bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss
Authors: Cornelisse Cees J. , Kuipers‐Dijkshoorn Nel , van Vliet Margreethe , Hermans Jo , Devilee Peter 
Published: February 2007

AbstractWe have previously reported a complete allelotype study of 86 primary breast carcinomas, in which each non‐acrocentric chromosome arm was studied with at least one polymorphic DNA‐marker for the presence of allelic imbalance (Al, allelic loss or allelic gain) in the tumor. Here we report the statistical analysis of this data set, investigating the relationships between Al, DNA aneuploidy and several clinico‐pathological parameters of tumor progression. Al on 13 different chromosome arms, including 3p, 11 p, and 17p, correlated significantly with the total number of Al events at other sites, suggesting that they are progression‐related events. Al at 1q and 16q did not show such a correlation and may thus represent earlier events. Mean fractional allelic imbalance (FAI) was significantly higher in flow cytometrically aneuploid tumors than in diploid tumors (0.27 vs. 0.17, p = 0.007), and was highest in hypotetraploid tumors (0.37). This suggests that tetraploidization followed by chromosome segregation may underlie the development of Al at multiple sites. No correlation was found between mean FAI and clinico‐pathological variables such as lymph‐node involvement, stage, age, estrogen‐receptor content and development of distant metastases, although there was a noticeable trend towards impaired survival for those patients with a higher‐than‐median FAI value.
Patients with cervical cancer produce an antibody response to an HSV‐inducible tumour‐specific cell polypeptide
Authors: MacNab Joan C. M. , Nelson J. S. , Daw S. , Hewitt R. E. P. , Lucasson J.‐F. , Shirodaria P. V. 
Published: February 2007

AbstractAnti‐sera raised against HSV‐2‐infected cells (Wl) and the sera of animals bearing tumours (TBS) to HSV‐2 transformed cells contain antibodies to a set of tumour‐specific cell‐coded polypeptides. The specificity of these polypeptides for tumour cells is monitored by the ability of [35S]‐L‐methionine labelled proteins to be immunoprecipitated by these anti‐sera, in contrast to control cells from which the polypeptides are not precipitated. The polypeptides which share an epitope and are co‐precipitated are of MWs 90, 000 (a doublet), 40, 000 and 32,000. The upper 90,000‐MW polypeptide (U90) is induced by HSV‐2 infection. This communication deals with the 40,000‐MW polypeptide which was shown to be immunoprecipitated by TBS and a monoclonal antibody (MAb) raised to the DNA‐binding proteins of HSV‐2‐infected cells. Immunological and biochemical studies reveal that the 40,000‐MW protein which is immunoprecipitated comprises more than one polypeptide, and that the proteins may need to interact to produce the peptide pattern specific for the tumour form of the immunoprecipitated 40, 000‐MW protein. Wl antisera and TBS both recognise antigens specific for tumour cells in sections of cervical‐carcinoma tissue. Sera from patients with cancer of the cervix contain antibodies to a cell‐coded polypeptide of MW 40, 000, which by peptide analysis is indistinguishable from the 40, 000‐MW polypeptide induced by HSV‐2 infection and immunoprecipitated by Wl and TBS.
SDZ PSC 833, A non‐immunosuppressive cyclosporine: Its potency in overcoming P‐glycoprotein‐mediated multidrug resistance of murine leukemia
Authors: Keller Roland P. , Altermatt Hans J. , Nooter Kees , Poschmann Guenter , Laissue Jean A. , Bollinger Pietro , Hiestand Peter C. 
Published: February 2007

