Expression of Growth Hormone-Releasing Hormone and Its Receptor Splice Variants in Primary Human Endometrial Carcinomas: Novel Therapeutic Approaches.

Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various tumors, including endometrial carcinomas (EC). However, tumoral receptors that mediate the antiproliferative effects of GHRH antagonists in human ECs have not been fully characterized. In this study, we investigated the expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors (GHRH-R) in 39 human ECs and in 7 normal endometrial tissue samples using RT-PCR. Primers designed for the PCR amplification of mRNA for the full length GHRH-R and SVs were utilized. The PCR products were sequenced, and their specificity was confirmed. Nine ECs cancers (23%) expressed mRNA for SV1, three (7.7%) showed SV2 and eight (20.5%) revealed mRNA for SV4. The presence of SVs for GHRH-Rs could not be detected in any of the normal endometrial tissue specimens. The presence of specific, high affinity GHRH-Rs was also demonstrated in EC specimens using radioligand binding studies. Twenty-four of the investigated thirty-nine tumor samples (61.5%) and three of the seven corresponding normal endometrial tissues (42.9%) expressed mRNA for GHRH ligand. Our findings suggest the possible existence of an autocrine loop in EC based on GHRH and its tumoral SV receptors. The antiproliferative effects of GHRH antagonists on EC are likely to be exerted in part by the local SVs and GHRH system.

Intention-to-Treat Analysis of Radical Trachelectomy for Early-Stage Cervical Cancer With Special Reference to Oncologic Failures: Single-Institutional Experience in Hungary.

OBJECTIVE: The aim of our study was to evaluate clinical and pathological data in order to draw eligibility criteria for oncologically sufficient radical trachelectomy (RT) in early-stage cervical cancer. Reviewing all cases of attempted RT performed at our unit, we focused attention on prognostic indicators of the need for additional oncologic treatment following RT. The analysis was extended by extensive literature review to include previously published cases of oncologic failures. METHODS: The authors retrospectively analyzed data of patients who underwent RT at the Department of Obstetrics and Gynecology, University of Debrecen. Electronic records and case notes of RT cases were reviewed to determine the incidence of abdominal and vaginal route, distribution of clinicopathologic data, and follow-up results of individual cases. Individual procedures were categorized as oncologically insufficient if additional oncologic treatment was necessary following RT. Theoretical eligibility criteria for RT in early-stage cervical cancer were determined retrospectively by selecting prognostic features that were associated with oncologic insufficiency from clinicopathologic indicators of the complete series. RESULTS: Twenty-four cases of RT were performed by the authors, 15 vaginal RTs with laparoscopic pelvic lymphadenectomy and 9 abdominal RTs with open pelvic lymphadenectomy. Fifteen of 24 cases proved oncologically sufficient. Three cases required immediate conversion to radical hysterectomy because of positive sentinel nodes and/or positive isthmic disc on frozen section. In further 5 cases, final pathology results indicated additional oncologic treatment, that is, radical hysterectomy (n = 2), chemoradiotherapy (n = 2), or chemotherapy (n = 1). One patient among immediately converted cases and another 3 among those who required additional oncologic treatment died of their disease later. There were no other cases of recurrences over a median follow-up of 34 months (range, 12-188 months). Factors that may predict oncologic insufficiency of RT were stage IB1 or greater, tumor size of greater than 2 cm in 1 dimension or greater than 15 mm in 3 dimensions, G3, nonsquamous/adeno histological type, stromal invasion of greater than 9 mm, and lymphovascular space involvement in the primary tumor. CONCLUSIONS: Most cases of oncologically insufficient RTs have significant risk features that can be identified preoperatively. There is a need for more clinicopathologic data on oncologic failure of RT cases in order to improve patient selection.

[Proposal for the modernization of cervical screening procedure in Hungary]. / Javaslat a hazai méhnyakszurési eljárásrend korszerusítésére.

