bluuebunny/crossref_metadata_2025_split huggingface dataset:
The capacity of human malignant B‐lymphocytes to disseminate in scid mice is correlated with functional expression of the fibronectin receptor α5β1 (CD49E/CD29)
Authors: Blase Lutz , Daniel Peter T. , Koretz Karin , Schwartz‐Albiez Reinhard , Möller Peter 
Published: February 2007

AbstractThe α5β integrin (CD49e/CD29), a heterodimeric membrane protein, is the “classical” fibronectin receptor on many cell types. During B‐cell ontogeny, expression of the α5‐subunit is developmentally regulated. The αβ1 is decisive for migration on fibronectin substrate and very likely cooperates with other adhesion molecules in transvascular trafficking. To test whether α5β influences local growth vs. disseminative spread of neoplastic B‐cells in vivo, human B‐cell lines mimicking different maturational stages were transferred s.c. into severe combined immunodeficiency (SCID) mice and examined for α5β expression and for adherence on fibronectin substrate in vitro and ex vivo. All cell lines were locally tumorigenic. Dissemination was observed in all animals carrying Nalm‐6 tumors, in one animal with a BL 60 and in 2 mice carrying a Raji tumor. By contrast, Daudi, BJAB and U266 tumors did not disseminate. As evidenced by immunohistochemistry and flow cytometry, all lines and their tumors were to various extents β1‐positive but showed considerable differences in α5 expression. The functional surface expression of α5β1correlated with fibronectin adherence of the lines. Daudi expressed α5β1 in a non‐functional configuration which was rendered functional only upon applying high concentrations of Mg++ and Mn++. B‐cell lines functionally expressing α5β1 at high or moderate levels disseminated in SCID mice while α5‐negative lines and Daudi did not. These results support the conclusion drawn from an earlier in situ analysis of human B‐cell lymphomas/ leukemias that the α5β1 integrin contributes to the disseminative phenotype of malignant B cells.
Prognostic value of cytosolic thymidine kinase activity as a marker of proliferation in breast cancer
Authors: Romain Sylvie , Christensen Ib J. , Chinot Olivier , Balslev Ingegerd , Rose Carsten , Martin Pierre‐Marie , Thorpe Susan M. 
Published: February 2007

AbstractThymidine kinase (TK) is involved in DNA synthesis by the salvage pathway. In this study, thymidine kinase (TK) was determined in routinely prepared cytosols of primary tumors from 290 breast‐cancer patients. Enzyme activity was measured using a radioenzymatic method optimized for detection of the fetal isoenzyme. High levels of TK (≥ 126 mU/mg protein) were positively associated with histological grade in both pre/peri‐and post‐menopausal patients. In pre/peri‐menopausal patients, high concentrations of TK were also found more frequently in progesterone receptor (PgR)‐negative tumors than in PgR‐positive samples. In post‐menopausal patients, high levels of TK were associated with large tumor size, estrogen receptor (ER) negativity and PgR negativity. In univariate analysis, high levels of TK were strongly associated with shorter overall survival in both pre/peri‐ (p = 0.001) and post‐menopausal patients (p = 0.02). Pre/peri‐menopausal patients whose tumors had high levels of TK also had an increased risk of relapse (p = 0.001). In multivariate analysis (including treatment protocol, patient age, lymph‐node involvement, tumor size, histological grade, ER and PgR status), TK status was found to be an independent prognostic factor for recurrence‐free survival in pre/peri‐menopausal patients with a weight similar to that of PgR status. In post‐menopausal patients, TK was the only factor selected for overall survival. © 1995 Wiley‐Liss, Inc.
Fibronectin isoforms are differentially expressed in normal and adenomatous human anterior pituitaries
Authors: Farnoud M. Reza , Farhadian Farahnaz , Samuel Jane L. , Derome Patrick , Peillon Françoise , Li J. Yuan 
Published: February 2007

