Experimental biotherapy by leptospiral infection. IX. Quantitative titration of the tumoricidal effect of leptospiral exoproducts by means of 51Cr-labeled target cells of mouse ascites tumors.

New substances with cytotoxic and antitumor effects. IV. In vitro effect of some veratrum alkaloids and their derivatives on leukemia P388 cells.

Some Veratrum alkaloids and their derivatives exhibited an in vitro cytotoxic effect on leukemia P388 cells, depending on the structure of the skeleton of the molecule, particularly on the type of the heterocycle attached to C-20. Veracintine and 20-(2-methyl-1-pyrrolin-5-yl)-4-pregnen-3-one, which proved to be the most effective, inhibited incorporation of uridine, and to a lesser extent that of L-valine into P388 cells fractions. After a brief reaction (15 min), these substances became irreversibly bound in the P388 cells and stopped their further in vitro proliferation. The cytotoxic effect of veracintine became enhanced by sublethal doses of tubercidine (phase of maximum lethality of G1).

Antileukemic effects of 5-(2-dimethylaminoethoxy)-7-oxo-7H-benzo(c) fluorene, substance VUFB 13 468, on L1210 and La leukemia.

The antineoplastic effect of 5-(2-dimethyl-aminoethoxy)-7-oxo-7H-benzo(c) fluorene, substance VUFB 13 468, was studied in leukemia L1210 and leukemia La. It was found that the test substance, in the form of base and in the form of hydrochloride, influenced favorably the survival of leukemic mice, in which the life span increased in dependence on the dose and the scheme of its application.

The effect of hyperthermia alone or in combination with actinomycin D on the RNA metabolism of solid tumors in children.

The incorporation of 3H-uridine into the RNA was studied under normothermia 37 degrees C/120 min, hyperthermia 42.5 degrees/120 min, and both in combination with Actinomycin D by an autoradiographic in vitro method in 19 solid tumors of children: 6 Wilms' tumors, 5 neuroblastomas, 4 osteogenic sarcomas, and 4 different tumors. Hyperthermia invariably reduces the 3H-uridine incorporation into RNA by 11.7--86.4%, with an average of 47.5%. Actinomycin D consistently inhibits the 3H-uridine incorporation between 27.7 and 99.8%, with the average inhibition of 62.0% being far greater than that recorded for hyperthermia. The highest degree of 3H-uridine incorporation inhibition is obtained using hyperthermia in combination with Actinomycin D. The inhibition varies from 45.5--99.8%, with an average of 81.4%. In spite of the general regularity, the effect of hyperthermia and Actinomycin D are characterized by individual patterns. Obviously, they are dependent on proliferative activity rather than upon the particular type of tumor. The use of supranormal temperatures for the treatment of malignant tumors in man, also in combination with radiation or cytostatic drugs, is a possible and promising method of therapy.

Optical and ultrastructural pathology of vitamin A pretreated hamster cheek pouch--exposed to lime (Ca(OH)2) and tobacco over total life span.

A close correlation is postulated between tobacco chewing and the high incidence of oral cancer and precancer in many South East Asian nations. However, attempts to induce malignancy in laboratory animals by exposure to ingredients of betel quid are unsuccessful. This is another attempt to induce malignancy in the hamster cheek pouch epithelium by exposure to the ingredients of betel quid - lime and tobacco, for the total life span of the animals - 100 to 110 weeks. Parallel conditioning by exposure to vitamin A is also included. The cheek pouch epithelium of animals exposed to the test substances for total life span shows only epithelial dysplasia of a marked degree, but no evidence of malignancy. It is concluded that it is not possible to simulate the time-dose relationship in human addiction to tobacco or to betel chew in experimental animals due to their comparatively small life span.

Evaluation of radiocurability in uterine cervix cancer with a simple cytological test.

Value of karyopyknotic index (KPI) was estimated in a series of 95 radiation treated uterine cervix cancer patients. The patients were divided into two groups according to the age and the menstrual history. More than 10% of the mature squamous cells exhibiting pyknotic nucleus after radical treatment, were indicative of persistent malignant growth. Conversely, a decrease in the KP cells under 10% after treatment was considered a favorable prognostic omen. Our results also imply that a high KPI value before treatment signalizes a better prognosis.

