Bacterial infection of urine in patients with bladder cancer.

In this retrospective study on 226 patients with bladder cancer before radiotherapy following diagnostic or conservative surgery, bacterial infection of the urine was evaluated. The incidence of urine infection was 65.5%. 12.3% of the patients had sterile urine and in 22.1% of patients the investigation for urine infection was not performed. 77% of infections were caused by Gram-negative bacilli. No dependence of infection incidence on the tumor-T-stage, incidence of diabetes mellitus, prostatic gland size and tumor location near the internal ostium of the urethra was found. Thus, the cancer itself, transurethral diagnostic and/or transurethral or abdominal operation and the hospital stay appear to be of primary importance for the development of infection. To prevent serious late postradiation reactions it is important to manage infection before the start of radiotherapy. Some features of infection therapy in bladder cancer patients are discussed.

Comparison of some environmental pollutants on the incidence of digestive tract malignancies mapped in district Blansko (Czechoslovakia).

The basic economic and geographic regionalization and the rate of environmental pollutants in the investigated district were firstly defined. The incidence of digestive tract malignancies in years 1976-1984 was compiled with the aid of a computer, and modelling by isolines a as graphic representation was used. The state of environment is compared with the geographical places of maximal and minimal incidence of the cancer types studied. The combined load of environmental pollution (above all water sources) seems to correlate considerably with high cancer incidence. The study will continue in view of accurate verification of these results.

Transnitrosating activity of N-nitroso-N-methyl-p-toluenesulfonamide in rats and human gastric juice.

N-nitroso-N-methyl-p-toluenesulfonamide (NMTS, diazald, CAS 80-11-5) is a widely used compound for laboratory production of diazomethane. The present results showed that the noncarcinogenic NMTS reacts as a transnitrosating agent with amino nitrogen of secondary amines and amide both in vitro (human gastric juice) and in vivo (rats) to yield N-nitroso compounds. Since all compounds formed (NMOR, NDMA, NPIP, NPZ, NMU) are known animal carcinogens, caution should be taken by users handling NMTS.

Activated fos oncogene in rat embryo fibroblasts transformed by ras and myc oncogenes.

Rat embryo fibroblasts (REF) were transformed by simultaneous gene transfer of the complementary oncogenes ras and myc using the calcium phosphate coprecipitation method. Cell lines derived from transformation foci expressed in addition to ras and myc cellular oncogene fos while normal REF did not express ras, myc and fos according to the hybridization methods used. The transformed cell lines produced colonies in soft agar and tumors in newborn syngeneic rats. From one tumor a cell line was established which was characterized by a high level of fos gene expression.

Factor X-activating activity from Guerin epithelioma.

The procoagulant activity (PCA) was examined in extracts from primary tumor and metastases of experimental Guerin epithelioma transplanted into Wistar rats. PCA was evaluated by measurement of the level of activation of coagulation factor X using specific chromogenic substrate S-2222. We observed that extracts from both primary tumor and metastases were able to activate factor X in vitro. This activity was not factor VII-dependent, it was inhibited by phenylmethylsulfonyl fluoride (PMSF) and mercuric chloride, and in a smaller degree by p-chloromercuric benzoate (p-CMB) and iodoacetic acid (IAA). No difference between procoagulant activity in extracts from primary tumor and from metastases was observed.

Prognostic significance of vascular density and a malignancy grading in radiation treated uterine cervix carcinoma.

In a retrospective study of 95 patients with squamous cell carcinoma of the uterine cervix (Stage IB, IIA, III) treated by radiation only, pretreatment biopsy material was used for assessment of the prognostic value of histopathological multifactorial malignancy grading and a morphometric estimation of vascular density in stroma. By comparison of the two systems, vascular density has been proved superior to malignancy grading with respect to prognostic value.

Quantification of histoautoradiographic evidence of DNA repair synthesis in the liver.

