Landscape of Immune-Related Markers and Potential Therapeutic Targets in Soft Tissue Sarcoma

Roszik, Jason; Mustachio, Lisa Maria; Livingston, J. Andrew; Groisberg, Roman; Pestana, Roberto Carmagnani; Subbiah, Vivek; Conley, Anthony P.

doi:10.3390/cancers13205249

Cited by 4 publications

(8 citation statements)

References 31 publications

(39 reference statements)

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“…Саркомы мягких тканей Soft tissue sarcomas 73,30 1 [62,12; 84,43] (n = 6) р 1 = 0,0414 7,12 1, 3 [5,4; 13,36] (n = 6) р 1 = 0,0000; р 3 = 0,0051 340,8 1 [242,1; 416,8] (n = 12) р 1 = 0,0037 0,25 [0, 16; 0,34] (n = 6) р 1 = 0,4467 0,0255 1, 3 [0,016; 0,035] (n = 6) р 1 = 0,0014; р 3 = 0,0049 Рецидивы Recurrences 58,88 1, 2 [45,77; 65,25] (n = 10) р 1 = 0,0001; р 2 (G 1 ) = 0,0505; р 2 (G 3 ) = 0,0014 477,4 1, 2 [459,3; 502,2] (n = 5) р 1 = 0,0017; р2 = 0,0019 352,1 1, 3 [304,1; 356,9] (n = 5) р 1 = 0,0027; р 2 = 0,95; р 3 = 0,0012 0,10 1, 2 [0,098; 0,126] (n = 5) р 1 = 0,0002; р 2 = 0,0137 0,16 2 [0,15; 0,18] (n = 5) р 1 = 0,0721; р 2 = 0,0081; р 3 = 0,0216 1 Значимость различий по сравнению с донорами. 2 Значимость различий по сравнению с группой первичных сарком: р 2 (G 1 )по сравнению с первичными больными с опухолью G 1 ; p 2 (G 3 ) -по сравнению с первичными больными с опухолью G 3 . 3 Значимость различий показателей при опухолях G 3 и G 1 .…”

Section: результатыunclassified

“…1 Significance of differences compared to donors. 2 Significance of differences compared to the primary sarcomas group: р 2 (G 1 ) -compared to primary patients with G 1 tumors; р 2 (G 3 ) -compared to primary patients with G 3 tumors. 3 Significance of differences for G 3 and G 1 tumors.…”

Section: результатыmentioning

confidence: 99%

“…Studied group IGF1, нг/мл IGF2, нг/мл IGF1/IGF2 медленно прогрессирующие slow progressing 12,14 1 [6,96; 19,24] (n = 10) р 1 = 0,0002; р 2 = 0,4801; р 3 = 0,3008 611,7 1, 2 [350,3; 700,2] (n = 10) р 1 = 0,0413; р 2 = 0,0037; р 3 = 0,1306 0,0235 1 [0,021; 0,036] (n = 10) р 1 = 0,0002; р 2 = 0,4465; р 3 = 0,9682 1 Значимость различий по сравнению с группой доноров. 2 Значимость различий по сравнению с группой первичных сарком. 3 Значимость различий показателей группы медленно прогрессирующего рецидивирования по сравнению с показателями группы быстро прогрессирующего рецидивирования.…”

Section: группа исследуемыхunclassified

“…1 Significance of differences compared to donors. 2 Significance of differences compared to the primary sarcomas group. 3 Significance of differences between the slowly progressing recurrence and fast progressing recurrence.…”

Section: группа исследуемыхmentioning

confidence: 99%

“…Эти опухоли имеют более 100 гистологических подтипов и характеризуются различным клиническим течением, что затрудняет разработку стандартизированного подхода к их лечению. Несмотря на проводимую терапию, СМТ рецидивируют и часто становятся метастатическими при средней или высокой степени злокачественности [1,2].…”

