Research

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13 pages, 591 KiB

Open AccessArticle

Serum Paraoxonase-1 Activity in Prostate Cancer Patients Treated with Brachytherapy as a Measure of Irradiation Efficacy

by Dorota Olszewska-Słonina and Miłosz Jasiński

Antioxidants 2023, 12(2), 212; https://doi.org/10.3390/antiox12020212 - 17 Jan 2023

Cited by 1 | Viewed by 1047

Abstract

We investigated changes in the activity of antioxidant paraoxonase-1 (PON1) in patients with prostate cancer (PCa) undergoing radiotherapy (RT), as well as the relationship of the PON1 activity with the degree of PCa advancement. We included 84 men with PCa. Blood samples were [...] Read more.

We investigated changes in the activity of antioxidant paraoxonase-1 (PON1) in patients with prostate cancer (PCa) undergoing radiotherapy (RT), as well as the relationship of the PON1 activity with the degree of PCa advancement. We included 84 men with PCa. Blood samples were obtained before irradiation and after the completion of RT. The control group was composed of 60 healthy men. There was no significant difference in the PON1 activity between the control group and patients pre-radiotherapy. Irradiation was associated with a significant decrease in the PON1 activity; thus, it could be a measure of the efficacy of RT. No significant correlations between the PON1 activity and Gleason score, prostate volume, BMI (body mass index), or adipose tissue thickness were found. However, there was a positive correlation between the PON1 activity and the PSA concentration in the group of PCa patients. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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19 pages, 2599 KiB

Open AccessArticle

Gradient Boosting Machine Identified Predictive Variables for Breast Cancer Patients Pre- and Post-Radiotherapy: Preliminary Results of an 8-Year Follow-Up Study

by Elisabet Rodríguez-Tomàs, Meritxell Arenas, Gerard Baiges-Gaya, Johana Acosta, Pablo Araguas, Bárbara Malave, Helena Castañé, Andrea Jiménez-Franco, Rocío Benavides-Villarreal, Sebastià Sabater, Rosa Solà-Alberich, Jordi Camps and Jorge Joven

Antioxidants 2022, 11(12), 2394; https://doi.org/10.3390/antiox11122394 - 02 Dec 2022

Cited by 1 | Viewed by 1461

Abstract

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb [...] Read more.

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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14 pages, 1708 KiB

Open AccessArticle

Evaluation of Paraoxonase-1 and Pentraxin-3 in the Diagnosis and Prognosis of Endometrial Cancer

by Mateusz Kozłowski, Kaja Michalczyk, Grzegorz Witczak, Sebastian Kwiatkowski, Aneta Mirecka, Katarzyna Nowak, Ewa Pius-Sadowska, Bogusław Machaliński and Aneta Cymbaluk-Płoska

Antioxidants 2022, 11(10), 2024; https://doi.org/10.3390/antiox11102024 - 13 Oct 2022

Cited by 2 | Viewed by 1288

Abstract

It is relevant to find new prognostic and diagnostic biomarkers for endometrial cancer. The study group consisted of 94 cases of endometrial cancer, the control group of 65 cases of normal endometrium. We evaluated PON1 and PTX3 serum levels. The ROC curve was [...] Read more.

It is relevant to find new prognostic and diagnostic biomarkers for endometrial cancer. The study group consisted of 94 cases of endometrial cancer, the control group of 65 cases of normal endometrium. We evaluated PON1 and PTX3 serum levels. The ROC curve was plotted. The area under the curve was calculated to characterize the sensitivity and specificity of the studied parameters. Univariate and multivariate analyses were performed simultaneously using the Cox regression model. The Kaplan–Meier curve was used to assess survival. The cut-off level of PON1 was 142.6 ng/mL, with a sensitivity and specificity of 79 and 84% (p = 0.0321). The cut-off level of PTX3 was 4.2 ng/mL, with a sensitivity and specificity of 63 and 57% (p = 0.028). The favorable prognostic factor determined in serum was PON1 (for PFS: HR 0.93, 95% CI 0.86–1.03, p = 0.046; for OS: HR 0.96, 95% CI 0.89–1.08, p = 0.009). PON1 may be considered a potential biomarker in the diagnosis of endometrial cancer. Considering multivariate analysis, the PON1 serum level above the median is an independent favourable prognostic factor affecting PFS and OS. Considering Kaplan–Meier curves, longer recurrence-free survival and overall survival were found in patients with PON1 levels below the median. In view of the inconclusive results, we suggest that further studies should be conducted. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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10 pages, 966 KiB

Open AccessArticle

Serum Paraoxonase-1 Activity and the Risk of Prostate Cancer Recurrence in Patients Treated with Radiotherapy

by Milosz Jasinski and Dorota Olszewska-Slonina

Antioxidants 2022, 11(2), 346; https://doi.org/10.3390/antiox11020346 - 10 Feb 2022

Cited by 6 | Viewed by 1340

Abstract

The antioxidant paraoxonase-1 (PON1) may be involved in the response to radiation-induced oxidative stress and possibly prevent cell apoptosis. The correlation of PON1 with the risk of cancer recurrence after radiotherapy (RT) is not yet explored. We investigated changes in the activity of [...] Read more.

