bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidrug‐resistant human kb carcinoma cells are highly resistant to the protein phosphatase inhibitors okadaic acid and calyculin A. Analysis of potential mechanisms involved in toxin resistance
Authors: Chambers Timothy C. , Raynor Robert L. , Kuo J. F. 
Published: February 2007

AbstractIn this study we show that multidrug‐resistant (MDR) human KB‐VI cells are highly resistant to the cytotoxicity of okadaic acid and calyculin A, 2 toxins from marine sponges that are potent inhibitors of type‐I and type‐2A protein phosphatases (PP1 and PP2A). Cytotoxicity and colony‐forming assays indicated that, relative to parental drug‐sensitive KB‐3 cells, KB‐VI cells are 35‐fold more resistant to okadaic acid and 70‐fold more resistant to calyculin A. Cytotoxicity of the toxins was associated with mitotic arrest characterized by chromosome scattering and over‐condensation, with KB‐3 cells being more sensitive than KB‐VI cells and calyculin A being more potent than okadaic acid. The resistance of KB‐VI cells to both okadaic acid and calyculin A was completely reversed by verapamil, suggesting that the toxins may be transported by P‐glycoprotein (P‐gp). To further assess the possibility of an interaction with P‐gp, the toxins were employed as potential modulators of the photoaffinity labeling of P‐gp by [3H]azidopine. Relative to vinblastine, which effectively competed with [3H]azidopine for P‐gp photolabeling, calyculin A was 100‐fold less potent and okadaic acid did not inhibit photolabeling at concentrations up to 50 μM. To determine whether the resistance mechanism involved differences in toxin‐sensitive phosphatase activity, the activity was assayed in extracts from both cell lines and found to be slightly higher (1.6‐fold) in KB‐VI than in KB‐3 cells. Our results demonstrate a novel, marked resistance of MDR KB‐VI cells to these phosphatase inhibitors and suggest that a major mechanism of resistance may involve toxin transport by P‐gp at sites apparently different from those which bind azidopine.
De Novo expression of intercellular adhesion molecule 1(ICAM‐1, CD54) in pancreas cancer
Authors: Schwaeble Wilhelm , Kerlin Mariola , Meyerzum Büschenfelde Karl‐Hermann , Dippold Wolfgang 
Published: February 2007

AbstractWe examined the expression of intercellular—adhesion molecule‐I (ICAM‐I, CD54) in 6 surgically removed pancreatic tumors and 8 pancreatic tumor cell lines. Immunohistochemistry revealed a varying percentage of ICAM‐I‐positive pancreas tumor cells, while normal pancreatic tissue (except for slight reactivity of endothelial cells) was not stained. The presence of the ICAM‐I molecule on the cell surface and the expression of ICAM‐I mRNA were investigated for 8 different pancreatic tumor cell lines. Three of these (Capan‐I, Capan‐2, QGP‐I) expressed ICAM‐I constitutively. In 4 of the ICAM‐I‐negative pancreas cancer cell lines, it was possible to induce a remarkable expression of ICAM‐I by incubating the cells in the presence of inflammatory cytokines, whereas one cell line, 818‐4, remained ICAM‐I‐negative. The responsiveness to either IFN‐γ, TNF‐α, or IL‐Iβ treatment was shown to vary from cell line to cell line, indicating complex mechanisms that regulate the expression of ICAM‐I at both, the transcriptional and the post‐transcriptional level. Interestingly, ICAM‐I is shed by pancreatic tumor cells, since soluble SICAM‐I was detected in the cell‐culture supernatants. In comparison with normal sera, the mean level of sICAM‐I in sera of patients with pancreas carcinoma is elevated 2‐fold.
Molecular and serological studies of human papillomavirus among patients with anal epidermoid carcinoma
Authors: Heino P. , Goldman S. , Lagerstedt U. , Dillner J. 
Published: February 2007