Section: Introductionunclassified

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Insulin-like growth factors and their transfer protein in the blood of patients with primary and recurrent soft tissue sarcomas

Goroshinskaya

Kaplieva

Sagatelyan

et al. 2022

jour

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Introduction. Soft tissue sarcomas (STS) are rare diseases but their characteristic tendency for recurrence and high mortality dictate the need for the search for prognostic biomarkers for identification of patients with the risk of recurrence. In this context, the system of insulin-like growth factors (IGF) and their insulin-like growth factor-binding proteins (IGFBP) is of interest because it was shown that disruption of the IGF system regulation leads to cancer cell proliferation and migration and chemotherapy resistance.The study objective is to investigate the levels of the IGF system components in blood of patients with primary and recurrent STS.Materials and methods. In total, 54 patients with STS, T2bN0M0, were examined: 12 men and 12 women with primary STS, 10 men and 20 women with recurrent STS, as well as healthy donors (10 men and 10 women). Mean patient age was 63.1 ± 0.9 years. In blood sampled prior to treatment, the levels of insulin-like growth factor 1 (IGF1), insulin-like growth factor 2 (IGF2) and insulin-like growth factor-binding protein 2 (IGFBP2) were measured by ELISA using Mediagnost kits (Germany). Statistical analysis was performed using Statistica 10 software and non-parametric Mann-Whitney test.Results. In primary STS, the levels of IGF1 in men with G3–4 tumors and all women decreased 14- and 20-fold, respectively, compared to healthy donors. Additionally, an insignificant decrease of IGF2 level in men and a decrease of IGF1/IGF2 ratio by the factor of 8.8 in men with G3–4 tumors and by the factor of 24.3 in women were observed. In recurrences, IGF1 level decreased by 40 % in men and by 78–85.5 % in women, while IGF2 level in men with G3–4 tumors decreased by 19 %, in women increased by 21–58 % compared to donors. In women with primary STS and recurrences of G3–4 tumors, IGFBP2 was also elevated. In men with G3–4 tumors, changes in IGFBP2 levels were less significant and had an opposite trend compared to women.Conclusion. STS recurrence is accompanied by imbalance of IGF system components in blood, especially in patients of both sexes with G3–4 tumors. Correlation between increased IGFBP2 level in STS and clinical characteristics of the disease, especially in recurrence, suggest prognostic significance of this molecule.

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Section: результатыunclassified

Section: результатыmentioning

confidence: 99%

Section: группа исследуемыхunclassified

Section: группа исследуемыхmentioning

confidence: 99%

Section: Introductionunclassified

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Insulin-like growth factors and their transfer protein in the blood of patients with primary and recurrent soft tissue sarcomas

Goroshinskaya

Kaplieva

Sagatelyan

et al. 2022

jour

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Redox status of blood lymphocytes in patients with soft tissue sarcomas

