Showing papers in "International Journal of Cancer in 1977"

Binding of soluble form of fibroblast surface protein, fibronectin, to collagen.

Abstract: Fibronectin, a plasma protein immunologically identical with a major surface protein of normal fibroblasts, was found to bind to collagen and gelatin. A solid phase enzyme immunoassay was used for the binding tests. Collagen, gelatin or various control proteins were adsorbed to a plastic surface. Binding of fibronectin was detected using purified fibronectin antibodies conjugated to alkaline phosphatase. Circulating fibronectin and fibronectin obtained from fibroblast cultures both showed specific binding to collagen and gelatin. Preparative affinity chromatography of plasma on gelatin coupled to Sepharose gave electrophoretically and immunologically pure fibronectin in high yields. Malignantly transformed fibroblasts lack surface fibronectin. Our findings suggest the possibility that this results in a lack of anchorage to the surrounding intercellular matrix, which could contribute to the malignant growth behavior.

Characterization of EBV‐genome negative “null” and “T” cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non‐Hodgkin lymphoma

Abstract: Sixty-two explants from peripheral blood, bone marrow and cerebral fluid of children with acute lymphoblastic leukemia (ALL) and leukemic transformed non-Hodgkin lymphoma (NHL) were cultivated for at least 8 weeks. Although lymphatic cells persisted up to 16 weeks in tissue culture, no proliferation was observed in 54 cultures. From the remaining cultures, eight permanently growing cell lines were obtained. Five of these were EBNA (Epstein-Barr virus-specific nuclear antigen)-positive. Three, however, were ENBA-negative and lacked Epstein-Barr virus genomes. Two cell lines (KM-3 and SH-2) expressed neither B nor T cell characteristics. One line (JM) expressed T cell characteristics and complement receptors. The growing lymphatic cells represented leukemic cells, since the pattern of cytochemical staining and that of membrane receptors of lymphoblasts from the same donor prior to cultivation were identical. All leukemic cell lines were derived from patients in relapse. In contrast, no proliferation of leukemic cells occurred in explains from patients revealing the first manifestation of the disease. These results suggest enhanced growth potential of lymphoblasts resisting antileukemic therapy.

Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France.

Abstract: A world-wide comparative study of the frequency and characteristics of latent carcinoma of the prostate was undertaken in seven areas, using standardized methods and "blind" microscopic evaluation in order to reduce selection and observer bias. The morphological features of 350 latent carcinomas found in 1,327 prostates were examined. Two Chinese populations, from Hong Kong and Singapore, showed a low frequency of latent carcinoma in comparison with western Europeans in Sweden and the Federal Republic of Germany and negroes from Jamaica; an intermediate position was found for Israelis and black Ugandans. The frequency of small latent carcinomas was about 12% in all the areas investigated and did not vary with age. Rates for larger latent carcinomas increased sharply with age ans showed an area-to-area variation resembling that of clinical carcinoma of prostate. The small carcinomas were almost exclusively situated in the outer half of the prostate and latent carcinomas of all sizes were evenly distributed between the anterior and posterior halves of the prostate and the right and left sides of the outer prostatic shell. Certain disagreements in diagnosis were noted when the sections from each area were evaluated independently by a different pathologist. Most of these disagreements were resolved by re-reading the sections; their occurrence had no significant effect on the geographical comparisons.

Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase.

Abstract: An undifferentiated human pancreatic carcinoma has been established in continuous culture and is grown in Dulbecco's modified. Eagle's medium fortified with 10% fetal calf serum and 2.5% horse serum. The established cell line (MIA PaCa-2) has a doubling time of 40 h. The cells are large with abundant cytoplasm, exhibit a high degree of aneuploidy and have a tendency to grow on top of other cells. MIA PaCa-2 grows in soft agar with a colony-forming efficiency of 19%. Both MIA PaCa-2 cells and a cell line from another pancreatic carcinoma obtained from National Cancer Institute (NCI) are sensitive to asparaginase, a property not shared by several other human tumor cell lines tested.

Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens.

