Management of patients with brain metastases of unknown origin.

During the years 1973-1987, 75 patients were irradiated for brain metastases of unknown origin at the Institute of Oncology in Ljubljana. Of these, 35 (47%) were previously treated by surgery: Metastases were completely removed in 22 patients and partially in 7, whereas biopsy alone was performed in 6 patients. Based on the examinations carried out during radiation therapy and at the time of follow-up, the primary sites of tumor were established as follows: The lung in 40 patients, the breast in 2, melanoma in 2, and the esophagus, kidney, and parotid gland in one patient, respectively. Primary tumor could not be detected in 28 (37%) patients. Metastases were microscopically verified in 48 cases in which anaplastic carcinoma and adenocarcinoma were most frequent. All the patients were irradiated on a cobalt unit, generally with doses of 10 x 300 cGy in 2 weeks. Median survival of the 22 patients with total removal of brain metastases was 9.5 months, one-year survival being achieved in 41% of cases. In the remaining patients median survival was 3 months, whereas only 12% of the patients survived one year. The cause of death were most frequently, i.e. in 45 patients, brain metastases.

Inhibition of DNA biosynthesis by vincristine and pentoxifylline in murine P388 leukemia cells resistant to doxorubicin.

Pentoxifylline (PTX) is a methylxanthine used clinically in the treatment of intermittent claudication. It is an active hemorheological agent used for the treatment of defective microcirculation. The use of the anticancer agent vincristine is limited by its toxicity to normal body tissues. The data presented in the present paper show that it is possible to achieve greater cell-kill by using vincristine in combination with pentoxifylline. The effect of pentoxifylline alone and in combination with vincristine was studied using membrane filtration technique in P388 leukemia (P388) and its subline P388/DOX resistant to doxorubicin and cross-resistant to vincristine. Pentoxifylline (100 mumol/l) had minimal inhibitory effect on DNA biosynthesis in P388 leukemia cells. Vincristine, at the concentration employed in this study did not show significant inhibition of DNA biosynthesis confirming multidrug resistant nature of P388/DOX cells. Pentoxifylline had a dose-sparing effect, wherein it enhanced the antiproliferative activity of vincristine at a clinically achievable concentration. The studies on reversibility of inhibition of DNA biosynthesis in P388/DOX cells pretreated with vincristine and pentoxifylline showed the irreversible nature of the effect of combination of vincristine and pentoxifylline. This observation warrants the possible use of pentoxifylline as an adjuvant in cancer chemotherapy.

Leukocyte alkaline phosphatase and carcinoembryonic antigen in breast cancer patients. Influence of the treatment on the markers.

Leukocyte alkaline phosphatase (LAP) scores and carcinoembryonic antigen (CEA) levels were analyzed in 53 patients suffering from breast cancer. All patients underwent mastectomy and received adjuvant treatment, and all lived more than 5 years after diagnosis without metastatic disease. Thirty-three patients received adjuvant radiotherapy, and 20 patients received adjuvant chemotherapy. The median LAP score before radiotherapy was 117 +/- 48; two months after the beginning of radiotherapy this value was 175 +/- 71, being significantly higher than the original value (p less than 0.001), and one year after the beginning of radiotherapy it was 105 +/- 63, which approximated the normal scores. The median LAP score before chemotherapy was 138 +/- 69; two months after the beginning of chemotherapy it was 194 +/- 63, i.e. significantly higher than before chemotherapy (p less than 0.002), and one year after the beginning of chemotherapy it was 150 +/- 56. Median CEA levels before radiotherapy were 6.4 +/- 5.1 ng/ml; two months after the beginning of radiotherapy this value was 6.0 +/- 5.0 ng/ml; and one year later 7.4 +/- 6.2 ng/ml. Median CEA levels before chemotherapy were 8.1 +/- 12.0 ng/ml; two months after the beginning of chemotherapy 12.6 +/- 13.0 ng/ml (p less than 0.05) in comparison with the values before chemotherapy; and one year after the beginning of chemotherapy it was 8.6 +/- 5.4 ng/ml. We concluded that the LAP scores were influenced by adjuvant radio- or chemotherapy, and the CEA levels were influenced by chemotherapy.

