Electronic Library of Scientific Literature
NEOPLASMA
Volume 42 / No. 1 / 1995
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Frequency analysis of cytotoxic T lymphocyte precursors in search for donors in bone marrow transplantation
V. CUKROVA, L. DOLEZALOVA, M. LOUDOVA, E. MATEJKOVA, P. KORINKOVA, M. LUKASOVA, J. STARY¹
Institute of Hematology and Blood Transfusion, 128 20 Prague 2, Czech Republic;
¹2nd Dept. of Pediatrics, 2nd Medical Faculty of Charles University, Prague, Czech Republic
The usefulness of cytotoxic T lymphocytes precursors (CTLp) frequency analysis in the search for donors in bone marrow transplantation was studied. The frequency of anti-recipient CTLp was approached by limiting dilution assay in HLA matched unrelated, HLA partially matched related and HLA genotypically identical donors. The majority of patients examined were affected with different hematological malignancies.
Alloreactive CTLp recognizing non-HLA gene products were not detected in pretransplant examination of two pairs of HLA identical siblings. However, an increased incidence of allospecific CTLp was identified in HLA matched MLC negative unrelated pairs. Thus, CTLp assay allowed to uncover the residual Class I incompatibilities that remained hidden in standard serotyping. In two matched unrelated pairs with high pretransplant CTLp frequency the severe acute graft-versus-host disease (GVHD) developed after bone marrow transplantation.
Examination of other relatives in patients lacking an HLA identical sibling showed the importance of Class I incompatibility for CTLp generation as well. The lack of correlation between CTLp frequency and HLA-D disparity could suggest that Class II antigens do not participate in CTLp induction.
With one exception we had good correlation between MLC and DNA analysis of Class II antigens demonstrating that MLC gives interpretable results even in unrelated pairs.
Our results demonstrate the significance of CTLp frequency assay in detection of residual Class I incompatibilities in matched unrelated pairs and in assessment of Class I compatibility in related pairs. For that it should be used in the final selection of BMT donors.
Key words: cytotoxic T lymphocyte precursors, bone marrow donors, compatibility.
pp. 3-8
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Chronic myeloid leukemia: Correlation between purine metabolism enzyme activities and membrane immunophenotype
A. MESAROSOVA, A. HRIVNAKOVA,¹ M. KLOBUSICKA, O. BABUSIKOVA
Cancer Research Institute, Slovak Academy ofSciences, 812 32 Bratislava, Slovakia;
¹National Cancer Institute, Bratislava, Slovakia
Peripheral blood or bone marrow of 24 patients with chronic myeloid leukemia (CML) were characterized for their surface membrane marker profiles using flow cytometry and fluorescence microscopy. Purine metabolism enzyme activities were compared with membrane immunophenotype and cytochemical stains.
CML subtypes were correlated with the expression of surface membrane antigens detected by the monoclonal antibodies. On the basis of immunophenotyping we found the following characteristic marker profiles: In stable phase of CML (CML-SP) - CD15, CD11b, CDw65, CD13, in accelerated phase of CML (CML-AP) - CD15, CDw65, CD11b, CD13 and CD33, in myeloid blastic phase of CML(CML-BP-M) - CD13, CD33, HLA-DR, CD11b, CD15, CDw65, in myeloid and lymphoid (mixed) blastic phase of CML (CML-BP-M+L) - CD13, CD33, CD34, HLA-DR, CD11b, CD10 and in chronic myelomonocytic leukemia (CMML) - CD14, CDw65, CD11b, CD33 and HLA-DR.
