bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of the Epstein‐Barr virus encoded EBNA‐I gene in stably transfected human and murine cell lines
Authors: Patel Geeta V. , Masucci Maria Grazia , Winberg Gösta , Klein George
Published: February 2007

Five murine and 3 human tumor cell lines were transfected with a retroviral vector that carries the EBV encoded EBNA‐I gene. All cell lines expressed intranuclear EBNA‐I as detected by anticomplement immunofluorexence and Western blot assays. The cell lines differed in the level of EBNA‐I expression and the size of the protein. The internal major late promoter of adenovirus was efficient in directing the transcription of EBNA‐I in the human lymphoma line BJAB, the murine T‐cell lymphoma Tikaut, RBL‐S, EL‐4 and in the mouse sarcoma line MSWBS but was less efficient in Ramos, an EBV negative Burkitt lymphoma line, the human T‐cell leukemia line 1301TK and the P815‐X2 mouse mastocytoma line. All transfected lines except MSWBS contained EBNA‐I in a truncated form. The truncated EBNA‐I polypeptide reacted with the conventional human antibody reagents in an EBNA specific fashion but failed to bind rabbit or human antibody directed against the glycine‐alanine repeat sequence. MSWBS contained a truncated as well as a full size EBNA‐I polypeptide. It also reacted with antibody directed against the glycinealanine repeat. This indicates that the repeat sequence is regularly affected by the truncation.
Comparative study of plasminogen activator antigens in colonic carcinomas and adenomas
Authors: Suzumiya Junji , Hasui Yoshihiro , Kohga Shin , Sumiyoshi Akinobu , Hashida Seiichi , Ishikawa Eiji
Published: February 2007

The correlation between malignant transformation and increased PA synthesis or secretion has been examined in a variety of cell lines. To study the relationship between content and composition of PAs and colorectal neoplasms, we measured u‐PA and t‐PA antigen levels in normal mucosa, tubular adenoma, adenocarcinoma in adenoma, and adenocarcinoma, using a sensitive sandwich enzyme immunoassay. This assay was very sensitive and was not hindered by the presence of serine protease inhibitors. Both adenomas and carcinomas had higher u‐PA antigen levels than normal mucosa. The u‐PA antigen level of adenomas was lower than that of carcinomas. Antigen level of t‐PA, however, was lower in both adenomas and carcinomas compared with that in normal mucosa, the values being lowest in carcinomas. Two cases of carcinoma in adenoma had PA contents similar to those of carcinomas. u‐PA antigen level of adenomas with dysplastic epithelium was higher than that of adenomas without dysplastic epithelium. Therefore, the increase of u‐PA content in adenomas could be a parameter of malignant changes in adenomas.
Phenotypic variability of cultured rat hepatoma cell population in respect to alpha‐fetoprotein synthesis
Authors: Eraiser T. L. , Khamzina L. S.
Published: February 2007

McA‐RH 7777 hepatoma cells were cloned on 2 occasions a week apart (test cloning). Alpha‐fetoprotein (AFP) phenotypes of primary and secondary clones from 55 primary clones were estimated. High interclonal heterogeneity of AFP expression was demonstrated. This variability exceeded by several orders of magnitude the mutation rate. We also found intraclonal differences in rates of variability. A “stabilizing” cloning was also carried out, aiming at the selection of AFP+ and AFP− stable cell lines. Stabilizing cloning included 7 cycles of cloning and selection of the most phenotypically stable clone. This stability was shown to be incomplete during the maintenance of clones in culture.
Immunochemical characterization of adenocarcinoma‐associated antigen yh206
Authors: Hinoda Yuji , Imai Kohzoh , Ban Toshihiro , Endo Takao , Yachi Akira
Published: February 2007

The antigen recognized by MAb YH206 is mainly expressed in adenocarcinomas and is also detected in the sera of cancer patients (Hinoda et al., 1987). This antigen (antigen YH206) was chemically characterized and purified by column chromatography. SDS‐PAGE analysis revealed a broad component in the high‐molecular‐weight range which was clearly detectable by carbohydrate (PAS) but not by protein (silver) stain. Agarose gel electrophoresis and immunoblotting of antigen YH206 indicated that it consists of a high‐molecular‐weight component (more than 2,000 kDa). Treatment of antigen YH206 with alkali suggested that the antigenic determinant consists of carbohydrate chains of mucin type. Density gradient ultracentrifugation revealed that the activity of antigen YH206 is localized at a density of 1.45 g/ml, suggesting that antigen YH206 is a mucin. Neuraminidase treatment of antigen YH206 indicated that the epitope is cryptic and contains an asialocarbohydrate chain. Once antigen YH206 has been purified by affinity chromatography, neither CA 19‐9 antigen nor DU‐PAN‐II antigen can be detected, although they were present at very high levels in the crude ascitic starting material; these last two are representative carbohydrate antigens which are widely used for serodiagnosis to detect adenocarcinomas.
The changing incidence of cancer in adults in New South Wales
Authors: McCredie Margaret , Coates Marylon S. , Ford Joyce M.
Published: February 2007

Data from the New South Wales (NSW) Central Cancer Registry comprising all new cases of cancer registered in persons aged I 5 years and over for the 10‐year period 1973 to 1982 were examined using log‐linear regression to determine whether the incidence of cancer had been changing in NSW. Allowing for the altered age and sex structure of the population over this period, the annual incidence rate for all sites combined increased significantly by 1.7% in men and 1.0% in women. Cancers which had increased at a rate significantly greater than that for all sites combined were those of unknown primary site (8.7% per year), lung (in women only, 5.6%), kidney (4.5%), bladder (2.7%) and rectum (2.6%) and lymphomas (2.6%). Other cancers which showed a significantly increased incidence rate per se were testis (3.5%), larynx (3.2%), prostate (2.1%), colon (1.7%), brain (1.6%), leukaemias (1.3%) and lung (in men only, 0.7%). Cancers which had decreased significantly in incidence were those of oesophagus ( −2.2%), cervix uteri ( −2.0%) and stomach ( −1.4%). No significant change in incidence over the 10 years had occurred for cancers of the corpus uteri, breast, ovary or pancreas.
Epstein‐barr virus‐positive recipient type B‐cells survive in a “complete chimera” after allogeneic bone‐marrow transplantation
Authors: Gerhartz Heinrich H. , Mittermüller Johann , Raghavachar Anand , Schmetzer Helga , Clemmi Christof , Kolb Hans‐J. , Bartram Claus C. , Wolf Hans
Published: February 2007

