Showing papers in "International Journal of Cancer in 1979"
TL;DR: The K562 cell expressed the major red cell sialoglycoprotein, glycophorin, on its surface as shown by immuno‐fluorescence and by immuneprecipitation from labelled membrane preparations, and it is concluded that the K562 is a human erythroleukemic line.
Abstract: We have studied the surface membrane properties of the human leukemic cell line K562 which previously has been reported to represent an early stage of granulocyte maturation. The surface glycoprotein pattern of the K562 cells obtained after galactose oxidase-NaB[3H]4 labelling and slab gel electrophoresis shows striking similarities with that of normal erythrocytes but is completely different from the patterns of normal and malignant cells of various stages of the myeloblast to granulocyte differentiation. Moreover, the K562 cell expressed the major red cell sialoglycoprotein, glycophorin, on its surface as shown by immunofluorescence and by immunoprecipitation from labelled membrane preparations. As glycophorin is exclusively found on erythroid cells in human bone marrow we conclude that the K562 is a human erythroleukemic line.
452 citations
TL;DR: An individually matched case‐control study of testis cancer in 131 men under age 40 was counducted to investigate antecedent risk factors including events during prenatal life, and a hypothesis linking these three factors is presented.
Abstract: An individual matched case-control study of testis cancer in 131 men under age 40 was conducted to investigate antecedent risk factors including events during prenatal life. Ten patients were born with an undescended testis compared to only two controls (p less equal to 0.02), a previously reported risk factor. Two new risk factors were uncovered: six patients-mothers received hormones during the index pregnancy compared to only one control-mother, and eight patient-mothers and two control-mothers reported excessive nausea as a complication of the index pregnancy. A hypothesis linking these three factors is presented: viz, that a major risk factor for testis cancer is a relative excess of certain hormones (in particular estrogen) at the time of differentiation of the testes.
353 citations
TL;DR: The results indicate that the NK activity of blood leukocytes from both normal subjects and melanoma patients who smoked was significantly lower against cultured melanoma cells than that of non‐smokers.
Abstract: Previous studies have shown that smoking is associated with a high incidence of certain malignancies and a high incidence of metastatic spread of melanoma. The purpose of the present study was to examine whether this high incidence of malignancy could be associated with certain aspects of immune function believed to be important in restricting tumour growth. Age-and sex-matched smoking and non-smoking normal subjects and male, smoking and non-smoking melanoma patients, were studied for the natural killing (NK) activity of their blood leukocytes against cultured melanoma and Chang cells. The levels of the various immunoglobulin classes in their sera and the E rosette levels of the normal subjects were also assessed. The results indicate that the NK activity of blood leukocytes from both normal subjects and melanoma patients who smoked was significantly lower against cultured melanoma cells than that of non-smokers. Smokers were also shown to have lower IgG and IgA Immunoglobulin levels in their sera compared to non-smokers but no differences in the percentage of E-rosetting (T) cells was detected. Recent studies provide some basis for the belief that the low NK activity and immunoglobulin levels in smokers may be related. These results further suggest that a closer examination of the effects of this environmental hazard on the immune system and its relation to malignancy is needed.
272 citations
TL;DR: On the basis of the clgM staining, NALM‐6‐M1 seems to be arrested at an early stage in B‐cell development and is considered to be of the pre‐B cell phenotype possessing a chromosomal abnormality.
Abstract: NALM-6-M1, one of eight leukemia cell lines cultured from the blood of a 19-year-old boy with non-T, non-B acute lymphoblastic leukemia (ALL) in relapse, was characterized. This cell line was found to be more than 90% cytoplasmic Immuno-globulin positive (clg+) for both mu heavy and lambda light chains, but surface immunoglobulln (slg) and complement receptor (CR) negative. NALM-6-M1 was clg∼ for alpha, delta, and gamma heavy chains and kappa light chain. About 45% of the cells exhibited sheep erythrocyte receptors. Approximately 12% of cells were positive for Fc receptors. Approximately 90% of the cultured cells had a deleted long arm of chromosome 5 (5q−) and a marker Y chromosome. The remaining 10% of cells were found to have some additional chromosomal material on the long arm of chromosome 12, suggesting a partial translocation. No other karyotypic abnormalities were found. The cell line was found to react strongly with anti-p23, 30, suggesting la-like activity, but it only weakly stimulated normal lymphocytes in mixed leukocyte culture (MLC). The cells expressed HLA antigens. NALM-6-M1 failed to react with anti-thymocyte serum (ATS), did not possess Epstein-Barr membrane or nuclear antigens, nor did it exhibit phagocytosis for zymosan. NALM-6-M1 reacted positively with oil red O and Sudan black stains. On the basis of the clgM staining, NALM-6-M1 seems to be arrested at an early stage in B-cell development and is considered to be of the pre-B cell phenotype possessing a chromosomal abnormality.
245 citations
TL;DR: These studies demonstrate that a soluble glucan preparation exhibits significant anti‐tumor and anti‐staphylococcal activity and may be preferable to particulate glucan in view of the inherent ease of parenteral administration.
