Electronic Library of Scientific Literature


Volume 43 / No. 3 / 1996

Paclitaxel (Taxol[^R]): A review of its antitumor activity in clinical studies. Minireview

R. Hajek, J. Vorlicek, M. Slavik

Department of Internal Medicine, Masaryk University Hospital, Brno-Bohunice, 639 00 Brno, Czech Republic;
Department of Veterans Affairs and Department of Internal Medicine, The University of Kansas, School of Medicine, Wichita, N. Kansas, USA

The paclitaxel represents first agent from novel class of antineoplastic drugs-taxoids. The clinical development of paclitaxel was initially hampered by hypersensitivity reactions. Current dosage regiments with premedication reduced the incidence of these side effects to less than 3%. The major dose-limiting adverse effect of paclitaxel is neutropenia. Significant activities have been reported in patients with advanced ovarian, breast, non-small cell lung cancer (NSCLC) and head and neck cancer. Combination of paclitaxel with platinum in the treatment of patients with advanced ovarian cancer has a potential to become first-line chemotherapy regimen in the treatment of this disease. Long-term follow-up will also allow to determine the effect of the drug on patient survival. The promising results of this drug in the treatment of patients with other malignancies need to be confirmed in ongoing clinical studies.

Key words: Antitumor activity, antineoplastic agent, clinical studies, paclitaxel, Taxol[^R].
pp. 141-154

Serum levels of interleukin-10 and interleukin-6 in patients with lung cancer

A. Wojciechowska-Lacka, M. Matecka-Nowak, E. Adamiak, J.K. Lacki, B. Cerkaska-Gluszak

Department of Radiotherapy, Wielkopolska Cancer Center, Poznan, Poland;
Department of Clinical Immunology and Allergy, K. Marcinkowski Medical Academy, 61-626 Poznan, Poland

Since the enhanced production of IL-10 by human bronchogenic carcinoma has already been documented, in the present study serum levels of IL-10 were measured serially in patients with lung cancer undergoing radiotherapy.
Thirty-one full diagnosed cancer patients underwent the radiotherapy procedures. The interleukin-10 (IL-10) and interleukin-6 (IL-6) serum levels were measured before therapy and after 3, 6 and 12 months after therapy. The interleukins concentrations were evaluated using a solid phase sandwich Enzyme-Linked-Immuno-Sorbent-Assay (ELISA).
In all patients the serum levels of IL-10 have been found elevated. Due to the treatment they progressively declined to almost normal ranges in responders, while they remained elevated in non-responders. Serum levels of interleukin-6 have been elevated in the majority of our patients. After 12 months observation they also decreased, mainly in patients responding to the treatment. No correlation between serum IL-10 and IL-6 level has been found.
The importance of serum IL-6 determination in lung cancer patients monitoring has already been established. The present study shows, that in spite of still unclear role of IL-10 in the process of carcinogenesis, it may be considered as a prognostic factor in lung cancer.

Key words: Interleukin-10, interleukin-6, lung cancer.
pp. 155-158

Serum tumor marker CYFRA 21-1 in the diagnostics of squamous cell lung cancer - comparison with CEA

P. Berzinec, H. Zuffova, M. Letkovicova, M. Arpasova

Department of Oncology, Institute of TB and Respiratory Diseases, 949 88 Nitra, Slovakia;
Department of Biochemistry, Regional Hospital, Nitra, Slovakia

The aim of the study was to test the diagnostic value of serum tumor marker CYFRA 21-1 for squamous cell lung cancer (SQCLC) in comparison with carcinoembryonic antigen (CEA). Ninety-one patients were included in this study: 56 with SQCLC - Group I, 25 with other types of lung cancer - Group II, 10 with benign respiratory tract diseases - Group III. Median CYFRA 21-1 serum concentration (ng/ml) was: in Group I: 4.52 (0.94 - >16), in Group II: 3.58 (1.72 - >16), in Group III: 2.05 (0.99 - 3.41). Median CEA serum concentration (ng/ml) was: in Group I: 4.49 (0.76 - >20), in Group II: 3.32 (1.17 - >20), in Group III: 3.09 (1.84 - 6.37). There was a highly significant difference between the levels of CYFRA 21-1 in Group I and III (p < 0.001), but there was no statistically significant difference between the levels of CEA in Group I and III. Sensitivity of CYFRA 21-1 by the cut-off 3.33 ng/ml in the diagnostics of SQCLC was 0.68, specificity 0.90, positive predictive value 0.91, negative predictive value 0.65. Sensitivity of CEA by cut-off 4.61 ng/ml was 0.5 by the same specificity 0.90. CYFRA 21-1 has high sensitivity, specificity and positive predictive value in the diagnostics of SQCLC. Sensitivity of CYFRA 21-1 is significantly higher than sensitivity of CEA in this setting.

