bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanoma antigen expression and metastatic ability of mutant B16 melanoma clones
Authors: Nozue Mutsumi , Sakiyama Hisako , Tsuchiya Kouji , Hirabayashi Yoshio , Taniguchi Masaru 
Published: February 2007

AbstractThe biological functions of murine melanoma‐associated antigens recognized by monoclonal antibodies (MAbs) (M562, M622 and M2590) were examined by using mutant clones which differed in their degree of expression of these antigens. Four clones of high expressors of 3 types of antigen (MEA group), 5 clones of low or non‐expressors of M562‐ and M622‐recognizing antigens (MEB group) and 4 clones of non‐expressor of GM3 recognized by M2590 (MEC group) were used. Attachment of these clones to components of extracellular matrix was different between the groups. Two clones of the MEA group showed the highest ability to adhere to laminin and type‐IV collagen, whereas the clones of the MEB and MEC groups significantly lost their ability to attach to laminin and type‐IV collagen. In experimental lung metastasis, metastasizing ability of MEA‐group cells was higher than that of MEB‐and MEC‐group cells. Our results suggest that these antigens play some functional role in metastasis mediated by increasing capacity for attachment to laminin and type‐IV collagen.
Polyamine‐directed preferential nutritional repletion of normal tissues in tumor‐bearing hosts
Authors: Nishioka Kenji , Grossie V. Bruce , Ajani Jaffer A. , Patenia Domitila , Chang Tai‐Hwa , Ota David M. 
Published: February 2007

AbstractOur previous study demonstrated that total parenteral nutrition (TPN) increases erythrocyte (RBC) polyamines selectively in cancer patients but not in non‐cancer patients, suggesting that these changes may relate to tumor presence. We therefore studied the possible relationship between RBC polyamine levels and potential tumor growth induced by TPN. In addition, we attempted to control tumor growth during TPN with α‐difluoromethylornithine (DFMO), a suicide inhibitor of ornithine decarboxylase (ODC), in a fibrosarcoma‐bearing rat model. Rats in a control group received chow ad libitum for 3 weeks and their tumors grew exponentially. A restricted intake (RI) tumor‐bearing group received 8 g chow per day per rat; this produced malnourished rats in which tumor growth significantly slowed. The third group (RI → TPN) received the RI diet for 2 weeks and TPN for 1 week, which resulted in an increase in tumor growth. The last group (RI → TPN + DFMO) received a 2‐week RI regimen and 1‐week TPN plus DFMO regimen, which inhibited tumor growth to the level of the RI group due to the addition of DFMO (1 g/kg/day). Although the addition of TPN to the RI regimen markedly increased tumor ODC activity, as well as tumor putrescine and RBC putrescine levels, the addition of DFMO to the RI → TPN regimen entirely abolished these increases. Despite DFMO treatment, liver ODC activity in RI → TPN + DFMO group was unaffected. The plasma albumin level, an indicator of host nutrition, of the RI → TPN + DFMO group was significantly higher than that of the RI group. Liver, spleen, kidney and total body weights of the RI → TPN or RI → TPN + DFMO group were significantly higher than those of the RI group. These results indicate that TPN can enhance tumor growth in malnourished hosts and that the addition of DFMO to TPN can effectively control this TPN‐enhanced tumor growth, leading to preferential nutritional repletion of the host.
Molecular and cellular characterization of drug resistant hamster cell lines with alterations in ribonucleotide reductase
Authors: Tagger Aaron Y. , Wright Jim A. 
Published: February 2007

AbstractRibonucleotide reductase consists of 2 protein components frequently called M1 and M2. Hydroxyurea specifically inhibits DNA synthesis by interacting with the M2 protein and destroying a unique tyrosyl‐free radical. We have carried out a molecular and cellular characterization of 2 Chinese hamster ovary cell lines exhibiting either low (HNR‐AT) or relatively high (HR‐R2T) resistance to the cytotoxic effects of hydroxyurea. Both drug‐resistant lines have an increased level of ribonucleotide reductase activity. EPR measurements for tyrosyl‐free radical content and studies with M1‐specific antibodies indicated that the elevation in enzyme activity was entirely due to an increase in the M2 component. Studies with M1 cDNA showed that both drug‐resistant cell lines contained a wild‐type level of M1 mRNA and a wild‐type M1 gene copy number. Studies with M2 cDNA indicated that the 2 drug‐resistant lines possessed elevated levels of M2 message that could explain the observed increase in M2 component. The elevation of M2 mRNA in the most resistant line, HR‐R2T, was due to an increase in M2 gene copy number. The low resistant cell line, HNR‐AT, exhibited a wild‐type M2 gene copy number, indicating that the increase in M2 gene message occurred through a process other than gene amplification. Enzyme kinetic studies with partially purified preparations from both drug resistant lines showed reduced sensitivity to hydroxyurea and to the negative allosteric effector, dATP. In addition to hydroxyurea, HR‐R2T cells were also resistant to several other drugs whose site of action is the M2 component. Furthermore, HR‐R2T cells were not cross‐resistant to colchicine or puromycin, suggesting that hydroxyurea‐resistant cells do not share the multi‐drug resistance phenotype, which is frequently associated with cross‐resistance to these drugs.
Immunosuppressive activity of human neuroblastoma tumor gangliosides
Authors: Floutsis Grace , Ulsh Lisa , Ladisch Stephan 
Published: February 2007

