bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of EGP‐2‐positive pulmonary metastases by bispecific‐antibody‐redirected T cells in an immunocompetent rat model
Authors: Kroesen B. J. , Helfrich W. , Bakker A. , Wubbena A. S. , Bakker H. , Kal H. B. , The T. H. , De Leu L. 
Published: February 2007

AbstractEffectiveness of bispecific‐monoclonal‐antibody (BsMAb)‐mediated cellular anti‐tumour activity was evaluated in vitro and in vivo in relation to the additional need for T‐cell activation in a new immunocompetent rat tumour model. L37 tumour cells, derived from a squamous‐cell carcinoma of the lung of Wag/Rij rats, were transfected with the cDNA coding for the human 38‐kDa transmembrane pan‐carcinoma‐associated antigen EGP‐2. Intravenous inoculation of EGP‐2‐positive L37 cells resulted in a rapid outgrowth of EGP‐2‐positive tumour nodules in the lungs. A BsMAb BIS‐19, recognizing EGP‐2 on the transfected tumour cells and the T‐cell receptor of the rat, was made and allowed specific lysis of EGP‐2‐transfected L37 tumour cells by activated rat T lymphocytes in vitro. In vivo T‐cell activation, assessed by up‐regulation of IL‐2‐receptor expression, could be induced by daily injection of rat rIL‐2. Intravenous treatment of tumour‐bearing EGP‐2‐positive L37 tumour with BIS‐19 together with rat rIL‐2 resulted in almost complete disappearance of established tumour. In contrast, animals treated with BIS‐19 alone, IL‐2 alone or a combination of anti‐EGP‐2, anti‐TcR and IL‐2 showed much less or no tumour reduction. These results show effectiveness of systemic treatment with BsMAbs to induce anti‐tumour activity in established tumours. Immune activation prior to or during treatment with BsMAbs, as achieved with IL‐2, appears to be a prerequisite for successful treatment. © 1995 Wiley‐Liss, Inc.
Chemoprevention by galanin against colon carcinogenesis induced by azoxymethane in wistar rats
Authors: Iishi Hiroyasu , Tatsuta Masaharu , Baba Miyako , Uehara Hiroyuki , Yano Hiroyuki , Nakaizumi Akihiko 
Published: February 2007

AbstractThe effects of the neuropeptide galanin on the development of colon tumors induced by azoxymethane (AOM) and on the labeling index of colon epithelial cells were investigated in Wistar rats. Treatment with galanin significantly decreased the incidence of colon tumors at week 45. Galanin did not influence the histological appearance of the colon tumors, but it slightly increased the frequency of sub‐mucosal adenocarcinomas. Furthermore, it significantly decreased the labeling index of colon mucosa during and after AOM treatment. These findings indicate that galanin inhibited the development of colon tumors and that this effect may be related to its suppression of colon‐epithelial‐cell proliferation. © 1995 Wiley‐Liss, Inc.
Menstrual and reproductive factors and pancreatic cancer risk in women
Authors: Fernandez Esteve , La Vecchia Carlo , D'Avanzo Barbara , Negri Eva 
Published: February 2007

AbstractTo investigate possible correlates of the systematically higher pancreatic cancer rates in males than in females, the role of menstrual, reproductive and hormonal factors in females have been assessed using data from a case‐control study conducted in Northern Italy. Cases were 133 women with histologically confirmed incident cancer of the pancreas, and controls were 377 women in hospital for acute, non‐neoplastic, non‐digestive‐tract disorders. After allowance for age, education, area of residence and smoking habit, an increased risk of pancreatic cancer was observed in women with early menarche (⩽ 13 years) (OR = 1.9; 95% Cl; 1.0–3.6), but no significant association was observed with age at menopause or length of fertile life. Parous women were at reduced risk as compared to nulliparous women (OR = 0.7), although the trend in risk with number of births was not significant. No association with spontaneous or induced abortions was observed. Pancreatic cancer risk was inversely related to early age at first birth (first birth < 25 versus nulliparae: OR = 0.5; 95% C1: 0.3–0.9; p‐value for trend < 0.01) and to age at last birth (last birth < 25 versus nulliparae: OR = 0.3; 95% C1: 0.1–0.8; p‐value for trend < 0.05). Ever‐users of estrogen replacement therapy showed a non‐significantly increased risk (OR = 2.2). Although no clear pattern of association is evident, the present results are in agreement with previous epidemiological observations and experimental research indicating that hormonal (menstrual and reproductive) factors could explain part of the male‐to‐female differential in incidence and mortality from pancreatic cancer. © 1995 Wiley‐Liss Inc.
Concurrent amplification of cyclin E and CDK2 genes in colorectal carcinomas
Authors: Kitahara Kenji , Yasui Wataru , Kuniyasu Hiroki , Yokozaki Hiroshi , Akama Yoshihiko , Yunotani Seiji , Hisatsugu Takeharu , Tahara Eiichi 
Published: February 2007

