5.7%, and 5-year overall survival was 72.5%.ConclusionsThe conditioning method described earlier preserves a cytotoxic effect allowing eradication of the malignant clone, and achieving a graft with acceptable toxicity, and low transplant related mortality, representing a good alternative for ASCT

El factor de crecimiento epidérmico induce transición epitelio-mesénquima en cultivos primarios de cáncer de mama

ResumenAntecedentesLa transición epitelio-mesénquima (TEM) es un proceso biológico en el que células epiteliales inmóviles y polarizadas se convierten en células mesenquimales con capacidad de migración. Este proceso produce cambios en el citoesqueleto de las células, siendo la pérdida de E-cadherina y la adquisición de N-cadherina, uno de los principales cambios bioquímicos que se dan en la TEM. En este estudio investigamos el papel del factor de crecimiento epidérmico (EGF) sobre la TEM inducida en líneas celulares y cultivos primarios de cáncer de mama.MétodosPara este estudio se empleó la línea celular de cáncer de mama MCF-7 y los cultivos primarios MBCD25 y MBCDF. Se indujo la TEM mediante el tratamiento continuo con EGF. Se evaluó si las células habían sido inducidas a un fenotipo mesenquimatoso con EGF mediante la técnica de western blot, midiendo la fosforilación de STAT3, el nivel de STAT3, y la represión de los marcadores como E-cadherina, así como la expresión del factor de transcripción Snail.ResultadosNuestros resultados demuestran que el tratamiento con EGF induce la fosforilación de STAT3 sin cambios en sus niveles totales en células MBCDF, MBCD25 y MCF-7. Asimismo, el tratamiento con EGF por 5 días induce una TEM, que se demostró por la pérdida de E-cadherina y la expresión de Snail.ConclusiónEn los cultivos primarios MBCD25 y MBCDF, así como en la línea celular MCF-7, el EGF es capaz de inducir TEM y en consecuencia producir un fenotipo más agresivo de las células de cáncer de mama.AbstractBackgroundEpithelial-mesenchymal transition (EMT) is a biological process where immobile and polarised epithelial cells acquire mesenchymal characteristics with high migration. This process produces changes in the cytoskeleton of the tumour cells, with the loss of E-cadherin and the acquisition of N-cadherin being the main biochemical changes of the EMT. This study investigates the role of epidermal growth factor (EGF) on the EMT induction in breast cancer cell lines and primary cultures.MethodsMCF-7 cell line and the primary cultures MBCDF and MBCD25 were used in this study. EMT was induced by continuous EGF treatment. Mesenchymal EGF-induced phenotype was evaluated by Western blot of the following markers: pSTAT3, STAT3, repression of E-cadherin, and expression of Snail.ResultsOur results demonstrate that EGF treatment induced STAT3 phosphorylation without changes in STAT3 in MBCDF, MBCD25 and MCF-7. Additionally, EGF treatment induced EMT, as shown by the loss of E-cadherin and Snail expression after 5 days.ConclusionEGF was able to induce EMT in primary breast cancer cell cultures, MBCDF, MBCD25, as well as MCF-7 cell line. These results suggest that EGF produces a putative aggressive phenotype

Global survival of patients with FLC at 6, 12, 24, 36 and 60 months was 66, 66, 53, 40 and 26% (median survival of 30 ± 6 months)

<p><b>Copyright information:</b></p><p>Taken from "Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma"</p><p>BMC Cancer 2005;5():142-142.</p><p>Published online 31 Oct 2005</p><p>PMCID:PMC1310628.</p><p>Copyright © 2005 Moreno-Luna et al; licensee BioMed Central Ltd.</p

Additional file 1: Fig. S1. of Primary breast cancer cell culture yields intra-tumor heterogeneous subpopulations expressing exclusive patterns of receptor tyrosine kinases

Effect of PDGFR silencing on Imatinib-induced cytotoxicity. MBCDF (a) and subclone F3 (b) cells were transfected with either specific PDGFR shRNAs (sh PDGFR) or scrambled shRNAs (sh control). Transfected cells were selected with 5 μg/ml of Puromycin. Selected cells were treated with the indicated doses of Imatinib for 48 h. Cell viability was evaluated by Crystal Violet assay (left panel). Silencing of PDGFR expression was corroborated by Western blot (right panel). Data represent the mean ± SEM of three independent experiments seeded in triplicate. * P < 0.05 versus sh control (EPS 4216 kb

Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma

<p>Abstract</p> <p>Background</p> <p>Fibrolamellar Carcinoma (FLC), a subtype of hepatocellular carcinoma (HCC), is a rare primary hepatic malignancy. Several aspects of the clinic features and epidemiology of FLC remain unclear because most of the literature on FLC consists of case reports and small cases series with limited information on factors that affect survival.</p> <p>Methods</p> <p>We did a retrospective analysis of the clinical and histological characteristics of FLC. We also determined the rate of cellular proliferation in biopsies of these tumors. We assessed whether these variables were associated with survival.</p> <p>Results</p> <p>We found 15 patients with FLC out of 174 patients with HCC (8.6%). Between patients with these neoplasms, we found statistically significant survival, age at onset, level of alpha fetoprotein, and an earlier stage of the disease. The 1, 3 and 5 year survival in patients with FLC was of 66, 40 and 26% respectively. The factors associated with a higher survival in patients with FLC were age more than 23 years, feasibility of surgical resection, free surgical borders, absence of thrombosis or invasion to hepatic vessels and the absence of alterations in liver enzymes. The size of the tumor, gender, cellular proliferation and atypia did not affect the prognosis.</p> <p>Conclusion</p> <p>We concluded that FLC patients diagnosed before 23 years of age have worse prognosis than those diagnosed after age 23. Other factors associated with worse prognosis in this study are: lack of surgical treatment, presence of positive surgical margins, vascular invasion, and altered hepatic enzymes.</p