Electronic Library of Scientific Literature


Volume 45 / No. 1 / 1998

Helper T lymphocyte precursor frequency analysis in alloreactivity detection

V. Cukrová, L. Doležalová, M. Loudová, A. Vítek

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

The utility of IL-2 secreting helper T lymphocyte precursors (HTLp) frequency testing has been evaluated for detecting alloreactivity. The frequency of HTLp was approached by limiting dilution assay.
High HTLp frequency was detected in 20 out of 30 HLA matched unrelated pairs (67%). The comparison of HTLp and CTLp (cytotoxic T lymphocyte precursors) frequencies in HLA matched unrelated pairs showed that the two examinations are not fully alternative in detecting alloreactivity. This could suggest the utility of combined testing of both HTLp and CTLp frequencies for alloreactivity assessment.
In contrast, five positive HTLp values were only found among 28 HLA genotypic identical siblings (18%). Previous CTLp limiting dilution studies showed very low or undetectable CTLp frequency results in that group. For that, HTLp assay remains to be the only cellular in vitro technique detecting alloreactivity in these combinations.

Key words: HTLp, CTLp, HLA, minor H antigens, alloreactivity, limiting dilution analysis, GVHD.
pp. 3-6

The effect of protein kinase C inhibitors on invasion of human ovary cancer cells

B. Szaniawska, K. Gawrychowski, P. Janik

Department of Cell Biology, The Maria Sklodowska-Curie Cancer Center, 02-781 Warsaw, Poland;
Department of Oncological Gynecology, The Maria Sklodowska-Curie Cancer Center, Warsaw, Poland

In the present work we tested whether invasiveness of ovarian carcinoma cells could be considered as protein kinase C (PKC) dependent process. The migration and invasion studies were performed in Transwell chambers. Staurosporine, sphingosine and tamoxifen were used as PKC inhibitors. Also the effect of prolonged treatment with TPA was the subject of observation. The obtained results indicated that invasion understood as three step process (attachment, migration and matrix degradation) was affected by PKC inhibitors. The detailed studies, however, showed that attachment and matrix degradation ability of ovarian cancer cells was not changed by PKC inhibitors as opposed to migration which was, at least partly, regulated by protein kinase C.

Key words: Ovarian cancer cell line, adhesion, migration, invasion, PKC inhibitors.
pp. 7-11

The significance of anti-sialyl-Tn antibodies in patients with colorectal and breast cancer

D.W.J. Coomber, N.J. Hawkins, D. Dalley, R.L. Ward

Department of Medical Oncology, St Vincent's Hospital, Darlinghurst, Sydney, 2010 NSW, Australia;
School of Pathology, University of NSW, Sydney, Australia

The sera of 54 individuals with colorectal or breast cancer, and 50 healthy volunteers were assayed for the presence of anti-bovine submaxillary mucin antibodies using an enzyme linked immunoassay. The serum levels of these antibodies were found to be significantly lower in people with breast (p < 0.001) or colorectal cancer (p < 0.001) with respect to healthy individuals. Within the colorectal cancer group the presence of antibodies was significantly lower in those individuals with poorly differentiated tumors compared to other histological grades (p < 0.05), but did not correlate with the presence of local or distant metastases or anatomical location of the tumor (p > 0.05). No correlation was found with respect to the age of the patient and the level of anti-sialyl-Tn antibodies (p > 0.05). Competition analysis with the anti-sialyl-Tn monoclonal antibody 3C2 indicated that the activity against bovine submaxillary mucin was primarily due to specificity for the sialyl-Tn epitope of the glycoprotein. In contrast to findings with other tumor associated antigens, we could find no evidence of an increase in the level of antibodies against this epitope.