Key words: Lung neoplasms, tumor marker, CYFRA 21-1, CEA.
pp. 159-161

Variations in steroid hormone receptor content throughout age and menopausal periods, and menstrual cycle in breast cancer patients

D. Nikolic-Vukosavljevic, N. Vasiljevic, M. Brankovic-Magic, D. Polic

Institute of Oncology and Radiology of Serbia, Department of Experimental and Clinical Oncology, 11 000 Belgrade, Yugoslavia

Variations in steroid hormone receptor contents throughout age and menopausal periods define three breast carcinoma groups: younger premenopausal carcinomas (aged up to 45), middle-aged carcinomas (pre-, peri- and postmenopausal aged 4559) and older postmenopausal carcinomas (aged over 59). Age-related steroid hormone receptor contents within premenopausal and postmenopausal carcinoma groups are characterized by the important increase of both receptor contents, while menopausal-related steroid hormone receptor contents within middle-aged carcinoma group (aged 4559) are characterized by the important decrease of progesterone receptor content and estrogen receptor functionality. No variations in steroid hormone receptor contents throughout menstrual cycle within the follicular and the luteal phases were obtained. The important decrease of estrogen receptor content in the mid-cycle phase versus the perimenstrual phase was found. Variations in steroid hormone receptor contents throughout age and menopausal periods, as well as throughout menstrual cycle could not be associated with variations in the blood steroid hormone concentrations. However, important association between steroid hormone receptor contents and the blood steroid hormone concentrations was found within the luteal phase carcinoma group and within older postmenopausal carcinoma group. It is interesting that within carcinoma group with the highest concentration of progesterone, progesterone receptor content increases with an increase of the ratio of estradiol and progesterone blood concentrations, while within carcinoma group with the lowest steroid hormone concentration and the highest content of estrogen receptor content, estrogen receptor content decreases with an increase of either the blood estradiol concentration or the ratio of the blood estradiol and progesterone blood concentrations.

Key words: Breast cancer, steroid hormone receptors, steroid hormones.
pp. 163-169

Lysosomal dipeptidyl-peptidases I and II in human squamous cell lung carcinoma and lung parenchyma

E. Krepela, J. Prochazka, H. Mynarikova, B. Karova, J. Cermak, H. Roubkova

Department of Molecular and Cellular Pneumology, Clinic of Pneumology and Thoracic Surgery, Medical Faculty Hospital Bulovka, 180 71 Prague 8, Czech Republic;
Department of Thoracic Surgery, Clinic of Pneumology and Thoracic Surgery, Medical Faculty Hospital Bulovka, Prague, Czech Republic;
Department of Pathology, Medical Faculty Hospital Bulovka, Prague, Czech Republic

In the present work we studied the levels of activities of dipeptidyl-peptidase I (or cathepsin C, DPP-I) and dipeptidyl-peptidase II (DPP-II) and examined their isoelectric focusing profiles in matched pairs of human squamous cell lung carcinoma (SQCLC) and the lung from surgically treated patients (n = 33). The mean specific activities of DPP-I and DPP-II were higher in SQCLC (Stages I and II) than in the lung, but only the activity of DPP-II in Stage I SQCLC was significantly higher compared to the lung. The activities of both enzymes were higher in the tumor than in the lung in 10 of 20 Stage I SQCLC patients, but only in 3 of 13 Stage II SQCLC patients. The specific activities of DPP-I and DPP-II in the lungs showed a good correlation while the correlation of both enzyme activities in SQCLCs was poor. We observed only a small and mutually comparable activation of DPP-I in extracts from SQCLCs and from the lungs by dithiothreitol. The isoelectric focusing profile of several DPP-II forms in SQCLCs and the lungs was similar and the single major DPP-II isoform revealed in the tumors and lungs showed a pI[_app] of 5.35.2. The isoelectric focusing profile of DPP-I showed multiple enzyme forms in SQCLCs (pI[_app] 6.34.5) as well as in the lungs (pI[_app] 6.44.8). In SQCLCs, as well as in the lungs, the activities of the DPP-I forms with pI[_app] values =< 5.6 were shifted by neuraminidase treatment to the site of the major DPP-I isoform with pI[_app] of about 6.0 and the zymograms then showed an another DPP-I with pI[_app] of 5.7, which was less discernible in the lung. In some patients, the DPP-I forms with pI[_app] values =< 5.6 from SQCLC retained a greater percentage of activity distribution than did the DPP-I pI[_app]-counterparts from the lung.

