Electronic Library of Scientific Literature


Volume 42 / No. 4 / 1995

Differences in cancer incidence between parts with different socio-economic structure within a Swedish big-city area


¹Primary Health Care Centre of Lovgardet, Gothenburg, Sweden;
²Department of Primary Health Care, Goteborg University, S-411 33 Gothenburg, Sweden

Two subareas with different socio-economic structure in the same big-city area were compared with respect to cancer incidence. Pulmonary cancer was overrepresented in the low socio-economic area. Smoking was more common in the same area, which may be a main contributory factor for the increased incidence of pulmonary cancer in that area. The results indicate that useful information, to be used as a base for local preventive measures, can be obtained from cancer statistics on the community level.

Key words: Socio-economic status, smoking, cancer incidence, preventive medicine.
pp. 149-153

Malignant tumors in family members of colorectal cancer patients


Institute of Epidemiology, School of Medicine, Belgrade University, 11 000 Belgrade, Yugoslavia;
¹School of Medicine, University of Kragujevac, Kragujevac, Yugoslavia

A case-control study comprised 286 colorectal cancer (CRC) patients and the same number of hospital controls individually matched by age, sex and place of residence. Both CRC and other malignant tumors were more frequent among first and second degree relatives of cases as compared to controls. The odds ratio (and 95 % confidence interval) for CRC was 6.67 (2.34-19.01) and for cancers of other sites 1.6 (0.97-2.62).

Key words: Colorectal cancer, family history.
pp. 155-157

Differential effect of protein kinase inhibitors (staurosporine and CGP 41 251) on TPA-induced homotypic aggregation and cell surface adhesion antigen expression in human monoblastoid cell line U-937


Cancer Research Institute, Slovak Academy of Sciences, 812 32 Bratislava, Slovakia

The phorbolester (TPA)-induced homotypic aggregation of human monoblastoid U-937 cells was completely abolished by staurosporine, but not by a new selective protein kinase C inhibitor, benzoylated staurosporine derivative CGP 41 251, a compound with known anti-tumor and drug resistance modulating activity. Staurosporine, a protein kinase inhibitor with broad profile of inhibitory activity on diverse protein kinases, but not CGP 41 251 substantially inhibited the TPA-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1, CD54) and to a lesser extent also its ligand CD11a. These results suggest that protein kinase C-independent mechanisms, inhibited by staurosporine but not by the selective PKC inhibitor CGP 41 251 are involved in the TPA-induced homotypic adhesion and modulation of cell surface adhesion antigens in the human monoblastoid cell line U-937.

Key words: Homotypic cell adhesion, U-937 cells, cell surface antigen, CD54, CD11a, CD15, CD45 antigens, TPA, staurosporine, CGP 41 251, protein kinase inhibitors.
pp. 159-165

Glutathione S-transferase isoenzymes and glutathione in renal cell carcinoma and kidney tissue


Department of Biochemistry, National Research Institute of Mother and Child, 00-211 Warsaw, Poland;
¹Department of Urology, Medical School, Lindleya 4, 02-005 Warsaw, Poland

Many studies have stablished the role of the glutathione S-transferases (GSTs) and glutathione (GSH) in the neoplastic process and the drug resistance of tumor. Using isoelectric focusing we separated different forms of GSTs in 28 renal cell carcinomas (RCCs) and in morphologically unchanged adjacent kidney. In addition we determined in RCCs and adjacent kidney the level of GSH and the activities of enzymes participating in synthesis and uptake of this thiol compound. We found higher activity of acidic GSTs and higher level of GSH in RCCs versus kidney. Therefore we suggest that both parameters may play the significant role in the well known phenomenon of intrinsic cytostatic drug resistance of RCC. We also observed the elevation of GSH synthetase activity in tumor tissues in comparison to the kidneys. It may indicate that GSH synthetase, catalysing the final step in GSH synthesis, may participate in the elevation of GSH concentration in RCCs. In this work we also compared the tested parameters in RCCs in relation to the size and local extent of primary tumor (T). We found significantly lower activity of gamma-glutamyl transpeptidase (GGT) as well as GSH synthetase in the group of T3 and T4 tumors than in T2 tumors. However, no substantial differences in GSH concentrations were observed between these distinguished groups.

