bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different behaviour of mouse‐human chimeric antibody F(ab')2 fragments of IgG1, IgG2 and IgG4 sub‐class in vivo
Authors: Buchegger Franz , Pèlegrin Andre , Hardman Norman , Heusser Christoph , Lukas John , Dolci Wanda , Mach Jean‐Pierre 
Published: February 2007

AbstractMouse‐human chimeric monoclonal antibodies (MAbs) of 3 different human IgG sub‐classes directed against carcinoembryonic antigen (CEA) have been produced in SP‐0 cells trans‐ fected with genomic chimeric DNA. F(ab')2 fragments were obtained by pepsin digestion of the purified chimeric MAbs of human IgG1, IgG2 and IgG4 sub‐class and of parental mouse MAb IgG. The 4 F(ab')2 fragments exhibit similar molecular weight by SDS‐PAGE. They were labelled with 125I or 131I and high binding (80 to 87%) to purified unsolubilized CEA was observed. In vivo, double labelling experiments indicate that the longest biological half‐life and the highest tumour‐localization capacity is obtained with F(ab')2 from chimeric MAb of human IgG2 sub‐class, whereas F(ab')2 from chimeric MAb IgG4 give very low values for these 2 parameters. F(ab')2 from chimeric MAb IgG1 and from parental mouse MAb yield intermediate results in vivo. Our findings should help to select the appropriate human IgG sub‐class to produce chimeric or reshaped MAb F(ab')2 to be used for tumour detection by immunoscintigraphy and for radioimmunotherapy.
Regulation of natural antibody binding and susceptibility to natural killer cells through Zn++‐inducible ras oncogene expression
Authors: Tough David F. , Haliotis Tina , Chow Donna A. 
Published: February 2007

AbstractChanges in the natural resistance phenotype were examined for the 2H1, 10T½ cells expressing the activated human H‐ros oncogene under the transcriptional regulation of the zinc‐ inducible mouse metallothionein‐1 promoter. Culture of the cells in 50 μM ZnSO4 induced an increase in ras protein p21 levels which were maximal within I day. Natural‐antibody (NAb) binding was significantly increased following 2 days of cell culture in ZnSO4 and continued to increase up to 4 days. The increased NAb binding returned to uninduced levels within 2 days following the removal of added zinc ions from the culture medium. The cells also exhibited a significant increase in natural killer (NK) cell sensitivity following 2 days in ZnSO4. This was maintained as long as the zinc was in the medium, but returned to uninduced levels within I day following its removal. The results show that NAb binding and susceptibility to NK cells increased following ras oncogene expression in 10T½ cells and that both parameters were regulated by p21 expression. Repeated i.v. administration of whole‐serum NAb prior to tumor inoculation reduced the number of early tumors following s.c. injection of Zn++‐induced 2HI cells into Zn++‐treated C3H/ HeN mice, consistent with an in vivo role for NAb in the defense against ras‐transformed cells. In contrast, small but statistically significant reductions in NAb binding were observed following v‐H‐ras transformation of NIH 3T3 cells or v‐src transformation of 10T½. The data argue for an NAb‐ and NK‐cell‐susceptible phase of ras‐induced tumor development which is a prerequisite for these mediators to contribute to a first line of defense against incipient neoplasia, and suggest that characteristics of the recipient cell and the transforming oncogene are important in determining the natural resistance phenotype.
Interleukin‐1 production by transformed fibroblasts. II. Influence on antigen presentation and T‐cell‐mediated anti‐tumor response
Authors: Zöller Margot , Douvdevani Amos , Segal Shraga , Apte Ron N. 
Published: February 2007