Latency of Epstein‐Barr virus infection may be generated by surviving immortalized B cells or by continuous re‐infection. EBV‐positive B‐cell tumors have been found following bone‐marrow transplantation (BMT) and were of donor type in the few cases investigated. We established a B‐cell line from the bone marrow of a patient in complete remission following allogeneic BMT for aplastic anemia 18 months post‐grafting. Differences in sex and isoenzymes allowed an exact determination of chimerism in our case. While the patient showed persistent complete chimerism of all cell lineages, cells grown in culture were of recipient type. They expressed B‐cell markers, showed a monoclonal rearrangement of the immunoglobulin genes and carried EBV‐associated antigens. As direct preparations of cells from the patient did not contain detectable recipient‐type cells, it appeared likely that small numbers of EBV‐transformed B cells of the recipient survived for long periods in this patient. For the development of secondary B‐cell neoplasms in vivo, additional patho‐physiological steps like severe graft versus host disease or T‐cell suppression are obviously required because the patient was still free of lyrnphoma 3 years post‐grafting.
Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: Relevance for early detection of ovarian cancer
Authors: Zurawski Vincent R. , Orjaseter Harald , Andersen Aage , Jellum Egil
Published: February 2007

To investigate the sensitivity of the CA 125 immunoradiometric assay for occult ovarian neoplasia, serum CA 125 levels were retrospectively determined “blind” in specimens collected from 105 women who subsequently developed ovarian neoplasia, and from 323 matched controls. The distribution of CA 125 levels was very different between the case and control populations (p = 0.0001) over the entire collection‐to‐diagnosis interval (range 1–143 months). Median CA 125 levels for all cases, and for those collected more than 24, 36 or even 60 months prior to diagnosis, were always 18 U/ml or greater, compared with a median of 10.9 U/ml for controls. Half of the cases collected within the 18 months preceding diagnosis had CA 125 levels of more than 30 U/ml and one‐third had levels greater than 65 U/ml. About one‐fourth of those collected prior to 60 months before diagnosis had levels above 30 U/ml. In contrast, approximately 7% and 0.9% of controls had levels in excess of 30 or 65 U/ml, respectively. Elevations occurred in cases eventually diagnosed with localized or advanced cancer, and with borderline or obviously malignant disease. These results provide an insight into the preclinical biology of ovarian neoplasia that may help in designing methods for early detection of this disease, and demonstrate the usefulness of the JANUS serum bank as a resource in evaluating serum tests.
Comparative studies on the expression of tumor‐associated glycoprotein (TAG‐72), CA 19‐9 and DU‐pan‐2 in normal, benign and malignant pancreatic tissue
Authors: Takasaki Hideaki , Tempero Margaret A. , Uchida Eiji , Büchler Markus , Ness Marsha J. , Burnett David A. , Metzgar Richard S. , Colcher David , Schlom Jeffrey , Pour Parviz M.
Published: February 2007

Expression of tumor‐associated glycoprotein (TAG‐72) was examined by immunohistochemistry in pancreatic specimens from normal donors, and from patients with chronic pancreatitis and pancreatic cancer, and was compared with expression of CA 19‐9 and DU‐PAN‐2. In the normal pancreas, TAG‐72 was expressed in fewer ductal and ductular cells than were CA 19‐9 (p < 0.05) and DU‐PAN‐2 (P < 0.01 and 0.001 respectively), whereas in chronic pancreatitis all 3 antigens were expressed in ductal cells but only CA 19‐9 and DU‐PAN‐2 in ductular cells (p <0.001). In the specimens from normal pancreas and chronic pancreatitis cases, TAG‐72 was localized in the Golgi region, whereas CA 19‐9 and DU‐PAN‐2 showed diffuse cytoplasmic and glycocalyx patterns. In pancreatic cancer, although the rate of expression of all 3 antigens was similar, their cellular localization differed significantly: only TAG‐72 was expressed in the Golgi region (p < 0.001), whereas CA 19‐9 showed mainly glycocalyx (p < 0.05) and/or intra‐luminal patterns (p <0.01) compared with that of the other 2 antigens. We conclude that, due to differences in expression of TAG‐72 in benign versus malignant cells, the monoclonal antibody against TAG‐72 (B72.3) may be suitable for radioimmunodetection or radio‐immunotherapy of pancreatic cancer.
c‐fos proto‐oncogene expression in human NK/LGL cells: Expression is not constitutive and is associated with functional activation
Authors: Colotta Francesco , Polentarutti Nadia , Pirelli Anna , Dibello Maria , Allavena Paola , Mantovani Alberto
Published: February 2007

Unlike mature myeloid and monocytic cells and cell lines committed to terminal myelomonocytic differentiation, highly purified preparations of human natural killer cells/large granular lymphocytes (NK/LGL) did not spontaneously express the c‐fos proto‐oncogene. Transient expression of c‐fos in NK/LGL was associated with functional activation with IL‐2, IFN‐γ, LPS and PMA, which increased their cytotoxic activity, lymphokine secretion and in vitro chemotaxis. These results, together with the finding that T‐cell receptor genes are in germ‐line configuration in the vast majority of peripheral blood NK/LGL, are compatible with the hypothesis that these cells represent a separate hematopoietic lineage.
Relations between ph, oxygen partial pressure and growth in cultured cell spheroids
Authors: Carlsson Jörgen , Acker Helmut
Published: February 2007

