bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site selective cyclic amp analogues are antagonistic to estrogen stimulation of growth and proto‐oncogene expression in human breast‐cancer cells
Authors: Katsaros Dionyssios , Ally Shamsia , Cho‐Chung Yoon Sang 
Published: June 2010

AbstractCyclic AMP (cAMP) analogues that selectively bind to either one of the two binding sites of cAMP‐dependent protein kinase demonstrate a potent inhibition of the growth stimulated by estrogen in MCF‐7 human breast‐cancer cells in culture. The site‐selective analogues, which are more potent activators of protein kinase than the analogues studied earlier, exhibit growth inhibition at micro molar concentrations. Among the analogues tested, 8‐CI‐cAMP (Site I‐selective) and N6‐benzyl‐cAMP (Site 2‐selective) are the 2 most potent inhibitors, causing 40‐70% inhibition of the estrogen‐stimulated growth at 10‐20 μM concentrations with no sign of toxicity. 8‐CI‐cAMP (I μM) in combination with N6‐benzyl‐cAMP (0.5 μM) almost completely blocks estrogen‐stimulated growth, demonstrating synergism between the Site 1‐and Site 2‐selective analogues. The growth inhibition parallels an increase in the R11cAMP receptor protein with a decrease in the R1 receptor as well as a reduction of c‐myc and c‐ras oncoproteins, whereas growth inhibition by tamoxifen does not affect the levels of the cAMP receptor proteins or the c‐myc and c‐ras protein levels. Site‐selective cAMP analogues are antagonistic to estrogen stimulation of breast‐cancer cell growth through a mechanism different from that of tamoxifen.
Influence of cyclosporin a on growth of an acute T‐cell leukaemia in PVG rats
Authors: Thomson A. W. , Forrest E. H. , Smart Louise M. , Sewell H. F. , Whiting P. H. , Davidson R. J. L. 
Published: June 2010

AbstractOur objective was to examine the effect of cyclosporin A (CsA; 25 or 12.5 mg/kg) on growth of an acute (Roser) T‐cell leukaemia in male PVG rats. The leukaemic blasts were shown (by immiunocytochemical analysis) to have a mature, T‐helpercell phenotype, i.e., OX‐19 (CD5)∓,W3/25 (CD4)∓,OX44∓MHC‐class I+, OX‐26+, corresponding to a population comprising 5% of normal rat medullary thymocytes. Animals received 20 × 102 viable tumour cells intramuscularly (day 0) and were given either CsA (25 or 12.5 mg/kg) or drug vehicle by gavage from day 0 or day 14, by which latter time leukaemic blasts normally appeared in the circulation. Administration of the higher dose of CsA from day 0 or day 14 significantly delayed the appearance of leukaemic cells in the peripheral circulation, whereas treatment with 12.5 mg/kg was without significant effect. CsA whole blood levels on day 17 were twice as high in leukaemic rats as in normal controls. Leukaemic infiltration of the spleen and the liver was reduced on day 17 after 25 mg/kg CsA, but no such effect was observed in lymph nodes or kidneys. A heterogeneous, host “reactive” cell population, which developed in response to the leukaemia, was inhibited by CsA, indicating that the effect of the drug was probably not mediated by host defence mechanisms. In CsA‐treated leukaemic animals, there was biochemical evidence of synergistic impairment of gtomerular and tubular function.
Biodistribution and tumour localization of a methotrexate‐monoclonal‐antibody 791T/36 conjugate in nude mice with human tumour xenografts
Authors: Pimm M. V. , Clegg Jane A. , Garnett M. C. , Baldwin R. W. 
Published: June 2010

