Search

Maintaining a balanced redox state within cells is crucial for the sustenance of life. The process involves continuous cytosolic disulfide reduction reactions to restore oxidized proteins to their reduced thiol forms. There are two main cellular antioxidant pathways-the thioredoxin (Trx) and glutathione (GSH)/glutaredoxin (Grx) systems. In the GSH/Grx system, glutathione reductase (GR; GSR) catalyses the reduction of GSH disulfide (GSSG) to its sulfhydryl form (GSH), which can then further reduce oxidized Grxs. GR is an essential enzyme that helps in maintaining the supply of reduced glutathione-GSH, which is a significant reducing thiol found in most cells and known for its antioxidant properties. Therefore, it can have a significant impact on cancer development. To investigate this further, we performed an immunohistochemical analysis of GR protein expression in colon adenocarcinoma samples collected from patients with primary colon adenocarcinoma (stage I and II) and patients with metastasis to regional lymph nodes (stage III). The results of our study revealed a significant relationship between the immunohistochemical expression of GR and tumour histological grade, depth of invasion, regional lymph node involvement, staging, and PCNA immunohistochemical expression. It was found that 95% of patients with stage I had low levels of GR expression, whereas 89% of patients with stage III had high levels of immunohistochemical expression. A high level of expression was also detected in the patients with stage II of the disease, where almost 63% were characterized by a high expression of GR. The Western blot method revealed that the highest level of expression was found in the LS 174T cell line, which corresponds to stage II. The results of our study indicate that the immunohistochemical expression of GR may act as an independent prognostic factor associated with colon adenocarcinoma patients' prognosis.

Glutaredoxin 2 (Grx2; Glrx2) is a glutathione-dependent oxidoreductase located in mitochondria, which is central to the regulation of glutathione homeostasis and mitochondrial redox, and plays a crucial role in highly metabolic tissues. In response to mitochondrial redox signals and oxidative stress, Grx2 can catalyze the oxidation and S-glutathionylation of membrane-bound thiol proteins in mitochondria. Therefore, it can have a significant impact on cancer development. To investigate this further, we performed an immunohistochemical analysis of Grx2 protein expression in colon adenocarcinoma samples collected from patients with primary colon adenocarcinoma (stage I and II) and patients with metastasis to regional lymph nodes (stage III). The results of our study revealed a significant relationship between the immunohistochemical expression of Grx2 and tumor histological grade, depth of invasion, regional lymph node involvement, angioinvasion, staging, and PCNA immunohistochemical expression. It was found that 87% of patients with stage I had high levels of Grx2 expression. In contrast, only 33% of patients with stage II and 1% of patients with stage III had high levels of Grx2 expression. Moreover, the multivariate analysis revealed that the immunohistochemical expression of Grx2 protein apart from the grade of tumor differentiation was an independent prognostic factors for the survival of patients with colon adenocarcinoma. Studies analyzing Grx2 levels in patients' blood confirmed that the highest levels of serum Grx2 protein was also found in stage I patients, which was reflected in the survival curves. A higher level of Grx2 in the serum has been associated with a more favorable outcome. These results were supported by in vitro analysis conducted on colorectal cancer cell lines that corresponded to stages I, II, and III of colorectal cancer, using qRT-PCR and Western Blot.

Glutaredoxin 1 (Grx1) is an essential enzyme that regulates redox signal transduction and repairs protein oxidation by reversing S-glutathionylation, an oxidative modification of protein cysteine residues. Grx1 removes glutathione from proteins to restore their reduced state (protein-SH) and regulate protein-SSG levels in redox signaling networks. Thus, it can exert an influence on the development of cancer. To further investigate this problem, we performed an analysis of Grx1 expression in colon adenocarcinoma samples from the Polish population of patients with primary colon adenocarcinoma (stages I and II of colon cancer) and those with regional lymph node metastasis (stage III of colon cancer). Our study revealed a significant correlation between the expression of Grx1 protein through immunohistochemical analysis and various clinical characteristics of patients, such as histological grade, depth of invasion, angioinvasion, staging, regional lymph node invasion, and PCNA expression. It was found that almost 88% of patients with stage I had high levels of Grx1 expression, while only 1% of patients with stage III exhibited high levels of Grx1 protein expression. Furthermore, the study discovered that high levels of Grx1 expression were present in samples of colon mucosa without any pathological changes. These results were supported by in vitro analysis conducted on colorectal cancer cell lines that corresponded to stages I, II, and III of colorectal cancer, using qRT-PCR and Western blot.

