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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e17530-e17530
    Abstract: e17530 Background: Despite the progress made in diagnosis and treatment, ovarian cancer (OC) is still the third most common genital cancer. Poor results of therapy for various forms of OC stimulate the search for fundamentally new approaches to the treatment. One of the main reasons for resistance to chemotherapeutic agents includes multidrug resistance (MDR) of tumor cells. The most characterized of its various mechanisms is the elevated activity of the ABC family protein - ABCB1 (Pgp or MDR1). The purpose of the study was evaluation of the expression of this ABC transporter as a predictive factor in platinum-containing chemotherapy in OC patients. Methods: 100 patients aged 29-79 years with advanced stage IIIC - IV OC with/without ascites were recruited between 2016 and 2020. Depending on the treatment results, patients were divided into 2 groups: group 1 (n = 59) - patients with platinum sensitivity; group 2 (n = 41) - patients with platinum resistance during the treatment or within 6 months after its completion. IHC analysis was performed using rabbit polyclonal anti-MDR1 antibodies (Affinity Biosciences) diluted 1:600 and the Reveal Polyvalent HRP-DAB Detection System. The percentage and the intensity of staining were assessed: 0, 1+ weak, 2+ moderate, 3+ strong. MDR1 expression was considered positive when staining was detected in more than 10% (cut-off) tumor cells with intensities of 2+ and 3+. Statistical analysis of results was performed in the Statistica 13.0 program (StatSoftInc., USA). Results: Patients with MDR1+ prevailed in group 2 (98%), and patients with MDR1- in group 1 (32%). The average expression of MDR1 in tumor cells in group 2 (64.0±7.0) was statistically significantly higher by 1.7 times (p = 0.003) than in group 1 (37.2±6.8) by the Mann-Whitney U-test. When distributed according to Pearson's χ2 criterion, positive MDR1 as a risk factor in the platinum-resistant group increased the risks of refractory to platinum therapy by 19 times (95% CI 2.4-148.8). Conclusions: The study demonstrated predictive significance of the MDR1 biomarker in platinum treatment in patients with ovarian cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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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. e17500-e17500
    Abstract: e17500 Background: Our purpose was to analyze the rates of polymorphic allelic variants of genes of hemostasis system and methionine exchange in patients with female reproductive tumors. Methods: The study included 51 patients with histologically verified gynecologic tumors (group 1), including 28 patients (group 1a) with malignant tumors (cervical cancer (CC) n = 8, ovarian cancer (OC) n = 8, endometrial cancer (EC) n = 8, other cancers n = 4) and 23 patients (group 1b) with benign tumors, and 47 women without tumors (group 2). 12 polymorphic loci were studied by RT-PCR in genomic DNA samples: 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, rs 1801133 and A1298C, rs1801131), MTR (А2756G, rs1805087), MTRR (A66G, rs1801394). Groups 1, 1a and 1b were compared with controls (p 1 ) and among themselves (p 2 ). Results: The ratio of genotype frequencies maintained in the Hardy-Weinberg equilibrium in all gene loci except F7 (G10976A) in group 1 (p = 0.03). An alternative allele in the F2 gene was found only in group 2 (1.1%). The frequency of an alternative allele in the F5 gene in group 1 was 2.9%, including 1a – 1.8%, 1b – 4.3%, group 2 – 2.1%; F7 – 16.7%, 14.3%, 19.6% and 17.0%; F13 – 23.5%, 23.2%, 23.9% and 34%; FGB – 26.5%, 25.0, 28.3% and 25.5%; ITGA2 – 53.9% (p 1 = 0.03, OR = 1.89 (1.07-3.33), 48.2%, 60.9% (p 1 = 0.01, OR = 5.21 (1.22-5.17) and 38.3%; ITGB3 – 13.7%, 10.7%, 17.4% and 16.0%; PAI-1 – 47.1% (p 1 = 0.03, OR = 0.53 (0.30-0.93), 46.4%, 47.8% and 62.8%; MTHFR (Т) – 28.4%, 30.4%, 26.1%, 34.0%; MTHFR (С) – 34.3%, 28.6%, 41.3% (p 1 = 0.04, OR = 2.17 (1.02-4.61) and 24.5%; MTR – 18.6%, 19.6%, 17.4% and 27.7%; MTRR – 63.7%, 71.4%, 54.3% and 62.8%, respectively. TT genotype at the ITGA2-α2 (C807T) locus was more frequent in group 1 than in group 2 (23.5% vs 19.1%, p 1 = 0.01, OR = 6.54 (2.61-16.40); CT genotype was more frequent in group 1a than in group 2 (67.9% vs 38.3%, p 1 = 0.004, OR = 3.40 (1.27-9.13), and more frequent in EC than in group 2 (87.5% vs 38.3%, p 1 = 0.03, OR = 11.28 (1.28-99.40). GG genotype at the MTRR (A66G) locus was more frequent in group 1a than in group 1b (53.6% vs 26.4%, p 2 = 0.042). 