Electronic Library of Scientific Literature


Volume 45 / No. 6 / 1998

The combination of heteroduplex analysis and protein truncation test for exact detection of the APC gene mutations

M. Tomka, T. Kirchhoff, ĵ. Kulcsár, V. Števurková, V. Zajac

Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovakia;
National Cancer Institute, 833 01 Bratislava, Slovakia

Familial adenomatous polyposis (FAP) is usually associated with mutation in the adenomatous polyposis coli (APC) gene. To examine the occurrence of these mutations in the number of FAP suspected families from the whole Slovakia effectively, we have applied heteroduplex analysis (HDA) and protein truncation test (PTT) for the analyses of 2-5 base pair deletions and point mutations of the APC gene. In the analyzed exon 15 of the APC gene determined by the primers 15Efor-15Grev for HDA and 15ET7-15J3 for PTT more than 70% of mutations should be deletions [3, 12], which are detectable by HDA. In our collection of 5 FAP families mutations in the APC gene were found in families 10, 27 and 41 using HDA. By PTT test the formation of truncated APC protein in FAP families 2, 10, 16 and 27 were revealed. The necessity of combination of at least HDA and PTT techniques for exact detection of APC mutations in analyzed APC region is discussed.

Key words: Colon cancer, familial adenomatous polyposis coli, APC gene, molecular diagnostics.
pp. 345-348

The single cell gel electrophoresis: A potential tool for DNA analysis of the patients with hematological malignancies

G. Baèová, A. Gábelová, O. Babušíková, D. Slameòová

Cancer Research Institute, 833 91 Bratislava, Slovakia

Single cell gel electrophoresis (SCGE) was used to evaluate the level of DNA damage in peripheral blood (PB), bone marrow (BM), and lymphatic node (LN) cells of patients with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML) and non-Hodgkin's lymphoma (NHL). The level of DNA damage was compared with the level of basal DNA damage in control group, represented by healthy donors.
Statistically significant increase of basal DNA damage was found in leukemia/lymphoma cells of patients suffered from AML, CML, ALL of T-cell subtype (T-ALL), and NHL, however, no difference in basal DNA damage was found in patients with ALL of early B-cell subtype (B-ALL) and CLL in comparison to control group. The mean basal DNA damage increased in the order CLL< early B-ALL< T-ALL<AML<CML<NHL (5.6, 7.2, 10.7, 11.9, 16.9, and 23.4% of tail DNA, respectively) what correlated with survival prediction of patients with particular hematological disease. A large heterogeneity was found in the level of basal DNA damage among patients with AML. By sorting this group according to the immunophenotypic markers and cell maturity a good correlation was found between the level of basal DNA damage and French-American-British (FAB) classification for AML (M1-M2 vs. M4-M5). Though T-ALL group manifested larger homogeneity in comparison with AML, the value of basal DNA damage was also dependent on T-cells maturity and coexpression of surface marker CD10.
Chemotherapy resulted in a significant but variable increase of DNA damage in leukemia/lymphoma cells. No increase of DNA damage was repeatedly observed in leukemia/lymphoma cells of patient who did not respond to therapy. The level of DNA damage in cells of patients in remission decreased more or less to the basal level in control cells.

Key words: Single cell gel electrophoresis, DNA damage, hematological malignancies, leukemia/lymphoma cells.
pp. 349-359

Angiogenesis in endometrial cancer

A. Mazurek, M. Telego, P. Pierzyñski, G. £apuĉ, W. Nikliñska, M. Juczewska, L. Chyczewski

Institute of Obstetrics and Gynecology, Medical University of Bia³ystok, 15-276 Bia³ystok, Poland;
Department of Pathological Anatomy, Medical University of Bia³ystok, Bia³ystok, Poland;
Department of Histology, Medical University of Bia³ystok, Bia³ystok, Poland;
II Radiotherapy Department, The Maria Sk³odowska-Curie Memorial Oncological Centre, Bia³ystok, Poland

