Human papillomavirus infections among Hungarian female sex workers.

The purpose of this study was to assess the human papillomavirus (HPV) prevalence in cervical, oropharyngeal and anal samples of the high-risk population of Hungarian female sex workers (FSWs). HPV testing of swab specimens from FSWs (n = 34) using polymerase chain reaction (PCR) methodology was performed. Results were compared with control group (n = 52) matched for age. Questionnaires were used to obtain data regarding participants' sexual behaviour. Data were analysed using SPSS. HPV DNA was detected in at least one location in a great majority of FSWs (82.4%), compared with 46.2% of the general female population (P < 0.05). Both the cervical and the anal samples of sex workers showed higher infection rates than those of controls (64.7% vs. 34.6% and 50.0% vs. 15.4%, respectively, P < 0.05). High-risk HPV prevalence was also significantly higher in sex workers (55.9% vs. 25.0%, P < 0.05). A significantly higher proportion of FSWs had a history of genital warts (26.5% vs. 3.8%, P < 0.05). The results suggest that condom use may not result in adequate protection from HPV infection. The high infection rates among FSWs should be viewed as a priority group for HPV and cervical cancer prevention programmes since they are sources of HPV infection for the general population.

Mena, a new available marker in tumors of salivary glands?

Mena (mammalian Ena) is an actin regulatory protein involved in cell motility and adhesion. Based on its potential role in malignant transformation revealed in other organs, we analyzed the Mena expression in normal salivary glands (SG) and salivary tumors. Mena expression was determined in normal SG (n=10) and also benign (n=20) and malignant (n=35) lesions of SG. For the immunohistochemical staining we used the anti-Mena antibody. All normal SG and the benign lesions (10 pleomorphic adenomas, 10 Warthin's tumors) were Mena negative. Salivary duct carcinomas (n=5), carcinomas in pleomorphic adenoma (n=5), acinic cell carcinomas (n=5), squamous cell carcinomas (n=10) and high-grade mucoepidermoid carcinomas (n=2) were positive. The lymphomas (n=5) and low-grade mucoepidermoid carcinomas (n=1) were Mena negative. In one case the lymphoblastic cells stained positive for Mena. Some of the endothelial cells, in the peritumoral vessels, were Mena positive. To the best of our knowledge, this is the first study in the literature about Mena expression in salivary tumors. Our study suggests that Mena protein seems to play a role in malignant transformation and its intensity is correlated with the type and grade of tumor and also with vascular invasion. Its positivity in endothelial cells may suggest its potential role in tumor angiogenesis.

Retinal and renal vascular permeability changes caused by stem cell stimulation in alloxan-induced diabetic rats, measured by extravasation of fluorescein.

AIM: To determine whether treatment with the stem cell stimulator Olimpiq® Stem×Cell prevents increase of retinal and renal vascular permeability in alloxan-induced diabetic rats. MATERIALS AND METHODS: Two groups of Wistar rats were made diabetic by single intraperitoneal injection of Alloxan. The third, the control group, received vehicle alone. One diabetic group received Olimpiq® Stem×Cell treatment for 4 weeks. The permeability of the blood-retinal barrier (BRB) and renal vessels were measured by the extravasation of fluorescein-labeled bovine serum albumin. RESULTS: Six weeks subsequently to Alloxan injection, significantly elevated the tissue fluorescence, the renal vascular leakage and BRB breakdown was demonstrated in the diabetic group, compared to the nondiabetic group. Olimpiq® Stem×Cell treatment significantly reduced the BRB breakdown, tissue fluorescence, and vascular leakage. CONCLUSION: Olimpiq® Stem×Cell would be a useful choice of treatment for complications associated with increased vascular permeability of diabetes, such as retinopathy or nephropathy.

Incomplete knowledge--unclarified roles in sex education: results of a national survey about human papillomavirus infections.