AbstractThe genetic changes of cyclin A, Dl, E and CDK2 were examined in human colorectal carcinomas by Southern‐blot analysis. Gene amplification of cyclin E was detected in 5 of 53 (9.4%) primary colorectal carcinoma tissues. Interestingly, in 3 of 5 tumors showing cyclin E gene amplification, the CDK2 gene was amplified simultaneously with rearrangements. No obvious correlation was detected between gene amplification and clinico‐pathological features of colorectal carcinomas. Out of 7 colon carcinoma cell lines, 2 showed gene amplification of cyclin E without gene amplification of CDK2. No amplification of cyclin A or Dl gene was found in any of the colorectal carcinoma tissues or colon carcinoma cell lines. Our results suggest that the concurrent amplification of cyclin E and CDK2 genes may play a role in colorectal carcinogenesis. © 1995 Wiley‐Liss Inc.
Apical release of base‐labile fatty acyl groups commensurate with stimulation of glycoprotein sialosyl Lewisa secretion in colorectal carcinoma cells
Authors: Liepkalns V. A. , Eboue D. , Kuksis A. , Beringer T. , Icard‐Liepkalns C. 
Published: February 2007

AbstractThe rate of polarized secretion of a putative adhesion ligand, sialosyl Lewisa (19–9), by SW1116 colorectal carcinoma cells is stimulated at least 20‐fold after pre‐incubation with, and the incorporation of, retinoic acid (RA). In order to investigate the possible involvement of fatty acylation in the export of the epitope, purified ligandsfrom carcinoma‐cell membranes, membrane subfractions and media were analyzed during RA‐induced secretion. Incorporation of radioactivity from (3H)palmitate into membrane subfractions and purified sialosyl Lewisa antigenic molecular species of Mr > 150,000 (SiaLeams) was stimulated by RA treatment. Most of the intracellular lipid radioactivity which bound to solid‐phase 19–9 antibody behaved chromato‐graphically, either like ganglioside or like NH2 OH‐labile acyl groups, but most of the (3H) bound to SiaLeams of post‐incubation media behaved like base‐labile fatty acyl groups, or free fatty acid. Release of base‐labile lipid radioactivity after 3 hr (associated with antigen) was almost exclusively into the apical media of membrane inserts. Gas‐liquid chromatography/mass spec, analyses of purified Sialeams revealed the presence of palmitate (16:0), as well as stearate (18:0) and oleate (18:1) fatty acyl groups. Our results suggest that fatty acylation of SiaLeams may be co‐ordinated with alterations in glycosylation and participate in directing these molecules to the apical surface. Lipid analyses were consistent with ganglioside chaperonage of SiaLeams to the apical surface, where N‐fatty‐acylated gangliosides remain for the most part integrated into the bilayer, but some oxyester or thioester bonds may be cleaved to permit release of SiaLeams to the apical medium. © 1995 Wiley‐Liss Inc.
Inhibition of cis‐diamminedichloroplatinum (II)‐induced DNA interstrand cross‐link removal by 7‐ethyl‐10‐hydroxy‐camptothecin in HST‐1 human squamous‐carcinoma cells
Authors: Masumoto Naoko , Nakano Shuji , Esaki Taito , Fujishima Hiromitsu , Tatsumoto Takashi , Niho Yoshiyuki 
Published: February 2007

