Malignant lymphoma with isolated kidney involvement.

A case of reticulum cell sarcoma with kidney involvement is described. The diagnosis was established by open renal biopsy only when the disease was far advanced. Treatment with combination chemotherapy and radiotherapy brought about very short remission and the patient died in uremia. Autopsy showed isolated kidney involvement with only metastasis in thyroid gland.

On the history of experimental oncology (centennial).

Investigation of the inhibitory activity of some mycobacterial strains on growth of the intratracheally transplanted Deals' sarcoma in guinea pigs.

In this paper the authors describe and analyse results that they obtained by infection of the guinea pig organism carried out by subcutaneous or intratracheal application with five mycobacterial strains, namely Myco bovis BCG-Praha, Myco the H37Ra, Myco Kansasii, Myco fortuitum and Myco smegmatis. At predetermined time intervals following subcutaneously or intratracheally performed infection (on 7th, 16th, 28th and 56th day after infection) transplantation of a Deals' guinea pig sarcoma cell suspension was carried out in guinea pigs by the intraltracheal route. As it appears from the results gained the applied mycobacteria exhibit a partial inhibition of growth od Deals' guinea pig sarcoma cells of different character. From among the utilized strains the Myco bovis BCP-Praha and the Myco tbc H37Ra exhibited the highest, Myco fortuitum and Myco smegmatis the lowest inhibitory activity. Intratracheally performed infections yielded in general better results on the growth inhibition than infections carried out with the same strain but by the subcutaneous route. Furthermore, in the experiments reported on in the present paper the authors could verify their earlier experience, namely that inhibition of growth of sarcoma cells is most pronounced at the time of maximal biological activity (logarithmic phase of multiplication) of the applied mycobacterium.

On the genesis of granulosa-cell ovarian tumors. Experimental data.

The ovaries and ovarian tumors induced in albino virgin mice of lines A and CC-57 by intravaginal treatment with different blastomogenic substances, such as polyurethan; 7,12-dimethylbenz-(alpha)anthracene; 8-hydroxyquinoline and synestrol, were studied histologically. 330 cases were under study, including 78 as control. The granulosa elements of ovarian follicles were found to be involved in the processes of epithelial transformation and tumorogenesis. Pretumor changes are reported to be under study in 56 cases, granulosa-cell tumors or proliferates morphologically identical to them -- in 26 cases. The data presented show close relations of the peculiarities of differentiation as well as proliferative processes in the epithelium of the women genitals and the ovarian granulosa tissue.

Some results and prospects of transplacental carcinogenesis studies.

Analysis of literary data and the author's findings have shown that the transplacental action of most of the compounds tested in experiments on rats manifested itself by a neurotropic carcinogenic effect. A marked neurotropism in transplacental carcinogenesis in rats is characteristic even for such drugs (e.g. dimethylbenzathracene) that have never induced neurogenic neoplasms in adult animals. To elucidate the relationship between teratogenesis and carcinogenesis the peculiarities of tumor development in brain against the background of malformations induced by combined transplacental treatment by methylnitrosourea (MNU) and ethylnitrosourea (ENU) in rats have been studied. Tumorigenesis was sharply inhibited by administration of ENU (on the 13th day) prior to MNU treatment (on the 15th day). There is reason to believe that the cytotoxic effect of MNU for microephaly results in the death of a considerable part of the cell population already transformed by ENU. In a special series of experiments characteristics of the permeability of polycyclic aromatic hydrocarbons through the placenta in rats have been specified.

Simultaneous occurrence of IgG3-kappa and IgG2-lambda paraproteins in a 12-year-old girl with malignant reticulosis.

Transient occurrence of IgG3-kappa and IgG2-lambda paraproteins in a 12-year-old girl with malignant reticulosis is reported. These paraproteins were demonstrated in a total amount of 3.4 g/100 ml after termination of cytostatic treatment; they disappeared after another 2 months.

Nucleoli of lymphocytes in the peripheral blood of patients with bronchogenic lung and gastrointestinal cancer.

