bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of abh antigen expression in bladder cancer is not caused by loss of heterozygosity of the ABO locus
Authors: Meldgaard Peter , Johnson Philip H. , Langkilde Niels C. , Wolf Hans , Ørntoft Torben F. 
Published: February 2007

AbstractThe significance of loss of heterozygosity (LOH) of chromosome 9 as an early event in human bladder tumors has been demonstrated by several studies. We have studied LOH of the ABO gene locus at 9q34.2 by means of polymerase chain reaction (PCR) genotyping of tumor preparations and leukocytes. Twenty‐two tumors, all of which were immunohistochemically negative for ABH antigens, were examined. Eleven tumors were from blood‐group O individuals, and were examined by denaturing gradient gel electrophoresis (DGGE). They showed normal band patterns with no sign of single base mutations or LOH. All 11 A and B tumors were sorted on a fluorescence‐activated cell sorter (FACS) according to DNA content, thereby making it possible to study differences in genotype between subpopulations of cells in the same tumor. In 2 genotypically AO cases, we found 2 aneuploid subpopulations. In both cases, the most abnormal, with the highest DNA content, showed complete loss of the O allele, leaving the A allele intact. As all tumors were ABH antigen‐negative, this study demonstrates that LOH of the ABO locus on chromosome 9q34 is not the cause of loss of blood‐group ABH expression in human bladder cancer.
CD66b, CD66c and carcinoembryonic antigen (CEA) are independently regulated markers in sera of tumor patients
Authors: Grunert Fritz , Daniel Susanne , Nagel Gerhard , Kleist Sabine Von , Jantscheff Peter 
Published: February 2007

AbstractNon‐specific cross‐reacting antigens (NCA‐95 = CD66b and NCA‐50/90 = CD66c) are members of the CEA (carcinoembry‐onic antigen = CD66e) family. Analysis of mRNA levels of CD66c in colon tumors suggests that this antigen is strongly up‐regulated compared to its normal counterpart and could, therefore, be of clinical interest. CD66c is also expressed in normal lung and spleen tissues and, above all, on granulocytes. The appearance of CD66b in serum, the only strictly granulocyte‐specific antigen, could point to the involvement of granulocytes in disease. Specific sandwich ELISAs have been established to determine CEA, CD66b and CD66c levels in serum. Controls have been carried out by testing sera from patients with benign tumors or inflammatory diseases and from healthy individuals. In sera of most patients suffering from solid tumors, sensitivities for CD66c are comparable to or lower than those for CEA. CD66c showed a much higher sensitivity in early colon tumor stages. Sensitivities over 40% have been determined for CD66b in sera of patients with uterine and kidney carcinomas. CML patients revealed sensitivities of 84% for CD66c and 47% for CD66b. Investigations of sera from patients with inflammatory colon diseases which are negative for CEA showed high sensitivity for CD66c but not for the granulocyte‐specific CD66b. Patients with mastopathy revealed sensitivities of over 40% for both CD66c and CD66b. CD66b, CD66c and CEA are independently regulated proteins in a high percentage of patients. The simultaneous determination of CEA and CD66b/c can increase the sensitivities for malignant tumors but high sensitivities of CD66b/c for benign diseases limit their usefulness as tumor markers. CD66b may be interesting as a marker for kidney and corpus carcinomas, for which good markers are not yet available.
Selective sensitivity of solid tumors to suramin in primary cultures of tumor cells from patients
Authors: Csoka Katalin , Nygren Peter , Graf Wilhelm , Påhlman Lars , Glimelius Bengt , Larsson Rolf 
Published: February 2007