Analysis of purine metabolism enzyme activities showed that there was a correlation between the values of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and various types of CML. ADA levels in CML-SP, CML-AP and CMML were comparable with those in normal cells. In CML-BP-M, which represents proliferation of less mature myeloid cells (similar to less mature AML subtypes), ADA activity increased and PNP activity decreased. ADA activity was significantly different between control group and CML-BP-M (p < 0.01), between CML-SP and CML-BP-M (p < 0.05). The values of PNP activity were the highest in stable phase of CML (125 pkat.0.000 001 cells) and the lowest (23 pkat.0.000 001 cells) in CML-BP-M+L. PNP activity in the other groups corresponded to control values. High ADA/PNP ratio was found in CML-BP-M and CML-BP-M+L (0.7 and 2.0, respectively) in comparison to CML-SP (0.2). It follows from our results that ADA/PNP ratio enables to discriminate between stable and blast phases of CML (p < 0.01). The level of the cytochemical enzymes (CHAE, MPO, SBB, ANAE and 5' NT) varied and reflected the degree of cell differentiation and maturation. CHAE and MPO were characteristic enzymes for CML, ANBE for CMML and 5' NT for CML-BP-lymphoid.
Key words: Chronic myeloid leukemia, immunophenotype, adenosine deaminase, purine nucleoside phosphorylase, cytochemical stains.
pp. 9-14
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Changes of natural killer cytotoxic activity and natural killer sensitivity during growth of Bomirski melanotic (Ma) and amelanotic (Ab) melanomas
A. MYSLIWSKI, J. BIGDA, J. MYSLIWSKA, J.M. WITKOWSKI, D., SOSNOWSKA
Department of Histology and Immunology, Medical University of Gdansk, Debinki 1, 80 210 Gdansk, Poland
Natural killer (NK) cytotoxic activity during the growth of melanotic (Ma) and amelanotic (Ab) variants of Bomirski hamster melanoma, in the blood and the spleen, was examined. The melanoma variants differed in their growth rate and metastatic pattern. Ability to form conjugates by effectors with targets and cytotoxic effects were compared. As targets K562 cells and tumor cells were used. It was found that during the growth of Ma melanoma activity of NK cells was not changing but the sensitivity of tumor cells was decreasing. However, during growth of Ab melanoma both NK activity and NK sensitivity were reduced.
Key words: Melanoma, natural killer cells, tumor growth, hamster.
pp. 15-19
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Cathepsin B in predicting the extent of the cervix carcinoma
R. MAKAREWICZ, G. DREWA,¹ W. SZYMANSKI,² I. SKONIECZNA-MAKAREWICZ²
Department of Brachytherapy, Regional Cancer Center, 85-796 Bydgoszcz, Poland;
¹Department of Biology, Bydgoszcz Medical Academy, Bydgoszcz, Poland;
²Department of Obstetrics and Gynecology, Bydgoszcz Medical Academy, Bydgoszcz, Poland
The value of cathepsin B activity in determining the extent of disease was investigated in 106 patients with carcinoma of the cervix uteri and in 20 women with dysplasia of the cervix uteri. The measurements of serum and tumor cathepsin B activity were performed before treatment. The levels of cathepsin B were estimated by direct fluorimetric assay based on the use of 2-Phe-Arg-NMec as a substrate. The results show that the mean serum and tumor activity of this enzyme increase with progression of neoplastic disease and was closely dependent on clinical stage of cervical carcinoma. Also, we found higher serum and tumor levels of cathepsin B activities in patients with clinical early disease (FIGO Stage Ib and IIa) in whom metastases to pelvic lymph nodes were detected than in patients with disease limited to the cervix uteri (p < 0.001, t-test). Enhanced activity of cathepsin B was observed in 64% of patients with cervical carcinoma.
Key words: Cathepsin B, cervical carcinoma, dysplasia, uterine cervix.
pp. 21-24
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Combined radioprotective effect of Broncho-Vaxom ® and WR-2721 on hemopoiesis and circulating blood cells
N.O. MACKOVA, P. FEDOROCKO
Department of Cellular and Molecular Biology, Faculty of Science, P.J. Safarik University, 041 67 Kosice, Slovakia
Possibilities of combined radioprotection, using preirradiation WR-2721 administration and post- or preirradiation Broncho-Vaxom administration in lethally whole-body gamma-irradiated mice were investigated. Combined modality treatments were more effective than individual treatments alone. The ameliorative influence of the combined radioprotection could be explained by the hemopoietic stem cell protection with WR-2721 and the stimulation by Broncho-Vaxom.
