bluuebunny/crossref_metadata_2025_split huggingface dataset:
CDK1 is a marker of proliferation in human lymphoid cells
Authors: Włowiec Dariusz , Deviller Philippe , Simonin Denis , Souchier Catherine , Rimokh Ruth , Benchaib Mehdi , Bryon Paul‐André , Ffrench Martine 
Published: February 2007

AbstractTo better understand the relationship between the proliferation of human lymphoid cells and the expression of cdk1, a catalytic subunit of the histone HI kinase (HIK), we examined its mRNA and protein content in 3 B‐cell lines: Ramos, Reh‐6 and IARC 963. Cells were elutriated according to their position in the cell cycle. Cell fractions were analyzed for cdk1 mRNA and protein cellular content by Northern blot and immunoblot, respectively, as well as for H1K activity. Both mRNA and protein amounts and H1K activity varied according to cell cycle phase, the lowest values being observed in G1‐enriched fractions. For comparison, elutriated fractions were also tested for the expression of cdk2 and cdk4 proteins. Both showed some variations among fractions, but they were less clear than those of cdk1. We also tested 29 samples of lymphoid neoplastic and non‐neoplastic tissues for proliferative activity (percentage of S and G2/M cells estimated by flow cytometry) and expression of cdk1, cdk2 and cdk4 proteins. We found a significant correlation between the percentage of cells in S or S + G2/M phases and cdk1 protein content but not cdk2 or cdk4 content. We conclude that cdk1 expression in human lymphoid cells varies during the cell cycle at both mRNA and protein levels. © 1995 Wiley‐Liss, Inc.
Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: A rationale for combination therapy with chemotherapeutic agents
Authors: Sacks Peter G. , Harris Daniel , Chou Ting‐Chao 
Published: February 2007

AbstractWe have previously shown that β‐all trans retinoic acid (RA) inhibits macrocellular growth of a multicellular tumor spheroid model for squamous carcinoma, as measured by spheroid size, but allows for continuing DNA synthesis and cell cycle progression, the two being reconciled by a cell death effect. DNA synthesis in the presence of growth inhibition suggested a rationale for examining combination chemotherapy with RA‐inhibited cells. To this aim, we have extended this observation to a series of 8 squamous carcinoma cell lines. Cells were treated with 1 μM RA for 7 days and cell growth parameters monitored. Although growth inhibition ranged from 0% (A431) to approx. 80% (MDA 886Ln), [3H]‐thymidine incorporation (cpm/μg protein) and percent S‐phase (by flow cytometry) in 7‐day RA‐treated cells was equal or higher than in their control vehicle‐treated cells in 7/8 SCC cell lines. Thus RA‐induced growth inhibition is not just cytostasis. Combination therapy was examined with MDA 886Ln, MDA 686Ln, 1483 and A431 cells pre‐treated for 7 days with 1 μM RA followed by cisplatin or 5‐fluorouracil treatment. An increased effectiveness for the combination was shown using 5‐day tetrazolium dye (MTT) growth assays when cells were growth‐inhibited by RA. Computerized analysis of data using median‐effect and isobologram techniques indicated that the interaction of RA with these chemotherapeutic agents was synergistic. With squamous carcinoma, RA treatment inhibits growth while allowing for continuing DNA synthesis, and these RA‐treated, growth‐inhibited cells exhibit increased sensitivity to chemotherapeutic agents. © 1995 Wiley‐Liss, Inc.
Systemic effects of cytokines released by gene‐transduced tumor cells: Marked hyperplasia induced in small bowel by γ‐interferon transfectants through host lymphocytes
Authors: Lollini Pier‐Luigi , D'Errico Antonia , De Giovanni Carla , Landuzzi Lorena , Frabetti Flavia , Nicoletti Giordano , Cavallo Federica , Giovarelli Mirella , Grigioni Walter F. , Nanni Patrizia 
Published: February 2007