Key words: Sialyl-Tn, serum antibodies, colorectal neoplasms, breast neoplasms.
pp. 12-16

Soluble TNF receptors release by polymorphonuclear cells and the serum levels in breast cancer patients before and after treatment

E.Jabłońska, M.Kiluk, W. Markiewicz

Department of Immunopathology, Medical Academy, 15-230 Białystok, Poland;
Department of Surgery, Regional Center of Oncology, Białystok, Poland

Soluble cytokine receptors by binding to circulating cytokines play an important role in the regulation of immune response of the host. Measurement of their release may be helpful in the evaluation of cytokine-mediated reactions in patients with cancer disease.
Soluble tumor necrosis factor receptors (sTNF-Rs) in the culture supernatants of PMNs and in the sera obtained from patients with breast cancer were determined. The examinations were carried out before and after treatment involving surgery and chemotherapy. The highest concentrations of sTNFRp55 and sTNFRp75 were observed in the culture supernatants of PMNs from patients before any treatment, the lower concentrations of them were found in the supernatants of PMNs after treatment.
Sera from breast cancer patients presented increased levels of sTNFRp55 and sTNFRp75. Surgery treatment resulted in higher concentrations of sTNFRp55 and sTNFRp75. Decreased sTNF-Rs serum levels were obtained in patients after adjuvant chemotherapy.
Different ability of PMNs to the release of TNF - regulatory proteins - sTNFRs appears to confirm PMNs participation in TNF-mediated reactions of the host during malignant process via sTNF-Rs release.

Key words: TNF-alpha, soluble TNF receptor p55, soluble TNF receptor p75.
pp. 17-20

The value of CYFRA 21-1, a new tumor marker, in nasopharyngeal carcinoma

Wan-Yu Lin, Tzu-Chen Yen, Kai-Yuan Cheng, Shyh-Jen Wang

Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan;
Department of Radiological Technology, Chung-Tai Junior College, Taichung, Taiwan;
Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Taipei, Taiwan;
Division of Nuclear Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

CYFRA 21-1 (CYFRA) is a newly-developed tumor marker which is useful in evaluating non-small cell lung carcinoma, especially the squamous cell type. The purpose of this study was to assess the clinical value of CYFRA in patients with nasopharyngeal carcinoma (NPC).
Serum levels of CYFRA (CIS bio-International, France) were measured in 80 patients with untreated NPC. The histologic diagnosis of all patients was confirmed by biopsy. Twenty two (27.5%) of the tumors were classified as undifferentiated carcinoma, and 58 (72.5%) as squamous cell carcinoma. All patients with malignancy were classified according to the International Union Against Cancer (UICC) TNM classification system. In addition, 77 patients without evidence of neoplasm were included as controls. The cut-off value of CYFRA, determined at the 95th percentile of the standard Gaussian variate of controls, was 2.48 ng/ml. The results show that (1) the mean values of serum CYFRA in patients with NPC were significantly higher than those in the control subjects, (2) the overall diagnostic sensitivity of CYFRA in patients with NPC is 58.75%, (3) there was no significant difference between the CYFRA concentrations in patients with squamous cell carcinoma and those in patients with undifferentiated carcinoma, and that (4) there was good correlation between CYFRA values and the tumor stage. There is a statistical difference between T1-T2 patients and T3-T4 patients, and between N0 to N1 patients and N2 to N3 patients.
Our results suggest that the CYFRA test may have a potential clinical role as a valuable test in patients with NPC.

Key words: CYFRA 21.1, nasopharyngeal carcinoma, squamous cell carcinoma antigen, squamous cell carcinoma.
pp. 21-24

Characterization of two new permanent glioma cell lines 8-MG-BA and 42-MG-BA

A.Peržeľová, I.Máčiková, P.Mráz, I.Bízik, J.Šteňo

Department of Anatomy, School of Medicine, Comenius University, 813 72 Bratislava, Slovakia;
Department of Neurosurgery, Dérer's Hospital, Bratislava, Slovakia

The establishment and characterization of two permanent glioma cell lines (8-MG-BA and 42-MG-BA) are described. Both cell lines were derived from the human glioblastoma multiforme. Analyzed cells were within the passage 200 to 220. The cells in both cultures showed similar morphology. In majority they consisted from flat polygonal cells. Growth kinetic studies demonstrated a population doubling time of 20 to 24 h in cell line 8-MG-BA and 48 to 54 h in cell line 42-MG-BA. The cell lines showed different hyperdiploid karyotypes. The immunofluorescence staining was performed for glial fibrillary acidic protein (GFAP) and vimentin. In the culture 8-MG-BA only a small amount of cells showed the GFAP-positive staining. At confluent 42-MG-BA culture the GFAP-positive cells reached 50 to 70% of all cells. Vimentin was found in all glioma cells in both cultures.

