bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation to 5‐fluorouracil of the heterogeneous human colon tumor cell line ht‐29 results in the selection of cells committed to differentiation
Authors: Lesuffleur Thécla , Kornowski Anne , Luccioni Catherine , Muleris Martine , Barbat Alain , Beaumatin Jacqueline , Dussaulx Elisabeth , Dutrillaux Bernard , Zweibaum Alain 
Published: February 2007

AbstractThe HT‐29 cell line contains a small proportion of differentiated polarized, enterocytic and mucus‐secreting cell types (< 95%) which can be selected under various pressure conditions, e.g., glucose deprivation or methotrexate. The purpose of the present work was to investigate whether this also applies to 5‐fluorouracil (FUra). Stepwise adaptation of exponentially growing cells to 1, 5, 10 and 20 μM FUra results, after a phase of high mortality, in the emergence of adapted sub‐populations with stable growth rates and curves, and IC50 6, 18, 37, and 110 times higher than in untreated cells respectively. FUra‐adapted cells are all differentiated, according to 2 phenotypes: (1) polarized dome‐forming cells which express carcinoembryonic antigen at their apical surface and (2) goblet cells which secrete a mucus of colonic immunoreactivity. These phenotypes are present in the parental population and are different from those selected e.g., by glucose deprivation or methotrexate. This differentiation pattern is maintained when the cells are sub‐cultured in drug‐free medium. Resistance to FUra is acquired through gene amplification as substantiated by a 4‐ to 6‐fold increase of thymidylate synthase gene copies in cells stably adapted to the drug. Whether the same mechanism or others are responsible for the first steps of resistance to FUra remains to be elucidated. Altogether, these results support the hypothesis that some of the cells which are present in the parental line and are committed to differentiation possess advantages which allow them to immediately resist and secondarily adapt to FUra. Comparison of the differentiation characteristics of FUra‐adapted cells with those from cells selected under other pressure conditions suggests that resistance and adaptation to either type of pressure may depend on the differentiated phenotype to which the cells are committed.
The lipoxygenase metabolite 12(S)‐hete induces a cytoskeleton‐dependent increase in surface expression of integrin αiibβ3 on melanoma cells
Authors: Chopra Hemi , Timar Jozsef , Chen Yong Q. , Rong Xianhui , Grossi Irma M. , Fitzgerald Laurence A. , Taylor John D. , Honn Kenneth V. 
Published: February 2007

AbstractIntegrin receptors are mediators of cell‐extracellular matrix and cell‐cell interactions. Biochemical and immunocytochemical evidence shows that the platelet integrin receptor αIIbβ3 is present on the cell surface, at focal adhesion plaques and in the perinuclear region of metastatic B16a murine melanoma cells. Antibody to the fibronectin receptor α5β1, inhibits basal adhesion by approx. 30%, whereas antibodies to αIIbβ3 are ineffective. The surface immunoreactivity of tumor cells for αIIbβ3 can be enhanced by pre‐treatment (5 min) with a lipoxygenase metabolite of arachidonic acid [i.e. 12‐(S)‐HETE] in a dose‐dependent manner (max. effect approx. 0.1 μM). Other lipoxygenase metabolites are ineffective. B16a cells possess a large intracellular pool of αIIbβ3, from which the receptor complex translocates to the cell surface following 12‐(S)‐HETE pre‐treatment. This pre‐treatment of tumor cells enhances their adhesion to fibronectin, which is mediated exclusively by αIIbβ3 receptors. 12‐(S)‐HETE also facilitates the redistribution of αIIbβ3 in the plasma membrane with localization at the focal adhesion plaques. The cytoskeleton of the B16a cell is characterized by an absence of distinct microtubules in interphase cells and the presence of prominent microfilaments and vimentin intermediate filaments. In B16a cells, the disruption of intermediate filaments and/or microfilaments prevents the 12‐(S)‐HETE‐induced increase in plasma membrane αIIbβ3, and enhanced tumor‐cell adhesion to fibronectin. The microtubule‐disrupting agent, colchicine, is ineffective in both respects. We conclude that the lipoxygenase metabolite of arachidonic acid, 120‐(s)‐HETE, regulates the surface expression and function of the αIIbβ3, integrin in B16a cells. Further, these data support the hypothesis that microfilaments and intermediate filaments have a profound role in regulating the expression of a multifunctional integrin in B16a tumor cells.
Mucin production by colon cancer cells cultured in serum‐free medium
Authors: Real Francisco X. , Egea Gustavo , Francí Clara , Schüssler Martina H. , Xu Mai , Welt Sydney 
Published: February 2007