Cross resistance studies with L1210 leukemia subline single and double resistant to cisplatin and iproplatin (CHIP).

Resistance to cisplatin (DDP) and/or iproplatin (CHIP) was induced in vitro in murine L1210 leukemia cells. Double-resistant sublines with combined resistance to both drugs were also developed. Cross resistance investigations with DDP, CHIP, oxoplatinum (OXO), carboplatin (CBDCA) and its quadrivalent derivative OXOCBDCA were performed in these resistant sublines. Lack of cross resistance between DDP and CHIP was found. A higher resistance to CHIP in the double-resistant sublines was observed. A multistep process in the development of resistance to this compound is supposed. The importance of the aminoligand and the role of different pharmacokinetics in the cross resistance are discussed.

Hemoblastoses in mice contaminated with low activities of 239Pu.

Female ICR mice were injected intravenously with low activities of 239Pu (3.0 kBq, 6.0 kBq, 12.3 kBq/kg). In these mice with high spontaneous incidence of hemoblastoses the occurrence of myeloid leukemia, lymphocytic leukemia, lymphosarcoma, reticulum-cell sarcomas and osteosarcoma was studied. Hemoblastoses, on the whole, remained in their numbers radiation-independent, nevertheless, the distribution into specific types changed, with moderate prevalence of myeloid and lymphocytic leukemia and lymphosarcoma. After plutonium injection the mean survival time of mice bearing myeloid and lymphocytic neoplasias was significantly shorter than the survival of mice that died of retothelosarcoma and from other causes. These contamination-dependent differences could not be observed in matched controls. As expected, 239Pu activities used in this experiment induced osteosarcomas. Whereas in leukemogenesis alpha-radiation appeared as a factor promoting and modifying the leukemogenic process, in osteosarcoma the alpha-particles acted rather as an initiator, the effect of which was dependent on the dose to the endosteal progenitor cells.

Release of granulocyte-macrophage colony-stimulating activity from human alveolar macrophages and its support of human myeloid blast cell proliferation.

The ability of human alveolar macrophages to support colony formation of precursor blast cells of the myeloid lineage was investigated. Myeloid blast cells were collected from patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and from the livers of fetuses aborted in the second trimester of gestation. It was found that the alveolar macrophages (AM) produced sufficient amount of colony-stimulating activity which culminated in the fourth week of in vitro cultivation. Conditioned media from AM supported the growth of multipotential blast cell colonies (GEMM-CFU) in AML and MDS, while in fetal hemopoiesis macrophage colonies preponderated. Preincubation with human interferon-alpha (IFN-alpha) can abrogate the production of the granulocyte-macrophage colony stimulating factor (GM-CSF) by AM. Media conditioned by AM were not able to compensate for cell-to-cell contact in long-term cultures of AML blast cells but CSFs released from AM in vivo can contribute to aggravation of the disease.

Identification and expression of human c-Ha-ras and c-sis sequences in NIH3T3 transformants.

High-molecular-weight DNAs from 5 bladder carcinomas were used in transfection of mouse NIH3T3 cells. The manifestation of heterologous oncogene(s) expression in NIH3T3 cells was morphological transformation very often accompanied by changes in growth characteristics of recipient cells. In DNA samples from secondary NIH3T3 transformants human c-Ha-ras and c-sis sequences were identified. In some secondary transformants these sequences were expressed. On the basis of change of the growth characteristics of some secondary transformants we could expect the integration and expression of another human gene(s) for growth factor or growth factor receptor or even activation of mouse genes. We did not manage to identify any Alu sequences in some secondary transformants carrying human c-Ha-ras sequences. On the other hand, it has not been revealed yet that BamHI DNA fragments carrying c-Ha-ras gene contained any Alu sequence. So, the identification of Alu sequences does not have to be the first step in investigation of DNA samples from NIH3T3 transformants.

