bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation of glycosphingolipids and sialic acid in YAC‐1 lymphoma variants with their sensitivity to natural killer‐cell‐mediated lysis
Authors: Yogeeswaran G. , Gronberg A. , Hansson M. , Dalianis T. , Kiessling R. , Welsh R. M.
Published: February 2007

Sialoglycoconjugates and glycosphingolipids were quantitated in a series of variants derived from the YAC‐1 lymphoma, known to be highly sensitive to natural killer (NK)‐cell‐mediated lysis. The variants, which had widely diverging sensitivities to NK cells, were obtained by a number of methods, including selection in the presence of NK cells, antibody to H‐2, or antibody to the murine leukemia‐virus‐induced antigen, and by fusion of sensitive cells with an NK‐resistant cell line, A9HT. The sensitivities of these cells to NK‐cell‐mediated lysis did not correlate with their sensitivities to anti‐H‐2a cytotoxic T cells. While no correlation could be made between the NK‐sensitivity of these variants and their total cellular sialic acid, a statistically significant inverse correlation was observed between the levels of percentage neuraminidase releasable surface sialic acid of total labelled sialyl components and sensitivity to NK cells. This correlation with cell surface sialic acid was observed with either endogenous or lymphocytic choriomeningitis virus‐induced activated NK cells as effectors. Neuraminidase treatment of insensitive target cells caused a moderate increase in sensitivity but failed to render the resistant targets as sensitive as YAC‐1. Analysis of glycosphingolipids among the variants revealed a strong positive correlation between the total cell neutral glycolipid with chromatographic migration of asialo‐GM2 and sensitivity to endogenous or activated NK‐cell‐mediated lysis. Significant correlations were not found with any other neutral glycolipids. However, ganglioside homologues with chromatographic mobility of GM1, GD1a, GD1b, and GT also showed a positive correlation with both endogenous and activated NK‐cell‐mediated lysis. The ratio of asialo‐GM2 to GM2 had a highly significant positive correlation with sensitivity. These correlative results suggest that asialo‐GM2 and certain gangliosides could be involved in binding or lytic events in NK cell:target cell interactions, and that high levels of sialic acid and sialylation on the cell surface may inhibit and/or modify such interactions. Further studies with these YAC variants should be useful for examining the biochemical bases of target cell‐effector cell interactions in the NK‐system.
Liver cell dysplasia in association with hepatocellular carcinoma, cirrhosis and hepatitis b surface antigen in Hong Kong
Authors: Ho Joana C. I. , Wu Piu‐Chee , Mak Tak‐Kwan
Published: February 2007

Liver‐cell dysplasia was identified in 60% of 558 cases of cirrhosis with and without hepatocellular carcinoma (HCC) in Chinese coming to necropsy in Hong Kong from 1963 to 1978. A significant correlation was found between liver‐cell dysplasia and the identification of hepatitis B surface antigen (HBsAg) in the livers, suggesting that dysplasia may be causally related to hepatitis B virus (HBV). Applying Bayes' theorem to our series of male deaths, we calculated that for Chinese male non‐cirrhotics showing liver‐cell dysplasia at necropsy, compared with male non‐cirrhotics showing no liver‐cell dysplasia, the approximate risk factor for HCC is 13:1, whereas for male cirrhotics with liver‐cell dysplasia, compared with male cirrhotics without liver cell dysplasia, the risk factor for HCC is approximately 2:1. In the presence of dysplasia, the risk for HCC is increased two‐fold in males who are also HBsAg‐positive. Thus, the presence of liver‐cell dysplasia in cirrhotic or non‐cirrhotic livers accompanies a significantly higher risk of developing HCC, especially in the presence of HBsAg.
Phenotypic changes of human neuroblastoma cells in culture induced by 12‐O‐tetradecanoyl‐phorbol‐13‐acetate
Authors: Påhlman Sven , Odelstad Lena , Larsson Erik , Grotte Gunnar , Nilsson Kenneth
Published: February 2007

SK‐N‐SH and SH‐SYSY human neuroblastoma cells treated by 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) express morphological and biochemical changes, which indicate that differentiation towards more mature cells has occurred. The most prominent morphological changes were the development in 40–60% of the cells of cell‐surface projections longer than 50 μm and cytoplasmic neurosecretory granules demonstrated by electron microscopy. At the biochemical level, TPA induced a two‐fold increase in the relative activity of neuron‐specific enolase and 30‐ to 40‐fold increase in noradrenaline and adrenaline concentrations. A decrease in proliferation rate of TPA‐treated cells was observed. The biological effects of TPA were slightly potentiated by nerve growth factor.
A single‐dose protocol for azaserine initiation of pancreatic carcinogenesis in the rat
Authors: Yager James D. , Roebuck Bill D. , Zurlo Joanne , Longnecker Daniel S. , Weselcouch Edward O. , Wilpone Seri A.
Published: February 2007

