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Biomedical subjects

A Evangelou

Publications and source records attributed to A Evangelou.

At least 19 recordsLinked to original sources

Selenium in serum and neoplastic tissue in breast cancer: correlation with CEA.

Trace element selenium (Se) is regarded to be a breast cancer preventive factor involved in multiple protective pathways. In all, 80 women with breast cancer who underwent a radical mastectomy were enrolled in the study. Serum Se and carcinoembryonic antigen levels were measured using a fluorometric and IRMA assay, respectively. Se tissue concentration was determined by a tissue extracting fluorometric assay. For statistical analysis purposes t-test was used and P-values <0.001 were regarded as statistically significant. Serum Se was 42.5+/-7.5 microg l(-1) in breast cancer patients and 67.6+/-5.36 microg l(-1) in the age-matched control group of healthy individuals. Serum carcinoembryonic antigen in patients was 10+/-1.7 U ml(-1) (normal <2.5 U ml(-1) in nonsmokers/<3.5 U ml(-1) in smokers). A statistically significant difference was found for both serum Se and CEA between two groups studied (P<0.001). Neoplastic tissue Se concentration was 2,660+/-210 mg g(-1) tissue; its concentration in the adjacent non-neoplastic tissue was 680+/-110 mg g(-1) tissue (P<0.001). An inverse relationship between Se and CEA serum levels was found in the two groups studied (r=-0.794). There was no correlation between serum/tissue Se concentration and stage of the disease. The decrease in serum Se concentration as well as its increased concentration in the neoplastic breast tissue is of great significance. These alterations may reflect part of the defence mechanisms against the carcinogenetic process.

Breast Neoplasms↗

Differentially androgen-modulated genes in ovarian epithelial cells from BRCA mutation carriers and control patients predict ovarian cancer survival and disease progression.

Epidemiological studies have implicated androgens in the etiology and progression of epithelial ovarian cancer. We previously reported that some androgen responses were dysregulated in malignant ovarian epithelial cells relative to control, non-malignant ovarian surface epithelial (OSE) cells. Moreover, dysregulated androgen responses were observed in OSE cells derived from patients with germline BRCA-1 or -2 mutations (OSEb), which account for the majority of familial ovarian cancer predisposition, and such altered responses may be involved in ovarian carcinogenesis or progression. In the present study, gene expression profiling using cDNA microarrays identified 17 genes differentially expressed in response to continuous androgen exposure in OSEb cells and ovarian cancer cells as compared to OSE cells derived from control patients. A subset of these differentially affected genes was selected and verified by quantitative real-time reverse transcription-polymerase chain reaction. Six of the gene products mapped to the OPHID protein-protein interaction database, and five were networked within two interacting partners. Basic leucine zipper transcription factor 2 (BACH2) and acetylcholinesterase (ACHE), which were upregulated by androgen in OSEb cells relative to OSE cells, were further investigated using an ovarian cancer tissue microarray from a separate set of 149 clinical samples. Both cytoplasmic ACHE and BACH2 immunostaining were significantly increased in ovarian cancer relative to benign cases. High levels of cytoplasmic ACHE staining correlated with decreased survival, whereas nuclear BACH2 staining correlated with decreased time to disease recurrence. The finding that products of genes differentially responsive to androgen in OSEb cells may predict survival and disease progression supports a role for altered androgen effects in ovarian cancer. In addition to BACH2 and ACHE, this study highlights a set of potentially functionally related genes for further investigation in ovarian cancer.

Acetylcholinesterase↗

Effects of cigarette smoking on the antioxidant defence in young healthy male volunteers.

