Flow cytometry (FCM) of early radiation response in epidermoid carcinoma of uterine cervix.

DNA flow cytometry (FCM) investigation of tumor specimens before and after 30 Gy 137Cs radiation treatment was performed in 33 cases of epidermoid uterine cervix carcinoma. Distinct differences in the type of FCM response to radiation were seen when the results of DNA index (DI) in diploid and aneuploid tumors and proliferation index (PI) values in diploid tumors from pretreatment and 30 Gy irradiated specimens were compared. We observed partial or total reduction of PI in 12 of 17 diploid and near diploid tumors, and total reduction of the aneuploid population in 14 of 16 aneuploid tumors. No significant correlation was found between the type of FCM response and clinical stage of the disease or the histological degree of differentiation.

Studies on the natural killer cell activity of human nonadherent mononuclear cells (nMNC) with tumor necrosis factor, interleukin-1, interferon-gamma and cisplatin.

The potential for additive or synergistic augmentation of NK cell activity of nMNC with recombinant tumor necrosis factor (TNF-alpha), interleukin-1 (IL-1), interferon-gamma (IFN-gamma) and cisplatin in different combinations was examined. Significant augmentation in NK activity of nMNC was observed when treated with cisplatin, rIFN-gamma, rIL-1 or rTNF-alpha in vitro. Combined treatment of nMNC with rIL-1 and rTNF-alpha resulted in moderate increase in NK cell activity. However, killing of K 562 target cells was markedly augmented by co-stimulation of nMNC with rIL-1 plus rIFN-gamma and rIL-1 plus cisplatin. Further, only a moderate augmentation of NK activity was observed when nMNC were treated with cisplatin plus TNF or IFN-gamma. These observations demonstrated the individual and co-stimulative effects on NK function of nMNC in vitro by rTNF-alpha, rIL-1, cisplatin and rIFN-gamma.

HPLC determination of a new anticancer agent (acylfulvene) in serum.

High performance liquid chromatography (HPLC) combined with effective preseparation steps (liquid extraction, solid-phase extraction, preconcentration procedures) was used in pharmacokinetic studies of a novel anticancer agent (acylfulvene) in serum. HPLC conditions were optimized for the analysis of model clinical samples and real serum samples with different contents of acylfulvene. Extraction recoveries for both extraction procedures were evaluated and linearity was achieved for a wide concentration range. Detection limit for acylfulvene in serum was 0.075 microgram/ml, preconcentration minimum 5 times was recommended, especially after the solid-phase extraction step. The HPLC assay was applied for pharmacokinetic studies of acylfulvene in dogs and rats and pharmacokinetic parameters were determined.

Sarcomas of the breast: a multicenter series of 70 cases.

A multicenter retrospective series of 70 breast sarcomas (malignant cystosarcoma phyllodes (25), osteosarcoma (12), liposarcoma (10), stromal sarcoma (8), angiosarcoma (7), mixed types sarcoma (4), malignant histiocytoma (3), leiomyosarcoma (1)) was reviewed. The average follow-up was 5.9 years. Diagnostic tests (palpation, mammography, sonography and cytology) were poorly sensitive, and a large proportion of cases, appearing as regular, sharp bordered, rounded masses were diagnosed as benign fibroadenomas. Surgery (limited (29), mastectomy (41)) was the treatment of choice. Axillary nodes were rarely involved (2 of 31) at pathologic staging. No significant predictors of local recurrences (12 cases) were observed although recurrences were more frequent in larger lesions (0-20 mm = 1.1%, 21-50 mm = 1.7%, > 50 mm = 6.1% women-year) and in cases treated with limited surgery (limited surgery 4.6%, mastectomy 2.0% women-year). Distant metastases (16 cases) were less frequent in malignant cystosarcoma phyllodes or liposarcoma patients, but no other significant predictors of distant metastases were evidenced. Five-year disease-free or overall survival was 50% or 66%, respectively. The study confirms that breast sarcomas are rare, difficult to diagnose, but can be cured by surgical treatment in a considerable proportion of cases.

Efficacy of a hospital based cytology screening program.