AbstractCyclosporin A (CsA, Sandimmune) is known to reverse P‐glycoprotein(P‐gp 170)‐mediated multidrug resistance as efficiently as other prototype compounds of resistance modifiers. The immunosuppressive activity and nephrotoxicity of CsA, however, may limit its clinical use. PSC‐833, a new cyclosporine, exerts a similar resistance‐modifying activity but lacks toxicity or immunosuppressive activity. We have tested its potency in vitro and in vivo on the L1210 leukemia cell line transfected with a full‐length cDNA copy of the human mdr I gene, which showed a stable 30‐fold resistance towards adriamycin as compared to the parental cell line. In vitro growth of the transfected cell was unchanged. In vivo growth was less aggressive; the survival time of inoculated mice was prolonged. In vitro, PSC‐833 was at least as potent as CsA or verapamil in reversing multidrug resistance. In vivo, the drug‐resistant L1210 leukemia was completely unresponsive to i.v. monotherapy with adriamycin at its maximum tolerated dose (MTD). PSC‐833 enhanced the activity and toxicity of adriamycin. The MTD of adriamycin was about 3 times lower than when given alone. On this basis, the MTD of i.v. adriamycin in combination with oral PSC‐833 successfully overcame refractoriness to treatment. Survival times of the mice were considerably prolonged and even some cures of leukemic mice occurred.
Analysis of tyrosine kinase mRNAs including four FGF receptor mRNAs expressed in MCF‐7 breast‐cancer cells
Authors: Lehtola Laura , Partanen Juha , Sistonen Lea , Korhonen Jaana , Wärri Anni , Härkzönen Pirkko , Clarke Robert , Alitalo Kari 
Published: February 2007

AbstractThe MCF‐7 cell line is a hormone‐responsive human breast‐cancer cell line, which has been extensively used in studies of estrogen regulation of cell growth. These studies have indicated that the growth stimulation of the MCF‐7 cells by estrogens may be effected by an autocrine mechanism involving several growth factors, such as EGF, TGFα and IGF‐I and their receptors. We have amplified and cloned tyrosine‐kinase‐related sequences from the MCF‐7 cell mRNA using the polymerase chain reaction and characterized the partial cDNAs obtained by nucleic acid sequencing. Nine tyrosine kinase cDNAs and one serine/threonine kinase cDNA were identified among the amplified sequences. Four different tyrosine kinase genes encoding receptors for fibroblast growth factors (FGFs) were found to be expressed by the MCF‐7 cells. In addition, differences were observed in the expression of these members of FGF receptor family in different breast‐cancer cells. A putative tyrosine‐kinase receptor and a novel serine/threonine kinase were preferentially expressed in estrogen‐responsive tumor cell lines. However, no estrogen‐dependent regulation of any of the novel tyrosine‐kinase receptor mRNAs was found in any of the cell lines including the MCF‐7 or ZR‐75‐1 cells, where the expression of the neu proto‐oncogene mRNA was decreased during estrogen treatment. The expression of several FGF receptors by breast‐cancer cells suggests that FGFs may be involved in their growth regulation and tumorigenesis.
Short‐term assays for detection of conditional cancerogens I. Construction of DR‐CAT Raji cells and some of their characteristics as tester cells
Authors: Polack Axel , Laux Gerhard , Hergenhahn Manfred , Kloz Ulrich , Roeser Helmut , Hecker Erich , Bornkamm Georg W. 
Published: February 2007

AbstractA number of agents including the tumor promoter 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA) can induce an abortive virus cycle in the EBV‐non‐producer Burkitt's‐lymphoma line Raji. Two distant regions, DL and DR, of the EBV genome with almost complete homology carry strong promoters which are induced in an abortive or lytic cycle and additionally function as lytic origins of viral DNA replication. To set up a system in which the activity of EBV‐inducing agents can be measured in a quantitative and reproducible fashion, we generated a cell line which carries multiple copies of a DR‐promoter chloramphenicol‐acetyltransferase (CAT) construct on an episomal vector. CAT activity is low in untreated cells, but high upon treatment of the cells with various EBV‐inducing agents. Combinations of different agents can produce an over‐additive effect. The Raji‐DR‐CAT cell line may provide a simple quantitative and reproducible test system for EBV‐inducing agents, especially for tumor promoters which activate protein kinases C.
The desmoplastic response: Induction of collagen synthesis by melanoma cells in vitro
Authors: Fearns Colleen , Dowdle Eugene B. 
Published: February 2007