Abstract: A soluble fraction of particulate glucan was prepared and evaluated for its anti-tumor and anti-bacterial activity. Thin-layer chromatographic analysis indicated that the soluble preparation was composed of a variety of polyglucoses. Intravenous administration of soluble or particulate glucan resulted in significant reductions in the growth of a syngeneic anaplastic mammary carcinoma and melanoma B16. Survival data demonstrated that intravenous administration of soluble or particulate glucan prolonged survival of A/J and C57BL/6J mice with subcutaneous tumor implants. As regards to bacterial infections, soluble and particulate glucan decreased renal necrosis in S. aureus challenged mice as compared to control mice. Although the exact nature of the active soluble fraction(s) of glucan remains to be delineated, these studies demonstrate that a soluble glucan preparation exhibits significant anti-tumor and anti-staphylococcal activity. The active soluble fraction of particulate glucan may be preferable to particulate glucan in view of the inherent ease of parenteral administration.
196 citations
TL;DR: The effect of restricting food intake by approximately 20% was studied in rats and mice, and in both species the incidence of tumours was reduced and the onset delayed, and the most common types in each species, liver tumours in mice, pituitary, mammary and skin tumour in rats, were significantly reduced.
Abstract: The effect of restricting food intake by approximately 20% was studied in rats and mice. Both species were fed as similar "natural" diet composed chiefly of cereals and bone meal. The duration of the rat study was 24 months, but mice were studied for their whole lifespan of 36 months. In the mice, restriction increased longevity, and in both species the incidence of tumours was reduced and the onset delayed. The effect upon the different types of tumour varied; some types appeared to be unaffected by restriction, but the most common types in each species, liver tumours in mice, pituitary, mammary and skin tumours in rats, were significantly reduced.
186 citations
TL;DR: Monocytes from the peripheral blood of normal adult human donors were found to have appreciable levels of cytotoxic activity against murine and human tumor‐cell lines, and monocyte‐mediated cytotoxicity on tumor cells was expressed in the presence of both fetal bovine serum and human AB serum.
Abstract: Monocytes from the peripheral blood of normal adult human donors were found to have appreciable levels of cytotoxic activity against murine and human tumor-cell lines. Adherent cells ( > 90% monocytes) were obtained from the peripheral blood of 29 normal healthy volunteers either by adherence on plastic and scraping with a rubber policeman or by adherence on microexudate-coated plastic and exposure to ethylene diamine tetra-acetic acid. Cytolytic capacity was tested by incubating effector cells for 72 h with murine and human tumor cell lines prelabelled with tritiated thy-midine. Cytostasis was evaluated by inhibition of [125I]iododeoxyuridine (125IdUrd) uptake. Tumor target cells employed were: a murine SV40-trans-formed kidney line (TU5), a murine chemically-induced sarcoma (1023), a human breast-cancer-derived cell line (G11) and a human lung-cancer-derived cell line (CaLu). Monocyte preparations at attacker to target cell ratios of 1:1 to 40:1, showed significant cytolytic and cytostatic activity against tumor target cells. Tumor cells showed different susceptibility to cytolytic activity, whereas comparable levels of cytostasls were observed with the various targets: TU5 and G11 tumor cells were more susceptible than 1023 and CaLu target cells to the cytolytic capacity of human monocytes and TU5 was used in most subsequent experiments. Peak isotope release from prelabelled target cells was observed after 72 h of incubation, whereas peak inhibition of [125I]dUrd uptake occurred after 24 h of culture. The cytotoxic capacity of monocytes isolated by either of the two methods mentioned above was similar. The monocytes had higher cytotoxic activity than unseparated mononuclear cells, and non-adherent cells showed minimal cytotoxic effects. Cytotoxicity by natural killer cells did not appear to have a major role in these assays, since adherent cells did not lyse K562 cells in a 4-h 51Cr release assay. Treatment with anti-human T-cell serum and complement did not inhibit the cytotoxic capacity of the monocyte preparations, whereas exposure to silica particles significantly inhibited the cytotoxic activity. Monocyte-mediated cytotoxicity on tumor cells was expressed in the presence of both fetal bovine serum and human AB serum.
163 citations
TL;DR: A syngeneic model system for the study of tumor metastases and cell‐mediated immunity is described and it is revealed that ESb but not Eb tumor cells had the ability to attach to and invade normal tissue and showed higher malignancy in vivo.
