METHODS: In an attempt to visualize the aggregation behavior of GA and its subsequent association with PTX, 100 ns molecular dynamics simulation of a 5 mM aqueous solution of GA with 10 molecules of PTX was conducted using GROMACS and an all-atom forcefield.
RESULTS: Aggregation of GA molecules was found to occur quickly at this level of saturation leading to two stable aggregates of 13 and 17 GA molecules with an effective radius of 10.17 nm to 10.92 nm. These aggregates form not in isolation, but together with PTX molecule embedded within the structures, which reduces the number of interactions and hydrogen-bonding with water.
CONCLUSION: GA aggregation occurs around PTX molecules in solution, forming co-joined GA-PTX cluster units at a ratio of 3:1. These clusters remain stable for the remainder of the 100ns simulation and serve to isolate and protect PTX from the aqueous environment.
AIM OF THE STUDY: This study aimed to investigate the effect of ionic liquid-Graviola fruit pulp extract (IL-GPE) on the metabolomics behavior of colon cancer (HT29) by using an untargeted GC-TOFMS-based metabolic profiling.
MATERIALS AND METHODS: Multivariate data analysis was used to determine the metabolic profiling, and the ingenuity pathway analysis (IPA) was used to predict the altered canonical pathways after treating the HT29 cells with crude IL-GPE and Taxol (positive control).
RESULTS: The principal components analysis (PCA) identified 44 metabolites with the most reliable factor loading, and the cluster analysis (CA) separated three groups of metabolites: metabolites specific to the non-treated HT29 cells, metabolites specific to the treated HT29 cells with the crude IL-GPE and metabolites specific to Taxol treatment. Pathway analysis of metabolomic profiles revealed an alteration of many metabolic pathways, including amino acid metabolism, aerobic glycolysis, urea cycle and ketone bodies metabolism that contribute to energy metabolism and cancer cell proliferation.
CONCLUSION: The crude IL-GPE can be one of the promising anticancer agents due to its selective inhibition of energy metabolism and cancer cell proliferation.
OBJECTIVE: The aim of this study was to compare the effect of paclitaxel loaded PLGA nanoparticle (PTX-NPs) on the cytotoxicity and apoptosis of the different MDA-MB type of cell lines.
METHOD: PTX-NPs were prepared by nanoprecipitation method and characterized earlier. The cytotoxicity of PTX-NPs was evaluated by MTT and LDH assay, later apoptosis was calculated by flow cytometry analysis.
RESULTS: The prepared NP size of 317.5 nm and zetapontial of -12.7 mV showed drug release of 89.1 % at 48 h. MDA-MB-231 type cell showed significant cytotoxicity by MTT method of 47.4 ± 1.2 % at 24 h, 34.6 ± 0.8 % at 48 h and 23.5 ± 0.5 % at 72 h and LDH method of 35.9 ± 1.5 % at 24 h, 25.4 ± 0.6 % at 48 h and 19.8 ± 2.2 % at 72 h with apoptosis of 47.3 ± 0.4 %.
CONCLUSION: We have found that PTX-NPs showed the cytotoxic effect on all the MDA-MB cancer cell lines and showed potent anticancer activities against MDA-MB-231 cell line via induction of apoptosis.
MATERIALS AND METHODS: This study aimed to assess the effects of commercial and recombinant bromelain on the cytokinetic behavior of MCF-7 breast cancer cells and their potential as therapeutic alternatives in cancer treatment. Cytotoxic activities of commercial and recombinant bromelain were determined using (sulforhodamine) SRB assay. Next, cell viability assays were conducted to determine effects of commercial and recombinant bromelain on MCF-7 cell cytokinetic behavior. Finally, the established growth kinetic data were used to modify a model that predicts the effects of commercial and recombinant bromelain on MCF-7 cells.
RESULTS: Commercial and recombinant bromelain exerted strong effects towards decreasing the cell viability of MCF-7 cells with IC50 values of 5.13 μg/mL and 6.25 μg/mL, respectively, compared to taxol with an IC50 value of 0.063 μg/mL. The present results indicate that commercial and recombinant bromelain both have anti-proliferative activity, reduced the number of cell generations from 3.92 to 2.81 for commercial bromelain and to 2.86 for recombinant bromelain, while with taxol reduction was to 3.12. Microscopic observation of bromelain-treated MCF-7 cells demonstrated detachment. Inhibition activity was verified with growth rates decreased dynamically from 0.009 h-1 to 0.0059 h-1 for commercial bromelain and to 0.0063 h-1 for recombinant bromelain.
CONCLUSIONS: Commercial and recombinant bromelain both affect cytokinetics of MCF-7 cells by decreasing cell viability, demonstrating similar strength to taxol.
METHODS: The objective of this study is to determine the safety and efficacy of a novel crystalline sirolimus-coated balloon (cSCB) technology in an unselective, international, large-scale patient population. Percutaneous coronary interventions of native stenosis, in-stent stenosis, and chronic total occlusions with the SCB in patients with stable coronary artery disease or acute coronary syndrome were included. The primary outcome variable is the target lesion failure (TLF) rate at 12 months, defined as the composite rate of target vessel myocardial infarction (TV-MI), cardiac death or ischemia-driven target lesion revascularization (TLR). The secondary outcome variables include TLF at 24 months, ischemia driven TLR at 12 and 24 months and all-cause death, cardiac death at 12 and 24 months.
DISCUSSION: Since there is a wealth of patient-based all-comers data for iPCB available for this study, a propensity-score matched analysis is planned to compare cSCB and iPCB for the treatment of de novo and different types of ISR. In addition, pre-specified analyses in challenging lesion subsets such as chronic total occlusions will provide evidence whether the two balloon coating technologies differ in their clinical benefit for the patient.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04470934.
METHOD: We searched PubMed, Embase, EBSCOhost and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of combined atezolizumab and nab-paclitaxel with nab-paclitaxel alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs).
RESULTS: A total of six RCTs were included in this MA. For efficacy, although OS was not significantly prolonged with combined atezolizumab and nab-paclitaxel (HR 0.90, 95% CI [0.79, 1.01], p=0.08), this combination therapy significantly improved PFS (HR 0.72, 95% CI [0.59, 0.87], p=0.0006) and ORR (RR 1.25, 95% CI [0.79, 1.01] p<0.00001). For safety, any AEs, haematological, gastrointestinal, and liver AEs showed no statistically significant differences between the atezolizumab and nab-paclitaxel combination group and nab-paclitaxel alone group. However, serious AEs, high grade, dermatological, pulmonary, endocrine, and neurological AEs were significantly lower with nab-paclitaxel alone compared to atezolizumab and nab-paclitaxel combined (p-value range from <0.00001 to 0,02).
CONCLUSION: Atezolizumab combined with nab-paclitaxel was associated with improved outcomes in the treatment of TNBC; however, this combination resulted in more toxicity compared to nab-paclitaxel alone. While nab-paclitaxel alone produced chemotherapy-related AEs, the combination of atezolizumab with nab-paclitaxel produced AEs, especially immune-related AEs such as haematological, pulmonary, endocrine, and neurological AEs.
TRIAL REGISTRATION: This research work of systematic review has been registered on PROSPERO (Registration number: CRD42022297952).