e12589 Background: Better efficiency and safety of Nab-P is known to be due to the advantages of pharmacokinetics and pharmacodynamics of the drug. The fraction of unbound paclitaxel in plasma is 2.6-fold higher with Nab-P than with P. The purpose of the study was to assess efficacy and safety of Nab-P in ≥2nd lines of chemotherapy (CT) in patients (pts) with mBC with VC. Methods: Inclusion criteria: mBC with VC, ≥ 2 line of CT, HR+, HER2neu+ or triple negative type (TN), normal liver and renal function. Pts received Nab-P 260 mg/m2 q 21 days. Pts with Her2/Neu + received trastuzumab 6 mg/kg q 21 days. Results: 32 mBC pts, mean age 51.34 years (CI 35-76) were included. Among 32 pts Her2/Neu + had 5 (15.6%), TN – 9 (28.1%), HR+ 18(56.3%). 13(40.6%) pts received Nab-P as 2 line of CT, 13 (40.6%) pts, as 3-4 lines, 7(21.9%) as ≥5 lines. Pts were divided into 2 groups: group A - pts with VC 17(53.1%), group B - without VC 15(46.9%). Groups were comparable by age, number of previous CT lines, immunohistochemical types of BC. Group A had 2.47±0.32 CT lines (CV51.83%), including 8(47%) pts, who had received paclitaxel (P) in previous CT lines. Group B had on average 2±0.27 CT lines (CV53.03%). The objective response rate (ORR) was 37.5%(12 pts). In the group A ORR was 35.3% (6 pts). Out of 8 pts with VC, who had received P in previous lines, ORR was achieved in 3 pts (37.5%). In the group B ORR was 33.34%(5 pts). TTP was 6.8 mos (95% CI 6.1-13.7) for all pts, in the group A – 5.7 mos (95% CI 5.9-10.2), in the group B 6 mos (95% CI 6.5-13.7) (p = 0.046). Median 3-year OS of pts in group A was 18.9 mos (95% CI 4.3-22.4), in group B - 22.5 mos (95% CI 8.2-26.7) (p = 0.038). Toxicity did not differ significantly in pts in groups A and B and was manageable. Pts, who previously received P, had no new or severe toxicity. Conclusions: The data obtained confirms the possibility of Nab-P application in pts with VC. The use of Nab-P in pts treated with taxanes in previous lines is supposed for further study.
e21035 Background: Immunotherapy with PD-1/PD-L1 check-point inhibitors (CPI) is a new trend in oncology. Their effect significantly depends on the patients` immune status. The aim of the study was to search the immunologic parameters of lung cancer (LC) patients receiving immunotherapy as factors that could predict their effect. Methods: 20 patients (12 male and 8 female) with LC had adenocarcinoma – 15 (75%), squamous cell carcinoma – 5 (25%). PD-1/PD-L1 CPI were used: 9 patients received atezolizumab (43%), 9 (43%) – pembrolizumab and 3 (14%) – nivolumab. The effect of therapy was evaluated according to imRECIST v.1.1. Factors of cell-mediated immunity were assessed by flow cytometry before treatment including immunotherapy. CD8+CD279+, CD4+CD279+, TLR2, TLR4, TLR3, TLR8 were studied. Results: Complete response was observed in 2 (9%) patients, partial response in 5 (24%), stabilization in 4 (19%) and progression in 8 (38%). In one patient the treatment was cancelled due to the development of immune-mediated complication (Guillain-Barre syndrome). The factors studied varied depending on different effect. In cases of LC stabilization/progression the initial amount of CD8+CD279+ cells were twice lower than in cases with complete/partial response. In the first group CD8+CD279+ cells` level before the treatment was 0,1-3,4%, while in the other group 4,1-9% (7,0±1,16%). In patients with stabilization/progression CD4+CD279+ cells` level before the immunotherapy was 0,1-3,3 and in patients with response to treatment 1,4-7,8% (3,4±0,8%) of total CD4+ lymphocytes. Besides, the LC patients with different effect of treatment had different initial amount of CD4+ Tem cells: stable response to CPI developed in patients with their higher levels (40,8±3,9%) vs 15,3±3,9% in cases of tumor progression (p < 0.05). Initial high expression of TLR2 and TLR4 as well as low expression of TLR3 and TLR8 on monocytes in patients with response to immunotherapy suggests the contribution of innate immunity to its effect. Conclusions: Complete or partial response should be expected in cases of initially high per cent of T lymphocytes (CD4+, CD8+) CD4+ Tem cells and TLR2+, TLR4+ as well as low amount of TLR3+ and TLR8+ monocytes. These factors should be studied in future as predictive factors for effectiveness of CPI.
