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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 4_suppl ( 2020-02-01), p. 90-90
    Abstract: 90 Background: Complete or partial deficiency of the DPD enzyme due to genetic polymorphisms of the DPYD gene causes acute toxicity of fluoropyrimidines, which are widely used in combination chemotherapy regimens for various malignant neoplasms. The purpose of the study: to identify polymorphisms of the DPYD gene significant for 5-fluorouracil-induced toxicity. Methods: Venous blood samples from Caucasian patients were used to identify alleles of *2А rs3918290, 5* rs1801159, *13 rs55886062 and rs67376798 DPYD by RT-PCR and direct sequencing. Inclusion criteria were: verified diagnosis of gastrointestinal tumors, age 〉 18 years old, fluoropyrimidine-containing regimes of treatment. Results: 104 pts were included, 54% were female. Mean age-61 years. Colorectal cancer was found in 80.7% pts, non-colorectal in 19.3% pts. Hematological and non-hematological toxicity Gd.3-4 was found in 24% pts. Allele * 5rs18011595, which causes enzyme deficiency was found in 28% of patients, (frequency was 0.281) which is significantly higher than the population frequency of the allele charactering for Caucasoid population (p 〈 0.05). Meanwhile genotyping did not reveal the *2A, *13 alleles and rs67376798 alleles in the DPYD gene. Conclusions: *5rs1801159 allele was found as the main DPYD polymorphism associated with fluoropyrimidine toxicity in Caucasian pts with gastrointestinal tumors.
    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
    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. e13072-e13072
    Abstract: e13072 Background: Breast cancer (BC) is the most common cancer in women worldwide. The purpose of the study was to analyze immediate and long-term results of treatment in patients with locally advanced primarily inoperable HER2-negative breast cancer depending on the time of progression. Methods: The study included 104 women with locally advanced primarily inoperable HER2-negative breast cancer who developed an early disease progression within 6 to 12 months after standard combination treatment. The blood levels of circulating tumor cells (CTCs) were measured in all patients during the progression stage. Results: An analysis of the overall (OS) and event-free (EFS) survival showed that median EFS in patients with luminal B subtype was 9 months, in patients with triple-negative (TNBC) subtype 8 months. EFS at 6 months was 87.5% in luminal B subtype and 79.4% in TNBC, p = 0.37985. Median OS in patients with luminal B subtype was 25 months, in patients with TNBC 26 months. One-year OS was 100% in luminal B subtype and 93.9% in TNBC, p = 0.138. 2-year OS was 54.2% in luminal B subtype and 55.9% in TNBC, p = 0.697. 3-year OS was 37.5% in luminal B subtype and 41.2% in TNBC, p = 0.639. CTCs were detected in all patients, with higher levels in patients with luminal B subtype than in TNBC patients. HER+ CTCs were found in 30% of patients with luminal B subtype but not registered in patients with TNBC. Such results were obtained for the first time. Conclusions: The absence of significant differences demonstrated the aggressive disease course in patients with luminal BC with identified primary hormone resistance, similar to the TNBC course. The results should be taken into account when predicting the course of the disease and developing further treatment tactics.
