Immunohistochemical detection of MnSOD in colon adenocarcinoma patients - clinical application.

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.

Crossroad between current knowledge and new perspective of diagnostic and therapy of late-onset schizophrenia and very late-onset schizophrenia-like psychosis: An update.

Schizophrenia is a chronic, highly individualized disease with many symptoms that can occur with varying severity in different patients. Schizophrenia affects 1% of the population, but occurs in almost 20% of patients after 40 years of age. It should be noted that the next peak in the incidence of schizophrenia occurs at the age of 60 years, affects mostly females, and is closely associated with a high risk of developing memory disorders. Therefore, postadolescent schizophrenia includes two distinct groups of patients: those whose symptoms onset at the age of 45 or 60. The purposes of this literature review were as follows: (1) synthetically characterize the clinical manifestations of schizophrenia; (2) discuss difficulties in the diagnosis of schizophrenia, especially in patients over 40 years of age; (3) discuss the clinical utility of different classes of marker in diagnostic and differentiating schizophrenia from neurodegenerative diseases in elderly people; (4) discuss therapeutic options for schizophrenia, pharmacotherapy, and psychotherapy, emphasizing the role of caregivers of people with psychosis in therapy, in preadolescence and postadolescence schizophrenia. We have tried to primarily discuss the findings of original articles from the last 10 years with an indication of their clinical implications with the issues discussed in the various subsections. Moreover, despite many years of research, no specific, precise algorithm has been developed that can be used in clinical practice during the diagnosis of schizophrenia. For this reason, the diagnosis of schizophrenia is primarily based on an interview with the patient and his family, as well as on the experience of a psychiatrist. It also seems that schizophrenia treatment should be carried out holistically, including pharmacotherapy, psychotherapy, and the support of caregivers of patients who have this psychosis, which increases the achievement of therapeutic success. Finally, we must be aware of the difficulties in diagnosing schizophrenia in the elderly and the need to modify pharmacological treatment. Currently, no guidelines have been developed for the differentiation of negative symptoms in elderly patients with schizophrenia from amotivation/avolition/apathy symptoms in elderly patients with neurodegenerative disorders.

The prognostic activity of transforming acidic coiled-coil 3 (TACC3) immunohistochemical expression in colon adenocarcinoma patients.

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.

Vimentin immunoexpression and its prognostic activity in colon cancer among Caucasian patients.

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.

Catalase immunoexpression in colorectal lesions.

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.

The clinical and prognostic evaluation of GRP94 immunoexpression in Caucasian patients with colorectal adenocarcinoma.

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.

Notch signalling pathway as an oncogenic factor involved in cancer development.

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.

The role of Snail1 transcription factor in colorectal cancer progression and metastasis.

Snail1 is a zinc-finger transcription factor, which plays a role in colorectal cancer development by silencing E-cadherin expression and inducing epithelialmesenchymal transition (EMT). During EMT tumour cells acquire a mesenchymal phenotype that is responsible for their invasive activities. Consequently, Snail1 expression in colorectal cancer is usually associated with progression and metastasis. Some studies revealed that about 77% of colon cancer samples display Snail1 immunoreactivity both in activated fibroblasts and in carcinoma cells that have undergone EMT. Therefore, expression of this factor in the stroma may indicate how many cells possess the abilities to escape from the primary tumour mass, invade the basal lamina and colonise distant target organs. Blocking snail proteins activity has the potential to avert cancer cell metastasis by interfering with such cellular processes as remodelling of the actin cytoskeleton, migration and invasion, which are clearly associated with the aggressive phenotype of the disease. Moreover, the link between factors from the snail family and cancer stem cells suggests that inhibitory agents may also prove their potency as inhibitors of cancer recurrence.

The aberrant overexpression of vimentin is linked to a more aggressive status in tumours of the gastrointestinal tract.

Vimentin is an intermediate filament protein normally expressed in cells of mesenchymal origin, e.g. myofibroblasts, chondrocytes, macrophages, and endothelial cells. The expression of vimentin, which has been thought of as the main mesenchymal marker, is also detected in tumour tissue. In tumours of the gastrointestinal tract vimentin expression is usually correlated with advanced stage of tumour, lymph node metastasis, and patient survival.

Tissue factor and tissue factor pathway inhibitor in chronically inflamed gallbladder mucosa.

We characterised a tissue factor (TF) and tissue factor pathway inhibitor (TFPI) expression in relation to severity of inflammatory infiltration of the gallbladder mucosa in a chronic cholecystitis. We prospectively studied the gallbladder specimens obtained from 54 patients who had undergone cholecystectomy due to chronic calculous cholecystitis and 16 calculosis-free gallbladder specimens obtained from patients who underwent cholecystectomy due to the polyp/polyps as well as in cases of gallbladder injury. To assess TF and TFPI immunoreactivity by immunohistochemistry, the monoclonal anti-human TF and TFPI antibodies were used. The inflammatory infiltration of the gallbladder mucosa was reflected by the number of CD3 and CD68 positive cells. The expression of TF and TFPI differed significantly between the cholecystitis and the control group. Most capillary endothelial cells of the cholecystitis group presented weak expression for TFPI. The mean number of CD3 positive lymphocytes in the cholecystitis group was 18.6 ± 12.2, but the mean number of CD68 positive cells was 29.7 ± 13.9. In the control sections, it was 3.1 ± 1.9 and 8.8 ± 3.9, respectively (P < 0.001). The results of the current study suggest that the tissue procoagulant state found may be engaged in the etiopathogenesis of the cholecystitis.

