bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation‐induced HIF‐1α cell survival pathway is inhibited by soy isoflavones in prostate cancer cells
Authors: Singh‐Gupta Vinita , Zhang Hao , Banerjee Sanjeev , Kong Dejuan , Raffoul Julian J. , Sarkar Fazlul H. , Hillman Gilda G. 
Published: September 2008

AbstractWe previously showed that treatment of prostate cancer cells with soy isoflavones and radiation resulted in greater cell killing in vitro, and caused downregulation of NF‐κB and APE1/Ref‐1. APE1/Ref‐1 functions as a redox activator of transcription factors, including NF‐κB and HIF‐1α. These molecules are upregulated by radiation and implicated in radioresistance of cancer cells. We extended our studies to investigate the role of HIF‐1α survival pathway and its upstream Src and STAT3 molecules in isoflavones and radiation interaction. Radiation induced phosphorylation of Src and STAT3 leading to induction of HIF‐1α. Genistein, daidzein or a mixture of soy isoflavones did not activate this pathway. These data were observed both in PC‐3 (AR‐) and C4‐2B (AR+) androgen‐independent cell lines. Pretreatment with isoflavones inhibited Src/STAT3/HIF‐1α activation by radiation and nuclear translocation of HIF‐1α. These findings correlated with decreased expression of APE1/Ref‐1 and DNA binding activity of HIF‐1α and NF‐κB. In APE1/Ref‐1 cDNA transfected cells, radiation caused a greater increase in HIF‐1α and NF‐κB activities but this effect was inhibited by pretreatment with soy prior to radiation. Transfection experiments indicate that APE1/Ref‐1 inhibition by isoflavones impairs the radiation‐induced transcription activity of NF‐κB and HIF‐1α. This mechanism could result in the inhibition of genes essential for tumor growth and angiogenesis, as demonstrated by inhibition of VEGF production and HUVECs tube formation. Our novel findings suggest that the increased responsiveness to radiation mediated by soy isoflavones could be due to pleiotropic effects of isoflavones blocking cell survival pathways induced by radiation including Src/STAT3/HIF‐1α, APE1/Ref‐1 and NF‐κB. © 2008 Wiley‐Liss, Inc.
The gene expression signature of genomic instability in breast cancer is an independent predictor of clinical outcome
Authors: Habermann Jens K. , Doering Jana , Hautaniemi Sampsa , Roblick Uwe J. , Bündgen Nana K. , Nicorici Daniel , Kronenwett Ulrike , Rathnagiriswaran Shruti , Mettu Rama K. R. , Ma Yan , Krüger Stefan , Bruch Hans‐Peter , Auer Gert , Guo Nancy L. , Ried Thomas 
Published: September 2008

AbstractRecently, expression profiling of breast carcinomas has revealed gene signatures that predict clinical outcome, and discerned prognostically relevant breast cancer subtypes. Measurement of the degree of genomic instability provides a very similar stratification of prognostic groups. We therefore hypothesized that these features are linked. We used gene expression profiling of 48 breast cancer specimens that profoundly differed in their degree of genomic instability and identified a set of 12 genes that defines the 2 groups. The biological and prognostic significance of this gene set was established through survival prediction in published datasets from patients with breast cancer. Of note, the gene expression signatures that define specific prognostic subtypes in other breast cancer datasets, such as luminal A and B, basal, normal‐like, and ERBB2+, and prognostic signatures including MammaPrint® and Oncotype DX, predicted genomic instability in our samples. This remarkable congruence suggests a biological interdependence of poor‐prognosis gene signatures, breast cancer subtypes, genomic instability, and clinical outcome. © 2008 Wiley‐Liss, Inc.
Functional significance of VEGFR‐2 on ovarian cancer cells
Authors: Spannuth Whitney A. , Nick Alpa M. , Jennings Nicholas B. , Armaiz‐Pena Guillermo N. , Mangala Lingegowda S. , Danes Christopher G. , Lin Yvonne G. , Merritt William M. , Thaker Premal H. , Kamat Aparna A. , Han Liz Y. , Tonra James R. , Coleman Robert L. , Ellis Lee M. , Sood Anil K. 
Published: September 2008

