bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous response to the growth factors [EGF, PDGF (bb), TGF‐α, bFGF, IL‐2] on glioma spheroid growth, migration and invasion
Authors: Pedersen Paal‐Henning , Ness Gro Oddveig , Engebraaten Olav , Bjerkvig Rolf , Lillehaug Johan R. , Laerum Ole Didrik 
Published: February 2007

AbstractThe effects of 5 different growth factors [EGF, PDGF(bb), TGF‐α, bFGF and IL‐2] were studied on tumour spheroids obtained from 5 different human glioma cell lines (U‐251MG, D‐263MG, D‐37MG, D‐54MG, GaMG). The expression of EGF and PDGF receptors as well as the endogenous production of TGF‐α and PDGF Were studied by Northern blot analyses. After growth‐factor‐exposure, tumour spheroid volume growth, and directional cell migration from the spheroids were studied. In addition, tumour‐cell invasion was studied In vitro, where foetal rat‐brain aggregates were used as a target for the tumour cells. In all the assays a common stimulator for most of the cell lines was EGF. The other growth factors had a more heterogeneous stimulatory effect. Tumour‐cell invasion, cell growth and cell migration are biological properties which are not necessarily related to each other. This may explain why the tumours often responded differently to the growth factors in the various assay systems. Two of the cell lines studied were non‐invasive (U‐25IMG, D‐263MG). It is shown that these were stimulated both in the directional migration assay and in the spheroid‐volume‐growth assay. However, their non‐invasive behaviour was not influenced by the growth factors studied.
Therapeutic effects of monoclonal antibody g250, interferons and tumor necrosis factor, in mice with renal‐cell carcinoma xenografts
Authors: van Dijk J. , Uemura H. , Beniers A. J. M. C. , Peelen W. P. , Zegveld S. Th. , Fleuren G. J. , Warnaar S. O. , Oosterwijk E. 
Published: February 2007

AbstractBecause renal‐cell carcinoma (RCC) is considered relatively resistant to radio‐and chemotherapy, RCC patients may benefit from new treatment modalities, e.g. immunotherapy. In vitro and in vivo studies suggest that combinations of cytokines such as interferon γ or interferon a (IFN‐γ, IFN‐α) and tumor necrosis factor a (TNF‐α) may act synergistically. In this study we tested whether a monoclonal antibody (MAb) G250, reactive with a RCC‐associated antigen, showed anti‐tumor effects in vivoin nude mice with established s.c. human RCC xenografts, and also whether this MAb could enhance the anti‐tumor effect of combinations of IFNs and TNF‐α. Treatment with combinations of IFN‐α/TNF‐α or IFN‐γ/TNF‐α, or with MAb G250 alone, resulted in a significant inhibition of tumor growth. Treatment with MAb G250, in combination with IFN‐γ/TNF‐α, did not result in an improve anti‐tumor effect as compared to that of either treatment alone. In contrast, MAb G250 combined with IFN‐α/TNF‐α resulted in a significantly enhanced anti‐tumor response. In one experiment, 3 out of 10 mice showed complete tumor regression, with no recurrence after 90 days. Large numbers of infiltrating macrophages were found surrounding viable and necrotic tumor tissue after treatment with G250 combined with IFN‐α/TNF‐α. These results suggest that combination therapy, consisting of IFN‐α, TNF‐α and MAbs, may have therapeutic value in the treatment of RCC.
Resistance to the anti‐proliferative effect of IL‐1 on human melanoma cell line is associated with endogenous production of IL‐1 and IL‐6
Authors: Araki Makoto , Yano Taishi , Hayashi Hidetoshi , Takii Takemasa , Suzuki Katsuya , Onozaki Kikuo 
Published: February 2007