Introduction: Colon adenocarcinoma (COAD) is one of the most frequently identified cancers of the digestive system. It is worth noting that the 5-year survival rates for patients diagnosed early are approximately 90%, whereas for patients with advanced diagnosis it is only 10%. It may indicate that metastasis is a critical cause of death for cancer patients., Aim: The current study investigated the immunohistochemical expression of MnSOD in individuals living in Poland, who were diagnosed as colon adenocarcinoma patients, to assess its prognostic significance by correlating its expression with the clinicopathological factors and overall survival (OS)., Material and Methods: Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for MnSOD protein. The relationship between MnSOD immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated., Results: Immunohistochemical expression of MnSOD protein was detected in colon adenocarcinoma samples and non-pathological samples of colon tissues. As demonstrated, the level of the MnSOD immunohistochemical reactivity was not correlated with clinicopathological factors. A multivariate analysis demonstrated that the grade of tumour differentiation and MnSOD immunoexpression in healthy tissues were independent risk factors for worse survival of patients., Conclusions: The high level of MnSOD immunoexpression in cancerous tissue was not associated with malignancy-related clinicopathological factors and 5-year overall survival of patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Termedia.)

Glutathione peroxidase 2 (Gpx-2) is a selenoenzyme with antioxidant capabilities that may play a role in cancer development. Hence, we investigated the immunohistochemical expression of Gpx-2 protein in colon adenocarcinoma samples derived from patients with colon adenocarcinoma who did not receive any form of treatment prior to the surgical procedure. The associations between the immunohistochemical expression of Gpx-2 and clinical parameters were analysed using the Chi 2 test and Fisher's exact test. A Kaplan-Meier analysis and the log-rank test were used to verify the relationship between the intensity of Gpx-2 expression and the 5-year survival rate of patients. In total, 101 (80.80%) samples had strong Gpx-2 protein expression and 24 (19.20%) samples were characterized with low expression. The high expression of Gpx-2 was correlated with the histological grade of the tumour ( p < 0.001), PCNA immunohistochemical expression ( p < 0.001), depth of invasion ( p = 0.001) and angioinvasion ( p < 0.001). We can conclude that high expression of Gpx-2 is correlated with reduced survival of colon adenocarcinoma patients (log-rank, p < 0.001).

(1) Background: Colorectal cancer (CRC) is the third most common cancer in terms of incidence and mortality. Approximately 90% of all colorectal cancer cases are adenocarcinomas, originating from epithelial cells of the colorectal mucosa. Upregulated gene 4 (URG4) is an oncogene involved in cancer development. The aim of the study was to assess the immunohistochemical expression of URG4 protein expression in Polish patients with colon adenocarcinoma who were not treated with any therapy before radical surgery. (2) Methods: The study used colon tissue samples taken from people with a confirmed diagnosis of colorectal adenocarcinoma after a thorough histopathological examination. The associations between the immunohistochemical expression of URG4 and clinical parameters were analyzed by the Chi2 test or Chi2Yatesa test. The study conducted an analysis of the correlation between the expression of URG4 and the five-year survival rate of patients through the application of the Kaplan-Meier analysis and the log-rank statistical test. The intracellular localization of URG4 was identified through the utilization of transmission electron microscopy (TEM) methodology. (3) Results: In univariate Cox regression analyses, immuno-histochemical expression of URG4, grade of histological differentiation, depth of invasion, angioinvasion, PCNA expression, stage of disease and lymph node involvement were found to be significant prognostic factors. Within our patient cohort, it was observed that the degree of tumour differentiation and URG4 expression were found to be distinct prognostic factors in regard to the 5-year survival rates of those with colon adenocarcinoma. (4) Conclusions: High immunohistochemical expression of URG4 correlates with poor prognosis in patients with colon adenocarcinoma.

Several studies revealed that expression levels of glutathione peroxidase 1 (Gpx-1) can be associated with cancer development, mainly through its role in hydroperoxide scavenging by regulating intracellular reactive oxygen species (ROS) levels. Therefore, our aim was to investigate the expression of Gpx-1 protein in a population of Polish patients with colon adenocarcinoma in the absence of any therapy prior to radical surgery. The study was carried out using colon tissue from patients with adenocarcinoma of the colon confirmed by histopathological examination. Gpx-1 antibody was used to determine the immunohistochemical expression of Gpx-1. The Chi 2 test or Chi 2 Yatesa test were used to analyse the associations between the immunohistochemical expression of Gpx-1 and clinical parameters. The relationship between Gpx-1 expression, and 5-year patient survival was examined using Kaplan-Meier analysis and the log-rank test. Intracellular localisation of Gpx-1 was detected by the use of transmission electron microscopy (TEM). Western blot analysis was used for the evaluation of Gpx-1 protein expression levels in cancer cell lines in vitro. Immunohistochemical study revealed that the high expression of Gpx-1 was associated with the tumour's histological grade, proliferating cell nuclear antigen (PCNA) immunohistochemical expression, depth of invasion, and angioinvasion (all p < 0.001) (4). The high immunohistochemical expression of Gpx-1 is correlated with poor prognosis of colon adenocarcinoma patients.