Previously, the induction of pancreatic carcinogenesis in the rat using azaserine has involved a multiple‐dose treatment protocol. The objective of the present study was to determine the effect of multiple azaserine treatments on pancreatic DNA synthesis and to develop a protocol for a single‐dose initiation of pancreatic carcinogenesis by azaserine in the rat. Pancreatic DNA synthesis in young rats, which was determined by measuring the amount of [3H]‐thymidine incorporation into DNA, was found to be elevated at 4.3 weeks of age and to decrease to a baseline level by 6.3 weeks. Treatment of 4‐week‐old rats with azaserine resulted in a dose‐dependent inhibition of [3H]‐thymidine incorporation into both pancreatic and liver DNA. Maximum inhibition was seen at 10 mg/kg body weight. This inhibition was followed by a gradual return of incorporation to normal values over a 48 h period. One week following pretreatment with four weekly injections of azaserine at 30 mg/kg, [3H]‐thymidine incorporation into pancreatic and liver DNA was significantly elevated, suggesting that multiple injection protocols cause enhanced DNA synthesis which could have a co‐carcinogenic and/or promotional effect. Single‐doses of azaserine (10, 30 and 60 mg/kg) given at 7 weeks of age caused the appearance of more atypical acinar cell nodules (AACN) than when given at 5 weeks of age. The most effective dose was 30 mg/kg. Using alkaline elution, we determined that this response was due to the occurrence of more DNA damage in the 7‐week‐old animals. Thus, these results demonstrate a rationale for the use of single‐dose initiation protocols in the pancreas. An effective single‐dose protocol for induction of AACN in azaserine‐treated rats fed semi‐synthetic diet is presented.
Incidence of ovarian cancer in relation to the use of oral contraceptives
Authors: Weiss Noel S. , Lyon Joseph L. , Liff Jonathan M. , Vollmer William M. , Daling Janet R.
Published: February 2007

Female residents of six counties in Washington and Utah in whom a diagnosis of ovarian cancer was made during 1975–79 were interviewed concerning prior use of oral contraceptives. Interviews with a random sample of women drawn from these same counties were obtained for comparison. A smaller proportion of women with epithelial ovarian tumors had taken oral contraceptives than had controls: the estimated risk of ovarian cancer in uses relative to that in non‐users was 0.57 (p = 0.04). The magnitude of the decreased risk depended on the duration over which oral contraceptives had been taken, as the negative association was present only after 4 or more years of use. In many ways, the use of oral contraceptives mimics the physiologic effects of pregnancy. The results of the present investigation, when interpreted together with those from other epidemiologic studies and from experiments in animals, suggest that, like pregnancy, the use of oral contraceptives has a protective effect against the development of ovarian cancer.
Dietary factors and breast cancer risk
Authors: Lubin Jay H. , Burns Patricia E. , Blot William J. , Ziegler Regina G. , Lees Alan W. , Fraumeni Joseph F.
Published: February 2007

As part of a case‐control study in northern Alberta, Canada, 577 women aged 30–80 with breast cancer diagnosed during 1976–77 and a population‐based agestratified random sample of 826 disease‐free female controls were questioned about certain aspects of their diet. Computing relative risks (RRs) by tertiles, significant increasing trends were found with more frequent consumption of beef (RRs of 1.0, 2.3, 1.5; test for trend, p <0.001), pork (RRs of 1.0, 1.6, 2.2; test for trend, p <0.001), and sweet desserts (RRs of 1.0, 1.3, 1.5; test for trend, p = 0.01). Elevated risks were also noted for use of butter at the table and for frying with butter or margarine, as opposed to vegetable oils. The association of total beef and pork consumption with breast cancer was not materially affected by controlling for age at first birth, family history of breast cancer, previous benign breast biopsy or socioeconomic status. Nor was the association reduced by controlling for ages of menarche and menopause, even though within the control series the intake of beef and pork reported in adult life was higher among those with a lower age at menarche or a older age at natural menopause.
Is testicular cancer incidence related to marital status?
Authors: Davies Joan M.
Published: February 2007

In Western countries there has been a striking rise in the incidence of testicular cancer among young men, but little is known about the aetiology of the disease. Epidemiological studies in the USA have yielded conflicting findings on a possible relationship between marital status and testicular cancer. National analyses of 1957‐61 deaths in England and Wales by marital status were published in 1964, and showed that under the age of 65 single men had higher death rates from this cause than married men. Possible interpretations of these findings are discussed.
Phenotypic drift of metastatic and cell‐surface properties of mammary adenocarcinoma cell clones during growth in vitro
Authors: Neri Anthony , Nicolson Garth L.
Published: February 2007

We have examined cell clones obtained from a 13762 mammary adenocarcinoma tumor and its spontaneous lung metastasis for phenotypic stability during serial culture passage in vitro. Two clones that varied markedly in their metastatic properties were chosen for further examination. One of these clones (MTC) obtained from the parental transplanted tumor initially failed to metastasize within 23 days post‐injection s.c. but gained the ability to form spontaneous pulmonary metastases after several serial passages in vitro. Another clone (MTLn3) derived from a spontaneous lung metastasis was initially highly metastatic after short‐term culture, but lost the potential to form large numbers of spontaneous lung metastases with long‐term culture. In contrast to MTA, clone MTLn3 displayed lymph‐node metastasis, and the frequency of lymph‐node involvement increased when late‐passage cultures of MTLn3 cells were assayed in vivo. Both clones from late‐passage cultures produced larger tumor sizes at the primary (mammary fat pad) injection sites compared to early passage cells. The morphologies of MTC cells changed with serial tissue culture passage, while the morphologies of MTLn3 cells did not change. The display of fibronectin on MTC cells by immunofluorescence did not change with culture passage; fibronectin was not detected in cultures of clone MTLn3. Fibronectin was also found on MTC cells by cell surface labelling using lactoperoxidase‐catalyzed iodination‐sodium dodecylsulfate polyacrylamide gel electrophoresis‐autoradio‐graphy. lodination of fibronectin on MTC cells did not vary with culture passage, and as in immunofluorescence experiments it was not detected on MTLn3 cells. There was a decrease in exposure of certain cell surface proteins on MTC cells with culture passage, but we did not detect modifications with this procedure that correlated with culture passage of MTLn3 cells. We conclude that prolonged culture in vitro can result in modifications of metastatic and cell‐surface properties of tumor cell clones.
Incidence and type of tumors induced in C57BL bg/bg mice and +/bg littermates by oral administration of DMBA
Authors: Argov Shmuel , Cochran Alistair J. , Kärre Klas , Klein Gunnar O. , Klein George
Published: February 2007