Two main considerations played roles in creation of new cervical screening system. One was the proven fact that high-risk human papilloma virus infection plays a role in the development of cervical cancer and pre-cancerous lesions. The other was the implementation of the HPV infection's biological behavior in the new screening strategy. The new screening procedure faithfully reflects the cervical carcinogenesis. An organised, population-based and age differentiated screening method could increase attendance of screening and could decrease the possibility of interval cancer rate due to increased sensitivity. Orv Hetil. 2017; 158(52): 2062-2067.

Sequence variation of human papillomavirus type 31 long control region: phylogenetic and functional implications.

About one-third of human papillomavirus (HPV) types infect the anogenital tract. High-risk genital HPV types (such as HPV 16, 18, 31, 33, and 35) are linked causally to the development of cervical cancer. The long control region (LCR) of the HPV genome regulates the replication and transcription of the viral genome. In this study, the functional significance of nucleotide sequence variation within the LCR of HPV 31 was investigated. The LCR was amplified by polymerase chain reaction (PCR) from 41 HPV 31 positive cervical samples of Hungarian women. A phylogenetic tree constructed from the nucleotide sequences of the LCR variants revealed the presence of three intratypic variant lineages of HPV 31, in accordance with previous results. In order to explore the functional consequences of sequence variation in the LCR of HPV 31, selected LCR variants were cloned into a luciferase reporter vector, transfected into C33-A cells and tested in luciferase reporter assays. Significant differences were found between the transcriptional activities of HPV 31 LCR variants belonging to different variant lineages. As the LCR is governing the transcription of the E6 and E7 oncogenes, the differences in the transcriptional activities of LCR variants may be associated with differences in their oncogenic potential.

Treatment patterns, health care utilization, and costs of ovarian cancer in Central and Eastern Europe using a Delphi panel based on a retrospective chart review.

OBJECTIVE: Despite the considerable disease burden of ovarian cancer, there were no cost studies in Central and Eastern Europe. This study aimed to describe treatment patterns, health care utilization, and costs associated with treating ovarian cancer in Hungary, Poland, Serbia, and Slovakia. METHOD: Overall clinical practice for management of epithelial ovarian cancer was investigated through a 3-round Delphi panel. Experts completed a survey based on the chart review (n = 1542). The survey was developed based on clinical guidelines and the International Federation of Gynecology and Obstetrics Annual Report. Means, ranges, and outlier values were discussed with the experts during a telephone interview. Finally, consensus estimates were obtained in face-to-face workshops. Based on these results, overall cost of ovarian cancer was estimated using a Markov model. RESULTS: The patients included in the chart review were followed up from presurgical diagnosis and in each phase of treatment, that is, surgical staging and primary surgery, chemotherapy and chemotherapy monitoring, follow-up, and palliative care. The 5-year overall cost per patient was €14,100 to €16,300 in Hungary, €14,600 to €15,800 in Poland, €7600 to €8100 in Serbia, and €12,400 to €14,500 in Slovakia. The main components were chemotherapy-associated costs (68%-74% of the total cost), followed by cost of primary treatment with surgery (15%-21%) and palliative care (3%-10%). CONCLUSIONS: Patients with ovarian cancer consume considerable health care resources and incur substantial costs in Central and Eastern Europe. These findings may prove useful for clinicians and decision makers in understanding the economic implications of managing ovarian cancer in Central and Eastern Europe and the need for innovative therapies.

[The emotions of oncologists]. / Az onkológusok érzelmei.

Emotions are parts of organizational reality to an ever increasing extent. Importantly, they are not just tools in the hand of healthcare workers to achieve better physician / healthcare professional-to-patient interactions but intrinsic processes and characteristics with psychic, cognitive and somatic actions. For a thorough investigation of the issue, a PANAS-X questionnaire was used to examine the emotions of 187 physicians and other healthcare professionals, all engaged in oncology, in 2009. The research succeeded in exploring the overall emotional state oncology professionals had assumed in relation with their job as well as enabled the authors of this study to draw the respondents' emotional map and assess their fundamental emotional attitudes. Furthermore, the authors managed to identify groups of respondents that had felt more intense positive, and/or less intense negative emotions that are socially accepted than others. They included those of senior experienced oncologists, males, individuals with families, childless individuals, ward workers, and skilled professionals. According to the findings, the range of emotions an oncologist experiences / feels intently during his everyday work is dependent upon a great number of factors.