AbstractAlthough many colon cancer cell lines are available for study, few of them exhibit differentiated properties. When cultured in medium containing fetal bovine serum, WiDr cells (WiDr‐FBS) show an undifferentiated phenotype: growth as a multilayer of cells adherent to plastic and lack of polarization, brush border, and much vacuoles. In contrast, WiDr cells cultured in a chemically‐defined serum‐free medium containing insulin, transferrin and selenium (WiDr‐ITS) grow as clusters of non‐adherent cells with abundant desmosomes and tight junctions, microvilli and electron‐lucid vacuoles. As WiDr‐FBS cells, WiDr‐ITS are not polarized. WiDr‐ITS cells show a marked enhancement in mucin synthesis as demonstrated by: periodic acid‐Schiff and Alcian blue stains, electron microscopy, immunohistochemistry using monoclonal antibodies (MAbs) reactive with mucin‐associated epitopes, immune electron microscopy and immunochemical analysis using Western blots. In comparison with WiDr‐FBS cells, WiDr‐ITS cells showed strong expression of Tn, sialyl‐Tn, blood group A and CEA. When mouse MAbs were used, higher levels of the MUCI gene product were detected in WiDr‐ITS than in WiDr‐FBS cells. The full spectrum of phenotypic changes was observed after 1 month of culture in ITS medium, and transfer of WiDr‐ITS cells to FBS medium was accompanied by a partial phenotypic reversal, suggesting that these phenotypic changes result from an adaptative–rather than selective–process.
Cancer in migrants to Argentina
Authors: Matos Elena L. , Khlat Myriam , Loria Dora I. , Vilensky Marta , Parkin D. Maxwell 
Published: February 2007

AbstractMortality rates from different cancers in migrants to Argentina from II individual countries and 6 groups of countries were compared with those in the Argentina‐born population and their countries of origin. Almost all countries of origin had higher mortality rates from gastric cancer than Argentina, but the risk declines in migrants, and for European migrants becomes similar to that of the Argentina‐born. In contrast, mortality from oesophageal cancer is significantly lower in European countries than in Argentina. For cancer of the colon and breast, most countries have lower mortality rates than the Argentina‐born, the exceptions being Uruguay and Germany, and migrants demonstrate a convergence of risk towards that of Argentina‐born. These results suggest that migrants to Argentina undergo changes in some environmental exposure, probably dietary, which give rise to substantial alterations in cancer risk within their lifespan.
Life‐time history of smoking and exocrine carcinoma of the pancreas: A population‐based case‐control study in the Netherlands
Authors: Bueno de Mesquita H. B. , Maisonneuve P. , Moerman C. J. , Runia S. , Boyle P. 
Published: February 2007

AbstractFrom 1984 to 1988 a population‐based case‐control study was carried out in the Netherlands in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between habitual, life‐time consumption of varieties of tobacco and exocrine pancreatic carcinoma in 176 cases and 487 controls. An interviewer‐administered questionnaire was used to list major life events and obtain estimates of usual frequency of tobacco consumption throughout life. About 58% of patients were interviewed directly.After adjustment for age, gender, response status, energy intake and consumption of vegetables compared with never‐smokers, a positive dose‐response effect of smoking of life‐time number of total cigarettes, i.e. non‐filter and filter, emerged (OR 1.00, 1.35, 1.40 and 2.10, p‐value trend < 0.05). Results of simultaneous estimation of the effects of life‐time smoking of non‐filter and filter cigarettes suggest that the effect was present primarily in non‐filter cigarettes. The dose‐response relationship was present in current smokers only. Compared with never‐smokers, the risk pattern among relatively recent quitters, i.e. 2 to 14 years previously, still suggested a positive effect of past smoking (OR for low smokers 1.99, 95% CI 0.79‐4.99 and for high smokers 1.69, 95% CI 0.63‐4.58). The risk of quitting 15 years or more could be examined in the low smoking group only and was no different from those who had never smoked (OR 1.02,95% CI 0.47‐2.20).In brief, our results suggest that, independent of usual past intake of energy and vegetables, life‐time smoking of cigarettes influences the development of exocrine pancreatic cancer, whereas cessation of smoking of cigarettes for 15 years or more reduces the risk to the levels found among those who have never smoked.
Positive correlation between parity and incidence of thyroid cancer: New evidence based on complete Norwegian birth cohorts
Authors: Kravdal øystein , Glattre Eystein , Haldorsen Tor 
Published: February 2007