    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
    detail.hit.zdb_id: 2005181-5
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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. e12550-e12550
    Abstract: e12550 Background: BC is still one of the main causes of death in women due to the tumor recurrence and/or resistance to anticancer therapy. The criteria to assess the effectiveness of BC treatment are important. The purpose of the study was to analyze blood levels of steroid and pituitary hormones in BC patients after two chemotherapy cycles. Methods: The study included 42 patients with various biological BC subtypes: luminal A, luminal B and triple-negative BC (TNBC). Levels of estradiol, testosterone, progesterone, prolactin, LH, FSH and cortisol were measured by RIA in the blood of all patients before and after two neoadjuvant chemotherapy cycles. Significance of differences was evaluated by the Student’s t-test. Results: Levels of many hormones were high before the treatment in patients with all BC subtypes. After two chemotherapy cycles, unidirectional changes in the values were found in patients with subsequent remission for more than three years. Levels of estradiol decreased in luminal A BC by 1.7 times (p˂0.05), in luminal B BC – by 11.6 times (p˂0.05), cortisol decreased by 2.4 and 1.7 times (p˂0.05) respectively, and prolactin – on average by three times (p˂0.05). LH levels increased in luminal A and luminal B BC by 1.65 times (p˂0.05). In patients with TNBC, levels of estradiol decreased by 1.8 times, and cortisol – by two times (p˂0.05). Patients with subsequent remission regardless of BC subtypes had unchanged levels of testosterone, progesterone and FSH. Patients with luminal B and TNBC subtypes with progression in 6-12 months did not show significant changes in prolactin and cortisol levels after two chemotherapy cycles, compared with the values before treatment. Conclusions: A decrease in blood levels of prolactin and cortisol after two chemotherapy cycles is an indicator of a long-term remission in patients with breast 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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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e15545-e15545
    Abstract: e15545 Background: For many years, colorectal cancer has been among the most frequently diagnosed cancers and one of the leading causes of cancer death. The effect of monoclonal antibodies on the immunological status remains relevant, since chemotherapy in combination with monoclonal antibodies (anti-EGFR, anti-VEGF) plays a key role in the treatment of patients with metastatic colorectal cancer. The purpose of this study was to reveal specific features of the cytokine profile of patients with metastatic colorectal cancer (mCRC) receiving bevacizumab in combination with chemotherapy before and after the treatment. Methods: The study included 15 patients with newly diagnosed mCRC receiving mFOLFOX6 chemotherapy combined with bevacizumab as the first-line treatment. Cytokine levels were determined in the blood serum (BS) by multiplex assay with the Bio-Plex Pro Human Immunotherapy 20-Plex Panel (GM-CSF, IFN-γ, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL-15, IL-17A, IL-18, IP-10, MCP-1, MIG, MIP-1α, MIP-1β, RANTES, TNF-α) (Bio-Rad, USA) before and after 4 cycles of the therapy. Results were evaluated using the Luminex 200 Analyzer (Bio-Rad, USA) with the Bio-Plex Manager Software. Results: Complete response to the therapy was registered in 5 (33.3%) patients, partial remission in 8 (53.3%) patients, progression in 13.3%. IL-6, IP-10, MIG, RANTES, and TNF-a were statistically significantly (p 〈 0.05) elevated in patients with complete response. IL-8 showed a tendency to decreasing after the therapy. Levels of IL-6, IL-8, IL-15, IL-17, and MIP-1a in patients with partial remission after the therapy reduced to zero values. An analysis of the cytokine profiles in patients with progression demonstrated a decrease of all the studied indices, except for elevated IL-15 and IL-17. Conclusions: Anti-VEGF agents together with chemotherapy changed the cytokine profiles in patients with mCRC. Probable mechanism may include the implementation of the antitumor response through the activation of some pro-inflammatory cytokines, since the complete response was accompanied by an increase in IL-6, IP-10, MIG, RANTES, TNF-a and a decrease in IL8.
    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
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e12551-e12551
    Abstract: e12551 Background: Breast cancer (BC) is still one of the main causes of death in women due to the tumor recurrence and/or resistance to anticancer therapy. The criteria to assess the risk of tumor progression in breast cancer after 2 chemotherapy cycles are required. The purpose of the study was to analyze blood levels of TGFβ, TGFR2, TNF, TNFα, TNFR1, TNFR2, MMP-9 and CD-44 in patients with various BC subtypes before and after 2 chemotherapy cycles. Methods: The study included 42 patients with various BC subtypes: luminal A, luminal B and triple-negative BC (TNBC). Levels of TGFβ, TGFR2, TNF, TNFR1, TNFR2, CD-44, MMP-9 were measured by ELISA in the blood of all patients prior to anticancer therapy and after 2 chemotherapy cycles. Statistical processing of results was performed using the Statistika 6.0 software by the Student’s t-test. Results: Levels of TGFβ, TGFR2, TNF, TNFα, TNFR1, TNFR2, CD-44, MMP-9 in patients with all BC subtypes were high before the treatment. After 2 chemotherapy cycles, the values decreased statistically significantly in all BC subtypes: CD-44 decreased by 25.2%, 30% and 54.7% in luminal A, luminal B and TNBC, respectively; TNFα – by 26.2%, 48.3% and 50.8%, respectively; TNFα-R1 – by 52.1%, 39.2% and 50.3% respectively; TNFα-R2 – by 31.7%, 32.8% and 41.9% respectively; MMP-9 – 35.3%, 32.6% and 43.3% respectively. The patients remained in remission for 3 years. When the levels were high or did not differ from initial values, the tumor progressed. Conclusions: We identified a set of criteria allowing with high probability to determine the growth and progression of tumors in various subtypes of breast cancer after two cycles of chemotherapy. A decrease in the levels of TGF-β, TNF, MMP-9, and CD-44 demonstrates remission; stabilization or increase of these indicators leads to further early progression of the disease.
