Electronic Library of Scientific Literature


Volume 46 / No. 1 / 1999


Cancer departments as a source of resistant bacteria and fungi?

V. Krèméry, Jr.

Department of Pharmacology, St. Elisabeth Cancer Institute, 812 50 Bratislava, Slovak Republic, and Dpt of Medicine, Univ of Trnava, School of Public Health, Trnava, Slovak Republic

Antimicrobial resistance increases worldwide. Among many factors, such as clonal spread of genes of resistance among and intra species, local epidemiology, nosocomial transmission, also consumption of antimicrobials may be responsible. Cancer departments, mainly in centers treating hematologic malignancies and organizing bone marrow transplantation (BMT) are known to have extensive consumption of either prophylactically or therapeutically administered antibiotics and antifungals. It is worthy to remember, that first strains of quinolone resistant E. coli, vancomycin resistant enterococci and staphylococci and fluconazol-resistant Candida albicans appeared in the patients treated for cancer with antineoplastic chemotherapy, resulting in profound granulocytopenia. Therefore, assessment of risks of antibiotic prophylaxis with quinolones and azoles and extensive use of empiric therapy with glycopeptides and polyenes needs to be considered. Intensive prophylactic strategies should be limited to group of high risk, leukemic patients or BMT recipients.

Key words: Antimicrobial resistance, cancer patients.
NEOPLASMA, 46, 1, 1999, pp. 3-6

Small cell carcinoma of the esophagus

B. Jereczek-Fossa, M. Airoldi, S. Gribaudo, M.G. Ruo Redda, G. Valente, R. Orecchia

Department of Radiotherapy, European Institute of Oncology, 20 141 Milan, Italy;
Faculty of Medicine, University of Milan, Milan, Italy;
Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland;
Department of Medical Oncology, Hospital of San Giovanni Antica Sede, Turin, Italy;
Department of Radiotherapy, Molinette Hospital, Turin, Italy;
Department of Radiotherapy, Sant'Anna Hospital, Turin, Italy;
Department of Pathology, University of Turin, Turin, Italy

Small cell carcinoma of the esophagus (SCEC) is a rare tumor with its particular biologic features, distinct from squamous and glandular carcinoma of esophagus. Although initial symptoms can be similar (with metastatic dissemination and paraneoplastic syndromes at presentation more frequent in SCEC), differences in age and sex distribution, tumor location, radiological and endoscopic findings, clinical course and prognosis have been observed between SCEC and other esophageal malignancies. SCEC should be considered a systemic disease, and by analogy to bronchogenic small cell carcinoma, multi-modality approach including chemotherapy is recommended. In patients with limited disease, irradiation or surgery should be offered after induction chemotherapy to manage local disease. However, optimal treatment schedule has not yet been defined. In the future, registration of all SCEC cases and careful analysis of prognostic factors in the larger multi-institutional series could contribute to further progress in treatment outcome.

Key words: Small cell esophageal cancer, radiotherapy, chemotherapy, surgery, prognosis.
NEOPLASMA, 46, 1, 1999, pp. 7-11

Cell surface immunophenotype and gelatinase activity of the human breast carcinoma cell line (MCF-7/6) with functionally defective E-cadherin

P. Hlavèák, O. Sedláková, J. Sedlák, ¼. Hunáková, J. Duraj, M. Šulíková, J. Bízik, V. Castronovo, B. Chorváth

National Cancer Institute, 833 10 Bratislava, Slovak Republic;
Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic;
Metastasis Research Laboratory, University of Liege, Liege, Belgium