From 1976 to 1986, a total of 117,471 women attending gynecologic outpatient departments of six hospitals in Delhi, India, were screened cytologically. The cytodiagnosis revealed 30,399 (25.9%) normal finding, 84,889 (72.3%) inflammatory changes, 1910 (1.6%) dysplasia of various grades and 213 (0.2%) malignant lesions. Of the 213 cases detected as malignant, clinical suspicion of cervical cancer was not present in 125 women (58.7%). Histologically malignancy was confirmed in 192 women (90.1%) of the 213 cytologically diagnosed malignant cases. The diagnosis revealed 94 (49.0%) as carcinoma in situ and the rest of the cases were invasive lesions. This was in contrast to only 5.2% (10/194) of cases with carcinoma in situ seen at the cancer clinic during 1983-1986 in one of the major collaborating hospitals of Delhi. The analysis of data according to age revealed that median age at detection of mild/moderate, severe dysplasia, carcinoma in situ (CIS) and invasive cancers was 34.0, 37.9, 38.6, and 47.8 years, respectively, indicating a latency period of one and a half decade from the onset of precursor lesions to invasive disease. Mass population screening in our country is not feasible in the near future and this may be true also for other developing countries. In its absence cytological screening of patients attending hospitals and maternity homes can give a large yield of early cervical cancers, which are curable.

Epidermal growth factor (EGF) in serum of patients with differentiated carcinoma of thyroids.

Serum levels of epidermal growth factor (EGF) were investigated in 31 patients with differentiated carcinoma of thyroid. Patients with carcinoma had significantly decreased basal levels of serum EGF, however this decrease in serum EGF occurred only in the group of patients which had been evaluated at an interval of six weeks after ablation of residues of normal thyroid with radioiodine. In patients that had been treated with radioiodine for cancer this decrease was not observed. The change in serum EGF was not dependent on thyroidal function and did not correlate with the serum thyreoglobulin level. It is presumed that decreased serum EGF is a consequence of functional changes of platelets after whole body irradiation at ablative dose of radioiodine.

Tumoricidal properties of rat peritoneal macrophages activated with various activators depend on nitrogen oxid synthesis.

Cytolytic activity of mineral oil elicited rat peritoneal macrophages activated by lipopolysaccharide (LPS) and/or rIFN-gamma, rIL-2, Zymosan and PMA (4-beta-phorbol-12-beta-myristate 13-alpha-acetate) was detected in the presence of various concentrations of L-arginine. This paralleled the NO2- production in the presence, but not in the absence, of L-arginine. Significant amount of NO2- was detected in the peritoneal macrophages cultured with 0.4 mmol of L-arginine 8 days and the last 24 h with LPS at a concentration of 1 microgram/ml. No significant differences were found between activated peritoneal macrophages obtained from normal (healthy) and/or from tumor bearing rats to induce tumoricidal activity and NO2- production under the same experimental conditions. The results showed that the major cytolytic mechanism against BP6-Tu2 and U 937 tumor cell lines is L-arginine-dependent nitrogen oxide synthesis of activated rat peritoneal macrophages.

Tumor necrosis factor as a potent effector molecule for tumor cell killing by activated rat peritoneal macrophages in vitro.

Tumor necrosis factor (TNF) sensitive (BP6-Tu2) and less or insensitive (B77, MC-1) target cell lines were used to examine the role of TNF in lytic phases of activated peritoneal macrophages and/or direct (murine)-TNF alpha cytolytic activity against these targets. Using antibody to murine TNF, it was shown that lysis of BP6-Tu2 cells was TNF-mediated. This macrophage lytic activity was markedly diminished or even abolished by anti-TNF alpha antiserum. Results indicated that TNF alpha is the critical effector of macrophage mediated killing of these targets. The tumoricidal activity and its level was dependent upon the length of cultivation of macrophages, induction period and concentration of activators. The findings not only support the thesis that macrophages possess various means of coping with tumor cells but also suggest that the mechanism becoming operative is determined predominantly by the pathway of macrophages activation and the properties of the tumor-cell type.

Monoclonal antibodies of IPO series against B cell differentiation antigens in leukemia and lymphoma immunophenotyping.