The PH gradients, oxygen partial‐pressure gradients and growth curves were measured for 7 different types of spheroids. Growth curves were measured in liquid overlay culture and thereafter the spheroids were attached to cover glasses and transferred to a chamber for micro‐electrode measurements. The spheroids were randomly divided for PH or pO2 measurements which then were made under conditions as identical as possible. The decreases in pO2 and pH, ΔpO2 and ΔPH were calculated as the difference between the values in the culture medium and the values 200 μm inside the spheroids. Each type of spheroid had a certain relation between ΔpO2 and ΔpH. The human colon carcinoma HT29, the mouse mammary carcinoma EMT6 and the hamster lung V79‐379A spheroids had high values of the quotient ΔpO2/ΔpH. The human thyroid carcinoma HTh7 spheroids and the 3 types of human glioma spheroids had lower quotients. There was a tendency for fast‐growing spheroids to have high quotients. Two extreme types of spheroids, HT29 (high quotient) and UII8 MG (Iow quotient) were analyzed for lactate production and oxygen consumption. The U‐II8 MG spheroids produced about 3 times more lactate and consumed about 3 times less oxygen than the HT29 spheroids. The differences in lactate production could not be explained by differences in the pyruvate Km values of lactate dehydrogenase. The results indicate that there are significant metabolic differences between the spheroid systems studied.
Increased formation of unintegrated viral DNA in skin fibroblasts from patients with familial polyposis coli shortly after infection with kirsten murine sarcoma virus
Authors: Miyaki Michiko , Tanaka Kiyoko , Sato Chicko , Akamatsu Noriko , Mori Takeo , Tsuchida Nobuo
Published: February 2007

Skin fibroblasts from patients with familial polyposis coli (FPC) exhibit increased frequency of morphological transformation, anchorage‐independent growth, and enhanced production of viral RNA and viral particles after infection with murine sarcoma virus(murine leukemia virus), MSV(MLV). These FPC fibroblasts form greater amounts of unintegrated viral DNA as compared to normal fibroblasts during the first 4 to 24 hr after infection with Kirsten MSV(KiMLV), suggesting that increased susceptibility of FPC cells to MSV is determined at an early stage of viral transformation. Several MSV‐transformed clones of both FPC and normal fibroblasts, isolated from agarose gel, were non‐producers having integrated viral genome which was expressed into viral RNA and rescued by infection with MLV.
The role of polymorphonuclear leukocytes (PMN) on the growth and metastatic potential of 13762nf mammary adenocarcinoma cells
Authors: Aeed Paul A. , Nakajima Motowo , Welch Danny R.
Published: February 2007

Circulating neutrophil (PMN) levels can increase in rats bearing subcutaneously growing clones of the 13762NF mammary adenocarcinoma and the level of increase correlates with the metastatic potential of the clone. In rats with poorly metastatic MTC tumors, numbers of circulating PMN did not rise, whereas PMN levels rose 50‐fold in rats bearing highly metastatic MTLn3, 12‐fold in rats with weakly metastatic MTLn2, and 14‐fold in those with moderately metastatic MTF7 tumors. Neutrophilia was caused partly by tumor size, but metastatic potential was a stronger determinant, suggesting that PMNs may play a role in the metastatic process. To determine whether circulating PMNs indeed contribute to cellular metastatic potential, we examined effects of PMN on various aspects of the metastatic process. Experimental metastasis assays involving i. v. co‐injections of PMNs yielded a dose‐dependent increase in extrapulmonary metastases for MTLn3, but no change in lung colonization potential for any of the clones examined. The change in the metastatic profile was not due to any modification in in vivo distribution of i. v. injected tumor cells or in adhesion to endothelial monolayers in vitro. PMNs also had no effect on in vitro DNA, RNA or protein synthesis and were not cytolytic (E:T 100: I). However, PMNs collected from high‐passage MTLn3 tumor‐bearing rats had a 50% increase in heparanase and type‐IV collagenolytic activity as compared to unstimulated PMNs isolated from normal rats. These results indicate that polymorphonuclear cells may contribute to the metastatic potential of highly metastatic clones from the 13762NF mammary adenocarcinoma cells by assisting in the degradation of basement membrane during extravasation.
Expression of the c‐Ha‐ras and neu oncogenes in DMBA‐induced, anti‐estrogen‐treated rat mammary tumors
Authors: Vuorio Tuula , Wärri Anni , Sandberg Minna , Alitalo Kari , Vuorio Eero
Published: February 2007

Dimethylbenzanthracene (DMBA)‐induced rat mammary tumors were analyzed for the structure and expression of the oncogenes c‐Ha‐ras and neu and the effects of anti‐estrogen treatment. Tumor samples were divided into 3 groups, the first consisting of untreated tumors, the second of anti‐estrogen (toremifene)‐treated unresponsive (growing) tumors, and the third of toremifene‐treated responsive (regressing) tumors. DNA and RNA derived from normal tissues of the same experimental animals were also analyzed. In Southern blot analysis of genomic DNAs, 2 tumors out of 23 contained new Xbal site in the Ha‐ras gene, indicating a point mutation in the second nucleotide of codon 61. Both of these tumors belonged to the group that had not received toremifene. No amplifications of the Ha‐ras or the neu genes were observed. Although greatly variable, the levels of Ha‐ras mRNA were highest in untreated tumors, lower in toremifene‐treated, unresponsive tumors and even lower in toremifene‐treated, regressing tumors, corresponding approximately to the levels detected in normal liver and uterus of untreated animals. Expression of the neu mRNA was variable and considerably lower than that of Ha‐ras mRNA. It was similar in all 3 groups and somewhat elevated than in several non‐malignant control tissues. Localization of c‐Ha‐ras expression by in situ hybridization revealed a relatively even distribution of the mRNA throughout the mammary tissue. The results suggest that mechanisms other than activation of the c‐Ha‐ras or neu genes are important for progression and regression of DMBA‐induced rat mammary carcinomas.
Effects of recombinant human tumor necrosis factor‐α on the surface phenotype and the growth of human malignant glioma cell lines
Authors: Zuber P. , Accolla R. S. , Carrel S. , Diserens A. C. , de Tribolet N.
Published: February 2007