CA 125 in monitoring chemotherapy of patients with ovarian cancer: early response to the treatment.

Using an immunoenzymatic technique, changes in serum levels of CA 125 were examined in 63 patients with ovarian carcinoma before treatment as well as following the first four courses of chemotherapy. Serum CA 125 level before treatment was dependent upon clinical advancement stage (20.0, 393.43 and 688.84 U/ml at the Stages I + II, III and IV, respectively). Good response to treatment was associated with decreased CA 125 levels, while tumor progression was linked to increasing levels of the marker. Treatment scheme including cisplatinum induced most pronounced decrease in serum CA 125 level which paralleled good clinical response to the treatment. Determination of CA 125 half-life time in serum seemed to provide a sensitive prognostic index in the disease. This index amounted to 10.73 +/- 4.0 days in patients with complete remission and 44.87 +/- 26.5 days in patients with progressive disease.

Multinucleated tumor cells and malignant melanoma.

Multinucleated cells (MC) were counted in cell preparations obtained by dissociation of representative part of tumor lesions immediately after excision. MC were present in almost all specimens examined (39 advanced primary lesions, 90 lymph node metastases and 33 dermal plus subcutaneous metastases); in one third of the samples they were very rare (less than 1% of all cells). There were no significant differences in quantity of MC between primary tumors, node metastases and dermal plus subcutaneous metastases, between node metastases seen early in the course of the disease and those seen later, and between regional node metastases taken from Stage II patients with rapidly progressing disease and regional node metastases taken from patients of the same stage whose disease-free intervals were longer. No unique pattern of similarities or differences in quantity of MC was found when comparing autologous tumor samples excised simultaneously and/or successively during the course of the disease.

Abrogation of human chronic myeloid leukemia cells insensitivity to adriamycin and mitoxanthrone cytotoxicity by quinidine.

The inherent, insensitive nature of human chronic myeloid leukemia (CML) cells to antiproliferative effects of adriamycin (ADR) disallows its utility in the clinics. Efforts were directed towards sensitizing CML cells to ADR and mitoxanthrone (MITO) cytotoxicity by employing quinidine, an antiarhythmic agent. Inhibition of radiolabeled thymidine incorporation into DNA was used as a measure of drug activity. A dose-dependent inhibition of DNA biosynthesis was observed with increasing concentrations of ADR (0.1 to 100 micrograms/ml), MITO (0.05 to 5 micrograms/ml) and quinidine (0.1 to 50 mumol/l). When the CML cells were exposed to quinidine and ADR/MITO simultaneously, the observed enhancement in the antiproliferative activity of the anticancer drug was markedly less as compared to the inhibition of DNA synthesis observed in CML cells pretreated with quinidine for 1 h prior to exposure to the cytotoxic drugs. Pretreatment of CML cells with quinidine resulted in a significantly (p less than 0.001) increased synergistic inhibition of DNA biosynthesis which was completely irreversible. Results highlight the utility of quinidine as a drug response modulator in a schedule-dependent manner to potentiate the cytotoxicity of ADR and MITO and warrants further studies into a possible role of quinidine to increase the chemotherapeutic efficacy of antineoplastic drugs in the clinics.

The subrenal capsule assay in immunocompetent mice--the inevitable role of histopathology in assessment of this method as a tool determining tumor sensitivity to cytostatic drugs.

The subrenal capsule assay (SRC) in immunocompetent mice became one of commonly used approaches to evaluating the efficiency of cytostatic therapy. A comparison of the classical macroscopic evaluation according to the Bogden diagram with results of the histopathologic examination in 118 mice with implanted Yoshida sarcoma or human rectal adenocarcinoma demonstrated the tumor to be present to different extent only in 26 out of 50 macroscopically positive cases and, on the other hand, it was found in 3 out of 68 macroscopically negative animals. Histological changes in these cases, as well as a study of the dynamics of the development of histopathologic changes after tumor implantation and the changes after implantation of inert materials demonstrated that the resorptive and reparative granuloma, originating in immunocompetent mice under the renal capsule after implanting the tumor or other materials, simulates perfectly the growth of the tumor infiltrate. For this reason we consider this method in immunocompetent mice as unreliable when there is no parallel histological examination.