Patients suffering from bronchogenic and gastrointestinal cancer without, as well as with metastases, were investigated to provide more information on the number of morphology of lymphocytes in their peripheral blood particularly in respect to the frequency of various nucleolar types in these cells. The decreased number of lymphocytes in the peripheral blood of the cancer patients was due to the decline of lymphocytes with ringshaped nucleoli representing resting cells which can be stimulated in respect to the RNA synthesis and blastic transformation. The decreased number of such cells was apparently more pronounced in the peripheral blood of the patients suffering from gastrointestinal cancer with metastases. The increased frequency of lymphocytes with compact nucleoli or nucleoli with nucleolonemas representing immature or stimulated cells was noted in most patients suffering from bronchogenic cancer without, and with metastases in lymph nodes, as well as in some patients with gastrointestinal cancer and, without metastases. On the contrary, the decreased number of these cells was observed in the peripheral blood of patients suffering from gastrointestinal cancer with metastases. All these changes provide further information on the changes of the lymphocytes in the peripheral blood of the patients suffering from malignant disease. The possible interpretation of these changes presented in the discussion is in accordance with the present conception on the relationship between the malignant growth and lymphocytes.

Multiple myeloma in two brothers. Immunoglobulin levels among their relatives.

The reports on the occurrence of myeloma in two or more members of the same family are very scanty, and until present, only about twenty observations of the familial occurrence have been reported. In this paper the observation of multiple myeloma in two brothers is described. The clinical diagnosis was confirmed by the bone marrow biopsy which showed an infiltration of abnormal plasma cells. X-ray examination of the skeleton revealed typical osteolytic changes in one patient and diffuse osteoporosis in the other. Moreoever both patients had a massive monoclonal protein fraction in serum and Bence-Jones protein in urine. In one case the monoclonal serum protein was of the IgG-K type and in the other, of the IgA-K type. Thus the antigenic determinants were different in the class specificity. Immunoglobulin studies among healthy relatives of the two brothers demonstrated much higher incidence of the polyclonal increase in one immunoglobulin class than could be expected in the population. Without evidence of monoclonal serum protein, unusally high IgA serum levels, more than 500 mg/100 ml, were observed in seven of seventeen healthy family members. This could be explained on genetic basis in connection with the familial occurrence of myeloma either by an abnormal distribution of plasma cell clones or by their abnormal activity. However, a defective control mechanism in protein synthesis may also be taken into consideration.

Metastases into the cervical lymph nodes from unknown primary focus.

The analysis bears on 33 patients with histologically verified metastases into the cervical region from an unknown primary tumor, which was found intra vitam in 7 cases and by resection in 2 of the cases (i. e. 27.2%) only. The best form of treatment is a surgical-radiological combination. The search for the primary focus is often difficult and necessitates the use of ORL investigation and the other diagnostic methods. Emphasis is laid on the need of regular and frequent check-ups in case the primary focus is not detected. An early detection of the origin favourably affects the results of treatment.

Carcinoma cervicis uteri. Treatment results from the period 1953--1968.

During the course of 16 years, i. e. from 1953 to 1968 inclusively, a total of 2111 patients with carcinoma of the uterine cervix were treated at the Oncological Institute in Brno. Of these, 1829 patients, i. e. 86.6% were irradiated, 282, i. e. 13.4% underwent primarily a radical excision and subsequently were irradiated. During the past years, approximately 95% of all such patients are being given radical irradiation. The mean age is 52.7 years, the sixth decade being numerically the highest in incidence -- 27.4%. The distribution pattern according to the tumor stage: I -- 29.3%, II -- 14.3%, III -- 48.2%, IV -- 8.2%. This distribution remained practically unchanged over the follow-up period of 16 years. The fundamental method treatment of practically 87% of all the patients was actinotherapy consisting in a combined application of radium and X-rays. Of the total number of 2111 patients, 1298, i. e. 61.5% have survived 5 years without any symptoms of the disease, 966 patients, i. e. 59.0% (out of a total of 1671 patients) survived 10 years. The five-year survival symptom-free period for the various stages ia as follows: I -- 82.5%, II -- 77.1%, III -- 52.8% and IV -- 9.8%. A comparison of the results of treatment in patients radically irradiated and those primarily operated upon then subsequently irradiated, i. e. in 619 patients of stage I showed the 5-year recovery to be superior by almost 4% in the former than in the latter group --84.1% as against 80.3%. Over the last 6 years of the follow-up, i. e. 1962--1968, this difference went up to 6.0% in favour of those radically irradiated--85.1% as against 79.2%. An increasing mortality rate due to carcinoma is noted with advancing age.

