Janina Didžiapetrienė

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 hosts 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.

Human papillomavirus infection in pregnant women.

IntroductionHuman papillomavirus (HPV) is the most common sexually transmitted infection in the world. It has been established that about 70% of the sexually active population are exposed to this infection. The HPV prevalence rate among pregnant women ranges from 5.5 to 65.0%. Studies on HPV infection in pregnant women have yielded inconsistent results, including HPV prevalence, and HPV clearance.AimOur aim is to determine the prevalence of HPV infection in pregnant women, to identify the types of the virus, and to evaluate the changes of prevalence of HPV infection depending on the trimester of pregnancy in Lithuania.MethodsTwo hundred and thirteen pregnant women who were attending centres of the central outpatient clinic of Vilnius city (Lithuania) in 2008–2010 were studied. These women were examined for HPV infection and its type by polymerase chain reaction. Tests were performed on the first and third trimesters. The statistical analysis was done using SPSS17 and Excel software.ResultsAt the beginning of the pregnancy (first trimester of pregnancy), HPV infection was detected in 17.8% of the pregnant women (38 from 213); high oncogenic risk HPV types were identified for 52.6% of the HPV-positive pregnant women. At the end of the pregnancy (third trimester of pregnancy), HPV was identified in 10.3% of the pregnant women (15 out of 146); high-risk HPV types were identified for 66.7%.ConclusionOur study shows the high prevalence of HPV infection in pregnant women in Lithuania. The majority of pregnant women’s HPV infection was cleared during the pregnancy. Only in a few cases a new HPV infection was detected.

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.

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 Hassalls 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.

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.

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.

NOTCH signalinio kelio ir ginekologinių piktybinių navikų sąsaja

Įvadas. Organizmo ląstelėse vykstančius procesus kontroliuoja įvairūs signaliniai keliai. Vienas iš jų yra NOTCH signalinis kelias. Nustatyta, kad dalinis NOTCH funkcijos praradimas arba nenormalus NOTCH signalo aktyvinimas susijęs su įvairiais žmogaus vystymosi sutrikimais ir ligomis. Medžiaga ir metodika. Pagrindinis informacijos šaltinis ieškant duomenų – PubMed duomenų bazė. Rezultatai. Straipsnyje nagrinėjama onkologinių ligų bei NOTCH signalinio kelio dalyvių sąsaja. NOTCH signalas, vystantis vėžiui, gali veikti dvejopai: kaip onkogenas ir kaip naviko augimo slopiklis. Tikslus tokio poveikio mechanizmas dar nėra žinomas. NOTCH signalinio kelio tyrimai svarbūs siekiant atrasti naujus vėžio gydymo būdus, farmakologiniais ir genetiniais metodais valdant NOTCH signalinį kelią. Šioje apžvalgoje daugiausia dėmesio skiriama ginekologiniams piktybiniams navikams, ypač gimdos kūno vėžiui. Išvados. Pastarųjų metų mokslinių tyrimų duomenys rodo, kad NOTCH signalinis kelias yra neabejotinai svarbus formuojantis gimdos kūno vėžiui, todėl jo komponentai gali būti potencialūs prognoziniai biožymenys ir molekuliniai terapiniai taikiniai. Siekiant patikslinti NOTCH signalinio kelio dalyvių reikšmę bei jų sąveiką su kitų signalinių kelių dalyviais, kurie taip pat gali būti svarbūs formuojantis ir progresuojant gimdos kūno vėžiui, reikalingi tolesni šios srities moksliniai tyrimai.

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.

Mikrosatelitų nestabilumas ir heterozigotiškumo praradimas sergant vėžiu

Straipsnyje pateikiami literatūros duomenys apie mikrosatelitų nestabilumą ir heterozigotiskumo praradimą sergant įvairių lokalizacijų vėžiu. Sie genetiniai pokyciai yra svarbūs kancerogenezei. Mikrosatelitų nestabilumo ir heterozigotiskumo praradimas gali būti prognoziniu, o kai kuriais atvejais predikciniu žymeniu (rodyti atsaką į gydymą). Daugiausia duomenų yra apie mikrosatelitų nestabilumą sergant storosios žarnos vėžiu. Duomenys apie mikrosatelitų nestabilumą kitų lokalizacijų vėžio atvejais dar kaupiami, taigi, sia tema publikuojamų straipsnių skaicius auga.