Modulation of CALLA (CD10) antigen on cultured ALL (REH) cells: effect of various modulators.

Phorbol ester (TPA)-induced down-regulation of the common ALL (CALLA) antigen was studied by continuous flow immunocytometry with the aid of several CD10 monoclonal antibodies, including a new CD10 monoclonal antibody (DGH-10-1-A9), shown to be of IgG1 isotype, recognizing a 100 kDa cell surface protein and effectively inhibited by a series of reference CD10 monoclonal antibodies. The TPA-induced down-regulation of CALLA on REH cells was demonstrated with the aid of the following CD10 monoclonal antibodies: J-5, VIL-A1 and DGH-10-1-A9. No major modulations in cell surface expression of CALLA on REH cells were observed after induction with 1,25-(OH)2 vitamin D3, retinoic acid, recombinant interferon (IFN) alpha 2a and recombinant interleukin 2.

Phosphorylation of acyclic nucleotide analogs HPMPA and PMEA in L1210 mouse leukemia cell extracts.

Acyclic nucleotide analogs (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA) were phosphorylated in the presence of ribonucleoside 5'-triphosphates by the crude extract from mouse leukemia cells L1210 affording the respective mono- and diphosphoryl derivatives. The donor efficiency was decreasing in the order CTP greater than UTP greater than ATP greater than GTP. The presence of an ATP regenerating system stimulated considerably the conversion of both compounds. The rate of PMEA phosphorylation was 5-times slower than that of HPMPA both with and without an ATP regenerating system.

Chromosome abnormalities in squamous cell carcinoma of the human oral cavity.

Cytogenetic studies carried out in tissues of 75 patients with squamous cell carcinoma of the oral cavity gave satisfactory results in 12 cases. Remarkable variation characterized the modal chromosome numbers of these tumors, ranging from marked hypodiploidy to tetraploidy. Chromosomes which were lost belonged to group A whereas chromosomes which were gained belonged to groups C, D, E, F and G. Marker chromosomes were present in three cases. There was no correlation between the chromosome abnormalities observed and the clinical stages of the disease. The pattern of chromosome abnormalities ranging from marked hypodiploidy to tetraploidy observed in oral cancer tissues suggests an association of DNA oncogenic virus possibly Herpes simplex virus Type I (HSV-1) with oral cancer.

Immunofluorescent detection of actin cytoskeleton in spontaneously transformed and B77-supertransformed cells using antibody to tropomyosin.

Differences in immunofluorescence of actin cytoskeleton between normal rat fibroblasts and two transformed cell lines SAMIV and SAMB77 were detected by antiserum to tropomyosin. In both transformed cell lines reduction in number and shortening of microfilament bundles (stress fibers) were observed. In some transformed cells ruffling membranes (peripheral ruffles) were seen. Differences were found in actin cytoskeleton among individual cells of spontaneous transformants (SAMIV) and supertransformants (SAMB77).

The effect of second generation platinum cytostatics on mammalian cell proliferation.

The effect of three second generation platinum complexes on proliferation of tumor cells (HeLa, C6) and nontumor cells (LEP) was studied, and compared with that of cis-DDP. The highest activity, comparable with cis-DDP, was exhibited by oxoplatinum. CBDCA was somewhat less active in this system, but had a greater effect on both lines of tumor cells than on nontumor cells. Cell proliferation was inhibited least of all by CHIP(IV). The differences observed are discussed from the point of view of the structure and oxidation state of the platinum complexes.

Humoral leukocyte adherence inhibition (H-LAI) test in screening of high risk group for lung cancer.

In the screening examinations of 150 ore miners the positive humoral immune response against lung tumor antigen was measured in 30 serum samples. Repeated testing of positive sera (after 1-3 years) was possible only in 15 cases. Among them, the reaction of 12 serum samples was again positive, and 2 persons died of lung cancer. The results obtained in these follow-up investigations are discussed.

Significance of lineage specific differentiation markers for complex classification of acute leukemias. I. Acute myeloid leukemias.

Acute leukemias are clonal malignant neoplastic diseases which do not originate from the transformation of totipotent hematopoietic stem cells but of progenitors committed to the myeloid, T-lymphatic or B-lymphatic differentiation lineage. The transforming event seems to be associated with a nonrandom aberrant DNA rearrangement. Although a leukemic population is clonal, originating from a single cell, it exhibits phenotypic, and sometimes even karyotypic, heterogeneity. Leukemic cells are allocated to a particular differentiation cell lineage on the basis of a positive finding of the lineage specific differentiation marker (LSDM) in the presented classification of acute leukemias. Criteria for common types of acute myeloid leukemias are described and the possible existence of several other types is discussed.

