Electronic Library of Scientific Literature


Volume 42 / No. 3 / 1995

Expression of the alpha[2]-macroglobulin receptor on human neoplastic fibroblastoid cells


Cancer Research Institute, Slovak Academy of Sciences, 812 32 Bratislava, Slovakia;
¹Department of Virology, University of Helsinki, Helsinki, Finland

The alpha[2]-macroglobulin membrane-associated receptor (alpha[2]MR) has been previously detected on hepatocytes, fibroblasts, macrophages, syncytiotrophoblasts and recently on human malignant blood cells of myelomonocytic leukemia. In cells growing in vitro from human germ cell tumors alpha[2]MR mRNA was detected by Northern blotting. Endocytosis of alpha[2]M from culture medium was detected in these cells by indirect immunofluorescence. In cell extracts alpha[2]M and its degradation products were detected by immunoblotting. The cells expressing alpha[2]MR and internalizing alpha[2]M were identified as fibroblasts both by their morphology and expression of vimentin intermediate filaments. The role and function of alpha[2]MR receptor in the analyzed neoplastic cells of teratomatous origin is discussed.

Key words: alpha[2]-macroglobulin, receptor, neoplastic fibroblasts.
pp. 97-103

Electrophoretic analysis of microheterogeneity of paraproteins in a patient with IgD myeloma


Institute for Immunology, Military Medical Academy JEP, 502 60 Hradec Kralove, Czech Republic;
¹Department of Internal Medicine, Charles University, Czech Republic;
²District Hospital, Department of Clinical Biochemistry, Zlin, Czech Republic

High-resolution two-dimensional polyacrylamide gel electrophoresis (2-DE) was used to analyze more precisely serum and urine specimens of a patient suffering from IgD myeloma associated with renal insufficiency. The application of 2-DE with immobilized pH gradient followed by immunoblotting revealed the presence of acidic monoclonal delta chains, hidden on 2-DE by albumin. This approach also enabled to detect two other forms of delta heavy chains expressing both reduced (45 kDa) and high (110 kDa) mol. weight. The analysis of urine specimen proved the presence of three acidic isoforms of monoclonal lambda light chains together with multiple monoclonal light chain fragments, which strongly suggests amyloidogenicity of these monoclonal light chains.

Key words: Two-dimensional gel electrophoresis, immunoglobulins, paraproteins, microheterogeneity.
pp. 105-108

Sensitization and photodynamic therapy (PDT) of gastrointestinal tumors with 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX). A pilot study


National Medical Laser Centre, University College London, Medical School, London, U. K.;
¹Department of Gastroenterology, National Cancer Institute, Bratislava, Slovakia

5-Aminolaevulinic acid (ALA) is a promising agent for photodynamic therapy (PDT) sensitization as it can be given orally and only causes skin photosensitivity for 1-2 days. In fluorescence and photodynamic studies 26 patients with benign and malignant gastrointestinal tumors were given 30-60 mg ALA orally (single or divided doses) and biopsies were taken of tumor and normal tissue at 1-24 hours for fluorescence microscopy. With 30 mg/kg, highest protoporphyrin IX (PPIX) levels were seen in esophagus, duodenum and less in colon, but without tumor selectivity. Better tumor selectivity was seen in colon after 60 mg/kg (5:1). Six patients had transient rises in transaminases and five mild nausea. Sixteen patients were later treated (after further ALA) with red light (628 nm, bare or diffuser fibre, 50-100 J at 50 mW at each site). All but two showed subsequent necrosis, but only 0.5-1.5 mm of depth. PDT with ALA is simple, safe and promising for tumors in the gastrointestinal tract. Modification of treatment parameters may make it suitable for larger lesions.