Cigarette smoking induces a significant oxidant effect related to variety of free radical-related diseases often affecting the upper respiratory tract, unless it is effectively compensated by the antioxidant barriers of the humans. In the present study, the evaluation of the antioxidant compensatory mechanisms, by estimating the antioxidant capacity of extracellular defence (saliva and plasma) and the intracellular resistance of peripheral lymphocytes to oxidative stress in young healthy smokers, was investigated. Twenty young healthy male smokers and 20 age-matched non-smokers with similar dietary profiles were enrolled in the study. Total saliva and plasma samples were collected from both groups, and total antioxidant capacity (TAC) and lag time were estimated. The latter was also repeated in smokers just after a cigarette smoking. Peripheral lymphocytes isolated from the subjects of both groups were also tested for their inherent DNA damage as well as for their ability to resist H2O2-induced DNA damage by using the comet assay. TAC of plasma was found significantly higher in smokers compared to non-smokers (p <0.004), whereas no difference was recorded in plasma lag time values. Lymphocytes of smokers manifested a significantly decreased oxidant resistance (increased DNA fragmentation) to H2O2, in comparison to non-smokers. Our results indicate that young smokers do not manifest different salivary antioxidant defence than non-smokers. They exhibit, however, a higher plasma antioxidant capacity, but a significantly reduced ability of blood lymphocytes, to resist to H2O2-induced DNA damage.

Adult↗

Antitumour and toxic effects on Wistar rats of two new platinum complexes.

BACKGROUND: Cancer chemotherapy in humans based on metal complexes started at the clinical level in the late 1970s with the use of cisplatin, which forms intra-strand cross-links with DNA. METHODS: Two new platinum complexes of cis-geometry with the amino acids inosine (ino) and l-alanine (ala), Pt(ino)2Cl2 and cis-[Pt(NH3)2(ala)](NO3), respectively, were synthesized and pure samples were obtained by means of flash chromatography. These complexes were tested on benzo(a)pyrene-induced tumours in Wistar rats to detect their antitumour and toxic effects. RESULTS: There was a statistically significant prolongation of the mean survival time of the animals in the two groups tested (272 +/- 18 days and 246 +/- 26 days, respectively) compared to the control group (195 +/- 22 days) (P < 0.001). Toxic effects included a decrease in leucocyte cell count, mild haemolysis, mild haematuria, mild hepatotoxicity, elevated body temperature and hair loss. All of these effects were reversible after drug discontinuation. CONCLUSIONS: The two new platinum complexes described here appear to have an effective antitumour activity without severe toxicity when tested on Wistar rats.

Animals↗

The role of CD44 in the development and prognosis of head and neck squamous cell carcinomas.

CD44, the product of a single gene, exists as several isoforms generated by alternative exon splicing and posttranslational modifications, and is widely distributed in different cells and tissues including those of squamocellular origin. CD44 is a cell surface glycoprotein involved in many cellular processes acting as a receptor for cell to cell or cell to matrix adhesion, as a signal transmitter and as a growth factor-presenting molecule. Numerous studies based on immunohistochemical analyses of paraffin-embedded or frozen tissue sections using different monoclonal antibodies to CD44 isoforms and molecular biological techniques have provided evidence that in many types of tumours there is overexpression of CD44 isoforms and aberrant processing of immature CD44 transcripts relative to non-neoplastic control tissues, suggesting a role of CD44 in tumour development and progression. In contrast to these malignancies, one or more of the CD44 splice-variant isoforms are down-regulated in squamous cell carcinomas of the head and neck. CD44-deficient mice develop normally without giving rise to spontaneous tumours, but CD44-negative cells appear to be more susceptible to oncogenic transformation. Reduction in the expression of CD44 may confer growth advantage and malignant properties to tumour cells. The clinical significance of CD44 in squamous cell carcinomas of the head and neck as a tumour marker for cancer diagnosis and prognosis is discussed.

Animals↗

Person identification from the EEG using nonlinear signal classification.