AbstractA human melanoma cell line (A375–6) became resistant to the anti‐proliferative effect of human IL‐I after a long period of culture. Two stable resistant sub‐clones were obtained, and the mechanism of the IL‐I resistance was investigated. Resistant cells, but not sensitive cells, appeared to produce constitutiveiy IL‐I activity. The activity was neutralized by anti‐IL‐I a antibody but not by anti‐IL‐I β antibody. Resistant cells expressed IL‐I α but not IL‐Iβ mRNA. Therefore, the resistant cells appeared to produce IL‐β α. mRNA for IL‐I receptor antagonist (IL‐I Ra) was not detected in resistant cells, indicating that the resistance is not attributable to IL‐IRa. These resistant cells were also resistant to the anti‐proliferative effect of human IL‐6, but not to that of human TNF. Resistant cells appeared to produce constitutively IL‐6 more than sensitive cells, and IL‐6 production both in sensitive and in resistant cells was augmented by exogenous IL‐I. Furthermore, constitutive production of IL‐6 in resistant cells was inhibited by IL‐I Ra. Type I IL‐I receptor (IL‐IR) mRNA was expressed equally in resistant and sensitive cells. These data indicate that the resistance is not the result of loss of functional IL‐IR and that IL‐I induces IL‐6 in an autocrine manner. It is, therefore, conceivable that endogenous IL‐I and IL‐6 contribute to IL‐I resistance.
Cell‐surface sulfoglycolipids are involved in the attachment of renal‐cancer cells to laminin
Authors: Kobayashi Takahiko , Honke Koichi , Kuramitsu Yasuhiro , Hisokawa Masuo , Miyazaki Tamotsu , Murata Jun , Saiki Ikuo , Ishizuka Ineo , Makita Akira 
Published: February 2007

AbstractWe investigated the role of sulfoglycolipids on human renal‐cell carcinoma cells (SMKT‐R3) in the attachment to a substrate adhesive protein, laminin. SMKT‐R3 cells over‐express sulfoglycolipids, including SM2, SM3 and SM4. When acidic glycolipid fractions were extracted from SMKT‐R3 cells, separated by HPTLC, and then overlaid with laminin, laminin bound specifically to SM3 and SM4. A monoclonal antibody, Sulph‐1, reacting with SM3 and SM4 inhibited attachment of the cells to laminin but not to fibronectin, in a dose‐dependent manner. In addition, when exogenous SM4 was incorporated into the cells, their attachment to laminin, but not to fibronectin, was enhanced. On the other hand, the incorporation of GalCer, which is a precursor of SM4, had no effect on adherence of the cells to laminin or to fibronectin. We also assayed haptotaxis, tumor‐cell migration along a gradient of substratum‐bound laminin. The incorporation of SM4 into the cells caused an approximately 3‐fold increase of the haptotactic response to laminin compared with non‐or GalCer‐incorporation. These results taken together suggest that sulfoglycolipids on renal‐cancer cells are involved in attachment to laminin and that they can modulate the metastatic potential of renal‐cell carcinoma cells.
Risk of multiple primary tumors following oral squamous‐cell carcinoma
Authors: Jovanoic Andreas , van der Tol Ignaz G. H. , Schulten Engelbert A. J. M. , Kostense Pieter J. , de Vries Nico , Snow Gordon B. , van der Waal Isaäc 
Published: February 2007

AbstractThe follow‐up of 727 patients with squamous‐cell carcinoma (SCC) of the lip and oral cavity has been used for the risk analysis of multiple primary tumors (MPTs) following SCC of the lip and oral cavity. Age‐, gender‐and site‐specific cancer‐incidence rates from the general population have been applied to the appropriate persons‐years of follow‐up of patients with SCC of the lip and oral cavity. The study indicates that patients with a primary SCC of the lip and oral cavity have, compared with the general population, a significantly elevated risk of developing an additional cancer of the oral cavity and/or pharynx, the risk being 74.7‐fold for males and 190.4‐fold for females. Furthermore, a 24.6 and 45.3 times higher risk of an additional esophageal tumor was found in males and females respectively. The risk of cancer of the lung and pharynx was less elevated compared with the risk of cancer of the upper digestive tract. No elevated risks were established in organs outside the respiratory and upper digestive tract.
p53 mutations in human bladder cancer: Genotypic versus phenotypic patterns
Authors: Cordon‐Cardo Carlos , Dalbagni Guido , Saez Guillermo T. , Oliva Maria R. , Zhang Zuo‐Feng , Rosai Juan , Reuter Victor E. , Pellicer Angel 
Published: February 2007

