bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co‐expression of urokinase, urokinase receptor and PAI‐1 is necessary for optimum invasiveness of cultured lung cancer cells
Authors: Liu Guohui , Shuman Marc A. , Cohen Robert L. 
Published: February 2007

AbstractWe investigated the importance of the urokinase (uPA)‐plasmin system in fostering invasion of human lung cancer cells through artificial basement membranes composed of Matrigel. Eight cell lines (including 1 small cell and 7 non‐small cell fines) were examined. One cell line did not express any components of the urokinase system. Four cell lines had substantial levels of endogenous uPA detectable on their surfaces. Three of these cell lines co‐expressed the plasminogen activator inhibitor PAI‐1 in addition to uPA. Assays for invasiveness revealed 4 cell lines capable of traversing a Matrigel barrier, including the 3 which co‐expressed uPA, PAI‐1 and uPA receptor. Surprisingly, the cell line expressing only uPA and uPA receptor displayed no invasive capacity despite levels of secreted uPA more than 20‐fold higher than the other cell lines studied. Based on these observations, we hypothesized that both uPA and PAI‐1 might be important for invasion by lung tumor cells, at least in vitro. We therefore tested polyclonal antibodies which inhibit uPA and PAI‐1 activity for their effects on the highly invasive H292 cell line. After 3 days, invasive capacity was inhibited by antibodies to both uPA and PAI‐1 in a dose‐dependent manner. The plasmin inhibitor aprotinin reduced H292 cell invasion by 70%. Taken together, our data demonstrate that in cultured human lung cancer cells the uPA‐plasmin system is important in promoting invasion into basement membranes and suggest that a critical balance between uPA and PAI‐1 is necessary for optimal invasiveness. Our data are consistent with results from recent clinical studies showing that PAI‐1 expression in tumor tissue is an adverse prognostic feature.
Suppression of Burkitt's lymphoma tumorigenicity in nude mice by co‐inoculation of EBV‐immortalized lymphoblastoid cells
Authors: Wolf JÜRgen , Draube Andreas , Bohlen Heribert , Jox Andrea , Mücke Susanne , Pawlita Michael , Möller Peter , Diehl Volker 
Published: February 2007

AbstractEBV‐immortalized B‐lymphoblastoid cell lines (LCL) inoculated s.c. into T‐cell‐deficient nude mice regress completely after a short initial growth period. We tested whether the putative host response underlying this phenomenon might also be directed against progressively growing Burkitt's lymphoma (BL) tumors in nude mice. Outgrowth of BL tumors was suppressed when cells of the highly tumorigenic BL cell line BL 60 were mixed with cells of the autologous LCL IARC 277 before s.c. inoculation into nude mice. Even when the cells were inoculated separately and simultaneously into contralateral flanks of the mice, regression of initially growing BL tumors could be observed, albeit with reduced frequency and dependent on the dose of LCL cells. Tumor growth of BL 60 cells could also be suppressed by co‐inoculation with the non‐autologous LCL IARC 174 and IARC 277 cells could suppress growth of the non‐autologous BL cell line Eli. Pronounced infiltration with murine (m)CD‐11b‐positive mouse macrophages and mCD‐8a‐positive mouse lymphoid cells, most probably natural killer cells, was seen in histological tissue sections of regressing BL 60 tumors when LCL cells were inoculated contralaterally. In regressing BL tumors, these mouse cells were present not only in necrotic areas but also in vital BL tissue, indicating that infiltration of mouse cells had taken place before the development of necrosis. Since tumor‐infiltrating mouse cells can be activated at least by some human cytokines, we measured cytokine production of BL 60 and IARC 277. High amounts of IL 6 and IL 10 were produced by the LCL cells, whereas IL‐6 and IL‐10 production by the BL 60 cells was beyond or close to the detection threshold. In addition, IL 8 was secreted up to 5‐fold more by the LCL than by the BL cells. The results presented here thus suggest a host response of the nude mouse, which is triggered by cytokines released from the LCL but, once induced, is directed also against BL cells.
Antiproliferative activity of taxol on human tumor and normal breast cells vs. effects on cardiac cells
Authors: Brouty‐Boye DaniéLe , Kolonias Dcspina , Lampidis Theodore J. 
Published: February 2007