Multimodal hyperspectroscopy ­ the use of digital technology in cervical cancer screening / Multimodális hiperspektroszkópia - elorelépés a digitális technológia felé a méhnyakszurésben.

Összefoglaló. Bevezetés: Bevezetés: A citológiai alapú méhnyakrákszurés átmeneti kategóriáinak optimális menedzselése a humán papillomavírus (HPV) szurése és tipizálása ellenére jelenleg is kihívás. Vizsgálatunk célja a modern cervixspektroszkópiának (multimodális hiperspektroszkópia - MHS), egy azonnali eredményt nyújtó, digitális technológiára épülo módszernek a vizsgálata volt a citológiai alapú méhnyakszurés találati biztonságának javítására. Betegek és módszer: Vizsgálatainkat 208, 18 és 75 év közötti nobeteg bevonásával végeztük, akiknél már indikálásra került valamely, a méhnyakon végzendo mutét, citológiai eredményük rendelkezésre állt (a HPV-tesztet, amennyiben nem történt meg, elvégeztük), valamint valamennyi betegnél elvégeztük a mutét elott az MHS-vizsgálatot. A szövettani mintavétel 166 betegnél történt meg. Eredmények: A citológiai vizsgálatot (az összes betegre tekintve) magas álpozitív arány jellemezte (69,28%), amely megfigyelések mindenképpen utalnak az újabb komponens alkalmazásának igényére a triázsban. Az összes citológiai kategóriára nézve az MHS-eredmények közül kiemelendo az álnegatív leletek rendkívül alacsony aránya (3/166 = 1,8%), mely a HPV-teszt esetén ennél magasabb volt (11/165 = 6,66%). A spektroszkópiás vizsgálat álpozitív aránya ugyanakkor kedvezotlenebbnek bizonyult (91/166 = 54,81%) a HPV-vizsgálat álpozitív arányánál (40/165 = 24,24%). Az atípusos laphámsejt (ASC-US/ASC-H) citológiai kategória esetén a spektroszkópia álnegatív eredményeinek aránya (3/126 = 2,38%) szintén kedvezobb volt, mint a HPV-vizsgálaté (9/126 = 7,14%). A cervicalis intraepithelialis neoplasia-2 vagy súlyosabb fokozatú hámelváltozások azonosításában a spektroszkópia szenzitivitása 94% (95% CI = 0,84-0,99), specificitása 22% (95% CI = 0,15-0,31), negatív prediktív értéke 90% (95% CI = 0,73-0,98), pozitív prediktív értéke 34% (95% CI = 0,26-0,43) volt (p = 0,00130). Következtetés: Az MHS fejlett innovatív technológián alapuló, azonnali eredményt adó vizsgálóeljárás, amely kiemelkedoen alacsony álnegatív eredménye miatt nagy segítséget nyújt a citológiai eltéréssel rendelkezo betegek további vizsgálatában. Orv Hetil. 2021; 162(20): 790-799. INTRODUCTION: Despite the use of human papillomavirus (HPV) testing, the management of the transitional categories of cytology-based screening still remains a challenge. The modern multimodal hyperspectroscopy (MHS) of the cervix is a novel digital technology based on artificial intelligence, providing an instant result in the assessment of cytology-based screening abnormalities. PATIENTS AND METHODS: 208 women (age 18-75) were enrolled. The patients already had cytology results and an operation on the cervix indicated at the time of inclusion. HPV and the hyperspectroscopy examination was performed pre-operatively. The pre-indicated operation was performed on 166 patients. RESULTS: Cytology-based screening alone (in the category of all patients) resulted in a high false-positive rate (69.28%). In this category, the MHS had an outstanding false-negative rate (3/166 = 1.80%) compared to the HPV (11/165 = 6.66%). The false-positive rate of the spectroscopy examination (91/166 = 54.81%) was higher than that of the HPV testing (40/165 = 24.24%). In the atypical squamous cell (ASC-US/ASC-H) category, the false-negative rate of the spectroscopy (3/126 = 2.38%) was also lower than that of the HPV test (9/126 = 7.14%). In the detection of high-grade abnormalities (cervical intraepithelial neoplasia 2 and worse), the spectroscopy had a 94% sensitivity (95% CI = 0.84-0.99), with a 22% specificity (95% CI = 0.15-0.31), an 90% negative predictive value (95% CI = 0.73-0.98), and a 34% positive predictive value (95% CI = 0.26-0.43) (p = 0.00130). CONCLUSION: In the case of cytological abnormality, the MHS provides an immediate result based on advanced digital technology, and because of its outstanding false negative rate it is a great aid and should be considered in the triage of such patients. Orv Hetil. 2021; 162(20): 790-799.