Abstract: A syngeneic model system for the study of tumor metastases and cell-mediated immunity is described. The system consists of two related, chemically induced murine lymphomas, the non-metastasizing parental line Eb and its metastasizing variant ESb. An unrelated, chemically induced tumor (MDAY) is included for specificity controls. Serological typing revealed that both Eb and ESb were of T lymphoid origin and expressed the H-2K and H-2D molecules of the host strain DBA/2. By various electron microscope techniques, morphological differences were observed between the two cell lines. In comparison to Eb cells, ESb tumor cells had a more polymorphic nucleus with many in vagi-nations of the nuclear envelope and a more prominent expression of microvilli on the cell surface. An in vitro organ culture test for tumor invasiveness, presented here for the first time in a syngeneic murine system, revealed that ESb but not Eb tumor cells had the ability to attach to and invade normal tissue. Accordingly, ESb tumor cells showed higher malignancy in vivo. This was apparent from their higher tumorigenicity and their ability to disseminate and metastasize and to kill recipient mice more quickly. Upon histological examination of the local primary tumors a striking difference was noticed with regard to the degree of infiltration by host-derived mononuclear cells, mostly histiocytes. The non-metastasizing tumor Eb was heavily infiltrated while tumor ESb contained only a few of these cells. The differences between the tumor lines ESb and Eb are considered in the light of their possible relevance for metastases in general. The etiology of the two tumors is discussed in particular with respect to their relatedness.
162 citations
TL;DR: Tumors derived from human metastases were no more prone to metastasizing in nude mice than were tumors derived from primary sites, but deep penetration of the body wall during growth of the tumor transplant was highly correlated with metastasis.
Abstract: The incidence of metastasis of xenogeneic tumors transplanted to nude mice is controversial. We studied 106 malignant human tumor lines in a total of 1,045 nude mice, and observed metastasis in only 14 instances (1.3%), involving 11 different tumor lines. Three of the lines showed repeated metastasis. Breast tumor lines metastasized with significantly greater frequency than other tumor types. None of the sarcoma lines metastasized. Tumors derived from human metastases were no more prone to metastasizing in nude mice than were tumors derived from primary sites. However, deep penetration of the body wall during growth of the tumor transplant was highly correlated with metastasis (p less than 0.001). Such factors as nude mouse health, tumor size and growth rate, and age and sex of the host mouse were not correlated with metastasis. Serial passage in nude mice did not select for a more malignant tumor line, since the incidence of metastasis did not differ at various passage levels. Thus, metastasis of human malignant tumors in nude mice would appear to depend primarily upon the site of tumor growth in the nude mouse, and upon the intrinsic metastasizing capability of the tumor line employed.
154 citations
TL;DR: It is concluded that the heavy consumption of “weak” alcoholic beverages may increase the risk of upper aero‐digestive tract cancers, and that part of the disease pattern associated with “alcoholism” is unrelated to alcohol consumption.
Abstract: Cancer morbidity and causes of death were examined in a retrospective cohort study of 14,313 male members of the Danish Brewery Workers' Union in order to determine health effects of heavy beer drinking, in particular in the aetiology of colorectal cancer. Brewery workers hold the right to consume 6 bottles (2,100 ml) of light pilsener beer (alcohol content 3.7 g1/00 ml) on the premises of the brewery per working day. The cohort included 1,063 mineral-water factory workers with no free ration of beer. Cancer morbidity and mortality were compared with those of the general population after adjustment for age, sex, area and time trends. Cancer morbidity, 1943–1972, was increased for cancer of the pharynx (RR = 2.09), oesophagus (RR=2.09), liver (RR=1.51) and larynx (RR = 1.98). The risk of these tumours was highest among workers who had had a ration of free beer during 30 or more years of employment. An increased risk of lung cancer (RR-1.16) corresponds with the risk among persons of low socio-economic class. These tumour sites accounted for a 9% excess of all malignant neoplasms among members of the BWU. No increased risk for either cancer of the colon (RR = 1.07) or cancer of the rectum (RR = 1.02) was observed. In contrast to studies on “alcoholics”, only deaths from the above-mentioned cancers, liver cirrhosis (RR=1.77) and motor vehicle accidents (RR = 1.33) were in excess; total mortality was only slightly above expectation (RR = 1.06). The present investigation suggests that the statistical association between beer and colo-rectal cancer is of a non-causal nature. It is concluded that the heavy consumption of “weak” alcoholic beverages may increase the risk of upper aero-digestive tract cancers, and that part of the disease pattern associated with “alcoholism” is unrelated to alcohol consumption.
150 citations
TL;DR: Data show that TIL have suppressive activity which may account for their poor performance in other assays of effector and memory function.
Abstract: Tumour-infiltrating lymphocytes (TIL) can be isolated from human lung and breast tumours by the stepwise application of velocity and density sedimentations on discontinuous Ficoll-Triosil or bovine serum gradients. The populations obtained showed variable composition with respect to lymphocyte subsets but generally corresponded to that of peripheral blood lymphocytes (PBL) containing primarily T cells (mean, 49% E rosettes; 15% EA rosettes). Comparison of reactivity to PHA in 15 individuals revealed a significant deficit in reactivity in the TIL population compared with blood and lymph-node lymphocytes. TIL showed no natural killer (NK) activity, no response to autologous tumour in mixed lymphocyte target interaction tests (MLTI) and no cytotoxicity against autologous tumour, in agreement with previous findings. In order to investigate this depressed reactivity, we measured the effect of admixture of mitomycin-treated TIL to PBL on PHA and MLTI responsiveness in nine individuals. Eight of these nine showed reduced reactivity to PHA (mean depression of responsiveness, 49%) and five subjects who were responsive to autologous tumour, showed markedly reduced reactivity in the presence of TIL (mean reduction, 65%). In a case of medullary carcinoma of breast it was possible to revover sufficient TIL to allow fractionation on nylon wool columns. Passage through these columns resulted in a higher level of inhibition of PBL reactivity than that seen in unpassed or column-attached lymphocytes. These data show that TIL have suppressive activity which may account for their poor performance in other assays of effector and memory function.