Abstract: Cryopreserved primary cultures of golden Syrian hamster embryo cells were used as the source of target and feeder cells for establishing an in vitro carcinogenesis bioassay. The primary culture giving the best overall response in a pretest before freezing gave positive results in 20 consecutive experiments when retested with 3-methylcholanthrene after cryopreservation, indicating that pretested cryo-preserved cultures can serve as a source of susceptible target cells in an in vitro carcinogenesis bioassay. Similarly prepared and cryopreserved cultures served satisfactorily as feeder cells. Susceptible positive cultures were used to test a large number of carcinogenic and non-carcinogenic chemicals in this system. The results showed a very high positive correlation (90.8%) between morphological transformation and the reported carcinogenic activity of the chemicals. Transformation was not observed when cells were treated with a few carcinogens that may not be metabolized to their active forms by early passage hamster embryo cells. N-2-acetylaminofluorene transformed cells only when tested in the presence of hamster liver micro-somes. No false positive results were obtained when non-carcinogens were bioassayed, nor was spontaneous transformation observed in control cultures treated with medium alone, 0.2% dimethylsulfoxide or other solvents. Cultures derived from morphologically transformed colonies arising after treatment of cells with several known carcinogens were tumorigenic in vivo, confirming the correlation of morphological transformation with tumorigenicity and the validity of altered morphology as an in vitro criterion for carcinogenicity in vivo.

Establishment in continuous culture of a new type of lymphocyte from a “burkitt-like” malignant lymphoma (line d.g.-75)

Abstract: The isolation and establishment in vitro of a hitherto undescribed type of lymphocyte designated D.G.-75 is reported. The original inoculum was derived from the pleural effusion of a child with a primary abdominal lymphoma, which clinically and histologically resembled Burkitt's lymphoma. In addition to the absence of the EBV genome and EBV receptors, this line possesses a number of other properties which distinguish it from previously described lymphoblastoid cell lines. It has different growth characteristics and morphology; does not form EAC or E rosettes (representative of B and T) cell surface markers, respectively); possesses IgM-kappa immunoglobulins on the cell surface (B lymphocyte), has an unusually high cap-forming ability and low agglutinability with fluorescent concanavalin A. One homologue of the No.14 chromosome pair possesses extra chromatin material as revealed on chromosome banding. This abnormal chromosome marker is similar to that described in biopsies and cultured tumor cells from patients with African Burkitt's lymphoma.

Augmentation of natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic target cells.

Abstract: The levels of natural cell-mediated cytotoxicity against tumor cells in young BALB/c and BALB/c nude mice could be augmented by inoculation of a variety of mouse tumor cells or of mouse thymocytes. In older mice with low levels of spontaneous cytotoxic reactivity, inoculation of tumor cells led to rapid appearance of cytotoxicity. This augmented cytotoxicity reached a peak 3 days after inoculation, and then declined rapidly. The specificity of the augmented cytotoxicity appeared to be the same as that seen with natural cell-mediated cytotoxicity. The detected antigens were restricted to mouse tumor cells and thymocytes, and were absent on cells from other species. The effector cells after boosting also had the same cell surface characteristics as the natural cytotoxic effector cells, being non-adherent, non-phagocytic, and only weakly sensitive to treatment with anti-theta serum plus complement. In addition to this boosting by mouse tumor cells, marked increases in the levels of cytotoxicity were caused by a variety of murine viruses, including murine sarcoma virus and lymphocytic choriomeningitis virus. These effector cells also had the same properties as those seen with natural cytotoxic effector cells. The results indicate that the levels of natural cell-mediated cytotoxicity in conventional and athymic BALB/c mice can be consistently and rapidly boosted by inoculation with tumor cells or viruses. This should provide a valuable tool for better understanding of the mechanisms responsible for the expression of natural cytotoxicity and its relevance to in vivo resistance to tumor growth.

Risk factors for lung cancer in Singapore Chinese, a population with high female incidence rates.

