bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of cytotoxic activity in human lymphocytes against autologous and allogeneic melanoma cells in vitro by culture with interleukin 2
Authors: Hersey P. , Bindon C. , Edwards A. , Murray E. , Phillips G. , McCarthy W. H.
Published: February 2007

The influence of interleukin 2 (IL2) on the cytotoxic activity of lymphocytes from patients with melanoma against autologous and a variety of allogeneic melanoma cells was studied. IL2 was produced from blood lymphocytes cultured for 24 h with phytohaemagglutinin (PHA) and purified by membrane chromatography to exclude PHA. Lymphocytes from 13 patients with melanoma at various clinical stages were cultured for 6 days with IL2 (2 U/ml) and then tested for cytotoxic activity against autologous melanoma cells, three allogeneic melanoma and three non‐melanoma cells. Autologous cytotoxicity was generated by culture with IL2 alone and was not increased by culture with both IL2 and autologous tumour cells. Marked increases in cytotoxic activity were also generated against the allogeneic target cells and were maximal against the NK‐insensitive Chang target cells. Similar degrees of cytotoxicity were induced by IL2 stimulation of lymphocytes from melanoma patients, patients with non‐melanoma carcinoma and normal subjects against the allogeneic target cells. Cold target inhibition studies were carried out against IL2 induced autologous cytotoxicity in five patients. In four of five studies the autologous target cells inhibited more than the allogeneic target cells. There was no significant difference between the inhibition produced by allogeneic melanoma cells and that produced by non‐melanoma cells. Similarly, in studies against allogeneic target cells, there was no significant difference in the inhibition produced by allogeneic melanoma compared to non‐melanoma target cells. This applied irrespective of whether effector cells were from melanoma or non‐melanoma subjects. These results suggest that lymphocytes from patients with melanoma are primed against autologous antigens in vivo and that provision of a second signal, IL2, in vitro can induce cytotoxicity against the autologous tumour. The cytotoxicity generated against the allogeneic target cells did not appear to have specificity to melanoma. Several results, such as the pattern of cytotoxicity against the target cells and changes in cell surface markers on the lymphocytes during culture, suggested that cytotoxicity was mediated by activated T cells rather than by natural killer cells. These findings appear to have important implications both in the understanding of tumour host relationships and for the use of IL2 in therapy.
Studies on long‐term T‐cell‐mediated immunity to epstein‐barr virus in immunosuppressed renal allograft recipients
Authors: Crawford D. H. , Edwards J. M. B. , Sweny P. , Hoffbrand A. V. , Janossy G.
Published: February 2007

Peripheral blood lymphocytes from normal seropositive donors and renal transplant recipients on various immunosuppressive regimens have been tested for their ability to mount a cytotoxic response when cultured with autologous EB virus‐infected B cells and thereby to cause regression of proliferating B‐cell foci. Cultures from 10 normal seropositive donors all showed the normal pattern of regression. Lymphocytes from patients receiving Cyclosporin A therapy with or without prednisolone completely failed to cause regression, thus allowing B‐cell lines to proliferate unchecked. Cells from two of 17 patients treated with azathioprine and prednisone also failed to cause regression. The cells from the remaining 15 individuals showed regression responses varying from minimal to normal. These results suggest a mechanism by which EB virus‐related tumours may arise in immunosuppressed renal allograft recipients.
Intestinal M3 antigen, A marker for the intestinal‐type differentiation of gastric carcinomas
Authors: Bara J. , Hamelin L. , Martin E. , Burtin P.
Published: February 2007

The mucus‐associated intestinal M3 antigen, normally restricted to intestinal goblet cells, was found in 35 out of 100 gastric adenocarcinomas belonging to intestinal (19/64) as well as diffuse (16/36) types according to Laurén's classification, often accompanying the other mucus‐associated gastric Ml and M2 antigens. This M3 antigen was predominant over the gastric M antigens in 25 of these 35 tumors; 18 of these belonged to the histological intestinal type. According to the WHO classification, the M3 antigen was found to predominate in all mucinous adenocarcinomas (7/7), was never present in the undifferentiated carcinomas (0/8), but was also found in some tubulo‐papillar (16/57) and signet‐ring cell (12/27) adenocarcinomas. This antigen could be used as a new criterion and incorporated into a point system containing morphological and tumor cell behavioral considerations; then it would appear to be a good marker for intestinal‐type differentiation. Indeed, 22 of these 25 gastric adenocarcinomas which produced predominantly M3 antigen showed such an intestinal‐like differentiation. The M antigenic pattern of gastric carcinoma suggested a duodenal rather than colonic‐type differentiation.
The role of chromosome 15 in murine leukemogenesis. I. Contrasting behavior of the tumor vs. normal parent‐derived chromosomes no. 15 in somatic hybrids of varying tumorigenicity
Authors: Spira Jack , Wiener Francis , Babonits Magda , Gamble Jenny , Miller Jacques , Klein George
Published: February 2007