TL;DR: It is concluded that there is a linear relationship between the logarithm of risk of oesophageal cancer and overall daily ethanol consumption, whatever the beverage and that the effect is more marked for strong beverages (digestives) than for lighter beverages.
Abstract: The role of alcohol consumption in oesophageal cancer in Normandy has been studied by a retrospective study of 312 male cases and 869 controls. The linear relationship between the logarithm of risk and overall daily alcohol consumption was confirmed after adjustment for tobacco. The role of each specific alcoholic beverage was further investigated by computing relative risks for individuals consuming a given beverage and for those drinking other beverages only, within each overall alcohol consumption category. It is concluded: (1) that there is a linear relationship between the logarithm of risk of oesophageal cancer and overall daily ethanol consumption, whatever the beverage; (2) that the effect is more marked for strong beverages (digestives) than for lighter beverages; (3) that there is an additional risk related to apple brandy and cider.
TL;DR: The data suggest that the effectiveness of P therapy is due to a redifferentiation and to a reduction of the estrogen‐dependent growth of neoplastic endometrial cells.
Abstract: The effect of progestin therapy on estrogen receptors (ERs) and Progestin receptors in neoplastic endometrium was assessed with respect to histopathological changes and clinical responses of the lesions. In normal endometrium of premenopausal women the ER maximum occurred just before the estradiol peak which is associated with a decrease in ER. In pre- and postmenopausal women a high PR value was never associated with a high ER value; however in postmenopausal women a high PR was only detected when the ER level was high and when there was histological evidence of estrogenic influence. In neoplastic endometrium a high degree of histological differenciation was associated with simultaneous low ER and high PR values and vice versa. Progestin therapy resulted in virtually no change either in ER level or in pathological state of the lesions where PR was initially undetectable. In contrast a positive clinical response was observed in a PR-positive lesion revealing a differentiated histological type. The effect of progestin therapy was a fall in both ER and PR to a low level for the former and an undetectable level for the latter. The reasons for PR disappearance involve a nuclear translocation (detected 4-8 hours after treatment) and a nonreplenishment of PR. Since the clinically responding patients were those with PR- and ER-positive lesions the relationship between the presence of PR and a differentiated histological state could reflect the hormonal sensitivity of the tissue. These data also suggest that the effectiveness of progestin therapy is due to a redifferentiation and to a reduction of the estrogen-dependent growth of neoplastic endometrial cells.
TL;DR: It seems justified, however, to advise persons with a low sun exposure tolerance to be cautious in following the sun‐tandemanding fashions, as highly significant differences were demonstrated as regards the tolerance of sun exposure and propensity to freckling.
Abstract: A case-control study including 78 patients with malignant melanoma of the skin and 131 controls with the diagnoses of malignant lymphoma, testicular cancer or bone and soft-tissue sarcoma, was performed at the Norwegian Radium Hospital 1974-1975. The questionnaire contained questions for evaluating the comparability between cases and controls, and questions bearing on the relation between sun exposure and malignant melanoma. No essential difference between cases and controls was found as regards hair and eye colour, time spent outdoors during leisure, and degree of solar exposure. The melanoma patients liked sunbathing less than controls, worked more outdoors, more often went to Southern Europe for sunbathing and more often used sun lotions. These differences, however, were not clearly statistically significant. Highly significant differences were demonstrated as regards the tolerance of sun exposure and propensity to freckling. The melanoma patients tolerated sun exposure less well and freckled more easily than the controls. Although attempts were made to eliminate bias, there are still limitations and loop-holes in the study, and the relative risks demonstrated are not large enough to be of great immediate practical or scientific value. It seems justified, however, to advise persons with a low sun exposure tolerance to be cautious in following the sun-tan-demanding fashions. The study may also provide certain clues for the planning of future epidemiological and clinical studies regarding the etiology of malignant melanoma.
TL;DR: The results suggest that virus‐infected individuals possess a pool of virus‐specific memory T cells capable of mounting a cytotoxic response when properly challenged in vitro.