As an attempt to study the effect of the beige (bg) mutation on chemical carcinogenesis, 64 C57Bl/bg/bg mice and 83 +/bglittermate controls received DMBA in five weekly intragastric doses. The incidence of tumors of different histological types was monitored through observation periods ranging between 165 and 500 days. By 165 days after the first DMBA feeding, 18% of the +/bg and 31% of the bg/bg mice had developed tumors. The beige mice had a higher incidence of epithelial and non‐epithelial tumors arising in cutaneous or subcutaneous sites than the controls. The total incidence of lymphomas was similar in the two groups. However, lymphomas appeared somewhat earlier in beige than in control mice. Altogether 33 +/bg and 27 bg/bg mice were followed for 500 days. By this time, 73% of the +/bg and 78% of the bg/bg mice had developed tumors. The beige group showed a higher incidence of non‐thymic lymphomas than the controls. In contrast, the incidence of thymic lymphoma, cutaneous epithelial tumors and bile‐duct adenomas was similar in the two groups or higher in +/bg than in bg/bg mice. The results suggest that the bg mutation causes a certain defect in a mechanism that may prevent or delay the onset of nonthymic lymphomas and of epithelial and non‐epithelial cutaneous tumors in DMBA‐treated mice. The differences between the two groups were smaller than those previously reported in relation to the increased susceptibility of beige mice to certain transplanted tumors, attributed to the known defect in natural killer (NK) activity in the beige mice. The reduced differential in the DMBA system may be due to the partial reduction of NK activity, induced by the carcinogen, as reported previously (Ehrlich et al., 1980) and confirmed in the present study.
Quantitative studies of natural immunity to solid tumours in rats. NK activity in animals with primary or transplanted spontaneous tumours
Authors: Flannery Graham R. , Brooks Colin G.
Published: February 2007

Natural killer (NK) cell activity was measured in a quantitative 6 h chromium release assay using sarcoma Mc7 cells as targets. The total NK lytic activity present in the spleen and blood of tumour‐bearing animals was compared with the corresponding values for age/sex/ parity‐matched animals. Rats with primary spontaneous tumours in the breast or subcutaneous sites showed normal levels of NK activity, while rats with primary spontaneous kidney tumours had elevated NK activity, the degree of augmentation being greater with increasing tumour size. A similar elevation of NK activity was generally found in animals with large, transplanted, spontaneous or chemically‐induced tumours. This augmentation could only be detected when total lytic activity was considered: when NK activity was measured merely on a cell‐for‐cell basis, it often appeared to be depressed in such animals, in agreement with previous reports. However, with one rapidly metastasizing spontaneous tumour, a real depression of both spleen and blood NK activity was found. Small inocula of cells from non‐immunogenic spontaneous mammary tumours or from other non‐immunogenic spontaneous tumours caused no early increase in systemic NK activity when injected into the mammary pad, a site where spontaneous tumours frequently arise. However, cells from one immunogenic spontaneous tumour and 2/3 immunogenic chemically‐induced tumours did occasionally stimulate significant early increases in NK activity when placed at this site. Early changes in peritoneal exudate NK activity were also investigated using small inocula of these tumours injected intraperitoneally. Augmentation of NK activity occurred with a 3‐fold greater frequency following inoculation with immunogenic tumour cells than with non‐immunogenic cells in this system. It can be concluded from these studies that: (1) spontaneous tumours do not selectively arise in members of an inbred strain with subnormal NK activity; (2) most large tumours in rats stimulate rather than depress NK activity; (3) early boosting of NK activity by small inocula of tumour cells placed in the mammary pad does not occur with non‐immunogenic spontaneous tumours; (4) early boosting of NK activity in the peritoneal site does occur with non‐immunogenic tumours, but with a very low frequency. The latter findings suggest that developing spontaneous tumours are unlikely to stimulate the NK system, and emphasize the importance of using syngeneic, spontaneous tumours for studying tumour‐host relationships in animals.
Heterotransplantation of small‐cell carcinoma of the lung into nude mice: Comparison of intracranial and subcutaneous routes
Authors: Gazdar Adi F. , Carney Desmond N. , Sims Harvie L. , Simmons Alfreda
Published: February 2007

We compared and contrasted intracranial (i.c.) and subcutaneous (s.c.) heterotransplantation of small‐cell carcinoma of the lung (SCCL) into athymic nude mice. Fresh human SCCL tumor specimens, tumor colonies grown in soft agarose and continuous cell lines were used. Tumors induced by the three types of specimens were similar, but s.c. and i.c. transplants differed. S.c. tumors had longer latent times, were non‐invasive and non‐lethal. l.c. tumors had shorter latent periods, invariably grew in the meninges, frequently invaded and destroyed the underlying brain, and were lethal. The tumor‐inducing dose for i.c. transplantation was 10 to 1,000 times lower than for s.c. transplantation. Pooled colonies of SCCL tumor specimens grown in soft agarose were inoculated i.c. While they contained relatively small numbers of cells (400–10,000), 83% of these colony specimens induced tumors after 58–243 days, confirming the «stem‐cell» origin of the colonies. l.c. and s.c. transplants retained the characteristic morphology of SCCL, and, with one exception, did not metastasize to distant organs. Continous cell lines could be established readily from both types of transplants, and they retained the characteristic cytology, growth and biochemical properties of the original SCCL tumors. l.c. heterotransplantation of SCCL is a useful tool, especially when small numbers of tumor cells are available, and may provide a model to study the biology and therapy of meningeal carcinomatosis.
Lysis of fresh human B‐lymphocyte‐derived leukemia cells by interferon‐activated natural killer (NK) cells
Authors: Pattengale Paul K. , Gidlund Magnus , Nilsson Kenneth , Sundstrom Christer , Sallstrom Jan , Simonsson Bengt , Wigzell Hans
Published: February 2007