Monoclonal antibodies (mAbs) of IPO series were developed following immunization with human B cell lines RPMI-1788, Daudi, and spleen cells from a patient with hairy cell leukemia. Reactivity of these mAbs was studied on 19 human cell lines, mononuclear cells of 50 healthy persons and 142 patients with leukemias and lymphomas. It was shown that mAbs IPO-3, IPO-10 and IPO-24 define B cell-specific antigens expressed at different stages of maturation. MAb IPO-3 reacted with activated B lymphocytes. MAb IPO-10 defined the antigen which appears on B cell progenitors following HLA-DR and proceeding CD19, CD10, CD22, CD37; cy mu and CD20 and have been lost during terminal differentiation. The antigen detected by mAb IPO-24 was expressed throughout B cell ontogeny from pre-B cell until the B-blasts. MAb IPO-4 detected an antigen of activated T and B lymphocytes. These mAbs are useful tools in the leukemia and lymphoma phenotypic characterization and classification.

Myeloma cell resistance to melphalan, BCNU and epirubicin determined in vitro with the 3H-thymidine incorporation technique prior to chemotherapy.

Drug resistance of marrow plasma cells had been measured in vitro before chemotherapy was started. Resistance to melphalan was found in 20, to BCNU in 27 and to epirubicin in 38 out of 65 myelomas. Nineteen myelomas were resistant to a single cytostatic, 14 to two cytostatics and further 13 to all three. Patients with plasma cells resistant to melphalan in vitro failed to reduce 50% of monoclonal Ig plasma level after therapy along the VBMCP (M2) protocol, whereas sensitive myelomas responded to this program satisfactorily. Patients with cells resistant to two or three cytostatics, beside a bad therapeutic response, had also a shorter survival time. Results in vitro were in conformity with in vivo effects in 78%.

Antineoplastic activity of mitoxantrone and its biological interactions in parental and multidrug resistant subline of P388 murine leukemia cells.

The antitumor effects of mitoxantrone (MITO) and the various mechanisms involved therein were investigated in the adriamycin sensitive (P388/S) and resistant (P388/ADR) P388 leukemia cells. Utilizing the MTT (3-[4,5/dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, MITO concentration less than 100 ng elicited 50% inhibition of P388/S tumor cell survival, while a 10 times greater dose of MITO was required to inhibit the P388/ADR cell survival by 50%. A MITO dose dependent inhibition of DNA, RNA and protein biosynthesis was observed in the sensitive cells, while MITO elucidated a negligible effect on the macromolecular biosynthesis in the resistant tumor cells. Induction of DNA strand scission was observed in P388/S cells exposed to 0.1 and 1 microgram/ml MITO, while a minimal formation of DNA lesions was evident in the P388/ADR cells treated with 5 micrograms/ml MITO. These strand breaks were found to be not associated with proteins in either P388/S or P388/ADR cells. Generation of free radicals due to MITO and formation of alkylating metabolites of MITO were found to be not involved in the cytotoxic response of MITO against P388/S and P388/ADR cells. MITO did not affect the glutathione based detoxification mechanism of the sensitive and resistant tumor cells. Results indicate that in spite of reduced intracellular drug retention and induction of DNA strand breaks in P388/ADR cells other hitherto unknown mechanisms besides DNA binding might be involved in the antitumorigenic potential of MITO.

Combined chemotherapy (cisplatin, cyclophosphamide, lomustine and vincristine) and multifractionation radiotherapy in inoperable nonmetastatic squamous cell lung cancer.

A modified protocol was used in the treatment of inoperable nonmetastatic squamous cell lung cancer which consisted of three courses of induction chemotherapy with cisplatin, cyclophosphamide, lomustine and vincristine. Radiotherapy was delivered in multifractionated regime, daily two fractions of 1.5 Gy, 4 hours apart up to the total dose of 51 Gy. During 1985-1989, 77 patients were entered into the study. Twenty-six patients did not complete treatment, but were evaluated for the response rate and in survival analysis. There were 29 patients with Stage I and II, and 48 patients with Stage III lung cancer. After combined treatment CR was 15%, PR 39% and RR 54%. One- to four-year overall survival of 48 evaluable patients with Stage III were: 58%, 30%, 17% and 7%, respectively. The overall survival of the whole treatment group was significantly better than the survival of historical control group of 65 patients treated by radiotherapy only.

An immunoglobulin-like antigen in human cell lines and sera of cancer patients.