5G5G genotype at the PAI-1 4G(-675)5G locus was more frequent in group 1 than in group 2 (31.4% vs 10.6%, p 1 = 0.04, OR = 3.84 (1.28-11.53), and more frequent in OC than in group 2 (75% vs 11%, p 1 = 0.0001, OR = 25.50 (3.96-160.20). AA genotype at the F7 (G10976A) locus was more frequent in CC patients than in group 2 (31.3% vs 17%, p 1 = 0.03, OR = 15.33 (1.20-195.75). Conclusions: Carriage of the AA genotype at the F7 (G10976A) locus may increase the risk of developing CC, and the CT genotype at the ITGA2-α2 (C807T) locus may increase the risk of EC. On the contrary, the alternative 4G allele at the PAI-1 4G(-675)5G locus was less common in patients with malignant tumors, especially OC, than in the group without cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e18025-e18025
    Abstract: e18025 Background: Young patients with early stages of gynecological cancers often go through surgical menopause which worsens the quality of life affecting social, sexual, psycho-emotional, cognitive spheres, and causes somatic diseases rare in a young age. The purpose of the study was to evaluate the clinical effectiveness of medical and hormone replacement therapy (HRT) in patients with endothelial (EC) and cervical cancers (CC) of the reproductive age after surgical treatment. Methods: Clinical data and adaptive reactions were studied in 346 patients with stage Ia-IIa EC and CC aged 20-45 years after combination treatment. Patients were divided into 3 groups: group 1 – 192 patients, estrogen/gestagen HRT; group 2 – 112 patients, treatment with phytoestrogens; group 3 – 42 patients choosing not to have any adjuvant therapy. The Kupperman index was used to evaluate the severity of a post-castration syndrome. Results: In group 1, 158 women (82.3%) showed normal somatic and psychoemotional status and adequate cognitive functions, the Kupperman index ≤20; 34 (17.7%) patients of group 1 needed additional sedation, the Kupperman index = 30; adaptive reactions included reactions of training and adaptation. In group 2, 112 patients (100%) demonstrated moderate hormonal imbalance signs: vegetative and emotional disorders, decreased libido, manifestations of the metabolic syndrome, the Kupperman index = 30-35; adaptive reactions included reactions of training and stress. All patients of group 3 (n = 42) developed metabolic disorders shortly after surgical castration, with social, sexual and psycho-emotional disadaptation, the Kupperman index = 35 (reactions of stress). Conclusions: Combination HRT after surgical castration contributes to full adaptation in the social, sexual, psycho-emotional spheres of life in patients of the reproductive age, restoring the quality of life without affecting the prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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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. e17507-e17507
    Abstract: e17507 Background: The purpose of this study was to evaluate perirectal blocks in prevention of radiation-induced rectal injuries in patients with cervical cancer. Methods: The study included 18 patients diagnosed with stage III cervical cancer (T3bNxM0) receiving chemoradiotherapy. All patients showed pronounced inflammatory and dystrophic changes in tissue planes and organs of the small pelvis due to comorbidities (diabetes mellitus, hypertension, pelvic varicose veins, proctitis, inflammatory and adhesive processes in the small pelvis reducing chemoradiotherapy effectiveness due to impaired microcirculation and increasing the risk of post-radiation complications). All patients received brachytherapy with additional perirectal administration of drugs relieving pain and inflammation and improving neurotrophic processes and microcirculation in tissues (novocaine 0.25% -20.0; milgamma 2.0; ceftriaxone 1 g; dexamethasone 8 mg). The combined administration causes drug potentiation, positively affects the nervous and neuromuscular systems, restores microcirculation and venous outflow, decreases swelling, improves tissue trophism, reduces blood vessel permeability, and improves reflexes from interoceptors. Radiation therapy was completed on schedule with the introduction of radical doses in all patients, which is challenging in patients with comorbidities leading to impaired trophism and tissue hypoxia. Results: Complete tumor regression confirmed by MRI and ultrasound was observed by the end of the treatment in 90% of patients, apparently due to the radiosensitizing effect on cervical cancer and the radioprotective effect on surrounding tissues. Conclusions: Parametrial blocks during brachytherapy improve the status of tissues of the small pelvis which, in turn, prevents radiation damage, contributes to the timely radiotherapy completion, and improves the treatment effectiveness and the quality of life of patients. This technique is especially relevant in view of the increasing number of diseases that disrupt microcirculation, and hence the oxygenation of tissues, causing tumor radio- and chemoresistance.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 5