Thiamine metabolism in the liver of mice with Ehrlich ascites carcinoma.

Thiamine pyrophosphate (TPP) content, activities of thiamine pyrophosphokinase (TPKase), thiamine pyrophosphatase, transketolase (TK), pyruvate (PDG) and oxoglutarate dehydrogenases (OGDG) were measured in the liver and cells of Ehrlich ascites carcinoma (EAC) on the 5th, 10th and 15th day after transplantation of the tumor to mice fed a thiamine-deficient diet. The TPP level gradually decreased in the liver of tumor-bearing mice but remained constant in tumor cells (1.06 +/- 0.02 microgram/g tissue). Deprivation of dietary thiamine lowered the liver TPP level even to a greater extent, and subsequent daily 10 micrograms thiamine/mouse injections did not restore it. The TPKase activity in the liver of mice with EAC decreased by 24% and in thiamine deficiency, by 44%. The liver PDG, OGDG and TK activities were reduced but slightly in mice with EAC, whereas thiamine deprivation resulted in a decrease of the enzyme activities: PDG by 60%, OGDG by 25% and TK by 45%. TK activity in tumor cells was 90 mumol S-7-P/g tissue/h, and the TPP effect amounted to 24%. Thiamine deprivation decreased the TK activity by 45% and raised the TPP effect up to 180%. Thiamine injections restored the TK activity in tumor cells and reduced the TPP effect.

On participation of the autonomic nervous system in the mechanisms of chemical carcinogenesis.

With the view of studying the role of autonomic nervous system in chemical carcinogenesis mechanism in outbred white male rats, chronically treated with NDEA, there has been investigated the modifying effect of some neurotropic pharmacological drugs which cause either stimulation or inhibition of: 1. adrenergic processes (noradrenalin, isoproterenol, clonidine, pyrroxane and propranolol); 2. cholinergic processes (proserine and atropine); 3. the function of the central nervous system (CNS)--caffeine and ethanol. Pharmacological activation of alpha-adrenoreceptors or blocking of both beta-adrenoreceptors and cholinoreceptors has been revealed to stimulate hepatocarcinogenesis. On the contrary, the administration of alpha-adrenoreceptors antagonist or beta-adrenoreceptor and cholinoreceptors agonists inhibited the process of carcinogenic transformation. Caffeine, being the CNS stimulator, has significantly promoted carcinogenesis, while ethanol has practically prevented NDEA effect. Clonidine has also demonstrated its anticarcinogenic action. The obtained data are being discussed in connection with chemical carcinogenesis influence upon the CNS integrative function in control and regulation of tissue homeostasis.

The particular traits of carcinogenesis induced in Wistar rats by aflatoxin B1. IV. Porphyrins and the activity of gamma-glutamyltranspeptidase in Wistar rats bearing transplantable hepatoma.

In inbred Wistar rats bearing transplantable hepatoma induced by aflatoxin B1 tissue porphyrins and the level of the serum gamma-glutamyltranspeptidase (GGTP) were studied. A liver reaction in carriers of transplants was ascertained, that was expressed especially by an increase in porphyrins, mainly the protoporphyrin fraction, and by morphological changes. The content of porphyrins in lung metastases was higher than in hepatomas and livers. The level of serum GGTP was higher in females up to the 40th passage, and up to the 90th passage higher in males. Hormonal conditioning of the early AFB1-hepatoma passages is supported by a lower level of serum GGTP in females and higher in males, and the liver and tumor porphyrins in animals previously castrated in comparison with uncastrated rats. Comparative data of the quantity and quality of porphyrins in different rat tissues with primary and transplantable AFB1-hepatomas demonstrate that systemic metabolic disorders of porphyrins are greater in rats with primary than in the case of transplantable tumors.

Inhibition of RNA dependent DNA polymerases by anthracycline antibiotics.