AbstractCells transduced with cytokine genes are currently used to enhance the anti‐tumor and immunomodulatory effects of these molecules in cancer therapy. The sustained release of cytokine thus obtained can perturb many homeostatk systems of the host. We have previously shown that the murine mammary adenocarcinoma TS/A transfected with the murine γ‐in‐terferon (IFN‐γ) gene stimulates a strong immune response that impairs tumor growth. Mice bearing tiny tumors have serum IFN‐γ levels constantly exceeding 100 IU/ml. Therefore, we asked which systemic effects can be triggered in mice by such transfectants. BALB/c mice bearing tumors produced by clone 16.6000 cells (which release 6,000 IU/ml of IFN‐γ in culture) were compared to normal mice and to mice with tumors produced by parent cells transfected with the neomycin resistance gene (NEO cells, no IFN‐γ release). Histological studies revealed a marked hyperplasia of small bowel tn mice bearing 16.6000 tumors; the villi and crypts of these mice were >1.5 times longer than those of normal mice and of mice bearing NEO tumors. In vivo administration of bromodeoxyuridine evidenced a 2.5–3 times increase in the proliferative score of the intestinal crypts of mice bearing 16.6000 tumors compared to control mice. No intestinal alterations were observed in nude mice bearing 16.6000 tumors. T lymphocytes thus appear to play a causal role in this phenomenon. © 1995 Wiley‐Liss, Inc.
Is the risk of cancer of the corpus uteri reduced by a recent pregnancy? A prospective study of 765,756 norwegian women
Authors: Albrektsen Grethe , Heuch Ivar , Tretli Steinar , Kvåle Gunnar 
Published: February 2007

AbstractWe have examined the relations between the incidence of cancer of the corpus uteri and pregnancies in a cohort of 765,756 Norwegian women, contributing a total of 9,307,118 person–years in the age interval 30–56 years. Incidence rate ratios (IRR) were calculated by Poisson regression analyses of person–years at risk. Separate analyses were carried out for the 2 main histological subtypes, endometrial carcinomas (554 cases) and sarcomas (112 cases). We observed a decrease in risk of endometrial carcinoma with an increasing number of fullterm pregnancies (p < 0.001). The reduction in risk associated with the first pregnancy was more pronounced than that observed for any subsequent pregnancy. The risk of endometrial carcinoma increased with increasing time since last birth (IRR = 1.20, 95% CI = 1.08–1.34 per 5‐year time interval). The reduction in risk among parous women compared to nulliparous women diminished with increasing time since last birth. For endometrial carcinoma, the decrease in risk with increasing age at first and last birth disappeared after adjustment for time since last birth. For sarcomas, however, the relation with age at births remained in analyses adjusted for time since birth, and time since birth seemed to be of minor importance as an independent risk factor. Our results support the hypothesis that the reduction in risk of endometrial carcinoma associated with a pregnancy is related to a mechanical shed of malignant or pre‐malignant cells at each delivery. © 1995 Wiley‐Liss, Inc.
A single chain Fv derived from a filamentous phage library has distinct tumour targeting advantages over one derived from a hybridoma
Authors: Verhaar Marlies J. , Chester Kerry A. , Keep Patricia A. , Robson Lynda , Pedley R. Barbara , Boden Joan A. , Hawkins Robert E. , Begent Richard H. J. 
Published: February 2007

AbstractSingle‐chain antibodies (scFvs) can be derived from a monoclonal antibody (MAb) or produced directly using filamentous phage technology, where antibodies with desired binding and purification characteristics can be readily selected from libraries. To test the hypothesis that the latter approach is more useful, we compared 2 anti‐carcinoembryonic antigen (CEA) scFvs produced by these 2 different approaches. Our study showed that, both in the purification process and in the biodistribution pattern, MFE‐23, produced by filamentous phage technology, gave favourable results compared to A5‐SC, which is derived from the A5B7 MAb. This indicates the value of the filamentous phage approach for obtaining tumour‐targeting scFvs. © 1995 Wiley‐Liss, Inc.
MCF‐7 human mammary adenocarcinoma cell death in vitro in response to hormone‐withdrawal and dna damage
Authors: Wilson James W. , Wakeling Alan E. , Morris Ian D. , Hickman John A. , Dive Caroline 
Published: February 2007

AbstractAnti‐oestrogens exert a tumoristatic effect on estrogen‐receptor‐positive breast carcinomas in vivo. At a cellular level this may reflect inhibition of cell proliferation and/or cell death counterbalanced by continued proliferation of a cell subpopulation. We evaluated the MCF‐7 human mammary adenocarcinoma cell line as an in vitro model to study the effects of the novel oestrogen antagonist ICI 182,720 on cell population dynamics (cell gain vs. cell loss). After oestrogen‐withdrawal monolayer cell number declined over 10 days, accompanied by cell detachment. This decrease in viable cell number was elevated 2‐fold by ICI 182,780. Detached cells exhibited DNA fragments of 50 and 300 kbp, typical of apoptotic cells. How‐ever, internucleosomal cleavage to 180 bp integer fragments was not seen, and these detached cells exhibited a morphology which was not consistent with apoptosis. The remaining attached monolayer cells were morphologically viable (>99%) with regard to both nuclear morphology and plasma membrane integrity. There was no difference in cell cycle phase distribution between oestrogen‐withdrawn and ICI 182,780‐treated cells; both induced accumulation in Gr phase. MCF‐7 cells were also exposed to a variety of DNA damaging agents known to induce apoptosis in other cell types. We could demonstrate only limited induction of morphologically recognisable apoptosis in MCF‐7 cells treated with methyl methanesulphonate. Our results add to the controversy surrounding the ability of the MCF‐7 cell line to undergo apoptosis in vitro in response to anti‐oestrogen therapies. © 1995 Wiley‐Liss, Inc.
Human breast cancer cell lines resistant to pure anti‐estrogens are sensitive to tamoxifen treatment
Authors: Lykkesfeldt Anne E. , Larsen Søren S. , Briand Per 
Published: February 2007