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    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 6035-6035
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 6035-6035
    Abstract: 6035 Background: Photodynamic therapy (PDT) is an effective treatment for various cancers ensuring maximum preservation of the viability of healthy tissues surrounding the tumor. The purpose of the study was to reveal the effectiveness of PDT in treatment for preinvasive cervical cancer. Methods: The study included 45 patients aged 22-53 years with preinvasive cervical cancer. The patients were divided into two groups depending on the type of the transformation area and the tumor site: group 1–on the exocervix (type I-II), n=24; group 2–on the endocervix (type III), n=21. Infection with high-risk genotypes of HPV (16, 18, 31, 33, 35, 45, 56) was detected with PCR in 37 (82%) women. All patients received PDT with the semiconductor Latus laser up to 3 W, a single-use diffusing fiber for the exocervix irradiation and a single-use cylindrical diffusing fiber for tumors in the cervical canal. Photoditazine and photolon were used as photosensitizers. Effectiveness criteria included the normalization of the colposcopic picture, the absence of atypical cells, and the pathogen elimination confirmed by PCR. Results: A normal cytogram profile was observed after PDT in 84% of group 1 and in 88% of group 2. PCR 3 months after PDT showed a positive HPV reaction in 9.1%. Neither group of patients had negative changes in cytogram after 6 and 12 months. Repeated HPV DNA tests detected HPV DNAs in 2.8% in group 1 and 3.2% in group 2. The effectiveness of PDT did not depend on the photosensitizer. The maximum follow-up period has lasted for 4.5 years, with no recurrences registered. During this period, three young women successfully gave birth to healthy children. Conclusions: PDT is an alternative treatment for pre-tumor and initial tumor pathology of the cervix with preservation of the anatomical and functional integrity of the organ, which is important for the female reproductive function. The results support the use of PDT in treatment for preinvasive cervical cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 6
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e17528-e17528
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e17528-e17528
    Abstract: e17528 Background: Photodynamic therapy (PDT), with its high efficiency and selective impact on tumor cells without damaging healthy tissues, is an organ-sparing treatment preserving the anatomy and function of the cervix. Preservation of the reproductive function is the most significant criterion for the efficacy of an organ-sparing treatment. The purpose of this study was to evaluate the efficacy of PDT for early cervical cancer. Methods: PDT results were studied in 74 patients aged 18-40 years with early cervical cancer. The patients were divided into 3 groups depending on the type of transformation zone (TZ), the degree of invasion and the tumor site: group 1 - 36 patients with preinvasive cancer in the exocervix (TZ type I-II); group 2 - 34 patients with preinvasive cancer in the endocervix (TZ type III); group 3 - 4 patients with microinvasive cancer T1a1N0M0 with invasion of no more than 1 mm as an alternative to surgical intervention. Infection with high-risk genotypes of HPV (16, 18, 31, 33, 35, 45, 56) was detected with PCR in 62 (84%) women. All patients received PDT with the semiconductor Latus laser up to 3 W, a single-use diffusing fiber for the exocervix irradiation and a single-use cylindrical diffusing fiber for tumors in the cervical canal. Chlorin e6 was used as a photosensitizer. The efficiency criteria included the normalization of the colposcopic and morphological picture, and the HPV elimination confirmed by the PCR test. 4 to 8 procedures were required to restore the normal layer of stratified squamous epithelium. Results: PDT was followed by direct photocoagulation necrosis caused by the destruction of cellular structures, and ischemic necrosis as a result of damage and destruction of the microvasculature of the initial tumor changes in the cervical epithelium. Epithelialization of the cervix was completed by days 35-40. Normal morphological picture was observed in 96% of patients in group 