Key words: Renal cell carcinoma, glutathione S-transferases, glutathione, glutathione-linked enzymes.
pp. 167-172

Effect of trypan blue on the activity of lysosomal enzymes, tumor growth and cell ultrastructure in B16 melanotic melanoma in mice


Department of Biology, University of Medicine, 85-092 Bydgoszcz, Poland;
¹Department of Pathomorphology, University of Medicine, Bydgoszcz, Poland

Trypan blue is known to act as a lysosome membrane destabilizer. We investigated the effect of this dye on the activity of cathepsin D, acid phosphatase and arylsulfatase in tissue homogenates of B16 melanotic melanoma, transplanted subcutaneously in C57BL/6J black male mice. We also examined the tumor growth and the ultrastructure of its cells. The mice were given subcutaneous injections of the suspension of B16 cells (10.000.000), and then received the trypan blue solution intraperitoneally in four divided doses, reaching the total dose of 0.1 mg/g b.w. (group I) or 0.4 mg/g b.w. (group II). The dye was administered each other day after the tumor transplantation. The control mice were injected with melanoma cells only. The animals were killed 2 weeks after the beginning of the experiment.
We found that the activity of lysosome hydrolases was increased by 30 % to 50 % in groups I and II, respectively, as compared to the control animals. The tumor growth in groups I and II was accelerated, and some ultrastructural changes in the melanoma cells were observed. These included irregular shape of the nucleus, uneven dispersion of the chromatin, increased number of premelanosomes and Golgi structures. The number of lysosomes, however, remained unaltered. We postulate that the trypan blue promotes tumor growth through the enhancement of the activity of lysosomal hydrolases; this may be due to the increased permeability of lysosome membranes caused by the trypan blue.

Key words: Melanoma, trypan blue, cathepsin D, arylsulfatase, acid phosphatase, ultrastructure.
pp. 173-178

Iron-responsive element-binding protein mRNA levels during erythroid differentiation of murine erythroleukemia cells


Institute of Hematology and Blood Transfusion, 128 20 Prague 2, Czech Republic

The levels of iron-responsive element-binding protein (IRE-BP 1) mRNA throughout the course of erythroid differentiation were investigated in several lines of murine erythroleukemia (MEL) cells (Friend 745, 707 and Fw cells). Fw cells are not inducible for ferrochelatase activity and heme synthesis. Cytoplasmic ferrochelatase mRNA and transferrin receptor (TfR) mRNA levels are only insignificantly increased in Fw cells after induction. We have found increased levels of (IRE--BP 1) mRNA during erythroid differentiation of MEL cells of all lines investigated. Run-on transcription reactions using isolated nuclei from Friend 707 cells showed increased (IRE-BP 1) gene transcription following induction of erythroid differentiation with 5 mmol hexamethylenebisacetamide (HMBA). The increase in (IRE-BP 1) gene transcription is only about 2-fold in comparison with 8-fold increase in the level of (IRE-BP 1) mRNA during 96 hours of Friend 707 cells induction. These findings indicate that the stability of (IRE-BP 1) mRNA might also play a role in the increase of (IRE-BP 1) mRNA levels after Friend 707 cells induction. The possible role of increased (IRE-BP) mRNA levels in the elevation of TfR numbers during erythroid differentiation is discussed.

Key words: Murine erythroleukemia cells, iron-responsive element-binding protein mRNA levels, erythroid differentiation
pp. 179-185

Organomercury (II) complexes with anti-carcinogenic agents.
I. Synthesis and characterization


Department of Chemistry, University of Delhi, Delhi, India;
¹Department of Biotechnology, Punjabi University, Patiala, India;
²Department of Chemistry, S.G.T.B. Khalsa College, University of Delhi, Delhi-110 007, India

A few organomercury (II) complexes involving anti-carcinogenic ligands have been synthesized. The compounds are of the type p-MeOC[6]H[4]HgL¹ (I), p-NO[2]C[6]H[4]HgL² (II), p-MeOC[4]H[4]HgL³ (III) and p-MeC[6]H[4]HgL[4] (IV) (HL¹ - 6-mercaptopurine, HL² - 6-thioguanine, HL³ - 5-fluorouracil, L[4] - phenyldithiocarbazate). Their composition has been determined from elemental analysis. Thin layer chromatography (TLC) studies demonstrate that the compounds are pure. Conductance measurement reveal that these derivatives are non-electrolytes. From IR and UV spectral studies the bonding modes of the ligands to the mercury (II) ion have been elucidated. The stoichiometry of the compounds has been confirmed on the basis of ¹H and ¹³C NMR spectra. Some preliminary results of anti-neoplastic activity are reported.