New potential cytotoxic and antitumor substances. II. Effect of hydroxyanthraquinones and their glucosides on Ehrlich ascites carcinoma cells in vitro.

Mono and dihydroxyanthraquinones and their derivatives affected the utilization of 14C-labeled precursors nucleic acid and protein synthesis into Ehrlich ascites carcinoma (EAC) cells. Inhibitory effect of the substances markedly increased when one acetyl group was introduced into the basic molecule. As the tested substances inhibited mainly incorporation of 14C uridine into the cold TCA insoluble fraction of EAC cells, their mechanism of action can be explained by the inhibition of RNA synthesis.

Pharmacokinetics of Cytembena in chronic renal impairment.

Renal excretion of Cytembena in subjects with a normal renal function amounted on the average to 7.8% of the given dose during 15 hours following a single intravenous administration of 200 mg of this cytostatic drug. In patients with an impaired renal function there was a further decrease in the urinary Cytembena excretion and this in direct relation to the decrease in endogenous creatinine clearance rate. The decline in renal Cytembena clearance is slower than that of glomerular filtration rate due, probably, to a lowered tubular reabsorption of Cytembena in residual nephrons. This change in tubular resorption of Cytembena is related to a decrease of the fractional reabsorption of sodium in residual nephrons. Serum Cytembena concentrations proved to be significantly lower in patients with impaired renal functions than in subjects with normal renal functions. This peculiarity of the pharmacokinetics of Cytembena is discussed from the aspect of a possible increase of its distribution volume in consequence of an increased concentration of the diffusible component.

Preliminary analysis of failures in the radiotherapy of uterine cervix cancer with a dynamic dose-fractionation in combination with breathing oxygen at ambient pressure.

Complementary to a previous preliminary analysis of the results obtained in treating head and neck tumors, this paper summarizes observations in testing uterine cervix cancers with a dynamic dose-fractionation regime using Cobalt 60 radiation in combination with oxygen breathing at ambient pressure. A total of 30 cases in different stages are reviewed which had no treatment prior to radiotherapy. In agreement with previous observations, normal tissue reactions were decreased in comparison to those seen after conventional dose-fractionation. Exophytic type of tumors with relatively good vascularization appears to react better to the treatment then less vascularized endophytic tumors. For the evaluation of the possible role of the dynamic fractionation in these results collection of further data is needed.

Peripheral blood lymphocyte counts and survival in breast cancer.

The lymphocytes in the peripheral blood of patients with breast cancer were studied. Peripheral blood lymphocyte counts were found to be significantly lower in the short-survivors when compared with the long survivors. Lymphocyte count may be a host factor, that influences survival in breast cancer.

Chemotherapy of advanced malignant lymphomas comparative evaluation of results with single agent and combination therapy.

86 patients with advanced malignant lymphomas (stage III and IV) were treated either with Vinblastine given as a single agent (49 cases) or with combination chemotherapy MOPP or COP (37 cases). In both, Hodgkin's disease and non-Hodgkin's lymphomas, induction of remission, relaps-free survival and prognostic significance of initial clinical stage were evaluated, in relation to the therapeutic modality. In patients with Hodgkin's disease, combination chemotherapy was found to produce significantly more durable remissions, when compared with single agent therapy. However, difference in the response rate, which was found to be more effective following the combination chemotherapy, was not statistically significant. In patients with non-Hodgkin's lymphomas overall lower response was recorded, regardless of the therapy applied. In all patients, better response rate and longer lasting remissions correlated with initial stage III.