AbstractOncogene‐transformed fibroblasts which expressed IL‐1, spontaneously or after activation with conditioned medium (CM) and lipopolysaccharide (LPS), regressed in the syngeneic host. Since regression was significantly influenced by the immune competence of the host (see companion report), we speculated that regression was T‐cell‐mediated. Frequencies of cytotoxic T‐cell precursors (CTLp) were in the same range for activated and non‐activated, transformed fibroblasts. Furthermore, it was found that lysability of transformed fibroblasts was not influenced by expression of IL‐1. These findings exclude the possibility that regression of CM‐ and LPS‐treated transformed fibroblasts may have been due to the appearance of new, strongly immunogenic epitopes. On the other hand, frequencies of CTL were significantly increased after in vivo immunization with IL‐1‐expressing as compared to IL‐1‐non‐expressing transformed fibroblasts. The in vivo maturation/expansion of CTL could have been the consequence of activation of helper T cells (TH), transformed fibroblast‐associated IL‐1 delivering the co‐ stimulatory signal. Analysis of frequencies and proliferation rates of TH confirmed this assumption. Both parameters were significantly increased after stimulation with transformed fibroblasts expressing IL‐1, in comparison to transformed fibroblasts not expressing IL‐1. Furthermore, purified T cells apparently depleted of cells expressing MHC class‐II antigens, i.e. antigen‐ presenting cells, proliferated in the presence of transformed fibroblasts expressing IL‐1. Since IL‐1 rather than MHC class‐II antigen expression was the limiting factor, antigen presentation by IL‐1‐expressing transformed fibroblasts appears unlikely. Instead, maturation of antigen‐presenting cells could well have been initiated by tumor‐associated IL‐1. We conclude that IL‐1 expression of transformed fibroblasts plays an important role in the induction of a T‐cell‐mediated anti‐tumor response. The effect is due to increased efficiency in the activation of helper T cells and may be supported by activation of antigen‐presenting cells.
Induction of synthesis of manganous superoxide dismutase in L‐M(pNtnF) cells carrying an inducible TNF gene
Authors: Himeno Takeshi , Watanabe Naoki , Yamauchi Naofumi , Maeda Masahiro , Okamoto Tetsuro , Tsuji Naoki , Tsuji Yasushi , Akiyama Shinichiro , Sasaki Hiroyoshi , Niitsu Yoshiro 
Published: February 2007

AbstractBased on findings that the cytotoxic effects of tumor necrosis factor (TNF) are closely related to levels of intracellular oxygen radicals, and on the results of TNF gene transfection studies, the hypothesis was made that endogenous TNF (enTNF) acts as a protective factor against exogenous TNF by inducing inhibitors or scavengers of oxygen radicals. In order to test this hypothesis, we investigated the intracellular levels of manganous superoxide dismutase (MnSOD) and glutathione (GSH) in L‐M(pNTnF) cells carrying a TNF gene induced by dexametha‐ sone (DM). When L‐M(pNTnF) cells were treated with DM they expressed enTNF, and acquired resistance to exogenous TNF. There was no change in the GSH concentration after enTNF induction, but a 1.9‐ to 3.9‐fold increase in MnSOD levels was noted. Our findings suggest that enTNF exerts its protective function against the cytocidal effect of exogenous TNF by inducing MnSOD production.
Influence of dose and schedule on the therapeutic efficacy of 131I‐labelled monoclonal antibody 139H2 in a human ovarian cancer xenograft model
Authors: Molthoff Carla P. M. , Pinedo Herbert M. , Schlüper Hennie M. M. , Boven Epie 
Published: February 2007