AbstractVascular endothelial growth factor receptor (VEGFR) has recently been discovered on ovarian cancer cells, but its functional significance is unknown and is the focus of this study. By protein analysis, A2780‐par and HeyA8 ovarian cancer cell lines expressed VEGFR‐1 and HeyA8 A2774, and SKOV3ip1 expressed VEGFR‐2. By in situ hybridization (ISH), 85% of human ovarian cancer specimens showed moderate to high VEGFR‐2 expression, whereas only 15% showed moderate to high VEGFR‐1 expression. By immunofluorescence, little or no VEGFR‐2 was detected in normal ovarian surface epithelial cells, whereas expression was detected in 75% of invasive ovarian cancer specimens. To differentiate between the effects of tumor versus host expression of VEGFR, nude mice were injected with SKOV3ip1 cells and treated with either human VEGFR‐2 specific antibody (1121B), murine VEGFR‐2 specific antibody (DC101) or the combination. Treatment with 1121B reduced SKOV3ip1 cell migration by 68% (p < 0.01) and invasion by 72% (p < 0.01), but exposure to VEGFR‐1 antibody had no effect. Treatment with 1121B effectively blocked VEGF‐induced phosphorylation of p130Cas. In vivo treatment with either DC101 or 1121B significantly reduced tumor growth alone and in combination in the SKOV3ip1 and A2774 models. Decreased tumor burden after treatment with DC101 or 1121B correlated with increased tumor cell apoptosis, decreased proliferative index, and decreased microvessel density. These effects were significantly greater in the combination group (p < 0.001). We show functionally active VEGFR‐2 is present on most ovarian cancer cells. The observed anti‐tumor activity of VEGF‐targeted therapies may be mediated by both anti‐angiogenic and direct anti‐tumor effects. © 2008 Wiley‐Liss, Inc.
Antigenicity of clones of mouse prostate cells transformed in vitro
Authors: Embleton M. J. , Heidelberger Charles 
Published: September 2008

AbstractNew cell‐surface antigens were detected on nineteen of twenty‐four malignant lines of 3‐methylcholanthrene (MCA)‐ or MCA‐epoxide‐transformed cells derived from cloned C3H mouse prostate cells. Exhaustive cross‐tests between lines derived from single control clones showed that in all but two lines these antigens were individually distinct and did not cross‐react. Eight spontaneously transformed cell lines were also examined but only two of these were antigenic. The remaining six lines appeared to be non‐immunogenic in syngeneic mice, although cell surface alloantigens were detectable. Non‐transformed cells were not immunogenic in syngeneic hosts, whether or not they had been treated with MCA.
The short‐term effects of 4‐nitroquinoline 1‐oxide on the immune response in mice
Authors: Phillips Jennifer M. 
Published: September 2008

AbstractThe short‐term effects of the carcinogen 4‐Nitroquinoline 1‐oxide (NQO) on the number of plaque‐forming spleen cells (PFC) after immunization with sheep erythrocytes have been tested in (C57BL × IF) mice. The number of PFC was reduced in the NQO‐treated mice and this reduction was greater with higher doses of carcinogen. The times of appearance of the peaks of the 19S and 7S antibody response do not appear to be altered. Two non‐carcinogenic analogues of NQO, chloroquinoline‐N‐oxide (CQO) and nitropyridine N‐oxide (NPO) had no such immunodepressive effect. NQO had its maximum immunosuppressive effect when administered two days after the antigen, at the time of maximum division of the antibody‐producing cells. Reconstitution experiments suggest that the rapidly dividing bone‐marrow cells are most affected by NQO and there is no evidence that the thymus cells are affected. Correspondingly, no depression of cell‐mediated immunity by NQO was found, either in rejection time of skin allografts or of the graft‐versus‐host reaction.These findings are discussed in relation to suggestions that immune depression by chemical carcinogens is of aetiological significance.
Polyps of the colon and rectum in cali, Colombia
Authors: Correa Pelayo , Duque Edgar , Cuello Carlos , Haenszel William 
Published: September 2008

AbstractA systematic search for polyps was carried out in 1,499 autopsy specimens of large intestine from Cali, Colombia, a low‐incidence area for colo‐rectal carcinoma. No cases of carcinoma were found in the series studied. The prevalence of each of the main types of polyps, namely adenomatous, hyperplastic and retention, is described. Retention polyps tend to disappear with age. Hyperplastic polyps appear around the 4th decade of life, are often multiple, are mostly found in the sigmoid and rectum and their prevalence does not increase appreciably with age; these findings are interpreted as added evidence against an association between hyperplastic polyps and carcinoma of the colon and rectum. Adenomatous polyps increase in prevalence with age and are more often multiple and in males tend to be concentrated in the sigmoid; tentative comparisons of Cali data with findings from countries at high risk for colo‐rectal cancer suggest a statistical association between prevalence of adenomas and incidence of carcinoma of the colon and an even stronger association between colon cancer and atypical cellular changes in adenomas. It is suggested that populations at high risk to colon cancer are probably characterized by an increased prevalence of adenomatous polyps, particularly in the sigmoid colon of males, and display a larger proportion of multiple polyps and atypical cellular changes.
Facilitation of polyoma tumor growth in rats by blocking sera and tumor eluate
Authors: Bansal S. C. , Hargreaves R. , Sjögren H. O. 
Published: September 2008