Abstract: Experiments have been conducted to determine the role played by immune T cells in the regression of EB-virus-induced transformation which is exclusively seen in leukocyte cultures from sero-positive donors. Kinetic studies suggest that, in virus-infected cultures from such donors, a population of T cells proliferates within the first 2 weeks apparently in response to the appearance of virus-infected B cells. This proliferation continues to some extent during the period of regression. Nonspecific induction of T-cell proliferation by PHA did not induce regression in virus-infected cultures from seronegative donors and acutally prevented the regression in seropositive donor cultures. T cells harvested from seropositive donor cultures 11-14 days post infection were generally much more inhibitory to the growth of the autologous EB-virus-transformed cell line than were T cells either freshly prepared from whole blood or harvested from corresponding uninfected cultures; this inhibitory activity was either absent or much diminished when assayed against allogeneic target cell lines. The results suggest that virus-specific memory T cells capable of mounting a cytotoxic response when properly challenged in vitro.
TL;DR: In this article, the syngeneic cytotoxic T-cell response against a metastasizing murine lymphoma variant was investigated and compared with the response against the non-metastasizing parental tumor line Eb.
Abstract: The syngeneic cytotoxic T-cell response against a metastasizing murine lymphoma variant was investigated and compared with the response against the non-metastasizing parental tumor line Eb. Anti-tumor cytotoxicity was not detectable in a 4-h 51Cr release assay in spleens taken directly from tumor-bearing animals (primary CMC). After restimulation in vitro (secondary CMC) however, high anti-tumor cytotoxic activity was detected. This activity was mediated by immune T lymphocytes as shown by its sensitivity to treatment with anti-Thy 1.2 serum and complement. Ten cells of the metastasizing tumor ESb, inoculated subcutaneously, were sufficient to raise a local tumor and metastases and to induce cytotoxic T memory cells in the spleens. In contrast, about 104 cells were required to raise a local tumor and to induce splenic cytotoxic T memory cells, when the parental tumor Eb was tested. The specificity studies of the anti-tumor cytotoxic activity demonstrated that cytotoxic T cells could distinguish unrelated, chemically induced syngeneic tumors and also recognize antigenic differences between the parental tumor Eb and its variant ESb. Eb and ESb tumor cells were recognized as carrying distinct antigens at the responder cell level, the stimulator cell level and the target cell level. The in vivo significance of these findings is discussed.
TL;DR: Medroxyprogesterone acetate treatment for an average of 4 weeks significantly reduced the concentrations of cytosol oestrogen and progestin receptors in hyperplastic and carcinomatous tissue.
Abstract: Sex hormone receptors in endometrial tissue were quantified to achieve more information about the hormonal factors responsible for the normal and abnormal growth of the endometrium and about the biochemistry of this tissue during steroid treatment. Estrogenic and progestogenic receptros were measured from the cytosol fraction of normal hyperplastic and carcinomatous human endometrial tissue taken at curettage and hysterectomy. The highest amount of progesterone receptor was found in the hyperplastic tissue followed by proliferative and secretory normal endometrium. Adenocarcinomatous tissue contained the lowest amount of progesterone receptor and this was further differentiated by stage of tumor differentiation with well differentiated carcinomas containing higher receptor levels than poorly differentiated ones. Compared with results of cytosol progesterone receptor content there were no major differences in the estrogen receptor values among the various tissues studied. However it was noted that poorly differentiated adenocarcinomas tended to have lower receptor levels than others. Most adenocarcinomas (80%) contained both estrogen and progesterone receptors; this finding can be contrasted with that in breast cnacer where only half fo the tumors posses the 2 receptors simultaneously. Hormonal parameters (levels of serum estradiol-17-beta progesterone follicle stimulating hormone or luteinizing hormone) showed no correlations. In the tissue group which had been receiving medroxyprogesterone acetate for an average of 4 weeks receptor concentrations of both cytosol receptors were significantly reduced in abnormal endometrial tissue. Progesterone receptor declined to 10-20% of the initial value during short-term treatment; however the depression in the cytosol receptor content may be detrimental for a beneficial hormone action to occur during a long-term progestin treatment of endometrial carcinoma. (Summary in FRE)
TL;DR: With 214 subclones of the BALB/c myelomonocytic leukemia WEHI‐3B, the granulocyte‐macrophage colony‐stimulating factor in impure or purified form consistently increased the proportion of colonies exhibiting partial or complete differentiation in agar cultures.
Abstract: With 214 subclones of the BALB/c myelomonocytic leukemia WEHI-3B, the granulocyte-macrophage colony-stimulating factor (GM-CSF) in impure or purified form, consistently increased the proportion of colonies exhibiting partial or complete differentiation in agar cultures. GM-CSF also increased colony size and content of daughter colony-forming cells. Serial recloning of WEHI-3B colonies in the presence of GM-CSF showed that when colonies differentiated completely, self-replication of the colony-forming cell was suppressed (clonal extinction). However, WEHI-3B cells exhibited clonal instability and even in the continuous presence of GM-CSF many colony-forming cells still generated cells able to form undifferentiated colonies. It appears unlikely that GM-CSF can completely suppress the progressive proliferation of a myeloid leukemic population of the WEHI-3B type.
TL;DR: Permanent cell lines have been established in vitro from lymphoid tumors induced in C57BL/Ka mice by fractionated X‐irradiation or by inoculation of the radiation leukemia virus (RadLV).