AbstractThe antiproliferative activity of the chemotherapeutic agent taxol was evaluated on 2 normal and 2 carcinoma human breast‐cell lines and compared with its effects on newborn rat cardiac cells growing in vitro. Relatively little difference in ID50 response (ranging from 0.6 to 2.0 ng/ml) to taxol was found between normal and tumorous breast epithelial cells. Arrhythmias and slowing of beat frequencies of cardiac cells were induced by taxol but at doses approximately 10 times higher than those necessary to inhibit proliferation in dividing cells. Microtubules assayed by immunostaining appeared to be similarly retracted around the nucleus in both breast and heart cells. Overall, our results suggest that taxol does not selectively inhibit the growth of tumor vs. normal human breast cells. They also support the hypothesis that effects on microtubule integrity are associated with effects on cardiac function and that the clinical cardiac activity of taxol already reported may be due, at least in part, to a direct effect of taxol on cardiac cells as demonstrated in these in vitro studies. Thus, caution is needed, in view of possible cardiac effects, when using taxol in future clinical protocols, especially when combined with other cardioactive agents such as Adriamycin.
Production of soluble HLA‐class‐I molecules by IFN‐γ‐induced colon‐adenocarcinoma cells
Authors: Le Junming , Hua Jia‐Cheng 
Published: February 2007

AbstractHigh levels of soluble HLA‐class‐l molecules (sHLA) were found to be produced in a time‐ and dose‐dependent manner by colon‐adenocarcinoma Colo20S cells in response to IFN‐γ stimulation. Among other cytokines tested, only IL‐6, TNF, IFN‐α and IFN‐β showed weak inducibility. IFN‐γ‐induced production of sHLA was synergistically enhanced by IL‐lα, IL‐6 or TNF, and combined treatment with TNF and IL‐6 exhibited an additive to synergistic induction. Expression of sHLA is unlikely to result from IFN‐γ‐induced enhancement of overall HLA‐class‐l expression, as at low concentrations IFN‐α, IFN‐β and IFN‐γ stimulated increased expression of cell membrane HLA‐class‐l molecules in Colo205 cells with almost equal efficiency, whereas only IFN‐γ induced high level production of sHLA. Immunoblot‐ting with a monoclonal antibody recognizing, β2‐microglobulin‐free HLA‐class‐l heavy chain revealed 3 major forms of sHLA heavy chain, i.e., 45/43‐, 37‐ and 33‐kDa molecules, in the culture supernatants of IFN‐γ‐induced Colo20S cells. The 45/43‐kDa proteins can be partitioned into Triton X‐114, representing intact HLA‐class‐l heavy chains shed from the cell membrane. The hydrophilic 37‐ and 33‐kDa heavy chain, which remained almost exclusively in the aqueous phase after extraction with Triton X‐l 14, could well be due to alternative RNA splicing, with deletion of exon 5 encoding the hydrophobic transmembrane region of membrane‐anchored HLA‐class‐l heavy chain.
Reduction of the systemic toxicity of cisplatin by intra‐arterial hepatic route administration for liver malignancies
Authors: Vexler Akiva M. , Mou Xiaode , Gabizon Alberto A. , Gorodetsky Raphael 
Published: February 2007

AbstractCisplatin (CDDP) administration by the intra‐arterial hepatic route (i.a.h.) in patients with primary or metastatic liver malignancies could enhance the anti‐tumor activity of the drug and reduce its systemic toxicity. The aim of the present study was to compare Pt pharmacokinetics and the toxicity of the circulating drug after i.a.h. versus intravenous (i.v.) administration. CDDP pharmacokinetics was followed‐up in 11 i.a.h. courses given to 7 patients with liver malignancies and compared with 19 i.v. courses in 15 patients with cancer of different origins. The Pt level in blood was monitored by sensitive atomic absorption spectrometry. The dose given was in the range of 25–80 mg/m/treatment. For analysis and for comparison purposes, the data from both CDDP treatments were normalized to a standard dose of 35 mg/m2. The mean peak Pt level for i.a.h. treatment was found to be about half of the mean peak value for i.v. administration with a similar dose‐independent bi‐exponential rate of elimination i.a.h. CDDP treatment was relatively well tolerated with no symptoms of either nephro‐ or neurotoxicity. For in vitro evaluation of peripheral CDDP toxicity, a sensitive ovarian carcinoma cell line, OV‐1063, was used. A cytotoxic effect was recorded only within 2 hr following high‐dose i.v. CDDP treatment. A substantial fraction of the drug given by the i.a.h. route was found to be extracted by the liver in the first passage, with reduced drug level in the peripheral blood plasma relative to the dose given. This may explain the apparent diminution of side‐effects following i.a.h. CDDP treatment.
The role of hyaluronan in tumour neovascularization (review)
Authors: Rooney P. , Kumar S. , Ponting J. , Wang M. 
Published: February 2007

