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1.
Sci Rep ; 14(1): 12546, 2024 05 31.
Article in English | MEDLINE | ID: mdl-38822068

ABSTRACT

Nanosecond pulsed electric field (nsPEF) has emerged as a promising approach for inducing cell death in melanoma, either as a standalone treatment or in combination with chemotherapeutics. However, to date, there has been a shortage of studies exploring the impact of nsPEF on the expression of cancer-specific molecules. In this investigation, we sought to assess the effects of nsPEF on melanoma-specific MAGE (Melanoma Antigen Gene Protein Family) expression. To achieve this, melanoma cells were exposed to nsPEF with parameters set at 8 kV/cm, 200 ns duration, 100 pulses, and a frequency of 10 kHz. We also aimed to comprehensively describe the consequences of this electric field on melanoma cells' invasion and proliferation potential. Our findings reveal that following exposure to nsPEF, melanoma cells release microvesicles containing MAGE antigens, leading to a simultaneous increase in the expression and mRNA content of membrane-associated antigens such as MAGE-A1. Notably, we observed an unexpected increase in the expression of PD-1 as well. While we did not observe significant differences in the cells' proliferation or invasion potential, a remarkable alteration in the cells' metabolomic and lipidomic profiles towards a less aggressive phenotype was evident. Furthermore, we validated these results using ex vivo tissue cultures and 3D melanoma culture models. Our study demonstrates that nsPEF can elevate the expression of membrane-associated proteins, including melanoma-specific antigens. The mechanism underlying the overexpression of MAGE antigens involves the initial release of microvesicles containing MAGE antigens, followed by a gradual increase in mRNA levels, ultimately resulting in elevated expression of MAGE antigens post-experiment. These findings shed light on a novel method for modulating cancer cells to overexpress cancer-specific molecules, thereby potentially enhancing their sensitivity to targeted anticancer therapy.


Subject(s)
Exocytosis , Melanoma-Specific Antigens , Melanoma , Humans , Melanoma/metabolism , Melanoma/pathology , Melanoma/genetics , Melanoma/immunology , Cell Line, Tumor , Melanoma-Specific Antigens/metabolism , Melanoma-Specific Antigens/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic , Antigens, Neoplasm/metabolism , Antigens, Neoplasm/genetics
2.
Life (Basel) ; 14(4)2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38672771

ABSTRACT

Harris Lines (HLs) are transverse, sclerotic lines that can be visualized by X-ray imaging and that occur in long bones, most commonly in the tibia and femur. HLs are associated with disrupted bone mineralization during endochondral ossification, affecting the normal growth process. The etiology of HLs is debated, with some claims linking their presence to detrimental factors such as inflammation, malnutrition, alcohol abuse, and diseases. The age at which HLs form can be estimated based on their location, which allows for a retrospective assessment of the individual's health status during childhood or youth. The current study is concerned with providing new equations to estimate the age of Harris Line occurrences using a simple calculating tool. Bone growth curves were derived based on a dataset provided by Byers in 1991 using non-linear estimation. The best model was chosen with the Akaike Information Criterion. New and old methods were compared through Bland-Altman plots. As a result, we managed to produce reliable, well-fitted growth curves, concordant with previous methods.

3.
Cytokine ; 110: 116-125, 2018 10.
Article in English | MEDLINE | ID: mdl-29730384

ABSTRACT

INTRODUCTION: Despite the widely described role of IL10 in immune response regulation during carcinogenesis, there is no established model describing the role of its receptor. The aim of this study is to elucidate the relationship between the subunit alpha of IL10 receptor (IL10RA) in the pathogenesis of colorectal cancer (CRC). METHODS: The study was conducted on archived paraffin blocks of 125 CRC patients, from which tissue microarrays (TMA) were made. These were subsequently used for immunohistochemistry to assess the expression of IL10RA, IL10, phosphorylated STAT3 (pSTAT3) and the Ki67 proliferation index. The intensity of both reactions was assessed by independent researchers using two approaches: digital image analysis and the Remmele and Stegner score (IRS). To assess the possible correlations between the two investigated markers and the clinical stage of CRC, the Pearson correlation coefficient was calculated. The expression of aforementioned proteins was assessed in tumor samples, healthy surgical margins and healthy control samples, obtained from cadavers during autopsy from the Department of Forensic Medicine. Statistical analysis was conducted using Statistica ver. 13.05 software. RESULTS: The final analysis included 105 CRC patients with complete clinical and pathological data, for whom the expressions of IL10RA, IL10, pSTAT3 and Ki67 were assessed using two independent methods. There was a positive correlation between the IL10RA expression and Ki-67 proliferation index (R = 0.63, p < 0.001) and a negative correlation between the IL10RA expression and the clinical stage of CRC (R = -0.21, p = 0.022). IL10RA correlated positively with pSTAT3 and IL10 in neoplastic tissue and tumor margin (with p < 0.01 for all correlations). We also observed a significantly higher expression of IL10RA in healthy surgical margins when compared to the actual tumor (p = 0.023, the paired t-test). The expression of IL10 was significantly higher in tumors than in healthy intestinal endothelium from control group. CONCLUSIONS: The correlations between the expression of IL10RA and the proliferation index or the clinical stage of CRC seem to confirm the importance of IL10RA in the pathogenesis of CRC. The higher expression of IL10RA in healthy surgical margins than in the tumor itself may suggest that IL10RA plays a role in regulating immune response to the neoplasm.


Subject(s)
Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Receptors, Interleukin-10/genetics , Adult , Aged , Aged, 80 and over , Female , Humans , Interleukin-10/genetics , Ki-67 Antigen/genetics , Male , Middle Aged , STAT3 Transcription Factor/genetics
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