Significance of lineage specific differentiation markers for complex classification of acute leukemias. II. Acute lymphoblastic leukemias.

Acute lymphoblastic leukemias originate from cells committed either to the T-lineage (T-ALL) or B-lineage (nonT-ALL). Leukemic cells are allocated to these lineages according to the expression of lineage specific differentiation markers (LSDM), which are T-cell antigen receptors for the T-cell lineage and immunoglobulins for the B-cell lineage. T-ALL seem to be one type of disease, among nonT-ALL it is possible to distinguish several types of diseases according to the immunoglobulin expression and clinical findings. The specificity of monoclonal antibodies and other markers is discussed with regard to the classification of ALL and "hybrid acute leukemias" (hAL), the latter with cells differentiating into myeloid and lymphoid lineages. The existence of a single hAL has not yet been reliably proved with the use of LSDM. Short-term cultures of leukemic cells represent useful diagnostic tools particularly for acute unclassifiable leukemias. Present knowledge of karyotype findings in acute leukemias classified according to LSDM is reviewed and the necessity to introduce a complex classification on this basis stressed.

Biochemical and immunological phenotype alterations in human monoblastoid cell line U-937 induced by physiological (interferon-alpha, retinoic acid) and nonphysiological (phorbol ester) inducers.

Human monoblastoid cell line U-937 was induced by recombinant or leukocyte human interferon-alpha, retinoic acid, by their combination, or by 12-0-tetradecanoyl-phorbol-13-acetate (TPA), to express some differentiation-associated markers and characteristics. Induced biochemical alterations were studied with the aid of two-dimensional electrophoretic analysis (isoelectrofocusing/SDS-PAGE) of 125I-lactoperoxidase radioiodinated cell surface proteins, 35S-methionine metabolically radiolabeled cell proteins and 32P orthophosphate radiolabeled cell phosphoproteins. Alteration of immunophenotype markers was studied by continuous flow immunocytofluorometry with a panel of monoclonal antibodies directed to leukocyte antigens, cell proliferation, DNA, RNA, and protein synthesis by radioactive precursor incorporation techniques. Furthermore, cytochemical markers, cell adherence and nitroblue tetrazolium (NBT) reduction were utilized to follow the induction of differentiation-associated characteristics. Differential alterations of some immunophenotype markers induced by diverse inducers were observed. Major induced alterations included down-regulation of CD4 (induced by TPA, and to a lesser extent by IFN-alpha), TPA-induced decrease of cell surface expression of transferrin receptor (unmodified by IFN-alpha) and IFN-alpha induced increase of antigen density (fluorescence intensity) of MHC class I antigen. Marked retinoic acid and interferon-alpha induced increase in membrane expression of antigen(s) detected by monoclonal antibodies BraC6 and BraC8, elicited with healthy donor's granulocytes, was also observed.

Some electrochemical characteristics of synthetic analogs of nucleic acid components. I. Derivatives of cytidine and arabinosylcytosine. An attempt to find correlation among some of their properties.

The polarographic reduction and parameter tg alpha of a series of natural and synthetic pyrimidine nucleosides, cytidine derivatives, and the cancerostatic agent arabinosylcytosine were studied. Correlations were found between these newly determined characteristics and capacity factor kappa from HPLC analysis, growth inhibition of E. coli B bacteria, deamination of nucleosides by cytidine deaminase, DNA synthesis, and rate of biotransformation and lipophilicity expressed as log P. It was confirmed that the molecule of nucleosides is complex to such an extent that no linear correlation could be revealed among the respective parameters. Linear correlation was found only in smaller, structurally similar groups of derivatives.

Tumor inhibition and hematological improvements by dopamine analog 3,4-dihydroxybenzylamine in mice bearing transplantable carcinoma.

