bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in cellular differentiation, mitogenesis, cytoskeleton and growth characteristics during syrian hamster embryo cell multistep In vitro, transformation
Authors: Isfort Robert J. , Cody David B. , Doersen Claus‐Jens , Kerckaert Gary A. , Leboeuf Robert A. 
Published: February 2007

AbstractIn vitro, Syrian hamster embryo (SHE) cell transformation is a neoplastic process that proceeds through several identifiable consecutive stages including in vitro, morphological transformation (mt), acquisition of immortality (I+), acquisition of tumorigenicity (T+) and tumor‐derived cells (I TD). Eight transformed lineages consisting of cells at the mt, I+, T+ and I'TD stages were assayed for alterations in general markers of cell differentiation, mitogenic signaling pathways, cytoskeleton and cellular growth in 3D matrix. Alterations in cellular differentiation markers included a decrease in HI9, gene expression and placental alkaline phosphatase enzymatic activity at the mt stage in all lineages examined with a complete absence of HI9, gene expression and placental alkaline phosphatase enzymatic activity by the I'TD stage in a majority of transformed lineages. Changes in mitogenic signaling pathways included the production of autocrine growth factors and alterations in growth factor‐induced immediate early gene expression by the I'TD stage of transformation in the majority of transformed lineages investigated. By the I'TD stage of transformation in most lineages, changes in both the cytoskeleton (including a decrease in tropomyosin‐1 gene expression) and the Matrigel growth characteristics of SHE cells were observed.
Myeloid and lymphoid cell alterations in normal mice exposed to chemotherapy with doxorubicin and/or the multidrug‐resistance reversing agent SDZ PSC 833
Authors: Froidevaux Sylvie , Loor Francis 
Published: February 2007

AbstractThe cyclosporin SDZ PSC 833 (PSC) is a potent in vivo chemosensitizer for tumor cells with P‐glycoprotein(Pgp)‐dependent multidrug resistance (MDR). However, Pgp expression also occurs in CD8+ T cells, NK cells, macrophages and stem cells. In order to find whether PSC might display specific myelotoxicity or potentiate the toxicity of anti‐cancer drugs, healthy mice were exposed to single doxorubicin (DOX) and combined (DOX + PSC) chemotherapy protocols known to be near or above the borderline of toxicity for tumor‐bearing mice. Mice treated with DOX alone or with (DOX + PSC) showed transient spleen hypoplasia, with a general decrease of all leucocyte lineages and a persistent fall in the numbers of B cells in the bone marrow. In (DOX + PSC)‐treated mice, PSC only potentiated the DOX effects without inducing specific depletions of the Pgp‐expressing leukocytes (CD8+ and Mac‐l+ cells). Hematopoietic cell grafts from normal mice to (DOX ± PSC)‐treated mice did not correct their B‐cell lineage deficiency. When lethally irradiated mice were rehabilitated with hematopoietic cells from (DOX ± PSC)‐treated mice (including those with very reduced survival), all chimeras survived for at least 8 months after the cell graft, at which time their leucocyte population profiles were similar to those of control chimeras.
Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma, lung and breast carcinoma cell lines
Authors: Zabrenetzky Vivian , Harris Curtis C. , Steeg Patricia S. , Roberts David D. 
Published: February 2007

AbstractThrombospondin (TSP) is a member of a family of extracellular matrix glycoproteins that may participate in multiple aspects of the metastatic cascade. We report an inverse correlation of steady‐state Thbs‐1 mRNA and protein expression with malignant progression among murine melanoma and human lung and breast carcinoma cell lines. Murine K‐1735 melanoma cell lines of low metastatic potential, including K‐1735 lines transfected with the murine nm23‐1 cDNA, expressed higher TSP levels than related highly metastatic lines. In a model system of lung carcinoma malignant progression, immortalized human bronchial epithelial cells expressed higher TSP levels than v‐Ki‐ras, v‐Ha‐ras or n‐ras transfectants, which in turn expressed higher TSP levels than tumor‐derived, more aggressive variants. Among 3 unrelated breast carcinoma cell lines, Thbs‐1 steady‐state mRNA levels were greater in the 2 nonmetastatic lines than the metastatic line. Our data show that malignant progression in some cell lines is associated with reduced TSP expression. The suppressive effects of nm23‐1 transfection on metastatic potential are also associated with increased TSP expression; ras transfection, which results in increased tumorigenesis, is associated with decreased TSP expression.
Effect of sialoadenectomy on medroxyprogesterone‐acetate‐induced mammary carcinogenesis in BALB/c mice. Correlation between histology and epidermal‐growth‐factor receptor content
Authors: Kordon Edith C. , Guerra Fabiana , Molinolo Alfredo A. , Elizalde Patricia , Charreau Eduardo H. , Pasqualini Christiane Dosne , Montecchia Fernanda , Pazos Patricia , Dran Graciela , Lanari Claudia 
Published: February 2007