Key words: Brain neoplasm, human glioma cell lines, glioblastoma, GFAP, vimentin, heterogeneity.
pp. 25-29

Antitumor action of bovine seminal ribonuclease. Cytostatic effect on human melanoma and mouse seminoma

P. Poučková, J. Souček, J. Jelínek, M. Zadinová, D. Hloušková, J. Polívková, L. Navrátil, J. Činátl, J. Matoušek

Institute of Biophysics, Medical Faculty, School of Medicine, Charles University, 121 08 Prague 2, Czech Republic;
Institute of Hematology and Blood Transfusion, Prague, Czech Republic;
Institute of Medical Biology, Department of Hematology and Oncology J.W. Goethe-University, Frankfurt a.M., FRG and Clinical Laboratories, Prague, Czech Republic;
Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Liběchov, Czech Republic

This paper reports on the antitumor activity of BS RNase on human melanoma and mouse seminoma. Human melanoma cells established in culture were extremely susceptible to BS RNase, administered in concentrations ranging from 1-100 µg/ml. Concentrations of BS RNase over 10 µg/ml caused complete inhibition of cell growth. Bovine pancreatic ribonuclease (RNase A), a prototype of the ribonuclease superfamily, did not exert any effect under these conditions. Based on our previous results, athymic mice bearing human melanoma or mouse seminoma were treated with intratumoral administration of BS RNase (12.5 mg/kg b.w.). This dose was injected for five consecutive days excluding weekends. The intratumoral administration of BS RNase to nude mice bearing human melanoma showed a significant antitumor effect. There were no tumors seen in eighty percent of mice treated for three weeks, and tumors in the other mice diminished significantly. After some delay the tumors started to regrow. Prolonging of the treatment to five weeks had a similar effect. The effect of BS RNase on mouse seminoma was well pronounced. Five to seven doses of BS RNase were sufficient to eliminate tumors in all treated mice. However, as in the previous experiment, the growth of tumor tissue later reappeared.

Key words: Bovine seminal ribonuclease, antitumor activity, melanoma, seminoma, nude mice.
pp. 30-34

Granulocyte colony-stimulating factor demonstrates antitumor activity in melanoma model in mice

J. Gołąb, R. Zagożdżon, T. Stokłosa, A. Kaca, A. Dąbrowska, A. Giermasz, W. Feleszko, M. Jakóbisiak

Department of Immunology, Institute of Biostructure, Medical School of Warsaw, 02-004 Warsaw, Poland

Granulocyte colony-stimulating factor (G-CSF) was found to exert antitumor activity against murine MmB16 melanoma when administered intratumorally. However, subcutaneous administration of this cytokine at a site distant from the growing tumor did not show any antitumor effects. G-CSF did not influence the proliferative activity of MmB16 in vitro. Intraperitoneal administration of G-CSF resulted in decreased secretion of nitric oxide (NO) by peritoneal macrophages and their decreased tumoricidal activity against MmB16.

Key words: Granulocyte colony-stimulating factor, melanoma MmB16, nitric oxide, macrophages.
pp. 35-39

Signal-averaged ECG in patients after anthracycline therapy for childhood cancer

B. Mladosievičová, A. Foltinová, M. Bernadič, P. Hubka, H. Petrášová, I. Hulín

Institute of Pathophysiology, School of Medicine, Comenius University, 811 08 Bratislava, Slovakia;
Children´s University Hospital, Bratislava, Slovakia