AbstractWe have examined the effect of parity on the incidence of thyroid cancer within a hazard model framework, using individual data on all (1.1 million) Norwegian women born 1935‐1969. This unique data source was established by linking information from the Cancer Registry with maternity histories derived from the Central Population Register of Norway. The relative effects on the total incidence of thyroid cancer, net of age, place residence and birth cohort, are 1.00 for the childless (arbitrarily chosen baseline group), 1.13 for parity I, 1.30 for parity 2, 1.39 for parity 3 and 1.46 for parity 4+. The latter 3 figures are significantly higher than 1.00. The effects are larger for follicular carcinoma, and for this type of thyroid cancer there are also indications of a recent‐pregnancy effect. Among women with 2 or more children, those who became pregnant less than 45 months previously have a higher cancer incidence than others at the same parity. Moreover, we have found that parity has virtually the same effect at all ages, in all birth cohorts and in both parts of the country. Age at first birth as well as the length of the interbirth interval appear to be unrelated to the thyroid‐cancer risk. Our findings are consistent with previous case‐control studies from other countries.
Expression of β1‐integrins, H‐CAM (CD44) and LECAM‐1 in primary gastro‐intestinal B‐cell lymphomas as compared to the adhesion receptor profile of the gut‐associated lymphoid system, tonsil and peripheral lymph node
Authors: Möller Peter , Eichelmann Anette , Mechtersheimer Gunhild , Koretz Karin 
Published: February 2007

Abstractβ1‐Integrins (VLA‐1 to ‐6) are cell‐surface molecules binding to matrix molecules such as collagen, fibronectin and laminin. VLA‐4 is the human homologue to the murine Peyer's patch homing receptor mediating cell/cell adhesion required for lymphocyte extravasation or “homing”. Other structures which have a homing‐receptor function through recognition of venular endothelium are H‐CAM (CD44) and LECAM‐1 (LAM‐ 1, human MEL‐14 equivalent). In order to elucidate whether these adhesion receptors are expressed in primary gastro‐intestinal malignant B‐cell lymphomas (GI BmL) which, in this case, might contribute to the initial confinement to this extranodal site, 31 extensively characterized tumors were examined together with reactive lymphoid tissues from small and large intestine, tonsil and lymph node using monoclonal antibodies (MAbs) against these receptors. All types of adhesion receptors were differentially expressed in the cytologically and microtopographically defined B‐cell subsets [follicular center cells (FC), mantle‐zone cells (MZ), extrafollicular cells (EF) and plasma cells (PC)] of the normal B‐cell system. With the exception of differences in LECAM‐1 levels among EF and PC of intestinal vs. nodal vs. tonsillar sites, receptor profiles were almost identical in different lymphoid organs. The expression pattern of these molecules in GI BmL was markedly heterogeneous, mimicking to some extent the receptor equipment of their reactive cellular counterpart. Thus, we failed to find a unifying adhesion receptor profile indicative of a tissue‐specific homing of reactive and neoplastic B‐cells.
A novel 21‐kDa protein as a serum marker for benign and malignant urogenital tumors: Preliminary communication
Authors: Shalitin C. , Epelbaum R. , Valansi C. , Segal R. , Mekori T. , Lover B. , Robinson E. 
Published: February 2007