AbstractThe blood kinetics and tumour localization of a conjugate of methotrexate (MTX) and MAb 79IT/36 were examined in nude mice with human tumour xenografts. The antibody moiety of the conjugate was detected by labelling with 125I and the drug moiety was assayed using a radioimmunoassay for methotrexate. After radio rodination, the drug moiety was co‐precipitable with the radiolabel when TCA or rabbit anti‐mouse IgG antiserum was used. Following i.v. injection, serum kinetics of both the antibody and the drug moieties of the conjugate were essentially similar, and the integrity of serum‐borne conjugate was confirmed by the co‐precipitation of radiolabel and drug. The radiolabelled antibody moiety of the conjugate localized in tumour xenografts, with 5‐7% of the injected dose being present per gram of tissue within 6 hr of injection, and the levels were maintained for up to 4 days. Analysis of tumour levels of the MTX moiety showed a progressive uptake over the 4‐day observation period with up to 4% of the injected dose being present per gram of tumour when the experiment was terminated. Parallel studies with free MTX showed rapid clearance from the blood and a maximum of 0.354b of the dose/g of tumour 30 min after injection. Control immunogiobulin conjugated to MTX did not show tumour localization of either the antibody or the drug moieties. These studies confirm that in vivo MTX remains bound to antibody in this type of drug antibody conjugate and demonstrate site‐specific targeting of this therapeutic agent.
Immortalization of a human colorectal adenoma cell line by continuous in vitro passage: Possible involvement of chromosome 1 in tumour progression
Authors: Paraskrva Christos , Finerty Susan , Powell Susan 
Published: June 2010

AbstractA non‐tumorigenic epithelial cell line designated PC/AA, derived from a large pre‐malignant colorectal adenoma from a patient with familial polyposis coli (also referred to as hereditary adenomatosis of the colon and rectum) has became immortal in vitro. PC/AA has been passaged in vitro continuously for over A years and shows no signs of senescence. At early passage, PC/AA has a normal diploid karyotype but with late passage is showing signs of progression, becoming aneuploid and displaying signs of morphological transformation. Every cell examined of late‐passage PC/AA has an isochro‐mosome (Iq), and one other marker chromosome which is probably derived from an additional chromosome 8. The majority of cells examined have 48 chromosomes. Despite showing signs of progression in vitro, late‐passage PC/AA has remained non‐tumorigenic in athymic nude mice and retained morphological differentiation characteristics of colonic cells, in particular the ability to synthesize and secrete mucin. Two other cell lines derived from small adenomas did not become immortal in vitro and were also non‐tumorigenic in athymic nude mice. The isolation of an immortal pre‐malignant human epithelial cell line could prove invaluable in studies on human careinogenests and tumour progression. Our results, showing that only a large adenoma and no small adenomas have given rise to immortal cell lines, raise the possibility that the acquisition of in vitro immortality is associated with a relatively late stage in the adenoma‐carcinoma sequence. The possible involvement of chromosome I in tumour progression is discussed.
Correlation between viral dna load and serum anti p19 antibody concentrationtn symptomless human T‐lymphotropic virus type‐I (HTLV‐I)‐infected individuals
Authors: Morand‐Joubert Laurence , Mariotti Martine , Reed Donna , Petit Jean‐Claude , Lefrere Jean‐Jacques 
Published: June 2010

AbstractIn order to determine whether serum anti‐human T‐cell lymphotropic virus type I (HTLV‐I) antibody concentration is correlated with cellular viral DNA load, these 2 biological parameters were established in 22 symptomless HTLV‐I carriers. The proviral copy (PVC) number was determined through quantificative polymerase chain reaction. Specific antibody titers were determined by Western blot with the end‐point dilution method; the quantification of each antibody was performed through ScanGlot by determination of the peak height of each Western‐blot band. A positive correlation was observed between the PVC number and the titer of total antibodies. When the association between the peak height of each antibody and the PVC number was studied, a significant positive correlation was observed only with anti‐p 19. Further evaluation through follow‐up studies of symptomless HTLV‐I individuals is needed to clarify the value of anti‐HTLV‐l antibody titer as a predictor of disease progression. © 1995 Wiley‐Liss, Inc.
Smoking and cancer mortality among U.S. veterans: A 26‐year follow‐up
Authors: McLaughlin Joseph K. , Hrubsec Zdenek , Blot William J. , Fraumeni Joseph F. 
Published: June 2010

