NOTCH1, NOTCH3, NOTCH4, and JAG2 protein levels in human endometrial cancer.

BACKGROUND AND OBJECTIVE: Notch signaling is a conserved developmental pathway, which plays an important role in the regulation of cell proliferation, differentiation and death. Deregulation of Notch pathway has been connected with the carcinogenesis in a variety of cancers. The aim of this study was to investigate the level of the Notch signaling pathway proteins (NOTCH1, 3, 4 and JAG2) in the samples from human endometrial cancer. MATERIALS AND METHODS: The amount of the Notch receptors NOTCH1, 3, 4 and ligand JAG2 protein was determined by Western blot analysis in the samples from stage I endometrial cancer and adjacent nontumor endometrial tissue of 22 patients. RESULTS: The level of NOTCH4 receptor was 1.7 times lower in stage I endometrial cancer as compared with the healthy tissue of the same patients (P=0.04). The protein level of ligand JAG2 was significantly reduced by 2.5 times in stage IB endometrial adenocarcinoma samples (P=0.01). It was reduced in the majority of stage IB adenocarcinomas. There were no significant changes in the protein amount of NOTCH1 and NOTCH3 receptors comparing stage I endometrial adenocarcinoma and healthy tissues. CONCLUSIONS: The reduced amount of NOTCH4 and JAG2 proteins and the decreased level of mRNA coding Notch proteins, as reported in our previous studies, supports the notion that Notch pathway has rather tumor-suppressive than oncogenic role in human endometrial cancer cells. It suggests that Notch pathway activation is a potential therapeutic target.

The significance of reduced glutathione and glutathione S-transferase during chemoradiotherapy of locally advanced cervical cancer.

BACKGROUND AND OBJECTIVE: To determine changes in reduced glutathione (GSH) and glutathione S-transferase (GST) during neoadjuvant chemotherapy followed by concurrent chemoradiation for patients with stage IIB-IIIB cervical cancer, and to evaluate their significance to the efficacy of the treatment. MATERIALS AND METHODS: According to the prospective phase II study protocol, 36 patients with stage IIB-IIIB cervical cancer were enrolled. A short course of intensive weekly neoadjuvant cisplatin and gemcitabine chemotherapy followed by concurrent weekly cisplatin and gemcitabine-based chemoradiation was administered. Blood samples for GSH, GST analysis were collected and analyzed before the start of the treatment, after neoadjuvant chemotherapy, and after the end of the chemoradiation. RESULTS: A statistically significant increase in the concentration of GSH after neoadjuvant chemotherapy was identified. After chemoradiation, values of this rate significantly decreased in contrast with GSH concentration after neoadjuvant chemotherapy in cases of stage IIB, regional metastases negative patients group, patients with a positive response to treatment, and patients who had no progression of the disease during the first 2 years after treatment. Statistically significant changes in GST during the treatment were not identified; the GST concentration after chemoradiation showed a statistically significant difference in GST concentrations in terms of the progression of the disease and disease without progression. CONCLUSIONS: The results suggest that changes in the concentration of GSH during the treatment of locally advanced cervical cancer might be important for the prediction of the efficacy of the treatment. Statistically significant changes in GST concentration levels during the treatment were not observed.

Changes of reduced glutathione and glutathione S-transferase levels in colorectal cancer patients undergoing treatment.

PURPOSE:: The available data concerning reduced glutathione (GSH) and glutathione S-transferase (GST) levels in colorectal cancer patients during the treatment process are contradictory and insufficient. METHODS:: Forty patients with metastatic colorectal cancer receiving FOLFOX4 chemotherapy with or without bevacizumab and 40 healthy volunteers were included in the study. Blood samples were taken before treatment, after 2 months and at the end of treatment in the patient group and once in the healthy volunteer group. The levels of GSH and GST in blood serum were evaluated by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions. RESULTS:: The serum level of GSH was significantly lower in colorectal cancer patients before treatment than in healthy volunteers (37.84 ± 19.39 µg/mL and 52.78 ± 19.39 µg/mL, respectively; p<0.001). After treatment, the level of GSH increased significantly, while the level of GST decreased significantly. These changes were observed only in the groups of patients with partial or complete response, having metastases only in the liver, receiving FOLFOX4 chemotherapy with bevacizumab, or undergoing resection or radiofrequency ablation of liver metastases. CONCLUSIONS:: GSH and GST levels change significantly during the treatment process and these changes depend on the response to treatment, treatment type, and site of metastases. Further analysis of the changes in GSH and GST levels during treatment would allow the assessment of the predictive potential of this molecular marker.

Alterations of human immune system functions in relation to environmental contamination, gender and alcohol consumption intensity.