AbstractThe antineoplastic activity of suramin is currently the subject of clinical trials. We therefore used the semi‐automated fluoro‐metric microculture cytotoxicity assay (FMCA) to evaluate the cytotoxicity of suramin in vitro in primary cultures of cells from patients with hematological or solid tumors. The activity patterns of some standard cytotoxic agents were included for comparison. A total of 159 samples were tested using continuous drug exposure. Suramin showed relatively high activity against solid tumors, with colorectal, adrenal and kidney carcinomas being the most sensitive, whereas hematological malignancies were more resistant. Suramin and standard drugs showed very low cross‐resistance. The results indicate that suramin is differentially active against some solid tumors with comparatively little activity against hematological tumors. The study provides an experimental motive for evaluation of suramin therapy in patients with solid tumors and exploration of less toxic suramin analogues.
Lack of interleukin‐2 (IL‐2) expression and selective expression of IL‐10 mRNA in human renal cell carcinoma
Authors: Nakagomi Hiroshi , Pisa Pavel , Pisa Eva K. , Yamamoto Yasuyoshi , Halapi Eva , Backlin Karin , Juhlin Claes , Kiessling Rolf 
Published: February 2007

AbstractFreshly isolated tumor‐infiltrating lymphocytes (TIL) are often functionally deficient. Since one of the key functional parameters of an immune response is the local production of cytokines, we studied the expression of cytokine genes in freshly isolated renal cancer tissue. Using a PCR‐assisted mRNA amplification assay, the constitutive expression of mRNA for 10 different cytokines was assessed in renal cancer tissue. We compared the cytokine mRNA expression in freshly isolated samples of renal carcinomas, renal cancer cell lines established from the tumor samples, peripheral blood mononuclear cells (PBMC) and non‐tumor kidney tissue isolated from the same patients. IL‐10 mRNA expression was detected only in tumor samples, while renal cancer lines, PBMC and non‐tumorous kidney tissues were devoid of this cytokine. One‐third of the tumor samples but none of the normal kidney samples also expressed G‐CSF mRNA. IL‐6, TNF‐α and IFN‐γ mRNA were expressed non‐selectively in tumors, PBMC and normal renal tissue. Expression of IL‐2, IL‐3 and IL‐4 mRNA was not detected in any of the tissues analyzed. Established renal cancer lines exhibited expression of IL‐lα, IL‐6, TNF‐α and GM‐CSF. Culture of tumor‐derived T cells with anti‐CD3 monoclonal antibody (MAb) resulted in expression of IL‐2, IL‐3 and IL‐4 mRNA. In contrast, none of these cytokines was detected in culture with recombinant human IL‐2 alone. Since IL‐10 is known to suppress antigen presentation, these findings have important implications for the possible in vivo role of IL‐10 as a suppressor of local anti‐tumor response.
Growth of ovarian‐carcinoma cell lines at physiological folate concentration: Effect on folate‐binding protein expression in vitro and in vivo
Authors: Miotti Silvia , Facheris Patrizia , Tomassetti Antonella , Bottero Federica , Bottini Cristina , Ottone Francesca , Colnaghi Maria I. , Bunni Marlene A. , Priest David G. , Canevari Silvana 
Published: February 2007