AbstractThe therapeutic efficacy of various doses and schedules of 131I‐labelled anti‐episialin monoclonal antibody (MAb) 139H2 was assessed in the NIH:OVCAR‐3 human ovarian cancer xenograft model. Radioimmunotherapy was started at the time s.c. tumors were well established (100 to 300 mm3). The anti‐tumor effects induced by i.v. injections of 131I‐MAb 139H2 were dose‐ and schedule‐dependent. Optimal growth inhibition and long‐lasting complete tumor regressions were obtained with 2 injections of 500, 700 or 750 μCi 131I‐MAb 139H2 per mouse given with a 2‐week interval. The percentage of tumors with more than 50% reduction of their initial volume after treatment with a total dose of 1,000 μCi 131I‐MAb 139H2 per mouse, given as 10 injections of 100 μCi (3 ± /week), 4 injections of 250 μCi (2 × /week), 10 injections of 100 μCi (5 ×/week) within a period of 3 weeks, or 2 injections of 500 μCi with a 2‐week interval, was 9%, 40%, 64% and 75% respectively. Unlabelled MAb 139H2 did not affect tumor growth, while the effects of 131I‐control MAb were minor and transient. 131I‐MAb 139H2 treatment did not select for outgrowth of episialin‐ negative cells in the OVCAR‐3 xenografts. Highest absorbed doses of whole‐body‐radiation were calculated for 2 injections (500 to 750 μCi 131I‐MAb 139H2) given with the 2‐week interval. The radiation dose to, the tumor after a single injection of 500 μCi 131I‐MAb 139H2 was 1,300 cGy over 7 days, which appeared slightly lower than the dose calculated after administration of a tracer dose of iodinated MAb 139H2.
Growth‐inhibitory effect of quercetin and presence of type‐II estrogen‐binding sites in human colon‐cancer cell lines and primary colorectal tumors
Authors: Ranelletti Franco O. , Ricci Riccardo , Larocca Luigi M. , Maggiano Nicola , Capelli Arnaldo , Scambia Giovanni , Benedetti‐Panici Pierluigi , Mancuso Salvatore , Rumi Carlo , Piantelli Mauro 
Published: February 2007

AbstractWe studied the effect of quercetin (Q) on the proliferation of HT‐29, WiDr, COLO 201, and LS‐174T human colon cancer cell lines. Q, between 10 nM and 10 μM, exerted a dose‐dependent, reversible inhibition of cell proliferation. Cell‐cycle analysis revealed that the growth‐inhibitory effect of Q was due to a blocking action in the G0/G1 phase. Using a whole‐cell assay with 17β‐[3H]‐estradiol as tracer, we demonstrated that all these cell lines contain type‐II estrogen‐binding sites (type‐II EBS). By using Q and other chemically related flavonols (3,7‐4′‐trimethox‐ yquercetin, 3,7,3,4′‐tetramethoxyquercetin, kaempferol, morin, and rutin), we observed that the affinities of these compounds for type‐II EBS are correlated with their growth‐inhibitory potential. Furthermore, the Q sensitivity of the colon cancer cell lines was correlated with the number of type‐II EBS/cell. Then Q could regulate colon cancer cell growth through a binding interaction with type‐ll EBS. This mechanism could also be active in vivo as we have observed that cytosolic type‐II EBS are present in primary colorectal cancers and that Q is effective in inhibiting the in vitro bromodeoxyuridine incorporated by neoplastic cells in these cancers.
Enhanced insulin‐receptor tyrosine kinase activity associated with chromosomal translocation (1;19) in a pre‐B‐cell leukemia line
Authors: Newman Julie D. , Harrison Leonard C. , Eckardt Glenn S. , Jack Ian 
Published: February 2007

AbstractThe gene for the insulin receptor has been assigned to chromosome 19 near the breakpoint of the translocation t( 1; 19) which occurs in 25% of pre‐B‐cell leukemias. Insulin receptors in a pre‐B‐cell leukemia cell line (ACV) with t(1;19) were found to have 2‐fold higher affinity for insulin, 5‐fold higher basal and insulin‐stimulated p sub‐unit autophosphorylation, and 2‐fold higher basal and 4‐fold higher insulin‐stimulated β sub‐unit kinase activity on the synthetic peptide poly(Glu,Tyr), compared to receptors in a B‐cell line (ADD) with normal karyotype from the same patient. ACV cells had a novel 13‐kb receptor mRNA species and expressed a DNA polymorphism localized to the tyrosine kinase domain of the receptor gene. These findings suggest that t(l;19) in the ACV cell may result in rearrangement of the insulin receptor gene and translation of a receptor with enhanced tyrosine kinase activity.
Expression and characterization of two differentiation antigens in human stratified squamous epithelia and carcinomas
Authors: Quak Jasper J. , Schrijvers Ad H. G. J. , Brakkee Joost G. P. , Davis Hugh D. , Scheper Rik J. , Meijer Chris J. L. M. , Snow Gordon B. , van Donoen Guus A. M. S. 
Published: February 2007