Human malignant glioma cell lines and clones were incubated with various concentrations of recombinant human TNF‐α, either alone or in combination with recombinant human IFN‐γ. The surface expression of HLA‐ABC (class I) antigens and β2‐microglobulin, was significantly enhanced by TNF‐α alone on every cell line and clone tested. After incubation with both TNF‐α and IFN‐γ, the surface expression of HLA‐ABC antigens was only slightly higher than that observed with each cytokine alone. In contrast to IFN‐γ, TNF‐α had no effect on the surface expression of HLA‐DR (class II) antigens. Moreover, the surface expression of HLA‐DR induced by IFN‐γ was unaffected by TNF‐α. The increased expression of HLA‐ABC antigens after treatment with TNF‐α or IFN‐γ correlated with increased levels of HLA‐ABC‐specific mRNA. In addition, TNF‐α, like IFN‐γ, selectively enhanced the surface expression of a tumor‐associated antigen, Me14‐D12, while it had no effect on the expression of various other surface antigens. In the absence of actinomycin D, TNF‐α exhibited no direct cytotoxic/cytostatic effect on the glioma cell lines tested. These results indicate that TNF‐α can enhance the surface expression of HLA‐ABC antigens on human glioma cells in the absence of a direct cytotoxic/cytostatic effect.
Utilization of human hematopoietic cell lines for the propagation and characterization of HBLV (human herpesvirus 6)
Authors: Ablashi Dharam V. , Lusso Paolo , Hung Chia‐Ling , Salahuddin S. Zaki , Josephs Steven F. , Llana Ted , Kramarsky Bernhard , Biberfeld Peter , Markham Phillip D. , Gallo Robert C.
Published: February 2007

Details of the productive infection of established human cell lines of diverse origin by HBLV (also designated Human Herpesvirus 6) are described in this report. The infection and replication of HBLV in several T and B lymphoid and other cell lines was observed by electron microscopic examination, by the detection of viral antigen expression by indirect immunofluorescence assay (IFA) and by the presence of HBLV DNA by Southern blot hybridization. Several of these cell lines produced large amounts of virus. For this reason and because of the absence of other human herpesviruses, these lines have provided a valuable resource for the preparation of reagents and the development of assays for the detection and characterization of HBLV. The isolation and characterization of new HBLV isolates from patients with chronic fatigue syndrome were also facilitated by using some of the cell lines reported here. The host range of HBLV in established cell lines, therefore, does not appear to be limited to the B lymphocytes, as initially suggested by in vivo studies. The infection of T and B lymphocytes, megakaryocytes and neuronal cells in vitro suggests a need for the evaluation of diverse hematological and neurological disorders to shed light on a possible HBLV involvement.
Monoclonal antibodies against doxorubicin
Authors: Balsari Andrea , Alzani Rachele , Parrello Daniele , Morelli Daniele , Tagliabue Elda , Gianni Luca , Isetta Anna Maria , Menard Sylvie , Colnaghi Maria Ines , Ghione Mario
Published: February 2007

Hybridomas which secrete monoclonal antibodies (MAbs) reacting with doxorubicin (DXR), a widely used anthracycline cytotoxic antibiotic, have been obtained by fusing NSO/P3 mouse myeloma cells with spleen cells from BALB/c mice immunized with DXR‐BSA conjugate. The best producer among the several clones obtained was expanded and the secreted MAb (MAD2) purified and characterized. MAD2 cross‐reacts to varying degrees with anthracycline compounds such as some DXR analogues and derivatives, but does not recognize anthracene and anthraquinone structures, with the exception of weakly reacting Mitoxantrone. MAD2 and the panel of MAbs which are at present being purified may become a tool for studying the relevance of different domains of the anthracyclin molecule in terms of biologic activity.
Possible role of certain antioxidant enzymes in dimethy lnitrosamine‐induced liver carcinogenesis
Authors: Liotti F. S. , Menghini A. R. , Guerrieri P. , Mariucci G. , Locci P. , Bruschelli G.
Published: February 2007

An investigation was carried out to establish whether the reduction in catalase, glutathione peroxidase and superoxide dismutase activity, normally observed in liver tumours, is an early event and therefore of pathogenetic importance, or whether it is a late occurrence. Experiments performed on dimethylnitrosamine‐treated hepatectomized and non‐hepatectomized rats show that the decrease in activity of these enzymes is entirely due to hepatectomy, since the tumourinducing doses of dimethylnitrosamine failed to provoke variations in the activity of these enzymes, in either normal or regenerating liver.
Immunophenotypic similarities of mediastinal clear‐cell lymphoma and sinusoidal (monocytoid) b cells
Authors: Möller Peter , Matthaei‐Maurer D. Ulrike , Hofmann Walter J. , Dörken Bernd , Moldenhauer Gerhard
Published: February 2007

Using 14 well‐defined (clustered) monoclonal antibodies (MAbs) against B‐cell restricted/associated differentiation and activation (CD) antigens and 12 mediastinal clear‐cell lymphomas (MCCL), 46 follicular‐center‐cell lymphomas (FCCL), and 20 non‐neoplastic lymph nodes—including toxoplasmic and HIV‐associated lymphadenitis—were immunohistochemically examined to determine the histogenesis of MCCL. Antigenically, MCCL was characterized as CD5−, CD10−, CD19+, CD20+, CD21−, CD22+, CD30−, CD37+, CDw40+, and by a frequent expression of CD11c and CD23, while other antigens were inconsistently expressed. The antigenic profiles of MCCL and FCCL showed statistically significant differences in 4/14 distinct antigens. When the neoplastic cells of both tumor groups were compared with morphologically defined normal B‐cell types, the overall resemblance of their immunophenotypes was even closer between MCCL and sinusoidal (monocytoid) B cells than between FCCL and follicular‐center B cells. We conclude that MCCL is a lymphoma type distinct from FCCL, most probably representing a highly malignant neoplasm corresponding to sinusoidal B‐cell reaction.
Elevated cerebrospinal fluid fibronectin concentration at diagnosis indicates poor prognosis in children with acute lymphoblastic leukemia
Authors: Rautonen Jukka , Koskiniemi Marjaleena , Siimes Martti A. , Salonen Eeva‐Marjatta , Vaheri Antti
Published: February 2007