Key words: Conductance, organomercury, spectral studies.
pp. 187-190

Organomercury(II) complexes with anti-carcinogenic agents.
II. Anti-neoplastic activity


Department of Chemistry, University of Delhi, Delhi, India;
¹Department of Biotechnology, Punjabi University, Patiala, India;
²Department of Health and Human Services, National Institute of Health, National Cancer Institute, Bethesda, Maryland, USA;
³Department of Chemistry, S.G.T.B. Khalsa College, University of Delhi-110 007, India

Organomercury(II) complexes of the type, p-MeOC[6]H[4]HgL¹ (I), p-NO[2]C[6]H[4]HgL² (II), p-MeOC[6]H[4]HgL³ (III) and p-MeC[6]H[4]HgL[4] (IV) (HL¹ - 6-mercaptopurine, HL² - 6-thioguanine, HL³ - 5-fluorouracil, L[4] - phenyldithiocarbazate) have been screened against the following cell panels: leukemia, non-small cell lung cancer, small cell lung cancer, brain cancer, melanoma, ovarian cancer and renal cancer. The variation in anti-neoplastic activity has been correlated with the structural parameters of the complexes.

Key words: Anti-neoplastic effects, cell lines, cell panels, organomercury.
pp. 191-193

Decreased sensitivity of multidrug-resistant tumor cells to cisplatin is correlated with sorcin gene co-amplification


Institute of Chemical Physics at Chernogolovka, Russian Academy of Sciences, Russia;
¹ Institute of Cancerogenesis, Cancer Research Center, Russian Academy of Medical Sciences 115 478 Moscow, Russia

A set of multidrug resistant (MDR) murine leukemia P388 sublines possessing 30-50-fold mdr1 gene amplification was obtained as a result of experimental chemotherapy with rubomycin, ruboxyl, vinblastine, vincristine, or combination of rubomycin and vincristine. Significant differences of developed MDR sublines in response to treatment with cisplatin, tiophosphamide, sarcolysin, and dopad were found. Strong correlation between drug sensitivity and a copy number of gene coding for 19-22 kDa calcium-binding sorcin gene co-amplification were hypersensitive to cisplatin and alkylating agents, the cell sublines showing amplification of sorcin DNA sequences did not possess such collateral sensitivity and even acquired cross-resistance. The dependence of sensitivity to cisplatin on sorcin gene co-amplification was confirmed by analysis of Djungarian hamster DM15 cell sublines that selected for MDR in vitro by colchicine.

Key words: Multidrug resistance, cisplatin, gene amplification, mdr and sorcin genes, P388 mouse leukemia
pp. 195-201

Radiotherapy plus fifth day carboplatin in locally advanced bladder cancer


Institute of Oncology and Radiology, 11 000 Belgrade. Yugoslavia;
¹Institute of Epidemiology, School of Medicine, University of Belgrade, Yugoslavia;
²Urology Clinic, Serbian Clinical Centre, Belgrade, Yugoslavia

The goal of our prospective nonrandom study was to improve treatment results in advanced bladded cancer and possibility of cure with acceptable toxicity and reduced rate of late complications.
Fifty-tree patients with locally advanced bladder cancer (clinical stage T3a and b) treated by radical radiotherapy (65 Gy, conventional fractionation) and concomitant carboplatin (150 mg in bolus infusion, once a week, every fifth day an hour prior to the irradiation, up to total dose of 900 mg, during the treatment course.
Out of 53 evaluable patients, complete response was achieved in 47/53 (88.7 %) and partial response in 2/53 patients (3.8 %). Hematological toxicity grade I and II occurred in the majority of patients. Mean follow-up was 16 months (range 4-24), 2-year overall survival has been achieved in 85 % and disease free survival of 49 responding patients in 84 %.

Key words: Bladder cancer, radiotherapy, carboplatin.
pp. 203-206