bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent clinical, histological and quantitative prognostic factors in transitional‐cell bladder tumours, with special reference to mitotic frequency
Authors: Lipponen P. K. , Eskelinen M. J. , Jauhiainen K. , Harju E. , Terho R. , Haapasalo H. 
Published: February 2007

AbstractA cohort of 537 transitional‐cell bladder cancers (TCC) was followed up for a mean of 9 years. Clinical stage, WHO grade, papillary status, 6 nuclear factors and volume‐corrected mitotic index (M/V index) were related to progression and survival. Classic and quantitative prognostic factors were significantly interrelated (p< 0.001). In Ta‐TI tumours M/V index predicted progression independently (p< 0.001) and in the entire cohort progression was related independently to the M/V index (p= 0.0001) and to the WHO grade (p= 0.0022). In survival analysis, clinical stage (p< 0.0001), M/V index (p< 0.0001), WHO grade (p< 0.0001), papillary status (p< 0.0001) and nuclear factors (p< 0.0001) were significant predictors. In papillary tumours, clinical stage (p< 0.0001), M/V index (p< 0.0001), WHO grade (p< 0.0001) and nuclear factors (p= 0.0001–0.0133) were related to survival. In a multivariate analysis T‐category (p< 0.001), WHO grade (p< 0.001), M/V index (p= 0.002) and papillary status (p= 0.034) predicted survival independently in the entire cohort whereas in papillary tumours T‐category (p< 0.001) and M/V index (p< 0.001) were independent predictors. If tumours with pelvic lymphnode metastases or distant metastases at diagnosis were excluded from the analysis, T‐category (p< 0.001), M/V index (p< 0.001) and WHO grade (p< 0.001) were independent predictors. In papillary tumours T‐category (p< 0.001), M/V index (p< 0.001) and WHO grade (p= 0.048) predicted survival. The results emphasize the importance of mitotic activity as a most important histological prognostic factor in TCC, second only to clinical stage. In Ta‐TI tumours quantitative mitotic frequency analysis includes all the available independent prognostic information. Accordingly, TCC can be graded by mitotic frequency analysis in place of subjective grading systems.
Capacity of adipose tissue to promote growth and metastasis of a murine mammary carcinoma: Effect of estrogen and progesterone
Authors: Elliott Bruce E. , Tam S.‐P. , Dexter D. , Chen Z. Q. 
Published: February 2007

AbstractPreviously we have shown that a murine mammary carcinoma cell line, designated SPI, grows and metastasizes more efficiently in the mammary gland than in the subcutis. In this report, we examine the tissue specificity of this phenomenon. Our results show that SPI cells grow best in the mesenteric and ovarian fat pads and well in the mammary gland, but very poorly in the subcutis or peritoneal cavity. Massive dissemination of tumors from the ovarian and mesenteric sites occurs to the liver, spleen and diaphragm. In contrast, metastases from the mammary site occur primarily in the lung. Co‐transplantation of a threshold number of SPI cells with mammary or ovarian fat fragments into the subcutis results in increased tumor growth, whereas very few tumors form in sham controls receiving no fat fragments. Removal of the ovaries of donor and recipient mice abrogates tumor growth in adipose tissue transplants. Estrogen can stimulate growth of SPI in adipose tissue sites, whereas progesterone inhibits growth. In contrast, in vivo growth of a stable metastatic variant selected from SPI cells was not inhibited by progesterone. SPI cells growing in ovarian and mesenteric fat pads showed increased expression of estrogen receptors and progesterone receptors, as well as detectable levels of epidermal‐growth‐factor receptors, whereas receptor levels decreased to baseline on tumors in the subcutis. The levels of estrogen‐receptor mRNA reflect the corresponding functional expression of receptors; this finding suggests that the regulation of estrogen‐receptor expression in this system is, at least in part, at the mRNA level. Our results are consistent with the model that adipose tissue exerts an estrogen‐dependent positive regulatory effect on primary SPI tumor growth, and promotes the formation of metastases.
Pharmacologic interactions between the resistance‐modifying cyclosporine sdz psc 833 and etoposide (VP 16–213) enhance In Vivo cytostatic activity and toxicity
Authors: Keller Roland P. , Altermatt Hans J. , Donatsch Peter , Zihlmann Hans , Laissue Jean A. , Hiestand Peter C. 
Published: February 2007

