bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in the tumorigenic and metastatic properties of tumor cells treated with quercetin or 5‐azacytidine
Authors: Ishikawa Makoto , Okada Futoshi , Hamada Jun‐Ichi , Hosokawa Masuo , Kobayashi Hiroshi 
Published: February 2007

AbstractThe effect of quercetin, a flavonoid derivative, on the transplantability (tumorigenicity) and metastatic behavior of mouse tumor cells was studied. BMT‐11 cl‐9 fibrosarcoma cells were treated in vitro with quercetin, and after cloning by limiting dilution, cell suspensions of each clone were injected subcuta‐neously (s.c.) into syngeneic C57BL/6 mice at a dose of 2 × 105 cells per mouse. Out of 17 clones examined, 8 were nontumorigenic in normal mice (“regressor” clones), whereas these clones were able to grow in immunosuppressed (600‐rad‐irradiated) mice. Furthermore, 1 out of 9 tumorigenic clones metastasized spontaneously to the lungs despite the very low metastatic potential of the parent BMT‐11 cl‐9 cells. In contrast, all 15 clones selected from the untreated parental line grew progressively in normal mice with no evidence of metastases. The appearance of both regressor and metastatic clones was also observed after treatment with a DNA hypomethylating agent, 5‐azacytidine. These altered phenotypes resulting from treatment with both chemicals, however, were not necessarily stable if maintained in culture for several months. The data suggest that quercetin may be a useful new material for obtaining regressor or metastatic clones from parental tumor lines.
Transformation‐related changes in the expression of endogenous cell lectins
Authors: Raz Avraham , Meromsky Leonid , Zvibel Isabel , Lotan Reuben 
Published: February 2007

AbstractEndogenous lectins purified from UV‐2237‐IP3 murine fibrosarcoma cells by affinity chromatography consisted of two polypeptide species of Mr 14,500 (L‐14.5) and Mr 34,000 (L‐34). Antibodies against this material immunoprecipitated the lectins from cells radiolabelled on the cell surface as well as in the cytoplasmic compartment. Similar analyses of normal rat embryonal fibroblasts revealed the presence of only the L‐14.5. In contrast, both L‐14.5 and L‐34 were found in oncogenetransfected, immortalized cell clones derived from the normal rat cells, as well as in untransformed BALB/c‐3T3 clone A31 and its descendant subclones selected for expression of the transformed, the tumorigenic and the metastatic phenotypes. Among the cells constituting the latter system, a marked increase in the amount of cellular and cell‐surface lectins was observed upon progression to the metastatic phenotype. These results suggest that the expression of endogenous tumor‐cell‐surface lectins is associated with transformation and metastasis.
Lack of fibronectin‐binding plasma membrane proteins may explain defective pericellular matrix formation in transformed fibroblasts and fibrosarcoma cells
Authors: Virtanen Ismo , Lehto Veli‐Pekka , Vartio Tapio 
Published: February 2007

AbstractAffinity of iodinated fibronectin (Fn) and its defined proteolytic fragments to electrophoretically separated polypeptides of normal and malignant cells was studied in an overlay assay. Cellular 125I‐Fn and a major 125I‐Fn fragment (Mr 120,000 ‐ 140,000), containing the cell‐binding site, revealed in fibroblasts Mr 170,000, Mr 140,000, and Mr 47,000 Fn‐binding polypeptides of which the first two could also be found in the plasma membrane preparations. Binding of 125I‐Fns to Mr 170,000 and Mr 140,000 polypeptides was inhibited by the synthetic peptide Arg‐Gly‐Asp‐Ser and to all 3 polypeptides by Fns and Mr 120,000‐140,000 fibronectin fragment. Both fibrosarcoma cells and SV40‐virus‐transformed fibroblasts appeared to lack the Mr 140,000 Fn‐binding polypeptide. Binding was similar when Fn from normal fibroblasts or fibrosarcoma cells was used in the assay, while plasma 125I‐Fn had weaker affinity towards the Mr 140,000 polypeptide. Instead, proteolytic Fn‐fragments, lacking the cell binding site, did not bind to any proteins in the assay. Radioactive cell‐surface labelling showed differences in the corresponding surface polypeptide profiles of normal and malignant cells. The results suggest that the failure of pericellular matrix deposition in malignant cells could be due to either defective surface exposition or defective binding property of the Fn‐receptor‐like polypeptides.
Thrombin stimulates arachidonate metabolism in murine tumor cells
Authors: Lampugnani Maria Grazia , Donati Maria Benedetta 
Published: February 2007