In our experimental work we intended to study the effect of certain anthracycline antibiotics, like Adriamycin, Daunomycin, Carminomycin on the RNA dependent DNA polymerase, i.e. reverse transcriptase (RT) system. Over the direct effect on the RT our aim was to find out the rate of selectivity of above antibiotics on the RT. For doing this we compared the above effects to those found on natural nucleic acid polymerases. These experiments were confirmed using synthetic polynucleotid template poly(rA)n(dT)12-18 for the Rauscher RT enzyme and poly(dA)n . poly(dT)n for E. coli DNA polymerase I. In our work we have shown that Carminomycin, in contrast to Adriamycin and Daunomycin, possesses a highly specific inhibitory effect on the RT enzyme system.

Effect of levamisole treatment on immunological parameters and the early course of cervical cancer.

Immunological parameters and the early course of the disease have been studied in 153 cases of cervical cancer. Fifty-two patients were given levamisole as an adjuvant. At the end of a 9-month observation period, immunological parameters of apparently clinically tumor-free patients were compared for two groups: traditional treatment versus traditional treatment plus levamisole. Low IgM concentrations and reduced cutaneous reactivity to phytohemagglutinin were found in both groups, but reduction of the two parameters was slighter in the levamisole group. With reference to pertinent literature and the authors' results, the possible effects of levamisole are discussed, as well as possibilities and place of the drug in the therapy of cervical cancer.

The radioimmunoassay of a carcinoembryonic antigen fraction.

A qualitative and clinical evaluation of a radioimmunoassay for a carcinoembryonic antigen (CEA) fraction in serum is presented. The technique shows cross-reactions with normal organs' extracts lower than 0.05% and a 0.9977 correlation coefficient. The coefficients of variation indicate satisfactory precision. In the clinical study it was found that sensitivity for lung cancer was higher than for colorectal cancer. Specificity for cancer was 98.3%. These results suggest that the CEA fraction employed shows more lung cancer determinants than for digestive cancer.

Effect of two antiproteinases on the growth of transplantable tumors and the proliferation of untransformed and transformed cells in culture.

The paper reports on the experiments carried out for the evaluation of the effect of two antiproteinases, aprotinin, and epsilon-amino caproic acid (EACA), on several transplantable tumors and cells in culture. It was demonstrated that aprotinin has a preferential therapeutic effect on the solid form of L1210, in comparison with its ascitic form. Treatment with aprotinin of Lewis lung carcinoma, Melanoma B16, and Hepatoma 22, in a limited chronic time schedule 1-9, and 1-11 brought no significant increase in survival; positive therapeutic effects had been shown for the first and the last of the tumors mentioned with life-time injections of the drug. Moreover, aprotinin treatment increased the number of lung nodules for the Lewis lung carcinoma inoculated either subcutaneously or intravenously. EACA applied same schedule had no effect on the survival of tumor-bearing animals. These data are discussed in terms of their relevance to antiproteinase therapy in human cancer. No selective inhibition of proliferation for more tumorigenic cell culture lines of spontaneous and viral origin was demonstrated after treatment with both compounds.

A further study on the number of silver stained granules of active nucleolus organizer regions in mitotic Yoshida and Zajdela rat experimental tumor cells.

Yoshida ascitic sarcoma and Zajdela ascitic hepatoma were investigated in Norway rats to provide more information on active nucleolus organizer regions (NORs) represented by silver stained granules (SSGs). Diploid Yoshida sarcoma cells were characterized by the presence of 6 (3 doublets) of SSGs in the metaphase and 3 + 3 SSGs in future daughter nuclei in the anaphase or telophase. In contrast Zajdela hepatoma cells (frequently hypoploid) possessed 6 SSGs less frequently in the metaphase and the number of anaphasic or telophasic cells with 3 SSGs in future daughter nuclei was also reduced. The number of SSGs in future nuclei of anaphasic or telophasic Yoshida sarcoma cells was usually the same, i.e. such anaphases or telophases were symetric. In Zajdela hepatoma cells the number of symetric anaphases and telophases was substantially reduced in favor of asymetric anaphases or telophases which contained different number of SSGs in future nuclei.

Dependence of the structural MuMTV protein expression on hormone-induced murine mammary carcinoma GR/mt cell differentiation in vitro.