AbstractThe combination of cis‐diamminedichloroplatinum(II) (CDDP) and 7‐ethyl‐10‐[4‐(I ‐piperidino)‐I ‐piperidino]carbonyloxycamptothecin (CPT‐I I), a topoisomerase‐l inhibitor, has been shown to be synergistic in vitro and clinically active against several human cancers refractory to chemotherapy. To elucidate the mechanism of the synergistic cytotoxicity of CDDP and 7‐ethyl‐10‐hydroxycamptothecin (SN‐38), an active metabolite of CPT‐11, we studied the interaction of these agents using an HST‐I human squamous‐carcinoma cell line. Cells were exposed to the IC50 concentration of SN‐38 (5.0 ng/ml) for I hr and various concentrations of CDDP for 1 hr in several different treatment schedules. SN‐38 augmented the anti‐tumor activity of CDDP in all schedules, with maximal synergy observed with simultaneous administration. Evaluation of the kinetics of the removal of DNA interstrand cross‐links, measured by alkaline elution, showed significant reduction of this removal in the cells exposed to SN‐38 and CDDP, as compared with the cells exposed to CDDP alone. No differences, however, were found in the initially attained level of DNA interstrand cross‐links induced by CDDP between these cells. Moreover, the intracellular accumulation of platinum measured by atomic‐absorption spectrophotometry, was virtually identical between these cells. These results indicate that SN‐38 can modulate the removal of platinum‐DNA adducts, thereby potentiating the cytotoxicity of CDDP, suggesting a critical role for topoisomerase I in the repair of DNA interstrand cross‐links. © 1995 Wiley‐Liss Inc.
The effect of active oxygen generated by xanthine/xanthine oxidase on genes and signal transduction in mouse epidermal JB6 cells
Authors: Singh Neeta , Aggarwal Sudeepta 
Published: February 2007

AbstractTo gain insight into the gene regulation and signal transduction effects of active oxygen in tumour promotion and progression, we studied the effect of active oxygen generated extracellulariy by xanthine/xanthine oxidase (X/XO) in promotion‐insensitive (P−), promotion‐sensitive (P+) and transformed (Tx) mouse epidermal JB6 cells. Active oxygen inhibited growth, particularly of P− cells and increased poly ADPR transferase activity and PKC activity more significantly in P− cells. No phenotypic differences in the distribution pattern of PKC isotypes α, β and γ were seen in JB6 cells. PKCα was expressed abundantly, whereas β and γ were not detected. Basal levels of the antioxidant enzymes catalase and CuZn. Superoxide dismutase were higher in P+ and Tx cells. X/XO resulted in an initial decrease in the activity of these enzymes, followed by recovery or transient induction in Tx and P+ cells. X/XO induced c‐myc and c‐fos expression in JB6 cells, with c‐fos induction being more pronounced in P− cells, whereas a biphasic increase in c‐jun was seen in P+ cells. These early genes may play a role in proliferation whereas post‐translational poly ADP‐ribosylation and, perhaps, phosphorylation suggest a genetic‐epigenetic mechanism in oxidant tumour promotion and progression. © 1995 Wiley‐Liss Inc.
Establishment and characterization of an uveal‐melanoma cell line
Authors: De Waard‐Siebinga Itte , Blom Derk‐Jan R. , Griffioen Marieke , Schrier Peter I. , Hoogendoorn Ed , Beverstock Geoff , Danen Erik H. J. , Jager Marline J. 
Published: February 2007