Histoautoradiography was used to detect dimethylnitrosamine-induced 3H-thymidine incorporation in vivo into G phase hepatocytes. A description of the standard procedure for counting the grains as well as the mode of mathematical evaluation is presented. The results exhibited higher sensitivity than those in the investigation of the DNA repair synthesis by means of a scintillation counter using the method of detection of hydroxyurea-resistant incorporation of 3H-thymidine. Thus it was possible to simplify the investigation by lowering the number of evaluated cells. A suitable compromise between precision and laboriousness will probably be achieved by counting 20 hepatocytes per animal. In case that there are striking differences between the experimental and the control group, a qualitative conclusion may be drawn even without counting the grains.

Quality control study of estradiol and progesterone receptor determination.

Lyophilized calf uterine tissue cytosol standards for estradiol receptor (ER) and progesterone receptor (PR), and freeze-dried tissue powders for PR determination were prepared. For the ER assay 4 standards were produced with no, low, medium, and high ER levels. The ER binding capacities (mean +/- SD) were low--261 +/- 46 (Brno) and 221 +/- 64 (Budapest), medium--451 +/- 100 and 340 +/- 59, high--712 +/- 139 and 581 +/- 102 fmol/mg protein, respectively. Two receptor-positive tissue powders and two positive cytosol standards in lyophilized form were used for the PR assay with receptor contents of 110, 148, 787, and 786 fmol/mg assayed in Brno, and 148, 250, 693, and 671 fmol/mg protein determined in Budapest. The stability of the standards was good for 10 months. All parameters tested in the two laboratories (specific binding capacities, Kd values, variation coefficients of the results) were in good correlation. Lyophilized calf uterine cytosol standards for ER and PR, and freeze-dried tissue powders for PR proved to be suitable materials for interlaboratory quality control of steroid receptor determination.

Induction of tumor associated macrophage-mediated lysis of autologous tumor cells by lectins.

Lectin dependent cell mediated cytotoxicity (LDCC) to autologous tumor cells (ATC) by the tumor associated macrophages (TAM) was studied by 4 h 51Cr release assays at early and late stages of growth of a murine transplantable ascites tumor, S-180, in presence of different concentrations of wheat germ agglutinin (WGA) and Concanavalin A (Con A). Induction of LDCC by the unstimulated resident macrophages (RM) to S-180 tumor cells was also assayed. Both WGA and Con A induced significant tumoricidal activity in the TAM at different states of activation and in RM in a dose-dependent manner, the activated TAM showing expression of cytotoxicity with the lowest doses of the lectins used. Addition of N-acetylglucosamine (NAcGle) or D-mannose (D-man) in the assay completely inhibited LDCC induced by WGA and Con A, respectively. Effector-target contact alone not sufficient for inducing lysis in LDCC was evident from the observations that low doses of the lectins augmented target binding by the inactivated TAM and RM with no subsequent cytolysis.

The use of protein as a carrier of methotrexate for experimental cancer chemotherapy. III. Human serum albumin-methotrexate derivative, its preparation and basic testing.

The preparation and a more detailed characterization of human serum albumin-methotrexate derivative (HSA-MTX) is described. The synthesis of the derivative was performed by means of 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (in methoiodide form) (WSC). Results of many experiments showed that, on the average, about 26 molecules of methotrexate (MTX) were coupled to one molecule of human serum albumin (HSA). The relative molecular weight of the formed derivative was estimated by gel chromatography on Sepharose 6B or on high-pressure liquid chromatography (HPLC) on SWK column, respectively. From the obtained data it follows that a considerable part of the HSA-MTX derivative formed protein-protein conjugate (up to about 4 X Mr HSA), nevertheless the derivative retains its good solubility as a native albumin. In order to eliminate the possibility of influencing the cytostatic activity of the derivative with byproducts of its synthesis, human serum albumin-folic acid derivative (HSA-FA) was prepared and tested by the same method. All demonstrated experiments proved that MTX was the only compound possessing the cytostatic activity. During the experimental therapy of Gardner lymphosarcoma (LSG) the following was found: (1) The intratumorous application of the drug was the most effective way of administration. (2) Any type of administration of the HSA-MTX derivative exerted a better effect than the same way of administration of free MTX. (3) The comparison of two (repeated) administrations of both drugs showed clearly that the HSA-MTX derivative was more efficient than free MTX. After HSA-MTX derivative treatment all animals survived without tumor. (4) For the estimation of the toxicity of the HSA-MTX derivative, three times and five times repeated intraperitoneal administration was performed. It was concluded that although the derivative was more toxic than free MTX, its therapeutic activity was better. After the elimination of the toxic manifestation of the HSA-MTX derivative by a suitable arrangement of drug doses, five times higher efficacy of the derivative was reached, as compared with free MTX. (5) The therapy by the HSA-FA derivative did not exhibit any therapeutic effect. The reason why HSA was used as a macromolecular carrier for cytostatics is discussed.