Abstract: Permanent cell lines have been established in vitro from lymphoid tumors induced in C57BH/Ka mice by fractionated X-irradiation or by inoculation of the radiation leukemia virus (RadOV). The cultured cells are lymphoblastic, replicate rapidly in vitro, and are tumorigenic in vivo. The cell surface markers Thy 1, Ly 1, Ly 2,3 and GIX are expressed by the lymphoid tumor cells in the mouse and persist in the corresponding cell lines; expression of the H-2 and TL antigens is greatly reduced during in vitro passage, but is restored on in vivo transplantation. The cell lines derived from RadLV-induced tumors (BL/VL lines) produce a virus population (RadLV/LTC) with the thymotropic and leukemogenic attributes of RadLV. Those derived from radiation-induced, virus-negative lymphomas (BL/RL lines) are initially devoid of MuLV expression, but frequently become spontaneous virus producers during in vitro cultivation.
TL;DR: The predilection of these selected cells to form tumors in the liver was clearly demonstrated following injection of the cells intra‐arterially.
Abstract: Liver-colonizing tumor cells were selected from B-16 melanoma by a stepwise procedure: (1) injection of the original cells through the portal circulation; (2) removal of tumor cells from the hepatic tumor nodules for culture in vitro; (3) reinjection of such cells through the portal circulation and repetition of steps 2 and 3 eight times. The predilection of these selected cells to form tumors in the liver was clearly demonstrated following injection of the cells intra-arterially. The accuracy of the injection technique was controlled by monitoring amounts of injected radioactively labelled Sephadex microspheres. This liver-colonizing preference was not exclusive, but relative.
TL;DR: The in vitro regression phenomenon was strongly T‐cell‐dependent but did not require the presence of either monocytes or, as a potential antigenic stimulus, the residual viral envelope material on the surface of virus‐infected B cells.
Abstract: Regression of EB-virus-induced transformation occurs exclusively in cultures of leukocytes from seropositive donors. Studies have shown that the strength of regression could be assayed in terms of the proportion of T cells which must be added to the autologous EB virus-infected T-cell-depleted population in order to establish regression in the culture. The in vitro regression phenomenon was strongly T-cell-dependent but did not require the presence of either monocytes or, as a potential antigenic stimulus, the residual viral envelope material on the surface of virus-infected B cells. The T-cell-depleted population from seropositive donors sometimes transformed (7/60 cultures) without the experimental addition of virus. Regression appeared to be independent of cytotoxic mechanisms involving anti-viral antibodies and not to be mediated by soluble factors released into culture medium.
TL;DR: Indirect immunofluorescence and radioimmuno‐assay with specific rabbit antisera demonstrated the occurrence of alphafetoprotein (AFP), carcino‐embryonic antigen (CEA) and placental alkaline phosphatase (PLAP) in primary testicular tumor cells.
Abstract: Indirect immunofluorescence and radioimmunoassay with specific rabbit antisera demonstrated the occurrence of alphafetoprotein (AFP), carcinoembryonic antigen (CEA) and placental alkaline phosphatase (PLAP) in primary testicular tumor cells. Embryonal carcinomas had AFP- and CEA-containing cells, sometimes PLAP. PLAP and sometimes CEA were found in seminoma cells. Sera from patients with advanced non-seminomatous tumors could contain any of these antigens or any combination of them. Sera from patients with seminomas had raised PLAP or CEA. PLAP appears to be a new marker for seminoma.
TL;DR: It was observed that dimethyl sulfoxide, when used as a solvent, could significantly affect the measurement of an antioxidant's efficiency as an inhibitor of carcinogen‐induced mutagenesis, prior to drawing any conclusions as to the potential use of the antioxidant as a carcinogen inhibitor.
Abstract: The Salmonella mutagenesis assay was used to study the influence of antioxidants on the mutagenic activities of carcinogens. The assay allowed us to determine which antioxidant would affect a carcinogen's in vitro mutagenic activity as well as to estimate the relative effectiveness of each antioxidant as a carcinogen inhibitor. Antioxidants studied included cysteamine, disulfiram, butylated hydroxyanisole, propyl gal late, sodium selenite, sodium bisulfite, α-tocopherol succinate and sodium ascorbate. The mutagenic activity of N-methyl-N'-nitro-N-nitrosoguanidine was most effectively inhibited by cysteamine and sodium bisulfite with selenite, propyl gallate and sodium ascorbate being only slightly less effective. Propyl gal late, selenite and cysteamine had a similar ability to inhibit N-acetoxy-2-acetylaminofluorene-induced mutagenesis, whereas the addition of sodium bisulfite, sodium ascorbate and disulfiram had no detectable inhibitory effect on this carcinogen. Butylated hydroxyanisole and α-tocopherol succinate did not affect the mutagenic activity of either carcinogen. It was also observed that dimethyl sulfoxide, when used as a solvent, could significantly affect the measurement of an antioxidant's efficiency as an inhibitor of carcinogen-induced mutagenesis. The results obtained indicate the necessity of studying an antioxidant's effect on numerous carcinogens prior to drawing any conclusions as to the potential use of the antioxidant as a carcinogen inhibitor.