Key words: Photodynamic therapy, protoporphyrin IX, gastrointestinal tumors.
pp. 109-113

Induction of single strand DNA breaks in workers professionally exposed to polycyclic aromatic hydrocarbons


Institute of Medical Biology, School of Medicine, P. J. Safarik University, 040 60 Kosice, Slovakia;
¹Institue of Medical Chemistry and Biochemistry, School of Medicine, P. J. Safarik University, Kosice, Slovakia

An epidemiological study was performed on 42 workers from coke works with the aim to evaluate the usefulness of monitoring single strand DNA breaks (SSBs) in human lymphocytes to assess exposure to polycyclic aromatic hydrocarbons (PAHs) as well as the usefulness of SSBs induction as an indicator of biological effects of PAHs. SSBs can be readily quantitated by a simple fluorometric assay of DNA unwinding. Compared with the control group, statistically significant increase in SSBs was observed in coke oven workers occupationally exposed to PAHs. These findings are in agreement with previous results obtained by a different method of measuring DNA damage in subjects exposed to high PAH levels. The findings confirmed that SSBs determination in human lymphocytes reflected the exposure to PAHs and the FADU method appears to be useful in the revelation of effects of occupational exposure to industrial air pollutants such as PAHs.

Key words: Single strand breaks, polycyclic aromatic hydrocarbons, coke oven workers, alkaline unwinding, fluorometric analysis, genotoxicity.
pp. 115-118

Radiosensitizer AK-2123 as modulating agent in the chemotherapy of experimental metastases


Institute of Chemical Physics of Russian Academy of Sciences 142 432 Chernogolovka, Moscow Region, Russia;
¹Kinki Invention Center, Yoshida Kawaramachi-cyo 14 Sakyo-ku, Kyoto 606, Japan

Therapeutic effect of Cyclophosphamide (CPA) and radiosensitizer AK-2123 (AK) combination versus CPA alone in the same doses was investigated on transplanted LL carcinoma and B 16 melanoma. Antimetastatic efficacy of different doses of CPA and combined therapy was evaluated. Our data demonstrate that the effect of combined treatment by CPA at low uneffective doses (60 mg/kg, 40 mg/kg, 20 mg/kg at the 3rd and the 7th day after transplantation) and AK at low daily doses (1 mg/kg and 0.1 mg/kg for 3-9 days after transplantation) is equal or superior to the effect of CPA alone at the therapeutic dose (120 mg/kg).

Key words: Chemosensitization, metastases, cyclophosphamide, low doses.
pp. 119-122

Action of retinoic acid on human glioblastoma-astrocytoma - 14 cells in culture


Department of Tissue Culture, Chittaranjan National Cancer Institute, Calcutta - 700 026, India

Monolayer and agar culture techniques were used to examine the antiproliferative activities and morphological alterations of glioblastoma-astrocytoma (G1-As-14) cells induced by 20 micromol retinoic acid (RA). RA treated cells assumed flattened appearance and formed multilayers no longer. Most of the cells formed cross-bridges with one another. RA treatment caused time-dependent, dose-dependent and cell seeding-dependent reduction of growth in both monolayer and in agar cultures. RA-induced growth inhibition was also affected by concentration of fetal bovine serum in the culture medium. All these effects could be reversed within 48 h after withdrawal of RA from the growth medium. The results demonstrated that the respective cell line was sensitive to RA-induced growth inhibition and morphological alterations which were generally associated with reduced expression of malignant phenotype.

Key words: Retinoic acid, glioblastoma-astrocytoma, growth inhibition.
pp. 123-128

Evaluation of the anticancer property of a new alpha-methylene-gamma-lactone derivative of phthalimide


Department of Chemotherapy, Chittaranjan National Cancer Institute, Calcutta 700 026, India

The anticancer property of a new alpha-methylene-gamma-lactone derivative of phthalimide (2, NSC 640168) was evaluated in two murine ascitic tumors namely Ehrlich ascites carcinoma (EAC) and sarcoma-180 (S-180) by in vivo screenings and in a battery of human tumor cell lines by in vitro screening. It was found that the compound has exhibited marginal to moderate in vivo activity in EAC and S-180, respectively, and significant in vitro cytotoxicity in SF-268, a human CNS tumor cell line. The compound, however, has not reached the criteria of significant anti-HIV activity.