Expression of differentiation and adhesion cell surface antigens (LewisX - CD15, CD44, syndecan 1 - CD138 and basigin/EMMPRIN - CD147) were determined on the cell surface of human breast carcinoma MCF7 cells in vitro with the aid of flow cytometry and compared with that of MCF-7/6 cells, with functionally defective E-cadherin system and increased biological aggressiveness. The major cell surface alterations in MCF-7/6 cells compared with the parental MCF-7 cell line were a markedly increased CD15 (LewisX) and CD44 antigen cell surface expression on MCF-7/6 cells. There were no major differences between parental MCF-7 and MCF-7/6 cells in cell surface syndecan 1, basigin/EMMPRIN, E-cadherin and high affinity non-integrin laminin receptor expression. The constitutive cell surface gelatinase A and B activities were absent on MCF-7 and faint in MCF-7/6 cells. Both phorbol ester TPA and tumor necrosis factor TNF-alpha induced a marked up-regulation of gelatinase B only in MCF-7/6 cells. No marked differences in penetration of MCF-7 vs. MCF-7/6 cells into collagen/fibroblast matrix in vitro were observed. The increased expression of CD15 (LewisX), CD44 antigen and TNF-alpha-inducible gelatinase B on MCF-7/6 cells may represent auxiliary factors contributing to the increased biological aggressiveness of MCF-7/6 cells.

Key words: Human breast carcinoma, MCF-7, MCF-7/6 cell line, cell surface antigens, CD15, syndecan, basigin/EMMPRIN, E-cadherin, gelatinase activity, penetration into collagen/fibroblast matrix.
NEOPLASMA, 46, 1, 1999, pp. 12-16

Study of in vitro conditions modulating expression of MN/CA IX protein in human cell lines derived from cervical carcinoma

J. Lieskovská, R. Opavský, ¼. Žáèiková, M. Glasová, J. Pastorek, S. Pastoreková

Institute of Virology, Slovak Academy of Sciences, 842 46 Bratislava, Slovak Republic;
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic

In an effort to better understand the biological significance of MN/CA IX human tumor-associated protein, we have investigated its expression in human cervical carcinoma cell lines in vitro. SiHa cells that naturally express MN/CA IX were used as a model for expression study at the protein level. In addition, we have transfected MN/CA9 gene-negative but transcription-competent C33A cells with a plasmid carrying CAT reporter gene under a control of MN/CA9 promoter. By this way, we have generated a stable cell line C33A/MNP-CAT that was employed in analysis of MN/CA9 regulation at the level of promoter activity as estimated by CAT protein abundance. For the purpose of our study, we have chosen experimental conditions relevant to growth characteristics and phenotypic features of malignantly transformed cells. Both the level of MN/CA IX protein and the gene promoter activity were found to be substantially elevated either in culture of high density or when the adherent carcinoma cells grew in suspension, but were not markedly affected by diminished serum concentration and in the cell cycle progression. These observations support the involvement of MN/CA IX protein in aberrant cell-cell and cell-matrix interactions that facilitate loss of contact inhibition and anchorage independence of cancer cells.

Key words: MN/CA IX protein, cervical carcinoma cell lines, contact inhibition, anchorage independence.
NEOPLASMA, 46, 1, 1999, pp. 17-24

Expression of bcl-2 protein in non-small cell lung cancer: Correlation with clinicopathology and patient survival

J. Laudanski, L. Chyczewski, W.E. Niklinska, M. Kretowska, M. Furman, B. Sawicki, J. Niklinski

Department of Thoracic Surgery, Medical University of Bialystok, 15 276 Bialystok, Poland;
Department of Pathological Anatomy, Medical University of Bialystok, Bialystok, Poland;
Department of Histology, Medical University of Bialystok, Bialystok, Poland;
Institute of Computer Science, Technical University, Bialystok, Poland