G‐banding analysis was carried out on a series of hybrids derived from the fusion of a chromosome 15‐trisomic murine T‐cell leukemia of AKR origin and normal diploid fibroblasts or lymphocytes of the CBT6T6 strain. Due to the 14; 15 translocation involved in the generation of the T6 marker, the chromosomes No. 15 and 14 derived from the normal and the tumor parent can be distinguished cytogenetically. Highly tumorigenic, in vitro maintained hybrids, and high‐tumorigenic segregants of originally low‐tumorigenic in vitro hybrids, selected by in vivo passage, showed a similar cytogenetic pattern. It was characterized by the amplification of the tumor‐derived chromosomes No. 15 from the expected 3 to 5.5 ± 0.2 copies and a concomitant decrease of the normal derived T(14;15)6 from 2 copies to 0.9 ± 0.2. All other autosomes except No. 14 showed only minor random variations, around the expected number of 4 copies. The tumor‐derived chromosome 14 was amplified from the expected 2 to 3 copies. The lowtumorigenic hybrids showed the opposite pattern with a decrease in the number of the tumor‐derived 15 chromosome from 3 to 2.6 ± 0.1 and the maintenance of the two normal parent derived T(14;15)6 chromosomes. These findings suggest the existence of a qualitative difference between the 15 chromosomes derived from the tumor vs. the normal parent, due to mutation or proviral DNA insertion in the tumor‐derived homologue. Amplification of the changed locus and a decrease in the dosage of its normal counterpart appear to favor tumorigenicity.
Luteinizing hormone‐releasing factor increases release of human chorionic gonadotrophin in isolated cell columns of normal and malignant trophoblasts
Authors: Bützow R.
Published: February 2007

The effect of synthetic luteinizing hormone‐releasing factor (LRF) on release of human chorionic gonadotrophin (hCG) was studied by isolated cell columns of normal syncytiotrophoblasts and choriocarcinoma (BeWo) cells. After LRF stimulation the release of hCG by the normal trophoblasts increased up to 4‐fold and release by the malignant trophoblasts increased up to 6‐fold, indicating a specific effect of LRF on normal and malignant trophoblast cells.
Age at menarche, probability of ovulation and breast cancer risk
Authors: Macmahon Brian , Trichopoulos Dimitrios , Brown James , Andersen A. P. , Aoki Kunio , Cole Philip , Dewaard Frits , Kauraniemi Tapani , Morgan Robert W. , Purde Maret , Ravnihar Božena , Stormby Nils , Westlund Knut , Woo Ngai‐Chen
Published: February 2007

An analysis is undertaken of the frequency of ovulation in 17 groups of women aged 15 to 19 who had been the subjects of other studies. A urine specimen of at least 8 h accumulation had been provided on the 20th or 21st day of a menstrual cycle by 681 women. Analysis is restricted to 431 specimens which had been collected between 11 and 3 days prior to the onset of the subsequent menstrual period. A pregnanediol concentration of less than 1 mg per litre in such a specimen was taken as evidence that the cycle was anovular. The probability of a cycle being anovular was inversely and significantly related to the number of years since menarche, and, with years since menarche held constant, was positively but not significiantly associated with age at menarche. This observation indicates that women with early menarche do not have a longer duration of exposure to anovular cycles than do those whose menarche is delayed, and that variation in the duration of exposure to post‐menarcheal anovular cycles does not explain the association of breast cancer risk with early age at menarche. The 17 groups of women were classified into four categories according to ethnic origin and breast cancer incidence in the populations from which they derived. Anovular cycles were not more common in the high‐risk groups; indeed, the two centers in the lowest risk category had the highest proportion of anovular cycles.
Serum concentrations of total and non‐protein‐bound oestradiol in patients with breast cancer and in normal controls
Authors: Moore J. W. , Clark G. M. G. , Bulbrook R. D. , Hayward J. L. , Murai J. T. , Hammond G. L. , Siiteri P. K.
Published: February 2007

In premenopausal women with breast cancer, total serum oestradiol (E2) concentrations are normal but nonprotein‐bound E2, concentrations are significantly raised. This is not due to low sex‐hormone‐binding‐globulin (SHBG) binding capacities which are within the normal range and is unlikely to be due to the small but significant decrease in albumin concentrations. In post‐menopausal patients, both total and non‐protein‐bound E2 are significantly raised: this may be explained partially by lower SHBG binding capacities. In patients and controls there is a highly significant correlation between non‐protein‐bound E2 and SHBG but, for a given SHBG binding capacity, the patients have more non‐bound E2 than controls. It is concluded that the breast in women with breast cancer may be exposed to elevated levels of biologically active E2 although the reasons for this remain obscure.
Modulation of T leukaemic cell phenotype with phorbol ester
Authors: Delia D. , Greaves M. F. , Newman R. A. , Sutherland D. R. , Minowada J. , Kung P. , Goldstein G.
Published: February 2007

A panel of monoclonal antibodies and other markers (e.g., terminal deoxynucleotidyl transferase, sheep erythrocyte rosettes, peanut agglutinin) have been used in conjunction with flow cytometry and biochemical analysis to monitor the induction of maturation in human thymic (T) leukaemic cell lines by phorbol ester (TPA). Seven cell lines underwent multiple phenotypic alterations in response to TPA but were unresponsive to synthetic thymic hormones (TP5, FTS) or to other compounds (e.g. DMSO, retinoic acid) which induce maturation in other types of leukaemia. The changes parallel those observed in normal T‐cell differentiation and partly reflect alterations in glycosyl transferase activity, altered synthesis of proteins and regulation of cell surface receptors (for transferrin) associated with rapid growth and metabolism. These studies further illustrate the reversibility of maturation arrest in human leukaemia and provide support for the view that leukaemia may involve regulatory defects in the coupling of proliferation and maturation. Induction or promotion of terminal differentiation in leukaemic equivalents of T‐cell precursors may provide a convenient system for the study of biochemical and molecular events involved in T‐cell development and diversification.
Characterization of human cells persistently infected with cytomegalovirus and exposed to a chemical carcinogen
Authors: Li Jui‐Lien H. , Albrecht Thomas
Published: February 2007