The Notch signalling pathway is one of the most conserved and well-characterised pathways involved in cell fate decisions and the development of many diseases, including cancer. Among them, it is worth noting the Notch4 receptor and its clinical application, which may have prognostic value in patients with colon adenocarcinoma. The study was performed on 129 colon adenocarcinomas. Immunohistochemical and fluorescence expression of Notch4 was performed using the Notch4 antibody. The associations between the IHC expression of Notch4 and clinical parameters were analysed using the Chi 2 test or Chi 2 Yatesa test. The Kaplan-Meier analysis and the log-rank test were used to verify the relationship between the intensity of Notch4 expression and the 5-year survival rate of patients. Intracellular localisation of Notch4 was detected by the use of the immunogold labelling method and TEM. 101 (78.29%) samples had strong Notch4 protein expression, and 28 (21.71%) samples were characterised by low expression. The high expression of Notch4 was clearly correlated with the histological grade of the tumour ( p < 0.001), PCNA immunohistochemical expression ( p < 0.001), depth of invasion ( p < 0.001) and angioinvasion ( p < 0.001). We can conclude that high expression of Notch4 is correlated with poor prognosis of colon adenocarcinoma patients (log-rank, p < 0.001).

Background: The Apoptotic protease activating factor 1 (Apaf-1) protein, as one of the factors involved in the activation of the mitochondrial apoptotic pathway, plays an important role in cancer biology. Apaf-1 expression in tumour cells has been shown to be downregulated, with significant implications for tumour progression. Hence, we investigated the expression of Apaf-1 protein in the Polish population of patients with colon adenocarcinoma without any therapy prior to radical surgery. Moreover, we assessed the relation between Apaf-1 protein expression and the clinicopathological factors. The prognostic activity of this protein was analyzed in relation to 5-year survival of patients. In order to show the localization of Apaf-1 protein at the cellular level, the immunogold labelling method was used., Methods: The study was conducted using the colon tissue material from patients with histopathologically confirmed colon adenocarcinoma. Immunohistochemical expression of Apaf-1 protein was performed using Apaf-1 antibody at dilution 1:600. The associations between the immunohistochemistry (IHC) expression of Apaf-1 and clinical parameters were analyzed using the Chi2 test and Chi2Yatesa test. Kaplan-Meier analysis and the log-rank test were used to verify the relationship between the intensity of Apaf-1 expression and 5-year survival rate of patients. The results were considered statistically significant when p < 0.05., Results: Apaf-1 expression was evaluated by immunohistochemical staining in whole tissue sections. Thirty-nine (33.23%) samples had strong Apaf-1 protein expression and 82 (67.77%) samples were characterized by low expression. The high expression of Apaf-1 was clearly correlated with the histological grade of the tumour ( p = 0.001), proliferating cell nuclear antigen (PCNA) immunohistochemical expression ( p = 0.005), age ( p = 0.015), depth of invasion ( p < 0.001) and angioinvasion ( p < 0.001). The 5-year survival rate was significantly higher in the group of patients with high expression of this protein (log-rank, p < 0.001)., Conclusions: We can conclude that Apaf-1 expression is positively correlated with reduced survival of colon adenocarcinoma patients., Competing Interests: The authors declare no conflict of interest. Prof. Łos’es role in the compay is dedicated to the development of specific cellular elements within artificial corneas; it has nothing to do with the research area presented in our paper., (© 2023 The Author(s). Published by IMR Press.)