AbstractCyclosporin A reverses multidrug resistance (MDR) and increases the in vivo cytostatic activity and toxicity of the anticancer agent etoposide (VP 16–213). SDZ PSC 833 (PSC 833), a non‐immunosuppressive, non‐toxic cyclosporin and very active modifier of P‐gp 170‐mediated MDR, elicits similar effects when administered with adriamycin. The underlying mechanisms, however, are not yet understood. The present pharmacological interaction study with PSC 833 and VP 16–213 was carried out to reveal the nature of this enhancement of cytostatic activity and toxicity. Rats pre‐treated with either PSC‐833 or solvent received a single dose of VP 16–213. Plasma levels of VP 16–213 were measured by high‐performance liquid chromatography (HPLC). The resulting increase in cytostatic activity and toxicity of VP 16–213 mediated by PSC 833 was paralleled by marked changes in the pharmacokinetic parameters of VP 16–213 in vivo. Bioavailability and blood levels of VP 16–213 were significantly increased 30 min after administration if PSC 833 had been given before. The disappearance rate of VP 16–213 from the intravascular compartment was considerably slowed down by PSC 833. In drug‐sensitive xenografts of human colon carcinoma, the PSC‐833‐induced pharmacologic changes in vivo could be counteracted by dose reduction of VP 16–213 while a full therapeutic potential was maintained. Doses of VP 16–213, 1.5 to 2 times smaller, combined with PSC 833, were as effective in terms of tumor‐growth inhibition as the maximum tolerated dose of VP 16–213 alone. Thus, pharmacologic interactions between PSC 833 or other resistance modifiers and VP 16–213 and other cytostatic agents require careful attention if they are to be used in humans to overcome MDR.
Pleiotropic actions of suramin on the proliferation of human breast‐cancer cells in vitro
Authors: Foekens John A. , Sieuwerts Anieta M. , Stuurman‐Smeets Elisabeth M. J. , Dorssers Lambert C. J. , Berns Els M. J. J. , Klijn Jan G. M. 
Published: February 2007

AbstractSuramin, a non‐specific growth factor antagonist, is currently under investigation for treatment of cancer patients. We studied its action on 6 different human breast‐cancer cell lines in vitro. In complete growth medium, pleiotropic effects were observed with respect to cell proliferation, i.e. suramin is stimulatory at low concentrations and inhibitory at higher concentrations, for 4 of the 6 cell lines studied. The various cell lines showed marked differences with respect to the antiproliferative action of suramin, the Evsa‐T cells being by far the most sensitive ones. A suramin concentration of 100 μg/ml brought about a 100% stimulation of the proliferation of ZR/HERc cells, ZR 75.1 cells ectopically expressing a human epidermal growth factor receptor (EGF‐R) cDNA. Although less pronounced (10 to 60% stimulation), a similar response was observed for the parent ZR 75.1 cells, as well as for T‐47D and MDA‐MB‐231 cells. The non‐specificity of the action of suramin was established by the observation that suramin‐induced inhibition of cell proliferation could be abolished by insulin‐like growth factor‐1 (IGF‐I) or basic fibroblast growth factor (bFGF), and even by estradiol, both in complete growth medium and under defined serum‐free conditions. Our data indicate that suramin exerts pleiotropic effects on the proliferation of human breast cancer cells in vitro, and confirm the non‐specific nature of its action. The stimulatory effect of low concentrations of suramin on the proliferation of breast cancer cells may have important consequences for breast cancer patients treated with suramin.
Expression of integrins and other adhesion molecules in epstein‐barr virus‐transformed B lymphoblastoid cells and Burkitt's lymphoma cells
Authors: Rincon Jorge , Prieto Jacqueline , Patarroyo Manuel 
Published: February 2007

AbstractLymphocytes adhere to cells or extracellular matrices to perform functions relating to cytotoxicity, extravasation and tissue localization, as well as modulation of lymphocyte growth and maturation. This adherence is mainly mediated by 3 families of cell‐surface adhesion molecules: integrins, immunoglobulin‐related molecules and selectins. Since variations in the degree of adherence may affect the pathophysiology of lymphoproliferative disorders, the expression of a large number of adhesion molecules was analysed on Epstein‐Barr virus (EBV)‐transformed lymphoblastoid cell lines (LCLs), and on EBV‐positive or EBV‐negative Burkitt's lymphoma (BL) lines, by immunofluorescence flow cytometry and immunoprecipitation with monoclonal antibodies. With regard to the β1, β2 and β3 integrin subfamilies, LCLs strongly expressed CD49d/CD29 (VLA‐4), CDIIa/CD18 (Leu‐CAMa, LFA‐1) and CD5I/CD6I (vitronectin receptor). These cells also abundantly expressed CD54 (ICAM‐I) and CD58 (LFA‐3) as well as the „homing receptors”︁ L‐selectin (LECAM‐I) and CD44, BL lines had considerably lower amounts of VLA‐4 than LCLs, and ICAM‐1 was expressed only by some of the tumor lines. All other adhesion molecules were absent or minimally expressed in the BL cells.
SOD2: A new type of tumor‐suppressor gene?
Authors: Bravard A. , Sabatier L. , Hoffschir F. , Ricoul M. , Luccioni C. , Dutrillaux B. 
Published: February 2007