    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: 2020
    detail.hit.zdb_id: 2005181-5
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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. e19554-e19554
    Abstract: e19554 Background: The purpose of this study was to assess NT-proBNP as a marker of renal dysfunction in patients with diffuse large B-cell lymphoma receiving immune polychemotherapy. Methods: The study involved 24 patients aged 23-69 years (median 57 years) with a primary diagnosis of diffuse large B-cell lymphoma (DLBCL). The renal status was assessed by the blood serum levels of creatinine, urea, NT-proBNP (Vitros 5600, USA), sodium (Cobas b221, Switzerland) with the calculation of the glomerular filtration rate (GFR) according to the CKD-EPI formula, as well as urine levels of albumin (Cobas Integra 400 plus, Switzerland). The tests were conducted before and 48 hours after induction immune polychemotherapy (R-CHOP). Statistical evaluation of results was made using the Statistica 13.0 program. Results: The patients were divided into 2 groups depending on the GFR levels before the start of therapy: group 1 (n = 16) - GFR 108.04±13.9 mL/min/1.73 m 2 (normal levels); group 2 (n = 8) - GFR 59.57±12.04 mL/min/1.73m 2 (reduced levels). The studied parameters in group 1 were within the reference values before treatment: NT-proBNP 109.38±13.6 pg/mL, creatinine 72.67±7.96 μmol/L, urea 5.39±0.99 mmol/L, albumin in urine 4.34±0.51 mg/L. After 48 hours, a moderate increase in NT-proBNP up to 207.5±48.2 pg/mL (p 〉 0.05) was observed, without significant changes in other parameters. In group 2, a pronounced increase in NT-proBNP was observed initially: 694±206.47 pg/mL, which was 5.6 times higher than the upper limit of the reference interval (p 〈 0.001) and 6.4 times higher than the levels in group 1 (p 〈 0.001), together with a significant increase in urine levels of albumin - 43.93±12.03 mg/L. Creatinine (80.67±4.35 μmol/L) and urea (6.4±1.41 mmol/L) remained within the reference range. After 48 hours, NT-proBNP increased by 3.8 times, reaching 2675±602.4 pg/mL (p 〈 0.001), which was accompanied by an increase in urine albumin - 57.8±8.86 mg/L and serum creatinine – 102.2±5.37 μmol/L in comparison with the initial levels. The levels of urea remained unchanged (6.6±0.43 mmol/L). The sodium levels did not differ significantly between the groups and was 141.65±2.24 mmol/L in group 1 and 140.85±3.4 mmol/L in group 2 and did not change over time. According to the results, patients with an initially decreased GFR demonstrated an increase in the levels of NT-proBNP and albumin in the urine even before the start of polychemotherapy. Conclusions: NT-proBNP can be considered an early marker of renal dysfunction in patients with diffuse large B-cell lymphoma.