We evaluated the level of angiogenesis in endometrial adenocarcinoma and investigated the relationship between tumor vascularity and clinicopathological parameters. The level of angiogenesis in noninvaded uterine smooth muscle was also studied. Angiogenesis was studied in uteri of 29 post-menopausal women operated on for endometrial cancer.
DAKO EPOS Anti-Human von Willebrand Factor/HRP antibodies were applied to mark endothelial cells. Both vessels and endothelial cells were counted on a light microscope equipped with computerized morphometric appliance. The highest density of vessels and endothelial cells was found in disease-free uterine smooth muscle tissue situated distant to the tumor. Density of vessels and endothelial cell counts were higher in the outer as compared to the central parts of the tumor. We found statistically significant differences in total angiogenic points' density between groups of various clinical FIGO staging, specifically between Ia and Ib, Ic, II. A positive correlation was found between the clinical stage of the disease (according to FIGO) and the total angiogenic points' density, density of endothelial cells and the density of vessels with viable lumen (counts/sq. mm calculated from the central parts of the tumor). These results suggest that the analysis of angiogenesis may be a useful biologic parameter and additional study of neovascularization in endometrial cancer is warranted.

Key words: Angiogenesis, endometrial adenocarcinoma.
pp. 360-364

Cathepsin B, p53 expression and AgNORs in transitional cell carcinoma

I. Akpolat, Y.S. Bariş, A.F. Yilmaz, M. Bakirtaş, A. Saylik, F. Karagöz, B. Kandemir

Department of Pathology, Ondokuz Mayis University School of Medicine, 55139 Samsun, Turkey;
Department of Urology, Ondokuz Mayis University School of Medicine, Samsun, Turkey

The aim of this study was to assess the relation between silver-strained nucleolar organizer regions (AgNOR), tumor stage, tumor grade and p53 expression with cathepsin B staining in transitional cell carcinoma of bladder. Tissue sections from 64 transitional cell carcinomas of the bladder were evaluated for the relation between AgNOR, tumor stage, tumor grade and p53 expression with cathepsin B staining in the neoplastic and stromal cells. Mean AgNOR values were significantly higher and the presence of p53 expression were different in cathepsin B positive and negative tumor and stromal cells. Although the number of cases is limited, this pilot study shows that cathepsin B staining may have a prognostic value in transitional cell carcinoma, but more studies are needed for a definite conclusion.

Key words: Cathepsin B, p53, AgNORs, bladder carcinoma.
pp. 365-368

Estimation of oncostatin M (OSM) secretion by peritoneal macrophages with regard to the progression of transplantable melanomas

K. Koz³owska, M. Cichorek, M. Zarzeczna

Department of Embryology, Medical University, 80-211 Gdañsk, Poland

The authors have studied the influence of two kinds of transplantable melanomas on the secretion of oncostatin M (OSM) and total proteins by peritoneal macrophages.
Culture supernatant samples were tested by ELISA. The macrophages of melanoma-bearing animals released a lower amount of OSM than those of the controls. At the same time the results showed statistically significant increase of protein content in the supernatants of cultured macrophages from melanoma-bearing hamsters in comparison with the controls.
However, it has not been possible to demonstrate any relationship between melanoma progression and changes in the secretion of OSM by peritoneal macrophages.