AbstractThe activity of superoxide dismutases (SOD) I and 2 was analysed in correlation with mRNA and chromosome content in 6 SV40‐transformed (TF) and in non‐transformed (NF) human fibroblast cell lines. Total SOD activity was fairly constant, whereas the ratio SOD2/SOD I was much lower in TF than in NF. The decrease in SOD2 activity was correlated with a low mRNA content, and with the presence of various chromosomal rearrangements leading to deletions of the long arm of chromosome 6 where the gene is mapped. In contrast, chromosome 21, carrying the gene for SODI, was not found to be deficient and the SODI activity was high. This shows that in TF, the activity of SOD2 is largely determined by gene dosage. It has been proposed that SOD activity could be inversely correlated with cell proliferation, and that SOD2 activity, in particular, was related to cell differentiation. Thus, there is a cascade of events occurring in cell transformation, involving gene deregulation, chromosome (gene) deletion, low mRNA and protein content, low enzyme activity, and acquisition of growth advantage which makes the SOD2 gene a possible new type of tumor‐suppressor gene.
Expression of mRNA for cytokines in tumor‐infiltrating mononuclear cells in ovarian adenocarcinoma and invasive breast cancer
Authors: Vitolo Domenico , Zerbe Tony , Kanbour Anisa , Dahl Carol , Herberman Ronald B. , Whiteside Theresa L. 
Published: February 2007

AbstractCytokine gene expression in tumor‐infiltrating lymphocytes (TIL) in frozen‐tissue sections of 2 types of human solid tumor—ovarian adenocarcinoma and invasive breast cancer—was examined by in situ hybridization with 35S‐labeled cDNA probes for human cytokines. The proportion of cells containing mRNA able to hybridize to the antisense c‐DNA probes for interleukin 2 (IL‐2), tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ) or receptors for IL‐2 (either p55 or p70) was also determined in human normal peripheral lymphoid tissues and inflammatory tissues. Few cells were positive for IL2 and TNFα mRNA in reactive human lymph nodes and tonsils. Inflammatory lesions, such as salpingitis or chronic active hepatitis, contained 10‐20 times more cells positive for cytokine mRNA than reactive lymphoid tissue. In contrast, tumor‐infiltrating lymphocytes (TIL) in the stroma of ovarian carcinomas or most ductal breast tumors only rarely expressed mRNA for TNFα, IL2 or IFNγ. The intensity of mononuclear cell infiltration in these tumors correlated positively with the percentage of cells which expressed mRNA for IL‐2, TNFa and IL‐2R. In those ductal breast carcinomas which contained intracellular or intraductal mucins, up to 30% of lymphoid cells in the tumor stroma were positive for IL‐2, TNFα, IFNγ and IL‐2R. Thus, strong evidence for local activation of mononuclear cells in situ, exemplified by the expression of genes for cytokines, was obtained only in inflammatory lesions and in mucin‐producing breast carcinomas. In most carcinomas studied, few TIL expressed genes for cytokines as measured by in situ hybridization. Thus, human solid tumors appear to differ in their ability to induce gene expression for cytokines in TIL.
Prevalence of human papillomavirus (HPV) infection in basque country women using slot‐blot hybridization: A survey of women at low risk of developing cervical cancer
Authors: Herckenrode Carmen Mugica‐Van , Malcolm Alan D. B. , Coleman Dulcie V. 
Published: February 2007

AbstractCervical smears from 1, 178 women with cytologically normal cervices and 67 women with cervical intra‐epithelial neoplasia (CIN) or cervical carcinoma were analyzed for the presence of HPV 6, 11, 16 and 18 DNA by slot‐blot hybridization. HPV DNA was detected in 17% (95% CI: 14%‐19%) of the women with a normal smear; 11% of infected women harboured HPV 16 and 18 (95% CI: 9%‐13%, each). HPV DNA was detected in 54% (95% CI: 41 %‐66%) of patients with abnormal smear; the most prevalent virus type in this group was HPV 16 (45%; 95% CI: 32%‐38%). In order to verify the slot‐blot results, a proportion of the samples was also investigated by PCR. There was 88% correlation between the 2 tests. The high prevalence of HPV 16 and 18 infection demonstrated in our low‐cervical‐cancer‐risk area further support the role of as yet unidentified co‐factors as determinants of the different geographic rates of cervical‐cancer incidence.
Unusual expression and localization of heat‐shock proteins in human tumor cells
Authors: Ferrarini Marina , Heltai Silvia , Zocchi M. Raffaella , Rugarli Claudio 
Published: February 2007