Abstract: The high incidence of lung cancer in Chinese females in Singapore, especially among those belonging to the Cantonese dialect group, and the relatively high rates in Chinese males have been studied by means of interviews of cases and controls. A significant dose-response effect of cigarette smoking was found for all male and female groups, but neither smoking nor any other exposure explains the high incidence of lung cancer observed in Cantonese females who exhibit high rates of adenocarcinoma appraently unrelated to smoking. In general, persons with a low consumption of green vegetables were at higher risk for lung cancer. This finding might be due to an increased susceptibility in the presence of a relative deficiency of vitamin A.

Tumorigenicity of human hematopoietic cell lines in athymic nude mice

Abstract: Human hematopoietic cell lines, which had been classified on the basis of studies on clonality, and morphological, chromosomal and functional parameters as lymphoblastoid cell lines (LCL) of presumed non-neoplastic origin, and lymphoma, myeloma and leukemia lines of proven malignant origin, were tested for tumorigenic potential on subcutaneous transplantation to nude mice and for capacity to grow in semi-solid medium in vitro. Recently established LCL failed to grow both in nude mice and in agarose. In contrast, some of the LCL which had developed secondary chromosomal alterations during continuous cultivation for periods exceeding several years were tumorigenic and/or had the capacity to form colonies in agarose. Most lymphoma lines formed colonies in agarose and tumors in the mice. One of the two myeloma lines formed subcutaneous tumor which, however, showed no progressive growth. The other myeloma line failed to grow. Both myeloma lines, however, formed colonies in agarose. The myeloid leukemia line was tumorigenic while two of the three tested lymphocytic leukemia lines failed to grow in the mice. All leukemia lines formed colonies in agarose. We conclude from this study that: (1) Of the two types of Epstein-Barr virus containing cell lines [LCL and Burkitt lymphoma (BL) lines], only BL lines were shown to form tumors when inoculated subcutaneously in nude mice and had the capacity to grow in agarose in vitro. This shows that EBV transformation per se does not necessarily render lymphocytes tumorigenic in nude mice. The capacity to form colonies in agarose is not acquired either. (2) Changes of the karyotype and several phenotypic characteristics which occur in the originally diploid LCL during prolonged cultivation in vitro may be accompanied by the acquisition of the potential to grow subcutaneously in nude mice and in agarose in vitro. (3) The inconsistency with regard to the capacity of come of the neoplastic cell lines to grow in nude mice or in agarose seems to underline that neither of the two tests is a reliable criterion for malignancy of human lymphoma, leukemia and myeloma cell lines.

"Sternberg-reed" giant cells of Hodgkin's Disease: cultivation in vitro, heterotransplantation, and characterization as neoplastic macrophages.

Abstract: Cells from the involved spleens of 25 patients with Hodgkin's disease have been grown in long-term culture and compared with normal spleen macrophage cultures from control cases. The Hodgkin's spleen cell culture contained mono-, bi-, and multi-nucleate giant cells, many closely resembling Sternberg-Reed cells, which were adherent, phagocytically active and neoplastic by the dual criteria of aneuploidy and heterotransplantability. Lysozyme secretion was consistently observed in all Hodgkin's cultures tested. The giant cells possessed both Fc and complement (c3b) receptors, and lacked lymphocyte markers such as (c3b) receptors, surface IgM, and the capacity to form E-rosettes. Binucleate and multinucleate cells, as well as mononuclears, were capable of active DNA synthesis, and binuclear mitotic figures were observed. It is concluded that these cells are the in vitro descendants of the Sternberg-Reed and Hodgkin neoplastic cell population, and that they are derived from macrophages or closely related cells of the mononuclear phagocyte system.

Establishment of a human medulloblastoma cell line.

Abstract: A cell line consisting of polygonal and fusiform cells was derived from a cerebellar medulloblastoma. Cells grew to high population density in liquid medium and formed colonies in agar medium. No neural or glial elements could be demonstrated in the cultured cells by electron microscopy nor were virus particles detected. The cells formed tumors in nude mice and in antithymocytic serum (ATS)-treated hamsters. The tumors had a microscopic appearance similar to that of the medulloblastoma from which the cell line was derived. The cell line and lines derived from the transplant tumors in two hosts had four common "marker" chromosomes as well as non-specific cytogenetic changes.