The purpose of this study was to evaluate the awareness of human papillomavirus (HPV) infections both in male and female adults in Hungary. A self-administered, anonymous questionnaire was completed by 785 college students and parents between January and May, 2009. The results were analysed by gender and age. Participants' knowledge about HPV and HPV-associated conditions was relatively incomplete. One-third of the respondents had never heard about HPV prior to the survey. Almost half of the respondents (42%) thought that the only sexual way of spreading HPV was vaginal intercourse, while the role of skin-to-skin contact was disregarded (6%). More than one-third of the participants (38%) believed that condoms give full protection from HPV infection. Encouragingly, the majority of respondents (64%) were open to further information about sexually transmitted diseases. The most trusted sources of information were health professionals. When talking about children, parents attributed the major role in delivering information about sexually transmitted diseases to schools. Primary prevention through carefully planned educational programmes may further raise the awareness about HPV-associated conditions, thus reducing the comparatively high mortality of cervical carcinoma in Hungary.

Effects of artificial sweeteners on body weight, food and drink intake.

Artificial sweeteners are widely used all over the world. They may assist in weight management, prevention of dental caries, control of blood glucose of diabetics, and also can be used to replace sugar in foods. In the animal experimentation mice were given oral doses of water solutions of table top artificial sweeteners (saccharin, cyclamate based, acesulfame-K based, and aspartame) the amount of maximum Acceptable Daily Intake (ADI) ad libitum. The controls received only tap water with the same drinking conditions as the treated groups. The mice were fed chow ad libitum.We measured food intake and body weight once a week, water and solutions of artificial sweeteners intake twice a week. The data were analysed by statistical methods (T-probe, regression analysis).Consumption of sweeteners resulted in significantly increased body weight; however, the food intake did not change.These results question the effect of non-caloric artificial sweeteners on weight-maintenance or body weight decrease.

The immunohistochemical aspects of protein Mena in cervical lesions.

UNLABELLED: The proteins Ena/VASP (Enabled/Vasodilator-Stimulated Phosphoprotein) family is involved in the regulation of actin cytoskeleton which activity is very important for physiological tissue formation but is sometimes implied in pathological processes. In this study, we analyzed the immunohistochemical expression of Mammalian Ena (Mena), which is a member of this family, in the cervical intraepithelial neoplasia (CIN) and also in the cervical squamous cell carcinomas. We analyzed 30 cases with CIN (1, 2 and 3), and 10 squamous carcinomas. We used the EnVision system by LabVision. The Mena antibody, izotype mouse IgA, clone 21, provided by BD Biosciences. RESULTS: We observed that Mena was not expressed in the normal cervical squamous epithelium but its expression was increased in parallel with the increasing grade of CIN, with up-regulation upon transition to CIN3 and further to invasive carcinoma. This is the first study in the literature about Mena expression in cervical lesions.

Chemopreventive effect of Panax ginseng.

Asian ginseng (Panax ginseng C. A. Meyer) has been used in Chinese medicine for two thousand years. The root of ginseng contains several saponins (ginsenosides) which are biologically active compounds. Individual ginsenosides suppress tumor cell growth, induce cell differentiation, regulate apoptosis and inhibit metastasis formation. The aim of this study was to evaluate its chemo-preventive effects in an animal test model, through its regulatory effects on apoptosis and the cell cycle.The expression of genes (Bcl-2, Bcl-x and Cyclin D1) which affect apoptosis were examined, in different organs of animals which had consumed a ginseng-containing diet in the presence of a known carcinogen (DMBA). The pattern of gene expression was determined by Q-RT-PCR. The increase of antiapoptotic gene expression after carcinogenic exposure was suppressed by consumption of ginseng which promoted apoptosis.The population is exposed to numerous physical and chemical insults in the modern environment and these include compounds which are known carcinogens. Research has shown that it is possible to interfere with the multi-step process of carcinogenesis through the use of compounds with chemo-preventive effects, such as the inhibition of the activation of antiapoptotic genes.These results support the efficacy of ginseng-containing diets and dietary supplements in the prevention of cancerous diseases.

