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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15055-e15055
    Abstract: e15055 Background: Enhanced generation of reactive oxygen species (ROS) is an important factor in cell damage when exposed to metal nanoparticles (NPs), which can be used to develop antitumor strategies based on ROS level modulation. However, an increase in ROS can cause oxidative stress in the body. The aim of this study was to evaluate the parameters of the redox-regulating system in the blood erythrocytes of tumor-bearing rats at different efficiencies of exposure to copper NPs (CuNPs) and iron NPs (FeNPs). Methods: Outbred male rats with transplantable fusiform cell fibrosarcoma (S45) were treated with copper (group S45+CuNPs, n = 37) or iron NPs (group S45+FeNPs, n = 33). During 15 days, 35 rats received 8 intratumoral injections and 35 rats received 8 intraperitoneal injections of NPs in total doses of 10 mg/kg bw, the control S45 rats (n = 20) received saline i.p. Levels of malondialdehyde (MDA) and glutathione (GSH), the activities of catalase (CA), superoxide dismutase (SOD), and glutathione peroxidase (GPO) in the red blood cells were determined one week after the end of the treatment. Results: Complete or near complete tumor regression was recorded in 13 (35 %) rats with CuNPs treatment and 6 (27%) rats with FeNPs treatment. Decrease in tumor size by 30 to 80% in 14 (38%) rats in CuNPs group and in 14 (43%) rats in FeNPs group was observed. In other cases, tumor growth in rats with S45 treated with metal nanoparticles was similar to animals in the control group. The values of the studied parameters in rats with complete tumor regression after exposure to CuNPs did not differ from those in the group of healthy rats. Unidirectional changes in the studied parameters were observed in rats with partial S45 regression or with no effect. GPO activity increased by 43-57% (p = 0.02-0.002) and GSH level by 20-27% (p = 0.034-0.005), but MDA level was 62-65% (p = 0.027-0.007) higher than normal values. Animals with complete tumor regression after the administration of FeNPs showed changes in the activity of peroxide-inactivating enzymes: an increase in GPO by 84% (p = 0.009) and a decrease in catalase by 31% (p = 0.016) relative to normal values. In animals with partial response or without response, GPO activity increased by 75% and 57%, respectively (p = 0.031-0.042), while CA activity decreased by an average of 37% (p = 0.002-0.0002). No increase in MDA was observed in the S45+FeNPs group. The levels of MDA in rats of the control group were increased by 46% (p = 0.0032), which was combined with an increase in GSH by 19%, a decrease in catalase activity by 16%, and an increase in GPO activity by 41% (p˂0.05 in all cases), compared to the values in intact animals. Conclusions: Regardless of the route of administration, copper and iron NPs did not cause an increase in oxidative stress in rats with fibrosarcoma. The maximum antitumor effect of metal NPs was accompanied by normalization or positive reorganization of the redox-regulating system of erythrocytes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e19559-e19559
    Abstract: e19559 Background: About 30-40% of patients with diffuse large B-cell lymphoma (DLBCL) do not respond to treatment, they subsequently relapse or remain refractory, so the search for predictive factors for the treatment effectiveness is relevant. TGF-β is a pleiotropic regulator of many pathophysiological processes, including carcinogenesis and immune responses, and its signals are initiated via its binding with proteins, including TGF-β receptor type 1 and type 2 (TGFBR2). The purpose of this study was to analyze the TGFβ1 and TGFBR2 blood levels and their ratio in patients with DLBCL depending on the treatment efficacy. Methods: The study included 63 patients (32 men and 31 women aged 23-88 years, median age 55.6 years) diagnosed with DLBCL. Blood levels of TGFβ1 and TGFBR2 were determined by ELISA before and after treatment. Stage I DLBCL was registered in 6 (9.5%) patients, stage II in 25 (39.7%), stage III in 5 (7.9%), stage IV in 27 (42.9%). All patients received standard treatment with R-CHOP, R-CHOEP, R-EPOCH. Direct results of the treatment were assessed by Cheson’s criteria. By their response to the therapy, patients were divided into 3 groups: group 1 (25.4%) – relapsed disease, group 2 (25.4%) – refractory disease, and group 3 (49.2%) – remission. A group of healthy donors included 20 men and women. All patients gave their informed consent to the study. Results: Blood levels of TGF-β1 in all patients before the treatment were higher than in donors by 2.1 times, and after the treatment by 2.4, 1.9 and 1.9 times, respectively, in groups 1, 2 and 3. The values between the groups did not differ significantly. Levels of TGFBR2, on the contrary, were lower in patients before treatment than in donors by 3 times, and after treatment by 3.5 in group 1, by 4 times in group 2, and similar to the norm in group 3. The TGFβ1/TGFBR2 ratios in patients before treatment were 6.1 times higher than the norm. After treatment, the ratio in patients of groups 1 and 2 were 8.6 and 7.2 times higher than in healthy donors. The ratio in patients of group 3 was 2.3 times higher than in healthy donors, and the value differed significantly from the values in groups 1 (3.8 times lower) and 2 (3.2 times lower). Conclusions: Monitoring the TGFβ1/TGFBR2 ratio in DLBCL patients before and during the treatment will allow promptly determination of adverse outcomes and changing the treatment regimen.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15613-e15613
