Evaluation of [99mTC(CO)3]-labeled ERBB-2-targeting peptides for breast carcinoma imaging [abstract]

The purpose of this study was to radiolabel a novel ErbB-2-avid peptide, discovered from bacteriophage display, with [99mTc(H2 O)3 (CO)3 ]+ and evaluate the in vitro cellular targeting and in vivo tumor imaging properties of the peptide in a mouse model of human breast cancer

Effect of Grafting Rootstock on the Antioxidant Capacity and Content of Heirloom Tomatoes (Solanum lycopersicum L.) in Hydroponic Culture

Heirloom tomato varieties are in demand by consumers due to high antioxidant levels. However, these varieties are difficult to produce and are prone to disease. To overcome these problems, heirloom tomatoes may be cultivated in hydroponic systems and grafted onto disease-resistant rootstocks. However, it is unknown if the antioxidant content and capacity are affected by grafting. In this study, heirloom (Black Krim and Green Zebra) and standard (Big Beef) varieties were grafted onto wild type (WT) or productive rootstocks (Arnold and Supernatural). The tomatoes were harvested at maturity, freeze-dried, and ground into a powder. Lycopene was extracted using hexane, and the content was determined spectrophotometrically at 503 nm. The antioxidant capacity of methanol extracts was evaluated by the 2,2′-azino-di[3-ethylbenzthiazoline sulfonsyr]sulphonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, whereas the phenolic content was determined using the Folin–Ciocalteu assay. Interestingly, the grafting of Big Beef and Green Zebra onto Supernatural rootstock resulted in an increased antioxidant capacity, as determined by the DPPH assay. Moreover, the phenolic content was changed for Big Beef grafted onto Arnold, and Big Beef and Green Zebra grafted onto Supernatural. Taken together, these results indicate that certain combinations of standard and heirloom tomato varieties and productive rootstocks may influence the antioxidant capacity and phenolic content. These results may be used to guide producers when choosing rootstocks for cultivating hydroponic tomatoes

Compounds from Morchella esculenta as Potential Inhibitors of RNA-Binding Protein La in Ovarian Cancer: A Molecular Modeling and Quantum Mechanics Approach

Ovarian cancer (OC) is implicated in most gynecological cancer-related deaths. Currently, the primary treatments for OC are surgery and chemotherapy using platinum-based drugs to induce remission. However, OC recurs in 70-80% of patients within two years, which usually results in the death of most OC patients. La protein is significantly expressed in various malignant tumors, including OC. Previous studies reported that OC patients have significantly higher levels of La protein expression in their serum than healthy individuals, which is related to the poor response to platinum-based chemotherapy. Inhibiting La protein could control the expression of the potential downstream genes involved in promoting proliferation and chemotherapy resistance to OC, which could serve as a therapeutic intervention in treating OC. Extract from Morchella esculenta (morel mushroom) has been reported to contain anti-cancer properties, but no study has reported the interaction of its bioactive compounds with La protein in OC. This study examines the interaction of La protein with some bioactive compounds of Morchella esculenta, as well as their pharmacokinetics and thermochemical properties using structural bioinformatics and advanced theoretical chemistry techniques. Molecular modeling techniques incorporating molecular docking, free energy calculation, MD simulation, drug-likeness, and quantum chemical calculations, including the global hybrid and long-range corrected density functional theory approximations, were employed in this study. Thus, the results identify hits compounds from morchella esculanta, which could serve as a starting for the development of novel LA protein inhibitors for OC therapeutics

Ovarian Cancer Targeting Phage for In Vivo Near-Infrared Optical Imaging

Ovarian cancer is often diagnosed at late stages due to current inadequate detection. Therefore, the development of new detection methods of ovarian cancer is needed. This may be achieved by phage nanoparticles that display targeting peptides for optical imaging. Here, two such phage clones are reported. Ovarian cancer binding and specificity of phage clones (pJ18, pJ24) and peptides (J18, J24) were investigated using fluorescent microscopy and modified ELISA. Further, AF680-labeled phage particles were subjected to biodistribution and optical imaging studies in SKOV-3 xenografted mice. Fluorescent microscopy and ELISA of phage and peptides showed significantly increased binding to SKOV-3 cells compared to controls. Additionally, these studies revealed that J18 exhibits specificity for ovarian cancer SKOV-3 and OVCAR-3 cell lines. Further, peptides displayed increased SKOV-3 binding compared to N35 (non-relevant peptide) with EC50 values of 22.2 ± 10.6 μM and 29.0 ± 6.9 (mean ± SE), respectively. Biodistribution studies of AF680-labeled phage particles showed tumor uptake after 4 h and excretion through the reticuloendothelial system. Importantly, SKOV-3 tumors were easily localized by optical imaging after 2 h and 4 h and displayed good tumor-to-background contrast. The fluorescent tumor signal intensity was significantly higher for pJ18 compared to wild type (WT) after 2 h

Computational Evaluation of Bioactive Compounds from Viscum album (Mistletoe) as Inhibitors of p63 for Pancreatic Cancer Treatment

Pancreatic ductal adenocarcinoma is an aggressive malignancy usually detectable at the advanced stage, with a 5-year survival rate of less than 8%. It has been reported that a gene called tumor-protein 63 (TP63) is expressed in an aggressive form of pancreatic cancer with a squamous signature. Thus, inhibiting the activity of p63 can be a means of treating and managing PDA. Different studies have shown that plant constituents are rich and can be a promising source for discovering drug candidates. The extract from mistletoe (Viscum album) is known to contain anticancer compounds; however, the specific molecular mechanism of the bioactive compounds is unknown. This study examines the pancreatic cancer therapeutic potential of the bioactive compounds in the flavonoid and phenolic acid constituents of mistletoe by adopting structural bioinformatics and advanced theoretical chemistry techniques via molecular docking, molecular dynamics simulation, molecular mechanics/ generalized Born surface area (MM/GBSA) calculations, pharmacokinetic analysis, and density functional theory analysis. The six best compounds from the flavonoid constituent with the highest binding affinity ranging from -6.8 kcal/mol to -6.7 kcal/mol were selected with the control gemcitabine (-5.5 kcal/mol) for further computational analysis after molecular docking. Furthermore, MM/GBSA calculation showed the highest binding energy for the selected docked compounds, which validates their inhibitory potential. Hence, the molecular dynamics simulation, post-simulation analysis, pharmacokinetics model, and DFT results showed that mistletoe compounds are reliable due to their stable interaction with the target protein and drug-likeness properties