Natural cell-mediated cytotoxicity in mice against non-lymphoid tumor cells and some normal cells

Abstract: Lymphocytes from normal mice were found to have cell-mediated cytotoxicity, in a short-term 51Cr release assay, against a variety of non-lymphoid tumor cells as well as against lymphomas. Some of the non-lymphoid tumors were as susceptible to natural cytotoxicity as the standardly used lymphoid lines. Some tissue culture cell lines and in vivo passaged tumor lines were susceptible to lysis, as were some primary virus-induced lymphomas. Tumor which arose in nude mice, which have high levels of natural cytotoxic activity, were all resistant to lysis. In addition to the susceptibility of transformed cells to natural cell-mediated cytotoxicity, some untransformed cultured cells and cells from normal tissues were targets for this mechanism. Low levels of cytotoxicity were seen with normal thymus cells, bone-marrow cells, and short term cultures of macrophages, whereas normal spleen and lymph-node cells were completely resistant to lysis. These results indicate a broader spectrum for mouse natural cell-mediated cytotoxicity reactivity than has been previously recognized.

Asbestos and lung cancer: An analysis of the epidemiological evidence on the asbestos—smoking interaction

Abstract: Three simple models for the asbestos-smoking interaction on human lung cancer production are considered. In the first model the excess incidence of lung cancer independently due to asbestos and to smoking adds together when both agents are present (additive model). In the second the addition of each one of the two agents produces an effect (increase in lung cancer incidence) which is proportional to the effect of the other (multiplicative model). In the third, asbestos can only increase lung cancer incidence in the presence of smoking. As previously found by other investigators, the additive model appears the least plausible in the light of the data from two published epidemiological studies. A discrimination between the other two models is attempted through a detailed analysis of the five published epidemiological studies today available which provide information on occupational asbestos exposure, smoking habits and lung cancer risk. Although the data do not allow a definitive discrimination, the multiplicative model appears to be more plausible, being also consistent with a multi-stage carcinogenic mechanism and with evidence from animal (rat) experiments. It is relevant both for biology and for public health that in this model asbestos and smoking are regarded as independently capable of producing lung cancer in humans and that they act synergistically when exposure to both occurs.

Epidemiology of hodgkin's disease in the young.

Abstract: Many features of Hodgkin's disease (HD) among adolescents and young adults suggest that it has an infectious etiology However, the proposal that HD is a contagious disease which can be transmitted by patients or their close contacts has not been substantiated An alternative infectious disease model is suggested by analogy with paralytic poliomyelitis (PP) For both diseases, the peak age of incidence is delayed as living conditions improve For both, increased risk is associated with higher social class and small family size Like PP, HD may be a rare manifestation of a common infection with the probability of disease development increasing as age at infection is delayed This analogy is supported by the report that the risk of HD is higher for persons who had a low frequency of childhood infectious diseases If this model is valid, HD patients represent no hazard to their contacts However, the incidence of HD among young adults may increase in the coming decade because of the current high standard of living and small family size

Relationship between the Epstein-Barr virus and undifferentiated nasopharyngeal carcinoma: correlated nucleic acid hybridization and histopathological examination.

Abstract: In order to examine critically the closeness of association between Epstein-Barr virus (EBV) DNA and nasopharyngeal carcinoma (NPC) a correlated histopathological and nucleic acid hybridization study was performed on 51 undifferentiated NPC, 4 NPC with some signs of squamous differentiation, 7 nasophayngeal tumors of other histological types and 14 head and neck carcinomas located outside the nasopharynx. All 51 undifferentiated NPCs contained significant numbers of EBV-genome copies per cell. Two of the somewhat differentiated NPCs were also EBV-DNA-positive, whereas 2 were negative. Of the 7 other nasopharyngeal tumors, 1 was EBV-DNA-positive. Histological examination, however, showed that this was a typical Burkitt lymphoma. The other 6 tumors were all EBV-DNA-negative lymphoproliferative malignancies. All 14 had head and neck carcinomas located outside the nasopharynx were EBV-DNA-negative. The sera of undifferentiated NPC patients had elevated antibody titers against the EBV-determined antigens, the EA (D) componet in particular. These findings confirm that there is a regular association between EBV-DNA and undifferentiated NPC.

