Components of NOTCH Signaling for Uterine Cancer Patients' Prognosis.

New molecular biomarkers that could have an independent prognostic value in endometrial cancer are currently under investigation. Recently, it was suggested that genetic changes in the Notch signaling pathway could be associated with the development of endometrial carcinoma. This study aimed to determine the expression of the Notch signaling pathway components in tumour and adjacent normal uterine tissue and to evaluate their importance for the survival of uterine cancer patients. The present study was performed on uterine body samples collected from 109 patients and paired adjacent noncancerous endometrial tissue samples. Kaplan-Meier curves and Cox regression were used for survival analyses. Expression alterations of NOTCH2, NOTCH3, NOTCH4, JAG2, and HES1 were evaluated as independent and significant prognostic factors for uterine cancer patients.

Oxidant/Antioxidant Status of Breast Cancer Patients in Pre- and Post-Operative Periods.

BACKGROUND AND OBJECTIVES: The purpose of this study is to evaluate the level of oxidative stress before and after breast cancer surgery. MATERIALS AND METHODS: Malondialdehyde (MDA) level was tested using a thiobarbituric acid (TBA) assay based on the release of a color complex due to TBA reaction with MDA. The glutathione S-transferase (GST) activity was evaluated by enzymatic conjugation of reduced glutathione (GSH) with 1-chloro-2,4-dinitrobenzene. The level of total glutathione (reduced GSH and oxidized GSSG) was detected using a recycling system by 5,5-dithiobis(2-nitrobenzoic acid). The levels of the indices were determined in the serum of 52 patients before surgery, two hours and five days after surgery, and in 42 healthy women. RESULTS: In the patients over 50 years old the level of MDA was higher after surgery in comparison with before surgery, and GST activity was lower in comparison with the control. The GSH + GSSG level in both ages groups after surgery was lower than in the control. Significant differences of MDA level were detected in patients with stage III after surgery compared to the control. The level of GSH + GSSG was significantly lower in the patients with I-III stages compared to the control. CONCLUSION: The most expressed changes demonstrate the significance of MDA as a marker to evaluate oxidative stress in breast cancer patients. The degree of oxidative stress depends on the patient's age and stage of disease.

Changes in the expression of Notch and Wnt signalling molecules in human endometrial cancer.

BACKGROUND: Endometrial cancer is the  sixth most frequent type of cancer among women worldwide. Type  I adenocarcinomas account for 80-85% of endometrial cancer cases and sometimes require more aggressive treatment than the remaining part of this group. Therefore, molecular markers to stratify adenocarcinomas are needed. MATERIALS AND METHODS: In this study, we analysed Notch and Wnt signalling in human endometrial cancer cases to evaluate these pathway elements as potential biomarkers for type  I endometrial cancer. Endometrial samples were obtained from 47 women undergoing surgery for stage I-IV endometrial cancer in the National Cancer Institute (Vilnius, Lithuania) in 2015-2016. The expression at the mRNA level of signalling molecules genes (NOTCH1, NOTCH2, NOTCH3, NOTCH4, JAG1, JAG2, DLL1, HES1, AXIN2 and CTNNB1) was analysed by the quantitative real-time polymerase chain reaction. Relative expression of NOTCH1, NOTCH4, HES1 and ß-catenin proteins in endometrioid adenocarcinoma was evaluated by the Western blot method. RESULTS: The  expression level of Notch receptors, ligands, and the target gene, as well as CTNNB1 and AXIN2, was reduced in stage I endometrioid adenocarcinoma if compared to the adjacent non-tumour tissue. The expression of all receptors, ligands, and target molecules was reduced in adenocarcinomas of later stages. The statistically significant correlations between transcript amounts of Notch receptors and ligands were found. There was a statistically significant difference in the  gene expression of Notch signalling pathway components between different tumour differentiation grade samples. A positive correlation between mRNA and protein the expression level of NOTCH1, NOTCH4, HES1 was determined in stage I samples. CONCLUSIONS: Analysis of 47 human endometrial cancer samples revealeda reduction in the transcript levels of Notch and Wnt signalling molecule compared to the adjacent non-tumour tissue. These results suggest tumour suppressor function of Notch and Wnt signalling in human endometrial cancer. More detailed research on these signalling pathways should reveal their importance as potential biomarkers.

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.

NOTCH signalinio kelio ir ginekologiniu piktybiniu naviku sasaja.