AbstractThrombin can be formed in the tumor cell microenvironment following activation of the clotting cascade by procoagulants of cancer or host cells. We have tested here the effects of thrombin, either “endogenous” or “exogenous” (see below), on arachidonate mobilization from membrane phospholipids of mouse mammary tumor virus‐induced (MMTV) carcinoma cells. These tumor cells exhibit in vitro a tissue type procoagulant activity (130 thromboplastin units/10cells) and are therefore able to induce thrombin formation in a plasmatic milieu.To verify the effect of thrombin formation by tumor cell procoagulant (“endogenous thrombin”), either human or mouse platelet‐free plasma (20% in DMEM) was added to the cell layer (prelabelled for 5 hr with a trace amount (0.013 μm) of H‐arachidonate) and the system was recalcified (15 mm CaCl2). Thin‐layer radiochromatography of the culture medium showed a significant release of H‐labelled arachidonate products PGE2, PGF2α and 6‐ketoPGFIα after 1 hr of incubation.To verify the effect of thrombin formation from host sources (“exogenous thrombin”), either bovine or purified human α‐thrombin (0.1–10 U/ml) was added to the cells for different periods (from 5 min to 20 hr). Exogenous thrombin stimulated arachidonate release and metabolism in a dose‐related manner. With short labelling periods (0.013 μm H‐arachidonate for 30 min‐1 hr) thrombin stimulated the release of unmetabolized H‐arachidonate, but not of H‐arachidonate metabolites. These processes were inhibited by a specific inhibitor of thrombin enzymatic activity (α‐NAPAP, 140 μm) and by a cyclo‐oxygenase inhibitor (ASA 4mm). Tumor‐associated procoagulants may thus contribute not only to fibrin deposition but also to generation of multipotent mediators such as arachidonate metabolites.
Cytogenetic studies on B‐cell leukemias of akr origin
Authors: Trakhtenbrot Luba , Peled Alpha , Haran‐Ghera Nechama 
Published: February 2007

AbstractThe karyotype of B‐cell leukemias of AKR origin was studied by G‐banding. In contrast to previous observations indicating trisomy of chromosome 15 in spontaneous and chemically‐induced B‐cell leukemias, 11 out of 15 tumors analyzed had normal diploid karyotypes. Four tumors with the modal number 39‐41 had different chromosome markers specific for each tumor. The possible correlation between non‐random chromosomal changes and the target cell involved in the initial transformation in AKR leukemogenesis is discussed.
Transformation sensitivity in early S‐phase and clonogenic potential are target‐cell characteristics in liver carcinogenesis by n‐methyl‐N‐nitrosourea
Authors: Maguire S. , Rabes H. M. 
Published: February 2007

AbstractChanges in the transformation sensitivity of hepatocytes during the cell cycle were in relation to clonogenicity investigated in partially resected rat liver. The hourly rate of the G1‐S transit was measured in a control group by means of tritium‐labelled thymidine (H‐TdR). At defined periods after partial hepatectomy the animals were injected with a single dose of N‐methyl‐N‐nitrosourea (MNU) (25mg/kg) and subsequently exposed to phenobarbital (0.05% in the diet) for 80 days. ATPase‐deficient cell populations which arise by clonal growth (Rabes et al., 1982) were determined in the liver 90 days after MNU treatment and served as a marker for the initiating action of the carcinogen. The number of foci appeared to be related to the hourly rate of influx of hepatocytes into DNA synthesis at the time of MNU administration. Few foci were observed after MNU exposure in G1 and their frequency increased steeply when MNU treatment coincided with the first peak of cellular G1‐S transit. As the rate of influx into S‐phase decreased, so did the number of foci, despite the proportion of cells in S‐phase still being at a maximum. The possibility of a gradient of clonogenicity existing within the cells of the liver lobule is envisaged. It is suggested that proliferative cells of the peri‐portal region, which begin DNA synthesis early after partial hepatectomy, have the greatest ability to form clones of ATPase‐deficient putative pre‐neoplastic foci after initiation by a carcinogen and might thus represent, if exposed to carcinogen in early S‐phase, the effective target cell population for the induction of hepatocellular carcinomas.
EBV‐transformed lymphoblastoid cell lines down‐regulate ebna in parallel with secretory differentiation
Authors: Wendel‐Hansen Vidar , Rosén Anders , Klein George 
Published: February 2007