The antioxidant paraoxonase-1 (PON1) may be involved in the response to radiation-induced oxidative stress and possibly prevent cell apoptosis. The correlation of PON1 with the risk of cancer recurrence after radiotherapy (RT) is not yet explored. We investigated changes in the activity of PON1 in patients with prostate cancer (PCa) undergoing RT, and the relation of PON1 activity to the risk of recurrence after RT. We included 56 men with PCa. Blood samples were obtained before irradiation and after the completion of RT. Patients were followed for an average of 51.2 months. Each case of biochemical recurrence was confirmed with biopsy. The control group was composed of 60 healthy men. There was no significant difference in PON1 activity between the control group and patients pre-radiotherapy. Irradiation was associated with a significant decrease in PON1 activity. Patients with PCa recurrence had significantly higher serum PON1 activity than those recurrence-free, both before and after RT. PON1 activity was a predictor of PCa recurrence, with sensitivity over 80% and specificity over 64%. Our results suggest that PON1 activity may be a predictor of PCa recurrence risk after RT. Studies with a larger number of patients and longer follow-up are needed to confirm this hypothesis. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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18 pages, 1754 KiB

Open AccessArticle

Intestinal and Hepatic Uptake of Dietary Peroxidized Lipids and Their Decomposition Products, and Their Subsequent Effects on Apolipoprotein A1 and Paraoxonase1

by Xueting Jiang, Pragney Deme, Rajat Gupta, Dmitry Litvinov, Kathryn Burge, Sampath Parthasarathy and Chandrakala Aluganti Narasimhulu

Antioxidants 2021, 10(8), 1258; https://doi.org/10.3390/antiox10081258 - 06 Aug 2021

Cited by 2 | Viewed by 1826

Abstract

Both pro- and antiatherosclerotic effects have been ascribed to dietary peroxidized lipids. Confusion on the role of peroxidized lipids in atherosclerotic cardiovascular disease is punctuated by a lack of understanding regarding the metabolic fate and potential physiological effects of dietary peroxidized lipids and [...] Read more.

Both pro- and antiatherosclerotic effects have been ascribed to dietary peroxidized lipids. Confusion on the role of peroxidized lipids in atherosclerotic cardiovascular disease is punctuated by a lack of understanding regarding the metabolic fate and potential physiological effects of dietary peroxidized lipids and their decomposition products. This study sought to determine the metabolic fate and physiological ramifications of 13-hydroperoxyoctadecadienoic acid (13-HPODE) and 13-HODE (13-hydroxyoctadecadienoic acid) supplementation in intestinal and hepatic cell lines, as well as any effects resulting from 13-HPODE or 13-HODE degradation products. In the presence of Caco-2 cells, 13-HPODE was rapidly reduced to 13-HODE. Upon entering the cell, 13-HODE appears to undergo decomposition, followed by esterification. Moreover, 13-HPODE undergoes autodecomposition to produce aldehydes such as 9-oxononanoic acid (9-ONA). Results indicate that 9-ONA was oxidized to azelaic acid (AzA) rapidly in cell culture media, but AzA was poorly absorbed by intestinal cells and remained detectable in cell culture media for up to 18 h. An increased apolipoprotein A1 (ApoA1) secretion was observed in Caco-2 cells in the presence of 13-HPODE, 9-ONA, and AzA, whereas such induction was not observed in HepG2 cells. However, 13-HPODE treatments suppressed paraoxonase 1 (PON1) activity, suggesting the induction of ApoA1 secretion by 13-HPODE may not represent functional high-density lipoprotein (HDL) capable of reducing oxidative stress. Alternatively, AzA induced both ApoA1 secretion and PON1 activity while suppressing ApoB secretion in differentiated Caco-2 cells but not in HepG2. These results suggest oxidation of 9-ONA to AzA might be an important phenomenon, resulting in the accumulation of potentially beneficial dietary peroxidized lipid-derived aldehydes. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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Review

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36 pages, 1352 KiB

Open AccessReview

The Relationship between Cancer and Paraoxonase 1

by Irma Martha Medina-Díaz, Néstor Ponce-Ruíz, Aurora Elizabeth Rojas-García, José Francisco Zambrano-Zargoza, Yael Y. Bernal-Hernández, Cyndia Azucena González-Arias, Briscia S. Barrón-Vivanco and José Francisco Herrera-Moreno

Antioxidants 2022, 11(4), 697; https://doi.org/10.3390/antiox11040697 - 31 Mar 2022

Cited by 11 | Viewed by 3237

Abstract

Extensive research has been carried out to understand and elucidate the mechanisms of paraoxonase 1 (PON1) in the development of diseases including cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. This review focuses on the relationship between PON1 and cancer. The data suggest [...] Read more.