A non‐productive, persistent human cytomegalovirus (CMV) infection was developed in human embryo lung (LU) cells by initially using supraoptimal temperatures to restrict the replication of a recent CMV isolate (76‐24). Although CMV replication was observed in some cells within a few weeks of shifting the cultures to 37°C and subculturing, CMV cytopathic effects and infectious CMV were not detected with further subculturing during the next 5 weeks. CMV‐specific nuclear antigens were, however, observed in most cells (designated LU‐76‐24) for 38 additional culture passages made during the following 12 months. Although the LU‐76‐24 cells were morphologically distinct from LU cell cultures carried in parallel as controls, the LU‐76‐24 were contact‐inhibited in spite of a somewhat disoriented growth pattern. Treatment of LU‐76‐24 cells with 0.05 μ/ml of the chemical carcinogen 4‐nitroquinoline I‐oxide (NQO) induced a lytic CMV infection from which a clone of cells (designated LUC‐NQO) was isolated. No effect was seen when LU cells were treated with the same dose of NQO. LUC‐NQO cells were morphologically altered from LU‐76‐24 cells and had lost contact inhibition. Even though CMV‐specific nuclear antigens were observed in LUC‐NQO cells, infectious CMV was not detected in lysates of these cells, nor was CMV rescued by co‐cultivation of these cells with susceptible cells or by induction with 5‐iodo‐2′‐deoxyuridine. LUC‐NQO, but not LU or LU‐76‐24 cells, plated with good efficiency in semi‐solid medium. The results indicate that long‐term, non‐productive, persistent CMV infections can be established in vitro and suggest that such cells may be more susceptible than non‐infected cells to the action of chemical carcinogens.
Synergistic effect of cis‐dichlorodiammineplatinum and 5‐aza‐2′‐deoxycytidine on mouse leukemic cells in vivo and in vitro
Authors: Veselý J.
Published: February 2007

cis‐Dichlorodiammineplatinum and 5‐aza‐2′‐deoxycytidine display a considerable synergistic effect in L1210 and La mouse leukemia in vivo; the combination of both drugs is also clearly synergistic in vitroas evidenced by the effects on cell growth and cell survival in soft‐agar medium. In exponential but not in stationary growth of L1210 cells, the drugs interfere with DNA and RNA synthesis.
Clinical evaluation of NCA in patients with chronic myelocytic leukemia
Authors: Wahren B. , Rudén U. , Gahrton G. , Hammarstöm S.
Published: February 2007

NCA, a normal colon and granulocyte antigen, which has been found in large amounts in myelocytes and metamyelocytes and in smaller amounts in neutrophil granulocytes, was studied in 50 CML patients in various stages of the disease. Radioimmunoassay was used to demonstrate NCA in serum. Untreated CML patients had a mean level of 732 μg NCNI, poorly controlled patients 421 μg/l and well‐controlled patients 160 μ/I. These valuer differ significantly from the mean of healthy persons, which was 71 μg NCN/I. The serum NCA levels were related to the number of maturing myeloid cells in blood, and to the clinical course in the chronic phase of CML In blast crisis low values with a mean of 109 μg NCNI was found. Patients with ANLL had a low mean level, 50 &I. Low levels of NCA could not be attributed to antibodies to NCA. NCA is a normal myeloid differentiation antigen. Despite this, its Occurrence in serum in leukemic patients differs from normai. This probably has to do with the abnormal amount as well as the release of NCA by leukemic maturing myeloid cells.
The detection of glucocorticoid receptors in breast cancer by immunocytochemical and biochemical methods
Authors: Ioannidis Constantine , Papamichail Michael , Agnanti Niki , Garas John , Tsawdaroglou Nikos , Sekeris Constantine E.
Published: February 2007

Glucocorticoid receptors have been detected in 90 human breast tumors and tumor‐like conditions by the immunoperoxidase method using a specific antibody against the glucocorticoid receptor isolated from rat thymocytes. In some of the specimens the [3H]‐dexamethasone binding assay was also performed and the results obtained were compared with those of the immunoperoxidase method. When the biochemical method was used, no strict correlation between the degree of binding of [3H]‐dexamethasone and malignancy on the basis of histological findings could be demonstrated. In contrast, the immunoperoxidase method was in full agreement with the histological type of the tumor. Thus, nearly all malignant breast tumors (carcinomas) were positive by the immunoperoxidase method to a varying degree. Most of the examined benign tumor‐like conditions (fibrocystic disease) were found to be negative. Intermediate situtations, such as atypical duct or lobular hyperplasia, papillomatosis etc., were mostly positive. These findings suggest that the immunoperoxidase method, apart from its usefulness for the detection of glucocorticoid receptors in breast tissue, may be used as an early biological marker to detect early conversion of normal to hyperplastic tissue and/or malignancy of the mammary gland.
High‐resolution analysis of chromosome markers in burkitt lymphoma cell lines
Authors: Zhang Sichong , Zech Lore , Klein George
Published: February 2007

Using a high‐resolution chromosome banding technique, which provided more elongated and distinctly banded chromosomes, some new evidence was obtained for localization of break points in Burkitt lymphoma marker chromosomes. As a result, the characteristic translocation between chromosomes 8 and 14 was designated as t(8;14) (q24.1;q32.5) and the deletion of chromosome 15 was designated as del(15) (q13q15).
Regulation and role of different macrophage‐ and granulocyte‐inducing proteins in normal and leukemic myeloid cells
Authors: Liebermann Dan , Hoffman‐Liebermann Barbara , Sachs Leo
Published: February 2007