We investigated whether the concentration of fibronectin (FN) in the cerebrospinal fluid (CSF) could be used for identifying patients with subclinical blast‐cell infiltration in the central nervous system (CNS) and an increased risk of CNS relapse later in the course of their leukemia. Our series comprised 36 children with newly diagnosed acute lymphoblastic leukemia (ALL). The mean follow‐up time was 54 months (range 5 to 96 months). The median concentration of CSF‐FN at diagnosis was 2.24 mg/l (range 0.78 to 7.04 mg/l). The 3‐year continuous complete remission rate for the 16 patients with CSF‐FN concentrations <2mg/l was 93% as compared with 37% for the 19 patients with CSF‐FN >2mg/l (p = 0.001). When multivariate analysis was performed, the CSF‐FN concentration retained its prognostic significance. When all relapses were considered as failures, the relative risks of relapse for patients with CSF‐FN <2mg/l and >2mg/l were I and 15.8 (95% confidence limits 1.8‐135.6, p<0.02), respectively. If only CNS relapses (isolated and combined) were considered as failures, relative risks for the above‐mentioned groups were I and 11.6 (1.4‐99.5, p<0.05), respectively. We conclude that determination of the CSF‐FN concentration may provide a new means of evaluating the CSF in children with ALL and may prove to be a sensitive indicator of leukemic CNS infiltration.
Detection of iga antibodies against human papillomavirus in cervical secretions from patients with cervical intraepithelial neoplasia
Authors: Dillner Lena , Bekassy Zolian , Jonsson Nils , Moreno‐Lopez Jorge , Blomberg Jonas
Published: February 2007

Although human papillomavirus (HPV) is involved in the etiology of cervical carcinoma, there are no cervical carcinoma‐specific HPV serologic tests available. We investigated the presence of broadly cross‐reactive IgA antibodies to papillomavirus (PV) in cervico‐vaginal secretions from patients with condylomata and cervical intraepithelial neoplasia (CIN). Purified bovine PV (BPV) virions were used as antigen in an enzyme‐linked immunosorbent assay (ELISA). Forty‐two women whose ages ranged from 20 to 50 participated in the study. Eight of 9 patients with CIN had IgA antibodies against PV in their cervical secretions. Three of 9 patients with koilocytosis and condylomas but no CIN had IgA antibodies to PV. Six of 24 women with normal Pap‐smear and colposcopy also had IgA antibodies against PV in their cervical secretions. The proportion of IgA‐positive cervical secretions was significantly higher in the CIN group than in the normal group (p<0.005). Our data suggest that IgA antibodies to PV may be a useful marker for CIN.
Epstein‐barr virus‐infected b cells persist in the circulation of acyclovir‐treated virus carriers
Authors: Yao Q. Y. , Ogan P. , Rowe M. , Wood M. , Rickinson A. B.
Published: February 2007

In this study, infectious Epstein‐Barr virus (EBV) shedding in the oropharynx and numbers of virus‐infected B cells in the blood have been monitored in long‐term virus carriers receiving acyclovir (ACV) therapy for herpes zoster. Eleven patients on oral ACV were followed prospectively before, during and for 2 weeks after treatment. As expected, the low levels of EBV shedding in these virus carriers (measured as cord‐blood lymphocyte transforming activity in throat washings) were eliminated during the period of ACV treatment and returned at later times. Over the same period, however, the frequency of virus‐infected B cells in the blood (measured by spontaneous transformation in limiting dilution assay) remained completely unchanged. Regression assays showed that these same patients had normal levels of EBV‐specific cytotoxic T‐cell immunity, so that the in vivo persistence of virus‐infected B cells could not be ascribed to a defect in T‐cell surveillance. We infer that the in vivo half‐life of the virus‐infected B‐cell pool in long‐term virus carriers is measured in months rather than days. We further suggest that such persistence requires a novel form of virus: B‐cell interaction distinct from the type of “latent” infection displayed by in vitro‐transformed cells.
Glycosphingolipids in lectin‐resistant variants of mouse lewis lung carcinoma cells
Authors: Ugorski Maciej , Påhlsson Peter , Dus Danuta , Nilsson Bo
Published: February 2007

Neutral glycolipids and gangliosides from murine Lewis lung carcinoma cell line LL2 and its lectin‐resistant variants, differing in metastatic properties, were studied by fast‐atom‐bombardment mass spectrometry (FAB‐MS), exoglycosidase treatment and an immunostaining procedure. The neutral glycolipids identified in all cell lines studied included CMH, CDH, CTH, asialo GM2, globoside and a glycolipid with a preliminary structure of Hex‐Hexl‐4HexNAc‐Hex‐Hex‐Cer. The major gangliosides were GM3, GM2, GM1 and GD1a. No qualitative differences in glycosphingolipid expression were found between the metastatic cell lines (LL2 and LL2AAA) and the weakly metastatic variants (LL25, LL28, LL230 and LL2RCA II). Some quantitative differences were observed between the cell lines, e.g., in the level of ganglioside‐bound sialic acid, which was not apparently correlated with the metastatic capacities.
Inhibition of experimental metastasis of murine fibrosarcoma cells by oligopeptide analogues to the fibronectin cell‐binding site
Authors: Bretti Sergio , Neri Paolo , Lozzi Luisa , Rustici Mauro , Comojlio Paolo , Giancotti Filippo , Tarone Guido
Published: February 2007