Introduction: Adenocarcinoma of the colon and rectum (COAD) is one of the most commonly diagnosed cancers of the gastrointestinal system. Acylglycerol kinase (AGK) is a known lipid kinase producing lysophosphatidic acid (LPA) from monoacylglycerol. It is widely expressed in the heart, brain, kidney, and muscle. Moreover, AGK is a significant cancer-related gene and is upregulated in many human malignancies, e.g. prostate cancer, breast cancer, oral squamous cell carcinoma, hepatocellular carcinoma, and renal carcinoma. However, the expression pattern and clinical significance of AGK in colon adenocarcinoma patients, especially in individuals living in Europe, remain unclear., Aim: The current study investigated the expression of AGK protein in colon adenocarcinoma samples to assess its prognostic significance by correlating its immunohistochemical expression with the clinicopathological variables and survival of individuals living in Poland., Material and Methods: Tissue specimens were received from 110 colon adenocarcinoma patients who underwent surgical resection at the Municipal Hospital in Jaworzno in 2013-2015. The paraffin-embedded specimens were cut into 4-µm-thick sections and incubated with rabbit polyclonal antibody to AGK (final dilution 1 : 500) (Invitrogen; cat. number PA5-28566)., Results and Conclusions: AGK was strongly expressed in colon adenocarcinoma tissues in comparison to non-pathological colon specimens. The high level of AGK immunoexpression was demonstrated to be clearly correlated with the malignancy-related clinicopathological factors and 5-year overall survival rate of patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Termedia.)

Introduction: Colon cancer is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still not satisfactory., Aim: To investigate the prognostic role of Notch3, an immunohistochemical study was performed on samples of colon adenocarcinoma tissues and adjacent non-pathological mucosa in Caucasian patients., Material and Methods: Paraffin-embedded colon adenocarcinoma samples were assessed immunohistochemically for Notch3 protein. Connections between Notch3 immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated., Results: The level of the Notch3 immunohistochemical reactivity was correlated with the grade of the histological differentiation ( p < 0.001). A strong expression of Notch3 protein was detected more frequently in patients with G3 tumours than in patients with G1 tumours. Moreover, the significant difference was also detected between the patients with G1 tumour and those with G2. In the G2 patients a strong reactivity was described more frequently. The Kaplan-Meier survival analysis showed that the overall survival rate in the group of patients with a low expression level of Notch3 was significantly greater than that for patients with a moderate or strong level of Notch3 immunoreactivity ( p < 0.001). A multivariate analysis demonstrated that the grade of tumour differentiation ( p = 0.001) and Notch3 expression ( p < 0.001) were independent risk factors for worse survival., Conclusions: The high level of Notch3 immunoexpression was demonstrated to be associated with malignancy-related clinicopathological factors and 5-year overall survival of patients., Competing Interests: The author declares no conflict of interest., (Copyright © 2022 Termedia.)

Introduction: It is generally accepted that colon cancer is the most commonly diagnosed gastrointestinal cancer and a major public health problem. As revealed by studies, the clinical outcomes of patients, especially those with lymph node-positive status, are still unsatisfactory., Aim: The current study investigated the expression of vimentin protein in colon adenocarcinoma samples from proximal and distal parts of the colon to assess its prognostic significance by correlating its immunohistochemical expression with the clinicopathological variables and survival of Caucasian patients., Material and Methods: To investigate the clinicopathological and prognostic roles of vimentin expression, the immunohistochemical analysis was performed in colon cancer tumour samples and adjacent non- pathological mucosa. As revealed, the level of vimentin immunohistochemical reactivity correlated with the grade of the histological differentiation (H [2.97] = 37.949; p < 0.001)., Results: The Kaplan-Meier survival analysis showed that the overall survival rate in the group of patients with low vimentin immunoreactivity was significantly greater than that for patients with a moderate or strong level of vimentin protein expression. Multivariate analysis demonstrated that the grade of tumour differentiation (HR = 2.150; 95% CI: 1.380-3.349, p = 0.001) and vimentin expression (HR = 3.901; 95% CI: 2.436-6.247, p < 0.001) were independent risk factors for worse survival., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Introduction: Colorectal cancer is most common in developed countries. Each year, more than one million people develop colon cancer, and nearly 70,000 people die from the disease. Although medicine has made great strides in the treatment of colorectal cancer, the prognosis of patients is still poor. It is difficult to find the main cause of colon cancer, so it is necessary to introduce new methods that will accurately diagnose the cause of this malignancy., Material and Methods: Paraffin-embedded colon adenocarcinoma samples ( n = 97) were assessed immunohistochemically for TACC3 protein. Connections between TACC3 immunoexpression and clinicopathological factors, including the 5-year overall survival (OS), were evaluated., Results: Immunohistochemical expression of TACC3 protein in colon adenocarcinoma samples and non-pathological samples of colon tissue was described as weak, moderate, or strong. As demonstrated, the level of the TACC3 immunohistochemical reactivity was not correlated with demographic factors including gender and age, and clinicopathological factors. The average survival time for all the patients was 36.8 months (95% CI: 33.134-40.536). A multivariate analysis demonstrated that the grade of tumour differentiation (HR = 2.740; 95% CI: 1.864-4.027, p < 0.001) and TACC3 immunoexpression in healthy tissues (HR = 1.700; 95% CI: 1.073-2.694) were independent risk factors for worse survival of patients., Conclusions: The high level of TACC3 immunoexpression in cancerous tissue was not associated with malignancy-related clinicopathological factors and 5-year overall survival of patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