AbstractTo evaluate the possible involvement of the salivary glands in the modulation of medroxyprogesterone (MPA)‐induced mammary tumorigenesis, 48 sialoadenectomized virgin BALB/c female mice and 47 controls were treated with 40mg MPA depot s.c. every 3 months for 1 year. Mammary tumors developed in 11 sialoadenectomized and in 34 control mice with similar latencies. In both groups, 75% of the tumors were ductal and progestin‐dependent (PD) while the remainder were lobular and progestin‐independent (PI). Epidermal growth factor (EGF) levels were measured in salivary glands (SG‐EGF) and serum (S‐EGF) in both groups. MPA induced a significant increase in SG‐EGF and in S‐EGF that became evident only after 1 month of MPA treatment. No increase in S‐EGF was detected in MPA‐treated sialoadenectomized mice, indicating that salivary glands are the major source of S‐EGF. The presence of EGF receptors (EGF‐R) was investigated in ductal PD and PI tumor lines and compared with 8 PI tumor lines of lobular origin. A significant difference in EGF‐R content was found between lobular and ductal tumors. No increase in EGF‐R was noted when ductal tumors became autonomous. EGF‐R did not correlate with tumor growth rate and there was an inverse correlation between EGF‐R and steroid receptors. When the effect of sialoadenectomy on tumor growth was tested in vivo in syngeneic transplants of 2 ductal PD, I ductal PI and 2 lobular PI mammary adenocarcinomas, it was not found to be significant when compared with the controls. It may be concluded that SG‐EGF plays an important role in the induction of mammary adenocarcinomas by MPA, while it has no significant effect on the growth of established tumors.
DT‐diaphorase as a determinant of sensitivity to adriamycin in non‐small‐cell lung‐cancer cell lines
Authors: Kasahara Kazuo , Shibata Kazuhiko , Bando Takuma , Numata Yuka , Fujimura Masaki , Matsuda Tamotsu 
Published: February 2007

AbstractWe have reported the establishment of a mitomycin‐C (MMC)‐resistant non‐small‐cell lung‐cancer cell line, PC‐9/MC4. As determined by an MTT assay, this resistant cell line was found to be 4 times more sensitive to adriamycin (ADM) than was the parental PC‐9. There were no significant differences in sensitivity to etoposide, mitoxantrone, daunomycin, epirubicin, pirarubicin, 9‐aminoanthracycline or 3'‐deamino‐3'‐morpholino‐13‐deoxo‐10‐hydroxy carminomycin. These data suggest that neither qualitative or quantitative changes in DNA topoisomerase 11 nor the enhanced repair of DNA can explain the differing sensitivity to ADM observed. No significant differences were found in the accumulation of ADM and glutathione (GSH) in these cell lines. Although total glutathione‐S‐transferase (GST) activity in PC‐9/MC4 cells was lower than that observed in PC‐9 cells and treatment with ethacrynic acid (EA) reduced sensitivity to ADM in both cell lines, relative resistance was unaffected. NADH‐cytochrome b5 reductase (B5R) activity in PC‐9/MC4 cells showed a 3‐fold greater decrease than that in PC‐9 cells, and DT‐diaphorase (DTD) activity in PC‐9/MC4 cells showed an approximately 200‐fold greater decrease than that in PC‐9 cells. Addition of dicumarol, an inhibitor of DTD, decreased the sensitivity of ADM of PC‐9 but not of PC‐9/MC4. DTD activity in the PC‐9 cell line was inhibited by treatment with dicumarol while in PC‐9/MC4 it remained unchanged. These data suggest that DT‐diaphorase is a determinant of sensitivity to ADM in the 2 cell lines.
Induction of multidrug resistance (MDR) by transfection of MCF‐10A cell line with c‐Ha‐ras and c‐erbB‐2 oncogenes
Authors: Sabbatini Antonietta R. M. , Basolo Fulvio , Valentini Paola , Mattii Letizia , Calvo Simonetta , Fiore Lisa , Ciardiello Fortunato , Petrini Mario 
Published: February 2007