Fresh neoplastic B cells from 14 untreated patients with naturally occurring B‐cell leukemias were found to be susceptible to lysis by human natural killer (NK) cells. The observed lysis of the fresh, non‐cultured, neoplastic B cells was mediated by a population of interferon‐augmentable, FcR‐positive, non‐adherent lymphoid cells, which were also able to kill the “standard” NK target K562. A further finding was the correlation of NK susceptibility with disease activity in 11 patients with chronic lymphocytic (CLL) and one patient with lymphosarcoma cell leukemia (LSCL). Enriched neoplastic B cells from seven untreated patients with non‐progressive CLL, whose disease activity was stable throughout the 6 month period of study, exhibited persistent and essentially unchanged NK susceptibility profiles. In contrast, four untreated patients with progressive CLL also had a measurable fraction of NK‐susceptible, neoplastic targets, but these cells subsequently disappeared after successful cytoreductive therapy, and later re‐emerged when these patients again developed progressive disease. Furthermore, one patient with LSCL was found to have persistent, measurable NK susceptibility in his tumor‐enriched fraction after unsuccessful cytoreductive therapy. An additional finding in the peripheral blood of patients with chronic B‐cell leukemias was the presence of significantly lower NK effector‐cell activity against K562 as compared to normal donor peripheral blood lymphocytes (PBLs). The implications of these findings are discussed.
The use of three‐dimensional collagen gels for the study of tumour cell invasion in vitro: Experimental parameters influencing cell migration into the gel matrix
Authors: Schor Seth L. , Schor Ana M. , Winn Brian , Rushton Graham
Published: February 2007

We have been using three‐dimensional gels of native collagen fibres as a substratum for the study of cell migratory behaviour. The objective of this work has been to develop an experimental model system for the study of tumour cell invasion. Data are presented in this communication concerning the effects of a number of experimental parameters on the migration of human foreskin fibroblasts (normal) and a Syrian hamster melanoma cell line (tumour) into three‐dimensional gels of native collagen fibres. We find that the migration of both these cell types into the gel matrix is affected by the concentration of collagen in the gel, as well as by the initial density of cells plated onto the gel and the density of cells in the stock culture dishes. These results are discussed in terms of the control of cell migration into the gel and also demonstrate the potential utility of this model system for the study of tumour cell invasion.
A ts T mutant of Schmidt ruppin strain of rous sarcoma virus restricted at 39.5°C for the morphological transformation and the tumorigenicity of chicken embryo fibroblasts
Authors: Poirier F. , Lawrence D. , Vigier P. , Jullien P.
Published: February 2007

In order to investigate a possible correlation beween in vitro transformation and tumorigenicity in ovo, a new temperature‐sensitive class T mutant of Rous Sarcoma Virus was isolated with a lower (39·5C) restrictive temperature for morphological transformation. This lower restrictive temperature was compatible with the survival of chicken and duck eggs for the tumorigenicity studies. In chicken embryo fibroblasts (CEF) infected by this new mutant, PA 17, and cultured at 39·5C, increase of hexose uptake, plasminogen activator production and anchorageindependent growth were only partially restricted, requiring incubation at 41·5C for a complete shut‐off. Tumorigenicity in chicken and duck eggs inoculated with CEF infected and transformed by PA 17 was restricted at 39·5C, correlating well with the restriction of morpholgical transformation at this temperature. The kinase activity of the transforming protein pp in lysates of PA 17 infected cells cultured at permissive or restrictive temperatures was labile in RIPA buffer, as in the case of some previously examined tsT mutants. In the non‐ionic detergent NP40 buffer, the kinase activity of PA 17 infected cell lysates was better conserved and showed a moderate temperature dependence. These results suggest that, in spite of the correlations between the transformed cell phenotype in vitro and cell tumorigenicity in ovo, it is difficult to establish a quantitative relationship.
Detection of Epstein‐Barr viral DNA internal repeats in the nasopharyngeal mucosa of chinese with IgA/ebv‐specific antibodies
Authors: Desgranges C. , Bornkamm G. W. , Zeng Y. , Wang P. C. , Zhu J. S. , Shang M. , De‐Thé G.
Published: February 2007

Fifty‐six South Chinese individuals exhibiting IgA antibodies to EBV for 18 months and presenting naso‐pharyngeal abnormalities were biopsied. Four nasopha‐ryngeal carcinomas, two at a very early stage, were detected. In 14 further individuals, without clinical or his‐topathological evidence of tumor, EBV/DNA internal repeats and/or EBNA were detected in the biopsied mucosae. The presence of IgA/EBV antibodies and/or EBV markers in the nasopharyngeal mucosa may characterize pre‐cancerous conditions.
Serological mass survey for early detection of nasopharyngeal carcinoma in wuzhou city, china
Authors: Zeng Y. , Jan M. G. , Zhang Q. , Zhang L. G. , Li H. Y. , Wu Y. C. , Wang Y. S. , Su G. R.
Published: February 2007

