Adrenal incidentalomas--analysis of 23 cases discovered by ultrasound.

Frequent use of abdominal ultrasonography (USG) increases discovery of incidental adrenal tumors. Our experience and concise review of recent opinions on management of adrenal incidentalomas is presented. In four out of 23 patients with adrenal incidentalomas false positivity of USG was found (all on the left side), 4 cases were identified as pseudoadrenal masses. Hormonal activity was proved in 4 out of 15 true adrenal masses (2 pheochromocytomass, 2 aldosteronomas). Five out of 11 hormonally inactive tumors were benign adenomass, 2 myelolipomas, 2 simple cysts, 1 metastasis of bronchogenic carcinoma and 1 tuberculotic involvement. The smallest tumor was aldosteronoma (2 cm in diameter), the largest was myelolipoma (more than 10 cm). Size of benign adenomas ranged between 2.5-4.8 cm. Three main ultrasonic patterns of adrenal tumors were recognized: (1) anechogenic cysts, (2) complex but predominantly hyperechogenic myelolipomas, (3) hypoechogenic all other masses.

Occurrence of ras mutations in human lung cancer. Minireview.

Members of ras family of oncogenes, when activated by a point mutation, have been implicated in many types of human cancers. In several types of human solid tumors, point mutations of the K-ras gene are relatively frequent. Among lung cancers, a subset of non-small cell lung carcinomas, mostly adenocarcinomas, contains activated K-ras. The examination of K-ras mutations in samples obtained for diagnostic reasons, such as bronchial biopsies or bronchoalveolar lavage fluid, may be used as a supplement in the early diagnosis of lung adenocarcinoma.

Alcohol intake and risk of breast cancer: the euramic study.

To evaluate the association of alcohol intake with the risk of breast cancer in post-menopausal women, we analyzed the data from an international case-control study conducted in five European countries (FRG, Switzerland, Northern Ireland, the Netherlands and Spain). Information on alcohol intake was available in 315 cases and 364 controls. Medians for the tertiles of alcohol intake among current drinkers were 1.7, 6.0, and 20.0 g/day. Adjusted relative risks (and 95% confidence intervals) of breast cancer for each tertile of intake in current drinkers, compared to never drinkers, were 1.00 (0.60-1.67), 1.01 (0.60-1.73), and 1.18 (0.69-2.03). The adjusted relative risk for ex-drinkers was 1.73 (1.07-2.79). Among both current drinkers and ex-drinkers, the relative risk was higher for those with body mass index above the median compared to those with body mass index below the median. These results do not support a dose-response effect of alcohol on breast cancer risk, although consumption levels were too low to exclude increased risk with high regular intake. Further research is necessary to evaluate the risk of developing breast cancer among ex-drinkers and the potential interaction between body mass index and alcohol drinking.

Characterization of human breast adenocarcinoma SK-BR-3 cells resistant to doxorubicin.

Doxorubicin shows a wide spectrum of activities in solid tumors, especially against breast carcinoma. The aim of this study was to examine if doxorubicin, when given at lower concentrations than applied in clinic, may induce changes in treated cells. With this purpose we developed human breast adenocarcinoma SK-BR-3 cell line resistant to doxorubicin. The sensitivity of these cells to doxorubicin and to some other cytostatics used in cancer treatment was determined by colorimetric MTT assay. Some parameters which may be of importance as prognostic factors in treatment of breast cancer were analyzed as well. The expression of genes involved in mitotic signal pathway (EGF, TGF alpha, EGF-R, erbB-2, erbB-3, c-myc and c-H-ras) was determined immunocytochemically. The concentrations of cathepsins were determined using quantitative immunoreactive assays (cathepsins B and L) or immunoradiometric assay (cathepsin D). The results revealed that even low doses of doxorubicin can induce numerous changes in treated cells: they become resistant to doxorubicin, and cross-resistant to several other cytostatics. The expression of the above mentioned genes involved in mitotic signal transduction, as well as cathepsins D and L, was similar in both parental and doxorubicin treated cells.