AbstractTo investigate the relationship between oncogene activation and appearance of multidrug resistance (MDR) we transfected the human breast epithelial cell line MCF‐10A, negative for the expression of the P‐glycoprotein, with c‐Ha‐ras and/or c‐erbB‐2 oncogenes. The appearance of the MDR phenotype was then studied by evaluating mdr‐1 mRNA expression, the presence of P‐glycoprotein on the cell membrane and the onset of doxorubicin resistance, together with the effect of the reversing agent verapamil. We found that only MCF‐10A transfected with both c‐Ha‐ras and c‐erbB‐2 oncogenes acquired the MDR phenotype.
Daunorubicin efflux against a concentration gradient in non‐P‐glycoprotein multidrug‐resistant lung‐cancer cells
Authors: Mülder H. Sipko , Lankelma Jan , Dekker Henk , Broxterman Henk J. , Pinedo Herbert M. 
Published: February 2007

AbstractMultidrug‐resistant, human non‐small‐cell lung carcinoma SW‐I573/2RI20 (2RI20) cells, not containing the drug efflux pump P‐glycoprotein (Pgp), have reduced initial daunorubicin (DN) accumulation rates and decreased cellular steady‐state drug concentrations. Previously we found indications of the presence of a plasma membrane “vacuum cleaner”, pumping DN directly from the membrane, and reported evidence of active DN pumping using digitonin. Further evidence of active DN pumping is now provided via a different methodology and the active drug pump flux is estimated. Cells were exposed to a flowing medium containing the cytotoxic agent DN. After reaching a steady state, in which net DN uptake equals net DN efflux, high concentration pulses of vincristine (VCR) were injected into the flowing medium. A rapid increase in cellular DN content was observed, while only a minimal effect was seen in SW‐I573 wild‐type cells. After passage of the VCR pulse, the extra accumulated DN was effluxed against a concentration gradient. Upon increasing the VCR concentration, a maximum pump inhibition was reached which was similar to the effect of cellular energy depletion. Similar effects were observed for Pgp‐containing SW‐I573/2RI60 (2RI60) cells as well as non‐Pgp MDR human small‐cell lung carcinoma GLC4/ADR cells. With increasing extracellular DN concentrations, saturation of the VCR‐induced DN influx was observed (DN medium concentration 2.5 μM at 1/2 Vmax). At an extracellular DN concentration of 5 μM, higher concentrations of VCR were needed to reach the maximum effect in 2RI20 cells than at 0.5 μM DN. This is an indication of competitive interaction between DN and VCR for the putative DN efflux system. In summary, we found indications of inhibition of active DN efflux by VCR and DN efflux against a concentration gradient in non‐Pgp MDR 2RI20 and GLC4/ADR cells. These features are consistent with the presence of a multidrug transporter, different from Pgp, in the plasma membrane of these cells.
Expression of MUC2‐mucin in colorectal adenomas and carcinomas of different histological types
Authors: Blank Monika , Klussmann Enno , Krüger‐Krasagakes Sabine , Schmitt‐Gräff Anette , Stolte Manfred , Bornhoeft Gudrun , Stein Harald , Xing Pei‐Xiang , McKenzie Ian F. C. , Verstijnen Cees P. H. J. , Riecken Ernst Otto , Hanski Christoph 
Published: February 2007

AbstractThe expression of mucin MUC2 was investigated in normal colonic tissue, in colonic adenomas and in carcinomas of the mucinous and non‐mucinous type. The latter were subdivided into carcinomas originating from the adenoma‐carcinoma sequence (ACS) and de novo (DN) carcinomas. The expression was assayed by immunohistochemistry with the monoclonal anti‐MUC2 antibody CCP58 and by mRNA semiquantitation. MUC2 protein epitope CCP58 was strongly expressed in 21 % of normal colonic tissues, in 40% of villous and in 48% of tubular adenomas. Mucinous carcinomas exhibited strong expression in 72%, ACS carcinomas in 21 % and DN adenocarcinomas in none of the tumors investigated. Compared with the adjacent non malignant tissue (transitional mucosa), CCP58 epitope expression in the tumor was higher in 74% of mucinous carcinomas, but equal or lower in 69% of ACS carcinomas and in 100% of de novo carcinomas. The alterations of MUC2 expression detected by immunohistochemistry in adenocarcinomas were confirmed on mRNA level. These data indicate that the MUC2 expression pattern is different in the 3 carcinoma types investigated. MUC2 over‐expression occurs in the adenomatous tissue. It is always maintained in mucinous carcinomas, but frequently decreased in non‐mucinous ACS carcinomas. DN carcinomas are most frequently associated with decreased expression of MUC2. © 1994 Wiley‐Liss, Inc.
Human papillomavirus DNA in cervical carcinoma—correlation with clinical data and influence on prognosis
Authors: Ikenberg Hans , Sauerbrei Willi , Schottmüller Ursula , Spitz Christian , Pfleiderer Albrecht 
Published: February 2007