Effect of three hormones on the clonal cell line, originating from the stable GR/mt mammary carcinoma (MC) cell line was studied. In the hormones free media the cells had fibroblast-like shapes. Normal differentiation markers and MuMTV protein processing could not be revealed. Insulin favors epithelial cell shape and growth pattern induction, Thy 1.2 antigen expression, as it was shown by FIF test and increased clonogenicity in semisolid medium. Prolactin produces elongated, fusiform cells, milk protein synthesis and loss of clonogenicity. Both hormones exert no influence on the MuMTV protein precursors processing, as it was revealed in RIP test. Dexamethasone renders no visible influence on the cell differentiation except influence on the actin filament expression and intensification of the morphogenetic insulin action. Besides, dexamethasone switches on the env (but not the gag) product precursor processing, however, expression of the mature envelope protein on the cellular membranes occurred only in cells, entering the insulin-induced type of differentiation, as it was shown by RIP test with iodinated cells and MIF test. The gag precursor processing occurred only in extracellular virions. Delay of this process might be responsible for the preferential A-particle production by the cells described.

Cytostatic activity and metabolic effect of N-trichloromethylthio-4-cyclohexane-1,2-dicarboximide on Ehrlich ascites carcinoma cells.

Effect of N-trichloromethylthio-4-cyclohexane-1,2-dicarboximide (NTCD) on energy-yielding and energy-requiring processes in Ehrlich ascites carcinoma (EAC) cells have been investigated. At concentrations higher than 10 micrograms/ml NTCD causes a rapid and practically full inhibition of both aerobic glucose uptake and lactate formation. On the other hand, at concentrations lower than 10 micrograms/ml, these metabolic parameters are stimulated. The stimulation of glycolysis, according to our previous results, suggests the interference of NTCD with mitochondrial functions. This image is supported by the marked inhibitory effect on NTCD on respiration of isolated mitochondria. The inhibition of glycolysis with higher concentrations of NTCD is the consequence of inactivation of hexokinase (EC 2.7.1.1), eventually of 6-phosphofructokinase (FC 2.7.1.11). The described effects of NTCD are given into coherence with chemical modification of appropriate functional SH groups of EAC cells by the compound studied. Proportionally to the dose and time NTCD inhibits the synthesis of macromolecules in whole EAC cells as measured by the incorporation of labeled adenine and valine into the TCA-insoluble fractions. The inhibition of biosynthetic processes followed is the consequence of exclusion of key processes in the energy metabolism and leads to the loss of EAC cells transplantability.

The World Health Organization. Histological typing of lung tumours.

The WHO Histological Classification of Lung Tumours, published in 1967, has been revised. The main features are as follows: Squamous cell carcinoma (epidermoid carcinoma) has the same definition as in the original version, i. e., the identification of keratin and/or intercellular bridges by light microscopy. Three degrees of histological differentiation are described. Dysplasia and carcinoma in situ are discussed. Small cell carcinoma is divided into oat-cell carcinoma, an intermediate cell type and a category for oat-cell carcinomas combined with other major typed, Adenocarcinoma includes the acinar, papillary and bronchiolo-alveolar forms and the solid carcinomas with mucus formation (previously part of the large cell carcinoma group). Mesothelial tumours are divided into fibrous, epithelial and biphasic subtypes. A number of less common tumours and tumour-like lesions are defined.

BCG immunotherapy of lung cancer in a district oncology dispensary. I. Study of 860 patients with histologic diagnosis.