THE ASSOCIATION BETWEEN THE NOTCH SIGNALING PATHWAY AND GYNAECOLOGICAL MALIGNANCIES: Background. The body's cell behaviour is controlled by various signalling pathways, one of which is NOTCH. It has been found that a partial loss of the NOTCH function or abnormal strengthening of NOTCH signalling are related to various human diseases and developmental disorders. Materials and methods. PubMed was the main source of information for this paper. Results. The paper overviews the association between oncologic diseases and the participants of the NOTCH signalling pathway. In cancerogenesis, the NOTCH signalling pathway can act as a tumour suppressor or an oncogene. The mechanisms of such an effect are yet unknown. The NOTCH signalling pathway is an object of active research because its modulation by pharmacological and genetic approaches could be helpful in discovering new treatment methods of tumours. In this review more attention is paid to gynaecological malignancies, especially to uterine cancer. Conclusions. The findings of recently published studies show that the NOTCH signalling pathway is definitely important for the development of uterine cancer, therefore its components can be potential prognostic biomarkers and molecular therapeutic targets. However, further studies in this field are needed in order to clarify the role of the components of the NOTCH signalling pathway and their interaction with participants of other signalling pathways, which can be important in the development and progression of uterine cancer as well. Keywords: NOTCH signalling pathway, cancer, gynaecological malignancies.

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.

Sodium Valproate Enhances the Urethane-Induced Lung Adenomas and Suppresses Malignization of Adenomas in Ovariectomized Female Mice.

In the present study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in female mice has been evaluated. BALB/c mice (n = 60; 4-6 weeks old, females) were used in the following groups: (1) urethane-treated; (2) urethane-NaVP-treated; (3) only NaVP-treated; (4) control. In the same groups, ovariectomized female mice (n = 60) were investigated. Urethane was given intraperitoneally, with a total dose of 50 mg/mouse. In NaVP-treated mice groups, 0.4% aqueous solution of NaVP was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in ovariectomized mice and in those treated with urethane and NaVP was significantly higher than in mice treated with urethane only (8.29 ± 0.58 versus 6.0 ± 0.63, p < 0.02). No significant difference in the number of tumors per mouse was revealed while comparing the nonovariectomized urethane- and urethane-NaVP-treated groups (p = 0.13). A significant decrease of adenocarcinoma number in ovariectomized mice treated with a urethane-NaVP as compared with ovariectomized mice treated with urethane only was found (p = 0.031). NaVP together with low estrogen may have a protective effect on the malignization of adenomas in ovariectomized mice.

Sodium valproate effect on the structure of rat glandule thymus: Gender-related differences.

Sodium valproate (VPA) was shown to inhibit cell growth mechanisms such as cell cycle arrest, proliferation suppression, increase of apoptosis. Many aspects of the contribution of the VPA pharmacological mechanisms and their significance in gender-related processes have not been investigated. In our study, we have tested hypothesis that the influence of VPA on thymus weight and structure might be gender-related. The thymus of Wistar rats of both genders aged 8 weeks was investigated in the following groups (n = 6 each): controls, treated with VPA, castrated male and female treated with VPA, and the castrated control of both genders. The thymus weight, structural changes and area of cortical and medullar parts of the gland in slides stained with hematoxylin and eosin and immunohistochemically were assessed. A comparison of thymus weight of castrated male and of castrated VPA-treated male rats showed a significant thymus weight loss after VPA treatment (0.66 ± 0.04 g vs. 0.43 ± 0.03 g, p < 0.05). The treatment with VPA caused an about 6-fold (0.39 ± 0.12 vs. 0.07 ± 0.03) increase of Hassall's corpuscles (HCs) numbers per 1mm(2) in male and more than 4-fold increase (0.46 ± 0.07 vs. 0.10 ± 0.04) in female rats. In castrated males and females, the HCs number was also increased, but this increase was statistically significant only in male animals vs. controls (0.46 ± 0.10 vs. 0.07 ± 0.03, p < 0.001 in males; 0.29 ± 0.13 vs. 0.10 ± 0.04, p > 0.05 in females). When castrated male and female rats were treated with VPA, further increase of HC numbers was found. In our study, VPA has inhibited the proliferative capacity of thymocytes by diminishing the thymus weight and inducing a differentiation of thymic medullar epithelial cells into HCs. The diminishing of the gl. thymus weight under the influence of VPA was significant in castrated male rats. The number of HCs increased in animals of both genders under the influence of VPA. Gender differences in HCs development were noted in castrated animals.