AbstractOvarian‐carcinoma cell lines (OVCAR3, IGROVI, OVCA432, SW626 and SKOV3), grown in standard medium containing supra‐physiological (2.3 μM) folate concentration, display different levels of reactivity with the anti‐folate‐binding‐protein (FBP) monoclonal antibody MOv18, which recognizes the α‐iso‐form of the protein. Gel‐filtration and absorption experiments indicated that on IGROVI cells this molecule accounts for all folic‐acid binding at nanomolar concentrations. The aim of the study was to investigate the effect of extracellular folate levels on cells adapted to grow in medium containing physiological folate concentration (20 n M). By the ternary complex assay, all cell lines showed a marked depletion of intracellular reduced folates, compared with those in standard folate medium. The monitoring of FBP by MOv18 showed on IGROVI cells a transient up‐regulation of the protein, whereas on the other cell lines, except SKOV3, no changes were detected. These data suggest that in these cells further over‐expression of the molecule cannot generally be induced by lowering the extracellular folate concentration. On SKOV3, Scatchard analysis of 125I‐MOv18 binding, as well as the evaluation of total folate binding capacity, showed a 2‐ to 3‐fold stable increase of FBP expression after long‐term growth in low‐folate medium. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) analysis indicated in these cells a 1.5‐fold increase in α‐FBP mRNA. SKOV3 cells, maintained in vitro in medium containing supra‐physiological and physiological (i.e., low‐folate) concentrations were injected into nude mice. Weight differences, though not statistically significant, were observed in favour of low‐folate‐derived tumors. Immunohistochemical and immunochemical analysis of the tumor samples showed that in SKOV3 cells the receptor modulation can also be induced by restoring the physiological folate concentration in vivo.
Modulation of cisplatin sensitivity and accumulation by interferon α‐2A in human squamous carcinoma cell lines
Authors: Gupta Vicram , Jani Jitesh P. , Emerson Erling O. , Xu Bing H. , Scalamogna Domenic , Xia Hong , Katoh Arthur , Zaren Howard A. , Singh Shivendra V. 
Published: February 2007

AbstractThis study was undertaken to elucidate the mechanism(s) of potentiation of cisplatin (CDDP) cytotoxicity by interferon α‐2a (IFN α‐2a) in human squamous carcinoma cell lines SCC‐25 and SCC‐4. IFN α‐2a treatment significantly increased the cytotoxicity of CDDP in both cell lines in a dose‐dependent manner. In SCC‐25 cells, the cytotoxicity of CDDP was increased by about 2‐ and 4‐fold, respectively, by treating the cells with 400 and 800 1U/ml IFN α‐2a. Sensitivity of SCC‐4 cells to CDDP was increased by about 3‐ and 7‐fold, respectively, by 400 and 800 1U/ml IFN α‐2a treatment. Drug uptake experiments revealed approximately 1.4‐ to 5‐fold higher platinum accumulation in IFN α‐2a‐treated cells as compared to respective controls. Cellular levels of glutathione (GSH) and GSH transferase, which have been suggested to be important determinants of tumor cell sensitivity to CDDP, were not altered by IFN α‐2a treatment in either of the cell lines. Northern blot analysis showed a moderate increase (about 30–40%) in the level of MT‐IIA mRNA by IFN α‐2a treatment in these cells. Our results suggest that IFN α‐2a‐mediated sensitization of SCC‐25 and SCC‐4 cell lines to CDDP in vitro may be due to an increase in intracellular platinum accumulation.
Ethnic segregation of HTLV‐I and HTLV‐II carriers among South American native Indians
Authors: Fujiyoshi Toshinobu , Yashiki Shinji , Fujiyama Chihaya , Kuwayama Masahiro , Miyashita Hiroki , Ohnishi Hiroshi , Blank Michelle , Zaninovic Vladimir , Blank Abraham , Cartier Luis , Byrnes John J. , Harrington William J. , Miura Tomoyuki , Hayami Masanori , Tajima Kazuo , Sonoda Shunro 
Published: February 2007

AbstractThd investigate the genetic background of human T‐cell leukemia virus type I (HTLV‐I) and II (HTLV‐IIhd carriers among South American native Indians, we analyzed HLA DRBI*‐DQBI * haplotypes of the virus carriers from Andes highlands and Orinoco lowlands by the PCR‐RFLP genotyping method. It was revealed that the HTLV‐I‐carrying Andes natives had one of the 5 HLA haplotypes: DRBI*‐DQBI* 0403‐0302, 0802‐0402, 0901‐0303, 1406‐0302 and 0407‐0302, and that the Orinoco HTLV‐II carriers had one of the 3 HLA haplotypes: DRBI*‐DQBI* 1402‐0301, 1602‐0301 and 0404‐0302. The HLA haplotypes of Andes HTLV‐I carriers and Orinoco HTLV‐II carriers were mutually exclusive. The haplotypes associated with HTLV‐I carriers were commonly found among the Andes Indians and Japanese, which is the known HTLV‐I endemic population, while the haplotypes associated with HTLV‐II carriers were specifically found among the Orinoco Indians and North American Indians, among whom HTLV‐II is endemic. These reults suggested that HLA haplotypes might be ethnically segregated among South American natives and might be involved in the susceptibility to HTLV‐I and HTLV‐II infections.
Constitutional and somatic mutations in the WTI gene in wilms' tumor patients
Authors: Nordenskjöld Agneta , Friedman Eitan , Sandstedt Bengt , Söderhäll Stefan , Anvret Maria 
Published: February 2007