AbstractUsing viable cells of a human squamous‐cell carcinoma (SCC) cell line as immunogen, we generated 2 monoclonal antibodies, MAbs K984 and K928, to SCC surface antigens. Immunoperoxidase staining of frozen sections of normal epidermis revealed that MAb K984 reacts with the poorly differentiated basal cells, while MAb K928 is reactive with the more highly differentiated suprabasal cells. A similar complementary reaction pattern of these antibodies was demonstrated in the majority of well‐differentiated human tumors and some moderately differentiated SCCs. In contrast, simultaneous reactivity of MAb K984 and K928 was found for the majority of cells within other well‐and moderately differentiated SCCs, as well as all poorly differentiated SCCs. Further biochemical characterization indicated that the antigen recognized by MAb K984 is similar to the one recognized by MAb SF‐25. MAb K928 recognizes a 50‐to 55‐kDa molecule under non‐reducing conditions. Antibodies with similar features to MAb K928 have not been described previously. The antigens recognized by MAbs K984 and K928 can be regarded as novel markers associated with cellular maturation in squamous epithelia. The antigen detected by MAb K984 is probably associated with the proliferating fraction in SCCs.
A monoclonal antibody capable of detecting new differentiation antigen of the stomach
Authors: Yokozaki Hiroshi , Kvo Eikai , Ochiai Atsushi , Ito Masanori , Tio Hisao , Tabuchi Junji , Tahara Eiichi 
Published: February 2007

AbstractA monoclonal antibody (MAb) was raised against a gastric adenocarcinoma cell line TMK‐1 that shows parietal cell differentiation. This MAb, an IgMK, named 20D11, reacted immunohistochemically with the intracytoplasmic secretory canalicular membranes of normal parietal cells of the stomach. In the fetal stomach at 4 months of gestation, the luminal surface of fundic epithelia and developing parietal cells had MAb20D 11 immuno‐reactivity, but at 6 months of gestation only parietal cells showed immunoreaction. Out of 133 gastric carcinomas, 98 (74%) had MAb20D 11 immunoreactivity. In the well‐differentiated type, immunoreactivity was localized at the luminal surface of tumor cells and, in the poorly differentiated type, in the intracytoplasmic tubulovesicles of tumor cells. In Western‐blot analysis, the antigenic molecule had a molecular weight exceeding 300 kDa in the tumor tissues, but only a 62‐kDa immunoblot band was seen in the corresponding non‐cancerous gastric mucosa. However, there was no correlation between the expression of high‐molecular‐weight antigens and the histological types of gastric carcinoma. These results suggest that 20D11 antigen may be involved in differentiation of parietal cells in the fetal stomach and in stomach cancer.
Nucleoside diphosphate kinase/NM23 expression in breast cancer: Lack of correlation with lymph‐node metastasis
Authors: Sastre‐Garau X. , Lacombe M. L. , Jouve M. , Véron M. , Magdelénat H. 
Published: February 2007