Prognostic significance of tumor angiogenesis in advanced breast carcinoma: an Indian experience.

Angiogenesis is essential for tumor growth and metastasis. In the present study we investigated the prognostic significance of microvessels (MV) density using immunohisto-localization of factor VIII antigen in 51 breast cancer patients. We counted microvessels per 200x field in the most active areas of neovascularization by staining factor VIII related antigen and graded MV density and correlated with stage, LN involvement and histologic grade. Patients who subsequently developed metastases had significantly high MV counts than patients without metastatic disease (p < 0.001). Patients who subsequently died of the disease had significantly high mean microvessels counts than patients who remained alive at the end of 5 years (p < 0.001). As density of factor VIII antigen staining increased the survival decreased (p < 0.001). All the patients having > 25 MV per 200x field had tumor recurrence faster as compared with patients having < 25 MV (p < 0.02). Thus, the MV count correlates with the prediction for metastasis and poor survival. Such an indicator would be useful in selection of a subgroup of patients with breast cancer who are at high risk for having occult metastasis at presentation and subsequently would benefit from aggressive therapy.

Surfactant system in lung cancer. Endogenous lipid pneumonia.

The aim of the study was the evaluation of endogenous lipid pneumonia-type changes developing in the vicinity of primary tumors of the lungs. The postoperative material collected from 56 patients operated for non-small cell lung cancer was examined. The coexistence of endogenous lipid pneumonia-type changes with squamous cell carcinoma and large cell carcinoma of the lung was most common. Patients with these histopathological types of carcinoma had lower percentage of metastases to the lymph nodes. Endogenous lipid pneumonia was found to accompany most frequently the tumors 3 < or = 6 cm in diameter and it was slightly more common in the vicinity of peripheral tumors.

Taxol-enhanced cytotoxic effect of radiation in human promyelocytic leukemia cells: relative resistance of multidrug-resistant HL-60 cells in vitro.

Cytotoxic effects of sequential taxol (paclitaxel) and X-irradiation on drug-sensitive human cultured promyelocytic leukemia (HL-60) cell line and its multidrug-resistant sublines were examined using photometric MTT test and flow cytometry. Paclitaxel (at concentrations 1-10 nmol) stimulated the cytotoxic effect of irradiation in HL-60 and to a lesser extent also in HL-60/ADR, but not in HL-60/VCR cells. The stimulation of radiation-induced cytotoxic effect by paclitaxel correlated with its potential to induce cell cycle and viability alterations identified with flow cytometric analysis (i.e. increased propidium iodide staining, increased side scatter, decreased forward angle scatter, accumulation of necrotic cell detritus, apoptotic pre-G0 cells and cells in the G2/M phase of the cell cycle).

Distribution and photodynamic effect of zinc phthalocyanine disulfonate in nude mice bearing mammary carcinoma.

The distribution study of zinc phthalocyanine disulfonate (ZnPcS2) in nude mice bearing mammary carcinoma (T50/80) revealed a rapid uptake of the dye by tumor. In experimental photodynamic therapy (PDT), the tumors were exposed to laser radiation (670 nm, 100 mW/cm2, 150 J/ /cm2) after intravenous administration of ZnPcS2 in saline. The results showed the maximum tumor destruction to be achieved for the time interval between injection of the drug (2 mg/kg) and exposure to laser light of 5 min, while a significantly less damage was observed when the time interval was 24 h (p < 0.0001). The degree of damage produced by the treatment was monitored in vivo by means of noninvasive NMR-imaging and subsequently confirmed histologically.

Effects of intracellular chelatable iron and oxidative stress on transcription of classical cellular glutathione peroxidase gene in murine erythroleukemia cells.