1 and in 95% of patients in group 2; all patients in group 3 had a pronounced positive response. PCR 3 months after PDT showed a positive HPV reaction in 5.1% of patients. No negative changes in the cytogram were detected 6 and 12 months after PDT. The maximum follow-up period has lasted for 5.1 years. No relapses of the disease have been registered. During the follow-up period, four patients with preinvasive cancer and one patient with microinvasive cancer successfully gave birth to healthy children. Conclusions: PDT is an alternative treatment for precancerous and early malignant tumors of the cervix; it preserves the anatomical and functional integrity of the organ, which is important for the female reproductive function. The results of the study allow recommending PDT in the treatment of early cervical cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e17506-e17506
    Abstract: e17506 Background: Ionizing radiation inhibits the immunological reactivity of the body and the system of nonspecific antitumor resistance in patients with cervical cancer (CC). The purpose of this study was to activate the system of nonspecific antitumor resistance using visible electromagnetic radiation in CC patients receiving chemoradiotherapy. Methods: The study included 30 patients, mean age 61 years, with stage IIIb CC (T 3b N x M 0 ). The main group (n = 15) received standard chemoradiotherapy (CRT): irradiation of the primary focus 80 Gy, lymphatic paths 55 Gy, with radiomodification with cisplatin 40mg/m2; the patients were additionally exposed to visible electromagnetic radiation: the red spectrum λ = 640 nm on the cubital vein projection (exposure time 5 minutes, dose 6.86 J/cm2), twice a week (the total of 14 sessions). The method is based on the ability of monochrome red light to induce photobioadaptive processes in the body, leading to the formation of non-specific antistress reactions, activation of reparative and regenerative tissue reactions with an increase in the synthetic, phagocytic activity of neutrophils and the growth of the immunity lymphoid indicators. The control group included 12 patients receiving only standard CRT. Parameters of nonspecific antitumor adaptation reactions were evaluated. Results: Lower abdominal pain and discomfort were managed in 20% of patients of the main group on day 8, in 30% on day 10, and in 50% on day 14. In the control group, the symptoms were managed in 40% of patients only on day 22. More rapid regression of the cervical tumor was registered in patients of the main group, as well as decreased infiltration of the parametrium and vaginal fornices, disappearance of bloody discharge, management of intoxication syndrome. Gastrointestinal toxicity (nausea, diarrhea, flatulence) was noted in 10% of patients in the main group and in 100% controls. 7 patients in the control group developed leukopenia; in the main group, it was not observed. MRI-confirmed complete tumor regression amounted to 88% in the main group and 65% in the control group. CRT was completed within 7 weeks in the main group and 8.5 weeks in the control group. Conclusions: Low doses of electromagnetic radiation of the red spectrum activate endogenous nonspecific antitumor resistance of the body by forming nonspecific antistress reactions of activation and increasing the immunity lymphoid indicators, which improves the efficacy of CRT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 8
  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15003-e15003
    Abstract: e15003 Background: Taxanes and platinum compounds are widely used in cervical cancer chemotherapy. In particular, a combination of 75 mg/m 2 cisplatin and 175 mg/m 2 paclitaxel, which suggests a doses ratio of 1:2.3, is recommended as first-line systemic chemotherapy. Although this combination has performed well in clinical practice, little is known about its effect on cervical cancer cell biology in vitro. This study assessed the effect of combined application of cisplatin and paclitaxel in a dose ratio of 1:2.3 on HeLa cells. Methods: HeLa cells were seeded at 3000 cells per well in a 96-well plate (Eppendorf, Germany) and incubated for 24 hours in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) at 37°C in an atmosphere containing 5.0% CO 2 . After 24 hours, the culture medium was replaced with a medium containing chemotherapy drugs in combination or as standalone agents in a series of two-fold dilutions: 0.03 - 32 µg/mL cisplatin and 0.07 - 73.6 µg/mL paclitaxel. After 2 h exposition to studied compounds the medium was replaced and cells were incubated for another 72 hours. At the end of the experiment, the number of living cells was