AbstractCertain types of human papillomavirus (HPV) are associated with anogenital carcinomas, including carcinomas of the anal canal. Whereas several serological studies have found an association between papillomavirus antibody responses and cervical carcinoma, the antibody response against papillomavirus antigens among patients with anal carcinoma has not been investigated. The present study has examined the antibody responses to a panel of papillomavirus‐derived antigens and compared the serological profile with the histology and HPV carrier state of the tumor, as well as with the stage and prognosis of the disease. Sera from 64 patients with anal cancer and from 79 healthy blood donors were studied in ELISA for the presence of IgA and IgG antibodies to 5 previously described HPV16‐derived synthetic peptide antigens. Serum IgA antibodies to a peptide antigen derived from the E2 region of HPV16 were found in 89% of patients with anal cancer as compared to 24% of controls (p = 0.0001). The IgA reactivity to the 4 other antigens showed only low and non‐significant increases in mean titer. Serum IgG responses were similar among patients and controls. Among patients who had progressive disease, 21/21 were seropositive for IgA anti‐E2 at diagnosis, as compared to 36/43 patients who were in remission after a mean follow‐up of 41 months (p = 0.05). Forty‐seven cases of anal carcinoma were also studied for the presence of HPV by in situ hybridization using a probe mix of 7 anogenital HPV types. Sixteen patients (35%) carried HPV in their anal cancer and one patient had an HPV‐positive benign lesion adjacent to the tumor. Patients with HPV‐carrying anal cancer were significantly younger than those with HPV‐negative anal cancers (mean age: 57 and 68 years, respectively, p = 0.03). No differences in seroreactivity or HPV carrier state were seen depending on the stage or histological type of the tumor.
Concordant p53 and DCC alterations and allelic losses on chromosomes 13q and 14q associated with liver metastases of colorectal carcinoma
Authors: Ookawa Keizou , Sakamoto Michiie , Hirohashi Setsuo , Yoshida Yutaka , Sugimura Takashi , Terada Masaaki , Yokota Jun 
Published: February 2007

AbstractTo identify genetic alterations associated with acquisition of metastatic ability in colorectal carcinoma, 31 liver metastases and 40 primary tumors of colorectal carcinoma from 55 patients were analyzed for loss of chromosomal heterozygosity using 46 polymorphic DNA markers covering 15 chromosomes. Loss of heterozygosity (LOH) and/or rearrangement at the TP53 and DCC loci were detected in all liver metastases (10 of 10 at TP53 and 19 of 19 at DCC), and were observed in 59% (10 of 17) at TP53 and 75% (18 of 24) at DCC respectively in the primary tumors. Furthermore, the incidence of LOH on chromosomes 13q and 14q was higher than that on other chromosomes in liver metastasis, and it was higher in liver metastases than in primary tumors (20/30 vs. 18/39, p = 0.072 on chromosome 13q and 21/31 vs. 16/40, p = 0.018 on chromosome 14q). In 4 cases, LOH or rearrangement at loci on chromosomes I3q. 14q and 18q not detected in primary tumors was observed in liver metastases from the same patients. These results suggest that concordant p53 and DCC alterations and inactivation of several other tumor‐suppressor genes, especially those on chromosomes 13q and 14q, play important roles in the acquisition of metastatic potential of colorectal carcinoma.
Isolation and characterization of an oestrogen‐responsive breast‐cancer cell line, eff‐3
Authors: Healicon R. M. , Westley B. R. , May F. E. B. 
Published: February 2007

AbstractA novel oestrogen‐responsive breast‐tumour cell line, EFF‐3, has been established from a pleural exudate of a patient with metastatic breast cancer. The cells show morphological and immunohistochemical features consistent with their origin from a metastatic breast carcinoma. The cells aggregate and form sheets in culture, and electron microscopy confirms the presence of cell‐surface microvilli and intercellular tight junctions. The epithelial origin of EFF‐3 cells was confirmed by their expression of low‐molecular‐weight cytokeratins and carcinoembryonic antigen. The karyotype of the cells is markedly abnormal and there are large numbers of structurally abnormal chromosomes. EFF‐3 cells express oestrogen receptor, oestrogen‐receptor mRNA, their growth is oestrogen‐responsive, and specific genes are regulated by oestrogens. The pNR‐2/p52 and pNR‐25 oestrogen‐regulated mRNAs are induced 15‐ and 13‐ fold respectively by oestrogen, whereas the oestrogen‐receptor and cathepsin D mRNAs are not regulated. This pattern of regulation differs from that reported previously for other cell lines. The EFF‐3 cell line should be useful for studying the mechanisms involved in oestrogen‐stimulated proliferation and the factors determining the regulation of specific genes by oestrogens.
Structure‐activity relationships of four anti‐cancer alkylphosphocholine derivatives In Vitro and In Vivo
Authors: Sobottka Stephan B. , Berger Martin R. , Eibl Hansjörg 
Published: February 2007