Protective effect of intermittent clamping of the portal triad in the rat liver on liver ischemia-reperfusion injury.

BACKGROUND: Intermittent clamping (IC) of the portal triad is an effective method of protecting the liver from ischemia-reperfusion injury (IR). In clinical practice, this method is employed during a resection, but its mechanism is still not clear. OBJECTIVES: To evaluate the effect of IC on rat liver and determine its mechanisms. MATERIALS AND METHODS: Wistar rats were submitted to 60-min IC (cycles of 12-min clamping followed by 4-min reperfusion), and the samples were collected after 1, 6, and 72 hrs of reperfusion. We determined the serum activity of alanine aminotransferase (ALT), and measured the concentration of TNF-α, malondialdehyde (MDA) and myeloperoxidase (MPO) in liver homogenates. The apoptosis of hepatocytes was evaluated immunohistochemically. RESULTS: When compared to the IR rats, the activity of ALT decreased in the IC group in all periods of observation (the highest decrease of ~48% after 1 hr of reperfusion). When compared to the IR group, a statistically significant decrease (p < 0.05) in the TNF-α concentration (~33%) in the IC rats occurred only after 1 hr of reperfusion, and it was accompanied by a decrease in the MPO concentration after 1 and 6 hrs of reperfusion. IC reduces the effects of reactive oxygen species (ROS) activity, which has been confirmed by a statistically significant decrease in MDA concentration by 25%-35% in all studied periods. The limitation of hepatocytes apoptosis due to IC occurs in the early (~26%; p < 0.05) and late (~45%; p < 0.01) phases of reperfusion. CONCLUSIONS: The use of IC in early phase of reperfusion brings about a decrease in TNF-α release, which can be related to liver injury due to neutrophil infiltration and apoptotic cell reduction. It seems that the reduction of lipid peroxidation may also limit the liver injury.

[Transforming growth factor beta (TGF-beta): its structure, function, and role in the pathogenesis of systemic lupus erythematosus]. / Transformujacy czynnik wzrostu beta (TGF-beta)--budowa, mechanizmy oddzialywania oraz jego rola w patogenezie tocznia rumieniowatego ukladowego.

TGF-beta is a cytokine of great importance in many common diseases because it takes part in many physiological processes such as angiogenesis and stimulation of the synthesis and degradation of extracellular matrix proteins. It also regulates the entrance of cells to the apoptotic pathway and can stimulate the division of mesenchymal cells and inhibit hemopoietic, endothelial, and lymphatic cells. There are five genes which encode TGF-beta in vertebrates, of which only three are present in mammals. The best known member of the family of TGF-beta proteins is TGF-beta 1. TGF-beta is synthetized as a precursor protein which, after enzymatic modification, is present as a small or large complex. Three membrane receptors, serine/threonine kinase, are arranged for signal transduction with TGF-beta. Smad proteins are responsible for sending the signal into the cell nucleus; its influence on different transcriptive factors in the cell nucleus promotes the expressions of different genes. Disturbances in TGF-beta expression have been noted in many diseases. Current results clearly indicate an important role of this cytokine in autoimmunological disorders, especially in systemic lupus erythematosus. Studies on an animal model revealed that endogenic TGF-beta can control the progression of systemic lupus erythematosus.

RNA and protein synthesis in different organs of rat offspring after chronic cadmium exposure during pregnancy.

Despite binding by placental metallothionein, cadmium (Cd) relatively easily enters fetal circulation and may be harmful to tissues and organs of offspring. Although Cd toxicology is relatively well described in the literature there are only few studies on Cd toxicity exerted during fetal life. We examined the influence of cadmium exposure during pregnancy on RNA and protein synthesis in different organs of the rat offspring. Their dams were fed diet containing cadmium chloride-treated drinking water during the whole pregnancy period at 50 ppm dose level. The offspring, 6-weeks-old male Wistars rats, weighing 105 + 10 g were subjected to examination. Synthesis of RNA and proteins was quantitated by scintillation technique, which measured incorporation of tritiated uridine and alanine, respectively. A set of 17 organs and tissues was examined. RNA synthesis increased significantly in buccal mucosa, tongue, parotid gland, cardiac muscle, brain and bone marrow. A strong induction of RNA synthesis in all four studied brain regions attracts special attention. The activation of RNA metabolism may be partly explained by the increased expression of genes involved in detoxication and adaptation (e.g., metallothionein, stress response proteins, etc.). A profile of protein synthesis was much more heterogenous with elevated H3-alanine uptake in 12 organs of experimental animals, however without any statistical significance. Since the study of protein synthesis did not demonstrate any significant changes in Cd-treated animals, the profile of RNA synthesis cannot be simply extrapolated on protein synthesis, probably because of complex post-transcriptional and post-translational genetic modifications.