The use of protein as a carrier of methotrexate for experimental cancer chemotherapy. IV. Therapy of murine melanoma B16 by human serum albumin-methotrexate derivative.

The influence of methotrexate bound to human serum albumin (HSA-MTX) and of free methotrexate (MTX) on B16 melanoma growth, dissemination and survival time of tumor-bearing animals was investigated. It was found that the growth of tumor was slower after therapy with the HSA-MTX derivative than after free MTX treatment. The reduction in tumor size recorded on day 21 after tumor transplantation was more significantly pronounced after HSA-MTX derivative therapy than in case of free MTX treatment. Contrary to our expectation there was no proportional difference in life span prolongation after therapy with these drugs. Comparing metastatic dissemination, the number and size of pulmonary metastatic colonies after HSA-MTX administration was more significantly reduced than after free MTX therapy.

Combined treatment including postoperative chemotherapy in lung cancer patients.

The results of a cooperative randomized study performed in Poland, Bulgaria, Czechoslovakia, Hungary, and the Soviet Union on the treatment of lung cancer patients are presented. Three hundred and sixty patients were treated only surgically, 360 patients received combined therapy. Adjuvant chemotherapy was performed using 3 preparations (cyclophosphane, methotrexate, 5-fluorouracil) within 2-3 weeks after operation (first course) followed by another 3 courses at intervals of 8-9 weeks. The combined therapy increased the 5-year survival rate of patients with Stage III squamous cell carcinoma with thoracic lymph node metastases. Better results were achieved when 3-4 courses of adjuvant chemotherapy were performed. In patients with Stage I-II squamous cell carcinoma of the lung without regional lymph node metastases the used regimen of combined therapy had no significant effect.

Spontaneous acute lymphoblastic leukemia in Sprague-Dawley rats. II. Clinicopathologic observations.

Spontaneous acute lymphoblastic leukemia (ALL-SD) was diagnosed in a breeding colony of isohistogenic Sprague-Dawley rats. Animals younger than one year of age died approximately 1 to 2 weeks after the onset of the disease and represented approximately 17% of the total rat population. Clinically, the affected rats showed mainly spinal cord paralysis and enlargement of mandibular lymph nodes. Gross lesions were characterized by hepatosplenomegaly and enlargement of visceral lymph nodes. Histological examination of affected tissues and cells revealed generalized infiltration of blast cells accompanied by focal hemorrhages and necrosis. According to the FAB classification, it was concluded that ALL-SD corresponds to ALL type L2 in man. Therefore this leukemia of young rats may be an important model system for the study of human leukemia.

Vinblastine, cisplatin and bleomycin (VPB) adjuvant therapy does not induce dose-dependent damage in human chromosomes.

Chromosome aberrations and sister chromatid exchanges were examined in testicular tumor patients treated by 4 cycles of vinblastine, cisplatin and bleomycin adjuvant therapy. The predominant aberrations in cells varied among the patients, and due to interindividual variability no time- or dose-dependent changes were observed in cytogenetic data. There was found an overdispersion of aberrations which might be explained by the effect of bleomycin. Sister chromatid exchange (SCE) frequency was slightly increased and showed also an individual variability in the response to vinblastine, cisplatin and bleomycin (VPB) therapy. No correlation with chromosome aberration rate was found. Further data are required for the real estimation of long-term effects of VPB therapy.

Detection of blood group A antigen expression in human colon cancer using monoclonal antibodies with different specificities.