AbstractThis study was carried out to investigate whether structureactivity relationships of alkylphosphocholines, a new group of anti‐neoplastic agents, which had been detected in methylnitrosourea(MNU)‐induced rat mammary carcinoma, can be transferred to in vitro systems. Therefore, the anti‐neoplastic activity of 4 alkylphosphocholines (APCs) was compared in 6 tumor cell lines in vitro and in MNU‐induced rat mammary carcinoma in vivo. The in vitro system consisted of 2 rat mammary‐carcinoma‐derived cell lines (I/C2 and I/C32), as well as 2 human mammary‐gland (MDA‐MB‐231 and MCF‐7)‐and gastrointestinal tract (HT‐29 and KB)‐derived tumor cell lines. As assessed by both cell counting and MTT‐assay, the ranking of concentrations effecting 50% growth inhibition (IC50) was parallel in all cell lines for octadecylphosphocholine (18:0‐PC), octadecenyl‐(trans‐9.IO)‐phosphocholine (t‐ 18:1‐PC) and octadecenyl‐(cis‐9.10)‐phosphocholine (c‐ 18:1‐PC). Only hexa‐decylphosphocholine (16:0‐PC) differed in its activity, being least active in I/C2, I/C32 and MDA‐MB‐231 cells, moderately active in KB and MCF‐7 cells, and most active in HT‐29 cells. The IC50 concentrations of APCs in the 2 rat mammary carcinoma cell lines significantly correlated with dosages effecting a 50% tumor growth delay in vivo. Remarkably, the 2 gastrointestinal cell lines were more sensitive to APC exposure than the mammary‐carcinoma cell lines. In all cell lines except KB cells, growth‐stimulation effects were seen in the concentration range preceding the anti‐proliferative activity; in vivo, however, no accelerated cancer growth was observed. The in vitro system failed to describe the superior therapeutic ratio of c‐18:1‐PC, as assessed in vivo, because it does not take the relative sensitivity of tumor vs. normal cells into account. Complementary in vivo trials are therefore indispensable for a final evaluation. Comparison of the 2 in vitro assays shows good agreement of the interrelationship of IC50 values, those obtained by MTT assay being on average 25% higher than those obtained from cell counting.
Combination effect of vaccination with IL2 and IL4 cdna transfected cells on the induction of a therapeutic immune response against lewis lung carcinoma cells
Authors: Ohe Yuichiro , Podack Eckhard R. , Olsen Kristin J. , Miyahara Yuki , Ohira Tatsuo , Miura Kaoru , Nishio Kazuto , Saijo Nagahiro 
Published: February 2007