The investigation refers to lung cancer patients registered in an oncology dispensary from 1965 to 1975. The conventional treatment (surgery, radiotherapy and chemotherapy) has covered 35.9% of all patients, whereas immunotherapy with BCG or with its soluble fraction has been applied in 46.2% of them. Immunotherapy has mainly been applied to epidermoid carcinoma and large-cell carcinoma. Comparing the survival of immunotherapy treated with non-immunotherapy treated patients it was found that in Stage I-II group the difference in favor of immunotherapy was significant in the second year of observation and in Stage III group a significant difference was found in all observation periods (1-5 years). In Stage I-II the 5-year survival rate of immunotherapy treated patients (13.2%) was similar to the survival rate of operated patients (13.7%). Immunotherapy in large cell carcinoma showed significantly better results than immunotherapy in epidermoid carcinoma. Immunotherapy with BCG and F70 was applied as an independent treatment of lung cancer. When applied to patients primarily operated, radiation or chemotherapy treated, the survival was significantly higher than the survival of patients submitted to conventional treatment or to immunotherapy separately.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. VIII. The influence of proton-donor on reduction of carcinogenic nitrogen compounds in dimethylformamide.

The authors have studied the electrochemical behavior of a series of carcinogenic and inactive heterocyclic compounds in anhydrous medium in the presence of a proton-donor. As anhydrous medium the authors used anhydrous dimethylformamide as proton-donor phenol. In the presence of proton-donor there had occurred on polarographic reduction of the employed carcinogenic heterocyclic compounds changes in the number of polarographic waves. Between the two original waves in these compounds there arose in the presence of phenol a new wave. In non-carcinogenic heterocyclic compounds such an effect of phenol was not noted. In the present paper the authors discuss the possible mechanism of electroreduction of carcinogenic and inactive heterocyclic compounds in anhydrous medium in the presence of a proton-donor.

Characterization of murine leukemia viruses activated during N-nitroso-N-methylurea-induced leukemogenesis in mice. I. Host range of activated viruses.

Interactions between the growth effects of a kidney epithelial cell growth inhibitor and extracellular concentrations of cyclic nucleotides.

The effect of dibutyryl cyclic nucleotides, dbcAMP and dbcGMP, on the growth of BSC-1 cells has been studied in the presence and absence of kidney epithelial cell growth inhibitor. The growth response of the cells was dependent on concentrations of the dibutyryl cyclic nucleotides and on the presence or absence of serum in the medium. In the presence of serum, a high concentration (10(-3) M) of dbcGMP largely overcame the action of the kidney epithelial cell growth inhibitor. In the absence of serum, a high concentration (10(-3) M) of dbcAMP increased growth inhibition observed with the growth inhibitor. In the presence of serum, low concentrations of dbcAMP were growth stimulatory and partially overcame the action of the growth inhibitor.

Epstein-Barr virus is not associated with head and neck neoplasms other than nasopharyngeal carcinoma.

Cell surface alterations of avian sarcoma virus B77- and 3,4-benzo(a)pyrene-transformed rat fibroblasts. I. Cell surface proteins characterized by two-dimensional electrophoresis.

Plasma membrane proteins of avian sarcoma virus B77-, 3,4-benzo(a)pyrene- and spontaneously transformed rat fibroblasts were metabolically- and cell surface radiolabeled and analyzed by electrophoresis under denaturing conditions (SDS-PAGE) or by two-dimensional electrophoresis. Most extensive series of protein alterations on transformed cells was detected by two-dimensional electrophoresis of cell surface proteins radiolabeled by lactoperoxidase catalyzed radioiodination: a fibronectin-like 220k protein with two isoelectric forms (pI 5.9 and 6.2-6.6), a 180k protein of pI 6.2-6.6 and two proteins of 48k and 50k with pI approximately 5.4-all decreased on examined transformed cells. In addition to these proteins, a series of proteins more markedly detectable on transformed cells was found: a 110-120k (pI 5.6) protein found particularly on 3,4-benzo(a)pyrene- and spontaneously transformed cells, a series of proteins in the region of molecular weights 46-54k with pI 5.5-6.0, two proteins of 35k (pI 6.2 and 6.4) and two further, basic proteins of 38k (pI approximately 7.2 and 7.8). Some of these changes were visualized also by further techniques for radiolabeling of proteins, i.e. reductive methylation of cell surface proteins, metaboling radiolabeling by 3H-leucine followed by plasma membrane isolation, as well as by protein staining after two-dimensional electrophoresis of isolated plasma membrane proteins. A 70k and a 120k radioiodinated proteins were immunoprecipitated from all transformed cells and, to a markedly lesser extent from untransformed fibroblasts by the immune serum against rat type-C endogenous virus. A similar 70k protein was immunoprecipitated from avian sarcoma virus B77-transformed cells also by the antiserum against Friend murine leukemia virus envelope glycoprotein gp70.