The metastatic spread of kidney and prostate cancers in man.

This research was performed on 66 autopsy reports of kidney cancers and 58 autopsy reports of prostate cancers. Two alternative hypotheses were tested, i.e. whether metastases spread at random from the primary tumor throughout the body or whether the metastatic spread occurs in steps, referred to as a cascade spread, requiring one or more disseminating sites. It was found that in cancer of the prostate two disseminating sites exist, i.e. bones and lungs. Metastases from the primary tumor appear first in the skeleton and then in the lungs, not vice versa. In cancer of the kidney, the lungs are the major disseminating site. The lymphatic areas did not seem to play a major role in the dissemination of both cancers; on the contrary, the presence of metastases in the lymph nodes seem to depend on the presence of carcinomatous cells in key sites, i.e. the skeleton and the lungs. These results, however, should be interpreted with caution, as explained in the text. Considerations were proposed for future research.

An assay for selecting high risk population for gastric cancer by studying environmental factors.

Gastric cancer mortality incidence data registered in two different areas of Eastern Transylvania (Roumania) were reported related to 325,000 inhabitants from the period of 1951-1972. The findings were compared to some geographical environmental factors deriving from an area of 13,300 km with 905,700 inhabitants. A 2-3.5 times larger incidence of gastric cancer (75-140 per 100,000/year) was found in some selected geographical areas of the intermontane depressions of Gheorgheni and Ciuc in comparison to hilly area of Transylvanian Tableland. The difference might be explained by some unknown environmental gastric cancer risk factors. Of the natural factors, the presence of magmatic substrata shows a significant degree of correlation. The main pedological factor seems to be badly drained pseudoglyied podzolic and peaty soils of low pH and high content of organic matter. Sofs drinking waters also may be involved as risk factor. High altitude, cold climate determining a restricted assortiment of cultivated plants, the successive production of vegetal and animal food on the same soil for livelong periods and several generations, especially in isolated rural areas, seem to represent gastric cancer risk factors. According to authors' opinion a survey of the high-risk population selected on the basis of the environmental factors, especially of the persons suffering from gastric disorders considered today possible precursors of gastric cancer, may offer some progress in detecting early gastric malignancy in the future.

Immune response to rauscher virus-induced leukemia in DBA mice. I. Role of cellular and humoral immunity in spontaneous regression.

DBA/1 and DBA/2 mice infected with the Rauscher leukemia virus developed a biphasic erythroleukemia. Transitory regression of the disease was closely associated with the appearance of tumor-specific antibodies and the exacerbation was preceded by the gradual decrease of antibody titer. The antibody-dependent cellular cytotoxicity could be detected earlier, than the complement-dependent cytotoxicity. Moreover, in each case the titer of antibody-dependent cellular cytotoxicity was higher than that of complement-dependent cytotoxicity. The results suggest that the antibody-dependent cellular cytotoxicity is mainly responsible for the rejection of tumor cells.

Lung colony assay in normal, irradiated and tumor bearing mice.

Lung colony assay performed in normal, X-ray whole body irradiated and tumor bearing mice showed that both irradiated and tumor bearing animals developed much more lung metastases than normal animals.

Sacharose density gradient separation of Ehrlich ascites carcinoma and L-5178Y tumor cells in different cell cycle phases.

Optimal conditions were determined for the distribution of Ehrlich ascites carcinoma (EAC) and L-5178Y mouse tumor cells, proliferating in vivo, by their age within the cell cycle by sedimentation in a buffered linear sacharose density gradient. Measurements of cell size, DNA content and incorporation of tritiated thymidine in successive parts of the gradient confirmed the actual separation of cells of different age: in the upper fractions there were cells in G1 phase, in the middle fractions in S phase and in the lower layers of the gradient there were cells in G2 and/or M phase.