AbstractThe objective of this study was to characterize the pattern of p53 mutations in bladder cancer. The sensitivity and specificity to detect these mutations using clinical material was assessed for the following assays: immunohistochemistry, restriction‐fragment‐length polymorphism, single‐strand‐conformation polymorphism, and sequencing.Discrepancies of reported results aimed at the identification of genetic alterations in the p53 gene may be due to differences in methodology, as well as to deficient morphological evaluation of the source of tissue utilized. In order to address these critical issues, we have implemented a novel experimental design that permits analysis by molecular genetics and immunopathology techniques in any given tissue specimen, allowing morphological correlation with genotypic and phenotypic characteristics of the tissue analyzed.Forty‐two patients affected with bladder tumors in whom paired normal and tumor tissues were available were used for the present study. Nuclear immunoreactivities were observed in 26 out of 42 bladder tumors analyzed. Abnormal shifts in mobility were noted in 14 of the 42 cases in distinct exons, with one tumor revealing 3 mutations. There was a strong association between p53 nuclear over‐expression and 17p LOH, as well as p53 nuclear over‐expression and detection of mutations by SSCP and sequencing. According to receiver‐operating‐curve statistical analysis, the accuracy of detecting p53 mutations by IHC was estimated to be 90.3%. It is our conclusion that, when properly used, this is a highly sensitive and specific method with simple application using clinical material.
Moderate elevation of body iron level and increased risk of cancer occurrence and death
Authors: Stevens Richard G. , Graubard Barry I. , Micozzi Marc S. , Neriishi Kazuo , Blumberg Baruch S. 
Published: February 2007

AbstractThe purpose of the study was to address the hypothesis that elevated body iron increases the risk of cancer occurrence and death, and to determine the dose response. Subjects were 3, 287 men and 5,269 women participating in the first National Health and Nutrition Examination Survey who had a transferrin saturation determination at enrollment (1971–1975), who remained alive and cancer‐free for at least 4 years, and who were followed to 1988 for cancer outcome. Among 379 men who developed cancer over the study period, the mean transferrin saturation at enrollment was 32.1 % whereas among 2,908 who remained cancer‐free it was 30.7%; the difference for mortality was 32.3% among 233 deaths vs. 30.8% among 3,054 men not dying of cancer. The mean differences among women were hot significant. The mean differences in TIBC and serum iron among men were consistent with the findings for transferrin saturation, and all 3 differences were stable over time when examined by years since blood test. Men and women were divided into 5 groups on the basis of baseline transferrin saturation: 0 to 30%, 30–40%, 40–50%, 50–60%, and 60% and higher. Nineteen percent of men had a baseline transferrin saturation above 40% (the last 3 groups), whereas only 10 percent of women had transferrin saturation above 40%. For men and women combined, risk of cancer occurrence in each group relative to the first was 1.0, 0.95, 1.16, 1.38 and 1.81; for mortality the relative risks were 1.0, 0.96, 1.22, 1.29 and 1.73. There is evidence, in this cohort, of elevated cancer risk in those with moderately elevated iron level. This pattern was seen in women as well as in men.
Growth control of embryonic stem cells injected into mouse uterus on fifth day of pregnancy
Authors: Monzo M. , de Anta J. M. , Peris B. , Ruano D. 
Published: February 2007

AbstractPrevious studies have shown that embryonic stem cells (ES) may participate in normal embryonic development when they are injected into the blastocyst. In contrast, ES cells develop into tumors if injected in ectopic sites in adult mice. In this study we injected ES‐D3 cells, with the LacZ gene incorporated, into 5‐day pregnant mouse uteri, into pregnant unilaterally salpingectomized uteri, into pseudo pregnant uteri and into non‐pregnant uteri. X‐gal staining enabled us to identify injected ES cells on the 7th, 9th, 10th, 12th and 15th days post‐injection. In pregnant decidua, the ES cells were located initially in the mesometrial decidua and later distributed in the basal and capsular decidua and in the endodermic layer of the visceral yolk sac. In pregnant, unilaterally salpingectomized mouse uteri, ES cells were mainly located in the uterine lumen and tumors were not observed in either case. In contrast, ES cells injected into pseudopregnant uteri often developed into tumors and those injected into non‐pregnant uteri always developed into teratocarcinomas. We conclude that the pregnant‐uterine microenvironment may participate in the control of ES cell growth.
Expression of the 100‐kDa glucose‐regulated protein (grp100/endoplasmin) is associated with tumorigenicity in a model of rat colon adenocarcinoma
Authors: Ménoret Antoine , Meflah Khaled , Pendu Jacques Le 
Published: February 2007