e15063 Background: The study of the possible antitumor activity of secondary plant metabolites either in the form of individual agents or in combination with clinically used drugs is considered as a promising direction in the therapy of malignant tumors. The aim of this study was an estimation of antitumor activity of secondary plant metabolites in the in vitro experiment on the HeLa cell line. Methods: Secondary metabolites were extracted from plant raw materials and were isolated by preparative chromatography. Determination of their composition was carried out using HPLC; obtained compound structures were identified by NMR. We selected 4 secondary metabolites from Petasites hybridus for testing: (2,4-dihydroxy-2,5-dimethylfuran-3 (2H), 5-(hydroxymethyl) furan-2-carbaldehyde, 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde, Corynan), and 1 secondary metabolite from Berberis vulgaris : a berberine chloride (BBR, C20H18NO4+Cl- is a derivative of 5,6-dihydrobenzo[a,g] isoquinolinium). HeLa CCL2 cultivation was carried out under standard conditions in the MEM medium. When reaching the 75-80% confluence level we replaced nutrient medium with the introduction of secondary metabolites (concentration 4 and 12 μg/ml) and cultured for 24 and 72 hours. Cell survival was determined on a NanoEnTek JuliFl counter (Korea) in the presence of 0.4% trypan blue. Apoptosis was assessed on a flow cytometer BD FACSCanto II using FITC Annexin V Apoptosis Detection Kit I. Post-exposure copy number and expression were assessed by Real-time PCR with a panel of genes CASP9, CASP8, CASP3, TP53, MDM2, BAX, BCL2, CDK1, BRCA1, BRCA 2, RB1. Results: All obtained data were normalized by negative control. When we used 4 μg/ml berberine solution with 72-hour exposition, the proapoptogenic effect was maximal, causing the death of 67.2% of HeLa cells (29.3% early apoptosis, 37.2% late apoptosis, 0.7% necrosis). Within 24 hours, berberine at the same concentration caused a 2-fold increase in TP53 expression relative to MDM2. An increase in its concentration to 12 μg/ml and exposure for up to 72 hours led to a 31-fold increase in TP53/MDM2. The terpenoid 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde at a concentration of 12 μg/ml after 72 hours of cultivation caused a 6.5-fold increase in the TP53/MDM2 ratio. The corynan alkaloid (12 μg/ml) at an exposure of 72 hours increased the BAX/BCL ratio by 2.4 times. There were no statistically significant differences in the expression and copy number of the remaining genes studied. Conclusions: Berberine, corynan, 2,2,8-trimethyldecahydroazulene-5,6-dicarbaldehyde showed high promise in the HeLa cell line in vitro, since they surpassed the antitumor activity of other metabolites of Berberis vulgaris and Petasites hybridus.
e16011 Background: The purpose of the study was to analyze the rates of polymorphic allelic variants of genes of the hemostasis system and methionin exchange in patients with gastrointestinal cancers (GICs). Methods: The study included 69 patients with histologically verified GICs (main group): gastric cancer (GC) – 17, colon cancer (CC) – 42, other tumors – 10 (pancreatic cancer – 6, liver cancer – 3, gallbladder cancer – 1) and 50 patients without cancer (control group). 12 polymorphic loci were determined in genomic DNA samples by Real-time PCR: F2 (G20210А, rs1799963), F5 (G1691A, rs6025), F7 (G10976A, rs6046), F13 (G226A, rs5985), FGB G(-455)A (rs1800790), ITGA2-α2 (C807T, rs1126643), ITGB3-b (Т1565С, rs5918), PAI-1 4G(-675)5G, rs1799889), MTHFR (С677Т, rs1801133 and A1298C, rs1801131), MTR (А2756G, rs1805087), MTRR (A66G, rs1801394). Results: The ratio of genotype frequencies maintained in the Hardy-Weinberg equilibrium in all gene loci except FGB G(-455)A in GC patients (p = 0.02). The rate of an alternative allele in the F2 gene among patients with GICs was 1.4%, in the control group – 1.0%; F5 – 1.0% and 4.0%; F7 – 13.0% and 11.0%; F13 – 31.9% and 32.0%; FGB – 29.7% and 22.0%; ITGA2 – 37.7% and 38.0%; ITGB3 – 17.4% and 21.0%; PAI-1 – 55.1% and 56.0%, MTHFR (Т) – 26.6% and 31.3%; MTHFR (С) – 33.0% and 27.5%; MTR – 29.8% and 26.3%; MTRR – 51.1% and 57.5%, respectively (p > 0.05). AA homozygotes at the FGB G(-455)A locus were more frequent in the main group, compared to controls: 4.3% vs 4.0%; p = 0.02. No differences in the frequency of alternative alleles of the studied genes were found between patients with GC and CC. GG genotype at the FGB G(-455)A locus was found in GC patients in 29.4%, in controls – in 60.0% (OR = 0.28, 95% CI 0.08-0.91); GA genotype – in 70.6% and 36.0% (OR = 4.27, 95% CI 1.29-14.06), AA genotype – in 0% and 4.0% (p = 0.04, χ2 = 6.34), respectively. Conclusions: The univariate analysis demonstrated that carriage of the GA genotype at the FGB G(-455)A (rs1800790) locus could be found more often in patients with GC.
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