Significance of blood serum catalase activity and malondialdehyde level for survival prognosis of ovarian cancer patients.

BACKGROUND AND OBJECTIVE: Several markers were found to be potential prognostic factors in ovarian cancer. Among markers resembling systemic changes in the host's organism are markers of the oxidative stress. In this study we attempted to analyze the oxidant and antioxidant parameters of ovarian cancer patients. MATERIALS AND METHODS: A total of 42 patients with newly diagnosed stages I-IV primary ovary cancer were examined. Level of malondialdehyde (MDA) and catalytic activity catalase (CAT) were determined spectrophotometrically. RESULTS: Significantly lower CAT (28.2±15.5 vs. 36.1±14.6nmol/L/min, P=0.019) activity and higher MDA levels (8.7±3.0 vs. 6.7±2.7nmol/L, P=0.002) were observed in cancer patients compared with healthy volunteers. Both variables were not confirmed as prognostic factors according to Kaplan-Meier survival estimates. CONCLUSIONS: MDA and CAT demonstrate oxidative stress in cancer patients: CAT activity was significantly lower and MDA levels higher in cancer patients compared to healthy controls. These variables were not confirmed to be prognostic factors in ovarian cancer, possibly due to small size of the study group.

Nevomelanocytic atypia detection by in vivo reflectance confocal microscopy.

BACKGROUND AND OBJECTIVE: In vivo reflectance confocal microscopy (RCM) is a promising novel technology for non-invasive early diagnostics of cutaneous melanoma. However, the possibility to detect melanocytic atypia in nevi by means of in vivo RCM remains unknown. The aim of the study was to evaluate the significance of in vivo RCM features of melanocytic atypia for the diagnosis of melanocytic nevi, dysplastic nevi and cutaneous melanoma. MATERIALS AND METHODS: A total of 138 melanocytic skin lesions comprising 25 melanocytic nevi, 69 dysplastic nevi and 44 melanomas were analyzed by means of dermoscopy, in vivo RCM and routine histopathology. In vivo RCM images were analyzed for the arrangement of keratinocytes in epidermis, pagetoid cells and junctional melanocytic nests and correlated refractivity aspects of nests with histopathology. RESULTS: Separately and all together taken the in vivo RCM features of melanocytic atypia were significant in differential diagnosis of benign and malignant melanocytic skin lesions, though none of the features was significant in discriminating nevi without cytologic atypia of dysplastic nevi. In vivo RCM feature of dense cell clusters corresponded with melanin containing nevomelanocytes on histopathology though exact correspondence of non-homogeneous and atypical sparse cell clusters remained questionable. CONCLUSIONS: Nevus with histopathologically confirmed nevomelanocytic atypia (dysplastic nevus) could not be distinguished from nevus without atypia using analyzed in vivo RCM features of melanocytic atypia. More accurate diagnostics by means of in vivo RCM needs further investigation on reflectance of single and nested cutaneous melanocytes in benign and malignant skin lesions.

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.

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.

Relationship of MDA plasma concentrations to long-term survival of breast cancer patients.

AIMS AND BACKGROUND: Malondialdehyde (MDA) is a product of polyunsaturated fatty acid oxidation. Changes in MDA concentrations have been found in patients with various types of cancer. The aim of this study was to analyze the relationship of MDA plasma concentrations to the long-term survival of patients with breast cancer. METHODS AND STUDY DESIGN: We conducted a retrospective study which included 106 patients at various disease stages (I - n = 2; II - n = 30; III - n = 51; IV - n = 23). Plasma MDA concentrations were measured at the time of diagnosis. Study participants were divided into groups according to age (<55 years vs ≥55 years), disease stage, and MDA concentration (<9 mmol/L vs ≥9 mmol/L). Survival rates between groups were compared using the Kaplan-Meier method. RESULTS: We found that higher MDA concentrations were associated with lower survival rates in stage I and II breast cancer. No significant association was found in patients with stage III and IV disease. Multivariate analysis showed that the MDA level was the only independent prognostic factor for patient survival in the total study group (hazard ratio 1.57, P = 0.03). CONCLUSION: MDA can be used as a prognostic factor in early stages of breast cancer.