Key words: Transplantable melanomas, peritoneal macrophages, oncostatin M.
pp. 369-372

Very low sensitivity of Wistar:Han female rats to chemocarcinogens in mammary carcinogenesis induction

I. Ahlers, P. Solár, A. Burešová, E. Ahlersová

Institute of Animal Physiology, Faculty of Science, P.J.Šafárik University, 041 67 Košice, Slovakia

Recently a great variability of various mouse and rat strains in the sensitivity for mammary tumors induction by means of physical (ionizing radition) or chemical (mostly 7,12-dimethylbenz/a/anthracene, DMBA and N-methyl-N-nitrosourea, NMU) initiating agents was noted. The categorization into four groups was recommended in rats; the first group with high sensitivity (the incidence of tumors practically 100%, the frequency of tumors per entire treated group 2.0), the second with average type of sensitivity (incidence below 100%, frequency between 1.0-2.0), the third with low sensitivity (frequency 0.3-0.4) and the fourth with zero sensitivity as the response to single standard dose of DMBA.
After initial observations we decided to analyze the sensitivity to mammary carcinogenesis in the female rats of Wistar: Han strain, used frequently in central European region. Twenty mg of DMBA by gavage as single dose, or three-times 10 mg by gavage as repeated consecutive doses in three-day intervals, or 30 mg/kg b.w. of NMU intraperitoneally were administered, always between 50-55 postnatal days (single doses) or between 50-60 days (repeated doses of DMBA). The average incidence of mammary tumors did not exceed 10% and the entire group tumor frequency was about 0.1 for both carcinogens used. The data allowed us to indicate the female Wistar: Han rats as animals with "very low" sensitivity for the initiation of mammary tumors by single dose of DMBA or NMU; being in this way very close to the insensitive strains. The fact of "sensitivity" improvement to higher range after repeated doses of DMBA indicated a non-genetic background of the changed sensitivity.
Our results support the need to use more then one rat strain for initiation of mammary carcinogenesis, and for assessing the bright range of the biological response. In this situation the concept of "multi-strain" assay seems to be the optimal.

Key words: Mammary carcinogenesis, rat strains, chemocarcinogen, susceptibility.
pp. 373-376

Comparison of the treatment results in the vulvar and clitoris squamous cell carcinoma

L. Masák, G. Hudáková

St. Elizabeth Cancer Institute, 812 50 Bratislava, Slovakia;
National Cancer Institute, Bratislava, Slovakia

Treatment results in 360 patients with vulvar carcinoma during the time period from 1975 to 1994 were evaluated. Out of the whole group radical vulvectomy with bilateral inguinal lymphadenectomy was performed in 215 patients. After excluding 35 patients having the Stage IV of the disease, 11 with malignant melanoma and 9 missing, in the group of remaining 160 cases with squamous cell carcinoma the survival rates of 3, 5 and 10 years were evaluated. Squamous cell carcinoma involvement of the clitoris in 40 patients out of this 160 cases has not confirmed clitoris localization as a poor prognostic factor.

Key words: Vulvar carcinoma, clitoris, prognosis, treatment results.
pp. 377-379

The value of postoperative radiotherapy in advanced renal cell cancer

R. Makarewicz, M. Zarzycka, G. Kuliñska, W. Windorbska

Department of Radiation Oncology, Bydgoszcz Regional Cancer Center, 85-796 Bydgoszcz, Poland

The study reviews experience with the treatment of advanced renal cell cancer at Bydgoszcz Regional Cancer Center within a 10-year period from 1985 to 1996. The aim of this paper was to evaluate the value of postoperative radiotherapy.
The medical records of 186 patients with locally advanced renal cell cancer were reviewed retrospectively. Postoperative radiation therapy with a median dose of 50.0 Gy/t was given in 114 patients. The overall and disease-free survival, the pattern of recurrences, time interval to recurrence were assessed.
For all patients, the 5-year overall and disease-free survival rates were 36.2% and 30.5%, respectively. Non significant difference was observed in terms of 5-year overall and disease-free survival between the group of patients with postoperative radiotherapy and without, 37.9%/29.5% vs. 35.5%/31.3%, respectively. A total of 29 patients (15.6%) developed local recurrences. Local failure by stage was as follows: T3N0 without postoperative radiation therapy - 15.8%, with irradiation - 8.8%; T3N(+) without radiation therapy - 33.3%, with irradiation - 33.3%; T4N0 without radiation therapy - 33.3%, with irradiation - 33.3%, T4N(+) without radiation therapy - 33.3%, with irradiation - 25.0%. 73 patients (39.3%) had distant metastases as a first symptom of renal cell cancer relapse. The median time to relapse for local recurrence or distant metastases were approximately two times longer in patients with adjuvant radiotherapy compared to those without, 27.0/21.0 months vs. 16.0/12.5 months, respectively.
In our opinion postoperative radiotherapy reduces the probability of local recurrences in selected patients, mainly with pathologic stage T3N0, but its impact on survival is minimal.