Age-specific prevalence of high-risk human papillomavirus infection in a Hungarian female population with positive cytology.

OBJECTIVE: Patients with positive screening results and persistence of high-risk human papillomavirus (HPV) infection represent the population at the highest risk for developing cervical cancer. To describe the epidemiology in this high-risk population, data were collected and analysed at the referral centre for patients with positive cytology. STUDY DESIGN: Between January 1997 and December 2002 the authors performed 3480 virus identifications using the Digene Hybrid Capture system in a female population with positive cytology at cervical cancer screening. Age-specific prevalence data were evaluated and compared between the age groups by running the chi(2) and Pearson chi(2) tests. Subgroup analysis was performed to estimate monthly clearance rates among eligible women with positive HR-HPV results. RESULTS: Low-risk (LR), high-risk (HR) and double infections were detected in 91 cases (2.6%), 1072 cases (30.8%) and 59 cases (1.7%), respectively. A significantly higher incidence of high-, rather than low-risk HPV infections was found in all age groups (p<0.001). Also, in this high-risk population with positive screening a significant decrease was detected in the prevalence of both high- and low-risk infections beyond 35 years of age (p<0.001). However, the decline in the HR-HPV types occurred later than in the case of LR infections, and HR-HPV was of remarkable frequency in the older age groups, which might represent both incidental and prevalent cases. Subgroup analysis for estimating monthly clearance rates revealed no significant differences between the various age groups and between women with various cytology results. CONCLUSIONS: In a population with positive cytology the prevalence of HPV drops with age while the relative frequency of high-risk HPV infection remains at the same level as that of the youngest age group.

[Study of career motivators affecting the emotional labour of health care professionals in oncology]. / Az onkológiai szakdolgozók érzelmi munkájának vizsgálata a pályaválasztási motivációk tükrében.

In the course of their everyday work health care professionals (HCPs) often have to change their true feelings. The literature labels this performance as emotional labor. This article is presenting data on the characteristics of HCPs' most endangered by the negative consequences of emotional labor. Our simple choice question survey was conducted at Debrecen University Medical Healthcare Center with the help of 50 oncology HCPs volunteers. Nearly 90% of the HCPs examined change their true feelings in the course of work. It is very difficult to classify those threatened by the negative upshot of this emotional labor. Due to our research we found appalling differences of work motivation that were tightly interconnected with the respondents' emotional labor and their perceived role/emotional expectations. We succeeded in establishing three clusters and defining each cluster's characteristics. Figures suggest that only somewhat more than the half of the HCPs is authentic professional helper, and 45% of them does not or only slightly perceive the patients' demands concerning their work. Therefore, it is important that the work environment does not only assist the work of HCPs by professional means, but along emotional dimensions as well.

Cell adhesion molecule profiles, proliferation activity and p53 expression in advanced epithelial ovarian cancer induced malignant ascites-Correlation of tissue microarray and cytology microarray.

