Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer.

Introduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polymeric nanoformulation could overcome these limitations. Methods: In this study, PLGA-PTX nanoparticles (NPs) were assayed in breast cancer cell lines, breast cancer stem cells (CSCs) and multicellular tumor spheroids (MTSs) analyzing cell cycle, cell uptake (Nile Red-NR-) and α-tubulin expression. In addition, PLGA-PTX NPs were tested in vivo using C57BL/6 mice, including a biodistribution assay. Results: PTX-PLGA NPs induced a significant decrease in the PTX IC50 of cancer cell lines (1.31 and 3.03-fold reduction in MDA-MB-231 and E0771 cells, respectively) and CSCs. In addition, MTSs treated with PTX-PLGA exhibited a more disorganized surface and significantly higher cell death rates compared to free PTX (27.9% and 16.3% less in MTSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX's mechanism of action and increased its cell internalization. Interestingly, PTX-PLGA NPs not only reduced the tumor volume of treated mice but also increased the antineoplastic drug accumulation in their lungs, liver, and spleen. In addition, mice treated with PTX-loaded NPs showed blood parameters similar to the control mice, in contrast with free PTX. Conclusion: These results suggest that our PTX-PLGA NPs could be a suitable strategy for breast cancer therapy, improving antitumor drug efficiency and reducing systemic toxicity without altering its mechanism of action.

Associations Between Maternity Care Practices and 2-Month Breastfeeding Duration Vary by Race, Ethnicity, and Acculturation.

Objectives This study examines the associations between specific maternity care practices and breastfeeding duration for Spanish-speaking Hispanic, English-speaking Hispanic, non-Hispanic Native American, and non-Hispanic White women. Methods We analyzed data from the 2012-2014 New Mexico Pregnancy Risk Assessment Monitoring System. We used survey language as a proxy measure of acculturation and categorized women as Spanish-speaking Hispanic, English-speaking Hispanic, non-Hispanic Native American, and non-Hispanic White. We conducted bivariate analyses to compare rates of breastfeeding at 2 months and experiences of maternity care practices and logistic regression analysis to estimate the effects of these practices on breastfeeding duration for each group. Results Hispanic women were less likely than non-Hispanic women to breastfeed for at least 2 months (67.9% vs. 76.6%; p = 0.000); however, this varied significantly by acculturation level: 78.1% of Spanish-speaking Hispanic women compared to 66.1% of English-speaking Hispanic women breastfed for at least 2 months (p = 0.000). The effects of specific maternity care practices on duration varied across groups. Among non-Hispanic White, Native American, and English-speaking Hispanic women, breastfeeding while at the hospital had the strongest effect (AOR 2.09, 95% CI 1.67-2.61; AOR 2.71, 95% CI 2.08-3.52; and AOR 1.99, 95% CI 1.76-2.25, respectively). Among Spanish-speaking Hispanic women, being encouraged to breastfeed on demand had the strongest effect (AOR 5.179, 95% CI 3.86-6.94). Conclusions for Practice The effects of maternity care practices on breastfeeding duration vary by race, ethnicity, and acculturation level. Health care systems must acknowledge the diversity of their patient populations when seeking to develop and implement breastfeeding-friendly practices.

A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer.

Paclitaxel (PTX), a chemotherapy agent widely used to treat lung cancer, is characterised by high toxicity, low bioavailability and the need to use of excipients with serious side effects that limit its use. Paclitaxel encapsulation into nanoparticles (NPs) generates drug pharmacokinetic and pharmacodynamic advantages compared to free PTX. In this context, a NP carrier formed from a copolymer of lactic acid and glycolic acid (PLGA) has demonstrated high biocompatibility and low toxicity and therefore being approved by FDA to be used in humans. We synthesised a new PLGA NP and loaded it with PTX to improve drug efficacy and reduce side effects. This nanoformulation showed biocompatibility and no toxicity to human immune system. These NPs favor the intracellular uptake of PTX and enhance its antitumor effect in human and murine lung cancer cells, with up to 3.6-fold reductions in the PTX's IC50. Although PLGA NPs did not show any inhibitory capacity against P-glycoprotein, they increased the antitumor activity of PTX in cancer stem cells. Treatment with PLGA-PTX NPs increased apoptosis and significantly reduced the volume of the tumorspheres derived from A549 and LL2 cells by up to 36% and 46.5%, respectively. Biodistribution studies with PLGA-PTX NPs revealed an increase in drug circulation time, as well as a greater accumulation in lung and brain tissues compared to free PTX. Low levels of PTX were detected in the dorsal root ganglion with PLGA-PTX NPs, which could exert a protective effect against peripheral neuropathy. In vivo treatment with PLGA-PTX NPs showed a greater decrease in tumor volume (44.6%) in immunocompetent mice compared to free PTX (24.4%) and without increasing the toxicity of the drug. These promising results suggest that developed nanosystem provide a potential strategy for improving the chemotherapeutic effect and reducing the side effects of PTX.