AbstractIn order to develop a more effective method of immunotherapy we have transfected mouse interleukin‐2 (IL2) or mouse interleukin‐4 (IL4) cDNA into a spontaneous non‐immunogenic murine lung cancer, Lewis lung carcinoma (LLC). IL2 cDNA transfection more strongly decreases tumorigenicity of LLC than IL4 cDNA transfection. Recombinant‐human‐IL2 treatment of mice that were transplanted with untransfected LLC could not prolong their survival. In contrast, vaccination with IL2‐cDNA‐transfected LLC (LLC‐IL2) and LLC‐ILZ mixed with IL4‐cDNA‐transfected LLC (LLC‐114) could significantly suppress tumor growth of LLC in a tumor‐specific manner. The vaccination with LLC‐IL2 mixed with the same number of LLC‐IL4 cells was more suppressive to the growth of LLC than that with LLC‐ILZ cells alone, while LLC‐IL4 vaccination alone was ineffective. Nude, severe‐combined‐immune‐deficient (SCID) and beige mice were unable to reject LLC‐IL2 cells. However, immunodeficient mice responded to LLC‐IL2, but not to LLC, since their survival times after transplantation with LLC‐IL2 cells were significantly longer than the survival time of normal or immunodeficient mice transplanted with untransfected LLC cells. We conclude that vaccination with IL2‐producing tumors and, with more pronounced effect, in combination with IL4‐producing tumors, is able to induce an immune response to this normally non‐immunogenic tumor. Tumor rejection appears to be achieved by the combined activity of CTL and NK cells. This strategy has potential for new immunotherapeutic interventions in cancer patients.
Down‐regulation of riα subunit of camp‐dependent protein kinase induces growth inhibition of human mammary epithelial cells transformed by c‐ha‐ras and c‐erbb‐2 proto‐oncogenes
Authors: Ciardiello Fortunato , Pepe Stefano , Bianco Caterina , Baldassarre Gustavo , Ruggiero Angela , Bianco Cataldo , Selvam Mouna P. , Raffaele Bianco A. , Tortora Giampaolo 
Published: February 2007

AbstractMCF‐ 10A is a spontaneously immortalized, non‐transformed human mammary epithelial cell line. We have recently obtained MCF‐ 10A clones (MCF‐ 1OA HE cells) that are transformed following over‐expression of both a human point‐mutated c‐Ha‐ras and the c‐erbB‐2 proto‐oncogenes. Two isoforms of the cAMP‐dependent protein kinase (cAK) have been described in mammalian cells. Enhanced levels of type‐I cAK (cAKI) are generally found in tumor cells. To determine whether inhibition of cAKl expression may interfere with ras and erbB‐2 oncogene‐induced transformation of human mammary epithelial cells, we have tested the effects of 2 agents that specifically down‐regulate cAKI, such as 8‐chloro‐cAMP and an anti‐sense oligodeoxynucleotide targeted against the R1α regulatory subunit of cAKl on MCF‐10A HE cells. Treatment of MCF‐10A HE cells with 8‐chloro‐cAMP induces a dose‐dependent growth inhibition under both monolayer and soft‐agar growth conditions, that is correlated with an accumulation of MCF‐10A HE cells in G0/G, phases of the cell cycle and a reduction of the number of cells in S phase. In contrast, 8‐chloro‐cAMP has no effect on MCF‐10A cell growth. Furthermore, 8‐chloro‐cAMP treatment of MCF‐10A HE cells induces a 4‐ to 6‐fold reduction in p185erbB‐2 expression and brings p21 ras expression to levels comparable to those found in MCF‐10A cells. Treatment of MCF‐10A HE cells with an Rlα anti‐sense oligodeoxynucleotide determines a comparable inhibition of both anchorage‐dependent and anchorage‐independent cell growth. Our results suggest that cAKl may act as a mediator of ras and erbB‐2 oncogene action in human breast cells and that interference with cAKl action provides a potential tool for inhibiting the growth‐promoting effects of these oncogenes.
The role of the urokinase receptor in extracellular matrix degradation by ht29 human colon carcinoma cells
Authors: Reiter Lars S. , Kruithof Egbert K. O. , Cajot Jean‐Francois , Sordat Bernard 
Published: February 2007