We have analyzed the effect of the synthetic oligopeptides Gly‐Arg‐Gly‐Asp‐Ser‐Pro (GRGDSP) and Gly‐Arg‐Gly‐Glu‐Ser‐Pro (GRGESP), analogues to the fibronectin cell‐binding sequence, on the formation of experimental lung metastasis. SR‐BALB were injected alone or in conjunction with GRGDSP or GRGESP in the tail vein of BALB/c mice. Co‐injection with GRGESP reduced by approximately 70% the number of metastatic colonies per mouse. However, co‐injection with the closely related peptide GRGDSP, containing the conservative substitution Glu/Asp, did not affect metastatic behavior. GRGESP peptide anti‐metastatic activity was not due to a toxic effect on tumor cells or on mice. In vitro adhesion assays testing for a possible effect of the peptide on cell‐matrix interactions indicated that the GRGESP peptide did not affect cell adhesion to the matrix proteins tested.
Hyposialylation of high‐molecular‐weight membrane glycoproteins parallels the loss of metastatic potential in wheat‐germ agglutinin‐resistant friend leukemia cells
Authors: Benedetto A. , Elia G. , Sala A. , Belardeli F.
Published: February 2007

From the highly metastatic in vivo‐passaged Friend leukemia cells (FLC), WGA‐resistant (WR) tumor cell variants were selected. These WR FLC had lost their capacity to metastasize when injected i.v. or s.c. into DBA/2 mice. We have characterized the plasma membrane glycoproteins of the different FLC types by: (i) metabolic labelling with (3H)‐galactose; (ii) surface labelling with galactose oxidase‐borohydride; (iii) direct binding of (125l)‐lectins on glycoproteins separated by SDS‐PAGE. The ensemble of these approaches showed that the 100‐ to 200‐kDa glycoproteins of in vivo‐passaged FLC and WR FLC exhibited a very similar distribution of the terminal galactose in their oligosaccharide moieties. In contrast, the expression of terminal sialic acid was reduced in WR FLC with respect to in vivo‐passaged counterparts as appreciated by: (i) binding experiments with (125l)‐WGA; (ii) cathodic shift of the 100‐ to 200‐kDa glycoproteins in 2‐dimensional electrophoresis studies, and (iii) thiobarbituric acid assay after FLC treatment with neuraminidase. Moreover, binding experiments with (125l)‐LPHA, (125l)‐ConA and (125l)‐WGA (after Smith degradation) indicated that, in the 100‐to 200‐kDa region, virtually identical asparagine‐linked tri‐ or tetra‐antennary complex‐type oligosaccharides were expressed in both cell types. We conclude that the sialylation of high‐molecular‐weight surface glycoproteins (particularly in the 150‐kDa region) is strongly associated with the metastatic potential of FLC, especially to the liver.
Characterization of a metastasis‐deficient lectin‐resistant human melanoma mutant
Authors: Ishikawa M. , Kerbel R. S.
Published: February 2007

A mutant (3S5), almost completely deficient in pulmonary metastatic ability in nude mice, was recently isolated from a human malignant melanoma cell line (MeWo). The WGA‐resistance (WGA) phenotype of 3S5 cells was accompanied by a collateral hypersensitivity to the lectin BSII (Bandeiraea simplicifolia), similar to that observed previously in class‐I non‐metastatic WGAr recessive genetic mutants isolated from a highly metastatic mouse tumor. The lectin‐resistance/sensitivity profile of 355 cells was completely stable in tissue culture for 9 months when the cells were grown in the absence of WGA. Twenty independent clones of 3S5 were analyzed and all manifested a similar lectin‐resistance pattern, and severe deficiency in pulmonary metastatic ability following i.v. or s.c. inoculation, when compared to the parent MeWo cells. Some heterogeneity in metastasis was noted, especially with respect to occasional extrapulmonary spread. The majority of the small number of metastases obtained after i.v. inoculation of 3S5 cells maintained the lectin‐resistance profile and deficient metastatic potential characteristic of 3S5 cells upon re‐inoculation into other nude mice. The results provide further evidence that cell‐surface glycosylation changes can significantly alter metastatic potential, including that of human tumors.
Plasminogen activator and its enhancement in differentiating mouse friend erythroleukemia cells
Authors: Amici Carla , Benedetto Arrigo , Saksela Olli , Salonen Eeva‐Marjatta , Vaheri Antti
Published: February 2007

Urokinase‐type plasminogen activator (u‐PA) activity was found in the medium as well as in the lysates of cultured uninduced Friend leukemia (FL) cells. PA activity progressively increased during the cell differentiation induced by dimethyl sulphoxide (DMSO), 4‐hydroxy‐3‐methoxybenzaldehyde or hypoxanthine. Both the differentiation and the enhancement of PA activity in cultures of DMSO‐induced cells were blocked by treating the cells with 1 μM dexamethasone. A highly significant correlation (rs = 0.93) was found between the number of hemoglobinized cells and the rate of PA secretion, indicating that the increase in PA activity coincides with late events of the differentiation process. FL cells specifically adhere to fibronectin‐coated surfaces but tend to lose this property during the differentiation process. Anti‐u‐PA IgG antibodies promoted the attachment of differentiating cells to fibronectin‐coated surfaces, suggesting that u‐PA plays a role in the detachment of FL cells from fibronectin immobilized on the growth substratum.
A monoclonal antibody (Bl2‐10D1) reacting with a bladder‐cancer‐associated antigen
Authors: Longin A. , Hijazi A. , Berger‐Dutrieux N. , Escourrou G. , Bouvier R. , Richer G. , Mironneau I. , Fontaniere B. , Devonec M. , Laurent J. C.
Published: February 2007