AbstractGangliosides are shed in substantial amounts by some tumors, including human neuroblastoma, and these molecules modulate experimental tumor formation in vivo. We now demonstrate that neuroblastoma tumor gangliosides have potent immunoregulatory activity. Gangliosides of every one of 17 tumors studied were highly inhibitory for the normal in vitro human lymphoproliferative responses to the soluble antigen, tetanus toxoid; 30 nmol ganglioside/ml caused 43% to >99% inhibition and the mean concentration causing 50% inhibition was only 17.3 nmol/ml. Furthermore, gangliosides isolated from clinically more aggressive tumors (Stage III or IV) were up to twice as immunosuppressive as those of the generally less aggressive tumors (Stage I or II) (p<0.05). Taken together with the lack of immunosuppressive activity of normal plasma gangliosides, the potent activity of neuroblastoma gangliosides supports the hypothesis that one mechanism by which these shed molecules may act to enhance tumor formation in vivo is through abrogation of the host cellular immune response at the site of tumor formation.
Coffee, alcohol, smoking and cancer of the pancreas: A case‐control study
Authors: Clavel Françoise , Benhamou Ellen , Auquier Ariane , Tarayre Michèle , Flamant Robert 
Published: February 2007

AbstractA hospital case control study on smoking, alcohol and coffee consumption as risk factors for pancreatic cancer, in which 161 cases were matched to 268 control patients, was conducted in France between 1982 and 1985. The results showed no association between tobacco or alcohol consumption and cancer of the pancreas, whereas coffee consumption was associated with an increased risk [OR of 2 or more cups per day vs. less: 2.27 (1.11–4.64) and 1.45 (0.82–2.55) among females and males respectively]. A dose‐response relationship was observed with coffee consumption in both sexes, stronger among females than among males: the linear increase estimates were 2.00 (1.22–3.29) and 1.32 (0.91–1.92) respectively. No interaction was found between coffee and tobacco, whereas the effect of coffee appeared to be limited to non‐drinkers of alcohol.
Chemical carcinogen epstein‐barr virus (ebv) synergism: Ebv genome amplification and site‐specific mutation during transformation
Authors: Henderson Earl E. , Franks Carol , Fronko Gerald 
Published: February 2007

AbstractWhen treated with chemical carcinogens, peripheral blood lymphocytes (PBLs) from normal adults or patients with acquired immunodeficiency syndrome (AIDS) were more readily transformed than non‐treated PBLs into immortalized lymphoblastoid cell lines (LCLs) by the Epstein‐Barr virus (EBV, FF41‐I). Chemical carcinogens also enhanced spontaneous transformation in both PBL populations. Co‐cultivation of lethally ultraviolet (UV)‐irradiated uninfected PBLs with EBV‐infected PBLs resulted in a dose‐related enhancement of transformation, providing evidence that enhancement is in part mediated by carcinogen‐induced diffusible trans‐acting factors. Analysis of the EcoR1 J region of resident EBV genomes showed that LCLs established from carcinogen‐treated PBLs frequently had EBV genome amplification higher than that seen in controls. Carcinogen‐induced EBV genome amplification was shown to be dose‐related. The organization of the terminal region of the EBV genome was analyzed in LCLs derived from carcinogen‐treated PBLs and compared to that of FF4I‐1 and B95‐8. LCLs established from N‐methyl‐N′‐nitroso‐nitrosoguanidine (NNNG)‐and aflatoxin B1‐treated PBLs frequently had 2 circular forms of the EBV genome and several linear forms varying by numbers of terminal repeats (TRs) at the 3′ and 5′ end. This is in contrast to the single episomal circular and linear form of the EBV genome found in the parent FF41‐1 and single episomal circular form in control FF41‐1‐carrying LCLs. Linear forms of the EBV genome were only found in FF41‐1‐transformed LCLs derived from carcinogen‐treated PBLs and were associated with the production of unusually large amounts of infectious EBV. These results demonstrate that chemical carcinogen‐mediated enhancement of transformation is accompanied by quantitative and qualitative alterations in the physical structure, organization and expression of the EBV genome which may in turn be the result of a carcinogen‐induced cellular SOS response.
Cellular interactions determining the production of collagenase by a rat mammary carcinoma cell line
Authors: Lyons J. Guy , Siew Kenneth , O'Grady Robert L. 
Published: February 2007