Mixomas cardíacos: presentación clínica, resultados quirúrgicos y pronóstico a largo plazo / Cardiac Myxomas: Clinical Presentation, Surgical Outcomes and Long-term Prognosis

Introducción Los tumores cardíacos primarios constituyen una patología poco frecuente y de ellos el mixoma es el más común. Con el progreso acelerado de los métodos por imágenes se ha incrementado la frecuencia de su identificación in vivo. El cuadro clínico de presentación varía ampliamente de acuerdo con el tamaño y la localización tumoral. En Latinoamérica son escasas las comunicaciones acerca de los resultados quirúrgicos de la resección de mixomas cardíacos y del pronóstico a largo plazo. Objetivos Analizar la forma de presentación anatomoclínica, los resultados perioperatorios y la evolución de pacientes con mixoma cardíaco sometidos a resección quirúrgica. Material y métodos Revisión de 59 casos de mixomas cardíacos operados en nuestro centro entre 1992 y 2006. El seguimiento se realizó mediante consulta clínica, encuesta telefónica y ecocardiografía. Resultados La edad media fue de 53 ± 16,8 años. El 54,2% eran mujeres. La localización tumoral más frecuente fue en la aurícula izquierda en el 81% de los casos. La forma clínica de presentación fue obstructiva en el 52,5%, embólica en el 37,2%, constitucional en el 27,1%, arritmia supraventricular en el 22% y asintomática en el 10,1%. En dos casos (3,4%) se trató de recurrencias tumorales. El diámetro tumoral mayor se relacionó con la presentación obstructiva y la arritmia supraventricular. El diámetro tumoral menor se asoció con la presentación embólica. La localización ventricular se observó en pacientes más jóvenes. Se realizó resección tumoral asociada con revascularización coronaria en el 8,4% y cirugía valvular y/o de grandes vasos en el 13,5%. La mortalidad posoperatoria fue del 1,7% y las complicaciones más frecuentes fueron bloqueo auriculoventricular completo en el 23,7%, arritmia supraventricular en el 23,7% y bajo volumen minuto en el 18,6%. El seguimiento alejado se realizó en el 94,8% de los casos, con un promedio de 78,3 meses. El 65,5% de los pacientes evolucionaron asintomáticos. La complicación más frecuente durante el seguimiento fue la arritmia supraventricular en el 13,7%. Se constató un caso de recidiva tumoral. La mortalidad alejada fue del 6,8% (n = 4). Conclusiones El mixoma cardíaco habitualmente se diagnostica en pacientes sintomáticos. La cirugía posee una morbimortalidad baja, buen pronóstico a largo plazo y una tasa baja de recidiva en el seguimiento.

Background Primary heart tumors are very unfrequent, and among them, myxomas are most common. The development of new diagnostic imaging techniques has increased the in vivo diagnosis of cardiac myxomas. The clinical presentation varies with tumor size and location. In Latin America there is scanty information about the surgical results and long-term prognosis after the surgical resection of cardiac myxomas. Objectives To analyze the clinical presentation, pathological features, perioperative results and long-term outcomes of patients with cardiac myxoma undergoing surgical resection. Material and Methods We conducted a retrospective analysis of 59 cases of cardiac myxomas operated on in our center between 1992 and 2006. Follow-up was obtained through clinic visits, telephone interview and echocardiography. Results Mean age was 53±16.8 years and 54.2% were women. Myxomas were more frequently located in the left atrium (81%). The presence of symptoms related to obstruction was the most frequent clinical presentation (52.5%), followed by symptoms related to embolization (37.2%), constitutional symptoms (27.1%) and supraventricular arrhythmias (22%); 10.1% of cases were asymptomatic. Recurrences occurred in 2 cases (3.4%). The tumor diameter correlated with the presence of symptoms related to obstruction and with supraventricular arrhythmias. Embolism was associated with smaller tumors. Ventricular location was observed in younger patients. Tumoral resection was associated with coronary revascularization in 8.4% of cases and with heart valve and/or great vessel surgery in 13.5% of patients. Post-operative mortality was 1.7% and the most frequent complications were: complete atrioventricular block (23.7%), supraventricular arrhythmias (23.7%) and low cardiac output syndrome (18.6%). Complete long-term follow-up was achieved in 94.8% of cases; mean follow-up was 78.3 months. During follow-up, 65.5% of patients remained asymptomatic. Supraventricular arrhythmia was the most frequent complication (13.7%). A recurrence occurred in one patient. Late mortality rate was 6.8% (n=4). Conclusions Cardiac myxoma is usually diagnosed in asymptomatic patients. Surgery has low morbidity and mortality with favorable long-term outcomes and low recurrence rate during follow-up.