Blood group antigen expression in human colon cancer was studied by means of two monoclonal antibodies of broad anti-A (HE-14) and anti-type 3 and type 4 chain-based A and H (HE-10) specificity. These antigens were proved to reappear in tumors of the distal colon, the HE-10 antibody reacting more frequently (9 out of 12 samples) than HE-14 (5 out of 12 samples) and frequently with supranuclear staining of the cytoplasm probably in those places of the Golgi apparatus where carbohydrate antigens are synthesized. This staining pattern is characteristic of HE-10 in normal colonic mucosa as well. With HE-14, staining was often absent in less differentiated tumors, while HE-10 did react in such tumors. In this connection, the possible expression of type 3 and type 4 chain H antigens in the tumor tissue is discussed. In some cases, these two antibodies gave different staining patterns in parallel sections from the same tissue sample, primarily at the cellular level. Three out of 12 cases showed blood group antigen expression in the mucosa of the distal colon adjacent to the tumor only when HE-10 antibody was used.

The effect of indomethacin on nucleic acids in blood, hemopoietic and lymphoid tissues in continuously irradiated rats.

The effect of indomethacin--a nonsteroid antiinflammatory drug with potential antitumor activity--on the development of radiation-induced changes was followed in blood, bone marrow, spleen, thymus and testes of rats. Indomethacin administered in drinking water (0.7-1.0 mg/kg per day) during a continuous 7-day irradiation with gamma rays (dose rate of 2.055 Gy/day, total accumulated dose of 14.385 Gy) caused a higher and more rapid incorporation of 3H-thymidine into blood DNA, and an increase in blood RNA concentration. The results suggest some stimulation of hemopoiesis recovery by indomethacin treatment in continuously irradiated rats.

The effect of indomethacin on serum proteins in continuously irradiated rats.

Changes in serum albumin, A1-globulin, A1-macroglobulin, haptoglobin, hemopexin, and ceruloplasmin concentration in rats irradiated continuously with a daily dose of 2.055 Gy up to a total dose of 14.385 Gy of gamma rays after peroral indomethacin administration were followed by two-dimensional immunoelectrophoresis. The use of indomethacin evoked a beneficial response particularly in the serum concentration of albumin, A1-globulin, and A1-macroglobulin on the 21st day after irradiation. In contrast with the concentrations in the irradiated control group, protein values in rats treated with indomethacin were less reduced. We did not observed significant differences between the serum concentration of haptoglobin, hemopexin, and ceruloplasmin of irradiated, indomethacin-treated and irradiated control, up to the 58th day after irradiation.

Phenotypic variability of chemically induced primary rat mammary tumors.

Rat mammary tumors induced by DMBA (7,12-dimethylbenz(a)anthracene) or MNU (N-methyl-N-nitrosourea) were compared for frequency of histological types. Total tumor incidence in 50-day-old rats (Groups 3, 4, 5) was about 100% independently of the rat strain and carcinogen. There were found no distinct histological tumor types between DMBA and MNU carcinogenesis, although the distribution of fibroadenomas, adenocarcinomas and sarcomas varied markedly among rat groups. In 300-day-old female Wistar rats (Group 1) treated with DMBA, fibroadenomas and adenocarcinomas showed an incidence of 58% and 42% respectively. In 50-day-old rats (Group 3) the proportion of adenocarcinomas increased up to 72% of total DMBA tumors. MNU carcinogenesis induced adenocarcinomas in 98% of total tumors in the Lewis rat strain (Group 5), while only 53% in Wistar rats (Group 4). The rest of tumors were sarcomas occurring in opposite ratio to adenocarcinomas. The relatively high susceptibility of connective tissue to MNU as compared with mammary epithelium was due to the mode of MNU administration and seemed to be strain dependent. Both DMBA and MNU carcinogenic systems are valuable experimental models of mammary tumor. The cell phenotypes of the resulting tumors can be predicted with high probability by the choice of dose regimen of carcinogen and the route of its application.

Serum hormones in human breast cancer subjects.