INTRODUCTION: Peritoneal dissemination accompanied by ascites formation is common in epithelial ovarian cancer (EOC). Adhesion molecules are crucial in metastatic spread and the latter involves epithelial-mesenchymal transition (EMT). This study aimed at: (1) clarifying whether E-cadherin and ß-catenin expression and proliferative activity in metastatic ovarian cancer are inter-related; (2) Identifying possible correlations between cell adhesion molecular expression profiles, the proliferative activity and p53 expression of tumor cells and tumor grade and stage; (3) testing the cytology microarray (CMA) technique in analyzing metastasis formation. MATERIAL AND METHODS: Both tumorous and ascitic samples from 27 EOC patients were examined by using tissue microarray (TMA) and cytology microarray (CMA), respectively. CMA blocks were constructed using cores from each cell block of the ascitic specimens. Expression of E-cadherin, ß-catenin, Ki-67 and p53 was immunohistochemically detected both in TMA and CMA blocks. RESULTS: E-cadherin expression was higher in ascitic cells than in primary tumor cells (p = .294). ß-catenin expression was significantly lower in ascitic cells than in primary tumor cells (p = .006). Expression of Ki-67 was lower and expression of p53 was higher in primary tumors than in ascitic cells, for p53 the difference was significant (p = .001). Both Ki-67 and p53 expression elevated significantly in high-grade primary tumor cells and in ascites cells (p = .039, and p = .004, respectively). CONCLUSION: Epithelial-mesenchymal transition- mesenchymal-epithelial transition is suggested as the best descriptive term for our IHC observations which accompany increased proliferative activity of ascitic cells. The CMA method is an adequate and reliable method for the analysis of ascitic tumor cells disseminating from ovarian malignancies.

Nuclear ß-catenin positivity as a predictive marker of long-term survival in advanced epithelial ovarian cancer.

BACKGROUND: Classical features as histomorphology, grade, FIGO stage, and residual tumour mass have strong prognostic value in advanced epithelial ovarian carcinomas (AEOC). Most AEOCs are associated with early recurrence and poor overall survival (OS). Despite of early recurrence, general poor outcome, both high grade tumours or tumours with advanced FIGO stage at the time of diagnosis, in some of such cases, long-term survival (LTS) has been recorded . The aim of this study was to compare the utility of "classical" prognostic factors to molecular factors such as ß-catenin- E-cadherin-, mutated TP53-, and MiB-1 (Ki-67) labelling index determination in predicting long-term survival. METHODS: The expression of ß-catenin, E-cadherin, Ki-67, and p53 was determined by immunohistochemistry (IHC) in AEOC. Correlation was sought for between expression of these proteins and the status of classical features vis-á-vis overall survival of patients. Statistical evaluation of the data included Kaplan-Meier analysis, the log-rank test and Cox proportional hazards model. RESULTS: As expected, residual tumour size was an independent adverse prognostic factor for OS (univariate analysis: p=0.003, multivariate analysis: p=0.005). Nuclear expression of ß-catenin in advanced ovarian cancer of LTS patients proved to be not only an independent favourable predictor of OS (univariate analysis: p=0.025, multivariate analysis: p=0.041) but also showed strong correlation with platinum sensitivity and platinum re-induction. CONCLUSIONS: Translocation of stabilized ß-catenin from cytoplasm to the nucleus plays an important role in predicting platinum sensitivity. It also seems to support the chance for platinum re-induction in AEOC and thus enhances long-term survival.

Paclitaxel modifies the accumulation of tumor-diagnostic tracers in different ways in P-glycoprotein-positive and negative cancer cells.