AbstractFour monoclonal and one polyclonal lymphoblastoid cell line (LCL) were studied with regard to cytoplasmic immunoglobulin (clg) expression, presence of the Epstein‐Barr virus (EBV)‐determined nuclear antigen (EBNA) and DNA synthesis. Each line was found to consist of two subpopulations, with only minimal overlap. Proliferating, EBNA‐positive, clg‐negative cells formed the majority. The minority were EBNA‐negative, contained abundant clg and were largely non‐proliferating. This suggests the continuous occurrence of a maturation process within each LCL. The concomitant downregulation of EBNA raises the interesting question whether continued synthesis of the nuclear antigen is incompatible with differentiation for epigenetic reasons, or, alternatively, whether differentiation takes place when the viral genomes are suppressed or lost.
Increased therapeutic efficacy of CIS‐platinum complexes of poly‐L‐glutamic acid against a murine carcinoma
Authors: Schechter B. , Wilchek M. , Arnon R. 
Published: February 2007

AbstractCis‐diamminedichloroplatinum(II) (cis‐DDP) and cis diamminediaquoplatinum(II) nitrate (cis‐aq) were complexed to poly‐L‐glutamic acid (PG) of Mr 13,000 or 58,000. Soluble complexes were formed by mixing the platinum(II) compounds with the PG preparations in water at a molar ratio of one platinum(II) to 5 glutamyl residues of the PG. Compared to free cis‐DDP, the complexes were about 2 to 6 times less cytotoxic to F9 embryonal carcinoma cells in vitro. In vivo studies with this tumor indicated that when administered i.p. one day after the tumor cells, the complexes were somewhat less active than cis‐DDP. However, in comparison to the free drug which, due to its toxicity, was effective only within a very narrow dose range, the complexes were much less toxic, manifesting a wide therapeutic range in which no mortality occurred either from the tumor or as a result of the toxic effects of the drug. Cis‐DDP and cis‐aq complexes of PG Mr‐58,000 were somewhat more toxic than the complexes of PG Mr, 13,000. The in vivo anti‐tumor activity of most complexes was superior to that of free cis‐DDP when tested in mice carrying high tumor loads. Due to their wide therapeutic range, the complexes could be given at high drug doses resulting in increased life span of the tumor‐bearing mice. Moreover, 3 repeated injections of these high doses did not cause death from toxicity and resulted in partial or total eradication of advanced tumors.
A line of non‐tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth
Authors: Bennett Dorothy C. , Cooper Philip J. , Hart Ian R. 
Published: February 2007

AbstractAn immortal line of pigmented melanocytes, “melan‐a”, has been derived from normal epidermal melanoblasts from embryos of inbred C57BL mice. The conditions favouring proliferation of these cells largely resemble those for normal, non‐established mouse melanoblasts and melanocytes, and include a low extracellular pH and the presence of a tumour promoter, tetradecanoyl phorbol acetate (TPA) or teleocidin. Melan‐a cells have the diploid chromosome number and do not form tumours in syngeneic or nude mice. They are therefore the first known line of non‐tumorigenic mouse melanocytes, although an aneuploid melanocyte line of untested tumorigenicity has been reported (Sato et al., 1985). Melan‐a cells are syngeneic with the B16 melanoma and its sublines, and provide an excellent parallel non‐tumorigenic line for studies of the cellular and molecular basis of melanoma malignancy.
Use of oral contraceptives and risk of invasive cervical cancer in previously screened women
Authors: Ebeling K. , Nischan P. , Schindler Ch. 
Published: February 2007

AbstractWithin the context of a larger hospital‐based case‐control study carried out to assess the efficacy of cervical cancer screening, the possible association between oral contraceptives and risk of invasive cervical cancer has been studied as well. Because in the GDR cytological screening is an integral part of the gynaecological basic care, only a few women reported oral contraceptive use but had no Pap‐smears in that study. Thus, the analysis was confined to those 129 cases and 275 controls who had at least one screening Pap‐smear in their history and were below the age 55. The significantly increased relative risks for users decreased after adjustment for factors of sexual behaviour and interval since last Pap‐smear but remained statistically significant or at borderline significance for some categories of usage. This concerns, in particular, long‐term use (7+ years) and early onset of use (⩽ 24 years) with relative risks of 1.8 and 3.0, respectively.
Comparison of circulating mam‐6 and cea levels and correlation with the estrogen receptor in patients with breast cancer
Authors: Hilkens J. , Bonfrer J. M. G. , Kroezen V. , Van Eykeren M. , Nooyen W. , De Jong‐Bakker M. , Bruning P. F. 
Published: February 2007