Different sera from cancer patients were tested for the presence of C1-GMA, an antigen described by us, which was shared by HeLa-like human cell lines and gastric mucosa. Using the immunodiffusion test, dot-blotting and electrophoresis followed by immunoblotting, we failed to reveal the antigen in the sera of patients. However, an Ig-like 56-60 kD antigen was found in the sera of patients with ovary and stomach carcinoma and lymphoid tumors. The Ig-like antigen was also revealed in 2 out of 5 tested human cell lines of non-leukocyte origin (HEp-2 and E16-B).

An inactive cathepsin B-like enzyme and cysteine proteinase inhibitors in colon cancer ascites.

The ascitic fluid of a patient with colon cancer was found to contain an inactive cathepsin B-like enzyme. The inactive enzyme with a molecular weight of 40 kDa was converted by pepsin treatment into an active form with a molecular weight of 28 kDa as revealed by Sephadex G-75 gel chromatography. The inactive cathepsin B-like enzyme was considered to represent a precursor form and not an enzyme-inhibitor complex. The activated cathepsin B-like enzyme resembled human liver cathepsin B in its enzymatic characteristics. Cysteine proteinase inhibitor activity was also detected in the same ascitic fluid, and it was separated into two main forms by Sephadex G-75 gel chromatography. The high molecular weight inhibitor fractions reacted with antiserum against alpha-CPI and the low molecular weight fractions reacted with antiserum against cystatin B.

Prognostic significance of testicular relapse in boys with acute lymphoblastic leukemia.

Among 107 boys with acute lymphoblastic leukemia who achieved initial complete remission after treatment according to two therapeutic protocols for standard and high risk leukemias, respectively, in 14 (13%) testicular leukemia was observed. Isolated testicular involvement was noted in 4, and combined with medullary relapse in 10 patients. The prognosis was worse in children with high risk leukemias (mainly in those with more than 20 x 10(9)/l white blood cells and/or with less than 50 x 10(9)/l platelets). Prognosis depended also on the type of relapse. It was better in isolated as well as in late testicular relapse. It was worse in combined relapses as well as in early testicular involvement. Bilateral wedge biopsy of the testes was performed in 16 boys at the end of chemotherapy and leukemic infiltration was shown in none of them. Two to 13 months thereafter, in four boys testicular relapse developed, and in 2 boys bone marrow relapse followed 9 and 13 months later. Wedge biopsy of the testes in boys with leukemia does not seem to be of importance neither for diagnosis of testicular relapse nor for improving prognosis.

Concomitant boost radiotherapy of supraglottic cancer--preliminary results, morbidity.

Forty-two patients with supraglottic squamous cell carcinoma were irradiated with Co60 using concomitant boost technique, a variant of accelerated fractionation. This technique is characterized by administering the boost as a second daily fraction during the basic wide-field irradiations. Daily dose in the first 4 weeks was 1.8 Gy and during the last 2 weeks it was 1.6 Gy twice daily with 4-6 hours separation. Total dose ranged from 60 to 76 Gy, median 66 Gy. The treatment time ranged from 36 to 56, median 42 days. Acute mucosal reactions were more severe than those of conventional irradiation but acceptable. The follow-up time ranged from 9 to 31 months, median 16 months. The actuarial 18 months survival for all patients was 75%. The actuarial 18 months control for primary site and lymph node was 75% for T1-2 stage, and 47% for T3-4 stage. Severe late complications were not observed so far.

Endocrine function in premenopausal and postmenopausal advanced breast cancer patients treated with CMF or tamoxifen.

The effect of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) or tamoxifen treatment on endocrine function was investigated in premenopausal and postmenopausal breast cancer patients. CMF therapy resulted in ovarian failure but pituitary and adrenal functions were unaffected in premenopausal patients. Although amenorrhea was achieved within two to five months in older patients, younger patients required large cumulative doses of cytotoxic drugs to exhibit ovarian dysfunction. CMF therapy had no effect on hormonal levels in postmenopausal patients indicating that in this group therapeutic response is not mediated via the endocrine system. On the other hand, tamoxifen therapy in postmenopausal patients resulted in hyperestrogenemia.

Dystrophy of the vulva locally treated with 13-cis retinoic acid.