An experimental immunoscintigraphic study with anti-CEA monoclonal antibody (DG2).

Monoclonal antibody D11-DG2 (DG2) against carcinoembryonic antigen (CEA) was examined for suitability for radioimmunodetection of human tumors grown in nude mice. Antibodies DG2 and a control antibody of the same IgG1 subclass were labeled with 131I and injected into mice bearing one of three types of CEA-containing tumors (cell lines LS 174T, HT-29 and Rec S) and/or a CEA-negative tumor (Rec R). Gamma-camera imaging and distribution studies revealed that CEA-containing tumors selectively accumulate DG2 but Rec R does not. As the tumors differ in CEA-content, the highest accumulation of 131I-DG2 (corresponding to the best scintigraphic imaging) was found in LS 174T tumors, intermediate in Rec S and lowest in HT-29 tumors. The mean tumor-to-blood ratios on the sixth day after antibody administration were 4.6, 3.2, and 2.1, respectively, in the control experiments the value of this parameter was always lower than 1. The results showed the applicability of DG2 for immunoscintigraphic studies in patients. Furthermore, a positive correlation was found between the uptake of anti-CEA antibody and CEA-content in the tumors.

Modulation of in vitro chemosensitivity by extracellular Ca++ in adriamycin sensitive and resistant P388 leukemic cells.

P388 mouse lymphocytic leukemia cells sensitive (P388/S) and resistant to adriamycin (P388/Adr), respectively, were exposed in vitro to 3 dose concentrations of adriamycin, mitoxantrone, vincristine and cisplatin in the presence and absence of extracellular Ca++ at 37 degrees C for 1 h. The absence of extracellular Ca++ enhanced the cytotoxicity of all the four drugs by 25 to 30% in P388/S cells. P388/Adr cells retained their resistance to adriamycin irrespective of the presence or absence of Ca++, however, vincristine and cisplatin to which P388/Adr cells, in normal course, show cross-resistance, exhibited a 30-40% enhancement of cytotoxicity in the absence of extracellular Ca++. Cross-resistance of P388/Adr to mitoxantrone was totally circumvented in the absence of extracellular Ca++.

Action of retinoids during transformation of 10T1/2 cells.

The effect of three retinoids, 13-cis-retinoic acid, arotinoid ethyl sulfone and retinal acetate, on methylcholanthrene (MCA) induced transformation of 10T1/2 cells was studied. It appears that 13-cis-retinoic acid and arotinoid ethyl sulfone prevent transformation in a direct way at the last stage of carcinogenesis. Retinal acetate, however, requires cell-to-cell contacts to inhibit the transformation of 10T1/2 cells.

Influence of "nuclear" estrogen receptor content on prognosis of early stage carcinoma of the uterine body. A short-time follow-up.

Sixty-five patients with Stage I and II endometrial carcinoma were investigated. After a short-time follow-up (17-24 months) significant differences in frequency of relapses were observed between patients with tumors containing low amounts of estrogen receptor (ER less than 60 fmol/mg DNA) in the nuclear pellet, and those with tumors containing greater than 60 fmol ER/mg DNA (p = 0.01). Other prognostic factors showed no differences in frequency of relapses. In this small patient material with a short-time follow-up we therefore suggest that ER in the nuclear pellet may be an important prognostic factor.

Increased cathepsin B activity in human lung tumors.