AbstractMAM‐6 and CEA serum levels of 136 staged breast cancer patients were determined concomitantly. The sensitivities of the MAM‐6 assay using monoclonal antibody (MAb) II5D8 and a polyclonal CEA assay were equally low and only a limited number of patients with early stages of breast cancer showed elevated antigen levels. However, the sensitivity rose to 75% for MAM‐6 and to 60% for CEA in stage‐IV patients. The levels of both antigens correlated well in the sera of these patients, although MAM‐6 serum levels were elevated more frequently, while only in a few cases were MAM‐6‐negative sera CEA‐positive. A group of stage‐II breast cancer patients who eventually developed distant metastases was followed in a longitudinal study. Tumor progression or regression was clinically determined and compared with the MAM‐6 and CEA serum levels in order to establish the value of each assay for the monitoring of breast cancer. The course of the disease correlated significantly better with changes in MAM‐6 antigen levels than with changes in CEA levels (p<0.05), being 79% and 42% respectively. The lower correlation of CEA levels with the course of the disease was mainly due to a lower sensitivity of the CEA assay for advanced breast cancer. The specificity of changing MAM‐6 and CEA levels was not significantly different. The main advantage of the MAM‐6 assay over the CEA assay is the higher sensitivity of the former. In a preliminary study among stage‐IV patients a correlation was found between elevated MAM‐6 levels and the presence of the estrogen receptor in the primary tumor.
Analysis of the results of the micronucleus test in patients presenting upper digestive tract cancers and in non‐cancerous subjects
Authors: Mandard A. M. , Duigou F. , Marnay J. , Ph.‐Masson  , Qiu‐Song‐Lang  , Yi‐Jing‐Shu  , Barrellier P. , Lebigot G. 
Published: February 2007

AbstractA micronucleus test was performed on 75 subjects of whom 38 presented with cancer of the upper digestive tract and 37 were free of disease; the absence of cancerous or pre‐cancerous lesions in this latter group was confirmed by endoscopy and vital staining. The daily levels of alcohol and tobacco consumption of the 75 subjects were determined by precise questioning: 78% of the non‐cancerous subjects smoked less than 10 g of tobacco per day whereas 79% of the cancer patients smoked 10 g or more daily. The alcohol intake of 78% of the non‐cancerous subjects and 63% of the cancer patients was less than 101 ml per day. Only 10% of the cancer patients had combined daily intake levels corresponding to the threshold of sensitivity of the micronucleus test as defined by previous studies. The mean frequency of micronucleated buccal cells was 0.26% in the cancer patients and 0.13% in the non‐cancerous subjects. All non‐cancerous patients presented a negative test. Only 5% of the cancer patients presented a micronucleated cell frequency above 1% and could thus be considered as positive. It thus appears that the micronucleus test was not significantly positive in our population of 38 cancer patients.
Characterization of a murine monoclonal‐antibody‐defined B‐lymphocyte carcinoma cross‐reacting antigen (BLCa) from nasopharyngeal carcinoma tissues
Authors: Yip T. C. , Chan K. H. , Choy Damon , Chan C. W. , Ng M. H. 
Published: February 2007

AbstractBiopsies were obtained from 12 patients suspected of having nasopharyngeal carcinoma (NPC). A portion of the tissue was submitted for histopathology and another for Western blotting using a murine monoclonal antibody (MAb), MA6. Touch smears of the tissues were also prepared immediately prior to extraction and Western blotting for immunoenzymic staining. The results showed that a B‐lymphocyte carcinoma cross‐reacting antigen (BLCa), or an antigen similar to it, was the major antigen in the tumor tissue recognized by MA6. The antigen was detected in tissues from 8 patients, of whom 7 had confirmed NPC and one had eskimoma, but not in tissue from the remaining 4 patients who did not have histologically confirmed malignancy. Immunocytology showed that tumour cells were present in the touch smears from all but one of the tumour patients but not in the other patients, and that the tumour cells comprised the large majority of the MA6‐reactive cell population. The other MA6‐reactive cell types present included certain weakly reactive epithelial cells and occasional lymphoid cells, presumably B lymphocytes. However, these cell types were similarly distributed between the tissues obtained from patients with or without malignant diseases. It was concluded, therefore, that the tumour cells in these tissues are the principal source of BLCa and, as such, the antigen may constitute an objective and reliable marker of NPC.
Characterization of a human B‐lymphocyte carcinoma cross‐reacting antigen (BLCa) in B lymphocytes identified by two murine monoclonal antibodies
Authors: Yip T. C. , Chan K. H. , Ng M. H. 
Published: February 2007