AbstractThe cellular interactions regulating the production of collagenase by a cell line derived from a spontaneously arising rat mammary carcinoma have been studied. The cell line, BC1, was grown permanently under defined serum‐free conditions, so that the poorly characterized and variable effects of serum on collagenase expression were avoided. Two stable subpopulations of cells present in BC1 cultures were defined as epithelioid cells (“E‐cells”) and myoepithelioid cells (“M‐cells”). These subpopulations differed in their morphology, pattern of growth and susceptibility to detachment from culture vessels by trypsin. Seven clones of M‐cells and 7 clones of E‐cells, obtained by the limiting dilution technique, were used to determine the cellular source of collagenase and the interactions which led to its expression. M‐cells displayed an absolute dependence on a soluble factor produced by E‐cells for their survival in vitro. The presence of both cellular types in culture was necessary for collagenase secretion to occur, E‐cells being the major source of enzyme in mixed cultures. A soluble factor produced by M‐cells was largely, if not completely, responsible for the induction of collagenase secretion by E‐cells. Clones representative of both subpopulations were tumorigenic in syngeneic host animals. These results suggest that the phenotypic diversity which occurs within populations of neoplastic cells may give rise to subpopulations of cells which display a more aggressive phenotype in coexistence than in isolation.
The influence of syngeneic anti‐idiotypic antibody on the biodistribution of an anti‐tumour monoclonal antibody in balb/c mice
Authors: Pimm M. V. , Durrant L. G. , Baldwin R. W. 
Published: February 2007

AbstractBALB/c mice were immunized against syngeneic murine 791T/36 monoclonal antibody (MAb) by intraperitoneal (i.p.) injection of the antibody conjugated to ricin toxin A chain. Subsequently, in these and control mice, the biodistribution of radioiodinated 791T/36 antibody and isotype‐matched (IgG2b) control immunoglobulin was examined. Pre‐treated mice showed marked perturbation of biodistribution of the 791T/36 antibody but not of control IgG2b. This was manifest as rapid hepatic clearance of the antibody which was followed by accelerated catabolism and excretion of the radiolabel. Anti‐idiotypic antibodies were identified in immunotoxin pre‐treated mice by their ability to inhibit the binding of FITC‐labelled 791T/36 antibody to tumour target cells. These studies show that antibody responses, even to only the idiotype of a MAb, may produce marked perturbation of its biodistribution. This has implications for the clinical use of human or chimeric MAbs for tumour imaging or targeting of therapeutic agents since, if anti‐idiotypic antibodies are evoked, they could still prevent tumour localization of antibody or conjugate.
Levels of myc protein, as analyzed by flow cytometry, correlate with cell growth potential in malignant b‐cell lymphomas
Authors: Holte Harald , Stokke Trond , Smeland Erlend , Watt Rosemary , Blomhoff Heidi Kiil , Kaalhus Olav , Ohlsson Rolf 
Published: February 2007

AbstractWe have analyzed c‐myc protein expression during the cell cycle in malignant B‐cell lymphomas by dual flow cytometric detection of a fluoresceinated polyclonal anti‐myc antibody and propidium iodide which binds stochiometrically to DNA. The data obtained were correlated to other parameters of cell activation such as histopathological grading, expression of the activation antigen 4F2, light scatter (proportional to cellular volume), DNA synthesis and percentage of S‐phase cells. The c‐myc protein level was strongly correlated to parameters of DNA synthesis/content. In addition, the oncoprotein level was largely unvarying from the late G1 phase through the rest of the cell cycle in both malignant cells and normal purified B cells stimulated to proliferate in vitro.
Seroprevalence of HTLV‐I in portugal and evidence of double retrovirus infection of a healthy donor
Authors: Cardoso E. A. , Robert‐guroff M. , Franchini G. , Gartner S. , Moura‐Nunes J. F. , Gallo R. C. , Terrinha A. M. 
Published: February 2007