Molecular genetic studies have revealed mutations in a number of oncogenes and tumor suppressor genes in lung cancer. The bcl-2 gene product (bcl-2 protein) is implicated in oncogenesis by its ability to prolong cell death through the inhibition of apoptosis. We investigated expression of bcl-2 in 84 resected human non-small cell lung cancers (NSCLC) and correlated this phenomena with clinicopathology and survival. Immunohistochemical analysis with a monoclonal antibody specific for bcl-2 (Clone 124; Dako) was used to detect the protein in tumor samples.
Overall, bcl-2 was detectable in 39 of 84 (46%) NSCLC. The percentage of bcl-2 positive cases varied according to the histological type. Positive bcl-2 immunostaining was observed in 27 of the 46 squamous cell carcinomas (59%), 7 of the 25 adenocarcinomas (28%) and 5 of the 13 large cell carcinomas (38%). The frequency of positive bcl-2 expression in squamous cell carcinomas was significantly higher than that in other histological two types (p = 0.037).
Statistical comparisons between the patients' clinical characteristics and bcl-2 status revealed no significant differences in the frequency of bcl-2 expression with respect to sex, T and N factors, as well as TNM stage. The relationship between bcl-2 protein expression and postoperative survival was analyzed in 84 patients. Patients with bcl-2 negative tumors showed significantly shorter survival times than those with bcl-2 positive tumors. In univariate analysis of various potential prognostic factors only TNM stage and bcl-2 test were significant prognostic factors (p < 0.009 and p < 0.008, respectively). In multivariate analysis (Cox proportional hazard model), bcl-2 status (negative test) was independent unfavorable prognostic factor (p = 0.017).
In conclusion, this set of observations suggests that assessment of the expression status of bcl-2 by tumors may provide prognostic information on the clinical behavior of NSCLC.

Key words: Tumor markers, bcl-2, lung cancer, prognosis.
NEOPLASMA, 46, 1, 1999, pp. 25-30

Positive staining for p53 and expression of c-erbB-2 in endosalpinx hyperplasia: Analysis of 48 cases and review of literature

J.K. Rabczynski, A.T. Kochman

Department of Pathology, Medical University of Wroclaw, 50-368 Wroclaw, Poland

To establish the diagnostic value of p53 and c-erbB-2 expression, forty-eight cases of endosalpinx hyperplasia were analyzed. p53 protein and c-erbB-2 oncoprotein expression was examined using an avidin-biotin peroxidase complex method. The accumulation of p53 protein and c-erbB-2 oncoprotein was used as objective evidence to support morphologic differential diagnosis of endosalpinx hyperplasia and early cancer. In all cases various forms of endosalpinx hyperplasia were seen. Only in 4 cases staining for p53 showed positive reaction without staining for c-erbB-2. In one case positive reaction for c-erbB-2 was showed and no expression of p53 protein was detected. It is concluded that immunohistochemical detection of the mutant p53 protein and c-erbB-2 oncoprotein might be useful tools in differential diagnosis among various forms of hyperplastic changes of endosalpinx. The presence of these markers may be associated with the risk of malignant transformation in various forms of the tubal hyperplasia.

Key words: Fallopian tube, endosalpinx hyperplasia, p53, c-erbB-2.
NEOPLASMA, 46, 1, 1999, pp. 31-34

Soluble IL-6 and TNF receptors release by polymorphonuclear and mononuclear cells in cancer patients

E. Jablonska

Department of Immunopathology, Medical Academy, 15-230 Bialystok, Poland

Immune response of the host to tumor is regulated by soluble mediators, such as cytokines. Data including the release of soluble mediators by polymorphonuclear cells (PMNs) are controversial. In the present investigation we studied the ability of spontaneous and LPS-stimulated PMNs derived from the patients with oral cavity cancer to the release of soluble IL-6 receptor (sIL-6R) and soluble TNF receptors (sTNF-Rs). Obtained results were compared to the release of sIL-6R and sTNFRs by peripheral blood mononuclear cells (PBMC) as well as the serum levels.
The culture supernatants of spontaneous and LPS-stimulated PMNs derived from the patients with oral cavity cancer contained unchanged concentrations of sIL-6R and higher concentrations of sTNFRp55 and sTNFRp75 in comparison with the control. The amounts of sIL-6R and sTNF-Rs released by PBMC were higher than those released by PMNs in both control and patient groups. Demonstrated results indicate that PMN contribution in the immune response is mediated by TNF-alpha, via the release of sTNFRp75 mainly. Profile measurement of the soluble cytokine receptors in the culture supernatants of PMNs and PBMC and the serum levels may be useful for estimation of the actual immunity in patients with oral cavity cancer.