A serological mass survey was carried out in Wuzhou City of the Guangxi Autonomous Region, China. Sera were collected from 12,932 persons between the ages of 40 and 59. The positive rate of VCA/IgA antibody‐positive persons was 5.3%, but no EA/IgA antibody was found in sera from VCA/IgA‐negative persons. Thirteen and nine nasopharyngeal carcinoma (NPC) patients were detected from the VCA/IgA and EA/IgA antibody‐positive persons, respectively. With the present combination method the detection rate of NPC for 12,932 persons was 100.5/100,000 and for 680 VCA/IgA antibody‐positive persons it was 1,900/100,000. Thus, the rate was twice and 37 times higher, respectively, than the annual incidence rate of NPC in persons of the same age group from 1975‐1978 in Wuzhou City. Of 13 NPC patients, 9 were in stage 1(70%) and 4 in stage II (30%). Therefore, it is possible to reduce the mortality rate of NPC in Wuzhou City by radiotherapy of NPC patients in the early stage of the disease. The present results further suggest that EB virus is closely associated with NPC.
Analysis of human genital warts (condylomata acuminata) and other genital tumors for human papillomavirus type 6 DNA
Authors: Gissmann Lutz , De Villiers Ethel‐Michele , Hausen Harald Zur
Published: February 2007

32P‐labelled cloned HPV 6 DNA was used as probe to analyze human genital tumors for DNA sequences homologous to HPV 6 DNA. Ninety three percent of all condylomata acuminata (41 out of 44) were found to harbor HPV 6 DNA. Of the remaining three, one contained HPV 1 DNA. No papillomavirus DNA was identified in the two other tumors. All three invasively growing giant condylomata acuminata (Buschke‐Löwenstein tumors) investigated also contained HPV 6 DNA. Two out of six atypical condylomata of the cervix hybridized with HPV 6 DNA under stringent conditions, one only under conditions of low stringency. All DNA preparations from malignant tumors studied (54 cervical carcinomas, 10 penile carcinomas, two vulvar carcinomas) failed to anneal with HPV 6 DNA, even under conditions of low stringency. Although all HPV 6‐positive condylomata acuminata analyzed in this study revealed HPV 6 DNA of regular molecular weight (5.1 × 106), two of the Buschke‐Löwenstein tumors, as well as one of the two positive atypical condylomata of the cervix, contained HPV 6 DNA with a remarkable size hetergeneity. Apparently all size classes occurred in a supercoiled form without evidence for integration into host cell DNA.
Nasopharyngeal carcinoma in american children: Epstein‐Barr virus‐specific antibody titers and prognosis
Authors: Naegele Robert F. , Champion John , Murphy Sharon , Henle Gertrude , Henle Werner
Published: February 2007

Seven American juvenile patients with undifferentiated or nonkeratinizing nasopharyngeal carcinoma (NPC) were examined serially for Epstein‐Barr virus (EBV)‐specific antibody spectra and titers in sera. At diagnosis, all showed antibody patterns characteristic of NPC: i.e., high titers of IgG antibodies to viral capsid antigen (VCA) and to the diffuse (D) component of the early antigen complex. Six patients had IgA antibodies to VCA, and four to the D component. In the patients who responded to therapy with complete and maintained remissions, the IgG antibodies to D and the IgA antibodies to VCA and D decreased to undetectable levels within 12 to 30 months. By contrast, of the four patients who responded only transiently to therapy, three showed substantial increases and one continuously high titers of IgG anti‐D and IgA anti‐VCA. The increases in antibody titers preceded clinical recognition of recurrent tumors by 1 to 6 months. Three of these patients have died and the fourth is alive with disease. These data indicate that American juvenile NPC does not differ from the adult disease observed anywhere in the world. They reaffirm the potential usefulness of EBV‐specific serology in the diagnosis and prognosis of NPC and the monitoring of patients following therapy.
2′ and 3′ Ribonucleoside monophosphate in leukocytes of acute myeloid leukemia: Markers for early diagnosis of relapse
Authors: Scavennec JoëLle , Cailla Hélène , Gastaut Jean‐Albert , Maraninchi Dominique , Carcassonne Yves
Published: February 2007

Levels of 2′ and 3′ purine and pyrimidine ribonucleoside monophosphates (2′‐, 3′‐NMP) in leukocytes from blood and/or bone marrow were measured in three adult patients with acute non‐lymphoblastic leukemias. The measurements of 2′‐, 3′‐NMP were made by high‐performance liquid chromatography (HPLC) at various times in the course of the disease. Complete remission (CR) was obtained for all three patients but two of these have since died after relapsing at 8 and 9 months, respectively. The third patient remains in CR at 1½ year. The levels of 2′‐, 3′‐NMP in the leukocytes of the patient remaining in remission have not changed since the beginning of his remission. However, in the patients who relapsed 2′‐ and 3′‐NMP levels increased first in bone marrow then in blood leukocytes. These increases occured about 3 months before the relapse was detected by morphological criteria. These data suggest that 2′‐, 3′‐NMP measurements may have a prognostic value if used to monitor patients with acute myeloid leukemia in CR.
Complement‐fixing antibody to epstein‐barr virus soluble antigen in populations at high and low risk for nasopharyngeal carcinoma
Authors: Levine Paul H. , Connelly Roger R. , Mestre Miguel , Ebbesen Peter , Das Saroj , Middleton Moses
Published: February 2007