AbstractWhen cells from the human malignant melanoma cell line, UCT‐Mel 7, were injected into athymic nude mice, tumours developed that were intensely infiltrated with fibrous tissue. In an attempt to reproduce this desmoplastic response in vitro, we co‐cultured fibroblasts with UCT‐Mel‐7 cells, and observed a 2‐fold increase in the rate of fibroblast collagen synthesis. This was associated with an increase in the amount of collagen mRNA present in co‐cultured fibroblasts. The stimulation was both dose‐ and time‐dependent, with maximal stimulation at a melanoma cell:fibroblast ratio of 1:1. Analysis of the kinetics of proline incorporation into collagen showed that co‐culture affected the maximal rate of proline incorporation; no effect was observed on the concentration of proline required for 50% maximal collagen synthesis. The induction of fibroblast collagen synthesis showed an absolute requirement for close proximity between the fibroblasts and the melanoma cells. No soluble fibrogenic factor released by melanoma was detected.
Enhancement by vaso‐active intestinal peptide of gastric carcinogenesis induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine in rats
Authors: Iishi Hiroyasu , Tatsuta Masaharu , Baba Miyako , Okuda Shigeru , Taniguchi Haruo 
Published: February 2007

AbstractThe effects of vaso‐active intestinal peptide (VIP) on gastric carcinogenesis induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine (MNNG) were investigated in Wistar rats given VIP every other day for 27 weeks after oral administration of MNNG for 25 weeks. In week 52, administration of VIP caused a significant increase in the incidence of gastric cancers, but did not influence their histological appearance. VIP significantly increased the labeling indices of the antral mucosa. Our findings indicate that VIP enhances gastric carcinogenesis, and that this effect may be related to its effect in increasing cell proliferation of the antral epithelial cells.
Relationship between sensitivity to natural killer cells and MHC class‐I antigen expression in colon carcinoma cell lines
Authors: Blottière Hervé M. , Zennadi Rahima , Burg Cedric , Douillard Jean‐Yves , Meflah Khaled , Pendu Jacques Le 
Published: February 2007

AbstractThe sensitivity of colorectal tumors to NK‐cell‐mediated cytotoxicity and their expression of major histocompatibility complex (MHC) class‐I antigens were studied in an attempt to determine whether such antigens play a role in the susceptibility of colorectal tumors to NK‐cell lysis. In a rat colon‐carcinoma model, 2 clones differing in their sensitivity to NK‐cell‐mediated cytotoxicity were tested for class‐I expression; it was seen that the more sensitive cells (REGb) expressed less class‐I products than did the resistant cells (PROb). However, when MHC class‐I antigen expression was increased by IFN‐γ treatment, no change in NK‐cell lysis was found with the PROb cells, while an increase in cytotoxicity was obtained with the REGb cells. After in vivo or in vitro selection of NK‐resistant REGb cells, we observed in the selected cells an important decrease in RT‐I class‐I antigen expression. Fifteen different human colorectal cell lines were also studied for HLA class‐I expression and NK‐cell susceptibility, and no quantitative correlation between these 2 features was seen. However, cell lines which were deficient in HLA class‐I antigens were more sensitive than class‐I‐positive cells.
N‐ras gene mutations in acute myeloid leukemia: Accurate detection by solid‐phase minisequencing
Authors: Syvänen Ann‐Christine , Söderlund Hans , Laaksonen Eveliina , Bengtström Marina , Turunen Minna , Palotie Aarno 
Published: February 2007