It has previously been shown that there are different molecular forms of macrophage‐ and granulocyte‐inducing (MGI) proteins; one form, MGI‐I, induced the formation of colonies with differentiated cells from normal myeloblasts and another form, MGI‐2, induced normal differentiation in MGI+D+ leukemic myeloblasts that no longer require MGI‐I to form colonies. The present results indicate that MGI‐2 can also induce differentiation (without inducing colony formation) in the normal cells, and that MGI‐I induced MIG‐2 in the normal but not in the leukemic cells. It is suggested from these results that MGI‐2 is the differentiation‐inducing protein for normal and leukemic cells whereas MGI‐I is the growth‐inducing protein that induces colony formation by the normal cells, and that induction of differentiation in the normal cell colonies is due to induction of MGI‐2 by MGI‐I.
Different t‐cell subtypes are associated with pathologically distinct forms of moloney leukemia virus (m‐mulv)‐induced lymphoma
Authors: Åsjö Birgitta , Fenyo Eva Maria , Klein George , Skoog Lambert
Published: February 2007

The T‐cell enzyme markers, terminal deoxy‐nucleotidyl transferase (TdT) and 20 α hydroxysteroid dehydrogenase (20 α SDH), were used to classify lymphomas induced by the Moloney leukemia virus (M‐MuLV). Different subtypes of T cells were shown to be involved in different types of lymphoma. Thymomas were TdT‐positive and grew as subcutaneous solid tumors at the site of inoculation. Spleen cells from mice with generalized lymphoma were of two types. In the majority of cases the lymphomas consisted of 20 α SDH‐positive cells that homed to spleen and lymph nodes upon transplantation. In a few cases the cells of enlarged spleens were TdT‐positive and, like the TdT‐positive thymomas, could be transplanted as subcutaneous tumors. Thus, TdT‐positive and 20 α SDH‐positive T‐cell lymphomas can be distinguished by their homing properties. Preleukemic thymus cells from M‐MuLV inoculated mice can, after transfer to 400‐R irradiated syngeneic hosts, induce new lymphomas by virus release or grow in an autonomous fashion in the recipients. Whether of donor or recipient type, these lymphomas are TdT‐positive. In contrast, preleukemic bone marrow cells give lymphomas of donor type which are as heterogeneous for T‐cell enzymes as are lymphomas induced by neonatal inoculation of M‐MuLV.
Syngeneic and allogeneic cell‐mediated cytotoxicity against marek's disease lymphoblastoid tumor cell lines
Authors: Schat K. A. , Shek W. R. , Calnek B. W. , Abplanalp H.
Published: February 2007

Cell‐mediated cytotoxicity (CMC) of lymphocytes obtained from chickens infected with Marek's disease (MD) virus against allogeneic MD lymphoblastoid cell lines has been reported by several research groups. Recently, we established a number of cell lines from MD tumors obtained from highly inbred chickens and characterized for major and minor histocompatibility antigens. Allogeneic versus syngeneic CMC was studied using those cell lines and lymphocytes obtained from chickens 6‐8 days post infection with 5B‐1, a non‐oncogenic MD virus. Allogeneic cytotoxicity could be easily demonstrated, while syngeneic cytotoxicity was a rare event. However, increase of the CMC assay period from 4 to 8 h did enhance syngeneic cytotoxicity. Cold inhibition assays demonstrated that the allogeneic cytotoxicity was directed against alloantigens present on spleen lymphocytes sharing the same major histocompatibility antigens as the target cells. Cytotoxicity was not influenced by the sex of either target or effector cells or by the level of virus infectivity of the effector cells.
In vivo reduction of nk activity with anti‐nk 1 serum: Direct evaluation of nk cells in tumor clearance
Authors: Pollack Sylvia B. , Hallenbeck Linda A.
Published: February 2007

We have developed a new model to test the in vivo functions of NK cells. Injection of B6 mice with as little as 25 μl of an NK‐specific alloantiserum, anti‐NK I.I, significantly reduced the recipient's NK activity. The reduction, monitored in vitro as a decrease in the ability of spleen cells (SC) to lyse 51Cr‐labelled YAC‐I target cells, occurred rapidly, within 2 h of administration of the anti‐NK I.I serum. NK activity gradually returned to control levels but still was significantly depressed at 48 h. Comparable decreases were observed whether the serum was injected by the intravenous (i.v.) or the intraperitoneal (i.p.) route. Injection of the mice with exogenous complement (newborn rabbit serum) did not significantly increase the antiserum's effect. To test the requirement for NK cells in tumor clearance in vivo, mice were pre‐treated with anti‐NK I.I serum and subsequently injected i.v. with 125IdUrd (5‐iodo 2′‐deoxyuridine)‐labelled YAC‐I or RBL‐5 lymphoma cells. Tumor cell clearance in lungs, liver and spleen was reduced two to four‐fold in the antiserum‐treated mice compared to injection controls. These results provide direct evidence that NK cells are involved in the elimination of tumor cells in vivo.
Kinetics of the immune response of tumor‐bearing hamsters to two simian virus 40 coded non‐structural polypeptides present in simian virus 40 tumor cells
Authors: Ransom Janet H. , Thompson David L. , Tevethia Satvir S.
Published: February 2007

The kinetics of the immune response of hamsters transplanted with virus‐free SV40 tumor cells (TSV5) to two SV40‐coded non‐structural proteins of 94,000 daltons (T antigen) and 17,000 daltons (t antigen) was studied in order to determine if the variation in the immune reactivity of serum from tumor‐bearing animals towards these proteins can be explained on the basis of differential immune response during various stages of tumor growth. The results demonstrate that individual animals vary in their capacity to respond immunologically to T and t antigens in SV40‐transformed cells and that, further, the immune response to T and t antigens is influenced by the stage of tumor development.
Cancer of the oesophagus and the use of tobacco and alcoholic beverages in transkei, 1975‐6
Authors: McGlashan N. D. , Bradshaw Evelyn , Harington J. S.
Published: February 2007