AbstractThe pure steroidal anti‐estrogens ICI 164,384 and ICI 182,780 are very potent growth inhibitors of the estrogen receptor‐positive human breast cancer cell line MCF‐7. However, long‐term treatment of MCF‐7 cells with 10−7 M concentrations of these compounds results in selection of proliferating colonies of resistant cells. Our report describes 4 ICI 164,384‐ and 3 ICI 182,780‐resistant MCF‐7 sublines established after long‐term treatment. Resistant sublines are estrogen receptor‐positive, and all sublines have lost expression and estrogen inducibility of the progesterone receptor protein. Based on IC50 concentrations, all tested resistant sublines had a reduced sensitivity to pure anti‐estrogens on the order of 100‐ to 1000‐fold compared with parent MCF‐7 cells. All resistant cell lines have survived propagation for more than 15 subcultivations in the presence of 10−7 M pure anti‐estrogen. The MCF‐7/182R‐6 subline has been tested for stability of resistance and appeared to be stably resistant after 13 weeks of propagation without the selective pressure of ICI 182,780. Cell lines resistant to the ICI 182,780 compound are cross‐resistant to the ICI 164,384 compound and vice versa. However, the sublines resistant to pure anti‐estrogens are sensitive to tamoxifen. Our results show that although the pure steroidal anti‐estrogens are very potent growth inhibitors, they do not circumvent development of resistance. © 1995 Wiley‐Liss, Inc.
The urokinase inhibitor p‐aminobenzamidine inhibits growth of a human prostate tumor in scid mice
Authors: Billström Anita , Hartley‐Asp Beryl , Lecander Ingegerd , Batra Satish , Åstedt Birger 
Published: February 2007

AbstractMalignant cells possess a high degree of proteolytic activity in which the plasminogen activator system plays an important role. An increased expression of urokinase type plasminogen activator (uPA) is of significance for degradation of the extracellular tumor matrix, facilitating invasiveness and growth. Inhibition of the active site of uPA makes it possible to evaluate the significance of uPA in tumor growth. We report here experiments on a uPA‐producing human prostate xenograft (DU 145) using a competitive inhibitor of uPA, p‐aminobenzamidine. In vitro experiments with DU 145 cells showed that p‐aminobenzamidine caused a dose‐dependent inhibition of uPA activity. DU 145 cells were inoculated s.c. in SCID mice and, once tumors were established, treatment with p‐aminobenzamidine added to drinking water was started and lasted for 23 days. Mice receiving 250 mg/kg/day of p‐aminobenzamidine showed a clear decrease in tumor‐growth rate compared to the nontreated mice, resulting in 64% lower final tumor weight. In addition, uPA‐antigen levels in the membrane fractions of DU 145 tumors from p‐aminobenzamidine‐treated mice were found to be decreased by 59%. We also show that p‐aminobenzamidine has an anti‐proliferative effect in cell culture at low cell number, correlating with a dose‐dependent decrease in uPA production. In conclusion, we show that a low‐molecular‐weight uPA‐inhibttor, p‐aminobenzamidine, has a growth‐inhibitory effect on a solid uPA‐producing tumor. © 1995 Wiley‐Liss, Inc.
Addition of leucovorin in modulation of 5‐fluorouracil with methotrexate: Potentiating or reversing effect?
Authors: Van Der Wilt Clasina L. , Braakhuis Boudewijn J. M. , Pinedo Herbert M. , De Jong Marjon , Smid Kees , Peters Godefridus J. 
Published: February 2007