Goroshinskaya,

Kaplieva,

Frantsiyants

et al. 2023

jour

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Introduction. The proven significance of free radical disorders in oncopathology determines the relevance of their study in soft tissue sarcomas (STS), which are characterized by a tendency to recurrence and high mortality of patients.Aim. To study the indicators of free radical oxidation and antioxidant protection in blood lymphocytes in primary and recurrent STS, depending on the sex and age of patients.Materials and methods. In 51 patients with primary STS, T2bN0M0 (17 men and 34 women) and in 34 patients (14 men and 20 women) with relapses, the level of lipid peroxidation products – malondialdehyde and diene conjugates, activities of superoxide dismutase and glutathione peroxidase, total peroxidase activity, the level of reduced glutathione were studied by spectrophotometric methods. Patients were divided by age: ≤45 years and >45 years. The comparison groups (donors) consisted of 12 men and 17 women divided into the same age subgroups.Results. In men >45 years old with primary sarcomas, there was an increase in diene conjugates by 2.2 times, with relapses by 2.4 times, and in young men - only with relapses by 2.6 times. The level of malondialdehyde in men did not change with primary sarcomas, with relapses it was reduced in both age groups by 2.4–2.6 times. In women with primary STS, there was an increase in most of the studied parameters in both age groups by 1.6–1.9 times. The increase in diene conjugates level and superoxide dismutase activity was the most pronounced (>3 times) in patients of the older age group. The increase in glutathione peroxidase activity in primary STS in young women was 2.3 times, and in the older age group in patients of both sexes it was 5 times. In half of the women with relapses developed no earlier than 3 years after treatment, a decrease in both lipid peroxidation products by 2.6–3.4 times was found, and in all women almost 4-fold activation of superoxide dismutase and 8-fold glutathione peroxidase with an increase in the level of reduced glutathione by 7 times took place, which was significantly higher than in men. For women of the older age group, a 3-fold increase in the ratio of superoxide dismutase/total peroxidase activity is characteristic for primary STS and almost 5-fold for recurrence.Conclusion. In primary STS, the activation of lipid peroxidation products and antioxidant enzymes in women is more pronounced than in men. Changes in most indicators are more typical for patients of older age groups, in which relapse was accompanied by a decrease in malondialdehyde in patients of both sexes and maximum activation of superoxide dismutase and glutathione peroxidase in women.

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Indicators of free radical oxidation in neutrophils of patients with primary and recurrent soft tissue sarcomas

Goroshinskaya,

Kaplieva,

Frantsiyants

et al. 2023

Issled. prakt. med. (Print)

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Purpose of the study. To carry out a comparative analysis of lipid peroxidation intensity and antioxidant system indices in blood neutrophils of patients with primary and relapsed soft tissue sarcomas (STS) depending on sex and age.Patients and methods. Of the 81 patients included in the study, 48 had primary STS, 5 patients with continued growth, and 28 patients with recurrent STS. The patients were divided by sex and age; the level of lipid peroxidation products, superoxide dismutase (SOD) activity, total peroxidase activity (TPA), glutathione peroxidase (GPx) activity and reduced glutathione (RG) content in blood neutrophils were investigated by conventional spectrophotometric methods. The comparison groups (donors) consisted of 12 men and 17 women divided into the same age subgroups: ≤ 45 years and > 45 years.Results. In donors, there was a multiple decrease in the SOD/TPA ratio with age, especially in women, and in men this was accompanied by an age-related decrease in GPx activity. In primary sarcomas in older women and in men with continued growth and recurrence, there was an increase in diene conjugates (DC). In men over 45 years of age, there was an increase in SOD, TPA, and GPx. Women of the older age group were characterized by activation of SOD and GPx, expressed in the relapsed process to a significantly greater extent than in men, and an increase in RG was observed in women. The increase in both components of the glutathione system and SOD activity was especially significant in the development of relapses in women for periods exceeding three years, which was accompanied by a decrease in DC content. Conclusions. Neutrophils are characterized by an increase in DC content in patients of both sexes in the older age group with primary and recurrent STS, with its highest content in men with continued growth and relapses. GPx activity, increased in both men and women in the older age group in all variants of STS development, may play an important role in the antioxidant protection of blood cells in STS. Thus, the most pronounced activation of GPx, accompanied by a maximum increase in reduced glutathione and activation of SOD, contributes to a decrease in the level of DC and the absence of MDA increase in women with slow development of recurrences.

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Landscape of Immune-Related Markers and Potential Therapeutic Targets in Soft Tissue Sarcoma

Cited by 4 publications

References 31 publications

Insulin-like growth factors and their transfer protein in the blood of patients with primary and recurrent soft tissue sarcomas

Insulin-like growth factors and their transfer protein in the blood of patients with primary and recurrent soft tissue sarcomas

Redox status of blood lymphocytes in patients with soft tissue sarcomas

Indicators of free radical oxidation in neutrophils of patients with primary and recurrent soft tissue sarcomas

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