AbstractWhdlms' tumor development, like most tumors, involves multiple genetic alterations affecting divershd genes. Only one of these has thus far been identified, the Wilms' tumor I (WTI) gene on 11p 13, which functions as a tumor suppressor gene. We assessed the involvement of the WTI gene constitutionally and somatically in 26 Wilms' tumor patients. Of these, the clinical data suggest a constitutional pre‐disposition in 12 bilateral cases and 7 cases with early onset. We employed Southern blot analysis and PCR‐based markers for analyses of somatic allelic losses in chromosome bands 11 p 13, 11 p 15 and 16q and screened for point mutations in exons 2–10 of the WTI gene with denaturing gradient gel electrophoresis (DGGE). Of the 12 cases with multiple tumors, I exhibited a constitutional 11 p 13 deletion and a somatic stop mutation in exon 4 of the WTI gene and 2 harbored constitutional mutations in the WTI gene: a pre‐mature stop codon in exon 6 in a boy with bilateral cryptorchidism and bilateral Wilms' tumors and an intragenic deletion in a girl with bilateral WT. Three additional bilateral tumors displayed WTI rearrangements or allelic losses with 11 p 13 markers. Four of 7 patients with an early onset of unilateral tumor had losses of 11p 13, though no WTI mutations were detected. Two of the remaining cases that did not show any somatic or constitutional 11 p 13 alterations had Beckwith‐Wiedemann syndrome, known to involve the 11 p 15 region.
Oncogenic transformation alters cisplatin‐induced apoptosis in rat embryo fibroblasts
Authors: Basu Alakananda , Cline Jeffrey S. 
Published: February 2007

AbstractWe have investigated whether cellular transformation by different oncogenes alters their responsiveness to the chemotherapeutic agent cis‐diamminedichloroplatinum(lI) (cDDP). Rat‐6 (R6) embryo fibroblasts transformed by v‐myc, rc‐mos (rearranged mouse c‐mos), v‐src and activated c‐H‐ras oncogenes displayed differential sensitivities to cDDP, and the lC50 values of cDDP decreased by approximately 3.0‐, 1.2‐, 2.0‐ and 1.5‐fold, respectively. Over‐expression of rnyc, but not ras, srcor mos, induced apoptosis in R6 cells. Nevertheless, all oncogenes influenced cellular susceptibility to apoptosis triggered by cDDP as judged by the appearance of condensed chromatin, formation of apoptotic bodies and internucleosomal cleavage of genomic DNA to 180 bp multimers, yielding a “laddered” ectrophoretic profile on agarose gel. There was a correlation between the time‐ and concentration‐dependent enhancement of cDDP‐induced DNAfragmentation and potentiation of cDDP sensitivity by various oncogenes. Oncogenic transformation led to a decrease in expression of the PKCr isoform, and stable transfection of PKCr in R6 cells prevented cDDP‐induced apoptosis and protected cells against cDDP cytotoxicity. Our results indicate that the differential sensitivity of oncogenetransformed cells to cDDP may be associated with the ability of various oncogenes to influence cDDP‐induced apoptosis.
Anti‐tumor and anti‐angiogenic effects in mice of heparin conjugated to angiostatic steroids
Authors: Derbyshire Elaine J. , Comin Georgina A. , Yang Yong‐Ching , Overholser Jay , Watkins Linda , Thorpe Philip E. 
Published: February 2007