AbstractResistance to glucose starvation and expression of glucose regulated proteins (grp) were studied in a model of rat colon carcinoma. In this model, various clones originating from the same parental tumor showed distinct tumorigenic potential in syngeneic hosts. Some clones were tumorigenic while others were rejected by an immune‐based mechanism. It appeared that the more tumorigenic clones were more resistant to glucose starvation and able to synthesize larger amounts of grp100 than non‐tumorigenic clones in response to either glucose starvation or tunicamycin treatment. In contrast, there was no difference in the induced levels of synthesis of grp78 between tumorigenic and non‐tumorigenic clones. These results suggest that the ability of cells to synthesize large amounts of the stress protein grp 100 might allow them to resist marginal conditions imposed by fully immunocompetent hosts, thus conferring greater tumorigenicity.
TGF‐β receptor regulation mediates the response to exogenous ligand but is independent of the degree of cellular differentiation in human oral keratinocytes
Authors: Prime S. S. , Matthews J. B. , Patel V. , Game S. M. , Donnelly M. , Stone A. , Paterson I. C. , Sandy J. R. , Yeudall W. A. 
Published: February 2007

AbstractThis study examined the expression of TGF‐β cell‐surface receptors, the response to exogenous TGF‐β1 and the autocrine production of TGF‐β in normal and squamous cell carcinoma‐derived human oral keratinocytes with variable degrees of cellular differentiation. TGF‐β receptor expression, the response to exogenous ligand and the autocrine production of TGF‐β appeared unrelated to cellular differentiation. Cells expressed variable proportions of type‐I,‐II and‐III TGF‐β receptors. The expression of type‐III receptors correlated inversely with the expression of type‐I receptors, but there was no relationship between type‐II and either type‐I or type‐III TGF‐β receptors. Normal cells and the majority (7 of 8) of tumour‐derived keratinocytes were inhibited by exogenous TGF‐β1 and the degree of inhibition correlated with the expression of type‐I, but not type‐II or type‐III, TGF‐β receptors. One tumour‐derived cell line was refractory to exogenous TGF‐β1 although it expressed all 3 receptor types. Endogenous TGF‐β was produced by both normal and tumour‐derived keratinocytes and correlated inversely to the expression of type‐I, but not type‐II, TGF‐β receptors. Further, cells that produced more autocrine TGF‐β had a diminished response to exogenous TGF‐β1. The data indicate a complex interaction between the expression of TGF‐β cell‐surface receptors, endogenous ligand production and the cellular response to exogenous TGF‐β1.
Cyclic AMP increases the release of parathyroid hormone‐related protein from a lung‐cancer cell line
Authors: Rizzoli René , Aubert Michel Lucien , Sappino André Pascal , Bonjour Jean‐Philippe 
Published: February 2007

AbstractParathyroid hormone‐related protein (PTHrP) plays an important role in the pathogenesis of malignant hypercalcemia by stimulating bone resorption and/or renal tubular reabsorption of calcium. In cultured cancer cells, its production can be influenced by various factors or ions, but the regulation of its production is still poorly understood. We investigated the effects of stimulators of cAMP synthesis on PTHrP release by a human lung squamous‐carcinoma cell line (BEN). In supervised cells grown on microcarrier beads, PTHrP production was significantly increased after incubation with calcitonin for only 20 min. The release of immunoreactive and bioactive PTHrP was increased by incubating the cells with forskolin, 3‐isobutyl‐I‐methylxanthine or dibutyryl cAMP even in the presence of the protein‐synthesis inhibitor cycloheximide for 6 hr. The calcitonin‐mediated stimulation was not accompanied by. concomitant changes in PTHrP mRNA. The microfilament‐disrupter cytocha‐lasin D was shown to enhance the basal and calcitonin‐induced production of PTHrP. These results indicate that stimulators of cAMP synthesis enhanced PTHrP release by BEN cells.
Activation of the protein kinase a signal transduction pathway by granulocyte‐macrophage colony‐stimulating factor or by genetic manipulation reduces cytoskeletal organization in lewis lung carcinoma variants
Authors: Young M. Rita I. , Charboneau Susan , Lozano Yvonne , Djordjevic Andelka , Young Melvin E. 
Published: February 2007