Key words: Squamous cell lung carcinoma, dipeptidyl-peptidase I, cathepsin C, dipeptidyl-peptidase II, enzyme isoforms.
pp. 171-178

Effects of sequence and temperature of hyperthermia and peplomycin on human pharyngeal carcinoma KB cells in vitro

T. Ohtsubo, H. Saito, I. Noda, C. Sugimoto, T. Saito, E. Kano

Department of Otolaryngology Fukui Medical School, Matsuoka, Fukui, 910-11, Japan;
Department of Experimental Radiology and Health Physics, Fukui Medical School, Matsuoka, Japan

To maximize the interactive effect, we examined the time sequence of high (above 43C) or low (below 43C)-hyperthermia and peplomycin (PEP)(0.5 microg/ml). Simultaneous or post-hyperthermic PEP treatment at 44C resulted in a slight synergistic effect with thermoenhancement ratios (TER) of 1.30 or 1.34, respectively.
However, at 42C, maximal interaction was obtained (TER = 10.19) when KB cells were simultaneously heated with PEP. Furthermore, pre-treatment at 44C for 25 min or 42C for 4 h enhanced PEP cytotoxicity more than that of post-treatment at 44C for 25 min or 42C for 4 h, respectively. However, chemoenhancement ratios (CER) of pre-treatment at 44C for 25 min and at 42C for 4 h were 19.1 and 3.5, respectively, although the isothermic dose decreased the cell count to 60% in both cases. These results indicated that simultaneous or post-hyperthermic PEP treatment with high-hyperthermia, and simultaneous PEP treatment with low-hyperthermia, are the most effective means of PEP thermochemotherapy with hyperthermia.

Key words: Human pharyngeal carcinoma KB cells, peplomycin, hyperthermia, thermochemotherapy.
pp. 179-183

Detection of human papillomavirus (HPV) type 6, 16 and 18 in head and neck squamous cell carcinomas by in situ hybridization

Z. Cerovac, B. Sarcevic, Z. Kralj, J. Ban

Ruder Boskovic Institute, Department of Molecular Genetics, Laboratory for Experimental Cancerology, HR-10000 Zagreb, Croatia;
University Hospital for Tumors, Department of Pathology and Department of Head and Neck, Zagreb, Croatia;
University of Zagreb, Faculty of Science, Department of Biology and Molecular Biology, Zagreb, Croatia

Seventy seven squamous cell carcinomas (10 oral cavity, 15 tongue, 26 pharynx and 26 larynx), with different grading, were analyzed for the presence of HPV DNA by in situ hybridization. Positive signals were found on the nuclei of cancer cells in 25 (32.5%), in the epithelia adjacent to squamous cell carcinomas in 2 (8.7%), and in the resected margins in 1 (4.3%) case. HPV DNA positive signals were obtained in 42% of laryngeal, 34% of pharyngeal, in 20% of oral, and 20% of tongue carcinomas. Out of 25 HPV positive carcinomas a single HPV type was detected in at least 11 (44%), and double or multiple infection in 9 (36%) cases; altogether, HPV 6 DNA was determined in 15 (60%), and HPV 16 and/or 18 DNA in 17 (68%) head and neck tumors. The detection rate of HPV 6 was lower than of HPV 16 and/or 18 for tumors in oral cavity, tongue and larynx. Out of 25 HPV DNA positive carcinomas 21% were graded as G1, 27% as G2, and 44% were G3. The results indicate that HPV may be involved in the pathogenesis of head and neck squamous cell carcinomas.

Key words: HPV, head and neck carcinoma, histological grade, in situ hybridization.
pp. 185-194

The value of prognostic factors in the management of Stage I nonseminomatous germ cell testicular tumors (NSGCTT)

D. Ondrus, F. Goncalves, J. Kausitz, J., Matoska, V. Belan

Department of Urology, Comenius University Medical School, Derer Memorial Hospital, 833 05 Bratislava, Slovakia;
Department of Nuclear Medicine, Cancer Institute, St. Elisabeth Hospital, Bratislava, Slovakia;
Department of Pathology, Cancer Institute, St. Elisabeth Hospital, Bratislava, Slovakia;
Department of Radiodiagnostics, Postgraduate Medical Institute, Drer Memorial Hospital, Bratislava, Slovakia

