Electronic Library of Scientific Literature


Volume 44 / No. 2 / 1997

Increasing occurrence of oropharyngeal cancers among males in Slovakia

I. Pleško, A. Obšitníková, V. Vlasák

National Cancer Registry of Slovakia, National Cancer Institute, 833 10 Bratislava, Slovakia;
Cancer Research Institute of the Slovak Academy of Sciences, Bratislava, Slovakia

The gradual decline of oropharyngeal cancers in postwar period was followed by their rapid increase during recent two decades among males in Slovakia. Overall age-adjusted incidence rates of cancers of oral cavity and pharynx increased from 4.5 in 1968-1970 to 20.7 in 1990-1992 and corresponding mortality rates from 2.8 to 14.0 per 100 000 males. Oropharyngeal cancers have recently accounted for 6.5% of all newly diagnosed cancers yearly and present the fourth most frequent cancer site among males in this country. The cancers of tongue, floor of mouth, oropharynx and hypopharynx are responsible for the dramatic increase of this combined site in males. The culmination of the age-specific incidence and mortality rates of these cancers in the age groups 40-59 confirms the leading role of middle-aged men in their increase and dominant position. The occurrence of cancers of major salivary glands and nasopharynx in males, as well as the incidence and mortality rates of all oropharyngeal cancers in females remained very low and an unchanged (less than 1% of total). Increasing and extremely high incidence and mortality rates from oropharyngeal cancers among males in Slovakia require more effective primary prevention, above all substantial reduction of smoking.

Key words: Oropharyngeal cancer, incidence, Slovakia.
str. 77-83

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Expression of 65-kDa oncofetal protein in experimental hepatoma after anticancer therapy

M. Mirowski, M. Rozalski, U. Krajewska, M. Hanausek, R. Wierzbicki

Department of Biochemistry, Institute of Environmental Research and Bioanalysis, Medical University, 90-151 Lodz, Poland;
The University of Texas M D. Anderson Cancer Center, Science Park-Research Division, Smithville, TX, USA

We have tested the expression of a 65-kDa oncofetal protein (p65) after combined treatment with menadione and methotrexate in hamsters transplanted with Kirkman-Robbins hepatoma. The treatment of tumor-bearing animals with these compounds significantly inhibited both the tumor development and the expression of p65. This inhibition in tumor tissue was calculated from densitograms of Western blots. The inhibition of p65 expression was also confirmed in the serum of hepatoma bearing animals by using solid-phase radioimmunoassay (RIA) to quantify the specificity of polyclonal antibodies to fetal p65 molecules. Additionally, p65 was shown to localize both in cytoplasm and in the nuclear extracts prepared from hepatoma tissue.

Key words: p65 oncofetal protein, polyclonal anti-p65 antibody, menadione, methotrexate.
str. 85-89

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Increased efficacy of aphidicolin killing of human neuroblastoma cells in vitro by encapsulation in liposomes

J. Cinatl, Jr., P. Hernáiz Driever, J. Cinatl, D.G. Rückert, H.O. Gümbel, H. Rabenau, B. Kornhuber, H.W. Doerr

Centre of Hygiene, Institute for Medical Virology, J.W. Goethe-University, Frankfurt a.M., FRG;
Centre of Pediatrics, J.W. Goethe-University, 60590 Frankfurt a.M., FRG;
Centre of Experimental Surgery, E. Karl University, Tübingen, FRG;
Centre of Ophthalmology, J.W. Goethe-University, Frankfurt a.M., FRG

Aphidicolin is a tetracyclic diterpene antibiotic which kills human neuroblastoma cells (NB) in vitro while it has no significant effect on the viability of different human cell types including normal embryonal cells. In the present study, we tested whether aphidicolin encapsulated in liposomes kills NB cells with the efficacy superior to that of unencapsulated aphidicolin. The drug was entrapped in vesicles composed of phosphatidylcholine, phosphatidylserine and cholesterol in a molar ratio of 83 : 5 : 12. The treatment with encapsulated aphidicolin at a concentration of 200 nmol for 5 days killed all cells of three human NB cell lines. In contrast, at least 30% of the cells survived 5 days of treatment with 200 nmol unencapsulated aphidicolin. The results showed that aphidicolin killing of human NB cells may be increased by encapsulation in liposomes.