OBJECTIVES: This paper focusses on the person identification problem based on features extracted from the ElectroEncephaloGram (EEG). A bilinear rather than a purely linear model is fitted on the EEG signal, prompted by the existence of non-linear components in the EEG signal--a conjecture already investigated in previous research works. The novelty of the present work lies in the comparison between the linear and the bilinear results, obtained from real field EEG data, aiming towards identification of healthy subjects rather than classification of pathological cases for diagnosis. METHODS: The EEG signal of a, in principle, healthy individual is processed via (non)linear (AR, bilinear) methods and classified by an artificial neural network classifier. RESULTS: Experiments performed on real field data show that utilization of the bilinear model parameters as features improves correct classification scores at the cost of increased complexity and computations. Results are seen to be statistically significant at the 99.5% level of significance, via the chi 2 test for contingency. CONCLUSIONS: The results obtained in the present study further corroborate existing research, which shows evidence that the EEG carries individual-specific information, and that it can be successfully exploited for purposes of person identification and authentication.

Electroencephalography↗

Large infectious bladder stone after long delay in removing ureteral stent.

We herein present a case of formation of a large infectious bladder calculous resulted from placement of a double pigtail catheter for an extensive period. The concomitant poor function of the corresponding renal unit made selection of nephroureterectomy unavoidable in the management of our patient.

Device Removal↗

Seromucous maxillary sinusitis (SMMS): a clinicophysiological approach.

Chronic sinusitis, especially maxillary sinusitis is a common disorder in humans. Seromucous sinusitis is rarely described in the literature. The present study deals with the clinical and laboratory characteristics of a group of patients suffering from the above disorder. During the last 10 years, 32 patients suffering from seromucous maxillary sinusitis were enrolled in the study. Patients' charts were reviewed and tabulated according to age, sex, history, clinical symptoms and laboratory findings. Treatment was based on punction and drainage of the seromucous effluent. Results were also statistically evaluated. Flight trips and atypical episodes of nasal infection were the predisposing factors for seromucous maxillary sinusitis. The only clinical manifestation was coughing, for at least 12 weeks before diagnosis. Sinus effluent was composed by serous and mucous constituents with glue like structure. There were no differences between sexes in predisposing factors, or x-ray findings. The treatment is paracentesis and drainage and in one case of recurrence, middle meatotomy and sinus endoscopy.

Adult↗

Down-regulation of transforming growth factor beta receptors by androgen in ovarian cancer cells.

Steroid hormones have been implicated in the etiology and/or progression of epithelial ovarian cancer. As ovarian surface epithelial cells are growth inhibited by transforming growth factor beta (TGF-beta), we tested whether steroid hormones could regulate the expression of TGF-beta1 or its receptors in ovarian cancer cells, as assessed by quantitative reverse transcription-PCR. Treatment of ovarian cancer HEY cells with 500 nM 5alpha-dihydrotestosterone (DHT), but not estradiol-17beta or progesterone, for 60 h down-regulated the expression of mRNA for TGF-beta receptors I and II (TbetaR-I and TbetaR-II), betaglycan, and endoglin but had no effect on TGF-beta1 mRNA levels. Androgen receptor (AR) mRNA expression in HEY cells was compared to other ovarian cancer cell lines. OVCAR-3 cells expressed AR mRNA levels similar to that of androgen-responsive LNCaP prostate cancer cells, whereas SKOV-3 and HEY cells expressed only 3 and 0.01%, respectively. Western blot analysis and saturation binding assays confirmed the expression of AR protein in these three cell lines, but at the limit of detection in SKOV-3 and HEY cells. Treatment of SKOV-3 and HEY cells for 24 h with 1-50 nM DHT resulted in a dose-dependent down-regulation of TbetaR-II mRNA. The AR antagonist hydroxyflutamide did not reverse the effect of DHT on SKOV-3 cells but by itself down-regulated TbetaR-II mRNA. This apparent androgen-mimetic action of hydroxyflutamide and the ability of SKOV-3 and HEY cells to respond to DHT may be due to their expression of AR-associating protein 70, an AR co-activator reported to amplify AR transactivation and to result in agonist activity of AR antagonists. DHT was able to reverse TGF-beta1 growth-inhibitory action in SKOV-3 cells and in a primary culture of ovarian cancer cells derived from ascites. Thus, androgens may promote ovarian cancer progression in part by decreasing TGF-beta receptor levels, thereby allowing ovarian cancer cells to escape TGF-beta1 growth inhibition.