TL;DR: Extracellular membraneous vesicles of GRSL leukaemia cells were isolated from the ascites fluid bathing the cells in vivo, and from cell washes, and the possible participation of surface microvilli and sub‐lethal autolysis in the process of shedding is discussed.
Abstract: Extracellular membraneous vesicles of GRSL leukaemia cells were isolated from the ascites fluid bathing the cells in vivo, and from cell washes. Mammary tumour virus-induced antigens (MLr) expressed on the surface of the cells are enriched on these vesicles as compared to plasma membranes isolated from the cell homogenate. The lipid fluidity of the vesicles is much smaller than that of the plasma membranes, and the content of the pertinent lipid parameters, cholesterol and sphingomyelin, are accordingly greatly increased. The extracellular vesicles which are also enriched in sialic acid and 5'-nucleotidase are apparently derived from the plasma membrane, probably at least partly by exfoliation of selected parts or domains of the surface of living cells. An analogy between this shedding of vesicles, the formation of endocytotic vesicles and the budding of viruses is noted; all these processes select or assemble rigid lipid domains of the cell membrane. The possible participation of surface microvilli and sub-lethal autolysis in the process of shedding is discussed.
TL;DR: There seems to be a small excess in incidence of HD among patients with previous infectious mononucleosis (IM), but both diagnostic problems and possible confounding factors must be taken into account before a possible causal association is considered.
Abstract: Patients with a positive reaction to the Paul-Bunnell test in the period 1961–72 were identified at nine different laboratories in Norway and matched against cases of malignant lymphoma registered at the Cancer Registry of Norway in the period 1961–75. Among 5, 840 patients having a positive Paul-Bunnell test a total of six developed malignant lymphoma, three of these more than 1 year after the positive Paul-Bunnell test. The expected number of malignant lymphoma was 2.04. Of the six lymphoma cases, five were classified as Hodgkin's disease (HD). The present investigation agrees well with the findings of other epidemiological studies. There seems to be a small excess in incidence of HD among patients with previous infectious mononucleosis (IM), but both diagnostic problems and possible confounding factors must be taken into account before a possible causal association is considered.
TL;DR: Findings support the evidence emerging from case reports in humans showing an increased risk of cancer of the urinary bladder as well as of leukemia in patients treated with CP.
Abstract: In a lifelong experiment Sprague-Dawley rats received cyclophosphamide (CP) in drinking water. Daily doses of 2.5 (I), 1.25 (II), 0.63 (III), and 0.31 (IV) mg/kg body weight were given to groups of 40 male and 40 female rats five times a week. The median survival time (MST) of treated rats proved to be dose-dependent. In rats treated with dose I the MST was 638 days for males and 642 for females, in those given dose IV it was 906 days for males and 934 days for females. The percentage of control animals with malignant tumors was 11% for males and 15% for females. The corresponding figures for CP-treated animals ranged from 32 to 43% for male rats and from 30 to 35% for females. At doses I, II, and III CP proved to be carcinogenic (p vs control <0.05). No carcinomas of the urinary bladder were found in controls but one female showed a benign papilloma of the bladder. However, 17 CP-treated rats died with carcinomas of the urinary bladder and, remarkably, only one of these was a female. In addition, 18 male and 10 female animals showed benign tumors of the same organotropy. No leukemia was diagnosed in controls, but in CP-treated rats leukemia was found in 8 male and 11 female animals. These findings support the evidence emerging from case reports in humans showing an increased risk of cancer of the urinary bladder as well as of leukemia in patients treated with CP.
TL;DR: The results from investigations with these sera indicated that these major proteins were not related to EBV‐induced viral capsid antigens (VCA) or the virus‐associated early antigen (EA) complexes as defined by immunofluorescence.
Abstract: In an attempt to qualitatively identify the membrane antigen (MA) complex induced by Epstein-Barr virus (EBV) infection of lymphoblastoid cells, superinfected Raji cells were surface labelled with 125I by the lactoperoxidase method and solubilized with Triton X-100, then the 125I-labelled membrane proteins were precipitated by sera containing high antibody titers to MA. Analysis of these immune precipitates on sodium dodecyl sulfate polyacrylamide gel eletrophoresis identified four major EBV-specific membrane proteins with molecular weights (mol. wt) of 280,000, 250,000, 170,000 and 90,000. Sera from patients with Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC) and infectious mononucleosis (IM) and from EBV-infected disease-free individuals showed differential patterns of reactivity to these antigens with some sera only recognizing three or less of the antigens. The results from invesigations with these sera also indicated that these major proteins were not related to EBV-induced viral capsid antigens (VCA) or the virus-associated early antigen (EA) complexes as defined by immunofluorescence. Metabolic labelling of EBV-infected Raji cells with [14C]glucosamine, followed by Triton X-100 solubilization and radioimmune precipitation, identified the 280,000, 250,000 and 90,000 components as glycoproteins. The lactoperoxidase-labelled 170,000 molecular weight component was not significantly glycosylated and, therefore, could not be categorized as a glycoprotein on the basis of this study. In addition, a glycoprotein with a mol. wt of 130,000 was identified by this approach which also appeared to be specified by EBV. The results from these investigations, therefore, indicated that the EBV-induced MA complex was composed of four major glycoproteins and one nonglycosylated high mol. wt protein.