Topical application of 13-cis retinoic acid resulted in complete disappearance of dystrophy of the vulva in 33 out of 53 patients, among them in 9 patients with recurrence after vulvectomy and in 14 patients with previous unsuccessful conservative treatment. Partial disappearance of dystrophy was seen in 15 patients, usually after 1 to 2 months of daily retinoid treatment. Side-effects of treatment (except for one) could be managed. Serum retinol level in patients was found to be lower as compared to that in healthy subjects. The results suggest that patients with chronic epithelial vulvar dystrophies could benefit from local retinol treatment, especially in cases with recurrence after vulvectomy and in cases with advanced dystrophies qualified until now for vulvectomy.

Fusion-induced malignancy? A preliminary study. (a challenge to today's common wisdom).

Five fusions between mouse embryonic cells and syngeneic adult peritoneal macrophages were performed. The resulting hybrids as well as both parental cells (6 cultures of embryonal cells and 6 cultures of adult macrophages) were grown in vitro under the same culture conditions. All populations of explanted macrophages died during the second month in primary culture and five populations of cultured embryonic cells were lost within six months under in vitro conditions as well. One embryonic cell line survived and acquired transformed and/or malignant phenotype: When inoculated into either newborn or adult syngeneic mice, progressive growth of tumors with 100% take (6/6), histologically classified as poorly differentiated fibrosarcoma with areas of metaplastic bone and osteoid, was observed. Two out of five wild hybrid strains died within six months of cell culture. The resulting three hybrid cultures adapted themselves to in vitro conditions and finally permanent lines were established with all features of transformed phenotype in vitro and with the capacity to grow as undifferentiated fibrosarcomas with 100% take (6/6) when inoculated into syngeneic mice either s.c. or i.p. Cytogenetic studies were performed and phenotypic characteristics of these lines were explored as well. Biological assays performed for the presence of oncogenic viruses were negative and none of the malignant cell lines showed positive staining with the monoclonal antibody specific for large T-antigen. It is suggested that cell fusion of two normal partners may switch on the cascade of abnormal processes which may culminate in neoplastic conversion. Cell fusion might play also a significant role in the so called "spontaneous" transformation.

Characteristics of retinoid-induced adhesion in a cultured human oral carcinoma cell line.

Cultured epidermoid oral carcinoma cells KB were easily detached from plastic surface in an ethylene diamine tetra acetic acid (EDTA) mediated detachment assay. Treatment of KB cells with retinol (vitamin A) or retinoic acid (RA) induced growth inhibition and caused reversible enhanced adhesion to the substratum in a similar fashion as well. Different synthetic retinoids were tested for their ability to induce growth inhibition and adhesion. A relationship between structure and activity of retinoids was found to exist. Possible mechanisms of retinoid-induced enhanced adhesion are discussed.

Alterations in the growth and cycling status of granulocyte-monocyte colony-forming units (CFU-GM) in rats injected single doses of aflatoxin B1.

To determine the toxic effect of aflatoxin B1 (AFB1) on granulopoiesis in vitro, cultures of myeloid progenitor cells for granulocytes and macrophages CFU-GM in semisolid agar medium were used to evaluate colony formation and tritiated thymidine suicide technique for analysis of cycling status of CFU-GM. Male Fischer rats, 5 to 6 weeks old, were given a single i.p. injection of 1 mg/kg or 0.1 mg/kg of AFB1 which were approximately 1/5 or 1/50, respectively, of LD50 dose of AFB1. The administration of either dose of AFB1 caused a significant reduction of the number of CFU-GM derived colonies on the first and the second day after injection. This reduction was followed by a strong enhancement in CFU-GM colony formation on the third day, and by restoration to the normal level on the fourth day. The increase in percentage of CFU-GM in S-phase preceded one day the peak in CFU-GM colony formation. The two different doses of AFB1 exerted similar effects on the growth and cycling status of CFU-GM. Our data outline an early suppressive effect exerted by AFB1 to the rat granulopoiesis in vivo.

Cytogenetic effect of 235U neutrons and d(50)+Be fast neutrons.

Induction of chromosome aberrations in G0 lymphocytes of peripheral human blood exposed to 235U and d(50)+Be neutron radiation was studied. Dose--effect relationships for different types of chromosome aberrations were analyzed. Linear dependence of the effect was established for the studied neutron radiation, except for the yield of dicentrics exposed to d(50)+Be neutrons. Accordingly to the yield of dicentrics, the relative biological efficiency (RBE) of 235U and d(50)+Be neutrons was 19.5 and 4.14, respectively.