AbstractHuman papillomavirus (HPV) is a main factor in cervical carcinogenesis. However, data on the correlation of HPV with clinical features and the prognosis of cervical carcinoma remain controversial. The HPV status (positivity, type, copy number) in unfixed tissue specimens of 205 primary invasive cervical carcinomas was determined by Southern blot hybridization. A correlation with comprehensive clinical and histopathologic data and long‐time survival was evaluated. HPV DNA was detected in 73% of the cases; 83% of the HPV‐positive tumors contained HPV 16. HPV 16 was predominant among squamous‐cell carcinomas (SCC) (ρ = 0.05). HPV 16 copy number was higher in keratinizing tumors (ρ < 0.05), and elevated levels of the SCC antigen were more common in patients positive for HPV 16 (ρ < 0.03). No association was found between the HPV status and 8 other clinical and histopathologic variables. Multivariate analysis after a median follow‐up of 73 months demonstrated longer survival for patients with lower clinical stage (ρ = 0.001) and keratinizing SCC (ρ = 0.005). Women with HPV‐negative tumors had a higher risk of death (RR 1.51; ρ = 0.07). HPV analysis does not clearly define biologically distinct sub‐sets of cervical carcinoma. This underlines the importance of additional factors in cervical carcinogenesis. © 1994 Wiley‐Liss, Inc.
Urbanization gradients and cancer mortality in Uruguay, 1988–1992
Authors: Vassallo Alberto , De Stéfani Eduardo , Ronco Alvaro , Barrios Enrique 
Published: February 2007

AbstractCancer deaths occurring in Uruguay in the period 1988–1992 were classified by site, sex and residence according to the ninth version of the International Classification of Diseases (ICD‐9), in order to analyze gradients of urbanization. For this purpose, Uruguayan counties were classified as rural, suburban and urban, using population density as an ordinal indicator of the degree of urbanization. Significant increasing trends with urban excess were observed for cancers of the colon, rectum, lung and female breast. In addition, this study showed significant urban deficits for esophageal, gastric and uterine cancers, contrasting with previous studies. These differences seem to be real rather than artifactual due to misclassification. The study thus provides interesting new findings concerning urban differences between developed communities and a partially developing country. © 1994 Wiley‐Liss, Inc.
Repair of cisplatin‐DNA adducts by protein extracts from human ovarian carcinoma
Authors: Jones Sandra L. , Hickson Ian D. , Harris Adrian L. , Harnett Paul R. 
Published: February 2007

AbstractHuman ovarian carcinoma exhibits a spectrum of responses to treatment with cisplatin, ranging from marked sensitivity to relative resistance. Variations in the efficiency with which cells repair cisplatin‐DNA adducts may in part determine cisplatin sensitivity. We have investigated the use of a novel cell‐free assay of nucleotide excision repair of platinated DNA to assess the DNA repair capacity of direct biopsies of untreated human ovarian carcinoma. In this pilot study, ovarian carcinoma extracts performed in vitro excision repair of platinated DNA. Moreover, tumors from different individuals varied as much as I O‐fold in their repair capacity in this assay. © 1994 Wiley‐Liss, Inc.
Detection of neutralizing antibodies against human T‐cell leukemia virus type 1 using a cell‐free infection system and polymerase chain reaction
Authors: Haraguchi Yuji , Yang Da‐Wei , Handa Atsushi , Shimizu Nobuaki , Tanaka Yuetsu , Hoshino Hiroo 
Published: February 2007