AbstractA human uveal melanoma cell line (92–1) was established from a primary uveal melanoma, and has now been maintained in culture for over 2½ years. Light microscopy of the cultured cells demonstrated extremely pleiomorphic cells with large prominent nucleoli. Cell proliferation was determined with a non‐radioactive propidium‐iodide assay and indicated an in vitro doubling time of approximately 58 hr. Furthermore, the cell line was characterized by cytogenetic analysis, electron microscopy, immunocytochemistry and Northern blotting for HLA and c‐myc‐mRNA analysis. Cytogenetic analysis revealed numerical abnormalities of chromosome 8 and structural abnormalities of chromosome 6. By electron microscopy, different stages of melanosome development were observed. Immunocytochemical analysis demonstrated expression of the melanoma‐associated antigen gp100. Expression analysis of HLA antigens revealed a very low level of, in particular, the HLA‐B locus products, which could be induced by interferon‐α or ‐γ treatment. Likewise, Northern‐blot experiments revealed decreased levels of HLA‐B mRNA as compared with HLA‐A. In addition, high levels of c‐myc expression were observed. The phenotypic characteristics of the cultured cells indicate that we have established an uveal melanoma cell line. This now well‐characterized uveal melanoma cell line can be used in future studies. © 1995 Wiley‐Liss, Inc.
Evidence that a low‐fat diet reduces the occurrence of non‐melanoma skin cancer
Authors: Black Homer S. , Thornby John I. , Wolf John E. , Goldberg Leonard H. , Herd J. Alan , Rosen Theodore , Bruce Suzanne , Tschen Jaime A. , Scott Lynne W. , Jaax Suzanne , Foreyt John P. , Reusser Brenda 
Published: February 2007

AbstractThe effect of a low‐fat diet on occurrence of non‐melanoma skin cancer was examined in a 2‐year dietary intervention trial. A total of 101 skin‐cancer patients were randomized either to a control group that consumed, on average, 38% of caloric intake as fat, and in which no changes in dietary habits were introduced, or to a low‐fat dietary‐intervention group, in which patients were instructed to limit their calories from fat to 20% of total caloric intake. Patients were examined at 4‐month intervals by dermatologists blinded to their dietary assignments. Nutrient analyses, conducted at each of the 4‐month follow‐up visits, indicated that the % calories of fat consumed in the intervention group had been reduced to 21% at 4 months and remained below this level throughout the 2‐year period. There were no significant differences in total calories consumed, or in mean body weights, between the control and the intervention groups. Nor were there significant group differences in PJS ratios until month 24. Numbers of new skin cancers treated at each examination were analyzed in 8‐month periods of the 2‐year study. Comparisons of skin‐cancer occurrences revealed no significant changes in the control group from baseline values. However, cancer occurrence in the low‐fat intervention group declined after the first 8‐month period and reached statistical significance by the last 8‐month period. Patients in this group had significantly fewer cancers in the last 8‐month period than did patients in the control group. In addition, there was a significant reduction in the number of patients developing skin cancer in the last 8‐month period, as compared with the first 8‐month period, within the low‐fat intervention group. There were no significant changes in the control group. These data indicate that a low‐fat diet can significantly reduce occurrence of a highly prevalent form of cancer. © 1995 Wiley‐Liss, Inc.
Apoptosis of a fibrosarcoma induced by protein‐free culture involves DNA cleavage to large fragments but not internucleosomal fragmentation
Authors: Watanabe Hideomi , Kanbe Katsuaki , Shinozaki Tetsuya , Hoshino Hiroo , Chigira Masaki 
Published: February 2007

AbstractA murine fibrosarcoma clone, Gc‐4 SD, grows depending on fetal calf serum. In MTT assay, protein‐free cultivation resulted in a reduction of the viable cell number time‐dependently. Electron‐microscopic and flow‐cytometric analyses revealed that the reduction in growth was accompanied by the appearance of apoptotic cells. However, no internucleosomal fragmentation was observed even after SI‐nuclease treatment. On the other hand, pulse field gel electrophoresis revealed that cleavage of DNA into high‐molecular‐weight fragments estimated as SO to 150 kilobase pairs (kbp), with a peak of 100 kbp, was found in the serum‐deprived cells. Large fragments disappeared from the DNA extracts when the smaller cells with high blue fluorescence with Hoechst 33342 were removed by flow cytometry, suggesting direct correlation between the large DNA fragmentation and apoptosis. The addition of aurintricarboxylic acid neither abolished the large DNA fragmentation nor inhibited the reduction in the number of viable cells. Both cycloheximide and actinomycin D enhanced the reduction in the number of viable cells as well as the large DNA fragmentation. These results suggest that apoptosis of a fibrosarcoma induced by protein‐free culture involves a specific endogenous endonuclease, which may be distinct from and independent of the ATA‐sensitive endonuclease producing internucleosomal DNA fragmentation. © 1995 Wiley‐Liss, Inc.
Inhibition by dehydroepiandrosterone of growth and progression of persistent liver nodules in experimental rat liver carcinogenesis
Authors: Simile M. , Pascale R. M. , De Miglio M. R. , Nufris A. , Daino L. , Seddaiu M. A. , Muroni M. R. , Rao K. N. , Feo F. 
Published: February 2007

