Abstract We reported the new biphasic composites of calcium phosphate and mesoporous silica material (CaP@MSi) in the form of powders and pellets as a potential bone drug delivery system for doxycycline hydrochloride (DOX). The CaP@MSi powders were synthesized by cationic surfactant-templating method. The effects of 10, 20, and 30% CaP content in the CaP@MSi powders on the molecular surface structure, the cytotoxicity against osteoblast cells in vitro , and the mineralization potential in simulated body fluid were investigated . The CaP@MSi characterized by the highest mineralization potential (30% CaP content) were used for DOX adsorption and pelletization process. The CaP which precipitated in the CaP@MSi composites was characterized as calcium-deficient with the Ca:P molar ratio between 1.0 and 1.2. The cytotoxicity assays demonstrated that the CaP content in MSi increases osteoblasts viability indicating the CaP@MSi (30% CaP content) as the most biocompatible. The combination of CaP and MSi was an effective strategy to improve the mineralization potential of parent material. Upon immersion in simulated body fluid, the CaP of composite converted into the bone-like apatite. The obtained pellets preserved the mineralization potential of CaP@MSi and provided the prolonged 5-day DOX release. The obtained biphasic CaP@MSi composites seem to have an application potential as bone-specific drug delivery system.
As dissemination through blood and lymph is the critical step of the metastatic cascade, circulating tumour cells (CTCs) have attracted wide attention as a potential surrogate marker to monitor progression into metastatic disease and response to therapy. In patients with invasive breast carcinoma (IBC), CTCs are being considered nowadays as a valid counterpart for the assessment of known prognostic and predictive factors. Molecular characterization of CTCs using protein detection, genomic and transcriptomic panels allows to depict IBC biology. Such molecular profiling of circulating cells with increased metastatic abilities appears to be essential, especially after tumour resection, as well as in advanced disseminated disease, when information crucial for identification of therapeutic targets becomes unobtainable from the primary site. If CTCs are truly representative of primary tumours and metastases, characterization of the molecular profile of this easily accessible ‘biopsy’ might be of prime importance for clinical practice in IBC patients. This review summarizes available data on feasibility and documented benefits of monitoring of essential IBC biological features in CTCs, with special reference to multifactorial proteomic, genomic, and transcriptomic panels of known prognostic or predictive value.
Osseointegration is a fundamental process during which implantable biomaterial integrates with host bone tissue. The surgical procedure of biomaterial implantation is highly associated with the risk of bacterial infection. Thus, the research continues for biodegradable bone void fillers which are able to stimulate the bone tissue regeneration and locally deliver the antibacterial agent. Herein, we obtained bifunctional bioglass (BG) using novel, preoptimized, rapid one-pot synthesis. Following the ISO Standards, the influence of the obtained BG on osteoblast-mediated phenomena, such as osteoconduction and osteoinduction was assessed and compared to two commercial materials: bioactive glass powder 45S and bioactive glass powder 85S. Direct-contact tests revealed osteoblast adhesion to BG particles; whereas, tests on extracts confirmed high viability of cells incubated with BG extract. Analyses of gene expression, alkaline phosphatase activity, and calcium phosphates deposition confirmed the stimulation of early and late stages of osteoblast differentiation and mineralization. Additionally, an extended evaluation of intracellular calcium fluctuations revealed a possible correlation between osteoblast calcium uptake and extracellular matrix mineralization. Moreover, proposed bioglass exhibited satisfactory doxycycline adsorption capacity and release profile. The obtained results confirmed the bifunctionality of the proposed BG and indicated its potential as osseointegrative bone drug delivery system.
The amplification of estrogen receptor alpha (ERα) encoded by the ESR1 gene has been described as having a prognostic role in breast cancer patients. However, increased dosage of the ESR1 gene (tested by real-time PCR) is also observed in ER-negative breast cancers, which might suggest the expression of alternative isoforms of ERα (other than classical ERα of 66 kDa). In the current work, we have investigated the ESR1 gene dosage in 402 primary breast cancer patients as well as the expression of ERα isoforms—ERα66 and ERα36—on mRNA and protein levels. The obtained results were correlated with clinicopathological data of the patients. Results showed that increased ESR1 gene dosage is not related to ESR1 gene amplification measured by fluorescent in situ hybridization (FISH), but it correlates with the decreased expression of ERα66 isoform (p = 0.01). Interestingly, the short ER isoform ERα36 was expressed in samples with increased ESR1 gene dosage, suggesting that genomic aberration might influence the expression of that particular isoform. Similarly to ESR1 increased gene dosage, high ERα36 expression was linked with the decreased disease-free survival of the patients (p = 0.05), which was independent of the status of the classical ERα66 level in breast tumors.
Fibroblast growth factor receptor 2 (FGFR2) activation is associated with endocrine therapy resistance in luminal breast cancer (BC) in vitro, but clinical evidence remains inconsistent. Given the role of FGFRs in mediating tumour microenvironment (TME) interactions, the prognostic value of FGFR2 may depend on the stromal component. This study aimed to validate the association between FGFR-related profile of the stroma and FGFR2 prognostic value in oestrogen receptor-positive invasive ductal carcinoma (IDC). An in silico gene expression analysis identified 12 stromal factors (FAP, CXCL12, PDGFRA, COL1A1, HSPG2, CCL2, MMP14, S100A4, MMP9, PDGFA, MCAM, IL6) forming an "FGFR-related profile of the stroma". A cohort of 257 ER+ IDC patients from The Cancer Genome Atlas (TCGA) was analysed. Tumours were clustered using k-means based on stromal gene expression, and Cox proportional hazards regression models were used to assess the association between FGFR2 and overall survival (OS). Two clusters of ER+ IDC tumours were identified based on the stromal gene expression profile. While both clusters had similar tumour stages and hormone receptor statuses, multivariable analysis adjusted for clinical factors revealed a significant association between FGFR2 expression and cluster assignment. In Cluster I (high expression of stromal genes), high FGFR2 was linked to poor prognosis, whereas in Cluster II (low expression), high FGFR2 indicated favourable prognosis. FGFR1, FGFR3, and FGFR4 showed no significant prognostic value. Stromal profiles modulate the prognostic significance of FGFR2 in luminal breast carcinoma, highlighting the importance of TME profiling for biomarker assessment and explaining inconsistencies in FGFR2 studies.
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