The effect of intracellular chelatable iron levels and of oxidative stress on nuclear classical cellular glutathione peroxidase (GSHPx-1) RNA nascent chain elongation (run-on transcription) and on the stability of cytoplasmic GSHPx-1 mRNA was investigated in murine erythroleukemia (MEL) cells. The amount of iron in the intracellular low molecular mass iron pool was changed by incubation of MEL cells transformed by Friend virus with iron donors or iron chelators. Transcription in vitro in isolated nuclei from treated cells showed that the treatment with iron chelators (desferrioxamine (DFO), pyridoxal isonictinoyl hydrazone (PIH) decreased the rate of nuclear GSHPx-1 RNA nascent chain elongation in both uninduced and with 5 mmol hexamethylenebisacetamide (HMBA) to erythroid differentiation induced MEL cells. Iron donors (diferric transferrin, Fe-PIH or their combination) and t-butyl hydroperoxide (t-BuOOH) had the opposite effect on GSHPx-1 gene transcription in run-on experiments. On the other hand, 50 mumol DFO or 2.5 mumol t-BuOOH did not change the stability of cytoplasmic GSHPx-1 mRNA in both uninduced and induced MEL cells treated with 5 mumol actinomycin D and with or without these agents for 9 h. These findings indicate that iron and oxidative stress play their role at the transcriptional level of GSHPx-1 gene expression.

In vivo tumor necrosis factor-alpha induction following chlorin e6-photodynamic therapy in Buffalo rats.

Photodynamic therapy may induce in the in vivo conditions the cytokine tumor necrosis factor-alpha in Buffalo rats. The sensitizer, i.e. chlorin e6, in the doses 2.5, 5.0 and 7.5 mg/kg of body weight followed by light treatment with total doses 50, 100, 150, 200 and 250 J/cm2 resulted in the increase of serum levels of the cytokine. The levels of tumor necrosis factor-alpha have been determined at different time points using enzyme-linked immunosorbent assay (ELISA). In control animals these levels did not exceed the mean value of 189 pg/ml, whereas in photodynamically treated rats the levels were almost 3-4 times higher. The entire experiment has been carried out on healthy animals; control, tumor-bearing rats have also been included to the present experiment.

Chloroaceto hydroxamic acid as antitumor agent against Ehrlich ascites carcinoma in mice.

In vivo cell growth inhibition of Ehrlich ascites carcinoma (EAC) has been evaluated with chloroacetohydroxamic acid, (CHA), having -CH2 Cl, for the -NH2 group of hydroxyurea (HU). The inhibitory character of CHA against EAC in mice model has been found to be comparable with that of HU. Cell growth inhibition by CHA is accompanied by inhibitions of DNA and protein synthesis of the treated cells. The transplantability of EAC cells treated with a single dose of (100 mg/kg) CHA is found to be reduced. Enhanced intraperitoneal macrophage is observed in normal mice following CHA (100 mg/kg) treatment. Deviations of hematological parameters and alkaline phosphatase (ALKP) activity consequent to tumor growth are found to be recovered in tumor bearing mice treated with CHA. All these studies suggest the importance of CHA for further trial as a potent antitumor agent.

Apoptosis update: to be, or not to be, and how to arrange the latter. Meeting review.

It has become accepted that cell death is an essential mechanism for the maintenance of an animal's health. But how do cells know when they should die, and how do they do it? A recent conference titled "Programmed Cell Death" was held by the American Association For Cancer Research in Bolton Landing, New York state, USA, on October 19-23, 1996, which focused on the signals that push a cell towards its own self-destruction, and also on the biochemical tools used by these cells in making this ultimate sacrifice. The molecular vocabulary of programmed cell death is only recently being deciphered. At the heart of programmed cell death exists at least one intrinsic program for committing cell suicide, although it is still unclear if there is only one [3]. If only one program exists, it probably contains multiple branches, overlapping pathways, and redundant molecular interactions. One item is clear, however: there exist many mechanisms for inducing cells to suicide.