AbstractTumour growth and metastasis are totally dependant upon neovascularization. The target cell for tumour neovascularization is the blood‐vessel endothelial cell, and specific angiogenic molecules produced or induced by the tumour are believed to initiate the process. In this report, we review one of these angiogenic molecules, the glycosaminoglycan hyaluronan (HA), which appears to have differing roles in neovascularization depending on its molecular mass. High‐molecular‐mass HA is anti‐angiogenic whereas oligosaccharides of HA, of specific size, actively stimulate endothelial‐cell proliferation and migration, 2 of the key events associated with neovascularization, and induce angiogenesis in vivo. We provide details of the action of HA oligosaccharides on endothelial cells, from binding to cell‐surface receptors, through activation of signal transduction pathways and gene expression to protein synthesis, cell proliferation and cell migration. We also suggest a model to account for HA of differing molecular mass being present, at different locations, within a single tumour and how this HA aids both general tumour growth and tumour metastasis.
Mechanisms of MRP over‐expression in four human lung‐cancer cell lines and analysis of the MRP amplicon
Authors: Eijdems Elisabeth W. H. M. , de Haas Marcel , Coco‐Martin José M. , Ottenheim Cecile P. E. , Zaman Guido J. R. , Dauwerse Hans G. , Breuning Martijn H. , Twentyman Peter R. , Borst Piet , Baas Frank 
Published: February 2007

AbstractSome multidrug resistant cell lines over‐express the gene encoding the multidrug‐resistance‐associated protein (MRP). In all cell lines reported thus far, over‐expression is associated with gene amplification. We have studied the predominant mechanisms of MRP over‐expression in 4 human lung‐cancer cell lines that cover a range of drug‐resistance levels, and we have analyzed the MRP amplicon. In the SW‐1573‐derived, weakly resistant cell line 30.3M, MRP mRNA is elevated 3‐fold in the absence of gene amplification. Run‐on analysis shows that the increased MRP gene expression in this cell line is due to transcriptional activation. In the highly resistant GLC4/ADR and COR‐L23/R cells, MRP gene amplification predominates, whereas in the moderately resistant MOR/R cells, gene amplification is combined with a mechanism resulting in an additional increase in the level of MRP mRNA. Fluorescence in situ hybridization shows that, in the GLC4/ADR cells, amplified MRP sequences are present both in double minute chromosomes (DM) and in homogeneously staining regions (HSR). By pulsed‐field gel electrophoresis we show that the MRP‐containing DM are 1 Mb in length. Chromosome‐16‐specific repetitive sequences adjacent to the MRP gene are also present in the DM and HSR, compatible with the involvement of these sequences in recombination events underlying MRP gene amplification. Our results show that low levels of drug resistance may arise by transcriptional activation of the MRP gene, whereas at high levels of drug resistance amplification of the MRP gene predominates, possibly facilitated by the presence of recombination‐prone sequences.
The effect of E1A transfection on MMP‐9 expression and metastatic potential
Authors: Bernhard Eric J. , Hagner Beverly , Wong Christopher , Lubenski Irena , Muschel Ruth J. 
Published: February 2007

AbstractThe expression of MMP‐9 in rat embryo fibroblasts (REF) transformed with Ha‐ras or with Ha‐ras and v‐myc is associated with metastatic behavior. In contrast, REF transformed with Ha‐ras and the adenovirus EIA genes (EIA) are tumorigenic, do not release MMP‐9 and are rarely metastatic. In this report, we establish that EIA expression results in decreased levels of MMP‐9 mRNA in an Ha‐ras and v‐myc transformed cell line and examine which of the functional domains of EIA participate in the inhibition of MMP‐9 expression and which contribute to the suppression of metastasis. The metastatic 2.10 REF line, derived by co‐transfection with v‐myc and Ha‐ras, constitutively expresses high levels of MMP‐9 (92 kDa gelatinase). Transfection of E1A wild‐type plasmids into this cell line eliminates detectable MMP‐9 mRNA expression and greatly reduces MMP‐9 activity. Transfection of 2.10 with E1A plasmids encoding mutations in conserved region 2 (CR2) retained inhibition of MMP‐9 similar to the inhibition seen with wild‐type E1A. Transfection with E1A containing mutations in CRI or the amino terminal region diminished, but did not fully inhibit, MMP‐9 expression. In contrast, inhibition of MMP‐9 was lost in with E1A mutations in CR3. Cells transfected with E1A mutants in CRI, the amino terminal region or CR3 retained metastatic behavior. Our Findings delineate the regions of E1A responsible for MMP‐9 inhibition and further define the domains of E1A responsible for inhibition of metastasis.
Kinetics of cisplatin‐induced apoptosis in murine mammary and ovarian adenocarcinomas
Authors: Meyn Raymond E. , Stephens L. Clifton , Hunter Nancy R. , Milas Luka 
Published: February 2007