Depressed in vitro peripheral blood lymphocyte response to mitogens in cancer patients: the role of suppressor cells.

Abstract: The reactivity of peripheral blood lymphocytes from patients with advanced malignancy was assessed by mitogen-induced stimulation of protein synthesis as measured by 3H-leucine incorporation. It was confirmed that the lymphocyte response of patients was depressed. Furthermore, the lymphocytes of 15 out of 27 cancer patients, selected because of their low responses, inhibited the reactivity of normal lymphocytes in co-cultures. The lymphocytes from one patient with Hodgkin's disease were also inhibitory. In contrast, lymphocytes from healthy subjects, patients with chronic lymphocytic leukaemia, lymphosarcoma or multiple myeloma caused no suppression. Experiments with purified cell populations from patients with carcinoma indicated that purified T cells responded to mitogens while unseparated lymphocytes failed to respond and that the inhibitory activity was due to adherent cells, presumably monocytes. There was no evidence for B-cell-mediated suppression. However, in two cases inhibition was caused by isolated T cells of the patients and not by adherent cells. These experiments suggested that one mechanism for the depression of cell-mediated immunity seen in patients with advanced cancer may be the nonspecific suppresssion of certain T-cell functions by circulating monocytes.

Further evidence for a non-random chromosomal abnormality in acute promyelocytic leukemia

Abstract: We have previously reported on two patients with acute promyelocytic leukemia (APL) who had what appeared to be a deletion of chromosome No. 17. We now describe a third patient with APL. All three patients had a structural rearrangement involving No. 15 and No. 17. Our current interpretation of the chromosomal abnormality is that it is a reciprocal translocation, t (15; 17) (q22; q21). Evidence that this is a consistent rearrangement associated with APL comes not only from our three patients, but also from two other published cases of APL, studied with banding, who also had an identical abnormality.

Nasopharyngeal carcinoma: Significance of changes in epstein-barr virus-related antibody patterns following therapy

Abstract: Sera were collected at intervals of 3 to 8 months over a 4- to 5-year period from more than 103 patients with nasopharyngeal carcinomas (NPC) and examined for their spectra and titers of antibodies to Epstein-Barr virus (EBV)-related antigens. They were titrated for IgG, IgA and IgM antibodies to EB viral capsid antigen (VCA), for IgG and IgA antibodies to the D (diffuse) and R (restricted) components of the EBV-determined early antigen (EA) complex, and for antibodies to the EBV-associated nuclear antigen (EBNA). In the as yet untreated patients the incidences and titers of most of the antibodies increased with the stage of the disease; i.e., essentially with the total tumor burden. Such increases were observed in individual patients whose disease ultimately progressed to death, at times well in advance of the recognition of relapses or metastases. Increases were not noted or were only minor and delayed in some fatal cases if the tumor extended to the cranial cavity in the absence of significant involvement of cervical lymph nodes. In contrast, patients who responded well to therapy and remained clinically free of disease during the 4- or 5-year observation period after, at most, early minor relapses, showed gradual, steady declines in the titers of all antibodies except anti-EBNA. Thus, VCA-specific IgA and D-specific IgA and IgG became undetectable in time in many of the patients. In several long-term survivors the declines were arrested at given levels or a reversal to increasing titers was noted which was followed in time by detection of a recurrent tumor or metastases in some cases, but not in others who remain under close observation. It would appear that serologic monitoring of NPC patients may warn of recurrent tumor activity well before it becomes clinically evident.

Chromosome 14 translocation in african and north american burkitt's lymphoma

Abstract: Two established North American Burkitt lymphoma cell lines were studied by chromosomal banding techniques. The SU-AmB-1 line previously shown to be negative for the Epstein-Barr virus (EBV) was found to have, among other changes, a translocation from the long arm (q) of chromosome 8 onto 14q. The SU-AmB-2 line, which contains the EBV genome, also displayed the same 8/14 translocation. These results were compared with data from three EBV-positive tumor cell lines derived from patients with African Burkitt's lymphoma. Our findings indicate that a translocation from 8q onto 14q occurs in both African and North American Burkitt lymphomas, and that this abnormality apparently is not related directly to EBV. This chromosome translocation therefore may be an important event in the development of human lymphocytic malignancy, analogous to the occurrence of the Philadelphia chromosome rearrangement in chronic myelogenous leukemia.