AIM: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. METHODS: The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry. RESULTS: The (18)FDG measurements revealed that the glucose metabolic rate was significantly higher (p<0.01) in the P-gp-positive A2780AD cells than in the P-gp-negative cells. Paclitaxel (1-70microM) increased the (18)FDG uptake (up to 200%) of both P-gp-positive and P-gp-negative cells, whereas it did not modulate their (11)C-choline uptake. Paclitaxel reinstated the (99m)Tc-MIBI accumulation of the A2780AD cells (to 1500% of the control) in a concentration-dependent manner, while it increased the uptake of the P-gp-negative cells to a lesser extent (to a maximum of 200% of the control). CONCLUSION: Paclitaxel modifies the uptake of tumor-diagnostic tracers in both P-gp-dependent and independent manners. Interpretation of the multifactorial effects of paclitaxel may promote a correct in vivo diagnosis of P-gp-positive and P-gp-negative tumors.

Duration of HPV-associated risk for high-grade cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate the duration of high-risk HPV-associated cancer risk. STUDY DESIGN: Patients who had had a routine diagnostic Hybrid Capture Tube Test (HCT) due to squamous cell abnormalities of the uterine cervix were followed-up until the endpoint of histologically diagnosed cervical intraepithelial neoplasia (CIN). RESULTS: Six hundred and thirty-eight women were followed during a cumulative follow-up of 16,423 patient months. The adjusted relative risk associated with the positive HR-HCT test for high-grade CIN/52.0 (20.9-19.2)/ proved to be higher than that of the cytological atypia/5.44 (2.52-11.77)/. At the end of the 30 months of follow-up the crude and adjusted risks for CIN2+ were 214.3 (28.4-1615.7) and 196.7 (25.4-1525.2), respectively in the HPV 16/18 group, and after 30 months, the crude and adjusted RR decreased to 57.6 (10.4-318.9) and 29.2 (5.02-170.0). In the groups of other high-risk types and possibly high-risk types the general tendency was the same. However, new CIN2+ cases were not detected after the 30th month of follow-up in these later groups. CONCLUSIONS: HPV16/18 associated relative risk is nearly 200 times higher than that of the HPV negative population and an outstanding risk persists with duration of about 30 months. The risk is manifested in progression to high-grade CIN lesions mainly within a 2 years interval after the first detection of HPV 16/18 infection.

[The results of ovarian cancer therapy in the Hungarian Centers in 2002-2003]. / Petefészekrákos betegek kezelési eredményei a hazai centrumokban 2002-2003-ban.

UNLABELLED: Authors presented data of treatment results and course of disease in 487 ovarian cancer patients treated by primary surgery and paclitaxel-carboplatin combination chemotherapy between July 1, 2002 and December 31, 2003. PATIENTS: Most of our patients (87.8%) belonged to the age-group between 40-70 years. Distribution of their histological diagnosis was as 69.6% serous, 10.7% mucinous, 5.1% endometrial and 4.7% undifferentiated carcinoma. The grade distribution was found as 8.4% grade 1, 40.9% grade 2 and 35.9% grade 3. RESULTS: The primary surgery was evaluated as optimal in 41.7%, suboptimal in 37.3% and exploration was performed in 21.1%. Most patients started chemotherapy 20 days after surgery and 74.2% of them got six courses. During the evaluation period 61 intervallum laparotomies were performed, and resulted on 55.7% optimal debulking. Complete remission was found in 58.9%, and partial remission in 14.7% of patients. This treatment resulted on a complete remission in 40.9% at the follow-up of 12 months.

Quantitative and functional assay of MDR1/P170-mediated MDR in ascites cells of patients with ovarian cancer.

BACKGROUND: MDR1-associated P-glycoprotein-dependent multidrug resistance is a common cause of chemotherapy failure in patients with advanced ovarian cancer. Here, we describe a clinical method for simultaneously assessing the expression and function of the MDR1/Pgp in tumour cells from ascites of patients with malignant ovarian carcinoma. MATERIALS AND METHODS: Cells from ascites from 35 patients were collected. The expression and function of Pgp were detected by flow cytometry. For functional study, rhodamine 123 was used. RESULTS: Using the Pgp-specific UIC2 and MM6.15 antibodies, we demonstrated the presence of Pgp in 10-79% (38.9+/-20, 7; n=35) of the CA 125-positive cell subpopulations. The results of the functional assay showed strong correlation with the level of Pgp expression (r=0.976; p=3.2x10(-5)). CONCLUSION: Direct detection of the expression level and function of MDR1/Pgp in the ascites provide useful information for the more efficient treatment of malignant diseases by proper adjustment of the chemotherapeutic protocol.