    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. 38, No. 15_suppl ( 2020-05-20), p. e13107-e13107
    Abstract: e13107 Background: TACE is widely used in oncology in patients with metastasis in liver from GI tumors, meanwhile its opportunities in management pts with TNBC are unknown. The purpose of the study was to analyze the results of TACE of the liver metastases from TNBC. Methods: The study included 60 TNBC pts with unresectable liver metastases. 34 pts of the main group underwent chemotherapy including taxanes in standard regimens. After 6-12 chemotherapy cycles, the main group received 1-2 TACE procedures (doxorubicin 30 mg/m², 5-fluorouracil 600 mg/m², 10 ml of lipiodol and 1-2 ml of 300-500 µm HepaSphere microspheres). The control group (n = 32) received only 6-12 cycles of taxane-containing chemotherapy. Pts were aged 32-66 years, mean age in the main group 49.4, in controls 55 years. Primarily advanced breast cancer with unresectable liver metastases was diagnosed in 6 (17.6%) pts of the main group and in 5 (15.6%) controls. Progression after previous treatment was observed in 91.2% (31) main group and 90.6% (29) controls. Sizes of metastatic foci were 2.7-7.3 cm, average number 7.5. Bilobar metastases were most common. Liver metastases were own accompanied by metastases to the bones, intrathoracic lymph nodes, lungs and pleura. Obtained data were processed with software package “Statistica 7.0”. Results: Main group received a total of 46 TACE procedures performed for a maximal number of metastatic lesions, especially for those progressing after systemic therapy and the largest ones, when possible. Post-embolization syndrome after performing TACE, was observed in 60.86% (28) of cases, managed with conservative therapy for 2-7 days. Icterus was not observed. The tumor response rate was 94.1% in the main group vs. 80.6% in controls, with significant differences in PR (44.1% and 15.3% respectively, p 〈 0.05). Median of duration treatment response was 13.4 months in the main group and 9.3 months in control group (p 〈 0.05). CR was not achieved. Median follow-up was 17 months. 3-year disease-free survival was 63.2% in the main group and 43.8% in controls (p = 0.039). Conclusions: TACE resulted in better response to the therapy as well as improved disease-free survival in pts with TNBC. TACE is possible to be used to consolidate the achieved effect of the chemotherapy.
    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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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e12064-e12064
    Abstract: e12064 Background: Circulating tumor cells (CTC) are of great importance in modern cancer research. Biological characteristics of CTC allow using them as tumor markers of high prognostic value. Their quantitative evaluation during treatment can be used to monitor the response to treatment in patients receiving systemic chemotherapy (CT). The purpose of the study was to assess the role of CTC in the prognosis of treatment efficacy in patients with locally advanced Her-2 negative breast cancer. Methods: The study included 42 patients aged 30-65 years with stage IIIA, IIIB, IIIC locally advanced Her-2 negative breast cancer, ECOG-WHO Performance Status from 0 to 2, Karnofsky Performance Status from 100% to 80%. CTC were determined using the CellSearch Veridex System (Johnson & Johnson, USA), taking into account morphological characteristics and expression of epithelial cell adhesion markers EpCAM, CD45 and cytokeratins 8, 18 and 19. Results: CTC were found in 86% (36 of 42 patients) before treatment. CTC were not registered in 6 (14%) patients. 1 CTC was detected in 14% (6 patients); 2-3 CTC – 33% (14 patients); more than 3 CTC – 38% (16 patients). 12% (5) patients showed more than 10 CTC, with the maximum of 64 CTC in 1 patient. After 2 cycles of polychemotherapy, CTC were detected in 50% (21 patients). Other 21 patients did not show presence of CTC. Among CTC-positive patients, 1 CTC was detected in 4 patients (19%); from 2 to 3 CTC – in 9 patients (43%); more than 3 CTC – 8 patients (38%). 2 patients (10%) still showed more than 10 CTC – 28 and 33 CTC in the peripheral blood. After 2 cycles of polychemotherapy, the number of patients with more than 1 CTC decreased from 86% to 50%. Polychemotherapy regimen was changed for patients with increasing amounts of CTC. Conclusions: Determination of the CTC number allows evaluation of the treatment efficacy and is a specific marker for the change of applied polychemotherapy for such cancer type.