AbstractDehydroepiandrosterone (DHEA) inhibits the development of early pre‐neoplastic lesions and prevents tumor development in various tissues when given to animals during the initiation/ promotion stages of carcinogenesis. Our purpose was to evaluate whether DHEA can also arrest the growth and progression of late lesions, such as persistent nodules (PNs) of rat liver. Male F344 rats were subjected to initiation by diethylnitrosamine followed by selection according to the “resistant hepatocyte” (RH) protocol. Fifteen weeks after initiation, when PNs were present in the liver, the rats were fed a diet withJwithout 0.6% DHEA for a maximum of 15 weeks. Glucose‐6‐phosphate dehydrogenase (G6PD) activity was 17‐ to 20‐fold higher in PNs than in normal liver 15–30 weeks after initiation. It significantly decreased, in both liver and PNs, 16 hr after starting DHEA feeding. Further DHEA feeding for 3–15 weeks decreased G6PD activity by 55–58% in both tissues. Eight weeks after starting DHEA, a fall in the proportion of labeled cells, after continuous contact with 3H thymidine for 7 days, was found in nodules. Treatment for 15 weeks with DHEA caused a marked decrease in the number of nodules per liver, as well as in the incidence of PNs with diameters of 3–6 and > 6 mm, respectively, while it did not affect PNs with diameters < 3 mm. Nodules showing patterns of malignant transformation were present in 40% of rats not treated with DHEA, but not in DHEA‐treated rats. All of 8 surviving rats not treated with DHEA had carcinomas at the 56th week, while only I out of 4 surviving rats treated with DHEA had carcinoma. These data indicate that DHEA inhibits G6PD activity in rat liver and in PNs In vivo. This is associated with growth restraint of PNs and results in inhibition of their progression to malignancy. © 1995 Wiley‐Liss, Inc.
Mitochondria‐bound hexokinase as target for therapy of malignant gliomas
Authors: Oudard Stéphane , Poirson Florence , Miccoli Laurent , Bourgeois Yveline , Vassault Anne , Poisson Michel , Magdelénat Henri , Dutrillaux Bernard , Poupon Marie‐France 
Published: February 2007

AbstractHexokinase plays an important role in glucose‐utilizing tissues like normal brain and cancers. In these tissues, hexokinase (HK) is mainly bound to mitochondria (mHK). Our objectives were to evaluate total HK (tHK) activity and mHK fraction in gliomas and to determine whether mHK binding could be targeted for therapy. Tumors were obtained from 26 patients and 13 were xenografted. HK, lactate and ATP were measured in cytosol and mitochondria extracts. The tHK expressed in mU/mg protein were 147 ± 19 and 78 ± 12, in fresh gliomas and xenografts, respectively, and of 489 in the normal brain. The mHK fraction was 76% in normal brain, 74 ± 4% in fresh tumors and 53 ± 6% in xenografts. Lactate/mHK ratios were higher in gliomas than in normal brain. The ATP was 10,52 ± 31 and 19 ± 8 nmol/mg protein in normal brain, xenografts and fresh gliomas respectively. Loss of one copy of chromosome 10 which carries the HKI gene, was evidenced in 11 of the 13 xenografted gliomas. The anti‐tumor effect of lonidamine (LND), which affects glycolysis in interfering with mHK activity, was tested in nude mice bearing 4 gliomas. LND (125 mg/kg, given i.p., twice daily for 5 days) led to a growth inhibition of TG‐7‐RO of 72%, with 2‐fold growth retardation, and had no effect for TG‐8‐OZ. Intermediate LND‐sensitivities for TG‐II‐DU and TG‐IO‐PY were noted. The LND‐sensitivity was correlated with the mHK activity (R2 = 0.73) and mHK fraction (R2 = 0.88). HK binding to mitochondria is a key of glycolysis in malignant gliomas, and targetting this binding with appropriate agents could be an effective therapeutic approach. © 1995 Wiley‐Liss, Inc.
Insulin‐like growth‐factor‐binding protein 3 is decreased in early‐stage operable pre‐menopausal breast cancer
Authors: Bruning Peter F. , Van Doorn Jaap , Bonfrèr Johannes M. G. , Van Noord Paul A. M. , Korse Catharina M. , Linders Theodora C. , Hart Augustinus A. M. 
Published: February 2007