Key words: Aphidicolin, liposomes, neuroblastoma, cell killing.
str. 91-95

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Preclinical comparison of bis-diketopiperazine-propane (dexrazoxane) and bis-diketopiperazine-ethane (antimet) on the adriamycin-cardiotoxic effect

J. Kvìtina, V. Grossmann, Z. Svoboda, M. Šafáøová

Institute of Experimental Biopharmaceutics, Joint Laboratory of PRO.MED.CS, Prague; Czech Academy of Sciences, 50 002 Hradec Králové, Czech Republic

A cardiotoxic effect induced by adriamycin (by repeated i.v. administration to experimental rats in 7-day intervals of administration) begins to be manifested in the ECG record by prolongation of the SalphaT segment between days 14 and 20, on day 30 it is statistically significant. By means of this index, the known protective effect of dexrazoxane (the preparation cardioxan) against adriamycin cardiotoxicity has been successfully confirmed in a four-week experiment. A comparative study (using the identical frequency of the dosing scheme and SalphaT segment as the decisive parameter) has revealed that antimet - as another original substance of the diketopiperazines group - also involves (though less significantly) protective effects against the toxic action of adriamycin.

Key words: Adriamycin, bis-diketopiperazine derivatives, cardiotoxicity.
str. 97-99

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Ascorbic acid and 6-deoxy-6-chloro-ascorbic acid: Potential anticancer drugs

M. Osmak, I. Kovaèek, I. Ljubenkov, R. Spaventi, M. Eckert-Maksiæ

Department of Molecular Medicine, Ruðer Boškoviæ Institute, 10 000 Zagreb, Croatia;
Institute of Public Health, Zagreb, Croatia;
INAVINIL, Kaštel-Suæurac, Croatia

The role of ascorbic acid (AA) in prevention and suppression of carcinogenesis has been known for a long time. It was also found that AA may inhibit the growth of some tumor cells in vitro and in vivo. We examined the influence of ascorbic acid and 6-chloro-6-deoxy ascorbic acid (6-Cl-AA) on the growth of various human cell lines: lung fibroblasts (Hef), ovarian adenocarcinoma (OVCAR), colon adenocarcinoma (HT-29), laryngeal carcinoma (HEp2) cells, HEp2 cells resistant to vincristine (HEp2VA3), cervical carcinoma (HeLa) cells, HeLa cells resistant to cisplatin (Helacis), breast adenocarcinoma (SK-BR-3) cells, and SK-BR-3 resistant to doxorubicin (SK-BR-3-Dox), as well as mouse fibroblasts L929, mouse melanoma B16 (Mel B16) cells and Chinese hamster fibroblasts (V79). Both drugs arrested the growth of : HeLa, SKBR3, SK-BR-3-Dox, L929, and Mel B16 cells, but did not influence the growth of others: Hef, OVCAR, HEp2, HEp2VA3 and V79. 6-Cl-AA suppressed more the proliferation of HeLacis, SK-BR-3-Dox and Mel B16 cells than AA, while AA was active only against HT-29 cells. Inhibitory effect of 6-Cl-AA was confirmed by the in vivo experiments on solid melanoma B16 tumors. Our results indicate that AA and 6-Cl-AA could serve as potential antitumor agents, especially against some tumor cells resistant to chemotherapy.

Key words: Ascorbic acid, anticancer drugs, cell cultures, drug-resistance.
str. 101-107

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The radiosensitivity of human malignant melanomas evaluated by cytokinesis-block micronucleus assay

M. Wide³, M. Dobrut, B. M¹ka, B. Lubecka, A. Pluciennik

Laboratory of Radiobiology;
Clinic of Oncological Surgery, Gliwice, Poland;
Department of Histopathology, Maria Sk³odowska-Curie Memorial Institute, 44-101, Gliwice, Poland

Cytokinesis-block micronucleus assay (CB-MNA) was applied for comparison of radiation sensitivity of 25 human malignant melanomas in primary culture. Cells obtained from tumor specimens were irradiated (0-4.Gy) on dishes, incubated with cytochalasin B (2 µg/ml) to block cytokinesis, stained in situ and micronuclei (MN) scored in binucleate cells (BNC). Proportions of BNC in nonirradiated controls after fixed time of incubation (96 h) ranged from 2.3 to 38% indicating great differences (C.V. = 74%) in proliferative activity among tumors evaluated. No correlation was observed between proliferative activity and susceptibility of cells to induction of MN by radiation. The great inter-tumor heterogeneity was observed in respect of radiation sensitivity expressed either as normalized (Net) frequency (Fq) of BNC with MN or as number of MN per BNC. Both endpoints differed widely at 2 Gy and 4 Gy as well (Net FqBNC with MN = 0.28-25.4% or 1.5-45% and MN/BNC = 0.004-0.309 or 0.013-0.593 respectively at 2 Gy and 4 Gy) with coefficients of variation ranging from 44 to 57%. Extreme difference in MN frequency was also observed between one primary tumor and its metastasis indicating intra-tumor heterogeneity. Our results suggest that CB-MNA may contribute some clinically useful information for discriminating tumors that will eventually respond to radiotherapy and those that will probably not. However, studies aimed at comparison of MN induction in vitro with clinical radioresponsiveness of malignant melanomas are urgently required.