    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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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e19580-e19580
    Abstract: e19580 Background: Many studies have been devoted to the molecular profile of diffuse large B-cell lymphoma; however, a clear molecular and genetic picture of primary mediastinal large B-cell lymphoma (PMBLC) has not yet been described. Studies have reported various signaling pathways involved in PMBCL pathogenesis, with the best known JAK-STAT and NF-kB. This study was aimed at the detection of previously undescribed mutations, as well as the identification of signaling pathways that may be of interest in the search for new therapeutic targets for PMBCL. Methods: Tumor biopsy specimens from 23 PMBCL patients were examined by next-generation sequencing (NGS) on the Illumina NextSeq 550 system with an average coverage of at least 100x using the AVENIO Tumor Expanded Panel (Roche, USA) containing 77 genes. Analytical sensitivity of mutation detection was 5%. The pathogenicity of the identified nucleotide substitutions was assessed according to ACMG (American College of Medical Genetics and Genomics) and AMP (Association of Molecular Pathology) recommendations. Genomic DNAs were extracted from FFPE blocks using the Gene Read DNA FFPE Kit panel (Qiagen, USA) according to the standard protocol. DNA concentrations were measured fluorimetrically on the Qubit 2.0 fluorometer (Life Technologies, USA). The AVENIO Oncology Analysis Software was used to process the data and to search for clinically significant mutations. The genetic material was analyzed for clinically significant mutations among well-known databases: COSMIC: V83, TCGA 9.0, Exac: 1.0, DBSNP: 150, 1000 Genomes: phase_3_v5b, Snpeff: 4.2. Results: The targeted high-performance sequencing of PMBLC samples showed a newly revealed range of polymorphisms in 9 genes in patients with PMBLC (Alk, TP53, CCND3, RNF43, PIK3CA, FGFR3, SMO, MET, EZH2), previously not described for this cancer. We also interpreted signal pathways related to the mutated genes. Conclusions: The identified polymorphisms and the relationship of mutated genes with PMBLC signaling paths can serve as new therapeutic targets for patients with PMBLC.
    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
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e13040-e13040
    Abstract: e13040 Background: The kallikrein-kinin system is a complex multifunctional signaling cascade. Studies confirm its role in the development of cancer, as well as a role of some of its proteins with pro-inflammatory properties. Criteria for assessing the risk of breast cancer (BC) progression are required. The purpose of the study was to reveal the effect of blood levels of plasminogen, plasmin, precallikrein, and kallikrein in patients with triple-negative BC on the disease course. Methods: The study included 162 patients with triple-negative BC divided into 2 groups: group 1 – 58 patients with an early progression within 6 to 12 months after combination treatment; group 2 – 104 patients without progression during 2 years after combination treatment. Blood levels of plasminogen, plasmin, prekallikrein, and kallikrein were measured by ELISA before anticancer therapy and after 8 chemotherapy cycles. The levels in the blood plasma of healthy donors were reference values. Results were statistically processed using the Statistika 6.0 program with the Student’s T-test. Results: In patients with an early progression, plasminogen levels before the treatment were decreased by 1.7 times (p≤0.05), while plasmin was elevated by 1.9 times (p≤0.05). Kallikrein was increased by 1.9 times (p≤0.05), and prekallikrein was similar to the values in healthy donors. In patients with prolonged remission, plasminogen levels before the treatment were decreased on average by 2 times (p≤0.05). Plasmin was elevated by 2.3 times (p≤0.05), and kallikrein – by 1.8 times (p≤0.05). During this period of the study, prekallikrein levels decreased by 2 times (p≤0.05), compared with healthy donors. After chemotherapy, prekallikrein levels in the group with an early progression decreased by 1.4 times (p≤0.05), compared to the values before treatment, and kallikrein increased on the average by 1.3 times (p≤0.05). In patients with prolonged remission, no changes in the studied indices were registered. Conclusions: Patients with an early progression of BC demonstrated decreased levels of prekallikrein and increased kallikrein after the treatment, which allowed predicting resistance to chemotherapy and further tumor progression.
    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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