AbstractUrokinase (u‐PA) and the urokinase receptor (u‐PAR), are thought to play a critical role in the invasive and metastatic properties of cancer cells. The HT29 human colon‐carcinoma cell line was selected to evaluate these aspects. HT29 cells express u‐PA receptors (100,000 site/cell, KD = 1.5 nM), but no PA activity and therefore are unable to generate plasmin in the presence of plasminogen. These cells have been transfected with a human u‐PA cDNA to investigate whether secreted U‐PA would enhance in vitro extracellular matrix degradation, and whether the binding of u‐PA to the cell surface is determinant. Five clones were selected for stable expression of high PA activity. These clones were capable of marked plasminogen‐dependent degradation of R22 smooth‐muscle‐cell‐derived extracellular matrix, whereas the parental cell line contributed to an insignificant breakdown only. Aprotinin, polyclonal anti‐u‐PA IgG, recombinant PAI‐2, and co‐culture with human PAI‐I ‐ producing mouse L cells significantly inhibited this degradation. Furthermore, a peptide displacing u‐PA from its receptor as well as 2 different polyclonal anti‐u‐PA receptor lgGs decreased the breakdown after 24 hr by as much as 70% and 81%, respectively. These results show that the binding of U‐PA to its receptor plays an important role in in vitro matrix breakdown by HT29 u‐PA transfectants.
Distinct P‐glycoprotein expression in two subclones simultaneously selected from a human colon carcinoma cell line by cis‐diamminedichloroplatinum (II)
Authors: Yang Li‐Ying , Trujillo Jose M. , Siciliano Michael J. , Kido Yuichiro , Siddik Zahid H. , Su Yong‐Zhuang 
Published: February 2007

AbstractTwo drug‐resistant sublines, CP2.0 and RT, were simultaneously selected by cis‐diamminedichloroplatinum (CDDP) from the human colon carcinoma cell line LoVo by the conventional method of continuous drug exposure. The 2 sublines differed in morphology, growth kinetics and pattern of gene expression. Genetic signature analysis indicated that the lines were independent subclones but that both arose from LoVo. These sublines were maintained in a growth medium containing 2.0 μg/ml CDDP. However, CP2.0 cells were 3 times more resistant to CDDP than were RT cells. Although both were cross‐resistant to mustargen and 5‐fluorouracil, only CP2.0 was resistant to Adriamycin and vincristine. Western‐blot analysis, immunocytochemical staining and in vitro phosphorylation experiments indicated that the level of P‐glycoprotein was significantly elevated in CP2.0 but not in RT. Despite the differences between these sublines, they possess similar CDDP‐resistance mechanisms, including decreased intracellular CDDP accumulation, elevated levels of glutathione and metallothionein‐like proteins, increased glutathione transferase‐μ mRNA, and enhanced susceptibility to CDDP cytotoxicity after treatment with DL‐buthionine‐[S,R]‐sulfoximine. Nevertheless, our results suggest that, in certain tumor types, P‐glycoproteinmediated multi‐drug resistance and CDDP‐resistance phenotypes can coexist in cells with primary resistance to CDDP.
Cytokeratins expressed in experimental rat bronchial carcinomas
Authors: Kal H. B. , Van Berkel A. H. , Broers J. L. V. , Klein J. C. , Mijnheere E. P. , Roholl P. J. M. , Zurcher C. , Ramaekers F. C. S. 
Published: February 2007

AbstractCytokeratin expression in rat lung tumors was studied using polypeptide‐specific monoclonal antibodies (MAbs) to human cytokeratins 4, 5, 7, 8, 10, 13, 14, 18 and 19. Experiments were performed on tumor fragments derived from 5 experimental rat squamous‐cell lung tumors and one adenocarcinoma, as well as on cell lines obtained from the same tumors. The aims of this study were to investigate the differentiation profile of the rat tumor tissue and established tumor cell lines based on light and electron microscopical features and on cytokeratin phenotype, to characterize the tumor type and degree of differentiation of the lung tumors maintained during passaging in experimental animals, and to compare the cytokeratin expression pattern in transplanted tumors with that of the cultures derived from these tumors. Our results indicate that, in general, the antibodies used cross‐react with rat cytokeratins and that these MAbs can be used to phenotype rat lung carcinomas. Both the tumor fragments and the cultured cells revealed a similar pattern of cytokeratin expression. In addition, the degree of differentiation was maintained upon prolonged culturing in vitro. MAbs to cytokeratin sub‐types can therefore be used to distinguish the main sub‐types of rat lung tumors and can give an indication about the degree of differentiation.
Expression of functional PDGF β receptors in a human large‐cell lung‐carcinoma cell line
Authors: Forsberg K. , Berch J. , Westermark B. 
Published: February 2007