The leukocyte common antigen (CD45) on human pre-B leukemia cells: variant glycoprotein form expression during the cell exposure to phorbol ester is blocked by a nonselective protein kinase inhibitor H7.

The human pre-B acute lymphoblastic leukemia cell line REH6 was utilized for characterization of CD45 glycoprotein by monoclonal antibodies (mAb) recognizing four distinct CD45 antigen specificities, i.e. nonrestricted CD45, restricted CD45RA, CD45RB and CD45R0. Immunoprecipitation revealed two antigen specificities on REH6 cells of m.w. 220 kDa and 190 kDa, both presenting wide range of isoelectric point pI approximately 6.0-7.5. Nonrestricted CD45 epitopes were not affected by the sialyl acid cleavage with sodium metaperiodate or neuraminidase, but were sensitive to both, tunicamycin, the N-glycosylation inhibitor and monensin, an inhibitor of protein transport through the Golgi compartment. O-sialoglycoprotein endopeptidase from Pasteurella haemolytica A1 partially cleaved CD45RA and CD45RB epitopes, while nonrestricted CD45 determinants were not affected by this enzyme. Limited proteolysis of this antigen resulted in the appearance of 160-180 kDa peptide domains which retained CD45 epitopes. Further, the treatment of cells with phorbol myristate acetate (PMA) induced marked down-regulation of 220 and 190 kDa isoforms and the appearance of new 210, 180 and 170 kDa variant glycoprotein forms which were not found on parental cells. This PMA effect was not accompanied by the programmed cell death and was markedly blocked by a nonselective protein kinase (PK) inhibitor isoquinoline sulfonamide H7. Modulation of CD45 by phorbol esters might serve as an in vitro model for an additional insight into the function of CD45 in hematopoietic cells.

Circulation of progenitor cells after intensive chemotherapy followed by combination G-CSF and EPO in breast carcinoma.

Hematologic effects of granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) combination after printing intensive chemotherapy in the treatment of female breast carcinoma are presented. In a previous group treated with G-CSF alone, 36% of patients became anemic and had to be transfused for correction of their anemia. To the present study 11 consecutive patients with different stages of breast carcinoma were admitted. All were given priming intensive chemotherapy (epirubicin 150 mg/m2 and cyclophosphamide 1300 mg/m2 followed by subcutaneous application of G-CSF at a dose of 5 micrograms/kg/day and EPO 250 IU/kg/day. In cases where leucocyte counts dropped below 1 x 10(9)/l and hemoglobin levels fell to 85 g/l administration of growth factors was started. The therapy stopped when normal leucocyte count reached 4 x 10(9)/l for G-CSF and hemoglobin level rose to 115 g/l for EPO. Our results show significant difference between MNC/T1 (min.), CD34+ cells/microliters (min.), CFU-GM/ml (min.), BFU-E/ml (min.) and MNC/microliters (max.), CD34+ cells/microliters (max.), CFU-GM/ml (max.), BFU-E/ml (max.) p < 0.01, with mean peak values of 16.9-fold for circulating MNC/microliters, 7.8-fold for CD34+ cells/microliters 23.4-fold for CFU-GM/ml and 28.7-fold increase for BFU-E/ml. Side effects were minimal, no infectious complications occurred, body temperature did not rise over 38 degrees C and no corrections of anemia were needed. It is concluded that the administration of G-CSF plus EPO combination following intensive chemotherapy reduces hematologic toxicity and induces large amount of hemopoietic progenitors suitable for autologous transplantation in women with breast carcinoma.

Cathepsin B, thiols and cysteine protease inhibitors in squamous-cell lung cancer.