AbstractInsulin‐like growth factor 1 (IGF‐1) is a potent mitogen for human breast‐cancer cells in vitro. In circulation, most of IGF‐1 is bound to IGF‐binding protein 3 (IGFBP‐3). This high‐affinity binding is thought to have an important limiting effect on the availability of IGF‐1 for biological activity. To assess the availability of IGF‐1 for receptor binding, we determined serum levels of IGF‐1 and IGFBP‐3 and IGF‐1/IGFBP‐3 ratios. In a case‐control study, 150 women aged 38 to 75 years presenting with stage‐l or‐II breast cancer were investigated just prior to surgery (n = 76), or to irradiation one month after surgery (n = 74). The population‐based control group consisted of 441 women of the same age having no breast cancer. Women reporting diabetes mellitus or other hormonal abnormalities were excluded. Premenopausal cases showed elevated IGF‐1 serum concentrations, decreased IGFBP‐3 levels and increased IGF‐1/IGFBP‐3 ratios. The IGF‐1/IGFBP‐3 ratio was a significant breast‐cancer risk factor, also after adjustment for age, family history, height, body‐mass index, body‐fat distribution, and serum levels of C‐peptide. The relative risk was 7.34 for the highest compared with the lowest quintile of IGF‐1/IGFBP‐3. The presence or absence of tumor had no influence on these results. Increased levels of available IGF‐1 in the circulation of pre‐menopausal women may contribute to the development of breast cancer. © 1995 Wiley‐Liss Inc.
Expression and release of intercellular adhesion molecule‐1 in renal‐cancer patients
Authors: Santarosa Manuela , Favaro Daniela , Quaia Michele , Spada Antonella , Sacco Cosimo , Talamini Renato , Galligioni Enzo 
Published: February 2007

AbstractWe examined ICAM‐1 expression in 37 freshly dissociated renal‐cancer cell populations. Immunoperoxidase analysis revealed that 31 of the 37 renal tumors expressed ICAM‐I to various degrees; ICAM‐1 expression was significantly lower in tumor cells obtained from patients remaining tumor‐free after a median follow‐up of 60 months (mean value 24.4% ± 21) than in tumor cells obtained from the relapsed patients (mean value 40.8% ± 22), and the low expression of this molecule on the cell surface seemed to correlate with favorable clinical behavior. In 41 patients, the mean level of sICAM‐1 was 551 ± 260 ng/ml, significantly higher than normal. However, sICAM‐1 levels were significantly lower in the 20 tumor‐free (mean 467 ± 158 ng/ml) than in the 21 metastatic patients (mean 631 ± 318 ng/ml). Eleven renal‐cancer cell populations were cultured in order to examine the expression and release of ICAM‐1. All of these cells were positive for ICAM‐1 expression, which was elevated in 6 cases (> 50%) and low in the remaining 5 cases (18–35%). However, only the 5 cell populations expressing low levels of ICAM‐1 released this molecule, showing an inverse correlation with cellular expression. Five of the cell populations were treated for 48 hr with rIFN‐γ; in these cells, both ICAM‐1 expression and sICAM‐1 levels increased, although sICAM‐1 levels in the supernatants of the cell populations with constitutive high ICAM‐1 expression remained very low. © 1995 Wiley‐Liss Inc.