A hybridoma cell line secreting an IgM monoclonal antibody (MAb) was produced after immunizing a mouse with RT4 cells and a crude suspension of human bladder carcinoma cells (WHO grades II and III TCC). This MAb reacted with RT4 target cells derived from a human transitional bladder cancer but failed to react with a majority of non‐bladder cancer cell lines. Immunohistological studies indicate that this MAb reacts inconstantly with normal bladder: in positive cases only a few superficial cells (5% to 10% umbrella cells) are stained but not intermediate or basal cells of the urothelium. This MAb was evaluated on 118 tumors: it reacted with tumor tissue in a majority of grade 1 (79.5%) and grade II papillary TCC (77.3%), less with grade III papillary TCC (45%) and very rarely with invasive non‐papillary TCC (14%). In cases of flat lesions a strong reactivity of superficial, intermediate and/or basal layer cells was observed in 50% of moderate and severe dysplasia and in all cell layers of carcinomas in situ (CIS)(9/9).
Type of alcoholic beverage and oral cancer
Authors: Kabat Geoffrey C. , Wynder Ernst L.
Published: February 2007

The effect on oral cancer risk of different types of alcoholic beverage was investigated using data from a hospital‐based case‐control study. Owing to the small numbers of subjects drinking one beverage exclusively, it was necessary to classify drinkers as consumers of predominantly beer, wine, or hard liquor (i.e., more than 50% of their whiskey equivalents of alcohol derived from a specific beverage). The number of predominantly wine drinkers was too small to permit analysis. Logistic regression was used to obtain estimates of the risk associated with each predominant beverage, with adjustment for other risk factors and confounding variables. In males, the odds ratio for predominantly beer drinkers increased with increasing level of intake, reaching 4.87 (95% confidence interval: 2.51–9.46) in drinkers of 7 + oz. of whiskey equivalents/day. The odds ratio for predominantly hard liquor drinkers showed a similar increase, reaching 5.74 (95% confidence interval: 2.94–11.22) in predominantly hard liquor drinkers consuming 7+ oz. of whiskey equivalents/day, suggesting that the effect of these 2 major types of alcoholic beverage is of similar magnitude. The trends were less clearcut in women due to small numbers of drinkers.
Abrogated NK‐cell lysis of human papillomavirus (HPV)‐16‐bearing keratinocytes in patients with pre‐cancerous and cancerous HPV‐induced anogenital lesions
Authors: Malejczyk Jacek , Majewski Slawomir , Jablonska Stefania , Rogozinski Tomasz T. , Orth Gerard
Published: February 2007

Natural‐cell‐mediated cytotoxicity against K‐562 erythroleukemic cells and human papillomavirus (HPV)‐16 harboring Sk‐v keratinocytes was tested in 38 age‐ and sex‐matched healthy volunteers and in patients with HPV‐induced benign and malignant anogenital lesions: 9 persons with HPV‐16‐induced bowenoid papulosis (BP), 8 with anogenital carcinomas (5 with HPV‐16‐ or 33‐associated squamous‐cell carcinomas of Bowen's type and 3 with HPV‐6‐associated Buschke‐Loewenstein verrucous carcinomas) and 12 with HPV‐6‐induced condylomata acuminata. Both K‐562 and Sk‐v cells were killed by a non‐adherent CD16+ subset of PBMC as revealed by cell fractionation on the basis of their adherence to plastic and by treatment with Leu‐IIb monoclonal antibody (MAb) and complement. “Cold” target competitive assays demonstrated that both cell types inhibited lysis of labelled Sk‐v cells. In patients with BP and anogenital carcinomas induced by HPV‐16 or 33, there was a significant (at least at p < 0.01) decrease of Sk‐v cell lysis as compared with the healthy control group. Anti‐K‐562 activity was not affected. In patients with anogenital carcinomas the degree of Sk‐v lysis was decreased in proportion to the duration of lesions (correlation coefficient–r = ‐0.79). Neither anti‐K‐562 nor anti‐Sk‐v cytotoxicities were significantly affected in patients with condylomata and with HPV‐6 associated verrucous carcinomas. Short‐term (3 hr) pre‐incubation of normal PBMC with sera from patients with BP and HPV‐16‐associated anogenital carcinomas resulted in significant inhibition of their ability to lyse Sk‐v cells. Lysis of K‐562 cells remained unaffected. In patients with carcinomas, the suppressive effect of sera was associated with a lowering of the ability of their PBMC to lyse Sk‐v cells (r = ‐0.79). In patients with longer tumor persistence, the suppressive effect of serum was proportionally higher (r = 0.86).
An anti‐CD5 immunotoxin for chronic lymphocytic leukemia: Enhancement of cytotoxicity with human serum albumin‐monensin
Authors: Hertler Andrew A. , Schlossman David M. , Borowitz Michael J. , Blythman Hildur E. , Casellas Pierre , Frankel Arthur E.
Published: February 2007

Five patients with B‐cell chronic lymphocytic leukemia (B‐CLL) were treated with 6 courses of the anti‐CD5 immunotoxin T101‐ricin A chain (T101‐RTA). Each course consisted of 8 bi‐weekly infusions of T101‐RTA (7 or 14 mg/m2). The immunotoxin was well tolerated in all cases with no major toxicities. Though saturation of circulating leukemic cell‐associated target antigen was demonstrated by FACS analysis in all patients, no intact immunotoxin was detected in bonemarrow or lymph‐node aspirates. Pharmacokinetic studies revealed rapid clearance of T101‐RTA, with a half‐life of 43 min. None of the patients developed detectable titers of antibody against either T101 murine antibody or ricin A chain. Clinical response was limited to a rapid and transient fall in WBC count lasting less than 24 hr, most likely secondary to the antibody portion of the conjugate. In vitro, fresh B‐CLL cells were resistant to T101‐RTA at concentrations up to 10−8M, while fresh malignant T‐cells with a 10‐fold increase in expression of CD5 antigen were sensitive. In the presence of the enhancing agent human serum albumin‐monensin, fresh B‐CLL cells were sensitive to T101‐RTA, with an ID50 more than 2 logs below the maximal concentration of immunotoxin achieved in vivo. We conclude that T101‐RTA is a potentially useful agent in the treatment of T‐cell leukemias. In the presence of HSA‐monensin, this spectrum of activity may be extended to B‐CLL.
Screening for breast cancer in nijmegen. report of 6 screening rounds, 1975–1986
Authors: Peeters P. H. M. , Verbeek A. L. M. , Hendriks J. H. C. L. , Van Bon M. J. H.
Published: February 2007