The expression of cytoskeleton regulatory protein Mena in colorectal lesions.

The actin regulatory proteins Ena/VASP (Enabled/Vasodilator stimulated phosphoprotein) family is involved in the control of cell motility and adhesion. They are important in the actin-dependent processes where dynamic actin reorganization it is necessary. The deregulation of actin cycle could have an important role in the cells' malignant transformation, tumor invasion or metastasis. Recently studies revealed that the human orthologue of murine Mena is modulated during the breast carcinogenesis. In our study, we tried to observe the immunohistochemical expression of mammalian Ena (Mena) in the colorectal polyps and carcinomas. We analyzed 10 adenomatous polyps (five with dysplasia) and 36 adenocarcinomas. We used the indirect immunoperoxidase staining. BD Biosciences have provided the Mena antibody. We observed that Mena was not expressed in the normal colorectal mucosa neither in polyps without dysplasia, but its expression was very high in polyps with high dysplasia. In colorectal carcinomas, Mena marked the tumoral cells in 80% of cases. In 25% of positive cases, the intensity was 3+, in 60% 2+ and in the other 15% 1+. The Mena intensity was higher in the microsatellite stable tumors (MSS) and was correlated with vascular invasion, with intensity of angiogenesis marked with CD31 and CD105 and with c-erbB-2 and p53 expression. This is the first study in the literature about Mena expression in colorectal lesions.

The organisation and results of first screening round of the Hungarian nationwide organised breast cancer screening programme.

BACKGROUND: The aim of this paper is to give an overview of organisational issues of the Hungarian nationwide organised breast cancer screening programme and to provide the results of the first screening round of the programme for the years 2002-2003. PATIENTS AND METHODS: Data were derived from the financial database of the National Health Insurance Fund Administration covering the period 2000-2003. Women who underwent mammography screening were included into the study. RESULTS: Uptake of the organised screening programme in 2002-2003 was 45.09%, while the recall rate was 7.23%. Malignant cases represented 65.38% of total surgeries and 0.36% of total number of screened women yielding a cancer detection rate 3.6 per 1000 screened women. Malignant cases of 10.78% were identified as ductal carcinoma in situ, while 89.22% was invasive cancer. Benign to malignant ratio was 0.54 : 1. CONCLUSION: There is therefore an urgent need to closely monitor performance and to review programme policies and procedures with the aim of increasing both the participation rate and the proportion of women eligible to attend screening.

Early effects of transplatin on oncogene activation in vivo.

The aim of the study was to investigate the early effect of Transplatin (the stereo-isomer of Cisplatin) on oncogenes in inbred CBA/Ca mice. Cisplatin is commonly used for the treatment of squamous cell carcinomas of the head and neck. Cisplatin has a strong oncogene activation effect compared to the structural analogue Transplatin. Body weight equivalent amounts of a human dose of Transplatin were administered intra-peritoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the expressions of c-myc, Ha-ras and p53 genes were examined. Investigation of early changes showed no significant overexpression compared to Cisplatin, which had a significant effect on oncogene expression in the "short-term" in vivo test system.

Early effects of different cytostatic protocols for head and neck cancer on oncogene activation in animal experiments.

In vivo investigations on oncogenes and onco-suppressor genes may provide new findings on the potential carcinogenic effects of various cytostatic protocols inducing secondary tumours of the head and neck. Further surgeries are often necessary due to regional recurrence after the Cisplatin-supplemented BVM (Bleomycin, Vincristine, Methotrexate) protocol in the treatment of human head and neck tumours. Our earlier studies have illustrated the carcinogenic and mutagenic potential of Cisplatin. The effect of Cisplatin on the alteration of different onco- and suppressor genes has also been proven. Our present study aimed at investigating the early effects of the BVM and the CFu (Cisplatin, 5-Fluorouracil) protocols on early oncogene and tumour suppressor gene expressions in mice. Body weight equivalent amounts of cytostatics were administered intraperitoneally to 6- to 8-week-old, inbred, female CBA/Ca mice. Twenty-four, 48 and 72 hours after the treatment, RNA was isolated from the target organs and the quantitative expression of c-myc, Ha-ras and p53 genes were examined. The protocols caused detectable changes. A "short-term" in vivo test, the 24-hour examination of gene expression, is suitable for detecting early effects of carcinogen exposure. The alterations of gene expression, caused by the Cisplatin-containing protocol, draw attention to the probable role of Cisplatin in the development of regional recurrence and to the possibility of prevention.