AbstractThe prevalence of antibodies to HTLV‐I in 5,475 Portuguese from 6 regions spanning the country was studied. Overall seroprevalence was 0.55%, indicating that Portugal is not an endemic area for this virus. Seropositives were distributed throughout the country, and no geographic clustering was observed. The seroprevalence of individuals who had lived in former Portuguese colonies in Africa (0.7%) was significantly higher than that of individuals who had not been in Africa (0.36%). An increase in seroprevalence with age was noted, and more females than males were antibody‐positive, though not significantly so. Serum from one donor (1711), originating from Guinea‐Bissau, was shown by Western blot and radioimmune precipitation to react with various proteins of HTLV‐I, HIV‐I and ‐2, and SIV. Based on the serologic profiles and isolation of bona fide HTLV‐I from her lymphocytes (confirmed by immunologic analysis, molecular cloning of the provirus and restriction enzyme analysis and sequencing of the DNA), together with the reactivity of her sera with an HIV‐2 isolate obtained from her husband, we conclude that this donor was doubly infected with HTLV‐I and HIV‐2, rather than being the host to an as yet unidentified retrovirus.
Distribution of fibronectin and laminin in early and advanced signet‐ring‐cell carcinomas of the stomach
Authors: Sugihara H. , Hattori T. , Fujita S. , Fukuda M. 
Published: February 2007

AbstractAn immunoperoxidase method was used to compare the distribution of fibronectin and laminin between superficially spreading and deeply infiltrating parts of signet‐ring‐cell carcinoma of the stomach. In both parts, laminin‐containing basement membranes were generally scarce, but they were observed on some of the cancer cells which had differentiated to glandular cells. Intramucosal invasion fronts of superficially spreading cancers often showed a layered structure, consisting of a middle zone of small cancer cells together with a superficial and a deep zone of signet‐ring cells. In this structure, linear fibronectin and laminin deposits were common on the cancer cells in the deep zone, but rare in the superficial zone. However, fibrillar fibronectin deposits in the stroma were not considerably larger in either zone. At extramucosal invasion fronts of deeply infiltrating (advanced) cancers, a stromal remodelling with an increased amount of fibrillar fibronectin deposits was often observed around the cancer cells, whose cell surface fibronectin was largely lost even from some basement membranes. These findings suggest that invasive activity of signet‐ring‐cell carcinoma may not be related to the mere presence or absence of cell‐surface fibronectin and laminin but to the amount of stromal fibronectin, which could reflect a cell‐stroma interaction. Signet‐ring‐cell carcinomas have a stage of intramucosal growth in which cancer cells may live in dependence upon the pre‐existing stroma and form the layered structure, while in advanced stages cancer cells seemed to have acquired an ability to elicit their own “tumor stroma”.
Reversion of tumorigenicity and decreased agarose clonability after EBV conversion of an igh/myc translocation‐carrying be line
Authors: Torsteinsdóttir Sigurbjörg , Andersson Monika L. , Avila‐Cariño Javier , Ehlin‐Henriksson Barbro , Masucci Maria G. , Klein George , Klein Eva 
Published: February 2007

AbstractThe Epstein‐Barr virus (EBV)‐negative Burkitt lymphoma (BL) line BL‐41, and 5 independently established EBV‐converted sublines, derived by infection with a transforming (B95‐8) or a nontransforming (P3HRI) strain of EBV, were compared for clonability in semi‐solid agarose and for tumorigenicity in immuno‐suppressed mice. One P3HRI viral convertant and 3 out of 4 B95‐8 virus‐converted sublines had a high (>40%) agarose clonability, like the BL 41 parent, and were slightly more tumorigenic than BL‐41. In contrast, the fourth B95‐8 converted subline, BL‐41/95, was virtually non‐tumorigenic and its agarose clonability was much lower (3–23%). It showed a more drastic shift towards an LCL‐like phenotype than the other convertants as reflected by high HLA class‐I and EBV‐encoded latent membrane protein (LMP) expression. BL 41/95 still contains the 8;14 IgH/myc translocation, carried by the parental line, and maintains the same relatively high steady‐state level of c‐myc mRNA and protein as the highly tumorigenic convertants. We conclude that the tumorigenicity of BL41/95 has been suppressed by a gene that acts at a level beyond the expression of the activated oncogene, in the same way as the revertants isolated from ras and SV‐40‐transformed cultures (Klein, 1987b; Bassin and Noda, 1987).
Anti‐tumor and differentiation‐inducing activity of n,n‐dimethylformamide (dmf) in head‐and‐neck cancer xenografts
Authors: Van Dongen Guus A. M. S. , Braakhuis Boudewijn J. M. , Leyva Albert , Hendriks Hans R. , Kipp Bart B. A. , Bagnay Marian , Snow Gordon B. 
Published: February 2007