AbstractIt has been shown previously that sera of tumor‐bearing individuals are capable of blocking specifically the lymphocyte cytotoxicity in vitro against the tumor cells in question. The present investigation demonstrates that blocking material, in the form of sera of rats carrying progressively growing polyoma tumors and low pH eluates of polyoma tumor tissue inoculated into polyoma isografted rats, cause an enhanced tumor growth. Corresponding serum from rats carrying an MCA‐induced sarcoma and eluate from such tumor tissue had no significant enhancing effect. The administered blocking activity was detectable in the sera of the recipients for 3 days after inoculation. No delay or decrease in the level of cell‐mediated anti‐tumor immunity could be detected by in vitro tests for lymphocyte cytotoxicity against polyoma tumor cells. This indicates that the mechanism of the facilitated tumor growth in vitro is akin to a central or an efferent type of enhancement.
Studies on the reversal of the selective antitumour effect of the aziridinyl derivative cb 1954 by 4‐amino‐5‐imidazolecarboxamide
Authors: Connors T. A. , Mandel H. G. , Melzack D. H. 
Published: September 2008

AbstractThe selective toxicity of CB 1954 (5‐aziridinyl‐2,4‐dinitrobenzamide) for Walker tumour cells, previously shown in the whole animal and in an in vitro/in vivo system, has been confirmed in an in vitro system In each case its actions on the Walker tumour were reversed by 4‐amino‐5‐imidazolecarboxamide, the ribotide of which is a purine precursor, provided it was given before or soon after the CB 1954. Other purines also produced this reversal, while pyrimidines and several other compounds did not. This evidence suggested that CB 1954, in addition to its alkylating properties, had features of a purine antimetabolite. However, anthranilamide was also very effective in protecting against CB 1954, suggesting that reversal could be achieved by compounds structurally related to CB 1954 which competed with it for some receptor site.
Persistence of rous sarcoma virus in transformed non‐permissive cells: mechanism of virus induction by association with permissive cells in the absence of sendai virus
Authors: Vigier Philippe 
Published: September 2008

AbstractVirus induction by association of non‐permissive cells transformed by Rous sarcoma virus (RSV) and permissive chicken cells in the absence of Sendai virus has been studied with two clones of BHK21 hamster fibroblasts transformed respectively by Schmidt‐Ruppin strain RSV (clone RS2) and Bryan strain RSV (clone RB12), and with sub‐clones derived from these clones after many divisions. The main results have been the following: (1) All the transformed non‐permissive (TNP) cells presumably carry at least one complete viral genome since RSV could be recovered from all the subclones tested. (2) The first infective centers which appear in mixed cultures are presumably heterokaryons formed by spontaneous fusion of single TNP cells with chicken cells; and Rous cells (transformed chicken cells) which appear later on, arise by secondary infection of chicken cells. (3) The incidence of appearance of infective centers is low and can vary considerably depending on subclones in the case of RS2 cells. In the most highly inducible subclones, it never exceeds one center per 103 RS2 cells and it can be much less in other subclones. (4) No induction was observed with two RS2 subclones from which RSV was nevertheless recovered after Sendai virus‐mediated cell fusion. (5) In the case of one of these subclones, even heterokaryon formation was inefficient in removing the block of virus production in the TNP cells. (6) No induction was obtained by any other method than cell association and no subviral determinant able to give rise to virus in CE cells was recovered from TNP cells.The reasons for non‐permissiveness and the mechanism of induction are discussed.
Pancreatic cancer, blood glucose and beverage consumption
Authors: Hiatt Robert A. , Klatsky Arthur L. , Armstrong Mary Anne 
Published: September 2008