A population‐based screening programme for breast cancer was initiated in Nijmegen in 1975 with mammography as the only screening procedure. Up to January 1987, 6 screening rounds were carried out with a 2‐year screening interval. Rates of attendance, referral, biopsy and detection were calculated and numbers of interval cancers are presented in order to give a clear view of what repeated screening can accomplish in a population. At the first screening round the attendance rate was 87% for women under age 50 and 83% for women aged 50–64. For women aged 65 or over the initial attendance rate was 40%. Rates of attendance declined in subsequent years. Detection rates were highest for elderly women at their first examination: 9.5 per 1,000 screened women. Corresponding rates were 5.6 and 2.3 per 1,000 for women aged 50–64 and below 50 respectively. The positive predictive value for referral was, on average, 20% for women under age 50 and 50% for elderly women, although a sharp increase was seen in the last 2 screening examinations for all age‐groups. Predictive values for biopsy were higher: 30% on average for women aged under 50 and 60%–70% for elderly women, again with a sharp increase in the last 2 screening rounds. Interval cancer rates, calculated as the number of cancers occurring within 2 years among negatively screened women at risk, showed no particular trend and varied between 0.9–1.3 per 1,000 woman‐years after each screening round. Compared to screen‐detected cancers, interval cancers occurred more frequently in younger women. In women under age 50, the ratio between screen‐detected and interval cancer was about 1:1, while it was about 2:1 for elderly women.
Sequential therapy with recombinant interferons gamma and alpha in patients with unfavorable prognosis of chronic myelocytic leukemia: Clinical responsiveness to recombinant ifn‐α correlates with the degree of receptor down‐regulation
Authors: Bartsch H. H. , Pfizenmaier K. , Hanusch A. , Scheurich P. , Ücer U. , Nagel G. A.
Published: February 2007

Natural and recombinant interferons (IFNs) have already demonstrated therapeutic efficacy, including cytogenetic remissions, in patients with chronic myelocytic leukemia (CML). We investigated at the level of ligand‐receptor interaction the question whether heterogeneity of receptor number or affinity might contribute to primary or secondary treatment failures in CML. We therefore analyzed IFN‐γ and IFN‐α receptor expression and regulation during treatment with recombinant IFN‐γ and IFN‐α in 15 patients with advanced CML. We found no difference in number or affinity of constitutively expressed IFN‐γ receptors (mean 1,100) and, on average, a 30% reduction of IFN‐α receptors (mean 750) on peripheral blood mononuclear cells (PBMNC) of patients with chronic or accelerated CML as compared to mature granulocytes and/or bone marrow cells of healthy controls, which express on average 1,050 and 1,100 IFN‐γ and IFN‐α receptors, respectively. While IFN‐γ receptor expression on PBMNC is not influenced upon treatment with rIFN‐γ, there is a substantial downregulation of IFN‐α receptors in the course of rIFN‐α therapy. Our data also show a differential pattern of receptor down‐regulation between patients achieving complete hematologic remission (CHR) (4 out of 12) compared with patients with partial hematologic remission (PHR) and non‐responders. We conclude that differences in IFN receptor number cannot explain primary or secondary treatment failures. However, the differential ligand induced downregulation of IFN‐α receptors in patients achieving CHR compared to those with PHR or non‐responders suggest a prospective value of IFN‐α receptor determination.
Combined oral contraceptives and liver cancer
Authors: Molina Ramiro , Martinez Luis , Salas Oriana , Dabancens Aifredo , Yun Tao , Zhi‐Heng Chen , Yong‐Wei Hu , Cuadros Alvaro , Aristizabal Nubia , Modan Baruch , Ron Elaine , Alfandary Esther , Mati J. G. , Kenya Patrick , Kungu Alfred , Gatei D. , Ibeziako Patrick A. , Abioye A. A. , Junaid T. A. , Aghadiuno Patrick U. , Apelo Ruben A. , De LaCruz Julietta R. , Baens Jose , Canlas Benjamin D. , Silpisornkosol Suporn , Pardthaisong Tieng , Sivasomboom Boonlong , Theetranont Choti , Boosiri Banpot , Chutivongse Supawat , Virutamasen Pramuan , Wongsrichanalai Chansuda , Sindhvananda Sermsri , Koetsawang Suporn , Rachawat Duangdao , Kiriwat Orawan , Chantarakul Nivat , Anthony P. P. , Thomas David B. , Stanford Janet L. , Ray Roberta M. , Noonan Elizabeth A. , Holck Susan
Published: February 2007

A multi‐national, hospital‐based, case‐control study was conducted to evaluate the possible relationships of steroid contraceptives to 6 neoplasms. Based on data from 122 newly diagnosed cases of primary liver cancer and 802 matched controls, the relative risk of liver cancer in women who had ever used combined oral contraceptives was estimated to be 0.71 (95% Cl 0.4–1.2). No consistent trend in risk with months of use or time since first or last use was observed. Separate analyses also revealed no association between use of combined oral contraceptives and hepatocellular carcinoma (RR = 0.60) or cholangiocarcinoma (RR = 1.22). Most women in this study came from areas in which hepatitis B is endemic and rates of liver cancer are relatively high, and in most cases use of oral contraceptives was of short duration. These results provide no evidence that short‐term use of oral contraceptives enhances risk of liver cancer in countries where the determinants of this disease are similar to those observed in the countries where this study was conducted.