AbstractHeparin‐steroid conjugates have been prepared by linking a non‐anti‐coagulating derivative of heparin, which binds to endothelial cells, to an angiostatic steroid, which suppresses endothelial cell division. One such conjugate, heparin adipic hydrazide (HAH) linked to cortisol, has previously been shown to inhibit both angiogenesis and the growth of solid tumors in mice. In the present study, heparin hydrazide (HH) was linked to tetrahydro S, tetrahydrocortisone and tetrahydrocortisol, which are devoid of glucocorticoid and mineralocorticoid activity and hence were predicted to have low toxicity to animals. The tetrahydro steroid conjugates were compared with the cortisol conjugate for therapeutic effectiveness against solid Lewis lung carcinoma growing in mice. HAH‐cortisol reduced tumor growth by up to 75% whereas a simple mixture of HAH and cortisol was not significantly inhibitory. In contrast to HAH‐cortisol, the 3 tetrahydro steroid conjugates did not significantly inhibit tumor growth. The differences in anti‐tumor properties of the conjugates correlated with their ability to inhibit angiogenesis in a Matrigel implant model in mice. The tetrahydro steroid conjugates did not significantly inhibit angiogenesis whereas HAH‐cortisol inhibited angiogenesis by greater than 90%. Therefore, HAH‐cortisol is the most effective heparin‐steroid conjugate so far developed. © 1995 Wiley‐Liss, Inc.
Regulation of EGF‐induced tenascin‐C by steroids in tenascin‐C‐non‐producing human carcinoma cells
Authors: Sakai Takao , Kawakatsu Hisaaki , Furukawa Yusuke , Saito Masaki 
Published: February 2007

AbstractTenascin‐C, a 6‐armed extracellular matrix glycoprotein, is expressed in a temporally and spatially restricted pattern during tumorigenesis in association with stromal‐epithelial interactions. We have previously shown that de novo synthesis of tenascin‐C is induced by the diffusible factor EGF in tenascin‐C‐non‐producing human epidermoid carcinoma cells in stromal‐epithelial interactions. We now demonstrate that the addition of human tenascin‐C or tenascin‐C peptides to the culture medium of these cells had little effect on the induction of tenascin‐C. The physiological regulators of tenascin‐C induction through the EGF receptor, however, have not yet been characterized. We show that steroid hormones down‐regulate EGF‐induced tenascin‐C glycoprotein and its mRNA in these tenascin‐C‐non‐producing carcinoma cells. Of the steroids examined, hydrocortisone most effectively inhibited the secretion of tenascin‐C. These steroids did not affect EGF‐induced autophosphorylation or de novo synthesis of EGF receptors, nor did they compete for the binding of EGF to its receptor. Our results indicate that the induction of tenascin‐C by EGF and its down‐regulation by steroids might proceed in these carcinoma cells through separate signal transduction pathways. © 1995 Wiley‐Liss, Inc.
The essential role of endogenous IFN α/β in the anti‐metastatic action of sensitized T lymphocytes in mice injected with friend erythroleukemia cells
Authors: Gresser Ion , Maury Chantal , Kaido Thomas , Bandu Marie‐Thérèse , Tovey Michael G. , Maunoury Marie‐Thérèse , Fantuzzi Laura , Gessani Sandra , Greco Giampaolo , Belardelli Filippo 
Published: February 2007

