Enhancing 5-ALA-PDT efficacy against resistant tumor cells: Strategies and advances.

As a precursor of protoporphyrin IX (PpIX), an endogenous pro-apoptotic and fluorescent molecule, 5-Aminolevulinic acid (5-ALA) has gained substantial attention for its potential in fluorescence-guided surgery as well as photodynamic therapy (PDT). Moreover, 5-ALA-PDT has been suggested as a promising chemo-radio sensitization therapy for various cancers. However, insufficient 5-ALA-induced PpIX fluorescence and the induction of multiple resistance mechanisms may hinder the 5-ALA-PDT clinical outcome. Reduced efficacy and resistance to 5-ALA-PDT can result from genomic alterations, tumor heterogeneity, hypoxia, activation of pathways related to cell surveillance, production of nitric oxide, and most importantly, deregulated 5-ALA transporter proteins and heme biosynthesis enzymes. Understanding the resistance regulatory mechanisms of 5-ALA-PDT may allow the development of effective personalized cancer therapy. Here, we described the mechanisms underlying resistance to 5-ALA-PTD across various tumor types and explored potential strategies to overcome this resistance. Furthermore, we discussed future approaches that may enhance the efficacy of treatments using 5-ALA-PDT.

The combined anti-tumor effects of 5-fluorouracil and neurokinin receptor inhibitor, aprepitant, against colorectal cancer: In vitro and in vivo study.

BACKGROUND: Colorectal cancer (CRC) is one of the world's largest health concerns with growing global incidence and mortality. The potential value of the neurokinin-1 receptor as a therapeutic target has been reported in several tumor types, including CRC. Here we examined the potential anti-tumor effects of a clinically approved neurokinin-1 receptor antagonist, aprepitant, alone and its combination with 5-Fluorouracil (5-FU) as a first choice CRC chemotherapeutic drug, in both in vitro and in vivo models of CRC. METHODS: MTT assay was employed for assessing cell proliferation. mRNA expression levels were determined by quantitative real-time PCR (qRT-PCR). Flow cytometric analysis of apoptosis was performed using an Annexin-V/propidium iodide assay kit. We finally conducted an in vivo experiment in a mouse model of CRC to confirm the in vitro antiproliferative activity of aprepitant and 5-FU. RESULTS: We found that aprepitant and 5-FU significantly reduced CRC cell viability. The combination of drugs exhibited potent synergistic growth inhibitory effects on CRC cells. Moreover, aprepitant and 5-FU induced apoptosis and altered the levels of apoptotic genes (up-regulation of Bax, and p53 along with downregulation of Bcl-2). Importantly, the aprepitant and 5-FU combination showed a more pronounced impact on apoptosis and associated genes than either of the agents alone. Furthermore, aprepitant reduced tumor growth in vivo and led to significantly longer survival time, and this effect was more prominent when using the aprepitant and 5-FU combination. CONCLUSIONS: Collectively, combinatory treatment with aprepitant and 5-FU potentially exerts synergistic growth inhibition and apoptosis induction in CRC, deserving further consideration as a novel strategy for CRC patients.

miR-27a/b Level is Associated with ABCA1 Expression and is a Potential PBMC-Based Biomarker for Coronary Artery Disease

Abstract Background: Coronary artery disease (CAD) is the most common form of cardiac disease with high morbidity and mortality rates. Objectives: In this study, we evaluated the expression of miR-27a and miR-27b as biomarkers in peripheral blood mononuclear cells (PBMCs) of patients with CAD and investigated its correlation with cholesterol-efflux transporter, ATP-binding cassette transporter A1 (ABCA1). Method: This study was performed on 54 men with CAD and 51 healthy, sex- and age-matched control participants. The expression of miR-27a/b and ABCA1 genes in PBMCs were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of ABCA1 was assessed by Western blotting. Concurrently, the specificity and sensitivity of miR-27a/b was evaluated through receiver operating characteristic (ROC) curve. The significance level adopted in the statistical analysis was 5%. Results: We found that miR-27a and miR-27b expression were significantly increased, while both mRNA and protein expression of ABCA1 were markedly reduced in the PBMCs of CAD patients in comparison to non-CAD controls. miR-27a/27b expression was also shown to be inversely correlated with ABCA1. ROC analysis showed that the miR-27a had an area under the ROC curve (AUC) of about 92.6 (sensitivity 83.3٪ and specificity 86.6٪) and miR-27b had an AUC of about 93.0 (sensitivity 86.6٪ and specificity 80.0 (%, suggesting the diagnostic potential of miR-27a/b in CAD patients. Conclusions: Our data suggested a possible role of miR-27a/b in CAD pathogenesis. Additionally, we proposed that miR-27a/b expression in PBMCs may have potential clinical implications in the diagnosis of CAD patients, but further validations in large cohorts are required.