AbstractMutations in the N‐ras gene are found in one‐third of patients with acute myeloid leukemia. The N‐ras mutations could serve as markers for residual cells, if a highly sensitive method for detecting the mutations was available. We applied a new method, solid‐phase minisequencing, to analyze bone‐marrow cells from 16 patients with acute myeloid leukemia for mutations in codon 12, 13 and 61 of the N‐ras gene. In the solid‐phase minisequencing technique the mutations are identified by a primer extension reaction, in which a single labelled nucleoside triphosphate is incorporated into an immobilized DNA fragment previously amplified by the polymerase chain reaction. We identified N‐ras mutations in 5 of the patients (30%). In one patient, we observed 2 mutations that were shown to be located in different alleles. With the solid‐phase minisequencing method, we were able to determine the proportion of mutated cells in the samples. We found that in 4 of the samples only a fraction (7–64%) of the blasts carried an N‐ras mutation, and in one sample practically all blast cells were mutated. The method was highly sensitive, allowing us to identify N‐ras mutations even when the sample consisted of 99.7% normal cells and only 0.3% mutated blasts.
Visualization of the plasmin receptor on carcinoma cells
Authors: Correc P. , Zhang S. , Komano O. , Laurent M. , Burtin P. 
Published: February 2007

AbstractIn order to visualize the receptor for plasmin and plasminogen present on human carcinoma cells, SWI116 and MCF7‐MF cells were incubated with biotinylated plasminogen or plasmin and fluoresceinated streptavidin, and counterstained with propidium iodide. It was first demonstrated that biotinylation did not alter the binding properties of plasminogen and plasmin, provided that the biotinylation rate was around 2. Specific staining of tumor cells was obtained using these reagents. Images with green fluorescence were clearly visible as grains or contours at the surface of tumor cells. The localization of fluorescent grains was analyzed more precisely using confocal microscopy. The percentage of stained cells varied from one experiment to another between 10 and 60%. In no experiment were all the cells observed to be positive. Mitotic cells were more frequently stained than non‐mitotic cells, suggesting a relationship between the presence of plasmin receptors and cell proliferation. This was confirmed by the use of Ki67 monoclonal antibody (MAb), as B‐Pg‐binding tumor cells generally had their nucleus stained by this antibody. Other images indicated staining of the extracellular matrix. Finally, 2 rat tumor‐cell sub‐lines of colonic origin (DHD K12 Pro‐b and Reg‐b) were shown to bind human biotinylated plasminogen, confirming the strong interspecies reactivity of plasmin receptors.
Androgen regulation of prolactin‐receptor gene expression in MCF‐7 and MDA‐MB‐453 human breast cancer cells
Authors: Ormandy Christopher J. , Clarke Christine L. , Kelly Paul A. , Sutherland Robert L. 
Published: February 2007

AbstractLactogenic hormones which bind to the PRLR are likely to be growth‐stimulatory in human breast‐cancer cells. Oestrogen and progesterone control cellular expression of the PRLR; however, elevated androgen levels in some breast‐cancer patients raised the possibility that androgens may also influence breast‐cancer sensitivity to lactogenic hormones. This study investigated whether androgens could affect expression of the PRLR in the MCF‐7 breast‐cancer cell line. PRLR binding activity was increased approximately 2‐fold by treatment for 24 hr with 10 nM RI881, TEST, DHT, MPA and ORG 2058. Northern analysis indicated that DHT also increased the level of PRLR mRNA. The antiprogesterone, RU 38486, displaced tritiated ORG 2058 binding but not tritiated DHT binding to MCF‐7 cells; it completely antagonized ORG 2058 and partially antagonized RI881 induction of the PRLR, but had no effect on induction by DHT. The anti‐androgen, RU 23908, displaced tritiated DHT binding but not tritiated ORG 2058 binding, and antagonized DHT and RI881 induction of PRLR but not induction of the PRLR by ORG 2058. These data indicated that ORG 2058 acting via the PR and DHT acting via the AR were able to induce PRLR expression in MCF‐7 cells. In MDA‐MB‐453 cells, which express the AR but not the ER or PR, DHT and RI881 increased PRLR binding to 150% of control values at 0.1 nM. ORG 2058 was ineffective, demonstrating androgen induction of PRLR in the absence of PR and ER. These data indicate that PRLR can be regulated by androgens in MCF‐7 and MDA‐MB‐453 human breast‐cancer cells.
Detection of simian T‐lymphotropic virus type I using the polymerase chain reaction
Authors: Dezzutti Charlene S. , Lazo Aristides , Yee Joanne Y. , Blakeslee James R. , Mathes Lawrence E. , Brown Bobby G. , Lairmore Michael D. 
Published: February 2007

