No abstract

Conjugation of Herceptin to the surface of an optimized rGO-PLL/AgNP nanohybrid to achieve an efficient targeted DDS against Her2 positive breast cancer cells.

Understanding the cellular and molecular toxicity of graphene and its derivatives is essential for their biomedical applications. Herein, gene expression profile of graphene-exposed cells was retrieved from the Gene expression omnibus database.Differentially expressed genes and their functional roles were then investigated through the pathway, protein-protein interaction (PPI) network, and module analysis.High degree (hub) and high betweenness centrality (bottleneck) nodes were subsequently identified. The functional analysis of central genes indicated that these graphene-gene interactions could be of great value for further investigation. Accordingly, we also followed the expression of five hub-bottleneck genes in graphenetreated murine peritoneal macrophages and human breast cancer cell line by realtime PCR. The five hub-bottleneck genes related to graphene cytotoxicity; CDK1, CCNB1, PLK1, TOP2A, and CCNA2 were identified through network analysis, which were highly correlated with regulation of cell cycle processes. The module analysis indicated the cell cycle pathway to be the predominant one. Gene expression evaluation showed downregulation of these genes in the macrophages and cancer cells treated with graphene. These results provided some new intuitions concerning the graphene-cell interactions and unveiled targeting critical cell cycle regulators. The present study indicated some toxic effects of graphene-based materials through systems toxicology assessment. Integrating gene expression and PPI network may help explaining biological responses of graphene and lead to beneficial impacts in nanomedicine. K E Y W O R D Scell cycle, gene expression, graphene, protein-protein interaction network, systems toxicology

Background: Breast cancer (BC) is the most frequent cause of cancer death in women. The thoracic pectoral nerve (PECS) block has been described as the gold standard analgesic modality for BC surgery. It has been previously reported that PECS is associated with decreased BC recurrence post-mastectomy. Although several anesthetic drugs and techniques are used in surgical oncology, their effects on the behavior of cancer cells are yet to be known and the key question of whether the anesthetic technique affects cancer outcome remains unresolved. Objectives: Since anesthetic drugs and techniques and post-operative pain may affect BC recurrence, this study aimed to determine whether the anesthetic choice and technique, PECS II block, affects in vitro apoptosis of the MDA-MB-231 BC cell line. Methods: Twenty-two female BC patients, 20 to 75-years-old, with the same pathologic grades were included in this study. The patients were randomly divided into two groups. The first group received propofol general anesthesia (PGA) associated with PECS and the second group received standard PGA. Blood was sampled pre and post-operation from all patients. The sera were isolated and then exposed to the MDA-MB-231 human BC cell line. The mean percentage of apoptosis indices was analyzed by flow cytometry using Annexin V-fluorescein isothiocyanate 24 hours after treatment with patients’ sera. Results: A significant decrease was seen in the mean viability percentage of BC cell line in the PECS group, besides a significant increase in the mean percentage of necrosis and late apoptosis indices compared to the control group after exposure to sera collected from patients post-operation. Intra-group analysis of the control group showed that the exposure of the tumoral cell to post-operation sera resulted in a significant increase in the mean percentage of necrosis and late apoptosis index compared to pre-operation sera exposure. In the PECS group, the exposure of the tumoral cell to post-operation sera resulted in a significant increase in the mean percentage of cell viability and late apoptosis index compared to pre-operation sera exposure. Conclusions: In conclusion, anesthesia and BC surgery may induce apoptosis indices in the MDA-MB-231 human BC cell line. We also found that sera collected from PECS II block patients with BC could induce more apoptosis in the MDA-MB-231 cell line compared to collected sera from systemic analgesia alone after BC surgery.

Background Interleukin (IL)-1 and metalloproteinases (MMP) are thought to play a crucial role in the cartilage degradation of osteoarthritis (OA). Recently it has been proposed that CRP may be useful index of OA activity and severity. Objectives We studied the relationships between synovial fluid (SF) IL-1b, MMP1 and MMP3, and serum levels of CRP in patients with OA of the knee (KOA) to investigate the role of CRP in KOA. Methods In the SF from 25 patients with KOA (Altman criteria, Kellgren and Lawrence score of 2 or greater on X-ray plan films) we determined the levels of IL-1b, MMP-1 and MMP-3 (ELISA), along with WBC number. In the same patients serum concentration of CRP was analysed by ultrasensitive rate nephelometry. No patients were taking NSAIDs or other antirheumatic drugs. Results In SF, MMP1 was correlated with MMP3 (r = 0.61, p = 0.0009), and MMP3 with IL-1b (r = 0.67, p = 0.0002). In turn, serum CRP was correlated with MMP3 (r = 0.76, p < 0.0001) and, at lower level, with MMP1 (r = 0.49, p = 0.01) and IL-1b (r = 0.49, p = 0.01). Conclusion The correlations found between serum CRP and SF levels of substances believed to be crucial in OA cartilage degradation, such as MMPs and IL-1, confirm the role of marker of disease severity recently proposed for this acute phase protein.