Introduction: The current study investigated the expression of Snail1 protein in colon adenocarcinoma samples to assess its prognostic significance by correlating its expression with the clinicopathological variables and survival of Caucasian patients., Aim: To investigate the clinicopathological and prognostic roles of Snail1 expression, the immunohistochemical analysis was performed in colon tumour tissues and adjacent non- pathological mucosa., Material and Methods: It should be noted that only trace expression of this protein was revealed in adjacent non-tumour colorectal mucosa, whereas the high expression was demonstrated in well differentiated, moderately differentiated, and poorly differentiated tumours., Results: The Kaplan-Meier survival analysis showed that the overall survival rate in the group of patients with a low expression level of Snail1 was significantly longer than that for patients with a moderate or strong level of Snail1 immunoreactivity ( p < 0.001). The 5-year overall survival for patients with a low, moderate, or strong level of Snail1 immunoexpression was 100%, 25.7%, and 2%, respectively. The Snail1-moderate patients had an average survival time of 44.886 months (95% CI: 40.855-48.916), whereas the Snail1-strong expression groups had an average survival time of 21.706 (95% CI: 17.863-25.549). The statistical analysis revealed that the level of the Snail1 immunohistochemical reactivity was correlated with the grade of the histological differentiation. A multivariate analysis demonstrated that the grade of tumour differentiation (HR = 2.150; 95% CI: 1.380-3.349, p = 0.001) and Snail1 expression (HR = 3.901; 95% CI: 2.436-6.247, p < 0.001) were the independent risk factors for worse survival., Conclusions: In colon adenocarcinoma patients, the expression of Snail1 may act as the independent risk factors for worse survival., Competing Interests: The author declares no conflict of interest., (Copyright © 2021 Termedia.)

Introduction: Endothelial dysfunction is a critical part of heart failure (HF) pathophysiology. It is not clear, however, whether it is present at the similar level in the early and late HF stages., Material and Methods: von Willebrand factor (vWF) and its mRNA levels in biopsies of non-ischemic patients with HF secondary to dilated cardiomyopathy were studied. Consecutive patients with HF were divided into two groups: group A with disease duration ≤ 12 months (n = 59) and group B with disease duration > 12 months (n = 68). The immunoreactivity of the vWF was compared with autopsy sections of 19 control cases. Tissue vWF gene expression was analyzed at the mRNA level by RT-PCR., Results: In the group A, there was lower vWF immunoreactivity in the coronary microvessels compared to the group B [1.5 (1.0-2.0) vs. 2.0 (1.5-2.4), P = 0.001]. In the control group, only weak vWF expression was observed. Protein expression was not accompanied by vWF mRNA whose levels were significantly higher in the Group A as compared to the Group B [14671 (4932-51561) vs. 3643 (185.3-9030.8), P = 0.005]. Protein vWF expression was inversely associated with its mRNA levels (r = -0.34, P = 0.04)., Conclusions: High myocardial protein expression of vWF in patients with long-lasting HF symptoms may highlight the persistent nature of endothelial dysfunction in such a cohort of patients.