AbstractOn the 30th anniversary of the U.S. Surgeon General's report Smoking and Health, we present updated results from one of the original cohort studies that comprised the groundbreaking document. A 26‐year follow‐up of 248,046 U.S. veterans evaluating the risks of cigarette smoking revealed strong dose‐response effects between smoking and total cancer and a large number of cancer sites. Over 50% of cancer deaths among current smokers and 23% of cancer deaths among former smokers were attributable to cigarette smoking. These findings further demonstrate the large and unique role cigarette smoking plays in cancer etiology and the importance of smoking cessation to reduce this enormous public health burden. © 1995 Wiley‐Liss, Inc.
Effects of cytokine‐mediated modulation of nm23 expression on the invasion and metastatic behavior of B16F10 melanoma cells
Authors: Parhar Ranjit S. , Shi Yufei , Zou Minjing , Farid Nadir R. , Ernst Peter , Al‐Sedairy Sultan T. 
Published: June 2010

AbstractThe molecular mechanisms of tumor invasion and metastasis are yet to be fully elucidated. A potential tumor‐metastasis‐suppressor gene nm23 has been described in certain rodent and human tumors. In the present study, we examined the potential anti‐invasive and anti‐metastatic effect of nm23 gene in B16F10 cells, a malignant murine melanoma cell line. Transfection of nm23 gene into B16F10 melanoma ceils resulted in significant suppression of the invasiveness and metastatic ability of melanoma cells and significantly enhanced the survival of tumor‐bearing mice. B16F10 melanoma cells transfected with nm23 produced significantly less soluble ICAM‐I and were more susceptible to LAK‐cell‐mediated cytotoxicity. Co‐culture of B16F10 melanoma cells with IL‐2 had no effect on nm23 expression, whereas treatment with PGE2, TNF‐α and IFN‐γ resulted in down‐regulation of nm23 expression. Concomitantly, in vivo treatment with TNF‐α or IFN‐γ in experimental mice increased pulmonary metastases and lowered the overall survival period, as compared with IL‐2 treatment alone. These results provide evidence that nm23, in addition to its anti‐metastatic function, could also be involved in modulating tumor‐target‐structure expression, in down‐regulating invasive potential and in production of soluble intracellular adhesion molecules. The down‐regulation of nm23 by TNF‐α, IFN‐γ and particularly by PGE2 warrants re‐examination of current immunotherapeu‐tic protocols and of the role played by PGE2 in tumor progression. © 1995 Wiley‐Liss, Inc.
Mitogenic effect of the 15‐kDa gross cystic disease fluid protein (GCDFP‐15) on breast‐cancer cell lines and on immortal mammary cells
Authors: Cassoni Paola , Sapino Anna , Haagensen Darrow E. , Naldoni Carlo , Bussolati Gianni 
Published: June 2010

AbstractThe biological significance of a major protein component in the fluid of gross cystic breast disease and a recognized marker of apocrine metaplasia, i.e. the 15‐kDa glycoprotein (GCDFP‐15), is presently unknown. We have added GCDFP‐15 to cell culture medium and tested its effect on proliferation of 4 human breast‐cancer cell lines (MCF7, BT474, MDA‐MB231 and T47D) and a “normal” human immortal breast‐cell line (MCF10A). These breast‐cell lines showed a mitogenic response to GCDFP‐15 (10 μ/ml). GCDFP‐15 enhanced cell growth of the MCF10A, MCF7, BT474 and MDA‐MB231 cell lines at both 48 and 96 hr of exposure. The glycoprotein exerted a mitogenic effect on the T47D cell line at 48 hr but not at 96 hr. This may be due to an auto‐regulatory effect of endogenous GCDFP‐15 synthesized by the T47D cells. GCDFP‐15 was ineffective on 2 colon‐cancer cell lines (HT29 and NIC‐H7I6), on the IMR32 neuroblastoma cell line and on the NIC‐H209 small‐cell lung carcinoma cells. A separate major breast cystic disease fluid protein of 24 kDa (GCDFP‐24) was tested, following the same experimental design, on the 5 breast‐cell lines, and showed no mitogenic activity. The mitogenic effect of GCDFP‐15 observed in this study in both “normal” and malignant breast epithelial cells suggests a possible relationship between apocrine metaplasia in breast cystic disease and the development of breast epithelial hyperplasia. In addition, a possible role of GCDFP‐15 in breast‐cancer progression should be considered. © 1995 Wiley‐Liss, Inc.
Modulation of cellular chemoresistance in keratinocytes by activation of different oncogenes
Authors: Sanchez‐Prieto Ricardo , Vargas Juan Antonio , Carnero Amancio , Marchetti Elena , Romero Jesus , Durantez Alberto , Lacal Juan Carlos , Cajal Santiago Ramon Y 
Published: June 2010