Key words: Malignant melanoma, primary culture, micronucleus assay, radiation sensitivity, heterogeneity.
str. 109-116

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Radiosensitivity of different aged human lymphocytes following electron irradiation in vitro

G. Joksiæ, M. Nikoliæ, V. Spasojeviæ-Tišma

"Vinca", Institute of Nuclear Sciences, Medical Protection Center, 11 000 Beograd, Yugoslavia

Cytochalasin B-blocking micronucleus test and chromosomal aberration analysis were used in this study to estimate the yield of individual variability in radiation response of different aged human lymphocytes. Both analyses were performed in three groups of adults, aged 18-65 years, on two sampling times, following irradiation by therapeutical dose of 2 Gy e- in vitro. No statistically significant difference in the induced yield of exchange aberrations between individuals under consideration was found. The yield of total aberration data showed greater variability and was statistically significant in the oldest group against two other adult groups. Regarding to fixation times no statistically significant differences in the induced yield of chromosomal aberrations (exchanges as well as total aberrations) were observed. The study has shown a slight increase in spontaneously occurring micronuclei with age. Almost equal mean number of radiation induced micronuclei was observed in the groups of adults aged 18-20 and 45-55 years. The highest mean number was observed in the oldest group. Evident variation in number of radiation induced micronuclei among individuals from the same age group was observed. The results of micronuclei assay for all individuals under consideration show statistically significant difference in the yield of radiation-induced micronuclei regarding the second fixation time. This study has shown that cytochalasin-B blocking micronucleus test is more sensitive assay than chromosomal aberration analysis for the estimation of individual radiosensitivity.

Key words: Lymphocytes, chromosomes, micronuclei, individual variability, radiosensitivity.
str. 117-121

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Comparative study of blood insulin levels in breast and endometrial cancer patients

V.B. Gamayunova, Yu. F. Bobrov, E. V. Tsyrlina, T. P. Evtushenko, L. M. Berstein

Laboratory of Endocrinology, Prof. N.N. Petrov Research Institute of Oncology, 189 646 St.Petersburg, Russia

Blood insulin level was measured in 113 breast cancer (BC) patients, 18 endometrial cancer (EC) patients, and 35 women with benign breast disease (BBD), after fasting and after 120 min of oral glucose tolerance test (OGTT). A significant increase in reactive insulin level was shown in postmenopausal BC patients with abdominal obesity (waist/hip ratio > 0.85) and no differences in insulin level were found between BC and BBD patients. Menstrual status and overweight (Quetelet index) did not influence significantly blood insulin concentration in BC patients, but the basal insulin level was lower in those patients who had been moderate smokers. In EC patients, the level of insulin after fasting and following 120 min OGTT was much higher than in BC and BBD patients although they had a similar body mass to these groups of patients. The effect of age on insulin secretion in BC patients is discussed as well as the possible causes and consequences of hyperinsulinemia developing in EC and BC patients.

Key words: Insulin, breast cancer, endometrial cancer, benign breast disease, aging, upper type of obesity, smoking.
str. 123-126

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Prognostic value of DNA ploidy in breast cancer Stage I-II

T. Cufer, J. Lamovec, M. Bracko, J. Lindtner, M. Us-Krasovec

Institute of Oncology, 1000 Ljubljana, Slovenia

The DNA content of paraffin-embedded tumor tissue has been measured by flow cytometry in 169 patients with operable breast cancer Stage I-II. The medium follow-up period was 123 months. Aneuploid primary tumors were found in 49% of patients. Tumor ploidy significantly correlated with histological type of tumor (p < 0.05), whereas no clear correlation between DNA ploidy and tumor size, histological grade and lymph node involvement was found. After 10-year follow-up, recurrence-free survival (RFS) of patients with diploid tumors was slightly better than the survival of those with aneuploid tumors, but the difference was not statistically significant (p = 0.39). In a Cox multivariate analysis only the axillary lymph node involvement and tumor size proved to be independent prognostic factors for recurrence, whereas DNA ploidy lost its prognostic value already in the univariate analysis. Therefore, we can conclude that the information on DNA ploidy, obtained from archival material, does not contribute significantly to a better discrimination between good-risk and poor-risk operable breast cancer patients.