Key words: New anticancer agent, screening, murine EAC, murine S-180, human tumor lines.
pp. 129-132

Lung toxicity of chemotherapeutic agents detected by TC-99m DTPA radioaerosol inhalation lung scintigraphy

W. Y. LIN, C. H., KAO, S. J. WANG, S. H. YEH

Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, 407 Taiwan

We investigated the lung toxicity of chemotherapeutic drugs in patients with breast cancer by means of Tc-99m DTPA aerosol scintigraphy. Thirty three patients who underwent surgical resection for breast cancer were divided into two groups, those who received a combination of adjuvant chemotherapy and those who did not. Group 1 consisted of 19 patients who received adjuvant chemotherapy and group 2 consisted of 14 patients who did not received adjuvant chemotherapy. Chemotherapeutic agents included 5-fluorouracil 1000 mg, endoxan 1000 mg and MTX 50 mg, all given intravenously. Aerosol lung scintigraphy was performed in all patients, in the supine position. The degree of lung damage was presented as the half clearance time (T[1/2]) in minutes from the dynamic lung images. Only the right lung was used to analyze clearance, in order to avoid interference from stomach activity on the left side. The results show T[1/2] times of 68.18 ± 20.04 min and 94.46 ± 34.78 min, over the right lung, for groups 1 and 2, respectively. The difference is significant, with a p-value of 0.016, using the Mann-Whitney U test.
We conclude that some chemotherapeutic drugs such as MTX, may result in pulmonary damage and that aerosol lung scintigraphy can provide an objective mean for early detection of pulmonary damage during cytotoxic chemotherapy.

Key words: Lung scintigraphy, chemotherapy, lung toxicity, aerosol.
pp. 133-135

Normobaric oxygen as a sensitizer in radiotherapy for advanced head and neck cancer


Centre of Oncology, M. Sklodowska Curie Memorial Institute, branch Gliwice, 44-101 Gliwice, Poland

The aim of this study was to evaluate radiosensitizing effect of normobaric oxygen breathing in radiotherapy for advanced head and neck cancers.
Forty seven patients with advanced squamous cell carcinomas of the head and neck (7 % in Stage III and 93 % in Stage IV) were entered in the study. Breathing the pure, normobaric oxygen was given for 15-20 min in the treatment room. Irradiation started immediately after oxygen breathing. Conventional, megavoltage radiotherapy to the total doses in the range of 46-67.5 Gy was used. The control group was 46 patients with the same diagnosis and stage treated by radiotherapy alone.
Locoregional tumor control was 36 % in the study group compared to 15 % in the control (p < 0.05). Mean survival time was 15.8 and 11.8 months, and 3-year survival was 19 % and 2 %, respectively (p < 0.05). Survival depended on total tumor dose and total nodal dose. No significant influence of the tumor location on local control and importance of the size of dose per fraction and overall treatment time were found. The most common failure in both groups was persistent tumor. Mean recurrence time was 5 months in the study group and 8 months in the control. Present results suggest that the use of normobaric oxygen breathing prior to irradiation could increase effectiveness of conventional radiotherapy for advanced squamous cell carcinomas of head and neck.

Key words: Normobaric oxygen, head and neck, radiotherapy, hypoxia.
pp. 137-140

Treatment of advanced esophageal cancer by means of irradiation, cisplatinum and 5-fluorouracil


Institute of Oncology, 611 00 Ljubljana, Slovenia

In the years 1985-1990, 30 patients with locally advanced and/or disseminated cancer of the esophagus (Stages III and IV) were treated by radiotherapy (RT) and chemotherapy (ChT) containing cisplatinum and 5-fluorouracil (5-FU).
The median survival of the patients was 8 months (range 2.5-39 months); 13 Stage III patients survived 3-36 months respectively (median 11 months), while 17 Stage IV patients survived 2.5-27 months, respectively (median 6.5 months).
The survival depended statistically significantly (p < 0.05) only on the presence or absence of residual tumor after therapy and not on other parameters observed.
Clinical response to treatment was evaluated in 16/30 patients as follows: CR was obtained in 4 patients, PR in two, and NR in 10 patients. Median survival of 4 patients with CR was 31 months; relatively high rate of CR (4/16) could be explained by the small number of patients. However, favorable survival results in individual patients may be expected even in larger series, though the rate responders may be somewhat lower than that obtained in our study.

Key words: Esophageal cancer, radiotherapy, chemotherapy, cisplatinum, 5-fluorouracil.
pp. 141-145