AbstractResponse to chemotherapeutic agents in malignant tumors depends on many factors, most of which are as yet unknown. We investigated the correlation between the activation of different oncogenes and protein‐kinase‐C(PKC) modulation, and the cytotoxicity of some of the most widely used anti‐cancer drugs. We transformed the murine keratinocyte cell line PAM 212, with different oncogenes (v‐H‐ras, v‐myc and adenovirus El a) and a mutant p53 suppressor gene (mp53). The cytotoxic effect of cisplatin (CDDP), doxorubicin(DOX) and vincristine (VCR), together with the concomitant action of modulators of PKC, TPA and staurosporine were evaluated by the crystal‐violet method, thymidine incorporation and flow cytometry. We report that (a) the oncogene v‐H‐ras induces resistance to CDDP (> 50%), DOX (> 25%) and VCR (> 20%); (b) the E l a oncogene induces only resistance to VCR (>40%) and marked sensitivity to CDDP and DOX; (c) the mp53 oncogene induces more resistance to VCR and insignificant resistance to the other drugs; and (d) activation of PKC by TPA increases the resistance to VCR and DOX in cells transformed by the v‐H‐ras, while it significantly increases the lethality with CDDP of the E l a‐transformed cells. Staurosporine increases the cytoxicity of all the drugs, especially in the E l a‐transformed keratinocytes. In the flow‐cytometry analysis, the percentage of BUdR incorporation was related to sensitivity to anti‐cancer drugs. © 1995 Wiley‐Liss, Inc.
Reduction of translation initiation factor 4E decreases the malignancy of ras ‐transformed cloned rat embryo fibroblasts
Authors: Graff Jeremy R. , Boghaert Erwin R. , De Benedetti Arrigo , Tudor Dianna L. , Zimmer Constance C. , Chan Shung Kai , Zimmer Stephen G. 
Published: June 2010

AbstractExpression of the T24ras oncogene induces malignancy (tumor growth, invasion and metastasis) in cloned rat embryo fibroblasts (CREF T24). In CREF T24, the rate of phosphorylation of eukaryotic translation initiation factor 4E (elF‐4E) is increased, resulting in increased protein synthesis rates. We have recently shown that reducing the protein levels of elF‐4E in CREF T24 (AS4E line) markedly decreases soft‐agar colonization, increases tumor latency periods and increases tumor doubling times without significantly altering monolayer growth. In this study, cells with reduced elF‐4E had delayed and reduced invasiveness and decreased experimental metastasis. Furthermore, reduced elF‐4E levels correlated with decreased expression of the metastasis‐associated 92‐kDa collagenase type‐IV and exon‐6 variants of the CD44 adhesion molecule [CD44(6v)]. Reduced elF‐4E levels correlated inversely with increased levels of the putative metastasis‐suppressor protein nm23. Cell lines established from AS4E tumors and lung metastases exhibited increased levels of elF‐4E protein and protein synthesis rates compared to the AS4E line. Tumor‐derived AS4E had the shortened tumor latency periods of CREF T24 but displayed the slow tumor‐growth rates of AS4E. Tumor‐derived AS4E exhibited the metastatic capacity of CREF T24 controls. Furthermore, tumor‐ and lung‐nodule‐derived AS4E expressed levels of CD44 (6v) and the 92‐kDa collagenase type IV comparable to CREF T24 and displayed reduced levels of nm23 relative to AS4E. These results demonstrate that elF‐4E is an important effector molecule involved in oncogenic p2lras‐induced malignant transformation. © 1995 Wiley‐Liss, Inc.
Growth properties of a human melanoma cell line are altered by adeno‐associated parvovirus type 2
Authors: Bantel‐Schaal Ursula 
Published: June 2010