A large questionnaire‐based sample survey over a period of 2 years has collected information on tobacco and alcohol use among young and old, male and female respondents in three regions of Transkei selected on the basis of having proved contrasts of incidence experience from oesophageal cancer. Results show significant gradients of social fabric and of customary usage of tobacco and alcohol across the three incidence regions. In particular the concept is supported of a synergistic relationship between tobacco and alcohol when both are used by one individual, with the major role being played by tobacco, especially when smoked in pipes. Stress is also laid on contrasts between old and young on the assumption that dynamic shifts of mortality may be expected to follow as the young of today alter the patterns of intake established by their elders.
Hodgkin and sternberg‐reed cells contain antigens specific to late cells of granulopoiesis
Authors: Stein Harald , Gerdes Johannes , Uchánska‐Ziegler Barbara , Ziegler Andreas , Wernet Peter
Published: February 2007

The results of a recent investigation, in which an anti‐serum specifically directed against Hodgkin (H) and Sternberg‐Reed (SR) cells was prepared, indicated the existence of a granulocytic cell‐specific antigen on H and SR cells. In the present study, a large series of biopsies from patients with Hodgkin's disease were subjected to immunostaining with monoclonal mouse antibodies raised against acute myelomonocytic leukemia (AMML) cells. Among seven hybrids that secreted antibodies showing reactivity to AMML cells but not to Daudi cells, there were three (TÜ5, TÜ6 and TÜ9) whose antibodies selectively stained formalinresistant antigens in cells of granulopoiesis. The strongest staining was found in the more mature cells; only a few promyelocytes stained very faintly with TÜ9. H and SR cells showed distinct staining for TÜ9 in 57 (76%) of the 75 tested cases of Hodgkin's disease, whereas TÜ5 and TÜ6‐reactive H and SR cells were found in only 35 cases (47%). All cases of the nodular sclerosis type and almost all cases of the mixed cellularity type contained TÜ9‐reactive H and SR cells, although the percentage varied from case to case. TÜ9‐reactive H and SR cells were demonstrated in nine of 12 cases of the lymphocyte depletion type and in eight of 21 cases of the lymphocyte predominance type. The presence of granulocytic cell‐specific antigens in H and SR cells in most of the cases of Hodgkin's disease suggests that (1) H and SR cells (including the lacunar cell variant) are not heterogeneous, but rather homogeneous in origin and nature, at least in a majority of cases, and (2) H and SR cells are more closely related to cells of the granulocytic cell lineage than to any other type of cell of the hemato‐lymphoid system.
Serum sex steroid and peptide hormone concentrations, and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon
Authors: Kauppila A. , Cantell K. , Jänne O. , Kokko E. , Vihko R.
Published: February 2007

Five normally cycling healthy women were given daily subcutaneous injections of human leukocyte interferon (3 × 106 units/day) from the 3rd through 23rd day of the menstrual cycle, and serum steroid and peptide hormone concentrations monitored at 3‐day intervals during the treatment and the preceding control cycle. Concentrations of cytosol and nuclear estrogen receptors (ERc and ERn, respectively) and progestin receptors (PRc and PRn) were also measured from endometrial biopsies taken on the 24th day of the control and treatment cycle. In addition, an extensive monitoring of clinical chemical and hematological tests from the blood samples were performed. Serum estradiol and progesterone concentrations were significantly decreased during the treatment cycle, suggesting that interferon interacts in vivo with the function of both FSH and LH. No significant changes were observed in the serum peptide hormone concentrations measured (FSH, LH, prolactin, insulin, growth hormone and TSH); neither were the levels of endometrial ERc, ERn, PRc and PRn affected by interferon administration. As expected, interferon administration resulted in decreased leukocyte counts. Moreover, an increasing tendency in the activities of serum alkaline phosphatase and gamma‐glutamyltransferase during the interferon therapy shows that interferon may slightly interfere with the liver function. These results suggest that one of the mechanisms by which interferon treatment may affect the growth of hormone‐dependent neoplasms could be the interaction with production and/or function of circulating hormonal compounds.
Risk of cancer in the norwegian aluminium industry
Authors: Andersen Aage , Magnus Knut , Dahlberg Bjørn E. , Wannag Axel
Published: February 2007

The study comprises 7,410 male employees from the Norwegian primary aluminium industry, and presents overall mortality as well as cancer incidence. During the period 1953‐79, 428 new cases of cancer were observed compared to the expected number of 412.2. The only statistically significant difference for the four investigated plants combined was cancer of the lung with 57 observed against 35.9 expected cases. The increased risk was almost solely confined to two subgroups in processing departments; workers with a short duration of employment and workers with a very long duration of employment in the older plants. These results were difficult to interpret because of the problems in selecting the appropriate reference population for estimation of expected number of cases of lung cancer. Furthermore, the individual occupational histories were incomplete and there was no information on smoking habits. In order to determine whether there is an excess risk for workers with long periods of employment in the newer plants, it is necessary to wait for another 10‐20 years, when more conclusive data will become available.
Detection of simian virus 40 surface‐associated large tumor antigen by enzyme‐catalyzed radioiodination
Authors: Soule Howard R. , Lanford Robert E. , Butel Janet S.
Published: February 2007