Different serum hormones were studied in patients with benign breast diseases and breast carcinoma in respect of different phases of the menstrual cycle, as well as in postmenopausal women. In premenopausal breast carcinoma subjects 10% showed elevated serum estradiol alone, 7% showed elevated serum prolactin alone, and 12% subjects exhibited elevated levels of both serum estradiol and prolactin. Similarly, in postmenopausal breast carcinoma subjects 12% showed elevated serum estradiol alone, 10% showed elevated serum prolactin alone, and 22% exhibited elevated level of both serum estradiol and prolactin. On the other hand, in patients with benign breast disease only 5 showed an elevated level of prolactin alone. More than 50% of premenopausal women with carcinoma of the breast had low level of serum progesterone during the luteal phase as compared to normal subjects. No variations in serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were evident between normal subjects and women with breast carcinoma or benign breast disease. The increased level of serum estradiol and prolactin may be useful in the diagnosis of human breast cancer.

Separation and evaluation of changing pattern of glycosaminoglycans in 3-methyl cholanthrene induced fibrosarcoma.

The present study evaluates the glycosaminoglycans (GAGs) pattern associated with transplantable rat fibrosarcoma induced by 3-methylcholanthrene. The quantitative analysis of fractionation of GAGs in fibrosarcoma and fetal tissues was performed by enzymatic digestion. The average value of total GAGs in fibrosarcoma and fetal tissue was found to be 4 times higher than its value in the tissue of origin. GAG content showed a steady increase from 7th day onward to 25th day. Hyaluronic acid content in tumor tissue was observed to increase markedly (8-fold) against that of the normal tissue and was equivalent to that of the fetal tissue. Chondroitin sulfate level was also increased in the tumor as well as fetal tissue. The increase in the chondroitin sulfate and hyaluronic acid contents might possibly be due to the abnormal GAG metabolism in the increased production of both sulfated and nonsulfated GAGs.

Changes in the template activity of chromatin isolated from sarcoma-180 ascites cells treated with mitomycin C and gamma irradiation in vivo.

The murine ascites sarcoma 180 cells were used to test the in vivo effectiveness of mitomycin C (MMC) and gamma-radiation applied in combination. The action of intraperitoneal administration of MMC and/or whole-body gamma irradiation on sarcoma 180 tumor bearing Swiss albino mice was investigated by studying the template activity of isolated tumor chromatin. The Km value for transcription of 10 Gy-irradiated chromatin was found to decrease with time implying an increase in the template efficiency with respect to that of the unirradiated control. Maximum decrease in Km was observed after 24 h of irradiation. MMC treatment (7 mg/kg body weight of mouse) for 18 h resulted in an inhibition of the transcription rate. Severe inhibition in the template activity was found when cells were subjected to MMC treatment 18 h prior to irradiation with 10 Gy. Susceptibility of tumor chromatin to DNase II followed the same pattern as observed in the case of transcription indicating structural alteration of the treated chromatin. The data showed that DNA damage and its consequences produced in the ascites cells by prior treatment of MMC were not repaired during the 18 h period after which the application of radiation enhanced cytotoxicity.

Effect of inhibition of DNA synthesis on recovery of X-irradiated L5178Y-S cells. I. Aphidicolin.

Irradiated L51 78Y-S cells (LY-S) were characterized by an exponential survival curve and the potentiation effect of split--dose irradiation. Previously we showed [13] that in LY-S cells the reduction of DNA replicative synthesis rate affected the balance between the fixation and repair of sublethal damage (SLD) and of potentially lethal damage (PLD) in favor of repair. We report here that a block of DNA synthesis by aphidicolin (APC), an inhibitor of DNA polymerase alpha, was sufficient to protect LY-S cells from fixation of PLD and SLD induced by X-rays. Treatment with APC 0.5 micrograms/ml for 2 h, efficiently inhibited DNA replication (95%) with minimal effect on survival. Inhibition of DNA synthesis by combined irradiation and APC was not significantly different from APC treatment alone. The level of protection by APC was dependent on the length of time between irradiation and APC application. An opposite effect was observed when the drug treatment had proceeded irradiation: The killing effect of X-ray increased. The effect of aphidicolin treatment remained even after removal of APC and was dependent on the drug concentration and time between drug removal and irradiation. These results are interpreted as indicating that X-ray damage was fixed in LY-S cells, because of their lack of ability to maintain the nucleotide pool balance, and that fixation took place during progression through the cell cycle.