We investigated activities of the cysteine protease cathepsin B (CB; EC 3.4.22.1), the levels of reduced glutathione (GSH) and cysteine and the activity of gamma-glutamyltransferase (gamma-GT; EC 2.3.2.2) in squamous-cell lung carcinoma (SQCLC) and the lung parenchyma specimens from surgically treated patients. The basal CB activity, assayed in tissue extracts in the absence of exogenous activators, was significantly higher in SQCLC compared to the lung. The residual CB activity, remaining in tissue extracts after preincubation at 37 degrees C, was not any longer significantly different in SQCLC and the lungs. The inhibited CB activity, calculated as the difference between the basal and residual CB activities, was significantly higher in SQCLC compared to the lung. In the case of the cysteine protease cathepsin C (CC; EC 3.4.14.1), neither the basal nor the residual nor the inhibited CC activities in SQCLC and the lung were significantly different. Compared to CC, the powerfulness of endogenous cysteine protease inhibitors to inhibit CB was much higher in both SQCLC and the lung. The cysteine protease inhibitors from SQCLC and the lung which effectively inhibited CB could be related to the inhibitors with an apparent M(r) ranging from 10,000 to 30,000. Isoelectric focusing studies indicated significant differences in the progress of inhibition of the activity of CB isoforms in SQCLC and lung parenchyma extracts. The levels of both GSH and Cys were significantly higher in SQCLC compared to the lung and the level of GSH was significantly higher in Stage III tumors compared to Stage I tumors. The activity of gamma-GT was not significantly different in SQCLC and the lung but it was significantly higher in Stage I tumors compared to Stage III tumors and showed a significant negative correlation with GSH level in SQCLC. Dithiothreitol did not increase the basal activity of CB from SQCLC and the lung which indicates that reversibly oxidized forms of CB do not accumulate in the tumors and the lungs. The basal activity of CB from SQCLC and the lung was competitively inhibited by Cys. Moreover, increasing Cys concentrations had a modulatory effect on the basal activity of CB from SQCLC and the lung which was featured by Cys-induced inhibition of CB activity and by subsequent Cys-effected recovery of CB activity from its previous inhibition by Cys.

Antiproliferation activity and the mechanism of action of 9-bromo-5-morpholino-tetrazolo[1,5-c]quinazoline--potential anticancer drug.

9-Bromo-5-morpholino-tetrazolo[1,5-c]quinazoline (BMTQ) at the two highest tested concentrations (74.6; 29.8 mumol@l) induced retarded cytotoxic effect. After 24 hours of culturing 23.1-98.8% of the cell population proliferated but after 48 and 72 hours 6.4-80.4% of the cell population degenerated. Other concentrations induced toxicity that was concentration-and time-dependent. The cytolytic concentrations of BMTQ induced integrity damage of cytoplasmatic membrane. The inhibition of cell cycle and the elevated content of proteins in the cell exposed to the cytotoxic concentrations of BMTQ suggest that the cells synthesize protein without entering into mitosis and that dying cells are in the S-phase before death. BMTQ induced 1.75-3.01 times increase of the level of ssDNA in comparison with the control.

DNA-synthesis inhibition and repair DNA-synthesis in CHO Ade-C cells: an alternative approach to genotoxicity testing.

We describe an alternative assay to determine genotoxicity. Its main feature is that it combines two measures in a single experiment; the inhibition of replicative DNA synthesis together with the stimulation of DNA repair. We show that, in tests of four different genotoxic agents, the assay gives results that are entirely consistent with what is known about the mode of action of these agents. In addition, we have demonstrated that chemical carcinogens requiring metabolic activation can be examined using a standard procedure of incubation with a microsomal activating fraction. We consider the combined assay for DNA synthesis inhibition and repair synthesis to be a useful way for the rapid prescreening of chemicals suspected of genotoxic activity on the level of mammalian cells.

The influence of melatonin on metabolic changes in female rats induced by continuous irradiation and/or administration of 7,12-dimethylbenz/a/anthracene.