Biphasic accumulation kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands.

AIM: To study the accumulation and washout kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) in MDR positive and MDR negative tumour cells and how this is modified by lipophilic P-glycoprotein ligands. METHODS: The tumour cells were incubated in the presence and absence of the ligands and the uptakes of 99mTc-MIBI, rhodamine 123 and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) were measured. RESULTS: The accumulation of 99mTc-MIBI in the tumour cells followed biphasic kinetics. Verapamil and cyclosporin A increased the membrane fluidity and significantly enhanced the 99mTc-MIBI uptake of the MDR negative cells, while the rhodamine 123 uptake was not affected. Verapamil significantly increased the uptake of rhodamine 123 and 18FDG but did not modify that of 99mTc-MIBI in the MDR positive cells. Cyclosporin A significantly increased the 18FDG uptake of the MDR positive and negative tumour cells; these effects were ouabain-sensitive. Depolarization of the cytoplasmic membrane, acidification of the extracellular medium and the administration of CCCP decreased the accumulation of 99mTc-MIBI and rhodamine 123 uptake in the tumour cells. CONCLUSIONS: Lipophilic P-glycoprotein ligands modified the biphasic accumulation kinetics of the 99mTc-MIBI uptakes of MDR negative and positive tumour cells in different and complex ways and could therefore mask the P-glycoprotein pump-dependent changes in tracer accumulation.

Role of human papillomavirus (HPV) testing in the follow-up of patients after treatment for cervical precancerous lesions.

OBJECTIVE: To evaluate the role of human papillomavirus (HPV) testing in post-treatment follow-up of patients after therapeutic excision of the cervix due to positive screening tests. STUDY DESIGN: A hospital-based retrospective analysis was performed with prospective collection of patient data of women screened for cervical cancer at a Gynecologic Outpatient Clinic. Patients after therapeutic excision due to positive screening results were identified and followed up with HPV testing and serial cytology. RESULTS: After 61 treatment for cervicalis intraepithelialis neoplasia (CIN), high-risk HPV infection was detected during the post-treatment follow-up at 18 cases (29.5%), 10 of them had persisting cytological atypia (positive predictive value (PPV): 56%), 5 developed CIN (PPV: 28%). When the HPV test was negative (43 patients) in the post-treatment period, neither CIN nor persisting cytological atypia developed (negative predictive value (NPV): 100%) during 1201 patient months (median 26 months). CONCLUSIONS: A negative HPV test eliminates the risk of recurrent disease after treatment for CIN.

The prevalence of the HPV 16 genome, integrated viral status and p53 genotype in cervical cancer population of north-eastern Hungary, the correlation with the established markers of tumour progression.

OBJECTIVES: To evaluate the prevalence of the HPV 16 integrated status and the p53 genotype in cervical cancer in north-eastern Hungary and their correlation with the established prognostic factors. STUDY DESIGN: Parallel with the routine histological examination, Southern blot hybridisation and multiplex PCRs were used to detect type/physical state of HPV DNA in primary tumours and in regional lymph nodes combined with p53 genotyping of 83 patients. RESULTS: 46.9% (39/83) prevalence rate of HPV 16 genome was found. The frequency of viral integration (76.9% in primary tumours and 95.2% in regional lymph nodes) and that of the p53Arg homozygous genotype (64.1%) proved to be higher than reported from other parts of the world. The HPV 16 integration and the p53 genotype, failed to correlate with the FIGO stage and lymphatic spread. CONCLUSION: The prevalence of the integrated status of the HPV 16 genome combined with homozygous p53Arg genotype is relatively high in Hungary. These factors however failed to show a strong correlation with the established markers of tumour progression.