Key words: Breast cancer, DNA ploidy, prognosis.
str. 127-132

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Differential chemosensitivity of leukemic cells in the myeloid and lymphoid phases of stem cell leukemia (A case report)

V. Mihál, M. Hajdúch, J. Dušek, M. Jarošová, E. Weigl, Z. Pikalová, K. Indrák, M. Šafáøová, A. Janošťáková,

Department of Pediatrics, Faculty of Medicine, 775 15 Olomouc, Czech Republic;
Institute of Immunology, Faculty of Medicine, Olomouc, Czech Republic;
Institute of Pathology, Faculty of Medicine, Olomouc, Czech Republic;
Department of Oncohematology, Faculty of Medicine, Palacký University, Olomouc, Czech Republic

A five-year-old girl, initially diagnosed as having acute lymphoblastic leukemia (ALL; FAB - L1) relapsed with ALL 4 months after completion of chemotherapy (BFM 83). The initial ALL presentation and subsequent ALL relapse were analyzed using conventional morphology, cytochemistry, cytogenetics and immunophenotyping. The results were consistent with a diagnosis of B-lymphocyte precursor ALL. Bone marrow leukemic cells revealed a 46, XX karyotype at diagnosis and a 46, XX, del(7) (q22; qter) when the girl first relapsed. The case was managed with a BFM REZ-ALL 90 protocol.
Upon completion of the first cycle of the protocol, severe myelosuppression developed. This was treated with GM-CSF. Three days later, however, GM-CSF was stopped because the WBC reached 1.1 × 109 per liter with 60% of blasts in peripheral blood. Laboratory characteristics were typical of AML. Cytogenetic analysis revealed 46, XX, del(7) (q22; qter) karyotype as before. The bcr-abl fusion gene was not detected. Myeloid blasts were placed in a culture and maintained at 37°C and 7.5% CO2 for two weeks. During this period, formation of hemopoietic colonies was observed and subsequently analyzed using histology and electron microscopy. This showed that the colonies consisted of differentiating erythroid, megakaryocytic and myeloid cells.
Further, the chemosensitivity of leukemic cells was examined in both "lymphoid" and "myeloid" relapse instances. While the "lymphoid" phenotype was characterized by good sensitivity to corticosteroids, a typical feature of the "myeloid" phenotype was a high resistance to corticosteroids with marginally increased sensitivity to ARA-C.

Key words: Stem cell leukemia, chemosensitivity, MTT-assay.
str. 133-136

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Adrenal incidentalomas - analysis of 23 cases discovered by ultrasound

E. Goncalvesová, P. Hnilica, Z. Moťovská, F. Goncalves, A. Kováè

Department of Medicine, I. Dérer's Memorial Hospital, 833 05 Bratislava, Slovakia;
Department of Urology, Dérer's Hospital, Bratislava, Slovakia

Frequent use of abdominal ultrasonography (USG) increases discovery of incidental adrenal tumors. Our experience and concise review of recent opinions on management of adrenal incidentalomas is presented. In four out of 23 patients with adrenal incidentalomas false positivity of USG was found (all on the left side), 4 cases were identified as pseudoadrenal masses. Hormonal activity was proved in 4 out of 15 true adrenal masses (2 pheochromocytomas, 2 aldosteronomas). Five out of 11 hormonally inactive tumors were benign adenomas, 2 myelolipomas, 2 simple cysts, 1 metastasis of bronchogenic carcinoma and 1 tuberculotic involvement. The smallest tumor was aldosteronoma (2 cm in diameter), the largest was myelolipoma (more than 10 cm). Size of benign adenomas ranged between 2.5-4.8 cm. Three main ultrasonic patterns of adrenal tumors were recognized: (1) anechogenic cysts, (2) complex but predominantly hyperechogenic myelolipomas, (3) hypoechogenic all other masses.

Key words: Adrenal incidentaloma, management, ultrasound.
str. 137-141

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