Metabolic profile is an important biological marker of neoplastic processes not only in the tumor itself but also in the host organism. The neurohormone melatonin has been implicated in experiments as an oncostatic agent. Female Wistar:Han SPF rats (Velaz, Prague, Czech Republic) were irradiated continuously for 15 days using a daily gamma rays dose of 96 mGy. At the end of exposure one group of rats was administered 5 mg/kg b.w. of dimethylbenz/a/anthracene (DMBA) intragastrically. During the period of exposure to ionizing radiation a part of the animals was supplied with melatonin (M) at a concentration of 20 microliters/ml in drinking water. Selected parameters of lipid and carbohydrate metabolisms and levels of selected hormones were determined 2, 30 and 100 days post-irradiation. The irradiation itself caused only small changes in tissue lipids. The application of a single low dose (subthreshold from the point of view of induction of mammary tumors) of DMBA caused more pronounced changes in nonirradiated animals; of the changes observed an increase in lipids in the liver, triacylglycerols (TG) in the thymus and decrease in myocardial glycogen predominated. The intake (by drinking) of exogenous M prevented the biochemical pattern of fatty liver in animals administered DMBA in both groups, irradiated and nonirradiated. A prolonged effect of exogenous M, demonstrated by prevention of increase in TG in the thymus and of irradiated animals caused by administration of DMBA, was observed. The mechanism of metabolic effect of M is not known. Additional experiments are needed to explain the relationship between the beneficial effect of M on metabolic changes and its presumable oncostatic effect in rats.

The cytogenetic identification of high risk members in colorectal cancer families.

Family history of colorectal cancer is recognized as a risk factor for the disease and the development of colorectal cancer represents a suitable model for illustrating multistep tumor development. Bleomycin induced chromosome sensitivity studies were done in 7 colorectal cancer families consisting of 12 colorectal cancer patients and their 34 first degree relatives and 12 sporadic colorectal patients for comparison and identification of high risk family members with genetic instability. All patients and 4 unaffected relatives showed increased bleomycin sensitivity, which might be due to defective DNA repair system. These four relatives may be classified as high risk (without cancer at present) individuals. The study is being continued in more number of familial colorectal cancer patients and their relatives to arrive at definite conclusions.

ABVD chemotherapy of Hodgkin's disease.

The authors report on their results in ABVD therapy, which was given by 91 patients with Hodgkin's disease as first-line treatment. 78 patients (85% achieved complete, 10 (11%) partial remission, 3 (4%) did not respond to therapy. In the follow-up period (36-223 months) 6 patients (7%) died because of the progression of Hodgkin's disease. Serious side effects or treatment-related death did not occur. Based on their results of ABVD, the authors find ABVD chemotherapy effective as first-line treatment of Hodgkin's disease.

Cellular dysplasia in acquired cystic renal disease: comparison of histomorphometrically gauged nuclear parameters in normal kidneys, renal cell carcinomas and acquired cystic kidneys.

Nuclear parameters were assessed by computer-assisted image analysis in the cells of abnormal epithelial formations in the acquired cystic kidneys of two dialysis patients, the proximal and distal tubules of a normal kidney and two well differentiated renal cell carcinomas. One acquired cystic kidney contained many small clear celled foci and am 0.9 cm-size clear celled lesion and the second one a papillary microadenoma. The clear celled lesion was cytologically indistinguishable from the carcinomas. The histomorphometrically gauged nuclear parameters were maximal and minimal ferret diameters, averaged ferret diameter, aspect ratio, shape factor, area, volume and specific length and width. Statistical evaluation evidenced that the nuclear area, volume, aspect ration and shape factor allowed for the distinction between benign and malignant epithelial structures. The medians of the nuclear parameters of atrophic tubules, cysts, clear celled foci, papillary adenoma and clear celled lesion in the two acquired cystic kidneys deviation from those of normal renal tubules and in, increasing order of disparity, approached those of the carcinomas.

Reduction in the cumulative incidence rate of cervical cancer by one life time selective screening.