AbstractIt has been suggested that members of HSP families represent the surface target of immune responses leading to tumor rejection in mice. Here we report that tumor cells, compared with normal cells, constitutively expressed 2‐ to 10‐fold higher levels of intracellular HSP90. Moreover, in the absence of environmental stress, 2 lines (out of 6) expressed the “inducible” HSP72, which was also detectable in fresh tumor cells. HSP72 expression was not regulated during the cell cycle, in contrast with what has been observed with normal cells. Both HSP90 and HSP72 proteins exhibited a heterogeneous pattern of intracellular distribution in most cells, HSP72 being confined mainly to the nuclear compartment. Finally, we could detect both HSP90 and, to a lesser extent, HSP72 (that are generally believed to be located intracellularly) at the surface of some tumor cell lines. We conclude that tumor cells differ from normal cells in their pattern of HSP expression; this might imply a role of HSPs in eliciting an immune response against cancer.
Inhibition of tumor‐induced angiogenesis by the administration of recombinant interferon‐γ followed by a synthetic lipid‐a subunit analogue (GLA‐60)
Authors: Saiki I. , Sato K. , Yoo Y. C. , Murata J. , Yoneda Junya , Kiso M. , Hasegawa A. , Azuma I. 
Published: February 2007

AbstractThe effect of the administration of recombinant interferon‐γ. (rlFN‐γ) and a synthetic lipid A subunit analog (GLA‐60) on angiogenesis induced by B16‐BL6 melanoma was examined in syngeneic C57BLJ.6 mice. Intravenous administration of rlFN‐γ followed by GLA‐60 (referred to as rIFN‐γ/GLA‐60) induced endogenous production of tumor necrosis factor (TNF). This treatment on day 3 after tumor inoculation caused a marked decrease in the number of vessels oriented towards the tumor mass (angiogenic response) and tumor size over a period of 9 days. In contrast, neither rlFN‐γ nor GLA‐60 alone, nor GLA‐60/ rIFN‐γ (reverse sequence of administration), which is unable to induce the production of TNF in the serum, had any effect. Sera induced by the treatment with rIFN‐γJ.GLA‐60, and recombinant TNF, inhibited the in vitro growth of lung endothelial cells which is considered to be one of the essential events in tumor neovascularization. Multiple i.v. treatments with rIFN‐γ/ GLA‐60 on days 5, 8 and 11 after s.c. implantation of tumor, significantly inhibited primary tumor growth by the amputation time (day 20) and lung metastasis of BI6‐BL6 cells on day 34, while other treatment modalities had no such effect. Our results indicate that inhibition of lung‐tumor metastasis by rlFN‐γ/GLA‐60 treatment may be partly due to the inhibition of tumor‐associated angiogenesis.
The effect of retinoic acid on chemosensitivity of PA‐1 human teratocarcinoma cells and its modulation by an activated N‐ras oncogene
Authors: Le‐Ruppert Kim , Masters John R. W. , Knuechel Ruth , Seegers Silvia , Tainsky Michael A. , Hofstaedter F. , Buettner Reinhard 
Published: February 2007

AbstractCombination of chemotherapeutic drugs with agents that induce cell differentiation is a possible means of improving cancer chemotherapy. To explore this approach we used 4 cell lines established from the human teratocarcinoma‐derived cell line PA‐1; 2 retinoic acid (RA)‐sensitive lines compared to 2 RA‐resistant lines transformed by an activated N‐ras oncogene. Equal numbers of colony‐forming cells were exposed for 72 hr to 10−6M RA and subsequently to a range of concentrations of cisplatinum, etoposide or bleomycin. Enhanced cytotoxicity of cisplatin and etoposide (3‐ to 5‐fold) was observed in the N‐ras‐transformed cell lines compared to the non‐transformed lines. Treatment with RA caused an increase in the cytotoxicity of all 3 drugs to the 2 RA‐sensitive cell lines. In contrast, a reduction of cytotoxicity was observed in the 2 N‐ras‐transformed lines. Our results indicate that sensitivity to cytotoxic agents can be increased by RA in RA‐sensitive cells, but the opposite effect is seen in N‐ras transformed, RA‐resistant cells. Therefore, a general rationale for combination therapy with RA and cytotoxic drugs cannot be inferred.
Overexpression of a synthetic phosphotyrosine protein phosphatase gene inhibits normal and transformed cell growth
Authors: Ramponi Giampietro , Ruggiero Marco , Raugei Giovanni , Berti Andrea , Modesti Alessandra , Innocenti Donatella Degl' , Magnelli Lucia , Pazzagli Claudia , Chiarugi Vincenzo P. , Camici Guido 
Published: February 2007