The occurrence and levels of cathepsin B activity were investigated in primary human lung tumors and lung metastases of renal, colorectal and urinary bladder carcinomas as well as in the associated apparently normal lung parenchyma using a continuous rate enzyme assay with Ac-Leu-Arg-Arg-NHMec (7-(N-acetyl-L-leucyl-L-arginyl-L-arginylamido)-4-methylcoumarin) as the fluorogenic substrate. The inhibition studies of the enzymic hydrolysis of the substrate provided evidence for the catalytic action of the cysteine proteinase cathepsin B (CB) in the lung tumor tissues and the lung parenchyma under the assay conditions used. In the studied group of twenty-four patients with primary lung tumors of all major histological types, the level of CB activity in the tumor tissue was increased twofold and more over that in the associated lung parenchyma in 83% and 75% of cases, when expressed on the basis of wet tissue weight and tissue DNA, respectively. In patients with primary lung adenocarcinoma, the activity of the enzyme in the tumor tissue was elevated over that in the lung parenchyma in all cases studied. In both subgroups of patients with squamous cell lung carcinoma and adenocarcinoma, the mean cathepsin B activity was significantly higher in the tumor tissue than in the lung parenchyma. No obvious correlation was found between the tissue level of cathepsin B activity and the stage of primary lung tumor disease. In a limited number of patients with lung metastases, the level of cathepsin B activity was also higher in the tumor tissue than in the lung parenchyma.

IgG1-4 subclasses in paraproteinemias.

The concentration of IgG1-4 subclasses was determined in a series of 10 IgG1 paraproteinemias (5 multiple myelomas and 5 non-myeloma paraproteinemias) and in a series of 11 IgA paraproteinemias (7 multiple myelomas and 4 non-myeloma paraproteinemias). In the group of IgG1 myelomas, deficiency was established in the subclasses IgG2-4, in the group of IgA myelomas, deficiency was proved in all IgG1-4 subclasses as compared with non-myeloma paraproteinemias. Decreased IgG heterogeneity in IgG1 myelomas was demonstrated by the method of isoelectric focusing.

A new chemotherapeutic regimen in the treatment of advanced gastric cancer.

The results of different chemotherapeutic regimens used in the treatment of advanced gastric cancer are compared. Three groups of patients were evaluated. The first group (59 patients) was treated by a new regimen consisting of methotrexate, 5-fluorouracil, cyclophosphamide and lederfolin (MFC + CF), the second group (21 patients) was treated by COnFU regimen (cyclophosphamide, vincristine, 5-fluorouracil), and the third group (35 patients) was treated with 5-fluorouracil (5-FU) alone. The control group of 41 patients with advanced gastric cancer was not treated cytostatically. The percentages of positive responses were as follows: 49.2% in the group treated with the new regimen, 33.3% in the COnFU group, and 14.3% in the 5-fluorouracil group. Median survival time of patients treated with the new regimen was significantly longer than that in the control group. Toxicity resulting from the new regimen treatment was moderate. The results of the new regimen can be compared to those obtained by other authors using the FAM regimen.

The results of Vepesid therapy in the treatment of malignant lymphomas.

Twenty-three patients with Hodgkin's disease and non-Hodgkin's lymphomas were treated by Vepesid. The dose of the drug was 150 mg/m2 daily for 5 consecutive days. This schedule was repeated every 3 weeks. The percentage and response were estimated according to WHO scale. There were complete responses and 6 partial responses lasting 13.7 and 5 months, respectively, on the average. The results of Vepesid therapy depended on the efficiency of previous treatment.

Radiation associated eosinophilia and monocytosis in carcinoma of the uterine cervix: a simple reliable clinical and prognostic indicator.

Clinical and prognostic significance of radiation associated eosinophilia (RAE) and radiation associated monocytosis (RAM) was evaluated in 176 patients with squamous cell carcinoma of the uterine cervix followed up after radiotherapy. Significant RAE was noticed in patients with Stages I/IIA and IIB who remained disease-free after treatment. On the contrary, patients belonging to these two stages but who developed recurrent disease showed absence of RAE. These patients as well as those belonging to Stage III showed considerably higher levels of RAM as compared to those patients remaining disease-free. These observations showed the usefulness of these two simple inexpensively carried out parameters in prognosticating disease course in malignant cervical neoplasia.

Comparative study of breast cancer risk factors in Estonia and Slovakia. East-European Study Group of Breast Cancer Epidemiology.