Mass scale cervical cytology which is the most accepted strategy for the control of cervical cancer cannot be undertaken in developing countries in view of paucity of resources, hence a need arises to examine alternate strategy. The present exercise attempts to study the reduction in cumulative incidence rate of cervical cancer by one life time selective screening. The results revealed that cumulative incidence rate (CIR) of cervical cancer per 100,000 in cohort of women during the age of 20 to 64 years was found to be 2555.0 in the absence of screening. One life time selective screening at the age of 40 and 45 years showed the reduction of 11.6 and 17.2% in CIR respectively where as respective estimates in case of complete screening at mentioned age groups were found to be 21.5% and 25%. In order to further conserve the resources the strategy seems to be optimum for developing countries.

Report on the 4th Central European Lung Cancer Conference, September 26-29, 1996, Gdańsk, Poland.

Experimental chemotherapy of murine melanomas: is there a discrepancy compared to clinical experience?

There has been a discrepancy between promising results of experimental chemotherapy in animal melanoma models and clinical response rates. This inconsistency seems to reflect weak points of the assays used so far to monitor the response of melanoma cells to chemotherapeutic agents. Therefore a less usual approach was chosen in the present study: Tumor cells were cultured in peritoneal cavity (B16 melanoma in inbred C57BL/6J mice and Cloudman S91 melanoma in inbred DBA2 mice) to maintain normal in vivo conditions; the animals were receiving the tested agents in i.p. injections and the prolongation of their life span was considered as the principle parameter of therapeutic efficiency of the compounds tested. Previously described therapeutic potency both of vitamins (C, alpha-tocopherol acid succinate) and some phenols (hydroquinone, 4-hydroxyanisole) was confirmed. Benzoate, spin trap N-butyl-alpha-phenyl-nitrone and ammonium chloride as a lysosomotropic agent failed to increase the survival of melanoma-bearing mice. Free radical scavenger methimazole exerted a therapeutic effect in mice with pigmented B16 melanoma. Only classic cytostatic agents--cisplatin and cyclophosphamide--proved its therapeutic effect in both melanoma models studied. These results are in accord with the known resistance of human melanoma to conventional chemotherapy. Measurement of serum activity of gamma-glutamyltransferase was shown to be useful for monitoring therapeutic effect.

DNA ploidy in malignant melanoma, skin cancer and pigmented nevi.

The determination of DNA content in human cancers is the subject of increasing interest, particularly in view of its potential clinical applications. There are relatively few studies which describe DNA content of skin neoplasms and pigmented nevi. These studies have shown conflicting results. In the present investigation the authors measured DNA ploidy using flow and video-imaging cytometry in 51 malignant melanomas, 20 skin cancers and 48 pigmented nevi. For DNA measurement paraffin embedded tissues and fresh cell smears were used. Clinical and histological data of malignant melanomas were recorded and correlated with DNA ploidy. DNA histograms were examined for DNA aneuploidy by DNA Index. DNA ploidy in primary lesions of melanomas and their metastases were compared. The aneuploidy rate, found in our observation, was significantly higher in whole malignant melanoma group, in clinical Stage II and III, in tumors with thickness greater then 1.5 mm, tumors with Clark level III, IV and V. Another clinical and histological factors did not show significant correlation with ploidy. Aneuploidy was found in 8 of 20 (45.0%) skin cancers. In the whole population of pigmented nevi aneuploid DNA content was identified in 10 nevi (20.1%). The results of this study suggest that aneuploidy seems to be connected with advanced stage of malignant melanoma but it does not replace other prognostic factors. Both cytometric methods can be used for routine DNA ploidy analysis. Ploidy studies are not useful for predicting metastatic potential of primary melanoma. Results obtained from fresh cell smears and paraffin embedded tissues were identical.

A cell surface antigen that cross-reacts with My4, a monoclonal antibody to CD14, is expressed on human monoblastic cell line U937, B-lymphoma cells, and polymorphonuclear leukocytes.

