Preclinical Efficacy of Cabazitaxel Loaded Poly (2-alkyl cyanoacrylate) Nanoparticle Variants

\ua9 2024 Valsalakumari et al. This work is published and licensed by Dove Medical Press Limited.Background: Biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) are receiving increasing attention in anti-cancer nanomedicine development not only for targeted cancer chemotherapy, but also for modulation of the tumor microenvironment. We previously reported promising results with cabazitaxel (CBZ) loaded poly(2-ethylbutyl cyanoacrylate) NPs (PEBCA-CBZ NPs) in a patient derived xenograft (PDX) model of triple-negative breast cancer, and this was associated with a decrease in M2 macrophages. The present study aims at comparing two endotoxin-free PACA NP variants (PEBCA and poly(2-ethylhexyl cyanoacrylate); PEHCA), loaded with CBZ and test whether conjugation with folate would improve their effect. Methods: Cytotoxicity assays and cellular uptake of NPs by flow cytometry were performed in different breast cancer cells. Biodistribution and efficacy studies were performed in PDX models of breast cancer. Tumor associated immune cells were analyzed by multiparametric flow cytometry. Results: In vitro studies showed similar NP-induced cytotoxicity patterns despite difference in early NP internalization. On intravenous injection, the liver cleared the majority of NPs. Efficacy studies in the HBCx39 PDX model demonstrated an enhanced effect of drug-loaded PEBCA variants compared with free drug and PEHCA NPs. Furthermore, the folate conjugated PEBCA variant did not show any enhanced effects compared with the unconjugated counterpart which might be due to unfavorable orientation of folate on the NPs. Finally, analyses of the immune cell populations in tumors revealed that treatment with drug loaded PEBCA variants affected the myeloid cells, especially macrophages, contributing to an inflammatory, immune activated tumor microenvironment. Conclusion: We report for the first time, comparative efficacy of PEBCA and PEHCA NP variants in triple negative breast cancer models and show that CBZ-loaded PEBCA NPs exhibit a combined effect on tumor cells and on the tumor associated myeloid compartment, which may boost the anti-tumor response

Active Range Sensing for Mobile Robot Localization

This paper presents an active scheme for the localization of a mobile robot based on the detection of natural landmarks. Assuming that a partial 3D model of the environment is known a priori, an optimal and active choice of the landmark is supported on a new strategy for 3D map partition, yielding high updating rates of the location estimates. Good localization accuracy and robustness are achieved by combining laser range data with odometry, using Kalman filtering schemes. 1 Introduction Accurate localization is a fundamental issue in mobile robots navigation. Various factors may incurring the mobile robot in error during operation [3], and hence, reliable localization is a difficult and not yet completely solved problem. In one hand, complex environments present serious difficulties to overcome, such as dynamic and/or static unmodeled obstacles, human beings presence as well as coordination with other robots. On the other hand, inaccuracies on sensor measurements or inappropriate sen..

Unusual wooden foreign body in the palate

We report a case of a palatal calcified foreign body simulating an odontogenic lesion. Surgical exploration revealed a calcified mass that was analysed under light microscopy and identified as a vegetal foreign body. Further scanning electron microscopy analysis revealed that the foreign body was a piece of wood. Hard palate foreign bodies have been reported previously, however, it seems that this is the first case of its kind.2031057357

Novel on-line sequential preconcentration system of Cr(III) and Cr(VI) hyphenated with flame atomic absorption spectrometry exploiting sorbents based on chemically modified silica