The prospective study, carried out from February 1992 to January 1996, included 49 patients in clinical Stage I nonseminomatous germ cell testicular tumors (NSGCTT). They were aged 1640 years (mean, 25 years). Patients were stratified to different risk-adapted therapeutic approaches according to histopathologic findings of primary tumor removed by inguinal orchiectomy.
Eleven patients of the 1st group with vascular invasion and majority of embryonal carcinoma components in the primary tumor were treated with adjuvant chemotherapy (2 cycles of BEP). None of them had disease progression after the follow-up of 443+ months (mean, 20.9 months) after orchiectomy.
Five patients of the 2nd group with vascular invasion and majority of teratoma elements in the primary tumor were treated with primary retroperitoneal lymph node dissection (RPLND). They were followed-up 2945+ months (mean, 33.4 months) after orchiectomy. Two of them (40%) had pathologic Stage II after RPLND and underwent subsequent BEP chemotherapy. One of them died due to disease progression in disseminated stage 29 months after orchiectomy. The second one lives with no evidence of the disease (NED).
Thirty three patients in the 3rd group without vascular invasion were kept under surveillance. They were followed-up 348+ months (mean, 22.3 months) after orchiectomy. Disease progression was observed in 5 of them (15.1%), 710 months (mean, 8.8 months) following orchiectomy. These patients were treated with BEP chemotherapy and live with NED 116+ months (mean, 9.2 months) after completion of the therapy.
The overall survival rate in clinical Stage I patients was 97.9%. The authors recommend the surveillance policy only in clinical Stage I NSGCTT patients without vascular invasion in the primary tumor.

Key words: Testicular tumor, Stage I, surveillance, prognostic factors.
pp. 195-197

Gastric cancer in the province of Zaragoza (Spain): A survival study

A. Jimeno-Aranda, R. Sainz Samitier, G. Marcos Aragues

Delicias Sur Health Centre 50 007 Zaragoza, Spain; Medical School, Zaragoza University, Zaragoza, Spain

A study of the main prognostic factors and of the overall survival rate of gastric cancer (GC) is presented. It covered 895 cases diagnosed histopathologically in the province of Zaragoza (Spain) over a ten-year period (19801989). The analysis of the survival rate was carried out according to the Kaplan-Meier method and the Mantel-Haenszel test.
The average overall survival rate of the sample was 6.5 months and the five-year survival rate was 16.5%. Laurens intestinal histological type is associated with a better prognosis (a five-year survival rate of 25%) than the diffuse type (15%). The survival rate with regard to gastric wall invasion ranges from 78% for T1 tumors to 8% for T4 tumors (p < 0.0001).
There are significant differences in survival rate between the TNM classification stages, ranging from a five-year survival rate of 77% for Stage I to 0% for Stage IV.

pp. 199-203

Activity and characterization of sialyltransferase from serum of normal rats, of rats bearing Zajdela ascitic hepatoma, in normal host liver and in Zajdela hepatoma cells

D.G. Ivanov, V.K. Karaivanova, S.X. Ivanov, H. Chelibonova-Lorer

Institute of Experimental Pathology and Parasitology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria

Comparative studies on the content of sialic acid and on the sialyltransferase activity in normal serum and in serum of rats with Zajdela ascitic hepatoma in different phases of tumor development have been conducted. Unlike the serum from animals with tumors, in which the sialic acid quantity increases in dependence of the stage of tumor development, the activity of serum sialyltransferase statistically augmented only in serum of rats at the final stage of tumor progression. The sialyltransferase activity towards asialofetuin as an acceptor in normal liver and in Zajdela hepatoma cells, was measured and a decrease in this activity in tumor cells as well as in host liver was found. When lactose was used as acceptor, again lower enzyme activity in the tumor cells in comparison with that in liver was established, but in liver and in hepatoma cells the predominant [^14]C-labelled product of the sialyltransferase assay was alpha(2-6) sialyllactose isomer. The results contribute to the biochemical characterization of rat Zajdela hepatoma.

Key words: Sialic acid, sialyltransferase, alpha(2-3), alpha(2-6) sialyltransferase, serum, Zajdela ascitic hepatoma.
pp. 205-208

Evaluation of phthalmustine, a new anticancer compound. II. Tumor inhibitory effect in murine Ehrlich ascites carcinoma and sarcoma-180

S. Bhattacharya, M. Ghosh, U. Sadhu, S. Dutta, U. Sanyal

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

The antitumor activity of phthalmustine (Neoplasma, 41, 1994, 35) has been evaluated in murine Ehrlich ascites carcinoma (EAC) and sarcoma-180 (S-180). The hematological changes associated with the application of phthalmustine were also evaluated in tumor bearing as well as in normal male Swiss mice. The results indicate that phthalmustine induces marked inhibition of tumor growth and substantially prolongs host survival having curative effect while it does not adversely affect hematopoiesis at the optimum dose tested. No toxic symptoms were noted with respect to external appearance, body weight changes and behavioral pattern.

Key words: New anticancer agent, mice, EAC, S-180, tumor inhibition.
pp. 209-213