AbstractPotentiation of the anti‐tumor activity of 5‐fluorouracil (5FU) by methotrexate (MTX) and leucovorin (LV) requires careful scheduling to achieve the most favorable interactions between these 3 drugs. In vitro the triple combination of MTX/5FU/LV was tested at 4 time intervals and with 3 MTX concentrations in 3 cell lines. MTX/5FU/LV was never superior to both 5FU/LV and MTX/5FU, moreover LV reduced growth inhibition by MTX/5FU in 2 cell lines. MTX/5FU was associated with only moderately increased levels of the 5FU metabolite FdUMP, while LV/5FU reduced the free FdUMP levels. MTX/LV/5FU had a dual effect and FdUMP levels gave no clear indication regarding the anti‐proliferative effect that could be expected. In vivo the time‐dependent potentiation of MTX on the 5FU anti‐tumor activity was confirmed for the treatment of HNX‐I4C‐bearing mice. Addition of LV to the MTX/5FU combination failed to cause a gain in anti‐tumor efficacy. For the treatment of Colon‐26‐bearing mice, MTX/5FU was comparable to LV/5FU, but the triple combination of MTX/LV/5FU seemed to have a better anti‐tumor effect. However, the toxicity of the latter treatment was greater than that of LV/5FU. The data from both in vitro and in vivo experiments failed to support the addition of LV to MTX/5FU therapy, possibly due to a reversing effect of LV. © 1995 Wiley‐Liss. Inc.
Differential expression of the H‐ras mutated and normal alleles in rabbit dmba‐induced keratoacanthomas
Authors: Matesanz Fuencisla , Oliva Maria Rosario , Villamarin Alicia , Kamino Hideko , Pellicer Angel 
Published: February 2007

AbstractKeratoacanthomas (KAs) are benign and self‐regressing tumors in which a high incidence of the mutated H‐ras oncogene has been observed both in humans and in experimental models. To determine the level of expression of the mutated H‐rasallele with respect to its normal counterpart in 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced KAs in rabbit skin, we have utilized a quantitative technique based on reverse transcription polymerase chain reaction (RT‐PCR) and selective cleavage of the mutated molecules of the H‐ras gene. Analysis of 16 KAs showed that the mutated H‐ras transcripts were up to 3‐fold more abundant than the non‐mutated H‐ras transcript in the different tumors. This higher expression of the mutated allele appears to correlate with increased differentiation in the KAs and in turn may contribute to tumor regression. © 1995 Wiley‐Liss, Inc.
Selective cytokine gene expression in renal cell carcinoma tumor cells and tumor‐infiltrating lymphocytes
Authors: Wang Qiu , Redovan Christine , Tubbs Raymond , Olencki Thomas , Klein Eric , Kudoh Seiji , Finke James , Bukowski Ronald M. 
Published: February 2007

AbstractThe progression of tumors such as renal cell carcinoma (RCC), despite the presence of substantial lymphocytic infiltrates (TIL), suggests that the ability of the local immune response to control tumor growth is impaired. Cytokine gene expression was examined to further investigate the nature of this response. Initial studies were performed with frozen tumors using PCR‐assisted mRNA amplification with cytokine‐specific primers for interleukin 10 (IL‐10), interleukin 2 (IL‐2) and interferon‐gamma (IFN‐γ). IL‐2 mRNA was not detected, despite the presence of T cells as defined by the expression of CD3γ mRNA. In contrast, mRNA for IFN‐γ was expressed in 4/9 and for IL‐10 in 5/9 tumors. To confirm this, 5 fresh tumor specimens were examined, and PCR demonstrated that IL‐10 mRNA was detectable in 4/5 tumors from which RNA was isolated at the time of nephrectomy. In these experiments multiple cycles and dilutions were employed to semi‐quantitate the expression of IL‐10. To identify potential sources of this cytokine in the tumor bed, IL‐10 mRNA expression in freshly isolated lymphocytes and tumor cells, TIL lines, cultured RCC and established RCC lines was examined. Our studies demonstrate that within the tumor TIL may be one source of IL‐10. Lymphocyte‐enriched populations from 4/5 tumors expressed IL‐10 mRNA as did 4/6 freshly isolated tumor cell preparations. IL‐10 gene expression was not detected, however, in tumor cells after one passage in vitro in short‐term cultured RCC tumor cells (passages 2–5) or in established RCC tumor cell lines. Finally, 4/9 CD4+ and 2/5 CD8+ TIL lines expressed IL‐10 mRNA either constitutively or after stimulation with anti‐CD3 antibody. This finding was associated with IL‐10 production in vitro. Our studies demonstrate that IL‐10 mRNA is frequently present in RCC tumors and may originate from the tumor‐infiltrating mononuclear cell population. © 1995 Wiley‐Liss, Inc.
Natural killer (NK) cells as effectors of antibody‐dependent cytotoxicity with chimeric antibodies reactive with human squamous‐cell carcinomas of the head and neck
Authors: Sung Myung‐Whun , Yasumura Satoshi , Johnson Jonas T. , Van Dongen Guus A. M. S. , Whitesidi Theresa L. 
Published: February 2007