To facilitate detection of SV40 surface‐associated tumor antigen (T‐ag), conditions were established to surface label T‐ag on intact cells by lactoperoxidase‐catalyzed radioiodination (125I/LPO). SDS‐PAGE analysis of anti‐T immunoprecipitates of SV40‐transformed and ‐infected cells labelled with 125I/LPO revealed the presence of iodinated T‐ag. Several types of control experiments were employed to guarantee the surface specificity of the 125I/LPO labelling technique. When SV40‐transformed mouse cells were surface labelled with lactoperoxidase and glucose oxidase immobilized on insoluble beads, a preparation less readily internalized than soluble enzymes, T‐ag was iodinated. Selective immunoprecipitation of surface antigens demonstrated that lactoperoxidase did not iodinate internally localized T‐ag. A reconstruction experiment in which an extract of SV40‐infected cells was added to uninfected cells prior to surface labelling suggested that T‐ag released from lysed cells did not adhere significantly to monolayer surfaces and become iodinated. Finally, systematic omission of reactants from the iodination reaction revealed that exogenous addition of lactoperoxidase and H2O2 was necessary to generate an iodinated T‐ag, indicating that endogenous host cell reactants do not contribute significantly to the iodination of T‐ag. 125I‐labelled T‐ag was detectable on the surface of SV40 tsA‐infected cells at the nonpermissive temperature 24 h post infection, indicating that the tsA lesion does not prevent the interaction of T‐ag with the cell surface. When 125I/LPO‐labelled transformed or infected cells were chased for 2.5 h after labelling, iodinated T‐ag was no longer associated with the cell monolayer but was immunoprecipitable from culture supernatants. Cultures from which labelled T‐ag had been shed could then be relabelled with 125I/LPO and surface‐associated T‐ag was again detectable. These data suggest that surface‐associated T‐ag is continuously shed from the cell surface and is rapidly replaced in the membrane by intracellular T‐ag.
Characterization of a highly oncogenic murine leukemia virus from wild mice
Authors: Rasheed Suraiya , Pal Bijay K. , Gardner Murray B.
Published: February 2007

We have isolated a highly lymphomagenic wild mouse virus by passage of a weakly oncogenic amphotropic murine leukaemia virus (MuLV‐A) in NIH Swiss mice. This virus is similar in host range, interference and neutralization properties to that of the inoculated amphotropic virus but is distinct from it biochemically and causes lymphomas in 90‐100% of mice within 1‐2 months. Our results indicate that this highly oncogenic virus is a recombinant of wild mouse MuLV‐A and sequences related to env gene region of the endogenous xenotropic virus of NIH Swiss mice.
Familial breast cancer in iceland
Authors: Tuljnius Hrafn , Bjarnason Olafur , Geirsson Gunnlaugur , Johannesson Gudmundur , Sigvaldason Helgi , Bjarnadotitr Gudrun , Grimsdottir Kristin , Day Nicholas E. , Liceaga Gonzalez Maria A. De
Published: February 2007

Women who have relatives known to have had breast cancer are at an increased risk of getting the disease compared with the general population. On the basis of an extensive collection of family trees of women with breast cancer, the magnitude of this increase in risk is computed. Previously published results on other breast cancer risk factors are drawn upon and it has been possible to take account of some of these e.g., age, decade of birth, age at first childbirth and parity in the risk estimates. The relative risk with such adjustment is found to be 2.59 for mothers and 2.56 for sisters.
Studies of human natural killer cells. I. in vivo parameters affecting normal cytotoxic function
Authors: Pross Hugh F. , Baines Malcolm G.
Published: February 2007

The results of natural killer cell (NK) studies on 539 normal healthy donors tested from once to 213 times over a seven‐year time span have been presented. NK activity did not vary with donor blood group, Rh type or (in a small sample) HLA type. There was a slight but significant increase in NK activity from birth to adulthood, and between males and females. The male/female difference was present at birth and persisted through adulthood. The relative NK activity of individual donors tested repeatedly over many years was remarkably consistent in spite of variability in the absolute cytotoxidty observed. The expression of NK data in terms of relative NK was found to be superior to other methods, and the values obtained were found to be independent of the NK‐sensitive target cell used. Although age and sex differences in NK activity are slight, their existence should be considered when studies of NK activity in patients are analysed.
HLA antigen expression on urothelial cells: Detection by antibody‐dependent cell‐mediated cytotoxicity
Authors: O'Toole Carol M. , Tiptaft R. C. , Stevens A.
Published: February 2007

Antibody‐dependent cell‐mediated cytotoxkity (ADCC) was used to detect HLA‐A, ‐B and ‐C antigens on in vitro cultured urothelial cells of normal or malignant derivation. Alloantisera induced specific lysis of 51Cr‐labelted targets by effector lymphoid cells from non‐immune donors. HLA antisera were routinely titred to dilutions ≧ 10−3 on urothelial cells in primary or long‐term culture. The HLA phenotype was compared for lymphoid cells and urothelial cells from eight individuals. HLA antigens detected by complement mediated lymphocytotoxkity were also detected on urothelial cells. No deletions or gains in HLA antigens were found on normal or malignant urothelial cultures as compared with donor lymphocyte HLA typings. The results show that the established urothelial cells lines J82, TCCSuP and SCaBER have retained their donor HLA phenotype. The established cell lines T24 and RT4 derived from transitional cell carcinomas and HCV‐29 from urothelium were found to have distinctive HLA profiles although donor lymphocytes were not available for comparison. The serological crossreactions seen in complement mediated lymphocytotoxidty were clearly observed in ADCC. In particular, HLA‐Cw5 was found to crossreact with HLA‐Cw8. HLA‐Cw5 was detected on 6/8 cultures of transitional cell carcinomas and this was confirmed by absorption analysis.
Enzymes of collagen synthesis and type iii procollagen amino‐propeptide in serum from nigerians with hepatocellular carcinoma and other malignant diseases
Authors: Bolarin Debayo M. , Savolainen Eeva‐Riitta , Kivirikko Kari I.
Published: February 2007