The cancer chemotherapeutic efficacy of 3,4-dihydroxybenzylamine (DHBA), a dopamine analog with reduced neurotoxic effects, was evaluated in strain A mice bearing transplantable Ehrlich's ascites carcinoma. The analog was administered intraperitoneally on day 1 post-transplantation at dose schedules of 50, 100 and 200 mg/kg/day for 7 consecutive days. The results demonstrated a significant inhibition of tumor growth and prolongation of the survival time of EAC tumor bearing mice following DHBA treatment. Diminished activity of the growth-related respiratory enzyme succinate dehydrogenase along with the stimulated activity of the lysosomal enzyme beta-glucuronidase in the DHBA-treated tumor cells indicated inhibition of tumor growth as well as active lysis of the tumor cells. Tumor inhibition was accompanied by marked improvements in hemoglobin concentration. RBC count and bone marrow cellularity. The results demonstrated that DHBA did not adversely affect hematological profile of the host while it inhibited the growth of Ehrlich's ascites carcinoma.

HPLC determination of methotrexate and its metabolite in serum.

Determination of methotrexate (MTX) residues in biological samples (serum, cerebrospinal fluid) was worked out using liquid-liquid and solid-phase extractions and high performance liquid chromatography (HPLC) with UV detection. Clinical samples from patients treated by low and high doses of MTX were analyzed using reversed-phase and ion-pair liquid chromatography, and buffer-methanolic mobile phases. Chromatographic conditions were optimized for the simultaneous determination of MTX and its metabolite and the minimal analysis time was recommended. The results were statistically evaluated, elimination curves and chromatograms have been demonstrated. Solid-phase extraction recovery was 93.1 +/- 1.5% and the determination limit for methotrexate in serum samples was 5.10(-7) mol/l and after the preconcentration of samples 5.10(-8) mol/l.

In vitro activation of tumoricidal properties of rat peritoneal macrophages using lipopolysaccharide.

The peritoneal macrophages from normal Lewis rats were characterized by their capacity to phagocytose, by the presence of nonspecific esterase and Fc receptors. In vitro, these macrophages were maintained in culture 7 and/or 21 days, respectively, and for the last 24 h (activation period) were cultured with 0.1-4.0 micrograms/ml of lipopolysaccharide (LPS) and were found tumoricidal against different rat fibrosarcomas, at a ratio of 50:1 (BP6-Tu2, MC-1 and B77). Macrophage-mediated tumor cytolysis was determined using 51Cr-release assay. The sensitivity of used tumors to macrophage-mediated cyto-toxicity was different. In vivo the transfer of the activated macrophages together with the mentioned tumor cells to rats inhibited the growth of tumors. The adoptive transfer of macrophages activated with "activators" might lead to a new kind of immunotherapy of neoplastic diseases.

Inhibition of proliferation of HeLa cells by cocultivation with early mouse embryos (preliminary report).

Eight- to 16-cell zona-free mouse embryos were cocultivated with 5 to 10 HeLa cells in cultivation drops of 0.1 microliter containing D-PBS medium supplemented with 20% fetal bovine serum. The control group included HeLa cells alone cultivated in the same medium under the same culture conditions. The two cultures were evaluated after 72 hours. The control group showed 147 out of 181 cases of proliferation of HeLa cells (81.22%), whereas HeLa cells cocultivated with zona-free mouse embryos only proliferated in 2 out of 156 cases (1.28%). Proliferation of HeLa cells was inhibited even though these were not in direct contact with the embryos. The experiments suggest that the secretory activity of early embryos in culture medium inhibits proliferation of transformed cells via a special agent.

Hairy cell leukemia and other "hairy-cell" lymphoproliferative disorders (LPD-HC): the significance of morphologic, histologic and immunologic studies.

In this report the clinical, morphologic, histologic and immunologic findings of 41 patients with hairy lymphoid cells in peripheral blood and/or bone marrow are analyzed. In 27 patients the diagnosis of hairy cell leukemia was established. 14 patients had other variants of lymphoproliferative disorders: malignant lymphoma with hairy cells--7, chronic lymphocytic leukemia with hairy cells--5, and T cell lymphoproliferative disorder with hairy cells--2 patients, respectively. Several variants of malignant lymphoma with hairy cells were defined: lymphocytic, centrocytic and lymphoplasmacytic. The importance of combined use of bone marrow biopsy and immunophenotyping for the correct diagnosis of hairy cell leukemia and other "hairy-cell" lymphoproliferative disorders is stressed. The obtained data suggest relationship between characteristic clinical manifestation (isolated splenomegaly), presence of hairy cells and CD11c-antigen expression.

