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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. e15002-e15002
    Abstract: e15002 Background: Bleomycin is a glycopeptide antibiotic with anticancer properties. Clinical data indicate a relatively low efficacy of bleomycin in mono regimen, which is also accompanied by side effects from high doses. That’s why so it is more often used in relatively low doses in combination with other chemotherapy drugs. In particular, in cervical cancer, bleomycin is used in combination with cisplatin in a dose ratio of 0.8:1. Despite good clinical results, it is not known how the two drugs interact in vitro. The aim of this study was to evaluate the effect of combined application of bleomycin and cisplatin 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 0.012 – 12.8 µg/mL bleomycin. 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 bleomycin demonstrated significantly greater efficacy than pure cisplatin in the concentration range from 0.03 µg/ml to 8 µg/ml, and pure bleomycin in the range of 0.012 - 12.8 µg/ml. The difference between the mean viability values for each concentration of pure bleomycin or pure cisplatin and their 0.8:1 mixture was significant at α = 0.05 (df = 14). Observed decrease in the viability of HeLa cells in comparison with pure substances is most pronounced in the range of non-toxic concentrations for both substances in mono regimen, namely 0.03 - 0.5 μg/ml for cisplatin, and at concentrations less than 0.125 μg/ml for bleomycin. Here, the increase in the difference between the dose-response curves grows as the concentration of the studied drugs increases. At cisplatin concentrations of 0.5–32 μg/ml, the difference in HeLa cell viability between pure cisplatin and its combination with bleomycin, on the contrary, decreases linearly with increasing cisplatin concentration, becoming insignificant above 16 μg/ml. Conclusions: The combined use of bleomycin and cisplatin on HeLa culture in a dose ratio of 0.8:1 exhibits synergistic properties that are most pronounced in the concentration ranges of both substances that do not have a cytotoxic effect in mono regimen.
    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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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e17621-e17621
    Abstract: e17621 Background: An imbalance of sex hormones in endometrial cancer (EC) towards hyperestrogenism together with progesterone deficiency is considered to stimulate proliferation and suppress endometrial apoptosis. EC with squamous metaplasia is characterized by a more severe clinical course and the lack of an adequate response to standard treatment. The purpose of this study was to analyze the local hormonal profiles of tumors with squamous metaplasia in patients with obesity. Methods: The main group included 20 EC patients with squamous metaplasia, and control group included 35 patients with endometrioid adenocarcinoma: T1-3N0-1M0, mean age 64±3.2 years. Intact endometrial tissues were obtained during surgical treatment of patients with uterine fibroids (n = 20). All patients gave their written informed consent for the study. Levels of estradiol (E2), estrone (E1), testosterone (T), progesterone (P4), estrogen receptors ERα and ERβ, progesterone receptor RP4 and androgen receptors RA were measured by ELISA in samples of tumor and peritumoral (PT) tissues. Statistical processing of results was performed using the Statistica 10. Results: Tumor tissues of patients with EC, regardless of the histological structure, showed higher levels of estrogens and androgens and their receptors, compared with the intact endometrium, without significant changes in levels of progesterone and its receptor. In the main group, compared with the control group, E1 levels in tumors were lower by 1.6 times, E2 by 1.3 times (p 〈 0.05), but T higher by 2.4 times, ERα by 1.7 times, ERβ by 1.5 times (p 〈 0.05). PT, compared with the intact endometrium, had lower levels of E1 and E2 by 2 times and 1.5 times, P4 by 5.1 times, and T was lower only in PT with squamous metaplasia by 2.8 times. Levels of all steroid hormone receptors in PT were higher, regardless of the histological type of tumors. In PT of the main group, levels of E1 were 1.3 times lower (p 〈 0.05) than in controls, P4 – by 2.2 times, T – by 2.8 times, RP4 – by 1.7 times and ERβ by 1.8 times (p 〈 0.05), but ERα was 3.2 times higher. Conclusions: Tumors with squamous metaplasia, compared with endometrioid adenocarcinoma, are characterized by an imbalance of steroid hormones towards the predominance of androgens, and ERα plays a dominant role among estrogen receptors. The tumor probably synthesizes sex steroids independently and also pumps them over from the surrounding area. At the same time, malignant endometrial tumors, regardless of their histological structure, are more saturated with estrogens, androgens and their receptors, compared with the intact endometrium.
    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. 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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  • 4
    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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    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e17027-e17027
    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: 2016
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  • 6
    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.