Long-term administration of ddt or phenobarbital-na in wistar rats

Abstract: In lifespan studies, outbred male and female Wistar rats were given either technical DDT mixed into the diet at a dose of 500 parts per million (ppm) or phenobarbital-sodium dissolved in drinking water at a dose of 500 ppm. Liver-cell tumors developed in treated animals but not in controls. The incidence of liver tumors was 45% in the DDT-treated group and 44% in the phenobarbital-sodium-group. When evaluated by sex, DDT-treated females and males had incidences of 56% and 35%, respectively, while in the phenobarbital-sodium group, the respective incidences were 32% and 59% in females and males. These data show a varying susceptibility between the sexes, with regard to induction of liver-cell tumors by the two compounds. In both treated groups, the number of nodular tumors per rat and the average size increased with age and were greater in females. None of these tumors and metastasized. Histologically, the liver tumors were nodular growths, which compressed surrounding parenchyma did not infiltrate it. The total incidence of extrahepatic tumors was higher in controls than in treated animals. In this connection, we must mention the apparent, but not significant, reduction of adrenal tumors in treated rats compared to the controls.

Growth requirements of human mammary epithelial cells in culture

Abstract: Colony-forming epithelial cells can be separated from the non-dividing "foam cells" in human milk by differential adhesion to glass and freezing. The growth of such partially purified mammary epithelial cells is stimulated by co-culture with non-dividing feeder cells. Foam cells, mitomycin-treated mouse fibroblast lines and human mammary fibroblasts and calf lens epithelial cells are all effective in promoting mammary epithelial cell growth. Contact between epithelial cells and feeders is not required for the growth-promoting effect. The mitogenic effect of epidermal growth factor on mammary epithelial cells also requires feeder cell activity.

Human tumour—lymphocyte interaction in vitro. V. Comparison of the reactivity of tumour‐infiltrating, blood and lymph‐node lymphocytes with autologous tumour cells

Abstract: Lymphocytes prepared from the blood, tumour-draining lymph node and tumour were tested for immune reactivity with freshly isolated autologous tumour cells from biopsies. Reactivity was assessed by the autologous tumour stimulation assay and by lymphocytotoxicity. Activity was found in 6/11 blood preparations, 7/10 lymph nodes and 1/7 tumour-infiltrating lymphocytes in tumour stimulation assays and in 6/19 blood, 8/18 lymph-node and 5/20 tumour-infiltrating lymphocytes in cytotoxicity assays. Tests with material from patients with nasopharyngeal carcinoma showed a higher frequency of cytotoxicity in the tumour-infiltrating lymphocytes than in other solid tumours. There was a correlation between results of the two assays when performed on the same preparations and between the levels of reactivity in lymph node and blood from the same patient. Cytotoxicity in the lymph nodes showed specificity in that cells from a long-term culture (K562) known to be sensitive to natural killer activity and from allogeneic tumour biopsies were only rarely damaged. Cytotoxicity against K562 was more frequently determined in blood lymphocytes. Tumour-infiltrating lymphocytes were non-reactive in patients when the blood and lymph-node lymphocytes were active.

Fibrinolysis associated with human neoplasia: production of plasminogen activator by human tumours.

Abstract: The plasminogen-dependent fibrinolytic activity of several human tumours has been studied. The following neoplastic tissues, which were obtained from cancer patients by either surgery or biopsies, were examined: cervical, mammary, prostatic, ovarian, lung carcinomas, melanoma, basalioma. Fibrinolysis was measured in lysates either of tumour tissue specimens or of respective cell cultures. This measurement was based on release of radioactivity from 125I-fibrin-coated Petri dishes. All examined tumours showed elevated levels of plasminogen-dependent fibrinolytic activity. However, normal control tissues had little or no activity. These results indicate that the fibrinolysis might be useful in differentiating between malignant and normal tissues.