Differential effect of collaterally sensitive antimetabolites on P388 murine leukemia sensitive and resistant to adriamycin in vitro.

Experiments were carried out in vitro using DNA polymerase and ribonucleotide reductase inhibitors to investigate their cytotoxicity to P388 murine leukemia sensitive (P388/S) and resistant (P388/R) to adriamycin (ADR). DNA polymerase inhibitors such as cytosine arabinoside (ara-C) and aphidicolin elicited comparative inhibition of DNA biosynthesis in both parental and ADR-resistant tumor cells. However, ribonucleotide reductase inhibitors such as hydroxyurea (HU) and caracemide were collaterally more sensitive to P388/R cells. Inosine diglycolaldehyde (Inox) was ineffective in showing such a response. Pretreatment with HU significantly increased intracellular ADR levels and inhibition of RNA biosynthesis by ADR in P388/R cells while, in P388/S cells, sequential or concurrent treatment with HU did not enhance intracellular ADR levels. Mechanisms underlying such an effect, implications due to reduced intracellular ATP levels in drug-resistant cells, and the possible utility of using ribonucleotide reductase as a target in drug-resistant tumors for the therapeutic benefit are discussed.

Isoforms of leukocyte common antigen (CD45) on human neoplastic hematopoietic cell lines.

Leukocyte common antigen (LCA) isoform expression patterns were examined on different human hematopoietic cells and cell lines with the aid of the immunoblotting technique utilizing two anti-LCA monoclonal antibodies elicited by an ALL cell line and able to detect four isoforms (180, 195, 205 and 220 kDa) of LCA on peripheral blood lymphocytes from healthy donors and some neoplastic hematopoietic cell lines. Fourteen leukemia/lymphoma cell lines of different origin and immunophenotype, as well as three nonhematopoietic human tumor cell lines were examined by this technique. Human hematopoietic cell lines expressed two to four different polypeptide chains (180, 195, 205 and 220 kDa). Non-T, non-B cell lines, some B-cell lines and monocyte lymphoma cell line U 937 predominantly expressed higher molecular weight isoforms. In myeloid leukemia cell lines examined the expression of lower molecular weight isoform(s) predominated. Individual variability in LCA isoform patterns on cell lines precluded the strict correlation between these patterns and immunophenotype of the examined cell lines.

Immunohistochemical localization of alpha-lactalbumin in human breast cancer tissue.

One hundred and eleven formalin-fixed breast cancer tissue samples were examined for the presence of alpha-lactalbumin using our polyclonal antibodies to this specific milk protein. Alpha-lactalbumin was shown to be present in 67 tumor samples (60%), in 15% of cases the occurrence of alpha-lactalbumin was questionable. No relationship was found between alpha-lactalbumin positivity and the histological type of the tumor, differentiation grading, type of invasivity, or stromal reactivity. Disease progression occurred in an equal number of patients with tumors either alpha-lactalbumin positive or negative. However, negativity was often connected with a disease-free interval shorter than 24 months after primary operation.

Lectin histochemistry of human testicular germ cell tumors.

The lectin binding pattern (WGA, UEA-I, PNA, PSA, Con A, RCA and LCA) of 28 human testicular germ cell tumors (pure or combination tumors) was investigated. Lectin binding sites could be demonstrated in all germ cell tumor types. In classic and spermatocytic seminomas as well as seminomas with high mitotic index an equal distribution of lectin binding sites was observed. In embryonal carcinomas the lectin binding of UEA-I, PNA, WGA, LCA and RCA correlated to histological differentiation. A polarized staining of WGA, PNA, RCA and UEA-I, typical for embryonal carcinomas, yolk sac tumors and teratomas, was never seen in seminomatous tumors and may be of importance in differential diagnosis. By means of Con A decoration it was possible to distinguish cytotrophoblastic and syncytiotrophoblastic differentiation. Aspects of lectin histochemistry in tumor biology in general and in differential diagnosis of germ cell tumors in particular are discussed.