AbstractThere is mounting evidence to indicate that the mode of cell death known as apoptosis plays an important role in cancer therapy. Most supporting observations have come from experiments conducted in vitro, and it is important to extend such studies to in vivo systems. We have therefore evaluated the magnitude and kinetics of apoptosis induction in tumors from mice treated with cisplatin (CP). Two transplantable murine tumors were studied: a mammary adenocarcinoma, MCa‐4, and an ovarian adenocarcinoma, OCa‐l. Tumor‐bearing mice were injected with various doses of CP, and specimens were obtained over several days. Apoptosis was scored by morphometric analysis of histological sections of the tumors using the features characteristic of cells undergoing this mode of cell death. The results showed a significant apoptotic response in both tumors within a few hours after injection of the drug. The kinetics were very broad, with apoptotic cells present over essentially the entire time course studied. Dose‐response relationships for CP‐induced apoptosis were compared to the tumor response measured in terms of tumor growth delay.
Attributable risks for stomach cancer in Northern Italy
Authors: Vecchia Carlo La , D'Avanzo Barbara , Negri Eva , Decarli Adriano , Benichou Jacques 
Published: February 2007

AbstractThe proportions of gastric cancer cases attributable (or attributable risks, AR) to consumption of traditional foods (i.e., pasta, rice and maize), low intake of betacarotene and vitamin C, short duration of use of an electric refrigerator, low educational level, and family history of gastric cancer were computed using data from a casecontrol study conducted in Northern Italy. Between 1985 and June 1993 a total of 746 incident, histologically confirmed gastric cancer cases and 2,053 controls admitted to the same network of hospitals for acute, nonneoplastic, nondigestivetract diseases, unrelated to longterm modifications of diet, were interviewed. The ARs were 48% for low intake of betacarotene, 40% for high consumption of traditional foods, and 16% for low intake of vitamin C. Overall, these 3 dietary factors explained 73% of the gastric cancer cases in the population. Five percent of all cases were attributable to less than 30 years' use of an electric refrigerator, 15% to low educational level, and 5% to family history of gastric cancer. In individuals over age 60, a greater proportion of cases was attributable to traditional foods, low education and late adoption of electric refrigeration (58% vs. 32% aged under 60), suggesting that correlates of lower social class, influenced lifestyle and dietary habits more markedly in earlier than in more recent generations. According to our estimates, over 3 quarters of the gastric cancer cases in this area are explainable in terms of the risk factors considered. Increased consumption of vitamin C and betacarotene, and reduced consumption of traditional foods, would help to avoid over 10,000 out of 14,000 stomachcancer deaths in Italy every year. Consequently, stomach cancer, which is still the third leading cause of cancer death in Italy, would represent only about 2% of all cancer deaths. © 1995 Wiley‐Liss, Inc.
Receptor tyrosine kinases expressed in metastatic colon cancer
Authors: Craven Rolf J. , Xu Lihui , Weiner Timothy M. , Fridell Yih‐Woei , Dent Georgette A. , Srivastava Sudhir , Varnum Brian , Liu Edison T. , Cance William G. 
Published: February 2007

AbstractUsing a PCR‐based cloning technique, we have isolated a series of DNA fragments coding for tyrosine kinases that are expressed in a metastatic human colon tumor, and have subsequently analyzed their expression pattern at the protein level in human tumors. We identified both the α and the β forms of the platelet‐derived growth factor receptor (PDGFR), axl and 8 other genes, including 3 cytoplasmic tyrosine kinases. To study their expression in human colon cancer, we performed Western blots of matched sets of normal tissues and of carcinomas from the same patient. These revealed that the α‐PDGFR migrates predominantly as a 200‐kDa band in 8/8 normal tissues, and as a 170‐kDa band in 17/17 malignant tissues, as well as in colonic polyps, suggesting that expression of an isoform of this receptor may be a marker for the progression of colon cancer. Additional studies showed that the Axl receptor tyrosine kinase was expressed at 10‐fold higher levels in a peritoneal metastatic nodule than in other normal and malignant tissues. Immunohistochemistry revealed Axl over‐expression specifically in the malignant cells of the tumor. This indicates that over‐expression and possibly a differential processing event of tyrosine kinase receptors may be involved in colon cancer, and that they are potential markers for the progression of this disease. © 1995 Wiley‐Liss. Inc.
NM23 gene expression correlates with cell growth rate and S‐phase
Authors: Caligo Maria A. , Cipollini Giovanna , Fiore Lisa , Calvo Simonetta , Basolo Fulvio , Collecchi Paola , Ciardiello Fortunato , Pepe Stefano , Petrini Mario , Bevilacqua Generoso 
Published: February 2007