Key words: Polymorphonuclear cells, soluble interleukin-6 receptor, soluble TNF receptors, oral cavity cancer.
NEOPLASMA, 46, 1, 1999, pp. 35-39

Radiosensitivity of human lymphocytes in vitro correlates more with proliferative ability of cells than with the incidence of radiation-induced damages of the genome

G. Joksiæ, A. Petroviæ-Novak, M. Stankoviæ, M. Kovaèeviæ

"Vinèa", Institute of Nuclear Sciences, Medical Protection Center, 11 000 Belgrade, Yugoslavia;
Cytogenetics Laboratory of Institute of Hematology, Medical Center of Serbia, Belgrade, Yugoslavia

The purpose of this study was the estimate the extent of individual variability in radioresponse of human lymphocytes in vitro and to establish the reasons of variability. Individual variability in radiation-response was evaluated using the cytochalasin B micronucleus test among 82 healthy individuals (36 men and 46 women), of mean age 38 (range 30-48). Blood samples were irradiated with gamma (60Co) rays at a dose of 2 Gy in vitro. The yield of radiation-induced micronuclei (MN), cytochalasin blocked proliferation index (CBPI), fraction of micronucleated binucleate (BN) cells and mean incidence of MN per micronucleated BN cells at a sampling time of 72 hours were scored. Our results brought out a significant effect of gender on the level of spontaneously occurring micronuclei, the lack of statistical differences between gender in the yield of radiation-induced micronuclei and marked variability in radiation response among individuals. Likelihood of expressing hypersensitivity was correlated with ability of cells to proliferate in vitro (beta = 0.41, p < 0.000) more than with the incidence of radiation-induced micronuclei per micronucleated cell (beta = 0.20, p < 0.000).

Key words: Human lymphocytes, radiosensitivity, micronuclei, individual variability, gender.
NEOPLASMA, 46, 1, 1999, pp. 40-49

Crosslinking of cellular DNA by nitracrine and furocoumarin derivatives

K. Studzian, Z. Tolwinska-Stanczyk, D. Wilmanska, M. Palumbo, M. Gniazdowski

Department of General Chemistry, Institute of Physiology and Biochemistry, Medical University of Lódz, 90-131 Lódz, Poland;
Department of Pharmaceutical Sciences, University of Padova, 35131 Padova, Italy

The anticancer drug, nitracrine, a 1-nitro-9-aminoalkyl derivative of acridine exhibits potent cytotoxic effects which are due to its metabolic activation, followed by covalent binding to macromolecules - DNA being the target for the drug. The renaturable fraction of DNA from L-1210 cells pretreated with nitracrine is assayed by means of ethidium bromide fluorescence assay and chromatography on hydroxyapatite column. The effect of the drug was compared with furocoumarins of different DNA crosslinking potencies. The existence of crosslinks in DNA upon incubation of cells with nitracrine (1-4 microM) have been confirmed with two different methods under the conditions where 8-methoxypsoralen, a classic crosslinking agent induced the renaturation. The DNA preparation isolated from the drug pretreated cells exhibited decreased transcriptional template activity with E. coli DNA-dependent RNA polymerase.

Key words: Furocoumarins, 8-methoxypsoralen, nitracrine, L-1210 cells, DNA crosslinks.
NEOPLASMA, 46, 1, 1999, pp. 50-53

The influence of surgery and anesthesia on lymphocyte functions in breast cancer patients: in vitro effects of indomethacin