Greenland Eskimos comprise an ethnic group with one of the highest recorded incidence rates for nasopharyngeal carcinoma in the world. Sera from 625 Eskimos and 73 Danes (Caucasians) living in Greenland, as well as from 62 Danes living in Denmark, were tested for complement‐fixing antibody to Epstein‐Barr virus (EBV) soluble antigen and, from this study group, 129 donors were matched by age and sex for a study comparing antibody to viral capsid antigen, early antigen, and soluble antigen. Both Eskimos and Danes living in Greenland had significantly higher titers of EBV antibodies than Danes living in Denmark, suggesting that environment was more important than genetics or socio‐economic factors in determining the antibody response to EBV. Age and sex were also factors, higher titers occurring in females and young Eskimos.
Evidence that hamster fibroblast tumors emerge in nude mice through the process of two in vivo selections leading to growth factor “relaxation” and to immune resistance
Authors: Pérez‐Rodriguez R. , Franchi A. , Pouysségur J. , Deys B. F.
Published: February 2007

The Chinese hamster lung fibroblast cell line (CCI39), anchorage‐ and highly serum‐dependent for growth, is tumorigenic in nude mice. Tumors arise after 4 to 8 weeks following the inoculation of 5 × 105 cells. We have shown that all the emerging tumoral clones (more than 20 analyzed) have lost the growth factor dependence of the parental cells (Pérez‐Rodriguez et al., 1981 a). To mimic this selection which occurred in vivo, we selected in vitro growth‐factor‐independent variants. These variants, GFI304 and GFI461, can proliferate in a serum‐free medium supplemented with transferrin alone. This character is stable since it is not lost after the GFI variants have been cultivated in non‐selective medium (serum) for more than 20 generations. In spite of their “autonomous” growth and anchorage independence, GFI variants are poorly tumorigenic. The observation of nodule formation and subsequent regression in nude mice, immunosuppressed (irradiation or cyclophosphamide) or not, led us to the conclusion that at least two selections in vivo are required for the tumoral expression of CCI39 cells. One leads to a loss of growth factor requirement, the second towards a resistance to the immune surveillance mechanisms of the nude mice. The 4‐ to 8‐week lag period of tumor formation may be accounted for by the spontaneous emergence in vivo of the two new characters necessary to bypass host growth restraints. This report supports the concept of stepwise progression and clonal evolution of preneoplastic cells in vivo and also indicates that tumorigenicity tests in nude mice should be interpreted with caution.
Monoclonal antibodies to epstein‐barr virus‐induced, transformation‐associated cell surface antigens: Binding patterns and effect upon virus‐specific t‐cell cytotoxicity
Authors: Rowe M. , Rickinson A. B. , Epstein M. A. , Hildreth J. E. K.
Published: February 2007

Spleen cells from mice immunized with Epstein‐Barr virus‐transformed lymphoblastoid cells (EB‐LCL) were used to generate monoclonal antibodies to cell surface antigens associated with the EB virus‐transformed state. Radioimmune and immunofluorescence binding assays identified two antibodies, MHM6 and AC2, which reacted consistently with all EB‐LCL tested, with a subpopulation of cells in some but not all EB virus genome‐positive Burkitt lymphoma lines, but with none of a range of EB virus genome‐negative cell lines of lymphoma or leukaemia origin. While MHM6 appeared to bind an EB virus‐related antigen, AC2 bound some other cell surface antigen which was also found on a small subpopulation of cells in lymphocyte cultures stimulated with phytohaemagglutinin or with pokeweed mitogen. MHM6 and AC2 recognized single polypeptides with apparent molecular weights of 45 kd and 80 kd respectively as shown by sodium dodecylsulphate polyacrylamide gel electrophoresb (SDS‐PAGE) analysis of 125I‐labelled cell surface polypeptides immunoprecipitated with these antibodies. These polypeptides were induced on experimentally‐infected B cells within 24 h of the expression of the EB virus nuclear antigen, EBNA, at a time known to coincide with the appearance of the lymphocyte‐detected membrane antigen, LYDMA. However, saturating concentrations of MHM6 and of AC2 were unable to protect EB‐LCL target cells from lysis by LYDMA‐specific cytotoxic T cells in a chromium‐release assay.
Final case reporting from the ugandan prospective study of the relationship between ebv and burktit's lymphoma
Authors: Geser A. , De Thé G. , Lenoir G. , Day N. E. , Williams E. H.
Published: February 2007

A prospective epidemiological study was carried out in the West Nile District of Uganda from 1972 to 1979 in order to investigate the aetiological role of the Epstein‐Barr virus (EBV) in Burkitt's lymphoma (BL). By 1976, fourteen BL cases had been detected among the 42,000 children originally bled in the study area. Testing of sera from BL candidates and neighbourhood controls showed that children who develop BL later have EBV/VCA titres several dilutions higher than their age‐ and sex‐matched neighbours. This appearance of a strong EBV activity long before BL development was taken as evidence of a causal role of EBV in BL In order to add to the unique material of pre‐bled BL cases, BL detection was continued up to March 1979 when field work became impossible in Uganda. Two additional pre‐bled BL cases were found during this extension of the study. The serological and virological evaluation of these additional cases showed that the EBV/VCA titres, but not the EA and EBNA titres, were about two dilutions higher in the BL candidates than in the controls. Hybridization assays showed that both lymphomas contained EBV/DNA in the tumour cells. These additional results thus confirm the findings in the first 14 cases and strengthen the epidemiological evidence for a causal role of the EBV in endemic BL.
Sera from patients with undifferentiated nasopharyngeal carcinoma contain a factor which abrogates specific epstein‐barr virus antigen‐induced lymphocyte response
Authors: Sundar Syam K. , Ablashi Dharam V. , Kamaraju Lakshmi S. , Levine Paul H. , Faggioni Alberto , Armstrong Gary R. , Menezes José , Pearson Gary R. , Krueger Gerhard R. F. , Bertram G. , Sesterhenn K. , Hewetson John F.
Published: February 2007