AbstractTwo human NM23 genes have been identified: NM23.HI and NM23.H2 coding for the A and B subunit of a nucleoside diphosphate kinase (NDPK), respectively. NM23.HI gene has been proposed as a suppressor of metastatic ability in tumor cells, NM23.H2 is identical to the c‐myc transcription factor, PuF. The NM23 coding sequence is strongly preserved through different species. Indirect evidence of various types has been accumulated and seems to support an implication of NM23 in cell proliferation. This report shows that the NM23 gene expression is strictly related to the growth state of the cells. Two different in vitro systems (human peripheral blood lymphocytes and human breast epithelial cell line MCF‐ 10A) and one in vivo (human primary infiltrating ductal breast carcinomas) system have been investigated. The mRNA is present in PHAstimulated peripheral blood lymphocytes, whereas it is nearly undetectable in their resting counterparts. The level of the NM23 gene expression parallels the fraction of cells incorporating thymidine (S‐phase) in neoplastic mammary tissues. In synchronously cycling MCF‐10A cells NM23.HI mRNA reaches a maximum abundance in the S‐phase and is absent or only present at very low levels during G0/G1 phase, whereas NM23.H2 is present in growth‐ arrested cells but is upregulated following serum growth stimulation.
Alternative splicing of the neurofibromatosis 1 gene correlates with growth patterns and neuroendocrine properties of human small‐cell lung‐carcinoma cells
Authors: Koh Takashi , Yokota Jun , Ookawa Keizo , Kina Tatsuo , Koshimura Kunio , Miwa Soichi , Ariyasu Tetsuya , Yamada Hitoshi , Osaka Mitsuhiko , Haga Hironori , Hitomi Shigeki , Sugiyama Taketoshi , Takahashi Rei 
Published: February 2007

AbstractTwo distinct transcripts, type I and type II, of the neurofibromatosis I (NF) gene are generated by alternative splicing in the region corresponding to the gene's GTPase‐activating protein‐related domain (GRD). Relative expression levels of these 2 transcripts were previously correlated to neural differentiation. Since small‐cell lung carcinoma (SCLC) often exhibits neuroendocrine properties, we analyzed the type‐l to type‐ll mRNA ratio in 15 SCLC cell lines, using reverse transcriptase and polymerase chain reaction methods. The type‐l mRNA was predominant in 10 cell lines; 8 of them grew as floating aggregates in culture and had high L‐dopa decarboxylase (DDC) activity. The other 5 lines predominantly expressed type‐ll mRNA, adhered to the culture substrate, and expressed low or undetectable levels of neural cell‐adhesion molecule (NCAM) antigen and DDC activity. N2 + one of the subclones of NCI‐N417 cells, exhibited a higher type‐l to type‐ll ratio after the cells had adhered to a laminin‐coated plate and had emitted neurite‐like processes. These findings provide evidence that alternative splicing patterns of NFI mRNA correlate with the mechanisms that regulate the growth patterns and neuroendocrine properties of SCLC cells in vitro.
Reduced tumorigenicity of threshold syngeneic tumor inocula in XID‐bearing mice treated with natural antibodies
Authors: Chow Donna A. 
Published: February 2007

AbstractSeveral correlative experimental approaches have provided evidence that polyclonal serum natural antibodies (NAb) participate in the defense against small syngeneic tumor foci in vivo. The threshold subcutaneous tumor inoculum model of incipient neoplasia has consistently revealed an inverse relationship between tumorigenicity in vivo. and the NAb binding capacity of the tumor injected or the anti‐tumor NAb levels of the recipient animals, including B cell—deficient mice bearing the xid mutation of the CBA/N mouse strain. Now passive i.v. administration of whole normal syngeneic serum NAb in bolus injections, given I each day beginning on day ‐2, ‐ I or 0 prior to the threshold s.c. challenge of xid‐bearing CBA/N or male (CBA/N × CBA/ J)F1 mice with syngeneic RI‐28 lymphoma cells, consistently and significantly reduced their tumorigenicity assayed as tumor appearance and latency. Three similar injections of an ammonium sulfate—precipitated fraction of whole serum NAb also reduced tumor frequency and latency, while a combination of purified IgG and IgM NAb reduced the appearance of tumors slightly and increased the survival of recipients. The reconstitution of the xid‐defect in anti‐tumor NAb provides more direct evidence to substantiate a role for NAb in the defense against early tumor development in vivo and establishes a model for the dissection of the in vivo. mechanisms of the NAb anti‐tumor activity.