AbstractIn patients with cancer, antibody‐dependent cellular cytotoxicity (ADCC) may be used as a laboratory test or for enhancing immunotherapy with murine monoclonal or chimeric mouse/human anti‐tumor antibodies (mMAbs or cMAbs, respectively). We have established an ADCC assay with IgG1 cMAb SF‐25, using human squamous‐cell carcinoma of the head and neck (SCCHN) cell lines as targets. By flow cytometry, all SCCHN cell lines tested expressed the antigen recognized by cMAb SF‐25. Trypsinization of the cell monolayers facilitated binding of cMAb SF‐25 to the antigen on the cell surface of SCCHN targets. Using the PCI‐50 SCCHN cell line as a target coated with this cMAb at the optimal concentration of 1.0 μg/ml, normal human peripheral blood mononuclear cells (PBMC, n = 28) were found to mediate ADCC at a mean level of 283 ± 42 (SEM) lytic units (LU20/107 effector cells). Non‐adherent monocyte‐depleted PBMC and natural killer (NK) cells purified by negative selection mediated significantly higher levels of ADCC than unseparated PBMC against SCCHN targets. NK cells, defined as CD3‐CD56' cells, could be effectively armed by cMAb SF‐25, as confirmed by flow cytometry and ADCC assays. IL2‐activated armed NK cells mediated higher levels of ADCC than non‐armed NK cells. Binding of cMAb SF‐25 to NK cells and their ADCC were enhanced by pre‐incubation with polyethylene glycol. Arming of NK cells with chimeric antibodies should be considered in developing novel strategies for treatment of human SCCHN, especially in the adjuvant setting. © 1995 Wiley‐Liss, Inc.
Correlation between functional and molecular analysis of mdr1 P‐glycoprotein in human solid‐tumor xenografts
Authors: Broxterman H. J. , Feller N. , Kuiper C. M. , Boven E. , Versantvoort C. H. M. , Teerlink T. , Pinedo H. M. , Lankelma J. 
Published: February 2007

AbstractThe contribution of P‐glycoprotein (Pgp) to multidrug resistance in human solid tumors is generally estimated from bulk mRNA measurements or immunohistochemistry, while direct measurement of the effect of Pgp on intracellular drug concentrations has not been pursued. We investigated the feasibility and sensitivity of a method for probing Pgp‐mediated drug transport in cells isolated from solid tumors, using xenograft models. Human tumor xenografts (XG) were grown by s.c. injection of Pgp‐expressing cell lines 2780AD, BRO/mdrl and KB8‐5. Tumor uptake of doxorubicin (DOX) after administration of DOX to the mice was determined. XG from untreated mice were enzymatically dissociated. The effect of the Pgp modulator bepridil on steady‐state cellular daunorubicin (DNR) and vincristine (VCR) accumulation and chemosensitivity of these XG cells was compared with its effects in the cell lines (CL). mdrl mRNA and Pgp (by flow cytometry) were measured. Also, the dependence on intraceilular ATP concentration, [ATP]i, of the modulator effect was determined in intact KB8‐5 cells. The results showed that i.v. administration of DOX to the mice led to lower DOX levels in the Pgp‐expressing XG than in the “sensitive” XG, suggesting the presence of an in vivo functional Pgp in these XG tumor models. Dissociated, viable XG cells appeared to have ATP levels sufficient to sustain Pgp‐ATPase‐coupled drug transport. This was inferred from experiments using KB8‐ 5 CL, which showed half‐maximal inhibition of DNR transport at an [ATP]i of 1 to 2 mM. The effect of bepridii on DNR and VCR accumulation and chemosensitivity in the XG cells was in accordance with the XG expression of mdr1/Pgp, In KB8‐5 XG cells, Pgp function was hardly detectable, in accordance with decreased mdrl/Pgp expression in vivo. In conclusion, Pgp activity can be determined in freshly dissociated XG human tumor cells. The results obtained with the more necrotic KB8‐5 XG may represent some of the interpretation problems arising when low levels of Pgp expression occur within a heterogeneous cell population, such as may be expected in clinical human tumors. Also our results indicate that Pgp activity may be impaired in vivo at [ATP]i below 2 mM, which are realistic values for human solid tumors. © 1995 Wiley‐Liss, Inc.