Copy number of cancer genes predict tumor grade and survival of pancreatic cancer patients.

Pancreatic cancer is on the increase. While means of early diagnosis are being sought, it continues to present late. Prognostication is based on patient and tumor characteristics, including expression or mutation of cancer-related genes. Few studies have examined the impact of the amplification of these genes on the outcome of pancreatic cancer. We have now used a non-radioisotopic slot-blot technique to relate gene copy numbers of p53, c-myc and K-ras to tumor grade and survival. Outcomes were corrected for patient characteristics, tumor location and TNM staging. The Kaplan-Meier test for likelihood of survival showed that increase in copy number of the two oncogenes and loss of p53 were associated with non-significant reduction in survival. When these variations in cancer gene copy numbers were, however, examined by logistic regression analysis in the context of patient and tumor characteristics, survival was negatively related to K-ras amplification (p = 0.0291). Tumor grade, but not survival was positively related to loss of p53 gene copy (p = 0.0131) as well as c-myc amplification (p = 0.0248). Thus using a simple non-radioisotopic technique for the detection of cancer gene copy number in association with patients and disease characteristics, we could predict survival on the one hand and tumor behavior on the other. Such information could be used to plan initial and follow-up therapy.

C-myc amplification and cluster analysis in human gastric carcinoma.

The tumour samples ot 23 patients (9 male, 14 female, aged 28-85) were randomly selected for the study. DNA was isolated from paraffin embedded tissue for quantitative dot-blot hybridization, in order to determine the amplification values for the c-myc and K-ras oncogenes. The clinical and histological parameters studied were as follows: grade, TNM staging system, Lauren's histological type, localization and the severity of the disease. Amplified c-myc was found in 6 cases. Amplification was concomitant with c-myc overexpression detected with immunohistochemical staining. The amplification--9.1-fold on the average (ranging from 2.12 to 18.2) was significantly associated with the presence of distant metastasis (corr. coeff.: 0.5623, p < 0.01), but with none of the other parameters. No case with K-ras amplification was recorded. The result of the multivariate cluster analysis proved that age was the decisive factor in the segregation process. This age-related distribution (69 vs. 40, p < 0.001), however, did not coincide with either the incidence of distant metastasis or c-myc amplification.

Long-term effects of 1-nitropyrene on oncogene and tumor suppressor gene expression.

Late changes in the expression of oncogenes and tumor suppressor genes following carcinogenic exposure were examined in lung, liver and kidney. 1-Nitropyrene (1-NP), which is a high-risk exposure factor in urban and industrial zones, was used as a carcinogenic agent. c-myc, Ha-ras and p53 gene expression was investigated after administration of a single dose of 1-NP to sensitive CBA/Ca mice in lung, liver and kidney for one year. One week after a single dose 1-NP administration, the expression of p53 was elevated in the liver, but, decreased in the lung and kidney. There was no increase in the expression of c-myc or Ha-ras genes at that time. One month after the administration of the 1-NP, the expression of p53 was increased in the kidney while the expression of Ha-ras and p53 was elevated in the liver. There was no significant difference in gene expression between the treated and control animal groups at any of the investigated periods except for the above-mentioned organs and at the end point of the investigation. According to the literature, 1-NP and its metabolites remain at high concentrations in the kidney, liver and lung. The concentration of the carcinogenic agent and the expression of the studied genes did not seem to correlate with each other in this experiment.