AbstractWe have developed a cell‐free infection system to titrate neutralizing antibodies against human T‐cell leukemia virus type I (HTLV‐I) using the polymerase chain reaction (PCR). S+L‐CCC (8C) feline kidney or U‐251 MG human glioma cells were infected with a cell‐free culture supernatant derived from HTLV‐I ‐infected c77 feline cells. DNA was extracted from 8C or U‐251 MG cells after incubation for 24 hr and amplified by PCR. The c77 cell supernatant gave discrete bands, whereas those of HTLV‐I ‐positive T cells did not. When the inocula were treated with HTLV‐I antibody‐positive human sera or the monoclonal or polyclonal antibody against the peptide 190–199 of HTLV‐I envelope protein gp46, the subsequent formation of HTLV‐I proviral DNA was inhibited. We determined the titers of neutralizing antibodies by densitometrically scanning the intensity of the PCR bands. These titers correlated well with those determined by the plaque assay using a pseudotype of vesicular stomatitis virus bearing the envelope antigens of HTLV‐I. At high serum concentrations, many seronegative samples markedly inhibited the plating of the HTLV‐I pseudo‐type whereas they barely affected results obtained by PCR. Thus, the c77‐PCR system can detect neutralizing antibodies against HTLV‐I even at low titers. © 1994 Wiley‐Liss, Inc.
Childhood cancer incidence in relation to distance from the former nuclear testing site in semiplatnsk, kazakhstan
Authors: Zardze Daid G. , Li N. , Men Tamara , Duffy Spephen W. 
Published: February 2007

AbstractRates of childhood cancer between 1981 and 1990 in the 4 administrative zones of Kazakhstan were studied to asess the relationship, if any, with distance from nuclear testing sites. Risk of various cancers among children aged 14 years or younger were estimated in relation to distance from (1) a site where testing in air was performed before 1963, (2) a site where underground testing took place thereafter, and (3) a reservoir, known as “Atom Lake,” created by 4 nuclear explosions in 1965. Risk of acute leukaemia rose significantly with increasing proximity of residence to the testing areas, although the absolute value of the risk gradient was relatively small. The relative risk for those living less than 200 km from the airtesting site was 1.76 compared with those living 400 km or more away from the site. Similar relative risks were observed for the underground site and “Atom Lake.” There was also some evidence of increased risk of brain tumours in association with proximity to the test sites. In 2 of the 4 zones studied, there was substantial regional variation in acute leukaemia rates which was not attributable to distance from the test site. The findings may be affected by potential confounders, notably urban/rural status and ethnic factors. © 1994 Wiley‐Liss, Inc.
A case‐control study of reproductive risk factors associated with cervical cancer
Authors: Mukherjee Bishwa Nath , Sengupta Subrata , Chaudhuri Salil , Biswas Liton Naha , Maiti Pradip 
Published: February 2007

AbstractUsing the logistic‐regression technique, a hospital‐based case‐control study of 177 married women with invasive squamous‐cell cervical cancer and 149 hospital‐visiting controls enabled evaluation of selected reproductive factors as risks. Early age at marriage was found to be the single best predictor of the disease status. However, those who married late but gave birth to a large number of children were generally found to be suffering from cervical cancer. The results support the hypothesis that it is not so much parity per se that enhances the risk, but the rapidity of multiple pregnancies that matters. Logistic analysis also revealed the independent influence of birth interval on the risk of cervical cancer. These findings warrant serious consideration in future studies, given the obvious implications for prevention. Other implications for the prevention of cervical cancer are briefly discussed. © 1994 Wiley‐Liss, Inc.
Asbestos and erionite fibres can induce mutations in human lymphocytes that result in loss of heterozygosity
Authors: Both Katrin , Henderson Douglas W. , Turner David R. 
Published: February 2007

AbstractAlthough asbestos and erionite are proven human carcinogens, most studies have concluded that these fibres are not mutagenic to mammalian cells in vitro. We have studied the potential of these fibres and chrysotile fibres to induce mutations in human peripheral lymphocytes, using a mutation assay that measures mutation at the autosomal HLA‐A locus. Exposure of lymphocytes in culture to 400 μg/ml of crocidolite or erionite for 72 hr did not result in a statistically significant increase in the mutation frequency (MF) in the HLA‐A assay, although a trend towards increased MF was observed. Exposure to 400 μg/ml chrysotile resulted in no increase in MF; however a significant increase was observed at 50 μg/ml. Mutations in somatic cells can be classified according to their molecular basis. Molecular analysis of mutants obtained following exposure of lymphocytes to crocidolite and erionite demonstrated a statistically significant increase in the class of mutations arising from loss‐of‐heterozygosity (LOH) events involving the selection locus (HLA‐A) and more distal loci. Mutations following exposure to crocidolite and erionite showed a greater frequency of LOH than did spontaneous mutants (p < 0.02 and p < 0.005 respectively). Mutants following exposure to chrysotile did not display a significant difference in LOH when compared with spontaneous mutants. Thus, although an increase in overall mutation frequency following fibre exposure did not achieve statistical significance, the modest increase seen following exposure to erionite and crocidolite is translated into a highly significant change in those components of the spectrum of mutations which result in LOH. © 1994 Wiley‐Liss, Inc.