Effect of human leukocyte interferon on the growth of human osteosarcoma cells in tissue culture.

Abstract: Nine osteosarcoma cell lines, originally developed from six osteosarcoma tumours in five patients, and two cell lines of non-tumour origin (glia and fibro-blast) were grown in vitro in the presence of human leukocyte interferon (L-IF). L-IF exerted a dose-dependent inhibition of growth in all these lines. The inhibitory activity displayed characteristics typical of interferons. Inhibition of cell growth occurred at a much lower L-IF concentration for the osteosarcoma than for the non-tumour-derived lines. Inhibition of tumour cell growth was observed at concentrations obtained in the serum of osteosarcoma patients treated with interferon.

Lymphocyte cytotoxicity against autologous tumour biopsy cells in humans.

Abstract: By the application of separation techniques in a stepwise manner to mechanically prepared cell suspensions from human tumour biopsies it has been possible to isolate tumour cells having high viability and low contamination with host cells. These tumour cells have been used as targets in 51Cr release cytotoxicity assays using autologous lymphocytes from blood or lymph node as effectors. It has been possible to investigate this reactivity in 30 patients with malignant and four patients with benign tumours. Significant autologous cytotoxicity in the blood lymphocytes was detectable in two of 12 lung tumours, nine of 18 other carcinomas and sarcomas but in none of the benign cases. Cytotoxicity was not limited by the presence of obvious residual disease at the time of operation although reactivity was less frequently detectable in patients with secondary involvement. Reactivity in the tumour-draining lymph nodes largely paralleled that in the blood in the limited number of patients examined. The technical problems encountered during this study and the role of natural cytotoxicity in the interpretation of these data are discussed.

Association of human hepatocellular carcinoma and cirrhosis with hepatitis B virus surface and core antigens in the liver.

Abstract: Paraffin sections of livers obtained at autopsy from 50 cases of hepatocellular carcinoma (HCC), 58 cases of cirrhosis and 54 cases of other miscellaneous liver disorders (controls) were stained for both surface (HBsAg) and core (HBcAg) components of hepatitis B virus (HBV) by immunoperoxidase and immunofluorescence techniques and rigidly controlled for antigen specificity, and in addition stained by orcein for HBsAg. The material was collected from different regions of India and adequate amounts of tissue were examined in most specimens to overcome possible sampling error caused by random distributions of the antigens in liver. HBsAg was detected in 94% of HCC, 71% of cirrhosis and only 2% of control livers, while HBcAg was found in 22%, 31% and none respectively. Antigen positivity seems to be directly related to the amount of tissue examined. Peroxidase staining detected smaller amounts of HBcAg than fluorescence and was also much more convenient for identifying the antigen. Both antigens were present in 9 of 41 HCC cases, 12 of 39 cirrhosis and none of 25 controls. Most of these livers contained 1+ HBsAg and 1+ to 2+ HBcAg, an antigen expression pattern suggestive of a carrier state or, rarely, of mild chronic liver disease. Among all livers tested, HBsAg alone was present in 48, both antigens were found in 21, and HBcAg alone in none. HBsAg was seen inside tumour cells in four cases, but no tumour showed HBcAg. Most HCC was associated with cirrhosis (92%) and antigen-positive cirrhosis had a higher chance of harbouring HCC than antigen-negative disease. HBsAg was detected in all four non-cirrhotic livers associated with HCC, while two of these also had HBcAg. Active cirrhosis was very frequently associated with HBsAg. These results and the overwhelming evidence of sero-logical and epidemiological studies from various parts of the world suggest a strong association of the hepatitis B virus with HCC. The possible ways in which the two could be related are discussed.

Incidence of malignant melanoma of the skin in the five Nordic countries: significance of solar radiation.