Excretion of Dische positive compounds in rats after irradiation and after administration of some cytostatic drugs.

In order to verify some pathophysiological aspects in radio- and chemotherapy of tumors the excretion of Dische positive compounds in rats was followed. During fractionated whole-body irradiation of animals it was found that up to the exposure with 50 R/day the organism is able to repair the disturbances provoked by irradiation for a certain time and that within the course of irradiation a permanently higher excretion of Dische positive compounds occurs. On the contrary, following the exposure of 100 R/day after a short increase continual decrease occurs lasting until the death of the animal. The excretion of Dische positive compounds in rats was followed also after the application of Cyclophosphamide, cis-dichlorodiammineplatinum (II) and Vinblastine. All these three cytostatic drugs produce an increased excretion of Dische positive compounds on the first day after the application. In the case of Cyclophosphamide, it was demonstrated that the excreted amount of Dische positive compounds was dose dependent.

Mechanism of development and morphology of secondary carcinomas of the oviducts in primary uterine corpus carcinoma.

The rate of incidence and morphology of metastases in 284 Fallopian tubes from 148 patients with primary uterine corpus cancer have been investigated. In 44 patients metastases were discovered in inner organs, of which in 17 (11.5% patients) in 23 oviducts. In 10 of these patients the Fallopian tubes were the only localization of metastases. Macroscopical alterations in the form of thickening and condensation, tumor nodules on the surface of the affected oviducts were discovered in 7 cases. In the remainder no macroscopical changes have been noted. There predominated lymphogenic metastases, in a smaller number of cases there were implantation and lymphogeno-implantation type metastases, localized mostly in the ampullary regions of the oviducts. More often, one could observe involvement by lymphogenic metastases of the subserosal layers together with muscular tissue, less frequently of mucosal layers, and total involvement of all layers of the wall of Fallopian tubes in the form of single or multicentric tumor nests, or diffuse tumor infiltration of tissues of the oviduct wall. Implantation metastases in the form of micronodules, multicellular agglomerates were discovered on the serosa more often than on the mucosa of Fallopian tubes. Secondary oviduct carcinomas differ from primary ones by their histological structure and character of growth. The Fallopian tubes play an essential role in the dissemination of metastases in the presence of primary uterine corpus carcinoma.

Hodgkin's lymphoma -- prognosis as related to histology, clinical stage and treatment.

The rapid advances in modern chemotherapy and actinotherapy of Hodgkin's lymphoma and an improvement in its diagnosis have ushered in numerous novel procedures. This is a preliminary analysis of the results of treatment of 117 patients with actinotherapy, polychemotherapy, consisting of a chemotherapeutic four-combination as substitution for MOPP and a combined actino-chemotherapy. Actinotherapy was found more efficient in localized disorders of stages I and II, while polychemotherapy proved the more suitable when the disease was generalized -- stages III and IV. The analysis of our results has brought only partial support to the prognostic significance of the histological classification of Hodgkin's lymphoma according to Rye. No difference of statistical significance has been noted between the histological types of lymphocyte dominance, nodular sclerosis and mixed cellularity. Lymphocyte depletion alone showed a conspicuously worse prognosis than the other histological types.

Contribution to the mechanism of Stilbostat action.

The hormone-cytostatic drug Stilbostat does not influence the estradiol binding capacity of the rat uterus tissue and tissues of human and experimentally induced mammary tumors. It exhibits an alkylating potency similar to that of other cytostatic drugs used in the therapy of neoplasia. An in vitro splitting of Stillbostat into diethylstilbestrol by tissue slices could not be detected. It was impossible to demonstrate an excretion of splitting products of Stilbostat by rat urine.

Preliminary experience with Mitolactol in advanced tumors of the orofacial region and the larynx.