[Investigation of oncogene amplification or deletion, and oncoprotein expression in papillary thyroid cancer] / Onkogén-amplifikáció, illetve -deléció és onkoprotein-expresszió immunhisztokémiai vizsgálata papilláris pajzsmirigyrákban.

AIM: Assessment of occurrence and possible prognostic significance of c-myc and Ha-ras amplification, p53 deletion and overexpression of cyclin D1, p53 and p21 in papillary thyroid cancer. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor tissue from 24 patients were investigated. Dot-blot DNA hybridization was used to detect oncogene amplification or deletion. The expression of oncoproteins was determined by immunohistochemical method. RESULTS: In our samples neither Ha-ras amplification nor p53 deletion were found. Low c-myc amplification (mean: 2.55) occured in 4 cases (17%). p53 protein was detected in 16 samples (66.6%), with p21 expression (chi(2)=7.02, p<0.01) in 6 cases (25%). The p53 expression did not influence the tumor fenotype. Cyclin D1 overexpression was found in 12 cases (50%), it was often associated with p21 expression (chi2=10.1, p<0.001) and in inverse relation to the tumor lymphocytic infiltration (chi(2)=5.35, p<0.05). Increased expression of estrogen receptor was shown in 4 cyclin D1 positive samples (17%). CONCLUSIONS: The p53 detected in our study is likely not to be mutant protein in all cases because its presence was associated with p21 expression that the mutant protein cannot induce and also it did not mean more aggressive tumor phenotype. The connection of cyclin D1 overexpression with the lymphocytic infiltration of the tumor suggests that the increased expression of cyclin D1 means poor prognosis. The coexpression of cyclin D1 and p21 raises the modulative character of the p21 protein, thought to be a tumor suppressor originally, but we find a CDK-independent, estrogen receptor mediated effect of cyclin D1 more likely, which has been described in breast cancer and is also proved by the coexpression of cyclin D1 and estrogen receptor detected here.

[Stomato-oncological screening examinations: possibilities for early diagnosis] / Stomato-onkológiai szûrôvizsgálatok: a korai diagnosis lehetôségei.

The dramatic increase in the mortality of lip- and oral cancers in Hungary in the last decades points to the importance of primary and secondary prevention. Stomato-oncological screening examinations belong to the latter category, and might represent useful tools in the early diagnosis and treatment of oral carcinomas and precancerous lesions. The aim of the paper is to review the methods, results and effectivity of stomato-oncological screening examinations in Hungary. Between 1962 and 2000 nine screening examinations were performed: one on a population sample, one in an industrial setting, four connected to X-ray lung-screening examinations (one with the help of a mobile unit), one on voluntary persons, one on high risk people (homeless), one in general medical practice. Among these, in the last five years, in the course of the stomato-oncological examination of 17325 individuals, oral carcinoma has been found in 0.12%, and oral precanceroses in 2.63%. Although the general dentist is obliged by law to perform a stomato-oncological examination on the patients appearing in the practice, unfortunately, about 50-to-90% of the population does not visit a dentist regularly. The regular examination of these - high risk - groups by the help of the above methods, including the help of general medical practitioners is highly recommended.

[Mortality of breast cancer and frequency of mammography in Hungary]. / Emlórákos halálozás és mammográfiás vizsgálatok száma Magyarországon.

The Hungarian breast cancer mortality is above the European average. Because of the lack of effective primary prevention, the control has to be based on the improving results of treatment which is much more successful in the case of early detected cancers. Beyond the patients collaboration and the application of the recommended diagnostic protocols, the population based screening programs have high importance in achieving earlier diagnosis. This study aimed to describe the regional differences of mammography's application as an indicator of diagnostic and screening performance. The records of the outpatient services' reports containing the code for native X-ray examination of the breast were analysed in the period of 01/07/1998 to 30/04/2000. The age specific and the age standardised relative frequencies of mammographical examination were determined for the Hungarian counties and Budapest. The observed age specific frequency of mammography for the whole country was 17, 21, 11 and 4% for the age group of 40-49, 50-59, 60-69 and 70-74 years, respectively. The lowest observed values were 10 times smaller than the highest ones in every studied age group. The age standardised relative frequency of mammographical examination was higher than the national average in Tolna (2.52), Borsod-Abaúj-Zemplén (1.48), Zala (1.41), Baranya (1.33), and Csongrád (1.27) counties and in Budapest (1.35). The described data demonstrates that the Hungarian practice of mammography is far from acceptable considering the frequency of application. On the other hand, it was also explored that serious geographical differences exist within the country. It seems that there are providers that can achieve relative successes in diagnosing the breast cancers in as early stage as it is possible. The evaluation and utilisation of the experiences of these providers could increase the efficacy of interventions organised to improve the Hungarian epidemiological status of breast cancer.