AbstractWe studied the incidence of pancreatic cancer in 122,894 men and women who had previously reported amount and frequency of coffee, tea, and alcohol consumption; reporting was done at a multi‐phasic health check‐up (MHC) taken while subjects were members of a large prepaid health plan. We also tested the hypothesis that a pre‐clinical effect of pancreatic cancer on glucose homeostasis leads to mild hyperglycemia and a generally increased thirst. If true, this could partially explain the increased consumption of beverages (particularly coffee) reported in association with pancreatic cancer in some case‐control studies. However, in the 49 pancreatic cancer cases diagnosed during 6 years of follow‐up, we found no evidence of increased risk associated with coffee, tea, or alcoholic beverages. We also found no evidence to support the increased‐thirst hypothesis when we examined the 19 cases diagnosed within 12 months of having MHC. We did confirm a significantly increased risk among cigarette smokers (relative risk, 2.5; 95% confidence interval, 1.3‐4.7) which was progressive with increasing levels of cigarette use. In addition, risk of pancreatic cancer was greater for persons previously under treatment for diabetes mellitus (relative risk, 4.5; 95% confidence interval, 1.2‐16.7). Our results add to the growing body of evidence against a causal role of coffee in pancreatic cancer.
Plasminogen activator expression and steroid hormone receptors in female breast cancer: A multifactorial study
Authors: Pacheco Mercia M. , Brentani M. Mitzi , Franco Eduardo L. , Fontelles Jose A. , Chamone Dalton F. , Marques Lourdes A. 
Published: September 2008

AbstractIn order to evaluate the relationship of plasminogen activator (PA) activity to the expression of estrogen (ER) and progesterone (PR) receptors, we assayed primary tumor specimens from 121 cases of female breast cancer. Other clinical and histopathological variables were also investigated with respect to their possible association with PA activity in the samples. Statistical correlations were examined by stratified analysis techniques and by multiple regression methods. PA activity was higher in tumors which were ER +PR+ than in those exhibiting other subsets of joint receptor expression, a finding which was particularly predominant in tumors from post‐menopausal women. Of the other variables examined, only disease stage, nodal status and vascular infiltration presented marginal positive statistical associations with PA activity, although this was not confirmed by multivariate analysis. The latter technique showed that the presence of PR was sufficient to explain the variation in PA levels. However, ER emerged as the sole significantly explanatory factor when ER+PR− patients were removed from analysis. Both PR and age (negatively) were independent contributory factors for PA activity in the analysts of post‐menopausal women. None of the variables examined emerged as being significantly associated with PA when data from pre‐menopausal patients were used. These findings indicate that PA activity in breast tumor samples is statistically associated with the expression of functional estradiol receptors, although to a lesser extent than PR.
Site‐specific linkage of methotrexate to monoclonal antibodies using an intermediate carrier
Authors: Shih Lisa Beewen , Sharkey Robert M. , Primus F. James , Goldenberg David M. 
Published: September 2008

AbstractThe site‐specific conjugation of methotrexate, 4‐amino‐N10‐methylpteroylglutamic acid, to a monoclonal anti‐carcinoembryonic antigen (CEA) antibody, using an intermediate aminodextran carrier system, resulted in a ratio of 30‐50 molecules of MTX per molecule of immunoglobulin. The immunoreactivity of the conjugate was analyzed using flow cytometry or a competitive binding assay, which showed that the conjugate has significant retention of the antigen‐binding activity. The pharmacokinetic behavior of the immunoconjugate in BALB/c mice and tumor localization in hamsters indicated that the conjugate remained in the circulation with higher concentration than free antibody, and could recognize the tumor as efficiently as the unconjugated antibody. The high degree of drug incorporation with retained immunoreactivity makes this method preferable to direct antibody conjugation.
Tumor cells are protected from NK‐cell‐mediated lysis by adhesion to endothelial cells
Authors: Kaminski Marek , Auerbach Robert 
Published: September 2008

AbstractWe have examined the effect of various cell monolayers on the ability of mouse spleen cells to lyse tumor cell targets (natural cytotoxicity reaction). Natural killer (NK) cell activity was reduced by as much as 75% depending on the cell substrate, with the greatest protection afforded by endotheiial cells. Cell adhesion to the underlying cell monolayer was directly correlated with the degree of protection from lysis. Since it has previously been shown that tumor cells manifest selective adhesion to endothelial cells from those organs to which they are likely to metastasize, the experiments suggest a means by which natural surveillance mechanisms might be circumvented during the metastatic process.
Serial transplantation of an HTLV‐I‐transformed hamster lymphoid cell line into hamsters
Authors: Ecuchi T. , Kubonishi I. , Daikata M. , Yano S. , Imamura J. , Ohtsuki Y. , Miyoshi I. 
Published: September 2008