AbstractA novel 21‐kDa protein (p21) was isolated from auto‐immune complexes, found in sera of 14 patients with malignant urogenital tumors and isolated on Protein A‐Sepharose. Isolated complexes were analyzed in 15% polyacrylamide‐SDS minigels. After staining with Coornassie blue R, the bands were scanned with a clinical densitometer. The level of p21 in sera of cancer patients was 3 times higher than that found in normal individuals. An attempt was made to correlate consecutive levels of p21 in the sera of these cancer patients with the clinical course. In 4 cases a significant decrease (57‐75%) in the level of p21 was observed in parallel with response to treatment. In 9 of 10 cases where no response or tumor progression was observed, the relative abundance of p21 increased or remained unchanged. Thus, the level of p21 was indicative of progression or regression of the disease in 13 out of 14 patients. Similar high levels of p21 in sera were also found in 22 patients with benign hyperplasia of prostate. The p21 protein was not immunoreactive with known anti‐ras antibodies such as Y13‐259, 142‐24E05 and anti‐rap1. Partial amino acid analysis of this protein showed no complete homology to any known protein, but a partial homology to known bacterial proteins involved in DNA replication or transcription was observed. Monitoring of the novel p21 levels before and after treatment may be useful in follow‐up of cancer patients, providing evidence of response to treatment.
Hormonal content of combined oral contraceptives in relation to the reduced risk of endometrial carcinoma
Authors: Rosenblatt Karin A. , Thomas David B. 
Published: February 2007

AbstractThe relationship between the strength of the estrogenic and progestational components of combined oral contraceptives and risk of endometrial carcinoma was examined in a multinational hospital‐based case‐control study comparing 220 cases from 7 countries with 1,537 age‐ and hospital‐matched controls. Oral contraceptives were classified according to their relative content of estrogen and progestin. The risk was not altered in women who used preparations containing high‐dose estrogen/low‐dose progestin compounds [odds ratio (OR) = 1.10, 95% CI = 0.13‐9.96]. In contrast, the risk among users of low‐dose estrogen/high‐dose progestin oral contraceptives was greatly decreased (OR = 0,95% CI = 0‐1.08). Risks observed for users of high‐dose estrogen/high‐dose progestin (OR = 0.15, 95% CI = 0.045‐0.50) and low‐dose estrogen/low‐dose progesterone (OR = 0.59,95% CI = 0.26‐1.30) preparations were intermediate between those for users of the 2 other types of preparation. A significantly lower risk was observed for high‐dose progestin users than for low‐dose users [ratio of odds ratios (ROR) = 0.21, 95% CI = 0.05‐0.84]. Although the numbers are small, findings from this study suggest that combined oral contraceptives with varying strengths of estrogen and progestin have different effects on the risk of endometrial carcinoma.
Differential activation of ras genes by point mutation in human colon cancer with metastases to either lung or liver
Authors: Oudejans Joost J. , Slebos Robert J. C. , Zoetmulder Frans A. N. , Mooi Wolter J. , Rodenhuis Sjoerd 
Published: February 2007

AbstractTo study the possible role of ras oncogene activation in the dissemination of colon cancer, we determined point mutations in codons 12, 13 and 61 in K‐ and N‐ras in 3 groups of tumors: (A) primary tumors of patients who had undergone surgery for Dukes' B (early‐stage) colon cancer, (B) primary tumors and metastases from patients undergoing resection of isolated lung metastases and (C) primary tumors and metastases from patients undergoing resection of isolated liver metastases. In 129 samples from 93 patients, 54 (42%) were positive for point mutations in either K‐ or N‐ras. Most mutations (89%) were found in the K‐ras gene. In group A (n = 50) ras point mutations were detected in 16 cases (32%) (15 in K‐ras and 1 in N‐ras). Thirteen out of 23 cases in group B (57%) were positive for a ras point mutation: 10 in K‐ras and 3 in N‐ras. In group C (n = 20), point mutations in codon 12 of K‐ras, but none in H‐ or N‐ras, were found in 10 cases (50%). In 31 cases the primary tumors from the metastases in groups B and C were available for analysis and 15 contained a ras point mutation (48%). Not all mutations were present in both the primary tumor and the metastasis. In 3 instances, a mutation was detected in the metastasis but not in the primary tumor, whereas in 1 case a mutation was found in the primary tumor.
Adult T‐cell leukemia: Structures and expression of the p53 gene
Authors: Sugito S. , Yamato K. , Sameshima Y. , Yokota J. , Yano S. , Miyoshi I. 
Published: February 2007