AbstractTo develop the polymerase chain reaction (PCR) for the detection of simian T‐lymphotropic virus type I (STLV‐I) infection, cell lines or peripheral‐blood mononuclear cells (PBMC) from 2 non‐human primate species [African green monkeys (AGM), Cercopithecus aethiops; baboon, Papio cynocephalus] were evaluated for their STLV‐I status using oligonucleotide primer pairs and probes specific for the tax and pol gene regions of the closely related human T‐lymphotropic virus type I (HTLV‐I). These PCR results were compared with serologic (Western blot assay) and viral culture (p24‐antigen capture assay) data. PCR products for both gene regions were detected in established baboon, Japanese macaque and rhesus macaque STLV‐I‐producing cell lines. STLV‐1 tax and pol products were also detected in PBMC from 4 of 4 infected AGM and 4 of 4 infected baboons, each of which were also Western‐blot‐positive and p24‐antigen‐capture‐positive. Of the remaining AGM (n = 7) and baboon (n = 1) which were PCR‐negative, each was also Western‐blot‐negative and p24‐antigen‐capture‐negative. Two seronegative and virus‐culture‐negative AGM were classified as PCR indeterminate with weak reactivity using tax primers. These primer pairs failed to amplify DNA from uninfected human PBMC, an uninfected human lymphoid cell line, a simian immunodeficiency virus macaque (SIVmac251)‐infected cell line and a simian‐retrovirus‐type‐D(SRV‐D)‐infected cell line. HTLV‐II‐pol‐specific primer pairs failed to amplify DNA from STLV‐I‐infected cell lines and PBMC from STLV‐I‐infected monkeys. Further, HTLV‐I pol and tax primer pairs successfully amplified RNA from HTLV‐I‐ and STLV‐I‐infected cell lines by reverse transcriptase (RT)‐PCR. We have demonstrated excellent specificity in the detection of STLV‐I by PCR using these HTLV‐I‐derived primers and probes. Additionally, our data suggest that the tax and pol gene regions are conserved between HTLV‐I and STLV‐I strains found among these diverse species of non‐human primates.
Correlation of growth of tumours in NC‐cell‐depleted mice with NC‐ and NK‐cell‐mediated lysis in vitro
Authors: Smart Y. Cheng , Farrelly Margaret L. , Burton Robert C. 
Published: February 2007