Effect of cisplatin treatment of human monocyte cell line U937 on the induction of tumoricidal activity.

U937, a human monocyte-like, cell line was checked for cytotoxic activity against tumor target cells. Untreated U937 cells showed little cytotoxicity against tumor cells. Granulocyte-macrophage colony stimulating factor (GM-CSF) and LPS significantly activated the U937 cells to tumoricidal state. Treatment of U937 cells with cisplatin did not enhance the tumoricidal activity. Similarly, interferon gamma (IFN-Y) and macrophage colony stimulating factor (M-CSF) could also not activate either the tumoricidal activity of U937 cells. Pretreatment of U937 cells with GM-CSF for 24 h and then the treatment with cisplatin significantly augmented the tumoricidal activity as compared to that of GM-CSF alone.

Cell line specific abnormalities in expression of PNA, SBA and L-PHA binding sites by carcinogen induced rat urothelial carcinomas.

Bladder tumor cell lines derived from male F344 rats treated with N-buthyl N-(4-hydroxybuthyl) nitrosamine (BBN) or N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) have been established in vitro and characterized with respect to histology, karyotype, myc and c-Ha-ras oncogene expression or mutation, anchorage-independent growth and tumorigenicity in nude mice. This unique model system comprising 13 cell populations was employed to study common events during development of carcinogen-induced urothelial neoplasia. Differential expression of malignant phenotypes by these cell lines prompted us to examine their expression of carbohydrate structures binding peanut agglutinin (PNA), soy bean agglutinin (SBA) or leukoagglutinin (L-PHA), which are known indicators of tumor progression in rodents and humans. In the present study we analyzed the patterns of glycoproteins reactive with PNA and L-PHA by Western blotting. We also estimated quantitative differences in lectin binding to surfaces of normal rat urothelium and tumor cell lines by flow cytometry. The patterns of PNA or L-PHA reactive glycoproteins expressed by tumor cells were different from that of normal urothelium in culture. They were also different amongst the tumor cells. A unique non-sialylated, PNA binding glycoprotein (117 kD) was seen in the case of the highly tumorigenic F5 cell line and absent in normal urothelium as well as in other tumor cell lines. Normal cells did not express glycoprotein 60 kD binding PNA (only after desialylation), which was found in lysates of some but not all transformed cell lines. A very high molecular weight (much greater than 200), perhaps mucin-like sialoglycoprotein was found in normal urothelium but not in most of the tumor cell lines. Four major L-PHA reactive bands (greater than 200, 190, 100, 80 kD approximately) were found in normal urothelium. Some of those bands were overexpressed or missing in materials isolated from different tumor cell populations. Total cell surface binding of SBA and PNA by different tumor cell lines was very heterogenous (167-2% that of normal urothelium). No simple correlation between expression of the lectin binding glycoconjugates by urothelial carcinoma cells and other known functional, phenotypic or genetic alterations was found. We were also unable to demonstrate carcinogen-specific changes in expression of lectin binding to these tumor cell lines. Thus we conclude that lectin binding patterns are cell line specific. This may reflect distinct pathways of progression of individual cell lines. The potential sources of phenotypic variability between the cell lines were discussed.

Monoclonal antibodies distinguishing between two rat pancreatic carcinoma cell lines with different metastatic capacities.

Two new monoclonal antibodies, E5/E10 and E10/B4, were raised which reacted with surface antigens on the metastatic rat pancreatic adenocarcinoma cell line ASML, but not with antigens localized on the cell surface of the nonmetastatic rat pancreatic adenocarcinoma line AS. These two monoclonal antibodies are of the IgG1 subclass and recognize protein bands with molecular weight 28,000 and 35,000 D. E5/E10 and E10/B4 cross-reacted only with antigens on the human colon cancer cell line HT-29, as well as with normal rat kidney.

Effect of allogenic Dalton's lymphoma cells on the activation of murine peritoneal macrophages to tumoricidal state by cisplatin and lipopolysaccharide (LPS).