Dihydrotestosterone↗

Inhibition of puerperal lactation with 2-mercaptopropionyl-glycine.

OBJECTIVES: Thiols (sulfydryl compounds) have a prolactin-lowering effect in animals. The purpose of our study was to evaluate the effects of orally administered N-2-mercaptopropionyl-glycine (tiopronin) on suppression of lactation and plasma prolactin (PRL) levels in a group of women in the puerperium. METHODS: One hundred women aged 17-37 years were studied. We divided our population in four groups (25 patients in each group). In group I, no medication was administered but only conservative measures were taken (restriction of fluid intake, ice-bags applied on the breasts, tight breast binders). Subjects in group II received tiopronin (200 mg/day) for 14 days. In group III, tiopronin (500 mg/day) was administered for 14 days. Subjects in group IV, took bromocriptine (5 mg/day) for 14 days. Assessment of suppression of lactation was performed clinically and laboratory determinations were obtained before and after 1, 2, 3, 4, and 14 days of treatment. Furthermore, in seven healthy women plasma PRL responses to thyrotropin-releasing hormone (TRH) before and after one week of tiopronin therapy (500 mg/day) were studied. RESULTS: Statistically significant higher percentages of success of lactation suppression were obtained with tiopronin (84% and 88%) and bromocriptine (96%) compared to conservative treatment (60%). In the four groups a significant decrease of PRL was observed. However, in women who received tiopronin and bromocriptine, the levels of PRL after 14 days of therapy were lower compared to the conservative treatment group. Moreover, in the tiopronin groups and the bromocriptine group, lactation was stopped earlier. In the first group (conservative measures) the lactation was suppressed after 13.3+/-5.4 days of treatment. In the groups who received tiopronin (200 mg/day and 500 mg/ day) lactation was suppressed after 4.4+/-1.7 and 4.3+/-1.6 days of treatment. In the bromocriptine group the lactation was stopped after 1.2+/-0.4 days. Bromocriptine treatment was associated with more frequent side effects than the tiopronin. CONCLUSION: Administration of tiopronin in low to moderate doses is effective in suppression of puerperal lactation.

Adolescent↗

Synthetic analogs for oxovanadium(IV/V)-glutathione interaction: an NMR, EPR, synthetic and structural study of oxovanadium(IV/V) compounds with sulfhydryl-containing pseudopeptides and dipeptides.

The reaction of [VO(CH3COO)2(phen)] (phen = 1,10-phenanthroline) with the sulfhydryl-containing pseudopeptides (scp), N-(2-mercaptopropionyl)glycine (H3mpg), N-(2-mercaptopropionyl)cysteine (H4m2pc), N-(3-mercaptopropionyl)cysteine (H4m3pc) and the dipeptides glycylglycine (H2glygly) and glycyl-L-alanine (H2glyala), in the presence of triethylamine, results in the formation of the compounds Et3NH[VO(mpg)(phen)] (1), (Et3NH)2[VO(m2pc)] (4), [(Et3NH)2[VO(m3pc) (5), [VO(glygly)(phen)] x 2CH3OH (2 x 2CH3OH) and [VO(glyala)(phen)] x CH3OH (3 x CH3OH). Evidence for the molecular connectivity in 2 x CH3OH was established by X-ray crystallography, showing the vanadium(IV) atom ligated to a tridentate glygly2- ligand at the N(amine), N(peptide) and O(carboxylato) atoms. Combination of the correlation plot of the EPR parameters gz versus Az, together with the additivity relationship supported the prediction of the equatorial donor atom sets of the V(IV)O2+ center at various pH values for the V(IV)O2+-glutathione system considered in this study. Model NMR studies (interaction of vanadium(V) with the scp H3mpg) showed that there is a possibility of vanadium(V) ligation to glutathione.