assessed using the MTT test. Viability was determined as the number of living cells in % of the control without the addition of chemotherapy drugs. Results: The combination of cisplatin with paclitaxel demonstrated significantly greater efficacy than pure cisplatin in the concentration range from 0.03 μg/ml to 8 μg/ml. The difference between the mean viability values for each concentration between pure cisplatin and its 1:2.3 mixture with paclitaxel was significant at α = 0.05 (df = 14). The decrease in viability is especially dramatic at non-toxic concentrations of cisplatin (0.03 - 0.5 μg/ml) and is about 60% over this concentration range. However, when moving to toxic concentrations of cisplatin (0.5-32 μg/ml), the difference in the viability of HeLa cells between pure cisplatin and its combination with paclitaxel linearly decreases with increasing cisplatin concentration, becoming insignificant in the range of 8-32 µg/ml. However, when comparing the dose-response curves for pure paclitaxel and its combination with cisplatin, we see a significant reduction in cytotoxic activity compared with pure paclitaxel. The difference in cell viability reaches its maximum (45%) at a paclitaxel concentration of 2.3 µg/ml and is significant at α = 0.05 (df = 14). Conclusions: The combined use of cisplatin and paclitaxel in a dose ratio of 1:2.3 on HeLa culture has a greater cytotoxic activity compared to pure cisplatin. However, compared with pure paclitaxel, the effectiveness of its combination with cisplatin is significantly lower, which indicates the antagonism of the two substances.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 10
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    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e17561-e17561
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e17561-e17561
    Abstract: e17561 Background: Contribution of local inflammation to the course of endometrial cancer (EC) is of interest since it may aggravate the disease. Methods: The study included 25 women aged 62+1.6 years with histologically verified EC (group 1a), 29 women aged 48+8.4 years with uterine fibroids (UF) (group 1b) and 13 non-cancer women aged 42+2.3 years (group 2, controls). Vaginal swabs were taken prior to antitumor treatment. Relative expression of genes encoding the synthesis of IL1B, IL10, IL18, TNFA, TLR4, GATA3, and CD68 in comparison with the reference gene B2M was determined by Real-time PCR using the ImmunoQuantex kit (Russia). An integral parameter of an inflammation index was calculated using binary logistics, and the ratios of the listed indicators were also calculated. 12 parameters were analyzed in total. Groups Ia and Ib were compared with healthy people (p 1 ) and with each other (p 2 ). Results: 4 of 12 studied parameters in EC patients differed from control; no differences were found in UF patients. 7 statistically significant differences were registered between EC and UF. Relative expression of the gene encoding the synthesis of IL10 was maximal in EC (2.8+0.2 vs. 1.8+0.3 in healthy women (p 1 = 0.006) and 1.8+0.2 in UF (p 2 = 0.002)). The IL10/IL18 ratio in EC statistically significantly exceeded the ratios in UF patients and in healthy women (61.4+21.7 (p 1 = 0.003), 46.3+32.2 (p 2 〈 0.001) and 53.7+47.1 respectively). The TNFA/IL18 ratio in EC patients was also higher than in UF patients (1.1+0.7 vs. 0.5+0.2 (p 2 = 0.035)) due to higher TNFA levels (3.7+0.1 vs. 3.3+0.1 (p 2 = 0.006)), one of which effects includes stimulation of neoangiogenesis. The ratio of TLR4/GATA3, on the contrary, was lower in EC than in UF (0.7+0.3 and 1.5+0.9 respectively (p 2 = 0.001). Apparently, it characterized antimicrobial immunity because both of these genes are involved in the response to PAMP (TLR4) and in the genesis of intraepithelial lymphocytes related to innate immunity, as well as in the development of a humoral response via stimulation of Th2 (GATA3). The latter, in addition, is involved in the ontogenesis some organs, including the vagina and uterus. The highest TLR4/GATA3 ratio was found in UF, which, in our opinion, indicated the predominance of the inflammatory process in UF and local immunosuppression in EC. The inflammation index determined with the ImmunoQuantex test system did not differ between the studied groups of women. Conclusions: Some differences were observed in local reactions of immunity and inflammation in benign and malignant uterine tumors, involving the prevalence of immunosuppressive and angiogenic factors in EC and inflammatory factors in UF.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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