Abstract: The incidence of malignant melanoma of the skin has increased rapidly among white people during the last decades. Excellent possibilities for detailed epidemiological analysis of malignant melanoma are provided in the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden), where the five national cancer registries were established during the period 1942–1958. Their materials are based on reports from hospitals and histopathological laboratories and death certificates. The organization of the registries is largely similar, and efforts have been made to bring the materials into conformity. More than 14,000 cases are included in the analysis, which covers the period 1953–1972 in Denmark, Finland and Norway, 1955–1974 in Iceland and 1959–1971 in Sweden. The tumors have been grouped by anatomical site as follows: face, neck/trunk, upper limb, lower limb, and other and unspecified sites. The incidence of malignant melanoma is similar in Denmark, Norway and Sweden. Lower incidence rates are observed in Finland and Iceland. Time trends in incidence are remarkable and clearly statistically significant, except for Iceland where the number of cases was very small. The period for doubling the incidence rate ranged from 10 to 17 years. Striking contrasts by sex are observed when the material is grouped according to primary site. There is a male preponderance for incidence on the neck/trunk and the reverse is found for the lower limbs. There is only a slight increase in incidence of malignant melanoma of the face, whereas for the neck/trunk, particularly among males, and for the lower limbs, particularly among females, there is a consistent upward trend. A difference between the face, on the one hand, and the neck/trunk and lower limbs on the other, is also disclosed in the curves showing the age-specific incidence rates. In conclusion, the results indicate that there is a marked real increase in incidence of malignant melanoma of the skin in all the Nordic countries. This increase is in accordance with the hypothesis of the association between solar radiation and risk of cutaneous melanoma, and could possibly be ascribed to changes in habits of leisure and clothing. It ought to be possible to introduce control measures against malignant melanoma which is becoming a serious cancer problem. This is a challenge for future preventive medicine.

Geographic correlation between the occurrence of endemic nephropathy and urinary tract tumours in vratza district, Bulgaria

Abstract: Data on the occurrence of endemic nephropathy (EN) and urinary tract and other cancers in an endemic region of Vratza district, Bulgaria, for the years 1965-1974, are presented. In endemic villages a high incidence of urinary tract tumours, affecting in particular the renal pelvis and ureter, closely correlated with the EN incidence and mortality rates. In the villages with high and moderate EN incidences urinary tract tumours are the most common neoplasms. They account for 25% of all tumour sites in males and 30% in females. In hyperendemic villages age-adjusted incidences in EN and urinary tract tumours were 506/10(5) and 104/10(5) in females, and 315/10(5) and 89/10(5) in males respectively. EN mortality in these villages accounted for over 40% of all deaths in females and about 30% in males. Both diseases displayed peculiar geographic clustering. Females and middle-aged persons were most often affected. Urinary tract neoplasms were often multiple and nearly 90% of them originated in the uro-epithelium. In endemic and non-endemic villages of the region studied, the frequency and pattern of non-urinary tract cancers were rather similar, with statistical values close to those of the rural population of Vratza District and Bulgaria as a whole.

Inhibition of the growth of lymphoid tumours in syngeneic athymic (nude) mice

Abstract: A comparison of the growth of a number of BALB/c tumours in BALB/c, BALB/c.nu/ + (heterozygous nude) and BALB/c.nu (homozygous) nude mice has shown that a majority of BALB/c lymphoid tumours grow at a significantly reduced rate in BALB/c.nu mice. The three non-lymphoid BALB/c tumours (carcinomas and sarcomas) tested and a minority of lymphoid tumours, however, grew as well, or better, in the BALB/c.nu mice. Furthermore a correlation, without exception to date, has emerged from a comparison between the susceptibility of a tumour cell line to in vitro lysis by spleen cells from syngeneic nude mice and its growth in vivo in syngeneic nude mice. Only those lymphoid tumour cell lines lysed in vitro show the reduced growth rate in syngeneic nude as compared to syngeneic normal mice. Tumour cell lines, both lymphoid and non-lymphoid, which are resistant to in vitro lysis do not show the reduced in vivo growth rate in syngeneic nude mice. Both the in vivo and in vitro effect can be partially abolished by irradiating the nude mice prior to use, suggesting that a radiation-sensitive non-T-cell surveillance of lymphoid tumours is operating in nude mice. While the identity of the antigens is still unknown, the specificity of the phenomena suggest that C-type RNA oncogenic viral determined antigens are involved.