AbstractThe adeno‐associated parvoviruses (AAV) are known for their oncosuppressive activity. This report shows that infection of the human melanoma cell line MKr with AAV‐2 leads to chromosomal integration of the viral DNA. The resulting cultures show decrease of saturation density and reduction in their ability to form colonies from single cells and thus to resemble normal cells. After single‐cell cloning they may give rise to growth‐arrested, terminally differentiating large, multinucleated cells with dendrite‐like extensions, large nucleoli and the ability to synthesize melanin pigment. In cultured melanoma cells, melanin synthesis is correlated with cellular senescence, and since senescent cells cease to proliferate and withdraw from the cell cycle, the apparent induction of growth arrest and terminal differentiation in malignant cells by AAV may provide one explanation for the anti‐neoplastic activity of these viruses. © 1995 Wiley‐Liss, Inc.
Lung adenocarcinoma and indicators of asbestos exposure
Authors: Mollo Franco , Pira Enrico , Piolatto Giorgio , Bellis Donata , Burlo Paola , Andreozzi Armando , Bontempi Silvano , Negri Eva 
Published: June 2010

AbstractA case‐control study was carried out on 145 male lung‐cancer patients diagnosed at autopsy and 178 controls, in order to investigate the relationship between asbestos exposure and the cell type of pulmonary carcinoma. Adenocarcinomas (AD) were individually matched with other cell types and with controls. The relative risk (RR) of developing AD in relation with lung asbestos body (AB) content as the exposure indicator was calculated by using logistic‐regression analysis for matched sets. Two cutoff levels, 1,000 and 10,000 asbestos bodies per gram dry weight (AB/gdw), were used in the analysis. In addition, AB counts were treated as a continuous variable (log AB + 1). A significant association was found between AD and asbestos exposure, using levels and logarithmic transformation. However, an association of asbestos exposure with cell types other than AD could not be ruled out. © 1995 Wiley‐Liss, Inc.
Circulating gangliosides of breast‐cancer patients
Authors: Wiesner Douglas A. , Sweeley Charles C. 
Published: June 2010

AbstractGangliosides were isolated from the sera of recently diagnosed breast‐cancer patients and from individuals who were apparently free of disease. Quantitative and qualitative analyses were carried out by 2‐dimensional high‐performance thin‐layer chromatography and gas chromatography. The locations of isolated gangliosides on thin‐layer chromatograms were determined by visualization with resorcinol, and each spot was quantified by digital image densitometry. The ganglioside profiles of cancer patients were compared to those of the control group, revealing a significant increase in total lipid‐bound sialic acid and a specific increase in polysialogangliosides in the patients with breast cancer. Furthermore, an increase was noted in the ratio of gangliosides of the b‐series biosynthetic pathway over those of the a‐series in the cancer sera, as compared to the controls. Gas chromatographic analysis of the peracetylated methanolysis mixtures derived from the total ganglioside fraction of cancer patients supported the HPTLC data, with an increase in total sialic acid, galactose, and sphingosine residues. No unusual gangliosides were found in the mixture from breast‐cancer patients. © 1995 Wiley‐Liss, Inc.
Regional variations of urokinase‐type plasminogen activator in human colorectal cancer: A quantitative study by image analysis
Authors: Tan Kevin , Powe Desmond G. , Gray Trevor , Turner David R. , Hewitt Robert E. 
Published: June 2010