Cell surface alterations of avian sarcoma virus B77-and 3,4-benzo(a)pyrene-transformed rat fibroblasts. II. Cell surface glycoproteins characterized by two-dimensional electrophoresis.

Cell surface proteins of avian sarcoma virus B77-, 3,4-benzo(a)pyrene- and spontaneously transformed rat fibroblasts were tritium-radiolabeled by mild periodate oxidation followed by tritiated sodium borohydride reduction and by galactoseoxidase/NaB3H4 technique. Radiolabeled cell surface sialoglycoproteins were analyzed by electrophoresis under denaturing conditions (SDS-PAGE), or by two-dimensional electrophoresis (isoelectric focusing, SDS-PAGE). Following major glycoproteins were quantitatively decreased on all examined transformed cells: a 220k glycoprotein with pI of approximately 6.2, a 180k glycoprotein with pI of approximately 6.0-6.2, a 110k glycoprotein (pI 6.2). A series of further sialoglycoproteins was quantitatively increased on all examined transformed cells, as follows: a markedly increased 70k glycoprotein (pI approximately 4.8) and a 120k glycoprotein (pI 5.0-5.2) increased more markedly on onco-virus-transformed and spontaneously transformed cells. Further sialogalactoprotein (28k, pI 5.8) was visualized as increased on all examined transformed cells only by galactoseoxidase/NaB3H4 technique. A 70k sialoglycoprotein was immunoprecipitated from transformed cells by the immune serum against Friend murine leukemia virus envelop glycoprotein gp70 and, to a markedly lesser extent, from untransformed cells. A similar glycoprotein, together with an another 120k glycoprotein were precipitated from transformed cells and to a minor extent from untransformed cells also by an antiserum against endogenous rat type-C virus.

Studies on antibodies reactive with glycoproteins of primate type C viruses in patients with myeloid leukemias and with potential preleukemia.

Human blood plasma from patients with myeloid leukemias, potentially preleukemic disorders and healthy individuals contains antibodies which react with purified glycoproteins of the baboon endogenous virus and the gibbon ape leukemia virus. Experiments are presented which illustrate characteristic distributions of antiviral antibodies in the plasma of different investigated groups. The presence of high-titer antibodies is associated with remission of acute myeloid leukemia and longer survival of patients with preleukemia.

Reactivity of free and coordinated radicals in biology and chemical carcinogenity. I. Coordinated phenoxy radicals generated by hydrogen transfer from hydroxy derivatives of 3,4-benzopyrene.

The tautomeric keto form of 6-, 7- and 8-hydroxy-3,4-benzopyrene (BP) prevails in nonpolar solvents at laboratory temperature, in contrast with the enol form of 9-HO-BP and 3-HO-BP, as it was shown according to the ESR study of H-transfer reactions initiated by tert. butyl peroxy radicals coordinated upon the hydroxy derivative of cobalt(III)-acetylacetonate [HO-Co(acac)2]. A further hydroxylation of the keto form of 6-HO-BP, mainly in the position 3, in the thermal interval 40-60 degrees C and the presence of oxygen was observed. Because of lack of steric hindrance in the neighborhood of the position 3 or 9 the primarily formed phenoxy radical after H-abstraction remains stabilized as sigma-coordinated radical on CoIII. Such a radical complex can be destroyed after addition of polar solvents (e.g. methanol). During autooxidation of BP in aerated solutions, similarly as during enzymatic oxidation, a relatively great concentration of high-stable radicals accumulates in nonpolar solvents and in the absence of peroxides. The paramagnetic species is interpreted as a radical pair of two nondissociated semiquinones. In discussion of the carcinogenic activity of oxidative products of BP, not only the enzymatically formed, but also the randomly formed radical intermediates in the first steps of autooxidation must be taken into consideration, which reactivity to biological targets is mediated with the polarity of the biological medium.