AbstractThe expression of fibronectin (FN) isoforms containing the extradomains A and B (ED‐A+ and ED‐B+ FNs) as well as a differentially O‐glycosylated oncofetal form of the protein (onf‐FN) was investigated in 6 normal human anterior pituitaries and 25 human pituitary adenomas. In normal tissue, immunohisto‐chemical experiments showed the presence of FN molecules lacking the extradomains A and B (ED‐A− and ED‐B− FNs) without onf‐FN immunoreactivity. These proteins were localized in the connective tissue compartment and especially in the vessel walls. Analysis of FN mRNA demonstrated an in situ synthesis of ED‐A− and ED‐B− FNs in the normal anterior pituitary. By contrast, in the adenomas, immunoreactivity for ED‐A+ FN was observed in all cases. ED‐B+ and onf‐FN immunoreactivities were observed in 14 and 8 adenomas, respectively, regardless of the type, grade or invasiveness of the adenomas. ED‐A+ FN mRNA was expressed in all adenomas studied, and ED‐B+ FN mRNA was present in ED‐B+ immunoreactive cases only. In pituitary adenomas, these 3 forms of FN were specifically associated with the endothelium and vascular smooth‐muscle cells. Our results demonstrate that the processes of remodelling of the connective tissue compartment that occur in adenoma angiogenesis are associated with pre‐ and post‐translational alterations of FN synthesis leading to the expression of ED‐A+, ED‐B+ and oncofetal FNs. © 1995 Wiley‐Liss, Inc.
Expression of protein kinase C isoenzymes in colorectal cancer tissue and their differential activation by different bile acids
Authors: Pongracz Judit , Clark Penny , Neoptolemos John P. , Lord Janet M. 
Published: February 2007

AbstractExpression of protein kinase C (PKC) isoenzymes was determined in paired samples of normal mucosa and colorectal cancer tissue from 13 patients. Total PKC activity in cancer tissue was significantly decreased compared to that in normal mucosa. Western blotting, using PKC isoenzyme‐specific antibodies, showed that two PKC isoenzymes, PKC β and PKC ϵ, were significantly decreased in cancer tissue. The level of PKC δ was increased in cancer tissue and the expression of PKC α and ζ was not altered significantly. Primary bile acids—cholic acid (CA) and chenodeoxycholic acid (CDCA)—and the principal secondary bile acids—deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA)—were found to be potent and selective activators of partially purified PKC isoenzymes. PKC β I was the isoenzyme most effectively activated by secondary bile acids. Our data provide a model for the involvement of secondary bile acids in colorectal carcinogenesis through specific PKC isoenzyme modulation in colorectal mucosa. © 1995 Wiley‐Liss, Inc.
Transfected mutant p53 gene increases X‐ray‐induced cell killing and mutation in human fibroblasts immortalized with 4‐nitroquinoline 1‐oxide but does not induce neoplastic transformation of the cells
Authors: Kawashima Kunihiro , Mihara Koichiro , Usuki Hisashi , Shimizu Nobuyoshi , Namba Masayoshi 
Published: February 2007

AbstractWe introduced the mutant p53 gene (codon 273Arg‐His) into human fibroblasts (SUSM‐I cells) previously immortalized with 4‐nitroquinoline I‐oxide (4NQO) and obtained 2 clonal cell lines (SUSM‐I/p53‐I and SUSM‐I /p53‐6) expressing the mutant p53. Since the genetic background of SUSM‐I /p53 is the same as that of SUSM‐I except for the presence of the mutant p53, we expected to obtain more information on the mechanisms of p53 functions without the influence of other genetic differences by comparing cellular characteristics of both cell lines. SUSM‐I /p53 cells became about twice as sensitive to the cytotoxic effects of X‐rays as their parent SUSM‐I cells. Mutation frequency was determined by the appearance of hypoxanthine guanine phosphoribosyl transferase deficient (6‐thioguanine resistant) cells. As a result, the mutation frequency of SUSM‐I /p53 cells was about 5 times that of SUSM‐I cells transfected with or without the vector plasmid alone. Furthermore, when the SUSM‐I/p53 cells were exposed to X‐rays, the mutation frequency increased to about twice that of the non‐irradiated SUSM‐I /p53 cells. However, SUSM‐I /p53 cells showed neither anchorage‐independent growth in soft agar nor tumorigenicity in nude mice. These results indicate that the mutant p53 gene itself, which generally works in a dominant‐negative way on cellular carcinogenesis, is not sufficient for neoplastic transformation of immortalized human cells, and that additional genetic change(s) may be necessary for transformation. © 1995 Wiley‐Liss, Inc.
Regulation of lewis lung carcinoma invasion and metastasis by protein kinase A
Authors: Young M. Rita I. , Montpetit Michelle , Lozano Yvonne , Djordjevic Andelka , Devata Sandeep , Matthews John P. , Yedavallli Sreedhar , Chejfec Gregorio 
Published: February 2007