Introduction: It is generally accepted that the gastrointestinal tract, and especially the colon, is constantly exposed to reactive oxygen species (ROS) that may be responsible for the appearance of genetic mutations. To keep a steady-state control over ROS production-detoxification, organisms have evolved a defensive system. Nevertheless, many reports have described decreased level of antioxidant enzymes, especially catalase (CAT), in cancer tissues., Aim: In this work we try to assess the immunohistochemical expression of CAT protein in colorectal adenoma and adenocarcinoma samples., Material and Methods: This study was performed on resected specimens obtained from 122 patients who had undergone surgical resection for colorectal cancer, and from 120 patients who had undergone colonoscopy. Paraffin- embedded, 4 µm-thick tissue sections were stained for rabbit polyclonal anti CAT antibody obtained from GeneTex (cat. no. GTX110704)., Results: In adenoma strong immunoexpression was detected mainly in infiltrating mononuclear cells within lamina propria. High expression of CAT was significantly associated with grade of dysplasia (high grade vs. low grade, p = 0.037). In adenocarcinoma samples, the high level of CAT immunoexpression was significantly correlated with histological grade of tumour (G1 vs. G2 vs. G3, p = 0.001) and depth of invasion (T1 vs. T2 vs. T3 vs. T4, p = 0.003)., Conclusions: Development of colorectal cancer is associated with increased expression of CAT in the stage of adenoma and decreased expression in the stage of adenocarcinoma., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Introduction: Colorectal cancer (CRC) is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still not satisfactory., Aim: To investigate the clinicopathological and prognostic roles of Notch1 expression, the immunohistochemical investigation was performed in samples of CRC tumour tissues, adjacent non-pathological mucosa, and metastatic foci in regional lymph nodes in Caucasian patients., Material and Methods: Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for Notch1 protein and scored according to the percentage of cells with a positive reaction combined with staining intensity. Connections between Notch1 immunoexpression and clinicopathological factors including the 5-year overall survival (OS) were evaluated., Results: The level of the Notch1 immunohistochemical reactivity was correlated with the grade of the histological differentiation, size of the primary tumour, regional lymph node involvement, and perineural invasion (all p < 0.001). Kaplan-Meier survival analysis showed that the survival time for patients with a low expression of Notch1 was significantly longer than that for patients with moderate or strong level of Notch1 immunoreactivity ( p < 0.001)., Conclusions: The enhanced level of Notch1 immunoexpression was significantly associated with malignancy-related clinicopathological factors and reduced the 5-year overall survival in CRC patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Introduction: Colorectal cancer (CRC) is traditionally regarded as the most commonly diagnosed gastrointestinal malignant disease. Nevertheless, despite advances in diagnosis and novel therapeutic options, the clinical outcomes of patients are still unsatisfactory., Aim: To investigate the clinicopathological and prognostic roles of GRP94 expression, the immunohistochemical investigation was performed on samples of CRC tumour tissues, adjacent non-pathological mucosa, and metastatic foci in regional lymph nodes in Caucasian patients., Material and Methods: Paraffin-embedded adenocarcinoma samples were assessed immunohistochemically for GRP94 protein and scored according to the percentage of cells with positive reaction combined with staining intensity. Connections between GRP94 immunoexpression and clinicopathological factors including the overall survival (OS) were evaluated., Results: The level of the GRP94 immunohistochemical reactivity was correlated with the grade of the histological differentiation (H (2.92) = 25.906; p < 0.001), size of the primary tumour ( Z = -4.010; p < 0.001), regional lymph node involvement ( Z = - 6.547; p < 0.001), and perineural invasion ( Z = -6.235; p < 0.001). Kaplan-Meier survival analysis showed that the survival time for patients with a low expression of GRP94 was significantly longer than that for patients with a moderate or strong level of GRP94 immunoreactivity ( p < 0.001)., Conclusions: An enhanced level of GRP94 immunoexpression was significantly associated with malignancy-related clinicopathological factors and reduced the 5-year overall survival in CRC patients. However, a multivariate analysis demonstrated that GRP94 was not revealed as an independent risk factor for CRC prognosis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia Sp. z o. o.)

Primary hyperparathyroidism (PHPT) is defined by inappropriate elevation of parathormone, caused by parathyroid hyperplasia, also known as multi-gland disease (MGD), parathyroid adenoma (PA), or parathyroid carcinoma (PC). Although several studies have already been conducted, there is a lack of a definite diagnostic marker, which could unambiguously distinguish MGD from PA or PC. The accurate and prompt diagnosis has the key meaning for effective treatment and follow-up. This review paper presents the role of apoptosis in PHPT. The comparison of the expression of Fas, TRAIL, BCL-2 family members, p53 in MGD, PA, and PC, among others, was described. The expression of described factors varies among proliferative lesions of parathyroid gland; therefore, these could serve as additional markers to assist in the diagnosis.

Introduction: Colorectal cancer (CRC) is the third and second most commonly diagnosed cancer worldwide in males and females, respectively. Despite prominent progress in diagnosis and treatment, the recurrence rates are still high. A tumour hypoxic environment leads to an increase in glycolytic metabolism. The crucial intermediate component of glycolysis, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), could play a significant role in cancer progression. An increased level of GAPDH has been described in oncogene-induced transformation and anti-apoptotic function. In other studies, GAPDH has been involved in apoptosis induction., Aim: We examined colorectal adenocarcinoma samples to assess the immunoexpression of GAPDH protein. We also evaluated the correlation between the expression of GAPDH protein and apoptotic parameters including expression of Bcl2 and Bax., Material and Methods: Paraffin sections were incubated for 60 min with primary antibody against GAPDH, Bcl-2, and Bax., Results: Results of our study have shown that GAPDH expression in colorectal cancer is upregulated. We revealed significant positive correlation between expression of this protein and grade and size of tumour, and regional lymph node involvement. In the case of apoptosis-associated proteins, e.g. Bcl-2 and Bax, we found negative correlations between expression of these proteins and grade and size of tumour, lymphovascular invasion, and regional lymph node involvement. Finally, we demonstrated that GAPDH up-regulation is connected with down-regulation in Bcl-2 and Bax., Conclusions: Up-regulation of GAPDH protein and down-regulation of Bcl-2 and Bax may result in increased of cancer., Competing Interests: The authors declare no conflict of interest.