Selected more or less known risk factors of breast cancer were investigated and compared in this case-control study in Estonian and Slovak women. The results revealed that women who gave birth to the first child before the age of 20 years had one-fifth and one-third breast cancer risk in Estonia and Slovakia, respectively, in relation to nulliparous women. Concerning subsequent births, Estonian women with two children showed the lowest relative risk, while in Slovak women this risk decreased with increasing parity. Only in women from Slovakia who gave the first birth at, and after the age of 30 years, significantly elevated breast cancer risk was observed. In this study there was no evidence of an association between breast cancer risk and the age at menarche, although an increasing trend of the variable early menarche was apparent in both female populations studied. In addition, an increase in the risk was revealed among obese Estonian women, and thyroid diseases were found to be related with a twofold excess of breast cancer risk in Slovak women. The possible existence of differences in risk factors in the populations showing similar breast cancer incidence rates is discussed.

The cytostatic effects and mechanism of action of antiviral acyclic adenine nucleotide analogs in L1210 mouse leukemia cells.

The growth and DNA synthesis of mouse leukemic cells L1210 in vitro was inhibited by (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) by 50% at concentrations of 57.0 and 185.0 mumols/l, respectively, 9-(2-Phosphonylmethoxyethyl)adenine (PMEA) inhibited the cell growth and DNA synthesis at concentrations of 15.5 and 250.0 mumols/l. The 2-amino congeners of the above analogs were still more efficient: The corresponding values for 2-amino-PMEA were 6.0 and 10.0 mumols/l, and for 2-amino-HPMPA 19.5 and 50.0 mumols/l, respectively. The results suggest that probably at least a part of the growth inhibitory action of PMEA is due to mechanisms not related to its interference with the DNA synthesis.

Electrophoretic analysis of DNA modifications induced by cis- and trans-diamminedichloroplatinum (II) during heat-denaturation of conformation isomers of pBR322 DNA.

The use of conformation isomers of pBR322 DNA in the study of interactions of Pt complexes with DNA provided for a good monitoring of induced changes in the structure of DNA by gel electrophoresis. On the basis of characteristic changes in the gel electrophoretic mobility of platinated isomers of pBR322 DNA we detected the presence of Pt-DNA adducts representing both intra- and interstrand bifunctional binding of Pt complexes to DNA. Also, this method made it possible to distinguish between DNA modifications induced by the therapeutically active cis-diamminedichloroplatinum (II) (cis-DDP) alone, and those induced by its therapeutically inactive trans-isomer (trans-DDP). The electrophoretically detected DNA modifications were more effective if the interaction of the Pt complex took place with heat-denatured DNA. This process, as compared to that performed with native DNA, ran 100 times faster.

Functional heterogeneity of Sarcoma I cells in transplantation experiments.

Cell suspensions prepared from Sarcoma I (SaI) allografts at various stages of development in C57BL10/ScSn (B10) mice immunosuppressed with xenogeneic antithymocyte serum (ATS) were adoptively transferred into secondary syngeneic (A/Ph) and allogeneic (B10) recipients. In the syngeneic recipients, a gradual decrease in the tumorigenic capacity of transferred suspensions was proved, while in the allogeneic recipients the tumorigenic activity was proved in early and late periods. The suspensions from the period of both permanently and temporarily regressing tumors showed a suppressed growth capacity in syngeneic and immunosuppressed allogeneic recipients. On the other hand, the suspensions from growing tumors produced in both types of secondary recipients a sharp and permanent growth. The data obtained suggest changes in functional properties of SaI cells during the course of their development in allogeneic recipients.

Tumor size and prognosis of breast cancer with negative axillary nodes.