Murine peritoneal macrophages on treatment with cisplatin or LPS for 24 h showed enhanced tumoricidal activity. Co-incubation of macrophages with fresh allogeneic Dalton's lymphoma (DL) cells significantly inhibited the activation of macrophages to tumoricidal state by cisplatin or LPS. Incubation of macrophages with DL cell culture supernatants or paraformaldehyde (PFA) fixed DL cells also significantly down-regulated the activation of macrophages with cisplatin or LPS. On the other hand, preexposure of macrophages to DL cells for 24 h before activation with cisplatin and LPS enhanced the tumoricidal activity of murine peritoneal macrophages. These results may contribute to understanding the effect of tumor cells on macrophages.

Iron-tumor cell interaction and regulation of Ca2+ homeostasis: their implication in tumor growth.

Using [59Fe] ferric lactate, a direct relationship between iron concentration and [59Fe] uptake by Ehrlich ascites tumor cells was found. Deferoxamine and albumin inhibited this uptake. Electrophoresis showed that both molecules complexed iron from ferric lactate. [45Ca] uptake in the presence of ferric lactate showed the same inhibition, and an iron mass-dependence, these findings suggest an iron--cell membrane interaction as the cause of this phenomenon. The implication of iron--tumor cell membrane interaction in tumor growth regulation is discussed.

Alteration of brain catecholamines during growth of benzo(a)pyrene induced murine fibrosarcoma.

Brain catecholamines (CA) were studied in discrete brain areas of benzo(a)pyrene (b(a)p) induced fibrosarcoma bearing mice. Dopamine (DA) and norepinephrine (NE) levels decreased significantly in different brain areas especially in corpus striatum and hypothalamus with the tumor progression, indicating an inverse relationship between brain DA and NE levels and tumor growth. Since impaired hormonal and immunological functions are manifestation of systemic alteration during tumor growth, it appears that during malignant growth an alteration of these brain CA may play an important role in the regulation of systemic alterations.

Nuclear grading and prognosis in node negative breast cancer.

The authors evaluated retrospectively 287 node negative breast cancer patients treated solely with surgery and followed-up for at least five years. Cases were retrospectively classified according to nuclear grade. The prognostic value of T category and nuclear grade were compared at univariate and multivariate analysis. Five-year overall or relapse-free survival was dependent on T (T1 = 0.96 or 0.86, T2 = 0.88 or 0.76, T3 - 4 = 0.58 or 0.38, T2 - 4 = 0.86 or 0.72) and on nuclear grade (G1 = 0.94 or 0.82, G2 = 0.88 or 0.74, G3 = 0.80 or 0.72, G2 - 3 = 0.88 or 0.74). Nuclear grade was associated to T category, as low grading tumors were more frequent among T1 as compared to T2 - 4 cases (chi-square = .09, df = 2, p less than 0.05), but both nuclear grade (G2 - 3 vs. G1: relative risk = 1.89, p = 0.022) and T category (T2 - 4 vs. T1: relative risk = 2.23, p = 0.013) were independently and significantly associated to overall survival. Although their limited discriminating power does not justify their clinical use in selecting high risk node negative patients to adjuvant therapy, they should be used as prognostic factors as they are as efficient as other new indicators and by far cheaper and simpler to assess.

Lung cancer and smoking in Finland and the Czech Republic. Recent trends and predictions.

Trends of mortality from lung cancer in 1953-1989, age-specific lung cancer death rates of five-year birth cohorts, and the cigarette consumption were compared in Finland and the Czech Republic. While the lung cancer mortality and the smoking habits were fairly similar in Finland and the Czech Republic in the 1950s and early 1960s, contrasting differences gradually developed over the subsequent three decades in favor of Finland. In the year 1989, the Czech lung cancer death rates were much higher than the Finnish rates: in males 75.8 vs. 48.1 per 100,000; in females 9.3 vs. 6.6 per 100,000 (adjusted to the world standard population). Results obtained by descriptive epidemiologic methods support the opinion that a major part of the positive changes in the lung cancer epidemic in Finland can be explained as a consequence of the comprehensive smoking control program introduced in this country, including a significant decline in tar yield of cigarettes. In view of a long latency period between exposure and the development of disease, a continuing upward trend in lung cancer mortality is to be expected in the Czech Republic, particularly in females, resulting in an increase in the gap between Czech and Finnish lung cancer mortality. To achieve in future a falling trend in lung cancer rates even in the Czech Republic, amendments in the smoking control system according to the recommendations of the World Health Organization and International Union against Cancer are of importance.