Sodium is not required for chloride efflux via chloride/bicarbonate exchanger from rat thymic lymphocytes.

Sodium-dependent Cl(-)/HCO3 (-) exchanger acts as a chloride (Cl(-)) efflux in lymphocytes. Its functional characterization had been described when Cl(-) efflux was measured upon substituting extracellular sodium (Na(+)) by N-methyl-D-glucamine (NMDG). For Na(+) and Cl(-) substitution, we have used D-mannitol or NMDG. Thymocytes of male Wistar rats aged 7-9 weeks were used and intracellular Cl(-) was measured by spectrofluorimetry using MQAE dye in bicarbonate buffers. Chloride efflux was measured in a Cl(-)-free buffer (Cl(-) substituted with isethionate acid) and in Na(+) and Cl(-)-free buffer with D-mannitol or with NMDG. The data have shown that Cl(-) efflux is mediated in the absence of Na(+) in a solution containing D-mannitol and is inhibited by H2DIDS. Mathematical modelling has shown that Cl(-) efflux mathematical model parameters (relative membrane permeability, relative rate of exchanger transition, and exchanger efficacy) were the same in control and in the medium in which Na(+) had been substituted by D-mannitol. The net Cl(-) efflux was completely blocked in the NMDG buffer. The same blockage of Cl(-) efflux was caused by H2DIDS. The study results allow concluding that Na(+) is not required for Cl(-) efflux via Cl(-)/HCO3 (-) exchanger. NMDG in buffers cannot be used for substituting Na(+) because NMDG inhibits the exchanger.

Sodium valproate enhances urethane tumorigenicity in lungs of male but not female mice.

In the study, the possible effect of sodium valproate (NaVP) on urethane-induced lung tumors in mice has been evaluated. BALB/c mice (n = 120; 4-6 weeks old, both sexes) were used in the following groups: 1) urethane-treated, 2) urethane-NaVP-treated, 3) only NaVP-treated, 4) control. In the same groups, castrated male mice (n = 48) were investigated. Urethane was given by intraperitoneal injections 10 mg/mouse, twice a week, the total dose 50 mg/mouse. In NaVP-treated mice, the 0.4 % NaVP aqueous solution was offered to mice ad libitum. The duration of the experiment was 6 months. The number of tumors per mouse in urethane-NaVP-treated males was significantly higher than in those treated with urethane only (13.82 ± 1.12 vs 6.77 ± 0.43, p < 0.0001). No significant difference in the number of tumors per mouse was revealed while comparing the female urethane- and urethane-NaVP-treated groups (6.50 ± 0.79 vs 8.15 ± 0.55, p = 0.105). No difference in the number of tumors per mouse was found in urethane-NaVP-treated castrated males as compared with urethane-treated castrated males. However, in the urethane-NaVP-treated castrated males the number of tumors per mouse was significantly lower than in analogous non-castrated males (7.8 ± 1.67 vs 13.82 ± 1.12, p < 0.01). NaVP combined with urethane potentiates urethane tumorigenicity in BALB/c non-castrated but not in female and castrated male mice. These data indicate an important role of testosterone in the urethane-NaVP induced lung tumorigenesis.

Prevalence of human papillomaviruses in patients with head and neck squamous cell carcinoma in Lithuania and Belarus.

Overall, head and neck sqamous cell carcinoma accounts for more than 550,000 cases annually worldwide. It is well known that human papillomavirus (HPV) is the main risk factor for cervical cancer development. As the incidence and the mortality of cervical cancer are closely related to the HPV prevalence, we hypothesized that there is the same association between HPV prevalence and head and neck squamous cell carcinoma. Therefore we performed the study aiming to compare the level of HPV infection and HPV type distribution between two groups of Lithuanian and Belarusian patients with head and neck sqamous cell carcinoma. One hundred ninety head and neck sqamous cell carcinoma patients were included in the study, 75 from Lithuania and 115 from Belarus. PCR was used for HPV detection and typing. The distribution of HPV infection among head and neck sqamous cell carcinoma patients was similar in the Lithuanian (20.0%) and Belarusian (18.3%) patient groups, however differences were found in the distribution of HPV types.

Significance of MMP-9 expression and MMP-9 polymorphism in prostate cancer.