A report on 1877 consecutive node negative (N-) breast cancer cases is presented in which the prognostic value of the main clinico-pathologic features is evaluated. Tumor size (and UICC-TNM T category) and lobular infiltrating histologic type were significantly associated with a more favorable prognosis whereas no association was found for patient age, tumor site and number of examined axillary nodes. However tumor size (and T category) is not a very accurate prognostic predictor (71% of all recurrences observed occurred in cases with tumor diameter of more than 20 mm, which represented 58% of the total series), although its efficiency seems almost as good as that of other more recent prognostic predictors such as estrogen receptor content or labeling index. None of the prognostic predictors currently available, including tumor size, seems sufficiently specific and they do not allow for a reliable selection of high risk N-patients for adjuvant treatment.

Late age at first full-term pregnancy as a risk factor for women with malignant lymphoma.

Women with malignant lymphoma, non-Hodgkin's lymphoma and Hodgkin's disease were of a significantly later age at first full-term pregnancy (AFFP) than controls without malignant disorders. The odds ratio (OR) of having the first pregnancy at 30 years of fertility was 6.4 for women with malignant lymphoma. This ratio was higher than the ratio of 3.9 in a group of breast cancer patients. A low parity in the lymphoma group enhanced the risk associated with a late AFFP.

Hyperfractionation in radiation treatment of advanced head and neck cancer. A preliminary report.

The effects and side-effects of hyperfractionated therapy in advanced head and neck cancer were investigated in a prospective study. The data of 71 patients were available for evaluation and these were compared to a historical control group treated by a standard one-day fractionation schedule; they showed a tendency to local superiority of hyperfractionated irradiation.

Calculation of radiation doses in critical organs compared with in vivo dosimetry during brachytherapy of carcinoma of the uterine cervix.

In a group of 38 patients with carcinoma of the uterine cervix, radiation doses were measured by thermoluminiscent dosimeters (TLDs) placed in catheters introduced into the urinary bladder and rectum during a 24 h uterovaginal application of 226Ra. The values of radiation doses registered by the TLDs were compared to those calculated from roentgenograms made after 24 h. To calculate the radiation doses, we used the program Brachy 9.3-C of the planning unit Evados (Siemens, FRG). Using nonparametric comparison tests, no statistically significant differences were found between the values of radiation doses registered by TLDs and those calculated after 24 h of uterovaginal application of 226Ra. Only in the oral part of the rectum, at a distance of 10 cm and above from the anal orifice, there were differences between doses measured by TLDs and those calculated from roentegenograms made after 24 h of brachytherapy. These differences were caused by the movement of the flexible catheters carrying the TLDs.

Ovarian malignancies in the Czech Cancer Registry.

This report is a summary of epidemiological survey of ovarian cancer in the Czech Socialist Republic (CSR) during the period of 1977--1985; the incidence and mortality data have been recorded since the sixties up to the present. In 1985 we also described the morphology types and calculated the estimates of lifetime risk. All conventional epidemiological indicators are discussed and the geographic variations and international comparisons are presented together with the known risk factors and survival. The data can be used for comparisons among countries with similar conditions.

The use of protein as a carrier of methotrexate for experimental cancer chemotherapy. V. Alternative method for preparation of serum albumin-methotrexate derivative.

An alternative method for the preparation of human serum albumin-methotrexate derivative (HSA-MTX) using N-hydroxysuccinimide ester of methotrexate (MTX) was compared with that using the water-soluble carbodiimide (WSC) assistance. The prepared derivative was tested to find the advantages and drawbacks of this method. The N-hydroxysuccinimide ester method is more laborious than that using WSC but some reasons speak in favor of this method. The formation of protein-protein conjugates during the reaction was negligible and under specific conditions more MTX molecules could be bound to protein than by the WSC method. However, some disadvantages of this method were found: A laborious preparation, a small degree of denaturation of protein during the synthesis and, moreover, the binding of MTX to protein did not always take place through NH2-groups of protein but through some other groups (--OH, --SH) as well. These couplings were not so stable as an amidic (or peptidic) bond. In water environment they were hydrolyzed and MTX was slowly released. If there is no difference in a small fraction of protein-protein conjugates, the WSC-assisted method possesses evident advantages over the active MTX ester one, mainly because of the simple preparation of the stable derivative.