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)In the present study, a flow injection system using dual mini-columns, SiO2/Al2O3/TiO2 and silica gel functionalized with [3-(2-aminoethylamino)propyl] trimethoxysilane (SiO2/AAPTMS) for the sequential preconcentration of Cr(III) and Cr(VI), respectively, from water samples with FAAS detection was proposed. A two-level full factorial design (2(4)) and desirability function were employed for the optimization of variables related to the system performance. The detection limits of 0.66 and 0.27 mu g L-1 for Cr(III) and Cr(IV), respectively, were obtained under the optimized preconcentration conditions (flow rate of 7.0 mL min(-1)), pH 5.0, buffer concentration (acetate buffer) of 0.01 mol L-1, and eluent (2.5 mol L-1 HCl) flow rate of 5.0 mL min(-1). The other parameters including preconcentration factor (PF), consumptive index (CI), and concentration efficiency (CE) were found to be 17.62/32.98, 1.13/0.6 mL, and 6.2/11.54 min(-1) for Cr(III)/Cr(VI), respectively. The developed method was applied to the Cr(III) and Cr(VI) determination in water samples [tap, lake and mineral water, artificial saliva and parenteral solutions (physiological serum, water for injection, and glucose physiological solution)]. The method accuracy was checked by the analysis of standard reference materials (trace elements in water). (C) 2012 Elsevier B.V. All rights reserved.1007179Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)UFU (Universidade Federal de Uberlandia)UEL (Universidade Estadual de Londrina)UESB (Universidade Estadual do Sudoeste da Bahia)UFRJ (Universidade Federal do Rio de Janeiro)INCT for Bianalytics (Institut Nacional de Ciencia e Tecnologia de Bioanalitica)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Correlação interobservador das alterações morfológicas das vias biliares em pacientes com esquistossomose mansoni pela colangiorressonância magnética Evaluation of morphological changes of the biliary tree by magnetic resonance cholangiography in patients with schistosomiasis mansoni: interobserver agreement

OBJETIVO: Descrever as alterações das vias biliares pela colangiografia por ressonância magnética (CPRM) na esquistossomose hepatoesplênica e avaliar a concordância interobservador da CPRM na detecção de colangiopatia esquistossomótica. MATERIAIS E MÉTODOS: Estudo prospectivo e transversal em 24 pacientes com a forma hepatoesplênica da esquistossomose mansoni e em 6 pacientes sadios, como grupo controle, com avaliação da via biliar pela CPRM. As alterações da via biliar consideradas foram: distorção, afilamento, estenose, dilatação e irregularidade. Foi calculada a concordância interobsevador para alteração da via biliar com o teste de McNemar e o índice kappa (&#954;). RESULTADOS: A concordância interobservador na caracterização de distorção e afilamento da via biliar foi quase perfeita (&#954; = 0,867; intervalo de confiança [IC] 95% [0,512-1,0] e &#954; = 0,865; IC 95% [0,51-1,0], respectivamente). A concordância foi substancial para a estenose (&#954; = 0,78; IC 95% [0,424-1,0]), moderada para dilatação (&#954; = 0,595; IC 95% [0,247-0,942]) e regular para afilamento (&#954; = 0,229; IC 95% [0,095-0,552]). CONCLUSÃO: As alterações observadas nas vias biliares foram, em ordem decrescente de ocorrência: distorção, afilamento, estenose, dilatação e irregularidade. A concordância interobservador para sinais de colangiopatia esquistossomótica foi quase perfeita para distorção e afilamento e substancial para estenose.<br>OBJECTIVE: To describe changes of the biliary tree demonstrated by magnetic resonance cholangiography (MRC) in patients with the hepatosplenic presentation of schistosomiasis mansoni, and evaluating the interobserver agreement in the detection of schistosomal cholangiopathy. MATERIALS AND METHODS: Prospective, cross-sectional study involving 24 patients with hepatosplenic schistosomiasis and 6 healthy patients (control group) submitted to biliary tree evaluation by MRC. The following changes of the biliary tree were considered: distortion, thinning, stenosis, dilation and irregularity. The interobserver agreement in the detection of biliary tree changes was calculated with the McNemar's test and the kappa index of agreement (&#954;). RESULTS: The interobserver agreement in the detection of distortion and thinning of the biliary tree was almost perfect (&#954; = 0.867; confidence interval [CI] 95% [0.512-1.0] and &#954; = 0.865; CI 95% [0.51-1.0], respectively). There was a substantial agreement for stenosis (&#954; = 0.78; CI 95% [0.424-1.0]), moderate agreement for dilation (&#954; = 0.595; CI 95% [0.247-0.942]) and mild agreement for thinning (&#954; = 0.229; CI 95% [0.095-0.552]). CONCLUSION: In a decreasing order of frequency, the changes of the biliary tree were observed: distortion, thinning, stenosis, dilation and irregularity. The interobserver agreement for signs of schistosomal cholangiopathy was almost perfect for distortion and thinning, and substantial for stenosis