Serum immunoreactive prolyl hydroxylase protein (S‐IRPH), galactosylhydroxylysyl glucosyltransferase activity (S‐GGT) and the amino‐terminal propeptide of type III procollagen [S‐Pro(III)‐N‐P] were studied in 24 patients with primary hepatocellular carcinoma, 18 with secondary liver neoplasms and 35 with other malignant diseases but no evidence of liver involvement; this latter group included 13 patients with Burkitt's lymphoma, II with breast cancer and 11 with other neoplasms. Control values were determined for 60 apparently healthy Nigerians. S‐IRPH and S‐GGT were above the upper normal limit, defined as the mean+ 2 SD of the controls, in all the patients with primary hepatocellular carcinoma and all but one with secondary liver neoplasms, whereas only one S‐IRPH value and three S‐GGT values exceeded this limit in the patients with other malignant diseases. The mean S‐Pro(III)‐N‐P was even more elevated than S‐IRPH and S‐GGT in the primary and secondary liver neoplasm cases, but was also elevated in other malignant neoplasms; about one third of the patients with no evidence of liver involvement had a concentration exceeding the upper normal limit. A high correlation was found between the values for the three assays both in primary hepatocellular carcinoma and in the whole series of malignant diseases. The data suggest that primary and secondary malignant neoplasms of the liver have a high rate of collagen synthesis. The three assays may be of some value in the diagnosis of primary hepatocellular carcinoma and secondary liver involvement in other malignant diseases, and in monitoring the treatment provided.
Migration inhibition caused by ebv‐specific 48k subcomponent of ebna and the associated 53k cellular protein
Authors: Szigeti Robert , Luka Janos , Sternås Lars , Klein George
Published: February 2007

Leukocytes from EBV‐seropositive but not seronegative healthy donors responded with significant migration inhibition to the 48K subcomponent of the Epstein‐Barr virus determined nuclear antigen (EBNA), known to carry the virally determined antigenic specificity. A concentration of 10 μg/ml was still effective while 5 μg/ml had no detectable effect. EBNA‐associated cellular 53K protein had no effect by itself, but it potentiated the effect of 48K, even K the latter was added at the subliminal concentration of 5 μg/ml. The related 53K protein, isolated from EBV‐negative human lymphoma cells, was also effective, whereas the corresponding murine‐tumor‐associated 53K had no potentiating effect Immunization of mice with an extract of DNA‐binding proteins from EBV‐carrying Raji cells, known to contain both 48K and 53K, induced a significant macrophage migration inhibition response, to both human 48K and 53K. Murine 53K was ineffective, however. Human but not murine 53K increased the migration inhibitory activity of subliminal concentrations of 48K in the murine macrophage system as well. These findings suggest that human but not murine 53K may reconstitute with 48K (EBNA) to form a highly immunogenic complex.
Lectin‐resistant variants of mouse melanoma cells. I. Altered metastasizing capacity and tumorigenicity
Authors: Tao Tien‐Wen , Burger Max M.
Published: February 2007

From C57BL mouse melanoma B‐16 cells, variant clones were selected in vitro which were resistant to the lectins wheat‐germ agglutinin and ricin. Cells were also selected which survived toxic concentrations of concanavalin A. Four different In vivo assays using intradermal, intravenous, intraperitoneal and intramuscular injections were used to assess the tumorigenidty and metastasizing capacity of these lectin‐resistant variants. It was concluded that to obtain a complete picture of the malignant properties of a given cell line or clone, all four assays have to be carried out. In comparison with the parental cells, the WGA‐resistant cells showed a most dramatic decrease in metastasizing capacity through both lymphatic and vascular channels. Tumorigenidty was also reduced. The ricin‐resistant cells showed a defective development into lung tumors and thus displayed a reduction in metastasis through the hematogenous route. Since this line did not change its capacity to metastasize via the lymphatic route, and the tumorigenidty was not significantly altered, it will be a good model for studies seeking to dissociate these two properties. The Con‐A‐selected cells, when injected intravenously, developed tumor nodules in the liver in addition to those in the kings, while no striking alterations in tumorigenicity or metastasizing capacity could be detected in this line.
Non‐random chromosomal changes involving chromosomes 6 and 7 in spontaneous rat immunocytomas
Authors: Wiener Francis , Babonits Magda , Spira Jack , Klein George , Bazin Herve
Published: February 2007

G‐banding analysis of seven Ig‐secreting spontaneous rat immunocytomas showed a consistent translocation of the distal part of the q‐arm of chromosome 7 to the telomerk end of chromosome 6. The breakpoints were assigned to q3.3 on chromosome 7 and q3.2 on chromosome 6. Previously, we found a similar translocation pattern in mouse plasmacytomas induced by different agents. The distal part of die q‐arm of chromosome 15 was translocated to the telomerk end of chromosome 12, known to carry Igh, the immunoglobulin heavy chain cluster. The banding homologies between the chromosomes involved in the translocations in the two species suggest that a similar mechanism is responsible for plasmacytomagenesis in both. We also predict that the rat Ig heavy chain gene cluster will be located to the terminal segment of chromosome 6.
Carcinogenicity of phenacetin: Long‐term feeding study in B6C3F1 mice
Authors: Nakanishi Keisuke , Kurata Yasushi , Oshima Masato , Fukushima Shoji , Ito Nobuyuki
Published: February 2007