A unique association of Epstein‐Barr virus (EBV) with the undifferentiated nasopharyngeal carcinoma (NPC) is a well acknowledged phenomenon. We report here the detection of a factor present in the sera of NPC patients which inhibits the blastogenic response of lymphocytes from EBV seropositive individuals to EB virions or soluble antigens. This lymphocyte‐stimulation inhibitor (LSI) was found to be associated with the IgA fraction of the serum immunoglobulins. No inhibitory activity was detected in the sera and their immunoglobulin fractions from healthy (both EBV‐seropositive and seronegative) individuals and patients with other carcinomas of the head and neck region. Interestingly, the IgA‐LSI was absent in the sera of NPC patients who were successfully treated and remained in remission, while it was readily detectable in the sera of NPC patients in relapse. LSI‐positive IgA fractions did not inhibit mitogenic response of lymphocytes to phytohemagglutinin. Taken together, the data presented suggest that LSI is a specific inhibitor of the response of sensitized lymphocytes to EBV antigens and that it may indeed represent a marker of great clinical significance regarding undifferentiated nasopharyngeal carcinoma, particularly for its prognosis.
Induction or elimination of tumor‐specific immunity against a chemically‐induced rat tumor using auto‐anti‐idiotypic immunity
Authors: Binz Hans , Meier Beat , Wigzell Hans
Published: February 2007

DA rat sarcomas P, and P, were induced by dimethylbenz (a) anthracene. A tumor‐specific immune response of DA rats against P1‐tumor cells could be demonstrated at the humoral and cellular level. DA anti‐P1 antibodies were purified on fixed Prtumor cells and used as autoimmunogen in DA rats for the production of antiidiotypic antibodies. Such antiidiotypic antibodies could be demonstrated by using a solid‐phase radioimmunoassay and by their ability to induce secondary type of DA anti‐P1 responses in vitro. In addition, such antibodies were able to induce cytotoxic T lymphocytes capable of eliminating P1‐tumor cells but not control tumor cells. In some of the auto‐immunized DA rats enhanced P1‐tumor growth could be observed, indicating that the anti‐idiotypic immune response had led to a selective ablation of idiotypic, potential anti‐P1 reactive T cells.
Progression of carcinogen‐induced foci of y‐glutamyltranspeptidase‐positive hepatocytes to hepatomas in rats fed a choline‐deficient diet
Authors: Takahashi Seiichi , Lombardi Benito , Shinozuka Hisashi
Published: February 2007

Following previous findings that feeding a choline‐deficient (CD) diet to rats strongly promotes the evolution of liver cells, initiated by a chemical carcinogen, to foci of y‐glutamyltranspeptidase (yGT)‐positive hepatocytes, we investigated whether a CD diet could also promote the evolution of yGT‐positive foci to hepatomas. yGT‐positive foci were induced in male Sprague‐Dawley rats by administration of a single dose of diethyInitrosamine followed by 2 weeks' feeding on a CD diet containing 0.02% acetylaminofluorene. Immediately thereafter, one group of rats was fed a plain CD diet and the other a choline‐supplemented (CS) diet, and subgroups of animals were killed periodically for analysis of the number and size of yGT‐positive foci and development of hepatomas. During the first 7 weeks after switching the diets, the number and size of the foci increased in both groups. At 12 and 16 weeks, the number and size of foci began to decline in rats fed the CS diet However, in the CD group, there was a progressive increase in the size with coalescence of the foci, as well as development of neoplastic nodules. These lesions were followed at 20 and 28 weeks by development of hepatomas at a high incidence rate. In rats fed the CS diet, a few scattered yGT‐positive foci, and small neoplastic nodules remained in the liver at 20 and 28 weeks, but no hepatomas developed. These results show that the CD diet is a potent promoter of the evolution of foci of altered hepatocytes to hepatomas, and that most of the yGT‐positive foci are reversible lesions.
Lymphotoxin enhances the susceptibility of neoplastic and preneoplastic cells to natural killer cell mediated destruction
Authors: Ransom Janet H. , Evans Charles H.
Published: February 2007

Treatment of neoplastic guinea‐pig cells for 1‐14 days with 300 units of guinea‐pig lymphotoxin/ml medium enhanced 2‐ to 5‐fold their susceptibility to natural killer (NK) cell‐mediated cytotoxicity as measured by 4 h 51Cr and 72 h [3H]thymidine‐release assays. The NK susceptibility of human neoplastic and guinea‐pig non‐neoplastic cells refractory to guinea‐pig lymphotoxin growth‐inhibitory activity was unchanged after lymphotoxin treatment. Lymphotoxin preparations were free of detectable interferon and the enhancing activity copurified with lymphotoxin during diafiltration and isoelectric focusing. Treatment of NK cells with lymphotoxin preparations also augmented NK‐mediated lysis but that activity did not copurify with lymphotoxin. As with neoplastic cells, lymphotoxin‐sensitive preneoplastic cells previously treated with ultraviolet light, a chemical carcinogen, or carcinogen and the tumor‐promoting agent tetradecanoyl‐phorbol‐acetate also exhibited lymphotoxin enhancement to NK‐cell destruction. Thus, the immunologk hormone lymphotoxin enhances the susceptibility of lymphotoxin‐sensitive cells to NK‐cell destruction, indicating that these two natural immune mediators, lymphotoxin and NK cells, have the potential in concert to regulate carcinogenesis and neoplastic growth.
Dissection of the antigenic determinants expressed on the cell surface of rsv‐transformed fibroblasts by monoclonal antibodies
Authors: Ferracini Riccardo , Prat Maria , Comoglio Paolo M.
Published: February 2007