Mitolactol (Dibromodulcitol "DBD"; RlobromolR) an alkylating agent was applied in a clinical series of twenty advanced or relapsing cases of malignant tumors of the orofacial region and the larynx. It was administered orally in a mean total dose of 127 mg/kg/30 days. In 45% of the patients the treatment resulted in a diminution of tumors by more than 50%, with remission lasting 1-4 months. 30% of the patients responded by a retreat of the tumor volume smaller than 50%, while no therapeutic effect was noted in 25% of the patients, or the objective finding proved to be worse. Subsequent radiotherapy improved the results, and remissions which followed combined chemo-radiotherapy were prolonged up to 9 months. The effect of DBD treatment proved better in orofacial than in laryngeal carcinoma.

On surgical treatment of malignant melanoma.

An early and adequate surgical intervention may have a favorable effect on the course of malignant melanoma (m.m.). Despite the focused publicity given to problems relating to m.m., faulty nonradical excisions of suspected pigmented lesions are still performed rather frequently in surgical outpatient departments. One of the reasons may be the rather difficult clinical diagnosis due to pleiomorphism of m.m., but a lack of experience of certain physicians is also responsible. The authors indicate what effective course to pursue in these patients. On the evidence of their set of 48 patients operated upon, they have shown a radical reexcision of the scar with its wide vicinity, following a nonradical intervention, to be justified. In certain cases, it may affect an eventful dissemination of tumorous cases, it may affect an eventual dissemination of tumorous cells in the close vicinity of the scar after an inadequate excision. In addition, they have delimitated indications valid for a radical reexcision.

Classification and survival rate of patients with serous cystadenocarcinoma of the ovaries.

The comparative evaluation of two stage classifications including USSR Ministry of Health stage classification and TNM system was performed on the base of studies of the end results of 419 patients with serous cystadenocarcinoma of the ovaries. It has been established that TNM system is of a greater importance in establishing more accurate prognosis than the stage classification of the Ministry of Health. In TNM system four variants of the degree of extension correspond to each stage that allows to evaluate not only the extent of the primary tumor that also of the metastatic spread. The achieved results point to the superiority of the TNM system and serve as a base for transition to the TNM system in the classification of ovarian carcinoma.

Human neoplastic cells in tissue culture: two established cell lines derived from giant cell tumor and fibrosarcoma.

The establishment and cultivation of two human neoplastic cell lines is described. The cell line B-5GT was derived from bone giant cell tumor and B-6FS from poorly differentiated fibrosarcoma. In comparison to the normal skin fibroblasts both cell lines have a potential for "indefinite" multiplication in vitro and they exhibit growth properties which are associated with malignant transformation. The parameters investigated included cell morphology, chromosome characteristics, terminal cell density, growth pattern, residual DNA synthesis and growth in soft agar. Both cell lines exhibited human karyotype with aneuploidy and differed in their karyotype from each other.

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. III. Polarographic reduction potentials of carcinogenic nitrogen compounds in dimethylsulfoxide.

The polarographic reduction of a series carcinogenic and noncarcinogenic polycyclic nitrogen compounds in anhydrous dimethylsulfoxide containing tetrabuthylammonium perchlorate as supporting electrolyte has been studied. The obtained results were compared with the number or with the position of nitrogen atoms in the molecules and with their carcinogenic activity. The values of half-waves potentials generally confirmed the mechanism proposed for the reduction of aromatic polycyclic carcinogenic hydrocarbons based on the polarographic experiments in dimethylsulfoxide. Agreement of the obtained results with the data reported by polarographic study in anhydrous dimethylformamide indicates, that the polarographic behavior of polycyclic nitrogen compounds in dimethylsulfoxide is very similar.

Contribution to the study of excision repair following UV irradiation in mammalian cells cultivated in vitro.

The absence of pyrimidine dimer excision after UV irradiation in rat cell line was confirmed. The possibility of excision repair system depression by acidification of medium with H3PO4 in HeLa cells has been proved. The results obtained by two different methods of deproteinization and DNA isolation are in good conformity.