Aim: Differentiating between parathyroid lesions is still difficult and ambiguous. In cases of primary hyperparathyroidism, appropriate and prompt diagnosis is of great importance for effective treatment and follow-up. A great amount of mechanisms contribute to the pathogenesis of primary hyperparathyroidism, such as disturbance in balance between pro- and anti-apoptotic factors. Therefore, we examined whether immunohistochemical expression of apoptotic factors, TNF-related apoptosis-inducing ligand (TRAIL) and Fas, could have clinical utility as a marker of proliferative lesions of parathyroid gland., Materials and Methods: Parathyroid specimens of 58 consecutive patients who had undertaken surgery due to primary hyperparathyroidism were incubated with purified mouse monoclonal antihuman antibodies: anti-TRAIL and anti-Fas. Staining was considered positive when at least 5% of the cells showed immunoreactivity., Results: The percentage of cells which were positively stained for TRAIL in parathyroid hyperplasia was 9.65%, in parathyroid adenoma 8.31%, and in normal controls 2.24%. Immunoreactivity for TRAIL was detected in 91.89% of parathyroid hyperplasias, 85.71% of parathyroid adenomas, and none in healthy glands. The percentage of cells with a positive reaction to Fas in parathyroid hyperplasia was 8.92%, in parathyroid adenoma 8.09%, and in normal tissue 1.9%. The expression of Fas was found in 94.59% of parathyroid hyperplasias, 90.48% of parathyroid adenomas, and none in healthy glands., Conclusions: In our study, hyperplasias demonstrated the highest expression of TRAIL and Fas, whereas in adenomas it was increased compared to normal tissue, but lower than in hyperplasias. These factors could be an additive tool in the differential diagnosis of parathyroid lesions.

Background: Increasing evidence has demonstrated that Notch signaling is deregulated in human hematological malignancies and solid tumors. This signaling has a protumorigenic effect but may also act as a tumor suppressor. How induction of a single pathway gives rise to the opposite effects in different cell types is still unknown., Methods: This review article includes available data from peer-reviewed publications associated with the role of Notch signaling during cancer pathogenesis., Results: Numerous reports have indicated that alterations in Notch signaling and its oncogenic activity were originally associated with the pathogenesis of T‑cell acute lymphoblastic leukemia/lymphoma (T-ALL), an aggressive hematologic tumor affecting children and adolescents. The possibility that Notch could play a significant role in human breast cancer development comes from studies on mouse mammary tumor virus-induced cancer. Numerous findings over the past several years have indicated that alterations in Notch signaling are also responsible for ovarian cancer development. Mention should also be made of the connection between expression of Notch 3 and increased resistance to chemotherapy, which remains a major obstacle to successful treatment. Notch as an oncogenic factor is also involved in the development of colon cancer, lung carcinoma and Kaposi's sarcoma., Conclusion: Notch is a binary cell fate determinant and its overexpression has been described as oncogenic in a wide array of human malignancies. This finding led to interest in therapeutically targeting this pathway, especially by the use of gamma-secretase inhibitors (GSIs) blocking the cleavage of Notch receptors at the cell membrane by the inhibition of Notch intracellular domain (NICD) releasing. Preclinical cancer models have revealed that GSIs suppress the growth of cancers such as pancreatic, breast and lung cancer.