AbstractMetastatic Lewis lung carcinoma (LLC‐LN7) cells have increased protein kinase A (PKA) activity and are more invasive in vitro than are non‐metastatic (LLC‐C8) cells. To determine whether PKA mediates the in vitro invasiveness and in vivo metastatic capabilities of these tumor cells, the LLC variants were stably transfected to over‐express the Cα subunit of PKA, and thus to have increased PKA activity, or to express a mutant cAMP‐resistant PKA Rlα subunit which blocks PKA activation. Wild‐type LLC‐LN7 tumor cells were invasive in vitro and in vivo, recurred after tumor excision and metastasized to the lungs. However, they lost these properties after transfection to express the mutant Rlα that blocks PKA activation. The non‐invasive, non‐recurring and non‐metastatic LLC‐C8 cells gained the capacity to invade, to recur following tumor excision and to metastasize when transfected to express the PKA Cα subunit. © 1995 Wiley‐Liss, Inc.
International patterns in the occurrence of Hodgkin's disease in children and young adult males
Authors: Macfarlane Gary J. , Evstifeeva Tatiana , Boyle Peter , Grufferman Seymour 
Published: February 2007

AbstractIt was reported over 20 years ago that there were distinct age‐specific patterns of Hodgkin's disease incidence in countries with different levels of economic development, and that there was an inverse relationship between the incidence of Hodgkin's disease in children and young adults within countries. Such observations were important, leading to hypotheses on the possibly infectious aetiology of the disease. Since the initial report, diverging trends in the incidence of Hodgkin's disease in children and young adults have been observed, and data from a much larger number of countries and cancer registries have become available. This led us to reassess international age‐related incidence patterns of Hodgkin's disease occurrence. Recent data show distinct differences in age‐specific Hodgkin's disease incidence patterns in different geographic regions. In general, the United States (US) and European countries had the pattern of low childhood rates and high young adulthood rates. However, countries which are not part of the European Union (EU), mainly Baltic states and countries of central and eastern Europe, showed a variant of this pattern: similarly high young adult rates, but rates in children higher than those in the US and EU. Incidence‐rate patterns for Latin American countries differed from those previously observed, with a shift towards patterns observed in more economically developed countries. Analysis of incidence data from earlier sources dating back to 1963 confirmed the original finding of an inverse association in incidence rates (c. 1963‐1967) using a selected group of cancer registries, but not when all data were considered. This association has become weaker over the past 20 years. Using current incidence rates (1983‐1987), no association between Hodgkin's disease rates in children aged 5 to 14 years (as well as 0 to 9 years) and young adults (20 to 34 years) was found. © 1995 Wiley‐Liss, Inc.
Abortion and the risk of breast cancer: A case‐control study in greece
Authors: Lipworth Loren , Katsouyanni Klea , Ekbom Anders , Michels Karin B. , Trichopoulos Dimitrios 
Published: February 2007

AbstractWe have examined the association between induced or spontaneous abortion and breast cancer risk in Greece. In a hospital‐based case‐control study in Athens, 820 patients with confirmed breast cancer were compared with 795 orthopedic patient controls and 753 healthy visitor controls, matched to cases by age and interviewer. Logistic regression was used to analyze the data, controlling for demographic, reproductive and nutritional variables. Odds ratio (OR) patterns were similar for the 2 control series, which were therefore combined to increase precision of the estimates. The risk for breast cancer was not increased for women who had a history of abortion, compared to nulliparous women with no history of abortion. Thus ORs and 95% confidence intervals were for nulliparous women with spontaneous abortion, 1.17 (0.64–2.13); for nulliparous women with induced abortion, 0.98 (0.56–1.73); for parous women with no abortion, 0.56 (0.31–1.01); for parous women with spontaneous abortion, 0.61 (0.33–1.14) and for parous women with induced abortion, 0.99 (0.56–1.74). When the analysis was restricted to parous women, using parous women with no history of abortion as the baseline, ORs and 95% confidence intervals were for induced abortion before first full‐term pregnancy, 2.06 (1.45–2.90); for induced abortion after first full‐term pregnancy, 1.59 (1.24–2.04) and for spontaneous abortion, 1.10 (0.82–1.40). Our findings suggest that an interrupted pregnancy does not impart the long‐term protective effect of a full‐term pregnancy attributable to terminal differentiation. © 1995 Wiley‐Liss, Inc.
In vivo growth inhibition of leukemia by 4‐amidinoindan‐1‐one 2′‐amidinohydrazone (CGP 48664a), a new inhibitor of S‐adenosylmethionine decarboxylase
Authors: Dorhout Bernard , Velde Roelf Jakob Te , Kingma Harri Ferwerdaanneke W. , De Hoog Elly , Muskiet Frits A. J. 
Published: February 2007