TL;DR: In the light of the biological role of PP5 as trypsin and plasmin inactivator its presence in normal and absence from malignant trophoblast suggests that PP5 may be involved in the regulation of trophoblastic invasiveness.
Abstract: Placental protein five (PP5) was studied by radio-immunoassay in 360 serum samples from 334 pregnant women, 96 serum samples from eight patients with trophoblastic disease, and 80 samples from apparently healthy women. PP5 was not found in the serum of healthy controls. It became detectable in maternal serum 8 weeks after the last menstrual period, and the levels progressively increased as pregnancy advanced. The highest levels (mean 26–29 ng/ml) were seen between weeks 37–39 of gestation. PP5 was rarely found in the serum of patients with trophoblastic disease. The first pretreatment samples of two patients with hydatidiform mole had PP5 levels of 0.6 and 2 ng/ml when the concentrations of human chorionic gonadotrophin (hCG) and pregnancy-specific beta-1-glycoprotein (PSBG) were high, whereas the subsequent 17 samples were PP5-negative. All seven samples from a patient with invasive mole and 70 samples from five patients with choriocarcinoma were PP5-negative including those with high hCG and PSBG concentrations. Even a patient whose choriocarcinoma followed term pregnancy had no detectable PP5 in the serum. The occurrence of PP5 in tissue was studied by the three-layer bridge immunoperoxidase method. PP5 was localized in the syncytiotrophoblast between 6 and 42 weeks of gestation, but the cytotrophoblast was PP5-negative. The staining for PP5 was positive in all hydatidiform moles tested and in one of 10 cases of invasive mole. Choriocarcinomas were constantly PP5-negative (6 cases). In the light of the biological role of PP5 as trypsin and plasmin inactivator its presence in normal and absence from malignant trophoblast suggests that PP5 may be involved in the regulation of trophoblastic invasiveness. The absence of PP5 expression in malignant trophoblastic disease makes it possible to use the serum PP5 measurement for the differential diagnosis of trophoblastic disease and normal pregnancy: in normal pregnancy the placental proteins PP5, hCG and PSBG are all present in serum 10 weeks after the last menstrual period, whereas in malignant trophoblastic disease hCG and PSBG are expressed in the absence of PP5.
TL;DR: The lines obtained from nude mice inoculated with polyclonal LCL seem to have a restricted clonal representation, but were not monoclonal, as evidenced by analyses of their pattern of immunoglobulin synthesis.
Abstract: Human Epstein-Barr virus-carrying lymphoid cell lines which have 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 were inoculated intracerebrally into nude mice. All eighteen of them grew, killing the host mice within 7 to 25 days, except for 2 which grew more slowly. At autopsy, the brain of the nudes was found to be invaded by infiltrating lymphomas. Sixteen of these lymphomas, when recultured in vitro, gave rise to cell lines with growth properties and morphology indistinguishable from those of the inoculated LCL. Chromosomal examinations showed that 3/7 cell lines injected, which grew as lymphomas in the brain, were still normal diploid on reexplantation whereas the remaining four had become aneuploid. Four lines derived from intracerebral lymphomas (2 diploid, 1 aneuploid and 1 untested) were inoculated subcutaneously into adult nude mice. None of them grew. When the corresponding four original LCL lines were inoculated subcutaneously into newborn nude mice, they grew rapidly, but failed to do so in newborn normal mice or intracerebrally in adult normal mice. One such line, U-1450, was treated with anti-lymphocyte serum (ALS). Small nodules developed at the site of inoculation. From one nodule a cell line was cultured, 1450 ALSAD. It was morphologically indistinguishable from the line of origin. The lines obtained from nude mice inoculated with polyclonal LCL seem to have a restricted clonal representation, but were not monoclonal, as evidenced by analyses of their pattern of immunoglobulin synthesis.
TL;DR: A cytogenetic study, including prophase‐prometaphase chromosome analysis, of a patient with EBV‐genome‐negative acute lymphocytic leukemia of B‐cell type with Burkitt‐type cells is presented, finding a reciprocal 8;14 translocation of exactly the same type as in Burkitt's lymphoma.
Abstract: A cytogenetic study, including prophase-prometaphase chromosome analysis, of a patient with EBV-genome-negative acute lymphocytic leukemia of B-cell type with Burkitt-type cells is presented. All bone-marrow mitoses examined had a 14q + marker chromosome which was identified as a reciprocal 8;14 translocation of exactly the same type as in Burkitt's lymphoma.