The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

In order to evaluate the antioxidant properties of aqueous and methanol extracts of needles and berries of Juniperus oxycedrus subsp. oxycedrus (Joo) species, various antioxidant capacity assessment tests (free radical scavenging assays (DPPH• and ABTS•+ tests), ferrous ions (Fe2+) chelating activity and reducing power assay (FRAP) were conducted. In all of the tests, the extracts exhibited strong antioxidant activity. Furthermore, in-vitro cytotoxic activity assays of the methanolic extracts showed potent cytotoxic effects against two breast cancer cell lines (MDA-MB-468 and MCF-7), with no cytotoxicity towards normal cells (PBMCs). Reactive oxygen species generation was presumed to be a potential reason for the observed cytotoxic effects. According to all the above, and considering its appropriate composition of mineral elements and phenolic compounds, Joo could offer a beneficial and natural source of bioactive compounds that can be either used on the preventive side as it could potentially be used in the clinic without toxicity.

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Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer characterized by high morbidity and mortality. In the absence of targeted therapy, only chemotherapy is available in this case of cancer. The current study investigated the antitumor effect of new pyridazin-3(2H)-one derivatives on the human TNBC cell line, MD-MB-468. The in vitro cytotoxic activities were investigated using the tetrazolium-based MTT assay. Lipid peroxidation, H 2 O 2 content, and the specific activities of antioxidant enzymes were also determined. Two molecules, 6f and 7h, were found to be selectively highly active against tumor cells with IC 50 values of 3.12 and 4.9 µM, respectively. Furthermore, cells exposed to 6f showed a significant increase in H 2 O 2 and lipid peroxidation levels, accompanied by a decrease in the enzyme activities of glutathione reductase (GR) and thioredoxin reductase (TrxR). The cytotoxicity of the compound 6f may improve the therapeutic efficacy of the current treatment for TNBC via the inhibition of GR and TrxR activities.anticancer agent, cytotoxicity, oxidative stress, pyridazin-(2H)-3-ones, triple-negative breast cancer

The present study was conducted to evaluate a natural extract, obtained from the Beta vulgaris plant, for its phytochemical composition and its beneficial health effects. Therefore, total phenolic and flavonoid contents, as well as identification and quantification of phenolic compounds by HPLC, were assessed in leaves’ extract. Moreover, antioxidant activities were investigated using free radical scavenging tests, (ABTS+ and DPPH+) and reducing power assay (FRAP) as well as ferrous ions’ (Fe2+) chelating activity. The Antiglycation effect was also evaluated, using the BSA-fructose model, and the antidiabetic effect was determined by inhibition of α-amylase and α-glucosidase enzymes. Additionally, the in vitro antitumor effect was quantified using the MTT assay, and the antibacterial activity was evaluated using the agar disc diffusion and broth microdilution methods. Both aqueous and methanolic extracts exhibited potential antioxidant capacity with a higher effect for the methanolic extract. Furthermore, the in vitro antitumor activity of the methanolic extracts exhibited potent cytotoxic effects against two breast cancer cell lines, MDA-MB-468 and MCF-7. Moreover, Beta vulgaris extracts inhibit not only α-amylase and α-glucosidase, but also advanced glycation end-products’ (AGEs) formation, which would prevent diabetes’ complications. Beta vulgaris methanolic extract revealed also a high antibacterial effect against Proteus mirabilis and Bacillus subtilis. Taken together, these results revealed that Beta vulgaris leaves’ extracts constitute a valuable food and natural source of bioactive molecules that could be used for the development of new, natural drugs against cancer and diabetes.