Extensive research has been carried out to understand and elucidate the mechanisms of paraoxonase 1 (PON1) in the development of diseases including cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. This review focuses on the relationship between PON1 and cancer. The data suggest that PON1, oxidative stress, chronic inflammation, and cancer are closely linked. Certainly, the gene expression of PON1 will remain challenging to study. Therefore, targeting PON1, redox-sensitive pathways, and transcription factors promise prevention and therapy in the development of several diseases, including cancer. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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17 pages, 1079 KiB

Open AccessReview

Role of NRF2 in Ovarian Cancer

by Giovanni Tossetta, Sonia Fantone, Eva Montanari, Daniela Marzioni and Gaia Goteri

Antioxidants 2022, 11(4), 663; https://doi.org/10.3390/antiox11040663 - 30 Mar 2022

Cited by 64 | Viewed by 5300

Abstract

Among gynaecologic malignancies, ovarian cancer is one of the most dangerous, with a high fatality rate and relapse due to the occurrence of chemoresistance. Many researchers demonstrated that oxidative stress is involved in tumour occurrence, growth and development. Nuclear factor erythroid 2-related factor [...] Read more.

Among gynaecologic malignancies, ovarian cancer is one of the most dangerous, with a high fatality rate and relapse due to the occurrence of chemoresistance. Many researchers demonstrated that oxidative stress is involved in tumour occurrence, growth and development. Nuclear factor erythroid 2-related factor 2 (NRF2) is an important transcription factor, playing an important role in protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) activate NRF2 signalling, inducing the expression of antioxidant enzymes, such as haem oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), that protect cells against oxidative stress. However, NRF2 activation in cancer cells is responsible for the development of chemoresistance, inactivating drug-mediated oxidative stress that normally leads to cancer cells’ death. In this review, we report evidence from the literature describing the effect of NRF2 on ovarian cancer, with a focus on its function in drug resistance, NRF2 natural and synthetic modulators and its protective function in normal ovarian preservation. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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17 pages, 810 KiB

Open AccessReview

The Double-Edged Sword of Oxidative Stress in Skin Damage and Melanoma: From Physiopathology to Therapeutical Approaches

by Monica Emanuelli, Davide Sartini, Elisa Molinelli, Roberto Campagna, Valentina Pozzi, Eleonora Salvolini, Oriana Simonetti, Anna Campanati and Annamaria Offidani

Antioxidants 2022, 11(4), 612; https://doi.org/10.3390/antiox11040612 - 23 Mar 2022

Cited by 46 | Viewed by 4405

Abstract

The skin is constantly exposed to exogenous and endogenous sources of reactive oxygen species (ROS). An adequate balance between ROS levels and antioxidant defenses is necessary for the optimal cell and tissue functions, especially for the skin, since it must face additional ROS [...] Read more.

The skin is constantly exposed to exogenous and endogenous sources of reactive oxygen species (ROS). An adequate balance between ROS levels and antioxidant defenses is necessary for the optimal cell and tissue functions, especially for the skin, since it must face additional ROS sources that do not affect other tissues, including UV radiation. Melanocytes are more exposed to oxidative stress than other cells, also due to the melanin production process, which itself contributes to generating ROS. There is an increasing amount of evidence that oxidative stress may play a role in many skin diseases, including melanoma, being the primary cause or being a cofactor that aggravates the primary condition. Indeed, oxidative stress is emerging as another major force involved in all the phases of melanoma development, not only in the arising of the malignancy but also in the progression toward the metastatic phenotype. Furthermore, oxidative stress seems to play a role also in chemoresistance and thus has become a target for therapy. In this review, we discuss the existing knowledge on oxidative stress in the skin, examining sources and defenses, giving particular consideration to melanocytes. Therefore, we focus on the significance of oxidative stress in melanoma, thus analyzing the possibility to exploit the induction of oxidative stress as a therapeutic strategy to improve the effectiveness of therapeutic management of melanoma. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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25 pages, 3287 KiB

Open AccessReview

Glutathione S-Transferases in Cancer

by Rahul Raj Singh and Katie M. Reindl

Antioxidants 2021, 10(5), 701; https://doi.org/10.3390/antiox10050701 - 29 Apr 2021

Cited by 92 | Viewed by 11385

Abstract

In humans, the glutathione S-transferases (GST) protein family is composed of seven members that present remarkable structural similarity and some degree of overlapping functionalities. GST proteins are crucial antioxidant enzymes that regulate stress-induced signaling pathways. Interestingly, overactive GST proteins are a frequent feature [...] Read more.

In humans, the glutathione S-transferases (GST) protein family is composed of seven members that present remarkable structural similarity and some degree of overlapping functionalities. GST proteins are crucial antioxidant enzymes that regulate stress-induced signaling pathways. Interestingly, overactive GST proteins are a frequent feature of many human cancers. Recent evidence has revealed that the biology of most GST proteins is complex and multifaceted and that these proteins actively participate in tumorigenic processes such as cell survival, cell proliferation, and drug resistance. Structural and pharmacological studies have identified various GST inhibitors, and these molecules have progressed to clinical trials for the treatment of cancer and other diseases. In this review, we discuss recent findings in GST protein biology and their roles in cancer development, their contribution in chemoresistance, and the development of GST inhibitors for cancer treatment. Full article

(This article belongs to the Special Issue Oxidative Stress and Paraoxonases in Cancer)

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