    Abstract: e15613 Background: Colorectal cancer (CRC) is the third most commonly diagnosed cancer. More than 60% of all cases of CRC are colon cancer (CC). The role of individual units of the immune system in the development of this tumor is ambiguous. The purpose of this study was to characterize local populations and subpopulations of immunocompetent cells in colorectal cancer with different tumor locations. Methods: The study included 50 CC (adenocarcinoma) patients aged 35-86 years, women n = 26 (52%). Stage I tumors were registered in 4 patients (8%), stage II 25 (50%), stage III 21 (42%). 20 patients (40%) had right-sided CC (group 1), 9 (18%) left-sided CC (group 2), and 21 (42%) sigmoid CC (group 3). All patients received surgical treatment. Cell suspensions were obtained from tumor (TT) and peritumoral tissues (PT) (1-3 cm from the tumor), and then processed with an antibody panel in accordance with the manufacturer instructions (Becton Dickinson, USA) to identify the main populations and subpopulations of leukocytes and lymphocytes. The relative number of major populations and subpopulations of lymphocytes was determined on the BD FACSCanto flow cytometer. Results: A decrease in lymphocytic infiltration was noted left-sided tumors and sigmoid tumors compared to right-sided CC, by 46% and 51%, respectively. The percentage of CD3+ cells was almost the same regardless of the colon tumor location, and the number of main populations of T lymphocytes differed: in group 3, the content of CD4+ cells was 21% higher, and CD8+ cells were 22% lower compared with group 1, while group 2 had no differences. Group 2 differed in the tumor infiltration with both NK and NKT lymphocytes, which were higher by 25% and 22%, respectively, than in group 1. An increase in NK cells was noted in the sigmoid colon (group 3), and the relative number of NKT lymphocytes decreased. A common feature of TT in groups 2 and 3 was an increase in the content of B lymphocytes by 98% and 133%, respectively. PT of group 2 showed a decrease by 72%, 33%, 66%, and 46% in the relative number of lymphocytes, CD4+, NKT and B lymphocytes compared with group 1, together with an increased content of NK and CD8+ lymphocytes. PT in patients of group 3 had a decrease in the number of total and NK lymphocytes by 46% and 26%, respectively, and a significant increase by 85% in the content of CD8+ cells, with no changes in CD3+, CD4+ cells, B and NKT lymphocytes. Conclusions: The local immune status of CRC patients demonstrated a number of differences: right-sided tumors were characterized by a higher T-lymphocytic infiltration with the same tendency in the perifocal tissues, while left-sided and sigmoid tumors showed higher B-lymphocytic infiltration, which can help in the disease prognosis and choice of treatment strategy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e19560-e19560
    Abstract: e19560 Background: Diffuse large B-cell lymphoma (DLBCL) represents about 30-40% of all cases of non-Hodgkin lymphoma. The addition of rituximab to standard chemotherapy significantly improves survival, yet 30% of advanced-stage patients relapse. The International Prognostic Index (IPI) is used to evaluate the prognosis, but it cannot always accurately predict the outcome of therapy. The neutrophil-to-lymphocyte ratio (NLR) has recently been recognized as a prognostic factor in various types of solid tumors. The purpose of this study was to assess the prognostic value of NLR in DLBCL patients. Methods: Patients with DLBCL (n = 47) were recruited, including 31 patients in remission and 16 patients with relapsed DLBCL. All patients received 6-8 cycles of R-CHOP. Clinical parameters were studied, including IPI and complete blood count before treatment and after each chemotherapy cycle. Results: IPI predicted unfavorable outcome in 3 (18.75%) patients with relapses, and favorable outcome and high treatment efficacy in 13 (81.25%) patients. Among patients in remission, IPI predicted unfavorable outcome in 2 (6.5%) patients and favorable outcome in 29 (93.5%) patients. NLR calculation showed 100% low treatment efficacy for patients with relapses (NLR =4.1±0.51). At the same time, NLR predicted favorable outcome in 22 (70.96%) patients in remission (NLR =1.9±0.20), and relapses in 9 (29.04%) patients (NLR =4.83±0.55). 7 (22.6%) of the patients at risk developed relapses within 6-10 months after good treatment effects. Conclusions: Thus, NLR can be used as a prognostic factor in patients with DLBCL.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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