Key words: Radioprotection, WR-2721, Broncho-Vaxom, hemopoiesis.
pp. 25-30
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Analysis of monoclonal immunoglobulin light chains in urine using two-dimensional electrophoresis
M. TICHY, J. STULIK, H. KOVAROVA, F., MATEJA, P. URBAN¹
2nd Department of Medicine, Charles University, 500 36 Hradec Kralove, Czech Republic;
¹Department of Clinical Biochemistry, District Hospital, Zlin, Czech Republic
High-resolution two-dimensional electrophoresis was used to analyze kappa-type monoclonal immunoglobulin light chains in urine of two patients with multiple myeloma. The patients were treated, remission lasted about 2.5 years. In the period of relapse of the disease, acid isoforms of kappa chains, pI < 4,95, which had not been present in the urine of these patients before, were found in urine of both patients. Kappa-type Bence-Jones protein in urine of one patient showed unusual behavior: It failed to precipitate in the range of 40-60°C or on boiling.
Key words: Two-dimensional electrophoresis, monoclonal light chains in urine, nephrotoxicity.
pp. 31-34
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Bacteremia and fungemia in cancer patients with venous catheters
KUKUCKOVA, E., STUDENA, M., TRUPL, J., SVEC, J., KUNOVA, A., SUFLIARSKY, J., SORKOVSKA, D., MINARIK, T., SYCOVA, Z., KRCMERY, V. Jr.
Postgraduate Medical School and School of Medicine, 833 03 Bratislava, Slovakia; Department of Clinical Medicine, University of Trnava, Slovakia; National Cancer Institute, Bratislava, Slovakia
In 116 cancer patients with bacteremia and fungemia and neutropenia (71%) analysis for the cause was made with regard to the presence of venous catheter, previous therapy or prophylaxis, uderlying disease and immunosuppression and etiology. The incidence of bacteremia in patients with catheter was 12x higher (8.25% vs. 0.76%) in comparison to those without catheter and the mortality in respective groups was 26.3% and 15%. Among 206 isolates, 128 (63%) were grampositive aerobes, 58 (27.5%) gramnegative aerobes and 20 (9.5%) fungi. The mortality was the highest in patients with catheter and fungemia (66.6%) and relatively higher in patients with catheter and gramnegative bacteremia.
Key words: Bacteremia, fungemia, neutropenia, catheter related infection.
pp. 35-38
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Salvage chemotherapy for recurrent Ewing's sarcomas
T. OZAKI, S., SUGIHARA, M. HAMADA, Y. NAKAGAWA, H. INOUE
Department of Orthopaedic Surgery, Okayama University Medical School, Okayama 700, Japan
Metastatic disease tends to recur after remission of Ewing's sarcoma. The effectiveness of ifosfamide in patients with recurrent Ewing's sarcoma was reported in recent years. We administered IFOS combined with etoposide, pirarubicin, and cyclophosphamide to 4 Ewing's sarcoma patients with metastatic disease, and succeeded in inducing second remissions in all cases.
Key words: Ifosfamide, chemotherapy, Ewing's sarcoma, relapse, etoposide.
pp. 39-42
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Early diagnosis of medullary thyroid carcinoma in a 13 years old girl
Z. MISIKOVA, L. KOSTALOVA, S. PODANA,¹ J. KNOTEK,¹ A. CARADSKA²
2nd Pediatric Teaching Hospital, School of Medicine, Komensky University, 833 40 Bratislava, Slovakia;
¹National Cancer Institute, Bratislava, Slovakia;
²Pediatric Hospital, Topolcany, Slovakia
Early stage of medullary thyroid carcinoma was diagnosed in a 13 years old girl from the family with incidence of MEN IIa. High level of calcitonin after pentagastrin stimulation was crucial for the diagnosis. Pentagastrin test as a regular screening for medullary thyroid carcinoma for all children over 3 years of families with MEN IIa is recommended.
Key words: Medullary thyroid carcinoma, calcitonin, pentagastrin test, childhood carcinoma.
pp. 43-45