AbstractThe product of the nm23‐H1 gene, reported to be a meta‐static suppressor gene, was recently identified as the nucleoside diphosphate (NDP) kinase A, and was found to be over‐expressed in several types of malignant tumors as compared with normal tissues. In order to determine whether NDP‐kinase expression serves as a marker for metastatic potential and whether hyperproliferation of neoplastic cells would correlate with expression, we analyzed NDP‐kinase levels and activity by immunohistochemical staining and by an enzymatic assay in 13 benign and 98 malignant breast‐tissue specimens. Our results confirm that NDP‐kinase expression increases in malignant cells of breast carcinomas, but cannot be considered as a biological marker of metastatic dissemination. No correlation was found between NDP‐kinase activity and S phase, taken as an index of cell proliferation. Moreover, no correlation was observed between NDP‐kinase activity and tumor size, histoprognostic index, estrogen receptors or progesterone receptors. The mechanism of over‐expression of NDP in malignant cells and its role in tumor progression remain to be determined.
Differential expression of the CD44 molecule in human brain tumours
Authors: Kuppner M. C. , Van Meir E. , Gauthier Th. , Hamou M‐F. , De Tribolet N. 
Published: February 2007

AbstractExpression of the CD44 molecule was examined in a variety of human brain tumours, brain metastases and normal brain. Immunohistological staining with several CD44 antibodies demonstrated differential expression of the CD44 molecule among different brain tumour types. CD44 was strongly expressed in high‐grade gliomas and weakly expressed in meningiomas, medulloblastomas and normal brain. Northern blot analysis revealed the presence of 3 major CD44 mRNAs of 1.6, 2.2, and 5.0 kb in glioblastomas and a mRNA of 5.6 kb in meningiomas. CD44 expression was also detected by flow cytometric analysis on cultured cells derived from a variety of human brain tumours including glioblastomas and meningiomas.
Stimulation of the metastatic properties of lewis‐lung‐carcinoma cells by autologous granulocyte‐macrophage colony‐stimulating factor
Authors: Young M. Rita I. , Lozano Yvonne , Coogan Michael , Wright Mark A. , Young Melvin E. , Bagash Jamila M. 
Published: February 2007

AbstractUsing both polymerase‐chain‐reaction analysis and the soft‐agar colony‐forming unit assay, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) was shown to be expressed by cloned metastatic Lewis‐lung‐carcinoma (LLC‐LN7) cells but not by non‐metastatic LLC‐C8 cells. Furthermore, the metastatic LLC‐LN7 cells were shown to respond both to autologous GM‐CSF and to exogenous recombinant GM‐CSF (rGM‐CSF). In the presence of neutralizing anti‐GM‐CSF antibodies, the metastatic LLC cells became less able to migrate or to adhere and invade through a reconstituted basement membrane. Moreover, the addition of rGM‐CSF further enhanced the capacity of the metastatic LLC cells to adhere to the reconstituted basement membrane. This stimulation of metastatic properties of the LLC cells by either autologous or exogenous GM‐CSF was associated with enhanced endogenous protein phosphorylation. Two proteins of approximately Mr 45,000 and Mr 64,000 were the dominant target proteins to be phosphorylated by the presence of GM‐CSF. These results suggest that autologous GM‐CSF may function as an autocrine stimulator of the metastatic properties of metastatic LLC cells.
Potent anti‐tumorigenic effect of tubeimoside 1 isolated from the bulb of Bolbostemma paniculatum (maxim) franquet
Authors: Yu Lijian , Ma Rundi , Wang Yongqing , Nishino Hoyoku , Takayasu Junko , He Weizhen , Chang Mei , Zhen Jie , Liu Wensheng , Fan Suxian 
Published: February 2007

AbstractTubeimoside 1, one of the new triterpenoid saponins from the bulb of Bolbostemma paniculatum (Maxim) Franquet, had an anti‐inflammatory effect on mouse ear edema induced by arachidonic acid and 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). Furthermore, a potent anti‐tumorigenic effect of tubeimoside I was observed in 2‐stage carcinogenesis of mouse skin after oral administration as well as topical application. Thus, tubeimoside I appears to be a promising agent for cancer chemoprevention.
Malignant transformation of human fibroblasts previously immortalized with 60Co gamma rays
Authors: Mihara K. , Bai L. , Kano Y. , Miyazaki M. , Namba M. 
Published: February 2007