Late cardiac complications after anthracycline therapy is an increasingly common problem among survivors of childhood cancer. Routine clinical examination may be normal, but subclinical cardiac abnormalities, which may progress with time, are documented in high percentage of these patients. Microstructural myocardial alterations may result in production of micropotential level signals (late potentials, LP) and altered frequency components of signal-averaged ECGs (SAECG). SAECG abnormalities are valuable in risk stratification of patients with various heart diseases culminating in fatal arrhythmias or heart failure.
Forty-five pediatric oncologic patients (mean age 14.4 ± 4.1 years) were included in the study. SAECG was performed 3 months - 12 years (median 5.5 years) following completion of anthracycline therapy. The total cumulative doses of anthracyclines were 90-555 (median 230) mg/m2. The control group consisted of 30 healthy age-matched volunteers.
LP were present in six (13.3%) patients after anthracycline therapy at 40 Hz high-pass filter setting. Using frequency-domain analysis within the QRS complex, area ratio 1 (area of 20 to 50 Hz/ area of 0 to 20 Hz) and area ratio 2 (area of 40 to 100 Hz/area of 0 to 40 Hz) were calculated. Twenty (44.4%) and fourteen (31.1%) had abnormal values in area ratios 1 and 2, respectively, within the QRS complex. Area ratios 1 and 2 of patients after anthracycline therapy were significantly higher than those in control group (p = 0.0187 and p = 0.0043).
Our preliminary results suggest that chemotherapy with anthracyclines, even in low dosage, is associated with increased incidence of SAECG abnormalities. The potential of this simple, noninvasive method to detect subclinical anthracycline-induced myocardial alterations and facilitate prognostic stratification of cancer survivors is promising, however, the clinical value of SAECG remains to be established in a larger and a longer study.

Key words: Anthracycline cardiotoxicity, children, late potentials, frequency-domain analysis.
pp. 40-45

Granisetron in repeated cycles of chemotherapy with platinum

V.I.Tzekova, M.T.Velikova, K.D.Koynov

Clinic of Chemotherapy, University Hospital "Queen Joanna", 1527 Sofia, Bulgaria

The aim of the present study was to assess the antiemetic efficacy of granisetron in repeated cycles of chemotherapy with platinum derivatives.
The study included 50 patients (28 females, 22 males; aged 17-72, mean age 51 years). From 2 to 5 cycles of chemotherapy with cisplatin or carboplatin were performed. Granisetron was administered intravenously at a dose of 3 mg, 5 minutes before commencement of cytostatic chemotherapy. In case of 2 episodes of vomiting and severe nausea 2 additional doses of granisetron were given.
Total control of emesis was achieved in 60% of patients after the first cycle of chemotherapy, and this percentage did not change significantly over the 5 cycles of chemotherapy. There were no differences in the antiemetic efficacy of granisetron in relation to patient sex up to cycle III, while in cycles IV and V a tendency towards less efficacy in females was observed.
The adverse effects (headache, dizziness) were observed with the same frequency in the first 3 cycles of chemotherapy, while these were absent in cycles IV and V. Severe side effects were recorded only in cycle I, after that they were less expressed.
In conclusion, granisetron is highly effective in prevention of emesis, induced by platinum derivatives and its efficacy is maintained over repeated cycles of chemotherapy. The toxicity of granisetron is mostly expressed in the first cycle, while after that it decreases significantly.

Key words: Granisetron, antiemetic, platinum, chemotherapy.
pp. 46-49

The impact of diagnosis and treatment on the quality of life in breast cancer patients

Ö. Özyilkan, E. Baltali, G. Tekuzman, D. Firat

Division of Medical Oncology, Department of Internal Medicine, Bayindir Tip Merkezi - Medical Center, 06520, Ankara, Turkey;
Hacettepe University Institute of Oncology, Ankara, Turkey

Over the past years, quality of life (QOL) in patients with breast cancer has continued to be a noteworthy area of research. The diagnosis and management of cancer can have a major impact on every aspect of a patient's QOL. Sixteen women with breast cancer (during chemotherapy and 4 months after adjuvant chemotherapy) and 15 healthy women controls underwent 42-item QOL questionnaire in eight dimensions which assessed general well-being, physical symptoms and activity, sleep disturbance, appetite, sexual dysfunction, cognitive functions, medical interaction, social participation, and work performance. The subjects were asked to choose only one of five predefined constant options, which were scored from one to five in a Likert scale with multiple options, and total QOL scores were obtained. Although the total QOL score was not statistically different between the groups (p > 0.05), general well-being, physical symptoms and activity, and sleep disturbance showed significant regression in breast cancer patients compared to the controls (p < 0.05). Appetite (p < 0.02) and physical symptoms and activity (p < 0.05) significantly improved in the group after chemotherapy compared to the group during chemotherapy.

Key words: Quality of life, breast neoplasm.
pp. 50-52