BACKGROUND: The aim of the study was to assess the expression of the MMP-9 gene and -1562 C/T polymorphism in MMP-9 gene promoter in relation to clinicopathological parameters in predicting the clinical outcome of prostate cancer patients. METHODS: A total of 82 patients with histopathologically diagnosed prostate cancer were enrolled in the study. MMP-9 gene expression was assessed by reverse transcription-PCR method. MMP-9 (-1562 C/T) polymorphism variants were determined by the polymerase chain reaction-based restriction fragment length polymorphism method. RESULTS: MMP-9 expression and MMP-9 -1562 polymorphism variants in relation to disease pathological stage (P = 0.006; P <0.0001, respectively), as well as to prognostic group (P = 0.019; P <0.0001, respectively), were statistically significant. Only MMP-9 -1562 polymorphism variants in relation to tumor differentiation grade (P = 0.044) were found to be statistically significant. Positive MMP-9 gene expression was associated with 5-year survival rate of prostate cancer patients with pathological stage III (P = 0.036) and for the patients in prognostic group III (P = 0.012). Patients with tumor differentiation grade G2 and with the identified CC variant had a significantly longer survival time than patients with the identified TT variant (P = 0.007). CONCLUSIONS: MMP-9 gene expression and MMP-9 -1562 polymorphism variants were associated with prostate cancer pathological stage and prognostic group. MMP-9 -1562 polymorphism CC variant was associated with prostate cancer tumor differentiation grade. Five-year survival analysis showed the relationship between MMP-9 gene expression and pathological stage III, as well as prognostic group III, whereas MMP-9 -1562 polymorphism variants, with tumor differentiation grade G2.

Down-regulated expression of Notch signaling molecules in human endometrial cancer.

Notch signaling pathway is a highly conserved developmental pathway, which plays an important role in the regulation of cellular proliferation, differentiation and apoptosis. Deregulation of Notch pathway has been connected with the carcinogenesis in a variety of cancers. In this study, we investigated the expression of Notch receptors (NOTCH1, NOTCH2, NOTCH3 and NOTCH4), ligands (JAG1, JAG2 and DLL1) and target gene HES1. Fifty paired samples of endometrial cancer and adjacent nontumor endometrial tissue from endometrial cancer patients were analyzed by quantitative PCR. The mRNA levels of all investigated molecules were lower in endometrial cancer compared to adjacent nontumor tissue. The expression of NOTCH1, NOTCH4 and DLL1 in IB stage adenocarcinoma was significantly lower (P < 0.05) than the expression in IA stage adenocarcinoma. Significant correlations were found between mRNA expression levels of Notch target gene HES1 and several Notch signaling molecules: NOTCH1, NOTCH3, DLL1 (P < 0.001) and NOTCH2, JAG2 (P < 0.05). This supports the notion that Notch pathway can function as tumor suppressor in human endometrial cancer.

The effect of nanoparticles in rats during critical periods of pregnancy.

BACKGROUND AND OBJECTIVE. Nanotechnology works with substances at a nanometer scale, and it offers many solutions for biomedicine. Nanoparticles (NPs) have been shown as effective agents for imaging, drug delivery, pathogen detection, etc. However, to date, NP toxicity is poorly known. The aim of our study was to investigate the embryotoxicity and teratogenicity of quantum dots (QDs) at the different stages of rat embryogenesis. MATERIALS AND METHODS. Wistar rats were injected with CdSe/ZnS or CdTe QDs on the 6th, 13th, and 18th days of embryogenesis. Cyclophosphamide was chosen as a positive control of embryotoxicity. On the 21st day, the number of resorptions, weight, length, and external malformations of the embryos were estimated. Fluorescence spectroscopy and microscopy analysis were used to determine the accumulation of QDs in the tissues. RESULTS. Exposure to cyclophosphamide during the pregnancy decreased the embryonic weight and length when compared with the control group and produced numerous malformations. The effects depended on the stage of embryogenesis. Meanwhile, QDs did not cause any embryotoxic or teratogenic effects. However, CdTe QDs induced necrosis in the tissues of the peritoneal cavity. The necrotic tissues contained QDs with altered spectroscopic properties. Spectroscopic and microscopic tissue examination revealed that QDs accumulated in the placenta, but no penetration to the embryonic tissues was observed. CONCLUSIONS. QDs did not cause any direct embryotoxic or teratogenic effects, but they had adverse effects on the maternal organism. The observed QD effects and the long-term accumulation of QDs in the maternal organism may increase the risk of adverse effects on embryo development.