METHODS: Eucalyptol, a monoterpene oxide active, was used to formulate the NLC-Eu by using high pressure homogenization technique. The physicochemical characterization of NLC-Eu was performed to assess its morphology, particle size, polydispersity index, and zeta potential. The in vitro cytotoxic effects of this encapsulated eucalyptol on human (MDA MB-231) and murine (4 T1) breast cancer cell lines were determined using the MTT assay. Additionally, acridine orange/propidium iodide assay was conducted on the NLC-Eu treated MDA MB-231 cells. The in vivo sub-chronic toxicity of the prepared NLC-Eu was investigated using an in vivo BALB/c mice model.
RESULTS: As a result, the light, translucent, milky-colored NLC-Eu showed particle size of 71.800 ± 2.144 nm, poly-dispersity index of 0.258 ± 0.003, and zeta potential of - 2.927 ± 0.163 mV. Furthermore, the TEM results of NLC-Eu displayed irregular round to spherical morphology with narrow size distribution and relatively uniformed particles. The drug loading capacity and entrapment efficiency of NLC-Eu were 4.99 and 90.93%, respectively. Furthermore, NLC-Eu exhibited cytotoxic effects on both, human and mice, breast cancer cells with IC50 values of 10.00 ± 4.81 μg/mL and 17.70 ± 0.57 μg/mL, respectively at 72 h. NLC-Eu also induced apoptosis on the MDA MB-231 cells. In the sub-chronic toxicity study, all of the studied mice did not show any signs of toxicity, abnormality or mortality. Besides that, no significant changes were observed in the body weight, internal organ index, hepatic and renal histopathology, serum biochemistry, nitric oxide and malondialdehyde contents.
CONCLUSIONS: This study suggests that the well-characterized NLC-Eu offers a safe and promising carrier system which has cytotoxic effect on breast cancer cell lines.
METHOD: The extracts were prepared using Soxhlet apparatus for ethanol and hexane extracts while the water extracts were freeze-dried. In vitro cytotoxic activities of B. frutescens extracts of various concentrations (20 to 160 μg/mL) at 24, 48, and 72 hours time points were studied using MTT in chemically induced hypoxic condition and in 3-dimensional in vitro cell culture system. An initial characterisation of B. frutescens extracts was carried out using Fourier-transform Infrared- Attenuated Total Reflection (FTIR-ATR) to determine the presence of functional groups.
RESULTS: All leaf extracts except for water showed IC50 values ranging from 23 -158 μg/mL. Hexane extract showed the lowest IC50 value (23 μg/mL), indicating its potent cytotoxic activity. Among the branch extracts, only the 70% ethanolic extract (B70) showed an IC50 value. The hexane leaf extract tested on 3- dimensional cultured cells showed an IC50 value of 17.2 μg/mL. The FTIR-ATR spectroscopy analysis identified various characteristic peak values with different functional groups such as alcohol, alkenes, alkynes, carbonyl, aromatic rings, ethers, ester, and carboxylic acids. Interestingly, the FTIR-ATR spectra report a complex and unique profile of the hexane extract, which warrants further investigation.
CONCLUSION: Adaptation of tumour cells to hypoxia significantly contributes to the aggressiveness and chemoresistance of different tumours. The identification of B. frutescens and its possible role in eliminating breast cancer cells in hypoxic conditions defines a new role of natural product that can be utilised as an effective agent that regulates metabolic reprogramming in breast cancer.
METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).
RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).
CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.
OBJECTIVES: To systematically review the existing cost-effectiveness evaluations of breast-cancer medication in developing-countries.
METHODOLOGY: A systematic literature search was performed in PubMed, EMBASE, SCOPUS, and EconLit. Two researchers determined the final articles, extracted data, and evaluated their quality using the Quality of Health-Economic Studies (QHES) tool. The interclass-correlation-coefficient (ICC) was calculated to assess interrater-reliability. Data were summarized descriptively.
RESULTS: Fourteen pharmacoeconomic studies published from 2009 to 2019 were included. Thirteen used patient-life-years as their effectiveness unit, of which 10 used quality-adjusted life-years. Most of the evaluations focused on trastuzumab as a single agent or on regimens containing trastuzumab (n = 10). The conclusion of cost-effectiveness analysis varied among the studies. All the studies were of high quality (QHES score >75). Interrater reliability between the two reviewers was high (ICC = 0.76).
CONCLUSION: In many studies included in the review, the use of breast-cancer drugs in developing countries was not cost-effective. Yet, more pharmacoeconomic evaluations for the use of recently approved agents in different disease stages are needed in developing countries.