Environmental contamination and use of alcohol may be a cause of immune system disturbances and various diseases. The aim of this study was to evaluate changes of different alcohol consumption intensity on the immune condition of women and men living in a district contaminated with industrial siftings (Trakai) and in a relatively clean district (Sirvintos). The immune system parameters were investigated in 282 Trakai district inhabitants (127 males and 155 females) and in 282 Sirvintos district inhabitants (129 males and 153 females). Due to gender and alcohol consumption intensity the immune system functions were evaluated in the following groups: abstainers, light alcohol users, moderate alcohol users and alcohol abusers. Absolute number of CD5+, CD4+, concentration of IgA in blood serum and some other investigated indices of light alcohol users were significantly increased in the male group of Trakai district in comparison with females of this district. However, in the same group of light alcohol drinkers of Sirvintos district, males had lower indices (CD5+, CD4+, CD4+/CD8+, IgM) than females. Immune system parameters of males who were light and moderate alcohol users in Trakai district were stimulated in comparison with the same alcohol consumption groups of males in Sirvintos district. Our investigations showed that combination of environmental pollution and different intensity of alcohol consumption cause various alterations of immune system functions in males and females.

Glutathione and glutathione S-transferase levels in patients with liver metastases of colorectal cancer and other hepatic disorders.

BACKGROUND/AIMS: Glutathione and glutathione S-transferases (GST) are involved in cell defence against reactive oxygen species, which induces oxidative stress and are associated with different chronic diseases. The aim of the present study was to determine the differences in reduced glutathione (GSH) and GST levels in patients with different liver diseases. MATERIALS AND METHODS: Overall, 114 patients were enrolled in this study: 58 patients with colorectal cancer (18 without and 40 with liver metastases), 27 with liver steatosis, 29 with alcoholic cirrhosis and a group of 40 healthy volunteers. The levels of GSH and GST in blood serum were evaluated by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's guidelines. RESULTS: Significant differences in GSH and GST levels were observed in most of the groups compared to the healthy volunteers (GSH: 52.72 µg/mL, GST: 0.53 ng/mL): with hepatic steatosis (GSH: 17.04 µg/mL, p < 0.001; GST: 5.89 ng/mL, p < 0.001), alcoholic cirrhosis (GSH: 62.04 µg/mL, p < 0.003; GST: 0.94 ng/mL, p < 0.001) and liver metastases (GSH: 37.84 µg/mL, p < 0.001, GST: 1.25 ng/mL, p=0.747). CONCLUSION: The different GSH and GST levels in patients with colorectal cancer liver metastases, liver steatosis and alcoholic cirrhosis indicate the differences in antioxidative system damage and its compensatory possibilities and could serve as potential biomarkers for its correction.

[Changes in the parameters of immune and antioxidant systems in patients with cervical cancer]. / Serganciuju gimdos kaklelio veziu imunines ir antioksidacines sistemu bukle.

Taking into account the possibility of interaction of immune and antioxidant systems, the aim of this study was to investigate the changes in the parameters of immune and antioxidant systems in patients with cervical cancer and to compare them with the corresponding data obtained from healthy women. Ninety-four women with cervical cancer at II and III stage comprised the patient group and 69 healthy women were taken as the control group. The investigation results showed that the cellular immunity functions of patients with cervical cancer were suppressed in comparison with the same of healthy women. Though with respect to age, in 35-49-year-old women group with cervical cancer, some immune system indices were suppressed (quantity of T-, B-lymphocytes, NK); however in order to maintain the immune homeostasis of the organism other immune system functions were compensatorily stimulated (neutrophils and its phagocytic activity, CD8(+), IgG and IgA concentration were higher). The activity of the antioxidant system in patients with cervical cancer was impaired: the concentration of lipid peroxidation products was increased, the level of the endogenous antioxidant vitamin E and the activity of the antioxidant enzyme superoxide dismutase were decreased in comparison with the control group.

Disturbance of human immunohomeostasis by environmental pollution and alcohol consumption.

Environmental pollution and consumption of alcohol evoke various immunomodulations promoting the progress of different pathologies. The purpose of this study was to evaluate the influence of alcohol consumption intensity on the immune system functions of humans living in ecologically different regions, i.e. in a district polluted with industrial siftings (Trakai, n = 270) and in a relatively clean district (Sirvintos, n = 250). In the Trakai cohort 96% and in Sirvintos group 89% of persons consumed alcohol. With regard to alcohol consumption habits the immunohaematological indices were investigated in the following four groups: abstinents, light alcohol users, moderate alcohol users and alcohol abusers. We determined the compensatory mechanisms of immune system functions of moderate alcohol users and alcohol abusers in comparison with abstinents in the relatively clean Sirvintos district. In the Trakai district polluted with industrial siftings such compensatory reactions where not found. Thus, damage to the immune system functions is not only an endogenous risk factor for many diseases, but also an indicator of organism injury. This investigation stated, that immunity disturbance in humans depends on alcohol consumption intensity and place of residence.