N. Stanojeviæ-Bakiæ, L. Vuèkoviæ-Dekiæ, S. Radomiroviæ, Z. Juraniæ, N. Jovanoviæ

Institute for Oncology and Radiology of Serbia, 11 000 Belgrade, Yugoslavia

Surgical trauma and anesthesia may lead to the postoperative immunosuppression, the exact mechanism of which is still unresolved. Among various factors, the role of prostaglandine PGE2-mediated suppression was also proposed. We investigated the influence of surgery and two anesthetic regimes on lymphoproliferative response (LPR) to PHA and on NK cell activity (MTT) in breast cancer patients, as well as the effect of indomethacin, a PGE2 synthesis inhibitor, on these lymphocyte functions in vitro. In 36 previously untreated patients the lymphocyte functions were assayed before, 24 hours and seven days after the surgery. In regard to LPR, three distinct response patterns were observed: a) significant (p < 0.05) increase of initially lowered LPR; b) significant (p < 0.001) decrease of initially normal LPR 24 hours after operation, followed by normalization after seven days; c) no change of initially normal LPR. Indomethacin in vitro significantly (p < 0.05) enhanced the diminished LPR only before surgery, no effect being seen after the operation. The NK cell function was unaffected by surgery regardless the initial level of activity. Indomethacin had no effect on this lymphocyte function. There was no difference between the patient groups submitted to the different anesthetic regimes. In conclusion, our results show that surgical trauma variably affect the lymphocyte functions of cancer patients, the effect not being related to the particular anesthetic regime used. The PGE2-mediated suppression is not likely to be involved in postoperative immune function impairment.

Key words: Breast cancer, surgery, anesthesia, lymphoproliferative response, NK cell activity, indomethacin.
NEOPLASMA, 46, 1, 1999, pp. 54-60

Sequential standard dose mitoxantrone and cytosine arabinoside for newly diagnosed adult acute myeloblastic leukemia

S. Al Bahar, R. Pandita, K. Bavishi, B. Savani

Department of Hematology, Kuwait Cancer Control Centre, Shuwaikh, Kuwait

Twenty one adult patients with previously untreated acute myeloblastic leukemia (AML) were treated with sequential mitoxantrone and standard dose cytosine arabinoside remission induction therapy. The median age was 33 years (range 17-56 years). Complete remission (CR) was achieved in 80% (17/21 cases) and 76% (16/21 cases) achieved CR after one course of induction therapy. The median duration of disease free survival was 9 months with an actuarial disease free survival of 22% at 43 months. The non-hematological toxicity was acceptable. We conclude that sequential mitoxantrone and cytosine arabinoside combination therapy is an effective antileukemic regimen which produces high CR rates in previously untreated adult patients with AML.

Key words: Acute myeloblastic leukemia, mitoxantrone, cytosine arabinoside, chemotherapy.

NEOPLASMA, 46, 1, 1999, pp. 61-65

Comparative estimation of cure rates for supraglottic and glottic cancer in radiotherapy

M. Golen, K. Skladowski, B. Maciejewski

I Clinic of Radiotherapy, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, 44-100 Gliwice, Poland

There are some clinical evidences, that the same types of tumors originated from neighboring anatomical structures can significantly differ in their response to radiation therapy. Squamous cell cancer of supraglottis and glottis could be good examples of this phenomenon. The purpose of the study was to compare the radiocurability of cancers localized in the upper and medium level of the larynx.
From 1985 to the end of 1989, 544 patients with squamous cell cancer of the larynx were treated by radiotherapy alone. There were 388 patients with supraglottic cancer and 156 patients with glottic cancer. The total dose was in the range of 59-74 Gy. The end-point criteria were overall (OS) and disease-free survival (DFS).
Generally, 5-year overall and disease-free survival rates were significantly more favorable for glottic cancer patients than for supraglottic cancer (67 and 63% vs. 40 and 36%, respectively). Significant diferences in both disease-free and overall survival between supraglottic and glottic cancer in aspect of several analyzed clinical prognostic factors were found for: male sex, age, pattern of tumor growth, clinical performance status, radiation total dose lower than 70 Gy, fraction doses and overall treatment time. In all these prognostic categories 5-year survival rates were lower for supraglottic cancer patients. This tendency disappeared when the treatment results were compared in aspect of tumor stage (T). Tumor cure doses for 50% probability of local control (TCD50) in supraglottic cancer were estimated as: 61 Gy (T1+2) and 66 Gy (T3). In glottic cancer the lower TCD50 values of 54.5 Gy (T1+2) and 61 Gy (T3) were found in comparable treatment time.
The comparative estimation of cure rates (i.e. OS and DFS) of laryngeal cancer treated by radiation alone showed that in aspect of almost all analyzed prognostic factors the greater risk of treatment failure was significantly associated with supraglottic origin.

Key words: Supraglottic, glottic cancer, radiotherapy.
NEOPLASMA, 46, 1, 1999, pp. 66-71