AbstractThe anti‐tumor activity of the putative differentiation‐inducing agent dimethylformamide (DMF) was assessed in 7 head‐and‐neck xenograft (HNX) lines transplanted into nude mice. The drug was administered intra‐peritoneally at the maximum tolerated dose. A significant growth‐inhibitory effect was observed in 3 out of 7 tumor lines tested. When compared with 5 conventional drugs active in patients with squamous‐cell carcinoma of the head and neck (HNSCC), DMF was as effective as the most active drugs (cisplatin and bleomycin). The most sensitive xenograft line, the poorly differentiated tumor HNX‐14C, was used to test the hypothesis that differentiation induction might play a role in the antitumor activity of DMF. Light microscopic examination did not show clear‐cut alteration of differentiation characteristics such as keratin and keratin pearl formation. Furthermore, we used a monoclonal antibody to study the expression of cytokeratin 10 which is useful as a differentiation marker of human HNSCC tumors. Keratin 10, not present in HNX‐14C tumors grown under control conditions, became expressed in some cells upon DMF treatment. Further evidence for a differentiation‐inducing activity of DMF was found in electron‐microscopic studies. In treated HNX‐14C tumors, in addition to cells with normal ultrastructural features, better‐differentiated cells were observed, as manifested by an increase in the number of tonofilaments and desmosomes. The results show that DMF has a potential value for the treatment of patients with head‐and‐neck cancer, and that differentiation induction might play a role in the anti‐tumor action of the drug.
Suppression of transformation and immortality in human/chinese hamster fibroblast hybrids—a model for suppressor gene isolation
Authors: Wynford‐Thomas D. , Bond J. A. , Paterson H. 
Published: February 2007

AbstractSomatic cell hybrids were produced by fusion of normal human (foreskin) fibroblasts and a transformed Chinese hamster fibroblast line V79‐8. Overall, approximately 30% of hybrid clones showed stable reversion to normal morphology and growth control in vitro as shown by serum and anchorage dependence. In one‐third of these clones, senescence was observed after a number of generations similar to that required for the human fibroblast parent cells to senesce. The remainder appear to be immortal. Normal human chromosomes can therefore restore growth control with or without finite life‐span to this transformed cell. V79 cells were found to be transfectable at an efficiency compatible with detection of single‐copy gene transfer from genomic DNA. Furthermore, these cells were exceptionally sensitive to negative (“suicide”) selection. Taken together, our data suggest that the V79 line represents an ideal system for isolation of human tumour suppressor genes.
in vitro proliferative responses of spleen lymphocytes from rats bearing progressive or regressive tumors induced by cell variants of a syngeneic colon carcinoma
Authors: Dearden‐Badet Marie‐Théarèse , Pelletier Hélène , Caignard Anne , Martin François 
Published: February 2007

AbstractFrom one colonic carcinoma chemically induced in the rat, 2 sublines of tumor cells have been cloned, one (PROb) inducing progressive tumors, the other (REGb) generating tumors that regress a few weeks after s.c. injection into syngeneic hosts. Our study was aimed at comparing cellular immunity between animals bearing PROb or REGb tumors. Spleen cells were first tested for in vitro proliferation in response to mitomycin‐treated PROb or REGb cells. Only spleen cells from rats injected with REGb cells proliferated significantly when mixed with PROb or REGb cells. The proliferative response induced by REGb cells was considerably higher than the response to PROb cells. When spleen cells from rats bearing REGb tumors were cultured with a mixture of REGb and PROb cells at various PROb/REGb cell ratios, PROb cells significantly suppressed the strong proliferative response generated by the same number of REGb cells alone. REGb‐immune spleen cells, after in vitro stimulation by PROb or REGb cells, were not cytotoxic for either cell variant. REGb‐immune spleen cells did not differ in their content of T lymphocytes expressing CD4 or CD8 markers when they were stimulated by PROb or REGb cells in vitro, but REGb cells induced a larger number of activated lymphocytes expressing the IL‐2 receptor. Our results indicate that, compared to REGb cells, PROb cells are poorer stimulators of proliferation of tumor‐immune spleen cells, and that they are able to suppress the proliferative response induced by REGb cells.