AbstractIn this study we have investigated a panel of lung‐cancer cell lines, both of small‐cell carcinoma and non‐small‐cell type, for the expression of receptors for platelet‐derived growth factor. Although we found mRNA expression for the β‐type receptor on one small‐cell and one non‐small‐cell line and α‐type receptor mRNA expression on one small‐cell‐cancer cell line, only the β receptors of the non‐small‐cell line (H‐157) proved to be functional. Thus, the cell line H‐157 displayed specific binding of 125I‐PDGF‐BB in addition to mRNA expression of the 6‐kb transcript for the PDGF β type receptor. Further evidence for the presence of functional PDGF β receptors in H‐157 cells was obtained from an in vitro kinase assay, which demonstrated a ligand‐induced receptor autophosphorylation as well as the phosphorylation of a number of potential substrates associated with the activated receptor.
Dietary carcinogens and the risk for glioma and meningioma in Germany
Authors: Boeing Heiner , Schlehofer Brigitte , Blettner Maria , Wahrendorf Jürgen 
Published: February 2007

AbstractA population‐based case‐control study was performed in South‐West Germany in 1987/88 with 115 histological confirmed glioma and 81 meningioma cases and 418 randomly selected controls. On the basis of information from a foodfrequency questionnaire and questions on food preparation and food supply, the role of dietary carcinogens, in particular N‐nitroso compounds or their precursors, on risk for glioma and meningioma were analyzed by multiple logistic regression. Eleven food groups were investigated. The intake of processed meat was significantly associated with an increased risk of glioma. The intake of any food group was not significantly related to meningioma risk. Among single meat products, a significantly higher risk of glioma was found for cooked ham, processed pork meat and fried bacon. For the consumption of 3 N‐nitrosamines, assessed from the intake of processed meat and cheese, significant positive relations to glioma risk were found. These N‐nitrosamines were also related to meningioma risk, although to a less pronounced extent. The risk for occurrence of glioma was significantly increased for those using vegetable fat frequently for deep frying, as compared with non‐users. For the dietary intake of nitrate, nitrite, vitamin C, specific alcoholic beverages, total alcohol, and water from a non‐central supply, no elevated risk was found in this study.
Ganglioside expression on human malignant melanoma assessed by quantitative immune thin‐layer chromatography
Authors: Hamilton Wm. Bradley , Helling Friedhelm , Lloyd Kenneth O. , Livingston Philip O. 
Published: February 2007

AbstractThe ganglioside composition of 20 human malignant melanomas and 5 normal tissues (muscle, spleen, kidney, liver and brain) was analyzed by high‐performance thin‐layer chromatography (HPTLC) and immune HPTLC using a panel of antiganglioside monoclonal antibodies, and quantified by photoden‐sitometry. The most prominent gangliosides were GM3 and GD3, present in all 20 melanomas; however these were expressed in the 5 normal tissues as well. GD2, GM2, GT3 and 9‐O‐Ac‐GD3 were each expressed in at least 17 of 20 melanomas, but distribution on the normal tissues examined was largely restricted to brain. The detection of several additional glycolipids was studied. GMI was highly expressed in normal brain tissue, but was not detected in any melanoma biopsies, and SGPG was detected in neither. Fuc‐GM I was identified in melanoma specimens and a base‐sensitive ganglioside, not previously identified in melanoma, was detected in 4 of 20 melanomas with the anti‐GD2 MAb 3F8. This compound is most likely O‐acetylated GD2. GD3 lactones were identified in 16 of 20 melanoma biopsies, however the proportion that are naturally occurring rather than artifacts of extraction is unclear. The total expression of the more restricted gangliosides (GM2, GD2, GT3 and 9‐O‐Ac‐GD3) in these 20 melanomas ranged between 2.4 and 102.5 μg/g representing 8 × 106 to 3 × 108 ganglioside molecules per cell. This number of tumor‐surface antigens provides the rationale for a polyvalent anti‐melanoma vaccine containing GM2, GD2, GT3 and 9‐O‐Ac‐GD3.