AbstractThe anti‐tumour surveillance activity of natural cytotoxic (NC) cells was studied in vivo using the transplantable tumours WEHI‐164 fibrosarcoma, MPC‐11 plasmacytoma, WEHI‐7 T‐lymphoma, B16 melanoma and EL‐4 thymoma in syngeneic and semi‐allogeneic mice. Experimentally, mice were treated with the anti‐NC‐1.1 monoclonal antibody (MAb) 1C4 to abrogate splenic NC activity. This was followed by s.c. inoculation of MTD100 doses of the tumours. Comparison of the diameters of the tumours in the anti‐NC‐1.1 ‐treated mice with control mice using non‐parametric statistics showed significantly faster growth of WEHI‐164 (p < 0.01), MPC‐11 (p < 0.05) and WEHI‐7 (p < 0.05) when the mean tumour diameters were < 15mm in the anti‐NC‐1.1 ‐treated mice. Significantly faster growth was also observed in anti‐NC‐1.1 ‐treated mice with the B16 tumour (p < 0.05), but at a later stage of growth, when the tumour diameter was > 15 mm. In vitro, WEHI‐164, MPC‐11 and WEHI‐7 were shown to be predominantly sensitive to lysis by mouse splenic NC cells, while B16 was predominantly lysed by splenic natural‐killer (NK) cells. Anti‐NC‐1.1 treatment of mice did not affect the growth of EL‐4 in vivo and in vitro experiments with anti‐NK‐1.1 and anti‐NC‐1.1 MAb indicated that this tumour was lysed by sub‐sets of NK and NC cells distinct from those which lysed the other tumours. We conclude that, in mice at least, NC cells have an in vivo role in controlling the growth of some transplantable tumours, and this correlates with the in vitro NC cell lysis of these same tumours.
c‐myc over‐expression in human primary ovarian tumours: Its relevance to tumour progression
Authors: Tashiro Hironori , Miyazaki Kohji , Okamura Hitoshi , Iwai Akio , Fukumoto Manabu 
Published: February 2007

AbstractExpression of the c‐myc gene was analyzed in 56 human primary ovarian cancer tissues, including 51 common epithelial and 5 non‐epithelial tumours to determine molecular events in the carcinogenic process in ovaries. Over‐expression of the c‐myc gene was found in 37.3% of all ovarian tumour tissues, and in 63.5% of serous adenocarcinoma tissues. Significant over‐expression of the c‐myc gene at Stage III compared with other stages, and one remarkable case of over‐expression in a serous tumour of low malignant potential suggest that c‐myc expression is temporarily activated at some stage(s) during tumorigenesis of ovarian cancer, especially of serous tumours.
Recombinant interferon α‐2A combined with prednisone in metastatic renal‐cell carcinoma: Treatment results, serum interferon levels and the development of antibodies
Authors: Fosså Sophie D. , Lehne Gustav , Gunderson Ragnhild , Hielmaas Unni , Holdener Eduard E. 
Published: February 2007

AbstractFive partial responses were seen in 23 patients with metastatic renal‐cell carcinoma (MRCC) receiving interferon‐α 2a (IFN) + prednisone (P). Four of 24 subsequent patients responded to IFN + P (combined response rate 19%). The median response duration was 8 months (3 to 30 months). The one‐year survival for all eligible patients was 52%. Eight of 26 evaluable patients developed antibodies detected by an enzyme immunoassay. In 2 patients, high levels of neutralizing antibodies were also found, together with particularly low IFN levels. In one patient the development of neutralizing antibodies coincided with the loss of initial response. The treatment was well tolerated by most patients. Premature discontinuation of treatment was necessary in only 2 patients. In MRCC, combination treatment with IFN + P is as effective as IFN monotherapy (response rate 19%), with significantly reduced subjective toxicity. The clinical relevance of the development of antibodies against IFN requires further investigation.
The content of urokinase‐type plasminogen activator antigen as a prognostic factor in urinary bladder cancer
Authors: Hasui Yoshihiro , Marutsuka Kousuke , Suzumiya Junji , Kitada Shinichiro , Osada Yukio , Sumiyoshi Akinobu 
Published: February 2007

AbstractUrokinase‐type plasminogen activator (u‐PA) is thought to be implicated in cancer invasion and metastasis. The aim of this study was to determine whether the u‐PA content of cancer tissue is a prognostic factor in bladder cancer. Tissue samples from 46 patients with bladder cancer were assessed for u‐PA antigen by a highly sensitive enzyme immunoassay. The relationships between the u‐PA level in extracts of bladder cancer and the survival rates of the bladder‐cancer patients were examined. Patients with a high u‐PA level (8 ng/mg of protein and more) showed a statistically significantly higher rate of survival than those with a low u‐PA level (p < 0.005). The u‐PA antigen level in cancer tissue was significantly lower in low‐graded and non‐invasive cancers than in others (p < 0.01).