Fusion of P3/X63‐Ag8 mouse myeloma cells with splenocytes obtained from mice hyperimmunized with a BHK hamster fibroblast line transformed by an envstrain of Rous sarcoma virus (RSV) resulted in the production of antibody‐secreting hybridomas. Seven hybrid clones secreted antibodies binding to RSV‐transformed BHK fibroblasts but not to the parental control non‐transformed line. The antibodies produced by three of these clones did identify antigenic determinants expressed also on BHK cells transformed by SV40. The antibodies produced by four other clones reacted specifically with cells transformed by RSV but not with cells productively infected by the transformation‐defective Rous‐associated virus‐1; one of these reacted with RSV‐transformed hamster cells only, three others identified antigenic determinants common to RSV‐ transformed cells of different animal species. These data give further support to the idea that RSV‐transformed cells express a cell‐surface antigen, specific for transformation, the expression of which is controlled by the transforming src gene, and that the specificities carried on it follow a complex pattern, arising from the interaction between antigenic determinants of cellular and viral origin.
Cellular mechanisms underlying the adjuvant activity of Candida albicans in a mouse lymphoma model
Authors: Marconi P. , Tissi L. , Baccarini M. , Bistoni F. , Cassone A. , Garaci E. , Puccetti P. , Bonmassar E.
Published: February 2007

Inactivated Candida albicans (CA) possesses strong anti‐tumor activity when combined with cytoreductive chemotherapy in a mouse lymphoma model. In the present study, experiments were performed in order to elucidate the mechanism(s) underlying CA immunoadjuvant activity. In vivo chemotherapy studies proved that the synergistic anti‐tumor effects were lost in athymic (nu/nu) mice and were also abrogated by radiations. In vitro tests did not suggest a major involvement of natural cytotoxic effectors such as macrophages and natural killer cells nor did CA effects appear to be mediated by induction of interferon. It was concluded that the immunoadjuvant activity of CA largely relies on host responses against tumor‐associated transplantation antigens with no major involvement of natural resistance immune mechanisms.
Establishment and characterization of a human myeloma cell line (KMM‐1)
Authors: Togawa Atsushi , Inoue Nobumasa , Hyodo Huminori , Namba Masayoshi , Miyamoto Kanji
Published: February 2007

A new cell line (KMM‐1) was established from a subcutaneous plasmacytoma of a 62‐year‐old male with multiple myeloma. Immunological studies indicated that cultured cells were derived from the same clone of myeloma cells in vivo: smeared cells were stained with fluoresceinconjugated globulin of antisera monospecific to lambdachain, and lambda‐chains in the cell extracts and in culture media were identical to the Bence‐Jones protein found in the patient's urine. The cell line grew in suspension with a doubling time of 36‐40 h and contained primitive plasmablastoid cells with prominent nucleoli and rough endoplasmic reticulum. Cells had the karyotype of 47, X, ‐Y. lq+, ‐2, +t(1:2) (cen:cen), +7, 12q+, 14q+, +mar and carried no Epstein‐Barr virus‐determined nuclear antigen. Surface markers were as follows; E rosette (‐), IgG Fc receptor (‐), C3 receptor (‐), S‐lg (+), TdT (‐), asialo‐GM, (‐). The reasons for the successful establishment of the myeloma cell line are discussed.
Intra‐uterine exposure to saccharine and risk of bladder cancer in man
Authors: Jensen O. M. , Kamby C.
Published: February 2007

Animal experiments show that rats fed saccharine are more likely to develop bladder tumours if they have been exposed to saccharine in utero through their mothers' food. The risk of bladder tumours in humans following in utero exposure to saccharine has not been evaluated previously. In Denmark the use of saccharine increased sharply during the second World War as a result of scarcity of sugar, and import and export figures indicate that saccharine consumption was on average 4‐5 times higher during the war‐time period than in the pre‐war decade. The risk of bladder tumours at ages 20‐34 was 1.0 (95% confidence interval 0.7‐1.6) among men born in 1941‐1945 compared with men born 1931‐1940. Among women the risk was 0.3 (0.1‐1.0). This study provides no evidence of an increased risk of human bladder cancer during the first 30‐35 years of life associated with in utero saccharine exposure.
Detection of a human melanoma‐associated antigen, p97, in histological sections of primary human melanomas
Authors: Garrigues H. J. , Tilgen W. , Hellstrōm I. , Franke W. , Hellstroum K. E.
Published: February 2007

The unlabelled antibody technique of Sternberger was used to study the localization in histological sections of human melanoma‐associated antigen p97, which is defined by a monoclonal antibody. The antigen was detected in 8 of 10 primary skin melanomas, in 6 of 7 metastatic melanomas and in 2 of 2 compound nevi. It was localized at the cell surface, the cytoplasm and the nucleus always being negative. The antigen was not seen in cells from 3 basal cell carcinomas, I squamous cell carcinoma, I leiomyosarcoma, or in samples of normal skin (including keratinocytes, connective tissue consisting of collagenous and elastic fibers, fibroblasts, sebaceous glands, blood vessels, smooth muscles, or inflammatory cells such as granulocytes, lymphocytes and macrophages), kidney or lung. There was, however, staining of some cells in the secretory segment of eccrine sweat glands from 2 patients, possibly corresponding to myoepithelial cells. Antigen expression was somewhat variable between cells from different melanomas as well as between individual cells from the same melanoma. The possible diagnostic value of this procedure for identification and classification of melanomas is discussed.