Two cellular proteins that are precipitated by an antitumor-RSV rat serum.

Here we report studies on non-viral proteins specific for transformation precipitated by immune sera. These sera were from rats injected by PR-RSV transformed rat XC cells and from rabbits immunized by subcutaneous injections of cytoplasmic membranes from rat cells transformed by Fujinami avian sarcoma virus. Immune complexes were analyzed in one- or two-dimensional gel electrophoresis and by autoradiography. Only by using antisera obtained from rats bearing XC-cells induced tumors, two proteins were identified with an apparent molecular weight (Mr) of 105 000 (p105) and 98 000 (p98) and an isoelectric point of 6.4 and 6.2, respectively, in extracts of mammalian cells transformed by avian sarcoma viruses (ASV). These proteins were common to all ASV-transformed cell lines. In kinase reaction, the protein p98 can be phosphorylated. Similar proteins were neither detected in normal nor in chemically transformed cells. None of the proteins were precipitated with control serum from rat, rabbit, and goat.

Quantitative changes of tropomyosin synthesis in RSV-transformed mammalian cells in comparison with normal fibroblasts.

Protein profiles of three tumor mammalian cell lines and three control cell lines were analyzed by two-dimensional gel electrophoresis. Comparison of the cells labeled metabolically with 35S-methionine has revealed obvious differences in an area of molecular weights 34 000--36 000 daltons and pH 4.5-5.0. Two spots have been proposed to be alpha- and beta-tropomyosin subunits. Their synthesis decreases after cell transformation.

Our experience with the treatment of nasopharyngeal tumors.

An analysis of a group of 78 patients suffering from nasopharyngeal cancer treated during a period of 15 years is discussed. The ratio of males to females was 1.6 : 1, with a maximum incidence in the 4th and 5th decade. There was a predominance of carcinomas (60 patients) over malignant lymphomas (18 patients). With respect to the stage of the carcinomas, the largest group of patients (36 individuals) could be classified as Stage III. At the beginning of the treatment regional metastases were present in 68% of the carcinomas. Nasopharyngeal tumors were treated only by radiotherapy; in the earlier period by conventional roentgenotherapy, recently by telegammatherapy 60Co only. The 5-year survival rate of patients with carcinomas was 25%, of those with malignant lymphomas was 27.7%. Among carcinomas we found better results in lymphoepitheliomas, among the lymphomas in lymphocytic lymphomas. The present study also discusses the significance of some cofactors that may play a role in respect of prognosis, treatment and final clinical evaluation of patients with nasopharyngeal cancer.

Clinical controlled trial in advanced breast cancer: CMFV (cyclophosphamide, methotrexate, fluorouracil, vincristine) verus CD (carminomycin, dibromodulcitol).

A controlled study with two independent cytostatic combinations in advanced breast cancer was performed in total 236 patients. Results of the treatment in 218 evaluable patients are reported. The first combination included cyclophosphamide, methotrexate, 5-fluorouracil, and vincristine (CMFV, 108 patients), the second one carminomycin and dibromodulcitol (CD, 110 patients), both treatments having been administered intermittently. Those patients who became resistant to the first applied schedule or those after five CD cycles, were crossed over to the alternative schedule. Patients were perspectively stratified according to dominant sites of metastases and randomized then to the treatment schedule. Overall response (CR + PR + MR) was achieved in CMFV combination in 35/108 patients (32%), conventional response (CR + PR) in 31/108 patients (29%), complete response (CRP) in 7/108 patients (7%). In CD combination the corresponding values were 34/110 (31%), 27/110 (25%), 1/100 (1%). Response (CR + PR) in patients crossed over from CMFV to CD was seen in 2/37 patients (5%), and from CD to CMFV in 4/36 patients (11%). Median duration of response observed in the CMFV combination was 5.5 months (range 1-12 + months), in the CD combination 4.5 months (range 1-15 months). Toxic reactions were reversible, grade 3 and 4 cardiotoxicity in the CD combination in 4% of patients in the primary treatment and in 14% in patients when crossed over from the primary treatment and in 14% in patients when crossed over from the primary CMFV regimen.