AbstractQualitative histological studies in the distribution of urokinase‐type plasminogen activator (uPA) in human colorectal carcinomas have been well documented. However, to our knowledge the histological distribution of this enzyme has not been quantified in any tumour. For the present image analysis study, uPA was demonstrated in sections of human colorectal cancer using immunoperoxidase technique. A total of 9 colorectal carcinoma cases were used, in which 132 regions were analysed. Within each region, staining intensity measurements were made at evenly spaced intervals. Samples of normal mucosa from 6 cases were also studied. Enzyme levels were assessed with staining intensity measurements. For each section, a negative control section was included, in which the primary antibody was omitted. Staining for uPA was quantified for each region in the test section, and the measurement for the corresponding region of the negative control was then subtracted. The enzyme uPA was localised more at the tumour edge than in the tumour centre or distant host tissue. These differences were highly significant (p < 0.0001). There was also a highly significant difference in staining intensity when tumour regions adjacent to pushing edge were compared with those adjacent to infiltrating edge (p < 0.0001). Infiltrating tumours showed stronger staining for uPA than tumours with pushing edges. Since invasive activity is thought to be maximal at the edge of the tumour, localisation of uPA at this site is consistent with the role of this enzyme in the process of tumour invasion. © 1995 Wiley‐Liss, Inc.
Modulation of E‐cadherin expression and morphological phenotype in the intravascular component of adenocarcinomas
Authors: Cowley Gerard P. , Smith Mark E. F. 
Published: June 2010

AbstractE‐cadherin is a morphoregulatory epithelial cell/cell adhesion molecule whose loss from carcinomas probably contributes to a more invasive tumour phenotype. Employing an immunohisto‐chemical technique on 25 adenocarcinomas (8 from stomach, 10 breast, 7 colon) we compared E‐cadherin expression and tumour morphology of carcinoma that had invaded vascular spaces with that of extravascular carcinoma, both in primary tumours and in their lymph node metastases. In 40% of cases either at the primary site, in the lymph node metastasis or at both sites, E‐cadherin levels were higher in the often tiny intravascular tumour compartment than in the adjacent and much larger extravascular tumour compartment. In no tumour was the highest area of E‐cadherin expression present within the extravascular compartment. Increases in the differentiation and cohesion of intravascular tumour occurred in 16% and 20% of cases, respectively. In 3 of 4 cases showing increased differentiation, but in only 1 of 5 cases showing increased cohesion, these morphological changes were associated with increased intravascular E‐cadherin levels. © 1995 Wiley‐Liss, Inc.
Plasma levels of the atherogenic amino acid homocysteine in postmenopausal women with breast cancer treated with tamoxifen
Authors: Anker G. , Lonning P. E. , Ueland P. M. , Refsum H. , Lien E. A. 
Published: June 2010

AbstractLong‐term treatment of breast‐cancer patients with the anti‐oestrogen tamoxifen has been found to be associated with reduced cardiovascular mortality. Plasma homocysteine is an independent risk factor for atherosclerotic disease, and its level is determined by folate and cobalamin status, and possibly also by oestrogen status. We measured the effect of tamoxifen on plasma homocysteine, serum cholesterol, serum cobalamin and serum and erythrocyte folate in 31 post‐menopausal women with breast cancer. The plasma homocysteine level was decreased by a mean value of 29.8% after 9–12 months and by 24.5% after 13–18 months of treatment. Tamoxifen suppressed serum cholesterol by mean values varying between 7.2% and 17.6% after 3 to 19 months of treatment. There was no correlation between changes in plasma homocysteine and serum cholesterol. These findings suggest that the homocysteine‐lowering effect of tamoxifen may contribute to the reduction of cardiovascular mortality observed in patients on adjuvant therapy with tamoxifen. © 1995 Wiley‐Liss, Inc.