Expression of blood group A and B antigens in gastric cancer examined by monoclonal antibodies.

Fourty-eight patients with gastric carcinoma were histologically examined and classified according to Laurén as intestinal or diffuse type. Employing monoclonal antibodies, in all samples the expression of blood group A and B antigens was studied using the method of indirect immunoperoxidase reaction. In patients with blood groups A and AB the comparison of expression revealed marked differences between the intestinal and diffuse type carcinomas. In the intestinal type, the expression of the blood group antigens was highly heterogenous, while diffuse type carcinomas displayed a homogenous expression. The obtained differences support Laurén's classification. The staining of supranuclear regions of tumor cells by the monoclonal antibody HE 10 (which reacts with antigenic determinants A and H of type 3 and 4) was found more frequently in intestinal type carcinomas. The possible prognostic significance of these findings is discussed.

Sonography in the evaluation of treatment of differentiated thyroid cancer. First results in 158 patients.

Sonographic examination of soft tissues of the neck was used to search for recurrent thyroid cancer in 158 patients. Two hundred and thirty-six sonographic findings were evaluated. Specificity of the method, regardless of the type of recurrence, was 0.96, sensitivity 0.66, precision 0.81, predictive value of negative finding 0.72. This compares favorably with the results of examination by palpation (sensitivity 0.32 to 0.52, according to the type of recurrence), or with those of palpation combined with thyroglobulin estimation (sensitivity 0.50 to 0.60). Most important was the possibility of early detection of unpalpable recurrent lesions showing no radioiodine uptake, or relapses with low thyroglobulin production. Systematic evaluation of out-patients using sonography could lower the need for radioiodine scans that are necessarily connected with thyroid hormone therapy withdrawal and that are usually performed in in-patients.

Survival and mortality in a randomized study of lung cancer detection.

In a randomized prospective study of lung cancer detection in a high-risk population of over 6000 heavy smokers semiannual screening by X-ray and sputum cytology was compared to screening at a 3-year interval. The comparison of Kaplan-Meier estimates of survival curves done without and with correcting for lead-time bias disclosed a rather important impact of lead-time bias on survival comparisons. On the contrary, controlling for possible length bias had no obvious effect on the shape of survival curves. The evaluation of mortality from lung cancer, being used as a basic criterion, indicated no traceable benefit from semiannual screening. The higher incidence of lung cancer in the frequently screened group was paralleled by a higher mortality. It is concluded that currently available screening techniques will not solve the problem of lung cancer mortality in smokers. The results underline the importance of primary prevention for lung cancer.

Occupational risk factors for cancer of the larynx in Spain.

Spain is one of the countries with the highest incidence of laryngeal cancer and, together with France, is the country with the lowest percentage of women with this disease. In order to identify the occupational risk factors associated with laryngeal cancer in this country a case-control study was performed. Cases included 85 patients with epidermoid carcinoma of the larynx diagnosed in "La Paz" Hospital, Madrid, between 1985 and 1987. A sample of 170 patients from the same hospital was used as control. The results of the study revealed that 56.5% of larynx cancer patients had a sedentary occupation working in the service sector. Exposure to insecticides or silica were strongest risk factors for laryngeal cancer. An association between laryngeal cancer and exposure to fumes, chemical products, mineral dust, or wood dust was not found.

Risk for development of cancer in three urban areas of India.

The probability of developing cancer by using life table approach has been computed for the population of three metropolitan cities of India based on data of population based cancer registries located at Bangalore, Bombay and Madras. It was observed that the risk for development of malignancy of all sites from 20 to 64 years ranged from 4.73% to 5.28% in males, whereas it was 6.76% to 9.18% in females. The increased risk in females was mainly due to the high risk of development of cancer of the uterine cervix and breast. The available morbidity indices such as cumulative incidence rate and cumulative risk do not account for the mortality experiences of population. The present exercise will be useful in evaluating the changes in the disease spectrum as a result of change in the mortality experiences and population structure.

Flow cytometry (FCM) analysis of endometrial hyperplasia and carcinoma.