Dipeptides↗

Atrial natriuretic peptide and thyroid hormones' relation to plasma and heart calcium and magnesium concentrations of Wistar rats exposed to cold and hot ambients.

Plasma ANP (atrial natriuretic peptide), thyroid hormones, and calcium and magnesium levels as well as heart tissue calcium and magnesium concentrations were determined in male Wistar rats after exposure of 114 rats at low temperature (4 degrees C) and 95 rats at high temperature (35-36 degrees C) for 28 d. Plasma ANP, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), free T3, and free T4 were estimated by radioimmunoassay, and plasma and heart tissue levels of Ca and Mg by flame atomic absorption spectrophotometry. Results were compared to a control group exposed at 20-22 degrees C (76 rats). All the above parameters in control rats did not show statistically significant variations during the study. A significant increase of plasma ANP, T3, T4, Ca, and Mg concentrations developed during cold exposure, whereas a gradual decrease of plasma ANP, T3, T4, and Mg concentrations was revealed during hot exposure. A significant increase of heart tissue Mg concentrations developed during hot exposure. Results also indicate that plasma ANP and T3 levels are proportionally related, whereas an inverse relationship exists between plasma ANP and T3 levels and heart Mg concentrations, in both cold and hot exposed rats. In conclusion, ANP and thyroid hormones in relation to Ca and Mg play an important role in temperature adaptation.

Adaptation, Physiological↗

Atrial natriuretic peptide relation to plasma and heart zinc concentrations of Wistar rats exposed to cold and hot ambients.

Plasma atrial natriuretic peptide (ANP) and zinc levels, as well as heart tissue zinc concentrations were determined, in male Wistar rats after the exposure of 114 rats at low temperature (4 degrees C) and 95 rats at high temperature (35-36 degrees C) for 28 d. Plasma ANP was estimated by radioimmunoassay and Zn2+ concentrations by atomic absorption spectrometry. Values were compared to a control group exposed at 20-22 degrees C (76 rats). Plasma ANP and Zn2+ levels, as well as heart tissue Zn2+ concentrations of control rats did not show statistically significant variations during the study, whereas rats exposed to cold and hot ambients showed significant variations of the parameters. A significant increase of plasma ANP and plasma zinc and heart tissue Zn2+ concentrations developed during cold exposure, whereas a gradual decrease of plasma ANP and Zn2+ levels was revealed during hot adaptation. Results also indicate that plasma ANP and zinc levels are proportionally related, whereas there is an inverse relationship between plasma ANP levels and heart Zn2+ concentrations, in both cold and hot exposed rats. In conclusion, our results show that ANP in relation to zinc probably play an important role in cold and hot acclimatization of rats.

Adaptation, Physiological↗

Regulation of gonadotropin-releasing hormone (GnRH) gene expression by 5alpha-dihydrotestosterone in GnRH-secreting GT1-7 hypothalamic neurons.

Hypothalamic GnRH secretory neurons are precisely regulated by circulating gonadal steroids. However, the question of whether these cells are directly responsive to steroid hormones remains a central and controversial issue in reproductive science. In the present study, we demonstrate the expression of androgen receptor (AR) in a mouse hypothalamic GnRH-secreting cell line, GT1-7. AR messenger RNA was detected by Northern blot analysis of 10 microg total cellular RNA. Western blot analysis revealed a 110K AR immunoreactive band, and saturation binding analysis confirmed the presence of a high affinity low capacity androgen binding entity (Kd = 0.06 nM; Bmax = 12.4 fmol/mg protein). In addition, GT1-7 cells were found to express ARA70, an AR-specific coactivator that has been reported to enhance transactivational activity of the AR. GT1-7 cells transiently transfected with an androgen responsive MMTV-luciferase reporter construct displayed a 4.2-fold induction of luciferase reporter gene activity by 1 nM 5alpha-dihydrotestosterone (DHT), further demonstrating the presence of a functional AR. Treatment of GT1-7 cells with 1 or 10 nM DHT resulted in approximately 55% reduction in GnRH messenger RNA measured at 24 and 36 h after treatment. This repression was completely blocked by hydroxyflutamide, an AR antagonist. These results provide the first demonstration that androgen acts directly through an AR-mediated pathway to repress GnRH gene expression in hypothalamic GnRH-secreting neurons.