AbstractGranulocyte‐macrophage colony‐stimulating factor (GM‐CSF) that is produced by metastatic Lewis lung carcinoma (LLC‐LN7) cells functions as an autocrine stimulator of tumor‐cell motility through protein kinase A (PKA) signal transduction. This GM‐CSF‐mediated enhancement of LLC‐LN7 cell motility coincides with a reduction in the level of polymerized F‐actin. In contrast, non‐metastatic LLC‐C8 tumor cells, which have a diminished level of PKA signaling, do not produce GM‐CSF and do not respond to exogenous GM‐CSF, since they remain non‐motile and retain a high content of filamentous actin. The capacity of PKA to regulate the cytoskeletal organization of tumor cells was further studied with the use of LLC variants that had been stably transfected to over‐express the Cα subunit of PKA (CEV cells) or to express a mutant cAMP‐resistant PKA R1α subunit resulting in a defective PKA (REV cells). When compared with wild‐type metastatic LLC‐LN7 cells, in which the F‐actin staining was too diffuse to be clearly visualized microscopically, the PKA‐defective REV‐LN7 transfectants had an increased level of F‐actin. In comparison with the wild‐type non‐metastatic LLC‐C8 cells, which had a high content of F‐actin, the CEV‐C8 transfectants that over‐expressed PKA activity had a reduced level of F‐actin. The reduced polymerization of actin in these CEV‐C8 transfectants was accompanied by reduced levels of the intermediate filament protein vimentin and a shift in the distribution both of F‐actin and of vimentin to the periphery of the cells. These results show reduced cytoskeletal organization in metastatic LLC‐LN7 cells as compared with that of non‐metastatic LLC‐C8 cells, and indicate that elevation of PKA activity, either by autologous GM‐CSF or by genetic manipulation, diminishes cytoskeletal organization.
Qualitative and quantitative intratumoral changes in gene expression following cyclophosphamide injection and the adoptive transfer of t cells: The potential contribution of tumor‐associated macrophages
Authors: Evans Robert , Kamdar Sonya J. , Duffy Theodore M. 
Published: February 2007

AbstractAdoptive immunotherapy (AIT) of mice bearing the MCA/ 76‐9 rhabdomyosarcoma in combination with cyclophosphamide (CY) injection results in the permanent regression of tumors. This report is concerned with changes in the tumor‐associated macrophage (TAM) population and the influence of both CY injection and CY/AIT on their potential functions. Sequential analyses of FcR, MAC‐1 and Class‐II MHC antigen expressed by tumor‐associated cells (TAC) showed that CY injection or CY/AIT induced marked increases in the proportions of all 3 parameters as compared with the relatively stable levels in progressing tumors. These changes were time‐and treatment‐related. The mean MAC‐1 fluorescence (antigen density per cell) increased nearly 2‐fold by 48 hr after CY injection, regardless of subsequent AIT. In contrast, the density of Class‐II antigen per cell declined by as much as 75% within 48 hr after CY injection and did not recover by 7 days. This initial decline was also seen after CY/AIT and was followed by a rapid recovery to near‐normal values by day 7. Northern analysis of RNA isolated from whole tumor tissue indicated wide fluctuations in expression of the typical macrophage genes encoding the proteins MAC‐1, IL‐1α, IL‐1β, TNFα, IAβ) and c‐fms. However, with the exception of MAC‐1 and IL‐1α/IL‐1β mRNA, the modifications appeared to be qualitative rather than representing changes in the proportions of TAM. The data suggest that the changes in membrane antigen and gene expression by TAM reflect a complex interaction between TAM and their environment, in particular tumor cells and tumor‐infiltrating lymphocytes. In addition, it is evident that CY injection per se is responsible for defined fundamental changes that presumably influence the outcome of AIT.
Internal image anti‐idiotype antibodies related to renal‐cell carcinoma‐associated antigen G250
Authors: Uemura H. , Okajima E. , Debruyne F. M. J. , Oosterwijk E. 
Published: February 2007

AbstractThe potential usefulness of internal‐image anti‐idiotype antibodies (Ab2s) in modulating hosts' immune responses to tumor‐associated antigen (TAA) have stimulated considerable interest in the development and characterization of Ab2s. Six different mouse monoclonal Ab2s (NUH31, 44, 51, 71, 82 and 91) were generated against murine monoclonal antibody G250 (MAbG250) which recognizes a human renal‐cell carcinoma‐associated antigen. All 6 Ab2s showed specificity for the MAbG250 paratope in Western‐blot analysis. In inhibition assays, all Ab2s were able to compete with the nominal antigen, albeit with differing efficiency. Based on cross‐blocking studies for idiotope mapping, the Ab2s could be divided into 2 groups (group 1; NUH31, 51,71, group 2; NUH44, 82, 91). However, cross‐reactivity between these 2 groups was observed, indicating that they recognized partly overlapping epitopes on the paratope of MAbG250. Sera from rabbits immunized with Ab2s showed reactivity with G250 antigen‐positive cell lysates, but not with antigen‐negative cell lysates. Additional studies revealed that all Ab2s were able to induce anti‐anti‐idiotype antibodies resembling MAbG250 (Ab1). These findings suggest that the Ab2s functionally mimic the original G250 antigen and may be of use in the immunotherapy of human renal‐cell carcinoma.