In a series of 52 biopsy specimens (31 endometrial carcinomas, 10 atypical endometrial hyperplasias, and 11 cases of normal endometrium), DNA ploidy and S-phase cell fraction were estimated in paraffin-embedded material. DNA aneuploidy was detected in 2 of the 10 atypical endometrial hyperplasias and 7 of the 31 endometrial carcinomas. The majority of aneuploidy was found to be connected with the loss of tumor differentiation. No ploidy disturbances were found in normal endometrium. The S-phase cell fraction value of normal endometrium was significantly lower when compared with that of endometrial carcinoma. The broad variation in S-phase cell fraction values of the endometrial carcinomas and atypical endometrial hyperplasias was in contrast with the low variability of S-phase cell values of normal endometrium. Very low incidence of aneuploidy in the group of well differentiated endometrial carcinomas (Grade I) enables the suggestion that the presence of aneuploidy predicts a more aggressive disease and that the detection of an aneuploid stemline in atypical endometrial hyperplasia may already indicate the neoplastic transformation.

Microphotometric nuclear DNA analysis in cervical dysplasia of the uterine cervix: its relation to the progression to malignancy and regression to normalcy.

The present study was attempted to reveal the predictive value of DNA ploidy pattern of uterine cervical dysplasia cases in relation to cervical carcinogenesis. Microphotometric nuclear DNA analysis using Feulgen stain was carried out in 310 cervical smears of 80 dysplasia cases consisting of 53 cases which progressed to malignancy and 27 cases which regressed to inflammation or normalcy during their follow-up periods. Aneuploid DNA pattern was observed in initial as well as follow-up smears in 69.8% of cases of the progressive group, and in 7.4% of cases of the regressive group. This difference is statistically highly significant (chi 2 27.88, p less than 0.001). In the progressive group, an aneuploid DNA value was observed in 40.0% of mild dysplasia, 71.9% of moderate dysplasia and 90.9% of severe dysplasia. In the regressive group, DNA aneuploidy was observed in only 9.1% of moderate dysplasia. This difference is statistically significant. These findings indicate that an aneuploid DNA value is a risk indicator for malignant potential of dysplasia cases.

Modulation of glycoconjugate biosynthesis by 5-hexyl-2'-deoxyuridine in highly metastatic Lewis lung carcinoma cells.

The mechanism of action of 5-hexyl-2-'deoxyuridine (HUdR), a compound with antitumor activity, has been investigated in the HM cell lines derived from the highly metastatic variant of Lewis lung carcinoma (3LL-HH). It was shown that this pyrimidine analog did not inhibit the biosynthesis of nucleotides but modified the biosynthesis of glycoconjugates. The incorporation of [14C]-glucosamine into cytoplasmic glycoconjugates [glycosaminoglycan (GAG), glycolipid (GL), glycoprotein (GP), neutral polysaccharide (NP)] decreased to a similar level. The [14C]-glucosamine derived radioactivity was reduced to about 60-70% of the untreated controls in the presence of 15 micrograms/ml HUdR, which caused no inhibition of cell proliferation. These results might be explained by the reduced conversion of glucosamine into uridine-5'-diphospho-hexosamine. As more reduction was observed in the glucosamine labeling of glycoconjugates in nuclei and extracellular compartment, it may be conceivable that the intracellular transport of certain glycoconjugates (GAG, GP) is also affected by HUdR. In the extracellular compartment the reduced level of GAG labeling was the most apparent change. However, at a higher concentration of HUdR (75 micrograms/ml) there was a higher radioactivity in the combined GL + GP fraction. Using [35S]-labeling, the GAG fractions also showed a decreased radioactivity but only at the concentration of 75 micrograms/ml HUdR.

The role of polyamines as a marker of tumor progression and regression in experimental tumors.

The pattern of changes in the polyamine spectrum has been studied under the stress of Sarcoma 180, a transplanted tumor growing in the peritoneal cavity of mice. Retinol, a known inhibitor of ornithine decarboxylase, was used to modulate tumor growth pattern and subsequent changes in the level of polyamines. The polyamine levels showed an increase during tumor proliferation. In the treated group, however, the enhanced levels exhibited a tendency to decrease, along with tumor inhibition, indicating that a positive correlation exists between the polyamine content in the red blood cells of mice and the tumor growth pattern.

Stimulating effect of blood serums from tumor-bearing rats on cholesteryl ester synthesis in normal rat liver cytosol in vitro.