AbstractExperiments were undertaken to investigate a genetic event involved in leukemogenesis in adult T‐cell leukemia (ATL). For this purpose, the p53 gene was chosen for study, since alteration of the gene has been found in a wide variety of human cancers. Structures and expression of the p53 gene in ATL cells were investigated by Southern and Northern blot analyses and a polymerase‐chain‐reaction single‐strand conformation‐polymorphism (PCR‐SSCP) analysis. Either subtle alterations of the p53 gene or the absence of detectable level of p53 mRNA were found in 2 of 3 acute ATL cell lines and 2 of 12 acute ATL fresh samples. In contrast, no mutation was detected in 4 cases with less aggressive types of ATL (3 chronic and I smoldering ATL cases). Mutations found in acute ATL cells occurred in regions highly conserved in evolution and all the cells carrying p53 mutation showed loss of the other p53 allele. These results suggests that alteration of the p53 gene may contribute to progression of the disease in some cases of ATL.
Morphometric analysis and identification of infiltrating leucocytes in regressing and progressing shope rabbit papillomas
Authors: Okabayashi Masafumi , Angell Michael G. , Christensen Neil D. , Kreider John W. 
Published: February 2007

AbstractSpontaneous regressions of papillomavirus lesions frequently occur in both human and animal infections. The mechanism by which this occurs is currently unknown. Mononuclear infiltrates are found in regressing human and rabbit papillomas. To assess the potential functional role of these infiltrates in regression, we have characterized and quantitated the cell types present in regressing rabbit lesions.Forty New Zealand white rabbits were inoculated with cottontail rabbit papillomavirus (CRPV) at 2 sites on the dorsal skin. All tumors on 6 rabbits markedly decreased in volume within 6 to 8 weeks of inoculation. Tumors on 4 of these 6 regressor rabbits were studied by immunohistochemistry. Regressor papillomas had conspicuous leucocytic infiltrates, most concentrated at the epithelial basement membrane, and often obliterating the basal cells of the germinal layer. Infiltrating leucocytes were also concentrated in the subjacent dermis immediately beneath the basement membrane. The infiltrates gradually lessened at increased depths in the dermis. In contrast, progressor papillomas contained fewer leucocytes, which were randomly distributed in the dermis. The phenotype of the infiltrating leucocytes was examined in 4 regressing and 12 progressing papillomas. In regressing papillomas, infiltrating leucocytes were predominantly T cells (68.0%), with relatively few B cells (7.4%). Progressing papilloma dermis contained fewer T cells and B cells than regressing papillomas. Most of the infiltrating T cells in regressing papillomas were labelled with a rabbit MHC‐class‐II‐specific monoclonal antibody (MAC) (2C4), in contrast to only a small number in progressing papillomas. In addition to the leucocytic infiltrates, keratinocytes in regressing, but not in progressing, papillomas, frequently exhibited strong 2C4 staining. These results demonstrate that infiltration with T cells expressing rabbit class II is characteristic of regressing Shope papillomas and strengthens the assertion that cell‐mediated immunity is the mechanism of Shope papilloma regression.
Integrin expression in human melanoma cell lines: Heterogeneity of vitronectin receptor composition and function
Authors: Marshall John F. , Nesbitt Stephen A. , Helfrich Miep H. , Horton Michael A. , Polakova Katarina , Hart Ian R. 
Published: February 2007

AbstractTen human melanoma cell lines were examined for integrin‐receptor expression using a panel of antibodies directed against different integrin subunits. Considerable heterogeneity was detected for levels of expression of 7 integrins, including the αvβ3 vitronectin receptor where a correlation between tumorigenic capacity in athymic nude mice and αvβ3 levels was found. Detailed analysis of the vitronectin receptor on these lines revealed heterogeneity of composition. In one cell line, VUP, an αvβ1 association was detected and, by antibody‐inhibition studies, this receptor was shown to bind vitronectin as its ligand. In another line, DX3, evidence was obtained which indicated that apart from the qfi, receptor the αv was able to associate with another β subunit which was not β3. The existence of these alternative forms of the vitronectin receptor in this small sample of tumours of common origin might explain why the capacity to bind to fibrinogen and vitronectin substrates by these cells did not necessarily correlate with αvβ3 levels.