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    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. 37, No. 15_suppl ( 2019-05-20), p. e17007-e17007
    Abstract: e17007 Background: Extended hysterectomy with fixation of preserved ovaries to the round ligaments of the uterus and subsequent transposition of the gonads from the irradiation area have already become a routine procedure in the treatment of cervical cancer in young women in order to avoid castration syndrome. The aim of the study was to analyze clinical characteristics of patients with cervical cancer 10 years after treatment. Methods: Clinical and hormonal status of 216 patients with stage Ib cervical cancer after complex treatment was studied. The majority of women (160 patients, 74%) remained fertile at the time of the study, and 56 patients (26%) were peri- and postmenopausal (from 46-55 years). The presence or absence of climacteric symptoms was assessed by a questionnaire; functional ovarian insufficiency (FNU) was determined as mild, moderate, and severe. Plasma levels of steroid and gonadotropic hormones were evaluated by radioimmunoassay. Results: Analysis of menopausal complaints according to questionnaires showed that the symptoms increased with the age of patients. Only 8 patients of the reproductive age reported hot flashes (Table 1). In this group of patients, levels of sex and gonadotropic hormones were common for this age. Patients aged 45-50 years reported also dry skin and mucous membranes, dyspareunia and dysuric disorders, which indicated perimenopause. And in postmenopause, urogenital disorders were very persistent. This group included patients treated 6 and 10 years ago. Conclusions: Thus, the function of preserved ovaries "faded away" independently according to the age, providing a smooth transition to menopause and optimal medical and social rehabilitation of patients.[Table: see text]
    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: 2019
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  • 8
    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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    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 9
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    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. e17508-e17508
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e17508-e17508
    Abstract: e17508 Background: Cervical cancer (CC) is one of the main causes of death among patients with gynecological tumors. As a rule, patients die from relapses and metastases which rates reach 30-45%. According to research data, treatment of patients with distant metastases is ineffective, and half of them die within 9.7 months, while the average survival is 15.9±0.26 months. The development of many pathological processes is considered to be associated with an increase in free-radical reactions leading to oxidative damage to various biomolecules. The purpose of the study was to analyze some characteristics of the free-radical oxidation and antioxidant defence in metastasizing CC. Methods: The study included 56 patients aged 29-73 years with stage IIB-IV CC after antitumor treatment. The main group – 27 patients who developed metastases within 4 months to 8 years after the CC diagnosis; controls – 29 patients with non-metastatic CC; donors – 19 healthy women aged 27-61 years. The accumulation of carbonyl derivatives in blood plasma proteins was detected in the reaction with 2, 4-dinitrophenylhydrazine. The induced oxidative modification of proteins was stimulated with Fenton's reagent. Free-radical processes was evaluated by the intensity of peroxide-induced luminol-dependent plasma chemiluminescence and the content of nitric oxide metabolites; the intensity of lipid peroxidation - by the content of malondialdehyde (MDA); the activity of catalase and ceruloplasmin was also studied. Results: CC progression was accompanied by increasing lipid peroxidation and spontaneous oxidation of blood plasma proteins. MDA levels in patients with metastases increased by 57.8% compared to donors and by 34.3% compared to patients without metastases (p 〈 0.05). The concentration of 2, 4-dinitrophenylhydrozones increased on average by 4 times compared to donors and by almost 2 times compared to patients without metastases. Patients with metastasizing CC demonstrated elevated levels of products of the interaction of nitric oxide and its derivatives with proteins and peptides - 3-nitrotyrosine and nitrosoglutathione, compared to both donors (by 31.4% and 55.3%) and patients in remission (by 38.1% and 34.5%). Chemiluminescence activity increased by 54.5% compared to donors (p 〈 0.05) and by 93% (p 〈 0.01) compared to controls. Catalase activity in the blood plasma of patients with metastases increased by 54.1% compared to donors, but was lower than the values in the control group (by 22.1%). Ceruloplasmin activity was increased only in patients without metastases (by 33%). Conclusions: The process of CC metastasis is accompanied by a greater intensity of oxidative processes of both proteins and lipids, as well as depletion of the adaptive capabilities of the body's antioxidant system.
    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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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15077-e15077
    Abstract: e15077 Background: Plant metabolites are traditionally a valuable source of anticancer drugs. The huge variety of molecular structures found in plants makes it possible to isolate substances that possess not only antimitotic, but also anti-migratory properties on cancer cells. The objective of this study was to evaluate the anti-migratory activity of selected metabolites from Petasítes sp. plants. Methods: Cells of cancer cell cultures PC3 (prostate cancer), A431 (skin cancer), CaCo-2 (colorectal cancer), HeLa (cervical cancer) and T98G (glioma) were seeded in an amount of 15*10 4 cells per well of a 24-well plate (Biofil, China) in DMEM medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA). After cell adhesion the test substances at a concentration of 40 µM were added, and a wound healing assay was performed according to the standard procedure. The study included the following metabolites: 1) substance 1 (S1) - 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one; 2) substance 2 (S2) - 5-(hydroxymethyl)furan-2-carbaldehyde; 3) substance 3 (S3) - corynan. The wound area was measured using a Lionheart FX imager (BioTek, USA) at starting time point and after 48 hours of cultivation. Data are presented as mean±95% confidence interval (n = 12). Results: The studied cultures were found to be differently sensitive to the tested substances. Cells of CaCo-2 and PC3 cultures did not demonstrate a significant decrease in mobility, as the degree of scratch overgrowth did not decrease compared to the control without the addition of substances (α = 0.05, df = 22) in all variants of the experiment. However, the A431 skin cancer culture showed reduced motility in all three trials compared to the no-substance control. Namely, the wound area reduction was 81.52 ± 9.6% in the control, 63.77 ± 8.4% in S1 variant, 62.42 ± 6.3% in S2 variant, and 12.05 ± 7.1% in S3 variant. Also, a slowdown in cell motility was observed in HeLa (28.92±5.1% compared to 37.0±6.3% in control) and T98G cells (82.41±9.1% compared to with 97.35±1.9% in control) when incubated with S1. Taking into account the correction for multiple comparisons, only the results for A431 turned out to be significant, but the results obtained for HeLa and T98G cultures were not significant at a corrected significance level (α = 0.003, df = 22). Conclusions: Further studies of 2,4-dihydroxy-2,5-dimethylfuran-3(2H)-one anti-migratory properties are of particular interest, since it showed promising results in three of the five studied cancer cell cultures.
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    ISSN: 0732-183X , 1527-7755
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    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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