Addition of diluted blood serum from tumor-bearing rats stimulated significantly the synthesis of cholesteryl esters from labeled cholesterol and endogenous fatty acids in the cytosol derived from normal rat liver. With both Zajdela and Walker transplantable tumors this effect was found to be associated with the most intensive period of tumor growth. During chemical carcinogenesis induced by a single subcutaneous administration of benzo(a)pyrene the stimulating effect of sera was found to precede several weeks the appearance of palpable tumors and persisted during the period of progressive tumor growth. With all tumors used, sera in ultimate stages of tumor growth failed to show a stimulating effect. The stimulating effect was due to the presence of a yet unidentified lipid. Higher quantities of this substance may appear in the serum of tumor-bearing animals to meet higher requirements for cholesteryl esters during tumor growth. The stimulating effect of the blood serum on cholesteryl esters may be a useful marker of malignant tumors in humans.

Long-term carcinogenicity bioassay of the herbicide atrazine in F344 rats.

In Fischer F344/LATI rats of both sexes the herbicide atrazine was given in the diet at concentrations of 0, 375 and 750 ppm for 126 weeks. Food and water consumption was similar in the treated and control groups. Feeding of atrazine resulted in dose-dependent depression of body weight gain in both sexes. There was no difference in the survival among the females. The males in the treated groups lived significantly longer than the controls. Exposure to atrazine resulted in significantly increased incidence of mammary tumors in the high dose male group. Uterine carcinomas were observed at a dose-related, significantly increased incidence. The number of combined leukemias/lymphomas increased in the treated males and females, but it was statistically significant only for females. The total number of malignant tumors showed a dose-related increase in both sexes. Other tumors and nontumorous lesions occurred at background level and were not influenced by treatment.

Some electrochemical characteristics of synthetic analogs of nucleic acid components. II. Derivatives of uridine and arabinosyluracil. An attempt to find correlation between some of their properties.

The relation between half-wave potentials E1/2, parameter tg alpha, and chemical structure of a series of natural and synthetic compounds of nucleic acids were studied. This series included the pyrimidine nucleobase uracil, the natural pyrimidine nucleoside uridine and its deoxy-derivatives, the synthetic analog arabinosyluracil, its deoxy- and thio-analogs, and some cyclonucleosides. It was confirmed that the value of tg alpha, which may suggest a potential carcinogenic activity of the compounds studied, is dependent upon lipophilicity and rate of biotransformation of these compounds. Generally, it was shown that the complexity of nucleoside molecules makes it impossible to find parameters showing correlation. Linear correlation was found only in small, structurally similar groups of derivatives.

Treatment of murine EL4 leukemia in ascitic form with anti-Thy 1.2 specific immunotoxins.

C57BL/6 mice with EL4 leukemia cells in ascitic form were intraperitoneally treated with ricin A chain-multivalent antibody immunotoxins. The immunotoxins containing rabbit IgG anti-Thy 1.2 antibodies complemented by protein A of Staphylococcus aureus were able to interact specifically with the target cells and to induce an antitumor effect as revealed by an increase in survival time of the mice. No apparent secondary effects consecutive to a cytotoxic action on the normal Thy 1.2 antigen bearing cells were observed with the immunotoxin doses used.

On the background of differences in survival of female breast cancer patients in the German Democratic Republic and the Estonian SSR.

The aim of this study was to describe the age-specific survival patterns and to analyse the differences between the survival rates of female breast cancer patients in the German Democratic Republic in 1976-1977 and the Estonian SSR in 1968-1981. The estimated 5-year relative survival rate (RSR) was 64.1% in the GDR and 55.9% in Estonia. Patients aged 55 years or older at diagnosis had higher survival in the GDR (5-year RSR 62.6%) than in Estonia (49.5%). That result was clearly connected with higher proportion of advanced tumors among older patients in Estonia. For patients younger than 55 years the difference of the 5-year RSR between the both countries was not statistically significant (GDR 65.3%, Estonia 63.4%). The standardization of overall 5-year RSR by stage and age, but also only by stage of the disease produced virtually equal results for the GDR and Estonia. It means that the main source of the differences in overall breast cancer survival rates between the GDR and Estonia are the discrepancies in stage distribution, particularly in older age groups.

Antitumor activity of Borrelia burgdorferi cultures.

Cultures of B. burgdorferi, their supernatants as well as washed cells revealed in vitro a considerable antitumor activity against cells of Gardner lymphoma. Németh-Kellner lymphoma and LP-2 plasmacytoma. In in vivo tests an inhibition of tumor growth was evident, even if the treatment was started on day 4 after implantation of the tumor. The best results were obtained with the supernatants of the cultures.