AbstractA hamster lymphoid cell line, HCT‐2, transformed by human T‐ceM leukemia virus type I (HTLV‐I) was serially transplanted for 9 passages in newborn hamsters. A total of 34 newborn hamsters inoculated intraperitoneally (i.p.) with 0.2‐2 × 107 HCT‐2 cells developed fatal lymphomas with dissemination to various organs within 5‐10 days. The growth of i.p. inoculated HCT‐2 cells was found to be dependent on the age of recipients: all 21 suckling hamsters inoculated when aged 5‐10 days succumbed to disseminated lymphomas within 6‐7 days, while 4 of 12 older hamsters inoculated at the age of 15‐25 days developed less extensive disease with signs of tumor regression. To investigate the effect of immunosuppression on host resistance, 3 adult hamsters treated with anti‐thymocyte serum were inoculated i.v. with 2‐4 × 107 HCT‐2 cells; all 3 developed fatal leukemias in 5‐7 days. Irrespective of whether HCT‐2 cells were inoculated into newborn, suckling, or adult hamsters, histopathological findings were similar, with frequent involvement of liver, spleen, lungs, kidneys, lymph nodes, blood, and bone marrow. Cells harvested from tumors and peripheral blood of some tumor‐bearing hamsters could be readily recultured as cell lines. Chromosome analysis and Southern blot hybridization showed that tumors were caused by growth of HCT‐2 cells.
Transformation of rat 3Y1 cells by human papillomavirus type‐18 DNA
Authors: Watanabe Sumie , Yoshiike Kunito 
Published: September 2008

AbstractRat 3Y1 cell cultures transfected with human papiilomavirus type‐18(HPV 18) DNA produced foci of morphologically transformed cells capable of anchorage‐independent growth. Analyses of the transformed cell clones obtained after transfection with EcoRI‐cleaved linear HPV IS DNA showed that, although the viral DNAs integrated in the cell DNA had rearrangements (probably around the sites of integration), they appeared to retain the putative transcriptional control region and the downstream area containing E6E7 open reading frames (ORF) intact, and to be transcription ally active. The expression plasmids constructed from an 5V40‐derived expression vector (pSV2‐0) and HPV 18 DNA fragments containing either E6 or E7 ORF intact were examined for their transforming capacity. HPV IB E7 ORF was found to encode a transforming gene for rat 3Y1 cells.
Differential expression of hla antigen of HLA anigens on human B‐cell lines of normal and malignant origin: A consequence of immune surveillance or a phenotypic vestige of the progenitor cells?
Authors: Torsteinsdottir Sigurbjörg , Brautbar Chaim , Klein George , Klein Eva , Masucci Maria G. 
Published: September 2008

AbstractPairs of BL‐derived cell lines and in vitro EBV‐transformed LCLs, derived from the same patient, were compared for the expression of MHC class‐l antigenic determinants as shown both by monoclonal antibody (MAb) binding and by sensitivity to HLA‐specific CTL clones. BL lines expressed all polymorphic determinants tested at a lower level than the corresponding LCLs, as indicated by the binding of the MAbs AUF 5.13 (anti‐HLA A3,AII), GS 142.1 (anti‐HLA Al), GS 114.1 (anti‐HLA A24), GSP 35.1 (anti‐HLA A2.A28), GSP 55.1 (anti‐HLA A25.A32), TER MA32 (anti‐HLA A32), GSP 145.2 (anti‐HLA B27), B27 M.I (anti‐HLA B27,B7) and GSP 8.1 (anti‐HLA B8). The difference was most pronounced for HLA All and least for B27,AI and B8 with intermediate differences for the other specificities. The BL lines were also less sensitive to lysis by HLA‐specific CTL clones directed to the same and to additional antigens. The polymorphic determinants detected by the AUF 5.13 and GSP 35.1. MAbs were expressed at a lower level in resting T and B cells compared to mitogen‐ and EBV‐induced blasts. An analogous change in the expression of polymorphic determinants was observed in EBV‐converted sublines of originally EBV‐negative BLs that have become more “LCL‐like” after conversion. The appearance of B‐cell activation markers was paralleled by the up‐regulation of both the serologically defined and the CTL‐target epitopes. The findings suggest that the low expression of HLA determinants on the BL cells is a phenotypic vestige of the normal BL precursor.