Introduction: It is generally accepted that mitochondria are a primary source of intracellular reactive oxygen species (ROS). Under physiological circumstances they are permanently formed as by-products of aerobic metabolism in the mitochondria. To counter the harmful effect of ROS, cells possess an antioxidant defence system to detoxify ROS and avert them from accumulation at high concentrations. Mitochondria-located manganese superoxide dismutase (MnSOD, SOD2) successfully converts superoxide to the less reactive hydrogen peroxide (H 2 O 2 ). To the best of our knowledge, there are no available data regarding immunohistochemical expression of MnSOD in colorectal neoplastic tissues., Aim: To investigate the immunohistochemical expression status of MnSOD in colorectal premalignant and malignant lesions., Material and Methods: This study was performed on resected specimens obtained from 126 patients who had undergone surgical resection for primary sporadic colorectal cancer, and from 114 patients who had undergone colonoscopy at the Municipal Hospital in Jaworzno (Poland). Paraffin-embedded, 4-µm-thick tissue sections were stained for rabbit polyclonal anti SOD2 antibody obtained from GeneTex (clone TF9-10-H10 from America Diagnostica)., Results: Results of our study demonstrated that the development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages. Samples of adenocarcinoma with G2 and G3 grade showed significantly higher levels of immunohistochemical expression of this antioxidant enzyme. Moreover, patients with the presence of lymphovascular invasion and higher degree of regional lymph node status have been also characterised by higher levels of MnSOD expression. The samples of adenoma have been characterised by higher levels of MnSOD expression in comparison to normal mucosa as well. Interestingly, there was no significant correlation between expression and histological type of adenoma., Conclusions: Development of colorectal cancer is connected with increased expression of MnSOD both in adenoma and adenocarcinoma stages., Competing Interests: The authors declare no conflict of interest.

Notch signalling is an evolutionarily conserved signalling pathway, which plays a significant role in a wide array of cellular processes including proliferation, differentiation, and apoptosis. Nevertheless, it must be noted that Notch is a binary cell fate determinant, and its overexpression has been described as oncogenic in a broad range of human malignancies. This finding led to interest in therapeutically targeting this pathway especially by the use of GSIs, which block the cleavage of Notch at the cell membrane and inhibit release of the transcriptionally active NotchIC subunit. Preclinical cancer models have clearly demonstrated that GSIs suppress the growth of such malignancies as pancreatic, breast, and lung cancer; however, GSI treatment in vivo is associated with side effects, especially those within the gastrointestinal tract. Although intensive studies are associated with the role of γ-secretase in pathological states, it should be pointed out that this complex impacts on proteolytic cleavages of around 55 membrane proteins. Therefore, it is clear that GSIs are highly non-specific and additional drugs must be designed, which will more specifically target components of the Notch signalling.

Angiogenesis can be described as a formation of new vessels from the existing microvasculature and is a process of great importance to the tumor development. Parathyroid tissue can trigger spontaneous induction of angiogenesis in vitro and in vivo models in a vascular endothelial growth factor (VEGF)-dependent manner. Autotransplantated parathyroid tissue after thyroidectomy is able to form new vasculature and produce parathormone, maintaining calcium homeostasis. A great amount of factors contributes to the process of new vessel formation in primary hyperparathyroidism, such as VEGF, transforming growth factor β, and angiopoietins. Studies demonstrated that markers for angiogenesis can be useful in distinguishing between parathyroid hyperplasia and neoplasia, due to the increased angiogenesis in parathyroid proliferative lesions compared with parathyroid adenomas. These factors include, inter alia, VEGF, VEGFR2, CD105, and fibroblast growth factor-2. Although these differences appear promising in the differential diagnosis, there is an overlap between benign and malignant parathyroid lesions and there is no definite cutoff value. Loss of heterozygosity and comparative genomic hybridization studies revealed chromosomal regions frequently altered in parathyroid tumorigenesis at 9p21, 1p21-22, 1p35-36, and 11q13. Therefore, immunohistochemistry and genetic testing should be an additional diagnostic marker in combination with the traditional criteria. A better understanding of angiogenesis in primary hyperparathyroidism could result in more precise assessment of diagnosis and more effective treatment, especially in those cases, in which the commonly used parameters are insufficient., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Varicose veins (VVs) can be described as tortuous and dilated palpable veins, which are more than 3 mm in diameter. They are one of the clinical presentations of chronic venous disorders, which are a significant cause of morbidity. The prevalence of VVs has been estimated at 25-33% in women and 10-20% in men and is still increasing at an alarming rate. Family history, older age, female, pregnancy, obesity, standing occupations, and a history of deep venous thrombosis are the predominant risk factors. A great amount of factors are implicated in the pathogenesis of VVs, including changes in hydrostatic pressure, valvular incompetence, deep venous obstruction, ineffective function of calf muscle pump, biochemical and structural alterations of the vessel wall, extracellular matrix abnormalities, impaired balance between growth factors or cytokines, genetic alterations, and several other mechanisms. Nevertheless, the issue of pathogenesis in VVs is still not completely known, even if a great progress has been made in understanding their molecular basis. This kind of studies appears promising and should be encouraged, and perhaps the new insight in this matter may result in targeted therapy or possibly prevention., (Copyright © 2015 Elsevier Inc. All rights reserved.)