AbstractWe studied the in vivo growth‐inhibitory effect of the new S‐adenosylmethionine decarboxylase inhibitor 4‐amidinoindan‐I‐one 2′‐amidinohydrazone (CGP 48664A). L1210‐bearing DBA‐2 mice were treated with increasing CGP 48664A doses from 1 day after i.p. L1210 cell inoculation. Treatment was continued for 4 days, after which all mice were killed. CGP 48664A caused dose‐related exponential decreases of L1210 cell numbers and spermidine and spermine contents. Putrescine contents increased exponentially. Polyamine changes in spleen and liver were less profound. L1210 growth inhibition was not accompanied by changes in cell cycle phase distribution. It is concluded that CGP 48664A is an effective inhibitor of S‐adenosylmethionine decarboxylase but that CGP 48664A‐induced changes in intracellular polyamine compositions are not necessarily the cause of growth inhibition. © 1995 Wiley‐Liss, Inc.
Suppression of matrilysin inhibits colon cancer cell invasion in vitro
Authors: Yamamoto Hiroyuki , Itoh Fumio , Hinod Yuji , Imai Kohzoh 
Published: February 2007

AbstractMatrilysin is a member of the matrix metalloproteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We examined the effects of over‐ and under‐expression of matrilysin on the ability of colon cancer cells to migrate across an artificial membrane in vitro. Introduction of matrilysin caused colon cancer cells to become more invasive as assessed by an in vitro invasion assay. In contrast, expression of matrilysin was down‐regulated by all trans‐retinoic acid or by introduction of anti‐sense matrilysin in BM314 colon cancer cells. This down‐regulation caused these cells to become less invasive. We demonstrated a correlation between matrilysin level and the invasive potential of human colon cancer cells, implying an important role for matrilysin in the control of tumor invasion in vitro. © 1995 Wiley‐Liss, Inc.
A stress‐inducible 72‐kDa heat‐shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells
Authors: Multhoff Gabriele , Botzler Claus , Wiesnet Marion , Müller Eva , Meier Thomas , Wilmanns Wolfgang , Issels Rolf D. 
Published: February 2007

AbstractIt is suggested that members of the heat‐shock protein (HSP) 70 and 90 families are involved in intracellular antigen processing and the presentation of cell‐membrane‐anchored antigens. We show that non‐lethal heat shock (41.8°C) causes comparable rates of HSP72 (about 20x) and HSP73 (about 3x) synthesis in both tumor (including human Ewing's sarcoma, ES and osteosarcoma cells, HOS58) and normal cells (including EBV‐transformed B‐LCL, PBL and fibroblasts derived from healthy human volunteers). However, following non‐lethal heat stress and a recovery period at 37°C, flow cytometric analysis with a specific MAb showed HSP72 to be expressed only on the cell surface of tumor cells. The cell‐surface localization of HSP72 was confirmed by Western‐blot analysis of separated membranes and by immunoprecipitation with the HSP72‐specific MAb. In addition, co‐incubation of untreated tumor cells with supernatants from lethally heat‐shocked cells, which contain HSP72, did not lead to HSP72 cell‐surface expression. Thus, non‐specific association of HSP72 molecules with the outer plasma membrane is unlikely. In conclusion, despite comparable cytoplasmic HSP72 induction, human tumor cells differ from normal cells in their capacity to express HSP72 on their surface. This might imply clinical application as a means to target a stress‐inducible, tumor‐specific immune response. © 1995 Wiley‐Liss, Inc.
The presence of persistent high‐risk hpv genotypes in dysplastic cervical lesions is associated with progressive disease: Natural history up to 36 months
Authors: Remmink Ans J. , Walboomers Jan M. M. , Helmerhorst Theo J. M. , Voorhorst Feja J. , Rozendaal Lawrence , Risse Ellen K. J. , Meijer Chris J. L. M. , Kenemans Peter 
Published: February 2007