AbstractNormal human fibroblasts obtained from a whole embryo were malignantly transformed with only 60Co gamma rays, but after extensive passage. The fibroblasts were exposed intermittently to 60Co gamma rays, 13 times, 2,800 rads in total, from the primary culture to the 40th passage level. At the 50th passage level the cells became morphologically changed, showing chromosomal abnormalities, and serial passages showed them to be immortalized. They were not tumorigenic on transplantation into nude mice, but became malignant after extensive passage; i.e., at the 547th passage level and 2,800 days after initiation of the culture. Our results indicate that several different genotypic changes are necessary for malignant transformation of human cells over long periods. No mutation at codons 12 and 61 of H‐, K‐ and N‐ras was detected in the malignant cells. Thus, this system may be useful to detect other cellular genes that may contribute to the malignant phenotypes of human fibroblasts.
Response of FR3T3 cells transformed by HA‐ras oncogene and epidermal growth factor gene to differentiation induction by N,N‐dimethylformamide
Authors: Levine Alan E. , Chakrabarty Subhas 
Published: February 2007

AbstractTreatment of chemically transformed fibroblasts with N,N‐dimethylformamide (DMF) results in the restoration of a non‐transformed phenotype. In an attempt to identify more precisely the mechanisms by which DMF reverses the transformed phenotype, the effects of DMF on fibroblasts which were transformed by a single gene—specifically a synthetic epidermal growth factor (EGF) gene or the Ha‐ras oncogene—were examined. The constitutive expression of either the Ha‐ras oncogene or the EGF gene in FR3T3 fibroblasts resulted in cellular transformation. The effect of the differentiation‐inducing agent DMF on several properties of these transformed cell lines was examined. The EGF‐transfected cells were much more responsive to DMF than the ras‐transfected cells. DMF treatment of the EGF‐transfected cells resulted in the inhibition of anchorage‐independent growth, the restoration of a normal cellular morphology and growth rate in monolayer culture, and the down‐regulation of the proliferation‐associated nucleolar protein B23. DMF treatment had a much slighter effect on growth of the ras‐transfected cells in monolayer culture or under anchorage‐independent growth conditions. The high proliferation rate of the ras‐3 cells was associated with elevated expression of protein B23. The 19‐3 cells, but not the ras‐3 cells, expressed cell‐surface fibronectin. Treatment of the ras‐3 cells with DMF did not restore fibronectin expression. The binding of EGF was increased 3‐fold in the EGF‐transfected cells and decreased 20‐fold in ras‐transfected cells, but in neither case did DMF alter EGF binding. DMF treatment increased the secretion of EGF in the 2 transfected lines as well as in control cells. These results suggest that the aberrant‐growth control in the EGF‐transfected cells, but not in the ras‐transfected cells, could be modulated by DMF and that the aberrant‐growth control mechanisms were different in these 2 cell types.
Invasive and metastatic properties of MCF‐7 cells and rasH‐transfected MCF‐7 cell lines
Authors: Gelmann Edward P. , Thompson Erik W. , Sommers Connie L. 
Published: February 2007

AbstractIn vitro invasion and in vivo metastasis assays were performed with a panel of MCF‐7 cells transfected with isogenic constructs of mutated rasH genes. Both increased levels of rasH expression and rasH oncogene activation increased activity of derivative cell lines in in vitro invasion assays. In vivo formation of spontaneous metastases was assessed after intradermal inoculation of MCF‐7 cells in the vicinity of the mammary fat pads of ovariectomized nude mice. No metastases were seen in the absence of estradiol treatment of the mice. With estradiol supplementation of the mice both the rasH‐transfected and control transfected cell lines gave a higher incidence of metastases than parental MCF‐7 cells. Prolonged treatment of mice with exogenous estradiol (60 days vs. 21 days) resulted in more frequent metastases to liver and lung at the end of the 90‐day observation period. In contrast to activated rasH‐gene enhancement of metastatic capacity of rodent fibroblast and epithelial cell lines, there was no correlation of rasH expression with in vivo metastatic capacity of a human mammary carcinoma cell line.