AbstractWe studied the level of the cytosolic phosphotyrosine protein phosphatase (PTPase) (originally termed low‐Mr acid phosphatase) in normal NIH/3T3 and in v‐erb B‐transformed fibroblasts. The level of the enzyme, assayed by ELISA, was inversely related to cell proliferation, normally growing cells had less enzyme than their contact‐inhibited counterparts and v‐erbB transformants had less enzyme than normal NIH/3T3. In order to overexpress the enzyme and study its effects in normal and transformed cells, we transfected a synthetic gene coding for the PTPase in control NIH/3T3 and v‐erbB transformants. The overexpressed enzyme was recognized by antibodies raised against the native enzyme and, in cells overexpressing the PTPase, we observed a marked dephosphorylation of tyrosyl residues of cellular proteins. Cell proliferation, in both normal and v‐erbB transformants overexpressing the PTPase, was measured. We observed that PTPase overexpression was accompanied by significantly reduced thymidine incorporation in both cell types, either serum‐starved or serum‐stimulated. The ability of transformed v‐erbB cells to grow in soft agar was also markedly decreased by overexpression of the enzyme. Taken together, our results indicate that overexpression of PTPase might interfere with mitogenic signalling pathways in both normal and transformed cells, and propose a role for PTPase in the control of cell proliferation.
Menstrual and reproductive factors and breast cancer in women with family history of the disease
Authors: Parazzini Fabio , La Vecchia Carlo , Negri Eva , Franceschi Silvia , Bocciolone Luca 
Published: February 2007

AbstractThe relationship between socio‐economic indicators, body mass, reproductive and menstrual factors and risk of “familial” breast cancer has been analyzed using data from a large case‐control study of breast cancer conducted in Italy. A total of 3,037 breast‐cancer patients aged 75 years or less admitted to a network of hospitals in the Greater Milan area were interviewed. Controls were 2,569 women aged 75 or less, admitted for acute conditions to the same network of hospitals where cases had been identified. Women were not included as controls if they had been admitted for gynecological, hormonal or neoplastic diseases. A total of 331 cases and 121 controls reported a family history of breast cancer in their first‐degree relatives, with a family history tended to be more educated and of higher social class than controls with family history, but these differences were not statistically significant. No relationship emerged with marital status and body‐mass index. The estimated multivariate relative risks were, compared with nulliparous women, respectively 0.9, 1.2 and 1.2 for women reporting 1, 2 and 3 or more births. The risk of breast cancer was also greater in women reporting one or more spontaneous abortions: compared with those who did not, the estimated relative risk was 1.9 (95% confidence interval 0.8 to 3.7). Relative to women reporting their first birth below age 25, the estimated relative risks were 1.3 and 0.9 in those reporting it at age 25 to 29 and 30 or more respectively. Likewise, no consistent relationship emerged with lifelong menstrual pattern and menopausal status. These results suggest that menstrual and reproductive factors do not play an important role in the risk of breast cancer in women with a history of the disease in first‐degree relatives. © 1992 Wifey‐Liss, Inc.
Appearance and detection of multiple copies of the mdr‐1 gene in clinical samples of mammary carcinoma
Authors: Lönn Ulf , Lönn Sigrid , Nylen Urban , Stenkvist Björn 
Published: February 2007

AbstractTo examine the presence of multiple copies of the mdr‐1 gene in clinical tumor samples we have developed an approach where the cells are obtained by fine‐needle biopsies and the number of gene copies determined by PCR. The temporal appearance of amplified mdr‐1 was examined in 20 breast‐cancer patients with clinical stage‐IV disease receiving endocrine treatment. Tumor samples were obtained every 2nd to 3rd month from the same tumor lesion. None of the initial samples from each patient contained multiple copies of mdr‐1. Of 16 patients who showed increased tumor size, 4 developed multiple gene copies, showing that the event occurs without cytotoxic selection of cells with chemotherapy. © 1992 Wifey‐Liss, Inc.