AbstractAdoptive transfer of splenic T lymphocytes from DBA/2 mice immunized against Friend erythroleukemia cells (FLC) inhibited the development of visceral metastases and increased the survival time of DBA/2 mice challenged i.v. with parental FLC 24 hr to 2 months later. Immune spleen cells were ineffective in mice pre‐treated with potent neutralizing antibody to mouse IFN α/β (but not to IFN γ), demonstrating the essential participation of endogenous IFN α/β in the inhibitory action of immune T lymphocytes against FLC metastases. These findings suggest that the reported inability of immune T lymphocytes to exert an anti‐FLC effect in immunodeficient DBA/2 mutant beige (bg/bg) mice (unless these mice had also been treated with IFN α/β), may have been due to lower levels of endogenous IFN α/β in DBA/2 bg/bg mice than in normal DBA/2 +/bg mice. Experimental results in support of this hypothesis are presented. © 1995 Wiley‐Liss, Inc.
Effects of aminoglutethimide, alone and in combination with surgical castration, on pancreatic carcinogenesis in rats and hamsters
Authors: Visser Corjan J. T. , Meijers Michiel , Van Garderen‐Hoetmer Annemarie , Klijn Jan G. M. , Foekens John A. , Woutersen Ruud A. 
Published: February 2007

AbstractThe present 12‐month study was carried out to investigate the effects of the aromatase inhibitor aminoglutethimide, alone and in combination with orchiectomy, on pancreatic carcinogenesis in azaserine‐treated rats and N‐nitrosobis(2‐oxopropyl)‐amine‐treated hamsters. Treatment of the animals started 4 months after the last injection with the carcinogen. They were surgically castrated and/or treated with aminoglutethimide. Aminoglutethimide‐treated rats developed less pancreatic tumours than did untreated controls. Multiplicity of (pre‐)‐neoplastic acinar lesions was lower in orchiectomized rats than in intact rats. Inhibition of pancreatic carcinogenesis was most pronounced in rats that were both orchiectomized and treated with aminoglutethimide. These effects were statistically significant after 8 months, but not after 4 months, of treatment. In hamsters, aminoglutethimide showed an enhancing rather than an inhibitory effect on the formation of ductular pancreatic tumours. Castration appeared to have no effect on the development of N‐nitrosobis(2‐oxopropyl)amine‐induced ductular lesions in the pancreas, either alone, or in combination with aminoglutethimide. The present findings indicate that aminoglutethimide, alone and in combination with surgical castration, might be of value for the treatment of pancreatic acinar tumours, whereas the usefulness of aminoglutethimide for treatment of ductular adenocarcinomas of the pancreas is somewhat doubtful. © 1995 Wiley‐Liss, Inc.
Delayed development of retinoblastoma associated with loss of a maternal allele on chromosome 13
Authors: Kato Mitsuo V. , Ishizaki Kanji , Shimizu Takashi , Toguchida Junya , Kaneko Akihiro , Sasaki Masao S. 
Published: February 2007

AbstractLoss of heterozygosity (LOH) on chromosome 13, which is associated with the functional inactivation of the retinoblastoma (RB) gene, is critical for the development of RB. To date, we have found that LOH‐negative tumors develop earlier than LOH‐positive tumors in hereditary cases of RB, an observation which suggests that loss of one allele on chromosome 13 may be disadvantageous with respect to growth of RB tumors. In this study, the parental origin of the lost allele on chromosome 13 and the age at operation of 13 patients with non‐hereditary RB tumors that had been enucleated at the same stage were studied, in an attempt to determine whether there are any differences between tumors with loss of a maternal allele on chromosome 13 and tumors with loss of a paternal allele. Six tumors had lost the maternal allele and 7 tumors had lost the paternal allele on chromosome 13. The age (average 694 days) of patients at operation in the case of tumors with loss of the paternal allele was significantly lower than the age (average 1,079 days) of patients at operation for removal of tumors with loss of the maternal allele. RB tumors that had lost the maternal allele on chromosome 13 developed later than tumors that had lost the paternal allele. The possibility is discussed that loss of the maternal allele on chromosome 13 might be disadvantageous for growth of RB tumors. © 1995 Wiley‐Liss, Inc.