Animals↗

Comparison of the therapeutic effects of two vanadium complexes administered at low dose on benzo[a]pyrene-induced malignant tumors in rats.

The antitumor effects of low dose administration of the vanadium(III) complexes with L-cysteine (complex 1) and N-(2-mercaptopropionyl)-glycine (complex 2) were compared on benzo[a]pyrene (BaP)-induced tumors in Wistar rats. Male Wistar rats, injected with 10.0 mg of BaP, were divided into one control (C-G) and two treatment (TR-G) groups of 17 animals each. Animals of the first treatment group were administered complex 2 (TR-2 group) and those of the second group were administered complex 1 (TR-1 group) at doses of 100 microg of vanadium per os daily, starting from the day a palpable tumor was developed till their death. BaP injection induced a 100% tumor (leiomyosarcomas) development in the animals of all groups. Administration of complex 1 to the animals resulted in a significant prolongation of the mean survival time, a complete remission of 17.6% of the tumors developed, a significant reduction of the carcinogenic potency (CP) of BaP and of the tumor growth rate (TGR) in TR-1 group animals, compared to the control and the TR-2 group. In marked contrast, complex 2 failed at the doses administered to exert any significant modulation of the above mentioned parameters. Results indicate that at low (100 micro/day) concentrations of vanadium, complex 1 exerts a significant anticarcinogenic effect on experimentally-induced leiomyosarcomas in rats, whereas complex 2 has no effect when administered at the same low concentrations of vanadium.

Animals↗

Dose-related preventive and therapeutic effects of antioxidants-anticarcinogens on experimentally induced malignant tumors in Wistar rats.

A combination of antioxidants-anticarcinogens, consisting of vitamins C and E, selenium and 2-mercaptopropionyl glycine (2-MPG), was administered orally for the prevention (PRG) and treatment (TRG) of benzo(a)pyrene (BaP)-induced malignant tumors (leiomyosarcomas), in Wistar rats. In order to evaluate dose-related effects, a low dose vitamin (0.15 g/kg b.w. per day of vit.C and 0.05 g/kg b.w. per day of vit.E) and a high dose (1.5 g/kg b.w. per day of vit.C and 0.5 g/kg b.w. per day of vit.E) combination was administered, in prevention and treatment groups. Selenium was administered in doses of 2 microg/kg b.w. per day and 2-MPG in 15 mg/kg b.w. per day, in all groups. Daily estimations of 24 h urine volume levels of thiobarbituric acid reacting substances (MDA) were performed in 20 animals, divided into a control group, a BaP-injected group, a tricapryline-injected group and a BaP-injected and treated by the low dose combination group. Results revealed that the low dose combination failed to exert any beneficial effect on mean survival time of animals treated either preventitively or therapeutically. An increased number of animals bearing a second (lung) tumor was, in addition, found in autopsy and histological examination in the low dose combination (PRG and TRG) and the high dose TRG groups. The high dose combination groups manifested a significant prolongation of the mean survival time of animals; complete remission of tumors developed in 16.8% of the animals in the treatment group and a 5.2% prevention of tumor formation in the preventive group, without any evidence of an increased number of double tumor formation in the PRG group. Urine MDA increased significantly in animals injected by BaP during the first 10 days and since the 90th day (formation of palpable tumors) after injection, in relation to control and tricapryline-injected groups. Complete prevention of urine MDA-increased values was obtained in BaP-injected and treated by the low dose combination animals. Results indicate that high doses (megadoses) of the antioxidant-anticarcinogen vitamins C and E in combination with carefully selected other antioxidants possessing supplementary actions, are probably needed in order to achieve a sufficient prevention and treatment of malignant diseases.

Administration, Oral↗