AbstractThe murine monoclonal antibody (MAb) MA6 is selectively reactive against a large variety of human B lymphocytes including those in early stages of B‐cell differentiation such as committed progenitors of B lymphocytes, pre‐B lymphocytes, Burkitt lymphoma cells, and those at later stages of differentiation such as peripheral blood B lymphocytes and myeloma cells. The major antigen identified by this antibody on such B lymphocytes (BLCa) is a 55‐kDa glycoprotein or a group of similar glycoproteins, with the MA6‐reactive determinant localized on the carbohydrate moiety. On isoelectric focusing, this antigen exhibits a degree of charge microheterogeneity, migrating as a diffused band with an average isoelectric point at pH 5.7. BLCa was also identified by another murine MAb, MAS. The antigenic determinant recognized by this antibody is also localized on the carbohydrate moiety of the molecule, but, unlike the MA6‐reactive determinant, it is shared by other glycoproteins from different types of cells.
Susceptibility of various human tissues to transformation in vivo with human papillomavirus type 11
Authors: Kreider John W. , Howett Mary K. , Stoler Mark H. , Zaino Richard J. , Welsh Patricia 
Published: February 2007

AbstractHuman papillomaviruses (HPVs) are associated with proliferative lesions in a variety of human epithelial types. In some cases, the associations are highly specific in that a certain papilomavirus type may infect only one human epithelial cell phenotype. In other cases, one papilomavirus apparently infects several tissue types and not others. Further, HPV replication capacity varies considerably in different epithelia. Due to the lack of a suitable method, it has not been possible, until now, to define the role of the host cell phenotype in determining the outcome of infection with an HPV. We recently developed a system in which human epithelium was exposed to HPV‐II and transplanted to athymic mice. Cervix and skin grafts developed into typical condylomata. We now test the hypothesis that the outcome of infection of diverse epithelial types with a single human papillomavirus is largely determined by the phenotype of the original epithelial cell. For example, skin obtained from a number of disparate sites from a single patient varied dramatically in its capacity for morphological transformation with HPV‐II. Skin from penis was highly susceptible, but skin from abdomen did not transform. Vocal cord from 3 children and 2 adults responded to HPV‐II infection by producing typical laryngeal papillomata. A variety of tissues were obtained from 11 donor infants and infected with HPV‐II. Foreskin and cervical tissues of these children were transformed at a frequency of 100%. Vocal cord was transformed at an incidence of 88% and urethra at 73%. Only 37% of esophagus samples were transformed and both abdominal skin and urinary bladder from the same infants were totally resistant to morphological transformation. In a separate study, ureteral tissues from a child and an adult were completely resistant to HPV‐II infection. Papillomavirus replication was readily detected as capsid antigen in foreskin, cervix, and urethra, but was poorly expressed in morphologically‐transformed esophagi and vocal cords. In the last two tissues HPV‐II DNA and RNA were demonstrated in cells by in situ hybridization techniques. We conclude that the epithelial cell phenotype is a major determinant of HPV‐II infection, controlling both morphological transformation and viral replication.
Tumor progression in human malignant melanoma: Five stages defined by their antigenic phenotypes
Authors: Holzmann Bernhard , Bröcker Eva B. , Lehmann JüRgen M. , Ruiter Dirk J. , Sorg Clemens , Riethmüller Gert , Johnson Judith P. 
Published: February 2007

AbstractThe antigenic profile of melanocytic cells in the course of local and systemic tumor progression of human malignant melanoma was investigated by the reactivity of a panel of monoclonal antibodies (MAbs) in frozen sections of histologically defined melanocytic lesions. Specific antigenic phenotypes made it possible to distinguish 5 groups of lesions which could be ranked in relation to each other due to the sequential acquisition or loss of progression markers. On this basis, a scheme of antigenic changes which accompany the stepwise transformation of normal skin melanocytes into highly malignant metastatic melanoma cells is proposed. The steps of tumor progression identified solely by phenotyping with MAbs were in complete concordance with the concept of melanoma progression derived from histological, statistical and clinical analyses. Furthermore, our finding that the expression of gp89 as well as HLA‐DR antigens can be induced by interferon‐γ in vitro provides evidence that immune interferon may play a role in the regulation of genes leading to phenotypic changes in progressing melanoma cells.