The CD14 antigen was originally identified on monocytes as a differentiation marker and usually detected by a panel of monoclonal antibodies, including My4 and LeuM3. Recent studies have shown that CD14 antigen is expressed on Langerhans cells, a subject of normal B-lymphocytes, neutrophils, and subtypes of B-cell non-Hodgkin's lymphomas. These antigens, however, react with My4, but not with LeuM3, and the reason for this has not been elucidated. In this study, we found that similar My4+/LeuM3- epitopes are expressed on the human monoblastic cell line, U937. Northern blotting demonstrated that the U937 cells express neither 1.4 kb CD14 transcripts nor possible alternative spliced forms of CD14 transcripts. The molecule was resistant to phosphatidylinositol specific phospholipase C, which effectively hydrolyzes glycosyl-phosphatidylinositol anchored protein, decay accelerating factor, on the same cells. Lipopolysaccharide, which down-regulates the expression of CD14 on monocytes, did not alter the expression of the molecule. We concluded that the My4+/LeuM3- molecule on U937 cells is not CD14 antigen but another surface protein. A similar molecule was also detected on B-lymphoma cells from a patient with non-Hodgkin's lymphoma and on polymorphonuclear leukocytes from healthy donors.

Tumor angiogenesis in pulmonary adenocarcinomas: relationship with basic fibroblast growth factor, its receptor, and survival.

Tumor angiogenesis was examined in tissue specimens from 120 patients with a pulmonary adenocarcinoma. The microvascular density (MVD) was determined by the factor 8-related antigen (F8RA), and the basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) protein expressions were immunologically studied with the MVD. Patients with over 30 counts of the MVD showed significantly poorer prognosis than those with less than 30 counts. bFGF and FGFR1 expressions correlated with tumor angiogenesis and prognosis. Univariate analysis showed that the MVD, bFGF, and FGFR1 had a significant effect on prognosis, and multivariate analysis of three prognostic factors revealed the MVD correlated with survival. Our findings suggest that bFGF and FGFR1 expressions play an important role in tumor angiogenesis and that the bFGF and FGFR1 expressions promote angiogenesis and metastasis in pulmonary adenocarcinoma, and that the MVD is a useful prognostic marker for assessing the outcome of a pulmonary adenocarcinoma.

Prognostic factors in astrocytomas: relationship of p53, MDM-2, BCL-2 and PCNA immunohistochemical expression to tumor grade and overall patient survival.

The immunohistochemically detected expression of p53, BCL-2, MDM-2 and PCNA proteins in samples of tumor tissues of 42 patients with astrocytomas or glioblastoma multiforme was statistically compared to degree of malignancy and overall survival. We found relation between p53 protein expression and survival in the high grade astrocytomas group (more cases of p53 immunonegative tumors with longer survival), and significantly higher BCL-2 protein expression as well as significantly higher MDM-2 protein expression in the group of low grade astrocytomas. PCNA protein expression showed any relation to tumor grade or survival. Despite the rather small number of samples these results support the hypothesis that MDM-2 protein may be a potent regulator of functional p53, expressed in low grade astrocytoma only.

Does the concentration of alpha 1-proteinase inhibitor reflect the transformation of liver cirrhosis to liver carcinoma?

Serum concentration of alpha1-proteinase inhibitor (alpha1-PI) was determined by nephelometric method in forty seven patients with liver cirrhosis (LC) and fifteen patients with hepatocellular carcinoma (HCC). Our data show an increase in the concentration of alpha1-PI in the group with decompensated LC by 17% and in HCC by 29%. The level of alpha1-PI higher than (220 mg%) may be indicative of the disease progression towards decompensated LC or HCC. In the conclusion, an increase in alpha1-PI concentration in patients with LC may be considered as an alarming factor, but is not sufficiently specific to become a diagnostic tool for the detection of HCC development.

Androgen level variations, clinical response to LHRH agonists and changes in the quality of life subscales in metastatic prostate cancer--speculations about possible role of the monoamine system.

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result of the change in the level of monoamines in CNS under Zoladex.