Significance of serum sialoglycoproteins in patients with lung cancer.

Total sialic acid (TSA), lipid-bound sialic acid (LSA), hexoses (galactose and mannose) and mucoid proteins were analyzed by specific chemical methods from sera of 43 patients with lung cancer and 5 cases of benign lung diseases. The levels were compared with similar values obtained from 25 healthy individuals. The four biomarkers were significantly elevated in lung cancer patients as compared to controls as well as benign conditions (p less than 0.001). TSA, LSA and the hexoses levels were significantly higher in benign conditions as compared to controls (p less than 0.001, p less than 0.05, and p less than 0.001, respectively). Adenocarcinoma patients had lower mean values of all the four biomarkers than squamous-cell and small-cell carcinoma patients. Increased levels of LSA in squamous-cell carcinoma and TSA in small-cell carcinoma were statistically also significant as compared to adenocarcinoma (p less than 0.01 and p less than 0.05, respectively). LSA showed higher mean values in metastatic cancer than in primary lung cancer. The combination of these markers might be useful for differentiation between benign and malignant conditions and also for the diagnosis of metastatic lung cancer.

Energy supply of the mitotic cell cycle and the Na+/H+-antiport in ascites tumors.

The activation of Na+ transport is due to the exchange of protons formed via glucose conversion into lactate for Na+, i.e., to the stimulation of the Na+/H+-antiport. Experimental results and theoretical calculations suggest that in glucose-containing medium the Na+ transport increases from 0.75 to 1.78 pmol/hour per cell. The permeability of plasma membranes for K+ increases 2.75 fold, while the passive flux of Na+ diminishes. The intensity of O2 adsorption by ascites tumor cells does not practically depend on the monovalent cation concentration gradient between the cells and the culture medium, whereas the rate of glycolysis decreases simultaneously with the diminution of the concentration gradient. In synchronized cultures at the beginning of the mitotic cycle, the bulk of ATP resynthesized via glycolysis is utilized for the synthesis of biopolymers, whereas that at the end of the S-phase and in the G2-phase is utilized for cation transport across plasma membranes. From 35 to 100% of the whole amount of ATP resynthesized via glycolysis is utilized for transport purposes. It is concluded that the observed increase in the Na+/K+ ratio in ascites tumor cells is connected with their enhanced ability to synthesize lactic acid. Presumably, glycolysis is one of the regulatory mechanisms of intracellular ratios of monovalent cations.

Intraarterial infusion of carboplatin in the treatment of malignant gliomas: a phase II study.

Twenty-three previously treated patients with malignant gliomas were included in this phase II study of carboplatin (400 mg/m2) given as an intraarterial infusion every 4 weeks. Five patients (26% of 19 evaluable) achieved a partial response for 3 to 10 months and 5 patients presented a stabilization for 2 to 7 months. Toxicity was mild in most patients, with nausea, vomiting and myelosuppression being the most frequent side-effects. No renal or auditory toxicity was observed. One patient developed central nervous toxicity and another one a reversible fall in visual acuity. Finally, carboplatin infused by the intraarterial route seems to be an active drug, less toxic than cisplatin, in malignant gliomas, and further trials are warranted.

Selective decontamination of the digestive tract in hematological patients (Czechoslovakia-German Democratic Republic cooperative study.

A group of 55 hematological patients treated for the last 2.5 years by the method of selective decontamination was evaluated. Though both institutes (Bad Saarow, Hradec Králové) worked on the problem in the same conditions (indications for the treatment, characteristics of patients, basic drugs), many differences in details were found. However, the important clinical results were the same: A statistically significant decrease in infections and duration of fever in treated patients. A survey of therapy complications, surveillance of infections and incidence of microbes are presented. The evaluation showed that future research including microbiological and immunological investigation based on a standard protocol will be useful.