AbstractTo evaluate the clinical significance of HPV genotyping for the prediction of progressive cervical intraepithelial neoplasia (CIN) in women with cytomorphologically abnormal smears, a prospective, blind, non‐intervention study was performed. A total of 342 patients screened with cytomorphologically abnormal cervical smears were monitored every 3–4 months by cervical cytology, colposcopy and HPV testing using PCR. Women with progressive CIN disease were defined as patients developing lesions with a colposcopic impression of CIN III over more than 2 quadrants or resulting in a cytological smear equivalent to Pap 5. These patients were subsequently treated according to standard procedures. If any doubt arose about the true status of the patients (n = 75) these patients were censored and biop‐sied. The mean follow‐up time was 16.5 months (range 3–36 months). Nineteen women showed progressive CIN disease and all appeared to be continuously HPV‐positive from the start of the study. At biopsy, all these patients were histologically classified as CIN III. Seventeen of these women were positive for high‐risk HPV types. Two cases were classified as still unidentified HPV. No progression was seen in the absence of HPV DNA or in the presence of low‐risk HPV types. In life‐table analysis the cumulative rate of progressive, histologically verified CIN disease was 17% after 36 months. Further analyses showed that other risk factors such as age, sexarche, number of sexual partners or smoking hardly influenced the effect of HPV on progression. The results show that the continuous presence of high‐risk HPV types in women with cytomorphologically abnormal smears is a strong marker for progressive CIN disease. ©1995 Wiley Liss. Inc.
Human papillomavirus and cervical intraepithelial neoplasia grade II‐III: A population‐based case‐control study
Authors: Olsen Anne O. , Gjøen Kirsti , Sauer Torill , Ørstavik Ivar , Næss Oddvar , Kierulf Knut , Sponland Geir , Magnus Per 
Published: February 2007

AbstractThe association between certain human papillomaviruses (HPV) and cervical intraepithelial neoplasia (CIN) is well documented, but there is uncertainty about the strength of association and the role of co‐factors is unclear. This population‐based case‐control study in Norwegian women 20–44 years of age included 103 cases with histologically confirmed CIN II–III and 234 age‐matched and randomly selected controls. Cytological specimens from the cervix were analyzed using the polymerase chain reaction (PCR). In all, 91% of the cases and 15% of the controls were HPV DNA positive, giving a crude odds ratio (OR) of 67.2 (95% confidence interval: 28.6–157.5). The association between HPV 16 and CIN II–III was even stronger (crude OR = 123.9; 46.7 ‐ 328.5). In logistic regression analysis, additional to HPV, only a high number of sexual partners and a low educational level contributed independently to the risk. The adjusted OR for the association between HPV and CIN II–III was 72.8 (95% Cl: 27.6–191.9). The association between HPV and CIN remains very strong even after adjustment for proposed confounding factors. The results therefore support the role of HPV as a causative agent in the development of CIN. © 1995 Wiley‐Liss, Inc.
High frequency of EBV association with non‐random abnormalities of the chromosome region 1q21‐25 in aids‐related Burkitt's lymphoma‐derived cell lines
Authors: Polito Pietro , Cilia Anna M. , Gloghini Annunziata , Cozzi Marzia , Perin Tiziana , De Paoli Paolo , Gaidano Gianluca , Carbone Antonino 
Published: February 2007

AbstractChromosome lq abnormalities represent the second most frequent cytogenetic lesion of Burkitt lymphoma (BL) and acute lymphoblastic leukemia (ALL)‐L3. The most frequent change is partial duplication of the long arm of chromosome l, involving variable bands but consistently including 1q23. Among AIDS‐related BL similar chromosome 1q abnormalities have also been found. We have now characterized in detail the chromosome 1q abnormalities of 4 AIDS‐BL cell lines and compared them to other molecular features of the tumor clone, namely infection by Epstein Barr virus (EBV). Immunophenotypic characteristics were also assessed by conventional in situ immunocytochemical and flow cytometric procedures. The B‐cell origin of all cell lines was demonstrated by the expression of B‐cell‐restricted markers (e.g., CD 19). Analysis of 1g light chains confirmed their monoclonal nature. The t(8; 14) was present in 3 of the 4 lines, whereas variant translocation t(8;22) was detected in the remaining cell line. Additional chromosomal changes were found in all cases, with chromosome 1 being involved in all. Structural changes encompassed in each case the 1q21—25 bands, in either duplication or partial trisomy. EBER ISH studies identified EBV association in 3 of the 4 AIDS‐BL cell lines in contrast to previous studies of BL of immunocompetent individuals. Our findings of a high frequency of chromosome 1q abnormalities in EBV‐infected AIDS‐related BL cell lines demonstrate that such chromosomal abnormality and EBV positivity are not mutually exclusive and are possibly independent factors, whereas their close association in AIDS may be related to the immunodeficiency. © 1995 Wiley‐Liss, Inc.