Раковая наука и терапия

Objective: Active components of natural foods are increasingly receiving attention for their chemopreventive and chemotherapeutic potential in a wide variety of cancers. Rosmarinic acid (RA), a phenolic compound in various herbal plants, is well-recognized for its anti-oxidant, anti-inflammatory, anti-proliferative properties in a variety of cell types. In this report, we describe a novel role for RA as an inhibitor of epidermal growth factor (EGF) stimulated signaling in HNSCC and propose a cellular reactive oxygen species (ROS)-mediated mechanism for the observed effects.

Methods: Cellular growth, migration and reactive oxygen species (ROS) profiles were examined in RA-treated and untreated HNSCC cell lines (UM- SCC-6 and UM-SCC-10B) using the WST-1 viability assay, established in vitro migration assays, and the CM-H2DCFDA ROS assay, respectively. The influence of RA on EGF-stimulated phosphorylation and its downstream pathways was evaluated using Western-blotting techniques.

Results: RA inhibited cell viability, migration and cellular production of ROS in HNSCC cell lines. Furthermore, RA inhibited EGF-induced phosphorylation of the EGFR at tyrosine residues 992 and 845, which led to downregulation of the phosphatidylinositol 3-kinase Akt (PI3K/Akt) and mitogen-activated protein kinase ERK (MAPK/ ERK) pathways.

Conclusions: This is the first report describing both growth- and motility-inhibitory roles for RA in HNSCC cells. Additionally, our study is the first to demonstrate that treatment with RA can reduce EGF-induced activation of PI3K/ Akt in tumor cells. The present data suggests that RA holds promise as a chemotherapeutic agent against HNSCC.

??????????? ? ????: ?????? ????????????? ?????? (???) — ??????????????? ??????????? ?????????? ??????-????????????????. ?????? ??????????????? ??????? ????? ??? ?????????? ???????. ???????? ????????? ??????? CD44 ????????? ? ?????????????? ?????????? ?????????? ?????? ? ???????????????? ??????????????? ???????????????. CD44v6 — ?????? ???????? ????????? CD44. ??? ?????? ?????? ???? ? ????? ? ???????? ?????????? ??? ????????? ???????????????? ??????????????? ????????????????. ????? ??????? ???????????? ???????? ????????? ?????????? CD44 ? CD44v6 ? ????? ? ?????? ????????????? ???????? ? ?? ?????????? ? ????????? ? ??????? ???????????? ???????????????? ????????? ??? ???.

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??????????: ?????????? CD44 ???? ??????????? ???? ? ?????? I, ??? ? ?????? II (P=0,001), ? ?? ????? ??? ?? ???? ???????????? ??????? ????? CD44v6 ? ?????? I ? ?????? II. ???????? ????????????? ?????????? ????? CD44% ? ??????? ???, ????? ??????????? ?????????? ? ????????? ???????? ???????? ????? (r=0,64, P=0,001 ? r=0,62, P=0,001 ? r=0,92, P=0,001) ??????????????, ?????? ???? ????????????? ???????? ????????????? ?????????? ????? CD44%, ??????? ??????????? (HB) ? ??????????? ??????????? (r=-0,93, P=0,001 ? r=-0,92, P=0,001) ??????????????. CD44%, ?????????? ??????????, ??????? ??????? ? ??????????????? ?/??? ?????????????? ??? ??????????? ???? ? ????? ? ??????????????? ???????. ?? ???? ???????? ???????????? ??????? ????? ????????????? ? ??????????????? ??????? ? ????????? CD44v6 (P=0,1), ? ????? ?? ???? ???????? ?????????? ????? CD44 v6, ??????? HB, ??????????? ???????????, ??????????? ??????????, ??????? ??? ? ????????? ???????? ???????? ????? ? ????????? ? ???.

??????????: ?????????? CD44, ?? ?? CD44v6, ????? ??????? ?????? ??????????????? ???????? ??? ??? ? ?????, ????????? ? ?????? ?????????. ??????? ?????????? CD44 ?????????? ????????? ???????? ?????.

Background: Poor bone regeneration is a devastating complication after large tumor resection. Different synthetic bone-grafting materials have been used to restore skeletal defects. Several studies evaluated the capability of mesenchymal stem cells to improve the efficacy of bone regenerative potential of biomaterials. However, there are no data, in human, about the combinatory use of silicate granules with autologous Bone Marrow Mononuclear cells (BMMCs) to refill bone cavity.

Methods: BMMCs were prepared in accordance with the International Society for Cell Therapy guidelines. MTT assays and scanning electron microscopy evaluated the biocompatibility, and adhesion of BMMCs to the granular silicate bone substitute. In vivo study is based on twenty patients with malignant osteolytic lesions. The mean volume of the lesions, measured by pre-operative computed tomography (CT) was 18.5 cm2 (range 16-24 cm2). Sixteen patients were treated post-surgery with curettage and refilling with granular silicate alone, and four with a combination of granular silicate and BMMCs The follow-up was determined by clinical, Musculoskeletal Tumor Society functional state score system (MSTS), and radiograph examination, moreover, the callus type was classified according to the International System.

Results: Scanning electron microscopy showed that 90% of BMMCs adhered to silicate granules in a few minutes and long pseudopodia contacting extra-cellular matrix. Patients treated with autologous BMMCs and granular silicate developed bone callus after two weeks. The follow-up of limbs functional state measured by MSTS was a mean of 82% compared to mean of 60% obtained with granules alone. At the end of the follow-up (minimum one year), all the patients were cancer-free with an excellent outcome.

Conclusions: The encouraging results of our early study indicate that refilling at the osteotomy site with autologous BMMCs and granular silicate improves bone repair. A larger study cohort and longer follow-up times are required to identify additional predictors and indications.