Changes in expression of onco- and suppressor genes in peripheral leukocytes--as potential biomarkers of chemical carcinogenesis.

An animal model was developed to investigate the expression of two oncogenes (c-myc, Ha-ras) and a suppressor gene (p53) as early markers of the effects of carcinogenic exposure and/or tumourigenesis. Inbred Long-Evans rats were treated with 7,12-dimethylbenz(a)anthracene and the transient/permanent gene expressions were measured after 24 and 48 hours by dot blotting in potential target tissues (lung, liver, lymph nodes, kidneys, spleen) and in peripheral blood leukocytes. The aim of the study was to test blood leukocytes, as surrogate tissue, showed similar expression patterns of the selected genes following carcinogenic exposure. c-myc did not prove to be an applicable early biomarker due to the lack of or low level of its expression. However, remarkable of early elevations were detected in the expression signals of Ha-ras and p53.

Association between gastric cancer mortality and nitrate content of drinking water: ecological study on small area inequalities.

The carcinogenic feature of N-nitroso compounds has been well established. Similarly, the transformation of ingested nitrate to N-nitroso compounds in the stomach has been thoroughly documented, nevertheless nitrates' carcinogenic effect has not been proved convincingly in human. The present study was aimed to investigate a population of small villages provided by drinking water with high and widely variable nitrate content (72 mg/l median, 290.7 mg/l 95-percentile concentration). Empirical Bayes estimates for settlement-specific age-, sex-, and year-standardised mortality ratios of gastric cancer (GC) were related to the settlement level average nitrate concentrations in drinking water controlling for confounding effects of smoking, ethnicity and education. The log-transformed average nitrate concentration showed significant positive association with stomach cancer mortality in linear regression analysis (p = 0.014). The settlements were aggregated according to the nitrate concentration into 10-percentile groups and the standardised mortality ratios (SMRs) were calculated. Those groups with higher than 88 mg/l average nitrate concentration showed substantial risk elevation and the log-transformed exposure variables proved to be significant predictors of mortality (p = 0.032) at this level of aggregation also. The association seemed to be fairly strong (r2 = 0.46). Although this investigation constituting an ecological study has certain limitations, it supports the hypothesis that the high level of nitrate in drinking water is involved in the development of GC.

1-Nitropyrene induces elevated expression of oncogenes and tumor suppressor genes 24 hours after treatment in CBA/Ca mice.

In an earlier experiment we found that 1-nitropyrene treatment causes an increase in the expression of certain onco/suppressor genes in different organs of CBA/Ca mice. In order to further study the kinetics and significance of these gene expression changes, we determined the effect of 1-nitropyrene treatment on the expression of c-myc, p53, Ha-ras, N-ras, and Ki-ras genes, 24 hours after treatment. Expression of the ras family did not change during the studied interval, while elevated expression of c-myc and p53 genes was observed in the spleen, bone marrow and lymph nodes (only c-myc in the latter). The results suggest a different pattern for the involvement of the ras genes in 1-nitropyrene-caused carcinogenesis, and also underlines the differences in the organ specificity of chemical carcinogens in humans and in experimental animals. In the present study, we also confirmed the in vivo applicability of early gene expression changes as biomarkers of carcinogenic exposure.