Groups of 52 B6C3F1 mice of each sex were maintained on a diet containing 1.25 or 0.6% phenacetin for 96 weeks and then fed a basal diet for 8 weeks. Control groups consisted of 50 mice of each sex and were fed a basal diet for 104 weeks. All animals were killed at the end of the experiment and all organs were examined histopathologically. Mice that died during the experiment were also autopsied and those that survived for more than 57 weeks, when the first tumor was observed, were also included in the effective number of mice. Tumors were found in the kidney, liver, lung, skin, hematopoietic system (leukemia or lymphoma) and occasionally in some other organs. The dose‐related induction of renal cell tumors in the male mice fed phenacetin was clearly demonstrated in this experiment. Urinary bladder lesions that developed in the mice of either sex fed 1.25% phenacetin were also considered to be due to the tumorigenicity of phenacetin. Tumors of other organs in either the phenacetin‐treated or the control group were regarded as strain‐related spontaneous tumors of B6C3F1 mice.
Enrichment of cell populations containing terminal deoxynucleotidyl transferase activity by free flow electrophoresis
Authors: Sarin P. S. , Virmani M. , Gallo R. C.
Published: February 2007

Terminal deoxynucleotidyl transferase (TdT) is an enzyme that has been utilized as a biochemical marker for following certain leukemia patients during treatment and remission. The potential usefulness of this enzyme in predicting the onset of relapse before any morphological indications has been demonstrated in chronic myelogenous leukemia patients in blast phase of the disease. In order to be able to detect low levels of TdT activity, especially during remission phase, we have used the technique of free flow electrophoresis to enrich cell populations containing TdT. With this technique we have achieved up to 20‐fold enrichment of TdT‐positive cell populations from normal human bone marrow, cells from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia in blast phase of the disease. TdT positive cells were not detected in patients with acute myelogenous leukemia and B cell lines. This technique should prove to be useful in early detection of relapse in patients in remission and for enrichment of cell populations containing other biochemical markers.
A monoclonal antibody (B72.3) defines patterns of distribution of a novel tumor‐associated antigen in human mammary carcinoma cell populations
Authors: Nuti Marianna , Teramoto Yoshio A. , Mariani‐Costantini Renato , Hand Patricia Horan , Colcher David , Schlom Jeffrey
Published: February 2007

We report here both the range and patterns of reactivity of an IgG1, monoclonal antibody, B72.3, prepared against human metastatic mammary carcinoma cells. When the avidin‐biotin complex (ABC) immunoperoxidase technique was used on tissue sections, monoclonal B72.3 reacted with 19 of 41 (46%) primary mammary carcinomas and 13 of 21 (62%) metastatic lesions, either in axillary lymph nodes or at distal sites. Variable concentrations of antigen, recognized by B72.3, were observed among mammary tumors, as well as among different cell populations of a given tumor mass. Several patterns of antigen distribution were observed: membrane, diffuse cytoplasmic, focal, apical and marginal. No reactivity was observed to normal mammary epithelium, stroma, or lymphocytes of the breast, nor to any cell types in a variety of other normal human tissues, melanomas, and sarcomas. Reactivity with all of four colon carcinomas was also observed. Assay of serial sections of mammary carcinomas with B72.3 and a monoclonal antibody directed against carcinoembryonic antigen demonstrated that these antigens were both distinct and non‐coordinately expressed.
Selective depletion of nk cell activity in vivo and its effect on the growth of NK‐sensitive and nk‐resistant tumor cell variants
Authors: Kawase Ichiro , Urdal David L. , Brooks Colin G. , Henney Christopher S.
Published: February 2007

Intravenous injection of rabbit anti‐asialo‐GM1 serum, an antiserum previously shown to eliminate splenic natural killer (NK) activity in vitro, profoundly depressed NK activity in CBA, DBA/2 and BALB/c nu/nu mice. The effect on NK activity was selective, as treatment of mice with anti‐asialo‐GM1 serum did not affect the development of other cytotoxic cells including cytotoxic macrophages following injection of poly I:C, or cytotoxic T cells in response to allogeneic cells. The role of NK cells in controlling tumor cell growth was investigated using an NK‐sensitive (cl 27v‐IC2) and an NK‐resistant (cl 27av) subline of the murine lymphoma L5178Y. Initial studies showed that cl 27v‐IC2 cells were at least 100 times less tumorigenic than were cl 27av cells in both syngeneic DBA/2 mice and BALB/c nu/nu mice. In addition, treatment of DBA/2 mice with poly I:C, which boosted NK activity, markedly depressed the growth of cl 27v‐IC2 cells, but not of cl 27av cells. On the other hand, treatment of DBA/2 mice and BALB/c nu/nu mice with antiasialo‐GM11 serum led to a marked increase in tumorigenicity of cl 27v‐IC2 cells, but had no effect on the tumorigenicity of cl 27av cells. In addition, the protection against cl 27v‐IC2 growth afforded by poly‐I:C treatment was abrogated by injection of anti‐asialo‐GM1 serum. The possibility that the effects observed were caused by binding of the injected antibodies to the tumor cells was minimized by: (1) using a clone of tumor cells (cl 27v‐IC2) that lacks chemically detectable asialo‐GM1, and (2) pre treating animals with anti‐asialo‐GM1 rather than administering antiserum and tumor cells concurrently. These studies provided compelling evidence that NK cells could play an active role in controlling tumor growth. Selective depletion of NK activity by injection of antiasialo‐GM1 serum is a method which would be generally applicable to studying the role of NK cells in disease processes.