Key words: Renal cell cancer, radiotherapy, results, local recurrence.
pp. 380-383

On the possible use of a new boron compound, hydroxysalicylhydroxamato boron(III), and ultrasound in the treatment of female mice bearing the Ehrlich ascites carcinoma cells

P. Ghosh, P. Sur, S.P. Bag, B. Sur, S.N. Chatterjee

Department of Chemistry, Jadavpur University, Calcutta, India;
Department of Pharmacology, Indian Institute of Chemical Biology, Jadavpur University, Calcutta - 700 032, India;
Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Calcutta, India

The inhibitory effects of a new boron compound, hydroxy salicylhydroxamato boron (III) (SHB) and ultrasound of frequency 25 KHz (US) on the growth of ascites tumor in female Swiss mice were studied by monitoring the survival and the tumor growth in the treated tumor bearing mice and also the transplantability and the DNA synthesis in the treated tumor (Ehrlich ascites carcinoma) cells. While SHB alone produced a highly significant antitumor activity, US alone produced a small but significant effect. The combination of SHB and US produced significantly greater antitumor activity than SHB alone. The mechanisms of SHB and US actionary are discussed.

Key words: Boron compound, ultrasound, antitumor activity.
pp. 384-388

Evaluation of the nutritional status and tumor characteristics in premenopausal and postmenopausal breast cancer patients

N. Vasiljeviĉ, M. Pecelj-Gec, J. Jorga, D. Nikoliĉ-Vukosavljeviĉ, M. Brankoviĉ-Magiĉ, J. Marinkoviĉ, L. Mitroviĉ

Institute of Hygiene and Medical Ecology, Department of Nutrition, School of Medicine, Belgrade University, 11000 Belgrade, Yugoslavia;
Institute of Oncology and Radiology of Serbia, School of Medicine, Belgrade University, Belgrade, Yugoslavia;
Institute for Statistics, School of Medicine, Belgrade University, Belgrade, Yugoslavia

Evaluation of the nutritional status, fat tissue distribution, and tumor characteristics was carried out in patients with primary breast cancer. The patients were classified into two groups according to their menopause: premenopausal and postmenopausal. Breast cancer prevalence was considerably higher in postmenopausal patients (61%). The patients' nutritional status was shown through the body mass index. Based on this indicator, the patients were characterized as nonobese and obese. In the premenopausal group, there was no significant difference between these categories, whereas the number of obese patients was significantly higher (80%) in the postmenopausal group. The analysis of tumor parameters as related to menopause and body size did not yield any significant differences. However, the estrogen receptor content was significantly higher in postmenopausal patients (p < 0.0001). Distribution of fat tissue of the android type was higher in obese postmenopausal women than in premenopausal ones (77%). The investigation showed that the breast cancer incidence odds are 3.5 times higher in obese postmenopausal than in premenopausal patients.

Key words: Breast cancer, obesity, fat distribution, menopause, estrogen receptor, progesterone receptor.
pp. 389-394

Index of authors - NEOPLASMA 1998

pp. 395-396

Cancer departments as a source of resistant bacteria and fungi? (Review)

V. Krèméry, Jr.

Department of Pharmacology, St. Elisabeth Cancer Institute, Heydukova 10, 812 50 Bratislava

Key words: cancer resistance of bacteria
pp. 400-403